CN116712413A - 一种普拉克索透皮贴剂 - Google Patents
一种普拉克索透皮贴剂 Download PDFInfo
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- CN116712413A CN116712413A CN202310339476.7A CN202310339476A CN116712413A CN 116712413 A CN116712413 A CN 116712413A CN 202310339476 A CN202310339476 A CN 202310339476A CN 116712413 A CN116712413 A CN 116712413A
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- Prior art keywords
- adhesive layer
- transdermal patch
- pramipexole
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- pramipexole transdermal
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- FASDKYOPVNHBLU-ZETCQYMHSA-N pramipexole Chemical compound C1[C@@H](NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-ZETCQYMHSA-N 0.000 title claims abstract description 48
- 229960003089 pramipexole Drugs 0.000 title claims abstract description 45
- 239000003814 drug Substances 0.000 claims abstract description 47
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- 238000003756 stirring Methods 0.000 claims description 10
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- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims description 2
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 claims description 2
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- GHHURQMJLARIDK-UHFFFAOYSA-N 2-hydroxypropyl octanoate Chemical compound CCCCCCCC(=O)OCC(C)O GHHURQMJLARIDK-UHFFFAOYSA-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
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- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 2
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- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims 1
- WECGLUPZRHILCT-GSNKCQISSA-N 1-linoleoyl-sn-glycerol Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OC[C@@H](O)CO WECGLUPZRHILCT-GSNKCQISSA-N 0.000 claims 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 claims 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims 1
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- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims 1
- 239000004372 Polyvinyl alcohol Substances 0.000 claims 1
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims 1
- RZRNAYUHWVFMIP-HXUWFJFHSA-N glycerol monolinoleate Natural products CCCCCCCCC=CCCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-HXUWFJFHSA-N 0.000 claims 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims 1
- 229940074928 isopropyl myristate Drugs 0.000 claims 1
- 229960001855 mannitol Drugs 0.000 claims 1
- 229940057917 medium chain triglycerides Drugs 0.000 claims 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims 1
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- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims 1
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- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 3
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- 241000700159 Rattus Species 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
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- ARIWANIATODDMH-UHFFFAOYSA-N Lauric acid monoglyceride Natural products CCCCCCCCCCCC(=O)OCC(O)CO ARIWANIATODDMH-UHFFFAOYSA-N 0.000 description 1
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- 210000003169 central nervous system Anatomy 0.000 description 1
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- UHSKFQJFRQCDBE-UHFFFAOYSA-N ropinirole Chemical compound CCCN(CCC)CCC1=CC=CC2=C1CC(=O)N2 UHSKFQJFRQCDBE-UHFFFAOYSA-N 0.000 description 1
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- 230000001839 systemic circulation Effects 0.000 description 1
- VQMNWIMYFHHFMC-UHFFFAOYSA-N tert-butyl 4-hydroxyindole-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC(C)(C)C)C=CC2=C1O VQMNWIMYFHHFMC-UHFFFAOYSA-N 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
Classifications
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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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7084—Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
-
- 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
- A61K31/425—Thiazoles
- A61K31/428—Thiazoles condensed with carbocyclic rings
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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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Chemical Kinetics & Catalysis (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明提供一种普拉克索透皮贴剂,具体由背衬膜、药物储库层、控释膜、粘合层和防粘层组成,其药物储库层由普拉克索、丙烯酸共聚物、促渗透剂、增溶剂和结晶抑制剂组成;该贴剂对皮肤无刺激和过敏反应,其中丙烯酸共聚物、促渗透剂、增溶剂和结晶抑制剂协同,显著提高了药物的经皮透过量和生物利用度,通过控释膜控制药物持续稳定释放,并可以5‑20μg/cm2/h的稳定透皮速率持续经皮给药,药物的持续时间长,稳态透皮速率高,治疗效果更显著。
Description
技术领域
本发明涉及药物制剂领域,具体涉及一种普拉克索透皮贴剂。
背景技术
帕金森病(PD),是一种仅次于阿尔茨海默病的中枢神经系统慢性退行性疾病。目前主要是采用多巴胺受体激动剂相关药物进行治疗,如左旋多巴、普拉克索、罗匹尼罗等。普拉克索与其他麦角类多巴胺受体激动剂相比,不会造成心瓣膜损害,早期可以单独使用治疗帕金森氏病,能够延缓运动症状的出现,并较左旋多巴能改善患者的生存质量,晚期可与多巴胺合用治疗帕金森病,能够减少左旋多巴的剂量。普拉克索于1997年通过FDA批准,作为目前国内外PD诊疗指南推荐的一线用药,经过十余年的临床应用,现已在全球超过50多个国家被批准使用。
普拉克索(Pramipexole),化学名为(S)-2-氨基-4,5,6,7-四氢-6-丙胺基苯并噻唑,该活性成分在化学上是一种碱,目前临床使用的剂型盐酸普拉克索速释片和盐酸普拉克索缓释片均采用其盐酸盐的形式。
由于普拉克索的半衰期较短,需口服需多次给药,易形成血药浓度峰谷现象产生副作用。然而PD多发于老年人群体,需要长期甚至终身服药。口服给药方案复杂,且PD通常伴随的震颤、肌僵直、运动迟缓和记忆力下降,更加导致病人用药顺应性较差。因此,目前存在诸多普拉克索贴剂形式的给药方式。透皮给药可以有效地控制药物透过皮肤进入体循环,避免肝脏的首过效应并能维持较长时间的有效血药浓度,降低用药频率,提高患者顺应性,特别适合于帕金森病的长期治疗。
中国专利CN103610666A公开的透皮贴剂所使用的原料药为水溶性的盐酸普拉克索,其脂溶性差,透过皮肤能力较差,且只能维持三天的有效剂量。中国专利CN104510725B公开了一种普拉克索周效透皮贴剂,包括药物储库,防粘层和背衬层三部分,该发明采用亲水性基质混合促渗剂和迭层浇注法制备双层贴片有效解决了多层膜制备中的问题,虽能保证药物在七天内的恒速释,但处方复杂,制备工艺较难。中国专利CN109310526A公开的经皮贴片提供通量速度高于约0.8μg/cm2 /h与低于约10μg/cm2 /h之间,但仅可维持至约40小时。中国专利CN103432104B公开了一种含有普拉克索的透皮贴剂,普拉克索能够以高浓度溶解于混合压敏胶贴剂中不结晶,并可以大于5ug/cm2/h的相对稳定渗透速率持续经皮给药5-7天,但制备的贴剂中药物经皮渗透性能较差。
发明内容
基于上述技术方案,本发明具有的技术效果为:
相对于中国专利CN 104510725A,本发明优势在于:本发明将药物与丙烯酸酯聚合物等辅料制成药物储库,通过控释膜控制药物持续稳定释放,并可以5-20μg/cm2/h的稳定透皮速率持续经皮给药,且制备工艺简单。
本发明的普拉克索透皮贴剂工艺简单,人体与贴剂接触时,里面的普拉克索、丙烯酸共聚物、促渗透剂、增溶剂和结晶抑制剂协同复配,促进皮肤对药物的吸收,提高初始经皮透过量,药物得到高效吸收。
本发明提供一种普拉克索透皮贴剂,其特征在于,由背衬膜、药物储
库层、控释膜、粘合层和防粘层组成。
进一步研究地,所述的贴剂药物储库层组成为:普拉克索占比3~20
重量份,丙烯酸共聚物占比35~82重量份,促渗透剂占比5~20重量份,增溶剂占比5~20重量份,结晶抑制剂5-20重量份。
进一步研究地,所述的促渗剂可选N-甲基吡咯烷酮,薄荷醇,月桂氮
卓酮,肉豆蔻酸异丙酯,丙二醇,柠檬酸三乙酯,油酸,其中的一种或多。
进一步研究地,所述的丙烯酸酯共聚物为商品名为DURO-TAK,商
品名为EUDRAGIT,商品名为PLASTOID的聚合物中的一种或多种。
更进一步研究地,DURO-TAK87-2287、DURO-TAK87-4287、DURO-TAK87-4098、DURO-TAK87-2510、DURO-TAK87-2516、EUDRAGIT E100、EUDRAGIT EPO、EUDRAGIT RL100、EUDRAGITRL PO、EUDRAGIT RS100、EUDRAGIT RS PO、PLASTOID B。优选商品名为DURO-TAK聚合物。
进一步研究地,所述的增溶剂可选丙二醇、甘油、聚乙二醇、聚乙
烯醇、吐温、司盘、中链甘油三脂、单亚油酸甘油酯、单月桂酸丙二醇酯、聚甘油脂肪酸酯、单辛酸丙二醇酯、二乙二醇单乙醚等其中的一种或多种,优选甘油。
进一步研究地,所述的结晶抑制剂可选聚维酮、交联聚维酮、泊洛沙
姆、甘露醇、聚丙二醇、糊精、羟丙基纤维素、羟丙甲纤维素中的一种或几种。
进一步研究地,所述的控释膜为EVA控释膜或聚丙烯膜。
更进一步研究地,优选商品名为Cotran Membranes(3M公司)的EVA
控释膜,包括但不限于型号为9702、9712、9716、9728。
进一步研究地,所述的粘合层由含药储库层中的同种丙烯酸酯共聚物
物、促渗剂、结晶抑制剂组成。
进一步研究地,所述的防粘层为涂二甲基硅油聚酯膜、涂硅氧烷的聚
酯膜、涂碳氟化合物的聚酯膜中的一种。
本发明所述的普拉克索透皮贴剂的制备方法包含以下步骤:
步骤1:药物储库层制备:将处方量的促渗剂、增溶剂、结晶抑制剂溶于溶剂中,搅拌均匀后,加入原料搅拌至溶解,再加入丙烯酸酯共聚物搅拌至均匀,得到药物储库层胶液,将药物储库层胶液涂布于防粘层上,干燥后附上背衬膜,即得;
步骤2:接触粘合层制备:将处方量的促渗剂、结晶抑制剂溶于溶剂中,搅拌均匀后,加入丙烯酸酯共聚物搅拌至均匀,得到接触粘合层,将接触粘合层涂布于防粘层上,干燥后在胶面层上覆盖上控释膜,即得;
步骤3:复合层压和裁切:撕去药物储库层的防粘层,将含药胶层与粘合层的控释膜另一侧覆盖压合,裁切成规格,即得普拉克索透皮贴剂。
有益效果:其药物储库层由普拉克索、丙烯酸共聚物、促渗透剂、增溶剂和结晶抑制剂组成;该贴剂对皮肤无刺激和过敏反应,其中丙烯酸共聚物、促渗透剂、增溶剂和结晶抑制剂协同,显著提高了药物的经皮透过量和生物利用度,通过控释膜控制药物持续稳定释放,并可以5-20μg/cm2/h的稳定透皮速率持续经皮给药,药物的持续时间长,稳态透皮速率高,治疗效果更显著。
附图说明
图1是实施例1的普拉克索透皮贴剂在SD大鼠中的血药浓度曲线图。
具体实施方式
下面以具体实施例对本发明进行说明,特此申明,此处所选实施例仅用于说明和解释本发明,并不用于限定本发明。
聚合物组成及原料药占比具体实施例如表1所示:
表1.
采用上述配方制备普拉克索透皮贴剂,进行体外释放试验,得到24h的累计释放量结果如表2所示:
表2.
由表1,2可知,实施例5为最佳实施例,其聚合物组成及原料药占比为最佳组成和配比。
促渗剂种类具体实施例如表3所示。
表3.
*粘合层促渗剂种类与药物储库层相同
采用上述配方制备普拉克索透皮贴剂,进行离体巴马小香猪皮肤体外透皮试验,得到24h的累计透皮量结果如表4所示:
表4.
由表3,4可知,促渗剂选用N甲基吡咯烷酮为最佳促渗剂选择。
控释膜型号具体实施例:
处方及制备工艺同实施例1,实施例13为型号9702的控释膜,实施例14为型号9712的控释膜,实施例15为型号9716的控释膜。
采用上述配方制备普拉克索透皮贴剂,进行离体巴马小香猪皮肤体外透皮试验,得到24h的累计透皮量结果如表5所示:
表5.
由表5可知,实施例12-15的24h的累计透皮量少于实施例1,可见本发明采用型号为9728的控释膜为最佳型号,实施例1的普拉克索透皮贴剂应用用于大鼠,进行动物体内实验以确认普拉克索透皮贴剂能够达到稳态治疗要求,药时曲线如图所示:
可以看出普拉克索透皮贴剂能够持续稳定释放透过,血药浓度基本维持稳定达7天以上。
对比例1
对比例1与实施例1的不同之处在于,对比例1不添加增溶剂。
对比例2
对比例2与实施例1的不同之处在于,对比例2不添加结晶抑制剂。
对比例3
对比例3与实施例1的不同之处在于,对比例3不添加促渗透剂。
对比例4
对比例4与实施例1的不同之处在于,对比例4不添加丙烯酸共聚物。
采用上述配方制备普拉克索透皮贴剂,进行体外释放试验,得到24h的累计释放量结果如表6所示:
由表6可知,本发明的药物储存层采用由普拉克索、丙烯酸共聚物、促渗透剂、增溶剂和结晶抑制剂组成,具有协同作用,能增加药物的释放量以及药物的稳态释放速率。
最后所应当说明的是,以上实施例仅用于说明本发明的技术方案而非对本发明保护范围进行限制,尽管参照较佳实施例对本发明作了详细说明,本领域的普通技术人员应当理解,可以对本发明的技术方案进行修改或者等同替换,而不脱离本发明技术方案的实质和范围。
Claims (10)
1.一种普拉克索透皮贴剂,其特征在于,由背衬膜、药物储库层、控释膜、粘合层和防粘层组成。
2.根据权利要求1所述的一种普拉克索透皮贴剂,其特征在于,所述的贴剂药物储库层组成为:普拉克索占比3~20重量份,丙烯酸共聚物占比35~82重量份,促渗透剂占比5~20重量份,增溶剂占比5~20重量份,结晶抑制剂5-20重量份。
3.根据权利要求1所述的一种普拉克索透皮贴剂,其特征在于,所述的促渗剂可选N-甲基吡咯烷酮,薄荷醇,月桂氮卓酮,肉豆蔻酸异丙酯,丙二醇,柠檬酸三乙酯,油酸中的一种或多种。
4.根据权利要求1所述的一种普拉克索透皮贴剂,其特征在于,所述的丙烯酸酯共聚物为商品名为DURO-TAK,商品名为EUDRAGIT,商品名为PLASTOID的聚合物中的一种或多种。
5.根据权利要求1所述的一种普拉克索透皮贴剂,其特征在于,所述的增溶剂可选丙二醇、甘油、聚乙二醇、聚乙烯醇、吐温、司盘、中链甘油三脂、单亚油酸甘油酯、单月桂酸丙二醇酯、聚甘油脂肪酸酯、单辛酸丙二醇酯、二乙二醇单乙醚等其中的一种或多种,优选甘油。
6.根据权利要求1所述的一种普拉克索透皮贴剂,其特征在于,结晶抑制剂可选聚维酮、交联聚维酮、泊洛沙姆、甘露醇、聚丙二醇、糊精、羟丙基纤维素、羟丙甲纤维素中的一种或几种。
7.根据权利要求1所述的一种普拉克索透皮贴剂,其特征在于,所述的控释膜为EVA控释膜或聚丙烯膜。
8.根据权利要求1所述的一种普拉克索透皮贴剂,其特征在于,所述的粘合层由含药储库层中的同种丙烯酸酯共聚物物、促渗剂、结晶抑制剂组成。
9.根据权利要求1所述的一种普拉克索透皮贴剂,其特征在于,所述的防粘层为涂二甲基硅油聚酯膜、涂硅氧烷的聚酯膜、涂碳氟化合物的聚酯膜中的一种。
10.根据权利要求1-9任一项所述的一种普拉克索透皮贴剂,其特征在于,所述的普拉克索透皮贴剂的制备方法包含以下步骤:
步骤1:药物储库层制备:将处方量的促渗剂、增溶剂、结晶抑制剂溶于溶剂中,搅拌均匀后,加入原料搅拌至溶解,再加入丙烯酸酯共聚物搅拌至均匀,得到药物储库层胶液,将药物储库层胶液涂布于防粘层上,干燥后附上背衬膜,即得;
步骤2:接触粘合层制备:将处方量的促渗剂、结晶抑制剂溶于溶剂中,搅拌均匀后,加入丙烯酸酯共聚物搅拌至均匀,得到接触粘合层,将接触粘合层涂布于防粘层上,干燥后在胶面层上覆盖上控释膜,即得;
步骤3:复合层压和裁切:撕去药物储库层的防粘层,将含药胶层与粘合层的控释膜另一侧覆盖压合,裁切成规格,即得普拉克索透皮贴剂。
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