Stable gel form of azelaic acid
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to pharmaceutics. Gel form of azelaic acid is described. Gel form includes micronized azelaic acid and additional substances: benzoic acid, disodium edetate, carbomer Carbopol 980, propylene glycol, sodium hydroxide, glycoceramides purified, isopropylmiristate, polysorbate 20, purified water.
EFFECT: invention is provided by obtaining stable medication in form of gel, which does not produce local irritating action in case of long-term on-skin applications.
11 cl, 15 dwg, 5 tbl
The invention relates to medicine, in particular to the pharmaceutical industry, and describes a dermal pharmaceutical composition is in the form of gel for local application, including azelaic acid.
Treatment of one of the most common dermatoses - acne vulgaris (vulgaris, acne or seborrheic) still remains a challenge, despite numerous researches, devoted to the study of disease pathogenesis, and the development of new methods of pharmacotherapy. Acne vulgaris develops in 80-90% of teenagers in puberty, which determines the urgency of the problem and its socio-economic importance [Jansen T, Plewig G. Acne in childhood: Note the specific therapeutic norms. TW Padiatr 1997; 10:336-341].
Significant place in the treatment of acne belongs rationally selected external therapy. External therapy has quite rightly regarded as extremely important a part of complex treatment of dermatological patients. In the appointment of therapy should take into account the duration of the process, its prevalence, severity, and type of skin lesions and the formation 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. In this case, the doctor should be able to use this Arsenal in accordance with the clinical form and stage of the disease.
In recent years significantly expanded the possibilities of pharmacotherapy dermatoses. This 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 cream and cream-gel foundations 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 smahc�that are contributing to the skin [Handbook of Pharmaceutical Excipients: Second Edition / Ed. by Anley Wade and Paul J. Weller. Washington/London: Amer. Pharm. Association/The Pharm. Press, 1994. - 651 p. 11]. Rational combination of these excipients with the drug substance creates the preconditions for rational drug external therapy.
It should be noted the positive results of the use of a gel-like funds in the complex treatment of acne. The advantage of gels creams before is that they are easily applied to the skin, forming a thin moisturizing film, does not clog pores, does not provoke excessive greasiness, provide a more complete release of biologically active substances.
One of the most effective remedies for treating acne are drugs containing as the active ingredient azelaic acid, which has antibacterial activity, which manifests itself in delayed growth of propionic acid bacteria involved in acne formation. In addition, azelaic acid slows down the formation of fatty acids, which contribute to the formation of acne and prevents the formation of comedones, and combined with the cream-gel base provides hydrating (moisturizing and emollient action against skin.
The prior art discloses the following, registered in the Russian Federation, drugs azelaic acid in a gel base:
- Skinoren®in dosage forms� gel for external use 15% 5 g; 15g; 30g; 50g tubes manufactured by Intendis GmbH (Germany); reg. room P N014589/02 dated 08.12.2008;
- Azelic®in the dosage form gel for external use 15% 5 g and 30 g tubes manufactured by JSC "Chemical-pharmaceutical plant "Akrihin"; reg. room PL-001416 from 11.01.2012.
The most effective and widely represented in the Russian market drug azelaic acid is to Skinoren®gel for external use 15% production company Intendis GmbH (Germany). This product contains 15% azelaic acid on complex multicomponent cream-gel base. Drug Skinoren®gel for external use 15% is produced in aluminum lips 5 g, 15 g, 30 g and 50 g.
Drug Skinoren®gel for external use 15% includes the following components, %:
This formulation excipients provides the following functionality: lecithin - emollient providing a softening effect; benzoic acid - antimicrobial preservative; triglycerides - emollient providing a softening effect; polyacrylic acid gelling agent; propylene glycol non-aqueous hydrophilic solvent, wetting agent, the penetrator azelaic acid; Polysorbate 80 - emulsifier of type I; denetria edetate is a chelator; sodium hydroxide neutralizing polyacrylic acid, pH; purified water - the solvent and the dispersion medium gel base.
In the product Skinoren®gel for external use 15% oil phase serve as triglycerides at a concentration of 1%. Triglycerides are emollients, that is, the substance that provides skin softening effect.
There are two clinically proven way of dealing with dry skin:
1. The use in soft drugs substances that when absorbed into the skin bind and hold in moisture; these substances include, for example, propylene glycol.
2. Softening and moisturizing of the skin is provided by hydrophobic solvents (emollient), creating the skin occlusive film and prevents evaporation of moisture. Emolliency give the gels also other important functional characteristics associated with raspadaemosti, slide, touch sensations on the skin, etc.
Triglycerides are the structure of the acyl radical of an unsaturated acid and unsaturated communications that are in storage are oxidized with the formation of peroxides, initiating the decomposition of azelaic acid. In connection with the oxidation of triglycerides by the end of the shelf life of the drug Skinoren®gel for external use 15% acquires an unpleasant smell.
The authors present invention investigated the influence of aggressive factors such as lipid oxidation, UV light irradiation, alkali treatment and acid treatment, the stability of the substance azelaic acid. The results are shown in Fig. 1-5 and table 1.
According to the results, it was found that azelaic acid is resistant to acids and alkalis, is relatively resistant to in�light. The most dangerous for stability of azelaic acid is the oxidation, therefore, the basis of the preparation should not contain agents to promote oxidation.
Thus, there currently exists a need to develop a gel dosage form of azelaic acid with high chemical and physical stability during storage for a long time, and also allows you to expand the Arsenal of antimicrobial drugs of domestic production.
The aim of the present invention is to expand the list of medicines and the development of a new drug, pharmaceutically equivalenting (containing the same amount of the same active substance (same active ingredients) in the same dosage forms that meet the same or comparable standards) the drug Skinoren®gel for external use 15%, while devoid of shortcomings that affect the chemical stability of azelaic acid in a gel dosage form.
Taking into account the above-mentioned drawbacks affecting the stability of the active substance, the authors present invention it was decided to use as the hydrophobic solvent - isopropylmyristate [Cutina®CBS. - Material Safety Data Sheet according o 91/155/EEC - ISO 11014-1. - Cognis. - 4 p.], similar to triglycerides functionality. Isopropyl myristate is a chemically stable substance, resistant to oxidation [Handbook of Pharmaceutical Excipients: Second Edition / Ed. by Anley Wade and Paul J. Weller. Washington/London: Amer. Pharm. Association/The Pharm. Press, 1994. - 651 p.].
In addition, the emulsifier of triglycerides in the product Skinoren®gel for external use 15% Polysorbate 80, which is included in the composition in a concentration of 1.5 and performs the role of stabilizer suspension azelaic acid. However, Polysorbate 80 has an unsaturated alkyl chain, which is critical for the stability of azelaic acid. The solution to this problem was found through the inclusion of a nonionic surfactant ("surfactant") is Polysorbate 20 at a concentration of 1.5% is used for emulsification of the oil phase and the stabilization of the suspension azelaic acid in the composition of the drug, which unlike the Polysorbate 80 has a saturated alkyl chain, and is stable to lipid oxidation.
In the absence of nonionic surfactants in the composition is designed gel form azelaic acid last gathered in large conglomerates that were visible both to the naked eye when you run a test on the homogeneity by the method of GF X [State Pharmacopoeia of the USSR X ed. - M.: Medicine, 1968. - 180 p.], and the study with a microscope (Fig. 6). The formation of conglomerates in the absence of nonionic surfactants occurred even when the rotational speed of a turbine stirrer to 10,000 rpm by increasing the concentration of Polysorbate 20 to 1% conglomerates azelaic acid was significantly decreased but not completely disappeared (Fig. 7). By increasing the concentration of Polysorbate 20 to 1.5% above the conglomerates of azelaic acid was absent (Figs 8, 9).
On reapeatedly gel with azelaic acid concentration of Polysorbate 20 is affected only slightly (Fig. 10).
It is known that the composition of the drug Skinoren®gel 15% is another emulsifier - lecithin at a concentration of 1%. However, in the composition of the drug Skinoren®gel for external use 15% lecithin is an emulsifying agent and a stabilizer dispersed systems, and performs the function of a cushioning substance that helps restore the lipid layer of the skin and reduces the irritating effect of azelaic acid on the skin.
During storage lecithin is easily oxidized, which can lead to the formation of impurities of azelaic acid, in addition, lecithin gives the gel a yellowish tint, which degrades the aesthetic appearance of the drug. In this regard, as an alternative to lecithin in the present invention was examined the possibility of introducing in RA�relatively drug picokernel treated (Ceramides LS), which in the literature have significant advantages.
Ceramides LS is a concentrated and purified of glycolamide, similar in composition to the 4/5 ceramides of human skin. They included the smaller content of cholesterol and phospholipids. Glycolamide peeled - product of natural origin [Cutina®CBS. - Product Data Sheet. - Cognis. - 2 p.].
Ceramides LS have dermolipectomy action in the upper layers of the epidermis - they act as glycolamide, and also as a precursor of ceramide. The composition of the Ceramides LS is the following content of components: glycolamide 65-100%; cholesterol 1-3%; phospholipids 25-38%.
Ceramides LS reinforce, retain and restore the damaged or weakened bilayers of lipids and ceramides (placed between corneocytes) using the relevant physiological and functional lipids. They physiologically renew, restore and enhance lipid lamellar system of intercellular spaces, which are very sensitive to external attacks. Ceramides LS enhance the terminal differentiation of the epidermis [Cutina®CBS. - Product Data Sheet. - Cognis. - 2 p.].
Fig. 11 presents the estimation results of studies of lotion glycolamide (0,1%) in 216 patients with atopic dermatitis, and Fig. 12 - kinetics of manifestation of clinical signs of disease
The use picokernel helps to reduce erythema, dryness, peeling. The above and the results of many other studies with the use of ceramides demonstrate the feasibility of using such emollients in the treatment of patients with dermatoses. Therefore, in the gel composition of the present invention as emollient, emollient effect and contributing to the restoration of barrier lipid layer of the skin, included glycolamide peeled (Ceramides LS) in a concentration of 0.1%.
The technical result of the invention is to obtain stable drug in gel form, containing as active substance azelaic Kioto - medium exhibiting antibacterial, zit and depigmenting effects. The drug should have a balanced antibacterial activity when applied to skin. In addition, this gel formula is not expected to have local irritating effects of chronic skin applications.
Given the physico-chemical properties of active and excipients included in the composition in gel form, the authors had to choose their qualitative and quantitative composition the results of physico-chemical, microbiological, technological, analytical and biopharmaceutical research.�tions. The rationality of the selected composition had to be confirmed by the results of preclinical studies specific actions and safety, including local irritating effect.
Critical characteristics of the dosage form are:
- thermodynamic stability of the suspension azelaic acid;
- consistency and physical stability of the gel as a dispersed system with a liquid dispersion medium;
- storage temperature of the drug, which may affect the chemical stability of azelaic acid and excipients, as well as physical stability of the gel as a dispersed system;
- the excipients, namely the presence of legkookisljajushchihsja substances, which are a critical factor for the stability of azelaic acid;
- microbiological purity, which must comply with pharmacopoeial requirements [European Pharmacopoeia 7th Edition. - Strassbourg: European Directorate for the Quality of Medicines &Health Care (EDQM) - Council of Europe, 67075 Strasbourg Cedex, France 2010. - Vol.1., Vol.2. - 3536 p.; State Pharmacopoeia of the Russian Federation. - M.: Publishing house "Scientific centre of medical products", 2008. - 704 p.].
In the process of selection of the composition of substances, included in this gel form, the authors of the present invention conducted the following research:
- The choice of the gelling agent, it�of relistor and justification of the pH range gels. Based on the study of physico-chemical properties (primarily, rheological properties and pH) of samples of gels having different compositions were chosen the type of carbomer and its concentration, and sodium hydroxide as substances neutralizing carbomer and causing gelation. As the gelling agent was selected carbomer Carbopol®980, allowing the use of the gelling agent in a minimum concentration of 1.0% and eliminate the stickiness of the drug and the rolling carbomer in clumps when rubbed into the skin.
- The choice of the composition of the dispersion medium. As the dispersion medium were selected propylene glycol and water.
- The choice of the composition of the oil phase. The oil phase was chosen as isopropyl myristate, which is a substance that is stable to oxidation unlike triglycerides, performing the function of the oil phase in the product Skinoren®gel for external use 15%. It was shown that the easily oxidizable with formation of peroxide compounds triglycerides impart an unpleasant odor to the specified drug during storage and contribute to the accumulation of impurities of azelaic acid.
- The selection of the surfactants. As a surfactant was chosen Polysorbate 20, which, unlike Polysorbate 80, which is part of the drug Skinoren®gel for external application�Oia 15% and having unsaturated alkyl chain, has saturated alkyl chains and is stable to lipid oxidation. Polysorbate 29 is introduced into the composition in a concentration of 1.5%, which corresponds to the surfactant concentration in this drug.
Lecithin, which is part of the above drug at a concentration of 1%, was replaced with glycolamide in a concentration of 0.1%. Glycolamide, unlike lecithin, does not oxidize and does not impart a yellowish tint to the gel.
- The choice of antimicrobial preservatives. According to the results of research on the effectiveness of the antimicrobial preservative action, it was found that in the selected concentration of azelaic acid and benzoic acid function as antimicrobial preservatives and together provide an effective antimicrobial preservative action, on the effectiveness of the requirement in criterion A of the European Pharmacopoeia [European Pharmacopoeia 7th Edition. - Strassbourg: European Directorate for the Quality of Medicines &Health Care (EDQM) - Council of Europe, 67075 Strasbourg Cedex, France 2010. - Vol. 1., Vol. 2. - 3536 p.].
- The stability, compatibility, and storage conditions. It is shown that the drug should be stored at temperature not above 25°C. by liquid chromatography shows the stability of azelaic acid and excipients.
Stability data are presented in table. 5 and Fig. 13-15. For the long-term stability tests at 25°C for 6 month� (study period stability) significant changes in the indicators of the quality of the drug has not occurred; the drug has withstood the test of over all performance specifications. According to the results of extrapolating the results of analyses using the upper and lower acceptance limits for the indicators "Quantitative content of azelaic acid", "Quantitative content of benzoic acid and pH was determined shelf life 2 years at 25°C.
As a result of comprehensive research, experimentally, the authors present invention was obtained a gel dosage form azelaic acid, physico-chemical and biological properties and quality indicators which confirm the rationality of the selected composition to achieve the objective of the present invention and the solution stability of the active substance.
Specified the gel form is most preferable, but not necessarily, contains the following components in wt. (g/100g):
|Components||Content, g/100 g|
|Azelaic acid micronized||10,00-20,00|
|Denetria edetate (Trilon B)||0,05-0,30|
|Purified water||to 100 g|
In the prior art of similar composition in gel form with azelaic acid could not be detected. Moreover, this composition of substances provides the following functionality: azelaic acid micronized - active substance antibacterial, zit and depigmenting action; benzoic acid - antimicrobial preservative; denetria edetate is a chelator; carbomer 980 - gelling agent; glycolamide peeled (glycosphingolipids and phospholipids, and cholesterol) - emollient providing a softening effect and helps restore bar�cluster lipid layer of the skin; Polysorbate 20 - emulsifier first kind and a suspension stabilizer; isopropyl myristate - emollient providing a softening effect on the skin; propylene glycol - hydrophilic non-aqueous solvent, providing skin moisturizing effect and promotes penetration of azelaic acid; sodium hydroxide pH regulator and Converter of carbomer; purified water - solvent.
Specific versions of the formulations of the claimed compounds are presented in tables 2-4.
Method of manufacture of these formulations is preferably, but not necessarily, is as follows:
- In enamel container, weigh out approximately 1/3 part by weight of purified water required to prepare a 10% solution of sodium hydroxide at stage 1. Then in enamel container load pre-weighed sodium hydroxide and stirred until complete dissolution of sodium hydroxide. Then pour the remaining portion of purified water required to prepare a 10% solution of sodium hydroxide at stage 1. The resulting solution was thoroughly mixed.
Stage 2. In an enamel container, weigh out isopropyl myristate, heated to a temperature (75±5)°C, in enamel container loads of pre-weighed glycolamide and stirred until full dissolution at a temperature (75±5)°C. After dissolution of glimmered�load in pre-weighed Polysorbate 20 and stirred to obtain a homogeneous mixture.
- Weighed on the scales or measure using a meter the required amount of purified water and loaded into the reactor homogenizer. Then weighed on the scales of benzoic acid and denetria edetate, was charged into the reactor homogenizer and dissolved with stirring frame and a paddle mixer. If necessary to expedite the process can be heated to a temperature of (35±5)°C. After complete dissolution of benzoic acid and denetria of edetate mass in the reactor homogenizer cooled to a temperature of 20-25°C.
- Weighed on the scales of carbomer Carbopol® 980 and charged into the reactor homogenizer, 3-4 portions, evenly distributing it on the surface of the reactor content. After the introduction of each portion of the mass in the reactor was stirred for about 5 min frame and paddle mixer until complete wetting of carbomer. The mass in the reactor leave without stirring for swelling of carbomer for 1 hour. Then the mass in the reactor was stirred with a homogenizer by using a frame, impeller and turbine agitators under vacuum depth of -0.05 MPa to -0,07 MPa to form a uniform dispersion within 40-60 min.
- Weighed in the balance propylene glycol, and then charged into the reactor homogenizer, stirring the mass in the reactor homogenizer frame and paddle mixer until complete mixing of the solvent with a dispersion of carbomer. Then in R�actor-homogenizer load hydrophobic phase with stage 2. In the reactor-homogenizer to produce a vacuum depth of -0.05 MPa to -0,07 MPa and emulsify using the frame, blade and turbine agitators under vacuum for 15-20 minutes.
- Weighed in the balance azelaic acid micronised and charged into the reactor homogenizer 5-6 portions. After the introduction of each portion of the mass in the reactor was stirred for about 5 min frame and a paddle mixer.
- In reactor-homogenizer load 10% solution of sodium hydroxide with stage 1. Stir the contents of the reactor homogenizer for 10-15 min under vacuum depth of -0.05 MPa to -0,07 MPa frame, impeller and turbine agitators to obtain a homogeneous gel.
1. Stable gel form azelaic acid containing micronized azelaic acid in an amount of from 10 to 20 g/100 g, auxiliary substances, which are benzoic acid, disodium edetate (Trilon B), carbomer Carbopol 980, propylene glycol, sodium hydroxide, purified water, contains emollients isopropyl myristate and glycolamide peeled, and as the surfactant contains Polysorbate 20.
2. Stable gel form according to claim 1, where the specified baie�sauna acid is contained in an amount of from 0.05 to 0.30 g/100 g
3. Stable gel form according to claim 1, where the specified denetria edetate (Trilon B) is contained in an amount of from 0.05 to 0.30 g/100 g
4. Stable gel form according to claim 1, where the specified carbomer 980 is contained in an amount of from 0. 5 to 2.0 g/100 g
5. Stable gel form according to claim 1, where the specified glycol is contained in an amount of from 10.0 to 15.0 g/100 g
6. Stable gel form according to claim 1, where the specified glycolamide treated contained in an amount of from 0.05 to 0.2 g/100 g
7. Stable gel form according to claim 1, where the specified contains isopropyl myristate in an amount of from 0.5 to 2.0 g/100 g
8. Stable gel form according to claim 1, where the specified Polysorbate 20 is contained in an amount of from 1.0 to 3.0 g/100 g
9. Stable gel form according to claim 1, where the specified sodium hydroxide is contained in an amount of from 0.15 to 0.50 g/100 g
10. Stable gel form according to claim 1, where the specified contains purified water up to 100 g.
11. Stable gel form according to claims. 1-10, where azelaic acid contains micronized in the amount of 15,00 g/100 g of benzoic acid contained in the amount of 0.10 g/100 g, disodium edetate (Trilon B) is contained in the amount of 0.10 g/100 g, carbomer 980 is contained in the amount of 1.00 g/100 g, contains propylene glycol in the amount of 12,00 g/100 g, glycolamide treated contained in an amount of 0.10 g/100 g, contains isopropyl myristate in an amount of 100 g/100 g, Polysorbate 20 is contained in the amount of 1.50 g/100 g sodium hydroxide contained in the amount of 0.20 g/100 g, purified water contained in the number 69,00 g/100 g
SUBSTANCE: method involves administering an anthelminthic agent in the period of stationary process stage; the anthelminthic treatment is preceded by administering chophytol 200 mg 3 times a day before meals for 14 days; the anthelminthic treatment involves administering Osinol food supplement 2 tablets 3 times a day during meals for 14 days; thereafter, chophytol is taken in a dose of 200 mg 3 times a day before meals for 14 days; 7 days later, the repeated course of the anthelminthic treatment with Osinol food supplement 2 tablets 3 times a day during meals is prescribed to be administered for 14 days; the entire therapeutic course involves washing the face with the Setaphyldermocontrol foaming facial cleanser 2 times a day followed by applying an SPF30 product on the face once after the morning wash.
EFFECT: reducing the number of complications and the high efficacy of the anthelminthic treatment.
SUBSTANCE: praziquantel is administered in a single dose of 20 mc/kg for the first day of treatment in the daytime, and withdrawn; on the following day, the conducted therapy is added with introducing Gelmicide, a biologically active food supplement, in a dose of 2 capsules with meals for 21 days; the course is repeated 10 days later in a dose of 2 capsules 2 times a day with meals for 14 days.
EFFECT: reducing the rate of complications and increasing the high dishelminthisation efficacy.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to field of pharmaceutics, namely, deals with compounds of formula , suitable for reduction of regulation of biological activity of melanocortin-5 receptor (MC5R). Such diseases and/or conditions include, but are not limited by, acne, seborrhoea, seborrheic dermatitis, cancer and inflammatory diseases.
EFFECT: compounds of claimed invention can be applied for treatment of diseases and/or conditions, in which reducing regulation of MC5R is favourable.
3 cl, 109 ex, 7 tbl
SUBSTANCE: invention relates to a compound of formula (I) : or a salt thereof, wherein R1 and R5 are independently selected from H, OH and alkoxy; R2-R4 and R6-R8 are independently selected from H, OH, F, Cl, Br and I; R9 and R10 are C2-C8 alkenyl; under the condition that at least one of R1, R5 and R7 is OH or alkoxy; at least one of R2-R4, R6 and R8 is F, Cl, Br or I; and R2 and R6 are Cl. The invention also relates to an antibacterial composition and treatment methods.
EFFECT: improved properties.
18 cl, 7 ex, 10 tbl
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
SUBSTANCE: present group of inventions refers to medicine, namely to dermatology, and concerns treating telangiectasia or related symptoms. To this effect, an involved skin area is coated with a composition containing from approximately 0.4 wt % to approximately 0.6 wt % brimonidine providing its blood serum or plasma concentration, Cmax of approximately 54±28 pg/ml or less and AUC0-24h of approximately 568±277 pg·h/ml or less.
EFFECT: method provides the effective treatment of telangiectasia or related symptoms with no side local and systemic effects.
20 cl, 6 dwg, 6 tbl, 3 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to the pharmaceutical industry and represents a composition for treating acne, rosacea and hyperpigmentation, in the form of a gel which contains anchoic acid, a hydrophobic ingredient, a non-aqueous solvent, an emulsifying agent, a gel-forming polymer, a preserving agent, a pH control agent and additionally methylpyrrolidone with anchoic acid having a particle size of less than 100 mcm, while anchoic acid is related to methylpyrrolidone as 1:0.025 to 1:4.
EFFECT: invention provides easy penetration of anchoic acid through a horny layer and its resolution into the oil grand ducts and between skin cells, providing high concentration of anchoic acid that promotes better antibacterial, keratolytic and de-pigmentation effects.
5 cl, 2 tbl, 1 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: claimed invention relates to a compound of Formula
where Y represents a group of formula -(CR9R10)-; X is selected from the group, consisting of -C(=O)-, -OC(=O)-, -NHC(=O)-, -(CR11R12)- and -S(-O)2-; Z represents a group of formula -(CR13R14)q-; R1 is selected from the group, consisting of C1-C12alkyl, optionally substituted with one substituent, selected from naphthyl, indole and biphenyl; C2-C12alkenyl, substituted with a substituent, selected from thienyl, naphthyl and phenyl, with the said phenyl being optionally substituted with 1-2 substituents; selected from halogen, trifluoroalkyl, C1-C6alkyl, methoxy and hydroxy; C3-C6cycloalkyl; C6-C10aryl, optionally substituted with 1-2 substituents, selected from halogen, phenyl, amino, phenoxy, C1-C6alkyl, methoxy, hydroxyl and carboxy; and C4-C9heteroaryl, selected from indole, quinoline, quinoxaline, benzofuranyl, benzothiophene, benzimidazole, benzotriazole, benzodioxin, benzothiasole, pyrazole, furyl and isoxazole, optionally substituted with a substituent, selected from C1-C6alkyl and phenyl; R2 and R3 each is independently selected from the group, consisting of H and C1-C12alkyl; R4a is selected from the group, consisting of H, C1-C12alkyl, optionally substituted with phenyl; C2-C12alkenyl, C3-C6cycloalkyl, C6aryl, C(=O)R15, C(=O)NR15R16, C(=O)OR15, SO2R15 and -C(=NR15)-NR16R17; R4d represents hydrogen or R4a and R4b, taken together with a nitrogen atom, which they are bound to, form an optionally substituted heterocyclic fragment, selected from piperidine, morpholine, pyrrolidine and azetidine, where the substituent is selected from C1-C12alkyl, hydroxy, halogen, carboxy and oxo; each R5a and R5b represents H, or R6, R7 and R8 each is independently selected from the group, consisting of H, C1-C12alkyl, C3-C6cycloalkyl, C6-C10aryl, optionally substituted with halogen, or taken together with a carbon atom, which they are bound to, two or more of R6, R7 and R8 form a fragment, selected from the group, consisting of C2-C12alkenyl; C3-C6cycloalkyl, optionally substituted with C1-C6alkyl; C6aryl, optionally substituted with 2 substituents, selected from halogen; each R9 and R10 represents H or C1-C12alkyl, substituted with naphthyl; each R11 and R12 represents H; R13 and R14 represent H, or each R15, R16 and R17 is independently selected from the group, consisting of H, C1-C12alkyl, C3-C6cycloalkyl, C6aryl, substituted with one substituent, selected from C1-C6alkyl; and C5-heteroaryl, additionally containing one nitrogen atom, with the said heteroaryl representing pyridyl; q represents an integer number, selected from the group, consisting of 2, 3 and 4; r represents 1; or its pharmaceutically acceptable salt. The invention also relates to particular compounds of 1,4-diazepan-2-one derivatives.
EFFECT: obtaining 3-aminoalkyl-1,4-diazepan-2-one melanocortin-5 receptor antagonists.
21 cl, 7 tbl, 110 ex
SUBSTANCE: invention refers to medicine, namely to dermatology, and can be used for selecting a therapeutic approach to acne in females by examining biological fluids and prescribing preparations depending on the clinical findings. The biological fluids are blood and urine; blood serum hormones and steroid urine profile are tested, and the derived values are compared to the standard norms specific for the absence of acne, while the preparations are prescribed according to the comparison results. Specifically, if observing an increase of blood luteinising hormone up to 16 mIU/ml, testosterone up to 4 ng/ml, an increase of urine androsterone up to 20 mcmole/24 hours, etiocholanolone up to 11 mcmole/24 hours, total 17-ketosteroids up to 35 mcmole/24 hours, van de Calseyde's discriminant up to 3, the combined oral contraceptive Jess with the anti-androgenic effect. If also observing an increase of immunoreactive protein up to 12.90 mcUnit/ml and insulin-line growth factor 1 up to 361.04 ng/ml, the combined oral contraceptive Jess and Metformine or Metformine are prescribed. If observing a decrease of blood oestradiol up to 140 pmole/l or an increase of the concentration of luteinising hormone up to 7 mIU/ml, dihydroepiandrosterone sulphate up to 4 mmole/l, 17 - hydroxyprogesterone up to 4 nmole/l and testosterone up to 4 nmole/l in blood and an increase of urine androsterone up to 17 mcmole/24 hours, etiocholanolone up to 17 mcmole/24 hours, 11 - ketoandrosterone up to 2.5 mcmole/24 hours, 11 - ketoetiocholanolone up to 2.5 mcmole/24 hours, 17 - ketosteroids up to 50 mcmole/24 hours and van de Calseyde's discriminant up to 3, the glucocorticoid Metypred is prescribed. The high blood concentration of luteinising hormone up to 15 mIU/ml, dihydroepiandrosterone sulphate up to 6.82 mcmole/l, 17 - hydroxyprogesterone up to 4 nmole/l and an increase of urine androsterone up to 19.5 mcmole/24 hours, etiocholanolone up to 16 mcmole/24 hours, dihydroepiandrosterone up to 7 mcmole/24 hours, 17 - ketosteroids up to 45 mcmole/24 hours and van de Calseyde's discriminant up to 3.5 enables using the combined oral contraceptive Jess and the glucocorticoid Metypred. And the preparation Dostinex is prescribed in observing the above values in a combination with an increase of blood prolactin up to 750 IU/ml and a decrease of blood oestradiol up to 95.48 pcg/ml.
EFFECT: method enables providing higher therapeutic selectivity and clinical effectiveness in acne without the need of thorough examination to be conducted.
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
FIELD: medicine, pharmaceutics.
SUBSTANCE: claimed invention relates to pharmaceutical composition, which contains compound of insulin in concentration, sufficient for supplying therapeutically effective level of insulin compound in blood plasma for at least 3 days. Insulin compound relates to pro-medical compound, which represents insulin conjugate with linker, bound with hydrogel carrier. Also described is suspension, containing pharmaceutical composition of insulin conjugate, method of suspension obtaining, set, including pharmaceutical composition of insulin conjugate and container for introduction of composition.
EFFECT: pharmaceutical composition of insulin conjugate by invention is characterised by the fact that it has pharmacokinetic profile in vivo in fact without release of insulin compound.
26 cl, 9 dwg, 21 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to pharmaceutical industry and represents medication, possessing virucidal activity, for preventive and therapeutic treatment of viral infections, caused by virus of herpesviridae family, characterised by the fact that said medication contains pyroxican in carrier substance.
EFFECT: invention provides extension of arsenal of means, possessing virucidal activity.
SUBSTANCE: ointment contains wax 13-15 wt %, glycerol 15-20 % and vegetable oil; the prepared ointment mass is exposed to ozone for 15-20 min in a yield amount of 10 mg/l.
EFFECT: invention provides the advanced healing efficacy with no side effects by reducing the time of wound cleansing from purulo-necrotic tissues.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to the pharmaceutical industry and represents a pharmaceutical composition for the external application for the treatment of skin diseases in the form of a cream, which includes as an active substance methylprednisolone aceponate in a therapeutically effective amount and a lipophilic base, characterised by the fact that as the lipophilic base it contains petrolatum, liquid paraffin and oil of castor oil plant seeds and additionally white bee wax, with the components of the composition being in a specified ratio in g/100 g of the composition.
EFFECT: invention provides the creation of the stable composition, improved pharmacological properties and absence of an irritating effect.
SUBSTANCE: group of inventions refers to a pharmaceutical composition in the form of a soft dosage form for treating locomotor disorders, possessing anti-inflammatory, anaesthetic and anti-oedematous action, containing a combination of heparin sodium salt, dexpanthenol, diethylene glycol monoethyl ether and/or dimethylsulphoxide and target additives. The latter are presented by a gelation agent, a solvent/a solubiliser, a neutraliser, a flavouring agent/a moistening agent and water. The invention also discloses a method for producing the pharmaceutical composition.
EFFECT: reducing side actions, particularly allergic responses; it is characterised by high pharmacological activity, and simplified method for producing.
15 cl, 5 ex, 3 tbl
SUBSTANCE: pharmaceutical composition possessing a therapeutic action on various skin pathologies contains triptantrin, chitosan and distilled water, a lanoline and Vaseline mixture and protein-nucleic hydrolyzate of the salmonid fishes milt in a certain mixture ratio.
EFFECT: composition enables increasing the clinical effectiveness in the skin pathologies of various origins and extending the range of pharmaceutical compositions having the therapeutic effect on the various skin pathologies.
3 tbl, 4 dwg, 7 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to pharmaceutical industry, namely to production of medications for treating dermatosis. Medication according to invention, made in form of cream, contains mometasone furoate, preservative, hydrophilic no-aqueous solvent, emulsifying agent of 1st kind, emulsifying agent of 2nd kind, emollient, disodium edetate (trilon B), pH-regulating agent, and purified water in quantities, given in invention formula.
EFFECT: invention can be applied for treating inflammatory diseases and itching in case of dermatosis, yielding to glycocorticosteroid therapy.
9 cl, 3 tbl, 3 ex
SUBSTANCE: pharmaceutical composition contains drug substances and a consistency-forming base. According to the invention, it contains anaesthetics as drug substances specified in a group: anaesthesine, lidocaine, promedol and antiseptic specified in a group of: ethacridine lactate, Furacilin, dioxidine, chlorhexidine, boric acid, 0.5% silver solution in the following ratio, g in 1 ml of the mixture: anaesthetics 0.00001-0.5; antiseptics 0.00001-0.5; consistency-forming base - the rest. Besides, it contains lysozyme in an amount of 0.1-0.3 g per 1 ml of the mixture, alpha-lipoic acid as an antioxidant in an amount of 0.00001-0.5 g per 1 ml of the mixture, regenerants specified in a group of: pantothenic acid, calcium pantotenate, beta-carotene, coenzyme Q, sodium deoxyribonucleate, inosine, vitamins A, D, E, K in an amount of 0.00001-0.5 g per 1 ml of the mixture, anabolics specified in a group of: methyluracil, riboxinum, potassium orotate, orotic acid, L-carnitine in an amount of 0.00001-0.5 g per 1 ml of the mixture, glycyrrhizic acid and/or its salts in an amount of 0.00001-0.5 g per 1 ml of the mixture, recombinant interferon specified in a group of: recombinant interferon-alpha, recombinant interferon-beta, recombinant interferon-gamma in an amount of 100-1,000,000 International units, glucocorticoids specified in a group of: hydrocortisone, prenisolone, polcortolone in an amount of 0.00001-0.5 g per 1 ml of the mixture. The consistency-forming base contains the components specified in a group: hypromellose, sodium alginate, acetyl phthalyl cellulose, macrogol, polyvinylpyrrolidone.
EFFECT: improving the properties of the composition.
9 cl, 11 ex
SUBSTANCE: what is described is a bioactive wound coating of a hydrogel nanocomposite, which contains antimicrobial and antioxidant ingredients: silver-modified montmorillonite and fullerenol used to optimise the clinical course of the wound process, to prevent and suppress a wound infection. The wound coating can be used to treat gun-shot injuries, severe mechanical injuries, infected and uninfected wounds, including septic and persistent, granulating wounds following deep thermal, chemical and radioactive burns, in the combined therapy of trophic ulcers and bed sores at hospital, in the outpatient setting and in the field. The wound coating is elastic, not fragmented in dressing that facilitates wound care. A high sorption ability of the wound coating matrix, including of coarse-molecular ingredients of the wound effluent, provides the fast elimination of the wound bed. Using the hydrogel, i.e. possessing high degree of hydration, the wound coating meets the modern wound management in the humid medium.
EFFECT: optimum conditions for the early activation of the repair processes.
5 dwg, 2 tbl, 4 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention relates to compositions for local application for the prevention and treatment of local eye pathologies, in particular inflammatory keratites and conjunctivitis and the dry eye syndrome, which contain as active ingredients polyunsaturated fatty acids of the omega-3 and omega-6 type, namely, EPA (eicosapentaenoic acid), DHA (docosahexaenoic acid) and GLA (γ-linolenic acid), mixed with vitamin E acetate and combined into a stable composition in a hydrogel, that is in the disperse form in a water solution, containing one or more gel-forming polymers. The claimed compositions are especially recommended for application as artificial tears.
EFFECT: invention provides an increased efficiency of the prevention and treatment of eye pathologies.
15 cl, 15 tbl, 3 dwg, 7 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions refers to pharmaceutics and concerns a water-based formulation of a follicle-stimulating hormone (hFSH) for treating sterility, containing one or more stabilising agents, L-methionine, Polysorbate 20, phosphate buffer providing pH within the range of 6.5 to 8, water for injections; it additionally contains sodium chloride as a thermally stable agent, and also concerns using sodium chloride as the thermally stable agent in the water-based formulation of hFSH.
EFFECT: group of inventions provides the stability of the water-based formulation of hFSH for a long period of time, and prevents dissociations of alpha- and beta- subunits of human FSH.
9 cl, 5 dwg, 3 tbl, 4 ex