DE102005029388A1 - Combination, useful as cosmetic deodorant and antitranspirants, comprises glycopyrronium bromide and active materials e.g. boundary surface-active substances, polyols and hydrocolloids - Google Patents

Abstract

Active agent combinations (I) comprises glycopyrronium bromide (II) or their derivatives and/or isomers, in combination with one or more active materials (III) (e.g. polyethylene glycol(2)stearylether; boundary surface-active substances; partially neutralized esters of monoglyceride; polyols; dialkyl-substituted acetic acids; hydrocolloids; oils; perfume materials; phenoxyethanol; and water-in-silicon emulsion). Active agent combinations (I) comprises glycopyrronium bromide (II) or their derivatives and/or isomers, in combination with one or more active materials (III) ((a) polyethylene glycol(2)stearylether and polyethylene glycol (21)stearylether; (b) boundary surface-active substances (glucose derivatives of formula (1), one or more groups (2) of formula (R 3-O-(CH 2-CH(O-R 4)-CH 2-O) n-R 5)); (c) one or more partially neutralized esters of monoglyceride and/or diglyceride saturated fatty acids with citric acid; (d) one or more polyols (ethylene glycol, glycerin, octoxyglycerin (2-ethylhexylglycerinether) or 4-12C alkandiols); (e) one or more dialkyl-substituted acetic acids; (f) one or more hydrocolloids (organically natural or modified natural, organically synthetic or inorganically water-soluble polymers; (g) one or more mono, oligo and/or polysaccharide); (h) silicates in combination with oils; (i) oils (alkylbenzoate, ester oils, dialkyl carbonate and -ether, linear and/or branched, aliphatic hydrocarbons and/or short chain hydrocarbon esters (preferably isopropylester); (j) perfume materials (aldehydes, ester, ionone, methylionene, damascene, salicylate, acetals and/or wood bodies); (k) phenoxyethanol; (l) antimicrobially effective silver-containing glasses; (m) water-in-silicon emulsion; (n) oil-in-water gel; (o) soap gel paste; or (p) surfactant containing cleaning formulation). R : 1-24C alkyl; R 1H or 1-24C alkyl; R 2H or 1-24C acyl; R 3-R 5H or 8-24C fatty acid groups (up to three of aliphatic H atoms are substituted with OH); and n : 2-8. An independent claim is also included for a cosmetic preparation comprising (I). [Image].

Description

The The present invention relates to drug 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 effective Principle of cosmetic deodorants and antiperspirants.

Of the Humans have two different forms of sweat glands. The eccrine sweat glands but mainly Salt and water and usually wear not to smell. For The smell is caused by apocrine sweat glands, fatty acids, cholesterol and excrete other connections. These substances are made by Bacteria on the skin decomposes, the degradation products typical of sweat Create smell.

Around the smell of sweat over one longer Suppress period the use of cosmetic preparations is essential. The usual cosmetic deodorants are based on different active principles which can also be combined: On the one hand Deowirkstoffe are used, which is the growth of the smell of sweat suppress causative bacteria. These germ-inhibiting (bacteriostatic) agents include, for example Triclosan, chlorhexidine or the naturally occurring compounds such as farnesol and phenoxyethanol.

To the Others use antiperspirants, which are sweat secretions hamper by blocking sweat gland exits. In by far the most antiperspirants may be due to astringents - predominantly Aluminum salts such as aluminum hydroxychloride (Aluchlorhydrat) or Aluminum / zirconium salts - the Formation of sweat be reduced.

Also The combination of astringents with antimicrobial effective Substances in one and the same composition are in use. Furthermore, perfumes for coverage the smell of sweat used.

adversely when using Aluchlorhydrat is, for example, that residues the Clothes in unattractive Discolor way can and the low pH (acidic) of the cosmetic preparation is biological Balance of skin unfavorably influenced.

Known and in use are next to the liquid Deodorants such as atomizers and rollon also solid preparations, for example deodorant sticks ("sticks"), powders, powder sprays, Intimate cleanser, etc.

At a satisfactory deodorant means the following conditions subject: 1) Protecting the natural Skin biology 2) Fragrance neutrality 3) Activity only in relation to for deodorization, i. only avoidance and / or removal 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 (e.g., as a liquid) and universal usability in various cosmetic and external preparations. 9) Excellent Skin and mucous membrane compatibility 10) Use of environmentally friendly substances

A Object of the present invention was therefore to preparations develop which as a basis for cosmetic deodorants or antiperspirants are suitable, and the disadvantages of the prior art not have the technology.

Farther So it was an object of the invention to provide cosmetic bases for cosmetic Develop deodorants that are characterized by good skin tolerance distinguished.

The WO03 / 026585 describes the use of glycopyrronium bromide for Inhibition of eccrine transpiration in humans - though the action of glycopyrronium bromide and its use against Hyperhidrosis already much longer is known.

Glycopyrronium bromide (International Free Name for (±) - (R *) - 3 - [(S *) - (cyclopentylhydroxyphenylaceto xy] -1,1-dimethylpyrrolidinium bromide) is a known since 1960 anticholinergic and spasmolytic. It is referred to as "glycopyrrolate", especially in English, and is characterized by the following chemical structure:

• (i) Glycopyrroniumbromid und
• (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

• (i) glycopyrronium bromide and
• (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 from glycopyrronium bromide to one or more partially neutralized Esters of monoglycerides and / or diglycerides of saturated fatty acids with citric acid from the range of 100: 1 to 1: 100, preferably 50: 1 to 1 : 50, particularly preferably 20: 1 to 1: 20 to choose.

Corresponding the use according to the invention the deodorants are particularly advantageously characterized that the glycopyrronium bromide is present in concentrations of 0.01-10.00% by weight, preferably 0.05-5.00 Wt .-%, particularly preferably 0.1-3.00 Wt .-%, each based on the total weight of the composition, present or present.

Corresponding the use according to the invention the deodorants are particularly advantageously characterized that the partially neutralized esters of monoglycerides and / or Diglycerides saturated fatty acids with citric acid, in concentrations of 0.01-10.00 Wt .-%, preferably 0.05-5.00 Wt .-%, particularly preferably 0.1-3.00 Wt .-%, each based on the total weight of the composition, available.

Corresponding the use according to the invention can the cosmetic deodorants in the form of aerosols, ie aerosol containers, squeeze bottles or by sprayable preparations by a pumping device or in the form by means of roll-on devices orderable liquid Compositions, as deodorant sticks (deodorant sticks) and in the form of normal bottles and containers coatable W / O or O / W emulsions, e.g. creams or lotions. Furthermore you can the cosmetic deodorants advantageously in the form of deodorants Tinctures, deodorizing deodorants, deodorizing Shampoos, deodorizing shower or bath preparations, deodorising Powder or deodorising powder sprays are present.

It is the expert of course known that cosmetic preparations are usually not without the usual Auxiliaries and additives are conceivable. The cosmetic according to the invention and dermatological preparations may accordingly further contain cosmetic excipients, such as those commonly used in such preparations be used; For example, bodying agents, preservatives, Stabilizers, fillers, perfumes, Pigments, the coloring Have thickening agents, surface-active substances, emulsifiers, softening, moisturizing and / or moisturizing substances, anti-inflammatory Substances, additional Active ingredients such as vitamins or proteins, light stabilizers, insect repellents, Bactericides, virus cides, water, salts, antimicrobial, proteolytic or keratolytic substances, medicines or other common ingredients a cosmetic or dermatological formulation such as alcohols, Polyols, polymers, foam stabilizers, organic solvents or electrolytes.

electrolytes can for example, chosen are selected from the group of salts with the following anions: chlorides, also organic oxo element anions, of these in particular sulfates, Carbonates, phosphates, borates and aluminates. Also on organic Anion-based electrolytes are advantageous, e.g. Lactates, acetates, Benzoates, propionates, tartrates, citrates, amino acids, ethylenediaminetetraacetic acid and their salts and others more. As cations of the salts are preferred Ammonium, alkylammonium, alkali metal, alkaline earth, magnesium, Iron or zinc ions used. There is no need to mention that in cosmetics only physiologically harmless electrolytes used should be. 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 donors (such as. For example, diazolidinyl urea (trade name Germall II from ISP), imidazolidinyl urea (trade name Germall 115), or DMDM hydantoin, which, for example, under the trade name Glydant ^™ from available from Lonza), methylisothiazolinone and corresponding derivatives (trade name Kathon CG), iodopropyl butylcarbamates (for example those available under the trade names Glycacil-L, Glycacil-S from Lonza and / or De kaben 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 also advantageous, the preparations according to the present Invention usual Add antioxidants. According to the invention can as favorable Antioxidants all for cosmetic and / or dermatological applications suitable or common Antioxidants are used.

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, especially 1-10 Wt .-%, based on the total weight of the preparation.

Especially For the purposes of the present invention, oil-soluble antioxidants may be advantageous be used.

Especially For the purposes of the present invention, water-soluble antioxidants may be advantageous be used, such as vitamins, eg. As ascorbic acid and their 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.

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.

Especially Mixtures of the abovementioned solvents are used. at alcoholic solvents Water can be another ingredient.

The oil phase of Emulsions, oleogels or hydrodispersions or lipodispersions in the context of the present invention is advantageously selected the group of esters from saturated and / or unsaturated, branched and / or unbranched alkanecarboxylic acids of a chain length of 3 to 30 carbon atoms and saturated and / or unsaturated, branched and / or unbranched alcohols of 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 of a chain length of 3 to 30 carbon atoms. Such ester oils can then chosen advantageous are 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-octyl dodecyl palmitate, oleyl oleate, oleyl erucate, erucyl oleate, erucyl erucate as well as synthetic, semi-synthetic and natural mixtures of such esters, e.g. Jojoba oil.

Further can the oil phase chosen favorably are from the group of branched and unbranched hydrocarbons and waxes, the silicone oils, the dialkyl ether, the group of saturated or unsaturated, branched or unbranched alcohols, as well as the fatty acid triglycerides, namely the triglycerol esters of saturated and / or unsaturated branched and / or unbranched alkanecarboxylic acids of a chain length of 8 to 24, especially 12-18 C-atoms. The fatty acid triglycerides can for example, advantageously chosen are 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 more.

Also any mixtures of such oil and wax components are advantageous in the sense of the present Use invention. It may also be advantageous, waxes, For example, cetyl palmitate to use as the sole lipid component of the oil phase.

Advantageously, the oil phase is selected from the group consisting of 2-ethylhexyl isostearate, octyldodecanol, isotridecyl isononanoate, isoeicosane, 2-ethylhexyl cocoate, C _12-15 alkyl benzoate, caprylic capric acid 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.

From The hydrocarbons are paraffin oil, squalane and squalene advantageous to be used in the sense of the present invention.

Advantageous can the oil phase also have a content of cyclic or linear silicone oils or Completely from such oils although it is preferred, except the silicone oil or silicone oils additional Content of other oil phase components to use.

Advantageous Cyclomethicone (Octamethylcyclotetrasiloxan) is used as a silicone oil to be used according to the invention. But also other silicone oils are advantageous for the purposes of the present invention to use for example, hexamethylcyclotrisiloxane, polydimethylsiloxane, poly (methylphenylsiloxane).

Especially also advantageous are mixtures of cyclomethicone and isotridecyl isononanoate, from cyclomethicone and 2-ethylhexyl isostearate.

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

cosmetic Preparations within the meaning of the present invention may also as gels, in addition to an effective content of the active ingredient according to the invention and usually used solvents, preferably water, still organic and / or organic thickeners contain. 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". Particularly advantageous are the Pemulen ^® types TR 1, TR 2 and TRZ from. Goodrich (Noveon).

Also Carbopols are advantageous gelling agents for such preparations. Carbopols are polymers of acrylic acid, especially acrylate-alkyl acrylate copolymers. Advantageous Carbopols are for example the types 980, 981, 984 1342, 1382, 2984 and 5984. Also the ETD types 2001, 2020, 2050 and Carbopol Ultrez 10, PVM / MA Decadiene Crosspolymer (trade name Stabileze 06), polyglyceryl methacrylate and polyacrylamide. Further advantageous gelling agent 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, silica and aluminum silicates.

The Thickener is in the gel, dispersion or emulsion e.g. in an amount between 0.01 and 5 wt .-%, preferably between 0.1 and 2 wt .-%, contained.

When Propellant for from aerosol containers sprayable Cosmetic and / or dermatological preparations in the sense of present invention are the usual known volatile, liquefied propellant, For example, hydrocarbons (propane, butane, isobutane) suitable, which can be used alone or mixed with each other. Also Compressed air is advantageous to use.

Of course, the expert knows that there are nontoxic propellants, which are basically for the realization of the present invention in the form of aerosol preparations However, because of harmful effects on the environment or other accompanying circumstances should be waived, especially fluorocarbons and Chlorofluorocarbons (CFCs).

Advantageous it is the pH value of preparations according to the invention in the range from 4.5 to 7.5.

• pH-Wert eingestellt auf 6.0

2. Rezepturbeispiel: (O/W-Emulsion)

• pH-Wert eingestellt auf 5.5

3. Rezepturbeispiel: (O/W-Emulsion)

• pH-Wert eingestellt auf 5.5

4. Rezepturbeispiel: (O/W-Emulsion)

• pH-Wert eingestellt auf 6.0

Following are advantageous embodiments of the present invention. 1. Formulation example: O / W emulsion

• pH adjusted to 6.0

2. Formulation example: (O / W emulsion)

• pH adjusted to 5.5

3. Formulation example: (O / W emulsion)

• pH adjusted to 5.5

4. Formulation example: (O / W emulsion)

• 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 Citric acid. Active substance combinations according to claim 1, in which the molar ratio from glycopyrronium bromide to one or more partially neutralized Esters of monoglycerides and / or diglycerides of saturated fatty acids with citric acid from the range of 100: 1 to 1: 100, preferably 50: 1 to 1 : 50, particularly preferably 20: 1 to 1: 20 is selected. Active substance combinations according to Claim 1, characterized as a partially neutralized ester of monoglycerides and / or Diglycerides saturated fatty acids with citric acid the glyceryl stearate citrate was chosen becomes. Preparations according to Claim 1, characterized 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 the claims Containing 1-4. Cosmetic preparations according to claim 5, in which glycopyrronium bromide in concentrations of 0.01-10.00 Wt .-%, preferably 0.05-5.00 Wt .-%, particularly preferably 0.1-3.00 Wt .-%, each based on the total weight of the composition, is present. Cosmetic preparations according to claim 5, in which a or more partially neutralized esters of monoglycerides and / or Diglycerides saturated fatty acids with citric acid in concentrations of 0.01-10.00 Wt .-%, preferably 0.05-5.00 Wt .-%, particularly preferably 0.1-3.00 Wt .-%, each based on the total weight of the composition, present Use of active compound combinations according to claim 1 or 2 as effective principle of cosmetic deodorants and antiperspirants.