WO2007027118A1 - Composition dermatologique - Google Patents

Composition dermatologique Download PDF

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Publication number
WO2007027118A1
WO2007027118A1 PCT/RU2005/000439 RU2005000439W WO2007027118A1 WO 2007027118 A1 WO2007027118 A1 WO 2007027118A1 RU 2005000439 W RU2005000439 W RU 2005000439W WO 2007027118 A1 WO2007027118 A1 WO 2007027118A1
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Prior art keywords
skin
glycol
therapeutic
group
solution
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PCT/RU2005/000439
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English (en)
Russian (ru)
Inventor
Victor Stanislavovich Polyakov
Anatoli Pavlovich Gorshkov
Natalia Aleksandrovna Vorotyagina
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Victor Stanislavovich Polyakov
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Priority to PCT/RU2005/000439 priority Critical patent/WO2007027118A1/fr
Publication of WO2007027118A1 publication Critical patent/WO2007027118A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/25—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids with polyoxyalkylated alcohols, e.g. esters of polyethylene glycol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A61K8/345—Alcohols containing more than one hydroxy group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/39—Derivatives containing from 2 to 10 oxyalkylene groups
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02—Local antiseptics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A—HUMAN NECESSITIES
    • A62—LIFE-SAVING; FIRE-FIGHTING
    • A62D—CHEMICAL MEANS FOR EXTINGUISHING FIRES OR FOR COMBATING OR PROTECTING AGAINST HARMFUL CHEMICAL AGENTS; CHEMICAL MATERIALS FOR USE IN BREATHING APPARATUS
    • A62D3/00—Processes for making harmful chemical substances harmless or less harmful, by effecting a chemical change in the substances
    • A62D3/30—Processes for making harmful chemical substances harmless or less harmful, by effecting a chemical change in the substances by reacting with chemical agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/58—Metal complex; Coordination compounds
    • A—HUMAN NECESSITIES
    • A62—LIFE-SAVING; FIRE-FIGHTING
    • A62D—CHEMICAL MEANS FOR EXTINGUISHING FIRES OR FOR COMBATING OR PROTECTING AGAINST HARMFUL CHEMICAL AGENTS; CHEMICAL MATERIALS FOR USE IN BREATHING APPARATUS
    • A62D2101/00—Harmful chemical substances made harmless, or less harmful, by effecting chemical change
    • A62D2101/02—Chemical warfare substances, e.g. cholinesterase inhibitors

Definitions

  • the invention relates to pharmaceuticals used to protect the skin from damaging factors of a chemical and biological nature, bacterial and fungal infections, to prevent the occurrence of occupational skin diseases, to prevent contact dermatitis, including allergic nature, as well as to provide first aid and further healing of wound defects of the skin, soft tissues, mucous membranes and can be used as labor protection organs in industry, construction ie, agriculture, and medicine, and everyday life.
  • Skin is a “borderline” organ that acts as a protective barrier between the environment and the body. Natural protective and barrier functions of the skin are aimed at compensating for the negative effects of environmental factors. However, the adaptability of the skin to the effects of external factors is not unlimited, and if you overcome the highest threshold of resistance, local or extensive skin damage develops, which ultimately leads to impaired various functions of the body. In real conditions in production, the skin, as a rule, is subjected to the combined effects of chemical, biological and mechanical factors, resulting in a sharp degreasing and drying of the stratum corneum of the epidermis, and, consequently, a violation of the normal function of the skin and the natural self-healing mechanism, which leads to the development occupational skin diseases.
  • An external manifestation of a decrease in protective and barrier properties is the occurrence dermatitis, peeling of the skin, erythema, as well as cuts, abrasions, abrasions, etc. This can be observed not only when working with harmful substances, but also when using detergents, with prolonged wearing of rubber gloves, with a sharp change in temperature and humidity.
  • various cosmetic, hygienic and pharmacological agents are used.
  • Known cosmetic cream for care and protection of the skin from the harmful effects of organophosphorus pesticides in agriculture, chemical industry and household (see patent RU 2038072) [2].
  • the cream contains glycerin, ethyl alcohol, polyethylene glycol, alkali metal hydroxide, lanthanum salt, or cerium, or praseodymium, or neodymium and water at a certain ratio of components.
  • the use of this cosmetic product is limited and is used only when working with specific hazardous organophosphorus substances.
  • this tool may not be effective, because it contains ethyl alcohol, which, as you know, negatively affects the natural protective and barrier properties of the skin due to delipidization of the epidermis, which significantly increases the permeability of the skin and the absorption of the toxicant.
  • An additional introduction to this cream of succinic and hyaluronic acids according to the patent RU 2159105 [3] does not lead to the manifestation of universal protective properties, make it expensive and less competitive.
  • a complex compound of ferrocene with nitrogen-containing components is also known for the treatment of diseases of the skin and mucous membranes by applying a finely divided composition in a safe carrier to the lesion site 1-3 times a day (see patent RU 2132187) [6].
  • This complex compound has bactericidal activity and contributes to the regulation of blood and lymph microcirculation, but these properties are not enough to create a protective, prophylactic and dermatoprotective therapeutic composition.
  • a complex chelate compound of the antibiotic azithromycin with a salt of a divalent and / or trivalent metal, in particular lanthanum, is known to have bactericidal activity and is used to obtain an antiulcer drug in the form of a gel (see patent RU2039061) [7]. It is used only for internal use.
  • Known therapeutic and prophylactic agent for protecting the skin from adverse environmental factors which is a cream containing nitrate or hydrochloride of lanthanum or cerium in an amount of 0.4-0.8% of the total mass, analgin, vitamins and a base including glycerin, PEG, ethylene glycol, alcohol, potassium hydroxide, water and oil (see patent RU2210356) [8].
  • This tool does not provide the necessary antiseptic effect, which limits the possibility of its use in a number of skin lesions. It practically does not have bacteriostatic and fungistatic effects, because it has a small “buffering capacity” and maintains a neutral skin pH for a short time (up to 3 hours). At the same time, for the destruction of pathogenic fungi and microorganisms, it is necessary for a long time to maintain a neutral pH value on the skin, which creates the conditions for stopping the development of colonies of microorganisms.
  • the closest technical solution to the invention is a pharmaceutical composition for topical treatment of a wound process, comprising a complex compound of podands with rare earth elements of the general formula Me (NO 3 ) 3 L mH 2 0 or a mixture thereof, or an auxiliary solution and a pharmaceutically acceptable carrier.
  • the latter is selected from biologically inert water-soluble hydrophilic compounds, mainly organic solvents.
  • the pharmaceutical composition is used for external treatment of a wound defect of the skin or mucous membrane of various localization, regardless of etiology at all stages of the wound process and exhibits reparative properties that encompass antimicrobial, osmotic, dehydrating, analgesic and regenerating activities (see patent RU 2221802) [9]. This decision does not disclose the possibility of using to protect against chemical and toxic skin lesions. In addition, the tool does not show a sufficiently effective fungicidal effect, as well as a therapeutic effect in relation to contact dermatitis.
  • the protective agent not only protects the skin from the penetration of exogenous substances, but also inactivates them, and also promotes skin self-healing processes.
  • the objective of the present invention is to provide a pharmaceutical composition exhibiting a complex effect with a wider range of lesions of the skin and mucous membranes, due to protective and preventive, dermatoprotective, antiseptic and wound healing properties and meeting the following requirements:
  • the object of the present invention is a therapeutic and prophylactic dermatological composition for topical application, which contains the active principle in the form of complex compounds of salts of rare earth elements of the general formula: Ln (X,) (X 2 ) 2 (L) p . m H 2 O (1) where: Ln is the cation of the rare-earth element of the cerium subgroup, which includes lanthanum, cerium, praseodymium, neodymium, or mixtures thereof; Xi - denotes the residue of a compound having basic properties selected from the group: —OH, —O — Ci. b- alkyl, -amine of the formula NHR 2 where R 2 represents hydrogen or a Ci- 4 alkoxy group;
  • X 2 is nitrate or chloride
  • L - denotes the ligand of the complex compound ⁇ R0 [(CHR,) m 2 O] m, R ⁇ p , in which
  • R - is H, C ] -8 alkyl, linear or branched R 1 - is H, methyl, ethyl, propyl or isopropyl, fields - (- CH2-CH2-OH) mi - is an integer, the number is 1 or 2, m 2 - is an integer equal to 1, 2 or 3 p - is an integer equal to 1 or 2 m - is an integer equal to 1, 2 or 3 in an effective amount and a pharmaceutical acceptable carrier.
  • the ligand of the complex compound is preferably selected from the group of polyoxy compounds and is preferably triethylene glycol, propylene glycol, ethyl carbitol,
  • Complex compounds of salts of rare-earth elements form a chemical group with a certain stoichiometry and are crystalline substances. Their structures are established by the usual methods of elemental and X-ray diffraction analysis. Complexes having the general formula (1) are used as exhibiting dermatoprotective, inactivating, and wound healing properties that promote processes self-healing skin, and exhibiting desensitizing effect.
  • the complex compounds of mixtures of salts of rare-earth elements include homogeneous ligands which are polyoxy compounds, such as triethylene glycol, propylene glycol, diethylene glycol mono- and diesters, 1,3-butylene glycol, as well as polyethylene, polypropylene oxides and hydroxypropyl cellulose with different molecular weights.
  • Said pharmaceutically acceptable carrier is preferably selected from the group of polyoxy compounds, including predominantly glycerol, triethylene glycol, diethylene glycol mono- and diesters, polypropylene glycol, polyethylene glycol, hydroxypropyl cellulose, or mixtures thereof.
  • the pharmaceutical composition is expediently performed in the form of a liquid dosage form, such as a solution, emulsion, or in the form of a soft dosage form, such as an ointment, gel, paste, liniment, which may contain acceptable excipients, for example, effective solvents, surfactants, emulsifiers, perfumes.
  • a liquid dosage form such as a solution, emulsion
  • a soft dosage form such as an ointment, gel, paste, liniment
  • acceptable excipients for example, effective solvents, surfactants, emulsifiers, perfumes.
  • the amount of active substance varies depending on the degree and nature of the lesion, the age, gender and weight of the patient.
  • the active substance is administered in an effective amount, which, as a rule, is 3-8% of the total weight of the composition.
  • composition of the pharmaceutical composition it is advisable to additionally introduce substances of natural or synthetic origin, performing the role of a potentiator and increasing the effectiveness of the pharmaceutical composition.
  • potentiating agents for example, glycerin, mono- and diesters of glycols, sea buckthorn, mink and other oils, fats, waxes, surfactants, both ionic and nonionic, drugs, in particular antimicrobial and / or fungicidal, such as miramistin, urotropin, salicylic acid, etc., herbal extracts that have a daily exposure in a safe and effective amount at the site of exposure to harmful exogenous factors on the skin.
  • extracts are oil extracts of chamomile, sea buckthorn, potentiating wound healing effect, water-alcohol solution of rose hips, potentiating effectiveness in the treatment of dermatitis, etc.
  • An effective and safe amount of potentizing agent refers to such an amount that is sufficient to create the desired result without side effects such as toxicity, irritation, allergic reactions commensurate with a reasonable benefit / risk ratio when used in Compliant with the present invention. It changes due to factors such as the specific type of exogenous substance, condition of the skin, predisposition to allergic reactions. As a rule, these funds are used in doses generally accepted for certain pathologies.
  • One of the preferred options is the combination of the compounds of formula (1) and miramistin, which is added in an amount of 0.5-1% by weight of the composition. This combination allows significantly increase antimicrobial activity, the effectiveness of the treatment of mycoses, acne, as well as the wound healing effect.
  • the application of the pharmaceutical composition to the skin and mucous membranes is carried out mainly in the form of applications of a liquid or thickened form using hands, spatula, tampons, turunda or by irrigation.
  • the claimed composition When applied topically, the claimed composition is applied, as a rule, at the rate of 0.2-0.5 g / dm 2 .
  • the dosage can be increased, and vice versa, for example, for cosmetic purposes, reduced.
  • the pharmaceutical composition can be obtained by introducing a pre-prepared crystalline active substance using methods known in the art of pharmacy into a pharmaceutical acceptable carrier and, optionally, additionally containing excipients, depending on the dosage form.
  • the pharmaceutical composition can also be obtained without additional isolation of a crystalline substance, by obtaining a solution of the complex compound in excess of ligand (auxiliary solution). This method is more appropriate.
  • a salting-out method was used to prove the formation of a solution of the complex compound of the general formula (1) in excess of the ligand: acetonitrile or dichloroethane was carefully added to the solution of the complex compound, and a complex compound crystallized at the phase boundary, identical to that obtained by the first method, using the same reagents.
  • a method of obtaining complex compounds of General formula (I). A -0.01 M solution of a water-soluble salt of the rare-earth elements of the cerium subgroup is prepared (for example, nitrate hexahydrate or lanthanum, cerium, praseodymium or neodymium hydrochloride hexahydrate) in acetonitrile.
  • alkaline agent Slowly, dropwise with vigorous stirring and room temperature add an equimolar amount of alkaline agent to the first jump according to the potentiometer.
  • Alkolates, aqueous solutions of alkalis, monoethanolamine, etc. can be used as the alkaline agent.
  • a solution of ligand in acetonitrile is immediately added to the resulting solution in the ratio: per 1 mol of REE salt, 1 mol of a ligand containing more than 2 oxygen atoms (for example, triethylene glycol, ethyl carbitol, tetraethylene glycol); or per 1 mol of REE salt, 2 moles of a ligand containing 2 oxygen atoms (e.g. 1, 2-propylene glycol,
  • the resulting complex compound is dissolved in the excess of the ligand used to obtain an auxiliary solution of the complex compound, which is used to prepare the pharmaceutical composition.
  • aqueous solution of a water-soluble salt of the rare-earth element of the cerium subgroup for example, nitrate hexahydrate or hydrochloride hexahydrate of lanthanum, cerium, praseodymium or neodymium, or mixtures thereof.
  • a ligand triethylene glycol, or tetraethylene glycol, or 1,2-propylene glycol, or 1,3-propylene glycol, or ethylcarbitol, or 1, 3-butyl glycol
  • a ligand triethylene glycol, or tetraethylene glycol, or 1,2-propylene glycol, or 1,3-propylene glycol, or ethylcarbitol, or 1, 3-butyl glycol
  • compositions (FCs) containing complex compounds of the general formula (I) are prepared from an auxiliary solution (BP), which is a solution of the complex compound in excess of the ligand (see Table 2).
  • the auxiliary solution containing complex compounds according to the formula (I) has a combination of the following properties and qualities:
  • auxiliary solution as such can be used as a protective, prophylactic, dermatoprotective agent, and can serve as the basis for the creation of pharmaceutical compositions
  • FC can be additionally introduced substances of natural or synthetic origin, acting as a potentiator and increasing its effectiveness.
  • a potentiating agent for example, bactericidal preparations
  • polyethylene oxides of various molecular weights used in the pharmacopeia are added.
  • effective complexing agents oxy compounds with a sufficiently high pK ⁇ value
  • activators polyhydric alcohols, glycerin, sorbitol, glucose, etc.
  • silicones and polyfluorinated compounds are introduced into the composition of auxiliary solution N ° 5 and optimize the viscosity of the medium; in order to impart hydrophobic properties to the pharmaceutical composition, silicones and polyfluorinated compounds are introduced.
  • hyaluronic acid, ascorbic acid, and biological active additives can be added to any composition.
  • Glycerin, mono- and diesters of glycols, sea buckthorn, mink and other oils, fats, waxes, surfactants, both ionic and nonionic, drugs can also be used as potentiators.
  • compositions of the pharmaceutical compositions are given in table.Z. Table 3
  • composition of some pharmaceutical compositions are provided.
  • Example 1 Obtaining an auxiliary solution.
  • the data of IR spectroscopy prove the formation of the indicated complex compound: the absorption band at 415 cm "is observed on the spectrogram, which refers to La-O stretching vibrations; the bands at 670-680 cm “ 1 , which are characteristic for OH deformation vibrations in La-OH planes; in the region of 1730-1770 cm “1 , several bands appear confirming the existence of a bidendant nitrate ion.
  • a complex compound of the indicated composition was isolated from the resulting solution.
  • IR spectrum of the complex compound isolated from the auxiliary solution, RG spectrum of the solution after dissolving of the complex compound in triethylene glycol and the RJ spectrum of the auxiliary solution are identical.
  • Coordination polyhedron lan the tana is an irregular 16-faceted atom.
  • the lanthanum atom coordinates 10 oxygen atoms: 4 from two bidendant nitrate ions; 4 from a triethylene glycol molecule; 1 from a hydroxo group; 1 from water.
  • Example 2 Obtaining the drug in the form of a solution (hereinafter - “Lantaderm solution”) 25 g of ethylcarbitol are poured into 75 g of the auxiliary solution (obtained from the recipe of Example 1) and stirred at a temperature of 40-50 0 C.
  • Example 3 Preparation of the preparation in the form of a gel (hereinafter referred to as “Lantaderm gel”) ⁇ 100 g of hydroxypropyl cellulose is added to 100 g of Lantaderm solution (obtained from the recipe of Example 2), intensively stirred at a temperature not exceeding 5O 0 C until formation homogeneous mass and cool.
  • Example 4 Obtaining the drug in the form of an ointment (hereinafter - “Lantaderm-ointment)
  • Examples 5 to 11 illustrate the harmlessness of FC. They are not toxic, do not affect the indicators of the general condition of the body, do not have a sensitizing and mutagenic effect.
  • Example 5 Assessment of acute toxicity
  • Liderm-gel No negative effects were found on the functions of the cardiovascular and endocrine systems, the activity of the kidneys and liver, the hematopoiesis system, and the fluctuations in the weight coefficients of internal organs. Clinical and biochemical studies of blood and urine, anatomical and histological studies of the liver, spleen, kidneys, organs of the cardiovascular and nervous systems, respiratory and digestive systems showed that the drug does not cause any pathological changes.
  • Irritation of the skin of rabbits when applying FK-4, FK-6, FK-5 and the drug "Lantaderm” (solution, gel, ointment) for 10 days with an exposure of 6 hours is absent.
  • Irritation of rabbits' eyes was characterized by short-term blindness of their eyes for (35 + 21) seconds, slight hyperimia passing through 1 - 4 hours, and in some cases - lacrimation. After 4 hours and the following days, no changes in the eyes were observed.
  • the mutagenicity of the Lantaderm preparations (solution, gel, ointment) and FK-9 was studied by the method of accounting for chromosomal aberrations in a human whole blood culture. Found that the drug
  • Lantaderm solution, gel, ointment
  • FK-9 do not have a damaging cytogenetic effect on human blood cells in vitro.
  • Example 10 Tolerance. Tests of tolerability of the Lantaderm-solution in experiments on healthy volunteers (2 groups of 20 people) included clinical observation, examination of a dermatologist, studies of clinical blood and urine tests, blood biochemistry, determination prothrombin index and fibrinogen concentration in the blood, the study of detailed electrocoagulograms. The results showed that repeated application of the drug does not have a general and local toxic effect on humans, including the blood coagulation process.
  • FCs exhibit antimicrobial and fungicidal activity, have a fairly wide range of prophylactic effects, inactivate various classes of chemicals, protecting the skin from exposure to harmful substances.
  • Example 12 The study of the bactericidal and bacteriostatic properties of the drugs "Lantaderm” (solution, ointment) and FC-6 was carried out in relation to clinical strains of pathogenic staphylococcus, Escherichia coli and Pseudomonas aeruginosa, Proteus according to standard methods.
  • Epterobastereasae Starhulossossus aureus, Pseudomopas aeschipos.
  • Example 13 The study of microbial contamination of the hands was carried out on volunteers.
  • the drug “Lantaderm-solution” was applied to the skin of the hands with a flow rate of 0.3-0.5 g / dm 2 of the skin surface, the excess of the drug was removed with a paper towel in blotting movements. 6 hours after application of the drug, hygienic washings were carried out, in which the presence of microorganisms was determined. It was established that 6 hours after the start of the experiment, the skin surface remains sterile, no bacteria of the E. coli group and other microorganisms were found in hygienic washings. According to the subjective assessment of the subjects, the drug "Lantaderm-solution” has a softening effect.
  • Example 14 The study of the fungistaticity of the preparations “Landerderm-gel”, “Lantaderm-oil” and FC-5 was carried out according to standard methods for Fusarium solapi, Fusarium pivella, Vutrutis siperia,
  • Asrergillus piger as well as in relation to pathogenic fungi that cause fungal skin diseases: corynebacteria, Malassesia
  • Example 15 Complexation with salts of heavy metals.
  • the drug “Lantaderm-solution”, FK-4, FK-9 contain up to 85% (total) acidic solvents (triethylene glycol, ethylcarbitol, glycerin, propylene glycol, tetraethylene glycol), which have quite a lot of active centers (oxygen atoms with lone electron pairs) and are able to enter into a complexation reaction with salts of heavy metals.
  • active centers oxygen atoms with lone electron pairs
  • the indicated classes of chemical compounds are fat soluble. They disrupt the water-lipid balance of the skin, "washing out” lipids from the epidermis, easily penetrate the skin and can cause a number of pathological processes in the skin.
  • the composition of the FC includes hydrophilic solvents that are not miscible with fat-soluble substances.
  • organophosphorus compounds including insecticides
  • the skin-resorptive toxicity of organophosphorus compounds for warm-blooded animals varies widely.
  • An important property of substances of this group is the cumulative effect. Therefore, even substances with sufficiently low toxicity (for example, isopropylurethane phosphoric acid dimethyl ether, LD 5O more than 5000 mg / kg for white mice) can cause severe poisoning.
  • substances with sufficiently low toxicity for example, isopropylurethane phosphoric acid dimethyl ether, LD 5O more than 5000 mg / kg for white mice
  • One of the most characteristic manifestations of the biological effect of organophosphorus compounds is the inactivation of blood cholinesterase.
  • Example 18 Protection of the skin from aqueous solutions of acids and alkalis.
  • Lantaderm preparations (solution, gel, ointment) are a buffer system with a neutral value of the conditional pH. 10 ml of the Lantaderm-solution preparation completely neutralizes ⁇ 15 g of a 10% aqueous solution of caustic soda and ⁇ 18 g of a 10% aqueous solution of sulfuric acid, while the conditional pH of the preparation remains almost constant.
  • preliminary application of the drug to the skin due to the neutralization reaction provides effective prevention of chemical burns in case of accidental contact with drops of caustic alkalis and strong acids.
  • Examples 19-21 indicate the ability of FCs to optimize skin self-healing processes and confirm efficacy in the treatment of chemical burns, professional contact dermatitis of an allergic and non-allergic form, damage to the skin and soft tissues.
  • Example 19 The skin is the only self-healing organ. A special mechanism for self-healing and reorganization is activated immediately after any damage. Depending on the exposure factor, the response of the body is, first of all, a change in the condition of the skin, expressed in the form of inflammation and aimed at reducing the degree of this effect. Inflammation of the skin occurs as a result of damage to its tissues by a wide variety of agents: mechanical (injuries, bruises, injuries), physical (burns, frostbite, irradiation), chemical (damage by strong acids, alkalis, ADHD, toxic chemicals, surface-active substances), biological (the introduction of bacteria, fungi, viruses). In case of overcoming the higher threshold of resistance, local or generalized skin damage develops. Therefore, one of the main tasks of a topical pharmaceutical product is to create optimal conditions for the manifestation of the regenerative abilities of tissues and the body as a whole.
  • the developed skin lesion in the first group of animals After the developed skin lesion in the first group of animals, they were treated with the Lantaderm-Maz drug in a dose of 0.5 g / dm 2 (4 hours after the toxicant was applied, then 1 time per day for 10 days); in the second group of animals - the preparation of the prototype [9] at a dose of 0.5 g / dm 2 (4 hours after application of the toxicant, further 1 time per day for 10 days); in the third (control) group - without treatment.
  • the first group On the second day, the edema is insignificant, localized in places where the toxicant was applied, there is no redness of the skin. After 5 days, the condition of the skin significantly improved: the thickness of the skin fold began to approach normal, hyperemia and swelling of the skin were not observed, in the places where the toxicant was applied, there was a soft scab under which growing granulations are visible. After 7-10 days, the skin is completely restored. The second group. On the second day, edema decreased significantly.
  • the third group (control).
  • a maximum level of damage develops, which is characterized by ulceration and areas of necrosis that capture the deep layers of the skin.
  • the toxicant drops In places where the toxicant drops are applied, there are coarse crusts, in some cases intense melting of skin tissues.
  • ulcers with purulent hemorrhagic effusion formed on the skin of animals.
  • Example 20 The treatment of chemical burns with the drug "Lantaderm-maz” and FC-8.
  • the experiments were carried out on white rats.
  • the first group - a chemical burn of 3 degrees when exposed to concentrated sulfuric acid; treatment under dressings with the drug "Lantaderm-maz”; dressing change 1 time per day.
  • the second group - a chemical burn of 2 degrees with exposure to 50% aqueous sodium hydroxide solution; treatment under dressings FK-8; dressing change 1 time per day.
  • the third group (control) treatment of a chemical burn of the 2nd degree under dressings with the drug Dermazin, traditionally used to treat burns.
  • Example 21 Prevention and treatment of contact dermatitis.
  • a big problem is professional contact dermatitis that occurs when direct contact with aggressive chemicals (solutions of salts of acids and alkalis, gasoline and organic solvents, fuels and lubricants, cement, detergents and cleaners, etc.).
  • aggressive chemicals solutions of salts of acids and alkalis, gasoline and organic solvents, fuels and lubricants, cement, detergents and cleaners, etc.
  • the effectiveness of the treatment of professional contact dermatitis is considered on the example of contact latex dermatitis (allergic and non-allergic forms) when using the drug “Lantadermaz”.
  • Example 22 The effectiveness of the drug in the treatment of damage to the skin and soft tissues.
  • “Lantaderm” preparations solution, ointment) were used in high altitude conditions (1800-3200 m above sea level), where reparative processes are significantly reduced due to oxygen deficiency and wounds are infected.
  • In the treatment of injuries to the skin and soft tissues of various sizes and depths marked a decrease in the healing time of wounds, the absence of infection and the manifestation of allergic reactions.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Epidemiology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Dermatology (AREA)
  • Birds (AREA)
  • Emergency Medicine (AREA)
  • Toxicology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Inorganic Chemistry (AREA)
  • Business, Economics & Management (AREA)
  • Emergency Management (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention appartient au domaine des préparations pharmaceutiques utilisées pour protéger le derme contre les facteurs nocifs d'origine chimique ou biologique, les infections bactérienne et fongique, dans la prévention des maladies professionnelles de la peau, des dermatites de contact, y compris celles d'origine allergique ainsi que pour les premiers secours et les secours médicaux et un traitement ultérieur des affections de la peau, des tissus mous et de la muqueuse. Elle peut s'utiliser en industrie, en construction, en agriculture, en médecine et dans le ménage. L'invention concerne une composition dermatologique de traitement et de prévention destinée à l'usage topique, qui comprend un principe actif se présentant comme des compositions complexes de sels d'éléments de terres rares et un excipient pharmaceutiquement acceptable. Lors de l'utilisation de la composition pharmaceutique à base de compositions complexes de terres rares avec des composés polyoxydés sous une forme médicamenteuse molle ou liquide on a noté d'importants effets prophylactique, protecteur, curatif et dermoprotecteur.
PCT/RU2005/000439 2005-08-29 2005-08-29 Composition dermatologique WO2007027118A1 (fr)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014074007A1 (fr) * 2012-11-12 2014-05-15 Polyakov Viktor Stanislavovich Composition dermatologique avec propriétés indicatrices
CN110938565A (zh) * 2019-12-06 2020-03-31 江西理工大学 一种蜡样芽胞杆菌及其用于稀土离子回收的方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2050849C1 (ru) * 1992-03-17 1995-12-27 Войсковая часть 61469 Средство для лечения гнойных ран
RU2137465C1 (ru) * 1997-04-29 1999-09-20 Государственный научно-исследовательский институт органической химии и технологии Состав для защиты и дегазации кожи от фосфорорганических отравляющих веществ и инсектицидов и способ его получения
RU2177314C2 (ru) * 2000-03-22 2001-12-27 Кривошеин Юрий Семенович Состав с антисептическими, репаративными и болеутоляющими свойствами
RU2221802C1 (ru) * 2002-07-04 2004-01-20 Поляков Виктор Станиславович Комплексы подандов с редкоземельными элементами, проявляющие репаративные свойства, способ их получения и фармацевтическая композиция на их основе

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2050849C1 (ru) * 1992-03-17 1995-12-27 Войсковая часть 61469 Средство для лечения гнойных ран
RU2137465C1 (ru) * 1997-04-29 1999-09-20 Государственный научно-исследовательский институт органической химии и технологии Состав для защиты и дегазации кожи от фосфорорганических отравляющих веществ и инсектицидов и способ его получения
RU2177314C2 (ru) * 2000-03-22 2001-12-27 Кривошеин Юрий Семенович Состав с антисептическими, репаративными и болеутоляющими свойствами
RU2221802C1 (ru) * 2002-07-04 2004-01-20 Поляков Виктор Станиславович Комплексы подандов с редкоземельными элементами, проявляющие репаративные свойства, способ их получения и фармацевтическая композиция на их основе

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014074007A1 (fr) * 2012-11-12 2014-05-15 Polyakov Viktor Stanislavovich Composition dermatologique avec propriétés indicatrices
CN110938565A (zh) * 2019-12-06 2020-03-31 江西理工大学 一种蜡样芽胞杆菌及其用于稀土离子回收的方法

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