JPS63313731A - Piroxicam external liquid preparation - Google Patents
Piroxicam external liquid preparationInfo
- Publication number
- JPS63313731A JPS63313731A JP15072187A JP15072187A JPS63313731A JP S63313731 A JPS63313731 A JP S63313731A JP 15072187 A JP15072187 A JP 15072187A JP 15072187 A JP15072187 A JP 15072187A JP S63313731 A JPS63313731 A JP S63313731A
- Authority
- JP
- Japan
- Prior art keywords
- piroxicam
- liquid preparation
- external liquid
- oleate
- dissolved
- 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
- 229960002702 piroxicam Drugs 0.000 title claims abstract description 42
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 title claims abstract description 41
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 239000007788 liquid Substances 0.000 title claims abstract description 21
- 238000010521 absorption reaction Methods 0.000 claims abstract description 28
- 206010040880 Skin irritation Diseases 0.000 claims abstract description 9
- 230000036556 skin irritation Effects 0.000 claims abstract description 9
- 231100000475 skin irritation Toxicity 0.000 claims abstract description 9
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 claims abstract description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229940096992 potassium oleate Drugs 0.000 claims abstract description 5
- MLICVSDCCDDWMD-KVVVOXFISA-M potassium;(z)-octadec-9-enoate Chemical compound [K+].CCCCCCCC\C=C/CCCCCCCC([O-])=O MLICVSDCCDDWMD-KVVVOXFISA-M 0.000 claims abstract description 5
- 239000003623 enhancer Substances 0.000 claims description 11
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical class CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 8
- 230000000694 effects Effects 0.000 abstract description 7
- 239000000203 mixture Substances 0.000 abstract description 3
- 230000001737 promoting effect Effects 0.000 abstract description 3
- 230000002378 acidificating effect Effects 0.000 abstract description 2
- 150000002888 oleic acid derivatives Chemical class 0.000 abstract 2
- 229940035676 analgesics Drugs 0.000 abstract 1
- 239000000730 antalgic agent Substances 0.000 abstract 1
- 239000002260 anti-inflammatory agent Substances 0.000 abstract 1
- 230000001741 anti-phlogistic effect Effects 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
- 239000012488 sample solution Substances 0.000 description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- 230000000699 topical effect Effects 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 239000007853 buffer solution Substances 0.000 description 6
- 241000283973 Oryctolagus cuniculus Species 0.000 description 5
- 230000036470 plasma concentration Effects 0.000 description 5
- 210000003491 skin Anatomy 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 239000000523 sample Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- 239000005642 Oleic acid Substances 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 238000007664 blowing Methods 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- 229960005480 sodium caprylate Drugs 0.000 description 2
- BYKRNSHANADUFY-UHFFFAOYSA-M sodium octanoate Chemical compound [Na+].CCCCCCCC([O-])=O BYKRNSHANADUFY-UHFFFAOYSA-M 0.000 description 2
- WYPBVHPKMJYUEO-NBTZWHCOSA-M sodium;(9z,12z)-octadeca-9,12-dienoate Chemical compound [Na+].CCCCC\C=C/C\C=C/CCCCCCCC([O-])=O WYPBVHPKMJYUEO-NBTZWHCOSA-M 0.000 description 2
- FIWQZURFGYXCEO-UHFFFAOYSA-M sodium;decanoate Chemical compound [Na+].CCCCCCCCCC([O-])=O FIWQZURFGYXCEO-UHFFFAOYSA-M 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 229940100613 topical solution Drugs 0.000 description 2
- 230000009278 visceral effect Effects 0.000 description 2
- MAQAGRJURDEYDQ-UHFFFAOYSA-N 6-methylpyridine Chemical compound CC1=C=CC=C[N]1 MAQAGRJURDEYDQ-UHFFFAOYSA-N 0.000 description 1
- 208000019300 CLIPPERS Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical group OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010034464 Periarthritis Diseases 0.000 description 1
- 206010053262 Skin swelling Diseases 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 208000021930 chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids Diseases 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000003631 expected effect Effects 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
- 150000004665 fatty acids Chemical class 0.000 description 1
- 238000005558 fluorometry Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 229940124641 pain reliever Drugs 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 239000000565 sealant Substances 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 231100000245 skin permeability Toxicity 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000005406 washing Methods 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：
本発明はピロキシカムを含宵する外用液剤に関する。更
に詳しくは、水を基剤とし、経皮吸収促進剤としてオレ
イン酸塩類を含むことにより優れたピロキシカムの吸収
性が発現し、かつ、皮膚刺激の少ないことを特徴とする
外用液剤に関する。DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application: The present invention relates to a topical solution containing piroxicam. More specifically, the present invention relates to a liquid preparation for external use that is water-based and contains oleate salts as a transdermal absorption enhancer, exhibits excellent piroxicam absorption, and is characterized by less skin irritation.
従来の技術：
ピロキシカムは作用持続性の長い、酸性非ステロイド系
世炎鎮痛剤で、広い領域において使用される優れた薬剤
である。整形外科領域おける変形性関節炎、肩関節周囲
炎、臓・臓鞘炎、筋・筋膜炎などによる疼痛や腫脹、熱
感の治療にも経口投与され、優れた効果が示されている
。しかし、消化管に対する副作用もしばしば見られ、投
与継続が困難になる場合もあり、十分な治療効果が期待
できなくなる場合もある。このようなピロキシカムの経
口剤による副作用の欠点を克服する方法の一つとして、
外用液剤が考えられる。Conventional technology: Piroxicam is an acidic nonsteroidal pain reliever with a long duration of action, and is an excellent drug used in a wide range of areas. It has also been orally administered to treat pain, swelling, and heat sensation caused by osteoarthritis, shoulder periarthritis, visceral and visceral inflammation, and myofasciitis in the orthopedic field, and has shown excellent efficacy. However, side effects on the gastrointestinal tract are often observed, making it difficult to continue administration, and sufficient therapeutic effects may not be expected. One way to overcome the drawbacks of side effects caused by oral piroxicam is to
Possible solutions include topical solutions.
しかし、他の多くの薬物と同様にピロキシカムも角質が
バリヤーとなり、この層の透過が経皮吸収の律速段階と
なる。その水溶液を皮膚に投与しても殆ど吸収されず、
十分な治療効果が得られない。このように皮膚透過性の
低い薬物の透過性改善の方法として、経皮吸収促進剤を
用いる方法が考えられる。However, like many other drugs, the stratum corneum acts as a barrier for piroxicam, and penetration through this layer is the rate-limiting step for transdermal absorption. Even when the aqueous solution is administered to the skin, it is hardly absorbed.
A sufficient therapeutic effect cannot be obtained. One possible method for improving the permeability of drugs with such low skin permeability is to use transdermal absorption enhancers.
しかし、従来経皮吸収性がよく、かつ、皮膚刺激性の少
ないピロキシカム外用液剤の実用的な経皮吸収促進剤は
見出されていなかった。However, no practical transdermal absorption enhancer for topical liquid preparations of piroxicam that has good transdermal absorption and less skin irritation has been found.
発明の目的：
本発明の目的は本来皮膚からの吸収性の乏しいピロキシ
カムに経皮吸収促進剤を添加して、吸収性が高く、かつ
、皮膚刺激性の弱いピロキシカム外用液剤を提供するこ
とにある。Purpose of the invention: The purpose of the present invention is to provide a topical liquid preparation of piroxicam that is highly absorbable and less irritating to the skin by adding a transdermal absorption enhancer to piroxicam, which originally has poor absorption through the skin. .
発明の詳細な説明：
本発明者らはピロキシカムの経皮吸収性を向」−させる
目的で、ピロキンカムの経皮吸収に有効と思われる化合
物を系統的に分類し、多くの試験を行った結果、水を基
剤とし、水に溶解性の高いオレイン酸塩類を吸収促進剤
とした処方の外用液剤が、ピロキシカムの経皮吸収性が
著しく高く、皮膚刺激性が弱いことを見出し、本発明を
完成した。Detailed Description of the Invention: The present inventors have systematically classified compounds that are thought to be effective for the transdermal absorption of piroxicam, and have conducted numerous tests to improve the transdermal absorption of piroxicam. discovered that a water-based topical liquid formulation with highly water-soluble oleate salts as an absorption enhancer has significantly high transdermal absorption of piroxicam and low skin irritation, and has developed the present invention. completed.
本発明において使用される基剤は水である。The base used in this invention is water.
本発明において使用される経皮吸収促進剤はオレイン酸
塩類であり、このオレイン酸塩類はオレイン酸ナトリウ
ム及びオレイン酸カリウムである。経皮吸収促進剤は全
組成の０．５〜１０重量％、好ましくは１〜５％であり
、１重量％以下では期待する効果が得られ難く、５重量
％以上では水への溶解度が困難になる。The transdermal absorption enhancers used in the present invention are oleate salts, and the oleate salts are sodium oleate and potassium oleate. The amount of percutaneous absorption enhancer is 0.5 to 10% by weight, preferably 1 to 5% of the total composition. If it is less than 1% by weight, it is difficult to obtain the expected effect, and if it is more than 5% by weight, solubility in water is difficult. become.
本発明のピロキシカム外用液剤は、水酸化ナトリウム炭
酸ナトリウム、重炭酸ナトリウムあるいはその他の緩衝
液などのピロキシカムの溶解補助剤を加えることが出来
る。また、パラベン類などの防腐剤を加えることができ
る。The topical piroxicam solution of the present invention may contain a solubilizing agent for piroxicam, such as sodium hydroxide, sodium carbonate, sodium bicarbonate, or other buffers. Additionally, preservatives such as parabens can be added.
発明の効果：
本発明で使用されるピロキンカム外用液剤は、経皮吸収
促進剤としてオレイン酸ナトリウムあるいはオレイン酸
カリウムを含有することにより、ピロキシカムの経皮吸
収性が著しく向上し、また、皮膚刺激性が少なく実用性
がよい。その結果として治療効果が著しく優れている。Effects of the invention: The topical liquid preparation of piroxicam used in the present invention significantly improves the percutaneous absorption of piroxicam by containing sodium oleate or potassium oleate as a percutaneous absorption enhancer, and also reduces skin irritation. It is practical because there is less. As a result, the therapeutic effect is significantly superior.
実施例：
以下に本発明を実施例でしめして具体的に説明するが、
本発明は以下の実施例にのみ限定されるものではない。Examples: The present invention will be specifically explained below with reference to Examples.
The present invention is not limited only to the following examples.
実施例−１
ピロキシカム５０ｍｇをとり、ｐＨ９，２の重炭酸ナト
リウム緩衝液２０ｍ１に溶かし、更にオレイン酸ナトリ
ウム２００ｍｇを加えて溶かし外用液剤を得た。Example 1 50 mg of piroxicam was taken and dissolved in 20 ml of a sodium bicarbonate buffer solution of pH 9.2, and 200 mg of sodium oleate was further added and dissolved to obtain a liquid preparation for external use.
この２ｍｌを試料液Ｉとした。This 2 ml was used as sample solution I.
ピロキシカム５０ｍｇをとり、ｐＨ９，２の重炭酸ナト
リウム緩衝液２０ｍ１に溶かし、更にオレイン酸ナトリ
ウム４００ｍｇを加えて溶かし外用液剤を得た。50 mg of piroxicam was taken and dissolved in 20 ml of sodium bicarbonate buffer solution of pH 9.2, and 400 mg of sodium oleate was further added and dissolved to obtain a liquid preparation for external use.
この２ｍｌを試料液■とした。2 ml of this was used as sample solution (■).
ピロキシカム５０ｍｇをとり、ｐＨ９，２の重炭酸ナト
リウム緩衝液２０ｍ１に溶かし、更にオレイン酸ナトリ
ウム８００ｍｇを加えて溶かし外用液剤を得た。50 mg of piroxicam was taken and dissolved in 20 ml of sodium bicarbonate buffer solution of pH 9.2, and 800 mg of sodium oleate was further added and dissolved to obtain a liquid preparation for external use.
この２ｍｌを試料液■とした。2 ml of this was used as sample solution (■).
対照例−１
ピロキシカム５０＋ｎｇをとり、ｐＨ９，２の重炭酸ナ
トリウム緩衝液１０ｍｌに溶かし外用液剤を得た。Control Example-1 50+ ng of piroxicam was taken and dissolved in 10 ml of sodium bicarbonate buffer of pH 9.2 to obtain a liquid preparation for external use.
この２ｍｌを試料液とした。2 ml of this was used as a sample solution.
実施例１及び対照例１の試料液につき、ウサギを用いて
経皮吸収実験を実施した。即ち、平均体重３ｋｇ’のウ
サギ（雄性ニューシーラントホワイト種）３羽を使用し
、電気バリカンで除毛した腹部に内径６ｃ１１（面積：
２Ｂ、３ｃ♂）のロートの広い部分をアロンアルファー
で接着した。ロートの細い部分から試料を入れ、パラフ
ィルムで包んだ。試料適用後、１時間、２時間、４時間
及び８時間後に、ウサギの耳介動脈より各々４ｍｌずつ
を採血した。採取血液はヘパリン５０単位を入れたポリ
スビッツ中で混和後、遠心分離（３０００ｒ、ｐ、ｍ、
、 １０分間）し、血漿を分取した。A transdermal absorption experiment was conducted on the sample solutions of Example 1 and Control Example 1 using rabbits. That is, three rabbits (male New Sealant White breed) with an average weight of 3 kg' were used, and their abdomens, which had had their hair removed with electric clippers, had an inner diameter of 6c11 (area:
2B, 3c♂) The wide part of the funnel was glued with Aron Alpha. A sample was introduced into the narrow part of the funnel and wrapped in parafilm. 1 hour, 2 hours, 4 hours, and 8 hours after the sample application, 4 ml of blood was each collected from the auricular artery of the rabbit. The collected blood was mixed in Polyvitz containing 50 units of heparin, and then centrifuged (3000 r, p, m,
, 10 minutes), and the plasma was collected.
血漿１ｍｌに６Ｎ硫酸０．２ｍｌを加えてクロロホルム
５ｍｌで抽出し、クロロホルム４ｍｌを分取して空気を
吹き込みながらクロロホルムを留去した。６Ｎ硫酸１ｍ
ｌを加えて１０５°Ｃの油浴中で１８時間加熱し、ピロ
キシカムを２−アミノピリジンに分解した。0.2 ml of 6N sulfuric acid was added to 1 ml of plasma, extracted with 5 ml of chloroform, 4 ml of chloroform was taken out, and the chloroform was distilled off while blowing air. 6N sulfuric acid 1m
The mixture was heated in an oil bath at 105°C for 18 hours to decompose piroxicam into 2-aminopyridine.
これに内部標準として１００ｎｇ／ｍｌの２−アミノ−
６−メチルピリジン水溶液ｆｍｌを加え、酢酸エチル３
ｍｌを加えて２回洗浄した後、炭酸水素ナトリウム０．
７ｇを加えてアルカリ性とし、酢酸エチル３ｍｌで２回
抽出し、０．ＩＮ塩酸メタノール２５μｌを加えて、空
気を吹き込みながら酢酸エチルを留去した。これに移動
相０．２ｍｌを加えて溶かし、この５０μｌを試料とし
、下記の条件の液体クロマトグラフ法でピロキシカム濃
度を測定した。その結果を表−１に示す。This was supplemented with 100 ng/ml 2-amino-
Add fml of 6-methylpyridine aqueous solution and add 3 ml of ethyl acetate.
After washing twice by adding 0.ml of sodium bicarbonate.
Add 7 g to make alkaline, extract twice with 3 ml of ethyl acetate, and reduce to 0. 25 μl of IN hydrochloric acid methanol was added, and ethyl acetate was distilled off while blowing air. To this was added 0.2 ml of mobile phase to dissolve it, and using 50 μl of this as a sample, the concentration of piroxicam was measured by liquid chromatography under the following conditions. The results are shown in Table-1.
［条件］
カラム：ヌクレオジルＣｒ７（７μｍ）、 ＋５０ｎ
ｕｎ Ｘ ４．１ｌｉｎｏｎφ力ラム温度：室温
流速： １．７ｍｌ／＋＋ｉｎ
移動相：クエン酸・リン酸塩緩衝液（ｐｌ（３，０）−
アセトニトリル（５０：Ｉ）検出：蛍光光度法
Ｅｘ ： ３１０ ｎｍ
ＥＸ ： ３８０ ｎｍ
表−１ピロキシカム血漿中ｌ１度推移 （ｎｇ／ｍｌ）
表−１の結果より明らかなように本発明の実施例１の試
料液は対照例１の試料液に比へて著しく高いピロキシカ
ム血漿中濃度を示した。本発明による吸収促進効果は従
来になく優れたものであり、また、いずれも肉眼的に皮
膚刺激性もなく優れたピロキシカムの外用液剤を可能成
らしめるものである。[Conditions] Column: Nucleozil Cr7 (7 μm), +50n
un
Acetonitrile (50:I) detection: Fluorometry Ex: 310 nm EX: 380 nm Table 1 Piroxicam plasma l1 degree change (ng/ml)
As is clear from the results in Table 1, the sample solution of Example 1 of the present invention showed a significantly higher plasma concentration of piroxicam than the sample solution of Control Example 1. The absorption promoting effect of the present invention is unprecedented and excellent, and it also enables the preparation of external liquid preparations of piroxicam that are macroscopically free from skin irritation.
参３１１−
ピロキシカム５０ｍｇをとり、ｐＨ９，２の重炭酸ナト
リウム緩衝液２０ｍ１に溶かし、更にカプリル酸ナトリ
ウム４００＋ｎｇを加えて溶かし外用液剤を得た。50 mg of 311-piroxicam was taken and dissolved in 20 ml of sodium bicarbonate buffer of pH 9.2, and 400+ ng of sodium caprylate was added and dissolved to obtain a liquid preparation for external use.
この２ｍｌを試料液Ｉとした。This 2 ml was used as sample solution I.
ピロキシカム５０ｍｇをとり、ｐＨ９，２の重炭酸ナト
リウム緩衝液２０ｍ１に溶かし、更にカプリン酸ナトリ
ウム４００ｍｇを加えて溶かし外用液剤を得た。50 mg of piroxicam was taken and dissolved in 20 ml of sodium bicarbonate buffer solution of pH 9.2, and 400 mg of sodium caprate was further added and dissolved to obtain a liquid preparation for external use.
この２ｍｌを試料液■とした。2 ml of this was used as sample solution (■).
ピロキシカム５０ｍｇをとり、ｐＨ９，２の重炭酸ナト
リウム緩衝液２０ｍ１に溶かし、更にリノール酸ナトリ
ウム４００ａｇを加えて溶かし外用液剤を得た。50 mg of piroxicam was taken, dissolved in 20 ml of sodium bicarbonate buffer solution of pH 9.2, and 400 ag of sodium linoleate was added and dissolved to obtain a liquid preparation for external use.
この２＋ｎｌを試料液■とした。This 2+nl was used as the sample solution (■).
参考例２
ピロキシカム５００ｍｇをとり、Ｎ−メチル−２−ピロ
リドン５ｍｌに溶かし、遊離オレイン酸５ｍｌを加えて
外用液剤を得た。この２ｎ＋１を試料液とした。Reference Example 2 500 mg of piroxicam was taken, dissolved in 5 ml of N-methyl-2-pyrrolidone, and 5 ml of free oleic acid was added to obtain a liquid preparation for external use. This 2n+1 was used as a sample solution.
これらの試料液につき実施例１と同様にウサギ皮膚に投
与して、血漿中濃度を測定した。その結果を表−２に示
す。These sample solutions were administered to rabbit skin in the same manner as in Example 1, and the plasma concentrations were measured. The results are shown in Table-2.
表−２ピロキシカム血漿中濃度推移 （ｎｇ／ｍｌ）上
記の結果より、オレイン酸ナトリウムと同じ高級脂肪酸
ナトリウムであるカプリル酸ナトリウム、カプリン酸ナ
トリウム及びリノール酸ナトリウムについて、ピロキシ
カム外用液剤での経皮吸収促進効果を調べたが、経皮吸
収促進剤を含まない対照例１と同程度のピロキシカム血
漿中濃度しか示さず、経皮吸収促進効果はなかった。Table 2 Changes in plasma concentration of piroxicam (ng/ml) Based on the above results, the topical liquid preparation of piroxicam promotes transdermal absorption of sodium caprylate, sodium caprate, and sodium linoleate, which are the same higher fatty acid sodiums as sodium oleate. The effect was investigated, but the plasma concentration of piroxicam was only comparable to that of Control Example 1, which did not contain a transdermal absorption enhancer, and there was no effect on promoting transdermal absorption.
また、ピロキシカムをを機溶剤であるＮ−メチル−２−
ピロリドンに溶かし、これに遊離オレイン酸を経皮吸収
促進剤として添加した外用液剤にはピロキシカムの著し
い経皮吸収効果を認めたが、皮膚に腫脹を生じ強い皮膚
刺激性を認める点で実用的ではない。In addition, piroxicam was used as a solvent, N-methyl-2-
A topical solution prepared by dissolving pyrrolidone and adding free oleic acid as a transdermal absorption enhancer was found to have a remarkable transdermal absorption effect on piroxicam, but it is not practical as it causes skin swelling and strong skin irritation. do not have.
実施例２
ピロキンカム５０ｍｇをとり、ｐＨ９，２の重炭酸ナト
リウム緩衝液１０ｍｌに溶かし、更にオレイン酸カリウ
ム５００ｍｇを加えて溶かし外用液剤を得た。この２＋
ｎｌを試料液とした。Example 2 50 mg of pyroquincum was taken, dissolved in 10 ml of sodium bicarbonate buffer solution of pH 9.2, and further 500 mg of potassium oleate was added and dissolved to obtain a liquid preparation for external use. This 2+
nl was used as the sample solution.
これらの試料液につき実施例１と同様にウサギ皮膚に投
与して、血漿中濃度を測定した。その結果を表−３に示
した。肉眼的に皮膚刺激性は認められなかった。These sample solutions were administered to rabbit skin in the same manner as in Example 1, and the plasma concentrations were measured. The results are shown in Table-3. No skin irritation was observed macroscopically.
Claims (2)
剤としてオレイン酸塩類を含有することを特徴とする吸
収性が優れ、また、皮膚刺激性の少ないピロキシカム外
用液剤。(1) A liquid preparation for external use of piroxicam, which is water-based and contains piroxicam and oleate salts as a transdermal absorption enhancer, and has excellent absorbency and low skin irritation.
イン酸カリウムである特許請求の範囲（１）のピロキシ
カム外用液剤。(2) The liquid preparation for external use of piroxicam according to claim (1), which is an oleate salt, sodium oleate, or potassium oleate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15072187A JPS63313731A (en) | 1987-06-16 | 1987-06-16 | Piroxicam external liquid preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15072187A JPS63313731A (en) | 1987-06-16 | 1987-06-16 | Piroxicam external liquid preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS63313731A true JPS63313731A (en) | 1988-12-21 |
Family
ID=15502958
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15072187A Pending JPS63313731A (en) | 1987-06-16 | 1987-06-16 | Piroxicam external liquid preparation |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63313731A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005047908A (en) * | 2003-07-16 | 2005-02-24 | Taisho Pharmaceut Co Ltd | Antiinflammatory/analgesic composition for external use |
-
1987
- 1987-06-16 JP JP15072187A patent/JPS63313731A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005047908A (en) * | 2003-07-16 | 2005-02-24 | Taisho Pharmaceut Co Ltd | Antiinflammatory/analgesic composition for external use |
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