CN101069692B - 含积雪草总甙的药物制剂及其制备方法 - Google Patents
含积雪草总甙的药物制剂及其制备方法 Download PDFInfo
- Publication number
- CN101069692B CN101069692B CN2006100506146A CN200610050614A CN101069692B CN 101069692 B CN101069692 B CN 101069692B CN 2006100506146 A CN2006100506146 A CN 2006100506146A CN 200610050614 A CN200610050614 A CN 200610050614A CN 101069692 B CN101069692 B CN 101069692B
- Authority
- CN
- China
- Prior art keywords
- triterpenes
- total
- gross weight
- accounts
- pharmaceutical preparation
- 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.)
- Active
Links
- 238000000034 method Methods 0.000 title claims abstract description 13
- 239000003814 drug Substances 0.000 title abstract description 10
- 238000002360 preparation method Methods 0.000 title abstract description 9
- 229940079593 drug Drugs 0.000 title description 4
- 241000167550 Centella Species 0.000 title description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 26
- 239000003921 oil Substances 0.000 claims abstract description 13
- 239000002562 thickening agent Substances 0.000 claims abstract description 13
- 239000003995 emulsifying agent Substances 0.000 claims abstract description 12
- 239000000203 mixture Substances 0.000 claims abstract description 7
- 150000003648 triterpenes Chemical class 0.000 claims description 31
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol group Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 24
- 239000000463 material Substances 0.000 claims description 14
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 12
- 230000002421 anti-septic effect Effects 0.000 claims description 10
- 239000003961 penetration enhancing agent Substances 0.000 claims description 7
- AMUTYVGRCVFCCD-UHFFFAOYSA-N 5,6-diaminopyridine-3-carboxylic acid Chemical group NC1=CC(C(O)=O)=CN=C1N AMUTYVGRCVFCCD-UHFFFAOYSA-N 0.000 claims description 6
- -1 Palmic acid isobutyl ester Chemical class 0.000 claims description 6
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical group OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 6
- 239000000080 wetting agent Substances 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 4
- 229920001577 copolymer Polymers 0.000 claims description 4
- 239000008213 purified water Substances 0.000 claims description 4
- 229920002545 silicone oil Polymers 0.000 claims description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 2
- LADGBHLMCUINGV-UHFFFAOYSA-N tricaprin Chemical compound CCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCC)COC(=O)CCCCCCCCC LADGBHLMCUINGV-UHFFFAOYSA-N 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 abstract description 5
- 244000146462 Centella asiatica Species 0.000 abstract description 4
- 235000004032 Centella asiatica Nutrition 0.000 abstract description 4
- 239000003795 chemical substances by application Substances 0.000 abstract description 2
- 229930182470 glycoside Natural products 0.000 abstract 2
- 150000002338 glycosides Chemical class 0.000 abstract 2
- 230000003204 osmotic effect Effects 0.000 abstract 1
- 239000003755 preservative agent Substances 0.000 abstract 1
- 230000002335 preservative effect Effects 0.000 abstract 1
- 239000000725 suspension Substances 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- QCYLIQBVLZBPNK-UHFFFAOYSA-N asiaticoside A Natural products O1C(C(=O)C(C)C)=CC(C)C(C2(C(OC(C)=O)CC34C5)C)C1CC2(C)C3CCC(C1(C)C)C45CCC1OC1OCC(O)C(O)C1O QCYLIQBVLZBPNK-UHFFFAOYSA-N 0.000 description 11
- WYQVAPGDARQUBT-XCWYDTOWSA-N asiaticoside Natural products O=C(O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@H]2[C@H](O)[C@H](O)[C@H](O[C@H]3[C@H](O)[C@H](O)[C@@H](O)[C@H](C)O3)[C@@H](CO)O2)O1)[C@@]12[C@@H]([C@@H](C)[C@H](C)CC1)C=1[C@](C)([C@@]3(C)[C@@H]([C@@]4(C)[C@H]([C@@](CO)(C)[C@@H](O)[C@H](O)C4)CC3)CC=1)CC2 WYQVAPGDARQUBT-XCWYDTOWSA-N 0.000 description 10
- 229940022757 asiaticoside Drugs 0.000 description 10
- WYQVAPGDARQUBT-FGWHUCSPSA-N Madecassol Chemical compound O([C@@H]1[C@@H](CO)O[C@H]([C@@H]([C@H]1O)O)OC[C@H]1O[C@H]([C@@H]([C@@H](O)[C@@H]1O)O)OC(=O)[C@]12CC[C@H]([C@@H]([C@H]1C=1[C@@]([C@@]3(CC[C@H]4[C@](C)(CO)[C@@H](O)[C@H](O)C[C@]4(C)[C@H]3CC=1)C)(C)CC2)C)C)[C@@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@H]1O WYQVAPGDARQUBT-FGWHUCSPSA-N 0.000 description 9
- 239000012071 phase Substances 0.000 description 9
- 239000002674 ointment Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 6
- 208000027418 Wounds and injury Diseases 0.000 description 5
- 210000003491 skin Anatomy 0.000 description 5
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 4
- WSDISUOETYTPRL-UHFFFAOYSA-N dmdm hydantoin Chemical compound CC1(C)N(CO)C(=O)N(CO)C1=O WSDISUOETYTPRL-UHFFFAOYSA-N 0.000 description 4
- WLAMNBDJUVNPJU-UHFFFAOYSA-N 2-methylbutyric acid Chemical compound CCC(C)C(O)=O WLAMNBDJUVNPJU-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000003623 enhancer Substances 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 230000035515 penetration Effects 0.000 description 3
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 208000002260 Keloid Diseases 0.000 description 2
- 206010023330 Keloid scar Diseases 0.000 description 2
- 206010039710 Scleroderma Diseases 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 2
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 description 2
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 229940075507 glyceryl monostearate Drugs 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 210000001117 keloid Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- 239000003871 white petrolatum Substances 0.000 description 2
- WYVVKGNFXHOCQV-UHFFFAOYSA-N 3-iodoprop-2-yn-1-yl butylcarbamate Chemical compound CCCCNC(=O)OCC#CI WYVVKGNFXHOCQV-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 208000028006 Corneal injury Diseases 0.000 description 1
- 241000125183 Crithmum maritimum Species 0.000 description 1
- 206010063560 Excessive granulation tissue Diseases 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010023421 Kidney fibrosis Diseases 0.000 description 1
- BNMGUJRJUUDLHW-HCZMHFOYSA-N Madecassoside Chemical compound O([C@@H]1[C@@H](CO)O[C@H]([C@@H]([C@H]1O)O)OC[C@H]1O[C@H]([C@@H]([C@@H](O)[C@@H]1O)O)OC(=O)[C@]12CC[C@H]([C@@H]([C@H]1C=1[C@@]([C@@]3(C[C@@H](O)[C@H]4[C@](C)(CO)[C@@H](O)[C@H](O)C[C@]4(C)[C@H]3CC=1)C)(C)CC2)C)C)[C@@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@H]1O BNMGUJRJUUDLHW-HCZMHFOYSA-N 0.000 description 1
- BNMGUJRJUUDLHW-HLUHVYOBSA-N Madecassoside Natural products C[C@@H]1CC[C@@]2(CC[C@]3(C)C(=CC[C@@H]4[C@@]5(C)C[C@@H](O)[C@H](O)[C@@](C)(CO)[C@@H]5[C@H](O)C[C@@]34C)[C@@H]2[C@H]1C)C(=O)O[C@@H]6O[C@H](CO[C@@H]7O[C@H](CO)[C@@H](O[C@@H]8O[C@H](C)[C@H](O)[C@@H](O)[C@H]8O)[C@H](O)[C@H]7O)[C@@H](O)[C@H](O)[C@H]6O BNMGUJRJUUDLHW-HLUHVYOBSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000005141 Otitis Diseases 0.000 description 1
- 229920002651 Polysorbate 85 Polymers 0.000 description 1
- ILRCGYURZSFMEG-UHFFFAOYSA-N Salidroside Natural products OC1C(O)C(O)C(CO)OC1OCCC1=CC=C(O)C=C1 ILRCGYURZSFMEG-UHFFFAOYSA-N 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 206010040943 Skin Ulcer Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- 238000001354 calcination Methods 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 230000000739 chaotic effect Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 230000035617 depilation Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 208000019258 ear infection Diseases 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 210000001126 granulation tissue Anatomy 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 210000000835 hypertrophic cicatrix Anatomy 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 229940090813 madecassoside Drugs 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 210000002640 perineum Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229940113171 polysorbate 85 Drugs 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- ILRCGYURZSFMEG-RQICVUQASA-N salidroside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)OC1OCCC1=CC=C(O)C=C1 ILRCGYURZSFMEG-RQICVUQASA-N 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 201000009890 sinusitis Diseases 0.000 description 1
- 231100000019 skin ulcer Toxicity 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 238000007483 tonsillectomy Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000002569 water oil cream Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及一种含积雪草总甙的药物制剂，由积雪草总甙、渗透促进剂、乳化剂、润湿剂、增稠剂、防腐剂、碱化剂、油和水组成。其特征在于积雪草总甙占总重量的1～20％，渗透促进剂占总重量的2～10％，乳化剂占总重量的3～10％，润湿剂占总重量的2～10％、助悬、增稠剂占总重量的0.1～6％、防腐剂占总重量的0.2～2％、碱化剂占总重量的0.2～2％、油占总重量的1～20％，水占总重量的60～80％。本方法的优点提高了药物在局部的浓度，有利于更好发挥药效，治疗疾病。
Description
技术领域
本发明属于药物制剂技术领域，特别是用于治疗外伤、手术创伤、烧伤，疤痕疙瘩、硬皮病、抑郁、乳腺增生、肝肾纤维化等，含积雪草总甙的药物制剂及其制备方法。
背景技术
积雪草总甙为伞形科植物积雪草的干燥全草的水溶性有效部位。药理研究发现积雪草总甙具有激活上皮细胞，促进正常肉芽组织形成的作用，可使创伤面迅速愈合；能够抑制成纤维细胞的增殖，对无秩序的瘢痕疙瘩增生具有抑制及缓和作用，可防止粘连发生和缓解粘连的形成。临床应用于对静脉功能不良引起的长期不愈的下肢溃疡，手术或其它伤害造成的创伤面和肌腱粘连，灼烧等因素所致的伤面恢复后形成的增生性瘢痕疙瘩，炎症引起的损伤性粘连，其它因素产生的长期皮肤溃疡损伤，以及硬皮症等。此外，积雪草总甙还用于治疗子宫颈损伤、产科创伤、会阴侧切开手术、乳房裂口；窦炎、扁桃体切除术、耳炎、鼓室成形术；角膜损伤、白内障、视网膜剥离等。
已有国家标准的积雪甙霜软膏的主要成分为：甘油、十二烷硫酸钠、三乙醇胺、吐温-80、单硬脂酸甘油酯、硬脂酸、白凡士林、液状石腊、叔丁基对甲酚、羟苯乙酯。这一剂型可使积雪甙通过皮肤吸收。
公开号为CN20051000001.8的中国专利含积雪草水溶性有效组分的中药缓释制剂及其制备方法，其制剂处方包括：积雪草提取物(按积雪草总昔计)18g，羟丙基甲基纤维素30—250g，微晶纤维素20—70g，聚维酮k30醇溶液适量，硬脂酸镁适量。该发明专利申请解决了积雪草水溶性有效组分的缓释问题。
发明内容
本发明的目的是促进积雪草总甙的皮肤吸收，提高局部药物浓度，进一步增强其疗效。
已有的积雪甙霜软膏的主要成分为：甘油、十二烷硫酸钠、三乙醇胺、吐温-80、单硬脂酸甘油酯、硬脂酸、白凡士林、液状石腊、叔丁基对甲酚、羟苯乙酯。本发明在此基础上，使用了渗透增强剂以及其他促进吸收的辅料，进一步提高了皮肤对积雪草总甙的吸收。
为了达到本发明的目的，本发明采用棕榈酸异辛酯为渗透增强剂。棕榈酸异辛酯为脂肪酸酯，其化学稳定性和热稳定性好，不氧化，不变色，无刺激性，致敏性。同时还具有赋形、润滑等功效，能有效促进药物表皮渗透。
为了达到本发明的目的，本发明采用了以下的技术方案：
一种含积雪草总甙的药物制剂，由积雪草总甙、渗透促进剂、乳化剂、润湿剂、增稠剂、防腐剂、碱化剂、油和水组成。其特征在于积雪草总甙占总重量的1～20％，渗透促进剂占总重量的2～10％，乳化剂占总重量的3～10％，润湿剂占总重量的2～10％、助悬、增稠剂占总重量的0.1～6％、防腐剂占总重量的0.2～2％、碱化剂占总重量的0.2～2％、油占总重量的1～20％，水占总重量的60～80％。
作为优选，渗透促进剂主要指可有效增强积雪草总甙通过哺乳动物皮肤的脂肪酸酯，优选的为棕榈酸异辛酯、棕榈酸异丁酯中的一种。
作为优选，乳化剂主要指天然乳化剂，优选的为DRA-CE(为硬脂酸甘油酯柠檬酸盐、硬脂酸甘油酯的混合物)。
作为优选，润湿剂为甘油。
作为优选，助悬、增稠剂为高分子聚合物，优选的为丙烯酸聚合物，Carbopol934(为丙烯酸聚合物)、NovemerEC-1(为丙烯酸酯、丙烯酸酰胺共聚物、白矿油、聚山梨醇酯-85的混合物)中的一种或其混合物。
作为优选，防腐剂为Glydant Plus，其主要成分为1，3-二羟基-5，5-二甲基乙内酰脲(DMDMH)和碘代丙炔基氨基甲酸酯(IPBC)。
作为优选，碱化剂为三乙醇胺。
作为优选，油为辛酸/癸酸三甘油酯、C16-18混合醇、硅油200/100中的一种或其混合物。
作为优选，水相的配制方法为将水相的水浴加热至适宜的温度，纯化水中加入助悬、增稠剂，完全分散均匀后，加入处方量的积雪草总甙、甘油溶解成均匀物料。
作为优选，油相的配制方法为将油相的水浴加热至适宜的温度，油、渗透增强剂、乳化剂溶解成均匀物料。
作为优选，将水相物料均匀加入油相物料，直至成为匀质，冷却后加入防腐剂、碱化剂；并加入适量增稠剂。
本方法的优点提高了药物在局部的浓度，有利于发挥药效，治疗疾病。
具体实施方式
下面结合实施例对本发明作进一步描述，但本发明并不为实施例所限制。
实施例1：
方法：将水相的水浴加热至70-80℃后，纯化水中加入Carbopol934，搅拌使之完全分散均匀，再加入处方量的积雪草总甙、甘油溶解成均匀物料。将油相的夹层水加热至70-80℃，棕榈酸异辛酯、天然乳化剂、辛酸/葵酸三甘油脂、C16-18混合醇、硅油200/100溶解成均匀物料。然后将油相的物料抽到主锅中搅拌，缓缓将水相成分加入，搅拌成匀质后，冷却后加入防腐剂Glydant Plus，使用碱化剂三乙醇胺调节pH值至人体可接受的弱酸性至中性范围；并视制剂稠薄程度，加入适量增稠剂Novemer EC-1。
经机器罐装成12g或者20g/支的软膏剂
实施例2：
方法：将水相的水浴加热至70-80℃后，纯化水中加入Carbopol934，搅拌使之完全分散均匀，再加入处方量的积雪草总甙、甘油溶解成均匀物料。将油相的夹层水加热至70-80℃，辛酸/葵酸三甘油脂、棕榈酸异辛酯、天然乳化剂、C16-18混合醇、硅油200/100溶解成均匀物料。然后将油相的物料抽到主锅中搅拌，缓缓将水相成分加入，搅拌成匀质后，冷却后加入防腐剂Glydant Plus，使用碱化剂三乙醇胺调节pH值至人体可接受的弱酸性和中性范围；并视制剂稠薄程度，加入适量增稠剂Novemer EC-1。
经机器罐装成12g或者20g/支的软膏剂
实施例3：
积雪草总甙软膏长期稳定性试验结果
注：积雪甙含量的测定方法为高效液相法，因为本品辅料峰保留时间、积雪草甙、羟基积雪草甙保留时间都不同，辅料与主药峰分离良好，说明辅料、羟基积雪甙对积雪甙含量测定无干扰。
实验结果表明，本发明的软膏，在为期24月的稳定性考察中，能保持均一的油水乳化性状。采用精密的高效液相测定法对主要有效成分：积雪甙的研究发现，积雪甙能够维持其含量。
实施例4：
透皮吸收实验
根据《中国药典》2005版第二部附录XC“溶出度测定法”、附录XD“释放度测定法”中的方法测定。
大鼠处死，脱毛取皮剪成直径5厘米左右的圆形，精确称取4g积雪草总甙软膏(含积雪草总甙100mg)，涂于鼠皮外层。将鼠皮固定于溶出度测定仪的碟桨装置的网碟中，测定0.5、1、2、4、8、12小时各时间点内层鼠皮溶出的积雪甙量。采用容量法测定积雪草总甙含量。
| 时间(h) | 累计释药量 | 累积释药百分率 |
| 0 | 0 | 0 |
| 0.5 | 18.7 | 18.7 |
| 1 | 27.5 | 27.5 |
| 2 | 35.7 | 35.7 |
| 4 | 42.3 | 42.3 |
| 8 | 47.8 | 47.8 |
| 12 | 52.1 | 52.1 |
实验结果表明，本发明的软膏，有效的促进了积雪草总甙的透皮吸收，提高了局部药物浓度。
Claims (10)
1.一种含积雪草总甙的药物制剂，由积雪草总甙、渗透促进剂、乳化剂、润湿剂、增稠剂、防腐剂、碱化剂、油和水组成，其特征在于积雪草总甙占总重量的1～20％，渗透促进剂占总重量的2～10％，乳化剂占总重量的3～10％，湿润剂占总重量的2～10％、增稠剂占总重量的0.1～6％、防腐剂占总重量的0.2～2％、碱化剂占总重量的0.2～2％、油占总重量的1～20％，水占总重量的60～80％，其中所述的渗透促进剂为棕榈酸异辛酯、棕榈酸异丁酯中的一种，各组分重量百分比之和为100％。
2.根据权利要求1所述的含积雪草总甙的药物制剂，其特征在于乳化剂为硬脂酸甘油酯柠檬酸盐和硬脂酸甘油酯的混合物。
3.根据权利要求1所述的含积雪草总甙的药物制剂，其特征在于润湿剂为甘油。
4.根据权利要求1所述的含积雪草总甙的药物制剂，其特征在于增稠剂为丙烯酸聚合物、NovemerEC-1中的一种或其混合物。
5.根据权利要求1所述的含积雪草总甙的药物制剂，其特征在于防腐剂为1，3-二羟基-5，5-二甲基乙内酰脲。
6.根据权利要求1所述的含积雪草总甙的药物制剂，其特征在于碱化剂为三乙醇胺。
7.根据权利要求1所述的含积雪草总甙的药物制剂，其特征在于油为辛酸/癸酸三甘油酯、C16-18混合醇、硅油200/100中的一种或其混合。
8.根据权利要求1所述的含积雪草总甙的药物制剂，其特征在于水相的配置方法为将水相的水浴加热至适宜的温度，纯化水中加入增稠剂，完全分散均匀后，加入处方量的积雪草总甙、甘油溶解成均匀物料。
9.根据权利要求1所述的含积雪草总甙的药物制剂，其特征在于油相配置方法为将油相的水浴加热至适宜的温度，油、渗透促进剂、乳化剂溶解成均匀物料。
10.根据权利要求1或10所述的含积雪草总甙的药物制剂，其特征在于将水相物料均匀加入油相物料，直至成为均质，冷却后加入防腐剂、碱化剂；并加入适量增稠剂。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2006100506146A CN101069692B (zh) | 2006-05-08 | 2006-05-08 | 含积雪草总甙的药物制剂及其制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2006100506146A CN101069692B (zh) | 2006-05-08 | 2006-05-08 | 含积雪草总甙的药物制剂及其制备方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101069692A CN101069692A (zh) | 2007-11-14 |
| CN101069692B true CN101069692B (zh) | 2011-04-20 |
Family
ID=38897209
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2006100506146A Active CN101069692B (zh) | 2006-05-08 | 2006-05-08 | 含积雪草总甙的药物制剂及其制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101069692B (zh) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103191163B (zh) * | 2013-04-29 | 2014-07-09 | 崔新明 | 一种皮肤创面修复药物组合物 |
| CN103494877B (zh) * | 2013-09-25 | 2016-01-27 | 南阳市汇博生物技术有限公司 | 一种用于治疗疤痕的组合物及其制备方法 |
| EP3551182A1 (en) | 2016-12-06 | 2019-10-16 | Topical Innovations B.V. | Topical pharmaceutical composition containing phenytoin and a (co -)an algesic for the treatment of chronic pain |
| JP7264813B2 (ja) * | 2016-12-06 | 2023-04-25 | トピカル・イノベーションズ・ベー・フェー | 末梢神経障害性疼痛の治療に使用するための局所作用用フェニトイン |
| CN110201217B (zh) * | 2019-06-13 | 2021-12-07 | 西安医学院 | 一种用于宫颈糜烂术后创伤出血的止血微球及其制备方法 |
| CN111481528A (zh) * | 2020-03-23 | 2020-08-04 | 北京和正堂生物科技有限公司 | 基于穴位经皮给药的药物载体与药物组合物及其制备方法与应用 |
-
2006
- 2006-05-08 CN CN2006100506146A patent/CN101069692B/zh active Active
Non-Patent Citations (3)
| Title |
|---|
| 中药保护、中药部颁标准.1997, * |
| 张光杰.药用辅料应用技术 1.中国医药科技出版社,1991,247. |
| 张光杰.药用辅料应用技术 1.中国医药科技出版社,1991,247. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101069692A (zh) | 2007-11-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101069692B (zh) | 含积雪草总甙的药物制剂及其制备方法 | |
| CN101569640A (zh) | 积雪草总苷用于制备预防或治疗妊娠纹的药物或化妆品的用途 | |
| CN115487112A (zh) | 用于皮肤抗炎舒缓的组合物 | |
| CN104981258A (zh) | 用于组织再生的组合物和方法 | |
| CN101310734A (zh) | 用于治疗奶牛子宫内膜炎的中西药复方子宫灌注液 | |
| US6468553B1 (en) | Formula and preparation method of an improved ointment for treating burns and scalds | |
| CN111700846A (zh) | 一种舒缓型光子冷凝胶及其制备方法 | |
| CN110507710A (zh) | 一种组合物及其制备方法、中药制剂、用途 | |
| WO1998018478A1 (fr) | Huiles de tortues terrestres et marines, compositions les contenant et leur procede de preparation | |
| CN114146051A (zh) | 生肌愈疡中药凝胶剂及其制备方法 | |
| CN105411998B (zh) | 含有五味子乙素的治疗烧烫伤的外用组合物 | |
| CN108853369B (zh) | 天然植物抗菌液PAMs水凝胶贴剂的制备方法及应用 | |
| CN101536977A (zh) | 3β,12,13-三羟基-齐墩果烷-28-酸为活性成分的凝胶 | |
| CN109528693A (zh) | 一种雷帕霉素巴布剂及其制备方法 | |
| CN110772473B (zh) | 一种合适于糖尿病病人皮肤的护肤品 | |
| CN118340812A (zh) | 一种促进骨骼修复的中药组合物及其制备方法 | |
| CN109200014B (zh) | 一种醋酸曲安奈德乳膏及其制备方法 | |
| CN108434299B (zh) | 用于治疗肩周炎的药物组合物及其制备方法与喷雾剂 | |
| CN113559052A (zh) | 一种聚肌胞外用制剂及其制备方法 | |
| CN114129629A (zh) | 一种痔疮凝胶及其制备方法 | |
| CN100596279C (zh) | 治疗妇科炎症的妇康舒乳膏剂及其制备方法 | |
| CN116869926A (zh) | 一种地奈德乳膏及其制备方法 | |
| CN118319980A (zh) | 一种具有皮肤再生修复作用的乌药提取物凝胶及其制备方法 | |
| IT202100008303A1 (it) | Formulazione ad uso topico, a base di estratti vegetali secchi a titolo noto, per il trattamento delle lipodistrofie e relativo metodo di produzione | |
| CN111905044A (zh) | 用于治疗硬皮病的药物组合物及其制备方法和应用 |
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 | ||
| ASS | Succession or assignment of patent right |
Owner name: ZHEJIANG RUIDA PHARMACEUTICAL CO., LTD. HANGZHOU S Owner name: HAINAN PULIN PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: FAN MINHUA Effective date: 20110801 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 310009 HANGZHOU, ZHEJIANG PROVINCE TO: 571127 HAIKOU, HAINAN PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20110801 Address after: 571127 Guilin economic and Technological Development Zone, Meilan District, Hainan, Haikou Co-patentee after: Zhejiang Ruida Pharm Co.,Ltd. Patentee after: Hainan Poly Pharm Co.,Ltd. Co-patentee after: HANGZHOU SHARPLY PHARM R&D INSTIT. Co.,Ltd. Address before: 310009, 10, combed lane, Shangcheng District, Zhejiang, Hangzhou Patentee before: Fan Minhua |
|
| C56 | Change in the name or address of the patentee |
Owner name: HAINAN PLOY PHARMACEUTICAL CO., LTD. Free format text: FORMER NAME: HAINAN PULIN PHARMACEUTICAL CO., LTD. |
|
| CP01 | Change in the name or title of a patent holder |
Address after: 571127 Guilin economic and Technological Development Zone, Meilan District, Hainan, Haikou Patentee after: HAINAN POLY PHARM. Co.,Ltd. Patentee after: ZHEJIANG POLY PHARMACEUTICAL Co.,Ltd. Patentee after: HANGZHOU SHARPLY PHARM R&D INSTIT. Co.,Ltd. Address before: 571127 Guilin economic and Technological Development Zone, Meilan District, Hainan, Haikou Patentee before: Hainan Poly Pharm Co.,Ltd. Patentee before: Zhejiang Ruida Pharm Co.,Ltd. Patentee before: HANGZHOU SHARPLY PHARM R&D INSTIT. Co.,Ltd. |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20230116 Address after: 571127 Guilin Ocean Economic Development Zone, Meilan District, Haikou City, Hainan Province Patentee after: HAINAN POLY PHARM. Co.,Ltd. Patentee after: ZHEJIANG POLY PHARMACEUTICAL Co.,Ltd. Address before: 571127 Guilin Ocean Economic and Technological Development Zone, Meilan District, Haikou City, Hainan Province Patentee before: HAINAN POLY PHARM. Co.,Ltd. Patentee before: ZHEJIANG POLY PHARMACEUTICAL Co.,Ltd. Patentee before: HANGZHOU SHARPLY PHARM R&D INSTIT. Co.,Ltd. |
|
| DD01 | Delivery of document by public notice | ||
| DD01 | Delivery of document by public notice |
Addressee: Zhu Xulei Document name: Notification of Conformity |