CN1676120A - 一种难溶性药物凝胶制剂制备方法 - Google Patents
一种难溶性药物凝胶制剂制备方法 Download PDFInfo
- Publication number
- CN1676120A CN1676120A CN 200410030747 CN200410030747A CN1676120A CN 1676120 A CN1676120 A CN 1676120A CN 200410030747 CN200410030747 CN 200410030747 CN 200410030747 A CN200410030747 A CN 200410030747A CN 1676120 A CN1676120 A CN 1676120A
- Authority
- CN
- China
- Prior art keywords
- preparation
- weight
- gel
- consumption
- insoluble drug
- 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
- 239000000203 mixture Substances 0.000 title claims description 10
- 238000000034 method Methods 0.000 title claims description 5
- 238000009472 formulation Methods 0.000 title description 3
- 238000002360 preparation method Methods 0.000 claims abstract description 35
- 239000003814 drug Substances 0.000 claims abstract description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000000126 substance Substances 0.000 claims abstract description 13
- 239000013543 active substance Substances 0.000 claims abstract description 7
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims description 33
- 229940079593 drug Drugs 0.000 claims description 27
- 239000000499 gel Substances 0.000 claims description 24
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 15
- 229960003276 erythromycin Drugs 0.000 claims description 14
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 12
- 239000000758 substrate Substances 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- -1 polyoxyethylene Polymers 0.000 claims description 8
- XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 claims description 7
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 claims description 7
- 229960004125 ketoconazole Drugs 0.000 claims description 7
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 6
- 229940097572 chloromycetin Drugs 0.000 claims description 6
- 239000006184 cosolvent Substances 0.000 claims description 5
- 229960004063 propylene glycol Drugs 0.000 claims description 5
- 239000004094 surface-active agent Substances 0.000 claims description 5
- OCAPBUJLXMYKEJ-UHFFFAOYSA-N 1-[biphenyl-4-yl(phenyl)methyl]imidazole Chemical compound C1=NC=CN1C(C=1C=CC(=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 OCAPBUJLXMYKEJ-UHFFFAOYSA-N 0.000 claims description 4
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 4
- 229920002125 Sokalan® Polymers 0.000 claims description 4
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 claims description 4
- 229960004099 azithromycin Drugs 0.000 claims description 4
- 229960002206 bifonazole Drugs 0.000 claims description 4
- 229960001631 carbomer Drugs 0.000 claims description 4
- 235000011187 glycerol Nutrition 0.000 claims description 4
- 229920001983 poloxamer Polymers 0.000 claims description 4
- 239000000661 sodium alginate Substances 0.000 claims description 4
- 235000010413 sodium alginate Nutrition 0.000 claims description 4
- 229940005550 sodium alginate Drugs 0.000 claims description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 3
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 3
- 230000000845 anti-microbial effect Effects 0.000 claims description 3
- 239000004599 antimicrobial Substances 0.000 claims description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 3
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 3
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 3
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 2
- 108010010803 Gelatin Proteins 0.000 claims description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 2
- 239000000194 fatty acid Substances 0.000 claims description 2
- 229930195729 fatty acid Natural products 0.000 claims description 2
- 239000008273 gelatin Substances 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- 235000011852 gelatine desserts Nutrition 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 235000010981 methylcellulose Nutrition 0.000 claims description 2
- 229960000502 poloxamer Drugs 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 2
- 229920003091 Methocel™ Polymers 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 239000000725 suspension Substances 0.000 description 8
- WLAMNBDJUVNPJU-UHFFFAOYSA-N 2-methylbutyric acid Chemical compound CCC(C)C(O)=O WLAMNBDJUVNPJU-UHFFFAOYSA-N 0.000 description 7
- 229940082484 carbomer-934 Drugs 0.000 description 7
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 6
- 229940073647 emgel Drugs 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 4
- 229940044519 poloxamer 188 Drugs 0.000 description 4
- 229920001993 poloxamer 188 Polymers 0.000 description 4
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 3
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 3
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 description 3
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 3
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 3
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 3
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 3
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 3
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 3
- 229960002216 methylparaben Drugs 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000001194 polyoxyethylene (40) stearate Substances 0.000 description 2
- 235000011185 polyoxyethylene (40) stearate Nutrition 0.000 description 2
- JBJWASZNUJCEKT-UHFFFAOYSA-M sodium;hydroxide;hydrate Chemical compound O.[OH-].[Na+] JBJWASZNUJCEKT-UHFFFAOYSA-M 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- RCEAADKTGXTDOA-UHFFFAOYSA-N OS(O)(=O)=O.CCCCCCCCCCCC[Na] Chemical compound OS(O)(=O)=O.CCCCCCCCCCCC[Na] RCEAADKTGXTDOA-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- 210000000416 exudates and transudate Anatomy 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 238000003475 lamination Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical class CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960004418 trolamine Drugs 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明涉及一种难溶性药物凝胶制剂制备方法。该凝胶剂的生理活性物质为难溶性药物，其制备方法特征为在凝胶的制备过程中加入亲水性物质，增大主药在水中的溶解度，使主药在凝胶中分散均匀，凝胶稳定性良好。
Description
技术领域
本发明涉及以难溶性药物为生理活性物质的凝胶制备方法。
技术背景
难溶性药物红霉素(Erythromycin)、氯霉素(Chloramphenicol)、阿奇霉素(Azithromycin)、酮康唑(Ketoconazole)、联苯苄唑(Bifonazole)等抗菌类难溶性药物制成外用制剂，不仅避免了口服给药存在的胃肠道首过效应，而且使副作用大大减少。但是，由于乳膏剂的皮肤涂附舒适性差，而凝胶剂具有更易于涂展和洗除、无油腻感、同时能够吸收组织渗出液、不妨碍皮肤正常功能等优点，所以将难溶性药物制备成凝胶制剂具有更广泛的发展空间。难溶性药物在基质中溶解量低，不易分散均匀。因此，制备难溶性药物凝胶剂应考虑改善难溶性药物在基质中的溶解和均匀分散性。
本发明是基于改善上述技术中存在的问题而提出的，其目的是提供一种难溶性药物凝胶剂的制备方法。
本发明者为了达到上述目的，进行了反复深入的研究和试验，结果发现在凝胶制备过程中加入亲水性物质，可增大难溶性药物在基质中的溶解，使得生理活性物质在凝胶中分散均匀，凝胶稳定性良好。
实施发明的技术措施
本发明涉及一种难溶性药物凝胶制备方法。由于难溶性药物在凝胶基质中溶解量低，不易分散，因此，在该凝胶制剂制备过程中加入了有助于难溶性药物溶解的亲水性物质，从而增大生理活性物质在凝胶中的溶解，制备分散均匀、稳定性良好的凝胶。
本发明的生理活性成分为难溶性药物，可以为红霉素、氯霉素、阿奇霉素、酮康唑、联苯苄唑，优选抗菌类难溶性药物。难溶性药物的用量为0.5％-10％(重量)，优选1％-5％(重量)。
本发明中凝胶的基质包括卡波姆、羧甲基纤维素钠、甲基纤维素、羟丙基纤维素、海藻酸钠、明胶或它们的组合物，可采用改变上述物质浓度或调节pH等方法使上述基质构成的凝胶具有适宜的粘度。基质的用量为0.5％-10％(重量)，优选卡波姆，用量为0.5％-2％(重量)。
本发明中为了增大难溶性药物在水中的溶解度，在制剂制备过程中加入了亲水性物质助溶剂包括丙二醇、异丙醇、甘油、乙醇及它们的组合物。助溶剂的用量为1％-30％(重量)，优选5％-20％(重量)。
本发明中为了改善难溶性药物在基质中的分散性，在凝胶组合物中加入了亲水性物质表面活性剂，包括泊洛沙姆、十二烷基硫酸钠、聚氧乙烯脂肪酸酯及其相互混合物。在生理活性物质中加入基质前，可将其溶于亲水性物质的水溶液中进行分散乳化，再加入到凝胶基质中搅拌，分散。表面活性剂的用量为0.1％-3％(重量)，优选0.3-1.5％(重量)。
本发明在制剂组合物中除加亲水性物质包括助溶剂和表面活性剂等物质外，还可以加入其他辅料，如络合剂乙二胺四乙酸二钠；pH调节剂氢氧化钠、三乙醇胺；防腐剂对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯等。
用上述制剂制备方法制备的难溶性药物凝胶具有以下优点：凝胶细腻，稠度适宜，易于涂展，生理活性物质分布均匀，稳定性好，以及美观，容易洗除。
实施例
下面结合实施例对本发明作进一步详细说明。
结合实施例具体说明本发明，但并不局限于下述的实施例。其中“％”是指“重量％”。对比实施例
| 红霉素卡波姆934氢氧化钠水 | 2％1％0.38％96.62％ |
制备工艺：
卡波姆934搅拌加入红霉素和水的混悬液。在快速搅拌的情况下，加入氢氧化钠溶液，混匀，得红霉素凝胶。
实施例1
| 红霉素卡波姆934泊洛沙姆188丙二醇乙二胺四乙酸二钠氢氧化钠水 | 2％0.9％2％10％0.1％0.38％84.62％ |
制备工艺：
卡波姆934搅拌加入乙二胺四乙酸二钠的水溶液中，待完全溶解后，加入红霉素、泊洛沙姆188、丙二醇和水的混悬液。在快速搅拌的情况下，加入氢氧化钠溶液、混匀，得红霉素凝胶。
实施例2
| 红霉素卡波姆934十二烷基硫酸钠异丙醇乙二胺四乙酸二钠氢氧化钠水 | 2.5％1％1％5％0.1％0.4％90％ |
制备工艺：
卡波姆934搅拌加入乙二胺四乙酸二钠的水溶液中，待完全溶解后，加入红霉素、十二烷基硫酸钠、异丙醇和水的混悬液。在快速搅拌的情况下，加入氢氧化钠溶液、混匀，得红霉素凝胶。
实施例3
| 红霉素海藻酸钠泊洛沙姆188丙二醇对羟基苯甲酸甲酯水 | 3％3％1％12％0.1％80.9％ |
制备工艺：
海藻酸钠搅拌加入水中，待完全溶解后，加入泊洛沙姆188和水的混悬液，在快速搅拌的情况下，加入红霉素、对羟基苯甲酸甲酯和丙二醇的混悬液，混匀，得红霉素凝胶。
实施例4
| 红霉素羧甲基纤维素钠聚氧乙烯(40)硬脂酸酯甘油乙二胺四乙酸二钠对羟基苯甲酸乙酯水 | 8％4％1.1％12％0.1％0.2％72.2％ |
制备工艺：
卡波姆934搅拌加入乙二胺四乙酸二钠的水溶液中，待完全溶解后，在快速搅拌的情况下，加入红霉素、聚氧乙烯(40)硬脂酸酯、甘油、对羟基苯甲酸乙酯和水的混悬液，混匀，得红霉素凝胶。
实施例5
| 氯霉素卡波姆940三乙醇胺甘油对羟基苯甲酸乙酯水 | 1％0.6％1％5％0.1％92.3％ |
制备方法：
卡波姆940搅拌加入水中，待完全溶解后，在快速搅拌的情况下，加入氯霉素、甘油、三乙醇胺、对羟基苯甲酸乙酯和水的混悬液，混匀，得氯霉素凝胶。
实施例6
| 酮康唑卡波姆940泊洛沙姆188乙醇甘油氨试液水 | 5％2％2％10％20％10％51％ |
制备工艺：
卡波姆940搅拌加入水中，待完全溶解后，加入氨试液。在快速搅拌的情况下，加入酮康唑、乙醇、泊洛沙姆188、甘油和水的混悬液，混匀，得酮康唑凝胶。
如上述对比实施例制备的凝胶，难溶性药物在基质中溶解度小，分散不均匀，观察粒径部分大于180um，不符合药典附录要求；且稳定性不好，放置后有分层现象。按照本发明，实施例制备的凝胶，含有亲水性物质助溶剂，难溶性药物在基质中溶解度较大，有良好的释放、穿透性，能保证药物疗效的发挥；药物经亲水性物质表面活性剂乳化，难溶性药物在基质中分散均匀，稳定性好，贮存时无酸败、变质、分层等现象。
Claims (5)
1.一种含有难溶性药物凝胶制剂的制备方法，其特征为该方法包括在凝胶的制备过程中加入亲水性物质，增大主药在水中的溶解度。
2.权利要求1所述的制备方法，所加的亲水性物质为可作为药用辅料的助溶剂，包括丙二醇、异丙醇、甘油、乙醇及其相互混合物，其用量为1％-30％(重量)，优选5％-20％(重量)。
3.如权利要求1所述的制备方法，所加的亲水性物质为可作为外用药用辅料的表面活性剂，包括泊洛沙姆、十二烷基硫酸钠、聚氧乙烯脂肪酸酯及其相互混合物，其用量为0.1％-3％(重量)，优选0.3％-1.5％(重量)。
4.如权利要求1所述方法得到的制剂，其中生理活性物质为难溶性药物，可以为红霉素、氯霉素、阿奇霉素、酮康唑、联苯苄唑，优选抗菌类难溶性药物，其用量为0.5％-10％(重量)，优选1％-5％(重量)。
5.如权利要求1所述方法得到的制剂，可采用卡波姆、羧甲基纤维素钠、甲基纤维素、羟甲基纤维素、海藻酸钠、明胶或它们的组合物为基质，其用量为0.5％-10％(重量)，优选卡波姆，用量为0.5％-2％(重量)。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100307478A CN100404073C (zh) | 2004-04-02 | 2004-04-02 | 一种难溶性药物凝胶制剂制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100307478A CN100404073C (zh) | 2004-04-02 | 2004-04-02 | 一种难溶性药物凝胶制剂制备方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1676120A true CN1676120A (zh) | 2005-10-05 |
| CN100404073C CN100404073C (zh) | 2008-07-23 |
Family
ID=35048971
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2004100307478A Expired - Lifetime CN100404073C (zh) | 2004-04-02 | 2004-04-02 | 一种难溶性药物凝胶制剂制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100404073C (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102525885A (zh) * | 2011-11-21 | 2012-07-04 | 程雪翔 | 一种酮康唑凝胶及其制备方法 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1194664C (zh) * | 2002-08-19 | 2005-03-30 | 上海兴康医药研究开发有限公司 | 可滴眼用在体凝胶制剂及其制备方法 |
-
2004
- 2004-04-02 CN CNB2004100307478A patent/CN100404073C/zh not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102525885A (zh) * | 2011-11-21 | 2012-07-04 | 程雪翔 | 一种酮康唑凝胶及其制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100404073C (zh) | 2008-07-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69919713T2 (de) | Pharmazeutische zubereitung mit verzögerter wirkstofffreisetzung von phenytoin natrium | |
| CA2749941C (en) | Ibuprofen for topical administration | |
| US20050208122A1 (en) | Biodegradable biocompatible implant and method of manufacturing same | |
| WO2009066146A2 (en) | Stable solutions of sparingly soluble actives | |
| AU2004274000B2 (en) | Pharmaceutical delivery system | |
| CN100341577C (zh) | 经皮吸收制剂 | |
| WO2012017077A1 (en) | Combination of compounds for treating or preventing skin diseases | |
| CN111544381A (zh) | 一种包含壬二酸的皮肤局部给药组合物 | |
| CN1989956B (zh) | 一种阿达帕林凝胶组合物及其制备方法 | |
| CN1857239A (zh) | 辅酶q10注射乳剂及制备方法 | |
| CN101422431B (zh) | 胰岛素经鼻给药制剂 | |
| CN101209251A (zh) | 含有紫杉醇或多烯紫杉醇的弹性纳米囊泡制剂及其制备方法 | |
| CN1868455A (zh) | 奥沙利铂磷脂复合物静脉给药的纳米混悬注射剂 | |
| CN1676120A (zh) | 一种难溶性药物凝胶制剂制备方法 | |
| CN111481559B (zh) | 一种高浓度的氟维司群组合物及其制备方法 | |
| US9161981B2 (en) | Non-aqueous oily injectable formulation exhibiting preservative efficacy | |
| CN102058545A (zh) | 一种注射用美罗培南冻干制剂及其制备方法 | |
| CN106539759B (zh) | 一种高稳定性的非囊泡型纳米颗粒及其在治疗痤疮丙酸杆菌感染中的应用 | |
| CN1739519A (zh) | 伊曲康唑注射乳剂及其制备方法 | |
| CN1500492A (zh) | 含抗寄生虫药物的兽用混悬注射剂 | |
| CN1256092C (zh) | 注射用甲基红霉素制剂 | |
| CN111904932A (zh) | 一种含有糖皮质激素的胶束制剂及其制备方法 | |
| CN113713000B (zh) | 用于治疗疮痈、烧烫伤和痤疮的主药成分组合物、缓控释药物制剂及其制备方法和应用 | |
| Vovesná et al. | Innovative cerosomes as carriers for an enhanced dermatoses’ therapy | |
| US20200179286A1 (en) | Carrier structure and drug carrier, and preparing methods thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| PP01 | Preservation of patent right |
Effective date of registration: 20120611 Granted publication date: 20080723 |
|
| PD01 | Discharge of preservation of patent |
Date of cancellation: 20121211 Granted publication date: 20080723 |
|
| PP01 | Preservation of patent right |
Effective date of registration: 20121211 Granted publication date: 20080723 |
|
| RINS | Preservation of patent right or utility model and its discharge | ||
| PD01 | Discharge of preservation of patent |
Date of cancellation: 20130611 Granted publication date: 20080723 |
|
| RINS | Preservation of patent right or utility model and its discharge | ||
| PP01 | Preservation of patent right |
Effective date of registration: 20140530 Granted publication date: 20080723 |
|
| RINS | Preservation of patent right or utility model and its discharge | ||
| PD01 | Discharge of preservation of patent |
Date of cancellation: 20150530 Granted publication date: 20080723 |
|
| RINS | Preservation of patent right or utility model and its discharge | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20201126 Address after: No. 279 Nanhai Road, Xiuying District 570314 Hainan city of Haikou Province Patentee after: AVENTIS PHARMA (HAINAN) Co.,Ltd. Address before: 100089, Wanquan mansion, three Jin Zhuang, Haidian District, Beijing, Sijiqing Patentee before: BEIJING VENTUREPHARM TECHNOLOGY Corp. |
|
| DD01 | Delivery of document by public notice | ||
| DD01 | Delivery of document by public notice |
Addressee: Song Xuemei Document name: Notice of conformity |
|
| CX01 | Expiry of patent term |
Granted publication date: 20080723 |
|
| CX01 | Expiry of patent term |