Compositions, including at least one derivative of naphthoic acid, benzoylperoxide and at least one film-forming component, methods of their obtaining and application

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of pharmaceutics, in particular represents composition for topic application, which includes, into physiologically acceptable medium at least one derivative of naphthoic acid, benzoylperoxide and at least one film-forming component.

EFFECT: invention is characterised by the fact that said compound of naphthoic acid and benzoylperoxide are in dispersed in said composition form.

23 cl, 14 ex

 

The present invention relates to compositions for topical application, methods of producing such compositions and their applications as cosmetic or pharmaceutical products, and these compositions are, in particular, for the treatment of acne.

Acne is a frequent multifactorial pathology, which affects the skin rich in sebaceous glands (face, shoulder area, shoulder area and intertriginoznoy region). Acne most often represents dermatitis. The following five pathogenic factors play a decisive role in the Constitution of acne:

genetic predisposition;

overproduction sebum (seborrhea);

androgeny;

violations of follicular keratinization (comedogenic);

bacterial colonization and inflammatory factors.

There are several forms of acne, which all together represent a disease related to the hair follicles and sebaceous glands of the skin. Can be called, in particular, ball acne, occipital keloid folliculitis, acne medication, recurrent miliary acne, necrotic acne, newborn acne, premenstrual acne, occupational acne, erythematous acne, senile acne, solar acne and common acne.

Common acne, also called polymorphic youthful acne is the most common. It includes four stages, but the passage through all stages is optional:

stage 1 corresponds to comedonal acne characterized by a large number of open and/or closed comedones and microcyst;

- stage 2, or papulopustulosa acne, is a slight to moderate risk of disease. It is characterized by open and/or closed comedones, Microtest, as well as red papules and pustules. It affects mainly the face and leaves little scarring;

- stage 3, or popularmedia acne is more dangerous and covers back, thorax and shoulders. She is accompanied by a more significant number of scars;

- stage 4, or nodulocystic acne, accompanied by numerous scars. At this stage there are nodules, as well as voluminous purple and painful pustules.

Various forms of acne described above, can be treated biologically active agents such as protivoseborainey and anti-infective means, as, for example, benzoyl peroxide (in particular, the product Eclaran®manufactured by Pierre Fabre), retinoids such as tretinoin (in particular, the product Retacnyl®manufactured by Galderma) or isotretinoin (Roaccutane®manufactured by Laboratoires Roche), or derivatives naphthoic acid. Derivatives naphthoic acid, such as, in particular, 6-[3-(1-and omantel)-4-methoxyphenyl]-2-naphthoic acid, usually called adapalene (product Differine®manufactured by Galderma), widely described and recognized as of the beginning, as effective as tretinoin to treat acne.

The combination of several local treatments (antibiotics, retinoids, peroxides, zinc) are also used in dermatology to achieve the possibility of increasing the effectiveness of existing and began reducing their toxicity (Cunliffe W.J., J. Dermatol. Treat.,11(Appendix 2), S. 13-14 (2000)), however, the repeated application of various dermatological products can be quite difficult and painful for the patient.

Therefore, understandable interest in striving to achieve a new effective treatment of dermatological diseases due to stable composition having good "physicians need"that allows only the use and enjoyable for patient use.

From this set of therapeutic tools offered by the specialist in this field, nothing makes it to the mix, in the same composition, benzoyl peroxide and retinoid.

In fact, in the composition of this song there are some problems.

First, the effectiveness of benzoyl peroxide is associated with its decomposition with the introduction of it in contact with the skin. In fact, it is the oxidizing properties of free radicals, abrazos is, for example by transferring them during this decomposition, which lead to the desired effect. Also, to maintain the benzoyl peroxide optimum efficiency is important to prevent its decomposition before use, i.e. during storage.

However, benzoyl peroxide is an unstable chemical compound, which hinders its use in obtaining the final product.

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

In addition, this document will pinpoint that on the stability of benzoyl peroxide is strongly influenced by chemical composition and storage temperature. Benzoyl peroxide is highly reactive and decomposes in solution at low temperature in accordance with the instability of its peroxide connection.

The authors also state that the benzoyl peroxide in the solution decomposes more or less rapidly in all studied solvents depending on the type of solvent and its concentration.

The time decomposition of benzoyl peroxide in PEG 400 (0.5 mg/g), in ethanol and propylene glycol are, respectively, 1, 4, 29 and 53 days at 40°C.

Such a decomposition is not possible to obtain commercially availab the th product.

Another difficulty that must be overcome in the case of obtaining a composition containing both benzoyl peroxide and a retinoid, is that most of retinoids are particularly sensitive to natural oxidation, visible light and ultraviolet radiation, and, since benzoyl peroxide is a strong oxidizing agent, the chemical compatibility of these compounds with the same composition causes numerous problems in terms of stability with the physical and chemical point of view.

A study was conducted stability of two retinoids by combining two commercially available products, one containing a retinoid (tretinoin or adapalene), and second on the basis of benzoyl peroxide (B. Martin and others, Br. J. Dermatol.,139(Appendix 52), 8-11 (1998)).

The presence of the composition on the basis of benzoyl peroxide causes a very rapid decomposition oxidation-sensitive retinoids: determine that 50% of the tretinoin is decomposed in 2 hours, and 95% for 24 hours. In the case of compositions in which the retinoid is adapalen, no decomposition adapalene not found within 24 hours. This study confirms that benzoyl peroxide degrades and decomposes sensitive to oxidation retinoids over time, gradually increasing the content of benzoic acid in the final product.

However, clear is, the decomposition of benzoyl peroxide and retinoids is undesirable because it degrades the effectiveness of the compositions containing them.

There is nothing that motivates the combination of these two active components in order to obtain a stable composition, as is commonly known that the presence of benzoyl peroxide is chemically and physically destabilizes this type of composition.

In addition, the person skilled in the art are constantly striving to improve the effectiveness and tolerance of compositions comprising benzoyl peroxide and derived naphthoic acid. One solution for improving the efficiency is to increase the quantities of biologically active agents present in the composition, or increase the duration of treatment. Such modifications are usually the consequence of an increase in induced irritation. Therefore, it is necessary to implement compositions that can improve the tolerance effectors.

One problem proposed to be solved according to the invention, is to obtain stable and less irritating compositions than those according to the prior art. Such compositions must also be conducive to local penetration of active principles in dispersed form.

Discovered, unexpectedly found by the applicant that the ingredients that are well known for giving to whom is osili film-forming effect, also can improve the tolerance of the combination of two annoying effectors, such as biologically active components against acne and, in particular, benzoyl peroxide and derivatives naphthoic acid, such as adapalene.

Thus, one of the purposes of the present invention to provide a particularly effective composition for topical application comprising at least one derived naphthoic acid and benzoyl peroxide, without explicitly irritating effect, preclude its use by the patient more or less long time.

The first object of the present invention is a composition for topical application comprising, in a physiologically acceptable medium, at least one derived naphthoic acid and benzoyl peroxide and at least one film-forming component, and specified derivative naphthoic acid is dispersed in a specified composition form.

Thus, the first object of the invention is a composition, preferably a pharmaceutical composition, especially for topical application, comprising, in a physiologically acceptable medium, at least:

(i) one derived naphthoic acid,

(ii) benzoyl peroxide

(iii) one film-forming component,

and specified derivative naphthoic acid is you and the benzoyl peroxide are dispersed in a specified composition form.

Under biologically active component in dispersed form according to the invention understand the active principle in the form of solid particles, suspended in this excipient. Such particles, in particular, have a size higher than 10 μm.

Mainly, the grading of the retinoid and benzoyl peroxide is such that at least 80% of the number of particles and preferably at least 90% of the particles have a diameter less than 25 microns and at least 99% of the particles have a diameter below 100 microns.

The second object of the present invention is a method of obtaining a composition for topical application, characterized in that it includes a step of mixing a physiologically acceptable excipient containing at least one derivative naphthoic acid and benzoyl peroxide, with at least one film-forming component, and specified derivative naphthoic acid and benzoyl peroxide are dispersed in a specified composition form. Under physiologically acceptable excipients understand excipient, compatible with the skin, mucous membranes and/or skin appendages.

Finally, the third object of the present invention is the use of a composition such as described above, for obtaining a medicinal product intended for the treatment and/or prevention dermatol the environmental diseases, associated with impaired keratinization relating to differentiation and cell proliferation, and, in particular, for the prevention and/or treatment ramadanovic, ordinary, paulocoelho, nodulocystic acne, polymorphic acne, erythematous acne, ball acne, senile acne, or even secondary acne such as solar acne, acne medication and professional acne.

When the composition comprises in a physiologically acceptable medium, at least one derived naphthoic acid and benzoyl peroxide and at least one film-forming component, and specified derivative naphthoic acid and benzoyl peroxide are dispersed in a specified composition form, it has a very good tolerance without modification of the quantity of active start penetrating into the skin.

The composition according to the invention includes at least one derived naphthoic acid, benzoyl peroxide and at least one film-forming component.

Naphthoic acid is a compound of the formula:

Under derived naphthoic acid understands the compounds of formula (I):

where R means a hydrogen atom, a hydroxyl radical, a branched or no alkyl radical with 1-4 carbon atoms, CNS radical with 1-0 carbon atoms or substituted or not cycloaliphatic radical.

Under linear or branched alkyl radical with 1-4 carbon atoms understood, preferably, methyl, ethyl, propyl and butyl.

Under CNS radical with 1-10 carbon atoms understood, preferably, methoxy, ethoxy-, propoxy-, butoxy-, hexyl-oxy and decyloxy.

Under cycloaliphatic radical realize, preferably mono - or polycyclic radicals, such as 1-methyl-cyclohexyl or 1-substituted.

Among the derivatives of naphthoic acid, which can be included in compositions according to the invention, preferentially pick 6-[3-(1-substituted)-4-methoxyphenyl]-2-naphthoic acid (adapalene), 6-[3-(1-substituted)-4-hydroxyphenyl]-2-naphthoic acid, 6-[3-(1-substituted)-4-decyloxybenzoic]-2-naphthoic acid and 6-[3-(1-substituted)-4-hexyloxyphenyl]-2-naphthoic the acid.

These derivatives naphthoic acid are usually dispersed in the composition according to the invention form. Insoluble derivatives naphthoic acid, thus, distributed homogeneous in composition according to the invention.

In the compositions according to the invention derived naphthoic acid is used in concentrations below or equal to 10% of the mass. in relation to the total weight of the composition and preferably they comprise from 0.001% wt. up to 10% of the mass. in relation to the total weight of the composition and preferably from 0.01 mass. up to 5 wt. -%, more preferably from 0.05% of the mass. up to 2% of the mass. and highly preferably from 0.1% of the mass. to 0.3% of the mass. in relation to the total weight of the composition.

Throughout the present description, unless otherwise specified, understand that, when given intervals concentrations, they include the upper and lower limits of the specified interval.

Mainly derived from naphthoic acid used in the compositions according to the invention is 6-[3-(1-substituted)-4-methoxyphenyl]-2-naphthoic acid (adapalene). Preferably in the case adapalene composition according to the invention comprises from about 0.001% of the mass. up to 5% of the mass. and preferably from 0.01% by mass. up to 1% of the mass. adapalene in relation to the total weight of the composition, preferably from 0.01% by mass. to 0.5 wt. -%, preferably from 0.1% of the mass. to 0.4% of the mass. adapalene, even more preferably from 0.1% of the mass. to 0.3% of the mass. adapalene.

The composition also includes benzoyl peroxide (VRO).

In the compositions according to the invention benzoyl peroxide is used in concentrations of from 1% of the mass. up to 10 wt. -%, more preferably from 2% of the mass. up to 7 wt. -%, even more preferably from 2.5% of the mass. up to 5% of the mass. in relation to the total weight of the composition.

Benzoyl peroxide is also good can be used in free form or in encapsulated form, adsorbed on or absorbed in, any porous media form.

He may represent, for example, benzoyl peroxide encapsulated in a polymer system formed of porous microspheres, such as microporous materials, commercially available under the name of Microsponges P009A Benzoyle peroxyde manufactured by Cardinal Health.

The composition according to the invention comprises in addition at least one film-forming component.

Under the film-forming component understand hydrophilic, ionic or non-ionic polymer with a molecular weight of at least above 10000, which at the time of application to the skin forms a constant film. The applicant has found that these film-forming components provide the best tolerance compositions containing them.

As not limiting the scope of protection of the invention examples of film-forming components can be called polyvinylpyrrolidone, preferably water-soluble, and soluble copolymers, polysaccharides, with the exception of cellulose and its derivatives, especially hydroxypropylcellulose and xanthan resin, polyvinyl alcohols, acrylic copolymers, polyquaternium.

Of polyvinylpyrrolidone and derivatives can be called poly-1-vinyl-2-pyrrolidone, also known as povidone, or a copolymer of polyvinylpyrrolidone and vinyl acetate, also known as copovidone as Kollidon®VA64, Kollidon®30, Kollidon®90F, ollidon ®K17PF.

As examples of polysaccharides include cellulose and its derivatives like carboxymethyl cellulose, can also be called pectins, vegetable gums like gum karaya, sodium hyaluronate, sold under the name sodium hyaluronate firm Contipro.

As an example, polyvinyl alcohols can be called polyvinyl alcohols having a degree of polymerization, comprising from 500 to 5000, the degree of hydrolysis, comprising from 85% to 89%, the viscosity component of from 20 MPa·s to 65 MPa·s (4% (wt./mass.) in water at 20°C). More specifically, as examples, Mowiol 40-88, manufactured by Sigma Aldrich, having a degree of polymerization of the 4200, the degree of hydrolysis, component from 86.7% to 88.7 per cent, and the viscous component from 38 MPa·s to 42 MPa·s (4% (wt./mass.) in water at 20°C.

Of acrylic copolymers can be called, this list is not exhaustive, a copolymer of acrylates and dimethylaminoethylmethacrylate, marketed under the name Eudragit E100 firm Rohm and Haas, a copolymer of acrylate and methacrylate ammonium, marketed under the name Eudragit RS100 firm Rohm and Haas, Eudragit S100 by the company Rohm and Haas, a copolymer of acrylates and octyl-acrylamide, sold under the name Dermacryl 79 by the company National Starch.

From polyquaternium can be called, as an example, polyquaternium 1, polyquaternium 7 and polyquaternium 10, more to the particular, polyquaternium-10, sold under the name Celquat SC240C by the company National Starch.

Preferably the film-forming component is chosen among polyvinylpyrrolidone, preferably water-soluble polysaccharides, such as sodium hyaluronate, polyvinyl alcohols, acrylic copolymers and polyquaterniums.

Preferably the water-soluble film-forming component according to the invention is chosen among polyvinylpyrrolidone, preferably water-soluble, for example, Kollidon VA64, Kollidon 30, Kollidon 90F, manufactured by BASF, among polysaccharides such as sodium hyaluronate, sold under the name sodium hyaluronate of high molecular weight firm Contipro, among the polyvinyl alcohols, such as, for example, Mowiol 40-88, manufactured by Sigma-Aldrich, among polyacrylamides, such as, for example, Demacryl 79, manufactured by National Starch, among polyquaternium, such as, for example, polyquaternium 10, sold under the name Celquat SC240C company National Starch.

In the compositions according to the invention the film-forming components used in concentrations below or equal to 20%, preferably constituting 0.5% of the mass. up to 20% of the mass. in relation to the total weight of the composition and more preferably constituting 0.5% of the mass. up to 10% of the mass. and preferably from 0.5% of the mass. up to 6% of the mass. and in particular, 0,5%, 1%, 2%, 3%, 4% and 6%.

The presence of at least one p is encompassed component allows to improve tolerance and consequently, provides a particularly interesting effect in the case of compositions comprising adaptagen and benzoyl peroxide. In fact, derivatives naphthoic acid can be irritating, and can have a drying effect on the skin. Therefore, it is of interest reduction induced irritation to the possibility of increasing doses.

Compositions according to the present invention may be in any galenical form normally used for topical application, in particular in the form of aqueous, aqueous-alcoholic or oily dispersions, suspensions, aqueous, anhydrous or lipophilic gels, emulsions (lotions, creams or ointments) liquid, semisolid or solid consistency, obtained by dispersion of a fatty phase in an aqueous phase (oil-in-water; N/E) or the reverse (water-in-oil; F/N), in the presence or not of emulsifier, or microemulsions, of microcapsules, of microparticles or vesicular dispersions of ionic and/or nonionic type.

Preferably the compositions according to the invention are in the form of emulsions (lotions, creams, creams without emulsifier), suspensions, gels, and more preferably in the form of gels and emulsions.

Specialist in this field selects the excipients forming composition according to the invention, depending on the desired galenical form, and so not uh what was delici predominant properties of the composition according to the invention.

The composition of the gel type according to the invention, moreover, may include, in particular, one or more of the following ingredients:

a) one or more gel-forming component and/or suspendida agents and/or pH-independent gel-forming components;

b) optionally, one or more chelating components

C) optionally, one or more softening additives and/or moisturizing components

d) one or more wetting,

e) one or more additives.

Composition type emulsion (cream, lotion, cream without emulsifier) according to the invention, moreover, may include, in particular, one or more of the following ingredients:

a) one or more gel-forming component and/or suspendida agents and/or pH-independent gel-forming components;

b) optionally, one or more chelating components

C) optionally, one or more softening additives and/or moisturizing components

d) one or more of lipophilic excipients forming fatty phase,

e) optionally, one or more emulsifiers,

f) one or more wetting,

g) one or more additives.

As an example, not limiting the scope of protection of the invention, the gel-forming component and/or a suspending agent and/or pH-independent who's gel-forming components, which can be included in the composition according to the invention, can be called a cross-linked copolymer of acrylates and (C10-C30)-alkylacrylate, sold under the name Pemulen TR-1 and Pemulen TR-2 firm a Noveon, insensitive to electrolytes so-called carbomer, marketed under the name Ultrez 20®, Ultrez 10®, Carbopol 1382®or Carbopol ETD2020NF®, Carbopol 980®firm Societe a Noveon, polysaccharides, as not limiting the scope of protection of the invention examples, xanthan resin, such as Xantural 180®manufactured by Kelco, Gellan resin, marketed under the name Kelcogel®the company Kelco, guar resin, cellulose and its derivatives, such as microcrystalline cellulose and sodium carboxymethyl cellulose, sold under the name Avicel CL-611 firm FMC Biopolymer, hypromellose, in particular the product marketed under the name Methocel E4M premium by the company Dow Chemical, or hydroxyethylcellulose, in particular the product sold under the name Natrosol HHX 250®the company Aqualon, family manuallyselected, such as Veegum K, manufactured by the company Vanderbilt, a family of related hydrophobic chains of the acrylic polymer as a copolymer PEG-150/decyl/SMDI, sold under the name Aculyn 44 (polycondensate comprising at least, as components, a polyethylene glycol with 150 or 180 mol mol of ethylene oxide, etilogy alcohol and methylene-bis(4-cyclohexylidene) (SMDI), in the amount of 35 wt. -%, in a mixture of polypropylenglycol (39%) and water (26%), the family of modified starches such as modified potato starch sold under the name Structure Solanace, or mixtures thereof, and the gel-forming components of the family of polyacrylamides, such as a mixture of a copolymer of acryloyldimethyltaurate sodium, isohexadecane and Polysorbate 80, manufactured under the name Sepineo P 600®(or Simulgel 600 PHA®) by the company Seppic, the mixture of polyacrylamide, (C13-C14)-isoparaffin and Laureth-7, as such, sold under the name Sepigel 305 by the company Seppic, the collection carragenan, in particular, is divided into four large families: k, λ, β, ω, such as Viscarin®and Gelcarin®manufactured by IMCD.

The gel-forming component, such as described above may be used in preferred concentrations from 0.001% to 15% and more preferably from 0.15% to 5%.

The preferred gel-forming component can be called a collection carbonero and, in particular, Carbopol Ultrez-20®, Carbopol ETD 2020®family of polyacrylamides and, in particular, a mixture of a copolymer of acryloyldimethyltaurate sodium, isohexadecane, Polysorbate 80, manufactured under the name Sepineo P600®(or Simulgel 600PHA®), a family of polysaccharides, in particular xanthan resin, marketed under the name Xantural 180 ®family cellulose and their derivatives and, in particular, hydroxyethyl cellulose, sold under the name Natrosol 250HHX®and hypromellose, marketed under the name Methocel E4M Premium®, a family of related hydrophobic chains of acrylic polymers and, in particular, the copolymer PEG-150/decyl/SMDI, sold under the name Aculyn 44®.

The preferred gel-forming component can be called carbomer, polyacrylamides, associated hydrophobic chains, acrylic polymers, cellulose and its derivatives, such as, for example, hypromellose or hydroxyethyl cellulose, polysaccharides, in particular xanthan resin, and, in particular, those produced, in particular, under the names Sepineo P 600®(or Simulgel 600 PHA®), a copolymer of PEG-150/decyl/SMDI, Methocel E4M premium®, Natrosol HHX 250®, Xantural 180®, Carbopol Ultrez 20®.

The preferred suspending agent can be called microcrystalline cellulose and sodium carboxymethyl cellulose, sold under the name Avicel CL-611 firm FMC Biopolymer.

Among the chelating agents can be called, as not limiting the scope of protection of the invention examples, ethylenediaminetetraacetic acid (EDTU), diethylenetriaminepentaacetic acid (DTPA), ethylendiaminedi(O-hydroxyphenyl)acetic acid (EDDHA), 2-hydroxic indiaministry acid (HEDTA), ethylendiaminedi(O-hydroxy-p-were)acetic acid (EDDHMA) and ethylendiaminedi(5-carboxy-2-hydroxyphenyl)acetic acid (EDDCHA).

The preferred chelating agent can be called ethylenediaminetetraacetic acid (EDTU), produced, in particular, called Titriplex III®.

From moisturizing components and/or softening additives, whose role consists in hydrating the skin and facilitate application of the composition, use is optional, and this list is not exhaustive, compounds such as glycerol and sorbitol, sugar (as an example, glucose, lactose), polyethylene glycol (PEG) as an example, Lutrol T400), urea, amino acids (as an example, serine, citrulline, arginine, asparagine, alanine).

As the preferred moisturizing component and/or softening additives can be called glycerin.

From wetting, whose role is to reduce surface tension and create a more substantial spreading of the liquid, it is preferable to use, this list is not exhaustive, the wetting agent, which may preferably have a hydrophilic-lipophilic balance (products HLB) of from 10 to 14, the connection of the family of poloxamers and/or glycols and, more specifically, Synperonic PE/L44 and/or Synperonic PE/L62, and/or compounds such as propylenic is l, dipropyleneglycol, propilenglikolstearat, neuroglial, etokxidiglicol. Preferably the wetting are in liquid form, so that can easily be incorporated into the composition without having to heat it.

Particularly preferred wetting agent is propylene glycol and Synperonic PE/L44, produced by the company Uniqema.

The composition according to the invention may include one or more emulsifiers.

Emulsifiers are amphiphilic compounds that have a hydrophobic part having affinity to oil, and hydrophilic part having affinity to water, creating, thus, the link between the two phases. Ionic or non-ionic emulsifiers, therefore, stabilize the emulsion oil-in-water adsorbed on the phase boundary and forming a lamellar layers of liquid crystals.

Emulsifying ability of nonionic emulsifiers is closely related to the polarity of the molecule. This polarity is determined by the hydrophilic-lipophilic balance (products HLB).

Increased products HLB indicates that the hydrophilic part is predominant, and, on the contrary, minor products HLB indicates that the lipophilic part is predominant. For example, products HLB value above about 10 correspond to the hydrophilic surface-active substances.

The emulsifiers can be classified depending on their structure what s under the "generic" term "ion" (anionic, cationic, amphoteric) or "non-ionic". Nonionic emulsifiers are emulsifiers that do not dissociate into ions in water and, therefore, insensitive to pH changes.

As not limiting the scope of protection of the invention of example non-ionic emulsifiers with a high products HLB can be called complex sorbitane esters, such as POE(20)-servicemanual, sold under the name Tween 80®(Products HLB = 15); POE(20)-servicemonitor, sold under the name Tween 60®(Products HLB = 14,9); ethers of fatty alcohols, such as POE(21)stearyl ether (products HLB = 15,5), sold under the name Brij 721®the company Uniquema, or ceteareth 20, marketed under the name Eumulgin B2®(Products HLB = 15,5) by the company Cognis; esters of polyoxyethyleneglycol, such as literallayout and PEG-100 stearate, marketed under the name Arlacel 165 FL®(Products HLB = 11) by the company Uniquema; PEG-6 stearate and PEG 32 stearate, sold under the name TEFOSE 1500®(Products HLB = 10) by the company Gateffossé; esters of sugars with a high products HLB, such as PEG-20-methylglucose-sesquistearate, manufactured under the name glucamate SSE20 (products HLB = 15) by the company Amerchol, sucrose laurate, marketed under the name Surfhope C-1216®(Products HLB = 16), and sucrose stearate, marketed under the name Surfhope C-1811®(Products HLB = 11) and Surhope SE Pharma D-1816®palmitostearate sucrose, marketed under the name Surhope SE PharmaD-1616 ®firm Gatteffossé; polyglyceryl esters. Preferably, these non-ionic emulsifiers with a high products HLB have products HLB constituting from 10 to 18.

As not limiting the scope of protection of the invention, non-ionic emulsifiers with low products HLB (lipophilic) should be called complex sorbitane esters, such as servicemonitor (products HLB = 4,7), sold under the name Span 60 company Uniquema, glycerol esters, such as glycerylmonostearate, marketed under the name Cutina GMSVPH (products HLB = 3,8) by the company Cognis, esters of polyethylene glycol such as PEG-6-isostearate, marketed under the name Plepal isostearique®(Products HLB = 8) by the company Gatteffossé, esters of low sugar products HLB, such as methylglucoside, sold under the name Glucate SS®(Products HLB = 6) by the company Amerchol, and dilaurate sucrose, produced under the name of Surfhope C-1205®(Products HLB = 5), and tristearate sucrose, produced under the name of Surfhope C-1803®(Products HLB = 3) firm Gatteffossé.

As other non-ionic emulsifiers can also be called a self emulsifiable waxes that make it easy to obtain a stable emulsion by simple dispersion when heated. As examples, Cetearyl alcohol (and) Polysorbate 60, manufactured under the name Polawax NF firm Croda, Polawax GP 200, manufactured by Croda.

Preferably as amalyra the overall systems use one or more pairs of "non-ionic emulsifier with a high products HLB"/"non-ionic emulsifier with minor products HLB". In particular, we can talk about non-ionic emulsifying system comprising at least a non-ionic emulsifier having products HLB above about 10, and at least a non-ionic emulsifier having products HLB below about 10.

The ratio of each of the two emulsifiers, falling a couple of, most often determined by calculating the appropriate products HLB used fat phase.

As the preferred emulsifiers include:

hydrophilic emulsifiers of the type glycerylmonostearate and PEG-100-stearate, marketed under the name Arlacel 165FL®the company Uniquema; PEG-6 stearate and PEG-32 stearate, sold under the name TEFOSE 1500®firm Gatteffossé; PEG-20-methylglucose-sesquistearate, sold under the name Glucamate SSE 20®the company Amerchol; laurate sucrose, produced under the name of Surfhope SE Pharma D-1216®; sucrose stearate, marketed under the name Surfhope SE Pharma D-1816®; palmitostearate sucrose, produced under the name of Surfhope SE Pharma D-1616®; simple polyoxyethylene(21)-stearyl ether, sold under the name Brij 721®the company Uniquema, and ceteareth-20, marketed under the name Emulgin B2PH®the company Cognis; sorbitolovy esters, sold under the name Tween 80®and Tween 60®;

- lipophilic emulsifiers type methylglutaronitrile, such as Glucate SS®the issue is extent company Amerchol, dilaurate sucrose, such as Surfhope C-1205, and tristearate sucrose, such as Surfhope C-1205.

The composition according to the invention may also contain a fatty phase. This fatty phase may include, for example, 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, olive oil.

As butter or substitute vegetable origin can be called lanolin, squalene, fish oil, as derived, perhydrosqualene, marketed under the name Sophiderm®the company Sophim.

As synthetic oils can be called ester, such as clarissenhof, such as the product sold under the name Cetiol SN PH®the company Cognis France, diisopropylamide, such as the product marketed under the name Crodamol DA®the company Croda, isopropyl, such as the product marketed under the name Crodamol IPP®the company Croda, capillariasis triglyceride, such as Miglyol 812®manufactured by Univar.

As the silicone oil, the mod is but to call Dimethicone, as the product marketed under the name Q7-9120 Silicone Fluid®with a viscosity of 20 cSt to 12500 cSt by the company Dow Corning, collagenation, such as the product marketed under the name ST-Cyclomethicone 5NF®also the company Dow Corning.

As of hydrogenated polyisobutene can be called Parleam®manufactured by Rossow.

As heretofore alcohol include octyldodecanol, sold under the name Eutanol G by the company Cognis.

In the case of compositions according to the invention preferred paraffin and silicone oils and, more specifically, Marcol 152®and ST-Cyclomethicone 5NF®.

You can also include solid fats, such as natural or synthetic waxes, fatty acids such as stearic acid, fatty alcohols such as Speziol C18 Pharma, manufactured by Cognis, and texturemode agents tribewanted type, such as Compritol 888, manufactured by Gattefosse, or hydrogenated castor oils, such as Cutina HR, manufactured by Cognis. In this case, the technician adjusts the temperature of the heating means depending on the presence or not of these solids.

Compositions according to the invention may include, in addition, optionally, any additive usually used in cosmetics or pharmaceuticals, such as neutralizing components of conventional type, mineral or organic bases or acids (the example triethanolamine, 10%sodium hydroxide solution, the buffer on the basis of citric acid and sodium citrate, buffer-based succinic acid and sodium succinate), solar filters, antioxidants (type butylhydroxyanisole), fillers, electrolytes, preservatives, dyes, fragrances, essential oils, cosmetic biologically active components, hidratante, vitamins, essential fatty acids, sphingolipids, substances, tanning, such as dihydroxyacetone (DHA), soothing and protective ingredients to the skin, such as allantoin, proprietarty, or mixtures thereof and, optionally, the stabilizer of benzoyl peroxide (as an example, docusinate sodium, sodium-(C14-C16-reincorporate, lactic acid, citric acid), at a concentration of, preferably, from 0% to 2%, relative to the total weight of the composition.

Of course, the specialist must choose this or these possible additional compounds and/or their amounts so that not deteriorated or is not significantly deteriorated predominant properties of the composition according to the invention.

These additives may be present in the composition in an amount of from 0 wt%. up to 20% of the mass. in relation to the total weight of the composition.

As an example, preservatives can be called benzylaniline, bronopol, chlorhexidine, chlorocresol and its derivatives, etilovyj, Phenoxyethanol, potassium sorbate, diazolidinylurea, benzyl alcohol, parabens, or a mixture thereof.

As the preferred preservative can be called parabens, Phenoxyethanol or benzylaniline used individually or as a mixture.

According to a preferred variant, the composition is in gel form and includes:

from 0.1% to 0.3% derived naphthoic acid;

from 1% to 10% of benzoyl peroxide;

- from 30% to 95% water;

from 0.5% to 10% of at least one film-forming component;

- from 0,10% to 3% of one or more gel-forming component and/or suspendida agents and/or pH-independent gel-forming components;

- from 0% to 1.5% of one or more chelating components;

from 0.1% to 10% of one or more wetting;

- from 0% to 20% of one or more emollients and/or softening additives;

- from 0% to 20% of one or more additives.

In a special embodiment of the invention the composition is in the form of emulsions of oil-in-water (H/E) type of lotion, cream, cream without emulsifier and includes:

from 0.1% to 0.3% derived naphthoic acid;

from 1% to 10%, preferably from 2% to 5% benzoyl-peroxide;

- from 30% to 95% water;

from 0.5% to 10% of at least one film-forming component;

from 0.1% to 3% of one or more of heliobar the respective components and/or suspendida agents and/or pH-independent gel-forming components;

- from 0% to 1.5% of one or more chelating components;

from 0.1% to 10% of one or more wetting;

- from 0% to 20% of one or more emollients and/or softening additives;

- from 0% to 10% emulsifiers;

from 0.1% to 30% of fat phase;

- from 0% to 20% of one or more additives.

The object of the present invention is also a composition, such as described above, as a medicinal product. The composition can indeed be used as a medicine.

The object of the invention is also a method of obtaining a composition such as described above. This method is characterized by the fact that it includes a step of mixing a physiologically acceptable excipient, including at least one derived naphthoic acid and benzoyl peroxide, with at least one film-forming component with the purpose of obtaining a composition in which the specified derived naphthoic acid and benzoyl peroxide are in a dispersed form.

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

The introduction of the film-forming component is dependent on the polymer. So, as an example, Dermacryl 79 may be introduced into the fatty phase of the emulsion and/or water f the memory stage after neutralization. As an example, sodium hyaluronate, kollidon VA64, kollidon 30, kollidon 90F, moviola 40-88, celquat SC240C injected into the aqueous phase.

In particular, the present invention relates to a method for producing a composition, comprising the following stages:

a) preparation of the active phase 1, including one of the two biologically active components;

b) preparation of the active phase 2, including another biologically active component;

c) preparation of an aqueous phase;

d) (optional) preparation of film-forming phase;

e) a mixture of 2 active phase obtained in a) and b);

f) (optional) preparation of the fat phase;

g) (optional) emulsification phase mixture obtained in (f) and (c);

h) mixing phase obtained in (g) or C), with a single active phase obtained in e);

i) (optional) adding a polyacrylamide;

j) (optional) neutralization of the composition obtained in (h);

k) (optional) add a film-forming phase;

l) (optional) control of water.

The main way to obtain compositions according to the invention includes, as an example the following stages:

Stage a: preparation of the active phase 1:

A mixture of purified water and the beginning of the current 1 (adapalen) with at least one wetting agent until complete dispersion derived naphthoic acid, that is to get active phase 1.

Stage b: preparation of the active phase 2:

A mixture of purified water and the beginning of the current 2 (benzoyl peroxide) with at least one wetting agent until complete dispersion of the specified benzoyl peroxide, to obtain the active phase 2.

Stage C: preparation of aqueous phase:

In the glass are introduced with stirring, if necessary, when heated, purified water and gel or gel-forming components and/or pH-independent gel-forming components (except polyacrylamide) and/or suspendresume agents and, optionally, a chelating or chelating components, preservative or preservatives, hydrophilic hydrophilic emulsifier or emulsifiers, stabilizer or stabilizers, moisturizing component or moisturizing components and/or softening additives, film-forming or film-forming components.

Stage d: optionally, the mixture of at least plenkoobrazuyushchie component with water to obtain a film-forming phase.

Stage e: the mixture of active phases:

Two of the active phase obtained respectively in a) and b), mix, stirring is continued until complete homogenization.

Stage f: (optional, to obtain emulsion): the preparation of the fatty phase:

The mixture of oily compounds, solid fats and, optionally, lipophilic who emulsifiers, preservatives. The mixture is heated after homogenization finally introduce volatile silicone, if it is present in the composition.

Stage g (optional): emulsification:

When heated, the fat phase is introduced into the aqueous phase with the purpose of emulsification. Heating continued for a few minutes, then the product is cooled.

Stage h: add a single active phase:

The introduction of the single active phase obtained in (e), the aqueous phase obtained in C)in the case of gels or phase obtained in (g), in the case of emulsions.

Stage i (optional): adding polyacrylamide:

When mixing the injected polyacrylamide phase obtained in h). Stirring is continued until complete homogeneity.

Stage j: neutralization:

Agent to neutralize the gel-forming component is injected, if necessary, into the phase obtained in stage h) or i).

Stage k (optional): adding film-forming phase:

Adding film-forming phase, prepared in stage d), if the film-forming or film-forming components are not introduced into the aqueous phase.

Phase-l (optional): regulation of water:

If necessary, carry out the regulation of water.

An alternative method of obtaining the composition according to the invention includes, as an example the following stages:

Effective the beginning of the mix in the first stage of the method described above; thus, stages a) and b) replace stage a'):

a') preparing a single active phase, including two biologically active component.

The process then continues as described, starting from stage C) with the cancellation of stage e).

More specifically, the main way to obtain compositions according to the invention comprises the following stages:

Stage a: preparation of the active phase 1:

In a glass introduced, with stirring, purified water, active principle (adapalen), wetting (type Synperonic PE/L62, Synperonic PE/L44, propylene glycol). Stand under stirring until complete dispersion.

Stage b: preparation of the active phase 2:

In a glass introduced, with stirring, purified water, active principle (benzoyl peroxide), wetting (type Synperonic PE/L62, Synperonic PE/L44, propylene glycol). Stand under stirring until complete dispersion.

Stage C: preparation of aqueous phase:

In the glass are introduced with stirring, if necessary, when heated, purified water and gel or gel-forming components (type Carbopol Ultrez 20, ETD2020 NF, Xantural 180, Natrosol 250 HHX) and/or pH-independent gel-forming components (except Simulgel 600PHA) and/or suspendresume agents (type Avicel CL-611), optional, chelating or gelatin the matter components (like EDTA), the preservative or preservatives (methylparaben), the stabilizer or stabilizers (type docusinate sodium), a wetting agent or wetting and/or humectants (such as glycerin), film-forming or film-forming components (type of hyaluronate sodium).

Stage d: optionally, the mixture of at least plenkoobrazuyushchie component (type kollidon) with water to obtain a film-forming phase.

Stage e: the mixture of active phases:

Two of the active phase obtained respectively in a) and b), mix, stirring is continued until complete homogenization.

Stage f (optional): emulsion preparation:

The mixture of oils and solid fats (like Olépal isostéarique, Cetiol SN PH, Crodamol DA, Speziol C18, Cosbiol) and, optionally, emulsifiers (type Glucate SS and Glucamate SSE 20, BriJ 721, Téfose 1500), preservatives (Phenoxyethanol and propyl paraben). The mixture is heated after homogenization finally introduce volatile silicone (type cyclomethicone 5NF)if it is present in the composition.

Stage g (optional): emulsification:

When heated, the fat phase is introduced into the aqueous phase with the purpose of emulsification. Heating continued for a few minutes, then stop with the purpose of the cooling composition.

Stage h: add a single active phase:

The introduction of the single active phase obtained in (e)water f is at, obtained in C)in the case of gels and phase obtained in (g), in the case of emulsions.

Stage i (optional): add Simulgel 600PHA:

Under stirring, enter Simulgel 600PHA phase obtained in h). Stirring is continued until complete homogeneity.

Stage j: neutralization:

Agent to neutralize the gel-forming component (such as triethanolamine or 10%sodium hydroxide solution) is injected, if necessary, into the phase obtained in stage h) or i).

Stage k (optional): adding film-forming phase:

Adding film-forming phase, prepared in stage d), if the film-forming or film-forming agents are not introduced into the aqueous phase.

Phase-l (optional): regulation of water:

If necessary, carry out the regulation of water.

More specifically, the alternative method of obtaining the composition according to the invention comprises the following stages:

Effective the beginning of the mix in the first stage of the method described above; thus, stages a) and b) replace stage a'):

a') preparing a single active phase, including two biologically active component:

Mix derived naphthoic acid, benzoyl peroxide with at least one wetting agent in the water until complete dispersion of the specified benzoyl peroxide and specified proizvodi the th naphthoic acid with the aim of obtaining a single active phase in accordance with the same working conditions.

The process then continues as described, starting from the stage)and stage e) repeal.

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

In particular, the invention relates to the use of a composition such as described above, to obtain a pharmaceutical composition intended for the treatment and/or prevention of dermatological diseases associated with disorders of keratinization relating to differentiation and cell proliferation, in particular for the treatment of ordinary, ramadanovic, papulopustules, paulocoelho, nodulocystic acne, ball acne, occipital keloid folliculitis, recurrent miliary acne, necrotic acne, baby acne, occupational acne, senile acne, solar acne and acne medication. Specifically, an object of this invention is the composition according to the invention for the purpose of its use in the treatment and/or prevention of dermatological diseases associated with disorders of keratinization relating to differentiation and cell proliferation, in particular for the treatment of ordinary, ramadanovic, papulopustules, paulocoelho, nodulocystic acne, ball acne, occipital keloid folliculitis, recurrent miliary acne, necrotizes is their acne, baby acne, occupational acne, erythematous acne, senile acne, solar acne and acne medication.

More specifically, the invention relates to the use of a composition such as described above, to obtain a pharmaceutical composition intended for the prevention and/or treatment of common acne.

Preferably, the composition according to the invention is administered by topical. Under topical understand by application on the skin appendages of the skin or mucous membranes.

In addition, the invention also relates to the use in the cosmetic compositions according to the invention for the treatment of skin with tendency to acne, to fight against the greasy appearance of the skin or hair, for protection against the harmful effects of the sun or for the treatment of physiologically oily skin or to prevent and/or fight against photoinduced or chronological aging.

The present invention will now be illustrated by the following examples and data on physical and chemical stability, is presented below:

Physical stability of the compositions was controlled by macroscopic and microscopic observation of the composition stored at room temperature for time 0 (t0), T+ 1 month T+2 months T+3 months.

At room temperature macroscop the ical observation allows to guarantee the physical integrity of the products.

Microscopic observation allows us to estimate the variance of two biologically active components. If adapalene osushestvlyae observation in fluorescent light, whereas in the case of benzoyl peroxide was observed in polarized light.

The characteristics of the final product is complemented by the determination of the threshold yield stress and viscosity.

To determine the threshold yield stress used rheometer NAAKE type VT550 with the rotor for measuring SVDIN.

Rogramme were recorded at 25°C and a fixed speed from 0 to-1100-1. Value of viscosity was determined at constant shear values 4-1, 20-1, 100-1(γ). Under the threshold stress (τ0expressed in Pascals) understand the power required (minimum voltage when the shift) to overcome the forces of adhesion-type van der Waals and provoking the current.

For measurement of viscosity using viscometer, type Brookfield RVDVII+ and LDVDII+.

Range of viscosity, as measured using these two types of viscometers Brookfield, are as follows:

Viscometer RVDVII+: 100 SP - 40 SMEs

Viscometer LVDVII+: 15 JV - 6 SMEs

In the case of emulsions have come to expect at the initial moment t0:

cream, if the viscosity is above 30000 SP;

lotion, if the viscosity is below 30000 SP (Lucinda Bushe, ACPS, October 22,2003, "Pharmaceutical nomenclature-Issue and challenges").

Chemical stability is confirmed by determining adapalene by HPLC and by iodometric determination of benzoyl peroxide.

The results are expressed in g/g adapalene and benzoyl peroxide and in% with respect to theoretical percentage composition.

EXAMPLES

Example 1

The composition of the gel type, comprising 5% of benzoyl peroxide, 0.1% of adapalene and 4% Kollidon VA64 (copovidone) as film-forming component

Composition was prepared according to the method described in the main and/or alternative method.

Simulgel 600PHA
ComponentsContent (%wt./mass.)
Benzoyl peroxide5,00
Adapalene0,10
Propylene glycol4,00
Synperonic PE/L440,20
EDTU0,10
Glycerin4,00
Kollidon VA644,00
The sodium docusinate0,05
4,00
Purified water to total amount100%

Data stability:

Physical stability:

Characteristics at time 0 (t0)
Macroscopic viewThe white gel
Microscopic viewThe dispersion of active ingredients without aggregates >100 mm
pH4,47
Data on viscosityrheology by Haake
(4C-1/20s-1/100s-1)
143/208/356
viscometer Brookfield RVDVII+
(S29; 5.min)
95400 SP

T+1 monthT+2 monthsT+3 months
Macroscopic viewTHEsimilar with t0similar with t0similar with t0
Microscopic viewTHEsimilar with t0similar with t0similar with t0
pHTHE4,144,07as 4.02
rheology by Haake
(4C-1/20s-1/100s-1)
130/178/321130/184/327115/174/339
viscometer Brookfield RVDVII+(S29; 5.min)89600 SP98000 SP101000 SP

Chemical stability

- Adapalene

Conditions of stabilityTimeT0T+1 monthT+2 monthsT+3 months
THEg/g0,1060,1030,1110,099
% theoretical content10610311199

- Benzoyl peroxide

Conditions of stabilityTimeT0T+1 monthT+2 monthsT+3 months
THEg/gof 5.40equal to 4.975,464,89
% theoretical content1089910998

Example 2

The composition of the gel type, containing 2.5% benzoyl peroxide, 0.1% of adapalene and 2% of sodium hyaluronate as a film-forming component

Composition was prepared according to the method described in the main and/or alternative method.

ComponentsTable of contents
(% wt./mass.)
Benzoyl peroxide2,50
Adapalene0,10
Propylene glycol4,00
Synperonic PE/L440,20
EDTU0,10
Glycerin4,00
Sodium hyaluronate2,00
Simulgel 600PHA2,00
Purified water to total amount100%

Data stability:

Physical stability:

Characteristics at time 0 (t0)
Macroscopic viewThe white gel
Microscopic viewThe dispersion of active ingredients without aggregates > 100 mm
pH 5,15
Data on viscosityrheology by Haake
(4C-1/20s-1/100s-1)
241/433/564
viscometer Brookfield RVDVII+(S29; 5.min)135·103SP

T+1 monthT+2 monthsT+3 months
Macroscopic viewTHEsimilar with t0similar with t0similar with t0
Microscopic viewTHEsimilar with t0similar with t0similar with t0
pHTHE4,99with 4.644,87
rheology by Haake
(4C-1/20s-1/100s-1
221/412/625244/446/647266/456/677
viscometer Brookfield RVDVII+(S29; 5.min)135,103SP127,103SPof 129,000 SP

Chemical stability

- Adapalene

Conditions of stabilityTimeT0T+1 monthT+2 monthsT+3 months
THEg/g0,0900,0960,1000,101
% theoretical content9096100101

- Benzoyl peroxide

Conditions of stabilityTimeT0T+1 monthT+2 monthsT+3 months
THEg/g2,53of 2.512,602,52
% theoretical content101100104101

Example 3

The composition of the gel type, comprising 0.1% of adapalene and 2.5% benzoyl peroxide and 4% Kollidon 30 as film-forming component

Composition was prepared according to the method described in the main and/or alternative method.

ComponentsTable of contents
(% wt./mass.)
Benzoyl peroxide2,50
Adapalene0,10
Propylene glycol4,00
Synperonic PE/L440,20
EDTU0,10
Glycerin4,00
The sodium docusinate0,05
Kollidon VA64 4,00
Simulgel 600PHA4,00
Purified water to total amount100%

Data stability:

Physical stability:

Characteristics at time 0 (t0)
Macroscopic viewThe white gel
Microscopic viewThe dispersion of active ingredients without aggregates >100 mm
pH3,96
Data on viscosityrheology by Haake
(4C-1/20s-1/100s-1)
148/204/345
viscometer Brookfield RVDVII+(S29; 5.min)106·103SP

T+1 month
Macroscopic view THEsimilar with t0
Microscopic viewTHEsimilar with t0
pHTHE3,93
rheology by Haake
(4C-1/20s-1/100s-1)
160/226/368
viscometer Brookfield
RVDVII+(S29; 5.min)
115, 103SP

Chemical stability

- Adapalene

Conditions of stabilityTimeT0T+1 month
THEg/g0,0960,096
% theoretical content9696

- Benzoyl peroxide

Conditions of stabilityTimeT0T+1 month
THE g/g2,4572,440
% theoretical content9898

Example 4

The composition of the gel type, comprising 0.1% of adapalene and 2.5% of benzoyl peroxide and 2% polyvinyl alcohol as a film-forming component

Composition was prepared according to the method described in the main and/or alternative method.

ComponentsContent (%wt./mass.)
Benzoyl peroxide2,50
Adapalene0,10
Propylene glycol4,00
Synperonic PE/L440,20
EDTU0,10
Glycerin4,00
The sodium docusinate0,05
The moviola 40-882,00
Simulgel 600PHA4,00
Purified water up to about the quantity 100%

Data stability:

Physical stability:

Characteristics at time 0 (t0)
Macroscopic viewThe white gel
Microscopic viewThe dispersion of active ingredients without aggregates >100 mm
pH4,91
Data on viscosityrheology by Haake
(4C-1/20s-1/100s-1)
169/254/487
viscometer Brookfield RVDVII+(S29; 5.min)117,103SP

T+1 month
Macroscopic viewTHEsimilar with t0
Microscopic view THEsimilar with t0
pHTHE4,37
rheology by Haake
(4C-1/20s-1/100s-1)
186/313/611
viscometer Brookfield
RVDVII+(S29; 5.min)
114,103SP

Chemical stability

- Adapalene

Conditions of stabilityTimeT0T+1 month
THEg/g0,0980,097
% theoretical content9897

- Benzoyl peroxide

Conditions of stabilityTimeT0T+1 month
THEg/g2,5152,450
% eroticheskoe content 100,698

Example 5

The composition of the gel type, comprising 0.1% of adapalene and 2.5% benzoyl peroxide and 1% Celquat SC240C as film-forming component

Composition was prepared according to the method described in the main and/or alternative method.

ComponentsTable of contents
(% wt./mass.)
Benzoyl peroxide2,50
Adapalene0,10
Propylene glycol4,00
Synperonic PE/L440,20
EDTU0,10
Glycerin4,00
The sodium docusinate0,05
Celquat SC240C1,00
Natrosol 250HHX0,80
Purified water to total amount100%

Example 6

Composition type of a cream containing 0.1% of adapalene and 2.5% is benzoylperoxide and 0.5% of sodium hyaluronate as a film-forming component

Composition was prepared according to the method described in the main and/or alternative method.

ComponentsTable of contents
(% wt./mass.)
Benzoyl peroxide2,50
Adapalene0,10
Propylene glycol5,00
Synperonic PE/L440,20
EDTU0,10
Glycerin5,00
Carbopol Ultrez 200,70
Marcol 1527,00
Sodium hyaluronate0,50
BHA0,005
Purified water to total amount100%

Example 7

Composition type of a cream containing 0.1% of adapalene and 2.5% benzoyl peroxide and 6% Kollidon VA64 (copovidone) as film-forming component

Composition was prepared according to the method described in the/or alternative method.

ComponentsTable of contents
(% wt./mass.)
Benzoyl peroxide2,50
Adapalene0,10
Propylene glycol6,00
Synperonic PE/L440,20
The sodium docusinate0,05
EDTU0,10
Carbopol Ultrez 200,20
Glycerin3,00
Glucamate SSE3,50
Glucat SS3,50
Perhydrosqualene6,00
ST-Cyclomethicone 5NF13,00
Kollidon VA646,00
Purified water to total amount100%
Triethanolamine to pHData stability:

Physical stability:

Characteristics at time 0 (t0)
Macroscopic viewCream white
Microscopic viewThe dispersion of active ingredients without aggregates >100 mm
pH5,28
Data on viscosityrheology by Haake
(4C-1/20s-1/100s-1)
78/104/173
viscometer Brookfield RVDVII+(S31; 5.min)42560 SP

T+1 monthT+2 monthsT+3 months
Macroscopic viewTHEsimilar with t0identical to the K at t0 similar with t0
Microscopic viewTHEsimilar with t0similar with t0similar with t0
pHTHE4,954,89to 4.98
rheology by Haake
(4C-1/20s-1/100s-1)
64/94/15865/91/15558/84/140
viscometer Brookfield RVDVII+(S31; 5.min)41216 SP36544 SP32832 SP

Chemical stability

- Adapalene

Conditions of stabilityTimeT0T+1 monthT+2 monthsT+3 months
THEg/g0,0970,1260,107 0,096
% theoretical content9712610796

- Benzoyl peroxide

Conditions of stabilityTimeT0T+1 monthT+2 monthsT+3 months
THEg/g2,452,902,782,38
% theoretical content9811611295

Example 8

Composition type of cream, comprising 0.3% of adapalene and 5% benzoyl peroxide and 1% of sodium hyaluronate as a film-forming component

Composition was prepared according to the method described in the main and/or alternative method.

ComponentsTable of contents
(% wt./mass.)
Benzoyl peroxide5,00
Adapalene0,30
Dipropyleneglycol5,00
Synperonic PE/L440,20
Glycerin7,00
EDTU0,10
Eumulgin B2 PH3,00
Arlacel 165FL3,00
Speziol C18 Pharma2,00
Miglyol 812 N7,00
ST-Cyclomethicone 5NF6,00
Simulgel 600PHA2,00
Sodium hyaluronate1,00
Purified water to total amount100%

Data stability:

Physical stability:

Characteristics at time 0 (t0)
Macroscopic in the d Cream white
Microscopic viewThe dispersion of active ingredients without aggregates >100 mm
pHthe 5.25
Data on viscosityrheology by Haake
(4C-1/20s-1/100s-1)
162/265/364
viscometer Brookfield RVDVII+(S34; 5.min)89600 SP

T+1 monthT+2 monthsT+3 months
Macroscopic viewTHEsimilar with t0similar with t0similar with t0
Microscopic viewTHEsimilar with t0similar with t0 similar with t0
pHTHE4,854,754,79
rheology by Haake
(4C-1/20s-1/100s-1)
141/226/340146/239/348140/229/335
viscometer Brookfield RVDVII+(S34; 5.min)92240 SP90880 SP91136 SP

Chemical stability

- Adapalene

Conditions of stabilityTimeT0T+1 monthT+2 monthsT+3 months
THEg/g0,2890,2840,2900,295
% theoretical content96959797

- Benzoyl peroxide

Conditions of stabilityTimeT0T+1 monthT+2 monthsT+3 months
THEg/g4,994,874,894,88
% theoretical content10097,49898

Example 9

Composition type of a cream containing 0.1% of adapalene and 5% benzoyl peroxide and 4% Kollidon VA64 (copovidone) as film-forming component

Composition was prepared according to the method described in the main and/or alternative method.

ComponentsTable of contents
(% wt./mass.)
Benzoyl peroxide5,00
Adapalene0,10
Propylene glycol6,00
Synperonic PE/L440,20
EDTU0,10
Glycerin7,00
Natrosol 250HHX0,20
Eumulgin B2 PH3,00
Speziol C18 Pharma2,00
Miglyol 812 N7,00
Arlacel 165FL3,00
ST-Cyclomethicone 5NF6,00
Simulgel 600PHA2,00
Kollidon VA644,00
Purified water to total amount100%
Triethanolamine to pH5,5±0,5

Data stability:

Physical stability:

Characteristics at time 0 (t0)
Macroscopic view
Microscopic viewThe variance of the act the main components without aggregates > 100 microns
pH5,31
Data on viscosityrheology by Haake
(4C-1/20s-1/100s-1)
203/266/378
viscometer Brookfield RVDVII+(S29; 5.min)183·103SP

T+1 monthT+2 monthsT+3 months
Macroscopic viewTHEsimilar with t0similar with t0similar with t0
Microscopic viewTHEsimilar with t0similar with t0similar with t0
pHTHE4,774,59461
rheology by Haake
(4C-1/20s-1/100s-1)
227/274/402219/258/395218/274/413
viscometer Brookfield RVDVII+(S29; 5.min)149.103SP178.103SP175.103SP

Chemical stability

- Adapalene

Conditions of stabilityTimeT0T+1 monthT+2 monthsT+3 months
THEg/g0,0930,0920,0930,093
% theoretical content93929393

- Benzoyl peroxide

Conditions of stabilityTime T0T+1 monthT+2 monthsT+3 months
THEg/g4,894,674,784,72
% theoretical content98939694

Example 10

Composition type of liquid cream, containing 0.1% of adapalene and 2.5% benzoyl peroxide and 0.5% of sodium hyaluronate as a film-forming component

Composition was prepared according to the method described in the main and/or alternative method.

ComponentsTable of contents
(% wt./mass.)
Benzoyl peroxide2,50
Adapalene0,10
Propylene glycol5,00
Synperonic PE/L440,20
EDTU0,10
Glycerin 5,00
Carbopol Ultrez 200,70
Marcol 1527,00
Sodium hyaluronate0,50
Purified water to total amount100%
10%solution until the pH of the sodium hydroxide5,5±0,5

Data stability:

Physical stability:

Characteristics at time 0 (t0)
Macroscopic viewCream white
Microscopic viewThe dispersion of active ingredients without aggregates >100 mm
pH5,14
Data on viscosityrheology by Haake
(4C-1/20s-1/100s-1)
76/126/167
viscometer Brookfield RVDVII+(S31; 5.min) 39040 SP

T+1 monthT+2 monthsT+3 months
Macroscopic viewTHEsimilar with t0similar with t0similar with t0
Microscopic viewTHEsimilar with t0similar with t0similar with t0
pHTHEto 4.98equal to 4.975,16
rheology by Haake
(4C-1/20s-1/100s-1)
68/123/18774/126/18964/117/179
viscometer Brookfield RVDVII+(S31; 5.min)34816 SP33408 SP35328 SP

Chemical stability

- Adapalen/u>

Conditions of stabilityTimeT0T+1 monthT+2 monthsT+3 months
THEg/g0,0980,100,0990,099
% theoretical content981009999

- Benzoyl peroxide

Conditions of stabilityTimeT0T+1 monthT+2 monthsT+3 months
THEg/g2,622,532,61to 2.57
% theoretical content105101104103

Example 11

Composition type of a cream containing 0.1% of adapalene and 2.5% benzoyl peroxide and 4% Kollidon VA64 (copovidone) as film-forming component

Composition was prepared according to the method described in the main and/or alternative method.

ComponentsTable of contents
(% wt./mass.)
Benzoyl peroxide2,50
Adapalene0,10
Propylene glycol5,00
Synperonic PE/L440,20
Glycerin5,00
ST-Cyclomethicone 5NF7,00
Kollidon VA644,00
Simulgel 600PHA3,00
Purified water to total amount100%

Data stability:

Physical stability:

Characteristics at time 0 (t0)
Macroscopic viewCream white
Microscopic viewThe dispersion of active ingredients without aggregates > 100 mm
pHto 4.52
Data on viscosityrheology by Haake
(4C-1/20s-1/100s-1)
197/267/400
viscometer Brookfield RVDVII+(S29; 5.min)145·103SP

T+1 monthT+2 monthsT+3 months
Macroscopic viewTHEsimilar with t0similar with t0similar with t0
Microscopic viewTHEsimilar with t0 similar with t0similar with t0
pHTHE4,00a 3.873,81
rheology by Haake
(4C-1/20s-1/100s-1)
182/248/420180/251/403171/243/405
viscometer Brookfield RVDVII+(S29; 5.min)138.103SP131.103SP124.103SP

Chemical stability

- Adapalene

Conditions of stabilityTimeT0T+1 monthT+2 monthsT+3 months
THEg/g0,0980,0980,0960,099
% theoretical content9898 9699

- Benzoyl peroxide

Conditions of stabilityTimeT0T+1 monthT+2 monthsT+3 months
THEg/gto 2.572,46of 2.512,48
% theoretical content1039810099

Example 12

Composition type of a cream containing 0.1% of adapalene and 2.5% benzoyl peroxide and 4% Kollidon 90F as film-forming component

Composition was prepared according to the method described in the main and/or alternative method.

ComponentsTable of contents
(% wt./mass.)
Benzoyl peroxide2,50
Adapalene0,10
Propylene glycol 6,00
Synperonic PE/L440,20
The sodium docusinate0,05
EDTU0,10
Carbopol Ultrez0,20
Glycerin3,00
Glucamate SSE 203,50
Glucat SS3,50
Spiderm6,00
ST-Cyclomethicone 5NF13,00
Kollidon 90F4,00
Purified water to total amount100%
Triethanolamine to pH5,5 ± 0,5

Data stability:

Physical stability:

Characteristics at time 0 (t0)
Macroscopic viewCream white
<> Microscopic viewThe dispersion of active ingredients without aggregates > 100 mm
pH5,17
Data on viscosityrheology by Haake
(4C-1/20s-1/100s-1)
125/196/321
viscometer Brookfield RVDVII+(S28; 5.min)98300 SP

T+1 month
Macroscopic viewTHEsimilar with t0
Microscopic viewTHEsimilar with t0
pHTHE4,95
rheology by Haake (4-1/20s-1/100s-1)117/171/310
viscometer Brookfield RVDVII+(S29; 5.min)81800 SP

Production of the mini stability

- Adapalene

Conditions of stabilityTimeT0T+1 month
THEg/g0,0980,098
% theoretical content9898

- Benzoyl peroxide

Conditions of stabilityTimeT0T+1 month
THEg/g2,4842,436
% theoretical content9997

Example 13

Composition type of a cream containing 0.1% of adapalene and 2.5% of benzoyl peroxide and 2% of Dermatril 70 as a film-forming component

Composition was prepared according to the method described in the main and/or alternative method.

ComponentsWith the actual content of the
(% wt./mass.)
Benzoyl peroxide2,50
Adapalene0,10
Propylene glycol6,00
Synperonic PE/L440,20
EDTU0,10
Glycerin7,00
Natrosol HHX2500,20
Eumulgin B2 PH3,00
Speciol C18 pharma2,00
Miglyol 812 N7,00
Arlacel 165 FL3,00
ST-Cyclomethicone 5NF6,00
Simulgel 600PHA2,00
Dermatril 792,00
Purified water to total amount100%
Triethanolamine to pH5,5±0,5

Data stability:

Visionstatement:

Characteristics at time 0 (t0)
Macroscopic viewCream white
Microscopic viewThe dispersion of active ingredients without aggregates >100 mm
pH5,51
Data on viscosityrheology by Haake
(4C-1/20s-1/100s-1)
109/156/267
viscometer Brookfield RVDVII+(S28; 5.min)70000 SP

T+1 month
Macroscopic viewTHEsimilar with t0
Microscopic viewTHEsimilar with t0
pHTHE 5,55
rheology by Haake (4-1/20s-1/100s-1)84/132/232
viscometer Brookfield RVDVII+(S29; 5.min)114.103SP

Chemical stability

- Adapalene

Conditions of stabilityTimeT0T+1 month
THEg/g0,0980,096
% theoretical content9896

- Benzoyl peroxide

Conditions of stabilityTimeT0T+1 month
THEg/g2,4422,453
% theoretical content9898

Example 14

Composition type of cream on the expectation of 0.3% adapalene and 1.0% benzoyl peroxide and 3% Kollidon 90F as film-forming component

Composition was prepared according to the method described in the main and/or alternative method.

ComponentsTable of contents
(% wt./mass.)
Benzoyl peroxide1,00
Adapalene0,30
Avicel CL6111,50
Synperonic PE/L440,20
Methylparaben0,15
Brij 7213,00
Ariacel 165FL3,00
Propylparaben0,05
Spiderm5,00
Cetiol SN PH5,00
Dipropyleneglycol3,00
Simulgel 600PHA1,00
Kollidon 90F3,00
Purified water to total amount100%

Data is compared the stability:

Physical stability:

Characteristics at time 0 (t0)
Macroscopic viewThe lotion is white in color
Microscopic viewThe dispersion of active ingredients without aggregates >100 mm
pH6,10
Data on viscosityrheology by Haake
(4C-1/20s-1/100s-1)
34/70/158
viscometer Brookfield RVDVII+(S64; 5.min)33793 SP

T+1 month
Macroscopic viewTHEsimilar with t0
Microscopic viewTHEsimilar with t0
pH THE5,12
rheology by Haake (4-1/20s-1/100s-1)33/57/129
viscometer Brookfield RVDVII+(S29; 5.min)32193 SP

Chemical stability

- Adapalene

Conditions of stabilityTimeT0T+1 month
THEg/g0,2930,290
% theoretical content9897

- Benzoyl peroxide

Conditions of stabilityTimeT0T+1 month
THEg/g0,9760,989
% theoretical content9899

Example 15

The song is lotion, including 0,3% adapalene and 1% of benzoyl peroxide and 0.5% of sodium hyaluronate as a film-forming component

Composition was prepared according to the method described in the main and/or alternative method.

ComponentsTable of contents
(% wt./mass.)
Benzoyl peroxide1,00
Adapalene0,30
Avicel CL6111,50
Synperonic PE/L440,20
Methylparaben0,15
Brij 7213,00
Arlacel 165FL3,00
Propylparaben0,05
Spiderm5,00
Cetiol SN PH5,00
Dipropyleneglycol3,00
Simulgel 600PHA1,50
Sodium hyaluronate0,50
Purified water to total amount100%

Data stability:

Physical stability:

Characteristics at time 0 (t0)
Macroscopic viewThe lotion is white in color
Microscopic viewThe dispersion of active ingredients without aggregates >100 mm
pH6,03
Data on viscosityrheology by Haake
(4C-1/20s-1/100s-1)
53/92/139
viscometer Brookfield RVDVII+(S31; 5.min)30528 SP

T+1 monthT+2 monthsT+3 months
Macroscopic viewTA/td> similar with t0similar with t0similar with t0
Microscopic viewTHEsimilar with t0similar with t0similar with t0
pHTHE5,175,004,82
rheology by Haake
(4C-1/20s-1/100s-1)
47/75/12044/74/12138/61/109
viscometer Brookfield RVDVII+(S31; 5.min)25664 SP22336 SP21312 SP

Chemical stability

- Adapalene

Conditions of stabilityTimeT0T+1 monthT+2 monthsT+3 months
THEg/g 0,2860,2850,2850,306
% theoretical content959595102

- Benzoyl peroxide

Conditions of stabilityTimeT0T+1 monthT+2 monthsT+3 months
THEg/g0,980,960,950,96
% theoretical content98969596

1. Composition for cosmetic or dermatological use by topical application comprising, in a physiologically acceptable medium, at least adapalene and benzoyl peroxide and film-forming component, wherein the film-forming component is a sodium hyaluronate.

2. The composition according to claim 1, characterized in that the adaptation of the flax and/or benzoyl peroxide is dispersed in the above composition form.

3. The composition according to claim 1, characterized in that the concentration adapalene is from 0.001 wt%. up to 10 wt. -%, preferably from 0.01% by mass. up to 5% of the mass. and more preferably from 0.05% of the mass. up to 2% of the mass. in relation to the total weight of the composition.

4. The composition according to claim 3, characterized in that the concentration adapalene is about 0.1% of the mass. in relation to the total weight of the composition.

5. The composition according to claim 2, characterized in that the concentration adapalene is about 0.3% of the mass. in relation to the total weight of the composition.

6. The composition according to claim 1, characterized in that the concentration of film-forming component is from 0.5% of the mass. up to 20% of the mass. in relation to the total weight of the composition, preferably from 0.5% to 10%, preferably from 0.5% to 6%.

7. The composition according to claim 6, characterized in that the concentration of film-forming component is 0.5 wt. -%, 1 wt. -%, 2 wt. -%, 4% of the mass. or 6% of the mass. in relation to the total weight of the composition.

8. Composition according to any one of claims 1 to 7, characterized in that it is in the form of aqueous, aqueous-alcoholic or oily suspensions; aqueous, anhydrous or lipophilic gel, emulsion, liquid, semi-liquid or solid consistency, obtained by dispersion of a fatty phase in an aqueous phase, or Vice versa; or the suspension is soft, semi-solid or solid consistency; or even microemulsions, of microcapsules, of microparticles or of vesicles is situations suspensions ionic and/or nonionic type.

9. The composition according to claim 8, characterized in that it is in gel form.

10. The composition according to claim 8, characterized in that it is in the form of an emulsion.

11. The composition according to claim 10, characterized in that the emulsion is in the form selected from a lotion, cream or cream without emulsifier.

12. The composition according to claim 9, characterized in that it comprises, in water:
from 0.1% to 0.3% adapalene;
from 1% to 10% of benzoyl peroxide;
- from 30% to 95% water;
from 0.5% to 10% of the film-forming component;
- from 0,10% to 3% of one or more gel-forming component and/or suspendida agents and/or pH-independent gel-forming components;
- from 0% to 1.5% of one or more chelating components;
from 0.1% to 10% of one or more wetting; and
- from 0.01% to 3% preservatives.

13. The composition according to claim 9, characterized in that it comprises, in water:
from 0.1% to 0.3% adapalene;
- from 2% to 5% of benzoyl peroxide;
- from 30% to 95% water;
from 1% to 10% of the film-forming component;
from 0.1% to 3% of one or more gel-forming component and/or suspendida agents and/or pH-independent gel-forming components;
- from 0.01% to 1.5% chelating components;
from 0.1% to 10% of one or more wetting; and
from 0.1% to 20% softening additives;
- from 0.01% to 3% preservatives.

14. The composition according to claim 10, characterized in that it comprises, in water:
from 0.1% to 0.3% adapalene;
from 1% to 10%, preferably from 2% to 5% of benzoyl peroxide;
- from 30% to 95% water;
from 0.5% to 10% of the film-forming component;
from 0.1% to 3% of one or more gel-forming component and/or suspendida agents and/or pH-independent gel-forming components;
- from 0% to 1.5% of one or more chelating components;
from 0.1% to 10% of one or more wetting;
from 0.1% to 10% of one or more wetting;
- from 0% to 20% of one or more emollients and/or softening additives;
- from 0% to 10% emulsifiers;
from 0.1% to 30% of fat phase;
- from 0% to 20% of one or more additives.

15. Composition according to any one of claims 1 to 14 as a medicine.

16. A method of obtaining a composition according to any one of claims 1 to 15, characterized in that it comprises the following stages:
a) preparation of the active phase 1, including one of the two biologically active components;
b) preparation of the active phase 2, including another biologically active component;
c) preparation of an aqueous phase;
d) preparation of film-forming phase;
e) a mixture of 2 active phase obtained in a) and b);
f) (optional) preparation of the fat phase;
g) (optional) emulsification phase mixture obtained in (f) and (C);
h) mixing phase obtained in (g) or c), with a single active phase obtained in e);
i) (optional) - Rev. OE) the addition of polyacrylamide;
j) (optional) neutralization of the composition obtained in (h);
k) adding film-forming phase;
l) (optional) control of water.

17. The way of getting item 16, characterized in that the current beginning of the mix in the first stage of the method according to item 16; thus, stages a) and b) replace stage a'):
a') preparing a single active phase, including two biologically active component;
the process then continues as described, starting from stage C) of the method according to item 16.

18. The way of getting item 16, characterized in that it comprises the following stages:
Stage a: preparation of the active phase 1:
A mixture of purified water and the beginning of the current 1 (adapalene) with at least one wetting agent until complete dispersion derived naphthoic acid, to obtain the active phase 1.
Stage b: preparation of the active phase 2:
A mixture of purified water and the beginning of the current 2 (benzoyl peroxide) with at least one wetting agent until complete dispersion of the above-mentioned benzoyl peroxide, to obtain the active phase 2.
Stage C: preparation of aqueous phase:
In the glass are introduced with stirring, if necessary, when heated, purified water and gel or gel-forming components and/or pH-independent gel-forming components (except polyacrylamide) and/or WM is androusa agents and optionally, chelating or chelating components, preservative or preservatives, hydrophilic hydrophilic emulsifier or emulsifiers, stabilizer or stabilizers, moisturizing component or moisturizing components and/or softening additives, film-forming component.
Stage d: optional, mixing plenkoobrazuyushchie component with water to obtain a film-forming phase.
Stage e: the mixture of active phases:
Two of the active phase obtained respectively in a) and b), mix, stirring is continued until complete homogenization.
Stage f: (optional, to obtain emulsion): the preparation of the fatty phase:
The mixture of oily compounds, solid fats and, optionally, lipophilic emulsifiers, preservatives. The mixture is heated after homogenization finally introduce volatile silicone, if it is present in the composition.
Stage g (optional): emulsification:
When heated, the fat phase is introduced into the aqueous phase with the purpose of emulsification. Heating continued for a few minutes, then the product is cooled.
Stage h: add a single active phase:
The introduction of the single active phase obtained in (e), the aqueous phase obtained in c)in the case of gels or phase obtained in (g), in the case of emulsions.
Stage i (optional): adding polyacrylamide:
When paramasivan is injected polyacrylamide in phase, obtained in h). Stirring is continued until complete homogeneity.
Stage j: neutralization:
Agent to neutralize the gel-forming component is injected, if necessary, into the phase obtained in stage h) or i).
Stage k: adding a film-forming phase:
Adding film-forming phase, prepared in stage d), if the film-forming agent is not introduced into the aqueous phase.
Stage 1 (optional): regulation of water:
If necessary, carry out the regulation of water.

19. The way of getting p, wherein operating the beginning of the mix in the first stage of the method according to p; thus, stages a) and b) replace stage a'):
a') preparing a single active phase, including two biologically active component;
the process then continues as described, starting from stage c) of the method according to p.

20. The use of a composition according to any one of claims 1 to 15 for obtaining a pharmaceutical composition intended for the treatment and/or prevention of dermatological diseases associated with disorders of keratinization relating to differentiation and cell proliferation.

21. The application of claim 20, wherein the dermatological diseases associated with disorders of keratinization relating to differentiation and cell proliferation, choose among ordinary ramadanovic, PA is unapostolic, paulocoelho, nodulocystic acne, ball acne, occipital keloid folliculitis, recurrent miliary acne, necrotic acne, baby acne, occupational acne, erythematous acne, senile acne, solar acne and acne medication.

22. The use of a composition according to item 21 to obtain a pharmaceutical composition intended for the prevention and/or treatment of common acne.

23. Used in the cosmetic composition according to any one of claims 1 to 14 for the treatment of skin with tendency to acne, to fight against the greasy appearance of the skin or hair, for protection against the harmful effects of the sun or for the treatment of physiologically oily skin, or to prevent and/or fight against photoinduced or chronological aging.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to an herbal formulation of topical nanoemulsion for treating acne-related skin disorders. The above formulation contains an aqueous phase comprising a therapeutic agent, rose water and/or lemon juice, and an oil phase containing an essential oil, a non-ionic surfactant and an accessory surfactant. The aqueous and oil phases are related within the range of 1:1 to 1:2, while a particle size of the herbal formulation is less than 5 nm. The essential oil is presented by tea tree oil, basil oil, rosemary oil, lavender oil, jojoba oil, bergamot oil, clove oil and peppermint oil. The invention also refers to a method for preparing the herbal formulation which involves providing the aqueous and oil phases, mixing the above phases to produce a mixture to be emulsified with the non-ionic surfactant to prepare a macroemulsion. The prepared macroemulsion is mixed with ethanol to produce a nanoemulsion with a particle size less than 5 nm.

EFFECT: invention provides the herbal formulation with good penetration, prolonged effect causing no irritation.

8 cl, 4 dwg, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of the following formula , in which n equals integer number from 1 to 15, m equals 0, 1, 2 or 3, and R represents hydrocarbon chain of polyunsaturated fatty acid, selected from omega-3 and omega-6 polyunsaturated fatty acids, and to method of obtaining them.

EFFECT: development of pharmaceutical or cosmetic composition based on said compounds and to method of acne or seborrheic dermatitis treatment for cosmetic purposes.

16 cl, 4 dwg, 2 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to a compound of formula (I)

where Y represents a group of formula -(CR9R10)n-; X represents -C(=O)-; Z represents a group of formula -(CR13R14)q-; R1 is selected from a group, consisting of (a) C2-C12alkenyl, substituted with 4-chlorophenyl; or (b) C6-C10aryl, optionally substituted with one or two halogen atoms; R2 and R3 represent H; R4 is selected from a group, consisting of H, C1-C12alkyl, optionally substituted with hydroxyl, methoxy or benzyloxy, C3-C12cycloalkyl, C6aryl, optionally substituted with an amino group or pyperidine, C-bound C1-C18heteroaryl, selected from pyridine and imidazole, C(=O)R15, C(=O)NR16R17 and ONR16C(=NR17)NR18R19; each R5a and R5b represents H, each R6, R7 and R8 is independently selected from a group, consisting of H, C1-C12alkyl and C6-C18aryl, each R9 and R10 represents H; each R13 and R14 represents H; R15 represents H, each R16, R17, R18, R19 and R20 is independently selected from a group, consisting of H, C1-C12alkyl, C3-C12cycloalkyl, C6aryl and pyridyl, or any two of R16, R17, taken together with atoms, to which they are bound, form a cyclic group, containing 5 carbon atoms, or n equals to 1; q represents an integer number, selected from a group, consisting of 1, 2, 3, 4 and 5; r equals to 1; or its pharmaceutically acceptable salt.

EFFECT: invention relates to a pharmaceutical composition for treatment of MC5R-associated conditions, which contains a formula (I) compound and a pharmaceutically acceptable carrier, a diluent or a filling agent.

23 cl, 6 tbl, 53 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical industry, in particular to a composition, possessing immunomodulating and anti-inflammatory properties. The dermatological composition, possessing immunomodulating and anti-inflammatory properties, as an active ingredient, contains an extract of the aboveground part/parts of oat, collected before ear formation. The cosmetic composition, possessing immunomodulating and anti-inflammatory properties. Application of the extract of the aboveground part/parts of oat, collected before ear formation, possessing immunomodulating and anti-inflammatory properties, as a medication.

EFFECT: composition and extract possess expressed immunomodulating and anti-inflammatory properties.

15 cl, 1 tbl, 3 ex

FIELD: medicine.

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EFFECT: provided considerable reduction of retinoid-caused skin irritation and higher efficacy or retinoid.

11 cl, 3 ex, 7 tbl, 3 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, namely a method of treating acne. The method of treating acne by prescribing line seed oil 10 ml 2 times a day, sodium selenite 90 mcg 1 time a day, tocopherol acetate 100 mg 2 times a day for 1 month.

EFFECT: method of treating acne is effective and enables reducing the length of treatment.

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to cosmetology and dermatology, and represents a water-based formulation for local application for treating acne, containing water, a water-miscible organic solvent and benzoyl peroxide, wherein the organic solvent concentration is 1-4 times higher than the benzoyl peroxide concentration in the formulation; the water and organic solvent concentrations are related as at least 7:1, preferentially at least 10:1, more preferentially at least 20:1; the benzoyl peroxide concentration in the formulation makes less than 5.0 wt %, but at least 1.0 wt %.

EFFECT: invention provides the clinical effectiveness with the reduced active agent concentration, as well as reduced irritant action.

27 cl, 4 ex, 3 tbl

FIELD: medicine.

SUBSTANCE: invention refers to cosmetology and represents a cosmetic composition containing: hydrolised yeast proteins as an active substance, and at least one acceptable carrier, differing by the fact that the above hydrolised yeast proteins are prepared by exogenic enzymatic hydrolysis and/or acid hydrolysis and/or alkaline hydrolysis of the yeast membranes.

EFFECT: invention provides improved cosmetic activity, excellent time stability.

17 cl, 6 ex, 3 tbl, 2 dwg

FIELD: medicine.

SUBSTANCE: invention refers to medicine, specifically to dermatology, and may be used for treating the patients suffering acne. That is ensured by local applications of a therapeutically effective amount of a fixed-dose combination containing adapalene and benzoyl peroxide. That is combined with oral administration of a therapeutically effective amount of an antibiotic for a particular period of time.

EFFECT: method provides the effective treatment of these patients, manifested as a significant decrease of all types of acne involvements, prevents the further development of these involvements, including after the withdrawal of oral antibiotics and the development of resistance, due to the synergistic effect of the above local combination and oral antibiotic.

11 cl, 11 tbl, 4 dwg, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and cosmetics, more specifically to a topical pharmaceutical composition possessing comedolytic and antibiotic action, comprising an effective amount of the antibiotic clindamycin, salicylic acid and excipients. The pharmaceutical composition is presented in the form of a gel. The excipients are as follows: acrylate copolymer emulsion Salcare SC80, allantoin, antioxidant dihydroquercetin preservative Sharomix MCI, propylene glycol, cyclomethicone DC 345, tocopherol phosphate, UV filter Escalol 567, emulsifier DC 5329, trometamol and thermal water.

EFFECT: stabilised composition has strong comedolytic and antibiotic action, comprises the protective SPF factor which protects inflamed skin against the negative effects of UV radiation and has a shelf life of at least 3 years.

3 ex, 4 tbl

FIELD: medicine.

SUBSTANCE: invention relates to a haemostatic anti-burn and wound-healing composition in the form of a hydrogel, which contains an active gel-forming component, a plasticiser, active and auxiliary components, namely a water-soluble heteropolymer of chitosonium salt in an amount from 1.0 to 10.0 wt %, a dexpanthenol substance and/or a 2-allyloxyethanol substance in an amount from 1.0 to 10.0 wt %, immobilised medicinal substances of aminocaproic or tranexamic acid in an amount from 0.1 to 5.0 wt % and calcium chloride in an amount from 0.05 to 2.0 wt %, immobilised medicinal substances of lidocaine or anylocaine in an amount from 0.1 to 5.0 wt % and chlorhexidine in an amount from 0.005 to 0.1 wt % and water.

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10 cl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and describes a non-aqueous ointment containing a compound of vitamin D, corticosteroid and ester of N,N-di(C1-C8)alkylamino-substituted (C4-C18)alkyl(C2-C18)carboxylic acid in Vaseline, optionally containing mineral oil and tocopherol.

EFFECT: ointment is characterised by storage stability and high skin penetration of the corticosteroid.

23 cl, 4 dwg, 5 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the pharmaceutical industry, namely to an ointment for burns, folliculitis, furunculosis, vasculitis treatment and wound healing. The ointment for burns, folliculitis, furunculosis, vasculitis treatment and wound healing containing: bees wax, line seed oil, kerosene and visceral fat of pig taken in certain proportions.

EFFECT: ointment possesses a biostimulating effect, reduces the wound healing time with no post-therapeutic cicatrisation with good fixation, uniform distribution on the skin surface and ease of use.

9 dwg, 9 ex

FIELD: medicine.

SUBSTANCE: invention relates to the application of a solid medicinal product, which is heated under the impact of an alternating magnetic field, for further therapeutic treatment after surgical ablation of tumours and cancerous ulcers. The medicinal product represents a surgical implant, presented in the form of a physiologically acceptable fabric, sponge or film. The medicinal product contains magnetic particles, which generate heat when excited by an impact of the alternating magnetic field, and in this way, heat the medicinal product.

EFFECT: invention ensures considerable improvement of further treatment after operation on cancerous tumour in comparison with chemotherapy.

21 cl, 14 ex

FIELD: veterinary medicine.

SUBSTANCE: method of preparing the anti-inflammatory veterinary ointment for outward application consists in mixing while heating to the temperature of 40-50°C in the reactor of molten petrolatum, pine oleoresin, chlorophyll-carotene paste until homogenous consistency, then glycerine and olive oil is fed portionwise with continuous stirring, after which again mixing of the components is carried out for 10-30 minutes until the homogeneous mass, the resulting ointment is cooled and packaged, at that the components of the mixture are taken in the following ratio, wt %: pine oleoresin 3.0; chlorophyll-carotene paste 3.0; petrolatum 69.0; glycerine 5.0; olive oil 20.0.

EFFECT: improved efficacy of treatment.

2 ex

FIELD: medicine.

SUBSTANCE: drug preparation for treating tuberculosis contains an active substance isoniaside, and a pharmaceutical carrier tiozol gel with the isoniaside concentration of 5.7-54.5 wt % and the tiozol gel concentration of 45.5-94.3 wt %.

EFFECT: higher clinical effectiveness in tuberculosis and lower toxicity.

2 cl, 2 tbl

Burn ointment // 2523551

FIELD: medicine.

SUBSTANCE: ointment contains biologically active substances which are Apis mellifera in an amount of 21-23 wt %, St. John's wort oil in an amount of 12-14 wt %, propolis in an amount of 10-12 wt % and wax in an amount of 7-9 wt %, as well as Vaselin and lanolin as the ointment base.

EFFECT: invention accelerates cell regeneration processes considerably due to a synergetic action of the ingredients.

7 ex

FIELD: medicine.

SUBSTANCE: pharmaceutical composition can additionally contain ethylenediaminotetraacetic acid, polyvinyl pyrrolidone, polyvinyl alcohol, a preserving agent specified in a group: Nipagin, Nipasol, benzoic acid, sodium benzoate, sorbic acid, benzalkonium chloride. As a body-forming base, the composition can contain distilled water, polyethylene oxide 400, polyethylene oxide 4000, polyethylene glycol, propylene glycol, a phosphate buffer, a borate buffer, an acetate-borate buffer depending on a dosage form.

EFFECT: high therapeutic effectiveness, prolonged corneal contact of the preparation which reduces the number of instillations, avoids a risk of side effects and provides good tolerance.

5 cl, 5 ex

FIELD: medicine.

SUBSTANCE: invention refers to the veterinary science and is applicable for treating bovine digital dermatitis. A method involves applying a preparation in the form of an ointment of the following formulation, wt %: veterinary copper sulphate 35-45, zinc oxide 9-11, an ointment base - the rest. The preparation is made by mixing the ingredients until smooth. The preparation is applied on the involved regions 1-2 times with or without a protective dressing.

EFFECT: method is effective in treating bovine digital dermatitis.

1 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: topical gel composition for treating erythema or a related symptom contains brimonidine 0.4 wt % to 0.6 wt %, preferentially in the form of brimonidine tartrate, a gelatinising agent, and at least one polyol. The topical application of the gel composition on the skin involved in erythema or having a manifestation of the related symptom has an effect on a serum or plasma profile of brimonidine with an average Cmax approximately 54±28 pcg/ml or less and an average AUC0-24h approximately 568±277 pcg·h/ml or less.

EFFECT: safe and effective treatment of erythema causing no inadequate drug-related side effects.

19 cl, 3 dwg, 5 tbl, 3 ex

FIELD: veterinary medicine.

SUBSTANCE: smell simulator of hallucinogenic substance - lotus comprises an inert carrier and odour substance. The odour substance is used as a mixture containing benzoic acid and perfume agent "lotus".

EFFECT: use of the simulator enables to train the dogs quickly and effectively for searching hallucinogenic plant - blue lotus.

5 cl, 7 ex

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