Cream-gel which contains at least one retinoid and benzoyl peroxide

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of cosmetics and represents composition for treatment of dermatologic disorders characterised by the fact that it has form of cream-gel and contains in physiologically acceptable medium: from 0.0001 to 20% of dispersed benzoyl peroxide, from 0.0001 to 20% of at least one retinoid, at least one lipophilic compound, which contains fatty phase, and from 0.001 to 15% of at least one pH-independent gelling agent.

EFFECT: invention ensures homogeneity, physical and chemical stability of active composition ingredients.

18 cl, 4 ex

 

Description

The invention relates to compositions in the form of a cream-gel containing a physiologically acceptable medium, at least one retinoid and dispersed benzoyl peroxide.

The use of multiple classes of active substance is a therapeutic tool to which you often use, particularly for the treatment of dermatological disorders. Indeed, in the treatment of skin diseases usually combine various antifungal agents, such as derivatives of arylamino, triazoles, and antibacterial or antimicrobial agents, such as, for example, antibiotics, quinolones and imidazoles. It is also known about the use of peroxides, vitamin D and retinoids for the topical treatment of various pathologies associated with the skin or mucous membranes, in particular acne.

A combination of several types of local treatment (antibiotics, retinoids, peroxides, zinc) is also used in dermatology to improve the effectiveness of active substances and to reduce their toxicity (Cunliffe WJ,J. Dermatol. Treat., 2000, 11 (suppl2), S13-S14).

Taking several different dermatological products can be quite heavy and uncomfortable for the patient.

So clear interest in trying to get a new effective treatment of dermatological diseases with stable compositions, offering good is osmeticheskie properties, allowing only the acceptance and use, pleasant for the patient.

None of this Arsenal of treatment methods offered to the specialist, not causing him to combine in one and the same composition of benzoyl peroxide and a retinoid.

However, preparation of such compositions creates a number of problems.

First, the effectiveness of benzoyl peroxide is associated with its decomposition when it is brought into contact with the skin. Indeed, the oxidative properties of free radicals formed during this decomposition, lead to the desired effect. To maintain the optimum efficiency of benzoyl peroxide, it is important to prevent its decomposition to the application, i.e. during storage.

However, benzoyl peroxide is an unstable chemical compound that makes its preparation in the form of finished products.

The solubility and stability of benzoyl peroxide was studied Chellquist and others in ethanol, propylene glycol and various mixtures of polyethylene glycol 400 (PEG-400) and water (Chellquist E.M., Gorman W.G.,Pharm. Res., 1992, Vol 9: 1341-1346).

The solubility of benzoyl peroxide, in particular, PEG-400 and ethanol is as shown in the following table:

SolventThe solubility of benzoyl peroxide (mg/g)
39,6
Ethanol17,9
Propylene glycol2,95
Propylene glycol/water (75:25)0,36
Glycerin0,15
Water0,000155

This document specifies, moreover, that the stability of benzoyl peroxide is strongly dependent on the chemical composition of the formulation and the storage temperature. The benzoyl peroxide is a very reactive and decomposes in solution at low temperature due to the instability of peroxide connection.

The authors state that in all the investigated solvent solution of benzoyl peroxide decompose more or less rapidly depending on the type of solvent and its concentration.

Time decomposition of benzoyl peroxide in PEG-400 (0.5 mg/g), in ethanol and propylene glycol respectively equal to 1.4, 29 and 53 days at 40°C. Such a decomposition is not possible to obtain a product intended for sale.

In addition, it is known that benzoyl peroxide is more stable in water and propylene glycol when it is in suspension (i.e. in dispersed form), because it does not decay after 90 days of storage inthese solvents.

Thus, to cope with the problem of rapid instability of benzoyl peroxide in solution was found to be advantageous to introduce the benzoyl peroxide in the formulation in dispersed form. However, this type of formulation is not entirely satisfactory, because in the end product always found the decomposition of benzoyl peroxide.

Another difficulty that must be overcome to obtain a composition that contains both benzoyl peroxide and a retinoid, is that most retinoids are particularly sensitive to natural oxidation, oxidation by visible light and ultraviolet light, and since benzoyl peroxide is a strong oxidizing agent, the chemical compatibility of these compounds with the same composition creates many problems from the point of view of physical and chemical stability.

A study was conducted stability of two retinoids in combination of two commercially available products, one of which contains the retinoid (tretinoin or adapalene), and the second is a product on the basis of benzoyl peroxide (B. Martin et al.,Br.J.Dermatol.(1998) 139, (suppl. 52), 8-11). The presence of the composition on the basis of benzoyl peroxide causes a very rapid decomposition of retinoids, which are sensitive to oxidation: measured that 50% tretinoin falling apart after 2 hours and 95% within 24 hours. In compositions in which the retinoid is adapa the Yong, no decomposition adapalene within 24 hours was not measured. This study confirms that benzoyl peroxide is decomposed over time and decompose the retinoids, which are sensitive to oxidation, gradually increasing the content of benzoic acid in the final product.

However, it is clear that the decomposition of benzoyl peroxide and retinoids is undesirable because it adversely affects the efficiency of the compositions containing them.

Nothing prompted to combine these two active agent to obtain a stable composition by type of cream-gel, knowing what is commonly known that the presence of benzoyl peroxide is chemically and physically destabilizes compositions of this type.

Part of benzoyl peroxide and a retinoid in the form of a cream-gel, it may be preferable to topical treatment, such as treatment of acne, because, giving the mitigation, it excludes, in particular, that the skin will seem too greasy to the touch.

However, another difficulty that must be overcome to obtain such a composition containing, in particular, such dispersed active substance, as adapalene and benzoyl peroxide, is the deposition of active substances. Indeed, although the feeling of lightness this formula is due to the fact that the external phase is water, this feeling also depends on its composition, in particular, from the presence of sages is Italy. However, the content in the cream-gel thickeners fat phase, such as waxes, alcohols, and solid fatty esters, greatly reduced in favor of gelatinisation the aqueous phase. However, most gelatinization aqueous phase destabiliziruetsya benzoic acid liberated during the decomposition of benzoyl peroxide.

Indeed, thickeners, most commonly used for gel formula with benzoyl peroxide, are polymers of acrylic acid (carbomer), and cellulose, alone or in combination with silicates.

However, the use of carbomer in compositions of the type of water gels does not give good results from the standpoint of chemical stability of benzoyl peroxide and from the point of view of rheological stability. As described Bollinger (Bollinger,Journal of Pharmaceutical Science, 1977, vol 5), after 2 months at 40°C was observed loss of 5-20% of benzoyl peroxide, depending on the use of neutralizer carbomer. In addition, the allocation of benzoic acid causes the depolymerization of Carboneras, leading to a drop in viscosity, which may lead to the displacement of the phases.

In other gels, consisting of a mixture of hydroxypropylcellulose and silicate of aluminum-magnesium, also show a decrease in viscosity over time, which leads to sedimentation of the active substances from the suspension and heterogeneity of variance in the final product.

This instability g is LEU benzoyl peroxide degrades its effectiveness and its cosmetic properties, and it is likely that volatility will meet in cream-gels. The final product, particularly when it comes to pharmaceutical or cosmetic compositions, has throughout its shelf life to preserve physical and chemical parameters to ensure its pharmaceutical or cosmetic quality, respectively. One of these criteria is the need to maintain the rheological properties. They define the behavior and the texture of the composition during application, and characteristics of the selection of the active substance [Report of the Commission SFSTP 1998] and the homogeneity of the product, when the active substances are present in a dispersed state.

Thus, there is a need to physically and chemically stable cream gel containing benzoyl peroxide and a retinoid.

The applicant received a composition that satisfies this need. This composition is a cream-gel, which contains:

- dispersed benzoyl peroxide, in particular, in free form or encapsulated,

at least one retinoid,

- at least one lipophilic compound containing a fatty phase, and

- at least one non-pH-dependent gelling, having good physical stability, i.e., not detecting the drop in viscosity with time at temperature is x, components from 4°C to 40°C, and maintain good chemical stability of the two active agents (benzoyl peroxide and retinoid), that is, decomposition of the active substances with time at temperatures from 4°C to 40°C does not occur.

The compositions of the present invention may be in any galenical form normally used for topical application, in particular in the form of a cream-gel semi-liquid consistency of the type of milk, solid consistency of the type creams, obtained by dispersion of a fatty phase in an aqueous phase (M/B).

The specialist must choose excipients included in the compositions according to the invention, depending on the desired consistency and so does not impair the advantageous properties of the composition according to the invention.

The composition according to the invention, in addition to at least one retinoid, benzoyl peroxide, fatty phase and at least one is not dependent on the pH of the gel can contain, in particular, one or more of the following components:

a) one or more wetting,

b) one or more chelat forming agents

c) the aqueous phase,

d) one or more additives.

Unexpectedly, the Applicant has also discovered that excellent dispersion of the active substances can be obtained by following a specific method of obtaining. This method allows you to get obtain the optimal granulometric the resource distribution and homogeneous variance of the two active substances in the composition, ensuring the physical stability of the product.

Thus, the invention relates to compositions in the form of a cream-gel containing a physiologically acceptable medium, at least one retinoid and dispersed benzoyl peroxide.

The composition according to the invention preferably is in the form of aqueous cream gel.

The cream-gel is characterized by the presence of gelatinization aqueous phase and fat phase. On the contrary, no emulsifiers, what distinguishes cream-gels from emulsions.

Under emulsifiers understand amphiphilic compounds that contain a hydrophobic part having affinity with oil, and hydrophilic part having affinity with water, creating, thus, the link between the two phases. Thus, ionic or non-ionic emulsifiers stabilize emulsions M/adsorbed at the interface and forming a lamellar layers of liquid crystals.

In particular, the composition according to the invention is physically and chemically stable.

Under physiologically acceptable medium understand the environment that is compatible with topical application to the skin, mucous membranes and/or protective covers.

The composition according to the invention contains at least one retinoid. Under the retinoid understand any connection that communicates with receptors RAR and/or RXR.

As an example, retinoids can be called retinoic acid, tretinoin,tazarotene, as well as retinoids, are described in the following patents or patent applications: US 4666941, US 4581380, EP 0 210 929, EP 0 232 199, EP 0 260 162, EP 0 292 348, EP 0 325 540, EP 0 359 621, EP 0 409 728, EP 0 409 740, EP 0 552 282, EP 0 584 191, EP 0 514 264, EP 0 514 269, EP 0 661 260, EP 0 661 258, EP 0 658 553, EP 0 679 628, EP 0 679 631, EP 0 679 630, EP 0 708 100, EP 0 709 382, EP 0 722 928, EP 0 728 739, EP 0 732 328, EP 0 740 937, EP 0 776 885, EO 0 776 881, EP 0 823 903, EP 0 832 057, EP 0 081 832, EP 0 816 352, EP 0 826 657, EP 0 874 626, EP 0 934 295, EP 0 915 823, EP 0 882 033, EP 0 850 909, EP 0 879 814, EP 0 952 974, EP 0 905 118, EP 0 947 496, WO98/56783, WO99/10322, WO99/50239, WO99/65872.

For their ability to bind receptors RAR and/or RXR connection, the invention also includes derivatives of the family basically retinoids, which are described in patent application EP 0 199 636.

Preferably choose a derivative naphthoic acid, in particular:

6-(3-were)-2-naphthoic acid and its methyl ether

6-(4-tert-butylphenyl)-2-naphthoic acid and its methyl ether

6-(3-tert-butylphenyl)-2-naphthoic acid and its methyl ether

6-(3,4-acid)-2-naphthoic acid and its methyl ether

6-(n-(1-Adamantite)phenyl)-2-naphthoic acid and its methyl ether

6-(3-(1-substituted)-4-methoxyphenyl)-2-naphthoic acid (adapalene) and its methyl ether

methyl ester of 6-[3-(1-substituted)-4-tert-butyl-dimethylsiloxane)-2-naphthoic acid,

methyl ester of 6-[3-(1-substituted)-4-hydroxyphenyl)-2-naphthoic acid,

6-[3-(1-substituted)-4-hydroxyphenyl)-2-naphthoic acid,

m is tilby ester of 6-[3-(1-substituted)-4-decyloxybenzoic)-2-naphthoic acid,

6-[3-(1-substituted)-4-decyloxybenzoic)-2-naphthoic acid,

methyl ester of 6-[3-(1-substituted)-4-hexyloxyphenyl)-2-naphthoic acid,

6-[3-(1-substituted)-4-hexyloxyphenyl)-2-naphthoic acid,

methyl ester of 6-[3-(1-substituted)-4-methoxyphenyl)-4-acetoxy-1-methyl-2-naphthoic acid,

6-[3-(1-substituted)-4-methoxyphenyl)-4-hydroxy-1-methyl-2-naphthoic acid,

methyl ester of 6-[3-(1-substituted)-4-methoxyphenyl)-4-hydroxy-1-methyl-2-naphthoic acid,

methyl ester of 6-[3-(1-substituted)-4-methoxyphenyl)-1-methyl-2-naphthoic acid,

6-[3-(1-substituted)-4-methoxyphenyl)-1-methyl-2-naphthoic acid,

6-[3-(1-substituted)-4-methoxyphenyl)-2-naphthalenemethanol,

ethylamide 6-[3-(1-substituted)-4-methoxyphenyl)-2-naphthoic acid,

morpholin 6-[3-(1-substituted)-4-methoxyphenyl)-2-naphthoic acid,

methyl ester of 6-[3-tert-butyl-4-methoxyphenyl)-2-naphthoic acid,

6-[3-tert-butyl-4-methoxyphenyl)-2-naphthoic acid,

methyl ester of 6-[3-(1,1-dimethylbutyl)-4-methoxyphenyl)-2-naphthoic acid,

6-[3-(1,1-dimethylbutyl)-4-methoxyphenyl)-2-naphthoic acid.

In particular, the preferred adapalen and its salts.

Under salt adapalene understand salts formed with pharmaceutically acceptable base, in particular, mineral bases, such as soda, potassium hydroxide and ammonia, or organic bases such as lysine, argini is, N-methyl-glucamine.

Under salt adapalene see also salts formed with fatty amines, such as dioctylamine and stearylamine.

Of course, the amounts of these two active agents: benzoyl peroxide and retinoid in the composition of the invention will depend on the selected combination, and thus, in particular, of the retinoid and desirable quality of treatment.

The preferred concentration of the retinoid comprise from 0.0001 to 20 wt.% of the total weight of the composition.

Preferably, in the case adapalene, the composition according to the invention contains from 0.001 to 5%, more preferably from 0.01 to 1 wt.% adapalene, of the total weight of the composition, preferably from 0.01 to 0.5%, preferably from 0.1 to 0.4 wt.% adapalene, even more preferably 0.3 wt.% adapalene.

The benzoyl peroxide can be used both in free form or in encapsulated form, for example, in the form adsorbed on or absorbed in any porous substrate. For example, you can use benzoyl peroxide encapsulated in a polymeric system consisting of porous microspheres, such as, for example, microcube, marketed under the name Microsponges P009A Benzoyle Peroxyde company Amcol.

As an indication of order of magnitude, the composition according to the invention preferably contains from 0.0001 to 20 wt.% of benzoyl peroxide and from 0.0001 to 0 wt.% retinoid of the total weight of the composition, and more preferably, respectively, from 0.025 to 10 wt.% of benzoyl peroxide and from 0.001 to 10 wt.% retinoid of the total weight of the composition.

For example, in compositions for the treatment of acne benzoyl peroxide is preferably used in concentrations ranging from 2 to 10 wt.%, in particular, from 2.5 to 5 wt.% of the total weight of the composition. As for retinoid, it is used in this type of composition in concentrations that constitute typically from 0.01 to 1 wt.% of the total weight of the composition.

Preferably, the particle size composition of retinoid and benzoyl peroxide is such that at least 80% of the number of particles, and preferably at least 90% of the particles had a diameter less than 25 microns, and at least 99% of particles had a diameter less than 100 microns.

Preferably, the cream-gel according to the invention contains one or more of geleobrazovanie, and/or suspendida agents, and/or geleobrazovanie, not dependent on pH.

Under-neutral pH gel-understand gelatinization capable of imparting a sufficient viscosity of the composition to the retinoid and benzoyl peroxide remained in suspension, even in the result of changes in pH due to the increase in the content of benzoic acid from benzoyl peroxide.

As non-limiting examples of geleobrazovanie, and/or suspendida agents, and/or heliopaths the lei, not dependent on pH, which may be incorporated in compositions according to the invention, can be called a cross-linked polymer acrylates/C10-30alkyl, sold under the name Pemulen TR-1 and Pemulen TR-2 company a Noveon, carbomer called insensitive to electrolytes, marketed under the name Ultrez 20®, Carbopol 1382 or Carbopol ETD2020® company a Noveon, polysaccharides, as a non-limiting example xanthan gum, as Xantural 180®, manufactured by the company Kelco, guar gum, chitosans, carragenan, in particular, divided into four large families: κ, λ, β, ω, such as Viscarin® and Gelcarin®, manufactured by the company IMCD, cellulose and its derivatives, such as hypromellose, in particular the product marketed under the name Methocel E4 premium Dow Chemical company, or hydroxyethylcellulose, in particular the product sold under the name Natrosol HHX 250® by the company Aqualon, or the product microcrystalline cellulose and sodium carboxymethylcellulose", marketed under the name Avicel CL-611 company FMC Biopolymer, a family of silicates of aluminum-magnesium, as Veegum K, produced by the company Vanderbilt, the family of acrylic polymers, connected with hydrophobic chains, such as the copolymer of PEG-150/decyl/SMDI, sold under the name Aculyn 44 (polycondensate containing at least as elements, polyethylene glycol with 150 or 180 moles of ethylene oxide, decroly alcohol and m is tilen-bis(4-cyclohexylidene) (SMDI), a concentration of 35 wt.% in a mixture of propylene glycol (39%) and water (26%), the family of modified starches such as modified potato starch sold under the name Structure Solanace, or mixtures thereof, and geleobrazovanie family of polyacrylamides, such as a mixture of a copolymer of acryloyldimethyltaurate sodium/isohexadecane/Polysorbate-80, manufactured under the name Simulgel 600 PHA by the company Seppic, the mixture of polyacrylamide/isoparaffin C13-14/Laureth-7, as, for example, sold under the name Sepigel 305 by the company Seppic.

Preferred geleobrazovanie come from a family of polyacrylamides, such as Simulgel 600 or Sepigel 305; carbonero called insensitive to electrolytes, such as Carbopol ETD2020 NF; polysaccharides, such as xanthan gum; cellulose derivatives, such as hypromellose or hydroxyethylcellulose; silicates of aluminum-magnesium, individually or in a mixture.

Gelling or suspendisse agent described above may be used in preferred concentrations of the components of from 0.001 to 15%, more preferably from 0.1 to 5%.

Among chelat forming agents as non-limiting examples are ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), Ethylenediamine-di(O-hydroxyphenoxy) acid (EDDHA), hydroxy-2-ethylendiamine xunwu acid (HEDTA), ethyldiamine-(O-hydroxy-p-were)acetic acid (EDDHMA), and Ethylenediamine-di(5-carboxy-2-hydroxyphenyl)acetic acid (EDDCHA).

As the preferred chelat forming agent can be called ethylenediaminetetraacetic acid (EDTA).

Concentration chelat forming agent can vary from 0% to 1.5%, preferably from 0.05% to 0.5 wt.% of the total weight of the composition.

The composition of the invention can contain one or more wetting in concentration from 0 to 20%, preferably from 0 to 10 wt.% of the total weight of the composition. When these components are present compositions, they are in concentrations of from 0.001 to 20%, preferably from 0.1% to 10% and more preferably from 2 to 7 wt.% of the total weight of the composition. They should not be solubilisate active substances used in the content nor cause harmful peroxide benzoyl exothermic reaction, but should facilitate good dispersion of the active substances and have protivovspenivayushchie properties. Wetting ability is the tendency of a liquid to spread over the surface.

Preferably, use wetting, which may have products HLB (hydrophilic-lipophilic balance) of from 7 to 16. As a non-limiting example call poloxamer, in particular, Synperonic PE/L44 and/or Synperonic PE/L62, manufactured by the company Uniqema, glycol is, such as propylene glycol, dipropyleneglycol, propylene glycol dipelargonate, neuroglial, etokxidiglicol, esters of sorbitol, such as POE(20) sorbitan monooleate, sold under the name Tween 80 by the company Uniqema, and POE(20) sorbitol monostearate, sold under the name Tween-60 by the company Uniqema, ethers of fatty alcohols, such as ceteareth-20, marketed under the name Eumulgin B2 by the company Cognis, esters of glycerol, such as glycerol monostearate, marketed under the name Cutina GMS by the company Cognis, polyoxylene(21) stearyl ether, sold under the name Brij 721 by the company Uniqema, methylglucose sesquistearate produced under the name Glucate SS by company a Noveon, PEG-20 methylglucose sesquistearate, sold under the name Glucamate SSE-20 by the company a Noveon.

From wetting preferably employ a wetting, which may have products HLB is preferably from 10 to 14, such as (without limitation) the connection of the family of poloxamers, in particular, Synperonic PE/L44 and/or Synperonic PE/L62, or glycols, such as propylene glycol, dipropyleneglycol, propylene glycol dipelargonate, neuroglial, etokxidiglicol.

Particularly preferred wetting are propylene glycol or Synperonic PE/L44 (polyethylene-polypropylene glycol; a block copolymer of polyoxyethylene-polyoxypropylene).

According to the invention the cream-gel containing peroxide Banzai is a, and retinoid, also preferably includes at least water, at least one gelling, and/or suspendisse agent, and/or gelling, not dependent on pH, and may also contain one or more wetting.

The composition according to the invention also contains a fatty phase. This fatty phase may contain lipophilic compounds, alone or in a mixture, such as vegetable, mineral, animal or synthetic oils, silicone oils, and mixtures thereof.

As examples of mineral oils include, for example, paraffin oils of different viscosities, such as Primol 352®, Marcol 82®, Marcol 152®, manufactured by Esso.

As vegetable oils can be called sweet almond oil, palm oil, soybean oil, sesame oil, sunflower oil.

As the butter can be called lanolin, squalene, fish oil, mink oil squalane as a derivative, manufactured under the name Cosbiol® company Laserson.

As synthetic oils can be called ester, such as Cetearyl isononanoate, for example, the product sold under the name Cetiol SN PH® by the company Cognis, France, isopropyl, such as the product marketed under the name Crodamol IPP® by the company Croda, diisopropylamide, marketed under the name Crodamol DA by the company Croda, triglyceride Caprylic and capric acids, as is th sold under the name Miglyol 812® by the company Huls/Univar.

As volatile or non-volatile silicone oil can be called Dimethicone, for example, the products marketed under the name Q7-9120 (liquid silicone having a viscosity of 20 cSt to 12500 cSt), or the product marketed under the name ST-Cyclomethicone-5 NF® by the company Dow Corning.

You can also use solid lipids, such as natural or synthetic waxes. In this case, the technician must select the temperature of the heat treatment depending on the presence or absence of these solids.

For the composition according to the invention are preferred synthetic oils and silicone oils, in particular, Marcol 152® and ST-cyclomethicone-5 NF®.

The aqueous phase of the cream-gel according to the invention may contain water. This water can be, in particular, a floral water such as cornflower water, or thermal water or natural mineral water, for example, selected from water Vittel, waters of the Vichy basin, water Uriage, water from Roche Posay, water Avène or water from Aix les Bains.

Specified aqueous phase may be present in a content of 10 to 90 wt.% of the total weight of the composition, preferably from 20 to 80 wt.%.

In addition, the composition may contain any additive usually used in cosmetics or pharmacy, such as the stabilizer of benzoyl peroxide (e.g., docusinate sodium C14-16 reincorporate sodium), conventional is realnye or organic neutralizers either acidic or basic type (for example, triethanolamine, 10%soda solution, the buffer is citric acid/sodium citrate buffer, succinic acid/sodium succinate, antioxidants, sunscreens, preservatives, fillers, electrolytes, humectants and/or softeners, dyes, fragrances, essential oils, cosmetic active substances, hidratante, vitamins, essential fatty acids, sphingolipids, suntan products, such as DHA, agents, soothing and protecting the skin, such as allantoin. Of course, the specialist should choose this or these optional additional compounds and/or their amounts so as not deteriorated or did not significantly deteriorate the advantageous properties of the composition according to the invention.

These additives may be present in the composition at the rate of 0.001-20 wt.% of the total weight of the composition.

As examples of preservatives can be called benzalkonium chloride, bronopol, chlorhexidine, chlorocresol and its derivatives, ethyl alcohol, finitely alcohol, Phenoxyethanol, potassium sorbate, diazolidinylurea, benzalkonium chloride, Phenoxyethanol, benzyl alcohol, diazolidinylurea, parabens, or a mixture thereof.

As examples of moisturizers and/or a softener can be called glycerin, sorbitol, sugars (e.g. glucose, lactose), PEG (e.g. Lutrol E400), urea, amino acids (e.g. serine, citrulline, alamin).

In particular, the invention is tositsa also to pharmaceutical or cosmetic compositions in the form of a cream-gel, containing, in a physiologically acceptable medium compatible with topical application to the skin, a protective skin or mucous components selected from (expressed in weight percent):

from 0.001 to 5%, preferably from 0.01% to 0.5% of a retinoid, preferably derived naphthoic acid;

from 0.025 to 10%, preferably from 2 to 10%, benzoyl peroxide;

- 30% to 95%, preferably from 50% to 85% water;

- from 0.01% to 15%, preferably from 0.1% to 5% of one or more of geleobrazovanie, and/or suspendida agents, and/or geleobrazovanie, not dependent on pH;

- from 2% to 50%, preferably from 5% to 30% of fat phase;

- from 0% to 1.5%, preferably from 0.05% to 0.5% chelat forming agents;

- from 0% to 10%, preferably from 2% to 7% of one or more wetting;

- from 0% to 3%, preferably from 0.05% to 1% preservatives;

- from 0% to 20%, preferably from 2% to 15% humidifiers and/or a softener;

- from 0% to 3%, preferably from 0.05% to 2% stabilizers;

- from 0% to 10%, preferably from 0.1% to 5% of neutralizers.

The object of the present invention is also the composition described above as a drug.

The invention relates also to the use of the new compositions described above, in cosmetics and dermatology.

From the point of view keratolytic, antibacterial and protivovospalitel the th activity of benzoyl peroxide and visible activity of retinoids in the field of cell differentiation and proliferation, the composition according to the invention are particularly suitable for the following therapeutic areas:

1) for treating dermatological diseases associated with disorders of keratinization related to differentiation and proliferation, in particular for treating common acne, comedonic, polymorphic, pink, nodulocystic, nodular acne, senile acne, secondary acne such as solar acne, medication or occupational acne, suppurative hydradenitis,

2) for treating other types of disorders of keratinization, in particular ichthyosis, idiotphone States, disease Daria, Palmar-plantar keratoderma, leukoplakia and States like leukoplakia, cutaneous or mucous (buccal) lichen,

3) for treating other dermatological diseases associated with disorders of keratinization with inflammatory and/or immuno-allergic component, in particular all forms of psoriasis, whether cutaneous, mucous or ungual, and even psoriatic rheumatism, or cutaneous atopy, such as eczema, or respiratory atopy or gingival hypertrophy; and these compounds may also be used in certain inflammatory diseases, do not have disorders of keratinization, such as tinea

4) for the treatment of any termicheskih or epidermal of proliteracy, independently researched the mo, whether they are benign or malignant, have a viral or non-viral origin, such as common warts, flat warts, molluscum contagiosum, and epidermodysplasia type of warts, oral or intraductal papillomatosis, and proliferate, which can be caused by ultraviolet light, in particular, in the case of actinic keratoses,

5) to restore the skin or anti-aging, whether photoinduced or age, or to reduce pigmentation, or from all of the pathologies associated with actinic aging or age,

6) for the treatment, prevention or healing, healing disorders, skin ulcers, for the prevention or treatment of scars, or to facilitate healing,

7) for combating disorders of the sebaceous glands, such as Hyperborea acne or simple seborrhoea,

8) in the treatment of all diseases of fungal origin at the level of the skin, such as athlete's foot and multi-color zoster,

9) in the treatment of dermatological diseases with an immunological component,

10) in the treatment of skin disorders caused by exposure to UV irradiation, and

11) in the treatment of dermatological diseases associated with inflammation or infection of the tissues surrounding the hair follicles, in particular, caused by microbial colonization or detail what Ktsia, in particular, impetigo, seborrheic dermatitis, folliculitis, sycosis beard or disorders involving any other bacterial or fungal factor.

The composition according to the invention are particularly suitable for the treatment, prevention or treatment of common acne.

One object of the invention is also to obtain a pharmaceutical composition intended for the prevention and/or treatment of dermatological diseases associated with impaired cellular differentiation and/or proliferation and/or keratinization, preferably, ordinary acne.

The composition of the invention apply also for the hygiene of the body and hair.

The present invention relates also to the use of a composition according to the invention in cosmetics for skin treatment, prone to the formation of acne, for hair growth or struggle with their loss, for combating the greasy appearance of the skin or hair, for protection against the harmful effects of the sun or for preventing or combating photoinduced or age ageing.

These compositions according to the invention is preferably applied topical way.

The object of the invention is also a method of obtaining a composition described above. This method differs in that it includes a step of mixing a physiologically acceptable medium with at least one derivative is attoiney acid and at least benzoyl peroxide.

The introduction of other excipients and possible additives is carried out depending on the chemical nature of the compounds and selected galenical form.

Typically, the preparation of the compositions according to the invention is carried out, for example, according to the following main stages:

a) mixing at least one retinoid with water until complete dispersion, to obtain the active phase 1;

b) a mixture of benzoyl peroxide with water to the ideal dispersion, to obtain the active phase 2;

c) mixing at least one gelling, and/or a suspending agent, and/or not depending on the pH of the gel with water, optionally with one or more chelat forming agents, one or more preservatives, one or more humectants and/or softeners, one or more hydrophilic stabilizers and additives, to obtain the aqueous phase;

d) optionally, mixing at least two lipophilic compounds, to obtain the fatty phase;

e) mixing the two active phases obtained in stages a) and b)to get the only active phase;

f) introduction of the single active phase obtained in stage e), the aqueous phase obtained in stage c);

g) introduction of a single connection fatty phase or, optionally, the fatty phase obtained in stage d), to obtain a cream-gel is;

h) optionally adding heat-sensitive additives;

i) the introduction of the neutralizer of the gel in a cream-gel, obtained in stage h) or i);

(j) if necessary, add additional water.

As a rule, the preparation of the compositions according to the invention is carried out, for example, the following alternative method:

a') Stages a) and b) are combined to obtain the phase a'), which corresponds to a mixture of at least one retinoid, benzoyl peroxide with water and at least one wetting agent, until complete dispersion, to obtain a single active phase.

Stage c), (d), f), g), (h), (i), (j) primary method remain unchanged. With regard to stage (e), it overturned.

According to one private option of obtaining the composition according to the invention are, for example, according to the following main method:

a) a retinoid, preferably derived naphthoic acid is mixed with at least one wetting agent in the water as long as a specified derivative naphthoic acid is completely dispersed, to obtain the active phase 1;

b) benzoyl peroxide is mixed with at least one wetting agent in the water until it is completely dispersed, to obtain the active phase 2;

c) under stirring dissolved in water, if you want the tee with heating, one or more gelling agents and/or suspendida agents, and/or geleobrazovanie, not dependent on pH (with the exception of polyacrylamide), and the optional one or more chelat forming agents, one or more preservatives, one or more humectants and/or a softener, one or more stabilizers and hydrophilic, thermomechanically supplements. Mixing and possible heating is continued until homogeneity to obtain an aqueous phase;

d) optionally, mixing, optionally with heating, at least oil and, possibly, solid lipids, preservatives and thermomechanically lipophilic additives, to homogeneity to obtain a fatty phase;

e) active phases 1 and 2 are mixed to obtain a single active phase;

f) the only active phase obtained in stage e), added to the aqueous phase obtained in stage c);

g) optionally, enter the polyacrylamide in the phase obtained in stage f);

h) the only component of the fatty phase or optional, specified fatty phase obtained in stage d), is injected into the phase obtained in stage f) or (g), to obtain a cream-gel;

i) if necessary add heat-sensitive additives;

j) optionally, a cream-gel, obtained in stage f), enter the neutralizer of the gel that is to teach the desired pH,

k) if necessary add more water.

In particular, a composition according to the invention is carried out, for example, the following alternative method:

a') Stages a) and b) are combined to obtain the phase a'), which corresponds to a mixture of at least one retinoid, benzoyl peroxide with water and at least one wetting agent, until complete dispersion, to obtain a single active phase.

Stage c), (d), f), g), (h), (i), (j) primary method remain unchanged. With regard to stage (e), it overturned.

More precisely, the main method of obtaining the composition according to the invention includes, for example, the following stages:

Stage a: Getting active phase 1

In chemical beaker weighed the active substance (adapalene), part of the purified water, a wetting agent or wetting (such as propylene glycol, Synperonic PE/L62, Synperonic PE/L44). Dispersed under stirring until complete dispersion.

Stage b: Getting active phase 2

In chemical beaker weighed the active ingredient (benzoyl peroxide), part of the purified water, a wetting agent or wetting (such as propylene glycol, Synperonic PE/L62, Synperonic PE/L44). Dispersed under stirring until complete dispersion.

Stage c: Obtaining the aqueous phase

In chemical beaker with stirring enter, if necessary by heating the remaining purified water, one or more of geleobrazovanie (type Carbopol, Pemulen TR1, Xantural, Méthocel), and/or suspendida agents (type Avicel CL-611), and/or geleobrazovanie, not dependent on pH (except Simulgel 600PHA), optional one or more chelat forming agents (like EDTA), one or more humectants and/or a softener (like glycerin), one or more stabilizers (sodium docusinate), one or more preservatives (methylparaben), hydrophilic permaculturally supplements. Mixing and possible heating is continued until complete homogeneity.

Stage d: Getting fat phase (optional)

In a beaker, mix oil connection (type Olepal isostearique, Cetiol SN, Crodamol DA, Speziol C18, Miglyol 812, Cosbiol), lipophilic additives, not heat-sensitive, if you are heating, and possibly preservatives (Phenoxyethanol, propyl paraben). The mixture is heated before homogenization and introduce volatile silicone, if the latter is included in the composition;

Stage e: the Mixture of active phases

At temperatures below 40°C two active phases, obtained respectively in stages a) and b), mix, stirring is continued until complete homogeneity.

Stage f: the Introduction of the single active phase in the aqueous phase

The only active phase obtained in stage e), is introduced into the aqueous phase, polucen the th stage c);

Stage g (optional): Add Simulqel 600PHA

In the phase obtained in stage f), with stirring enter Simulqel 600PHA. Continue to stir until complete dispersion;

Stage h: Add oil or fatty phase obtained in stage d)

The only component of the fatty phase or, optionally, the fatty phase obtained in stage d)introducing the mixture obtained in stage f) or (g);

Stage i (optional): add a heat-sensitive additives

At temperatures below 40°C under stirring introduce possible additives. Continue to stir until complete homogeneity.

Stage j (optional): Neutralization

At temperatures below 40°C enter the neutralizer of the gel (the type of triethanolamine, 10%soda solution, the buffer is citric acid/sodium citrate buffer, succinic acid/sodium succinate), or if necessary, the pH buffer, until the desired pH. This product has a thicker consistency. If necessary, is adding water to 100%. The product is homogenized last time to ensure a good dispersion of the active substances adapalene and benzoyl peroxide (observation under the microscope detects a homogeneous dispersion without units), then the product is brought to the condition.

Stage j: Adjustment of water losses

Expect to sweat the ryu water upon receipt of the product and with stirring, add water lost, continue to stir until complete homogeneity.

Hereinafter the present invention will be illustrated in the following examples.

The following examples of formulations illustrate compositions according to the invention, but not limit its scope. Examples of methods for producing the compositions according to the invention are referred to as permissive.

More precisely, as an example, an alternative method of obtaining the composition of the invention comprises the following stages:

Stage a': a single active phase

a') Stages a) and b) the main way to unite, to get stage a'), which corresponds to a mixture of at least one retinoid, benzoyl peroxide with water and at least one wetting agent, until complete dispersion, to obtain a single active phase.

Stage c), (d), f), g), h), i), j), (k) primary method remain unchanged. With regard to stage (e), it overturned.

Hereinafter the present invention will be illustrated in the following examples and data on physical and chemical stability.

The following examples of formulations illustrate compositions according to the invention, but not limit its scope.

The physical stability of the composition refers to the implementation of the macroscopic and microscopic studies of temperature the re environment (TA) and at 40°C, held at time T=1 month T=2 months.

Microscopic observations allow us to estimate the variance of the two active substances. Adapalen see in fluorescent light, and benzoyl peroxide is observed in polarized light.

Characterization of the final product is completed by measuring the yield stress and viscosity.

To measure yield stress using a HAAKE rheometer, type VT550, with a movable measuring part SVDIN.

Rogramme shoot at 25°C, shear rate 4-1, 20-1and with 100-1(γ), measuring the shear stress. Under the yield stress (τ0, expressed in Pascals) understand the power required (minimum shear stress)to overcome the cohesive forces, such forces van der Waals forces, and to call for. The yield strength is equal to the value found for the shear rate at the 4-1.

For measuring the viscosity using a Brookfield viscometers RVDVII+ or LVDVII+. The ranges of viscosities, as measured by these two types of viscometers Brookfield, are as follows:

RVDVII+: 100 SP - 40 SMEs

LVDVII+: 15 JV - 6 SMEs

Chemical stability set by the analysis of active substances by HPLC.

The results are expressed in mg/g adapalene and benzoyl peroxide in % relative to the expected title.

Example 1: Composition type of cream-gel containing 0.1% hell is Alena and 2.5% benzoyl peroxide

The formula is prepared according to the method described above:

ComponentsContent (% m/m)
Peroxide benzoyl2,50
Adapalene0,10
Propylene glycol5,00
Synperonic PE/L440,20
EDTA0,10
Glycerin5,00
Xantural 1800,10
Carbopol Ultrez 200,70
Marcol 1527,00
Purified water100
Sodium hydroxideto pH 5,5±0,5

The stability data

Physical stability:

Characteristics at T=0
Macroscopic structureWhite cream-gel
View under the microscopeThe dispersion of the active substances without aggregates >100 mm
pH5,144
Data on viscosityHaake (4-1/20s-1/100s-1)94/123/187
Brookfield RVDVII+ (S28; 5 rpm)65620 SP

T=1 monthT=2 monthsT=3 months
Macroscopic structureTAIdentical T0Identical T0Identical T0
40°CIdentical T0Identical T0Identical T0
View under the microscopeTAIdentical T0Identical T0Identical T0
40°CEden is ichno T0 Identical T0Identical T0
pHTA5,105,035,09
40°C4,964,744,59
Rheology, Haake 4S-1/20s-1/ 100s-189/121/17287/117/168no data
Brookfield RVDVII+ (S28; 5 rpm)65775 SP63820 SP67505 SP

Chemical stability:

Adapalene
Time->
Conditions of stability
T=0T=1 monthT=2 months
TAg/g0,100,100,10
percent of the expected titre100/td> 100100
40°Cg/gno data0,100,11
percent of the expected titreno data100110

Peroxide benzoyl
Time->
Conditions of stability
T=0T=1 monthT=2 months
TAg/g2,72,72,7
percent of the expected titre108108108
40°Cg/gno data2,62,6
percent of the expected titreno data10414

Example 2:Composition type of thick cream-gel containing 0.1% adapalene and 2.5% benzoyl peroxide

The formula is prepared according to the method described above:

ComponentsContent (% m/m)
Peroxide benzoyl2,50
Adapalene0,10
Propylene glycol6,00
Synperonic PE/L440,20
Glycerin5,00
ST-Cyclomethicone 5 NF7,00
Simulgel 600 PHA4,00
Purified water100

The stability data:

Physical stability:

Characteristics at T=0
Macroscopic structureWhite cream-gel
View under the microscope The dispersion of the active substances without aggregates > 100 mm
pH3,542
Data on viscosityHaake(4-1/20-1/100-1)236/296/449
Brookfield RVDVII+(S29; 5 rpm)164650 SP

T=1 monthT=2 monthsT=3 months
Macroscopic structureTAIdentical T0Identical T0Identical T0
40°CIdentical T0Identical T0Identical T0
View under the microscopeTAIdentical T0Identical T0Identical T0
40°CIdentical T0Identical T0 Identical T0
pHTA3,473,363,50
40°C3,313,17with 3.27
Haake rheology
(4C-1/20-1/100-1)
223/286/389201/268/334No data
Brookfield RVDVII+
(S29; 5 rpm)
159070 SP150160 SP132720 SP

Chemical stability:

Adapalene
Time->
Conditions of stability
T=0T=1 monthT=2 months
TAg/g0,100,110,10
percent of the expected titre100110 100
40°Cg/gno data0,100,10
percent of the expected titreno data100100

Peroxide benzoyl
Time->
Conditions of stability
T=0T=1 monthT=2 months
TAg/g2,72,82,7
percent of the expected titre108112108
40°Cg/gno data2,62,6
percent of the expected titreno data104104

Example 3:The composition of the type of Jew who CSOs cream-gel, containing 0.3% adapalene and 1% of benzoyl peroxide

The formula is prepared according to the method described above:

Example 4:Composition type liquid cream-gel containing 0.1% adapalene and 0.25% benzoyl peroxide

The formula is prepared according to the method described above:

ComponentsContent (% m/m)
Peroxide benzoyl1,00
Adapalene0,30
Neuroglial2,00
Synperonic PE/L440,20
EDTA0,10
Methylparaben0,20
Methocel E4M prenium0,10
Carbopol ETD2020NF0,30
Olepal isostéarique2,00
Cosbiol8,00
Cetiol SN PH8,00
Propylparaben0,05
Sodium hydroxide 10% m/mto pH 5,5±0,5
Purified water100
ComponentsContent (% m/m)
Peroxide benzoyl0,25
Adapalene0,10
Propylene glycol2,00
Synperonic PE/L620,20
EDTA0,10
Glycerin5,00
Methylparaben0,20
Carbopol Ultrez-200,30
Veegum K0,20
Xanthan gum0,20
ST-Cyclomethicone 5 NF7,00
Propylparaben0,10
Triethanolamineto pH 5,5±0,5
Purified water100

1. Composition for treating dermatological disorders, characterized in that it has the form of a cream-gel, and the fact that it contains, in a physiologically acceptable medium:
from 0.0001 to 20% of dispersed benzoyl peroxide,
from 0.0001 to 20% of at least one retinoid,
at least one lipophilic compound containing a fatty phase, and
from 0.001 to 15% of at least one not dependent on the pH of the gel.

2. The composition according to claim 1, wherein the retinoid is adapalene.

3. The composition according to claim 1, wherein the benzoyl peroxide is encapsulated or free-form.

4. The composition according to claim 1, characterized in that it contains no emulsifier.

5. The composition according to claim 1, characterized in that it is physically and chemically stable.

6. The composition according to claim 1, wherein the lipophilic compound is selected from mineral, vegetable, animal, synthetic oils, silicone oils and mixtures thereof.

7. The composition according to claim 6, characterized in that the lipophilic compound is selected from paraffinic oils, sweet almond oil, palm oil, soybean oil, sesame oil, sunflower oil, lanolin, squalene, fish oil, mink oil, squalane, Cetearyl of isononanoate, Diisopropylamine, isop is pilalimata, diisopropylate, triglyceride Caprylic and capric acids, volatile or non-volatile silicone oils and natural or synthetic waxes.

8. The composition according to claim 1, wherein the gel is selected from compounds of the family of polyacrylamides; carbonero called insensitive to electrolytes; polysaccharides; cellulose and its derivatives; and silicates of aluminum and magnesium.

9. The composition of claim 8, wherein the gel is selected from a mixture of a copolymer of acryloyldimethyltaurate sodium/isohexadecane/Polysorbate-80, a mixture of polyacrylamide/isoparaffin C13-14/Laureth-7, Carbopol 1382, xanthan resin, hydroxypropylmethylcellulose and hydroxyethyl cellulose.

10. The composition according to claim 1, characterized in that it contains a wetting agent.

11. The composition according to claim 10, characterized in that it contains from 0.001% to 20% of wetting agent.

12. The composition according to claim 10, characterized in that the wetting agent is selected from poloxamer and propylene glycol.

13. Composition according to one of claims 1 to 12, characterized in that it contains components selected from (expressed in weight percent):
from 0.001 to 5%, preferably from 0.01% to 0.5%, retinoid, preferably derived naphthoic acid;
from 0.025 to 10%, preferably from 2 to 10%, benzoyl peroxide;
from 30% to 95%, preferably from 50% to 85%, water;
from 0.01% to 15%, preferably from 0.1% to 5%, one of the CSOs or more geleobrazovanie, and/or suspendida agents, and/or geleobrazovanie, not dependent on pH;
from 2% to 50%, preferably from 5% to 30%, of the fatty phase;
from 0% to 1.5%, preferably from 0.05% to 0.5%, chelat forming agents;
from 0% to 10%, preferably from 2% to 7%, of one or more wetting;
from 0% to 3%, preferably from 0.05% to 1%, preservatives;
from 0% to 20%, preferably from 2% to 15%, humidifiers and/or a softener;
from 0% to 3%, preferably from 0.05% to 2%, stabilizers;
from 0% to 10%, preferably from 0.1% to 5%, neutralizers.

14. Composition according to one of claims 1 to 13 as a drug for prevention or treatment of dermatological diseases associated with impaired cellular differentiation and/or proliferation and/or keratinization.

15. The method of obtaining the composition according to one of claims 1 to 13, characterized in that it comprises successively the following stages:
a) mixing at least one retinoid with water to the ideal dispersion, to obtain the active phase 1;
b) a mixture of benzoyl peroxide with water until complete dispersion, to obtain the active phase 2;
c) mixing at least one gelling, and/or a suspending agent, and/or is not dependent on the pH of the gel with water, optionally with one or more chelat forming agents, one or more preservatives, the ne or more humectants and/or softeners, one or more stabilizers and hydrophilic additives, to obtain the aqueous phase;
d) optional mixing of at least two lipophilic compounds, to obtain the fatty phase;
e) mixing the two active phases obtained in stages a) and b)to get the only active phase;
f) introduction of the single active phase obtained in stage e), the aqueous phase obtained in stage C);
g) introduction of a single connection fatty phase or optional fatty phase obtained in stage d), to obtain a cream-gel;
h) optionally adding heat-sensitive additives;
i) the introduction of the neutralizer of the gel in a cream-gel, obtained in stage g) or (i);
(j) if necessary, add additional water.

16. The method of obtaining the composition according to item 15, characterized in that it comprises the following successive stages:
a) derived naphthoic acid is mixed with at least one wetting agent in the water as long as a specified derivative naphthoic acid is completely dispersed, to obtain the active phase 1;
b) benzoyl peroxide is mixed with at least one wetting agent in the water until it is completely dispersed, to obtain the active phase 2;
c) under stirring dissolved in water, if necessary with heating is a W, one or more gelling agents and/or suspendida agents, and/or geleobrazovanie, not dependent on pH (with the exception of polyacrylamide), and the optional one or more chelat forming agents, one or more preservatives, one or more humectants and/or a softener, one or more stabilizers and hydrophilic, thermomechanically additives; mixing and possible heating is continued until homogeneity to obtain an aqueous phase;
d) optional mix, if necessary with heating, at least oil and, possibly, solid lipids, preservatives and thermomechanically lipophilic additives to homogeneity to obtain a fatty phase;
e) active phases 1 and 2 are mixed to obtain a single active phase;
f) the only active phase obtained in stage e), added to the aqueous phase obtained in stage C);
g) optional enter the polyacrylamide in the phase obtained in stage f);
h) the only component of the fatty phase or optional specified fatty phase obtained in stage d), is injected into the phase obtained in stage f) or (g), to obtain a cream-gel;
i) if necessary add heat-sensitive additives;
j) optionally, a cream-gel, obtained in stage f), enter the neutralizer of the gel to get the desire is the range of pH
k) if necessary add more water.

17. The use of a composition according to one of claims 1 to 13 for obtaining pharmaceutical drug intended for the prevention or treatment of dermatological diseases associated with impaired cellular differentiation and/or proliferation and/or keratinization.

18. The use of a composition according to one of claims 1 to 13 for obtaining pharmaceutical drug intended for the prevention or treatment of common acne.



 

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Toothpaste // 2455975

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine, namely to dentistry, and can be used as therapeutic-preventive preparation, used for tooth care and oral cavity care. Invention represents toothpaste, which contains abrasive component, binding agent, moisturisers, preservatives, biological additives, functional additives, surface-active substances (SAS), fragrances and water, as SAS paste contains lecithin and betaine surface-active substance, as biological additive - saccharin or maltose or aspartame or sodium cyclamate, essential oils of plants or water-alcohol extracts of medicinal plants, as functional additives - calcium glycerophosphate, soluble calcium salts or sodium fluoride, with specified ratio of components. Claimed toothpaste does not contain sodium laurylsulfate. Tooth application in short terms results in considerable improvement of state of periodontium and oral cavity tissues. Expressed effect appears already on 3-4 day from beginning of its application.

EFFECT: fast elimination of inflammatory process, reduction of edema, bleeding, sore gums are observed, easiness of cleaning, removal and prevention of stains and dental calculus are ensured.

7 cl, 3 ex

FIELD: medicine.

SUBSTANCE: invention relates to chemical-pharmaceutical industry and represents product for oral cavity care, which contains calcium salt, sodium phosphate and potassium phosphate, phosphate salts being incapsulated, and molar ratio of sodium salt to potassium salt being in range from approximately 3 to approximately 4.

EFFECT: invention ensures creation of favourable medium for mineralisation/remineralisation of teeth.

15 cl, 35 ex, 1 dwg, 9 tbl

FIELD: medicine.

SUBSTANCE: invention relates to cosmetology and represents preparation for taking baths, which contains surface-active substance, mineral salt and specific additives, characterised by the fact that it additionally contains bee pollen, skimmed whole milk powder, as surface-active substance - sodium laurylsulfate or sodium alkylbenzosulfonate, as mineral salt - sea salt, and as specific additives - fragrances identical to natural and coloring agents, components in preparation being in specified ratio in wt %.

EFFECT: invention ensures elimination of irritating effect on mucous membrane.

5 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: group of inventions relates to composition for oral cavity care in form of dental tape and methods of their application. In particular, invention relates to unconventional means for tooth care, made in form of shape capable of adhering to oral cavity and, in particular, to teeth, and intended for single application. Tape contains composition, capable of cleaning teeth and/or oral cavity when cleaning teeth with brush. One version of composition contains, at least one abrasive, at least one substance, increasing amount of foam, at least, one adhesive and, at least, one source of fluorine. Second version of composition contains, at least, one abrasive, at least, one surface-active substance, at least, one substance increasing amount of foam and, at least, one adhesive. In order to clean oral cavity of mammal tape is applied on oral cavity surface and perform impact on said tape for mechanical destruction of tape and/or facilitation of its dissolution. Means for oral cavity care in form of tape is compact and convenient for user.

EFFECT: application of tape ensures effective cleaning of oral cavity.

22 cl, 5 tbl, 4 ex, 1 dwg

FIELD: medicine.

SUBSTANCE: invention refers to personal hygiene, and concerns an absorbent product for urine odour elimination, specified in a group consisting of Pampers, panty liners, tampons, panties and liners for urinary incontinence containing pentane-1,5-diol as an active agent for urine odour elimination.

EFFECT: invention provides the absorbent products effectively eliminating urine odour.

4 cl, 4 ex

FIELD: medicine.

SUBSTANCE: invention refers to cosmetology, and concerns a cleansing formulation, a bar soap formulation and an antiperspirant formulation which contain an ethoxylated or ethoxylated and hydrogenated castor oil adduct and an additional material selected in a group containing carboxylic acid anhydrides, maleic anhydride, dicarboxylic acids, fumaric acid, maleic acid, amber acid, alpha-hydroxyacid, beta-hydroxyacid, lactic acid, glycolic acid, lactobionic acid, carnitine, salicylic acid and (meth)acrylic acid; with an average degree of ethoxylation in ethoxylated castor oil or ethoxylated and hydrogenated castor oil making 1-7 mole of ethylene oxide per one mole of oil; ethoxylated and hydrogenated castor oil has an iodine value less than 75. The invention also concerns a method for making such adducts and methods for improving skin moisture with using said compositions.

EFFECT: invention provides personal hygiene products enabling a higher level of skin moisture.

17 cl, 4 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: invention refers to cosmetology, and concerns an aerosol composition for hair styling and refreshing, containing i) clay with a net negative surface potential; and ii) a cationic polymer for hair styling with the weight ratio of clay to the cationic polymer for hair styling making 1:5 to 5:1, and the content of the cationic polymer for hair styling making 0.1 to 4 wt % of the total composition. Besides, the invention concerns using said composition for hair styling, and also a method for modifying hair smell by means of the disclosed composition.

EFFECT: invention provides the product which can be used for hair styling, and also for making hair clean and perfumed.

9 cl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to cosmetology, and concerns a dry and very dry skin care preparation containing a ceramide complex; an anti-irritant complex - mixed aloe vera gel and Echinacea, wild chamomile, marigold, gotu cola, mint, common witch-hazel and tillet extracts; Langerhans cell activator - sodium carboxyethyl-β-glucan; a prebiotic - mixed os-glucanoligosaccharides, yacon rhizome extract; maltodextrine and lactic acid bacilli; a hyaluronic acid synthesis activator - lucern extract; a natural moisturising factor - mixed natural betaine, glutamic acid sodium salt, sorbitol, glycine, glutamic acid, alanine, lysine, arginine, threonine and proline; as well as nickolipide, urea, glycerol, isononyl isononanoate, bequinyl alcohol, shea butter, caprylyl methicone, myritol, polydimethyl siloxanes, squalane, a perfume, methylparabene, xanthane gum, sodium hydroxide, buckwheat extract, Carbopol, tocopheryl acetate, trilon B, rape oil, propylparabene, kathon, dihydroquercetin and deionised water.

EFFECT: preparation shows high biological activity, improves and stabilises skin moisture content, possess high lifting and rejuvenating action.

3 dwg, 2 tbl, 12 ex

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