DK144358B - CREME CONTAINING ONE OR MORE TOPICALLY ACTIVE MEDICINES IN A CARRIER AND THEIR MANUFACTURING PRODUCTS - Google Patents
CREME CONTAINING ONE OR MORE TOPICALLY ACTIVE MEDICINES IN A CARRIER AND THEIR MANUFACTURING PRODUCTS Download PDFInfo
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- DK144358B DK144358B DK179474AA DK179474A DK144358B DK 144358 B DK144358 B DK 144358B DK 179474A A DK179474A A DK 179474AA DK 179474 A DK179474 A DK 179474A DK 144358 B DK144358 B DK 144358B
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- 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
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- 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
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Description
(19) DANMARK {\~:?)(19) DENMARK {\ ~:?)
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W (12) FREMLÆGGELSESSKRIFT on 144358 BW (12) PUBLICATION NOTICE on 144358 B
DIREKTORATET FOR PATENT- OG VAR EMÆR KEVÆSEN 5TDIRECTORATE OF PATENT AND WERE EMERY CHEESE 5T
(21) Ansøgning nr. 1794/74 (51) Int.CI.3 A 61 K 9/10 (22) Indleveringsdag 1 · apr. 1974 (24) Løbedag 1 . apr. 1974 (41) Aim. tilgængelig J>. o.kt. 1974 (44) Fremlagt 1. mar. 1982 (86) International ansøgning nr.(21) Application No. 1794/74 (51) Int.CI.3 A 61 K 9/10 (22) Filing date 1 · Apr. 1974 (24) Race day 1. April 1974 (41) Aim. available J>. o.kt. 1974 (44) Submitted Mar 1 1982 (86) International application no.
(86) International indleveringsdag (85) Videreførelsesdag - (62) Stamansøgning nr. -(86) International filing day (85) Continuation day - (62) Master application no. -
(30) Prioritet 2. apr. 1975, 15758/75, GB(30) Priority 2 Apr 1975, 15758/75, GB
(71) Ansøger GLAXO LABORATORIES LIMITED, Greenf ord, GB.(71) Applicant GLAXO LABORATORIES LIMITED, Greenf ord, GB.
(72) Opfinder Michael Joseph Bus se, GB: Michael Harold Franks, GB.(72) Inventor Michael Joseph Bus se, GB: Michael Harold Franks, GB.
(74) Fuldmægtig Internationalt Patent-Bureau.(74) International Patent Bureau.
(54) Creme indeholdende et eller flere topisk aktive lægemidler i en bæ= rer samt middel til fremstilling deraf.(54) Cream containing one or more topically active drugs in a carrier as well as means for preparing them.
Den foreliggende opfindelse angår en creme indeholdende et eller flere topisk aktive lægemidler i en bærer samt et middel til fremstillipg af denne creme bestående af en farmaceutisk bærer.The present invention relates to a cream containing one or more topically active drugs in a carrier and an agent for the preparation of this cream consisting of a pharmaceutical carrier.
Farmaceutiske cremer har i mange år været almindelig anvendt inden for medicinen til topisk påføring af lægemidler. Det menes nu, at bærerens sammensætning kan spille en vigtig rolle ved bestemmelse af den hastighed, hvormed lægemidlet 00 gQ frigøres fra cremen, og dets absorption gennem huden, hvorpå den er påført topisk.Pharmaceutical creams have been widely used in medicine for topical application of drugs for many years. It is now believed that the composition of the carrier may play an important role in determining the rate at which the drug 00 gQ is released from the cream and its absorption through the skin to which it is applied topically.
^ Der kendes såvel cremer, hvis bærer er i det væsentlige vandfri og ΓΟ indeholder ikke-vandige opløsningsmidler, såsom glycoler, som cremer, hvis bærer ^ indeholder en væsentlig mængde vand. Der er i de senere år især blevet fremsat adskillige forslag til formulering af cremer af den førstnævnte art.^ Both creams whose carrier is substantially anhydrous and ΓΟ contain non-aqueous solvents such as glycols, and creams whose carrier ^ contains a substantial amount of water are known. In recent years, in particular, several proposals have been made for formulating creams of the former kind.
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OISLAND
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Cremer af den sidstnævnte art, med en vandig bærer, kendes f.eks. fra patenthavernes engelske patentskrift nr. 1.261.650. Disse bærere indeholder omkring 70% vand sammen med ca. 20% voks og desuden paraffin og et overfladeaktivt middel.Creams of the latter kind, with an aqueous carrier, are known e.g. from the patent holder's English Patent No. 1,261,650. These carriers contain about 70% water along with approx. 20% wax and also paraffin and a surfactant.
Det har nu ifølge opfindelsen vist sig, at der kan opnås værdifulde fordele ved anvendelsen af visse nye vandige bærere (som vil blive nærmere beskrevet nedenfor) ved formuleringen af topisk aktive lægemidler.It has now been found, according to the invention, that valuable benefits can be obtained from the use of certain novel aqueous carriers (which will be described in detail below) in the formulation of topically active drugs.
Sagt meget generelt Består-de nye bærere af en dispersion af mindst eet voks eller vokslignende materiale i en vandig fase, der også indeholder et med vand blandbart opløsningsmiddel, der tåles af huden, fortrinsvis et hydroxylgruppehol-digt opløsningsmiddel, hensigtsmæssigt mindst een glycol og/eller glycerol. Det har vist sig,at disse nye bærere frembyder visse meget værdifulde fordele såvel med hensyn til formulering som påføring.Said very generally, the new carriers consist of a dispersion of at least one wax or wax-like material in an aqueous phase which also contains a water-miscible solvent tolerated by the skin, preferably a hydroxyl group-containing solvent, suitably at least one glycol and / or glycerol. It has been found that these new carriers offer some very valuable advantages in terms of both formulation and application.
Det har endvidere vist sig, at der kan opnås særligt fordelagtige resultater ved anvendelsen af voks, vand og hydroxylgruppeholdigt opløsningsmiddel i bærerne i de nedenfor angivne mængder, idet tilstedeværelsen af forholdsvis små mængder voks i bærerne medfører særlig gunstige resultater.Furthermore, it has been found that particularly advantageous results can be obtained by the use of wax, water and hydroxyl group-containing solvent in the carriers in the amounts indicated below, the presence of relatively small amounts of wax in the carriers giving particularly favorable results.
Cremen ifølge opfindelsen er ejendommelig ved, at bæreren er i det væsentlige oliefri og består af en dispersion af voks i en vandig fase omfattende vand og et med vand blandbart hydroxylgruppeholdigt opløsningsmiddel, hvilken dispersion yderligere indeholder et overfladeaktivt middel, idet voks, vand, hydroxylgruppeholdigt opløsningsmiddel og overfladeaktivt middel er tilstede i mængder på henholdsvis 5,0 til 30%, 7,0 til 75%, 10 til 80% og 0,1 til 10% baseret på den totale vægt af bæreren, hvorhos cremen eventuelt indeholder yderligere, sædvanlige farmaceutiske hjælpestoffer.The cream according to the invention is characterized in that the carrier is substantially oil-free and consists of a dispersion of wax in an aqueous phase comprising water and a water-miscible hydroxyl group-containing solvent, which further comprises a surfactant, wax, water, hydroxyl-group-containing solvent. and surfactants are present in amounts of 5.0 to 30%, 7.0 to 75%, 10 to 80%, and 0.1 to 10%, respectively, based on the total weight of the carrier, where the cream optionally contains additional conventional pharmaceuticals. excipients.
Opfindelsen angår som nævnt også et middel til fremstilling af den omhand-. lede creme. Dette middel er ejendommeligt ved det i krav 10's kendetegnende del angivne.The invention also relates, as mentioned, to a means for the preparation of the present invention. joint cream. This agent is peculiar to the characterizing part of claim 10.
De bedste resultater opnås med cremer indeholdende en bærer med den i et eller flere af kravene 2-9 angivne sammensætning, henholdsvis med midler med en sådan sammensætning.The best results are obtained with creams containing a carrier of the composition of one or more of claims 2-9, or of agents of such composition, respectively.
I den omhandlede ny„e. bærer kan lægemidler med lav opløselighed i vand forekomme i opløsning, i det mindste delvis og fortrinsvis i overvejende grad, i den vandige fase, hvilket letter afgivelsen af lægemidlet fra bæreren. En anden faktor, der har vist sig at styre hastigheden af lægemidlets frigivelse fra cremen, er tilstedeværelsen eller fraværelsen af olier i cremen. Man har tidligere fremstillet cremer som olieagtige emulsioner indeholdende op til 50 % olie. Tilstedeværelsen af væsentlige mængder olie i en creme vil, især hvis lægemidlet har relativ god opløselighed i olien, i almindelighed hæmme frigivelsen af lægemidlet i 3 144358 større eller mindre udstrækning. Selv om lægemidlet opløses i cremens vandige fase, vil tilstedeværelsen af en olieagtig fase have en ugunstig virkning på frigivelsen af lægemidlet, idet en del af dette vil gå over i oliefasen. I modsætning hertil undgås anvendelsen af væsentlige mængder af en oliekomponent i den omhandlede nye hærer.In the new “e. carrier, low-solubility drugs in water can occur in solution, at least partially and preferably predominantly, in the aqueous phase, which facilitates delivery of the drug from the carrier. Another factor that has been shown to control the rate of drug release from the cream is the presence or absence of oils in the cream. Creams have previously been prepared as oily emulsions containing up to 50% oil. The presence of significant amounts of oil in a cream, especially if the drug has relatively good solubility in the oil, will generally inhibit the release of the drug to a greater or lesser extent. Although the drug dissolves in the aqueous phase of the cream, the presence of an oily phase will have an adverse effect on the release of the drug, part of which will go into the oil phase. In contrast, the use of significant amounts of an oil component in the new armies is avoided.
Hertil kommer, at indholdet af væsentlige mængder vand i den nye bærer formindsker den potentielle irritation af huden sammenlignet med de tidligere bærere, der i det væsentlige var baseret på Ikke-vandige opløsningsmidler, såsom glycoler, f.eks. propylenglycol.In addition, the content of significant amounts of water in the new carrier reduces the potential irritation of the skin compared to the previous carriers which were essentially based on non-aqueous solvents such as glycols, e.g. propylene glycol.
Desuden har indholdet af vand i de nye- bærere vist sig at lette deres fremstilling. Ved fremstillingen af de ovenfor nævnte vandfri bærere har det været almindeligt at anvende et eller andet overfladeaktivt middel til opnåelse af sammenblandingen af ingredienserne. Selv om der anvendes et egnet overfladeaktivt middel, er det imidlertid stadig nødvendigt at anvende en særlig fremstillingsteknik, da det overfladeaktive middel ikke kan udøve sin normale befugtningsvirkning tilfredsstillende i fraværelse af vand. I modsætning hertil indeholder den nye bærer vand,og de overfladeaktive midler kan let anvendes deri. Desuden kan de nye bærere let fremstilles under anvendelse af sædvanlig teknik, såsom blanding, omrøring, afkøling osv.,og kræver ikke anvendelse af specielle arbejdsbetingelser eller speciel teknik.In addition, the content of water in the new carriers has been shown to facilitate their preparation. In the preparation of the above-mentioned anhydrous carriers, it has been common to use some surfactant to obtain the mixing of the ingredients. However, although a suitable surfactant is used, it is still necessary to use a special preparation technique, since the surfactant cannot adequately exert its normal wetting effect in the absence of water. In contrast, the new carrier contains water and the surfactants can be readily used therein. In addition, the new carriers can be readily prepared using conventional techniques such as mixing, stirring, cooling, etc., and do not require the use of special working conditions or techniques.
De nye bærere indeholder mindst eet voks. Udtrykket "voks" benyttes her i bredeste forstand og omfatter ikke blot almindelige voksarter, men andre materialer, der har vokslignende fysiske og/eller kemiske egenskaber. Eksempler på voks, der kan anvendes i bærerne, er monoestere af langkædede (f.eks. C16_C24^ fedtsyrer og glycerol, fortrinsvis mættede fedtsyreestere, såsom glyce-rolmonostearat; voksagtige triglycerider, derunder acetoglycerider,dvs. acetylere-de mono— og diglycerider; fede alkoholer, f.eks. mættede fede alkoholer, fortrinsvis indeholdende 16-24 carbonatomer, især cetylalkohol, stearylalkohol, cetostea-rylalkohol, behenylalkohol osv.; mættede fede syrer af voksagtig natur, fortrinsvis indeholdende 14-26 carbonatomer, især stearinsyre; og naturlige og syntetiske voksarter, såsom bivoks.The new carriers contain at least one wax. The term "wax" is used here in the broadest sense and includes not only ordinary waxes, but other materials having wax-like physical and / or chemical properties. Examples of waxes that can be used in the carriers are long chain monoesters (e.g., C 16 -C 24 fatty alcohols, for example, saturated fatty alcohols, preferably containing 16-24 carbon atoms, especially cetyl alcohol, stearyl alcohol, cetostearyl alcohol, behenyl alcohol, etc .; saturated fatty acids of waxy nature, preferably containing 14-26 carbon atoms, especially stearic acid; and synthetic waxes such as beeswax.
De ovenfor nævnte voksarter er alle af hydrofob natur og danner med et passende overfladeaktivt middel en dispersion i vand. Om ønsket kan der yderligere være hydrofile voksarter til stede. Disse opløses i den vandige komponent. Eksempler på sådanne hydrofile voksarter er polyethylenglycoler af voksagtig natur, f.eks. med en molekylvægt på 1500-6000.The above-mentioned waxes are all hydrophobic in nature and form with a suitable surfactant a dispersion in water. If desired, hydrophilic waxes may also be present. These are dissolved in the aqueous component. Examples of such hydrophilic waxes are polyethylene glycols of waxy nature, e.g. with a molecular weight of 1500-6000.
Vokskomponenterne er fortrinsvis til stede i en total mængde på 10-20 % af bærerens vægt.The wax components are preferably present in a total amount of 10-20% of the weight of the carrier.
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De nye bærere indeholder som nævnt et hydroxylgruppeholdigt opløsningsmiddel i en mængde på 10 til 80% af bærerens totale vægt, og de adskiller sig herved fra de fra det ovennævnte engelske patentskrift nr. 1.261.650 kendte bærere. Tilstedeværelsen af et hydroxylgruppeholdigt opløsningsmiddel medfører den fordel, at lægemidlet i cremen lettere overføres til huden.The new carriers, as mentioned, contain a hydroxyl group-containing solvent in an amount of 10 to 80% of the total weight of the carrier, and are thereby different from the carriers known from the above-mentioned English patent No. 1,261,650. The presence of a hydroxyl group-containing solvent has the advantage that the drug in the cream is more easily transferred to the skin.
Det hydroxylgruppeholdige opløsningsmiddel kan f.eks. bestå af en eller flere glycoler, fortrinsvis glycoler, hvori lægemidlet er opløseligt, i det mindste i nogen udstrækning, hvorved opnås, at lægemidlet kan bevæge sig i bæreren og nå den overflade, der skal behandles. Arten af og mængden af glycolop-løsningsmiddel kan således hensigtsmæssigt vælges med henblik på at sikre delvis eller fuldstændig opløsning af lægemidlet deri. Eksempler på særligt foretrukne glycolopløsningsmidler til anvendelse i den nye creme henholdsvis den nye basrer er propandioler, såsom 1,2-propandiol, 1,3-propandiol, flydende polyethylenglycoler, især sådanne med en molekylvægt fra 100-800, dipropylenglycoler og blandinger deraf.The hydroxyl group-containing solvent may e.g. consist of one or more glycols, preferably glycols, wherein the drug is soluble, at least to some extent, thereby obtaining that the drug can move in the carrier and reach the surface to be treated. Thus, the nature and amount of glycol solvent can be suitably selected to ensure partial or complete dissolution of the drug therein. Examples of particularly preferred glycol solvents for use in the new cream and the new bacer, respectively, are propanediols such as 1,2-propanediol, 1,3-propanediol, liquid polyethylene glycols, especially those having a molecular weight of 100-800, dipropylene glycols and mixtures thereof.
De hydroxylgruppeholdige opløsningsmidler kan bestå af eller omfatte triva-lente alkoholer, såsom glycerol, idet denne er særlig nyttig til dermatologiske formål, hvor man ønsker en mild creme, f.eks. i salver til pediatrisk brug.The hydroxyl group-containing solvents may consist of or comprise trivalent alcohols such as glycerol, being particularly useful for dermatological purposes where a mild cream, e.g. in ointments for pediatric use.
I almindelighed udgør det hydroxylgruppeholdige opløsningsmiddel fortrinsvis 25-70 % baseret på den totale vægt af bæreren, især når opløsningsmidlet er en glycol. I det særlige tilfælde, hvor der anvendes sådanne trivalente alkoholer som glycerol, udgør disse imidlertid fortrinsvis kun indtil 40 %, fortrinsvis indtil 25 %, af bærerens totale vægt.In general, the hydroxyl group-containing solvent is preferably 25-70% based on the total weight of the carrier, especially when the solvent is a glycol. However, in the particular case where such trivalent alcohols as glycerol are used, these preferably constitute only up to 40%, preferably up to 25%, of the total weight of the carrier.
De nye cremer og bærere indeholder fortrinsvis 20-60 % vand baseret på bærerens totale vægt.The new creams and carriers preferably contain 20-60% water based on the total weight of the carrier.
Som ovenfor nævnt indeholder bærerne et overfladeaktivt middel. Dette tjener som dispergeringsmiddel for vokset, og også som stabiliseringsmiddel for den resulterende dispersion. Det overfladeaktive middel, der kan være en enkelt forbindelse eller en blanding, kan være ikke-ionisk og har fortrinsvis en HLB-værdi på mindst 8.As mentioned above, the carriers contain a surfactant. This serves as a wax dispersant, and also as a stabilizer for the resulting dispersion. The surfactant, which may be a single compound or mixture, may be nonionic and preferably has a HLB value of at least 8.
Eksempler på overfladeaktive midler er polyoxyethylenethere eller -estere, såsom Cetomacrogol 100Q (polyethylenglycol 1000 monocetylether), polyoxyethylen-stearat eller en blanding af stearater, især polyoxyethylen 40 stearat, eller polyoxyethylenlanolinderivater, især polyoxyethylen 25 lanolin. Der kan også anvendes et anionisk overfladeaktivt middel, såsom natriumlaurylsulfat, natrium-dioctylsulf o succinat osv.. De nye bærere indeholder fortrinsvis 1-5% overfladeaktivt middel, idet mængden og arten af det overfladeaktive middel vælges på grundlag af et forudgående forsøg til opnåelse af en tilfredsstillende afgivelse af lægemidlet.Examples of surfactants are polyoxyethylene ethers or esters such as Cetomacrogol 100Q (polyethylene glycol 1000 monocetyl ether), polyoxyethylene stearate or a mixture of stearates, especially polyoxyethylene 40 stearate, or polyoxyethylene lanolin derivatives, especially polyoxyethylene lanolin. An anionic surfactant such as sodium lauryl sulfate, sodium dioctyl sulfo succinate, etc. may also be used. The new carriers preferably contain 1-5% surfactant, the amount and nature of the surfactant being selected on the basis of a prior experiment to obtain a satisfactory delivery of the drug.
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Cremer med den her angivne sammensætning kan f.eks. anvendes til behandling af beskadigede hudpartier. Cremer til dette formål kan især indeholde lægemidler til topisk lindring af betændelsestilstande. Sådanne lægemidler er f.eks. antiinflammatoriske steroider,især af corticoidtypen. Særlige klasser af antiinflammatoriske steroidforbindelser, der med fordel kan indgå i de nye cremer,er de i beskrivelserne til de engelske patenter nr. 1.047.518, 1.047.519, 1.070.751, 1.139.506, 1.253.831, 1.281.689, 1.261.650, 1.384.372, 1.438.940 og 1.440.064 beskrevne.Creams of the composition herein may e.g. used to treat damaged skin areas. Creams for this purpose, in particular, may contain drugs for topically alleviating inflammatory conditions. Such drugs are e.g. anti-inflammatory steroids, especially of the corticoid type. Particular classes of anti-inflammatory steroid compounds which may advantageously be included in the new creams are those in the disclosures of English Patents Nos. 1,047,518, 1,047,519, 1,070,751, 1,139,506, 1,253,831, 1,281,689, 1,261,650, 1,384,372, 1,438,940 and 1,440,064 described.
Særlige steroidforbindelser, der med fordel kan indarbejdes i de omhandlede cremer,er f.eks. be t ame thas on-17-valerat, 21-chlor-21-des oxybetame thas on-17- propionat (21-chlor-9a-fluor-11β-hydroxy-Ιδβ-methyl-17oc-propionyloxy-pregna-1,4-dien-3,20-dion), betamethason-17-benzoat, fluocinolonacetonid (6a,9a-difluor-ΙΙβ, 21-dihydroxy-16a,17 a-isopropylidendioxy-pregna-1,4-dien-3,20-dion) og det tilsvarende 21-acetat, 9a-fluor-16-methylen-prednisolon-21-acetat, 6a,9a-difluor-prednisolon-21-acetat-17-butyrat, 9a,l^-dichlor-6a,21-difluor-16a,17a-isopropy-lidendioxy-pregna-l,4-dien-3,20-dion, 11β,21-dihydroxy-16a,17a-isopropylidendi-oxy-pregna-1,4-dien-3,20-dion, 9a,llp-dichlor-6a-fluor-21-hydroxy-16a,17«-isopro-py1idendioxy-pregna-1,4-dien-3, 20-dion, beclomethason-17,21-dipropionat (9a-chlor-16P-methyl-prednisolon-17,21-dipropionat), 21-chlor-21-desoxy-ll-dehydro-beta-methason-17-butyrat, 21-desoxy-betamethason-17-propionat, betamethason-17-iso-butyrat-21-acetat, Δ v -16p-methyl-prednisolon-17,21-dipropionat og methyl-ΙΙβ-hydroxy-3-oxo-17a-propionyloxy-androst-4-en-^-carboxylat.Particular steroid compounds which may advantageously be incorporated into the disclosed creams are e.g. be thas on 17-valerated, 21-chloro-21-des oxybetame thas on 17-propionate (21-chloro-9a-fluoro-11β-hydroxy-Ιδβ-methyl-17oc-propionyloxy-pregna-1,4 -diene-3,20-dione), betamethasone-17-benzoate, fluocinolone acetonide (6a, 9a-difluoro-β, 21-dihydroxy-16a, 17a-isopropylidene dioxy-pregna-1,4-diene-3,20-dione ) and the corresponding 21-acetate, 9a-fluoro-16-methylene-prednisolone-21-acetate, 6a, 9a-difluoro-prednisolone-21-acetate-17-butyrate, 9a, 1,1-dichloro-6a, 21-difluoro -16a, 17a-isopropyl-lidenedioxy-pregna-1,4-diene-3,20-dione, 11β, 21-dihydroxy-16a, 17a-isopropylidene-oxy-pregna-1,4-diene-3,20-dione , 9a, 11p-dichloro-6a-fluoro-21-hydroxy-16a, 17β-isopropylpyridenedioxy-pregna-1,4-diene-3,20-dione, beclomethasone-17,21-dipropionate (9a-chloro 16β-methyl-prednisolone-17,21-dipropionate), 21-chloro-21-deoxy-11-dehydro-beta-methasone-17-butyrate, 21-deoxy-betamethasone-17-propionate, betamethasone-17-iso-butyrate -21-acetate, Δ v -16β-methyl-prednisolone-17,21-dipropionate and methyl-β-hydroxy-3-oxo-17α-propionyloxy-androst-4-ene-β-carboxylate.
Andre lægemidler,der med fordel kan inkorporeres i cremerne ifølge opfindelsen,er blandt andet antibiotika, lokalanæstetika, antibakterielle forbindelser, antifungale forbindélser og andre dermatologiske lægemidler.Other drugs which may be advantageously incorporated into the creams of the invention include antibiotics, local anesthetics, antibacterial compounds, antifungal compounds and other dermatological drugs.
De omhandlede nye cremer eller bærere kan også om ønsket indeholde andre sædvanlige bestanddele og/eller additiver, f.eks. konserveringsmidler såsom chlorcresol, parabener såsom methyl- og propylparabener, og kviksølvforbindelser, vandbindende midler såsom sorbitol, eller egnede stabilisatorer, når dette er påkrævet, såsom natriumiiietabisulfit eller ethylendiamintetraeddikesyre.The disclosed new creams or carriers may also contain other usual ingredients and / or additives, e.g. preservatives such as chlorocresol, parabens such as methyl and propyl parabens, and mercury compounds, water-binding agents such as sorbitol, or suitable stabilizers when required such as sodium tetabisulfite or ethylenediaminetetraacetic acid.
Selvom bærerne ifølge opfindelsen er i det væsentlige oliefri, kån de indeholde forholdsvis små mængder af olieagtige smøremidler, dvs. indtil ca. 57>, fortrinsvis 1-2%, af bærerens vægt. Sådanne smøremidler er f.eks. siliconolie, flydende paraffin, ricinusolie, isopropylmyristat osv.Pærerne kan også indeholde en eller flere pufferforbindelser.Although the carriers of the invention are substantially oil-free, they may contain relatively small amounts of oily lubricants, i. until approx. 57>, preferably 1-2%, of the weight of the carrier. Such lubricants are e.g. silicone oil, liquid paraffin, castor oil, isopropyl myristate, etc. The bulbs may also contain one or more buffer compounds.
En creme ifølge opfindelsen kan f.eks. indeholde 0,0001 til 5%, hensigtsmæssigt 0,005 til 0,50% og fortrinsvis 0,01 til 0,10% af et antiinflammatorisk steroid, idet den nøjagtige procentmængde, der skal benyttes, let kan fastlægges under hensyn til steroidets styrke. 1 tilfælde af 21-chlor-21-desoxybetamethason- 6 144358 17-propionat er en passende mængde 0,05%.A cream according to the invention can e.g. contain 0.0001 to 5%, conveniently 0.005 to 0.50% and preferably 0.01 to 0.10% of an anti-inflammatory steroid, the exact percentage to be used being readily determined taking into account the strength of the steroid. 1 case of 21-chloro-21-deoxybetamethasone 6-propionate is an appropriate amount of 0.05%.
De omhandlede cremer og bærere kan let fremstilles f.eks. ved passende sammenblanding af komponenterne, f.eks. på konventionel måde, som belyst i eksemplerne. Det bemærkes, at det topisk aktive lægemiddel kan tilsættes til den i forvejen fremstillede creme eller, hvilket foretrækkes, kan inkorporeres i én af cremens komponenter før emulgeringen.The disclosed creams and carriers can be readily prepared e.g. by appropriate mixing of the components, e.g. in a conventional manner, as illustrated in the Examples. It is noted that the topically active drug can be added to the pre-made cream or, preferably, can be incorporated into one of the cream's components prior to emulsification.
Opfindelsen belyses nærmere ved hjælp af følgende eksempler.The invention is further illustrated by the following examples.
Eksempel 1 Bærerens sammensætningExample 1 The composition of the carrier
Cetostearylalkohol 10% (blanding af faste alifatiske alkoholer, hovedsagelig stearyl-og cetylalkohol)Cetostearyl alcohol 10% (mixture of solid aliphatic alcohols, mainly stearyl and cetyl alcohol)
Acetoglycerid 10%Acetoglyceride 10%
Cetomacrogol 1000 1,5% 1,2-Propandiol 35%Cetomacrogol 1000 1.5% 1,2-Propanediol 35%
Methyl-p-hydroxybenzoat 0,08%Methyl p-hydroxybenzoate 0.08%
Propyl-p-hydroxybenzoat 0,02%Propyl p-hydroxybenzoate 0.02%
Natr iumd ihydrogenpho sphat 0,10%Sodium ihydrogen pho sphat 0.10%
Vand indtil 100,00%Water up to 100.00%
Frems tillingsmådeForward feeding method
De tre voksarter sammensmeltes og opvarmes til 75°C. Det meste af 1,2-pro-pandiolen og vandet sammenblandes,og de andre bestanddele opløses deri, idet der opvarmes til opløsning af hydroxybenzoaterne.Den dannede opløsning opvarmes til 75°C og blandes med de smeltede voksarter. Der omrøres og afkøles til 40°C.The three waxes are fused and heated to 75 ° C. Most of the 1,2-propanediol and water are mixed together and the other components dissolved therein, heating to dissolve the hydroxybenzoates. The resulting solution is heated to 75 ° C and mixed with the molten waxes. Stir and cool to 40 ° C.
21-Chlor-21-desoxybetamethason-17-propionat opløses enten i en lille mængde af 1,2-propandiolen, der tilsættes efter at voksarterne og den vandige fase er blevet sammenblandet,eller steroidet formales i kuglemølle i en vandig opløsning af det overfladeaktive middel,og den resulterende mikrofine suspension sættes til de andre komponenter som ovenfor.21-Chloro-21-deoxybetamethasone-17-propionate is either dissolved in a small amount of the 1,2-propanediol added after the waxes and aqueous phase have been mixed, or the steroid is ground in a ball mill in an aqueous solution of the surfactant. , and the resulting microfine suspension is added to the other components as above.
Den samme fremstillingsmåde anvendes i forbindelse med bærersammensætningen ifølge eksempel 2 nedenfor.The same method of preparation is used in connection with the carrier composition of Example 2 below.
144358 7144358 7
Eksempel 2Example 2
Stearinsyre 8,0%Stearic acid 8.0%
Cetostearylalkohol 8,0% 1,2-Propandiol 45,0%Cetostearyl alcohol 8.0% 1,2-Propanediol 45.0%
Cetomacrogol 1000 0,5%Cetomacrogol 1000 0.5%
Polyoxyethylen 40 stearat 2,00%Polyoxyethylene 40 stearate 2.00%
Chlorcresol 0,05%Chlorecresol 0.05%
Natriumcitrat 0,15%Sodium citrate 0.15%
Citronsyre 0,15%Citric Acid 0.15%
Vand indtil 100,00%Water up to 100.00%
Eksempel 3Example 3
Glycerylmonostearat (G.M.S.) 10,0%Glyceryl Monostearate (G.M.S.) 10.0%
Cetostearylalkohol (C.S.A.) 8,0%Cetostearyl Alcohol (C.S.A.) 8.0%
Polyoxyethylen 25 lanolinderivat 3,0% 1,2-Propandiol 67,0%Polyoxyethylene lanolin derivative 3.0% 1,2-Propanediol 67.0%
Thiomer s a l 0,017«Thiomer s a l 0.017 «
Natr iumdihydrogenphosphat 0,05%.Sodium dihydrogen phosphate 0.05%.
Dinatriumhydrogenphosphat 0,05% V and ind til 100,00%,Disodium hydrogen phosphate 0.05% V and up to 100.00%,
Frems t i11ingsmådeForward the way
Sammensmelt G.M.S., C.S.A. og lanolinderivatet og opvarm til 75°C. Bland det meste af propandiolen og vandet, tilsæt de øvrige bestanddele og opvarm til opnåelse af opløsning.Bland de to opløsninger ved 75°C, omrør og afkøl til 40°C.Merged G.M.S., C.S.A. and the lanolin derivative and heat to 75 ° C. Mix most of the propanediol and water, add the other ingredients and heat to obtain solution. Mix the two solutions at 75 ° C, stir and cool to 40 ° C.
Opløs steroidet i den resterende mængde propandiol og tilsæt opløsningen til ovennævnte bestanddele efter at faserne er blevet sammenblandet.Dissolve the steroid in the remaining amount of propanediol and add the solution to the above ingredients after the phases have been mixed.
Eksempel 4Example 4
Glycerylmonostearat (G.M.S.) 10,0%,Glyceryl monostearate (G.M.S.) 10.0%,
Cetostearylalkohol (C.S.A.) 5,0%,Cetostearyl alcohol (C.S.A.) 5.0%,
Bivoks 2,0%,Beeswax 2.0%,
Syrestabil selv-emulgerende monostearin 2,0%Acid stable self-emulsifying monostearin 2.0%
Glycerol 10,0%Glycerol 10.0%
Natriumcitrat 0,05%0.05% sodium citrate
Citronsyre 0,05%Citric acid 0.05%
Chlorcresol 0,10%Chlorecresol 0.10%
Vand indtil 100,0%Water up to 100.0%
Claims (9)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1575873 | 1973-04-02 | ||
| GB1575873A GB1478009A (en) | 1973-04-02 | 1973-04-02 | Pharmaceutical compositions |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DK144358B true DK144358B (en) | 1982-03-01 |
| DK144358C DK144358C (en) | 1984-04-09 |
Family
ID=10064952
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK179474A DK144358C (en) | 1973-04-02 | 1974-04-01 | CREME CONTAINING ONE OR MORE TOPICALLY ACTIVE MEDICINES IN A CARRIER AND THEIR MANUFACTURING PRODUCTS |
Country Status (11)
| Country | Link |
|---|---|
| JP (1) | JPS589081B2 (en) |
| BE (1) | BE813153A (en) |
| CA (1) | CA1045974A (en) |
| DE (1) | DE2347243A1 (en) |
| DK (1) | DK144358C (en) |
| FR (1) | FR2222998B1 (en) |
| GB (1) | GB1478009A (en) |
| IE (1) | IE39113B1 (en) |
| LU (1) | LU69751A1 (en) |
| NL (1) | NL7404378A (en) |
| ZA (1) | ZA742064B (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE8004580L (en) * | 1980-06-19 | 1981-12-20 | Draco Ab | PHARMACEUTICAL PREPARATION |
| KR830005852A (en) * | 1980-07-18 | 1983-09-14 | 미첼 페터 잭슨 | Preparation of topical treatments suitable for the treatment of viral infections on skin and mucous membranes |
| GB2080106B (en) * | 1980-07-18 | 1984-03-07 | Weelcome Foundation Ltd | Acyclovin preparations |
| DE3225848A1 (en) * | 1982-07-07 | 1984-01-19 | Schering AG, 1000 Berlin und 4709 Bergkamen | PREPARATION OF CORTICOIDS FOR TOPICAL APPLICATION |
| US4868169A (en) * | 1987-11-13 | 1989-09-19 | E. R. Squibb & Sons, Inc. | Steroid cream formulation |
| LU87457A1 (en) * | 1989-02-24 | 1990-09-19 | Oreal | USE, AS A COSMETIC COMPOSITION FOR HAIR, OF A WAX MICRODISPERSION, AND METHOD FOR TREATING HAIR WITH SUCH A COMPOSITION |
| US8491875B2 (en) * | 2010-08-18 | 2013-07-23 | Kao Corporation | Hair volumizing compositions |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB765600A (en) * | 1954-01-15 | 1957-01-09 | Drug Houses Of Australia Ltd | Salves for veterinary use |
| GB903407A (en) * | 1958-07-25 | 1962-08-15 | Upjohn Co | Improvements in or relating to antibacterial antiperspirant compositions |
| DE1198011B (en) * | 1962-08-04 | 1965-08-05 | Iwao Kawakami | Skin care products |
| BR6789910D0 (en) * | 1966-10-17 | 1973-05-17 | Fmc Corp | PROCESS TO PREPARE EDIBLE CONTAINING MICRO CRYSTALLINE COLLAGEN |
-
1973
- 1973-04-02 GB GB1575873A patent/GB1478009A/en not_active Expired
- 1973-09-19 DE DE19732347243 patent/DE2347243A1/en active Pending
-
1974
- 1974-04-01 LU LU69751A patent/LU69751A1/xx unknown
- 1974-04-01 ZA ZA00742064A patent/ZA742064B/en unknown
- 1974-04-01 NL NL7404378A patent/NL7404378A/xx unknown
- 1974-04-01 CA CA196,544A patent/CA1045974A/en not_active Expired
- 1974-04-01 BE BE142726A patent/BE813153A/en not_active IP Right Cessation
- 1974-04-01 JP JP49035716A patent/JPS589081B2/en not_active Expired
- 1974-04-01 DK DK179474A patent/DK144358C/en not_active IP Right Cessation
- 1974-04-01 FR FR7411572A patent/FR2222998B1/fr not_active Expired
- 1974-04-01 IE IE00703/74A patent/IE39113B1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU6724674A (en) | 1975-10-02 |
| NL7404378A (en) | 1974-10-04 |
| FR2222998B1 (en) | 1977-11-04 |
| JPS589081B2 (en) | 1983-02-18 |
| CA1045974A (en) | 1979-01-09 |
| LU69751A1 (en) | 1974-07-17 |
| BE813153A (en) | 1974-10-01 |
| IE39113L (en) | 1974-10-02 |
| IE39113B1 (en) | 1978-08-02 |
| FR2222998A1 (en) | 1974-10-25 |
| ZA742064B (en) | 1975-03-26 |
| JPS5058218A (en) | 1975-05-21 |
| DK144358C (en) | 1984-04-09 |
| GB1478009A (en) | 1977-06-29 |
| DE2347243A1 (en) | 1974-10-10 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PBP | Patent lapsed |