• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    The present invention is the use of a probiotic composition comprising S. thermophilus, L. acidophilus, L. plantarum, L. paracasei, L. delbrueckii, B. breve, B. longus, B. lactis in the preparation of a food supplement. for the complementary treatment of drug-resistant epilepsy. The composition corresponds to the probiotic brand SIVOY {reg}, which has several studies that have demonstrated its effectiveness and is a modified probiotic of VSL 3. A preferable aspect of the invention is that said treatment comprises a dosage of 450,000 million bacteria administered orally twice a day in a patient with drug-resistant epilepsy. (Machine-translation by Google Translate, not legally binding)
    公开号:ES2675811A1
    申请号:ES201730027
    申请日:2017-01-12
    公开日:2018-07-12
    发明作者:María GOMEZ EGUILAZ；José Ramón BLANCO RAMOS
    申请人:Fundacion Rioja Salud；
    IPC主号:
    专利说明:

    5
    10
    fifteen
    twenty
    25
    30
    USE OF A PROBIOTIC COMPOSITION FOR THE COMPLEMENTARY TREATMENT OF PHARMACORRESISTENT EPILEPSY
    DESCRIPTION
    TECHNICAL SECTOR
    The present invention is the administration of a probiotic as a complementary treatment to that of the usual antiepileptic therapy, in the field of applied clinical medicine.
    BACKGROUND OF THE INVENTION
    Epilepsy is a relatively frequent neurological disease. Despite the high number of antiepileptic drugs available, 20-30% of patients have a drug-resistant epilepsy, that is, one that fails to control seizures after having used at least two appropriate and appropriate treatments. This type of epilepsy severely limits the quality of life of patients and increases their morbidity and mortality.
    For the treatment of drug-resistant epilepsy, different additional or alternative therapeutic strategies have been proposed. Among them, the stimulation of the vagus nerve, which has an approximate efficacy of 50% in the reduction of seizures in 50% of patients. Another of them would be neurological surgery, which achieves up to 70% of crisis control in very well selected specific surgeries. The ketogenic diet is another option, but it is difficult to maintain and the most optimistic studies establish a 30% efficiency in the control of crises. All these procedures have important limitations, such as having to undergo surgical or neurosurgical intervention, or discomfort every time it causes a discharge in the case of vagus stimulation.
    In the present application, "probiotics" is understood as living microorganisms that administered in adequate amounts produce a health benefit to the host.
    The VSL # 3 probiotic contains Streptococcus thermophilus, Lactobacillus acidophilus, L. plantarum, L. paracasei, L. delbrueckii subs bulgaricus, Bifidobacterium breve, B. longus and B.infantis.
    5
    10
    fifteen
    twenty
    25
    30
    35
    This probiotic is approved for the treatment of irritable bowel syndrome, inflammatory bowel disease, mild to moderate ulcerative colitis, chronic pouchitis and episodes of diarrhea associated with radiotherapy, treatment with concomitant antibiotics, enteral nutrition or geriatric patients. hospitalized In addition, it has positive studies for other types of diarrhea and hepatic encephalopathy (Pratap Mouli V et al. “Effect of probiotic VSL # 3 in the treatment of minimal hepatic encephalopathy: A non-inferiority randomized controlled trial.” Hepatol Res, 2015; 45 (8): 880-9). None of these pathologies is related to epilepsy.
    The problem that arises in the technique is to find a treatment that allows reducing epileptic seizures in patients with drug-resistant epilepsy. The solution proposed by the present invention is the supplementation of the antiepileptic treatment with a probiotic containing S. thermophilus, L. acidophilus, L. plantarum, L. paracasei, L. delbrneckii, B. breve, B. longus and B. Lactis as nutritional supplement.
    DESCRIPTION OF THE INVENTION
    The present invention is the use of a probiotic composition comprising S. thermophilus, L. acidophilus, L. plantarum, L. paracasei, L. delbrueckii, B. breve, B. longus and B. lactis in the preparation of a food supplement for the complementary treatment of drug-resistant epilepsy. Or, the probiotic composition for use in said treatment. In a more restricted aspect, the invention consists in the use of said probiotic composition.
    In a preferable aspect, said probiotic composition also contains CD2, a cell adhesion molecule of the immunoglobulin superfamily that improves effectiveness, but does not imply any conditioner regarding probiotic activity.
    Within the scope of the present invention, "complementary treatment" means the administration of an additional probiotic for simultaneous or correlative use to the antiepileptic drugs that are administered to a patient for the treatment and control of their seizures.
    5
    10
    fifteen
    twenty
    25
    30
    35
    Within the scope of the present invention, "epilepsy treatment" is understood as the treatment of epileptic disease for the control or reduction of epileptic seizures and their symptoms.
    In the art, the SIVOY® brand probiotic corresponds to the composition of the invention and also contains the CD2 chain. SIVOY® is a modified probiotic of VSL # 3, and several studies have proven its effectiveness.
    SIVOY® is presented in envelopes of 450,000 million live bacteria. Thus, in a preferable aspect of the invention, said treatment comprises a dosage of 450,000 million bacteria orally twice a day in a patient of drug-resistant epilepsy.
    The present invention aims to achieve better control of epileptic seizures of patients with drug-resistant epilepsy. In an intention-to-treat analysis, 28.9% of patients treated with probiotics reduced the number of their seizures by at least 50%. This efficacy was 31.7% in a protocol analysis, the majority maintaining the beneficial effect after the suspension of probiotics four months later. The reduction of at least 50% of seizures is the requirement of effectiveness of clinical trials.
    An additional benefit was the improvement of the patients' quality of life, not only due to better crisis control, but also associated with a feeling of less anxiety.
    It can be postulated that the modification of the digestive microbiota with probiotics of the invention would contribute to improve the epileptic seizures of the patients through the release of neurotransmitters and / or the better absorption of the antiepileptic drugs.
    The ultimate cause of drug-resistant epilepsy is unknown. An indeterminate number of variables and an extensive series of processes related to epileptic seizures are postulated. The study by the inventors of each of them would have supposed an unbeatable amount of work, but once seen the effect of the invention it can be assumed that the beneficial effect of the administration of probiotics on the control of epilepsy may be due to the following causes:
    5
    10
    fifteen
    twenty
    25
    30
    35
    Probiotics have an anti-inflammatory effect. Inflammation is one of the possible etiopathogenesis of epilepsy and it is observed that when controlled, crises are also controlled. In all patients, regardless of whether they improve their seizures or not, a decrease in inflammatory interleukin IL-6 was observed.
    Probiotics may help improve absorption of antiepileptic drugs. There have been changes in their serum levels during administration, returning to previous values after the end of the probiotic administration.
    The administration of probiotics increases serum levels of GABA (gamma-aminobutyric acid). GABA is an important central nervous system inhibitor neurotransmitter, and its release is the mechanism of action of several drugs. In the trials of the present invention a release of this neurotransmitter is observed during the probiotic intake in all patients.
    In addition, an advantage of the present invention is that the administration of probiotics does not cause side effects, which is important because the side effects of epileptic drugs contribute greatly to their abandonment and the lower quality of life of this type of patient. .
    BRIEF DESCRIPTION OF THE FIGURES
    Figure 1: Percentage of patients who present an improvement in their crisis at the end of the study. All patients who started the study (intention-to-treat analysis) have been analyzed.
    Figure 2: Comparison of baseline quality of life scores (1); after finishing the treatment (2); 4 months after the end of the treatment (3). The scale scores translate into: very good quality of life (score from 10 to 19); good quality of life (score from 20 to 29); regular quality of life (score from 30 to 39); bad quality of life (score from 40 to 49), and very bad quality of life (score of 50). In line of points the patients in which the probiotic was effective are shown. The solid line shows the patients in whom the probiotics were not effective.
    5
    10
    fifteen
    twenty
    25
    30
    35
    Figure 3: Evolution of the median of the values of IL-6. The variation of the medians separated by groups according to their effectiveness is shown. The dotted line shows the patients in which it was effective; the continuous line in which it was not effective.
    Figure 4: Evolution of the median cD14 values throughout the study. The variation of the medians separated by groups according to their effectiveness is shown. The dotted line shows the patients in which it was effective; the continuous line in which it was not effective.
    Figure 5: Evolution of the median GABA values throughout the study. The variation of the medians separated by groups according to their effectiveness is shown. The dotted line shows the patients in which it was effective; the continuous line in which it was not effective.
    EXAMPLES
    Example 1: Selection of the sick
    Forty-five patients of both sexes with drug-resistant epilepsy were selected who met the inclusion criteria of being over 18 years of age, having a diagnosis of drug-resistant epileptic seizures, being in continuous treatment with antiepileptic drugs for at least 30 days before inclusion, and the presence of at least one seizure per month. Likewise, they should not present any exclusion criteria, namely:
    - Stable epilepsy.
    - Idiopathic generalized epilepsy.
    - Epileptic status in the previous 12 months.
    - Change in the dose or type of antiepileptic drug within 30 days prior to the start of the study.
    - Active consumption of alcohol or substances of abuse.
    - Pregnancy and / or nursing mothers.
    - Patients treated with probiotics from 30 days before the start of the study.
    - Chronic gastrointestinal problems (for example, irritable bowel).
    - Liver or kidney problems.
    - Lactose intolerant or celiac.
    - Immunosuppressed.
    5
    10
    fifteen
    twenty
    25
    30
    - Patients in chronic antibiotic treatment.
    - Impossibility to fill in a questionnaire on the part of the patient or his person in charge to follow the calendar of visits.
    - Additional progressive neurological deterioration (tumors or CNS metastases, Alzheimer's disease, vascular dementias).
    - Use of antiepileptics in research.
    - Patients with a life expectancy <1 year.
    The average age of the patients was 44 years. The average evolution of epilepsy was about 30 years, with an average of 7 crises per month. Patients had previously received administration of an average of seven commercially available antiepileptic drugs, typically valproic acid, carbamazepine, phenytoin, levetirazetam, lamotrigine, lacosamide and topiramate.
    Example 2: Probiotic administration.
    During the 3 months prior to the administration of the probiotic, a profile of its crises, a baseline analysis, and a quality of life questionnaire were carried out. After those 3 months, patients began to take two sachets per day of the SIVOY® product whose composition is 450,000 million live bacteria over S. thermophilus, L. acidophilus, L. plantarum, L. paracasei, L. delbrueckii, B. Brief, B. Longus, B. Lactis and the CD2 chain. The probiotic was administered orally 10 minutes before meals for 4 months. During the entire period of the study, patients performed a crisis registry, and a control of adherence to antiepileptic and probiotic treatment. The day they finished taking the probiotic, a new analysis and a quality of life questionnaire were made. The patients collected the possible side effects. Follow-up was carried out during the 4 months after the end of the probiotic. During this period, the frequency of epileptic seizures was controlled again and the patients' quality of life was evaluated.
    All results were calculated based on the 45 patients who started the study (intention-to-treat analysis). In this type of analysis, all patients who have been assigned to the treatment are included, regardless of whether they completed the treatment period and / or its follow-up. Thus, patients who did not attend their follow-up, for whatever reason, were considered as therapeutic failure.
    5
    10
    fifteen
    twenty
    25
    30
    35
    The characteristics of epilepsy and imaging tests are summarized in Tables 1 and 2, respectively.
    41 patients (91.1% of the total) had good adhesion to the probiotic. In addition, 43 patients (95.6%) claimed to follow their antiepileptic treatment correctly. Of these, 42 patients took probiotics more than 8 weeks (93.3%). A total of 3 patients (6.7%) required concomitant treatment with analgesics, omeprazole or antihistamine. None of them related to the probiotic intake. In addition, 3 other patients had adverse effects that could be related to taking probiotics: in 2 cases it was clearly related to it (mild self-limited diarrhea), and in another it was doubtful since it presented a respiratory infection of possible viral origin (cold) (table 3).
    Table 1. Characteristics of epilepsy.
    Variables N = 45
    Etiology of epilepsy (%)
    Temporary mesial sclerosis 4 (8.9)
    Cortical dysplasia 3 (6.7)
    Trauma 1 (2,2)
    Perinatal Complication 9 (20)
    Brain Infection 3 (6.7)
    Cryptogenic 20 (44.4)
    Other 5 (11.1)
    Years of evolution epilepsy (± SD) 30 (16)
    Focus location (%)
    Front 3 (6.7)
    Temporary 16 (35.6)
    Occipital 1 (2,2)
    Multifocal 9 (20)
    No focus 16 (35.6)
    No. drugs currently, mean (SD) 2.8 (1)
    No. of patients taking VPA 13 (28.9%)
    No. of patients taking CMZ 6 (13.3%)
    No. of previous drugs, mean (SD) 5.8 (2.3)
    5
    10
    fifteen
    twenty
    25
    30
    35
     No. patients had taken VPA  30 (66.7%)
     No. patients had taken CMZ  21 (46.7%)
     Other treatments (%)
     Do not  38 (84.4)
     Surgery  6 (13.3)
     ENV  1 (2.2)
     Average number of crises in a month (SD)  7 (7)
     Correct crisis perception: (SC-CR)  14 (31.1%)
    DE: standard deviation. VPA: valproic acid. CMZ: carbamazepine. ENV: vagus nerve stimulator. SC: sense of crisis. CR: real crises.
    Table 2. Alterations in the imaging tests. Alterations found N = 45
     Without modifications (%)  21 (46.7)
     With alterations (%)  24 (53.3)
     Unknown (%)  15 (62.2)
     Parietal Schiscephaly (%)  1 (4.2)
     Temporary area resection  1 (4.2)
     Poor occipital differentiation  1 (4.2)
     Cortical thickening  1 (4.2)
     Atrophy of the hippocampus  1 (4.2)
     Right Porencephaly  1 (4.2)
     Cavemen  1 (4.2)
     Brain bruising  1 (4.2)
     Migration Alterations  1 (4.2)
     Table 3. Evolution of the study.
     Variables  z ii I heard
     Patients who finished the study  43
     Adhesion to the probiotic (%)  41 (91.1)
     Adherence to the FAE (%)  44 (95.6)
    5
    10
    fifteen
    twenty
    25
    30
    35
     Probiotic treatment> 8 weeks (%) Adverse effects (%)  41 (91.1)
     YES  3 (6.7)
     Diarrhea  2 (4.4)
     Infections  1 (2.2)
     NO  42 (93.3)
     Concomitant treatments (%)
     YES  3 (6.7)
     Analgesia  1 (2.2)
     Omeprazole  1 (2.2)
     Antihistamines  1 (2.2)
     NO  42 (93.3)
    Note: FAE: antiepileptic drug.
    Example 3: Results on patients
    Crisis Reduction
    The main variable of the study was the reduction of seizures in each patient. The percentage of crisis reduction in each of them throughout the study was assessed individually. 28.9% (by intention to treat; 31.7% per protocol) of the patients reduced by at least 50% the number of habitual seizures (reference value accepted by medical consensus in clinical trials so that a drug Antiepileptic be accepted as useful for epilepsy) (Figure 1).
    A subgroup analysis of the baseline characteristics of patients who had reduced their seizures and those who had not been performed was not found statistically significant differences (Table 4).
    Table 4. Analysis by subgroups of effectiveness based on the different variables and hypothesis contrast tests.
    Variables Cash Non-effective p value
    Sex (%)
    Woman
    6 (28) 15 (71.4) 0.759
    5
    10
    fifteen
    twenty
    25
    30
    35
    Man
    Age, mean (± SD)
    Years of evolution (SD)
    Place of origin of epilepsy (%) Frontal Temporary Occipital Multifocal No focus
    No. FAES they are taking (DE) Na FAES they have taken (DE)
    In treatment with VPA (%)
    In treatment with CMZ (%)
    No. crisis average (SD)
     8 (33.3)  16 (66.7)
     44 (15)  45 (13) 0.886
     35 (19)  28 (15) 0,180
     0.927
     1 (33.3)  2 (66.7)
     4 (25)  11 (75)
     0  1 (100)
     3 (33.3)  6 (66.7)
     6 (37.5)  10 (62.5)
     2.6 (1)  2.9 (1.1) 0.531
     5.21 (2.1)  6 (2,4) 0,242
     8 (42.1)  11 (57.9) 0.174
     4 (30.8)  9 (69.2) 0.999
     5 (7.3)  8 (8) 0.194
    DE: standard deviation. N °: numbers; FAES: antiepileptic drugs. VPA: valproic; CMZ: carbamazepine.
    To assess whether there had been changes throughout the study in anthropometric measurements or analytical parameters, an analysis of paired samples was performed. The values of body mass index, systolic and diastolic arterial tensions, analytical parameters of liver function, hemoglobin, leukocytes and C-reactive protein in baseline measurements were analyzed, and after treatment, obtaining neither clinical nor statistically significant differences in the different measurements throughout the study (Table 5 and 6).
    Table 5. Average values of the anthropometric and hemodynamic variables.
     Variable  Minimum Maximum Average SD
     BMI  20 42.5 28.8 5.6
     TAS  97 180 134.32 19.6
     TAD  60 106 82.8 10.8
     FC  53 100 72 12
    Note: BMI: body mass index; TAS: systolic blood pressure; ADT: diastolic blood pressure, HR: heart rate.
    5
    10
    fifteen
    twenty
    25
    30
    Table 6. Analysis of the change of the variables shown, between the baseline sample and after the treatment (Student's t-test).
    Variable P value
     BMI  0.653
     TAS  0.136
     TAD  0.089
     GPT  0.119
     GOT  0.507
     GGT  0.743
     Hemoglobin  0.286
     Leukocytes  0.214
     PCR  0.455
    Note: BMI: body mass index; TAS: systolic blood pressure; TAD: diastolic blood pressure, GPT: alanine aminotransferase; GOT: aspartate aminotransferase; GGT: Gamma glutamyl transpeptidase; PCR: C-reactive protein.
    An analysis of the relationship between the effectiveness of the treatment and values such as body mass index and systolic and diastolic blood pressure was performed, not showing statistically significant differences (Table 7).
    Table 7. Relationship between the effectiveness of the study and variables such as body mass index and systolic and diastolic blood pressure.
     Variables  Cash Not effective Value of p
     BMI (DE)  27 (3.5) 29.6 (6.3) 0.092
     TAS (DE)  131 (20) 129 (19) 0.699
     TAD (DE)  80 (12) 29 (13) 0.744
    Note: BMI: body mass index, ASD: systolic blood pressure, ADT: diastolic blood pressure.
    5
    10
    fifteen
    twenty
    25
    30
    Quality of life
    After performing an analysis of paired samples for the quality of life scores, no statistically significant differences were observed between the initial and final moment of administration of the same (p 0.302), but when comparing the situation since the end of the administration of the same at the end of the follow-up (p 0.002).
    When analyzing by subgroups, the differences between the scores of the quality of life of the patients in whom the probiotics were effective (mean of 19.23 ± 6.04) compared to those that were not effective (mean of 26 , 45 ± 9.1 points) statistically significant differences were found (p 0.013). It is important to remember that, at a lower score, better quality of life (Figure 2). As can be seen in this figure, in patients in whom the probiotic was effective, there is an improvement in the quality of life after statistically significant treatment compared to those that were not effective. Apart from being statistically significant, it is proved that the changes in the quality of life could be substantial changes clinically, since in the group of people it goes from a situation of "good and bad" to a situation of "good" quality of life .
    By grouping patients in good quality of life (those with scores of quite good, and very good) and bad (scores between good and bad, and very bad) and it is analyzed if it is related to the subjective feeling of effectiveness, it is seen how there is a tendency to statistical significance (p 0.062). That is, the patient who believes that probiotics have controlled seizures, although objectively they have not controlled it, has better scores on life scales.
    The patients were asked if the probiotics had managed to improve "something", for example, alertness or mood, and some, despite not having improved the crises, had improved these aspects. However, by relating these Improvements with changes in quality of life, no statistically significant differences were observed (p 0.1).
    Example 4: Changes in analytical parameters.
    Of the 45 patients in whom the study began, finally only 39 complete samples were obtained for cytokine analysis. The analysis of the characteristics
    5
    10
    fifteen
    twenty
    25
    30
    Baseline of both samples found no statistically significant differences (Table 8).
    Table 8. Comparison of variables between the baseline sample and the cytokine analysis.
     Variables  Sample of 45 Sample of 39 Value
     Sex: Male (%)  24 (53.3) 22 (56.4) 0.95
     Age, mean (± SD)  44 (13.5) 45.4 (13.5) 0.61
     Etiology
     Cryptogenic (%)  20 (44.4) 15 (38.5) 0.75
     Mesial sclerosis (%)  4 (8.9) 4 (10) 0.99
     Focus location
     Temporary (%)  16 (35.6) 13 (32.5) 0.95
     No focus (%)  16 (35.6) 15 (37.5) 0.99
     Years of evolution epilepsy (ED)  30 (16) 32 (16) 0.57
     Previous FAES, mean (SD)  5.8 (2.3) 5.6 (2.2) 0.75
     Patients who took CMZ (%)  21 (46.7) 17 (43.6) 0.95
     Patients who took VPA (%)  30 (66.7) 26 (66.7) 0.99
     No. FAES currently, average (SD)  2.8 (1) 2.8 (1.1) 0.66
     No. of patients taking CMZ (%)  6 (13.3) 11 (28.2) 0.16
     No. of patients taking VPA (%)  13 (28.9) 16 (41) 0.35
     Average number of crises in a month (SD)  7 (7) 6.5 (7) 0.75
     Effectiveness of the probiotic (%)  14 (31.1) 12 (30.8) 0.99
    Note: DE: standard deviation; FAE: antiepileptic drugs; CMZ: carbamazepine; VPA: valproic.
    An overall analysis of their median has been performed for each cytokine. Subsequently, it was analyzed whether this median at different times showed statistically significant differences between the group in which the administration of probiotics was related to a crisis reduction ("effective group") and to which it was not related to a crisis reduction. ("non-effective group"). Once analyzed this,
    5
    10
    fifteen
    twenty
    25
    30
    35
    A second analysis revealed whether throughout the study each patient presented changes in their measurements both in the general group and by subgroups of efficacy.
    IL-6 levels
    The median IL-6 pretreatment was 34.6 pg / ml (Pc25 0 - Pc75 61.9). At the end of the probiotic intake, it was 33 pg / ml (Pc25 0 - Pc75 56.2), and 4 months after the end of it, 0 (Pc25 0 - Pc75 30.4).
    The medians by subgroups according to the effectiveness of the probiotics can be seen in Table 9. In this analysis there are no differences in the medians of pretreatment IL-6 (p 0.98), after the end of the probiotic treatment (p 0 , 41) or 4 months after completing it (p 0.85).
    Table 9 Summary of the medians by subgroups and the value of the differences (Pc25-Pc75)
     IL6 levels (pg / ml)  Cash Not effective Value of p
     Basal  30.2 (0-59.3) 34.6 (0-87) 0.98
     At the end of the treatment  23.8 (0-52.2) 35.2 (0-61) 0.41
     4 months later  9 (0-28.4) 0 (0-30.8) 0.85
    Figure 3 shows that there are statistically significant differences (p 0.001). Specifically, the differences are found between the baseline levels and the measurement at 4 months after the end of the treatment (p 0.002), and after taking the probiotics and 4 months later (p 0.009). When this analysis is carried out by subgroups, it is observed that within the subgroup of the patients who were treated with probiotics there are no statistically significant differences (p 0.48). On the contrary, in the group in which the treatment was not effective, there are statistically significant differences (p 0.005). Differences are also found between baseline levels and measurement at 4 months without treatment (p 0.021) and after taking probiotics and 4 months later (p 0.038).
    CD14 levels:
    Overall, the median pretreatment cD14 was 1904.92 pg / ml (Pc25 787 - Pc75 2197.7); at the end of taking the probiotic of 1875 pg / ml (Pc25 778.4 - Pc75
    5
    10
    fifteen
    twenty
    25
    30
    35
    2349.7), and 4 months after completion of 1806.3 pg / ml (Pc25 1046.6 -Pc75 2034.3). The medians by subgroups can be seen in Table 10. There are no differences between the patients in whom the treatment works or not based on the medians of cD14 pretreatment (p 0.065), after taking the probiotic (p 0.81) or 4 months after having suspended it (p 0.81).
    Table 10. Summary of the medians by subgroups and the value of the differences found between them (Pc25-Pc75).
    CD14 levels (pg / ml) Cash Not effective Value of p
    Baseline 2074 (1764-2199) 1660 (609-2197) 0.065
    At the end of the treatment 1983 (762-2364) 1875 (778-2350) 0.81
    4 months later 1763 (860-1988) 1807 (1158-2109) 0.81
    Figure 4 shows that there were no statistically significant differences in the patients at the different times the samples were collected (p 0.735). Nor were there statistically significant differences in any of the 2 groups, neither in which the probiotics were effective (p 0.17) nor in which they were not (p 0.89).
    GABA levels
    The median GABA pretreatment was 0 ng / ml (Pc25 0 - Pc75 13.9); at the end of the probiotic it was 5.7 ng / ml (Pc25 4.1 - Pc75 7.4), and 4 months after the end of it again 0 ng / ml (Pc25 0 - Pc75 10.5). The medians by subgroups can be seen in the following table (Table 11). There are no differences in the pretreatment GABA medians (p 0.96), after the end of the probiotic (p 0.65), or 4 months after the suspension of the probiotic (p 0.85) between those who worked or not the treatment .
    Table 11. Summary of the medians by subgroups and the value of the differences (pg / ml).
    GABA levels (ng / ml) Cash Not effective Value of p
    Baseline 0 (0-9.6) 0 (0-19.3) 0.954
    At the end of treatment 6.18 (4.9-8.4) 5.3 (0-7) 0.650
    4 months later 0 (0-29.8) 0 (0-9.7) 0.851
    According to Figure 5 there are no statistically significant differences (p 0.35) in patients at the different times at which the samples are collected. When this analysis is carried out by subgroups, it is observed that there are also no statistically significant differences between any of the groups, nor in which they were effective (p 0.72) and in those that were not (p 0.48).
    权利要求:
    Claims (3)
    [1]
    1. Use of a probiotic composition comprising S. thermophilus, L. acidophilus, L. plantarum, L. paracasei, L. delbrueckii, B. breve, B. longus and B. lactis in the
    5 preparation of a nutritional supplement for the complementary treatment of drug-resistant epilepsy.
    [2]
    2. Use according to claim 1, wherein said probiotic composition comprises the CD2 chain.
    [3]
    3. Use according to claim 1 or 2, wherein said treatment comprises a dosage of 450,000 million bacteria orally twice daily in a
    patient.
    Improvement of the quality of life
    h1 H h) DO W W ^
    O UL O UL O UL O UL O
    VO
    image 1
    UL
    OR
    (Q
    C
    0)
    Percentage of patients who experienced crisis reduction
    image2
    ¡33
    n>
    or.
    C
    HE
    n
    T3
    = 1
    OR
    3"
    |
    or
    or
    Q_
    you
    i
    ñ_
    m '
    AND'
    image3
    ^ ÜO'OS
    image4
    image5
    Figure 4
    image6
    Figure 5
    类似技术:
    公开号 | 公开日 | 专利标题
    López D'alessandro et al.2011|Combination of alpha lipoic acid and gabapentin, its efficacy in the treatment of Burning Mouth Syndrome: a randomized, double-blind, placebo controlled trial
    Cummins et al.2003|Treatment of primary sjögren's syndrome with low‐dose human interferon alfa administered by the oromucosal route: Combined phase III results
    Serfaty et al.2002|Double blind randomised placebo controlled trial of low dose melatonin for sleep disorders in dementia
    Kayser et al.2015|Magnetic seizure therapy in treatment-resistant depression: clinical, neuropsychological and metabolic effects
    Kumar et al.1974|Procarbazine hydrochloride in the treatment of brain tumors: Phase 2 study
    ES2770760T3|2020-07-03|Use of levocetirizine and montelukast in the treatment of traumatic injuries
    Chang et al.2016|Intraduodenal levodopa-carbidopa intestinal gel infusion improves both motor performance and quality of life in advanced Parkinson’s disease
    Findlay et al.2002|Fast track anesthesia for liver transplantation reduces postoperative ventilation time but not intensive care unit stay
    Lekoubou et al.2011|Effect of long-term oral treatment with L-arginine and idebenone on the prevention of stroke-like episodes in an adult MELAS patient
    ALTINDAĞ et al.2011|Intoxication due to high dose methotrexate in a patient with rheumatoid arthritis: a case report
    DE69031694T3|2007-10-18|Glutamine for the treatment of impaired immunity
    ES2675811B1|2019-04-26|USE OF A PROBIOTIC COMPOSITION FOR THE COMPLEMENTARY TREATMENT OF PHARMACORRESISTENT EPILEPSY
    Gunderson et al.2016|Lactation and progression to type 2 diabetes mellitus after gestational diabetes mellitus
    Lim et al.2011|Parkinson's disease and pain—Nondopaminergic mechanisms are likely to be important too
    Boymuradov et al.2021|Aspects of Maxillar osteomyelitis in patients Who had COVID-19 in Uzbekistan
    Kramer et al.1991|13‐cis‐retinoic acid in the treatment of elderly patients with acute myeloid leukemia. A phase II pilot study of the eastern cooperative oncology group
    Nagahori et al.2016|Lactation and progression to type 2 diabetes mellitus after gestational diabetes mellitus
    Zein et al.2006|Treatment of central pontine myelinolysis with thyrotropin-releasing hormone
    Inchingolo et al.2011|Combined occlusal and pharmacological therapy in the treatment of temporo-mandibular disorders
    Ramesh et al.2017|Infantile cortical hyperostosis of scapula presenting as pseudoparalysis in an Infant
    Lynch et al.1964|Vitamin D-Intoxicated Patient With Hypoparathyroidism: Hypercalcemia, Acute Cerebellar Ataxia, and EEG Changes: Magnesium Sulfate Therapy
    CN102389564A|2012-03-28|Compositions for use in treating myelodysplastic syndrome
    Abyad2016|Cobalamin Injection: Is it Useful in Lumbosacral Diseases?
    RU2601408C1|2016-11-10|Method of treating patients with facial pain with postherpetic ganglionitis of a head
    RU164766U1|2016-09-10|METHOD FOR TREATING PYELONEPHRITIS IN PREGNANT WOMEN
    同族专利:
    公开号 | 公开日
    ES2675811B1|2019-04-26|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    WO2011042333A1|2009-10-09|2011-04-14|Ab-Biotics S.A.|Lactobacillus plantarum strains as hypocholesterolemic agents.|
    WO2015021936A1|2013-08-16|2015-02-19|The University Of Hong Kong|Method and compositions for treating cancer using probiotics cross-reference to related application|
    法律状态:
    2018-07-12| BA2A| Patent application published|Ref document number: 2675811 Country of ref document: ES Kind code of ref document: A1 Effective date: 20180712 |
    2019-04-26| FG2A| Definitive protection|Ref document number: 2675811 Country of ref document: ES Kind code of ref document: B1 Effective date: 20190426 |
    2021-10-04| FD2A| Announcement of lapse in spain|Effective date: 20211004 |
    优先权:
    申请号 | 申请日 | 专利标题
    ES201730027A|ES2675811B1|2017-01-12|2017-01-12|USE OF A PROBIOTIC COMPOSITION FOR THE COMPLEMENTARY TREATMENT OF PHARMACORRESISTENT EPILEPSY|ES201730027A| ES2675811B1|2017-01-12|2017-01-12|USE OF A PROBIOTIC COMPOSITION FOR THE COMPLEMENTARY TREATMENT OF PHARMACORRESISTENT EPILEPSY|
    [返回顶部]