GB2203041A - Antiinflammatory and analgesic agents for external application - Google Patents
Antiinflammatory and analgesic agents for external application Download PDFInfo
- Publication number
- GB2203041A GB2203041A GB08806323A GB8806323A GB2203041A GB 2203041 A GB2203041 A GB 2203041A GB 08806323 A GB08806323 A GB 08806323A GB 8806323 A GB8806323 A GB 8806323A GB 2203041 A GB2203041 A GB 2203041A
- Authority
- GB
- United Kingdom
- Prior art keywords
- antiinflammatory
- external application
- analgesic
- biphenylyl
- fluoro
- 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.)
- Granted
Links
Classifications
-
- 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
-
- 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
-
- 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
-
- 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
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- 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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
An antiinflammatory and analgesic composition for external application comprises 2-(2-fluoro-4-biphenylyl) propionic acid (Flurbiprofen) as an effective component and a topical carrier. The antiinflammatory and analgesic composition for external application possesses a long lasting antiinflammatory and analgesic effect and is free from general side effects such as gastrointestinal disorders as in conventional oral antiinflammatory and analgesic agents.
Description
ANTI INFLAMMATORY AND ANALGESIC AGENTS FOR EXTERNAL
APPLICATION
Background of the Invention 1. Field of the Invention
The present invention relates to an anti inflammatory and analgesic composition for external application comprising 2-(2-fluoro-4-biphenylyl)propionic acid as an effective component.
2. Description of the Prior Art
As anti inflammatory and analgesic agents for external application, a salicylic acid ester compound such as methyl salicylate or the like has been widely used as a main component.
Further 2-(2-fluoro-4-biphenylyl)propionic acid exhibits an excellent pharmaceutical effect as an acidic non-steroidal anti inflammatory and analgesic agent and has been used as an antiinflammatory and analgesic agent for internal use.
However, the salicylic acid ester compound involves a defect that it requires a large dose to obtain a desired pharmaceutical effect, while the compound has an anti inflammatory and analgesic activity. Further 2-(2-fluoro-4-biphenylyl)propionic acid shows a potent anti inflammatory and analgesic activity but, on the other hand, encounters defects that it is accompanied by serious gastrointestinal disorders and its safety zone is narrow.
Summary of the Invention
As a result of extensive investigations to reduce side effects of 2-(2-fluoro-4-biphenylyl)propionic acid as an anti inflammatory and analgesic agent for internal use over long periods of time, the present inventors have come to accomplish the present invention. An object of the present invention is to provide preparations of 2-(2-fluoro-4-biphenylyl)propionic acid in which by allowing to percutaneously absorb 2-(2-fluoro-4-biphenylyl)propionic acid, a topical agent concentration is enhanced, general side effects such as gastrointestinal disorders, etc. are alleviated and its anti inflammatory and analgesic effect is effectively exhibited.
Namely, the present invention is directed to antiinflammatory and analgesic agent for external application comprising as an effective component 2-(2-fluoro-4-biphenylyl)propionic acid represented by formula:
and a base.
The anti inflammatory and analgesic agents for external application of the present invention is a very useful antiinflammatory and analgesic agent free from general side effects such as gastrointestinal disorders, etc. as in conventional oral anti inflammatory and analgesic agents, when applied to the skin with inflammation, in which the effective component directly permeates into the inflammatory tissue and a high concentration in the inflammatory tissue maintains over a long period of time to efficiently exhibit a durative anti inflammatory and analgesic effect.
Detailed Description of the Invention
A dose of the effective component in the anti inflammatory and analgesic agent is 2 to 200 mg, preferably 10 to 80 mg, per 1 application.
As the base used in the present invention, there are an oleophilic base and a hydrophilic base.
As the oleophilic base, mention may be made of vaseline, liquid paraffin, plastibase, silicone, vegetable oils, natural rubbers, synthetic rubbers, resins, polybutene, etc. The effective component can be mixed directly with these oily bases; however, it is advantageous that by use of the effective component together with organic compounds such as terpenes, higher fatty acid esters, etc., the property of the effective component being absorbed from the skin is improved by the action of the organic compounds as percutaneous absorption accelerators.
As the percutaneous absorption accelerators, mention may be made of, for example, terpenes such as a peppermint oil, an eucalyptus oil, etc., higher fatty acid resins.-such as isopropyl myristate, etc., hydrocarbons and the like.
Further the antiinflammatory and analgesic agent for external use can be used as all of medical preparations which are applicable to the skin. That is, by the use in the form of an ointment, a plaster, liquid, etc., the agert is continuously released from the preparations, efficiently absorbed from the skin and selectively reaches to the inflammatory region, whereby the objective antiinflammatory and analgesic effect can be exhibited.
Next, the present invention will be described in more detail with reference to the examples below but is not deemed to be limited thereto.
Example 1 (Preparation of the anti inflammatory and analgesic
composition of the present invention for external
application)
A solution of 5 g of 2-(2-fluoro-4-biphenylyl)propionic acid in 10 g of peppermint oil was homogeneously kneaded with 85 g of an oleophilic base having a composition described in the following Table 1 to give the antiinflammatory and analgesic composition of the present invention for external application.
Table 1
Synthetic rubber 70 parts
Natural rubber 30 parts
Polyolefin resin 40 parts
Ester gum 20 parts
Polybutene 30 parts
Liquid paraffin 10 parts
Stabilizer 1 part
Example 2
A solution of 5 g of 2-(2-fluoro-4-biphenylyl)propionic acid in 10 g of eucalyptus oil was homogeneously kneaded with 85 g of plastibase to give the anti inflammatory and analgesic composition of the present invention for external application.
Example 3 (percutaneous absorption from the back of rat)
The antiinflammatory and analgesic compositions of the present invention for external application were applied to the back of rats and time-dependent change of the effective component in a blood concentration was measured. The results are shown in the following Table 2.
Table 2
Concentration Content of of Effective Effective Blood Concentration
Component Component (Ug/ml of serum) (g) (mg/l.5 x 1.5 cm) 2 hrs. 4 hrs. 6 hrs.
3.0 0.6 2.0 1.8 1.5
10.0 2.0 5.8 5.0 4.5
It was noted a tendency that the blood concentration of the effective component showed the peak 2 hours after the application and then gradually decreased.
Example 4 (Carrageenin-induced edema inhibitory activity at the
back of rat)
Using 8 rats as a group, the hair at the back was shaved a day before experiment and then the antiinflammatory and analgesic composition of the present invention for external application was applied to the shaved back. Two hours after, the anti inflammatory and analgesic composition was withdrawn and 0.05 ml of 1% carrageenin solution was percutaneously injected to one side from the center line of the back and 0.05 ml of physiological saline to another side, respectively. Immediately after the injection, the composition to be tested was applied.
Three hours after the administration of carrageenin, blood was allowed to flow to death and the skin was torn off. The edema region and the control region were punched out with a leather puncher (orifice diameter of 15mm)to weight them. A difference obtained by subtracting the weight of the control at which physiological saline was injected from the weight of the edema region was made an edema weight. An edema inhibitory rate was determined by the following equation:
Edema inhibitory rate (%)
Mean weight of edema in the control group - - Mean weight of edema in each administration group x 100 Mean weight of edema in the control group
The results are shown in Table 3.
Table 3 AgentTested Edema Weight (mg) Inhibitory Rate (%3 Control (intact) 61.0 + 6.2
Base 59.0 + 5.3 3.3
Anti inflammatory
and analgesic
composition of 33.9 + 5.6** 44.4**
this invention
for external
application
** : p < 0.01 (significant difference from the
control: t assay)
The experimental results described above has proved that the anti inflammatory and analgesic composition of the present invention for external application markedly inhibits carrageenin-induced edema, indicating the antiinflammatory and analgesic effect of the effective component by percutaneous absorption.
Claims (7)
1. An antiinflammatory and analgesic composition for external application comprising 2-(2-fluoro-4-biphenylyl)propionic acid represented by formula:
as an effective component, and a base.
2. An antiinflammatory and analgesic composition for external application as claimed in claim l,wherein 2-(2-fluoro-4-biphenylyl)propionic acid is used together with a percutaneous absorption accelerator.
3. An antiinflammatory and analgesic composition for external application as claimed in claim 2,wherein said percutaneous absorption accelerator is an organic compound selected from a terpene and a higher fatty acid ester and hydrocarbon.
4. An antiinflammatory and analgesic composition for external application as claimed in any one of claims 1 through 3 wherein said base is an oleophilic base.
5. An antiinflammatory and analgesic composition for external application as claimed in claim 4 wherein said oleophilic base is vaseline, liquid paraffin, plastibase,
silicone, a vegetable oil, a natural rubber, a synthetic rubber,
a resin or polybutene.
6. The use of 2-(2-fluoro-4-biphenylyl)-propionic
acid in the manufacture of an antiinflammatory and analgesic
medicament for external application.
7. A composition as claimed in any one of claims 1 to 5 or the use as claimed in claim 6, with the modification that the acid is in the form of a pharmaceutically acceptable salt, ester or addition compound thereof.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP62061950A JP2764261B2 (en) | 1987-03-17 | 1987-03-17 | External anti-inflammatory analgesic |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB8806323D0 GB8806323D0 (en) | 1988-04-13 |
| GB2203041A true GB2203041A (en) | 1988-10-12 |
| GB2203041B GB2203041B (en) | 1991-10-30 |
Family
ID=13185985
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8806323A Expired - Lifetime GB2203041B (en) | 1987-03-17 | 1988-03-17 | Plaster having thereon an antiinflammatory and analgesic composition for external application. |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JP2764261B2 (en) |
| KR (1) | KR0138121B1 (en) |
| GB (1) | GB2203041B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991015241A1 (en) * | 1990-03-30 | 1991-10-17 | Yasunori Morimoto | Percutaneously absorbable composition of narcotic and nonnarcotic analgesics |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2506216B2 (en) * | 1990-03-08 | 1996-06-12 | テルモ株式会社 | Anti-inflammatory analgesic external preparation |
| KR100228514B1 (en) * | 1996-09-05 | 1999-11-01 | 한승수 | Transdermal flux enhancing compositions containing nonsteroidal anti-inflammatory drugs |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4230724A (en) * | 1979-07-16 | 1980-10-28 | Allergan Pharmaceuticals, Inc. | Method of treating vascularization of the eye with Flurbiprofen |
| GB2075837A (en) * | 1980-05-14 | 1981-11-25 | Hisamitsu Pharmaceutical Co | Topical pharmaceutical gel containing anti-inflammatory analgesic agents |
| EP0082921A1 (en) * | 1981-12-24 | 1983-07-06 | Kaken Pharmaceutical Co., Ltd. | Anti-inflammatory ophthalmic solution and process for preparing the same |
| EP0091964A1 (en) * | 1981-09-28 | 1983-10-26 | Nitto Denko Corporation | Base composition for preparing medicine for external application, medicinal composition for external application, and method for accelerating percutaneous absorption of medicinal agent |
| EP0206291A2 (en) * | 1985-06-24 | 1986-12-30 | Klinge Pharma GmbH | Sprayable pharmaceutical preparation for topical application |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS56154413A (en) * | 1980-04-30 | 1981-11-30 | Riide Chem Kk | Anti-inflammatory analgesic for external use |
| JPS5829706A (en) * | 1981-08-14 | 1983-02-22 | Toko Yakuhin Kogyo Kk | Antiphlogistic and analgesic agent for external use |
| US4559343A (en) * | 1982-09-07 | 1985-12-17 | Alcon Laboratories, Inc. | Nonirritating aqueous ophthalmic compositions comfort formulation for ocular therapeutic agents |
| US4473584A (en) * | 1982-12-06 | 1984-09-25 | The Upjohn Company | Treatment of Type I Herpes virus with flurbiprofen |
| JPS62270521A (en) * | 1986-05-16 | 1987-11-24 | Green Cross Corp:The | Flurbiprofen preparation for ophthalmic administration |
-
1987
- 1987-03-17 JP JP62061950A patent/JP2764261B2/en not_active Expired - Lifetime
-
1988
- 1988-03-16 KR KR1019880002767A patent/KR0138121B1/en not_active IP Right Cessation
- 1988-03-17 GB GB8806323A patent/GB2203041B/en not_active Expired - Lifetime
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4230724A (en) * | 1979-07-16 | 1980-10-28 | Allergan Pharmaceuticals, Inc. | Method of treating vascularization of the eye with Flurbiprofen |
| GB2075837A (en) * | 1980-05-14 | 1981-11-25 | Hisamitsu Pharmaceutical Co | Topical pharmaceutical gel containing anti-inflammatory analgesic agents |
| EP0091964A1 (en) * | 1981-09-28 | 1983-10-26 | Nitto Denko Corporation | Base composition for preparing medicine for external application, medicinal composition for external application, and method for accelerating percutaneous absorption of medicinal agent |
| EP0082921A1 (en) * | 1981-12-24 | 1983-07-06 | Kaken Pharmaceutical Co., Ltd. | Anti-inflammatory ophthalmic solution and process for preparing the same |
| EP0206291A2 (en) * | 1985-06-24 | 1986-12-30 | Klinge Pharma GmbH | Sprayable pharmaceutical preparation for topical application |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1991015241A1 (en) * | 1990-03-30 | 1991-10-17 | Yasunori Morimoto | Percutaneously absorbable composition of narcotic and nonnarcotic analgesics |
Also Published As
| Publication number | Publication date |
|---|---|
| GB8806323D0 (en) | 1988-04-13 |
| JPS63227524A (en) | 1988-09-21 |
| JP2764261B2 (en) | 1998-06-11 |
| GB2203041B (en) | 1991-10-30 |
| KR0138121B1 (en) | 1998-05-15 |
| KR880010761A (en) | 1988-10-24 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PE20 | Patent expired after termination of 20 years |
Expiry date: 20080316 |