JPH01279831A - Indomethacin ointment - Google Patents
Indomethacin ointmentInfo
- Publication number
- JPH01279831A JPH01279831A JP10850488A JP10850488A JPH01279831A JP H01279831 A JPH01279831 A JP H01279831A JP 10850488 A JP10850488 A JP 10850488A JP 10850488 A JP10850488 A JP 10850488A JP H01279831 A JPH01279831 A JP H01279831A
- Authority
- JP
- Japan
- Prior art keywords
- indomethacin
- weight
- ointment
- component
- homogenizing
- 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
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 title claims abstract description 55
- 229960000905 indomethacin Drugs 0.000 title claims abstract description 27
- 239000002674 ointment Substances 0.000 title claims abstract description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000002904 solvent Substances 0.000 claims abstract description 11
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims abstract description 10
- DNTGGZPQPQTDQF-XBXARRHUSA-N crotamiton Chemical compound C/C=C/C(=O)N(CC)C1=CC=CC=C1C DNTGGZPQPQTDQF-XBXARRHUSA-N 0.000 claims abstract description 9
- 229960003338 crotamiton Drugs 0.000 claims abstract description 9
- 239000002562 thickening agent Substances 0.000 claims abstract description 7
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000003262 carboxylic acid ester group Chemical class [H]C([H])([*:2])OC(=O)C([H])([H])[*:1] 0.000 claims abstract 2
- 239000003002 pH adjusting agent Substances 0.000 claims description 3
- 239000000203 mixture Substances 0.000 abstract description 8
- 230000000694 effects Effects 0.000 abstract description 5
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 abstract description 3
- 239000004615 ingredient Substances 0.000 abstract description 3
- 231100000245 skin permeability Toxicity 0.000 abstract description 3
- 150000005215 alkyl ethers Chemical class 0.000 abstract description 2
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 2
- 230000001747 exhibiting effect Effects 0.000 abstract description 2
- 238000004090 dissolution Methods 0.000 abstract 2
- 230000000202 analgesic effect Effects 0.000 abstract 1
- 230000001754 anti-pyretic effect Effects 0.000 abstract 1
- 238000002156 mixing Methods 0.000 abstract 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 11
- 239000008213 purified water Substances 0.000 description 11
- 210000003491 skin Anatomy 0.000 description 8
- FFJCNSLCJOQHKM-CLFAGFIQSA-N (z)-1-[(z)-octadec-9-enoxy]octadec-9-ene Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCCCCCCC\C=C/CCCCCCCC FFJCNSLCJOQHKM-CLFAGFIQSA-N 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- HBTAOSGHCXUEKI-UHFFFAOYSA-N 4-chloro-n,n-dimethyl-3-nitrobenzenesulfonamide Chemical compound CN(C)S(=O)(=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 HBTAOSGHCXUEKI-UHFFFAOYSA-N 0.000 description 4
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 4
- 229920002125 Sokalan® Polymers 0.000 description 4
- 150000001733 carboxylic acid esters Chemical class 0.000 description 4
- 229940031578 diisopropyl adipate Drugs 0.000 description 4
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 4
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 4
- CMCBDXRRFKYBDG-UHFFFAOYSA-N 1-dodecoxydodecane Chemical compound CCCCCCCCCCCCOCCCCCCCCCCCC CMCBDXRRFKYBDG-UHFFFAOYSA-N 0.000 description 3
- -1 alcohol ester Chemical class 0.000 description 3
- 210000002615 epidermis Anatomy 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 208000025747 Rheumatic disease Diseases 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- SEOVTRFCIGRIMH-UHFFFAOYSA-N indole-3-acetic acid Chemical group C1=CC=C2C(CC(=O)O)=CNC2=C1 SEOVTRFCIGRIMH-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000000552 rheumatic effect Effects 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- FDCJDKXCCYFOCV-UHFFFAOYSA-N 1-hexadecoxyhexadecane Chemical compound CCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCC FDCJDKXCCYFOCV-UHFFFAOYSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 201000005569 Gout Diseases 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000001760 anti-analgesic effect Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000001139 anti-pruritic effect Effects 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- DNTGGZPQPQTDQF-UHFFFAOYSA-N crotamiton Chemical compound CC=CC(=O)N(CC)C1=CC=CC=C1C DNTGGZPQPQTDQF-UHFFFAOYSA-N 0.000 description 1
- 239000005331 crown glasses (windows) Substances 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 210000004207 dermis Anatomy 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 229940031569 diisopropyl sebacate Drugs 0.000 description 1
- XFKBBSZEQRFVSL-UHFFFAOYSA-N dipropan-2-yl decanedioate Chemical compound CC(C)OC(=O)CCCCCCCCC(=O)OC(C)C XFKBBSZEQRFVSL-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000008311 hydrophilic ointment Substances 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 239000003617 indole-3-acetic acid Substances 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 230000007659 motor function Effects 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- KSCKTBJJRVPGKM-UHFFFAOYSA-N octan-1-olate;titanium(4+) Chemical compound [Ti+4].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-] KSCKTBJJRVPGKM-UHFFFAOYSA-N 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】 [産業上の利用分野] 本発明はインドメタシン軟膏剤に関するものである。[Detailed description of the invention] [Industrial application field] The present invention relates to indomethacin ointment.
[従来の技術]
インドメタシンとは、次の式
で表わされるように1−(p−クロロベンゾイル)−5
−メトキシ−2−メチルインドール−3−酢酸であり、
1961年より合成開発されたインドール酢酸系の消炎
乃至鎮痛解熱薬である。数多くのインドール系化合物な
スクリーニングした結果得られたもので、その作用は、
現在でも非ステロイド系消炎薬の中で最も強力といわれ
ており、主として関節リューマチや変形性関節炎、痛風
等リューマチ性又は非リューマチ性炎症性疾患の患者に
対し投与され、疼痛の軽減や炎症の鎮静、運動機能の改
善等の著効を奏することで良く知られている。[Prior Art] Indomethacin is 1-(p-chlorobenzoyl)-5 as represented by the following formula.
-methoxy-2-methylindole-3-acetic acid,
It is an indoleacetic acid-based anti-inflammatory, analgesic, and antipyretic drug that was synthesized and developed in 1961. This was obtained as a result of screening a large number of indole compounds, and its action is as follows.
Even today, it is said to be the most powerful non-steroidal anti-inflammatory drug, and is mainly administered to patients with rheumatic or non-rheumatic inflammatory diseases such as rheumatoid arthritis, osteoarthritis, and gout, to reduce pain and calm inflammation. It is well known for its remarkable effects such as improving motor function.
このインドメタシンは、当初経口投与により整形外科等
の診療科において使用されていたところ、食欲不振、嘔
吐、消化不良、下痢、更には胃潰瘍等が副作用として問
題視されたため、別の剤形として坐薬が開発され、経口
薬であるカプセル剤と共に使用されていたが、この坐薬
に関しても、軽減されたとはい^やはり上記と同様の副
作用が発生するという難点が指摘されていた。This indomethacin was initially used orally in clinical departments such as orthopedics, but problems such as anorexia, vomiting, indigestion, diarrhea, and even gastric ulcers were seen as side effects, so a suppository was developed as a different dosage form. This suppository was developed and used together with an oral drug capsule, but it was pointed out that this suppository also had the same drawbacks as the above, even though it was alleviated.
一方、上記慢性関節リューマチ等は局所性の疾患である
から、局所的に適用可能な剤形が開発されれば好適であ
るばかりか、患者にとって便利であり、このような観点
からもインドメタシンを主剤とする軟膏製剤の開発が要
望されるに至った。On the other hand, since chronic rheumatoid arthritis is a localized disease, it would be desirable if a locally applicable dosage form could be developed, and it would also be convenient for patients. There has been a demand for the development of an ointment formulation.
[発明が解決しようとする課題]
然しながら、本発明の発明者らが実験を重ねて得た知見
によれば、インドメタシンは、水にほとんど溶けず、又
、軟膏剤に通常使用される基剤にも溶けにくいという溶
解度の点その他の理由により、従来利用されている通常
の軟膏剤の製造方法によっては、上記優れた効果を発揮
することのできる製剤を得ることができず、従って上記
要望に応えられないおそれのあることが判明した。[Problems to be Solved by the Invention] However, according to the findings obtained through repeated experiments by the inventors of the present invention, indomethacin is hardly soluble in water and is insoluble in bases commonly used in ointments. Due to the solubility of ointment, which is difficult to dissolve, and other reasons, it has not been possible to obtain a preparation that can exhibit the above-mentioned excellent effects by the conventional manufacturing method of ointments, and therefore, it has not been possible to obtain a preparation that can exhibit the above-mentioned excellent effects. It has been found that there is a risk that it may not be possible.
本発明は上記の点を踏まえ、更に研究が進められた結果
完成されたものであり、その目的とするところは、皮膚
浸透性に優れ、インドメタシンの有する薬理効果を十分
に発揮させることのできる軟膏剤を提供することにある
。The present invention was completed as a result of further research based on the above points, and its purpose is to provide an ointment that has excellent skin permeability and can fully demonstrate the pharmacological effects of indomethacin. The aim is to provide agents for
[課題を解決するための手段]
上記の目的を達成するために本発明が採用した主たる構
成は、
インドメタシン0.5〜2.0重量%と、粘稠剤1.5
〜4.5重量%と、
グリコール成分0.1〜2.5重量%
カルボン酸エステル成分2.5〜7.5重量%
クロタミトン0.5〜1.5重量%
低級アルコール成分20〜6o重量%
水20〜60重量%
を含む溶剤と、
溶解補助剤5〜10重量%
とからなり、これらを均一化することにより得られるこ
とを特徴とするものである。[Means for Solving the Problems] The main components adopted by the present invention to achieve the above object are: 0.5 to 2.0% by weight of indomethacin and 1.5% by weight of a thickening agent.
-4.5% by weight, glycol component 0.1-2.5% by weight, carboxylic acid ester component 2.5-7.5% by weight, crotamiton 0.5-1.5% by weight, lower alcohol component 20-6% by weight. It consists of a solvent containing 20 to 60% by weight of water and 5 to 10% by weight of a solubilizing agent, and is characterized by being obtained by homogenizing these.
ここでインドメタシンとは、既に説明したように、次の
式
で表わされる1−(p−クロロベンゾイル)−5−メト
キシ−2−メチルインドール−3−酢酸である。As already explained, indomethacin is 1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid represented by the following formula.
又、粘稠剤とは、本発明軟膏剤における溶剤の主成分た
る低級アルコール−水の系をゲル化するもので、例えば
カルボキシビニルポリマーやヒドロキシプロピルセルロ
ース、ヒドロキシエチルセルロース、メチルセルロース
等からなる群より選ばれた一種以上のものが使用される
。The thickening agent is one that gels the lower alcohol-water system which is the main component of the solvent in the ointment of the present invention, and is selected from the group consisting of carboxyvinyl polymer, hydroxypropyl cellulose, hydroxyethyl cellulose, methyl cellulose, etc. One or more of the following are used.
一方、グリコール成分としては、プロピレングリコール
、1.3−ブチレングリコール、ポリエチレングリコー
ル等からなる群より選ばれた一種以上のものが使用され
、これがエタノール等の低級アルコール成分及び水とと
もに本発明軟膏剤の溶剤を構成するが、この溶剤には他
に、カルボン酸エステル成分及びクロタミトンが含まれ
ている。On the other hand, the glycol component used is one or more selected from the group consisting of propylene glycol, 1,3-butylene glycol, polyethylene glycol, etc., and this is used together with a lower alcohol component such as ethanol and water in the ointment of the present invention. This solvent also contains a carboxylic acid ester component and crotamiton.
即ち、このカルボン酸エステル成分は、インドメタシン
の皮膚内への移行を促進するためのもので、例えば、C
6乃至C3゜のジカルボン酸のC意、Csアルコールエ
ステルであり、具体的には、アジピン酸ジイソプロピル
、セバシン酸ジイソプロピル、セバシン酸ジエチル等か
らなる群より選ばれた一種以上のものが使用され、一方
のクロタミトンは、N−エチル−N−(2−メチルフェ
ニル)−2−ブテン酸アミドであり、−殻内には鎮痒作
用を発揮するものとして知られている。That is, this carboxylic acid ester component is for promoting the transfer of indomethacin into the skin, and for example, C.
C or Cs alcohol ester of dicarboxylic acid having 6 to C3°, specifically, one or more selected from the group consisting of diisopropyl adipate, diisopropyl sebacate, diethyl sebacate, etc., are used; Crotamiton is N-ethyl-N-(2-methylphenyl)-2-butenoic acid amide, and is known to exhibit an antipruritic effect within its shell.
更に、本発明においてはインドメタシンの溶解度を増加
させるための溶解補助剤が配合されており、これは、酸
化エチレンの付加モル数が7から15のC1,からC1
8アルキルエーテル及び酸化エチレンの付加モル数が6
から10のCI2からCI6脂肪酸エステルであり、こ
れらからなる群より選ばれた一種以上のものが使用され
る。具体的には、ポリオキシエチレン(以下POEと略
す)(9)ラウリルエーテル、POE(7)オレイルエ
ーテル、POE(10)セチルエーテル、POE(1o
)オレイルエーテル、POE (6)モノオレエート、
POE(10)モノラウレート、POE(1o)モノオ
レート等であるが、中でも、POE(10)オレイルエ
ーテルやPOE(9)ラウリルエーテル等の酸化エチレ
ンの付加モル数が9又は10のCOXからC+aアルキ
ルエーテルが好適である。Furthermore, in the present invention, a solubilizing agent is blended to increase the solubility of indomethacin, and this is a solubilizing agent for increasing the solubility of indomethacin.
The number of moles added of 8 alkyl ether and ethylene oxide is 6
to 10 CI2 to CI6 fatty acid esters, and one or more selected from the group consisting of these are used. Specifically, polyoxyethylene (hereinafter abbreviated as POE) (9) lauryl ether, POE (7) oleyl ether, POE (10) cetyl ether, POE (1o
) oleyl ether, POE (6) monooleate,
POE(10) monolaurate, POE(1o) monooleate, etc., but among them, COX to C+a alkyl with an added mole number of ethylene oxide of 9 or 10, such as POE(10) oleyl ether and POE(9) lauryl ether. Ether is preferred.
尚、インドメタシンはアルカリ性では分解し易く、酸性
では加水分解を受は易いというように、何れの液性でも
不安定であるので、例えば、ジイソパノールアミンのよ
うなpH調整剤を配合することが好ましい。Note that indomethacin is unstable in any liquid type, as it easily decomposes in alkaline conditions and is susceptible to hydrolysis in acidic conditions, so it is recommended to incorporate a pH adjuster such as diisopanolamine. preferable.
而して、上記説明した成分により本発明軟膏剤を製造す
る方法について、その−例を挙げれば、先ず水に粘稠剤
を膨潤乃至溶解させる一方、インドメタシン、グリコー
ル成分、クロタミトン、カルボン酸エステル成分及び溶
解補助剤を低級アルコールに溶解し、この溶液を上記水
により膨潤乃至溶解された粘稠剤と合せて混合し、更に
pH調整剤を添加して全体が均一になるまで攪拌するの
である。To give an example of the method for producing the ointment of the present invention using the above-described components, first, the thickening agent is swollen or dissolved in water, while indomethacin, glycol component, crotamiton, and carboxylic acid ester component are added. and a solubilizing agent are dissolved in a lower alcohol, this solution is mixed with the thickening agent swollen or dissolved in water, a pH adjusting agent is added, and the mixture is stirred until the whole is homogeneous.
このようにして製造された本発明の軟膏剤は、以下に述
べる実施例に明らかなように、皮膚浸透性に優れ、イン
ドメタシンの有する薬理効果を十分に発揮させることの
できる優れたものである。The ointment of the present invention thus produced has excellent skin permeability and is capable of fully exhibiting the pharmacological effects of indomethacin, as is clear from the Examples described below.
[実施例] 次に本発明を実施例により更に詳細に説明する。[Example] Next, the present invention will be explained in more detail with reference to Examples.
大1目I上
成分
1、インドメタシン 1.0 g2、プロピ
レングリコール 1.5 g3、クロタミトン
0.9g4、アジピン酸ジイソプロピル 4
.0 g5、エタノール 41.6 g
6、カルボキシビニルポリマー 2.0 g7、ヒドロ
キシプロピル
セルロース 1.Og
8、PE○(10)
オレイルエーテル 7.0 g
9、ジイソパノールアミン 0.25g10、精製
水 40.75g製法
ア、上記6を精製水20g、エタノール21.6gに膨
潤させる。Large 1st I upper ingredient 1, indomethacin 1.0 g2, propylene glycol 1.5 g3, crotamiton
0.9g4, diisopropyl adipate 4
.. 0 g5, ethanol 41.6 g
6. Carboxyvinyl polymer 2.0 g7. Hydroxypropyl cellulose 1. Og 8, PE○(10) Oleyl ether 7.0 g 9, Diisopanolamine 0.25 g 10, Purified water 40.75 g Production method A. Swell the above 6 in 20 g of purified water and 21.6 g of ethanol.
イ、上記7を精製水15gに溶解する。B. Dissolve the above 7 in 15 g of purified water.
つ、上記1を上記2.3.4.8及びエタノール20g
に溶解する。1, above 2.3.4.8 and 20g of ethanol
dissolve in
工、上記ア、イ、つを混合する。Mix A, B, and A above.
才、上記9を精製水5.75gに溶解し、上記工に添加
し、全体が均一になるまで攪拌する。9. Dissolve the above 9 in 5.75 g of purified water, add to the above solution, and stir until the whole is homogeneous.
K1■ユ
成分
1、インドメタシン 1.0 g2、プロピ
レングリコール 0,2 g3、クロタミトン
1.○ g4、アジピン酸ジイソプロピル
5.5 g5、エタノール 42.0g
6、カルボキシビニルポリマー 18 g7、ヒドロキ
シプロピル
セルロース 1.2 g
8、PE○(1o)
オレイルエーテル 8.0 g
9、ジイソパノールアミン 0.28g10、精製
水 39.02g製法
ア、上記6を精製水20g、エタノール20gに膨潤さ
せる。K1■U component 1, indomethacin 1.0 g2, propylene glycol 0.2 g3, crotamiton
1. ○ g4, diisopropyl adipate
5.5 g5, ethanol 42.0g
6. Carboxyvinyl polymer 18 g 7, Hydroxypropyl cellulose 1.2 g 8, PE○(1o) oleyl ether 8.0 g 9, Diisopanolamine 0.28 g 10, Purified water 39.02 g Production method A. Purify the above 6 Swell in 20 g of water and 20 g of ethanol.
イ、上記7を精製水15gに溶解する。B. Dissolve the above 7 in 15 g of purified water.
つ、上記1を上記2.3.4.8及びエタノール22g
に溶解する。Add 1 above to 2.3.4.8 above and 22g of ethanol.
dissolve in
工、上記ア、イ、つな混合する。Mix the above A, B, and Tuna.
才、上記9を精製水4.02gに溶解し、上記工に添加
し、全体が均一になるまで攪拌する。9. Dissolve the above 9 in 4.02 g of purified water, add to the above solution, and stir until the whole is homogeneous.
及立五ユ
成分
1、インドメタシン 1.0 g2、プロピ
レングリコール 2.0g3、クロタミトン
0.5g4、アジピン酸ジイソプロピル 3.
0g5、エタノール 42.0g6、カ
ルボキシビニルポリマー 2.0g7、ヒドロキシプロ
ピル
セルロース 1.5 g
8、POE (9)
ラウリルエーテル 7.5 g
9、ジイソバンールアミン 0.25g10、精製
水 40.25g製法
ア、上記6を精製水20g、エタノール22gに膨潤さ
せる。Ingredients 1, indomethacin 1.0 g2, propylene glycol 2.0 g3, crotamiton
0.5g4, diisopropyl adipate 3.
0g5, ethanol 42.0g6, carboxyvinyl polymer 2.0g7, hydroxypropyl cellulose 1.5g 8, POE (9) lauryl ether 7.5g 9, diisovanlamine 0.25g10, purified water 40.25g Manufacturing method a , Swell the above 6 in 20 g of purified water and 22 g of ethanol.
イ、上記7を精製水15gに溶解する。B. Dissolve the above 7 in 15 g of purified water.
つ、上記1を上記2.3.4.8及びエタノール20g
に溶解する。1, above 2.3.4.8 and 20g of ethanol
dissolve in
工、上記ア、イ、つを混合する。Mix A, B, and A above.
才、上記9を精製水5.22gに溶解し、上記工に添加
し、全体が均一になるまで攪拌する。9. Dissolve the above 9 in 5.22 g of purified water, add to the above solution, and stir until the whole is homogeneous.
匿軟主
成分
1、インドメタシン 1.0g2、局方親水
軟膏 99.0g製法
ア、上記lを上記2中に均一に分散する。Soft main ingredient 1, indomethacin 1.0g2, pharmacopoeia hydrophilic ointment 99.0gProduction method A. Uniformly disperse the above 1 in the above 2.
実験例
上記実施例1乃至3及び比較例で得られた製剤の薬物皮
膚(表皮)浸透量を、ヘアレスマウスの摘出皮膚を用い
て以下のように測定した。Experimental Example The amount of drug permeation into the skin (epidermis) of the formulations obtained in Examples 1 to 3 and Comparative Example above was measured as follows using the excised skin of a hairless mouse.
pH7,2のリン酸緩衝液を満たしたFRANZDif
fusion C411(CROWN GLASS C
o、、 Inc製)にヘアレスマウスの摘出皮膚を取り
付け、上記実施例1乃至3及び比較例で得られた製剤を
表面に一定量(30mg/c+++”)塗布した。FRANZDif filled with pH 7.2 phosphate buffer
fusion C411 (CROWN GLASS C
The excised skin of a hairless mouse was attached to the skin of a hairless mouse (manufactured by O. Inc.), and a certain amount (30 mg/c+++'') of the formulations obtained in Examples 1 to 3 and Comparative Example above was applied to the surface.
16時間後、ヘアレスマウス摘出皮膚から表皮を剥離し
、真皮及びJil衝液中に移行したインドメタシン量を
HPLCにより定量し、薬物皮膚(表皮)浸透量を算出
した。After 16 hours, the epidermis was peeled off from the skin of the hairless mouse, and the amount of indomethacin transferred to the dermis and Jil solution was quantified by HPLC, and the amount of drug permeated into the skin (epidermis) was calculated.
その結果は次表のとおりである。The results are shown in the table below.
(以下余白) インドメタシン皮膚(表皮)透過率 (単位−%) 特許出願人 同仁医薬化工株式会社(Margin below) Indomethacin skin (epidermal) penetration rate (Unit - %) Patent applicant: Dojin Pharmaceutical Kako Co., Ltd.
Claims (1)
.5〜4.5重量%と、 グリコール成分0.1〜2.5重量% カルボン酸エステル成分2.5〜7.5重 量% クロタミトン0.5〜1.5重量% 低級アルコール成分20〜60重量% 水20〜60重量% を含む溶剤と、 溶解補助剤5〜10重量% とからなり、これらを均一化することにより得られるこ
とを特徴とするインドメタシン軟膏剤。 2 pH調整剤を適宜量含むことを特徴とする請求項1
記載のインドメタシン軟膏剤。[Claims] 1. 0.5 to 2.0% by weight of indomethacin and a thickening agent 1
.. 5-4.5% by weight, glycol component 0.1-2.5% by weight, carboxylic acid ester component 2.5-7.5% by weight, crotamiton 0.5-1.5% by weight, lower alcohol component 20-60% by weight. An indomethacin ointment comprising a solvent containing 20 to 60% by weight of water and 5 to 10% by weight of a solubilizing agent, and obtained by homogenizing these. 2. Claim 1, characterized in that it contains an appropriate amount of a pH adjuster.
Indomethacin ointment as described.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP10850488A JPH01279831A (en) | 1988-04-30 | 1988-04-30 | Indomethacin ointment |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP10850488A JPH01279831A (en) | 1988-04-30 | 1988-04-30 | Indomethacin ointment |
Publications (1)
Publication Number | Publication Date |
---|---|
JPH01279831A true JPH01279831A (en) | 1989-11-10 |
Family
ID=14486454
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP10850488A Pending JPH01279831A (en) | 1988-04-30 | 1988-04-30 | Indomethacin ointment |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPH01279831A (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH04217925A (en) * | 1990-03-27 | 1992-08-07 | Nippon Saafuakutanto Kogyo Kk | New antipyretic, antiphlogistic and analgesic agent composition |
WO2004010994A1 (en) | 2002-07-29 | 2004-02-05 | Kowa Company, Ltd. | Indometacin preparation for external use |
-
1988
- 1988-04-30 JP JP10850488A patent/JPH01279831A/en active Pending
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH04217925A (en) * | 1990-03-27 | 1992-08-07 | Nippon Saafuakutanto Kogyo Kk | New antipyretic, antiphlogistic and analgesic agent composition |
WO2004010994A1 (en) | 2002-07-29 | 2004-02-05 | Kowa Company, Ltd. | Indometacin preparation for external use |
CN100438869C (en) * | 2002-07-29 | 2008-12-03 | 兴和株式会社 | Indometacin preparation for external use |
US7553865B2 (en) | 2002-07-29 | 2009-06-30 | Kowa Company, Ltd. | Indomethacin external preparation |
JP4494202B2 (en) * | 2002-07-29 | 2010-06-30 | 興和株式会社 | Indomethacin external preparation |
JP2010163454A (en) * | 2002-07-29 | 2010-07-29 | Kowa Co | Indomethacin-containing gel cream agent |
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