WO1996012504A1 - Formulation du type 'huile dans l'eau' pour application locale - Google Patents

Formulation du type 'huile dans l'eau' pour application locale Download PDF

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Publication number
WO1996012504A1
WO1996012504A1 PCT/DE1994/001238 DE9401238W WO9612504A1 WO 1996012504 A1 WO1996012504 A1 WO 1996012504A1 DE 9401238 W DE9401238 W DE 9401238W WO 9612504 A1 WO9612504 A1 WO 9612504A1
Authority
WO
WIPO (PCT)
Prior art keywords
formulation
formulation according
oil
oil phase
water
Prior art date
Application number
PCT/DE1994/001238
Other languages
German (de)
English (en)
Inventor
Martin Schmitt
Hans Burgschat
Original Assignee
Martin Schmitt
Hans Burgschat
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to DE9320586U priority Critical patent/DE9320586U1/de
Priority to DE4334600A priority patent/DE4334600C2/de
Application filed by Martin Schmitt, Hans Burgschat filed Critical Martin Schmitt
Priority to PCT/DE1994/001238 priority patent/WO1996012504A1/fr
Priority to AU79894/94A priority patent/AU7989494A/en
Publication of WO1996012504A1 publication Critical patent/WO1996012504A1/fr

Links

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
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/16—Ginkgophyta, e.g. Ginkgoaceae (Ginkgo family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/49—Fagaceae (Beech family), e.g. oak or chestnut
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
    • 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
    • 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
    • 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
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • 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
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin

Definitions

  • the invention relates to a topical oil-in-water formulation with an inner dispersed oil phase and an outer coherent water phase and with a ravon glycoside extract solubilized in the water phase, and to the use of such a formulation.
  • Ginkgo biloba extract contains ravones and ravone glycosides as the quantitatively most important fraction of the value-determining ingredients. Both antioxidative and anti-inflammatory as well as bactericidal and antiviral properties are described in the literature for ravones and ravone glycosides (Duduk et al, Arch. Exp. Veterinärmed. 26, 285 [19721; Bauman et al, Prostglandins 20, 627 [1080]; Takahama et al, Phytochemistry 24, 1443 [1985]; Alcaraz et al, Pharmazie 41, 299 [1986]; Ho et al, Agric. Biol. Chem. 49. 2173 [1985]; Waage et al, Phytochemistry 23, 2509 [1984] ; Vrijsen et al, Antiviral Res. 7, 35 [1987]).
  • Other plant extracts that contain ravone glycosides are, for example, leaf extracts from buckwheat, butcher's broom or holm oak.
  • the solvent-containing extracts are usually treated according to known processes for enriching the ravon glycosides and processed into dry extracts. Because of the rapid metabolism of the flavone glycosides in the intestine or in the liver, their beneficial properties, if at all, only have a short-term effect when used orally or parenterally. A meaningful therapeutic use of the properties mentioned above can therefore not be undertaken in this way. Oral use of flavone glycosides to treat inflammation and skin infections is also not possible. Topical application is therefore desirable to combat infections and inflammation of the skin, but this brings with it galenic problems.
  • Flavone glycosides have the disadvantage that they are very sparingly soluble in water and most of the solvents permitted for use in pharmaceuticals and cosmetics. It is therefore extremely difficult to prepare a topical formulation which contains a sufficiently dissolved concentration of the flavone glycosides in order to achieve a clear effect.
  • the galenical formulation must be demonstrably stable and free from loss of activity over a defined period. No crystal growth or precipitation of the flavone glycosides may occur during storage, nor should the topical formulation cause skin irritation.
  • the active ingredient in topical formulations is usually suspended in the oil phase in order to achieve good transdermal absorption.
  • Such formulations are described in French Patents 2,207,692 and 2,316,946 and in US Pat. No. 3,934,013.
  • German Offenlegungsschrift 3 840 832 describes preparations to be used externally, inter alia in the form of oil-in-water formulations which contain a liquid, ie. H. Ginkgo biloba extract containing solvents and also contain propylene glycol.
  • solvent-containing liquid extracts are undesirable because, on the one hand, they introduce undesirable solvent components into the formulation and, on the other hand, they have a volume that is undesirably large for transport and handling compared to dry extracts.
  • simple liquid extracts of Ginkgo biloba leaves contain undesired alk ⁇ lphenol derivatives for regular use.
  • the object on which the invention is based was therefore to obtain topical formulations using flavone glycoside dry extracts which, due to solubilization of the flavone glycosides, have good transdermal absorption and penetration and also have adequate shelf life.
  • this object is achieved with oil-in-water formulations which can be used in the middle with an inner dispersed oil phase and an outer coherent water phase and dissolved with flavone glycoside extract solubilized in the water phase, this formulation being characterized in that the aqueous phase is a combination of at least one water-miscible polyalcohol with dimethyl isosorbide (DMI) in a weight ratio of polyalcohol to DMS of 3: 1 to 1 : 1 and contains a solubilized dry extract as a flavone glycoside extract.
  • DMI dimethyl isosorbide
  • the invention is based on the synergistic effect of the water-miscible polyalcohols on the one hand and the dimethyl isosorbide on the other hand for solubilizing the flavone glycosides in dry extract form. If one tries to solubilize flavone glycoside extracts either with polyalcohol alone or with dimethylisosorbide alone, this fails or the preparation is not sufficiently stable. Surprisingly, however, the combination of both components brings the flavone glycoside dry extract in solution in the outer water phase, which results in high transdermal absorption and penetration and at the same time high storage stability of the formulation.
  • the formulation is usually in the form of an ointment or cream.
  • any extracts which contain flavone glycosides can be used as the flavone glycoside dry extracts.
  • Dry extracts are usually used in which undesired constituents have been removed by known processes and the flavone glycosides have been enriched, for example, up to 25% of the dry matter.
  • the formulation according to the invention can contain one or more water-miscible polyalcohols, ie. H. Alcohols with at least two hydroxyl groups.
  • polyalcohols are, for example and preferably, propylene glycols, polyethylene glycol, glycerol, sorbitol and mixtures thereof.
  • the formulations according to the invention can be applied topically for the treatment of bacterial and viral infections of the skin and mucosa and for the anti-inflammatory and antipruritic treatment of allergic and atopic eczema and other irritation conditions of the skin, such as, for. B. occupational dermatoses or prosthetic care. It can be used as a medicine or as a care product.
  • the formulations according to the invention for the treatment of various skin imperfections, such as acne vulgaris, for eliminating allergies and skin infections in areas of long-term contact of the skin with inanimate surfaces, such as in contact with hearing aids, epitheses, etc., as a deodorant for regulating the Skin flora and to remove hand and foot sweat or against mycotic infections.
  • the weight ratio of polyalcohol to DMI should be in the range from 3: 1 to 1: 1, although exceeding and falling below this weight ratio is not outside the scope of the invention, since then only one of the components is partially ineffective in the formulation.
  • the preferred weight ratio of polyalcohol to DMI is in the range from 2.5: 1 to 1.2: 1, the particularly preferred weight ratio in the range from 2: 1 to 1.5: 1. Weight ratios in these ranges solubilize a sufficient amount of dry flavone glycoside extract in the aqueous phase to give sufficiently effective formulations. The optimal release behavior with regard to the flavonyl glycosides is achieved by solubilizing them in the aqueous phase.
  • the total amount of polyalcohol (s) and dimethyl isosorbide is preferably in the range from 12 to 35% by weight, preferably in the range from 15 to 30% by weight and particularly preferably in the range from 19 to 27% by weight of the finished formulation. It is further preferred that the formulation according to the invention 0.05 to 2.5, preferably 0.1 to 2.0 and particularly preferably 0.2 to 1.2% by weight of the flavone glycoside extract, based on the total weight of the formulation including the oil phase. If we are talking about a flavone glycoside extract, this can of course consist of a mixture of different sources, such as a mixture of ginkgo biloba extract and buckwheat extract.
  • the weight percentage of dimethyl isosorbide in the formulation is expediently in the range from 1 to 20% by weight (w / w) and the content of polyalcohols in the range from 5 to 30% by weight (w / w), in each case based on the total weight the formulation including the oil phase.
  • the formulation can contain customary formulation auxiliaries in customary concentrations, such as emulsifiers for the oil phase, e.g. B. stearyl alcohol, cetostearyl alcohol, glyceryl monostearate or polyoxyethylene glycerol stearate or mixtures thereof.
  • the oil phase is expediently a fat and / or oil, such as liquid paraffin or mineral oil.
  • the Ginkgo biloba extract (1) is dissolved in a mixture of polyethylene glycol (2) and dimethylisorbide (3) at 70 ° C.
  • the mixture of glycerol (9) and water (1 1) is mixed in at 70 ° C.
  • the medium-chain triglycerides (4), liquid paraffin (8) and the emulsifiers (5, 6, 7) are mixed homogeneously at 70 ° C and homogenized at the same temperature with the water phase under vacuum. It is filled in glass or porcelain pots or aluminum tubes.
  • Sorbitol solution 70% 50.0 g 10. Purified water to 1000.0 g
  • the Ginkgo biloba extract (1) is dissolved in a mixture of polyethylene glycol (2) and dimethylisorbide (3) at 70 ° C.
  • the mixture of sorbitol solution 70% (9) and water (10) is mixed in at 70 ° C.
  • the medium-chain triglycerides (4), liquid paraffin (8) and the emulsifiers (5, 6, 7) are mixed homogeneously at 70 ° C and homogenized at the same temperature with the water phase under vacuum. The filling takes place in glass or porcelain pots or aluminum tubes.
  • the cream was also produced analogously to the production process described in Example 2.

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  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Botany (AREA)
  • Biotechnology (AREA)
  • Engineering & Computer Science (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention a pour objet une formulation du type 'huile dans l'eau' pour application locale, renfermant une phase huileuse dispersée interne et une phase aqueuse cohésive externe et un extrait de flavone-glycoside solubilisé dans la phase aqueuse, caractérisée en ce que la phase aqueuse renferme une association d'au moins un polyalcool miscible à l'eau avec du diméthyl-isosorbide (DMI), dans un rapport pondéral polyalcool/DMI de 3/1 à 1/1, et en ce que l'extrait de flavone-glycoside est un extrait sec solubilisé.
PCT/DE1994/001238 1993-10-11 1994-10-21 Formulation du type 'huile dans l'eau' pour application locale WO1996012504A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
DE9320586U DE9320586U1 (de) 1993-10-11 1993-10-11 Topische Formulierung eines solubilisierten Ginkgo-biloba-Extraktes
DE4334600A DE4334600C2 (de) 1993-10-11 1993-10-11 Topische Formulierung eines solubilisierten Ginkgo-biloba-Extraktes
PCT/DE1994/001238 WO1996012504A1 (fr) 1993-10-11 1994-10-21 Formulation du type 'huile dans l'eau' pour application locale
AU79894/94A AU7989494A (en) 1993-10-11 1994-10-21 Oil-in-water formulation for topical application

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE9320586U DE9320586U1 (de) 1993-10-11 1993-10-11 Topische Formulierung eines solubilisierten Ginkgo-biloba-Extraktes
DE4334600A DE4334600C2 (de) 1993-10-11 1993-10-11 Topische Formulierung eines solubilisierten Ginkgo-biloba-Extraktes
PCT/DE1994/001238 WO1996012504A1 (fr) 1993-10-11 1994-10-21 Formulation du type 'huile dans l'eau' pour application locale

Publications (1)

Publication Number Publication Date
WO1996012504A1 true WO1996012504A1 (fr) 1996-05-02

Family

ID=88404432

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE1994/001238 WO1996012504A1 (fr) 1993-10-11 1994-10-21 Formulation du type 'huile dans l'eau' pour application locale

Country Status (3)

Country Link
AU (1) AU7989494A (fr)
DE (2) DE9320586U1 (fr)
WO (1) WO1996012504A1 (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE9320586U1 (de) * 1993-10-11 1994-10-13 Hgb Pharma Service Gmbh Topische Formulierung eines solubilisierten Ginkgo-biloba-Extraktes
FR2755015B1 (fr) * 1996-10-25 1998-12-24 Sod Conseils Rech Applic Utilisation d'un extrait flavonoidique de ginkgo biloba substantiellement depourvu de terpenes, dans le domaine buccodentaire, et composition contenant un tel extrait
DE19829516B4 (de) * 1998-07-02 2004-08-26 Dr. Willmar Schwabe Gmbh & Co. Kg Wasserlöslicher nativer Trockenextrakt aus Gingko biloba mit hohem Gehalt an Terpenoiden und Flavonglykosiden
RU2172322C1 (ru) 1999-12-27 2001-08-20 Энтофарм Ко., Лтд. Аллофероны-иммуномодулирующие пептиды
IT201700104536A1 (it) 2017-09-19 2019-03-19 Cmed Aesthetics Srl Prodotti topici con sistema bifasico

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE9320586U1 (de) * 1993-10-11 1994-10-13 Hgb Pharma Service Gmbh Topische Formulierung eines solubilisierten Ginkgo-biloba-Extraktes

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SU491387A1 (ru) * 1974-07-18 1975-11-15 Всесоюзный Научно-Исследовательский Институт Лекарственных Растений Флавоноидные соединени , про вл ющие противогерпетическую активность
FR2613223B1 (fr) * 1987-04-03 1991-09-13 Biogalenique Laboratoires Forme galenique se presentant sous la forme de grains hydrosolubles, en particulier a base d'un extrait sec de ginkgo biloba, et son procede de preparation
DE3840832A1 (de) * 1988-12-03 1990-06-07 Mueller Robert Dr Aeusserlich anzuwendendes praeparat
DE3940092A1 (de) * 1989-12-04 1991-06-06 Schwabe Willmar Gmbh & Co Extrakt aus blaettern von ginkgo biloba, verfahren zu seiner herstellung und den extrakt enthaltende arzneimittel
FR2668063A1 (fr) * 1990-10-17 1992-04-24 Fabre Pierre Cosmetique Liposomes d'eaux thermales stabilises dans un gel d'adn.

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE9320586U1 (de) * 1993-10-11 1994-10-13 Hgb Pharma Service Gmbh Topische Formulierung eines solubilisierten Ginkgo-biloba-Extraktes

Also Published As

Publication number Publication date
DE4334600A1 (de) 1995-04-13
DE9320586U1 (de) 1994-10-13
DE4334600C2 (de) 1997-07-03
AU7989494A (en) 1996-05-15

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