nutritional product, method for its manufacture, and uses of an aqueous solution of a food grade bio

专利摘要:
abstract patent of invention: "cohesive thin liquids for the promotion of safe swallowing in dysphagic patients". nutritional products are provided having an improved cohesiveness to promote safer swallowing of food boluses for patients who have swallowing conditions, as well as methods for the manufacture and use of such products. nutritional products may include nutritional compositions and water-soluble high molecular weight polymers in such a way that nutritional products have extension viscosities that provide better cohesiveness for nutritional products. methods are also provided for administering such products to patients who have impaired swallowing capacity and / or dysphagia. 21530331v1 1/1 21530331v1
公开号:BR112014014147B1
申请号:R112014014147
申请日:2012-12-17
公开日:2020-05-05
发明作者:Burbidge Adam；Engmann Jan；Popa Nita Simina
申请人:Nestec Sa；Nestle Sa；
IPC主号:

专利说明:

Descriptive Report of the Invention Patent for NUTRITIONAL PRODUCT, METHOD FOR ITS MANUFACTURE, AND USES OF A WATER SOLUTION OF A FOOD GRADE BIOPOLYMER.
BACKGROUND [0001] This description refers to food products and the therapeutic use of these products. More specifically, the present description refers to nutritional products to promote safer swallowing of food boluses for patients who have swallowing conditions.
[0002] Dysphagia is the medical term for the symptom of difficulty swallowing. Epidemiological studies estimate a prevalence rate of 16% to 22% among individuals over 50 years of age.
[0003] Esophageal dysphagia affects a large number of individuals of all ages, but it is generally treatable with medication and is considered a less serious form of dysphagia. Esophageal dysphagia is almost always a consequence of diseases of the mucosa, mediastinal or neuromuscular. Mucosal diseases (intrinsic) narrow the lumen through inflammation, fibrosis or neoplasia associated with various conditions (for example, peptic stenosis secondary to gastroesophageal reflux disease, esophageal rings and nets [for example, sideropenic dysphagia or Plummer syndrome) Vinson], esophageal tumors, chemical lesion (eg, caustic soda ingestion, pill esophagitis, sclerotherapy for varicose veins), radiation damage, infectious esophagitis, and eosinophilic esophagitis). Diseases of the medium intestine (extrinsic) obstruct the esophagus through invasion or through enlargement of the lymph node associated with various conditions (tumors such as lung cancer, lymphoma], infections [such as tuberculosis, histoplasmosis], and cardiovascular [atrial dilation and vascular compression]). Neuro diseases
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2/56 muscles affect esophageal smooth muscle and innervation, interrupting peristalsis or lower esophageal sphincter relaxation, or both, commonly associated with several conditions (achalasia [both idiopathic and associated with Chagas disease] , scleroderma, other mobility disorders, and a consequence of surgery [ie, after fundoplication and anti-reflux interventions]). It is also common for individuals with foreign, intraluminal bodies to experience acute esophageal dysphagia.
[0004] Oral pharyngeal dysphagia, on the other hand, is a very serious condition and is not generally treatable with medications. Oral pharyngeal dysphagia also affects individuals of all ages, but is more prevalent in older individuals. Worldwide, oropharyngeal dysphagia affects approximately 22 million people over 50 years of age. Oral pharyngeal dysphagia is almost always a consequence of an acute event such as stroke, brain injury or surgery for oral or throat cancer. In addition, radiotherapy and chemotherapy can weaken the muscles and degrade the nerves associated with the physiology and nervous innervation of the swallowing reflex. It is also common for individuals with progressive neuromuscular disorders, such as Parkinson's disease, to experience increasing difficulty in the onset of swallowing. Representative causes of oropharyngeal dysphagia include those associated neurological diseases (brainstem tumors, head trauma, stroke, Guillain-Barré cerebral palsy syndrome, Huntington's disease, multiple sclerosis, polio, post-polio syndrome, Tardive dyskinesia, encephalopathies metabolic disorders, amyotrophic lateral sclerosis, Parkinson's disease, dementia), infectious diseases (diphtheria, botulism, Lyme disease, syphilis, mucositis [herpetic, cytomegalovirus, candida, etc.]), autoimmune diseases (lupus, scleroderma, Sjogren's syndrome ) diseases me
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3/56 tobacco (amyloidosis, Cushing's syndrome, thyrotoxicosis, Wilson's disease), myopathic diseases (connective tissue disease, dermatomyositis, myasthenia gravis. Myotonic dystrophy, oculopharyngeal dystrophy, polymyositis, sarcoidosis, paraneoplastic syndromes) inflammatory diseases (iatrogenic diseases) side effects of medication [such as chemotherapy, neuroleptics, etc.], surgical, muscle or neurogenic powders, radiation therapy, corrosives [injury by pills, intentional), and structural diseases (cricopharyngeal bar, Zenker's diverticulum, cervical webs , tumors of the oropharynx, osteophytes and skeletal abnormalities, congenital [cleft palate, diverticulum, bags, etc.]).
[0005] Dysphasia is not usually diagnosed although the disease has a greater effect on the patient's health and health care costs. Individuals with more severe dysphagia generally experience difficulty in getting food from the mouth to the stomach, which occurs immediately after swallowing. Among individuals in the housing community, perceived symptoms can lead patients to see a doctor. Among institutionalized individuals, health professionals can observe symptoms or hear comments from the patient and / or limb that suggest difficulties in swallowing and recommend that the patient be evaluated by a specialist. As the general awareness of swallowing difficulties is low among frontline professionals, dysphagia is often not diagnosed and is not treated. However, by referral to a swallowing specialist (for example, a speech therapist), a patient can be assessed clinically and the diagnosis of dysphagia can be determined.
[0006] General awareness of swallowing deficiency is low among frontline doctors. Many people (especially those who are older) suffer from impairments in swallowing
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4/56 reported and untreated. One reason is that frontline community care professionals (eg, general practitioners / geriatric home care nurses, physical therapists, etc.) usually do not screen for the disease. If they are aware of the severity of the swallowing deficiency, they generally do not use a method based on screening evidence. In addition, office-based dysphagia assessment occurs rarely.
[0007] The severity of dysphagia can vary from (i) minimal (perceived) difficulty in swallowing food and liquids, (ii) an inability to swallow without a significant risk with respect to aspiration and choking, and (iii) complete inability to swallow. Commonly, the inability to swallow food and liquids properly may be due to the bolus being broken into smaller fragments, which can enter the airways or leave undesirable residues in the oropharynx and / or esophageal tract during the swallowing process (for example, example, by aspiration). If enough material enters the lungs, it is possible that the patient can drown in the food / liquid that has accumulated in the lungs. Even small amounts of aspirated food can lead to bronchopneumonia infection, and chronic aspiration can lead to bronchiesctasia and can cause some cases of asthma.
[0008] Silent aspiration, a common condition among the elderly, refers to the aspiration of oropharyngeal content during sleep. People can compensate for less severe swallowing difficulties by self-limiting their diet. The aging process itself, coupled with chronic diseases such as hypertension or osteoarthritis, predisposes the elderly to dysphagia (subclinical) that may not be diagnosed and left untreated until a clinical complication such as pneumonia, dehydration, malnutrition (and at
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5/56 related complications). However, the differential diagnosis of aspiration pneumonia is not necessarily indicated as a result of current care practices.
[0009] The economic costs of dysphagia are associated with hospitalization, rehospitalization, loss of reimbursement due to payment for performance (P4P), infections, rehabilitation, loss of working time, clinical visits, medication use, work, time caregiver, childcare costs, quality of life, increased need for specialized care. Dysphagia and aspiration impact quality of life, morbidity and mortality. Twelve-month mortality is high (45%) among individuals and institutional care who have had dysphagia and aspiration. The economic burden of the clinical consequences resulting from the lack of diagnosis and the early treatment of dysphagia are significant.
[00010] Pneumonia is a common clinical consequence of dysphagia. The condition almost always requires acute hospitalization and visits to the emergency room. Among those who develop pneumonia due to aspiration, the differential diagnosis of aspiration pneumonia is not necessarily indicated as the result of current care practices. Based on health care utilization surveys from the United States in recent years, pneumonia was responsible for more than one million hospital discharges and an additional 392,000 were attributable to aspiration pneumonia. Individuals who had general pneumonia as the primary diagnosis had an average hospital stay of 6 days and incurred more than $ 18,000 in hospital care costs. Aspiration pneumonia is expected to lead to higher costs for hospital care, based on an average duration of eight days of hospital stay. Pneumonia is a threat to life among people with dysphagia, the chances of death in
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6/56 3 months is about 50% (van der Steen et al., 2002). In addition, an acute insult, such as pneumonia, often starts the downward spiral in health among the elderly. An insult is associated with poor intake and inactivity, resulting in malnutrition, functional decline and fragility. Specific interventions (such as to promote oral health, assist in restoring normal swallowing, or reinforcing a safe bolus to be swallowed) could benefit people at risk for, or experiencing recurrent pneumonia (due to aspiration of oropharyngeal content, including silent aspiration).
[00011] Similar to pneumonia, dehydration is a life-threatening clinical complication of dysphagia. Dehydration is a common comorbidity among hospitalized individuals with neurodegenerative diseases (and for this reason, prone to difficulty swallowing). The conditions of Alzheimer's disease, Parkinson's disease and multiple sclerosis account for approximately 400,000 hospital discharges in the United States annually, and up to 15% of these patients suffer from dehydration. Having dehydration as the primary diagnosis is associated with a duration of 4 days of hospitalization and over $ 11,000 in hospital care costs. Nevertheless, dehydration is a clinical complication of dysphagia that can be avoided.
[00012] Malnutrition and related complications (such as infections [urinary tract], pressure ulcers, increased severity of dysphagia {need for further restrictions on food choice, tube feeding and / or PEG placement and reduction in quality of life], dehydration, functional decline and related consequences [falls, dementia, frailty, loss of mobility and loss of autonomy]) may appear when swallowing difficulties lead to fear of choking on food
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7/56 and liquids, decreased consumption rate, and choice of self-limited food. If not corrected, inadequate nutritional intake exacerbates dysphagia as the muscles that help facilitate normal swallowing weaken as the physiological reserves are depleted. Malnutrition is associated with having a more than 3 times higher risk of infection. Infections are common in individuals with neurodegenerative diseases (and therefore, likely to have a chronic disability that compromises the adequacy of the diet). The conditions of Alzheimer's disease, Parkinson's disease, multiple sclerosis and account for approximately 400,000 hospital deaths per year in the United States, and up to 32% of these patients suffer from urinary tract infection.
[00013] Malnutrition has serious implications for the recovery of patients. Malnourished patients have longer hospital stays, are more likely to be hospitalized again, and have higher costs in relation to hospital care. Having malnutrition as the primary diagnosis is associated with an average duration of eight days of hospitalization and about $ 22,000 in hospital care costs. In addition, malnutrition leads to involuntary weight loss and predominant loss of muscle strength and, ultimately, impairs mobility and the ability to take care of yourself. With the loss of functionality, the caregiver's burden in general becomes more serious, requiring informal caregivers and then formal caregivers, and then institutionalization. However, malnutrition is a clinical complication of dysphagia that can be avoided.
[00014] Among people with neurodegenerative conditions (such as Alzheimer's disease) unintentional weight loss (a marker of malnutrition) precedes cognitive decline. In addition, physical activity can help stabilize cognitive health
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8/56 tiva. For this reason, it is important to ensure adequate nutrition among people with neurodegenerative conditions to help them have the strength and stamina to participate in regular therapeutic exercises and guard against unintentional weight loss, muscle loss, weight loss. physical and cognitive functionality, fragility, dementia and progressive increase in caregiver charges.
[00015] Falls and related injuries are a special concern among the elderly with neurodegenerative conditions, associated with loss of functionality. Falls are the leading cause of death from injury among elderly adults. In addition, falls-related injuries among the elderly are responsible for more than 1.8 emergency room visits in the United States in a recent year. Direct medical costs totaled 179 M for fatal falls and 193.3 B for non-fatal falls over a year. As an effect of an ambitious non-payment for the initial performance introduced in US hospitals in October 2008, Medicare will no longer pay hospitals for the cost of treating falls and related injuries that occur during the hospital stay. Hospitals will face a loss of about $ 50,000 for each elderly patient who falls and suffers a hip fracture while in hospital care. This new quality initiative is based on the premise that falls are a medical error that can be avoided. In other words, falls are preventable within reason, through the application of evidence-based practices, including medical nutrition therapy to the extent that nutritional interventions are effective in preventing falls and related injuries (for example, fractures) among the elderly.
[00016] Chewing and swallowing difficulties are also
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9/56 recognized risk factors in relation to the development of pressure ulcers. Pressure ulcers are considered a medical error that can be avoided, preventable within reason, through the application of evidence-based practices (including nutritional care, as pressure ulcers are more likely when nutrition is inadequate). Pressure ulcers are a significant burden on the health system. In the United States hospitals in 2006, there were 322,946 cases of medical error related to the development of pressure ulcers.
[00017] The average cost of pressure ulcer healing depends on the stage, ranging from about $ 1,100 (for stage II) to $ 10,000 (for stage III and IV pressure ulcers with the development of ulcers) pressure in one year is in the range of $ 323m to $ 3.2b. As an effect of an ambitious non-payment for the initial performance introduced in US hospitals in October 2008, Medicare will no longer pay hospitals with regarding the cost of treating pressure ulcers that develop during hospital stay (up to $ 3.2 B annually. Pressure ulcers can be avoided within reason, in part, by ensuring that nutritional intakes are adequate. In addition, specific interventions that include the use of specialized nutritional supplements help to reduce the time required for the healing of pressure ulcers once they have developed.
[00018] In the United States, long-term care facilities, quality standards of care are enforced through frequent regulatory oversight. Inspectors will consider installations out of compliance when they have found evidence of actual or potential negative damage / results. The range of penalties includes fines, forced closure, as well as lawsuits and fees
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10/56 settlement. The Tag F325 survey (Nutrition) considers significant unplanned weight change, inadequate food / liquid intake, decreased early wound healing, inability to provide a therapeutic diet as ordered, functional decline, and fluid / electrolyte imbalance as evidence to provide sub-standard care. The Tag F325 survey [ressure ulcers] commands that the facility must ensure that the resident who is admitted without pressure ulcers does not develop pressure ulcers unless considered unavoidable. In addition, that a resident having pressure ulcers receive the treatment and services necessary to promote healing, prevent infection and prevent new pressure ulcers from developing.
[00019] Considering the prevalence of dysphagia possible complications related to it and the costs associated with it, it would be beneficial to provide nutritional products that promote safer swallowing of food boluses in patients who are suffering from such swallowing disorders. These nutritional products increase the lives of a large and growing number of people with swallowing difficulties. Specific interventions (for example, to promote oral health, assist in restoring normal swallowing or reinforcing a safe bolus to be swallowed) may allow people to feed orally (vs, tube feeding and / or requiring placement of PEG) and experience the psychosocial aspects of food associated with general well-being while protecting against the potentially negative consequences that result from the appropriate swallowing range. Improvements in nutrition intake by dysphagia patients may also allow these patients to swallow a greater variety of food products and drinks safely and comfortably, which can lead to a healthy general condition of the patient and
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11/56 prevent an even greater decline in health.
SUMMARY [00020] This disclosure relates to nutritional products and the therapeutic use of these products. More specifically, the present disclosure is related to nutritional products to promote safer swallowing of liquids.
[00021] In a first aspect, the invention relates to a nutritional product comprising an aqueous solution of a food grade biopolymer capable of providing the nutritional product with a shear viscosity of less than about 100 mPas, preferably less than about 50 mPas, when measured at a shear rate of 50 ^s-1 , and a relaxation time, determined by an Capillary Breakup Extensional Rheometry (CaBER) Rheometry experiment of more than 10 ms (milli seconds) at a temperature of 20 ° C.
[00022] In a preferred embodiment of the first aspect of the invention, the shear viscosity is at least about 1 mPas, preferably from at least about 1 mPas to less than about 50 mPas, and more preferably from at least 5 mPas to less than 20 mPas, when measured at a shear rate of 50s ^-1 .
[00023] It is still preferably that the relaxation time is less than about 2000 ms, preferably from about 20 ms to about 1000 ms, more preferably from about 50 ms to about 500 ms , and most preferably from about 100 ms to about 200 ms, at a temperature of 20 ° C.
[00024] In another preferred embodiment of the first aspect of the invention, the diameter of the filament of the nutritional product decreases less than linearly, and preferably exponentially in time during a CaBER experiment.
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12/56 [00025] It is also preferably that the biopolymer is comprised in the aqueous solution in a concentration from less than 0.01% by weight to 25% by weight, preferably from at least 0.1% by weight up to 15% by weight and more preferably from at least 1% by weight to 10% by weight.
[00026] Another preferred embodiment of the first aspect of the invention relates to the nutritional product in diluted form, preferably in an aqueous dilution ranging from 2: 1 to 50: 1, more preferably from 3: 1 to 20: 1 and most preferably from 5: 1 to 10: 1.
[00027] In another preferred embodiment of the first aspect of the invention, the food grade biopolymer is selected from the group consisting of botanical hydrocolloids, microbial hydrocolloids, animal hydrocolloids, algal hydrocolloids and any combinations thereof.
[00028] It is specifically preferred that algae hydrocolloids are selected from the group consisting of agar, carrageenan, alginate or any combination thereof. In another preferred embodiment, microbial hydrocolloids are selected from the group consisting of xanthan gum, gellan gum, curdlan gum or any combination thereof. In another preferred embodiment, botanical hydrocolloids are selected from the group consisting of gums extracted from plants, mucilages derived from plants and their combinations.
[00029] Gums extracted from plants can also be selected from the group consisting of okra gum, konjac gum, tara gum, locust bean gum, guar gum, fenugreek gum, tamarind gum, cassia gum, gum acacia, ghatti gum, pectins, celluloses, tragacanth gum, caraia gum, or any combination thereof. In a specific preference modality of the
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13/56 first aspect of the invention, the gum extracted from plants is okra gum.
[00030] Mucilages derived from plants can be chosen preferably from the group consisting of mucilage of kiwi fruit, mucilage of cactus (Ficus indica), mucilage of chia seeds (Salvia hispanica), mucilage of psyllium (Plantago ovata ), mallow mucilage (Malva sylvestris), flax seed mucilage (Linum usitatissimum), marshmallow mucilage (Althaea officinalis), ribwort mucilage (Plantago lanceolata), mullein mucilage (Verbascum), cetraria mucilage (Lichen island) , or any combinations thereof. In a preferred embodiment specific to the first aspect of the invention, the plant-derived mucilage is kiwi mucilage.
[00031] In another preferred embodiment of the first aspect of the invention, the food grade biopolymer is selected from okra gum and / or kiwi fruit mucilage, or a combination thereof. It is most preferred that the mucilage of the kiwi fruit is derived from the kernel of the kiwi fruit stem.
[00032] In a preferred embodiment specific to the first aspect of the invention, the aqueous solution comprises rigid particles, preferably in I the rigid particles have a size between 1 and 100 micrometers, and / or the rigid particle is comprised in an amount between 5 and 80% by volume; and / or the rigid particles are selected from the group consisting of sucrose crystals, coconut particles, microcrystalline cellulose particles, starch granules and modified starch, protein particles and any combinations thereof.
[00033] In an embodiment of the first aspect of the invention, nutritional products include a prebiotic. Prebiotic is preferably selected from the group consisting of acacia gum, alpha
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14/56 glucan, arabino galactans, betaglucano, dextrans, fructooligosaccharides, fucosylactose, galacto, galactomannans, gentile oligosaccharides, gluco oligosaccharides, guar gum, inulin, isomalt, lactoneotetraose, lactossaccharose, lactose, levanoxide, lactose, levano, malano partially hydrolyzed, pectic oligosaccharides, resistant starches, retrograded starch, sialo oligosaccharides, sialyl lactose, soy oligosaccharides, sugar alcohols, xyl oligosaccharides, their hydrolysates, and combinations thereof.
[00034] In another embodiment of the first aspect of the invention, nutritional products include a probiotic. The probiotic is preferably selected from the group consisting of Aerococcus, Aspergillus, Bacteroides, Bifidobacterium, Candida, Clostridium, Debaromyces, Enterococcus, Fusobacterium, Lactobacillus, Lactococcus, Leuconostoc, Melissococcus, Micrococcus, Peptococcus, Mucor, Ostrich , Pichia, Propionibacterium, Pseudocatenulatum, Rhizopus, Saccharomyces, Staphylococcus, Streptococcus, Torulopsis, Weissella, and combinations thereof. [00035] In yet another embodiment of the first aspect of the invention, nutritional products include an amino acid. The amino acid is preferably selected from the group consisting of alanine, arginine, asparagine, aspartate, citrulline, cysteine, glutamate, glutamine, glycine, histidine, hydroxyproline, hydroxyiserine, hydroxytyrosine, hydroxylisin, isoleucine, leucine, lysine, methionine, phenylalanine, phenylalanine , proline, serine, taurine, threonine, tryptophan, tyrosine, valine, and combinations thereof.
[00036] In yet another embodiment of the first aspect of the invention, nutritional products preferably include a fatty acid selected from the group consisting of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and combinations
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15/56 of them. DHA and EPA can preferably be derived from a source selected from the group consisting of fish oil, krill, plant sources containing ω-3 fatty acids, flaxseed, walnut, algae and combinations thereof. Certain fatty acids (eg 18:04 fatty acids) can also be easily converted to DHA and / or EPA. Nutritional product can also include α-linolenic acid.
[00037] In an embodiment of the first aspect of the invention, nutritional products include a phytonutrient, which is preferably selected from the group consisting of flavonoids, allied phenolic compounds, polyphenolic compounds, terpenoids, alkaloids, sulfur-containing compounds and combinations thereof. In another preferred embodiment, the phytonutrient is selected from the group consisting of carotenoids, plant sterols, quercetin, curuminum, limonine and combinations thereof.
[00038] In another preferred embodiment of the first aspect of the invention, nutritional products include an antioxidant, which is preferably selected from the group consisting of astaxanthin, carotenoids, coenzymes Q10 (CoQI O), flavonoids, glutathione Goji (wolfberry ), hesperidin, lactowolfberry, lignans, lutein, lycopene, polyphenols, selenium, vitamin A, vitamin C, vitamin E, zeaxanthin, and combinations thereof.
[00039] In another embodiment of the first aspect of the invention, the nutritional product is in a form that can be administered selected from the group consisting of pharmaceutical formulations, nutritional formulations, dietary supplements, functional food and beverage products or combinations of themselves.
[00040] A second aspect of the invention concerns the use of a nutritional product according to the first aspect of the invention or any of its modalities for the treatment of a disorder
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16/56 swallowing.
[00041] In a third aspect, the invention concerns the use of a nutritional product according to the first aspect of the invention or any of its modalities for the promotion of the safe swallowing of nutritional products in a patient who is in need of them.
[00042] In a fourth aspect, the invention refers to the use of a nutritional product according to the first aspect of the invention or any of its modalities to mitigate the risks of aspiration during the swallowing of nutritional products in a patient who is in need of the same.
[00043] A fifth aspect of the invention concerns a method for the manufacture of a nutritional product, the method comprising providing an aqueous solution and a food grade biopolymer capable of providing the nutritional product with a shear viscosity of less than about 100 mPas, preferably less than about 50 mPas, when measured at a shear rate of 50s ^-1 and a relaxation time, determined by a Capillary Breakup Extensional Rheometry (CaBER) experiment, greater than 10 ms (milliseconds) in a temperature of 20 ° C.
[00044] In a preferred embodiment this aspect, the shear viscosity is at least about 1 mPas, preferably from at least 1 mPas to less than about 50 mPas, more preferably from at least 5 mPas to less than 20 mPas, when measured at a shear rate of 50s ^-1 .
[00045] In another preferred embodiment of the method of the invention, the relaxation time is less than about 2000 ms, preferably from about 20 ms to about 1000 ms, more preferably from 50 ms to about 500 ms, and more preferably at
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17/56 from about 100 ms to about 200 ms.
[00046] In a preferred embodiment specific to the fifth aspect of the invention, the diameter of the filament of the nutritional product decreases less than linearly and preferably exponentially in time during a CaBER experiment.
[00047] In another preferred embodiment of the fifth aspect of the invention, the aqueous solution comprises a food grade biopolymer in a concentration from at least 0.01% by weight to 20% by weight, preferably from at least 0.1% by weight to 15% by weight, and most preferably from at least 1% by weight to 10% by weight.
[00048] In another embodiment, the method according to the fifth aspect of the invention also comprises the step of diluting the nutritional product, preferably in an aqueous dilution ranging from 2: 1 to 50: 1, more preferably from from 3: 1 to 20: 1 and more preferably from 5: 1 to 10: 1.
[00049] In yet another modality of the fifth aspect, the food-grade biopolymer is selected from the group consisting of botanical hydrocolloids, microbial hydrocolloids, animal hydrocolloids, algal hydrocolloids and any combinations thereof.
[00050] In yet another embodiment of the fifth aspect of the invention, algae hydrocolloids are selected from the group consisting of agar, carrageenan, alginate or any combination thereof. In another preferred embodiment, microbial hydrocolloids are selected from the group consisting of xanthan gum, gellan gum, curdlan gum or any combination thereof. In another preferred embodiment, botanical hydrocolloids are selected from the group consisting of gums extracted from plants, mucilages derived from plants and their combinations.
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18/56 [00051] One preferred embodiment of the invention relates to the method according to the fifth aspect of the invention, in which the gums extracted from plants are selected from the group consisting of arachis, konjac gum, tara gum, gum locust bean, guar gum, fenugreek gum, tamarind gum, cassia gum, acacia gum, ghatti gum, pectins, celluloses, tragacanth gum, caraway gum, or any combination thereof. In a specific preferred embodiment, the gum extracted from plants is okra gum.
[00052] Another preferred embodiment of the invention concerns the method according to the fifth aspect, in which the mucilages derived from plants are selected from the group consisting of mucilage of the kiwi fruit, mucilage of cactus (Ficus indica), mucilage of chia seeds (Salvia hispanica), mucilage of psyllium (Plantago ovata), mucilage of mallow (Malva sylvestris), mucilage of flax seeds (Linum usitatissimum), mucilage of marshmallow (Althaea officinalis), mucilage of ribwort (Plantago lanceolata ), mullein mucilage (Verbascum), literary mucilage (Lichen islandicus), or any combination thereof. In a specific preferred embodiment, the plant-derived mucilage is kiwi mucilage.
[00053] In another preferred embodiment of the method of the invention, the food grade biopolymer is selected from okra gum and / or mucilage from the kiwi fruit, or a combination thereof. It is most preferred that in this method the mucilage of the kiwi fruit is derived from the marrow of the kiwi fruit stem.
[00054] In a preferred embodiment specific to the fifth aspect of the invention, the aqueous solution comprises rigid particles, preferably in which the rigid particles are between 1 and 100 micrometers in size and / or the rigid particles are composed
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19/56 in an amount of about 5 and 80% by volume and / or the rigid particles are selected from the group consisting of sucrose crystals, coconut particles, microcrystalline cellulose particles, starch granules and modified starch , protein particles and any combinations thereof.
[00055] In another embodiment of the fifth aspect of the invention, the method of the invention further comprises the addition to the nutritional product of a prebiotic, which is preferably selected from the group consisting of acacia gum, alpha-glucan, arabino galactans, beta-glucan, dextrans, fructo-oligosaccharides, fucosilactose, galacto, galactomannans, gentile oligosaccharides, gluco oligosaccharides, guar gum, inulin, isomalto, lactoneotetraose, lactosaccharose, lactulose, levano, dextrin malty, oligosaccharides, partially oligosaccharides resistant starches, retrograded starch, sialo oligosaccharides, sialyl lactose, soy oligosaccharides, sugar alcohols, xyl oligosaccharides, their hydrolysates, and combinations thereof.
[00056] In another embodiment of the fifth aspect of the invention. the method of the invention also comprises the addition to the nutritional products of a probiotic which is preferably selected from the group consisting of Aerococcus, Aspergillus, Bacteroides, Bifidobacterium, Candida, Clostridium, Debaromyces, Enterococcus, Fusobacterium, Lactobacillus, Lactococcus, Leuconostoc, Melissococcus, Micrococcus, Mucor, Oenococcus, Pediococcus, Penicillium, Peptostrepococcus, Pichia, Propionibacterium, Pseudocatenulatum, Rhizopus, Saccharomyces, Staphylococcus, Streptococcus, Torulopsis, Weissella, and the combinations of the same.
[00057] In another embodiment of the fifth aspect of the invention, the method of the invention also comprises the addition to nutritional products of an amino acid, which is preferably selected from
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20/56 of the group consisting of alanine, arginine, asparagine, aspartate, citrulline, cysteine, glutamate, glutamine, glycine, histidine, hydroxyproline, hydroxyiserine, hydroxytyrosine, hydroxylysine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine taurine, threonine, tryptophan, tyrosine, valine, and combinations thereof.
[00058] In another embodiment of the fifth aspect of the invention, the method of the invention also comprises the addition to the nutritional products of a fatty acid, preferably selected from the group consisting of docosahexanoic acid (DHA), eicosapentaenoic acid ( EPA) and their combinations. DHA and EPA can preferably be derived from a source selected from the group consisting of fish oil, krill, plant sources containing ω-3 fatty acids, flaxseed, walnut, algae and combinations thereof. Certain fatty acids (eg 18:04 fatty acids) can also be easily converted to DHA and / or EPA. Nutritional product can also include α-linolenic acid. [00059] In another embodiment of the fifth aspect of the invention, the method of the invention also comprises the addition to the nutritional products of phytonutrient selected from the group consisting of flavonoids, allied phenolic compounds, terpenoid polyphenolic compounds, alkaloids, sulfur-containing compounds and their combinations. It is also preferably that the phytonutrient is selected from the group consisting of carotenoids, plant sterols, quercetin, curumina, limonine and combinations thereof.
[00060] In one embodiment, the method according to the fifth aspect of the invention further comprises the addition to the nutritional product of an antioxidant selected from the group consisting of astaxanthin, carotenoids, coenzymes Q10 (CoQI O), flavonoids, glutathione Goji (wolfberry), hesperidin, lactowolfberry, lignans, lutein,
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21/56 lycopene, polyphenols, selenium, vitamin A, vitamin C, vitamin E, zeaxanthin, and combinations thereof.
[00061] In another embodiment the method of the invention comprises the step of placing the nutritional products in a form that can be administered, which is preferably selected from the group consisting of pharmaceutical formulations, nutritional formulations, dietary supplements, food and drinks functional combinations.
[00062] An advantage of the aspects above one to five of the invention and the modalities thereof is that of providing nutritional products, and specifically that of providing improved liquid nutritional products.
[00063] A specific advantage of these aspects and modalities is to provide improved liquid nutritional products for patients who have dysphagia.
[00064] Yet another specific advantage of the above aspects and modalities of the invention is that of providing nutritional products that are useful for the treatment of patients who have dysphagia.
[00065] Yet another advantage of the above aspects and modalities of the invention is that of providing nutritional products that are useful for promoting the safe swallowing of food boluses.
[00066] Additional features and advantages are described here in this patent application and will become apparent from the following Detailed Description.
DETAILED DESCRIPTION [00067] In the form used here, in this patent application, about is understood to refer to numbers in a range of numbers. In addition, all numerical ranges here, in this patent application, are to be understood as including all integers, totals or fractions, within the range.
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22/56 [00068] In the form used here, this patent application% by weight is understood to refer to the weight of the polymer by the total weight of the product.
[00069] The term amino acid is understood to include one or more amino acids. Amino acids can be, for example, alanine, arginine, asparagine, aspartate, citrulline, cysteine, glutamate, glutamine, glycine, histidine, hydroxyproline, hydroxyiserine, hydroxytyrosine, hydroxylsine, isoleucine, leucine, lysine, methionine, phenylalanine, praline, serine, proline taurine, threonine, tryptophan, tyrosine, valine, or combinations thereof.
[00070] In the form used here, this animal patent application includes, but is not limited to, mammals which include but are not limited to rodents, aquatic mammals, domestic animals such as dogs and cats, farm animals such as sheep, pigs, cows and horses, and humans. In which the term animal or mammal or its plurals is used, it is contemplated that it also applies to any animals if they are capable of the effect exhibited or intended to be exhibited through the context of the passage.
[00071] In the form used here, in this patent application, the term antioxidant is understood to include one or more of several substances such as beta carotene (a precursor to vitamin A), Vitamin C, vitamin E and selenium which inhibit oxidation or reactions promoted by Oxygen Reactive Species (ROS) and other radical and non-radical species. In addition, antioxidants are molecules capable of slowing or preventing oxidation of other molecules. Non-limiting examples of antioxidants include carotenoids, coenzyme Q10 (CoQlO), flavonoids, glutathione Goji (wolfberry), hesperidin, lactowolfberry, lignans, lutein, lycopene, polyphenols, selenium, vitamin A, vitamin B and vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, zeaxanthin, or combinations thereof
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23/56 [00072] Although the terms individual and patient are almost always used here, in this patent application, to refer to a human being, the invention is not limited in this way. Consequently, the terms individual and patient refer to any animal, mammal or human being who has or is at risk of having a medical condition that can benefit from the treatments.
[00073] In the form used here, in this patent application, non-limiting examples of sources of ω-3 fatty acids such as α-linolenic acid (ALA), docosahexanoic acid (DHA) and eicosapentanoic acid (EPA) include oil of fish, krill, poultry, eggs, or other vegetable or nut sources, such as flax seed, walnuts, almonds, algae, modified plants, etc.
[00074] In the form used here, in this patent application, food grade microorganisms means micro organisms that are used and generally recognized as safe to be used in food.
[00075] In the form used herein, this mammalian patent application includes, but is not limited to, rodents, aquatic mammals, domestic animals such as dogs and cats, farm animals such as sheep, pigs, cows and horses, and humans. Where the term animal or mammal or its plurals is used, it is contemplated that it also applies to any animals if they are capable of the effect exhibited or intended to be exhibited by the mammal.
[00076] The term microorganism is meant to include bacteria, yeasts and / or fungi, a cell culture medium with microorganisms or a cell culture medium in which the microorganism was grown.
[00077] In the form used here, in this patent application, the term minerals is understood to include boron, calcium, chromium, copper, iodine,
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24/56 iron, magnesium, manganese, molybdenum, nickel, phosphorus, potassium, selenium, silicon, tin, vanadium, zinc, or combinations thereof.
[00078] In the form used here, in this patent application, a non-replicating microorganism means that non-viable cells and / or colony forming units that can be detected using classical plating methods. Such classic plating methods are summarized in the book microbiology: James Monroe Jay, et al., Modern food microbiology, 7th edition, Springer Science, New York, N. Y. p. 790 (2005). Typically the absence of viable cells can be shown as follows; no visible colony on agar plates or any growing turbidity in liquid growth medium after inoculation with different concentrations of bacterial preparations (non-replicating samples) and incubation under appropriate conditions (aerobic and / or anaerobic atmospheres for at least 24 hours). For example, bifidobacteria such as Bifidobacterium longum, Bifidobacterium lactis and Bifidobacterium breve or lactobacilli, such as Lactobacillus paracasei or Lactobacillus rhamnosus, can be made non-replicating by heat treatment, in particular heat treatment at low temperature / long time.
[00079] In the form used here, in this patent application, nucleotide is understood to be a subunit of deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). It is an organic compound made from nitrogen, a phosphorus molecule, and a sugar molecule (deoxyribose in DNA and ribose in RNA). Individual nucleotide monomers (individual units) are linked together to form polymers, or long chains. Exogenous nucleotides are specifically provided for by dietary supplementation. The exogenous nucleotide can be in a monomeric form such as adenosine 5'-monophosphate (5'-AMP), 5 '
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25/56 guanosine monophosphate (5'-GMP), Cytosine 5'-monophosphate (5'CMP), uracil 5'-monophosphate (5'-UMP), Inosine 5'-monophosphate (5'-IMP) , 5'-thymine monophosphate (5'-TMP), or combinations thereof. The exogenous nucleotides can also be in a polymeric form such as, for example, intact RNA. There can be multiple sources of polymeric form, such as for example yeast RNA.
[00080] Nutritional compositions as used herein, in this patent application, are understood to include any number of optional additional ingredients including conventional food additives, for example one or more acidulants, additional thickeners, buffers or agents for adjustment pH, chelating agents, dyes, emulsifiers, excipients, flavoring agents, minerals, osmotic agents, a pharmaceutically acceptable carrier, preservatives, stabilizers, sugars, sweeteners, texture agents and / or vitamins. Optional ingredients can be added in any suitable amount.
[00081] In the form used here, in this patent application, the term patient is understood to include, including an animal, especially a mammal and more especially a human being receiving or intending to receive treatment, as defined herein, in this patent application.
[00082] In the form used here, in this patent application, phytochemicals or phytonutrients are non-nutritive compounds that are found in many foods. Phytochemicals are functional foods that have health benefits in addition to basic nutrition, and are composed of health promotion that comes from plant sources. Phytochemicals and phytonutrients refer to any chemical substance produced by a plant that confers one or more health benefits. Non-limiting examples of phytochemicals, phytonutrients, include those:
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26/56 [00083] phenolic compounds that include monophenols (such as, for example, apiola, carnosol, carvacrol, dilapiola, rosemarinol); flavonoids (polyphenols) including flavonoids (such as, for example, quercetin, fingerol, campferol, myricetin, rutin, isoramnetin), flavanones (such as, for example, fesperidin, naringenin, silybin, eriodicthiol), flavones (such as, for example , apigenin, mandarin, luteolin), flavan-3-ols (such as, for example, catechins, (+) - catechin, (+) - galocatechin, (-) - epicatechin, (-) - epigallocatechin, (-) gallate epigallocatechin (EGCG), (-) - epicatechin 3-gallate, teaflavine, teaflavine-3-gallate, teaflavine-3'-gallate, teaflavine-3, 3'-digalate, tearubigins), anthocyanins (flavonal) and anthocyanidins ( such as, for example, pelargonidin, peonidine, cyanidin, delfinidine, malvidin, pethunidine), isoflavones (phytoestrogens) (such as, for example, daidzein (formononetin), genistein (biocanine A), glycitein), dihydroflavonoids, chalconas coumestanos (phytoestrogens), and Coumestrol; phenolic acids (such as: ellagic acid, gallic acid, tannic acid, vanillin, curcumin); hydroxy cinnamic acids (such as, for example, caffeic acid, chlorogenic acid, cinnamic acid, ferulic acid, coumarin); lignans (phytoestrogens), silymarin, secaisolariciresinol, pinoresinol and lariciresinol); tyrosol esters (such as, for example, tyrosol, hydroxytyrosol, oleocanthal, oleuropein); stylbenoids (such as, for example, resveratrol, pterostilbene, piceatanol) and punicalagins;
[00084] terpenes (isoprenoids) which include carotenoids (tetraterpenoids) including carotenes (such as, for example, α-carotene, β-carotene, γ-carotene, δ-carotene, lycopene, neurosporene, phyto-fluene, phytoene), and xanthophylls (such as , for example canthaxanthin, cryptoxanthin, aeaxanthin, astaxanthin, lutein, rubixanthin); monoterpenes (such as, for example, limonene, peryl alcohol); saponins; lipids including: phytosterols (such as, for example, campesterol, beta sitosterol, gamma sitosterol, stigmasterol), tocopherols (vitamin E), and ω -3, -6,
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27/56
-9 and fatty acids (such as, for example, gamma linolenic acid); triterpene (such as, for example, oleanolic acid, ursolic acid, betulinic acid, moronic acid);
[00085] betaines, which include betacyanins (such as betaine, isobetaine, neobetaine) and bexanthin (non-glycosidic versions) (such as, for example, indicaxanthin and vulgaxanthone);
[00086] organosulfides, which include, for example, dithiolthiones (isothiocyanates) (such as, for example, sulforophane); and thiosulfonates (alium compounds) (such as, for example, allyl methyl trisulfide and diallyl sulfide) indoles, glucosinates, which include, for example, indole-
3-carbinol, sulforophane; 3-3'-diindolylmethane, sinigrine; allicin, alinine, allyl isothyanate, piperione, sin-propanothial-S-oxide;
[00087] protein inhibitors which include, for example, protease inhibitors;
[00088] other organic acids including oxalic acid, phytic acid, (inositol hexaphosphate); tartaric acid and anacardic acid, or [00089] combinations thereof.
[00090] In the form used here, in this disclosure and in the appended claims, the singular forms one, one and / or o include plural referents unless the context dictates otherwise clearly. Thus, for example, a polypeptide includes a mixture of two or more polypeptides and the like.
[00091] In the form used here, in this patent application, a prebiotic is a food substance that selectively promotes the growth of beneficial bacteria or inhibits the growth or adhesion to the mucosa of pathogenic bacteria in the intestines. They are not inactivated in the stomach and / or small intestine or absorbed from the gastrointestinal tract of the person who is ingesting them, but they are fermented by the gastrointestinal microflora and / or through probiotics. Prebiotics are for example defined by Glenn R. Gibson
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28/56 and Marcel B. Roberfroid, Dietary Modulation of the Human Colonic Microbiota: Introducing the Concept of Prebiotics, J. Nutr. 1995 125: 1401-1412. Non-limiting examples of prebiotics include acacia gum, alpha-glucan, arabinogalactans, betaglucan, dextrans, fruit oligosaccharides, fucosylactose, galactooligosaccharides, galactomannans, gentiooligosaccharides, glucooligoligosaccharides, lactam, lactose, lactose, lactose, lactose, lactose, lactose, lactose, lactose , maltodextrins, milk oligosaccharides, partially hydrolysed guar gum, pecticoligosaccharides, resistant starches, retrograded starch, sialooligosaccharides, sialyl lactose, soybean oliosaccharides, sugar alcohols, xylooligosaccharides, or the same hydrolysates.
[00092] In the form used here, in this patent application, probiotic microorganisms, (hereinafter probiotics) are food-grade microorganisms (live, including semi-viable or weakened and / or non-replicating), metabolites, preparations of microbial cells or components of microbial cells that can confer health benefits on the host when administered in adequate amounts, more specifically, which beneficially affect a host by improving the microbial balance of the intestine, leading to effects on health or well being host's being. See, Salminen S, Ouwehand A. Benno Y. et al., Probiotics: how should they be defined , Trends Food Sci. Technol. 1999: 10, 107-10. In general, it is believed that these microorganisms inhibit or influence the growth and / or metabolism of pathogenic bacteria in the intestinal tract. Probiotics can also activate the host's immune function. For that reason, there have been many different approaches to the inclusion of probiotics within food products. Non-limiting examples of probiotics include Aerococcus, Aspergillus, Bacillus, Bacteroides, Bifidobacterium, Candida,
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29/56
Clostridium, Debaromyces, Enterococcus, Fusobacterium, Lactobacillus, Lactococcus, Leuconostoc, Melissococcus, Micrococcus, Mucor, Oenococcus, Pediococcus, Penicillium, Peptostrepococcus, Pichia, Propionibacterium, Pseudococus, Sysococcus themselves.
[00093] The terms protein, peptide, oligopeptide or polypeptide in the form used herein, in this patent application, are understood to refer to any composition that includes a single amino acid (monomers), two or more amino acids linked together through a peptide bond (dipeptide, tripeptide or polypeptide), collagen, precursor, homolog, analog, mimetic, salt, prodrug, metabolite or fragment thereof or combinations thereof. For the sake of clarity, the use of any of the above terms is interchangeable, unless otherwise specified. It will be appreciated that polypeptides (or peptides or proteins or oligopeptides) almost always contain substances other than the 20 amino acids normally referred to as the naturally occurring 20 amino acids, and that many amino acids, including terminal amino acids, can be modified in a given polypeptide, through natural processes, such as glycosylation and other post-translation modifications, or by chemical modification techniques that are well known in the art. Known modifications that may be present in polypeptides of the present invention include, but are not limited to, acetylation, acylation, ADP ribosylation, amidation, covalent bonding of a flavonoid, or a heme part, covalent bonding of a polynucleotide or polynucleotide derivative, covalent bonding of a lipid or lipid derivative, covalent bonding of phosphatidyl inositol, crosslinking, cyclization, disulfide bonding, demethylation, crosslinking
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30/56 covalent sections, cystine formation, pyroglutamate formation, formulation, gamma carboxylation, glycation, glycosylation, glycosylphosphatidyl inositol, (GPI) membrane anchor formation, hydroxylation, iodation, methylation, myristylation, oxidation, proteolytic processing, phosphorylation, prenylation, racemization, selenoylation, sulfation, transfer RNA mediated by addition of polypeptide amino acids, such as arginylation, and ubiquitination. The term protein also includes artificial proteins which refer to linear or non-linear polypeptides, which consist of alternating repeats of a peptide.
[00094] Non-limiting examples of proteins include milk proteins, plant-based proteins, proteins of animal origin and artificial proteins. Dairy-based proteins include, for example, casein, caseinates (for example, all forms, including sodium, calcium, potassium caseinates), casein hydrolysates, whey (for example, all forms, including concentrate , isolated, demineralized), whey hydrolysates, milk protein concentrate, and milk protein isolates. Plant-based proteins include, for example, soy protein (for example, all forms, including concentrates and isolates), pea protein (for example, all forms, including concentrates and isolates), canola protein ( for example, all forms, including concentrates and isolates), other plant proteins which are commercially wheat proteins and fractionated proteins from wheat, maize and their fractions including zein, rice, oats, potatoes, peanuts, powdered green peas, green bean powder, and any proteins derived from beans, lentils and vegetables. Animal-based proteins can be selected from the group consisting of meat, poultry, fish, lamb, seafood, or their combinations.
[00095] All dosage ranges contained within this application
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Patent 31/56, are intended to include all integers or fractions, contained within those ranges.
[00096] In the form used here, in this patent application, symbiotics are a supplement that contain both a prebiotic and a probiotic that work together to improve the micro flora of the intestine.
[00097] In the form used here, in this patent application, the terms treatment, treat and to alleviate include both prophylactic or preventive treatment (which prevents and / or delays the development of a pathological condition or targeted disorder) and therapeutic curative treatment or disease modification, which includes therapeutic measures that cure or delay, decrease symptoms and, or stop the progression of a condition or pathological disorder diagnosed; and the treatment of patients at risk of contracting a disease or suspected of contracting a disease, as well as patients who are ill or who have been diagnosed as suffering from a disease or medical condition. The term does not necessarily imply that a patient is treated until full recovery. The terms treatment and treat also refer to maintaining and / or promoting health in an individual who is not suffering from a disease but who may be susceptible to the development of an unhealthy condition, such as nitrogen imbalance or loss of musculature. treatment, treatment and alleviation are also intended to include potentiation or otherwise improving one or more primary prophylactic or therapeutic measures. The terms treatment, treat and alleviate are also intended to include the management of nutritionals for a disease or condition or dietary management for the prophylaxis or prevention of a disease or condition.
[00098] In the form used here, in this patent application, the term vi
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32/56 tamine is understood to include any of the various fat-soluble or water-soluble organic substances (non-limiting examples include vitamin A, vitamin BI (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin or niacinamide), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine, pyridoxal or pyridoxamine, or pyridoxine hydrochloride), vitamin B7 (biotin), vitamin B9 (folic acid), and vitamin B 12 (various cobalamines; commonly cyanocobalamin in vitamin supplements) , vitamin C, vitamin D, vitamin E, vitamin K, folic acid and biotin) essential in minimal amounts for normal growth and body activity and obtained naturally from foods of plant and animal origin or made in synthetic form, for vitamins , derivatives, analogues.
[00099] This disclosure relates to nutritional products for the promotion of safe swallowing of food boluses for patients suffering from swallowing disorders, including, for example, dysphagia. The present disclosure also relates to methods for providing treatment with respect to a patient who has a swallowing disorder.
[000100] The normal swallowing of a human (or mammal) involves three distinct phases that are independent and well coordinated: the phases (i) the oral, (ii) pharyngeal, (iii) esophageal. In the oral phase, which is under voluntary control, the food that was chewed and mixed with saliva is formed into a bolus to be supplied through voluntary movements of the tongue to the bottom of the mouth, into the pharynx. The pharyngeal and involuntary phase is triggered by the passage of the bolus / liquid through the faucial pillars into the pharynx. Contraction of the three pharyngeal constrictors propels the bolus into the upper esophageal sphincter. Simultaneously, the soft palate closes the nasopharynx. The larynx moves upward to prevent food or liquid from entering the airways, which is aided by
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33/56 inclination behind the epiglottis and closing of the vocal folds. The esophageal phase is also involuntary and begins with relaxation of the upper esophageal sphincter followed by peristaltic movements that push the bolus down into the stomach.
[000101] Dysphagia refers to symptoms of difficulty in swallowing. The following general causes of dysphagia have been identified: [000102] Decreased swallowing capacity [000103] The tongue does not put enough pressure on the soft palate [000104] Iatrogenic [000105] Surgical removal of part of the tongue or soft palate [000106 ] treatment for snoring or sleep apnea [000107] Recession due to tumor (malignant or benign) [000108] Genetics [000109] Hypoplasia of the tongue or soft palate [000110] Hypo or lack of innervation in the tongue or soft palate [ 000111] Traumatic [000112] Tissue injury [000113] Disinervation / hypoinervation [000114] Neurological [000115] Local denervation / hypoinervation [000116] CNS [000117] after stroke [000118] Demilination [000119] Abnormal behavior of epiglottis [0001] ] not closing or opening at the appropriate times [000121] opening too early [000122] not closing in time [000123] delayed closing [000124] not closing completely (insufficient flexibility atrophy)
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34/56 [000125] semisó [000126] The consequences of untreated or poorly managed oropharyngeal dysphagia can be serious, including dehydration, malnutrition leading to dysfunctional immune response, and reduced functionality, airway obstruction with solid foods (choking) and aspiration through the airways of liquids and semi-solid foods, promoting aspiration pneumonia and / or pneumonitis. Severe oral dysphagia may require that nutrition be supplied by tube.
[000127] Mild to moderate oral pharyngeal dysphagia may require that the texture of food be modified in order to minimize the possibility of choking or aspiration. This may include thickening of liquids and / or pureing solid foods, both of which have been shown to be the most effective means of preventing choking and aspiration during the feeding process. The thickened liquids are intended to have three properties: (i) a more cohesive bolus that can be maintained through the entire swallowing action, (ii) slower throat supply, thereby compensating for the increased period in which reflexes swallowing preparations are made in relation to the thickened liquid, and (iii) providing a greater density to increase the awareness of the presence of boluses of food or liquid in the mouth.
[000128] Improving an individual's ability and efficiency to swallow, improves individual safety by reducing the risk of pulmonary aspiration. Efficient swallowing can allow greater independence from food assistance and / or reduction in the time spent on food assistance during meal consumption. Efficient swallowing also reduces the viscosity of liquids required for safety (such as the thickness of puddings and honey or nectar products) and can also limit the use of foods with modified texture. All of these factors
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35/56 previously described are aimed at improving the quality of life of an individual.
[000129] For this reason, the present disclosure provides nutritional products to promote safer swallowing of food boluses in patients with swallowing disorders (such as dysphagia patient) through preventing bolus penetration and aspiration through changes in the rheological properties of food and beverages.
[000130] The nutritional products of the present invention comprise an aqueous solution of a food grade biopolymer, which is capable of providing the nutritional product with a shear viscosity of less than about 100 mPas, preferably less than about 50 mPas, when measured at a shear rate of 50s ^-1 and a relaxation time determined through a Capillary Breakup Extensional Rheometry (CaBER) experiment, greater than 10 ms (milliseconds) at a temperature of 20 ° C.
[000131] Rheology is the study of the flow of matter, primarily in the liquid state but also in soft solids or solids under conditions in which they respond with a plastic flow instead of the deforming elasticity in response to the application of a force. The flow of substances cannot generally be characterized by a single viscosity value, although viscosity measurements at specific temperatures can provide valuable information about the properties of a material. A commonly measured rheological property of a material is its shear viscosity. Shear viscosity, often referred to simply as viscosity, describes the reaction of a material to an applied shear stress. In other words, shear stress is the relationship between effort (force per unit area) exerted on the surface of a fluid, in the lateral or horizontal direction, for the
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36/56 change in fluid speed as it moves downward in the fluid (a speed gradient). In a preferred embodiment of the nutritional product of the present invention, the shear viscosity is at least about 1 mPas, preferably from at least about 1 mPas to about 50 mPas, and most preferably from at least minus 5 mPas to less than 20 mPas, when measured at a shear rate of 50s ^-1 .
[000132] Another rheological property of a material is its extensional viscosity. Extensional viscosity is the ratio of the effort required to extend a liquid in its flow direction with respect to the extension rate. Extensional viscosity coefficients are widely used for the characterization of polymers, in which they cannot be simply calculated, or estimated from shear viscosity. Rheological studies are generally carried out with the use of rheometers that generally impose a specific strain or strain field in relation to the fluid and monitor the resulting strain or strain. These instruments can operate in a uniform flow or in an oscillating flow, as well as both shear and extension.
[000133] The Capillary Breakup Extensional Rheometry (CaBER), used here, in this patent application, is an example for a rheometer applying extensional effort. During the CaBER experiment as performed here, in this patent application for measuring the relaxation time of the nutritional product, a drop of said product is placed between two circular metal surfaces aligned vertically and in parallel, both having a diameter of 6 mm. The metal surfaces are then quickly linearly separated over a period of 50 ms (milliseconds). The filament formed through this stretching action then tapers under the action of interfacial tension and the thinning process is followed by
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37/56 in a quantitative way using a laser sheet measuring the diameter of the filament in its middle position. The relaxation time in a CaBER experiment is determined by plotting the normalized natural logarithm of the filament diameter during the thinning process versus time and determining the slope of the linear part (dln (D / D0) / dt) of this curve, at where D is the filament diameter, D0 is the filament diameter at time zero and t is the filament thinning time. The relaxation time in this context is then defined as one third less once (- 1/3) of the inverse of that slope, that is -1 (3dln (D) / D)) / dt).
[000134] In one embodiment of the nutritional product of the invention, the relaxation time determined in this way is less than about 2000 ms, preferably from about 20 ms to about 100 ms, more preferably from about 50 ms to about 500 ms, and most preferably from about 100 ms to about 200 ms, at a temperature of 20 ° C. It is even more preferably that the diameter of the filament of the nutritional product decreases less than linearly and preferably exponentially over time during a CaBER experiment.
[000135] During processing in the mouth and swallowing, the viscosity of a food product changes due to shear forces. It is generally known that the viscosity of a food product decreases when the shear forces and rate acting on the food product (such as, for example, chewing forces) increase. A known treatment for drinks and liquid foods is to increase the viscosity of the food / drink by adding starch or gum thickeners. This thickening is designed to improve bolus control and swallowing time. However, it is often not appreciated by patients because of the additional swallowing effort and also because it can leave residues
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38/56 at high viscosity levels. With regard to solid foods, puree diets are almost always described when problems with chewing and swallowing solid pieces occur in patients. However, these puree diets may not have the natural cohesion that the saliva provides to the actual food boluses. [000136] Extensional viscosity is generally only relevant in flows in which a fluid is stretched / stretched (such as when fluid through a constriction such as an esophageal sphincter), or when compressed (such as between the tongue and palate or tongue and pharynx). However, any compression force also implies an extension (for example, in another direction). Only in so-called simple shear flows, such as in a straight pipe, could the shear viscosity only determine the flow of the fluid. In a process such as swallowing, most bolus transport steps will also have a certain degree of extension. The difference between shear and extensional viscosities is usually expressed in terms of a Trouton ratio which is the ratio between extensional viscosity and shear viscosity at the same strain rate and as expressed in reciprocal seconds.
[000137] As such, and in opposition to the effects of shear viscosity, the nutritional products of the present disclosure aim to improve the cohesion of food boluses to prevent a food bolus from being broken into smaller fragments, which can enter the airways or leaving unwanted residues in the oropharynx and / or tract of the esophagus during the swallowing process. Saliva proteins naturally appear to have this function of increasing the cohesive capacity of a food bolus. Applicants have surprisingly found that the incorporation of food-grade biopolymers in nutritional products reaches a pos
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39/56 possible similar or identical enhanced effect of increasing the cohesion of the food bolus (for example, for patients who have impaired saliva secretion). This principle can be applied both to beverages, in which these polymers can be dissolved, and in semi-solid food products (for example, purees) that need to maintain sufficient integrity to be swallowed safely and in which solid and semi-solid particles are held together by a cohesive aqueous phase containing these polymers.
[000138] In the nutritional product of the present invention, the aqueous solution preferably comprises this food grade biopolymer in a concentration of at least 0.01% by weight to 25% by weight, preferably at least 0.1% by weight up to 15% by weight, and more preferably at least 1% by weight to 10% by weight. All percentages given in this specification refer to the weight of the polymer by the total weight of the product (% by weight).
[000139] Another embodiment of the present invention relates to the nutritional product of the invention in diluted form, preferably in an aqueous dilution ranging from 2: 1 to 50: 1, more preferably from 3: 1 to 20: 1 and most preferably from 5: 1 to 10: 1. As an example, a 2: 1 dilution means that 1 part of the nutritional product is diluted in 2 parts of water.
[000140] Applicants also found that providing nutritional products to dysphagia patients, having a greater bolus cohesion, due to their extensional viscosity, without drastically modifying other physical properties of the material, such as, for example, its shear viscosity , drastically reduces the amount of effort for swallowing in relation to the patient, as well as the risk of residue accumulation in the oropharyngeal and / or esophageal tracts. As such, products that have an increased cohesiveness provide improvements in the nutritional intake of dysphagic patients,
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40/56 allowing them to swallow a greater variety of food products and drinks safely and comfortably. This is achieved by improving the bolus integrity (cohesiveness) and thus giving the patient confidence to be able to consume the different products. The nutritional improvement achieved by an improved intake of food and water can lead to a healthy general state of the patient and prevent further fall.
[000141] The polymers included in the present nutritional products can include any high molecular weight, water-soluble biopolymer that is capable of improving the extensional viscosity and, for that reason, the cohesiveness (as for example, resistance to breakage) of the nutritional products . Such polymers can include, for example, botanical hydrocolloids, microbial hydrocolloids, animal hydrocolloids and algal hydrocolloids.
[000142] The algal hydrocolloids that can be used in the present nutritional products can include, for example, agar, carrageenan, alginate or combinations thereof. The microbial hydrocolloids that can be used in the nutritional products of the invention can be selected from xanthan gum, gelan gum, Kurd gum or combinations thereof; The botanical hydrocolloids that can be included in the present nutritional products can be selected from gums extracted from plant-derived mucilage plants and their combinations.
[000143] The gums that can be used in the present nutritional products may include, for example, okra gum, glucomannans (konjac manana), galactomannans (tara gum, locust bean gum, guar gum, fenugreek gum) , tamarind gum, cassia gum, arabic gum (acacia gum), ghatti gum, pectin, cellulosic, tragacanth gum, caraia gum, and combinations thereof, in which okra gum is preferred.
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41/56 [000144] In the context of this disclosure, gums are preferably food grade and can be obtained commercially from numerous suppliers. For example, xanthan gum is a long-chain, high molecular weight polysaccharide composed of sugars, glucose, mannose and glucoronic acid. The main structure is similar to that of cellulose, with side chains added with trisaccharides. Galactomannans are polysaccharides made of a main mannan structure with side chains (single) of galactose units. The ratio of galactose to mannose is different in different galactomannans, with the majority usually being mannose. Glucomannans are mostly unbranched with a main structure composed of D-glucose and D-mannose residues. Usually, approximately 60% of the polysaccharide is made of D-mannose and approximately 40% of D-glucose. In the context of this disclosure, galactomannans and glucomannans are food grade and can be obtained commercially from various suppliers.
[000145] Mucilages that can be used in the present nutritional products may include, for example, kiwi fruit mucilage, cactus mucilage, chia seed mucilage, psyllium mucilage, mellow mucilage, flax seed mucilage, flax seed mucilage marshmallow, ribwort mucilage, mulein mucilage, literary mucilage or combinations thereof.In a preferred embodiment of the nutritional product of the invention the food grade polymer is selected from okra gum and / or kiwi fruit mucilage, or a combination of them.
[000146] It is specifically preferred that the plant-derived mucilage is the mucilage of the kiwi fruit. Said mucilage is most preferably derived from the stem of the kiwi fruit. The stem of the kiwi fruit, which typically represents the discarded material from the remaining plant of the kiwi fruit agriculture, contains about 20% mucilage.
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42/56 [000147] In the context of this disclosure, mucilages are also food grade and can be obtained commercially from numerous suppliers.
[000148] Furthermore, according to the present invention, gums and mucilages can be obtained by any suitable extraction method, known in the art. A general protocol for the extraction of gums and mucilages involves immersing the raw plant material with 10 times its weight of distilled water and keeping it overnight. A viscous solution is obtained, which is passed through a muslin fabric. The gum or mucilage is precipitated by adding 95% by weight of ethanol in a ratio of about 1: 1 with continued stirring. A coagulated mass is obtained, which is then dried in an oven at 40 to 45 ° C, transformed into powder by passing through a sieve and stored in an airtight container.
[000149] In the nutritional product of the invention, it is still preferably that the aqueous solution specified above of a food grade biopolymer still comprises rigid particles. In the context of this disclosure, the term rigid means that the particles do not exhibit a measurable strain under the forces encountered during swallowing. These particles can be selected preferably from sucrose crystals, coconut particles, microcrystalline cellulose, starch granules and modified starch, protein particles and any combinations thereof.
[000150] The rigid particles defined in this way can have a size between 1 and 100 micrometers, more preferably between 1.5 and 80 micrometers, and most preferably between 2 and 50 micrometers.
[000151] In the present invention, the particle size is expressed in terms of the average diameter of the equivalent particle. In the context of this disclosure, the equivalent particle diameter refers to the
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43/56 diameter of a sphere of equal volume as the particle volume, which can be determined by any suitable method known in the art. Preferably the average equivalent particle diameter is determined using laser diffraction, for example, using a Malvern® Mastersizer instrument. In addition, in this context, the average equivalent particle diameter is based on a numerical average that is understood as the arithmetic mean of all particle diameters in a sample, usually reported as D [1.0].
[000152] Furthermore, it is preferably specific that the rigid particles have an elongated shape, which means that they have an aspect ratio greater than 1.0.
[000153] It is even more preferred that the above rigid particles are comprised in the aqueous solution of a food grade biopolymer in an amount of between 5 to 80% by volume, more preferably between 10 and 70% by volume, and most preferably between 15 and 50% by volume. In the context of this disclosure,% by volume means the percentage of the volume of all rigid particles in the solution as a whole, by the total volume of said solution.
[000154] The presence of such rigid particles in the nutritional product of the invention was found to improve the extensional flow locally and for that reason to increase the extension tensions, leading to a greater apparent extensional viscosity of said product.
[000155] The nutritional products of the invention may also comprise proteins of high molecular weight which may include, for example proteins derived from collagen such as gelatin, plant proteins such as proteins from potato, peas, lupine, etc., or other proteins of sufficiently high molecular weight (MW = 100 kDa and above).
[000156] In a preferred embodiment, the nutritional product
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44/56 of the invention may comprise a source of dietary protein which includes, but is not limited to, animal protein (such as meat protein or egg protein), dairy protein (such as casein, caseinates such as all forms of sodium, calcium and potassium caseinates) casein, whey hydrolysates (eg, all forms, including concentrate, isolated, demineralized), whey hydrolysates, milk protein concentrate, and isolates milk protein)), vegetable protein (such as soy protein, wheat protein, rice protein, pea protein
e), or combinations thereof. In one embodiment, the protein source is selected from the group consisting of whey, chicken, corn, caseinate, wheat, flax, soy, locust bean, pea, or combinations thereof.
[000157] In another embodiment, the nutritional products of the invention may comprise a carbohydrate source. Any carbohydrates can be used in the present nutritional products including but not limited to sucrose, lactose, glucose, fructose, corn syrup solids, maltodextrin, modified starch, amylose starch, tapioca starch, corn starch or combinations thereof. [000158] In another embodiment of the invention, the nutritional product includes a fat source. The fat source can include any suitable fat or fat mixture. For example, the fat source may include but is not limited to vegetable fat (such as olive oil, corn oil, sunflower oil, rapeseed oil, hazelnut oil, soy oil, palm oil, coconut oil , canola oil, lecithins, and the like), animal fats (such as milk fat) or combinations thereof.
[000159] In a preferred embodiment of the invention, nutritional products also include one or more prebiotics. Non-limiting examples of prebiotics include acacia gum, alpha glucan,
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45/56 arabinogalactans, beta glucan, dextrans, frucosoligosaccharides, fucosylactose, galacto oligosaccharides, galactomannans, gentile oligosaccharides, gluco oligosaccharides, guar gum, inulin, oligosaccharide isomalt, lactone, lactose, lactose, lactose, lactose, lactose hydrolyzed, pecticoligosaccharides, resistant starches, retrograded starch, sialo oligosaccharides, sialyl lactose, soy oligosaccharides, sugar alcohols, xyl oligosaccharides, hydrolysates, or combinations thereof.
[000160] In another preferred embodiment of the invention, nutritional products also include one or more probiotics. Non-limiting examples of probiotics include Aerococcus, Aspergillus, Bacteroides, Bifidobacterium, Candida, Clostridium, Debaromyces, Enterococcus, Fusobacterium, Lactobacillus, Lactococcus, Leuconostoc, Melissococcus, Peptococcus, Pocococcus, Pocococcus, Pocococcus, , Rhizopus, Saccharomyces, Staphylococcus, Streptococcus, Torulopsis, Weissella, or combinations thereof.
[000161] Furthermore, preferably, one or more amino acids can also be present in the nutritional products of the invention. Non-limiting examples of amino acids include alanine, arginine, asparagine, aspartate, citrulline, cysteine, glutamate, glutamine, glycine, histidine, hydroxyproline, hydroxyiserine, hydroxytyrosine, hydroxylisin, isoleucine, leucine, lysine, methionine, taurine, praline, serine, taurine, praline , threonine, tryptophan, tyrosine, valine, or combinations thereof.
[000162] In other modalities, nutritional products still include one or more symbiotics, sources of ω-3 fatty acids and / or phytonutrients. In the form used here, in this patent application, a symbiotic is a supplement that contains both a prebiotic and a probiotic that work together to improve the micro flora of the intestine.
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46/56
Non-limiting examples of sources of ω-3 fatty acids such as alpha linolenic acid (ALA), docosahexanoic acid (DHA) and eicosapentanoic acid (EPA) include fish oil, krill, poultry, eggs, or other sources vegetables or nuts, such as flax seed, walnuts, almonds, algae, modified plants, etc. Non-limiting examples of phytonutrients include quercetin, curcumin and limonine and combinations thereof.
[000163] According to the invention, one or more oxidants can also be present in nutritional products. Non-limiting examples of antioxidants include carotenoids, coenzyme Q10 (CoQlO), flavonoids, Goji glutathione (wolfberry), hesperidin, lactowolfberry, lignans, lutein, lycopene, polyphenols, selenium, vitamin A, vitamin B vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, zeaxanthin, or combinations thereof.
[000164] Nutritional products can also include fiber or a combination of different types of fiber. The fiber combination may contain a mixture of soluble and non-soluble fibers. Soluble fibers include, for example, oligosaccharide fruit, acacia gum, inulin, etc. Non-soluble fibers include, for example, outer pea fiber.
[000165] The nutritional products of the invention can also include other functional ingredients including chitosans and protein aggregates. Chitosans are linear polysaccharides composed of bound β (1-4) D-glucosamine (deacetylated unit) and N-acetyl-Dglycosome (acetylation unit) distributed at random. Among other potential advantages, chitosans have natural anti-bacterial properties, aid in the supply of drugs, and are known to clot blood quickly. Protein clusters are coalescences of miss - folded proteins driven through interactions between hydrophobic surfaces exposed to the
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47/56 solvent, which are normally hidden inside a protein.
[000166] Another aspect of the invention relates to methods for the manufacture of the aforementioned nutritional product. The methods include providing a food grade biopolymer solution capable of providing the nutritional product with a shear viscosity of less than about 100 mPas, preferably less than about 50 mPas, when measured at a shear rate of 50s ^{- 1} , and a relaxation time determined by a Capillary Breakup Extensional Rheometry (CaBER) experiment, greater than 10 ms (milliseconds) at a temperature of 20 ° C. In one embodiment the shear viscosity is at least about 1 mPas, preferably from at least about 1 mPas to about 50 mPas, and most preferably from at least 5 mPas to less than 20 mPas , when measured at a 50s ^-1 shear rate. In an embodiment of the method of the invention, the relaxation time is less than 2000 ms, preferably from about 20 ms to about 1000 ms, more preferably from about 50 ms to about 500 ms, and most preferably from about 100 ms to about 200 ms. In another preferred embodiment, the diameter of the filament of the nutritional product decreases less than linearly and preferably exponentially in time during a CaBER experiment. In yet another preferred embodiment, the aqueous solution comprises a food grade biopolymer in a concentration from at least 0.01% by weight, preferably from at least 0.1% by weight to 15% by weight and most preferably from at least 1% by weight to 10% by weight. In another embodiment, the method also includes diluting the nutritional product, preferably in an aqueous dilution ranging from 2: 1 to 50: 1, more preferably from 3: 1 to 20: 1, and from bigger
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48/56 preferably from 5: 1 to 10: 1.
[000167] In yet another aspect of the invention, a method is provided for increasing the cohesiveness of a nutritional product. This method includes adding to the nutritional product a solution of a food grade biopolymer capable of providing the nutritional product with a shear viscosity of less than about 100 mPas, preferably less than about 50 mPas, when measured at a shear rate 50s ^-1 , and a relaxation time determined by a Capillary Breakup Extensional Rheometry (CaBER) experiment, greater than 10 ms (milliseconds) at a temperature of 20 ° C, in such a way that the nutritional product does not break during the consumption of the nutritional product. Preferably the shear viscosity is at least 1 mPas, preferably from about 1 mPas to less than about 50 mPas and most preferably from 5 mPas to less than 20 mPas when measured at a rate shear of 50s ^-1 . It is also preferably that the relaxation time is less than 2000 ms, more preferably from about 20 ms to about 1000 ms, even more preferably from about 50 ms to about 500 ms, and from most preferred from 100 ms to about 200 ms. In another preferred embodiment of this aspect of the invention, the filament diameter of the nutritional product decreases less than linearly, and preferably exponentially in time during a Capillary Breakup Extensional Rheometry (CaBER) experiment. In yet another preferred embodiment, the aqueous solution comprises a food grade biopolymer in a concentration from at least 0.01% by weight to 25% by weight, preferably from at least 0.1% by weight to 15% by weight, and most preferably from at least 1% by weight to 10% by weight. In another form of preference, the nutritional product is further diluted, preferably
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49/56 in an aqueous dilution ranging from 2: 1 to 50: 1, more preferably from 3: 1 to 20: 1 and most preferably from 5: 1 to 10: 1.
[000168] The present invention further provides methods for promoting safe swallowing of food boluses. These methods include adding to a nutritional product a solution of a food grade biopolymer capable of providing the nutritional product with a shear viscosity of less than about 100 mPas, preferably less than about 50 mPas, when measured at a rate of 50s ^-1 shear, and a relaxation time determined by a Capillary Breakup Extensional Rheometry (CaBER) experiment, greater than 10 ms (milliseconds) at a temperature of 20 ° C, in such a way that the nutritional product does not break during consumption of the nutritional product. Preferably the shear viscosity is at least 1 mPas, preferably from about 1 mPas to less than about 50 mPas and most preferably from 5 mPas to less than 20 mPas when measured at a rate shear of 50s ^-1 . It is also preferably that the relaxation time is less than 2000 ms, more preferably from about 20 ms to about 1000 ms, even more preferably from about 50 ms to about 500 ms, and from most preferred from 100 ms to about 200 ms. In another preferred embodiment of this aspect of the invention, the filament diameter of the nutritional product decreases less than linearly, and preferably exponentially in time during a Capillary Breakup Extensional Rheometry (CaBER) experiment. In yet another preferred embodiment, the aqueous solution comprises a food grade biopolymer in a concentration from at least 0.01% by weight to 25% by weight, preferably from at least 0.1% by weight to 15% by weight, and most preferably alongside
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50/56 from at least 1% by weight to 10% by weight. In another preferred embodiment, the nutritional product is further diluted, preferably in an aqueous dilution ranging from 2: 1 to 50: 1, more preferably from 3: 1 to 20: 1 and most preferably from 5: 1 to 10: 1.
[000169] In yet another aspect of the invention, methods are provided for treating a patient who has a swallowing disorder. These methods include administration to a patient who is in need of a nutritional product that comprises an aqueous solution of a food grade biopolymer capable of providing the nutritional product with a shear viscosity of less than about 100 mPas, preferably less than about 50 mPas, when measured at a shear rate of 50s ^-1 , and a relaxation time determined by a Capillary Breakup Extensional Rheometry (CaBER) experiment, greater than 10 ms (milliseconds) at a temperature of 20 ° C, from such that the nutritional product does not break during the consumption of the nutritional product. Preferably the shear viscosity is at least 1 mPas, preferably from about 1 mPas to less than about 50 mPas and most preferably from 5 mPas to less than 20 mPas when measured at a rate shear of 50s ^-1 . It is also preferably that the relaxation time is less than 2000 ms, more preferably from about 20 ms to about 1000 ms, even more preferably from about 50 ms to about 500 ms, and from most preferred from 100 ms to about 200 ms. In another preferred embodiment of this aspect of the invention, the filament diameter of the nutritional product decreases less than linearly, and preferably exponentially in time during a Capillary Breakup Extensional Rheometry (CaBER) experiment. In yet another preferred embodiment, the aqueous solution
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51/56 sa comprises a food grade biopolymer in a concentration from at least 0.01% by weight to 25% by weight, preferably from at least 0.1% by weight to 15% by weight, and most preferably from at least 1% by weight to 10% by weight. In another preferred embodiment, the nutritional product is further diluted, preferably in an aqueous dilution ranging from 2: 1 to 50: 1, more preferably from 3: 1 to 20: 1 and most preferably from 5: 1 to 10: 1.
[000170] It is preferably specific in any of the above methods that the food grade biopolymer is selected from the group consisting of botanical hydrocolloids, microbial hydrocolloids, animal hydrocolloids and algal hydrocolloids and combinations thereof.
[000171] It is also preferably that the algal hydrocolloids are selected from the group consisting of agar, carrageenan, alginate or any combination thereof. In addition, microbial hydrocolloids are preferably selected from the group consisting of xanthan gum, gellan gum, curdlan gum or any combination thereof. In addition, botanical hydrocolloids are preferably selected from the group consisting of gums extracted from plants, mucilages extracted from plants and combinations thereof.
[000172] In any of the methods of the above invention, the gums extracted from plants are preferably selected from the group consisting of okra gum, konjac mannan, tara gum, locust bean gum, guar gum, gum fenugreek, tamarind gum, cassia gum, acacia gum, ghatti gum, pectins, celluloses, tragacanth gum, caraia gum, or any combination thereof. In preferred embodiments, the gum extracted from plants is okra gum. In addition, mucilages derive
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52/56 of the plant species can be selected preferably from the group consisting of kiwi fruit mucilage, cactus mucilage (ficus indica), chia seed mucilage (Salvia hispanica), psyllium mucilage (Plantago ovata), mucilage mallow (Malva sylvestris), flax seed mucilage (Linum usitatissimum), marshmallow mucilage (Althaea officinalis), ribwort mucilage (Plantago lanceolata), mullein mucilage (Verbascum), Cetraria mucilage (Lichen islandicus), or any combination thereof same. It is most preferred that the plant-derived mucilage is kiwi fruit mucilage, which is most preferably derived from the kernel of the kiwi fruit stem.
[000173] In preferred modalities of the methods mentioned above, the food grade biopolymer is selected from okra gum and / or mucilage from the kiwi fruit or a combination thereof.
[000174] In any of the methods of the above invention, it is preferably specific that the aqueous solution of the food grade biopolymer also comprises rigid particles. Such particles can preferably be selected from particles of sucrose crystals, coconut particles, microcrystalline cellulose, starch granules and modified starch, protein particles and any combinations thereof.
[000175] In addition, these rigid particles can have a size between 1 and 100 micrometers, more preferably between 1.5 and 80 micrometers, and most preferably between 2 and 50 micrometers. It is specifically preferred that the rigid particles are elongated, which means that they have an aspect ratio greater than 1.0.
[000176] It is still preferably that the rigid particles defined in this way are added to the aqueous solution of a food grade biopolymer according to the invention in an amount en
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53/56 between 3 and 80% by volume, more preferably between 10 and 70% by volume, and most preferably between 15 and 50% by volume. In the context of this disclosure,% by volume means the percentage of the volume of all rigid particles in the solution as a whole, by the total volume of said solution.
[000177] In the methods of the above invention, it is still preferably that the nutritional product comprises a source of dietary protein, including but not limited to animal protein (such as meat protein or egg protein), dairy protein (such as such as casein, caseinates such as all forms of sodium, calcium and potassium caseinates) hydrolyzates of casein, whey (eg all forms, including concentrate, isolate, (demineralised), hydrolyzates of whey milk, milk protein concentrate, and milk protein isolates)), vegetable protein (such as soy protein, wheat protein, rice protein, and pea protein), or combinations thereof. In one embodiment, the protein source is selected from the group consisting of whey, chicken, corn, caseinate, wheat, flax, soy, locust bean, pea, or combinations thereof.
[000178] In the methods of the above invention, it is also preferably that the nutritional product comprises a source of carbohydrates. Any suitable carbohydrate can be used in the present nutritional products, including but not limited to sucrose, lactose, glucose, fructose, corn syrup solids, maltodextrin, modified starch, amylose starch, tapioca starch, corn starch or combinations of themselves.
[000179] Nutritional products may also include a source of fat. The fat source can include any suitable fat or fat mixture. For example, the fat source may include but is not limited to vegetable fat (such as olive oil,
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54/56 corn, sunflower oil, rapeseed oil, hazelnut oil, soybean oil, palm oil, coconut oil, canola oil, lecithins, and the like), animal fats (such as milk) or combinations thereof.
[000180] In preferred embodiments of the above methods according to the invention, nutritional products still include one or more prebiotics. Non-limiting examples of prebiotics include acacia gum, alpha glucan, arabinogalactans, beta glucan, dextrans, fructosoligosaccharides, fucosylactose, galacto oligosaccharides, galactomannans, gentile oligosaccharides, gluco oligosaccharides, guar gum, lactose, lactose, lactose, lactose, lactose, lactose , maltodextrins, milk oligosaccharides, partially hydrolyzed guar gum, pecticoligosaccharides, resistant starches, retrograded starch, sialo oligosaccharides, sialyl lactose, soy oligosaccharides, sugar alcohols, xyl oligosaccharides, or the combinations thereof.
[000181] In other embodiments of preference of the above methods according to the invention, nutritional products also include one or more probiotics. Non-limiting examples of probiotics include Aerococcus, Aspergillus, Bacteroides, Bifidobacterium, Candida, Clostridium, Debaromyces, Enterococcus, Fusobacterium, Lactobacillus, Lactococcus, Leuconostoc, Melissococcus, Peptococcus, Pocococcus, Pocococcus, , Rhizopus, Saccharomyces, Staphylococcus, Streptococcus, Torulopsis, Weissella, or combinations thereof.
[000182] Furthermore, preferably, one or more amino acids can also be present in the nutritional products of the invention. Non-limiting examples of amino acids include alanine, arginine, asparagine, aspartate, citrulline, cysteine, glutamate, glutamine, glycine,
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55/56 histidine, hydroxyproline, hydroxyiserine, hydroxytyrosine, hydroxylysine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, taurine, threonine, tryptophan, tyrosine, valine, or combinations thereof.
[000183] In other embodiments of the methods of the invention, nutritional products further include one or more symbiotics, sources of ω-3 fatty acids and / or phytonutrients. In the form used here, in this patent application, a symbiotic is a supplement that contains both a prebiotic and a probiotic that work together to improve the micro flora of the intestine. Non-limiting examples of ω-3 fatty acid sources such as alpha linolenic acid (ALA), decosahexaanoic acid (DHA) and eicosapentanoic acid (EPA) include fish oil, krill, poultry, eggs, or other vegetable sources or of nuts such as flax seed, walnuts, almonds, algae, modified plants, etc. Non-limiting examples of phytonutrients include quercetin, curcumin and limonine and combinations thereof.
[000184] In other preferred embodiments of the above methods according to the invention, one or more antioxidants may also be present in the nutritional products. Non-limiting examples of antioxidants include carotenoids, coenzyme Q10 (CoQlO), flavonoids, glutathione Goji (wolfberry), hesperidin, lactowolfberry, lignans, lutein, lycopene, polyphenols, selenium, vitamin A, vitamin B1 vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, zeaxanthin, or combinations thereof.
[000185] In these methods, nutritional products can also include fibers or a combination of different types of fibers. The fiber combination may contain a mixture of soluble and non-soluble fibers. Soluble fibers include, for example, oligosaccharide fruit, acacia gum, inulin, etc. Non-soluble fibers include, for example, outer pea fiber.
[000186] In other modalities of the methods above, the products
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Nutritional supplements of the invention may also include other functional ingredients, which include chitosans and protein segregates.
[000187] Through the use of improved nutritional products and methods of their manufacture and administration, the nutritional intake of patients with dysphagia can be improved, by allowing the swallowing of a greater variety of food products and drinks with safety and comfort. These advantages can be achieved by improving the cohesion of a food bolus, which leads to the patient's confidence in being able to consume a variety of products, without the food bolus breaking and possibly being aspirated by the patient. These nutritional improvements can lead to a healthier general condition of the patient and prevent further health-related decline.
[000188] It should be understood that several changes and modifications with respect to the modalities presently preferably described here, in this patent application, will become apparent to those skilled in the art. These changes and modifications can be made without departing from the spirit and scope of this subject and without diminishing the intended benefits of it. It is for this reason that such changes and modifications are intended to be covered by the appended claims.

权利要求:
Claims (21)
[1]
1. Nutritional product, characterized by the fact that it comprises:
an aqueous solution of a food-grade biopolymer, capable of providing the nutritional product:
- a shear viscosity of less than about 100 mPas, preferably less than 50 mPas, when measured at a shear rate of 50s ^-1 , and
- a relaxation time determined by means of an Extensional Capillary Rheometry (CaBER) experiment, greater than 10 ms (milliseconds) at a temperature of 20 ° C.
[2]
2. Nutritional product according to claim 1, characterized by the fact that when the shear viscosity is at least 1 mPas, or from at least about 1 mPas to less than 50 mPas, or from at least minus 5 mPas to less than 20 mPas, when measured at a shear rate of 50s ^-1 .
[3]
3. Nutritional product according to claim 1 or 2, characterized by the fact that the relaxation time is less than 2000 ms, or from 20 ms to 1000 ms, or from 50 ms to 500 ms, or from 100 ms to 200 ms, at a temperature of 20 ° C.
[4]
4. Nutritional product according to any one of claims 1 to 3, characterized in that the diameter of the filament of the nutritional product decreases less than linearly, and preferably exponentially in time during a CABER experiment.
[5]
5. Nutritional product according to any one of claims 1 to 4, characterized in that the aqueous solution comprises a food-grade biopolymer in a concentration from at least 0.01% by weight to 25% by weight, Or the
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2/6 from at least 0.1% by weight to 15% by weight, or from at least 1% by weight to 10% by weight.
[6]
6. Nutritional product according to any one of claims 1 to 5, characterized in that it is in diluted form, in an aqueous dilution ranging from 2: 1 to 50: 1, or from 3: 1 to 20 : 1, or from 5: 1 to 10: 1.
[7]
7. Nutritional product according to any one of claims 1 to 6, characterized by the fact that the food grade biopolymer is selected from the group consisting of botanical hydrocolloids, microbial hydrocolloids, animal hydrocolloids, algal hydrocolloids and any combinations thereof .
[8]
8. Nutritional product, according to claim 7, characterized by the fact that algae hydrocolloids are selected from the group consisting of agar, carrageenan, alginate or any combination thereof.
[9]
9. Nutritional product according to claim 7 or 8, characterized by the fact that microbial hydrocolloids are selected from the group consisting of xanthan gum, gelan gum, curdlan gum, or any combination thereof.
[10]
10. Nutritional product according to any one of claims 7 to 9, characterized by the fact that botanical hydrocolloids are selected from the group consisting of gums extracted from plants, mucilages derived from plants and combinations thereof.
[11]
11. Nutritional product, according to claim 10, characterized by the fact that the gums extracted from plants are selected from the group consisting of okra gum, konjac gum, tara gum, locust bean gum, guar gum, gum greek hay, tamarind gum, cassia gum, acacia gum, ghatti gum, pectins, celluloses, tragacanth gum, caraia gum, or whatever
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3/6 want combinations thereof and preferably the gum extracted from plants is okra gum.
[12]
12. Nutritional product according to claim 10 or 11, characterized by the fact that plant-derived mucilages are selected from the group consisting of kiwi fruit mucilage, cactus mucilage, chia seed mucilage, psyllium mucilage, mallow mucilage, flax seed mucilage, marshmallow mucilage, ribwort mucilage, mulein mucilage, literary mucilage or combinations thereof, and preferably plant-derived mucilage is the kiwi fruit mucilage.
[13]
13. Nutritional product according to any one of claims 1 to 12, characterized by the fact that the food grade biopolymer is selected from okra gum and / or mucilage from the kiwi fruit or a combination thereof.
[14]
14. Nutritional product according to claim 12 or 13, characterized by the fact that the mucilage of the kiwi fruit is derived from the marrow of the kiwi fruit stem.
[15]
15. Nutritional product according to any one of claims 1 to 14, characterized in that the aqueous solution comprises rigid particles, preferably in which the rigid particles have a size between 1 and 100 micrometers; and / or the rigid particles are comprised in an amount between 5 and 80% by volume; and / or the rigid particles are selected from the group consisting of sucrose crystals, coconut particles, microcrystalline cellulose particles, granules of starch and modified starch, protein particles and any combination thereof.
[16]
16. Nutritional product, according to any of the
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4/6 claims 1 to 15, characterized by the fact that it comprises a prebiotic selected from the group consisting of acacia gum, alpha glucan, arabinogalactans, beta glucan, dextrans, fruit oligosaccharides, fucosylactose, galacto oligosaccharides, galactomannans, gentile oligosaccharides, gluco oligosaccharides , guar gum, inulin, isomalto oligosaccharides, lactoneotetraose, lactosaccharose, lactulose, levano, maltodextrins, milk oligosaccharides, partially hydrolysed guar gum, pecticoligosaccharides, resistant starches, retrograded starch, soya oligosaccharides, sugar, silylose xyl oligosaccharides, hydrolysates, or combinations thereof; and / or a probiotic selected from the group consisting of Aerococcus, Aspergillus, Bacteroides, Bifidobacterium, Candida, Clostridium, Debaromyces, Enterococcus, Fusobacterium, Lactobacillus, Lactococcus, Leuconostoc, Melissococcus, Peptoccus, , Propionibacterium, Pseudocatenulatum, Rhizopus, Saccharomyces, Staphylococcus, Streptococcus, Torulopsis, Weissella, and combinations thereof; and / or an amino acid selected from the group consisting of alanine, arginine, asparagine, aspartate, citrulline, cysteine, glutamate, glutamine, glycine, histidine, hydroxyproline, hydroxyserine, hydroxytyrosine, hydroxylisin, isoleucine, leucine, lysine, methionine, proline, phenylalan , serine, taurine, threonine, tryptophan, tyrosine, valine and combinations thereof; and / or a phytonutrient selected from the group consisting of flavonoids, allied phenolic compounds, polyphenolic compounds, terpenoids, alkaloids, sulfur-containing compounds and combinations thereof; and / or an antioxidant selected from the group consisting of
Petition 870190132295, of 12/12/2019, p. 63/70
5/6 taxanthin, carotenoids, coenzyme Q10 (CoQ10), flavonoids, glutathione Goji (wolfberry), hesperidin, lactowolfberry, lignans, lutein, lycopene, polyphenols, selenium, vitamin A, vitamin C, vitamin E, zeaxanthin or combinations thereof .
[17]
17. Nutritional product according to any one of claims 1 to 16, characterized by the fact that the nutritional product is in a form of administration selected from the group consisting of pharmaceutical formulations, nutritional formulations, dietary supplements, and functional food products and drinks, and combinations thereof.
[18]
18. Use of an aqueous solution of a food-grade biopolymer, as defined in any of claims 1 to 15, characterized by the fact that it is for the manufacture of a nutritional product for the treatment of a swallowing disorder.
[19]
19. Use of an aqueous solution of a food-grade biopolymer, as defined in any of claims 1 to 15, characterized by the fact that it is for the manufacture of a nutritional product to promote safe swallowing of nutritional products in a patient who is needing the same.
[20]
20. Use of an aqueous solution of a food grade biopolymer, as defined in any of claims 1 to 15, characterized by the fact that it is for the manufacture of a nutritional product to mitigate the risks of aspiration during the swallowing of nutritional products in a patient who is in need of it.
[21]
21. Method for manufacturing a nutritional product, characterized by the fact that it comprises the provision of an aqueous solution of a food-grade biopolymer capable of providing the nutritional product:
- a shear viscosity of less than 100 mPas, or
Petition 870190132295, of 12/12/2019, p. 64/70
6/6 less than 50 mPas, when measured at a 50s- ¹ shear rate, and
- a time of relaxation determined by an Experiment of Extensional Rheometry of Capillary Rupture (CaBER), greater than 10 ms (milliseconds) at a temperature of 20 ° C.

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法律状态:
2018-03-06| B07D| Technical examination (opinion) related to article 229 of industrial property law [chapter 7.4 patent gazette]|

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2018-05-02| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|

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2019-04-24| B07G| Grant request does not fulfill article 229-c lpi (prior consent of anvisa) [chapter 7.7 patent gazette]|Free format text: NOTIFICACAO DE DEVOLUCAO DO PEDIDO POR NAO SE ENQUADRAR NO ART. 229-C DA LPI. |

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2019-05-21| B06T| Formal requirements before examination [chapter 6.20 patent gazette]|

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2019-08-06| B15K| Others concerning applications: alteration of classification|Free format text: AS CLASSIFICACOES ANTERIORES ERAM: A23L 1/05 , A23L 1/0526 , A23L 1/30 , A23L 1/308 , A61K 31/715 , A61K 36/185 Ipc: A23L 29/20 (2016.01), A23L 29/206 (2016.01), A23L |

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2019-10-15| B25A| Requested transfer of rights approved|Owner name: SOCIETE DES PRODUITS NESTLE S.A. (CH) |

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2020-03-03| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|

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2020-05-05| B16A| Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 17/12/2012, OBSERVADAS AS CONDICOES LEGAIS. |

优先权:

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申请号 | 申请日 | 专利标题

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US201161570888P| true| 2011-12-15|2011-12-15|

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EP11193799|2011-12-15|

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PCT/EP2012/075697|WO2013087918A1|2011-12-15|2012-12-17|Cohesive thin liquids to promote safe swallowing in dysphagic patients|

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