RU2197971C1 - Biologically active composition - Google Patents

Abstract

FIELD: medicine, cosmetology, food industry. SUBSTANCE: invention deals with chitosan-based biologically active composition being the powerful stimulator in healing surface wounds, such as burns, ulcers and others. It, also, removes skin irritation, quickly restores cutaneous function in case of bedsores in severe patients. The suggested composition of biologically active composition contain chitosan gel or chitosan suspension at spheroidal nanogranules size being not above 100 nm and ions of precious metals at the quantity of 10 wt.%, not higher. The invention enables to achieve improved quality of biologically active composition due to increasing its penetrating capacity and healing and disinfecting action. EFFECT: higher efficiency. 2 cl, 5 ex

Description

 The invention relates to the production of cosmetic, medical-cosmetic, pharmacological preparations and food additives, including chitosan, and can be used in medicine, cosmetics and the food industry.

 In the production of food and medical and cosmetic preparations, various biologically active substances of both animal and vegetable or mineral origin are widely used. By activating the metabolism, they improve the physiological state of the skin when applied externally and the body's immune status when taken orally as a dietary supplement.

 The polycationic polysaccharide chitosan, a product of chitin deacetylation, is widely used in various industries, biotechnology, medicine and cosmetics.

 Known composition for skin care in the form of a gel, including chitosan, a vitamin preparation and distilled water, which additionally contains an antiseptic (vantol or nibazine with nibazole) and anesthetic, and as a vitamin preparation a complex of pyridoxine hydrochloride and water-soluble beta-carotene preparation "Vetoron" (RF patent 2085187, A 61 K 7/48, 07.27.1997).

 A drug is known to have anti-inflammatory and analgesic effects, containing an aqueous-alcoholic extract from plant materials and a pharmaceutically acceptable carrier, chitosan gel, using a poultry catcher as plant materials (Patent RF 2154488, A 61 K 35/78, 08.20.2000).

 Known agent for the treatment of infected wounds and burns. The product contains chitosan, medical phenol, resorcinol; boric acid; dimethyl sulfoxide; potassium iodide; glacial acetic acid; glycerol; anesthetic distilled water - the rest (RF Patent 2140264, A 61 K 31/00, 10.27.1999).

 Known water-soluble silver-containing bactericidal composition used to treat wounds and burns, which contains highly dispersed metallic silver and poly-N-vinylpyrrolidone with a metal content of 0.01-1.0 wt. % with high antimicrobial activity (RF Patent 2128047, A 61 K 31/79, 03/27/1999).

 The disadvantage of all known compositions is that they have a relatively low penetration into the subcutaneous layers due to the large size of chitosan granules in the gel, as well as low disinfecting ability.

 The objective of the invention is to improve the quality of the biologically active composition by increasing its penetrating ability and healing and disinfecting effects.

 The problem is solved by the proposed composition of the biologically active composition containing a chitosan gel or chitosan suspension with a size of spherical nanogranules of not more than 100 nm and noble metal ions in an amount of not more than 10 wt. % An increase in the content of noble metals leads to a rise in price of the composition without quality improvement, and in some cases it can cause allergic reactions.

 A chitosan gel is prepared by dispersing an acidic aqueous solution of chitosan in the presence of a hydrophobic surfactant and acetone by stirring at a speed of at least 1000 rpm, followed by modification of the emulsion obtained with additional stirring at the same speed, treatment with an alkali solution, washing to a neutral pH, wringing and stirring in an aqueous medium with the addition of acid, approved for use in cosmetology and pharmacopeia.

A chitosan suspension is prepared by dispersing an acidic aqueous solution of chitosan in the presence of a hydrophobic surfactant and acetone by stirring at a speed of at least 1000 rpm, followed by modification of the emulsion obtained with additional stirring at the same speed, adding distilled water, stirring for at least 2 min at a speed of at least 1000 rpm and pasteurization at a temperature of no higher than 80 ^o C for 3-5 hours

 The widespread use of chitosan as a cosmetic and therapeutic drug is limited by the fact that due to its insolubility in water and high viscosity of chitosan, its access to the deeper layers of the skin and mucous membrane is severely limited. Many developers see a solution to the problem in creating forms of chitosan with increased permeability to the skin and mucous membranes. Attempts to achieve this effect by reducing the molecular weight or adding low molecular weight forms of chitosan to ointment fatty preparations do not give the desired result due to the deterioration of the healing properties of chitosan and the ease of use of such drugs. Another approach to solving the problem is to obtain forms of chitosan with a submicron particle size similar to liposomes and able to penetrate the skin and mucous membrane, actively interacting with the skin barrier.

 A chitosan gel or suspension is prepared on the basis of natural chitosan obtained from the shells of king crab and converted to a microspherical form, which provides high ability to overcome the skin barrier and directly affect the function of deep tissues, including causing and increasing the immune properties of the subcutaneous layers and mucous membranes.

 In addition, chitosan gel based on microspheres / microgranules is a supplier of various substances necessary for the body to the subcutaneous layers.

 The invention is illustrated by the following examples.

 Example 1

Biologically active composition composition, wt.%:
Chitosan Gel - 99.5
Silver - 0.5
In the clinical department of the Research Institute of Clinical and Experimental Lymphology SB RAMS, a series of clinical trials was carried out to study the comparative effectiveness of chitosan gel and silver applications in the treatment of patients with lower limb lymphedema in a series of conservative methods.

 In order to evaluate the effectiveness of the proposed methodology of the drug, 65 case histories of patients with lymphedema of the lower extremities of stage 2-3 who were treated were analyzed. In the course of the work, the state of the local protective reaction of the body (Ribak test) was studied, changes in the state of the lymphatic region of the affected lower extremities (rheovasolymphography), and the dynamics of edema (anthropometry, ultrasound) were assessed. Treatment results were compared with traditional conservative treatments.

 As a result of the studies, it was proved that the use of chitosan gel applications with silver as part of the complex treatment of patients with lower limb lymphedema of the 2-3 stage allows to realize a positive clinical effect in 75% of patients.

 With local exposure, nonspecific activation of the local protective reaction of the body occurs with lymphedema of the lower extremities, which is manifested by a significant increase in the number of macrophages in the late phase of cell migration in the area of gel application by 67.7-70.5%.

 The use of applications allows a 2-fold increase in the volume of lymphatic outflow compared to traditional conservative treatment, which is accompanied by a pronounced decrease in limb edema.

 The use of applications can increase the rate of lymphatic outflow by 68% compared with traditional conservative treatment.

 Thus, the use of chitosan gel in lymphatic edema of the lower extremities, according to rheovasolymphography and ultrasound of the subcutaneous tissue, can significantly activate lymphatic outflow in the affected limb and reduce the degree of edema compared to existing treatment methods, which leads to the activation of sanogenic changes in the endoecological space of the lymphatic collector.

 Example 2

Biologically active composition (suspension) to normalize the activity of the gastrointestinal tract, increase the overall immunity of the body composition, wt.%:
Chitosan suspension (milk) - 99.5
Silver - 0.5
Chitosan milk with silver allows you to sharply and synergistically enhance the action of each of the components in the direction of normalizing the activity of the gastrointestinal tract and increasing the overall immune background of the body and can be used as a food supplement.

 Example 3

Biologically active composition (gel) with noble metal ions for a disinfecting effect on the skin - (antiparasitic drug) composition, wt.%:
Chitosan Gel - 99.9
Silver and Gold - 0.1
Ions of noble metals in small concentrations have the ability to suppress pathogenic microflora.

 Using the composition: "chitosan gel + noble metal ions" provides a sharply healing and disinfecting effect in skin fungal and parasitic diseases. Noble metal ions have a disinfecting effect, and chitosan gel ensures their active delivery to the deeper layers of the skin, and also causes an active immune response (the concentration of macrophages increases up to several times) at the place of application of the composition.

 Example 4

Biologically active composition for the treatment of burns composition, wt.%:
Chitosan Gel - 98.5
Silver - 1.5
On the basis of the Novosibirsk Inter-Territorial Burn Center, a cream containing chitosan gel and silver was tested. The object of the study was patients with thermal burns with an area of 1 to 10% and their consequences at the age of 15 to 68 years. In total, the drug was used in 94 people.

The following results were obtained:
With superficial burns of the 1st degree (in 56 people) in the first hours after the injury, the use of the cream leads to subsidence or complete disappearance of pain within 3-5 minutes. If the pain syndrome persists, repeated application after 3-4 hours leads to anesthesia. In the future, the pain did not recur and healing was observed after 1-2 days.

 The application of cream on deep burns of 3-4 degrees (in 10 people) after the restoration of the integrity of the skin led to an acceleration of the discharge of the crusts, prevented the drying out of the young epidermis, and helped to reduce discomfort.

 Example 5

Biologically active composition for cosmetic purposes, composition, wt.%:
Chitosan Gel - 99.5
Silver - 0.5
Chitosan gel forms a thin protective coating on the surface of the skin, protecting the skin from excessive moisture loss, as well as the harmful effects of the external environment, including the action of ultraviolet rays, and silver ions have a disinfecting effect.

 Thus, the proposed biologically active composition based on microgranular chitosan with spherical nanogranules no larger than 100 nm in size and containing noble metal ions is a powerful stimulator of healing of superficial wounds - burns, ulcers, etc., relieves skin irritations, quickly restores skin function in bedsores in severe patients and can be used for medical, cosmetic purposes, as well as as a dietary supplement.

 In addition, it is a powerful activator of the body's immune system, acting through stimulation of the synthesis of a number of lymphokines.

Claims (3)

 1. A biologically active composition for medical and cosmetic purposes, as well as for use as a food supplement, containing a chitosan gel or chitosan suspension with a spherical shape of granules of a spherical shape of not more than 100 nm and noble metal ions in an amount of not more than 10 wt.%.  2. The biologically active composition according to claim 1, characterized in that it contains a chitosan gel obtained by dispersing an acidic aqueous solution of chitosan in the presence of a hydrophobic surfactant and acetone by mixing at a speed of at least 1000 rpm, followed by modification of the emulsion obtained with additional stirring at the same speed, treatment with an alkali solution, washing to a neutral pH, spinning and stirring in an aqueous medium with the addition of acid approved for use in braids metrology and pharmacopeia. 3. The biologically active composition according to claim 1, characterized in that it contains a chitosan suspension obtained by dispersing an acidic aqueous solution of chitosan in the presence of a hydrophobic surfactant and acetone by stirring at a speed of at least 1000 rpm, followed by modification of the emulsion obtained with additional stirring at the same speed, adding distilled water, stirring for at least 2 minutes at a speed of at least 1000 rpm and pasteurization at a temperature of no higher than 80 ^o C within 3-5 hours