DE102005029388B4 - Active ingredient combinations of glycopyrronium bromide and one or more partially neutralized esters of monoglycerides and / or diglycerides of saturated fatty acids with citric acid - Google Patents

Abstract

Drug combinations from
(i) glycopyrronium bromide and
(ii) one or more partially neutralized esters of monoglycerides and / or diglycerides of saturated fatty acids with citric acid.

Description

The present invention relates to active ingredient combinations of glycopyrronium bromide and one or more partially neutralized esters of monoglycerides and / or diglycerides of saturated fatty acids with citric acid, cosmetic preparations containing such drug combinations and the use of such drug combinations as an effective principle of cosmetic deodorants and antiperspirants.

Humans have two different forms of sweat glands. The eccrine sweat glands secrete mainly salt and water and usually do not contribute to the formation of odors. The smell is caused by the apocrine sweat glands, which excrete fatty acids, cholesterols and other compounds. These substances are decomposed by bacteria on the skin, whereby the degradation products produce the typical smell of sweat.

In order to suppress the smell of sweat over a longer period of time, the use of cosmetic preparations is essential. The usual cosmetic deodorants are based on different principles of action, which can also be combined: On the one hand Deodorant agents are used, which suppress the growth of the odor causing bacteria. These antimicrobial (bacteriostatic) agents include, for example, triclosan, chlorhexidine or the naturally occurring compounds such as farnesol and phenoxyethanol.

On the other hand, antiperspirants are used, which hinder the sweating by blocking the sweat gland exits. In the vast majority of antiperspirants, the formation of perspiration can be reduced by astringents, predominantly aluminum salts such as aluminum hydroxychloride (aluminum chlorohydrate) or aluminum / zirconium salts.

The combination of astringents with antimicrobial substances in the same composition is also common. Furthermore, perfumes are used to cover the sweat odor.

A disadvantage of the use of Aluchlorhydrat is, for example, that residues can discolor the clothes in unsightly manner and the low pH (acidic) of the cosmetic preparation affects the biological balance of the skin unfavorably.

Besides the liquid deodorants such as atomizers and rollons, solid preparations are also known and customary, for example deodorant sticks ("sticks"), powders, powder sprays, intimate cleaning agents, etc.

The following conditions are attached to a satisfactory deodorant: 1) protection of the natural biology of the skin 2) odor neutrality 3) effectiveness only with respect to deodorization, i. only avoidance and / or elimination of body odor 4) prevention of the formation of resistant bacterial strains 5) avoidance of accumulation of the active ingredients on the skin 6) harmlessness in case of overdose or other improper use 7) good cosmetic application 8) easy handling (eg as liquid) and universal usability in a wide variety of cosmetic and external preparations. 9) Excellent skin and mucous membrane compatibility 10) Use of environmentally friendly substances

An object of the present invention was thus to develop formulations which are suitable as a basis for cosmetic deodorants or antiperspirants, and do not have the disadvantages of the prior art.

Furthermore, it was therefore an object of the invention to develop cosmetic bases for cosmetic deodorants, which are characterized by good skin compatibility.

The WO03 / 026585 describes the use of glycopyrronium bromide to inhibit eccrine transpiration in humans - although the effect of glycopyrronium bromide and its use against hyperhidrosis has been known for much longer.

DE 10136404 A1 discloses a drug formulation for the therapy and prophylaxis of hyperhidrosis comprising glycopyrrolate in an amount of 0.05 to 20% by weight. The vehicle system used here is a gel and / or colloid-containing carrier system.

In the US 5962505 A describes a method of relieving hot flashes by using a therapeutically effective amount of glycopyrrolate.

The DE 19802205 A1 describes cosmetic and dermatological preparations comprising one or more partially neutralized esters of monoglycerides and / or diglycerides of saturated fatty acids with citric acid. As preparation forms, in addition to O / W emulsions and gel preparations, deodorants are also disclosed.

Glycopyrronium bromide (International Free Name for (±) - (R *) - 3 - [(S *) - (cyclopentylhydroxyphenylacetoxy) -1,1-dimethylpyrrolidinium bromide) is an anticholinergic and antispasmodic agent known since 1960. It is known, especially in English "Glycopyrrolate" refers to and is characterized by the following chemical structure:

1. (i) Glycopyrroniumbromid und
2. (ii) und einem oder mehreren partiell neutralisierten Ester von Monoglyceriden und/oder Diglyceriden gesättigter Fettsäuren mit Zitronensäure,

bzw. kosmetische Zubereitungen, solche Wirkstoffkombinationen enthaltend, sowie die Verwendung solcher Wirkstoffkombinationen als wirksames Prinzip kosmetischer Desodorantien und Antitranspirantien, die Nachteile des Standes der Technik beseitigen.It was surprising and unpredictable after all this drug combinations

1. (i) glycopyrronium bromide and
2. (ii) and one or more partially neutralized esters of monoglycerides and / or diglycerides of saturated fatty acids with citric acid,

or cosmetic preparations containing such drug combinations, as well as the use of such drug combinations as an effective principle of cosmetic deodorants and antiperspirants that eliminate the disadvantages of the prior art.

• - sich durch bessere Pflegewirkung auszeichnen,
• - durch Hautneutralität das biologische Gleichgewicht der Haut weniger belasten,
• - besser als Vehikel für kosmetische und medizinische-dermatologische Wirkstoffe dienen,
• - sich durch bessere Bioverträglichkeit auszeichnen,
• - durch eine bessere physikochemische Stabilität der Rezeptur auszeichnet
• - bessere sensorische Eigenschaften, wie beispielsweise die Verteilbarkeit oder das Einzugsvermögen in die Haut, besitzen,

als die Wirkstoffe, Wirkstoffkombinationen und Zubereitungen des Standes der Technik.The addition of surface-active glucose derivatives enhances the antiperspirant effect of glycopyrronium bromide in a surprising and unpredictable manner. Furthermore, it was not foreseeable for the person skilled in the art that the active ingredient combinations according to the invention or cosmetic or dermatological preparations containing them

• - are characterized by a better care effect,
• - reduce the biological balance of the skin through skin neutrality,
• - better serve as a vehicle for cosmetic and medical dermatological agents,
• - are characterized by better biocompatibility,
• - characterized by a better physicochemical stability of the formulation
• - have better sensory properties, such as dispersibility or ability to penetrate the skin,

as the active ingredients, drug combinations and preparations of the prior art.

A particularly advantageous citric acid ester is glyceryl stearate citrate. Such citric acid esters are obtainable, for example, under the product name "IMWITOR® 370" from SASOL.

It is advantageous according to the invention, the molar ratio of glycopyrronium bromide to one or more partially neutralized esters of monoglycerides and / or diglycerides of saturated fatty acids with citric acid in the range of 100: 1 to 1: 100, preferably 50: 1 to 1: 50, particularly preferred 20: 1 to 1:20 to choose.

According to the use according to the invention, the deodorants are particularly advantageously characterized in that the glycopyrronium bromide is present in concentrations of 0.01-10.00% by weight, preferably 0.05-5.00% by weight, more preferably 0.1-3 , 00 wt .-%, each based on the total weight of the composition, is present or present.

According to the use according to the invention, the deodorants are particularly advantageously characterized in that the partially neutralized esters of monoglycerides and / or diglycerides of saturated fatty acids with citric acid, in concentrations of 0.01-10.00% by weight, preferably 0.05-5, 00 wt .-%, particularly preferably 0.1 to 3.00 wt .-%, each based on the total weight of the composition.

According to the use according to the invention, the cosmetic deodorants may be present in the form of aerosols, ie aerosol containers, squeeze bottles or preparations which can be sprayed by a pump device or in the form of liquid compositions which can be applied by means of roll-on devices, as deodorant sticks (deodorant sticks) and in Form of W / O or O / W emulsions which can be applied from normal bottles and containers, eg Creams or lotions. Furthermore, the cosmetic deodorants may advantageously be present in the form of deodorant tinctures, deodorizing intimate cleansing agents, deodorizing shampoos, deodorizing shower or bath preparations, deodorising powders or deodorising powder sprays.

It is of course known to the person skilled in the art that cosmetic preparations are usually not conceivable without the customary auxiliaries and additives. Accordingly, the cosmetic and dermatological preparations according to the invention may further comprise cosmetic adjuvants such as are conventionally used in such preparations; for example, bodying agents, preservatives, stabilizers, fillers, perfumes, pigments which have coloring properties, thickeners, surface-active substances, emulsifiers, softening, moisturizing and / or moisturizing substances, antiinflammatory substances, additional active ingredients such as vitamins or proteins, light stabilizers, insect repellents, bactericides, Viruszide, water, salts, antimicrobial, proteolytic or keratolytic active substances, medicaments or other conventional ingredients of a cosmetic or dermatological formulation such as alcohols, polyols, polymers, foam stabilizers, organic solvents or electrolytes.

Electrolytes can be selected, for example, from the group of salts with the following anions: chlorides, and also organic oxo element anions, of these in particular sulfates, carbonates, phosphates, borates and aluminates. Also, organic anion-based electrolytes are advantageous, e.g. Lactates, acetates, benzoates, propionates, tartrates, citrates, amino acids, ethylenediaminetetraacetic acid and its salts and others. As cations of the salts it is preferred to use ammonium, alkylammonium, alkali metal, alkaline earth metal, magnesium, iron or zinc ions. There is no need to mention that only cosmetically acceptable electrolytes should be used in cosmetics. Particularly preferred are potassium chloride, sodium chloride, magnesium sulfate, zinc sulfate and mixtures thereof.

Advantageous preservatives for the purposes of the present invention are, for example, benzyl alcohol, sorbic acid and its salts, formaldehyde releasers (such as diazolidinyl urea (trade name Germall II from ISP), imidazolidinyl urea (trade name Germall 115) or DMDM hydantoin, which is available, for example, under the trade name Glydant ™ from available from Lonza), methylisothiazolinone and corresponding derivatives (trade name Kathon CG), iodopropylbutylcarbamate (eg those available under the trade names Glycacil-L, Glycacil-S from Lonza and / or Dekaben LMB from Jan Dekker) , Parabens (ie, p-hydroxybenzoic acid alkyl esters such as methyl, ethyl, propyl and / or butylparaben), phenoxyethanol, ethanol, triclosan, benzoic acid, and the like. The preservation system according to the invention furthermore advantageously also comprises substances which improve the effectiveness of classical preservatives, for example hexanediol, pentanediol, butylene glycol and methylpropanediol.

It is likewise advantageous to add conventional antioxidants to the preparations for the purposes of the present invention. According to the invention, all antioxidants which are suitable or customary for cosmetic and / or dermatological applications can be used as favorable antioxidants.

The amount of antioxidants (one or more compounds) in the preparations is preferably from 0.001 to 30% by weight, particularly preferably from 0.05 to 20% by weight, in particular from 1 to 10% by weight, based on the total weight of the preparation ,

Particularly advantageous for the purposes of the present invention, oil-soluble antioxidants can be used.

Particularly advantageous for the purposes of the present invention, water-soluble antioxidants can be used, such as vitamins, eg. As ascorbic acid and its derivatives.

Preferred antioxidants are also vitamin E (α-tocopherol) and its derivatives.

• - Wasser oder wäßrige Lösungen
• - Öle, wie Triglyceride der Caprin- oder der Caprylsäure, Fettsäureether wie Dicaprylether, Kohlensäureester wie Dicaprylylcarbonat, ferner natürlich Öle wie z.B. Rizinusöl oder Sonnenblumenöl;
• - Fette, Wachse und andere natürliche und synthetische Fettkörper, vorzugsweise Ester von Fettsäuren mit Alkoholen niedriger C-Zahl, z.B. mit Isopropanol, Propylenglykol oder Glycerin, oder Ester von Fettalkoholen mit Alkansäuren niedriger C-Zahl oder mit Fettsäuren;
• - Alkohole, Diole oder Polyole niedriger C-Zahl, sowie deren Ether, vorzugsweise Ethanol, Isopropanol, Propylenglykol, Glycerin, Ethylenglykol, Ethylenglykolmonoethyl- oder -monobutylether, Propylenglykolmonomethyl, -monoethyl- oder - monobutylether, Diethylenglykolmonomethyl- oder -monoethylether und analoge Produkte.

Insbesondere werden Gemische der vorstehend genannten Lösungsmittel verwendet. Bei alkoholischen Lösungsmitteln kann Wasser ein weiterer Bestandteil sein.If the cosmetic or dermatological preparation in the sense of the present invention is a solution or emulsion or dispersion, it is possible to use as solvent:

• - water or aqueous solutions
• Oils, such as triglycerides of capric or caprylic acid, fatty acid ethers, such as dicapryl ether, carbonic acid esters, such as dicaprylyl carbonate, and, of course, oils such as castor oil or sunflower oil;
• Fats, waxes and other natural and synthetic fatty substances, preferably esters of fatty acids with lower C-number alcohols, for example with isopropanol, propylene glycol or glycerol, or esters of fatty alcohols with lower C-number alkanoic acids or with fatty acids;
• Alcohols, diols or polyols of low C number, and their ethers, preferably ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol, ethylene glycol monoethyl or monobutyl ether, propylene glycol monomethyl, monoethyl or monobutyl ether, diethylene glycol monomethyl or monoethyl ether and analogous products.

In particular, mixtures of the abovementioned solvents are used. For alcoholic solvents, water can be another ingredient.

The oil phase of the emulsions, oleogels or hydrodispersions or lipodispersions in the context of the present invention is advantageously selected from the group of esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids having a chain length of 3 to 30 carbon atoms and saturated and / or or unsaturated, branched and / or unbranched alcohols having a chain length of 3 to 30 carbon atoms, from the group of esters of aromatic carboxylic acids and saturated and / or unsaturated, branched and / or unbranched alcohols having a chain length of 3 to 30 carbon atoms. Such ester oils can then be advantageously selected from the group isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl oleate, n-butyl stearate, n-hexyl laurate, n-decyl oleate, isooctyl stearate, isononyl stearate, isononyl isononanoate, 2-ethylhexyl palmitate, 2-ethylhexyl laurate, 2-hexyldecyl stearate, 2 Octyldodecyl palmitate, oleyl oleate, oleyl erucate, erucyl oleate, erucyl erucate and synthetic, semi-synthetic and natural mixtures of such esters, eg Jojoba oil.

Furthermore, the oil phase can be advantageously selected from the group of branched and unbranched hydrocarbons and waxes, the silicone oils, the dialkyl ethers, the group of saturated or unsaturated, branched or unbranched alcohols, and the fatty acid triglycerides, in particular the triglycerol esters of saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids of a chain length of 8 to 24, in particular 12 to 18 carbon atoms. For example, the fatty acid triglycerides can be advantageously selected from the group of synthetic, semi-synthetic and natural oils, e.g. Olive oil, sunflower oil, soybean oil, peanut oil, rapeseed oil, almond oil, palm oil, coconut oil, palm kernel oil, and the like.

Any mixtures of such oil and wax components are also advantageous to use in the context of the present invention. It may also be advantageous, if appropriate, to use waxes, for example cetyl palmitate, as the sole lipid component of the oil phase.

The oil phase is advantageously selected from the group 2-ethylhexyl isostearate, octyldodecanol, isotridecyl isononanoate, isoeicosane, 2-ethylhexyl cocoate, C _12-15 -alkyl benzoate, caprylic-capric triglyceride, dicaprylyl ether.

Particularly advantageous are mixtures of C _12-15 -alkyl benzoate and 2-ethylhexyl isostearate, mixtures of C _12-15 -alkyl benzoate and isotridecyl isononanoate and mixtures of C _12-15 -alkyl benzoate, 2-ethylhexyl isostearate and isotridecyl isononanoate.

Of the hydrocarbons, paraffin oil, squalane and squalene are to be used advantageously in the context of the present invention.

Advantageously, the oil phase may further comprise a content of cyclic or linear silicone oils or consist entirely of such oils, although it is preferred to use an additional content of other oil phase components in addition to the silicone oil or silicone oils.

Advantageously, cyclomethicone (octamethylcyclotetrasiloxane) is used as the silicone oil to be used according to the invention. However, other silicone oils are also advantageous for the purposes of the present invention, for example hexamethylcyclotrisiloxane, polydimethylsiloxane, poly (methylphenylsiloxane).

Also particularly advantageous are mixtures of cyclomethicone and isotridecyl isononanoate, cyclomethicone and 2-ethylhexyl isostearate.

Very particularly preferred oil components are octyldodecanol, caprylic / capric triglyceride, cyclomethtrone, dimethicone, C12-15 alkyl benzoate and dicaprylyl carbonate.

Cosmetic preparations in the sense of the present invention can also be present as gels which, in addition to an effective content of the active ingredient according to the invention and solvents used for this purpose, preferably water, also contain organic and / or inorganic thickeners. Furthermore, these thickeners are part of cosmetic emulsions.

Advantageous thickeners for such preparations are, for example, copolymers of C _10-30 -alkyl acrylates and one or more monomers of acrylic acid, methacrylic acid or their esters. The INCI name for such compounds is "Acrylates / C 10-30 Alkyl Acrylate Crosspolymer". The Pemulen® types TR 1, TR 2 and TRZ from Goodrich (Noveon) are particularly advantageous.

Carbopols are also advantageous gelling agents for such preparations. Carbopols are polymers of acrylic acid, especially acrylate-alkyl acrylate copolymers. Examples of advantageous carbopols are types 980, 981, 984 1342, 1382, 2984 and 5984. Likewise ETD types 2001, 2020, 2050 and Carbopol Ultrez 10, PVM / MA Decadiene Crosspolymer (trade name Stabileze 06), polyglyceryl methacrylate and polyacrylamide. Further advantageous gelling agents for such preparations are xanthan gum, polyvinylpyrrolidone, cellulose derivatives, in particular cellulose ethers such as, for example, hydroxypropylmethylcellulose, starch and starch derivatives, hyaluronic acid locust bean gum, silicon dioxide and aluminum silicates.

The thickening agent is present in the gel, dispersion or emulsion e.g. in an amount of between 0.01 and 5% by weight, preferably between 0.1 and 2% by weight.

Suitable propellants for sprayable from aerosol containers cosmetic and / or dermatological preparations in the context of the present invention, the usual known volatile, liquefied propellants, such as hydrocarbons (propane, butane, isobutane) are suitable, which can be used alone or in mixture with each other. Also, compressed air is advantageous to use.

Of course, the person skilled in the art knows that there are per se nontoxic propellants which would in principle be suitable for the realization of the present invention in the form of aerosol preparations, but which should nevertheless be dispensed with because of a harmful effect on the environment or other concomitant circumstances, in particular fluorohydrocarbons and chlorofluorocarbons (US Pat. CFC).

It is advantageous to buffer the pH of preparations according to the invention in the range from 4.5 to 7.5.

Following are advantageous embodiments of the present invention.

Formulation example: O / W emulsion

Raw material (INCI) Wt .-% glyceryl stearate 1.50 Cetylstearylalkohol 1.00 Caprylic / Capric triglyceride 1.00 dicapryl carbonate 2.00 Dimethylpolysiloxane, cyclic (dimethicone) 4.00 Carbopol 0.15 Acrylic acid / C10-30 alkyl methacrylate copolymer 0.25 dimethicone 0.75 jojoba oil 1.00 tocopheryl acetate 0.75 glycerin 10.00 ethanol 1.00 glycopyrronium 1.50 Fillers / additives (distarch phosphate, BHT, talc, aluminum starchoctenyl succinate, cyclodextrin) 1.00 Perfume qs preservative qs water ad 100 pH adjusted to 6.0

Recipe example: (O / W emulsion)

Raw material (INCI) Wt .-% glyceryl stearate 3.00 stearyl 1.00 Caprylic / Capric triglyceride 1.00 octyldodecanol 1.00 dicapryl 1.00 glycopyrronium 0.50 aluminum chlorohydrate 3.00 Carbomer 0.15 glycerin 3.00 Perfume, preservatives, dyes, antioxidants, etc. qs water Ad 100 pH adjusted to 5.5

Recipe example: (O / W emulsion)

Raw material (INCI) Wt .-% glyceryl stearate 3.00 Cetylstearylalkohol 1.00 cyclomethicones 4.00 octyldodecanol 1.00 dimethicone 1.00 glycopyrronium 1.00 allantoin 0.10 Citric acid, sodium salt 0.10 Thanol, denatured 3.00 Aluminiumzirkoniumchlorohydrat 3.00 Ammonium acryloyl dimethyl taurate / VP copolymer 0.30 glycerin 10.00 Fillers (distarch phosphate, SiO2, talc,) 0.1 Perfume, preservatives, antioxidants, etc. qs water Ad 100 pH adjusted to 5.5

Recipe example: (O / W emulsion)

Raw material (INCI) Wt .-% glyceryl stearate 2.00 cetyl alcohol 1.00 cyclomethicones 3.00 Jojoba oil 0.30 Paraffinium liquidum 1.00 glycopyrronium 1.00 chitosan 0.50 glycerin 3.00 serine 0.10 tocopherol 1.00 xanthan gum 0.10 Perfume, preservatives, dyes, antioxidants, etc. qs water Ad 100 pH adjusted to 6.0

Claims (8)

Drug combinations from (i) glycopyrronium bromide and (ii) one or more partially neutralized esters of monoglycerides and / or diglycerides of saturated fatty acids with citric acid. Drug combinations according to Claim 1 in which the molar ratio of glycopyrronium bromide to one or more partially neutralized esters of monoglycerides and / or diglycerides of saturated fatty acids with citric acid is in the range from 100: 1 to 1: 100, preferably 50: 1 to 1:50, particularly preferably 20: 1 to 1: 20 is selected. Drug combinations according to Claim 1 , characterized in that as partially neutralized esters of monoglycerides and / or diglycerides of saturated fatty acids with citric acid, the glyceryl stearate citrate is chosen. Preparations after Claim 1 , characterized in that in addition a coemulsifier from the group cetyl alcohol, stearyl alcohol, glyceryl stearate, sorbitan stearate, steareth-2 is used. Cosmetic preparations, active ingredient combinations according to one of Claims 1 - 4 containing. Cosmetic preparations according to Claim 5 in which glycopyrronium bromide in concentrations of 0.01 to 10.00 wt .-%, preferably 0.05 to 5.00 wt .-%, particularly preferably 0.1 to 3.00 wt .-%, each based on the Total weight of the composition, is present. Cosmetic preparations according to Claim 5 in which one or more partially neutralized esters of monoglycerides and / or diglycerides of saturated fatty acids with citric acid in concentrations of 0.01-10.00% by weight, preferably 0.05-5.00% by weight, particularly preferably 0 , 1 - 3.00 wt .-%, each based on the total weight of the composition is present Use of active ingredient combinations according to Claim 1 or 2 as an effective principle of cosmetic deodorants and antiperspirants.