CN108653197A - 一种羧甲基壳聚糖季铵盐温敏凝胶及其制备方法 - Google Patents
一种羧甲基壳聚糖季铵盐温敏凝胶及其制备方法 Download PDFInfo
- Publication number
- CN108653197A CN108653197A CN201810459497.1A CN201810459497A CN108653197A CN 108653197 A CN108653197 A CN 108653197A CN 201810459497 A CN201810459497 A CN 201810459497A CN 108653197 A CN108653197 A CN 108653197A
- Authority
- CN
- China
- Prior art keywords
- quaternary ammonium
- ammonium salt
- carboxymethyl chitosan
- chitosan quaternary
- sensitive gel
- 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.)
- Granted
Links
- 229920001661 Chitosan Polymers 0.000 title claims abstract description 53
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 title claims abstract description 51
- 150000003242 quaternary ammonium salts Chemical class 0.000 title claims abstract description 50
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 238000001879 gelation Methods 0.000 title abstract description 10
- 229920001983 poloxamer Polymers 0.000 claims abstract description 25
- 229920000642 polymer Polymers 0.000 claims abstract description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000004909 Moisturizer Substances 0.000 claims abstract description 8
- 230000001333 moisturizer Effects 0.000 claims abstract description 8
- 238000003756 stirring Methods 0.000 claims abstract description 3
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 10
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 230000021523 carboxylation Effects 0.000 claims description 5
- 238000006473 carboxylation reaction Methods 0.000 claims description 5
- 229920001993 poloxamer 188 Polymers 0.000 claims description 5
- 229940044519 poloxamer 188 Drugs 0.000 claims description 5
- 238000006467 substitution reaction Methods 0.000 claims description 5
- 229960000502 poloxamer Drugs 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 235000010358 acesulfame potassium Nutrition 0.000 claims 1
- 239000003921 oil Substances 0.000 claims 1
- 239000000499 gel Substances 0.000 abstract description 33
- 238000000034 method Methods 0.000 abstract description 7
- 230000036760 body temperature Effects 0.000 abstract description 4
- 230000008569 process Effects 0.000 abstract description 3
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 230000000845 anti-microbial effect Effects 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 230000000844 anti-bacterial effect Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- 241000222122 Candida albicans Species 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 4
- 230000003115 biocidal effect Effects 0.000 description 4
- 229940095731 candida albicans Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000000017 hydrogel Substances 0.000 description 4
- 238000011065 in-situ storage Methods 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 3
- FFRBMBIXVSCUFS-UHFFFAOYSA-N 2,4-dinitro-1-naphthol Chemical compound C1=CC=C2C(O)=C([N+]([O-])=O)C=C([N+]([O-])=O)C2=C1 FFRBMBIXVSCUFS-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 241000191940 Staphylococcus Species 0.000 description 2
- 241000191967 Staphylococcus aureus Species 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 239000012085 test solution Substances 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 241000228212 Aspergillus Species 0.000 description 1
- 229920002511 Poloxamer 237 Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 206010072170 Skin wound Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 229940071110 amino-cerv Drugs 0.000 description 1
- 230000001775 anti-pathogenic effect Effects 0.000 description 1
- 238000013475 authorization Methods 0.000 description 1
- 230000002457 bidirectional effect Effects 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 238000010382 chemical cross-linking Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- NWFNSTOSIVLCJA-UHFFFAOYSA-L copper;diacetate;hydrate Chemical compound O.[Cu+2].CC([O-])=O.CC([O-])=O NWFNSTOSIVLCJA-UHFFFAOYSA-L 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 239000002114 nanocomposite Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229960002901 sodium glycerophosphate Drugs 0.000 description 1
- REULQIKBNNDNDX-UHFFFAOYSA-M sodium;2,3-dihydroxypropyl hydrogen phosphate Chemical compound [Na+].OCC(O)COP(O)([O-])=O REULQIKBNNDNDX-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
- 238000012549 training Methods 0.000 description 1
Classifications
-
- 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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/722—Chitin, chitosan
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0043—Nose
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/02—Local antiseptics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J3/00—Processes of treating or compounding macromolecular substances
- C08J3/02—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques
- C08J3/03—Making solutions, dispersions, lattices or gels by other methods than by solution, emulsion or suspension polymerisation techniques in aqueous media
- C08J3/075—Macromolecular gels
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2305/00—Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
- C08J2305/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08J—WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H
- C08J2371/00—Characterised by the use of polyethers obtained by reactions forming an ether link in the main chain; Derivatives of such polymers
- C08J2371/02—Polyalkylene oxides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Communicable Diseases (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Dispersion Chemistry (AREA)
- Gynecology & Obstetrics (AREA)
- Urology & Nephrology (AREA)
- Reproductive Health (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Ophthalmology & Optometry (AREA)
- Otolaryngology (AREA)
- Molecular Biology (AREA)
- Polymers & Plastics (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明公开了一种羧甲基壳聚糖季铵盐温敏凝胶，包括1％～3％羧甲基壳聚糖季铵盐、24％～35％泊洛沙姆系列聚合物、0.1％～1％保湿剂和60％～75％纯水。本发明还提供了羧甲基壳聚糖季铵盐温敏凝胶的制备方法，将1％～3％羧甲基壳聚糖季铵盐、24％～35％泊洛沙姆系列聚合物、0.1％～1％保湿剂和60％～75％纯水混合后在0～5℃下过夜，待所有成分完全溶解后，搅拌均匀，得到羧甲基壳聚糖季铵盐温敏凝胶。本发明的羧甲基壳聚糖季铵盐温敏凝胶的凝胶化温度与人体温度相同，凝胶化时间极短，抗菌性能显著；本发明的羧甲基壳聚糖季铵盐温敏凝胶制备方法操作方便，工艺简单，制备时间短，所需设备及原材料廉价，生产成本低，适合大规模生产，推广应用前景良好。
Description
技术领域
本发明属于医药工程的药物制剂领域，具体涉及一种羧甲基壳聚糖季铵盐温敏凝胶及其制备方法。
背景技术
温敏凝胶是指以溶液状态给药后，利用高分子材料对外界温度的响应发生相转变，由液态转化为非化学交联半固体凝胶的制剂。温敏凝胶可实现注射植入和药物缓释，在药学领域中发挥着重要的作用，成为近年来的研究热点。
授权公告号CN 103834045 B的中国发明专利“一种双向可逆温敏凝胶及其制备方法”，公开了一种采用壳聚糖、壳聚糖季铵盐以及甘油磷酸钠在室温下通过物理交联制备而成的温敏凝胶体系。该体系在10～25℃时具有较好的流动性，在43～45℃下放置5～6min形成凝胶，亦可在0℃下放置10～12min形成凝胶。但是，人体温度普遍在36～38℃，而该温敏凝胶体系的凝胶化温度在40℃以上或0℃，显然无法将其应用于皮肤创面或者妇科。
申请公布号CN 10488824 A的中国发明专利申请“一种两亲性多糖衍生物/泊洛沙姆温敏型原位水凝胶及其制备方法”公开了一种由两亲性多糖衍生物和泊洛沙姆系列聚合物以及疏水性药物发生相互作用形成稳定的原位水凝胶，其凝胶化温度为34～37℃，凝胶化时间为1～3min。与CN 103834045 B相比，该体系的凝胶化温度更接近于人体温度，凝胶化时间大幅缩小。但是，该凝胶体系的凝胶化时间长达1min以上，在凝胶化之前，该凝胶体系仍然具有很大的流动性，使得该凝胶体系不能及时、准确地应用在指定部位。
羧甲基壳聚糖季铵盐具有良好的水溶性、保湿性、抑菌性和絮凝性，在医药、护肤产品、食品和环境保护等方面的应用日趋广泛。然而，羧甲基壳聚糖季铵盐在温敏凝胶中的应用也存在一些问题。CN 10488824 A虽然公开了两亲性羧甲基壳聚糖衍生物/泊洛沙姆温敏型原位水凝胶，但是两亲性羧甲基壳聚糖衍生物在该凝胶体系中仅仅是用于改善泊洛沙姆温敏型原位水凝胶的性能，如提高凝胶化温度、水胶凝稳定性以及缓释药物的性能，并且该凝胶体系的制备方法非常复杂，制备时间过于漫长，不利于大批量生产。
发明内容
本发明的目的在于提供一种抗菌性能优良的羧甲基壳聚糖季铵盐温敏凝胶及其制备方法，该温敏凝胶在室温下呈溶液状态，在高温(≥35℃)状态下能够进行快速凝胶化。
本发明的羧甲基壳聚糖季铵盐温敏凝胶包括1％～3％羧甲基壳聚糖季铵盐、24％～35％泊洛沙姆系列聚合物、0.1％～1％保湿剂和60％～75％纯水。
所述羧甲基壳聚糖季铵盐的制备方法可参考申请号200910213899.4的中国发明专利“羧甲基壳聚糖季铵盐/累托石纳米复合材料及其制备方法”。在本发明中，羧甲基壳聚糖季铵盐的平均分子量优选为10～100KD，羧化度≥85％，取代度≥75％。
所述泊洛沙姆系列聚合物为泊洛沙姆407与任一种其它型号泊洛沙姆的混合物，优选为泊洛沙姆338、泊洛沙姆188、泊洛沙姆237或泊洛沙姆108，更优选为泊洛沙姆188。
本发明除了采用所述泊洛沙姆系列聚合物，还可复配适量的卡波姆、聚乙烯醇等。
所述保湿剂为甘油、丙二醇或聚乙二醇中的一种或几种。
所述羧甲基壳聚糖季铵盐温敏凝胶在20℃时的粘度为2000mPa·S-6000mPa·S，pH值为6-8。
本发明的羧甲基壳聚糖季铵盐温敏凝胶的制备方法如下：将羧甲基壳聚糖季铵盐1％～3％、泊洛沙姆系列聚合物24％～35％、保湿利0.1％～1％和纯水60％～75％混合后在0～5℃下过夜，待所有成分完全溶解后，搅拌均匀，得到羧甲基壳聚糖季铵盐温敏凝胶。优选的，所述羧甲基壳聚糖季铵盐的平均分子量为10～100KD，羧化度≥85％，取代度≥75％。优选的，所述泊洛沙姆系列聚合物为泊洛沙姆407与任一种其它型号泊洛沙姆的混合物。优选的，所述羧甲基壳聚糖季铵盐温敏凝胶在20℃时的粘度为2000mPa·S-6000mPa·S，pH值为6-8。
本发明采用两种型号的泊洛沙姆为凝胶基质，以羧甲基壳聚糖季铵盐为抑菌成分得到温敏凝胶体系，该体系的凝胶化温度为35℃～37℃，凝胶化时间为1min以内，对金黄色葡萄球菌、大肠埃希氏菌、铜绿假单胞菌、白色念珠菌、黑曲霉菌具有显著的抗菌效果，抗菌率达到99％以上。
本发明的制备方法操作方便，工艺简单，制备时间短，所需设备及原材料廉价，生产成本低，适合大规模生产，推广应用前景良好。
具体实施方式
以下结合具体实施例来进一步说明本发明，但实施例并不对本发明做任何形式的限定。
本发明的羧甲基壳聚糖季铵盐温敏凝胶的制备方法如下：将羧甲基壳聚糖季铵盐、泊洛沙姆系列聚合物、保湿剂和纯水混合后于低温下(0～5℃)过夜，待所有成分完全溶解后，搅拌均匀，得到羧甲基壳聚糖季铵盐温敏凝胶。表1给出了根据上述方法制备的组分含量不同的羧甲基壳聚糖季铵盐温敏凝胶。
其中，羧甲基壳聚糖季铵盐的制备方法参考申请号200910213899.4的中国发明专利，该羧甲基壳聚糖季铵盐的平均分子量为10～100KD，羧化度≥85％，取代度≥75％。
表2给出了实施例1-5的凝胶化时间、凝胶化温度以及抗菌率。根据2015版《中国药典》第三部中的通则1121抑菌效力检验法来检测抗菌率，具体方法如下：用接种环分别取适量对应菌种，加入10ml 0.9％无菌氯化钠溶液于干燥灭菌的试管中，混匀。将供试品溶液每10ml一支分装于无菌试管，取各菌液0.1ml加入供试品管，混匀，将试管放置于25℃恒温培养箱内避光保存，经过6h/24h/2d/7d，分时段取含(菌+供)试液溶液1ml，加入培养基(金黄色葡萄球菌、大肠埃希氏菌和铜绿假单胞菌的培养基为TSA，白色念珠菌和黑曲霉菌的培养基为SDA)，涂布均匀，倒置于恒温培养箱培养(金黄色葡萄球菌、大肠埃希氏菌和铜绿假单胞菌的培养温度为37℃，白色念珠菌和黑曲霉菌的培养温度为25℃)，逐日观察记录菌落数。同时做阳性对照实验和空白对照，抑菌率＝[1-(抑菌后的生长的菌落数/阳性对照实验菌落数)]×100％。
表1实施例
表2测试结果
从表2可以看出，实施例1-5的凝胶化温度均为37℃，凝胶化时间均在1min以内，最短时间为30s。实施例1-5对金黄色葡萄球菌、大肠埃希氏菌、铜绿假单胞菌、白色念珠菌、黑曲霉菌具有显著的抗菌效果，抗菌率达到99％以上。
本发明的羧甲基壳聚糖季铵盐温敏凝胶的凝胶化温度与人体温度相同，凝胶化时间短，有利于在眼部给药、鼻部给药或妇科用药中快速、准确地应用在指定部位，从而提高用药效率。采用本发明的制备方法工艺简单，操作方便，适合大批量生产。
以上所述仅是本发明的优选实施方式，应当指出，对于本领域技术人员来说，在不脱离本发明技术原理的前提下，还可以做出若干改进和润饰，这些改进和润饰也应视为本发明的保护范围。
Claims (10)
1.一种羧甲基壳聚糖季铵盐温敏凝胶，其特征在于：包括1％～3％羧甲基壳聚糖季铵盐、24％～35％泊洛沙姆系列聚合物、0.1％～1％保湿剂和60％～75％纯水。
2.根据权利要求1所述的羧甲基壳聚糖季铵盐温敏凝胶，其特征在于：所述羧甲基壳聚糖季铵盐的平均分子量为10～100KD，羧化度≥85％，取代度≥75％。
3.根据权利要求2所述的羧甲基壳聚糖季铵盐温敏凝胶，其特征在于：所述泊洛沙姆系列聚合物为泊洛沙姆407与任一种其它型号泊洛沙姆的混合物。
4.根据权利要求3所述的羧甲基壳聚糖季铵盐温敏凝胶，其特征在于：所述泊洛沙姆系列聚合物为泊洛沙姆407与泊洛沙姆188。
5.根据权利要求3所述的羧甲基壳聚糖季铵盐温敏凝胶，其特征在于：所述保湿剂为甘油、丙二醇或聚乙二醇中的一种或几种。
6.根据权利要求3所述的羧甲基壳聚糖季铵盐温敏凝胶，其特征在于：所述羧甲基壳聚糖季铵盐温敏凝胶在20℃时的粘度为2000mPa·S-6000mPa·S，pH值为6-8。
7.一种权利要求1至权利要求6任一项所述羧甲基壳聚糖季铵盐温敏凝胶的制备方法，其特征在于：将羧甲基壳聚糖季铵盐1％～3％、泊洛沙姆系列聚合物24％～35％、保湿剂0.1％～1％和纯水60％～75％混合后在0～5℃下过夜，待所有成分完全溶解后，搅拌均匀，得到羧甲基壳聚糖季铵盐温敏凝胶。
8.根据权利要求7所述的羧甲基壳聚糖季铵盐温敏凝胶的制备方法，其特征在于：所述羧甲基壳聚糖季铵盐的平均分子量为10～100KD，羧化度≥85％，取代度≥75％。
9.根据权利要求7所述的羧甲基壳聚糖季铵盐温敏凝胶的制备方法，其特征在于：所述泊洛沙姆系列聚合物为泊洛沙姆407与任一种其它型号泊洛沙姆的混合物。
10.根据权利要求7所述的羧甲基壳聚糖季铵盐温敏凝胶的制备方法，其特征在于：所述羧甲基壳聚糖季铵盐温敏凝胶在20℃时的粘度为2000mPa·S-6000mPa·S，pH值为6-8。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810459497.1A CN108653197B (zh) | 2018-05-15 | 2018-05-15 | 一种羧甲基壳聚糖季铵盐温敏凝胶及其制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810459497.1A CN108653197B (zh) | 2018-05-15 | 2018-05-15 | 一种羧甲基壳聚糖季铵盐温敏凝胶及其制备方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108653197A true CN108653197A (zh) | 2018-10-16 |
| CN108653197B CN108653197B (zh) | 2021-06-04 |
Family
ID=63779537
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810459497.1A Active CN108653197B (zh) | 2018-05-15 | 2018-05-15 | 一种羧甲基壳聚糖季铵盐温敏凝胶及其制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108653197B (zh) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114949169A (zh) * | 2022-06-29 | 2022-08-30 | 九江高科制药技术有限公司 | 大鲵多肽/羧甲基壳聚糖复合乳膏及其制备方法 |
| CN116891542A (zh) * | 2023-09-11 | 2023-10-17 | 青岛溯博生物技术有限公司 | 一种具有抑菌效果的阳离子型羧甲基壳聚糖及其应用 |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1737014A (zh) * | 2005-09-02 | 2006-02-22 | 中国科学院海洋研究所 | 一类羧甲基壳聚糖季铵盐及其制备方法 |
| CN101292952A (zh) * | 2008-06-12 | 2008-10-29 | 武汉华纳生物工程有限公司 | 甘草酸、甘草次酸或其盐或其衍生物温敏凝胶及其制法和应用 |
| CN101297973A (zh) * | 2008-05-22 | 2008-11-05 | 武汉华纳生物工程有限公司 | 高生物粘附温敏水凝胶及其制备方法和用途 |
| CN101735486A (zh) * | 2009-12-17 | 2010-06-16 | 华南理工大学 | 羧甲基壳聚糖季铵盐/累托石纳米复合材料及其制备方法 |
| CN102949754A (zh) * | 2012-05-25 | 2013-03-06 | 江西圣济药业有限公司 | 一种宫腔止血防粘连温敏凝胶及其制法 |
| CN104888224A (zh) * | 2015-03-25 | 2015-09-09 | 中山大学 | 一种两亲性多糖衍生物/泊洛沙姆温敏型原位水凝胶及其制备方法 |
| CN105147723A (zh) * | 2015-09-07 | 2015-12-16 | 山东赛克赛斯药业科技有限公司 | 一种温敏凝胶制剂、其制备方法及其在碎石术中防止结石转移中的应用 |
| CN105254811A (zh) * | 2015-11-10 | 2016-01-20 | 陕西科技大学 | 一种羧甲基壳聚糖季铵盐及其制备方法 |
| WO2016164903A1 (en) * | 2015-04-10 | 2016-10-13 | Hemcon Medical Technologies, Inc. | Bioadhesive chitosan gel for controlling bleeding and for promoting healing with scar reduction without obscuring or interfering with access to a surgical field |
| CN106167532A (zh) * | 2016-09-27 | 2016-11-30 | 江南大学 | 一种壳聚糖季铵盐的制备方法 |
-
2018
- 2018-05-15 CN CN201810459497.1A patent/CN108653197B/zh active Active
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1737014A (zh) * | 2005-09-02 | 2006-02-22 | 中国科学院海洋研究所 | 一类羧甲基壳聚糖季铵盐及其制备方法 |
| CN101297973A (zh) * | 2008-05-22 | 2008-11-05 | 武汉华纳生物工程有限公司 | 高生物粘附温敏水凝胶及其制备方法和用途 |
| CN101292952A (zh) * | 2008-06-12 | 2008-10-29 | 武汉华纳生物工程有限公司 | 甘草酸、甘草次酸或其盐或其衍生物温敏凝胶及其制法和应用 |
| CN101735486A (zh) * | 2009-12-17 | 2010-06-16 | 华南理工大学 | 羧甲基壳聚糖季铵盐/累托石纳米复合材料及其制备方法 |
| CN102949754A (zh) * | 2012-05-25 | 2013-03-06 | 江西圣济药业有限公司 | 一种宫腔止血防粘连温敏凝胶及其制法 |
| CN104888224A (zh) * | 2015-03-25 | 2015-09-09 | 中山大学 | 一种两亲性多糖衍生物/泊洛沙姆温敏型原位水凝胶及其制备方法 |
| WO2016164903A1 (en) * | 2015-04-10 | 2016-10-13 | Hemcon Medical Technologies, Inc. | Bioadhesive chitosan gel for controlling bleeding and for promoting healing with scar reduction without obscuring or interfering with access to a surgical field |
| CN105147723A (zh) * | 2015-09-07 | 2015-12-16 | 山东赛克赛斯药业科技有限公司 | 一种温敏凝胶制剂、其制备方法及其在碎石术中防止结石转移中的应用 |
| CN105254811A (zh) * | 2015-11-10 | 2016-01-20 | 陕西科技大学 | 一种羧甲基壳聚糖季铵盐及其制备方法 |
| CN106167532A (zh) * | 2016-09-27 | 2016-11-30 | 江南大学 | 一种壳聚糖季铵盐的制备方法 |
Non-Patent Citations (3)
| Title |
|---|
| 于广利: "《糖药物学》", 31 October 2012, 青岛：中国海洋大学出版社 * |
| 国家中医药管理局职业技能鉴定指导中心: "《中药固体制剂工》", 30 November 2009, 北京：中国中医药出版社 * |
| 李达恒，等: "壳聚糖-泊洛沙姆为凝胶基质的纳米银抗菌凝胶的制备与表征", 《生物医学工程学杂志》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114949169A (zh) * | 2022-06-29 | 2022-08-30 | 九江高科制药技术有限公司 | 大鲵多肽/羧甲基壳聚糖复合乳膏及其制备方法 |
| CN116891542A (zh) * | 2023-09-11 | 2023-10-17 | 青岛溯博生物技术有限公司 | 一种具有抑菌效果的阳离子型羧甲基壳聚糖及其应用 |
| CN116891542B (zh) * | 2023-09-11 | 2023-12-15 | 青岛溯博生物技术有限公司 | 一种具有抑菌效果的阳离子型羧甲基壳聚糖及其应用 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108653197B (zh) | 2021-06-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105597146B (zh) | 伤口愈合用多功能温敏凝胶复合物敷料及其制备与使用方法 | |
| CN103720713B (zh) | 一种高络合碘及其制备方法 | |
| CN1872026A (zh) | 阴道用新型药物制剂 | |
| CN107854424A (zh) | 一种阿奇霉素眼用原位凝胶及其制备方法 | |
| CN100457084C (zh) | 纳米银妇女外用抗菌凝胶的制备方法 | |
| CN103601898A (zh) | 一种温敏型壳聚糖-羧甲基纤维素凝胶及其制备方法 | |
| CN108653197A (zh) | 一种羧甲基壳聚糖季铵盐温敏凝胶及其制备方法 | |
| CN100467066C (zh) | 一种通过包含琼脂增强了眼用药物渗透性的滴眼液 | |
| CN101129385A (zh) | 含加替沙星和依碳酸氯替泼诺的眼用组合物及其制备方法 | |
| CN106146862A (zh) | 一种抗菌性的超分子杂合水凝胶及其制备方法和应用 | |
| CN104323987B (zh) | 一种乙酰甲喹注射液及其制备方法 | |
| CN110064070A (zh) | 含有机季铵盐或带硅烷端有机季铵盐抗菌水凝胶及其制备方法 | |
| Sapra et al. | Development and optimization of in situ periodontal gel containing Levofloxacin for the treatment of periodontal diseases | |
| CN103211753B (zh) | 一种凝胶剂基质 | |
| CN104606218A (zh) | 一种治疗奶牛泌乳期乳房炎的乳房注入剂及其制备方法 | |
| CN109846816A (zh) | 一种紫草素温敏性水凝胶及其制备方法和应用 | |
| LU503865B1 (en) | A mixed-drinkable nanocrystalline solid dispersion formulation of florfenicol, the preparation method and the use thereof | |
| CN106176625A (zh) | 注射用拉氧头孢钠的药物组合物 | |
| CN103040729A (zh) | 一种祛痘痕壳聚糖凝胶及其制备方法和医药应用 | |
| CN104800229B (zh) | 一种复方磺胺嘧啶混悬液及其制作方法 | |
| CN103720641A (zh) | 牛磺酸眼用在体凝胶制剂及其制备方法 | |
| CN110025502A (zh) | 一种高渗玻璃酸二甲基硅烷醇复合物溶液 | |
| CN102973601A (zh) | 一种预防奶牛乳房炎的药浴成膜剂及其制剂方法 | |
| CN105749293A (zh) | 一种含氧吨酮改性高分子药物及其制备方法以及作为制备抗菌药物上的应用 | |
| CN1459282A (zh) | 水溶性氟苯尼考的生产方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A carboxymethyl chitosan quaternary ammonium salt thermosensitive gel and its preparation method Effective date of registration: 20231222 Granted publication date: 20210604 Pledgee: Yingbin sub branch of Jiangxi Hukou Rural Commercial Bank Co.,Ltd. Pledgor: JIUJIANG HI-TECH PHARMACEUTICAL TECHNOLOGY Co.,Ltd. Registration number: Y2023980073531 |