CN112587508A - 一种米拉贝隆透皮贴剂 - Google Patents

一种米拉贝隆透皮贴剂 Download PDF

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CN112587508A
CN112587508A CN202011511520.0A CN202011511520A CN112587508A CN 112587508 A CN112587508 A CN 112587508A CN 202011511520 A CN202011511520 A CN 202011511520A CN 112587508 A CN112587508 A CN 112587508A
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mirabegron
sensitive adhesive
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张洪志
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Beijing Junhewei Pharmaceutical Technology Co Ltd
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    • A61K31/00—Medicinal preparations containing organic active ingredients
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    • 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
    • A61K31/426—1,3-Thiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • 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
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    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
    • A—HUMAN NECESSITIES
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    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
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    • 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
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7069—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide
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Abstract

一种米拉贝隆透皮贴剂，包含储药层、背衬层和防粘层，所述储药层由米拉贝隆、促渗剂和压敏胶基质组成。储药层中米拉贝隆的重量百分比含量为2％～4％。储药层中促渗剂的重量百分比含量为3％～5％，所述促渗剂为重量比10:2～4:0.5～1.5的二甲基亚砜、油酸和月桂氮卓酮。所述压敏胶基质为硅酮压敏胶基质。

Description

一种米拉贝隆透皮贴剂
技术领域
本发明涉及一种经皮给药制剂，尤其是涉及一种以米拉贝隆为活性成分的透皮贴剂。
背景技术
米拉贝隆(CAS:223673-61-8，Mirabegron)由日本安斯泰来(Astellas)制药公司开发，于2011年9月16日在日本上市，2012年6月28日经美国食品药品监督管理Chemicalbook局(FDA)批准用于治疗成年人膀胱过度活动症(OAB)。米拉贝隆是第一个用于治疗膀胱过度活动症的β3肾上腺素受体激动剂类药物。主要通过作用于β3受体使膀胱逼尿肌松弛并增加其稳定性。现有的米拉贝隆制剂为50mg的缓释片剂，其产生最常见的不良反应为***和心动过速。且肝、肾损伤患者使用米拉贝隆也受到限制。透皮贴剂作为一种经皮吸收制剂，可以通过皮肤贴敷给药，活性成分经皮肤吸收进入全身血液循环，可以延长作用时间，减少用药次数，用药方便，避免首过效应，减少胃肠道刺激。为了降低米拉贝隆的副作用，采用经皮给药方式提高给药效果，以减少副作用的发生成为现有技术中亟待解决的问题。
发明内容
为解决前述技术问题，本发明采取的技术方案是：
提供了一种米拉贝隆透皮贴剂，其特征是所述透皮贴剂包含储药层、背衬层和防粘层，所述储药层由米拉贝隆、促渗剂和压敏胶基质组成。
所述的一种米拉贝隆透皮贴剂，其特征是所述储药层中米拉贝隆的重量百分比含量为2％～4％。
所述的一种米拉贝隆透皮贴剂，其特征是所述储药层中促渗剂的重量百分比含量为3％～5％，所述促渗剂为重量比10:2～4：0.5～1.5的二甲基亚砜、油酸和月桂氮卓酮，所述二甲基亚砜、油酸和月桂氮卓酮的重量比优选为10:2.5～3.5:0.8～1.2。
所述一种米拉贝隆透皮贴剂，其特征是所述压敏胶基质为硅酮压敏胶基质。
所述一种米拉贝隆透皮贴剂的制备方法，包括以下步骤：
1)将二甲基亚砜、油酸和月桂氮卓酮酯混合，加入处方量米拉贝隆，搅拌至溶解。
2)将步骤1)溶液加入硅酮压敏胶基质，搅拌均匀，涂布于防粘层上，于65-85℃干燥后与背衬层复合，切割成贴剂，即得。
本发明提供的一种米拉贝隆透皮贴剂，优选了特定比例的二甲基亚砜、油酸和月桂氮卓酮作为促渗剂体系，并将上述促渗剂体系与优选的硅酮压敏胶结合，得到了一种米拉贝隆透皮贴剂。本发明提供的透皮贴剂，能够延长米拉贝隆在体内维持有效浓度的持续时间以减少用药次数。同时透皮贴剂还具有用药方便，避免首过效应，减少胃肠道刺激的优点。
具体实施方式
所有实施例中的百分比均为重量百分含量
实施例1
米拉贝隆2％
促渗剂总用量3％，二甲基亚砜、油酸和月桂氮卓酮的重量比为10:2:0.5；余量的硅酮压敏胶基质，
配制方法如下
1)将二甲基亚砜、油酸和月桂氮卓酮混合，加入处方量米拉贝隆，搅拌至溶解。
2)将步骤1)溶液加入硅酮压敏胶基质，搅拌均匀，涂布于防粘层上，于65-85℃干燥后与背衬层复合，切割成贴剂，即得。
实施例2
米拉贝隆3％
促渗剂总用量4％，二甲基亚砜、油酸和月桂氮卓酮的重量比为10:4:1.5；余量的硅酮压敏胶基质，
配制方法如下
1)将二甲基亚砜、油酸和月桂氮卓酮混合，加入处方量米拉贝隆，搅拌至溶解。
2)将步骤1)溶液加入硅酮压敏胶基质，搅拌均匀，涂布于防粘层上，于65-85℃干燥后与背衬层复合，切割成贴剂，即得。
实施例3
米拉贝隆5％
促渗剂总用量3％二甲基亚砜、油酸和月桂氮卓酮的重量比为10:2.5:0.8；余量的硅酮压敏胶基质，
配制方法如下
1)将二甲基亚砜、油酸和月桂氮卓酮混合，加入处方量米拉贝隆，搅拌至溶解。
2)将步骤1)溶液加入硅酮压敏胶基质，搅拌均匀，涂布于防粘层上，于65-85℃干燥后与背衬层复合，切割成贴剂，即得。
实施例4
米拉贝隆2％
促渗剂总用量5％，二甲基亚砜、油酸和月桂氮卓酮的重量比为10:.3.5:1.2；余量的硅酮压敏胶基质，
配制方法如下
1)将二甲基亚砜、油酸和月桂氮卓酮混合，加入处方量米拉贝隆，搅拌至溶解。
2)将步骤1)溶液加入硅酮压敏胶基质，搅拌均匀，涂布于防粘层上，于65-85℃干燥后与背衬层复合，切割成贴剂，即得。
实施例5
米拉贝隆3％
促渗剂总用量3％，二甲基亚砜、油酸和月桂氮卓酮的重量比为10:.3:1；余量的硅酮压敏胶基质，
配制方法如下
1)将二甲基亚砜、油酸和月桂氮卓酮混合，加入处方量米拉贝隆，搅拌至溶解。
2)将步骤1)溶液加入硅酮压敏胶基质，搅拌均匀，涂布于防粘层上，于65-85℃干燥后与背衬层复合，切割成贴剂，即得。
通过对实施例1～5的贴剂进行考察，可知其含量均匀度、释放度、初黏力、持黏力、和剥离强度均符合中国药典2015版二部附录IV贴剂中的相关规定。
药理实施例1一种米拉贝隆透皮贴剂的体外经皮渗透实验。
采用立式扩散池，有效扩散面积为2.8cm2，所用皮肤为去毛猪耳朵皮肤，皮肤厚度约为约600μm。将贴剂贴于去毛猪耳朵皮肤的角质层一侧，置于扩散池与接收池之间，角质层朝向扩散池，真皮层朝向接收池。接收池体积为6.5mL，加满pH7.4PBS并排除气泡，置于循环水浴磁力搅拌池中，磁子转速设为300r/min，水浴温度为37℃。透皮开始后第2h、4h、6h、8h、10h、12h、14h、24h取样1mL，取样后立即补充新鲜的接收液，将取样液用0.45μm微孔滤膜滤过后用高效液相色谱法测定米拉贝隆的浓度，计算经皮渗透速率和累积渗透量，结果如下表所示(means±SD，n＝3)
组别 经皮渗透速率(μg.cm<sup>-2.</sup>h<sup>-1</sup>) 累计渗透量(μg.cm<sup>-2</sup>)
实施例1 0.75±0.25 9.78±0.79
实施例2 0.89±0.19 11.41±0.91
实施例3 0.98±0.23 12.59±0.89
实施例4 0.89±0.18 11.61±0.98
实施例5 1.19±0.16 14.35±0.85
实验结果表明，本发明提供的透皮贴剂，在优选了压敏胶基质和促渗剂的情况下，能够实现米拉贝隆的体外透皮给药。

Claims (5)

1.一种米拉贝隆透皮贴剂，其特征是所述透皮贴剂包含储药层、背衬层和防粘层，所述储药层由米拉贝隆、促渗剂和压敏胶基质组成。
2.如权利要求1所述的一种米拉贝隆透皮贴剂，其特征是所述储药层中米拉贝隆的重量百分比含量为2％～4％。
3.如权利要求2所述的一种米拉贝隆透皮贴剂，其特征是所述储药层中促渗剂的重量百分比含量为3％～5％，所述促渗剂为重量比10:2～4:0.5～1.5的二甲基亚砜、油酸和月桂氮卓酮。
4.如权利要求3所述的一种米拉贝隆透皮贴剂，其特征是所述二甲基亚砜、油酸和月桂氮卓酮的重量比优选为10:2.5～3.5:0.8～1.2。
5.如权利要求1～4任一所述的一种米拉贝隆透皮贴剂，其特征是所述压敏胶基质为硅酮压敏胶基质。
CN202011511520.0A 2020-12-20 2020-12-20 一种米拉贝隆透皮贴剂 Pending CN112587508A (zh)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022174310A1 (en) * 2021-02-22 2022-08-25 The University Of Sydney Wound healing compositions
WO2023187116A1 (en) * 2022-03-30 2023-10-05 Rheinische Friedrich-Wilhelms-Universität Bonn Mirabegron formulation

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022174310A1 (en) * 2021-02-22 2022-08-25 The University Of Sydney Wound healing compositions
WO2023187116A1 (en) * 2022-03-30 2023-10-05 Rheinische Friedrich-Wilhelms-Universität Bonn Mirabegron formulation

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