Pharmaceutical composition with analgesic and anti-inflammatory action
The invention relates to medicine, specifically to non-steroidal anti-inflammatory drug Ketoprofen. Pharmaceutical composition with analgesic and anti-inflammatory action contains a therapeutically effective amount of Ketoprofen and targeted supplements. Targeted supplements are ethyl alcohol, nipagin, carbomer, trometamol, flavouring and water. Pharmaceutical composition in the form of gel. Gel Ketoprofen meets all the requirements of Gosfarmakapei XI edition, has satisfactory organoleptic properties and has a shelf life of not less than 3 years. 5 C.p. f-crystals, 2 tab.
The invention relates to medicine, specifically to non-steroidal anti-inflammatory drug Ketoprofen.
Ketoprofen exhibits anti-inflammatory, antipyretic, analgesic and antiaggregatory effect, but most use in the medical practice of its analgesic and anti-inflammatory effect. Apply Ketoprofen in rheumatoid arthritis, non-specific spondylitis, gouty arthritis, pseudogout, osteoarthritis, non-articular rheumatism, pain syndrome (polioviral ivy tendons and ligaments, muscle spasm, swelling).
First Ketoprofen mentioned in U.S. patent No. 3641127, 1972. “3-(Benzoylphenyl)alcamovia acid. Subsequently, on the basis of Ketoprofen were created in various dosage forms for oral, intramuscular, intravenous, rectal and topical applications (encyclopedia of drugs”, RLS, 2003, S. 395).
From topically applied dosage forms of Ketoprofen most widely gels. For cutaneous applications of the gel is slow transdermal absorption of Ketoprofen, which ensures the maintenance of its concentration in inflamed tissues within therapeutic level for a long time. Ketoprofen is well into the synovial fluid and connective tissue.
In U.S. patent No. 4849418, 1989, describes the preparation of a gel Ketoprofen, on the basis of 4.0 g of Ketoprofen, 15.0 g of isopropanol, 7.5 g of dimethylisoxazole, with 23.5 g of a copolymer of polyoxyethylene-polyoxypropylene and 50.0 g of water. The components are thoroughly mixed for 10 minutes, then the mixture on grebaut under stirring up to 85C with weak high pressure (~0.3 bar) and maintained at this temperature for 15 minutes. The solution is cooled with stirring to room temperature the gel, containing 4% Ketoprofen. The disadvantage of this method of producing gel is the need to use high pressure and relatively high temperature in the process of obtaining a gel.
In U.S. patent No. 4545992, 1985. describes the preparation of a gel-based derivatives arylpropionic acid (ibuprofen, flurbiprofen, Ketoprofen, and others) with various auxiliary additives, such as methyl-, ethyl - or monoglycosyl, peppermint oil, water 4% of carbopol 940, water 2% alkali treated water. gels containing 0.5%, and 1.0%, 2.0% and 3.0% of the Ketoprofen, however, these pharmacological tests for Ketoprofen is not indicated, and tested the gel flurbiprofen.
In German patent No. 3119017, 1982. describes how to obtain gels containing 0.5%, and 1.0%, 3.0% and 5.0% of Ketoprofen. As auxiliary substances used carboxyvinyl-polymer, propylene carbonate, propylene glycol, hydroxypropylcellulose dissolved in ethanol or water, and as the alkaline additive - ethanolamine, triethanolamine, diisopropanolamine. The disadvantages of these compositions are unsatisfactory organoleptic properties and a limited shelf life.
In addition, the Russian market insufficiently provided Yes is and abroad. All this makes the actual development of the gel Ketoprofen.
The objective of the invention is to provide a pharmaceutical composition with analgesic and anti-inflammatory gel Ketoprofen, which meets all the requirements of gosfarmakapei XI editions and requirements on the drug Ketoprofen, has satisfactory organoleptic properties and has a shelf life of not less than 3 years.
This is achieved by a pharmaceutical composition with analgesic and anti-inflammatory action, containing as active ingredient a therapeutically effective amount of Ketoprofen and targeted supplements, including geleobrazovanie, thickeners, preservatives, fragrances and solvents.
The results of this research suggest the following structure of the gel Ketoprofen, g:
Ethyl alcohol 36,0-48,0
Water to 100 g
Ethyl alcohol is selected as the solvent Ketoprofen as the least toxic solvent than acetone or methylene chloride. Because, on the one hand, Ketoprofen insoluble in water, but RA is de, as the dispersion medium of the gel it is necessary to use a two-component solvent consisting of water and ethyl alcohol, taken in a certain ratio.
As the gelling rational use of carbomer 940 or carbomer 980, representing a high molecular weight polymers of acrylic acid, crosslinked allyl ethers of pentaerythritol. Carbomer brands 940 and 980 have the same average molecular weight and viscosity solutions, but differ in the technology of production.
Gels based carbonero is infilled with the increase of pH the introduction of the alkaline components of the solutions of alkalis, ammonia, amines. In the proposed gel Ketoprofen as a thickener selected trometamol (trisamin), which, unlike other amino thickeners, such as di - and triethanolamines, has no irritant properties and less toxic, so you can use it even in injecting drugs (for example, a solution trisamina for injection).
As a preservative selected nipagin - methyl ester p-oksibenzoynoy acid. In addition, the preservative effect of ethyl alcohol.
As fragrances (perfumes) taken lavender oil and/or oil Nero is the mental way (see table.1) is optimal and allows to obtain a technical result that is appropriate to the task: gel Ketoprofen meets all the requirements of gosfarmakapei XI ed., regulatory requirements on Ketoprofen, has a pleasant organoleptic properties, and has a shelf life of 3 years or more (see table.2).
The following examples illustrate the invention.
Example 1. Moisten 22 ml of water and 1.7 g of carbomer 940 and the mixture was dispersed. To the resulting mass was added to 17.5 g of ethyl alcohol and stirred until a homogeneous dispersion carbomer. 2.5 g of Ketoprofen, 0.1 g nipagina, 0.06 g of lavender oil and 0.04 g neroli oil dissolve 13.6 g of ethyl alcohol rectified. The resulting solution was added to the aqueous dispersion of carbomer, stirred until a homogeneous mixture, then add aqueous-alcoholic (8,9 g of alcohol and 32.3 ml of water) solution of 1.3 g of trometamol and again stirred until a homogeneous gel. The prepared gel Packed in tubes. The obtained gel Ketoprofen meets all regulatory requirements and has a shelf life of over 3 years (see tab.2).
Example 2. gel Ketoprofen get analogously to example 1, on the basis of 2.25 g of Ketoprofen, 1,53 g carbomer 980 NF g of water. The obtained gel Ketoprofen on all indicators meet regulatory requirements (see tab.2).
Example 3. gel Ketoprofen get analogously to example 1, on the basis of 2.75 g of Ketoprofen, 1,87 g carbomer 940, 0.11 g nipagina, of 0.066 g of lavender oil, 0,044 g neroli oil, 1,43 g of trometamol, 44,0 g of rectified spirit and 49,73 g of water. The obtained gel Ketoprofen on all indicators meet regulatory requirements (see tab.2).
Example 4. Gel Ketoprofen get analogously to example 1, on the basis of 5.5 g of Ketoprofen, 0,93 g carbomer 980, 0.25 g nipagina, 0.20 g of lavender oil, 1.70 g of trometamol, 48,0 g of ethyl alcohol and 43,42 g of water. The obtained gel Ketoprofen on all indicators meet regulatory requirements (see tab.2).
Example 5. Gel Ketoprofen get analogously to example 1, on the basis of 1.50 g of Ketoprofen, 2,48 g carbomer 940, 0.05 g nipagina, 0.03 g neroli oil, 0.95 g of trometamol, 41,0 g of rectified spirit and 53,99 g of water. The obtained gel Ketoprofen on all indicators meet regulatory requirements (see tab.2).
1. Pharmaceutical composition with analgesic and anti-inflammatory effect, containing a therapeutically effective amount of ketoprofene, trometamol, flavouring and water in the following ratio of components, g:
Ethyl alcohol 36,0-48,0
Water To 100
2. The pharmaceutical composition under item 1, characterized in that as a fragrance it contains lavender oil and/or neroli.
3. The pharmaceutical composition under item 1 or 2, characterized in that as carbomer it contains carbomer 940 or carbomer 980.
4. The pharmaceutical composition under item 1, characterized in that it is made in the form of a gel.
5. The pharmaceutical composition according to p. 2, characterized in that it is made in the form of a gel.
6. The pharmaceutical composition according to p. 3, characterized in that it is made in the form of a gel.
which have the properties of receptor antagonists neirokinina-1(NK-1)
where X denotes a group of formula X-1, and Y denotes a group of formula Y-1
in which R15denotes halogen, nitro, (ness.)alkyl, PERFLUORO(ness.)alkyl; R16denotes hydrogen, halogen, nitro, (ness.)alkyl; R22and R23independently represent hydrogen, (ness.)alkyl, halogen or PERFLUORO(ness.)alkyl and at least one of the radicals R22and R23does not denote hydrogen, R24denotes hydrogen; or Y represents the group Y-3, which is a 3-7-membered ring of the formula
where R25denotes a group of formula R26-(CH2)e-; R26means (ness.)alkoxy, (ness.)alkylthio, (ness.)alkylsulfonyl, (ness.) alkylsulfonyl; Q represents a group -(CH2)f-; e represents an integer from 0 to 4; and f denotes an integer from 1 to 3
in which R1represents a hydrogen atom, a C1-6alkyl group, phenyl group, optionally substituted by a halogen atom, a C1-6alkylthio or C1-6alkylsulfonyl, or amino group, optionally substituted (i) C1-6alkyl group, or (ii) acyl group(C=O)-R5where R5represents C1-6alkyl group, phenyl or pyridyl; R2is6-14aryl group, optionally substituted by a halogen atom or C1-6alkoxy, or 5 - or 6-membered aromatic heterocyclic group containing one sulfur atom or one nitrogen atom; R3represents a phenyl group, optionally substituted by one or two C1-6alkyl groups or C1-6alkoxy; X represents a sulfur atom; Y represents O, S, SO2or NR4where R4represents a hydrogen atom or a C1-6alkyl group; and Z represents a bond, C1-6alkylenes group, optional zameshannuu oxo or C1-6alkyl group
in which R denotes hydrogen, C1-C7alkyl, C1-C7alkoxy, halogen or CF3, R1means H or halogen, or R and R1may together form-CH=CH-CH=CH-; R2means H, halogen, CF3, R3means H or C1-C7alkyl, R4means H or piperazine-1-yl; R5means H or C1-C7alkyl, X is-C(O)N(R5)-, -(CH2)mO-, -(CH2)mN(R5)-, -N(R5)C(O)- or N(R5)(CH2)m-; n is an integer from 0 to 4, m is 1 or 2, and their pharmaceutically acceptable acid additive salts