GB2122899A - Topical corticoid-containing preparations - Google Patents

Topical corticoid-containing preparations Download PDF

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GB2122899A
GB2122899A GB08318397A GB8318397A GB2122899A GB 2122899 A GB2122899 A GB 2122899A GB 08318397 A GB08318397 A GB 08318397A GB 8318397 A GB8318397 A GB 8318397A GB 2122899 A GB2122899 A GB 2122899A
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preparation
oil
water
group
emulsion
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GB8318397D0 (en
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Ingfried Zimmerman
Renate Reckers
Hans Wendt
Rainold Arndt
Wolfgang Stindel
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Bayer Pharma AG
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Schering AG
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44Oils, 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/56Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
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  • Pharmacology & Pharmacy (AREA)
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  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Dermatology (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Cosmetics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Steroid Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

Topical preparations comprise jojoba oil and 0.005 to 2% by weight of an anti-inflammatory cortoicoid. The preparations are stable even when substantially diluted.

Description

SPECIFICATION Corticoid-containing preparations for topical application The present invention is concerned with novel corticoid-containing preparations suitable for topical application.
The present invention provides a preparation suitable for topical application, which comprises jojoba oil and 0.005 to 2% by weight of an anti-inflammatorily active corticoid.
The novel preparations of the present invention are stable even when substantially diluted. The novel preparations cause much less side-effects (such as irritation, sensibilisation, maceration, burning and itching) than known corticoid-containing preparations.
The present invention also provides a preparation of the present invention, for use as a medicament.
In principle, any anti-inflammatorily active corticoid is suitable for the manufacture of the corticoid-containing preparations according to the present invention. However, preferred for this purpose are corticoids of the general formula I in which
- - - represents a single or double carbon-to-carbon bond, X represents a hydrogen or fluorine atom or a methyl group, Y represents a hydrogen, fluorine or chlorine atom, Z represents a hydroxyl group, an alkanoyloxy group containing 2 to 6 carbon atoms, an alkoxymethoxy group, a benzoyloxy group or a chlorine atom, and R, represents a hydrogen atom and, together with R2, an isopropylidenedioxy group, or R1 represents two hydrogen atoms, a hydrogen atom and a hydroxyl group, a methylene group, or a hydrogen atom and a methyl group, and R2 represents a hydrogen atom, a hydroxyl group, an alkanoyloxy group containing 2 to 6 carbon atoms, an alkoxymethoxy group or a benzoyloxy group.
Compounds falling within the scope of the general formula I are compounds of the general formula la
in which - - - represents a single or double carbon-to-carbon bond, X' represents a hydrogen atom or a methyl group, and R3 and R4 may have the same or different meanings and each represents a hydrogen atom, an alkanoyl group containing 2 to 6 carbon atoms, an alkoxymethyl group or a benzoyl group; compounds of the general formula Ib
in which Y has the meaning given above, X" represents a hydrogen or fluorine atom, and P5 represents a hydrogen atom, an alkanoyl group containing 2 to 6 carbon atoms or a benzoyl group; compounds of the general formula Ic
in which X and Z have the meanings given above, Y' represents a fluorine or chlorine atom, R6 represents two hydrogen atoms, a methylene group, or a hydrogen atom and a methyl group, and R7 represents a hydrogen atom, an alkanoyl group containing 2 to 6 carbon atoms or a benzoyl group; and compounds of the general formula Id
in which - - - represents a single or double carbon-to-carbon bond, Y, Z and X" have the meanings given above, and R8 and Ps each represents a hydrogen atom or together represent an isopropylidene group.
As corticoids of the general formula la suitable for the manufacture of the corticoid-containing preparations according to the present invention, there may be mentioned hydrocortisone, prednisolone, 6a-methylhydrocortisone and 6a-methylprednisolone and esters or acetals thereof, for example hydrocortisone 21-acetate, hydrocortisone 17-butyrate, hydrocortisone 17-valerate, prednisolone 21 acetate, prednisolone 1 7-valerate, 6-methylhydrncortisone 21-acetate, 6a-methylprndnisolone 21 acetate, Ga-methylhydrocortisone 1 7-butyrate-2 1-acetate, 6a-methylprednisolone 21-acetate-17 propionate,6cr-methylhydrocortisone 1 7,21 -dipropionate or 21 -acetoxy-17a-ethoxymethoxy-11 p- hydroxy-A1,4-pregnadiene-3,20-dione.
As corticoids of the general formula ib suitable for the manufacture of the corticoid-containing preparations according to the present invention, there may be mentioned, for example, fluocortolone, clocortolone, diflucortolone and desoximetasone and esters thereof, for example fluocortolone 21 acetate, fluocortolone 21 -caproate, fluocortolone 21 -trimethylacetate, clocortolone 21 -caproate, clocortolone 21 -trimethyiacetate and diflucortolone 21 -valerate.
As corticoids of the general formula Ic suitable for the manufacture of the corticoid-containing preparations according to the present invention, there may be mentioned, for example, betamethasone, beclomethasone, fluprednylidene, clobetasol, dexamethasone, flumetasone and 9-chloroprednisolone and esters thereof, for example betamethasone 17-valerate, betamethasone 1 7-benzoate, betamethasone 1 7,21 -dipropionate, beclomethasone 1 7,21 -dipropionate, fluprednylidene 21-acetate, clobetasol 17-propionate, flumetasone 21 -trimethylacetate, 9-chloroprednisolone 21 -acetate-1 7- propionate and 9-chloroprednisolone 17-butyrate-21 -propionate.
As corticoids of the general formula Id suitable for the manufacture of the corticoid-containing preparations according to the present invention, there may be mentioned, for example, triamcinolone, triamcinolone acetamide, halcinonide, fluocinolone, fluocinolone acetonide, desonide and fludroxicortide and esters thereof, for example fluocinonide.
However, anti-inflammatorily active corticoids that do not come within the scope of the general formula I are also suitable for the manufacture of the corticoid-containing preparations according to the present invention. As such compounds, there may be mentioned by way of example corticoids that differ from those of the general formula I in that, instead of the grouping
they carry a group
(Rao representing an alkyl group containing up to 6 carbon atoms)-disclosed in United States Patent Specification Nos. 3,824,260,3,919,421 and 3,944,577. There may be mentioned as an example of a corticoid having this class of structure fluocortin butyl ester.However, other suitable corticoids are, for example, those that differ from the corticoids of the formula I in that they carry a keto group instead of a hydroxyl group in the 11-position. Clobetasone 1 7-butyrate may be mentioned as an example.
The preparations of the present invention contain from 0.005 to 2% by weight, but preferably from 0.05 to 0.5% by weight, of the corticoid; the concentration of the corticoid is, of course, dependent on the relative activity of the corticoid.
The preparations of the present invention may contain the jojoba oil in an amount within the range of from 1 to 50% by weight, for example 1 to 25% by weight, preferably 3 to 1 5% by weight, more preferably 3 to 10% by weight.
As in the case of the previously known corticoid-containing preparations suitable for topical application, the preparations of the present invention may also be in the form of an oil/water emulsion (for example in the form of a milk or cream), in the form of a water/oil emulsion (for example in the form of a fatty ointment) or in the form of an oily suspension (for example in the form of a fatty spray).
According to the present invention, from 1 to 15% by weight, and preferably from 3 to 10% by weight, of jojoba oil is used in the case of the oil/water emulsions or water/oil emulsions and at least 50% by weight of jojoba oil is used in the case of the oily suspensions. The jojoba oil is preferably used in a purified form (for example puroba oil). The jojoba oil may, for example, have been decolorised and purified by means of active carbon.
The oil/water emulsions and the water/oil emulsions may be prepared in a conventional manner using conventional emulsifiers (Kirk Othmer: Encyclopaedia of Chemical Technology, 3rd edition, 1979; John Wiley Sons; New York etc. vol. 8, pages 900 to 930 and Dr. Otto-Albrecht Neumüller: Römpps Chemie Lexikon, 7th edition,1973; Franck'sche Verlagshandlung Stuttgart, pages 1 009 to 1013). The waxes, emulsifiers and other additives used for these emulsions may be the same as are conventionally used in emulsified skin-care agents (Dr. Otto-Albrecht Neumüller: Römpps Chemie Lexikon, 7th edition 1973; Franck'sche Verlagshandlung Stuttgart, pages 1427 and 1428).
A preparation according to the present invention in the form of an oil/water emulsion may comprise one or more hydrophilic and/or lipophilic active substances (one of which such substances is the jojoba oil), a fatty phase, an oil/water emulsifier, an aqueous phase and a preservative.
There may be used as the hydrophilic and/or lipophilic active substances humectant factors (hydro-complexes), for example glycerine, polyethylene glycols or amino acid mixtures, puroba oil(=jojoba oil), vitamins (preferably vitamins A and E), vital complexes (for example placenta extracts), enzymes, herb extracts (for example Hamamelis extract or camomile extract) or proteins (for example collagen). Suitable as the oily phase or the fatty phase in the oil/water emulsions are hydrocarbons, for example vaseline, paraffins or stearin, or waxes, for example beeswax.Suitabie oil/water emulsifiers are, for example, stearyl alcohol, polyoxyethylene stearates (for example MYRJ(R)), complex emulsifiers (for example AmphoterinlR)) and sorbitan fatty acid esters (for example SpanzR) or carboxyvinyl polymers (for example Carbopol(R). The aqueous phase may also contain a buffer substance, for example the disodium salt of ethylenediamine-N,N,N',N'-tetraacetic acid, and a preservative, for example chlorquinaldol, parabens or benzalkonium chloride.
In the oil/water emulsions, the proportion of the inner emulsion is preferably from 30 to 49% by weight and the particle size of the inner emulsion is preferably between 1 u and 50 .
A preparation according to the present invention, for example a cosmetic preparation, in the form of a water/oil emulsion may likewise comprise one or more hydrophilic and/or lipophilic active substances, of the type also used in the oil/water emulsions, a fatty phase, a water/oil emulsifier and an aqueous phase.There may be used as the oily phase or the fatty phase of the water/oil emulsions hydrocarbons, for example paraffins and vaseline, and synthetic, vegetable and animal oils and waxes (for example olive oil, ground-nut oil, fine bone oii, almond oil, lanolin, beeswax or sunflower oil), as the aqueous phase purified demineralised water and, as the water/oil emulsifier, wool fat (=lanolin), fatty alcohols, for example cetyl alcohol, myristyl alcohol, stearyl alcohol or ceryl alcohol, fatty acid esters, for example beeswax (cera alba) or wax alcohol esters or mixed esters (for example Dehymuls(R)).
The proportion of the inner emulsion in the water/oil emulsions is preferably from 30 to 49% by weight and the particle size of the inner emulsion is preferably between 1 y and 100 y. During the dispersion of the two phases, the particle size is reduced further and in the finished product it is less than 50 y.
The preparations of the present invention preferably contain the corticoid in a micronised form (particle size predominantly from 1 to 20,u) and may also contain a perfume, for example one of the Crematest(R) series. These components are uniformly dispersed in the preparations having been incorporated, for example, into the finely dispersed systems as described above by stirring.
A preparation according to the present invention containing a fatty phase and an aqueous phase may be in the form of a finely dispersed mixture of (i) an oil/water emulsion containing an oil/water emulsifier and a preservative and (ii) a water/oil emulsion containing a water/oil emulsifier. In such a preparation which may, for example, be in the form of an ointment, paste or cream, the jojoba oil is advantageously present in the oil/water emulsion. This type of preparation may also contain a hydrophilic and/or lipophilic active substance other than jojoba oil. The oil/water emulsion and the water/oil emulsion may have been produced in the manner already described above.
When using a cream of this type of constitution containing an extremely finely dispersed mixture of the two types of emulsion, a corresponding oil/water or water/oil hydrolipid film can be produced on the skin depending on the moistness in the various skin areas, or depending on the skin type.
In such a preparation according to the present invention, the particle size of the emulsion is preferably from 2 to 50 y.
There is also included within the scope of the present invention a process for the manufacture of the corticoid-containing preparation in the form of a finely dispersed mixture of an oil/water emulsion and a water/oil emulsion, for example an ointment, paste or cream, wherein an oil/water emulsion that has been produced from a fatty phase, an aqueous phase, an oil/water emulsifier and a preservative is intimately mixed, preferably in vacuo, at a temperature within the range of from 20 to 400C with a water/oil emulsion that has been produced from a fatty phase, an aqueous phase and a water/oil emulsifier, the oil/water emulsion and/or the water/oil emulsion containing jojoba oil, and then an anti inflammatorily active corticoid in a micronised form (particle size preferably predominantly 1 to 20,u) and also, if desired, a perfume is/are added to the resulting mixture, stirring then being carried out until these ingredients are uniformly dispersed.
If the two types of emulsion are combined in this way in a stirrer vessel at temperatures of between 20 and 400 C, preferably particularly gently at 300C in vacuo, but, whether or not under these preferred specific conditions, then very intensively, so that a very fine dispersion of the two emulsions is finely obtained, the particle size of which is between 2 and 50 4, preferably between 5 and 1 5 , then the two types of emulsion are maintained together in an unaltered state in, for example, a cream so produced. This emulsion system remains stable when substantially diluted, for example with a liquid phase. It is assumed that the particle size as well as the interaction of the emulsifiers is important for the stability of this emulsion system.It is essential that, when manufacturing such a corticoid containing preparation according to the present invention, the emulsions used are dispersed and not homogenised.
The two emulsions are combined preferably under a vacuum of from 0.5 torr to 50 torr. As is well known to the person skilled in the art, the stirring speed depends on the stirring apparatus used and must be ascertained in a manner known per se.
The mixture ratio of the oil/water emulsion and the water/oil emulsion is preferably from 20 to 80% by weight, and especially from 35 to 65% by weight, of the oil/water emulsion.
As indicated above, perfumes, for example those of the Crematest(R) series, may also be added to the finely dispersed system.
A corticoid-containing preparation according to the present invention in the form of a cream may, for example, consist of the following components: Table I Tolerances hydrocortisone 21-acetate, micronised 0.5% 0.1-1% (particle size predominantly from 1 to 20 y) puroba oil 5% 510% cera alba (beeswax) 1% 15% Dehymuls(R) 1% 13% stearyl alcohol 4% 4--8% hydrocarbons 30% 3050% Carbopol(R) 1% MYRJ(R) 3% 2--5% disodium edetate 1% chlorquinaldol 1% purified demineralised water 52% 3055% perfume oil 0.5% 3055% The percentages given are percentages by weight.
The following Examples illustrate the invention. The procedures described therein for the manufacture of the preparations may be carried out using any of the apparatus conventionally used for the manufacture of, for example, ointments and creams.
Example 1 Manufacture of an oil/water emulsion 10.00 g of disodium edetate and 10.00 g of chlorquinaldol were dissolved in 300.00 g of purified demineralised water and 1 0.00 g of Carbopol(R) were added thereto.
While stirring vigorously, this mixture was incorporated into a melt of 80.00 g of vaseline (DAB 8), DAB being the abbreviation for the Deutsche Arzneibuch (German Pharmacopoeia), official publication, 8th edition 1978, 40.00 g of stearyl alcohol, 30.00 g of MYRJ(R) and 50.00 g of puroba oil.
The mixture was further stirred until an emulsion having a particle size of from 20 to 70 N was formed.
Manufacture of a water/oil emulsion While stirring vigorously, 228.00 g of purified demineralised water were incorporated into a melt of 220.00 g of vaseline (DAB 8), 10.00 g of Dehymuls(R) and 10.00 g of cera aiba. The mixture was further stirred until an emulsion having a particle size of from 20 to 70 4 was formed.
Manufacture of a cream While stirring vigorously, the water/oil emulsion prepared as described above was incorporated at room temperature under a vacuum of 10 torr into the oil/water emulsion prepared as described above.
Stirring was continued until a dispersion having a particle size of from 10 to 50 N was formed; the vacum was then removed and, while stirring, 5.000 g of hydrocortisone 21-acetate-in a micronised form having a particle size of predominantly from 1 to 20 N-and 2.00 g of a Crematest(R) perfume were added and stirring was continued until the two components had been uniformly dispersed in the ointment base.
Example 2 Manufacture of an oil/water emulsion 10.00 g of disodium edetate and 10.00 g of chlorquinaldol were dissolved in 300.00 g of purified demineralised water and 10.00 g of Carbopol(RI were added thereto.
While stirring vigorously, this mixture was incorporated into a melt of 80.00 g of vaseline (DAB 8), DAB being the abbreviation for the Deutsche Arzneibuch (German Pharmacopoeia), official publication, 8th edition 1 978, 40.00 g of stearyl alcohol, 30.00 g of MYRJ(R) and 50.00 g of puroba oil.
The mixture was further stirred until an emulsion having a particle size of from 20 to 70 N was formed.
Manufacture of a water/oil emulsion While stirring vigorously, 227.00 g of purified demineralised water were incorporated into a melt of 220.00 g of vaseline (DAB 8), 10.00 g of Dehymuls(R} and 10.00 g of cera alba. The mixture was further stirred until an emulsion having a particle size of from 20 to 70,u was formed.
Manufacture of a cream While stirring vigorously, the water/oil emulsion prepared as described above was incorporated at room temperature under a vacuum of 10 torr into the oil/water emulsion prepared as described above.
Stirring was continued until a dispersion having a particle size of from 10 to 50 N was formed; the vacuum was then removed, and, while stirring, 1.000 g of 21 -acetoxy-1 1 Thydrnxy-6a-methyl-1 70,- propionyloxy-A' 4-pregnadiene-3,20-dionein a micronised form having a particle size of predominantly from 1 to 20 N-and 2.00 g of a Crematest(R perfume were added and stirring was continued until the two components had been uniformly dispersed in the ointment base.
Example 3 Manufacture of an oil/water emulsion 10.00 g of disodium edetate and 10.00 g of chlorquinaldol were dissolved in 300.00 g of purified demineralised water and 10.00 g of Carbopol(R) were added thereto.
While stirring vigorously, this mixture was incorporated into a melt of 80.00 g of vaseline (DAB 8), DAB being the abbreviation for the Deutsche Arzneibuch (German Pharmacopoeia), official publication, 8th edition 1978, 40.00 g of stearyl alcohol, 30.00 g of MYRJ(R) and 50.00 g of puroba oil.
The mixture was further stirred until an emulsion having a particle size of from 20 to 70 N was formed.
Manufacture of a water/oil emulsion While stirring vigorously, 227.00 g of purified demineralised water were incorporated into a melt of 220.00 g of vaseline (DAB 8), 10.00 g of DehymulslR) and 10.00 g of cera alba. The mixture was further stirred until an emulsion having a particle size of from 20 to 70 y was formed.
Manufacture of a cream While stirring vigorously, the water/oil emulsion prepared as described above was incorporated at room temperature under a vacuum of 10 torr into the oil/water emulsion prepared as described above.
Stirring was continued until a dispersion having a particle size of from 10 to 50 N was formed; the vacuum was then removed and, while stirring, 1.000 g of 21 -acetoxy-1 7a-butyryloxy-1 1 s-hydroxy- 6a-methyl-A4-pregnene-3,20-dione-in a micronised form having a particle size of predominantly from 1 to 20 N-and 2.00 g of a Crematest(R) perfume were added and stirring was continued until the two components had been uniformly dispersed in the ointment base.
Example 4 Manufacture of an oil/water emulsion 10.00 g of disodium edetate and 10.00 g of chlorquinaldoi were dissolved in 300.00 g of purified demineralised water and 10.00 g of Carbopol(R) were added thereto.
While stirring vigorously, this mixture was incorporated into a melt of 80.00 g of vaseline (DAB 8), DAB being the abbreviation for the Deutsche Arzneibuch (German Pharmacopoeia), official publication, 8th edition 1978, 40.00 g of stearyl alcohol, 30.00 g of MYRJ(R) and 50.00 g of puroba oil.
The mixture was further stirred until an emulsion having a particle size of from 20 to 70 y was formed.
Manufacture of a water/oil emulsion While stirring vigorously, 227.00 g of purified demineralised water were incorporated into a melt of 220.00 g of vaseline (DAB 8), 10.00 g of Dehymuls(R) and 10.00 g of cera alba. The mixture was further stirred until an emulsion having a particle size of from 20 to 70 N was formed.
Manufacture of a cream While stirring vigorously, the water/oil emulsion prepared as described above was incorporated at room temperature under a vacuum of 10 torr into the oil/water emulsion prepared as described above.
Stirring was continued until a dispersion having a particle size of from 10 to 50 was formed; the vacuum was then removed and, while stirring, 1.000 g of 21 -acetoxy-9a-chloro-1 1 I3-hydroxy-1 7a- propionyloxy-A14-pregnadiene-3,20-dionein a micronised form having a particle size of predominantly from 1 to 20 N-and 2.00 g of a Crematest(R) perfume were added and stirring was continued until the two components had been uniformly dispersed in the ointment base.
Example 5 Manufacture of an oil/water emulsion 10.00 g of disodium edetate and 10.00 g of chlorquinaldol were dissolved in 300.00 g of purified demineralised water and 10.00 g of Carbopol(R were added thereto.
While stirring vigorously, this mixture was incorporated into a melt of 80.00 g of vaseline (DAB 8), DAB being the abbreviation for the Deutsche Arzneibuch (German Pharmacopoeia), official publication, 8th edition 1978, 40.00 g of stearyl alcohol, 30.00 g of MYPJ(R) and 50.00 g of puroba oil.
The mixture was further stirred until an emulsion having a particle size of from 20 to 70 N was formed.
Manufacture of a water/oil emulsion While stirring vigorously, 227.50 g of purified demineralised water were incorporated into a melt of 220.00 g of vaseline (DAB 8), 10.00 g of Dehymuls(R) and 10.00 g of cera alba. The mixture was further stirred until an emulsion having a particle size of from 20 to 70 N was formed.
Manufacture of a cream While stirring vigorously, the water/oil emulsion prepared as described above was incorporated at room temperature under a vacuum of 10 torr into the oil/water emulsion prepared as described above.
Stirring was continued until a dispersion having a particle size of from 10 to 50N was formed; the vacuum was then removed and, while stirring, 0.500 g of clobetasol 1 7-propionate-in a micronised form having a particle size of predominantly from 1 to 20 N-and 2.00 g of a CrematestfR) perfume were added and stirring was continued until the two components had been uniformly dispersed in the ointment base.
Example 6 Manufacture of an oil/water emulsion 10.00 g of disodium edetate and 10.00 g of chlorquinaldol were dissolved in 300.00 g of purified demineralised water and 1 0.00 g of Carbopol(R) were added thereto.
While stirring vigorously, this mixture was incorporated into a melt of 80.00 g of vaseline (DAB 8), DAB being the abbreviation for the Deutsche Arzneibuch (German Pharmacopoeia), official publication, 8th edition 1978, 40.00 g of stearyl alcohol, 30.00 g of MYRJ(R) and 50.00 g of puroba oil.
The mixture was further stirred until an emulsion having a particle size of from 20-70 N was formed.
Manufacture of a water/oil emulsion While stirring vigorously, 227.00 g of purified demineralised water were incorporated into a melt of 220.00 g of vaseline (DAB 8), 10.00 g of Dehymuls(R) and 10.00 g of cera alba. The mixture was further stirred until an emulsion having a particle size of from 20 to 70 N was formed.
Manufacture of a cream While stirring vigorously, the water/oil emulsion prepared as described above was incorporated at room temperature under a vacuum of 10 torr into the oil/water emulsion prepared as described above.
Stirring was continued until a dispersion having a particle size of from 10 to 50 N was formed; the vacuum was then removed and, while stirring, 1.000 g of diflucortolone 21 -valerate-in a micronised form having a particle size of predominantly from 1 to 20 N-and 2.00 g of a Crematest(R) perfume were added and stirring was continued until the two components had been uniformly dispersed in the ointment base.
Example 7 Manufacture of an oil/water emulsion 10.00 g of disodium edetate and 1 0.00 g of chlorquinaldol were dissolved in 300.00 g of purified demineralised water and 10.00 g of Carbopol(R) were added thereto.
While stirring vigorously, this mixture was incorporated into a melt of 80.00 g of vaseline (DAB 8), DAB being the abbreviation for the Deutsche Arzneibuch (German Pharmacopoeia), official publication, 8th edition 1 978, 40.00 g of stearyl alcohol, 30.00 g of MYRJ(R) and 50.00 g of puroba oil.
The mixture was further stirred until an emulsion having a particle size of from 20 to 70,u was formed.
Manufacture of a water/oil emulsion While stirring vigorously, 227.00 g of purified demineralised water were incorporated into a melt of 220.00 g of vaseline (DAB 8), 10.00 g of Dehymuls(R) and 10.00 g of cera alba. The mixture was further stirred until an emulsion having a particle size of from 20 to 70 N was formed.
Manufacture of a cream While stirring vigorously, the water/oil emulsion prepared as described above was incorporated at room temperature under a vacuum of 10 torr into the oil/water emulsion prepared as described above.
Stirring was continued until a dispersion having a particle size of from 10 to 50 N was formed; the vacuum was then removed and, while stirring, 1.000 g of 21 -acetoxy-17a-ethoxymethoxy-11,B- hydroxy-A1'4-pregnadiene-3,20-dione-in a micronised form having a particle size of predominantly from 1 to 20 N-and 2.00 g of a Crematest(R) perfume were added and stirring was continued until the two components had been uniformly dispersed in the ointment base.

Claims (35)

Claims
1. A preparation suitable for topical application, which comprises jojoba oil and 0.005 to 2% by weight of an anti-inflammatorily active corticoid.
2. A preparation as claimed in claim 1, wherein the corticoid is present in an amount within the range of from 0.05 to 0.5% by weight.
3. A preparation as claimed in claim 1 or 2, wherein the corticoid is a compound of the general formula I in which
- - - represents a single or double carbon-to-carbon bond, X represents a hydrogen or fluorine atom or a methyl group, Y represents a hydrogen, fluorine or chlorine atom, Z represents a hydroxyl group, an alkanoyloxy group containing 2 to 6 carbon atoms, an alkoxymethoxy group, a benzoyloxy group or a chlorine atom, and R, represents a hydrogen atom and, together with R2, an isopropylidenedioxy group, or R, represents two hydrogen atoms, a hydrogen atom and a hydroxyl group, a methylene group, or a hydrogen atom and a methyl group, and R2 represents a hydrogen atom, a hydroxyl group, an alkanoyloxy group containing 2 to 6 carbon atoms, an alkoxymethoxy group or a benzoyloxy group.
4. A preparation as claimed in claim 3, wherein the corticoid is a compound of the general formula la in which
- - represents a single or double carbon-to-carbon bond, X' represents a hydrogen atom or a methyl group, and R3 and R4 each represents a hydrogen atom, an alkanoyl group containing 2 to 6 carbon atoms, an alkoxymethyl group or a benzoyl group.
5. A preparation as claimed in claim 3, wherein the corticoid is a compound of the general formula Ib
in which Y has the meaning given in claim 3, X" represents a hydrogen or fluorine atom, and P5 represents a hydrogen atom, an alkanoyl group containing 2 to 6 carbon atoms or a benzoyl group.
6. A preparation as claimed in claim 3, wherein the corticoid is a compound of the general formula Ic
in which X and Z have the meanings given in claim 3, Y' represents a fluorine or chlorine atom, P6 represents two hydrogen atoms, a methylene group, or a hydrogen atom and a methyl group, and R7 represents a hydrogen atom, an alkanoyl group containing 2 to 6 carbon atoms or a benzoyl group.
7. A preparation as claimed in claim 3, wherein the corticoid is a compound of the general formula Id in which
~ represents a single or double carbon-to-carbon bond, Y and Z have the meanings given in claim 3, X" has the meaning given in claim 5, and R8 and R8 each represents a hydrogen atom or together represent an isopropylidene group.
8. A preparation as claimed in any one of claims 1 to 7, wherein the jojoba oil has been decolorised and purified by means of active carbon.
9. A preparation as claimed in any one of claims 1 to 8, wherein the jojoba oil is present in an amount within the range of from 1 to 50% by weight.
1 0. A preparation as claimed in claim 9, wherein the jojoba oil is present in an amount within the range of from 1 to 25% by weight.
11. A preparation as claimed in claim 10, wherein the jojoba oil is present in an amount within the range of from 3 to 1 5% by weight.
12. A preparation as claimed in claim 11, wherein the jojoba oil is present in an amount within the range of from 3 to 10% by weight.
13. A preparation as claimed in any one of claims 1 to 12, which also contains a fatty phase, an aqueous phase and an emulsifier.
14. A preparation as claimed in any one of claims 1 to 13, which also contains a preservative.
15. A preparation as claimed in claim 13 or 14, which is in the form of an oil/water emulsion.
16. A preparation as claimed in claim 1 5, wherein the particle size is within the range of from 1 to 50y.
1 7. A preparation as claimed in claim 13 or 14, which is in the form of water/oii emulsion.
1 8. A preparation as claimed in claim 1 7, wherein the particle size is within the range of from 1 to 50y.
19. A preparation as claimed in any one of claims 1 to 14, which is in the form of a finely dispersed mixture of (i) an oil/water emulsion containing an oil/water emulsifier and a preservative and (ii) a water/oil emulsion containing a water/oil emulsifier.
20. A preparation as claimed in claim 19, wherein the jojoba oil is present in the oil/water emulsion.
21. A preparation as claimed in claim 19 or 20, wherein the mixture contains 20 to 80% by weight of the oil/water emulsion.
22. A preparation as claimed in claim 21, wherein the mixture contains 35 to 65% by weight of the oil/water emulsion.
23. A preparation as claimed in any one of claims 19 to 22, wherein the particle size of the emulsions is within the range of from 2 to 50 y.
24. A preparation as claimed in any one of claims 13 to 23, which also contains a hydrophilic and/or lipophilic active substance other than jojoba oil.
25. A preparation as claimed in any one of claims 1 to 8, which is in the form of an oily suspension.
26. A preparation as claimed in claim 25, wherein the jojoba oil is present in an amount of at least 50% by weight.
27. A preparation as claimed in any one of claims 1 to 26, which also contains a perfume.
28. A preparation as claimed in claim 1, which is in the form of a cream having a composition substantially as described in Table I herein.
29. Any one of the preparations as claimed in claim 1 and substantially as described in Examples 1 to 7 herein.
30. A preparation as claimed in any one of claims 1 to 29, for use as a medicament.
31. A process for the manufacture of a preparation as claimed in claim 1, conducted substantially as described herein.
32. A process for the manufacture of a preparation as claimed in claim 19, wherein an oil/water emulsion that has been produced from a fatty phase, an aqueous phase, an oil/water emulsifier and a preservative is intimateiy mixed at a temperature within the range of from 20 to 400C with a water/oil emulsion that has been produced from a fatty phase, an aqueous phase and a water/oil emulsifier, the oil/water emulsion and/or the water/oil emulsion containing jojoba oil, and then an anti-inflammatorily active corticoid in a micronised form is added to the resulting mixture.
33. A process as claimed in claim 32, wherein the mixing is carried out in vacuo.
34. A process as claimed in claim 32 or 33, wherein a perfume is added to the mixture of the oil/water and water/oil emulsions.
35. A process as claimed in claim 32, conducted substantially as described in any one of Examples 1 to 7 herein.
GB08318397A 1982-07-07 1983-07-07 Topical corticoid-containing preparations Withdrawn GB2122899A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE19823225849 DE3225849A1 (en) 1982-07-07 1982-07-07 PREPARATION OF CORTICOIDS FOR TOPICAL APPLICATION

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GB8318397D0 GB8318397D0 (en) 1983-08-10
GB2122899A true GB2122899A (en) 1984-01-25

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JP (1) JPS5976014A (en)
AT (1) ATE66596T1 (en)
AU (1) AU570638B2 (en)
CA (1) CA1202901A (en)
DE (2) DE3225849A1 (en)
DK (1) DK312483A (en)
GB (1) GB2122899A (en)
NZ (1) NZ204774A (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2539992A1 (en) * 1983-01-31 1984-08-03 Taisho Pharmaceutical Co Ltd OIL-IN-WATER TYPE CREAM COMPRISING HYDROCORTISONE BUTYRO-PROPIONATE, PREPARATION METHOD AND THERAPEUTIC APPLICATION
FR2539991A1 (en) * 1983-01-27 1984-08-03 Taisho Pharmaceutical Co Ltd FATTY OINTMENT CONTAINING IN PARTICULAR HYDROCORTISONE BUTYRO-PROPIONATE, PREPARATION METHOD THEREOF AND THERAPEUTIC APPLICATION THEREOF

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3225848A1 (en) * 1982-07-07 1984-01-19 Schering AG, 1000 Berlin und 4709 Bergkamen PREPARATION OF CORTICOIDS FOR TOPICAL APPLICATION
DE3836971C1 (en) 1988-10-31 1990-05-17 Weck, Wolfgang, Dr.Med., 6990 Bad Mergentheim, De

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FI44459B (en) * 1968-10-25 1971-08-02 K Rehtijaervi
US4070462A (en) * 1976-10-26 1978-01-24 Schering Corporation Steroid ointment
FR2471775A1 (en) * 1979-12-18 1981-06-26 Oreal Cosmetic oils based on jojoba and sunflower oils - contg. added unsaponifiable fraction, used as sun tan preparations, shaving creams etc.
FR2474310A1 (en) * 1980-01-25 1981-07-31 Oreal STABLE SOLUTION WITH OXIDATION OF VITAMIN F AND JOJOBA OIL AND COSMETIC COMPOSITIONS CONTAINING THE SAME
JPS56135416A (en) * 1980-03-27 1981-10-22 Mitsubishi Chem Ind Ltd Pharmaceutical preparation for skin
SE8004580L (en) * 1980-06-19 1981-12-20 Draco Ab PHARMACEUTICAL PREPARATION
DE3225848A1 (en) * 1982-07-07 1984-01-19 Schering AG, 1000 Berlin und 4709 Bergkamen PREPARATION OF CORTICOIDS FOR TOPICAL APPLICATION

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2539991A1 (en) * 1983-01-27 1984-08-03 Taisho Pharmaceutical Co Ltd FATTY OINTMENT CONTAINING IN PARTICULAR HYDROCORTISONE BUTYRO-PROPIONATE, PREPARATION METHOD THEREOF AND THERAPEUTIC APPLICATION THEREOF
FR2539992A1 (en) * 1983-01-31 1984-08-03 Taisho Pharmaceutical Co Ltd OIL-IN-WATER TYPE CREAM COMPRISING HYDROCORTISONE BUTYRO-PROPIONATE, PREPARATION METHOD AND THERAPEUTIC APPLICATION
GB2135576A (en) * 1983-01-31 1984-09-05 Taisho Pharmaceutical Co Ltd Hydrocortisone butyrate propionate creams

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DE3225849A1 (en) 1984-01-19
EP0098568B1 (en) 1991-08-28
AU570638B2 (en) 1988-03-24
GB8318397D0 (en) 1983-08-10
JPS5976014A (en) 1984-04-28
DE3382386D1 (en) 1991-10-02
ATE66596T1 (en) 1991-09-15
AU1646983A (en) 1984-01-12
CA1202901A (en) 1986-04-08
EP0098568A2 (en) 1984-01-18
DK312483A (en) 1984-01-08
DK312483D0 (en) 1983-07-06
NZ204774A (en) 1986-03-14
EP0098568A3 (en) 1985-05-15

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