WO2014201914A1 - Médicament liquide oral d'une nanoémulsion de praziquantel-mébendazole et son procédé de préparation - Google Patents

Médicament liquide oral d'une nanoémulsion de praziquantel-mébendazole et son procédé de préparation Download PDF

Info

Publication number
WO2014201914A1
WO2014201914A1 PCT/CN2014/076699 CN2014076699W WO2014201914A1 WO 2014201914 A1 WO2014201914 A1 WO 2014201914A1 CN 2014076699 W CN2014076699 W CN 2014076699W WO 2014201914 A1 WO2014201914 A1 WO 2014201914A1
Authority
WO
WIPO (PCT)
Prior art keywords
praziquantel
surfactant
distilled water
nanoemulsion
oral liquid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/CN2014/076699
Other languages
English (en)
Chinese (zh)
Inventor
张晓燕
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of WO2014201914A1 publication Critical patent/WO2014201914A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/10—Anthelmintics

Definitions

  • the present invention belongs to the field of medicine, and relates to a novel dosage form of praziquantel-benzimidazole, and particularly relates to a transparent and stable praziquantel-nonamazole imidazole nanoemulsion oral liquid.
  • Parasitic diseases are a common zoonotic disease.
  • the development of new drugs for the treatment of animal parasitic diseases plays an important role in ensuring the overall health of human beings and promoting the development of animal husbandry.
  • Praziquantel is a broad-spectrum antiparasitic drug. It is widely resistant to worms, and also has a killing effect on Schistosoma japonicum, Schistosoma japonicum, Schistosoma mansoni, Paragonimiasis, Clonorchis sinensis, Hydatid, cysticercosis, schistosomiasis, ginger worm, and aphids. Since its inception, it has been widely used in the treatment and prevention of schistosomiasis due to its advantages of high efficiency, low toxicity and low cost. Praziquantel is now the drug of choice for the treatment of a variety of endoparasites.
  • Indomethacazole is a broad-spectrum anthelmintic drug. It has been shown to directly inhibit the ingestion of glucose by nematodes in vivo or in vitro, resulting in the depletion of glycogen, which makes it unable to survive. It has significant killing of larvae and inhibition of egg development. Function, but does not affect the blood sugar level in the human body. It can be used to control intestinal parasitic diseases such as hookworms, mites, mites, whipworms, and faecalis. However, it has the disadvantage of being insoluble in water and poor in bioavailability.
  • praziquantel and indomethacazole are prepared into nanomedicines using nanoemulsion as a carrier.
  • the prepared new drug can overcome the disadvantages of low solubility and low bioavailability of praziquantel and indomethacin, and has the advantages of easy absorption and greatly improved therapeutic effect.
  • praziquantel and indomethacin nanotechnology a broad-spectrum, high-efficiency and safe new drug was developed to achieve The purpose of treating parasitic diseases in animals has important significance for the production and promotion of animal parasitic diseases.
  • the object of the present invention is to provide a praziquantel-benzimidazole nanoemulsion oral liquid which is uniform in content, stable in quality, high in bioavailability, and simple in preparation. .
  • the technical solution for achieving the above object of the invention is a praziquantel-benzimidazole nanoemulsion oral liquid, including mass percentage: surfactant 15.00% ⁇ 30.00%, cosurfactant 15.23% - 24.00%, ethyl acetate 5.00% ⁇ 15.00%, N,N_dimercaptoacetamide 5.00% - 18.00%, pyridoxal 0.10% ⁇ 1.50%, acetonide p sitting 0.10% ⁇ 1.50% and distilled water 5.80% ⁇ 53.40% composition, total The composition is 100%.
  • the praziquantel-benzimidazole nanoemulsion oral liquid of the present invention preferably comprises a mass percentage of surfactant: 20.00% ⁇ 30.00%, cosurfactant 18.00% ⁇ 24.00%, ethyl acetate 6.00% ⁇ 15.00% , N, N-dimercaptoacetamide 6.50% ⁇ 18.00%, praziquantel 0.50% - 1.50%, indomethacin 0.30% ⁇ 1.50% and distilled water 5.80% ⁇ 48.00%, the total composition is 100%.
  • the praziquantel-benzimidazole nanoemulsion oral liquid of the present invention preferably comprises a mass percentage of: surfactant phase 20.38%, cosurfactant 20.00%, ethyl acetate 10.00%, N, N - Didecyl acetamide 10.00%, praziquantel 1.00%, indomethacin 1.00% and distilled water 37.62%, the total component is 100%.
  • the co-surfactant is ethanol.
  • a non-toxic and biocompatible nonionic surfactant is selected for the selection of the surfactant.
  • Nonionic surfactants are relatively stable in solution, are not susceptible to strong electrolytes, inorganic salts, and are not susceptible to acid and alkali, and have good compatibility with other surfactants, and have less hemolysis.
  • the preparation of 0/W type nanoemulsion requires the HLB value of the surfactant to be between 8 and 18, considering the simplicity of the preparation process, that is, the easy formation of the nanoemulsion and the stability of the prepared nanoemulsion.
  • the present invention selects a liquid nonionic surfactant having an HLB of between 10 and 15.
  • the surfactant is Tween-80.
  • the interfacial tension can be further reduced, the flexibility and rigidity of the film can be increased, inserted into the interface film, and the formation of a film having a small radius of curvature can be promoted, and the nanometer can be expanded.
  • the present invention selects a stimulating small co-surfactant, mainly ethanol.
  • the present invention is based on the principle that the emulsion formed when the HLB of the surfactant required for emulsifying the oil phase is close to the surfactant, and the selected grease is ethyl acetate, N, N-didecyl Amide. This oil is liquid at normal temperature.
  • the preparation method of the praziquantel-indo-benzimidazole nanoemulsion oral liquid of the present invention specifically comprises the following steps:
  • the appearance of the invention is a light yellow transparent liquid with good stability.
  • the stability over time refers to the degree to which the appearance of the nanoemulsion oral solution changes with time when stored under natural changing conditions at room temperature.
  • the praziquantel-benzimidazole nanoemulsion oral solution is long-lasting and transparent, and no turbidity or precipitation is found, indicating that the stability over time is good. This is an important indicator for evaluating nanoemulsion oral liquid.
  • the praziquantel-benzimidazole nanoemulsion oral solution was placed in a test tube, sealed, and centrifuged at 12000 r/min for 20 minutes without delamination, and was clear and transparent.
  • the praziquantel-benzimidazole nanoemulsion oral liquid of the present invention has the following advantages as compared with the prior art:
  • the anti-corrosion performance is improved because the dispersed phase liquid is relatively small, which can prevent the invasion of bacteria and increase the solubility of some active ingredients; 4) It has a good solubilizing effect and can effectively improve the solubility of poorly soluble drugs;
  • Tween-80 30 Accurately weigh Tween-80 30. 00g, ethanol 15.23g, ethyl acetate 15. 00g, N,N-dimercaptoacetamide 15.15 into a beaker, at 20 °C, hand-mixed at room temperature The mixture was thoroughly mixed. 1.5 g of praziquantel and 1.5 g of the benzimidazole were directly added, and the mixture was stirred well. Then, distilled water was slowly added thereto, and the mixture was manually stirred while adding distilled water. The viscosity of the system was small at the beginning, with the amount of distilled water. The increase, the system will become sticky, continue to add and continue to stir, when the system suddenly becomes thin, then the stable yellowish transparent praziquantel-benzimidazole nanoemulsion oral liquid is produced, the total weight is 100. 0g.
  • Tween-80 18.00g, ethanol 24.00g, ethyl acetate 5.00g, N,N-dimercaptoacetamide 6.50, put into a beaker, mix thoroughly at room temperature under 20 °C 0.4 g of praziquantel and 0.4 g of imidazole were added directly, stirred until all dissolved, and then distilled water was slowly added thereto, and stirred while adding distilled water, initially, the viscosity of the system was small, with When the amount of distilled water increases, the system becomes viscous, continues to drip and stir constantly. When the system suddenly becomes thin, the stable yellowish transparent praziquantel-noniazole imidazole nanoemulsion oral solution is produced. The weight is 100.0g.
  • Tween-80 30.00g, ethanol 20.00g, ethyl acetate 15.00g, N,N-didecylacetamide 8.33, put into a beaker, mix thoroughly at room temperature under 20 °C 0.5 g of praziquantel and 1.5 g of benzimidazole were added directly, stirred until all dissolved, and then distilled water was slowly added thereto, and stirred while adding distilled water, initially, the viscosity of the system was small, and the amount of distilled water increased. It will become viscous, continue to drip and continue to stir. When the system suddenly becomes thin, the stable yellowish transparent praziquantel-noniazole imidazole nanoemulsion oral solution is produced, and the total weight is 100.0g.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Molecular Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Biophysics (AREA)
  • Dispersion Chemistry (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne un médicament liquide oral d'une nanoémulsion de praziquantel-mébendazole et son procédé de préparation, le diamètre des gouttelettes correspondantes étant situé entre 10 nm et 100 nm et la nanoémulsion étant préparée à partir de matières premières selon le pourcentage en poids suivant : 15,00 % – 30,00 % d'un agent tensioactif, 15,23 % – 24,00 % d'un coagent tensioactif, 5,00 % – 15,00 % d'acétate d'éthyle, 5,00 % – 18,00 % de N,N-diméthylacétamide, 0,10 % – 1,50 % de praziquantel, 0,10 % – 1,50 % de mébensazole et 5,80 % – 53,40 % d'eau distillée, la somme des constituants valant 100 %.
PCT/CN2014/076699 2013-06-20 2014-05-03 Médicament liquide oral d'une nanoémulsion de praziquantel-mébendazole et son procédé de préparation Ceased WO2014201914A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201310246303.7 2013-06-20
CN201310246303.7A CN103316005B (zh) 2013-06-20 2013-06-20 一种吡喹酮-甲苯咪唑纳米乳口服液以及制备方法

Publications (1)

Publication Number Publication Date
WO2014201914A1 true WO2014201914A1 (fr) 2014-12-24

Family

ID=49185239

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2014/076699 Ceased WO2014201914A1 (fr) 2013-06-20 2014-05-03 Médicament liquide oral d'une nanoémulsion de praziquantel-mébendazole et son procédé de préparation

Country Status (2)

Country Link
CN (1) CN103316005B (fr)
WO (1) WO2014201914A1 (fr)

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2310009B1 (fr) * 2008-07-24 2017-12-20 University Of Houston Formulations parentérales et orales de benzimidazoles

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
GAO, XUEJUN ET AL.: "Research advance of mechanism of action of benzimidazolcarbamate drugs on helminthes", JOURNAL OF NORTHEAST AGRICULTURAL UNIVERSITY, vol. 35, no. 4, 31 August 2004 (2004-08-31), pages 492 - 495 *
ZHANG, XIAOYAN.: "Preparation of Compound Praziquantel Nanoemulsion", CHINA MASTER DISSERTATIONS FULL-TEXT DATABASE ENGINEERING TECHNOLOGY I, 15 March 2013 (2013-03-15), pages B020 - 97 *

Also Published As

Publication number Publication date
CN103316005B (zh) 2015-03-04
CN103316005A (zh) 2013-09-25

Similar Documents

Publication Publication Date Title
CN102079794B (zh) 用于医药装置和药物制剂中的含有木葡聚糖的粘膜粘附性制剂
RU2668882C2 (ru) Жидкая фармацевтическая композиция
Li et al. Formation and stability of W/O microemulsion formed by food grade ingredients and its oral delivery of insulin in mice
EP3030225B1 (fr) Compositions à libération continue à base d'acide hyaluronique, et leurs applications thérapeutiques
CN102302449A (zh) 一种水包油型肉桂醛纳米乳药物
CN102973505A (zh) 一种阿苯达唑纳米乳及其制备方法
CN100448430C (zh) 一种水包油型石菖蒲油纳米乳口服液及其制备方法
CN102552134B (zh) 含有维生素k1的脂肪乳剂
RU2012104639A (ru) Способ и фармацевтические композиции для лечения постпрандиальной гипергликемии диабета ii типа введением через слизистую ротовой полости
EP3669879B1 (fr) Composition pharmaceutique sous la forme d'une suspension orale comprenant une fraction flavonoïque comprenant de la diosmine et de la gomme xanthane
JPS63166832A (ja) 鼻用溶液
EP2162491A1 (fr) Compositions liquides ou pateuses destinees a l'apport en elements essentiels a la synthese et a la constitution des proteoglycanes, notamment pour le traitement de la degradation du cartilage
KR20230098144A (ko) 당뇨병을 치료하기 위한 이온성 액체 제형
CN113558237A (zh) 一种负载辣椒碱双相网络油包水高内相乳液的制备方法
CN102552152B (zh) 兽用盐酸多西环素高分子复合物微粒及其制备方法
JP2017511371A (ja) エクセナチド含有組成物及びその製造方法
CN104013582B (zh) 一种阿司匹林peg-plga微球的制备方法
CN103301204B (zh) 一种复方连翘-柴胡油纳米乳制剂以及制备方法
CN103316005B (zh) 一种吡喹酮-甲苯咪唑纳米乳口服液以及制备方法
JP5969787B2 (ja) 生体内のメイラード反応抑制剤またはＡＧＥｓ生成抑制剤
JP7039197B2 (ja) Ｓ／ｏ型サスペンション及びその製造方法
CN101536983B (zh) 兽用盐酸氧阿苯达唑预混剂
WO2017198224A1 (fr) Composition pharmaceutique de rémimazolam
CN111658606A (zh) 一种泊那珠利溶液制剂及用途
CN113116818A (zh) 包埋体及其在制备药物或食品中的用途

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 14812941

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 14812941

Country of ref document: EP

Kind code of ref document: A1