IL42365A - Anti-inflammatory topical composition containing 2-(4-pyridyl-6,16alpha-dimethyl-11beta,17alpha,21-trihydroxypregna-4,6-dieno(3,2-c)-pyrazol-20-one - Google Patents

Anti-inflammatory topical composition containing 2-(4-pyridyl-6,16alpha-dimethyl-11beta,17alpha,21-trihydroxypregna-4,6-dieno(3,2-c)-pyrazol-20-one

Info

Publication number
IL42365A
IL42365A IL42365A IL4236573A IL42365A IL 42365 A IL42365 A IL 42365A IL 42365 A IL42365 A IL 42365A IL 4236573 A IL4236573 A IL 4236573A IL 42365 A IL42365 A IL 42365A
Authority
IL
Israel
Prior art keywords
pyridyl
propylene glycol
mixture
dimethyl
dieno
Prior art date
Application number
IL42365A
Other languages
Hebrew (he)
Other versions
IL42365A0 (en
Original Assignee
Merck & Co Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Merck & Co Inc filed Critical Merck & Co Inc
Publication of IL42365A0 publication Critical patent/IL42365A0/en
Publication of IL42365A publication Critical patent/IL42365A/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/76—Nitrogen atoms to which a second hetero atom is attached
    • C07D213/77—Hydrazine radicals
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • 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
    • A61K47/30—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
    • 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
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38—Cellulose; Derivatives thereof
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Organic Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Dermatology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Description

42365/2 MERCK & CO., IMC.
This invention relates to compositions containing 2 '-(4-pyridyl)-6 ,16a-dimethy 1-1 1 β , 17a , 21 -trihydroxypregna-4,6-dieno^3f 27-pyrazol-20-one, as anti-inflammatory agent.-More specifically, the invention relates to topical pharmaceutical compositions which contain said 21 -(4-pyridyl) 6 , 16a-dimethy 1-1 1 β , 17a , 21 -trihydroxypregna-4 ,6-dieno 3 , 2-c7-pyrazol-20-one as an active ingredient in a clear water-white gel vehicle. The anti-inflammatory agent disclosed herein is of value in the topical treatment of dermatological disorders of like conditions re-sponsive to anti-inflammatory drugs. Included within this category are diseases such as dermatitis (actinic, atopic, contact, eczematoid, seborrheic and stasis') , dermatitis herpetiformis, lichen planus, neurodermatitis, intitrigo, lichen simplex chronicus, pruritus , nd psoriasis.
The steroid must be in the molecular state such as a solution which obviates a dissolution rate in order to obtain maximum therapeutic activity. The topical clear water-white vehicle disclosed herein containing the steroid has the advantage of a solution, i.e., the product is a clear water-white gel that demonstrates the solubility of the steroid within the vehicle. This concept is in contrast with. the prior art's opague emulsion type cream which may mask crystallization of the steroid within the matrix of a water insoluble component or the aqueous phase. Also, said concept is in contrast with the prior art which disclose formulations which include a combination of miscible volatile and non-volatile solvent as a vehicle.
See German Offenlegungsschrift 2,015,300.
It is an object of this invention to provide a potent topically active anti-inflammatory agent which shows a good separation between local and systemic activities.
It is a further object of this invention to pro-vide a topical dosage form of the active agent having optimum stability and optimum release characteristics from a non-irritating vehicle to the skin to obtain maximum therapeutic effect.
Another object of this invention is to provide a vehicle which possesses maximum skin penetrating properties, thus requiring a smaller quantity of the active agent for an effective local treatment.
In accordance with this invention, it is found that 2'-(4-pyridyl) -6,16a-dimethyl-ll3,17a,21-trihydroxy-pregna-4,6-dieno [3,2-c] -pyrazol-20-one, an anti-inflam-matory steroid can be administered to humans by applying topically a solution of the steroid in a clear water-white gel vehicle to the skin of the patient thereby obtaining local activity of the steroid. Also, it is found that the topical administration of this composition results in local activity rather than systemic activity of the steroid thus alleviating the necessity of large dosages, side effects and other unfavorable conditions . The steroid in the clear water-white gel vehicle is highly substantive to the skin, possesses a high degree of local skin pen- etrating activity and in addition can be applied topically to the skin without occlusion.
The active ingredient employed in the practice of this invention is represented by Formula I below: The pharmaceutically acceptable salts of Formula I are to be considered within the scope of the invention. Re- presentative examples of said pharmaceutically acceptable salts are hydrohalide, perchlorate, picrate, acetate, sul- fate, phthalate, succinate, citrate, lactate and nitrate.
In order to ensure that a sufficient amount of the steroid, 2 ' - (4-pyridyl) -6, 16a-dimethyl-ll3, 17a, 21-tri- hydroxypregna- , 6-dieno [3,2-c] -pyrazol-20-one, is absorbed externally by topical application, it is necessary to em- ploy a vehicle which will permit an efficient absorption of the steroid through the skin. The essential ingredients of the clear water-white gel vehicle employed herein are water, at least one solvent and at least one thickening agent .
The solvent may constitute from about 60% to 90% of the gel vehicle. Representative solvents are ethyl alcohol, isopropyl alcohol, propylene glycol, glycerine, 2-octyl dodecanol and methyl pyrrolidine. Of particular preference is a combination of isopropyl alcohol and pro-pylene glycol at a 0.5 to 0.6 ratio constituting from about 80% to 90% of the gel vehicle. The solubility of the steroid in the solvent system should be at a minimum to obtain maximum partitioning of the steroid from the vehicle to the skin.
The thickening agent may constitute from 0.5 to 4% of the gel vehicle. Representative thickening agents are hydroxyethyl cellulose, hydroxypropyl cellulose and B.F. Goodrich Carbopol 940 (Merck Index, 8th Edition, page 210, 1968) .
Water may constitute from about 8% to 18% of the gel vehicle. Of particular preference is from about 10% to 15% by weight.
Optionally, a stabilizing agent may be employed in the practice of the invention. When employed, said stabilizing agent may constitute from about 0.02% to 0.1% of the gel vehicle. Representative stabilizing agents are disodium edetate, sodium citrate, dipotassium edetate and citric acid. Of particular preference is disodium edetate at 0.05% by weight.
The pharmaceutical compositions oi this invention contain a clear water-white gel vehicle and 2 ' - (4-pyridyl) - 6 , 16a-dimethyl-ll3, 17α, 21-trihydroxypregna-4 , 6-dieno [3, 2-c] -pyrazol-20-HDne as ingredients thereof. The vehicle may constitute from 99% to 99.999% of the total formulation weight. The active ingredient may constitute from 0.001% to 1.0% of the total formulation weight. Of particular preference is the combination of from about 0.01% to 0.25% of the active ingredient and 99.75% to 99.99% of the clear water-white gel vehicle to the total weight of the composition. The formulations included herein are effective in the treatment of topical inflammatory conditions in patients .
It will be understood, however, that the specific dose level for any particular patient will depend upon a variety of factors including the age, body weight, general health, sex, diet, time of administration, rate of excretion, drug combination and the severity of the particular area undergoing therapy. Of particular preference is the application of the formulation to the skin 2 to 4 times daily.
The steroid employed in this invention is disclosed in Patent Specification No. 40485, wherein it is taught as an anti-inflamma ory agent. Also, see U.S. Patent No. 3,067,194.
The active agent, 2 *- (4-pyridyl) -6,16a-dimethyl- 11β, 17a,21-trihydroxypregna-4, 6-dieno [3,2-c] -pyrazol-20-one, employed in the formulations herein above described, is prepared as follows : A mixture of 7.30 g. of 4-chloropyridine, 8.63 g. of benzoylhydrazine and 25 cc of anhydrous ethanol is heated in a bomb tube under pressure at a temperature of 120°C for a period of approximately 14 hours . The reaction mixture is cooled, extracted first with hot ethanol and then with hot water, and the aqueous and ethanol extracts are combined and evaporated to dryness. The residue material is crystal-lized twice from a mixture of one part methanol to two parts ethyl acetate to give N- (4-pyridyl) benzyhydrazide; m.p. 225-231°C.
A mixture of 2.08 g. of N- (4-pyridyl) benzhydra-zide and 15 cc of 23% aqueous hydrochloric acid solution is heated under reflux for a period of about 3 hours. The resulting mixture is cooled to about 0°C, filtered, and the filtered solution is evaporated to dryness . The cry-stalline product is washed with one 15 cc-portion of hot methanol, and with three 10 cc-portions of cold methanol; the crystalline material is then dried to give substantially pure 4-hydrazino-pyridine hydrochloride m.p. 245-250°C.
A solution containing approximately 0.4 g. of 4-hydrazino-pyridine hydrochloride dissolved in about 12 cc of an 8:2 mixture of ethanol-water is added to a solution containing two molecular equivalents of potassium acetate dissolved in 5 cc of water. To the resulting mixture is added a solution containing about one gram of 2-hydroxy-methylene-6 , 16a-dimethyl-ll -hydroxy-17 ,20:20, 21-bis (methy-lenedioxy) -pregna-4 , 6-diene-3-one dissolved in about 25 cc of warm ethanol. The resulting solution is heated at re- flux temperature for a period of approximately 4 hours, at the end of which time about 10 cc of solvent is evaporated, whereupon crystalline material separates from the reaction solution. The resulting crystalline slurry is diluted with an equal volume of water, and the insoluble material is re- covered by filtration and dried to give about 1.3 g. of crude product which, upon crystallization from methylene chloride-ethanol solution, gives substantially pure 2*(4-pyridyl) -6, 16a-dimethy1-11β-hydroxy-17 ,20:20 , 21-bis (methyl-enedioxy) -pregna-4, 6-diene [3, 2-c] -pyrazole; m.p. 276-283°C. The mother liquors lirom the recrystallization are subjected to thin-layer chromatography on silica gel, utilizing 8% methanol as eluting solvent, to give an additional 2,(4-pyridyl) -6, 16a-dimethyl-ll -hydroxy-17 ,20:20, 21-bis (methyl-enedioxy) -pregna-4, 6-diene [3,2-c] -pyrazole.
A solution containing 0.365 g. of 2 (4-pyridyl) -6,16a-dimethyl-ll3-hydroxy-17,20:20,21-bis (methylenedxoxy) -pregna-4, 6-dieno [3, 2-c] -pyrazole dissolved in 7 ml. of a 6:4 mixture of formic acid and water, is heated at a tem-perature of about 95-98°C for a period of approximately twenty-five minutes. The reaction mixture is cooled to about 0°C, made alkaline by the addition of aqueous sodium hydroxide solution, and the resulting suspension is ex-tracted with three 7 ml.-portions of ethyl acetate. The combined ethyl acetate extracts are dried over anhydrous magnesium sulfate, and the dry ethyl acetate solution is evaporated in vacuo to give crude material which, upon recrystallization from methylene chloride, gives substan-tially pure 2' -(4-pyridyl) -6, 16a-dimethyl-20-oxo-ll ,17a-21-trihydroxy-pregna-4, 6-dieno [2, ] -c] -pyrazole; m.p. 209-213°C. The mother liquors from the methylene chloride recrystallization are subjected to thinlayer chromatography on silica gel, utilizing a 9:1 mixture of chloroform-methanol as eluting solvent, to give additional 2' (4- - - - - - - The following examples illustrate the preparation of the various anti-psoriasis compositions of the invention. The examples should be construed as illustrations of the invention rather than limitations thereof.
Example 1 Topical Gel Ingredients % w/w 2 '- (4-pyridyl) -6 , 16a-dimethyl- 11β , 17a, 21-trihydroxypregna- 4,6-dieno [3,2-c] -pyrazol-20-one 0.25 Disodium edetate 0.05 Carbopol 940 1.00 Diisopropanolamine 0.80 Purified water 13.00 Isopropyl alcohol anhydrous 30.00 Propylene glycol 54.90 The Carbopol 940 is dispersed into approximately 80% of the isopropyl alcohol with continuous agitation at room temperatrue while adding a solution which contains disodium edetate in approximately 50% of the water. To this stirred mixture is added a solution which contains 2 (4-pyridyl) -6 , 16a-dimethy1-11β , 17a, 21-trihydroxypregna-4,6-dieno [3,2-c] -pyrazol-20-one in the remaining 20% of isopropyl alcohol and 20% of the propylene glycol. The balance of the propylene glycol is used to rinse the con-tainer. To the resulting mixture is added a solution con-taining the diisopropanolamine and the balance of the water. The gel mixture thus obtained is aged while stirring at 42365/2 Example 2 \ Topical Gel \ Ingredients % w/w 2 '-(4-pyridyl) -6, 16a-diinethyl- 11β , 17a, 21-trihydroxypregna- 4,6-dieno [3,2-c] -pyrazol-20-one 0.10 Disodium edetate 0.05 Purified water 13.00 Carbopol 940 1.00 Diisopropanolamine 0.80 Propylene glycol 85.05 \. The Carbopol 940 is dispersed into approximately 80 of the propylene glycol with continuous agitation at room temperature while adding a solution which contains disodium edetate in approximately of the water. To this stirred mixture is added a solution which contains 1 -( 4-pyridyl) -6 , 1 6cc-dimethyl-1 1 β , 1 7a , 21 -trihydroxypregna-4 , in the remaining 20 of the propylene glycol. To the resulting mixture is added a solution containing the diisopropanolamine and the balance of the water. The gel mixture thus obtained is a_ged while stirring at room temperature for approximately 1 5 minutes.
Example 3 Topical Gel Ingredients % w/w 2' -(4-pyridyl) -6, 16a-dimethyl- 11β,17α, 21-trihydroxypregna 4 , 6-dient [3 , 2-c] -pyrazol-20-one 0.1 Disodium edetate 0.05 Purified water 13.00 Hydroxypropyl cellulose 2.60 Propylene glycol 84.25 To an agitated hot water solution containing di-sodium edetate at 60°-80°C. is added the hydroxypropyl cell-ulose. This mixture is agitated until the hydroxypropyl cellulose is completely dispersed and wetted. While agita-ting said mixture, a solution which contains 2 '- (4-pyridyl) -6, 16a-dimethyl-ll3, 17a, 21-trihydroxypregna-4, 6-dieno [3, 2-c] -pyrazol-20-one and propylene glycol is added. The resulting gel mixture is aged while agitating at room temperature for approximately 15 minutes.
Example 4 Topical Gel Ingredients % w/w 2 (4-pyridyl) -6,16a-dimethyl- Ingredients % w/w Disodium edetate 0.054 Purified water 13.000 Hydroxypropyl cellulose 2.600 Propylene glycol 84.345 To an agitated hot water solution containing dis-odium edetate at 60°-80°C. is added the hydroxypropyl cell-ulose. This mixture is agitated until the hydroxypropyl cellulose is completely dispersed and wetted. While agita-ting said mixture, a solution which contains 21 - (4-pyridyl) -6, 16a-dimethyl-ll , 17a, 21-trihydroxypregna-4, 6-dieno [3, 2-c] -pyrazol-20-one and propylene glycol is added. The resulting gel mixture is aged while agitating at room temperature for approximately 15 minutes.
Example 5 Topical Gel Ingredients % w/w 2 '-(4-pyridyl) -6, 16a-dimethyl- 11β, 17a,21-trihydroxypregna- 4, 6-dieno [3, 2-c] -pyrazol-20-one 1.0 Disodium edetate 0.5 Purified water 13.00 Hydroxypropyl cellulose 2.60 Propylene glycol 82.90 i ate h tion containin dis- odium edetate at 60°-80°C. is added the hydroxypropyl cell-ulose. This mixture is agitated until the hydroxypropyl cellulose is completely dispersed and wetted. While agita-ting said mixture, a solution which contains 2 (4-pyridyl) -6, 16a-dimethyl-l^-17a,21-trihydroxypregna-4, 6-dieno [3, 2-c] -pyrazol-20-one and propylene glycol is added. The resulting gel mixture is aged while agitating at room temperature for approximately 15 minutes.
Example 6 Topical Gel Ingredients % w/w 2'-(4-pyridyl) -6, 16a-dimethyl- llfj, 17a, 21-trihydroxypregna- 4, 6-dieno [3, 2-c] -pyrazol-20-one 0.1 Disodium edetate 0.05 Purified water 13.00 Hydroxypropyl cellulose 2.60 Isopropyl alcohol anhydrous 30.00 Propylene glycol 54.25 To an agitated hot water solution containing dis-odium -edetate at 60e-80eC. is added,the.Jiydxoxypropyl cell-ulose. This mixture is agitated until the hydroxypropyl cellulose is completely dispersed and wetted. While agita-ting said mixture, a solution which contains 2 *- (4-pyridyl) -6 ,16a-dimethyl-113-.17a,21-trihydroxypregna-4 , 6-dieno [3, 2-c] - isopropyl alcohol pyrazol-20-one/and propylene glycol is added. The resulting gel mixture is aged while agitating at room temperature for approximately 15 minutes.

Claims (9)

42365/2 CLAIMS '^ An anti-inflammatory
1. L composition for topical administration comprising a clear water-white gel and an effective amount of 2'-(4-pyridyl)-6 , 16a-dimethyl-11 β , 17« f 21 -trihydroxypregna- ,6-dieno 5» 2-c7-pyraz.ol-20-one.
2. A composition according to Claim 1 , wherein the clear water-white gel is comprised of at least one solvent, at least one thickening agent and ater.
3. A composition according to Claim 2, wherein the solvent is selected from the group consisting of ethylalcohol, isopropyl alcohol, propylene glycol and glycerol; and the thickening agent is selected from the group consisting of hydroxyethyl cellulose, hydroxypropyl cellulose and Carbopol 940.
4. A composition according to Claim 3, wherein the solvent is propylene glycol and the thickening agent is Carbopol 940.
5. A composition according to Claim 3» wherein the solvent is a mixture of isopropyl alcohol and propylene glycol and the thickening agent is Carbopol 940.
6. A composition according to Claim 5, wherein the isopropyl alcohol and propylene glycol solvent mixture is at a 0.5 to 0.60 ratio
7. A composition according to Claim 3» wherein the solvent is propylene glycol and the thickening agent is hydroxypropyl cellulose.
8. A composition according to Claim 7, wherein the solvent is a mixture of isopropyl alcohol and propylene glycol and the thickening agent is hydroxypropyl cellulose. 42365/2
9. A composition according to Claim 8, wherein the isopropyl alcohol and propylene glycol solvent mixture is at a 0.5 to 0„60 ratio. \
IL42365A 1972-06-09 1973-05-28 Anti-inflammatory topical composition containing 2-(4-pyridyl-6,16alpha-dimethyl-11beta,17alpha,21-trihydroxypregna-4,6-dieno(3,2-c)-pyrazol-20-one IL42365A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US26118672A 1972-06-09 1972-06-09
US26774372A 1972-06-30 1972-06-30

Publications (2)

Publication Number Publication Date
IL42365A0 IL42365A0 (en) 1973-07-30
IL42365A true IL42365A (en) 1977-04-29

Family

ID=26948452

Family Applications (1)

Application Number Title Priority Date Filing Date
IL42365A IL42365A (en) 1972-06-09 1973-05-28 Anti-inflammatory topical composition containing 2-(4-pyridyl-6,16alpha-dimethyl-11beta,17alpha,21-trihydroxypregna-4,6-dieno(3,2-c)-pyrazol-20-one

Country Status (8)

Country Link
CA (1) CA1014856A (en)
DE (1) DE2329130A1 (en)
FR (1) FR2187340B1 (en)
GB (1) GB1397893A (en)
IE (1) IE37718B1 (en)
IL (1) IL42365A (en)
NL (1) NL7307072A (en)
PH (1) PH10968A (en)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS59501159A (en) * 1982-06-24 1984-07-05 スミス、ロバ−ト・アラン medicated gel composition
US5721275A (en) 1989-06-07 1998-02-24 Bazzano; Gail S. Slow release vehicles for minimizing skin irritancy of topical compositions

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK135267A (en) * 1971-02-25
BE786884A (en) * 1971-07-30 1973-01-29 Merck & Co Inc STERANIC PYRAZOLE AND PROCESS

Also Published As

Publication number Publication date
GB1397893A (en) 1975-06-18
NL7307072A (en) 1973-12-11
CA1014856A (en) 1977-08-02
IE37718B1 (en) 1977-09-28
IE37718L (en) 1973-12-09
FR2187340B1 (en) 1976-10-22
AU5625573A (en) 1974-12-05
PH10968A (en) 1977-10-18
FR2187340A1 (en) 1974-01-18
DE2329130A1 (en) 1973-12-20
IL42365A0 (en) 1973-07-30

Similar Documents

Publication Publication Date Title
EP0189738B1 (en) Topical compositions for preventing or treating dry skin
DE60130147T2 (en) USE OF ORAL FORMULATIONS TO TREAT THE FEMALE SEXUAL DISORDER
FI95350B (en) Procedure for the preparation of topically useful drug lotions for the management of inflammation
DE69524614T2 (en) MEDICINAL COMPONENTS, INCLUDING AN N-SUBSTITUTED O-TOLUIDE INDEXIVATIVE AND TRANSDERMALLY ABSORBABLE PREPARATION
CN105188758A (en) Topical compositions of flunisolide and methods of treatment
US3899580A (en) Anti-inflammatory topical gel
CN111904925A (en) Flurbiprofen sodium gel preparation and preparation method and application thereof
US3934028A (en) Acne and psoriasis treatment with retinoic acid analogs
CN108283620A (en) A kind of local medicine composition of inhibitors of phosphodiesterase-4 and preparation method thereof
US3928624A (en) Phenol compounds in treating pain, fever and inflammation
JPS6310716A (en) Beta-stimulation agent for external use
US2890152A (en) Topical anti-inflammatory compositions
CN103877118A (en) Medicine composition consisting of methylprednisolone aceponate and zinc oxide
JPH0774152B2 (en) Liquid for external use on skin
JPH03204815A (en) Therapeutic composition for treating dermatological disease carried by mast cell
IL42365A (en) Anti-inflammatory topical composition containing 2-(4-pyridyl-6,16alpha-dimethyl-11beta,17alpha,21-trihydroxypregna-4,6-dieno(3,2-c)-pyrazol-20-one
JPH05194219A (en) Fungicidal agent for topical application
JPH0481569B2 (en)
JPH11302167A (en) Ufenamate preparation for external use
DE19849737A1 (en) Combination agent for the treatment of inflammatory bowel disease
JP3142559B2 (en) Uses of platelet activating factor antagonists as antipruritics
RU2225208C1 (en) Pharmaceutical composition eliciting anti-inflammatory and anti-allergic effect
JP2838297B2 (en) Topical containing colchicine
EP0244937A2 (en) Pharmaceutical compositions containing (R,S) or (S) N-(2-[2-hydroxy-3-phenoxypropyl]aminoethyl)isobutyramide
JPH08208487A (en) External preparation for treating inflammatory skin diseases