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WO2016198999A1 - Crème médicinale préparée en utilisant du propionate de fluticasone et en incorporant un biopolymère et procédé pour la préparer - Google Patents

Crème médicinale préparée en utilisant du propionate de fluticasone et en incorporant un biopolymère et procédé pour la préparer Download PDF

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Publication number
WO2016198999A1
WO2016198999A1 PCT/IB2016/053258 IB2016053258W WO2016198999A1 WO 2016198999 A1 WO2016198999 A1 WO 2016198999A1 IB 2016053258 W IB2016053258 W IB 2016053258W WO 2016198999 A1 WO2016198999 A1 WO 2016198999A1
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WO
WIPO (PCT)
Prior art keywords
group
cream
amount
added
combination
Prior art date
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Ceased
Application number
PCT/IB2016/053258
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English (en)
Inventor
Subramaniam Vanangamudi Sulur
Murali S
Madhavan Srinivasan
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Individual
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Individual
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Priority to US15/368,559 priority Critical patent/US20170119788A1/en
Publication of WO2016198999A1 publication Critical patent/WO2016198999A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like

Definitions

  • Chitosan generally absorbs moisture from the atmosphere / environment and the amount absorbed depends upon the initial moisture content, temperature and relative humidity of the environment. It is regarded as a non-toxic and non-irritant material. It is biocompatible with both healthy and infected skin and has been shown to be biodegradable as it is derived from shrimps and crabs.
  • cream formulations are available as creams. Active compounds in cream formulations are available in ionized state, whereas in case of ointments these are present in non -ionized state.
  • the cream formulations are the first choice of the formulators in design and development of topical dosage forms, as the cream formulations are cosmetically elegant, and also as the active compound is available in ionized state, and the drug can penetrate the skin layer fast which makes the formulation totally patient friendly.
  • Fluticasone Propionate provides much wanted rapid relief of the pruritus. Therapy with only Fluticasone Propionate is recommended for severe eczematic eruptions to provide instant relief to patients from itching and burning. Also the monotherapy with Fluticasone Propionate will help in avoiding the allergenic response to antifungals and antibacterials.
  • the inclusion of Chitosan in the formulation takes care of many attributes, which are considered to be very much essential in treating skin ailments.
  • the combination of Chitosan with Fluticasone Propionate is unique and novel since this is not available commercially across the globe. The concept of the combination is justified by considering the Physical, Chemical and Therapeutic properties of Chitosan with Fluticasone Propionate. As Chitosan is a film forming, biocompatible, non-allergenic biopolymer, it protects the skin by acting as a barrier.
  • Chitosan helps in reducing the width of the wound, controls the oxygen permeability at the site, absorbs wound discharge and gets degraded by tissue enzymes which are very much required for healing at a faster rate. It also reduces the itching by providing a soothing effect. It also acts like a moisturizer.
  • the novel cream of the present invention are most stable/efficacious at ambient conditions and does not need special temperature control during transportation/storage - hence will go a long way in achieving the objectives.
  • currently available therapies do not address the issues like protecting the skin, arresting the bleeding etc.
  • the unique innovative formulation of the present invention takes care of the skin conditions by treating them along with controlling the superficial bleeding at the site. It is well understood that if the superficial bleeding is left untreated, it will lead to secondary microbial infections.
  • the present invention advantageously provides a solution to this unmet need.
  • Embodiment 1 A novel dermaceutical cream for topical treatment of skin inflammations, and for related wound healing, wherein said cream comprises Fluticasone Propionate, and a biopolymer provided in a cream base, said cream base comprising at least one of each of a primary and a secondary emulsifier, a waxy material, a co-solvent, a preservative, a chelating agent, a buffering agent, an acid, and water, preferably purified water.
  • Embodiment no. 2 A novel dermaceutical cream as disclosed in the embodiment no. 1, wherein said cream further comprising any of a group comprising an antioxidant, a humectant, or any combination thereof.
  • Embodiment no. 3 A novel dermaceutical cream as disclosed in the embodiment no. 1 wherein
  • Fluticasone Propionate is added in an amount between about 0.001% (w/w) and about 5% (w/w), preferably between about 0.01 % (w/w) and about 1% (w/w), and most preferably about 0.05% (w/w) and,
  • said primary and secondary emulsifiers are selected from a group comprising Cetostearyl alcohol, Cetomacrogol-1000, Cetyl alcohol, Stearyl alcohol, Isopropyl Myristate, Polysorbate-80, Span-80 and the like from about 1%> (w/w) to 25%o (w/w); said waxy materials is selected from a group comprising White Soft Paraffin, Liquid Paraffin, Hard Paraffin and the like, or any combination thereof, and added in an amount from about 5% (w/w) to 30%> (w/w); said co-solvent is selected from a group comprising Propylene Glycol, Hexylene Glycol, PolyEthylene Glycol-400 and the like, or any combination thereof, and added in an amount from about 5% (w/w) to 50% (w/w); said acid is selected from a group comprising HC1, H 2 SO 4 , HNO 3 , Lactic acid and the like, or any combination thereof, and added in an amount from
  • Embodiment no. 4 A novel cream as disclosed in the embodiment no. 1 and the embodiment no. 2, further comprising a buffering agent which is selected from a group comprising Di Sodium Hydrogen Ortho Phosphate, Sodium Hydrogen Ortho Phosphate and the like, or any combination thereof, and added in an amount from about 0.05% (w/w) to 1% (w/w).
  • a buffering agent which is selected from a group comprising Di Sodium Hydrogen Ortho Phosphate, Sodium Hydrogen Ortho Phosphate and the like, or any combination thereof, and added in an amount from about 0.05% (w/w) to 1% (w/w).
  • Embodiment no. 5 A novel cream as disclosed in the embodiment no. 1, 2, or 3, further comprising an antioxidant which is selected from a group comprising Butylated Hydroxy Anisole, Butylated Hydroxy Toluene and the like, either singly or any combination thereof, to form a proportion from about 0.001% (w/w) to 5% (w/w).
  • Embodiment no. 6 A novel cream as disclosed in the embodiments 1 to 4, further comprising a chelating agent which is selected from a group comprising Disodium EDTA and the like, or any combination thereof, and added in an amount from about 0.05% (w/w) to 1% (w/w).
  • Embodiment no. 7 A novel cream as disclosed in the embodiments 1 to 6, further comprising a humectant which is selected from a group comprising Glycerin, Propylene Glycol, Sorbitol, and the like, or any combination thereof, and added in an amount from about 5% (w/w) to 20% (w/w).
  • a humectant which is selected from a group comprising Glycerin, Propylene Glycol, Sorbitol, and the like, or any combination thereof, and added in an amount from about 5% (w/w) to 20% (w/w).
  • Embodiment no. 8 A process of making a cream is disclosed, said process comprising the steps of providing Fluticasone Propionate, and chitosan as a biopolymer in a cream base comprising at least one of each of a primary and a secondary emulsifier, a waxy material, a co-solvent, a preservative, a buffering agent, a chelating agent, an acid, and water, preferably purified water, and mixing all the ingredients together to form a homogeneous cream.
  • Embodiment no. 9 A process of making a cream as disclosed in the embodiment no. 8, wherein the ingredients further comprise any of a group comprising an antioxidant, a humectant, or any combination thereof.
  • said primary and secondary emulsifier is selected from a group comprising Cetostearyl alcohol, Cetomacrogol-1000, Cetyl alcohol, Stearyl alcohol, Isopropyl Myristate, Polysorbate-80, Span-80
  • said waxy material is selected from a group comprising White Soft Paraffin, Liquid Paraffin, Hard Paraffin and the like from about 5% (w/w) to 30% (w/w),
  • said acid is selected from a group comprising such as HC1, H 2 SO 4 , HNO 3 , Lactic acid and the like from about 0.005% (w/w) to 1% (w/w), said preservatives are selected from a group comprising Methylparaben, Propylparaben, Chlorocresol, Potassium sorbate, Benzoic acid,
  • Phenoxyethanol, Benzyl alcohol and the like from about 0.02% (w/w) to 0.5% (w/w)
  • said buffering agents are selected from a group comprising Di Sodium Hydrogen Ortho Phosphate, Sodium Hydrogen Ortho Phosphate and the like from about 0.05% (w/w) to 1% (w/w)
  • said water is added in the amount in the range of 20% (w/w) to 75% (w/w), preferably 35% (w/w) to 60% (w/w).
  • said chelating agents are selected from a group comprising Disodium EDTA and the like from about 0.05% (w/w) to 1% (w/w),
  • said antioxidant is selected from a group comprising Butylated Hydroxy Anisole, Butylated Hydroxy Toluene and the like, either singly or any combination thereof, to form a proportion from about 0.001% (w/w) to 5%
  • said humectants are selected from a group comprising Glycerin, Propylene Glycol, Sorbitol, and the like from about 5% (w/w) to 20% (w/w), and combining/mixing the above ingredients to make a pharmaceutically acceptable cream.
  • Embodiment no. 11 A novel cream as disclosed in any of the foregoing embodiments, wherein chitosan has a molecular weight range of 50 kDa to 5000 kDa.
  • the therapeutic efficacy of topically applied innovative anti-inflammatory cream with chitosan is due to the pronounced activity of the active Fluticasone Propionate - corticosteroid against skin inflammations - dermatitis & allergic conditions, the unique ability of actives to penetrate intact skin and skin regeneration & rejuvenation, wound healing and soothing properties of Chitosan.
  • API stability experiments were carried out using the product of the present invention and products currently commercially available. Tests were carried out to observe (or measure as appropriate) the physical appearance of the product, the pH value and assay of the API over a period of time. Tests were also carried out to assess the stability by subjecting the product to stress studies such as autoclave test and oxidative degradation test. Further Clinical studies and preclinical studies such as blood clotting, anti inflammatory studies were also carried out over a period of time. The product used for the stability studies, autoclave and oxidative degradation tests contained approximately 5% extra API (overages). The product of the present invention used for studies contained Fluticasone Propionate in cream base.
  • Composition Fluticasone Propionate BP 0.05%
  • Measured parameter pH Limits of measured parameter: 4.0 to 5.5
  • Measured parameter pH Limits of measured parameter: 4.0 to 5.5
  • Measured parameter pH Limits of measured parameter: 4.0 to 5.5 Method of measurement: Digital pH Meter
  • the cream is applied after thorough cleansing and drying the affected area. Sufficient cream should be applied to cover the affected skin and surrounding area. The cream should be applied two to four times a day depending on the skin conditions for the full treatment period, even if symptoms may have improved.
  • Blood clotting time was observed in both groups of animals, untreated control group and the test group of animals treated with the product of the present invention. Statistically significant decrease in the blood clotting time in treated group animals was observed when compared with that of the control group animals. The mean percent reduction of 32.20% was observed for the blood clotting time using the product of the present invention.
  • Burn wound healing activity was performed for the present invention.
  • the efficacy is measured by the rate of wound contraction.
  • Fluticasone Propionate Cream (invention) is better than the market product, as it is evident from its effect on wound contraction.
  • the observed finding on wound healing is because of difference in base added to Fluticasone Propionate Cream of invention. This finding is clinically useful in burn patients as Fluticasone Propionate cream not only controls infection but favors healing of burn wounds.
  • VAS Score data shows that mean Visual Analogue Scale Score for present invention is 0.3 whereas commercially available cream is 0.8 at visit 4, it clearly indicates that severity of wound is lesser in present invention.
  • GAI Global Score Index
  • Physician Global Evaluation Score shows that 90 % population from present invention achieved good and excellent results but only 70 % achieved good and excellent results with commercially available cream group at visit 4.
  • test product of present invention is superior to the commercially available product. Based on this trend, the superior benefits observed in the test product will be more pronounced & observable when used in a larger patient population.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Dispersion Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne une composition pour le traitement d'une inflammation cutanée (dermatite), la régénération et le rajeunissement et la cicatrisation des plaies contenant un composant de chitosane utilisé pour le traitement de régénération de la peau et de rajeunissement de la peau et de cicatrisation des plaies, du propionate de fluticasone utilisé dans le traitement d'inflammations cutanées, une base de crème contenant l'un quelconque des ingrédients choisis dans un groupe comprenant des émulsifiants primaires et secondaires, des substances cireuses, des cosolvants, des acides, des conservateurs, des agents tampons, des antioxydants, des chélateurs, et des humidifiants et de l'eau purifiée. L'invention présente l'avantage de réduire le temps de coagulation du sang, d'augmenter un effet épithélial et de soulager plus rapidement l'infection et l'inflammation. L'invention concerne également une thérapie à dose unitaire intégrée ou à dose unique jusqu'à présent indisponible dans des formulations dermaceutiques de prescription. En outre, l'invention est adéquatement stable/efficace en conditions ambiantes et ne nécessite pas de contrôle particulier de la température pendant le transport/stockage.
PCT/IB2016/053258 2015-06-10 2016-06-03 Crème médicinale préparée en utilisant du propionate de fluticasone et en incorporant un biopolymère et procédé pour la préparer Ceased WO2016198999A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US15/368,559 US20170119788A1 (en) 2015-06-10 2016-12-02 Methods and compositions for dermatological use comprising fluticasone and mometasone and biopolymers

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN2894CH2015 2015-06-10
IN2894/CHE/2015 2015-06-10

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2016/053261 Continuation-In-Part WO2016199002A1 (fr) 2015-06-10 2016-06-03 Crème médicale préparée en utilisant du furoate de mométasone et en incorporant un biopolymère et procédé pour la préparer

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US15/368,559 Continuation-In-Part US20170119788A1 (en) 2015-06-10 2016-12-02 Methods and compositions for dermatological use comprising fluticasone and mometasone and biopolymers

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WO2016198999A1 true WO2016198999A1 (fr) 2016-12-15

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010119366A2 (fr) * 2009-04-13 2010-10-21 Sulur Subramaniam Vanangamudi Crème médicale à base de propionate de fluticasone et de chitosane et son procédé de préparation
WO2012023079A1 (fr) * 2010-08-17 2012-02-23 Sulur Subramaniam Vanangamudi Crème d'acide fusidique médicinale utilisant du fusidate de sodium et incorporant un biopolymère, du propionate de fluticasone et du nitrate d'oxiconazole, et son procédé de fabrication

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010119366A2 (fr) * 2009-04-13 2010-10-21 Sulur Subramaniam Vanangamudi Crème médicale à base de propionate de fluticasone et de chitosane et son procédé de préparation
WO2012023079A1 (fr) * 2010-08-17 2012-02-23 Sulur Subramaniam Vanangamudi Crème d'acide fusidique médicinale utilisant du fusidate de sodium et incorporant un biopolymère, du propionate de fluticasone et du nitrate d'oxiconazole, et son procédé de fabrication

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