CN107613987A - The topical spray composition of momestasone furoate - Google Patents

The topical spray composition of momestasone furoate Download PDF

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Publication number
CN107613987A
CN107613987A CN201680029218.7A CN201680029218A CN107613987A CN 107613987 A CN107613987 A CN 107613987A CN 201680029218 A CN201680029218 A CN 201680029218A CN 107613987 A CN107613987 A CN 107613987A
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Prior art keywords
composition
topical spray
spray composition
aqueous
mixture
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Chinese (zh)
Inventor
L·帕尼格拉希
A·R·沙马尔
U·S·阿萨普
S·K·高希
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Dr Reddys Laboratories Ltd
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Dr Reddys Laboratories Ltd
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    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • 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
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7015—Drug-containing film-forming compositions, e.g. spray-on

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (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)

Abstract

The present invention relates to the stabilization of the spray form of momestasone furoate, quick-drying non-aqueous topical composition, said composition includes one or more solubilizer, one or more non-aqueous volatile solvents and film forming agent or softening agent.The method for preparing said composition is also provided.The invention further relates to application of the momestasone furoate topical spray composition in treatment psoriasis, atopic dermatitis (atopic eczema) and other dermatologic disorders and disease.

Description

The topical spray composition of momestasone furoate
Technical field
The present invention relates to the quick-drying non-aqueous topical spray composite of momestasone furoate, also provides and prepares these combinations The method of thing.
Background technology
Topical corticosteroid is a kind of with anti-inflammatory, antipruritic and vasoconstrictor effects compound.Their usual quilts For alleviating flush, hydroderma (swelling), itch, crusting, come off, chap, ooze out, psoriasis, atopic dermatitis (idiocrasy Eczema) and other skin diseases, such as contact dermatitis, seborrhea, eczema, dermatitis herpetiformis, neurodermatitis or Autoeczematization.
Momestasone furoate is the synthesis corticosteroid for having anti-inflammatory activity.The chemical name of momestasone furoate is 9 α, 21- bis- Chloro- 11 β, pregnant-Isosorbide-5-Nitrae-diene -3, the 20- diketone 17- (2- furoates) of the Alpha-Methyl of 17- dihydroxy -16, its empirical formula are C27H30Cl2O6, molecular weight 521.4, and there is following structural formula：
Momestasone furoate is white-cream coloured powder, and it is practically insoluble in water, is slightly soluble in octanol, in be dissolved in ethanol.
Momestasone furoate can be commercially available with various topical formulations, such as emulsifiable paste, ointment and washing lotion.Its withCommercially sold for brand name, and suitable for alleviating corticosteroid responsiveness skin 2 years old or more older Scorching inflammatory and pruritis.
US4775529 discloses the topical lotions composition of the corticosteroid included in the water alcohol matrix containing propane diols.
US4808610 is disclosed comprising momestasone furoate, hexylene glycol, water, Chinese wax, albolene (white Petrolatum) and other compositions topical cream composition.
EP1886686 (B1) discloses to be selected from comprising momestasone furoate, water and at least one aromatic alcohol and at least one Two different combinations of solvent organized and the local medicine composition for the other additives being optionally present.Said composition includes Solution, microemulsion, gel, washing lotion, emulsifiable paste or ointment.
EP2575822 (A2) discloses the local medicine composition for including momestasone furoate, hexylene glycol, water and oil phase.Should Composition is preferably moulded as cream.
The preparation of emulsifiable paste of many comprising topical corticosteroid and ointment is greasy, and is therefore being coated to big It is not pleasant when on areas of skin.In addition, some conventional emulsifiable pastes and ointment bases are excitant for skin , when especially generation effect usually requires to contact for a long time, and the fluidity of washing lotion causes physics coating to be difficult to control On desired area.Several commercially available topical formulations mainly can not provide in demand subtract to infected region The effect of hypopathia pain, illness and other dermatologic disorders especially for such as psoriasis.These preparations will not improve patient Compliance.Therefore it is usually preferred to spray composite, it can increase the ease for use of patient.
WO2000045795 discloses topical pharmaceutical's spray composite, and it is included in the one or more in volatile vehicle Medicine and one or more film forming polymers.When being sprayed on local location, said composition formed it is stable, can exhale The film of suction, and the medicine can be obtained by the film is transdermal.
WO2011026076 (A2) discloses no propellant, sprayable topical composition, its include steroidal compounds, Emulsifying agent, polymer, water, water-immiscible material and penetration enhancers.
However, conventional topical spray preparation can only retain the shorter time on spraying position.For example, their easy quilts Erasing, it is therefore desirable to frequent repetitive administration.In addition, some topical spray compositions often stimulate skin, and need after application The longer time is wanted to dry.Furthermore some spray agents can not provide uniform, thin closure film after spray coating, and this for It is desirable to treat psoriasis, to maintain the hydration of skin.Therefore, for can effectively treat such as psoriasis and idiocrasy The dermatologic disorders of dermatitis simultaneously can improve the topical spray composition of patient's compliance and still suffer from unsatisfied demand.
When attempting to develop the new non-aqueous topical spray composite of momestasone furoate, the present inventor is in surprise It was found that use one or more solubilizer, one or more non-aqueous volatile solvents and one or more film forming agents or softening agent Formed composition is stable, there is provided closure film, there is provided longer action time, there is more preferable patient's compliance, and Show the effect suitable with commercially available momestasone furoate composition in the market.The composition of the present invention can applied Rapid draing after on skin.These compositions can effectively treat psoriasis, atopic dermatitis (atopic eczema) with And other dermatologic disorders or disease.
The content of the invention
This specification is related to quick-drying non-aqueous topical spray composite of momestasone furoate and preparation method thereof.
In one aspect, this specification is related to quick-drying non-aqueous topical spray composite, and it is included：
(i) momestasone furoate,
(ii) one or more solubilizer, and
(iii) one or more non-aqueous volatile solvents.
In another aspect, this specification is related to quick-drying non-aqueous topical spray composite, and it is included：
(i) momestasone furoate,
(ii) one or more solubilizer,
(iii) one or more non-aqueous volatile solvents, and
(iv) one or more film forming agents.
In another aspect, this specification is related to quick-drying non-aqueous topical spray composite, and it is included：
(i) momestasone furoate,
(ii) hexylene glycol,
(iii) one or more non-aqueous volatile solvents, and
(iv) one or more film forming agents.
In another aspect, this specification is related to quick-drying non-aqueous topical spray composite, and it is included：
(i) momestasone furoate,
(ii) one or more solubilizer,
(iii) one or more non-aqueous volatile solvents,
(iv) one or more softening agents, and
(v) one or more acidulants.
In another aspect, this specification is related to quick-drying non-aqueous topical spray composite, and it is included：
(i) momestasone furoate,
(ii) one or more solubilizer, and
(iii) one or more non-aqueous volatile solvents；
Wherein said composition forms stable closure film.
In another aspect, this specification is related to quick-drying non-aqueous topical spray composite, and it is included：
(i) 0.01% to 1% (w/w) momestasone furoate,
(ii) 1% to 15% (w/w) one or more solubilizer, and
(iii) 75% to 95% (w/w) one or more non-aqueous volatile solvents.
In another aspect, this specification is related to quick-drying non-aqueous topical spray composite, and it is included：
(i) 0.01% to 1% (w/w) momestasone furoate,
(ii) 1% to 15% (w/w) hexylene glycol,
(iii) 75% to 95% (w/w) one or more non-aqueous volatile solvents, and
(iv) 1% to 10% (w/w) one or more film forming agents.
In another aspect, this specification is related to quick-drying non-aqueous topical spray composite, and it is included：
(i) 0.01% to 1% (w/w) momestasone furoate,
(ii) 1% to 15% (w/w) hexylene glycol,
(iii) 75% to 95% (w/w) one or more non-aqueous volatile solvents,
(iv) one or more softening agents, and
(v) one or more acidulants.
In another aspect, this specification provides the quick-drying non-aqueous topical spraying combination of the stabilization of momestasone furoate Thing.
In another aspect, the quick-drying non-aqueous topical spray composite that this specification is related to momestasone furoate is being controlled Application in treatment psoriasis, atopic dermatitis (atopic eczema) and other dermatologic disorders or disease.
Brief description
Fig. 1：Of the invention (embodiment 2) with it is commercially availablePharmacokinetics between ointment Comparative study.
Specific embodiment
This specification is related to quick-drying topical spray composition of momestasone furoate and preparation method thereof.
In one aspect, this specification is related to quick-drying non-aqueous topical spray composite, and it is included：
(i) momestasone furoate,
(ii) one or more solubilizer, and
(iii) one or more non-aqueous volatile solvents.
In another aspect, this specification is related to quick-drying non-aqueous topical spray composite, and it is included：
(i) momestasone furoate,
(ii) one or more solubilizer,
(iii) one or more non-aqueous volatile solvents, and
(iv) one or more film forming agents.
In another aspect, this specification is related to quick-drying non-aqueous topical spray composite, and it is included：
(i) momestasone furoate,
(ii) hexylene glycol,
(iii) one or more non-aqueous volatile solvents, and
(iv) one or more film forming agents.
In another aspect, this specification is related to quick-drying non-aqueous topical spray composite, and it is included：
(i) momestasone furoate,
(ii) one or more solubilizer,
(iii) one or more non-aqueous volatile solvents,
(iv) one or more softening agents, and
(v) one or more acidulants.
In another aspect, this specification is related to quick-drying non-aqueous topical spray composite, and it is included：
(i) momestasone furoate,
(ii) one or more solubilizer, and
(iii) one or more non-aqueous volatile solvents；
Wherein said composition forms stable closure film.
In another aspect, this specification is related to quick-drying non-aqueous topical spray composite, and it is included：
(i) 0.01% to 1% (w/w) momestasone furoate,
(ii) 1% to 15% (w/w) one or more solubilizer, and
(iii) 75% to 95% (w/w) one or more non-aqueous volatile solvents.
In another aspect, this specification is related to quick-drying non-aqueous topical spray composite, and it is included：
(i) 0.01% to 1% (w/w) momestasone furoate,
(ii) 1% to 15% (w/w) hexylene glycol,
(iii) 75% to 95% (w/w) one or more non-aqueous volatile solvents, and
(iv) 1% to 10% (w/w) of one or more film forming agents.
In another aspect, this specification is related to quick-drying non-aqueous topical spray composite, and it is included：
(i) 0.01% to 1% (w/w) momestasone furoate,
(ii) 1% to 15% (w/w) hexylene glycol,
(iii) 75% to 95% (w/w) one or more non-aqueous volatile solvents,
(iv) one or more softening agents, and
(v) one or more acidulants.
Rapid draing after term " rapid draing " as used herein refers to the composition on skin is applied to.Properly Ground, the drying time of the topical spray composition are less than 10 minutes, preferably shorter than 5 minutes, such as less than 2 minutes.
Term "non-aqueous" as used herein refers to that the composition is substantially anhydrous.In the present invention, " the composition It is substantially anhydrous " mean：Said composition is anhydrous, or, if said composition is aqueous, water content is very low 's.In the present invention, if aqueous, water content is the 5% or lower, preferably 3% or lower of composition weight, more preferably 2% or lower, and more preferably 1% or lower, even more preferably 0.5%.
Term " Mometasone " as used herein includes Mometasone or its any pharmaceutically acceptable salt or ester or derivative, example Such as momestasone furoate.In the composition usage amount of momestasone furoate for composition total weight 0.01% to 5% (w/w), 0.01% to 1% (w/w), such as 0.1% (w/w).
Term " solubilizer " as used herein refers to the component for contributing to momestasone furoate to dissolve.Suitable solubilizer includes oneself Glycol, propane diols, polyethylene glycol or its mixture.Preferable solubilizer includes hexylene glycol.Solubilizer makes in the composition Dosage is 1% to 20% (w/w) of composition total weight, such as 3% (w/w), 5% (w/w).
Term " solvent " as used herein refers to the composition for contributing to medicine to dissolve in the formulation.The solvent is substantially usual It is volatile.One of advantage comprising volatile solvent or volatile vehicle is that it promotes the composition rapid draing.Close Suitable volatile solvent can be selected from nonaqueous solvents.Volatile nonaqueous solvents may be selected from ethanol, ethyl acetate, isopropanol, Acetone, Ethyl formate, methyl acetate, methyl ethyl ketone, cyclomethicone (cyclomethicone), dimethiconol (dimethiconol), hexamethyldisiloxane or its mixture.The usage amount of solvent is composition total weight in the composition 50% to 99% (w/w), such as more than 70%, 75% or 80%.
The topical spray composition of this specification can further include cosolvent.Specifically, the addition of the cosolvent Improve dissolving of the momestasone furoate in the volatile solvent.Suitable cosolvent includes benzoic acid alkyl base ester, benzylalcohol, palm Sour isopropyl esters, isopropyl myristate, adipic acid diisopropyl ester, TC, 1-METHYLPYRROLIDONE Or its mixture.The usage amount of cosolvent is 1% to 20% (w/w) of composition total weight in the composition, such as 3% (w/w), 5% (w/w).
Term " film forming agent " as used herein refers to the material for providing smooth, uniform thin closure film after the solvent evaporates.Should Film is firmly adhered on skin and thus, it is possible to retain the suitable period on skin.The film forming agent includes but is not limited to Acrylate copolymer or copolymer, including methacrylate polymer and copolymer, such as methyl methacrylate and methyl-prop Olefin(e) acid butyl ester non-ionic copolymer (B), dimethylaminomethyl ethyl acrylate and neutral methacrylic acid esters Copolymer (E100), Type B ammonio methacrylate copolymer (RS), A types ammonium methacrylate is total to PolymersRL), A types methacrylic acid copolymer (LI00), Type B methacrylic acid copolymer (S100), acrylate/octylacrylamidoUrethane polymer is common Polymers, polyvinyl acetate, polyvinyl alcohol, PVP, alkylated polyvinyl pyrrolidone, vinyl pyrrolidone-acetic acid second Alkene ester (VA), cellulose acetate, hydroxypropyl methyl cellulose, Hydroxypropyl ethyl cellulose, hydroxyethyl cellulose, Methylcellulose, ethyl cellulose or its mixture.The usage amount of film forming agent is the 1% of composition total weight in the composition To 15% (w/w), 1% to 10% (w/w), 1% to 5% (w/w), such as 2% (w/w), 5% (w/w).
Term " softening agent " as used herein refers to the material of softening or submissive skin.Softening agent be used to correct skin Dry, Scaling, and closure barrier is also provided.Suitable softening agent includes such as stearyl alcohol, glycerin mono-fatty acid ester, glycerine list Ricinoleate, glyceryl monostearate, cetanol, isopropyl isostearate, stearic acid, isobutyl palmitate, different whale Ceryl alcohol stearate, oleyl alcohol, isopropyl laurate, lauric acid hexyl ester, decyl oleate, octadecane -2- alcohol, different cetanol, whale It is ceryl alcohol palmitate, dimethyl polysiloxane, decanedioic acid di-n-butyl ester, isopropyl myristate, stearic acid isopropyl esters, hard Resin acid butyl ester, polyethylene glycol, triethylene glycol, lanolin, sesame oil, coconut oil, peanut oil, castor oil, acetylated lanolin Alcohol, oil, mineral oil, butyl myristate, isostearic acid, palmitic acid, linoleic acid isopropyl esters, Lauryl lactate, lactic acid meat Cardamom ester, decyl oleate, myristyl myristate and their mixture.The usage amount of softening agent in the composition For 1% to 20% (w/w), 1% to 10% (w/w), 5% to 15% (w/w) of composition total weight, for example, 5% (w/w) or 10% (w/w).
The topical spray composition of this specification can include acidulant.Various available acidulants include but is not limited to lemon Acid, anhydrous citric acid, citric acid monohydrate, DL-LACTIC ACID, DL-malic acid, DL- tartaric acid, fumaric acid, L MALIC ACID, L- wine Stone acid, salicylic acid, glycolic (glycol acid), acid potassium tartrate, potassium citrate, DL- potassium hydrogen tartrates, potassium gluconate, Sodium lactate, L-TARTARIC ACID sodium, sodium citrate, ascorbic acid and their mixture.
The topical spray composition of this specification can include one or more antioxidant.The antioxidant may be selected from DL- Alpha- tocopherols, BHT (BHT), fourth hydroxyanisol (BHA), ascorbyl palmitate, no ascorbic acid, food Sub- propyl propionate or its mixture.The usage amount of antioxidant is 0.01 to about 0.5% (w/ of composition total weight in the composition Such as 0.07% (w/w) or 0.09% (w/w) w),.
The topical spray composition of this specification can include the added ingredient for improving the composition.These compositions include increasing Mould agent, surfactant, penetration enhancers, wetting agent, colouring agent, chelating agent.The example of these compositions is this area many institute's weeks Know.
The topical spray composition of this specification can be prepared by any suitable conventional method.For example, the part Spray composite can be by preparing including following method and step：Momestasone furoate is dissolved in solubilizer, then by institute Mixture is obtained to be added in one or more non-aqueous volatile solvents.Then, sequentially add the film forming agent, softening agent, its Its excipient, it is then sufficiently mixed until forming settled solution.
The topical spray composition of this specification can be applied on skin by using spray dispensing devices.Described point Fixed or variable dosing can be provided with device to apply, such as energy storage dosing pump (stored-energy Metered dose pump) or manual metered dose pump.
The topical spray composition of this specification can form stable closure film on skin after the drying.The closure film is Water-fast, and it will not easily be washed off, but retain longer time on skin.After use, the film can lead to Cross and wiped and be easily removed with tampon.
The topical spray composition of this specification can be used for treatment or prevention psoriasis or atopic dermatitis, and (idiocrasy is wet Rash) and other dermatologic disorders and disease.
The psoriasis can be chronic plate-like psoriasis or palm toe psoriasis.
The topical spray composition of this specification experienced the Journal of Sex Research steady in a long-term of acceleration.
This specification will obtain more detailed description by following non-limiting examples.
Embodiment
Embodiment 1
Method:
1. momestasone furoate is dissolved in hexylene glycol, the mixture is then added to isopropyl myristate and second In the mixture of alcohol.
2. Type B ammonio methacrylate copolymer and A types ammonio methacrylate copolymer are added to obtained in step 1 In solution, and it is stirred well to and forms settled solution.
Embodiment 2
Method:
1. momestasone furoate is dissolved in hexylene glycol, the mixture is then added to isopropanol and myristic acid isopropyl In the mixture of base ester.
2. acrylate/octylacrylamido and vinylpyrrolidone/vinyl acetate copolymer are added To in step 1 in obtained solution, and be stirred well to and to form settled solution.
3. said mixture is added slowly to dimethiconol-hexamethyldisiloxane carrier solvent under agitation In, and further be stirred well to form settled solution.
Embodiment 3
Method:
1. momestasone furoate is dissolved in hexylene glycol, the mixture is then added to isopropanol and myristic acid isopropyl In the mixture of base ester.
2. by glycerin mono-fatty acid ester and citric acid added in obtained solution, being then sufficiently stirred in step 1 until Form settled solution.
Embodiment 4
Method:
Momestasone furoate is dissolved in hexylene glycol, the mixture is then added to isopropyl myristate, diethyl In the mixture of glycol list ethylether and ethanol.Vinylpyrrolidone/vinyl acetate copolymer is finally added, and it is fully mixed Close until forming settled solution.
Embodiment 5
Method:
Momestasone furoate is dissolved in hexylene glycol, then by the mixture added to isopropyl myristate, the third two In the mixture of alcohol and ethanol.Acrylate copolymer is finally added, and is sufficiently mixed until forming settled solution.
Embodiment 6:
Method:
1. momestasone furoate is dissolved in hexylene glycol, the mixture is then added to isopropanol and myristic acid isopropyl In the mixture of base ester.
2. acrylate/octylacrylamido and vinylpyrrolidone/vinyl acetate copolymer are added To in obtained solution, be then sufficiently stirred in step 1 until formed settled solution.Then lemon is added in the mixture Acid is simultaneously sufficiently stirred.
3. slowly cyclomethicone is added in said mixture under agitation, then it is sufficiently stirred until forming clarification Solution.
Stability study
The stability of the topical spray composition of this specification is assessed by following acceleration for stabilization Journal of Sex Research.According to reality Apply the formula of example 3 and 6 and method prepares two kinds of compositions, and these compositions are carried out surely under the conditions of various temperature and humidities Qualitative research.It was found that these compositions are stable under acceleration conditions.Table 2 shows result of study data.
Table 2:
Assess in vivo：
The stability and effect of the topical spray composition of this specification pass through dermatology stability assessment and rat skin Pharmacokinetics research are assessed.
I, dermatology stability assessment：
The dermatology stability of the composition prepared according to embodiment 2 and 3 is in double blinding, nothing in toe psoriatic is slapped Assessed in control, multicenter study.Include 30 patients's (including 19 males and 11 are women) altogether, the age exists Between 18-65 year, all suffered from two palms slightly to the psoriasis of moderate.At about 10-15cm distance by described in Composition is equably sprayed on each palm 3-4 times.The security of these compositions is passed through in T0, product by dermatologist The clear and definite clinical sign on two palms (is seen by dermatologist when T, product are applied rear T+15 to 20 minutes immediately after Examine) and function sign (by patient perceptions and reporting to dermatologist) marking assess.Table 1 represents the physics of spray composite Characteristic, and table 2 represents the research evaluation scheme and the observation result of dermatologist.The composition is within 2-3 minutes Dry and form smooth uniform films.The clinical sign and functive is not observed when product is using rear 15-20 minutes Sign has increase relative to baseline (T0).
Table 1:
Table 2:
II, rat skin Pharmacokinetics research：
0.1% momestasone furoate topical spray composition is prepared according to embodiment 2.Said composition is sprayed on male rat Skin on.For the rat of another group, in an identical manner and the concentration similar with the spray composite coats city The 0.1% momestasone furoate topical ointment product sold --Ointment.After application 2 hours and 8 hours when receive Collect rat skin, and the amount of Mometasone is measured in the skin of two groups.Pharmacokinetics analysis shows, it is flat in skin Equal Mometasone concentration exceedes commercially available in the spray composite prepared according to embodiment 2Ointment (figure 1)。

Claims (16)

1. quick-drying non-aqueous topical spray composite, it is included：
(i) momestasone furoate,
(ii) one or more solubilizer,
(iii) one or more non-aqueous volatile solvents, and
(iv) one or more film forming agents.
2. topical spray composition as claimed in claim 1, wherein the solubilizer is the one or more in following： Hexylene glycol, propane diols, polyethylene glycol or its mixture.
3. topical spray composition as claimed in claim 2, wherein the solubilizer is hexylene glycol.
4. topical spray composition as claimed in claim 1, wherein the non-aqueous volatile solvent is one in following Kind is a variety of：Ethanol, ethyl acetate, isopropanol, acetone, Ethyl formate, methyl acetate, methyl ethyl ketone, cyclomethicone, poly- two Methylsiloxane alcohol, hexamethyldisiloxane or its mixture.
5. topical spray composition as claimed in claim 1, wherein the film forming agent is selected from：Methyl methacrylate and methyl The copolymer of butyl acrylate, the copolymer of dimethylaminomethyl ethyl acrylate and neutral methacrylic acid esters, Type B methyl-prop Olefin(e) acid ammonium copolymer, A types ammonio methacrylate copolymer, A types methacrylic acid copolymer, Type B methacrylic acid copolymer, third Olefin(e) acid ester/octylacrylamido, urethane polymer or copolymer, polyvinyl acetate, polyvinyl alcohol, poly- dimension Ketone, alkylated polyvinyl pyrrolidone, vinylpyrrolidone/vinyl acetate, cellulose acetate, hydroxypropyl methyl fiber Element, Hydroxypropyl ethyl cellulose, hydroxyethyl cellulose, methylcellulose, ethyl cellulose or its mixture.
6. topical spray composition as claimed in claim 1, wherein the composition is further included selected from following common molten Agent：Benzoic acid alkyl base ester, benzylalcohol, isopropyl myristate, isopropyl myristate, adipic acid diisopropyl ester, diethyl two Alcohol list ethylether, 1-METHYLPYRROLIDONE or its mixture.
7. topical spray composition as claimed in claim 1, wherein said composition further include acidulant.
8. topical spray composition as claimed in claim 1, wherein said composition form stable closure film.
9. topical spray composition as claimed in claim 1, it is included：
(i) 0.01% to 1% (w/w) momestasone furoate,
(ii) 1% to 15% (w/w) hexylene glycol,
(iii) 75% to 95% (w/w) one or more non-aqueous volatile solvents, and
(iv) 1% to 10% (w/w) one or more film forming agents.
10. quick-drying non-aqueous topical spray composite, it is included：
(i) momestasone furoate,
(ii) one or more solubilizer,
(iii) one or more non-aqueous volatile solvents,
(iv) one or more softening agents, and
(v) one or more acidulants；
Wherein said composition forms stable closure film.
11. topical spray composition as claimed in claim 9, wherein the solubilizer is one kind or more in following Kind：Hexylene glycol, propane diols, polyethylene glycol or its mixture.
12. topical spray composition as claimed in claim 10, wherein the solubilizer is hexylene glycol.
13. topical spray composition as claimed in claim 9, wherein the non-aqueous volatile solvent is one in following Kind is a variety of：Ethanol, ethyl acetate, isopropanol, acetone, Ethyl formate, methyl acetate, methyl ethyl ketone, cyclomethicone, poly- two Methylsiloxane alcohol, hexamethyldisiloxane or its mixture.
14. topical spray composition as claimed in claim 9, wherein said composition are further included selected from following common molten Agent：Benzoic acid alkyl base ester, benzylalcohol, isopropyl myristate, isopropyl myristate, adipic acid diisopropyl ester, diethyl two Alcohol list ethylether, 1-METHYLPYRROLIDONE or its mixture.
15. topical spray composition as claimed in claim 9, wherein said composition form stable closure film.
16. topical spray composition as claimed in claim 9, it is included：
(i) 0.01% to 1% (w/w) momestasone furoate,
(ii) 1% to 15% (w/w) hexylene glycol,
(iii) 75% to 95% (w/w) one or more non-aqueous volatile solvents,
(iv) one or more softening agents, and
(v) one or more acidulants.
CN201680029218.7A 2015-03-31 2016-03-31 The topical spray composition of momestasone furoate Pending CN107613987A (en)

Applications Claiming Priority (3)

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IN1670CH2015 2015-03-31
IN1670/CHE/2015 2015-03-31
PCT/IB2016/051827 WO2016157112A1 (en) 2015-03-31 2016-03-31 Topical spray compositions of mometasone furoate

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WO2019224035A1 (en) * 2018-05-24 2019-11-28 Almirall, S.A. Topical pharmaceutical compositions comprising a corticosteroid
EP4108234A1 (en) * 2021-06-25 2022-12-28 RaDes GmbH Topical pharmaceutical formulation

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000045795A2 (en) * 1999-02-05 2000-08-10 Cipla Limited Topical sprays comprising a film forming composition
CN1198563C (en) * 1998-03-31 2005-04-27 强生消费者公司 Acidified composition for topical treatment of nail and skin conditions
WO2011026076A2 (en) * 2009-08-31 2011-03-03 Dr. Reddy's Laboratories Ltd. Topical formulations comprising a steroid

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1198563C (en) * 1998-03-31 2005-04-27 强生消费者公司 Acidified composition for topical treatment of nail and skin conditions
WO2000045795A2 (en) * 1999-02-05 2000-08-10 Cipla Limited Topical sprays comprising a film forming composition
WO2011026076A2 (en) * 2009-08-31 2011-03-03 Dr. Reddy's Laboratories Ltd. Topical formulations comprising a steroid

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