CN114209646A - 一种聚维酮碘温敏凝胶制剂 - Google Patents
一种聚维酮碘温敏凝胶制剂 Download PDFInfo
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- CN114209646A CN114209646A CN202111643943.2A CN202111643943A CN114209646A CN 114209646 A CN114209646 A CN 114209646A CN 202111643943 A CN202111643943 A CN 202111643943A CN 114209646 A CN114209646 A CN 114209646A
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- CPKVUHPKYQGHMW-UHFFFAOYSA-N 1-ethenylpyrrolidin-2-one;molecular iodine Chemical compound II.C=CN1CCCC1=O CPKVUHPKYQGHMW-UHFFFAOYSA-N 0.000 title claims abstract description 80
- 229920000153 Povidone-iodine Polymers 0.000 title claims abstract description 80
- 229960001621 povidone-iodine Drugs 0.000 title claims abstract description 80
- 238000002360 preparation method Methods 0.000 title claims abstract description 30
- 239000011159 matrix material Substances 0.000 claims abstract description 15
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical group OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 56
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical group C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 53
- 229920001983 poloxamer Polymers 0.000 claims description 45
- 229960000502 poloxamer Drugs 0.000 claims description 44
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- 239000008213 purified water Substances 0.000 claims description 17
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- 239000007800 oxidant agent Substances 0.000 claims description 13
- 229920001992 poloxamer 407 Polymers 0.000 claims description 10
- 229920001993 poloxamer 188 Polymers 0.000 claims description 9
- 230000001590 oxidative effect Effects 0.000 claims description 8
- 230000003204 osmotic effect Effects 0.000 claims description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 238000009472 formulation Methods 0.000 claims description 6
- 229940044476 poloxamer 407 Drugs 0.000 claims description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 229940044519 poloxamer 188 Drugs 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- 229920002507 Poloxamer 124 Polymers 0.000 claims description 2
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- 229920002517 Poloxamer 338 Polymers 0.000 claims description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
- 229920001400 block copolymer Polymers 0.000 claims description 2
- 229910021538 borax Inorganic materials 0.000 claims description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 2
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- 239000000872 buffer Substances 0.000 claims description 2
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- 239000011780 sodium chloride Substances 0.000 claims description 2
- 239000001509 sodium citrate Substances 0.000 claims description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 2
- 235000010339 sodium tetraborate Nutrition 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- 229920000642 polymer Polymers 0.000 claims 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 claims 1
- 229920001661 Chitosan Polymers 0.000 claims 1
- 239000003002 pH adjusting agent Substances 0.000 claims 1
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 claims 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 claims 1
- 229940073585 tromethamine hydrochloride Drugs 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 7
- 201000010099 disease Diseases 0.000 abstract description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
- 208000015181 infectious disease Diseases 0.000 abstract description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 10
- 229910052740 iodine Inorganic materials 0.000 description 10
- 239000011630 iodine Substances 0.000 description 10
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 8
- 235000019345 sodium thiosulphate Nutrition 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 238000005303 weighing Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
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- 239000003814 drug Substances 0.000 description 5
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- 229940079593 drug Drugs 0.000 description 4
- 230000000857 drug effect Effects 0.000 description 4
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- 206010046914 Vaginal infection Diseases 0.000 description 3
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- 241000224527 Trichomonas vaginalis Species 0.000 description 1
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- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
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- 102000004169 proteins and genes Human genes 0.000 description 1
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- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 208000013464 vaginal disease Diseases 0.000 description 1
- 229940120293 vaginal suppository Drugs 0.000 description 1
- 239000006216 vaginal suppository Substances 0.000 description 1
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- 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
- A61K31/74—Synthetic polymeric materials
- A61K31/785—Polymers containing nitrogen
- A61K31/787—Polymers containing nitrogen containing heterocyclic rings having nitrogen as a ring hetero atom
- A61K31/79—Polymers of vinyl pyrrolidone
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/02—Drugs for genital or sexual disorders; Contraceptives for disorders of the vagina
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Abstract
本发明公开了一种含有聚维酮碘用于治疗感染引起的腔道疾病的温敏凝胶制剂,该制剂是由聚维酮碘、温敏凝胶基质、氧化剂、渗透压调节剂、pH调节剂及纯化水制备而成。本发明很好的解决了聚维酮碘与温敏凝胶基质间化学不相容的问题,从而成功制备出含有聚维酮碘的温敏凝胶制剂。
Description
技术领域
本发明属于医药制剂技术领域,具体涉及一种含有聚维酮碘用于治疗感染引起的腔道疾病的温敏凝胶制剂。
背景技术
聚维酮碘可直接使菌体内的蛋白质变性、沉淀,致使病原微生物死亡,从而高效消毒和杀菌,能杀死病毒、细菌、芽孢、真菌、原虫等,且毒性低。聚维酮碘水溶液对金黄色葡萄球菌、淋球菌、绿脓杆菌、梅毒螺旋体、乙肝病毒、艾滋病毒、阴道毛滴虫等都有强大药理活性。聚维酮碘可不断释放出游离碘,使皮肤和黏膜保持一定的有致碘浓度,抑杀细菌。
聚维酮碘的主要用途之一是用于妇科阴道感染,其可与阴道分泌物互溶,杀灭分泌物中的病原微生物,阻断性病的传播和侵袭,以及治疗其他细菌感染导致的阴道疾病。
目前已有较多的聚维酮碘的相关制剂用于妇科阴道感染的相关疾病,其中包括冲洗剂、凝胶剂、普通栓剂等。但在临床应用时,均出现了一些缺陷,如:冲洗剂的流失过快、接触时间过短;普通栓剂在阴道内融化后容易流出、疗效差;凝胶剂的铺展性较差,在阴道内覆盖面小,所以以上剂型还是不能完全满足临床需求。
因此,为了克服传统普通型栓剂的缺点,发明人开发了含有聚维酮碘的温敏型原位凝胶给药阴道栓剂,该制剂在常温下以液体状态给药后,能在体腔内因温度升高而在用药部位发生相转变,由液态变为非化学交联的半固体凝胶态,进而附着固定于病灶处,缓释并靶向性地持久发挥药物治疗作用,阴道用温敏型原位凝胶栓剂具有用药铺展性好、覆盖面大、滞留时间长、药效好、副作用小、患者用药方便等特点。
经调研,目前温敏凝胶基质应用最为广泛的是泊洛沙姆,其温敏特性以及安全性已得到验证,并且全球已有大量的关于泊洛沙姆作为温敏凝胶基质的制剂专利,但并未发现关于聚维酮碘与泊洛沙姆相结合的专利。发明人研究发现,聚维酮碘与泊洛沙姆存在严重的化学不相容的特性,聚维酮碘与泊洛沙姆混合后,聚维酮碘会迅速降解,由红棕色变为无色溶液。
因此,解决聚维酮碘与泊洛沙姆不相容的问题,从而进一步制备成具有用药铺展性好、覆盖面大、滞留时间长、药效好、副作用小、患者用药方便等特点的聚维酮碘温敏凝胶制剂变得尤为重要。
发明内容
本发明所要解决的技术问题在于针对聚维酮碘与泊洛沙姆不相容的问题,提供一种解决方案,使二者可以兼容且不影响药效以及温敏特性,最终制备成具有用药铺展性好、覆盖面大、滞留时间长、药效好、副作用小、患者用药方便等特点的聚维酮碘温敏凝胶制剂。
为解决上述问题,发明人采用的技术方案是:
一种聚维酮碘温敏凝胶制剂,包含以下组分:聚维酮碘、温敏凝胶基质、氧化剂、渗透压调节剂、pH调节剂及纯化水。
按重量计,所述聚维酮碘占0.1%~15%,所述温敏凝胶基质占0.1%~35%,所述氧化剂占0.01%~10%,所述渗透压调节剂占0.01%~10%,所述pH调节剂占0.01%~5%,余量为所述纯化水。
本发明以聚维酮碘作为主药,以泊洛沙姆为温敏凝胶基质,以双氧水为氧化剂、渗透压调节剂、pH调节剂制备成聚维酮碘温敏凝胶制剂。
本发明采用的泊洛沙姆为药用级辅料,可注射、外用、眼科等医用,使用安全,是由聚氧化乙烯与聚氧化丙烯组成的嵌段共聚物(PEO-PEO-PEO),属于非离子表面活性剂,具有独特的反向热凝胶性质,其20%~30%的水溶液具有在5℃至常温下为液态凝胶,当温度高至35℃~37℃时则变为固态凝胶的特点。
本发明所述的泊洛沙姆包含:泊洛沙姆407、泊洛沙姆188、泊洛沙姆124、泊洛沙姆237、泊洛沙姆338中的一种或多种。
由于泊洛沙姆407的水溶液具有温度敏感型原为凝胶的性质,其凝胶表面光滑柔软,无明显的异物感、无毒无刺激、生物相容性好。为了调节合适的胶变时间以及胶变温度,本发明以泊洛沙姆407与泊洛沙姆188组合来作为优选的温敏凝胶基质。
本发明所述的氧化剂包括无机氧化剂以及有机氧化剂,所述氧化剂优选为双氧水,双氧水为酸性强氧化剂,通过试验,我们惊奇的发现,双氧水可以有效的解决聚维酮碘与泊洛沙姆不相容的问题。具体的,通过分析,发明人发现,聚维酮碘之所以与泊洛沙姆不相容,是由于泊洛沙姆中存在的还原剂与聚维酮碘发生氧化还原反应,从而使聚维酮碘快速降解,而发明人惊奇的发现,通过加入氧化剂,使氧化剂提前与泊洛沙姆中的还原剂反应,从而消耗完还原剂的量,再将聚维酮碘与泊洛沙姆混合,聚维酮碘就能够与泊洛沙姆相容,聚维酮碘含量不再下降,且通过试验我们发现,即使泊洛沙姆中的还原剂全部被消耗后,也没有改变泊洛沙姆的温敏凝胶特性。
本发明采用的渗透压调节剂为选自氯化钠、甘露醇、葡萄糖、山梨糖醇、甘油、聚乙二醇、丙二醇中的一种或多种的组合。
本发明采用的pH调节剂为选自硼酸、硼酸钠、磷酸盐缓冲剂、氨丁三醇、氨丁三醇盐酸缓冲剂、氢氧化钠、盐酸、柠檬酸、柠檬酸钠中的一种或多种的组合。
本发明成功的解决了聚维酮碘与泊洛沙姆不相容的技术问题,提供了一种新的聚维酮碘温敏凝胶制剂。
本发明提供的聚维酮碘与泊洛沙姆的温敏凝胶制剂有效的弥补了目前临床上相关制剂用于妇科阴道感染的相关疾病的制剂缺陷。具体的,本发明之温敏凝胶制剂施于腔道后,能够迅速形成半固体凝胶,显示出强滞留以及缓释的作用,从而增加生物利用度;所形成的半固体凝胶能够滞留在给药部位,不会流失,并且可以逐步释放出聚维酮碘,杀灭涂抹部位的各种感染微生物。
本发明与现有技术相比具有如下优点:用药铺展性好、覆盖面大、滞留时间长、药效好、副作用小、患者用药方便等特点。
具体实施方式
下面通过具体实施例对本发明的技术方案做进一步的详细描述。实施例1:泊洛沙姆温敏凝胶的制备及考察。
泊洛沙姆温敏凝胶配方(100g)如下:泊洛沙姆(407)15g、泊洛沙姆(188)20g、纯化水65g。
制备方法如下:
(1)称取处方量的纯化水于烧杯中,将烧杯置于冰浴中放入搅拌器并搅拌。
(2)称取处方量的泊洛沙姆(P188,P407)缓缓加入到烧杯中,直至搅拌溶解,即得实施例样品1。
考察实施例样品1的温敏特性,结果见表1:
表1
从表1结果得知,泊洛沙姆在既定的种类以及用量条件下,是可以显示出明显的温敏凝胶特性的,在常温下为液态,35℃环境下可以迅速形成半固体状态,显示出其具有缓释的潜在功能。
实施例2:聚维酮碘温敏凝胶配制及考察。
2%聚维酮碘温敏凝胶处方如下:聚维酮碘2g,泊洛沙姆(407)15g,泊洛沙姆(188)20g,加纯化水至100g。
制备方法如下:
(1)按处方量量称取纯化水到烧杯中,并将烧杯置于冰浴中,放入搅拌器并搅拌;
(2)称取处方量的聚维酮碘,缓缓加入到烧杯中,搅拌至完全溶解;
(3)称取处方量的泊洛沙姆(P188,P407)缓缓加入到烧杯中,直至搅拌溶解,即得实施例2样品。
考察实施例样品2的温敏特性,结果见表2:
表2
从表2结果得知,聚维酮碘与泊洛沙姆结合后,聚维酮碘并没有影响泊洛沙姆的温敏凝胶特性,在常温下为液态,35℃环境下可以迅速形成半固体状态。
实施例样品2的聚维酮碘含量测定:
将实施例样品2用0.01mol/L硫代硫酸钠进行滴定,测定有效碘含量。结果见表3:
表3
样品 | 有效碘含量mg/g | 理论含量mg/g |
实施例样品2 | 1.41 | 2.13 |
从表3结果得知,虽然聚维酮碘并没有影响泊洛沙姆的温敏凝胶特性,但泊洛沙姆确明显显示出对聚维酮碘的影响,导致聚维酮碘显著的含量下降,显示出二者的化学不相容性。
实施例3:2%聚维酮碘(含过氧化氢)温敏凝胶的制备及考察。
处方如下:聚维酮碘2g,分别加入6%过氧化氢15g/10g/5g/2g/1g,泊洛沙姆(407)15g,泊洛沙姆(188)20g,加纯化水至100g。共5个配方样品,分别为实施例3样品1、实施例3样品2、实施例3样品3、实施例3样品4、实施例3样品5。
制备方法如下:
(1)按处方量量称取纯化水到烧杯中;
(2)分别加入处方量的过氧化氢到烧杯中,并将烧杯置于冰浴中,放入搅拌器并搅拌;
(3)称取处方量的聚维酮碘,缓缓加入到烧杯中,搅拌至完全溶解;
(4)称取处方量的泊洛沙姆(P188,P407)缓缓加入到烧杯中,直至搅拌溶解,即得实施例3样品1、实施例3样品2、实施例3样品3、实施例3样品4、实施例3样品5。
分别考察实施例3样品的温敏凝胶特性,结果见表4:
表4
从表4结果得知,1)过氧化氢的加入并不影响泊洛沙姆的温敏特性,依然显示出较为显著的温敏特性。2)过氧化氢的加入,从样品的性状角度初步来看,与实施例2样品的性状相比,真实的解决了聚维酮碘以及泊洛沙姆二者之间化学不相容的技术难点。
实施例3样品的聚维酮碘含量测定:
将实施例3中配置的5个样品分别用0.01mol/L硫代硫酸钠进行滴定,测定有效碘含量。结果见表5:
表5
名称 | 理论有效碘含量mg/g | 实际测定有效碘含量mg/g |
实施例3样品1 | 2.16 | 8.78 |
实施例3样品2 | 2.18 | 6.24 |
实施例3样品3 | 2.18 | 4.81 |
实施例3样品4 | 2.19 | 3.93 |
实施例3样品5 | 2.17 | 3.22 |
从表5结果得知,1)从定量的角度来看,通过对聚维酮碘含量的测定,确认聚维酮碘的含量与理论值相比,不再下降,其真实的说明了通过加入一定量的过氧化氢,本发明人解决了聚维酮碘与泊洛沙姆二者之间化学不相容的技术难点。2)通过加入不同量的过氧化氢,虽然解决了聚维酮碘与泊洛沙姆二者之间化学不相容的技术难点,但从测定结果来看,过氧化氢本身也在消耗硫代硫酸钠滴定液,并且过氧化氢加入量越高,消耗硫代硫酸钠滴定液也越多,这导致实际有效碘的含量测定并不准确,专属性不高。3)通过加入的不同量的过氧化氢以及实际测定的有效碘含量结果来看,本发明人需要进一步筛选出合适的针对2%聚维酮碘温敏凝胶制剂的双氧水的含量。
实施例4:2%聚维酮碘、0.25%的过氧化氢、温敏凝胶基质以及纯化水的温敏凝胶制备及考察。
处方如下:聚维酮碘2g,6%过氧化氢0.25g,泊洛沙姆(407)15g,泊洛沙姆(188)20g,加入纯化水至100g。
制备方法如下:
(1)按处方量量称取纯化水到烧杯中;
(2)加入处方量的过氧化氢到烧杯中,并将烧杯置于冰浴中,放入搅拌器并搅拌;
(3)称取处方量的聚维酮碘,缓缓加入到烧杯中,搅拌至完全溶解;
(4)称取处方量的泊洛沙姆(P188,P407)缓缓加入到烧杯中,直至搅拌溶解,即得实施例4样品。
考察实施例4样品的温敏凝胶,结果见表6:
表6
从表6结果得知,0.25%的过氧化氢的加入,从样品的性状角度初步来看,并不影响温敏凝胶的特性。
实施例4样品的聚维酮碘含量测定:
将实施例4样品用0.01mol/L硫代硫酸钠进行滴定,测定有效碘含量。结果见表7:
表7
从表7结果得知,针对2%聚维酮碘的投料,使用0.25%的过氧化氢,刚好中和了2%聚维酮碘与泊洛沙姆之间不相容的影响因素,并且过氧化氢不影响硫代硫酸钠的消耗。
实施例5:5%聚维酮碘、0.62%的(6%)过氧化氢、温敏凝胶基质以及纯化水的温敏凝胶制备及考察。
处方如下:聚维酮碘5g,6%过氧化氢0.62g,泊洛沙姆(407)12.85g,泊洛沙姆(188)17g,加入纯化水至100g。
制备方法如下:
(1)按处方量量称取纯化水到烧杯中;
(2)加入处方量的过氧化氢到烧杯中,并将烧杯置于冰浴中,放入搅拌器并搅拌;
(3)称取处方量的聚维酮碘,缓缓加入到烧杯中,搅拌至完全溶解;
(4)称取处方量的泊洛沙姆(P188,P407)缓缓加入到烧杯中,直至搅拌溶解,即得实施例5样品。
考察实施例5样品的温敏凝胶,结果见表8:
表8
从表8结果得知,0.62%的过氧化氢的加入,从样品的性状角度初步来看,并不影响温敏凝胶的特性。
实施例5样品的聚维酮碘含量测定:
将实施例5样品用0.01mol/L硫代硫酸钠进行滴定,测定有效碘含量。结果见表9:
表9
从表9结果得知,针对5%聚维酮碘的投料,使用0.62%的过氧化氢,刚好中和了5%聚维酮碘与泊洛沙姆之间不相容的影响因素,并且过氧化氢不影响硫代硫酸钠的消耗。
Claims (9)
1.一种聚维酮碘温敏凝胶制剂,其特征在于,包含以下组分:聚维酮碘、温敏凝胶基质、氧化剂、渗透压调节剂、pH调节剂及纯化水。
2.根据权利要求1所述的温敏凝胶制剂,其特征在于,按重量计,所述聚维酮碘占0.1%~15%,所述温敏凝胶基质占0.1%~35%,所述氧化剂占0.01%~10%,所述渗透压调节剂占0.01%~10%,所述pH调节剂占0.01%~5%,余量为所述纯化水。
3.根据权利要求1或2所述的温敏凝胶制剂,其特征在于,所述温敏凝胶基质为天然及改性聚合物、聚N-异丙基烯酞类聚合物、聚氧乙烯-聚氧丙烯共聚物或交联PLGA嵌段共聚物。
4.根据权利要求3所述的温敏凝胶制剂,其特征在于,所述温敏凝胶基质为泊洛沙姆或壳聚糖。
5.根据权利要求4所述的温敏凝胶制剂,其特征在于,所述泊洛沙姆为泊洛沙姆407、泊洛沙姆188、泊洛沙姆124、泊洛沙姆237、泊洛沙姆338中的一种或多种。
6.根据权利要求5所述的温敏凝胶制剂,其特征在于,所述温敏凝胶基质采用泊洛沙姆407与泊洛沙姆188的组合。
7.根据权利要求1或2所述的温敏凝胶制剂,其特征在于,其中,所述氧化剂为双氧水或醋酸。
8.根据权利要求1或2所述的温敏凝胶制剂,其特征在于,所述渗透压调节剂为氯化钠,甘露醇,葡萄糖,山梨糖醇,甘油,聚乙二醇,丙二醇中的一种或多种的组合。
9.根据权利要求1或2所述的温敏凝胶制剂,其特征在于,其中,所述pH调节剂包括硼酸,硼酸钠,磷酸盐缓冲剂,氨丁三醇,氨丁三醇盐酸缓冲剂,氢氧化钠,盐酸,柠檬酸,柠檬酸钠中的一种或多种的任意组合。
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Address after: Room 301, Building 1, No. 36 Hengqin Doukou Road, Zhuhai City, Guangdong Province, 519000 Patentee after: Aiwei Pharmaceutical (Zhuhai Hengqin) Co.,Ltd. Country or region after: China Address before: Room 210-216, building 20, creative Valley, 1889 Huandao East Road, Hengqin New District, Zhuhai, Guangdong 519000 Patentee before: AIWEI Pharmaceutical (Zhuhai) Co.,Ltd. Country or region before: China |