CN107007574A - 一种酮洛芬巴布膏 - Google Patents
一种酮洛芬巴布膏 Download PDFInfo
- Publication number
- CN107007574A CN107007574A CN201710342957.8A CN201710342957A CN107007574A CN 107007574 A CN107007574 A CN 107007574A CN 201710342957 A CN201710342957 A CN 201710342957A CN 107007574 A CN107007574 A CN 107007574A
- Authority
- CN
- China
- Prior art keywords
- ketoprofen
- phase component
- oil
- water
- filler
- 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.)
- Pending
Links
Classifications
-
- 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
- A61K9/7038—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
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
- A61K9/7061—Polyacrylates
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- 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
-
- 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
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
一种酮洛芬巴布膏,其特征是所述由背衬层、保护层和药物储库组成,所述药物储库由以下重量百分比的组分组成:作为活性成分的酮洛芬0.5%~3%;油相成分5~10%,所述油相成分由质量比为1:0.5~0.6的癸酸甘油酯和十六醇组成,酮洛芬分散于油相成分中;作为水相成分的部分中和聚丙烯酸钠5‑10%,丙三醇20~30%,聚乙二醇4000 5%~10%,卡波姆980 0.5%~1.5%、羟丙基甲基纤维素1.5~3%,甘羟铝0.2%~0.4%,依地酸钙钠0.1%~0.3%;L‑精氨酸0.5~1%,填充剂1~3%及余量的水;水相成分与水形成水凝胶,填充剂分散填充于水凝胶中,油相成分乳化分散于水凝胶中形成药物储库。
Description
技术领域
本发明涉及酮洛芬巴布膏。
背景技术
酮洛芬(CAS:22071-15-4)即酮基布洛芬,是一种非甾体抗炎药,具有消炎镇痛等作用,临床上可以用于局部炎症的治疗,现有的酮洛芬局部制剂为酮洛芬凝胶(有效成分含量0.25%),在临床治疗时,由于局部炎症的持续性,需现有的酮洛芬凝胶由于难于持续稳定的释放有效成分而影响了治疗效果,合用药的临床需要,提供一种能够快速起效,并实现持续长时间稳定释药的酮洛芬巴布膏成为现有技术中亟待解决的问题。巴布膏(Cataplasm)系指将药物溶解或混合于水溶性高分子材料基质中,涂布于被衬材料上,供皮肤贴敷使用的一种新型经皮给药剂型。与普通的外用药物制剂相比巴布膏具有载药量大,对水溶性组分和低离子强度成分的承载能力较强;含水量较高,能够加强皮肤中的水合作用以促进药物经皮透过,且对皮肤无过敏反应和刺激作用,剥离时无拉痛感且无残留等优点,但也正是由于巴布膏载药量大,敷贴时间较长,在进行巴布膏处方筛选需要兼顾促进药物透皮吸收与使其药物释放均匀,因此提供一种能够快速起效,并实现持续长时间稳定释药的酮洛芬巴布剂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,本发明提供了一种酮洛芬巴布膏,其特征是所述巴布膏由背衬层、保护层和药物储库组成,所述药物储库由以下重量百分比的组分组成:
作为活性成分的酮洛芬0.5%~3%;
油相成分5~10%,所述油相成分由质量比为1:0.5~0.6的癸酸甘油酯和十六醇组成;酮洛芬分散于油相成分中
作为水相成分的部分中和聚丙烯酸钠5-10%,丙三醇20~30%,聚乙二醇40005%~10%,卡波姆980 0.5%~1.5%、羟丙基甲基纤维素(HPMC)1.5~3%,甘羟铝0.2%~0.4%,依地酸钙钠0.1%~0.3%;L-精氨酸0.5~1%,填充剂1~3%及余量的水;水相成分与水形成水凝胶,填充剂分散填充于水凝胶中,油相成分乳化分散于水凝胶中形成药物储库。
所述部分中和聚丙烯酸钠优选为NP700;所述填充剂为高岭土。
在研究中发现,发明提供的酮洛芬巴布膏,通过筛选处方,得到一种既能够快速释放有效成分,又能在12h的敷贴时间内持续释放有效成分的酮洛芬巴布膏处方,在对处方进行研究中我们发现,本发明优选的油相成分配比与水相成分中聚乙二醇4000及L-精氨酸的配比是决定酮洛芬巴布膏有效成分释放特性的决定组分。正是上述组分的配合,解决了酮洛芬巴布膏在长时间(12h)敷贴下的快速起效与长效释放问题。
具体实施方式
本发明实施例中的酮洛芬巴布剂按照以下方法制备
1)油相成分配制,将油相成分的原料加热至50-70℃,加入酮洛芬微粉,搅拌分散得到油相液(1)
2)将水相成分分散于水得到水凝胶,将水凝胶加热至50~70℃后在用均混器搅拌的同时加入温度为50-70℃的油相液(1),油相加入后再加入填充剂后搅拌均匀;经静置真空脱气后得到膏状的药物储库;
3)将药物储库涂布于背衬层上,并在上表面贴附保护层。得到酮洛芬巴布膏。得到的酮洛芬巴布剂的规格为3g药物储库/34cm2背衬层
所有实施例中,所述部分中和聚丙烯酸钠为NP700(Showa Denko kk生产),保湿剂为丙三醇,填充剂为2%高岭土。
实施例1~6的配方见下表
对照例1~6的配方见下表
与实施例1~6相比,对照例1~6的配方中未加入聚乙二醇4000(对照例1、2)或L-精氨酸(对照例3、4)以及改变油相成分两种组分的配比(对照例5、6)
通过对实施例1~6得到的巴布剂进行考察,可知其外观平整、均匀,药物储库膏体光滑;成型性、含膏量、初粘力、粘附性以及膜残留量均符合要求。
药理实施例1体外释放实验
按照中国药典2010版第二部附录XD中释放度测定法中第三法(桨碟法,用于透皮贴剂)中提供的方法对实施例1~6得到的巴布贴紧急释放度测定。具体方法如下
试验以生理盐水为释放介质,将释放介质加入溶出杯内,预温至(32±0.5℃)将巴布膏除去保护层,裁剪成2.5cmx7.5cm大小,平放入透析袋(截留分子量14,000)中,释放面朝上,置于两层碟片之间,使碟片边缘夹住透析袋两端,再用皮筋缠绕固定,以固定碟片。于10min、20min、30min、45min、60min、90min、2h、2.5h、3h和4h分别从溶出杯内取样6mL,并补充等体积(32+0.5)℃新鲜释放介质,平行试验6片,取平均值计算。经过检测表明,本申请实施例中的巴布膏的体外释放度均在2h达到90%以上。
药理实施例2,体外透皮实验
采用改良Franz扩散池法,以离体3月龄大鼠腹部皮肤为屏障,用实施例1~6及对照例1~6制备得到的巴布膏进行进行体外透皮试验。具体实验方法为:
取3月龄健康大鼠麻醉处死后,用剪刀除尽腹部毛,取下无损伤的皮肤,除去皮下组织,洗净后分别固定于Franz扩散池的释放口,接受室中加入pH7.4磷酸缓冲液作释放介质,保持内皮层与溶液密切接触。将揭去保护层的巴布剂贴于皮肤上,调节水浴使外层套层温度恒定于(32±0.5)℃,搅拌速度为100rpm,分别于0、1h、2h、4h、6h、8h、12h小时吸取释放介质4ml,同时补加等量PBS液。计算累计吸收百分数(即累计透过的酮洛芬占药物储库中酮洛芬总量的百分比分数)结果如下表
上述结果表明,本发明提供的酮洛芬巴布膏,在进行体外透皮吸收实验时,12h的累计药物透过率均高于75%,且药物释放率随时间增加速度较为均匀、说明本发明采用的技术方案中,通过分别优选油相成分与水相成分的组成即提高了酮洛芬巴布剂的透皮吸收速度,有能够控制药物在整个敷贴时间段内较为均匀的释放。在处方筛选时我们发现,采用了基于癸酸甘油酯的油相成分处方,尤其是优选了癸酸甘油酯与十六醇的配比,并在水相中加入处方量的聚乙二醇4000和L-精氨酸后,实现酮洛芬快速均匀释放。通过以对照例进行对照实验表明,当改变癸酸甘油酯与十六醇的配比和不加入聚乙二醇4000或L-精氨酸均会影响巴布膏的酮洛芬释放效果,且在进一步实验中我们还发现,该辅料配方与酮洛芬均有关联性,当改变活性成分时,即使采用同样的辅料配方,也会无法产生本发明提供的酮洛芬巴布剂具有的快速均匀释药效果。
Claims (3)
1.一种酮洛芬巴布膏,其特征是所述巴布膏由背衬层、保护层和药物储库组成,所述药物储库由以下重量百分比的组分组成:作为活性成分的酮洛芬0.5%~3%;油相成分5~10%,所述油相成分由质量比为1:0.5~0.6的癸酸甘油酯和十六醇组成,酮洛芬分散于油相成分中;作为水相成分的部分中和聚丙烯酸钠5-10%,丙三醇20~30%,聚乙二醇40005%~10%,卡波姆980 0.5%~1.5%、羟丙基甲基纤维素1.5~3%,甘羟铝0.2%~0.4%,依地酸钙钠0.1%~0.3%;L-精氨酸0.5~1%,填充剂1~3%及余量的水;水相成分与水形成水凝胶,填充剂分散填充于水凝胶中,油相成分乳化分散于水凝胶中形成药物储库。
2.如权利要求1所述的一种酮洛芬巴布膏,其特征是所述部分中和聚丙烯酸钠优选为NP700。
3.如权利要求1所述的一种酮洛芬巴布膏,其特征是所述填充剂为高岭土。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710342957.8A CN107007574A (zh) | 2017-05-16 | 2017-05-16 | 一种酮洛芬巴布膏 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710342957.8A CN107007574A (zh) | 2017-05-16 | 2017-05-16 | 一种酮洛芬巴布膏 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN107007574A true CN107007574A (zh) | 2017-08-04 |
Family
ID=59449770
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201710342957.8A Pending CN107007574A (zh) | 2017-05-16 | 2017-05-16 | 一种酮洛芬巴布膏 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN107007574A (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108653262A (zh) * | 2018-06-29 | 2018-10-16 | 佛山市南海东方澳龙制药有限公司 | 酮洛芬外用药物及其制备方法和应用 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6423697B1 (en) * | 1999-01-14 | 2002-07-23 | Mark Friedman | Intraoral topical anti-inflammatory treatment for relief of migraine, tension-type headache, post-traumatic headache, facial pain, and cervical-muscle spasm |
CN1813702A (zh) * | 2005-11-29 | 2006-08-09 | 中国人民解放军第二军医大学 | 一种酮洛芬巴布剂及其制备方法 |
CN105287361A (zh) * | 2015-11-13 | 2016-02-03 | 北京泰德制药股份有限公司 | 含有非甾体抗炎药微乳的皮肤外用制剂 |
-
2017
- 2017-05-16 CN CN201710342957.8A patent/CN107007574A/zh active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6423697B1 (en) * | 1999-01-14 | 2002-07-23 | Mark Friedman | Intraoral topical anti-inflammatory treatment for relief of migraine, tension-type headache, post-traumatic headache, facial pain, and cervical-muscle spasm |
CN1813702A (zh) * | 2005-11-29 | 2006-08-09 | 中国人民解放军第二军医大学 | 一种酮洛芬巴布剂及其制备方法 |
CN105287361A (zh) * | 2015-11-13 | 2016-02-03 | 北京泰德制药股份有限公司 | 含有非甾体抗炎药微乳的皮肤外用制剂 |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108653262A (zh) * | 2018-06-29 | 2018-10-16 | 佛山市南海东方澳龙制药有限公司 | 酮洛芬外用药物及其制备方法和应用 |
CN108653262B (zh) * | 2018-06-29 | 2021-02-26 | 佛山市南海东方澳龙制药有限公司 | 酮洛芬外用药物及其制备方法和应用 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN106667970B (zh) | 氟比洛芬巴布剂 | |
CN102939075A (zh) | 经皮吸收促进剂及其外部皮肤制剂 | |
CN109806244B (zh) | 一种含有氟比洛芬的皮肤外用制剂 | |
CN103655710B (zh) | 一种马钱子总碱微乳及其制剂及制备方法 | |
US20120171274A1 (en) | Transdermal patch | |
MX2015000541A (es) | Formulaciones de diclofenaco. | |
CN107157962A (zh) | 氟比洛芬巴布剂 | |
PL194291B1 (pl) | Sposób wytwarzania układu do przezskórnego podawania leku | |
CN102697755A (zh) | 一种新型左旋肉碱水凝胶贴剂及其制备方法 | |
CN106822065A (zh) | 一种氟比洛芬巴布剂 | |
CN102657602B (zh) | 3,5-二羟基-4-异丙基二苯乙烯壳聚糖凝胶剂及其制备方法 | |
CN1647803A (zh) | 一种外用消炎镇痛的中药组合物贴膏 | |
CN107007574A (zh) | 一种酮洛芬巴布膏 | |
CN109172546A (zh) | 利多卡因凝胶贴膏 | |
CN108498491A (zh) | 一种奥昔布宁经皮吸收贴剂及其制备和应用 | |
CN106822326A (zh) | 新型中药贴剂颈痛贴膏及其制备方法 | |
CN102772417B (zh) | 包载睾酮的自黏性弹性体基质的周效经皮贴剂及制法 | |
PT88440B (pt) | Processo para a preparacao de emplastros contendo salbutamol | |
PT1865931E (pt) | Emplastro transdérmico | |
CN101612141B (zh) | 丁丙诺啡贴剂 | |
CN106822049A (zh) | 新型化药贴剂酮洛芬贴片及其制备方法 | |
CN106214624A (zh) | 用于治疗婴儿浅表血管瘤的马来酸噻吗洛尔制剂及其应用 | |
CN105147642A (zh) | 一种含福莫特罗或其富马酸盐的透皮贴剂 | |
CN107951864A (zh) | 氟比洛芬巴布剂 | |
CN113476489B (zh) | 一种川芎挥发油痛经贴膏剂及其制备方法和用途 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20190515 Address after: 102629 Second Floor and Third Floor of Building 12, No. 50 Huatuo Road, Daxing Biomedical Base, Beijing (Liandong U Valley Biomedical Science and Technology Park) Applicant after: BEIJING MINGZE ZHONGHE MEDICAMENT RESEARCH CO., LTD. Address before: 528139 No. 20, Dushugang New Village Team, Lubao Town, Sanshui District, Foshan City, Guangdong Province Applicant before: Cai Zhihao |
|
TA01 | Transfer of patent application right | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20170804 |
|
RJ01 | Rejection of invention patent application after publication |