• 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:
    Procedure of preparation of a nanostructured material of praziquantel and a silicate, material obtained and use as antiparasitic. The invention relates to a process for preparing a nanostructured material of a silicate having a laminar, fibrillar or tubular structure with praziquantel, a compound with antiparasitic activity. Other aspects of the invention relate to the material obtained by said preparation process and to the use thereof for the elimination of parasites, both in compositions for the treatment of parasitic diseases, particularly schistosomiasis, as well as in ventilation systems or water pipes. (Machine-translation by Google Translate, not legally binding)
    公开号:ES2696400A1
    申请号:ES201730934
    申请日:2017-08-03
    公开日:2019-01-15
    发明作者:Díaz Claro Ignacio Sainz；Sánchez Ana Borrego；Iborra César Viseras；Carola Aguzzi
    申请人:Consejo Superior de Investigaciones Cientificas CSIC；Universidad de Granada；
    IPC主号:
    专利说明:

    [0001]
    [0002] PROCEDURE FOR THE PREPARATION OF A NANOSTRUCTURED MATERIAL
    [0003]
    [0004] SECTOR OF THE TECHNIQUE AND OBJECT OF THE INVENTION
    [0005]
    [0006] The present invention is part of the field of compounds and pharmaceutical compositions for the treatment of parasitic diseases. The invention relates, in particular, to a process for the preparation of a nanostructured material of a silicate having a laminar, fibrillar or tubular structure with praziquantel, a compound with antiparasitic activity. Other aspects of the invention relate to the material obtained by said preparation method and to the use thereof for the elimination of parasites, both in compositions for the treatment of parasitic diseases, particularly schistosomiasis, as in ventilation systems, water pipes, etc.
    [0007]
    [0008] STATE OF THE ART
    [0009]
    [0010] Phyllosilicates are lamellar clay minerals with a nanometric interlaminar space. Its properties of high absorption, capacity of cation exchange and capacity of swelling provide it to be a peculiar nanostructured material. This solid can absorb and release organic molecules under controlled conditions, being a good candidate for the controlled release of drugs.
    [0011] On the other hand, praziquantel (PZQ), (RS) -2- (cyclohexylcarbonyl) -1,2,3,6,7,11b-hexahydro-4H-pyrazino- [2,1a] -isoquinolin-4-one, It is the drug of choice in the treatment of schistosomiasis, a parasitic disease widely spread throughout the world, mainly in tropical and subtropical areas. It is estimated that schistosomiasis affects more than 200 million people worldwide, out of a total of 783 million at risk. The affected population includes 24 million children of pre-school age and 65 million children of school age, at risk of a total of 72 million and 200 million, respectively. It is the second most prevalent disease in African children, after malaria. Therefore, it is necessary to look for new forms of application of said drug to increase its effectiveness and minimize adverse effects of resistance and side effects.
    [0012] The patent ES 2271714T3 provides a method for preparing pharmaceutical compositions with a porous solid for the oral application of anthelmintics, including Praziquantel, claiming the use of colloidal silica and improving the organoleptic characteristics of the drug by claiming its taste. The patent ES 2126506A1 provides a method for obtaining drug-clay complexes in a general way without specifying the drug by the method of dry route or joint or fusion milling, claiming the use of smectite and sepiolite. In none of the above patents is the alteration in the bioavailability properties or biopharmaceutical profile of praziquantel specified.
    [0013] The document XXIV Meeting of the Spanish Clays Society 2015, P5, pp. 13-14 refers to a theoretical study on the stability of crystalline, enantiomeric and racemic forms of praziquantel and its crystallographic and spectroscopic properties, in order to determine the possibility of access of this antiparasitic drug, useful for the treatment of schistosomiasis, to the interlaminar space of phyllosilicates. Thus, the adsorption complex of the praziquantel molecule is collected in the crystal structure of a montmorillonite, which includes the formation of a coordination complex between the oxygen of the praziquantel carbonyl group and the Na + cation.
    [0014] The document Antimicrobial Agents and Chemotherapy, 2015, Vol. 59, pp. 3501-3508 discloses a nanoformulation comprising the anti-schistosomiasis drug praziquantel and the montmorillonite clay as a carrier for the release of the drug, which allows to improve its bioavailability. The complex is prepared by intercalation of praziquantel, previously dissolved in aqueous solution, between the laminated structure of montmorillonite, which occurs easily due to the ion exchange reaction between the montmorillonite ions and the praziquantel molecules, having tested different weather conditions (0.25, 0.5, 1, 2, 4, 8 and 12 h) and pH (from 2 to 9) at a temperature of 60 ° C. In particular, four formulations montmorillonita-praziquantel were obtained being these in proportions 1: 1, 1: 2, 1: 3 and 1: 4, respectively, by adding the appropriate amounts of praziquantel on each of the solutions containing 0, 25 g of montmorillonite in 100 mL of water, stirring and filtering the mixtures.
    [0015] In C. Aguzzi et al .; Applied Clay Science 36 (2007), pp.22-36, a review is made on the use of clays in controlled drug release systems. Various types of clay materials are proposed and it is concluded that the choice of one or the other, as well as the possible addition of polymeric additives, should be based on the desired modulation effect of the release of the drug being sought. The preparation of clay-drug complexes is carried out by dispersing the clay in aqueous solutions of the drug.
    [0016] Other documents in which you can find examples of materials that include pharmaceuticals and laminated silicates are:
    [0017] - WO2006 / 088337 where materials with amlodipine, paroxetine, donepezil and subutramine are explicitly described, including the process of preparing the materials the dispersion of the layered silicate (for example montmorillonite, beidelite and illite) in an aqueous solvent and the addition of a polymer basic.
    [0018] - WO2004 / 052400 where pharmaceutical formulations comprising several drugs, such as praziquantel, are disclosed. The formulations are prepared by dissolving the active ingredient in a solvent which can be an oil or an organic solvent, adsorbing or absorbing this solution in a sorbent medium (for example, silicon dioxide) and subsequently dispersing the resulting mixture into a liquid. The exemplified organic solvent is glycerol monocaprylate (Capmul MCM).
    [0019] In short, from the state of the art referenced derives the interest to have materials that allow increasing the bioavailability of praziquantel and use of said materials for the treatment of parasitic diseases, particularly schistosomiasis.
    [0020]
    [0021] BRIEF EXPLANATION OF THE INVENTION
    [0022]
    [0023] A first method of the present invention is a method of preparing a nanostructured material comprising praziquantel and a silicate including the following steps:
    [0024] - preparation of a suspension comprising praziquantel, the silicate and a polar organic solvent,
    [0025] - homogenization of the suspension prepared in the previous stage,
    [0026] - solid separation - liquid applied to the suspension from the previous steps for the removal of the solvent.
    [0027]
    [0028] A second object of the invention is the nanostructured material obtained by the above method. Praziquantel is usually administered orally, however it is very poorly soluble in water and has a strong bitter taste, which makes it necessary to prepare complex galenic formulations, so that the nanostructured material of the invention has as a technical advantage its usefulness for be administered topically to be absorbed through the skin or mucous membranes, formulating it, for example, in plasters.
    [0029] Other aspects of the present invention constitute:
    [0030] - a pharmaceutical composition for topical use comprising said nanostructured material for the treatment of parasitic diseases.
    [0031] - the use of the nanostructured material defined in the preceding paragraph as a medicine or in the preparation of a medicament for the treatment of parasitic diseases, particularly schistosomiasis.
    [0032] - a process for eliminating parasites comprising contacting samples containing the parasites with said nanostructured material, in particular in ventilation systems, water pipes, etc.
    [0033] - Systems or devices for eliminating parasites comprising said nanostructured material.
    [0034]
    [0035] BRIEF DESCRIPTION OF THE FIGURES
    [0036] Figure 1.- Speed of dissolution in a simulated intestinal fluid without enzymes (pH = 6.8) of Praziquantel (blue), praziquantel absorbed in sepiolite (red) and montmorillonite (green). Figure 2.- X-ray diffractogram of montmorillonite (black) and of praziquantel absorbed in montmorillonite (red) according to the procedure described in example 1.
    [0037] Figure 3.- Differential scanning calorimetry profile (DSC) of montmorillonite (black), praziquantel absorbed in montmorillonite (red) and praziquantel (green) according to the procedure described in example 1.
    [0038] Figure 4.- X-ray diffractogram of montmorillonite (black) and of praziquantel absorbed in montmorillonite (red) according to the procedure described in example 2.
    [0039]
    [0040] DETAILED DESCRIPTION OF THE INVENTION
    [0041]
    [0042] The invention proposes a process for preparing a nanostructured material comprising a silicate and the antiparasitic praziquantel as well as the material obtained by said process and the use thereof as antiparasitic.
    [0043]
    [0044] For the purposes of the present invention, the term "praziquantel ' will refer to both the compound (RS) -2- (cyclohexylcarbonyl) -1,2,3,6,7,11b-hexahydro-4H-pyrazino- [2,1a] -isoquinolin-4-one, as to any racemic or any of the (R) or (S) enantiomers of praziquantel, as well as to combinations thereof in any proportion.
    [0045]
    [0046] The term "dispersant" refers to any agent that facilitates the dispersion of certain particles that a medium contains in suspension, more specifically to any agent that facilitates the dispersion of praziquantel particles in the silicate, for example by modifying the surface tension, as in the case of surfactants.
    [0047]
    [0048] As "amorphization" is meant the loss of the crystalline structure of a compound in the solid state, where said solid does not present sharp reflections in its X-ray diffractogram and that its differential scanning calorimetry profile does not present a peak of energy release when melting. The "degree of amorphization" is defined as the percentage of the initial product that has been amorphized.
    [0049]
    [0050] The term "treatment" or " treating " in the context of this document refers to the administration of a compound or a composition according to the invention to prevent, ameliorate or eliminate a disease, pathological condition or one or more symptoms associated with said disease or condition. in an animal, preferably in a mammal. "Treatment" also encompasses the improvement or elimination of the physiological sequelae of the disease. Specifically, the concept "treat" can be interpreted as:
    [0051] i. Prevent the disease or pathological condition in an animal, particularly when the animal has a predisposition for the pathological condition to occur, but has not yet been diagnosed to have it.
    [0052] ii. Inhibit the disease or pathological condition, that is, stop its development; iii. Alleviate the disease or the pathological condition, that is, cause the regression of the disease or the pathological condition;
    [0053] iv. Stabilize the disease or the pathological condition.
    [0054]
    [0055] Throughout the description and claims the term "comprises", which may also be interpreted as "consisting of", and its variants are not intended to exclude other technical characteristics, additives, components or steps. For those skilled in the art, other objects, advantages and characteristics of the invention will emerge partly from the description and partly from the practice of the invention.
    [0056]
    [0057] Procedure for the preparation of nanostructured materials comprising praziquantel and a silicate
    [0058]
    [0059] In the defined context, the present invention relates, in a first aspect, to a process for preparing a nanostructured material containing praziquantel and a silicate (hereinafter "process of the invention", comprising the following steps:
    [0060] - preparation of a suspension comprising praziquantel, the silicate and a polar organic solvent;
    [0061] - homogenization of the suspension prepared in the previous stage;
    [0062] - solid separation - liquid applied to the suspension from the previous steps for the removal of the solvent;
    [0063]
    [0064] By this preparation process an extremely intimate contact is achieved between the praziquantel and the silicate surface and, surprisingly, the drug remains in the amorphous state.
    [0065]
    [0066] In a particular embodiment, the silicate employed is a phyllosilicate. Preferably the silicate is selected from smectite, sepiolite, halloysite, paligorskite, montmorillonite, vermiculite, attapulgite, stevensite, bentonite, talc, beidelite, illite, kaolinite or combinations thereof and can include any cation or combination of cations. Preferably, the silicate used is montmorillonite or sepiolite, more preferably montmorillonite.
    [0067]
    [0068] In another particular embodiment, the polar organic solvent used is a polar organic carbon chain solvent having between 1 and 3 carbon atoms. In a more preferred embodiment, the solvent is selected from acetonitrile, acetone, ethanol, methanol, isopropanol, propanol and combinations thereof, with ethanol being selected as even more preferred embodiment.
    [0069]
    [0070] The polar organic solvent can also be combined with water, provided that it is present in a proportion of less than 10% v / v, preferably less than 5% v / v.
    [0071]
    [0072] In addition to the low solubility in water of praziquantel, the phyllosilicates are hydrophilic and when they are saturated with water it is difficult for the hydrophobic product to be absorbed by the clay, for which dispersants, in particular dispersing effect surfactants, are used to increase their solubility and, consequently, improve its absorption, bioavailability and therapeutic efficacy. Contrary to what could be deduced from the state of the art, the method of the invention allows increasing the solubility of praziquantel without the need to use surfactants or other dispersants as additives, by avoiding the presence of water molecules in the interlaminar space of the phyllosilicates. , which makes it difficult for the drug molecules to enter the internal surface of said silicates and which would make it necessary to use dispersants and / or surfactants.
    [0073] Therefore, in another particular embodiment, the process of the invention is carried out in the absence of dispersants and / or surfactants, preferably in the absence of surfactants.
    [0074]
    [0075] The preparation of the suspension comprising the silicate, the praziquantel and the polar organic solvent can be carried out in two different ways:
    [0076] - In a particular embodiment, the silicate is initially mixed with the polar organic solvent and subsequently the praziquantel is dissolved in said suspension. - In another particular embodiment, praziquantel is initially dissolved in the polar organic solvent and subsequently the silicate is added to form the suspension.
    [0077]
    [0078] The process conditions in particular modes of realization are:
    [0079] - temperature at which the process is carried out between -10 ° C and 50 ° C - range of pressures under which the extraction is carried out between 104 and 106 Pa, preferably 101325 Pa.
    [0080] - the amount (by weight) of praziquantel in the solution with polar organic solvent is in a range between 0.005 g / L and the limit of solubility in the medium
    [0081] - The agitation time to achieve the dissolution is between 5 min and 168 hours.
    [0082] - The ratio between the silicate and the praziquantel used for the range between 100: 1 and 1:10 (weight: weight). For example, a 50: 1 ratio refers to 50 g of silicate per 1 g of praziquantel.
    [0083]
    [0084] As regards the homogenization step, ultrasound can be used, preferably for a period of time between 5 min and 2 hours, and the solid-liquid separation step can be carried out by evaporation under reduced pressure or by centrifugation and drying.
    [0085]
    [0086] Nanostructured material of the invention
    [0087]
    [0088] Another object of the present invention is a nanostructured material, hereinafter "material of the invention", comprising praziquantel and a silicate, in particular a material obtained by a process as defined above, characterized in that the praziquantel has a degree of depreciation greater than 75%, preferably a degree of depreciation greater than 85% and, even more preferably, greater than 95%.
    [0089] The solid silicate comprised by the material of the invention can be montmorillonite, smectite, vermiculite, attapulgite, sepiolite, stevensite, bentonite, paligorskite, talc, beidelite, illite, halloysite, kaolinite and mixture of these minerals in any of the proportions.
    [0090]
    [0091] By means of the described preparation process an extremely intimate contact between the drug and the silicate surface is achieved. Surprisingly, by this procedure the praziquantel remains in an amorphous state. The x-ray diffraction analysis of the nanocomposite solid obtained by the present invention indicates that the drug enters the interlaminar space by increasing the spacing between the crystallographic planes (001) of the phyllosilicate.
    [0092]
    [0093] Several bioavailability studies of the praziquantel encapsulated in the material of the invention, in particular in the material, obtained by the method of the invention, indicated that the bioavailability of praziquantel is greater than that of the pure drug itself both absorbed in montmorillonite and in sepiolite ( Fig. 1).
    [0094]
    [0095] Some advantages presented by the material of the invention are:
    [0096] - a natural silicate is used as excipient for its therapeutic use
    [0097] - the industrial scale-up of the preparation process would be environmentally friendly when using natural materials
    [0098] - the use of solvents of lower boiling point than that of water will require a lower energy cost in the processes of solvent separation and drying of the solid than traditional methods in aqueous solutions.
    [0099] - The solvent can be reused. This will entail a lower economic cost and a lower emission of CO 2 to the environment.
    [0100]
    [0101] Pharmaceutical compositions comprising the material of the invention
    [0102]
    [0103] In another aspect, the invention provides pharmaceutical formulations, forms or compositions, hereinafter "compositions of the invention" comprising the material of the invention. Said formulations may contain any other active ingredient in the treatment of diseases caused by parasites or be characterized as containing as a sole active principle the praziquantel comprised in the material of the invention.
    [0104] In the sense used in this description, the term "therapeutically effective amount" refers to that amount of praziquantel which, when administered to an animal, is sufficient to produce the treatment of a disease or pathological condition of interest in the animal. The amount of praziquantel constituting a therapeutically effective amount will vary, for example, according to the metabolic stability and duration of action of the compound; the species (preferably human), the clinical form of the disease, age, body weight, general state of health, sex and diet of the patient; the route of administration; the mode and time of administration; speed; the combination of drugs; the severity of the particular disorder or pathological condition; and the subject who undergoes therapy, but can be determined by a person skilled in the art according to his own knowledge and that description.
    [0105]
    [0106] On the other hand, according to the present invention, the "pharmaceutical form" is the individualized arrangement to which the drugs (active ingredients) and excipients (pharmacologically inactive material) are adapted to constitute a medicament.
    [0107]
    [0108] In a particular embodiment, said pharmaceutical compositions also comprise one or more pharmaceutically acceptable carriers.
    [0109]
    [0110] The "pharmaceutically acceptable carriers" that can be used in the formulations of the invention are the vehicles known to those skilled in the art and commonly used in the preparation of therapeutic compositions.
    [0111]
    [0112] Optionally, the pharmaceutical composition may comprise another active principle. In addition to the requirement of therapeutic efficacy, which may necessitate the use of therapeutic agents, in addition to the compounds of the invention, there may be additional fundamental reasons that require or strongly recommend the use of a combination of praziquantel and another therapeutic agent, such and as in the treatment of diseases or conditions that directly or indirectly modulate the function of the substance.
    [0113]
    [0114] The formulations may also contain excipients.
    [0115]
    [0116] The excipients and vehicles used must be pharmaceutically and pharmacologically tolerable, so that they can be combined with other components of the formulation or preparation and do not exert adverse effects on the treated organism. The pharmaceutical compositions or formulations include those that they are suitable for oral or parenteral administration (including subcutaneous, intradermal, intramuscular and intravenous), although the best route of administration depends on the condition of the patient. The formulations can be in the form of simple doses. The formulations are prepared according to methods known in the field of pharmacology. The amounts of active substances to be administered may vary depending on the particularities of the therapy.
    [0117]
    [0118] Topical compositions
    [0119]
    [0120] In the context of the present invention, "topical route" is understood as the route of drug administration that uses the skin and mucous membranes.
    [0121]
    [0122] In a particular embodiment, the composition of the invention is suitable for topical administration, using, for example, the material of the invention to form plaster.
    [0123]
    [0124] Medical use of the material of the invention
    [0125]
    [0126] In another of its aspects, the invention relates to the use of the material of the invention as a medicament or for the preparation of a medicament. In particular, the material of the invention is used as a medicament or to prepare a medicament for the treatment of diseases that occur with parasitic activity, in particular with helminth activity.
    [0127]
    [0128] Similarly, the invention relates to a method of treating diseases that occur with parasitic activity, in particular with the activity of helminths.
    [0129]
    [0130] In a particular embodiment, the method of treatment invention comprises providing a composition comprising the material of the invention so that the material of the invention comes into contact with the parasites that cause the disease.
    [0131]
    [0132] Preferably the disease being treated is schistosomiasis, it is an acute and chronic parasitic disease caused by blood flukes (trematodes) of the genus Schistosoma.
    [0133]
    [0134] Parasite removal procedure
    [0135] Another object of the invention is a process for the elimination of parasites, preferably helminths, hereinafter referred to as the " parasite elimination process of the invention", which comprises contacting the material of the invention with the parasites.
    [0136]
    [0137] Systems or devices to protect against pollutants
    [0138]
    [0139] In a last aspect, the invention relates to systems or devices for eliminating parasites, hereinafter "parasite elimination systems of the invention", which comprise the material of the invention or allow carrying out the process of elimination of parasites of parasites. the invention.
    [0140]
    [0141] In particular, filters comprising the materials of the invention are subject of the invention. More particularly, the filters of the air conditioning or ventilation systems comprising the materials of the invention, the filters for water purification or filtering systems and the systems that incorporate them.
    [0142]
    [0143] MODE FOR CARRYING OUT THE INVENTION
    [0144]
    [0145] Some illustrative examples of the method of the invention are described below that should not be considered as limiting the scope of protection thereof.
    [0146]
    [0147] Example 1
    [0148] 0.5 g of praziquantel are dissolved in 100 mL of a suspension of 2.5 g of sodium montmorillonite in ethanol. After 24 h of constant stirring at 25 ° C, the solvent is evaporated under reduced pressure to dryness. The solid obtained was characterized by X-ray diffraction observing an increase in the interlaminar space from 12.45 Á to 14.45 Á (Fig. 2). The Differential Scanning Calorimetry (DSC) analysis indicated that the drug is in a non-crystalline form (Fig. 3).
    [0149]
    [0150] Example 2
    [0151] To a solution of 0.1 g of praziquantel in ethanol, 0.5 g of sodium montmorillonite are added and the mixture is left 24 h under constant stirring at 25 ° C and centrifuged. The solid is allowed to dry 24 h at 40 ° C. Analysis of said solid by X-ray diffraction indicated that the interlaminar spacing of the phyllosilicate increased from 12.45 Á to 13.84 Á (Fig. 4).
    [0152] Example 3
    [0153] 0.5 g of sodium montmorillonite are suspended in ethanol and in this suspension 0.1 g of praziquantel is dissolved. The mixture is treated in an ultrasonic bath for 1 h and then left 24 h in constant agitation at 25 ° C. After that time the solvent is evaporated under reduced pressure, obtaining a powdery and dry solid.
    [0154]
    [0155] Example 4
    [0156] 0.5 g of Praziquantel are dissolved in 100 mL of a suspension of 2.5 g of sepiolite in ethanol. After 24 h of constant stirring at 25 ° C, the solvent is evaporated under reduced pressure to dryness. Analysis by Differential Scanning Calorimetry indicated that the drug is in non-crystalline form.
    权利要求:
    Claims (22)
    [1]
    1. - Method of preparing a nanostructured material comprising praziquantel and a silicate including the following steps:
    - preparation of a suspension comprising praziquantel, the silicate and a polar organic solvent;
    - homogenization of the suspension prepared in the previous stage
    - solid separation - liquid applied to the suspension from the previous stages for solvent removal
    [2]
    2. - Method for preparing a nanostructured material according to claim 1, characterized in that the praziquantel is presented as racemic or as any of the enantiomers (R) or (S) or combinations thereof in any proportion.
    [3]
    3. - Method of preparation of a nanostructured material according to claims 1 or 2 characterized in that the silicate is selected from smectite, sepiolite, halloysite, paligorskite, montmorillonite, vermiculite, attapulgite, stevensite, bentonite, talc, beidelite, illite, kaolinite or combinations of them.
    [4]
    4. Process for the preparation of a nanostructured material according to any of claims 1 to 3, characterized in that the silicate includes any cation or combination of cations.
    [5]
    5. - Method according to any of the preceding claims, characterized in that the solvent used is a polar organic solvent with carbon chain that has between 1 and 3 C atoms.
    [6]
    6. Process for the preparation of a nanostructured material according to claim 5, characterized in that the polar organic solvent is selected from acetonitrile, acetone, ethanol, methanol, isopropanol, propanol and combinations thereof.
    [7]
    7. - Method for preparing a nanostructured material according to claim 6, characterized in that the polar organic solvent is ethanol.
    [8]
    8. - Method according to any of the preceding claims, characterized in that the dissolution is carried out in the absence of dispersants and / or surfactants.
    [9]
    9. - Method for preparing a nanostructured material according to any one of claims 1 to 8, characterized in that it is carried out in a temperature range between -10 ° C and 50 ° C and in a range of pressures comprised between 104 and 106 Pa, preferably 101325 Pa.
    [10]
    10. Process for the preparation of a nanostructured material according to any one of claims 1 to 9, wherein the praziquantel is dissolved in the polar organic solvent in a range comprised between 0.005 g / L and its solubility limit in said medium by stirring during a period comprised between 5 min and 168 hours and where the weight ratio between the silicate and the praziquantel is between 100: 1 and 1:10 (weight: weight).
    [11]
    11. Process for the preparation of a nanostructured material according to any one of claims 1 to 10, wherein the preparation of the suspension comprising the silicate, the praziquantel and the polar organic solvent is carried out by initially mixing the silicate with the polar organic solvent and subsequently dissolving the praziquantel in said suspension.
    [12]
    12. Process for the preparation of a nanostructured material according to any of claims 1 to 10, wherein the preparation of the suspension comprising the silicate, the praziquantel and the polar organic solvent is carried out by initially dissolving the praziquantel in the polar organic solvent and subsequently adding the silicate to form the suspension.
    [13]
    13. Process for the preparation of a nanostructured material according to any of claims 1 to 12, wherein the homogenization step includes the use of ultrasound for a period of time comprised between 5 min and 2 hours.
    [14]
    14. Process for the preparation of a nanostructured material according to any one of claims 1 to 13, wherein the step of solid-liquid separation is carried out by evaporation under reduced pressure or by centrifugation and drying.
    [15]
    15. - Nanostructured material comprising praziquantel and a silicate characterized in that the praziquantel has a degree of depreciation greater than 75%.
    [16]
    16. - Nanostructured material according to the previous claim, obtained by a method as defined in claims 1 to 14.
    [17]
    17. - Pharmaceutical composition comprising a nanostructured material as defined in claims 15 or 16 for the treatment of parasitic diseases.
    [18]
    18. - Pharmaceutical composition according to previous claim, suitable for topical use.
    [19]
    19. Use of a nanostructured material as defined in claims 15 or 16 or of the composition according to claims 17 or 18, for the preparation of a medicament for the treatment of parasitic diseases, particularly schistosomiasis.
    [20]
    20. Method of eliminating parasites comprising contacting samples containing the parasites with a nanostructured material as defined in claims 15 or 16.
    [21]
    21. - System of elimination of parasites that comprises a nanostructured material according to claims 15 or 16 and that allows carrying out the process of elimination of parasites according to previous claim.
    [22]
    22. - Filter comprising a nanostructured material according to claims 15 or 16.
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    同族专利:
    公开号 | 公开日
    WO2020012044A1|2020-01-16|
    ES2696400B2|2019-07-11|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    ES2126506A1|1996-12-31|1999-03-16|Consejo Superior Investigacion|Procedure for obtaining drug-clay complexes, and applications of the complexes so obtained|
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    WO2005018679A1|2003-08-21|2005-03-03|Nanohybrid Co., Ltd.|A hybrid of free-base amlodipine with a layered silicate and a process for preparing the same|
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    PCT/ES2018/070503| WO2020012044A1|2017-08-03|2018-07-13|Method for preparing a nano-structured material of praziquantel and a silicate, material obtained and use as an antiparasitic|
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