Pharmaceutical composition for treating acne and method for preparing it

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical industry, and represents a pharmaceutical composition in the form of gel, which contains clindamycin phosphate, a combination of gel-forming polymer and hydrophilic dispersion phase, pH control agent, allantoin and lauryliminodipropionate sodium tocopheryl phosphate; the ingredients of the composition are taken in certain ratio, in g per 100 g.

EFFECT: invention provides the high level of antibacterial activity and stability.

5 cl, 1 tbl

 

The invention relates to the field of medicine and pharmacy, specifically for the composition in gel form for topical use containing as an active ingredient of clindamycin phosphate is an antibiotic of broad-spectrum. The main purpose of this composition is the treatment of inflammatory and non-inflammatory forms of acne (usual acne and rosacea.

Acne (acne vulgaris) is one of the most common dermatoses. Acne is a polymorphic multifactorial disease of the hair follicles and sebaceous glands, which occurs in 80% of adolescents and young adults (girls - 10-17 years, boys in 14-19). Usually to 20 (sometimes 30) years phenomena acne subside, however, in some cases persist after 40 years. Sometimes acne first appears after the age of 25. Among different clinical types of acne most common acne vulgaris (acne vulgaris). This dermatosis affects up to 35% of adolescent males and 23% females. Only at the age of 24 years, this figure falls to 10% and below.

Acne develops on the background of seborrhea, and one of the main etiopathogenetic factors in the development and progression of this dermatosis, is a multiplication of pathogenic microorganisms in the blocked sebaceous glands with subsequent inflammation. Violation m�of krebiozen skin plays an important role in the pathogenesis of acne and can contribute to the development of infection in the sebaceous glands. Installed a natural secretion from inflamed and neosalanx follicles acne of propionibacteria and epidermal Staphylococcus. In severe forms of dermatosis mixed infection was observed with the presence of opportunistic and transient microflora.

In the early stages of the disease the main pathogenetic factor is the blockage of the sebaceous glands; however, on the background of existing microbial dysbiosis quickly joins infectious factor. Therefore, the elimination of microbiocenosis of the skin should begin as early as possible, before the appearance of inflammatory cells. Range of influence on microbiological violations in the foci of inflammation has increased with the advent of the exterior of antibacterial agents. It is very important that external means, not by acting on the body in General, can affect the pathogen directly in the lesions.

An integral part of therapy of acne now are antimicrobial agents which contain as active substance a broad-spectrum antibiotics, such as clindamycin, erythromycin, tetracycline, chloramphenicol, in the form of alcoholic solutions (lotions), gels, creams. Thus the leading role belongs to dosage forms clindamycin.

Clindamycin phosphate is an antibiotic, from�sasisa to lincosamides and providing antibacterial action. After application to the skin of clindamycin phosphate is rapidly hydrolyzed in vivo in the ducts of the sebaceous glands phosphatases with the formation of clindamycin having higher antibacterial activity.

Clindamycin exerts an antimicrobial effect on botulinum, Staphylococcus and other bacteria involved in the pathogenesis of acne. According to reference data in the local application in the form of gel average absolute bioavailability of less than 3% of the dose of clindamycin. Clindamycin rapidly accumulates in comedogenic acne patients. The average concentration of the antibiotic in the contents of the comedones after application of the gel was much higher than the MIC for all strains of Propionibacterium acnes, the causative agent of acne (0.4 ág/ml). When an external application of clindamycin decreases the amount of free fatty acids on the skin surface, which also facilitates its purification from acne.

For patients with inflammatory manifestations of acne external antibiotic therapy is very important because it allows you to quickly eliminate violations microbiocenosis, to reduce the risk of side effects and the timing of taking systemic drugs, extend the periods of clinical remission. In the appointment of therapy should take into account the duration of the process, its prevalence, severity, and type of skin lesions and images�tion of sebum. It is necessary to pay attention to the depth of the lesion of the skin, complications, hyperpigmentation, scarring, and physical characteristics of the patient, hormonal disorders, anamnestic data, previously used therapy and its adequacy, as well as on cosmetic products used by patients. Of great importance is the estimation of the psychoemotional sphere, social status, social adaptation of the patient. This required the creation of a wide range of medicines for external use, which would be a different mechanism of action and type of dosage forms.

There are various pharmaceutical formulations of clindamycin or its derivatives, in the form of soft medicinal forms (gels, creams). In U.S. patent No. 4621075 given pharmaceutical composition in the form of a gel for external use, contains clindamycin phosphate, zinc acetate and a carrier in the form of combination of hydrophobic and hydrophilic component. Pharmaceutical composition for the treatment of acne in the form of a cream comprising as active substance clindamycin or its derivative described in U.S. patent No. 3969516. As auxiliary substances it contains 2-pyrrolidone or its N-alkyl derivatives, preferably N-methyl-2-pyrrolidone, and the basis, including hydrophob�th, hydrophilic components and emulsifier.

In the patent of Russian Federation №2205011 (prototype) described a pharmaceutical composition comprising a salt or ester of clindamycin, the Foundation, which is a combination of hydrophobic and hydrophilic components and emulsifier, and optionally sodium benzoate. Known composition is characterized by an effective antibacterial action. However, the known composition, like other counterparts, does not provide sufficient submodalities effect.

In recent years significantly expanded the possibilities of pharmacotherapy dermatoses that is due not only to advances in fundamental biomedical disciplines, which made it possible to study important aspects of the pathogenesis of common dermatoses, but with the introduction into medical practice of new drugs on the basis of new generation containing new excipients that have directed action for the elimination of the pathological processes in the skin [Fitzpatrick D. E., D. L. Elling dermatology Secrets. - Saint-Petersburg.: Bean, Nevsky Dialect, 1999. - 512 p.; Dermatology. Atlas-directory / T. Fitzpatrick, R. Johnson, K. Wolff, M. Palano, D. Suurmond. M.: PRACTICE, 1999. - 1088 p.].

Such auxiliary substances include, for example, substances, moisturizing and softening the skin [Handbook of Pharmaceutical Excipients: Second Edition / Ed. by Aniey Wade and Paul J. Weller. Washington/London: Amer. Phrm. Association/The Pharm. Press, 1994. - 651 p.]. Rational combination of these excipients with the drug substance creates the preconditions for rational drug external therapy. To reduce the irritation of the skin, especially under the action of ultraviolet rays in the summer time, in the composition of medicinal products for the topical treatment of acne it is recommended to introduce cosmetic auxiliary substances with dermatoprotectivei properties and eliminating the irritant effect of the drug. Such substances include, for example derivatives of vitamin E. the Use of these substances eliminates irritating, reduces erythema, including those caused by ultraviolet irradiation. However, substances, softening the skin, such as vitamin E derivatives, are hydrophobic in nature and do not show relevant activity in the composition of the dosage forms gel (hydrophilic) basis. The additional presence of a derivative of vitamin E, which is poorly soluble in water, causes the complexity of stabilization composition

The objective of this invention is to provide pharmaceutical compositions for topical application in the form of a gel that combines anti-bacterial and submodularity properties that contain clindamycin phosphate, at a therapeutically effective concentration and intended�for internal cutaneous treatment of inflammatory and non-inflammatory forms of acne (common acne), rosacea, as well as in the development of a method for producing such composition.

To solve this problem is proposed pharmaceutical composition for the treatment of acne in the form of soft medicinal forms, preferably in the form of a gel, antibacterial and submodularity activity, which includes as an active ingredient of clindamycin phosphate in a therapeutically effective amount, special additives, a pH Adjuster and a basis. The latter includes a hydrophilic dispersion phase, the gelling agent and optionally a preservative.

Preferably, the ingredients are contained in the following ratio, wt.%

Clindamycin phosphate (equivalent to clindamycin)0,5-2,0
Special additives0,2-5,0
A pH AdjusterTo pH 4,0-7,0
BasisElse

As an active substance used in the composition of clindamycin phosphate in therapeutically effective amounts.

As additives can be used substances with anti-inflammatory, emollient and dermolipectomy properties (and�lanton together with bisabolol and/or derivatives of vitamin E), plant extracts and essential oils with anti-inflammatory and antiseptic properties in concentrations (g/100 g of composition):

Special additives0,2-5,0

Preferably be used as special additives combination of allantoin and vitamin E derivative (lauryldimethylamine Tocopheryl phosphate sodium) concentration (g/100 g of composition):

Allantoin0.05 to 1.0
Vitamin E derivativeof 0.15 to 4.0

As the pH regulator is permissible to use different agents, preferably sodium hydroxide or potassium, triethanolamine, diethanolamine, trometamol, most preferably sodium hydroxide. The amount of pH Adjuster is selected in such a way as to achieve a pH of from 4.0 to 7.0, more preferably from 4.5 to 6.5.

Antibacterial action in vitro by the method of diffusion in agar showed a high effectiveness of the proposed combination against clinical strains of propionibacteria that play an important role in the etiopathogenesis of acne, as well as clinical and reference strains of Staphylococcus, Micrococcus luteus, obligate �naerobic bacteria (Clostridium perfhngens, Bacteroides fragilis, Peptococcus, Peptostreptococcus and Streptococcus pyogenes strain). As a result of the conducted researches it was found that the inventive composition is significantly higher antibacterial effect of clindamycin phosphate in relation to the number of investigated strains (S. aureus ADS 6538 P, clinical strain of Staphylococcus aureus, M. luteus ADS 9341) as compared to compositions lacking lauryldimethylamine Tocopheryl phosphate sodium, or a pH Adjuster, i.e. the claimed combination of clindamycin phosphate, allantoin and lauryldimethylamine Tocopheryl phosphate sodium in the claimed pH range shows a synergistic effect.

When examining the claimed compositions in the treatment of acne of varying severity has been demonstrated its high clinical efficacy and safety, which allows to recommend its wider use as an antibacterial, anti-inflammatory and anticollagen/comedolytic the tool of choice in the treatment of acne of varying severity.

For the preparation of a patentable composition uses of clindamycin phosphate in powder form. The composition is prepared in a gel base, representing a complex disperse system which is simultaneously a solution, colloidal solution and the emulsion of the 1st kind (type m/C) due to the presence of special� additives.

The additional presence of a derivative of vitamin E, which is poorly soluble in water, determined the complexity of stabilization compositions and demanded the presence of the gel-forming polymer

As gelling agents can be used polyacrylic acid derivatives or cellulose derivatives in concentrations (g/100 g of composition):

Gel-forming polymer0,3-1,6

Preferred is the use as galeopithecus derivatives of polyacrylic acid (carbomer) and their combinations. In particular, it is preferable to use a combination of high molecular weight copolymer of acrylic acid and long-chain methacrylate, crosshair crosslinked with allyl ethers of pentaerythritol (carbomer 1342 or carbomer copolymer type b, for example Pemulen TR-1) and the copolymer containing blockcopolymer of polyethylene glycol and fatty acid ester (carbomer interpolymer type And, for example Carbopol Ultrez 10) concentration (g/100 g of composition):

Carbomer copolymer type b0,1-0,6
Carbomer interpolymer type a0.2 to 1.0

Carbomer 1342 contains in the molecule Alki�date radicals, due to which emulsifies and solubilities insoluble matter, and carbomer interpolymer type And additionally contains nonionic surfactant, which also provides emulsification and solubilization, the polymer is easily dispersed in water without forming lumps.

These substances at the indicated concentrations give plastic type of flow with thixotropic properties characteristic of gels that are applied externally to ensure good extrusion of the claimed composition from the package.

Hydrophilic dispersed phase may consist of water and a nonaqueous solvent in a concentration of % (g/100 g gel)

Non-aqueous solvents5,0-20,0
Water70,0 is 92.0

As non-aqueous solvents can act polyhydric alcohol (glycerol, propylene glycol, hexyleneglycol), PEO-400, diethylene glycol monoethyl ether, DMSO, ethanol and N-methylpyrrolidone. Predominant is the use of a combination of osmotically active components polyhydric alcohol and PEO-400 concentration in % (g/100 g gel)

Polyhydric alcohol0,0-19,5
PAO 1,0-15,0

As the polyhydric alcohol is preferable to use propylene glycol. PEO-400 and propylene glycol contribute to the penetration in the comedones of clindamycin phosphate, on the other hand, due to the osmotic activity contribute to the manifestation of anti-inflammatory and submodalities action.

As preservative can be used in different types of parabens, benzoic acid, sorbic acid, a preservative based on Phenoxyethanol, imagemotion. Preferably, the use as a preservative of the paraben in a concentration of 0.05 to 0.3% (g/100 g of composition).

The inventive composition is for topical application methylparaben is used in concentrations from 0.02% to 0.3%. Methylparaben has a broad spectrum of antimicrobial action against bacteria and fungi. Thus its action is enhanced by the presence of one of the supporting ingredients of the claimed composition is non-aqueous solvent is propylene glycol.

We investigated the effectiveness of the preservative action of samples laboratory series of the proposed drug. Research on the effectiveness of preservatives was carried out in accordance with EU regulations. Used the gel sample in which the content of clindamycin phosphate (equivalent to clindamycin) and methylparaben were to�icesto 9,0 mg in 1 g and 2.55 mg in 1 g, respectively. As follows from the results of studies on the antimicrobial preservative effectiveness of the action of the developed product meets the requirements of criterion A of the European Pharmacopoeia [European Pharmacopoeia 5. - 2005].

The choice of ingredients and their ratio significantly affects the method of receiving the drug.

The method of obtaining the claimed composition is that the salt or the ester of clindamycin and special additives in a part of the hydrophilic continuous phase is added a gelling polymer, then a special Supplement with hydrophobic properties, preferably lauryldimethylamine Tocopheryl phosphate of sodium, and a solution of pH Adjuster, and then stirred until uniform, adding an appropriate preservative.

In a preferred embodiment of the proposed method of obtaining basically the machine prepare a solution of active ingredients in a mixture of purified water and non-aqueous solvents when heated. Separately prepare a gel-based, dispersive in the water appropriate gelling agent (carbomer 1342/carbomer copolymer type b and carbomer interpolymer type a). And then adding the dispersion of polymers in the solution of active substance, preservative and additives are mixed to a homogeneous condition, simultaneously cooling the. Homogenize mA�su for uniform distribution of the components by volume.

In the framework of the gel is injected with special additive hydrophobic properties, homogenized, and then add a solution of pH Adjuster and the mixture stirred under vacuum until a homogeneous distribution of all components. Chilled gel to room temperature and discharged into the prepared container. The resulting product is a viscous homogeneous gel.

Distinctive features of the claimed method of production of the composition are:

- active ingredients (clindamycin phosphate and additives) are dissolved in a mixture of purified water and non-aqueous solvents, which allows to reduce the time of dissolution and the temperature of heating,

- complete dissolution of active ingredients (clindamycin phosphate and special additives) to control the introduction of polymers, which avoids partial to the availability of active substances in dissolved condition and to ensure their uniform distribution for thickening the basics

- special Supplement with hydrophobic properties is premixed with water to achieve a high yield of the emulsion and, consequently, a better mixing with the base.

Changing the boot order can lead to an inhomogeneous distribution of the active components by volume

The following examples illustrate the invention.

A typical example.

1. Cooking �of astora of clindamycin phosphate and allantoin.

In a laboratory reactor equipped with a stirrer, a homogenizer and a thermometer, load the bulk of purified water, non-aqueous solvent, such as PEO and propylene glycol, and heat the mass up to 60-65°C. Then load of clindamycin phosphate; allantoin, and, if necessary, methylparaben. Keep stirring until complete dissolution. The solution is then cooled with stirring to 45°C.

2. Preparation of dispersions of carbomer.

In a separate container load part of purified water and while stirring load of carbomer copolymer type B. Conduct stirring to obtain a homogeneous dispersion. In a separate container load part of purified water and while stirring load of carbomer interpolymer type A. Provide exposure to swell without stirring.

3. Preparation of a gel.

In the reactor with a solution of active components with a temperature of 45°C load dispersion carbonero. The mixture stirred for 15 min and loaded emulsion vitamin E derivative (lauramidopropyl Tocopheryl phosphate sodium, trade name - Vital ET). Stirred while cooling to a temperature of 30°C. Then add a solution of pH Adjuster (NaOH) and homogenized mass to a homogeneous condition. Mix the gel, ensuring a homogeneous distribution of the components at room temperature.

4. Unloading of the gel.

Specific examples OS�implementation of the invention are presented in table 1. The resulting compositions have a shelf life of 2 years and 3 months when stored at 25°C.

As gelling polymer in examples 1, 4, 5 use a combination of carbomer copolymer type b and carbomer of interpolymer type And ratio of 0.1 to 1.0, 0.6 to 0.6 to 0.2 and 0.3, respectively, in example 2 - carbomer 1342, in example 3 - oksipropilmetiltselljuloza. As a pH Adjuster in example 1 is used sodium hydroxide, in example 2, the potassium hydroxide in example 3 triethanolamine in example 4 - diethanolamine in example 5 - trometamol. As a preservative in example 1 is used methylparaben, in example 2 - combination of methylparaben and propylparaben in equal proportions, in example 3 - benzoic acid and example 5 - sorbic acid. As the nonaqueous solvent in example 1 is used, the monoethyl ether of diethylene glycol, in example 2, a mixture of glycerol and polyethylene oxide - 400 (PEO-400) in a ratio of 1 to 15.0, in example 3, a mixture of propylene glycol and PEO-400 in a ratio of 6.0 to 6.0, in example 4 - N-methylpyrrolidone, in example 5, a mixture of hexyleneglycol and PEO-400 in the ratio 19,0 to 1.0.

The choice of packaging materials

As a result of market study and needs of clinicians, it is preferable to dose clindamycin gel for external use in aluminium tubes of 30 grams each tube with gel POM�through in a cardboard box.

Gel dosed at 30 g in tube aluminum on THE 64-7-678-90 or another with internal lacquer coating on the basis of glue BF-2, permitted for medical use MOH.

Aluminum tubes when you extrude gel irreversibly deform, thus not sucking air. By preventing the ingress of air is less than the probability of oxidation, decomposition of the active substance, the less the likelihood of microbiological contamination of the finished product after opening the tube. Packing in such tubes meets pharmacopoeial requirements [European Pharmacopoeia 5. - Semi-Solid Preparations for Cutaneous Application. - P. 624-626]. Membrane and latex ring in the rear ensure the impermeability of the tube for air. This is especially important for soft drugs, containing water. In addition, such tubes can allow you to avoid the effects of light on the gel, which is important for the safety of the stated concentration of the active substance throughout the expiration date.

Each tube along with instructions for use are placed in a cardboard pack for consumer packaging subgroups of chrome or chrome-ersatz GOST 7933-89.

1. Pharmaceutical composition in form of gel for treatment of acne (acne), which includes clindamycin phosphate and base, which is a combination of a gel-forming polymer and a hydrophilic dispersion FA�s, characterized in that it further comprises a pH Adjuster and a special additive - allantoin and lauryldimethylamine Tocopheryl phosphate sodium, at the following content of ingredients, g/100 g of composition:

Clindamycin phosphate
(in terms of clindamycin)0,5-2,0
Allantoin0.05 to 1.0
Lauryldimethylamine
Tocopheryl phosphate sodiumof 0.15 to 4.0
A pH AdjusterTo pH 4,0-7,0
BasisElse

2. Pharmaceutical composition according to claim 1, characterized in that it further comprises a preservative.

3. Pharmaceutical composition according to claim 2, characterized in that it contains as a hydrophilic continuous phase polyethylene oxide 400, propylene glycol and water as the gel-forming polymer is a combination of carbomer copolymer type b and carbomer of interpolymer type A.

4. Pharmaceutical composition according to claim 3, characterized in that it comprises basics ingredients in the following ratio, GNA 100 g of composition:

Carbomer copolymer type b0,1-0,6
Carbomer interpolymer type a0.2 to 1.0
Propylene glycol0,0-19,5
PEO-4001,0-15,0
Water70,0 is 92.0

5. Pharmaceutical composition according to claim 4, characterized in that it contains as preservative methyl parahydroxybenzoate.



 

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,

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15 cl, 1 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: invention refers to cosmetic industry and represents a non-foaming cosmetic composition of an oil-in-water emulsion containing (i) retinol, (ii) at least one polar emollient specified in a group consisting of propylene glycol stearyl ester, propylene glycol isostearate and mixtures thereof (iii) at least one non-polar emollient specified in a group consisting of aromatic or linear esters, Gerbe ester, mineral oils, squalane, isohexadecane, squalene, liquid paraffin and mixtures thereof with the weight ratio of the above polar emollient and the above non-polar emollient is found within the range of approximately 95 to 5 to approximately 40 to 60.

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

11 cl, 3 ex, 7 tbl, 3 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to a balanced fat composition, suitable for probe feeding. The fat composition, suitable for the probe feeding, contains from 8 to 15 wt % of linoleic acid (LA); from 3.0 to 6.0 wt % of a mixture, consisting of ω-3 polyunsaturated fatty acids, alpha-linolenic acid (ALA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), where the quantity of ALA>2.5 wt % and the mixed quantity of DHA and EPA≤2.5 wt %l from 10 to 20 wt % of at least one medium-chain fatty acid (MCFA); and from 35 to 79 wt % of one monounsaturated fatty acid (MUFA). Claimed is a liquid nutritional composition, containing the said fat composition. Claimed is a method of supplying enteral feeding to patients, which includes the introduction of an effective quantity of the said liquid nutritional composition, containing the balanced fat composition by the invention.

EFFECT: invention makes it possible to obtain the balanced nutritional composition for long enteral feeding.

27 cl, 1 dwg, 5 tbl

FIELD: medicine.

SUBSTANCE: invention can be used for the local treatment of trophic ulcers, infected and persistent septic wounds, degrees I-II-IIIA burns, traumatic skin injuries, pyoinflammatory skin diseases, bed sores, etc. The invention refers to a preparation, which contains a streptocide powder 1-2.5 g, Ichthyol ointment 7-10 g and castol oil 87.5-92 ml.

EFFECT: reducing the length of treatment up to 14 days with no side effects.

4 ex

FIELD: medicine.

SUBSTANCE: invention provides a stable composition for treating damages associated with herpes-virus infections in a form specified in creams and gels containing low-level trichloroacetic acid. The amount of trichloroacetic acid makes less than 6% (wt / wt) of the cream or gel.

EFFECT: extending the range of products for treating the damages associated with herpes-virus infections.

25 cl, 3 ex

FIELD: chemistry.

SUBSTANCE: method includes milling glauconite with the content of rock from 20 to 95%, selection of a fraction of 1.0-10 mcm, preparation of a 40-80% suspension of glauconite in water. The obtained suspension is processed by ultrasound with a frequency of 15-25 kHz for 2-5 minutes. As a result obtained is a glauconite-based enterosorbent, which represents a 40-80% suspension of the glauconite 1.0-10 mcm fraction in water.

EFFECT: obtaining the glauconite-based enetrosorbent, which has the increased sorption ability in the form of a stable water suspension of glauconite.

2 cl, 2 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: therapeutic agent contains recombinant interferon specified in a group of: recombinant interferon alpha, recombinant interferon beta, recombinant interferon gamma, metronidazole, fluconazole and/or voriconazole, and a pharmaceutically acceptable base in the following proportions, g per 1 ml of the mixture: recombinant interferon, international units 100-10,000,000; metronidazole 0.00001-0.5; fluconazole and/or voriconazole 0.00001-0.5; pharmaceutically acceptable base - the rest. Besides, the therapeutic agent contains boric acid in an amount of 0.00001-0.5 g and hypromellose in an amount of 0.00001-0.5 g. As a pharmaceutically acceptable base, it contains macrogol 400 or macrogol 1500, or macrogol 4000.

EFFECT: higher efficacy of the compound.

2 cl, 5 ex

FIELD: medicine.

SUBSTANCE: invention represents an antibacterial pharmaceutical composition containing clotrimazole, propylene glycol, macrogol 400, macrogol 1,500, macrogol 4,000, poloxamer 338, cetostearyl alcohol, macrogol 20 cetostearyl alcohol, disodium edetate, purified water with the ingredients of the compositions taken in certain proportions, g/100 g.

EFFECT: higher antibacterial and antifungal action.

3 cl, 3 dwg, 5 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the pharmaceutical industry and represents a therapeutic agent used for treating or preventing palmar-plantar erythrodysesthesia syndrome (PPES) induced by a multifunction kinase inhibitor (MKI) therapy and containing a therapeutically effective amount of allopurinol or its pharmaceutically acceptable salt.

EFFECT: invention provides extending the range of products for treating or preventing palmar-plantar erythrodysesthesia syndrome (PPES) induced by the multifunction kinase inhibitor (MKI) therapy.

21 cl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutics and represents a vaccine composition for inducing an immune response in animals. The composition contains an antigen and a 40% oil-in-water emulsion diluted to 2.5%, wherein the above 40% oil-in-water emulsion contains 30 vl/vl % of light hydrocarbon non-metabolic oil, 10 vl/vl % of lecithin, 0.6 vl/vl % of sorbitan monooleate, 1.4 vl/vl % of polyoxyethylene sorbitan monooleate; the oil component is dispersed in an aqueous component by emulsification, while the vaccine composition is prepared by a microfluidiser. An average drop size in the composition makes less than 0.3 mcm.

EFFECT: composition possesses improved physical characteristics, enhanced immunising action, as well as high safety.

10 cl, 20 ex, 17 tbl, 11 dwg

FIELD: medicine.

SUBSTANCE: as an active substance, the composition contains butoconazol, a base that is a combination of a hydrophobic ingredient, a hydrophilic ingredient and an emulsifier, and also a gel-forming polymer. Hydroxypropylstarch phosphate is preferentially used as the gel-forming polymer. A method for preparing the declared composition consists in the fact that a mixture of butoconazol with a portion of the hydrophilic ingredient, the hydrophobic ingredient and emulsifier is added with a dispersion of the gel-forming polymer in the rest of the hydrophilic ingredient; the produced mixture is agitated homogenously with a preserving agent added where it might be necessary.

EFFECT: new pharmaceutical composition is characterised by a high level of antifungal activity, stability both at a storage temperature, and at a use temperature, and good pack extrusion.

14 cl, 2 tbl, 10 ex

FIELD: medicine.

SUBSTANCE: composition contains tacrolimus as an active substance in a therapeutically effective amount, a hydrophobic ingredient, a hydrophilic ingredient, an emulsifier and a stabiliser - disodium edentate and phenoxyethanol. As tacrolimus, the composition contains tacrolimus monohydrate. The composition contains phenoxyethanol in a combination with ethylhexyl glycerol in a ratio of 9:1. The composition is presented in the form of a semi-solid dosage form.

EFFECT: formulation is characterised by stability, uniform distribution of the active substance, usability and good pack extrusion.

6 cl, 2 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to surgery, and can be used for treating sternomediastinitis. That is ensured by introducing a therapeutic mixture prepared ex tempore containing a broad-spectrum antibiotic tropic to bone tissue in a half a compendially recommended average therapeutic daily dose, 1 ml of lidase 32 thousand units, 1 ml of a lincomycine solution in a dose of 0.3 g, 1 ml of ketorolac tromethamine in a dose of 0.03 g, 1 ml of dexamethasone solution in a dose of 0.004 g, 1 ml of a 10% lidocaine solution and 5 ml of a 40% glucose solution. The therapeutic mixture is administered into interspinous ligaments of the spinal column at Th2-Th3, Th3-Th4, Th4-Th5, at a depth of 1.5-2 cm in a dose of 3 ml into each injection point into a patient lying on his/her side with bringing the knees to the stomach and bending the head as forward as possible. The length of treatment makes 12-14 days with the first 3 injections performed daily; the residual injections - every second day, 8-9 injections in total.

EFFECT: invention provides reducing a dose of the administered preparations and a rate of administration as compared to the systemic antibacterial therapy by an ability of the administered mixture to be accumulated in the inflammation centre, providing the therapeutic concentration with the total dose of the administered preparations reduced as compared to the systemic antibiotic therapy.

2 ex

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