RU2659959C1 - Composition of the preparation for correction of skin defects - Google Patents

Abstract

FIELD: cosmetology.

SUBSTANCE: invention relates to cosmetology. Skin defect correction composition comprising hyaluronic acid and glycerin according to the invention further comprises palmitoyl dipeptide-5 diaminobutyroyl hydroxytreonine, palmitoyl dipeptide-5 diaminohydroxybutyrate, palmitoyl tripeptide-5, recombinant fibroblast growth factor basic, recombinant epidermal growth factor and DMEM F12 nutrient medium, the components in the composition being in a certain ratio, %.

EFFECT: invention provides production of its own components, namely hyaluronic acid, collagen and elastin, while it has a strong antioxidant property and a pronounced long-term effect of correction of skin defects.

2 cl, 4 tbl, 4 ex

Description

The invention relates to the composition of a drug containing hyaluronic acid for the correction of skin defects.

Closest to the claimed invention is the application for the grant of US patent No. US 20110230438 IPC A61K 31/728; А61Р 17/00 "Viscoelastic gel for dermatological use." A polysaccharide gel of natural origin, which is used for injection in dermatology, characterized in that it contains an aqueous solution of the polysaccharide in an amount of 0.1-5 wt.% / Vol. And a viscous and highly hydrophilic biocompatible alcohol at 0.5-5 wt. % / The volume obtained by preparing an aqueous solution of polysaccharide and alcohol, then sterilizing this solution and, optionally, adjuvants, which are usually used in dermatology, as a result of which sterilization after mixing the components has the effect of significantly increasing the viscosity of the resulting gel. The gel of claim 1, wherein the polysaccharide is hyaluronic acid. The gel of claim 1, wherein the biocompatible alcohol is glycerol. The gel according to claim 1, in which the aqueous solution contains 1.8 wt. % / The volume of hyaluronic acid with an average molecular weight (from 0.5 to 1.8 MDa) and 2 wt. % / Volume of glycerol. The gel according to claim 1, in which the aqueous solution contains 1.5 wt. % / Volume of high molecular weight hyaluronic acid (2.0-3.0 MDa) and 2 wt. % / Volume of glycerol.

The disadvantages of this gel for dermatological use is that the gel does not stimulate the production of its own components of the extracellular matrix, but is aimed exclusively at filling the tissues.

The objective of the invention is to create an active composition of the drug for the correction of skin defects, which additionally stimulates the production of its own components, namely: hyaluronic acid, collagen and elastin, while having strong antioxidant properties and a pronounced long-term effect of correction of skin defects of the skin.

The problem is solved due to the fact that the composition of the preparation for correction of skin defects includes: hyaluronic acid, glycerin, palmitoyl dipeptide-5 diaminobutyroyl hydroxytreonine, palmitoyl dipeptide-5 diaminohydroxybutyrate, palmitoyl tripeptide-5, recombinant basic growth factor fibroblast and culture medium DMEM F12. The composition of the drug for the correction of skin defects is performed in the following ratio of components, mass%: hyaluronic acid 1.0-2.0, glycerol 1.0-4.9, palmitoyl dipeptide-5 diaminobutyroyl hydroxytreonine 0.00001-0.001, palmitoyl dipeptide-5 diaminohydroxybutyrate 0.00001-0.001, palmitoyl tripeptide-5 0.00001-0.001, the main recombinant fibroblast growth factor 0.0000005-0.00001, the recombinant epidermal growth factor 0.0000005-0.00001, the medium DMEM F12 - the rest. The composition of the preparation for the correction of skin defects contains the following components in the following ratio of components, mass%: hyaluronic acid 1.0-2.0, palmitoyl dipeptide-5 diaminobutyroyl hydroxytreonine 0.00001-0.001, palmitoyl dipeptide-5 diaminohydroxybutyrate 0.00001-0.001, palmitoyl tripeptide-5 0.00001-0.001, the main recombinant fibroblast growth factor 0.0000005-0.00001, the recombinant epidermal growth factor 0.0000005-0.00001, the medium DMEM F12 - the rest.

People have always sought to look younger and fresher, therefore, from the time of Ancient Rome, they developed cosmetic products that rejuvenate the skin, these products were made on a plant and animal basis. Currently, we have enormous potential for changing the composition of funds intended for the correction of skin defects, all these changes are aimed at enhancing the effect. The main achievement of scientists in the field of cosmetology was the production of synthesized hyaluronic acid, which is the main participant in the skin regeneration process. The bulk of the compositions intended for the correction of skin defects includes hyaluronic acid.

However, hyaluronic acid alone is not enough to restore and correct the skin, so modern cosmetologists are constantly modifying the composition.

The authors of the proposed composition of the drug for the correction of skin defects have created an effective composition for skin correction, which can further stimulate the development of its own components of the extracellular matrix, thereby prolonging the effect of the drug. To do this, they introduced additional components in the form of vitamins, minerals, amino acids and a nutrient medium that had not previously been used for such drugs.

The essence of the claimed invention lies in the fact that the composition of the preparation for the correction of skin defects includes: hyaluronic acid, glycerin, palmitoyl dipeptide-5 diaminobutyroyl hydroxytreonine, palmitoyl dipeptide-5 diaminohydroxybutyrate, palmitoyl tripeptide-5, recombinant growth factor-1 recombinant growth factor and culture medium DMEM F12. The composition of the drug for the correction of skin defects is performed in the following ratio of components, mass%: hyaluronic acid 1.0-2.0, glycerol 1.0-4.9, palmitoyl dipeptide-5 diaminobutyroyl hydroxytreonine 0.00001-0.001, palmitoyl dipeptide-5 diaminohydroxybutyrate 0.00001-0.001, palmitoyl tripeptide-5 0.00001-0.001, the main recombinant fibroblast growth factor 0.0000005-0.00001, the recombinant epidermal growth factor 0.0000005-0.00001, the medium DMEM F12 - the rest. The composition of the preparation for the correction of skin defects contains the following components in the following ratio of components, mass%: hyaluronic acid 1.0-2.0, palmitoyl dipeptide-5 diaminobutyroyl hydroxytreonine 0.00001-0.001, palmitoyl dipeptide-5 diaminohydroxybutyrate 0.00001-0.001, palmitoyl tripeptide-5 0.00001-0.001, the main recombinant fibroblast growth factor 0.0000005-0.00001, the recombinant epidermal growth factor 0.0000005-0.00001, the medium DMEM F12 - the rest.

The most important role in stimulating the production of intrinsic extracellular matrix components - hyaluronic acid, collagen and elastin, was played by the addition of components such as DMEM F 12 nutrient medium in combination with growth factors to the composition of the skin to correct skin defects.

Nutrient medium DMEM F12 without an indicator for cell cultures, containing glucose, organic and inorganic salts, a complex of essential and non-essential amino acids, nucleotides and vitamins, provides optimal conditions for the functioning of skin fibroblasts. The balanced composition of the medium increases the synthetic and proliferative activity of skin fibroblasts and keratinocytes, and also enhances the ability of skin cells to withstand oxidative stress. Those. this environment is unique, from the point of view of cell physiology, for the normal development, division and operation of the main skin cells-fibroblasts, keratinocytes and skin immunity cells. And, as a result, filling the deficit of the intercellular matrix.

Nutrient medium DMEM F-12, is a mixture of inorganic salts, amino acids, vitamins, glucose and phenol red dissolved in water, sterilized through filters with a pore size of 0.1 μm. Nutrient medium DMEM F-12 is a mixture of nutrient media DMEM and F-12 in a ratio of 1: 1, but is prepared from individual components.

The drug is a clear liquid, reddish-orange in color, without opalescence and sediment. It does not contain antibiotics, pH from 7.0 to 7.4, osmolarity 300 +/- 20 mosmol / kg, buffer capacity: at least 3.7 ml.

Nutrient medium DMEM F-12 is used to cultivate a wide range of animal and human cells. It can be used as a basis for creating serum-free media.

The nutrient medium DMEM F-12 in a ratio of 1: 1 is used for growing a wide range of cell cultures. Due to its rich nutrient content, relatively small amounts of fetal bovine serum (FBS) can be added to the DMEM F-12 nutrient medium, or used without serum, but then factors such as insulin, transferrin, and epidermal growth factor must be added. and others. In the state register of medicines, the nutrient medium DMEM F-12 is located under No. 4603993000444 (Medium nutricum DMEM fluidum sterilis)

Recombinant human fibroblast growth factor FGF, the main one, is used for cultural work as an additive to nutrient media. Provides the growth and proliferation of fibroblasts in culture. It is a 154 amk polypeptide of size 17.2 kDa. Purity greater than 95% according to SDS PAGE.

Growth factors are protein molecules that regulate cell division and survival. Growth factors bind to receptors on the surface of cells, thereby activating cell proliferation and / or differentiation. Growth factors are quite universal and stimulate cell division in various types of cells, while some of them are specific only to certain types of cells. Growth factors are proteins that stimulate cell growth.

Fibroblast growth factor (FGF-) or basic fibroblast growth factor (basic - bFGF) (Recombinant Human Fibroblast Growth Factor-basic) is a member of a large family of structurally similar proteins that affect the growth, differentiation, migration and viability (survival) of cells of various origins . The FGF protein stimulates the growth and development of new blood vessels (angiogenesis), as well as normal wound healing and tissue growth. It can serve as a therapeutic agent for the treatment of wounds of various origins, and when it is introduced into the body, there are no significant side effects and general toxicity. FGF protein is effective both in the treatment of superficial wounds and burns, and in acute damage to internal organs. It contributes to the treatment of non-healing wounds of various origins, including wounds arising from radiation damage and diabetes. Currently, recombinant FGF preparations are considered as good agents for the treatment of wounds of various origins.

The method of obtaining.

The composition of the preparation for correction of skin defects is prepared as follows: all components of the composition, with the exception of sodium hyaluronate, are dissolved in the required concentrations and sterilely filtered through sterilizing membranes with a pore size of 0.22 μm into sterile vials. Separately, sodium hyaluronate is prepared by dissolving it in sterile physiological saline, then it is poured into sterile vials and sealed with cotton-gauze plugs, and then sterilized in a steam sterilizer. Next, all components of the composition of the preparation are mixed in order to correct skin defects, including sodium hyaluronate, in a sterile laminar box.

The composition of the preparation for the correction of skin defects “Dermal material is sterile for the correction of skin defects” is intended for the correction (restoration, replacement) of skin defects (for example, wrinkles, wrinkles, scars) that have arisen during aging as a result of trauma or degenerative damage, as well as stimulation of the production of its own components, namely: hyaluronic acid, collagen and elastin. The above effect of the composition of the drug for the correction of skin defects is confirmed by a description of the principle of operation of the components of the composition (see table 1).

The composition of the preparation for the correction of skin defects is a sterile absorbable substance intended for introduction into the dermis / hypodermis of the skin; the substance serves as a space-filling volumetric additive to the intracellular matrix of connective tissue; it is used to correct skin defects (wrinkles, wrinkles, scars) that have occurred during aging, as a result of trauma or degenerative damage. The preparation for the correction of skin defects is packaged in ampoules. A preparation for the correction of skin defects for single use. The preparation for the correction of skin defects refers to medical devices for plastic surgery, dermatology and cosmetology.

The invention is illustrated by the following examples, where all patients were introduced the composition of the drug for the correction of skin defects of 3 ml per procedure, 3-4 times with an interval of 2 weeks.

In this case, when choosing patients, one of the following indications for use was taken into account:

- Age-related skin changes.

- The need to prevent involutional skin aging.

- Dehydration of the skin.

- Change in skin color.

- The appearance of superficial wrinkles.

Also, when choosing patients, one of the following contraindications for use was taken into account:

- Active inflammatory processes in places of the alleged introduction and adjacent areas.

- Allergic reactions to one of the components of the drug.

- The tendency to form hypertrophic scars.

- Propensity to bleeding.

- Thrombolytic or anticoagulant therapy in the last 2 weeks.

- Acute viral or bacterial infections or related conditions.

- Pregnancy and lactation.

With the introduction of the composition of the drug for the correction of skin defects, the following methods of application and dosage were used:

Intradermal injections using the technique of deep dermal papules and linear retrograde technique. Thorough face cleansing and aseptic treatment with 0.05% aqueous solution of chlorhexidine digluconate 0.05%. In this case, a needle No. 30G or 32G with a length of 4, 6 or 13 mm was used. The maximum amount of drug administered per 1 injection was limited to no more than 0.1 ml (the number of injections is determined individually). When working on very painful and sensitive areas, the skin was captured in a crease to mitigate subjective pain.

At the same time, patients were recommended a course of 4-6 procedures with an interval of 15-20 days, with a flow rate of 1 ml of 3 ml and recommendations for repetition 1-2 times a year.

All patients were warned about the time and rules of the recovery period, in which:

- the injection site for the correction of skin defects should not be subjected to intense heating or strong cooling until the primary swelling and redness disappear.

- until complete restoration of the normal state of the skin after implantation, do not use laser irradiation, chemical peeling and other procedures that can contribute to the development of inflammatory reactions at the implantation site.

Patients were also warned of possible side effects, namely the occurrence of reactions characteristic of injection sites: redness, swelling, pain, tightening, itching, bruising, and soreness at the injection site. Typically, these phenomena disappear within a few days after an injection into the skin.

The authors conducted studies proving that the proposed composition of the drug for the correction of skin defects works with the following ratios, mass%:

.

.

Example 1

The patient is a woman, 50 years old.

Appeal December 19, 2016, wrinkled type of aging. Multiple wrinkles on the face and neck, dull skin color were observed.

The composition of the drug for the correction of skin defects in accordance with table 2 was injected with a needle of 0.3 × 6 mm and 13 mm, deep dermal papule technique and linearly retrograde. Up to 3 ml of the composition of the drug was introduced to correct skin defects.

After the first procedure, there was an increase in skin turgor, a marked reduction in the depth of wrinkles, especially on the neck.

The result after a course consisting of 4 procedures with an interval of 2 weeks:

- increase skin tone, lifting;

- smoothing of fine surface wrinkles and a significant reduction in the depth of deeper folds;

- skin hydration.

Example 2

The patient is a woman of 46 years old.

Appeal on December 21, 2016 regarding skin sagging. Shallow, combined with a tired morphotype of facial aging.

The composition of the drug for correction of skin defects in accordance with table 3 was injected with a needle of 0.3 × 6 mm and 13 mm, deep dermal papule technique and linearly retrograde. Up to 3 ml of the composition of the drug was introduced to correct skin defects.

After the first procedure, an improvement in skin tone and skin turgur was observed, the skin color became uniform, velvety.

After a course of 4 procedures with an interval of 2 weeks:

- visible lifting (including oval face);

- elastic skin with a blush, healthy appearance, smoothing small wrinkles.

Example 3

The patient is a woman of 36 years.

The composition of the drug for the correction of skin defects in accordance with table 2 was injected with a needle of 0.3 × 6 mm and 13 mm, deep dermal papule technique and linearly retrograde. Up to 3 ml of the composition of the drug was introduced to correct skin defects.

Appeal on January 6, 2017 about dry skin, fine wrinkles in the periorbital zone.

The composition of the drug for the correction of skin defects in accordance with table 2 was injected with a needle of 0.3 × 6 mm and 13 mm, deep dermal papule technique and linearly retrograde. Up to 3 ml of the composition of the drug was introduced to correct skin defects.

After one procedure, it was observed:

- increased turgor of the skin (significant thickening, the net of wrinkles in the periorbital zone was almost immediately smoothed out).

After a course of 3 procedures, with an interval of 7 days, the result:

- dense, firm, moisturized, nourished skin;

- wrinkles in the periorbital zone were smoothed out;

The drug was injected with a needle of 0.32 × 4 mm, the technique of a superficial papule.

Example 4

The patient is a woman of 53 years.

Appeal on January 6, 2017. Deformation, combined with a fine wrinkled morphotype, facial aging. There is wrinkling of the skin in the periorbital, perioral zones, the phenomenon of ptosis, a blurry oval, sagging skin in the neck area, deep interbrow wrinkle. After the first procedure, there was a noticeable tightening, an increase in skin tone.

The composition of the drug for the correction of skin defects in accordance with table 4 was injected with a needle of 0.3 × 6 mm and 13 mm, a deep dermal papule technique and linearly retrograde. Up to 3 ml of the composition of the drug was introduced to correct skin defects.

The result after a course of 5 procedures with an interval of 14 days:

- good lifting, tightened oval, reduction of wrinkles and smoothing of surface wrinkles, lip contour seals;

- dense, moisturized skin of the face and in the neck and decollete;

- pronounced lifting effect;

- alignment of skin color.

The advantages of the composition of the drug for the correction of skin defects:

1) an increase in the pool of young, healthy and functional fibroblasts;

2) an increase in the pool of young, healthy and functional keratinocytes;

3) an increase in the production of skin's own collagen, elastin and proteoglycans;

4) delivery directly to the skin of important structural elements — amino acids, peptides, vitamins, antioxidants, and trace elements;

5) normalization of skin immunity and proteolytic enzymes;

6) improving the quality of aging skin - the elimination of the phenomena of gravitational ptosis;

7) smoothing wrinkles and creases;

8) skin color alignment.

All these examples confirm the fulfillment of the task, namely: the creation of an active composition of the drug for the correction of skin defects, which additionally stimulates the production of its own components, namely hyaluronic acid, collagen and elastin, which has strong antioxidant properties and a pronounced long-term effect of correction of skin defects skin.

All the above examples confirm the industrial applicability of the proposed composition of the drug for the correction of skin defects.

Claims (25)

1. The composition for the correction of skin defects, including hyaluronic acid and glycerin, characterized in that it further comprises palmitoyl dipeptide-5 diaminobutyroyl hydroxytreonine, palmitoyl dipeptide-5 diaminohydroxybutyrate, palmitoyl tripeptide-5, recombinant recombinant growth factor fibroblast growth factor and recombinant growth factor medium DMEM F12, in the following ratio of components, mass. %: Hyaluronic acid 1.0 - 2.0, Glycerin 1.0 - 4.9, Palmitoyl Dipeptide-5 diaminobutyroyl hydroxytreonin 0.00001-0.001, Palmitoyl Dipeptide-5 diaminohydroxybutyrate 0.00001-0.001, Palmitoyl tripeptide-5 0.00001-0.001, Recombinant factor fibroblast growth main 0.0000005 - 0.00001, Recombinant epidermal growth factor 0.0000005 - 0.00001, Culture medium DMEM F12 rest. 2. The composition for the correction of skin defects, including hyaluronic acid, characterized in that it further comprises palmitoyl dipeptide-5 diaminobutyroyl hydroxytreonine, palmitoyl dipeptide-5 diaminohydroxybutyrate, palmitoyl tripeptide-5, recombinant fibroblast growth factor basic, recombinant growth factor epidermal recombinant DMEM F12, in the following ratio of components, mass. %: Hyaluronic acid 1.0 - 2.0, Palmitoyl Dipeptide-5 diaminobutyroyl hydroxytreonin 0.00001-0.001, Palmitoyl Dipeptide-5 diaminohydroxybutyrate 0.00001-0.001, Palmitoyl tripeptide-5 0.00001-0.001, Recombinant factor fibroblast growth core 0.0000005-0.00001, Recombinant epidermal growth factor 0.0000005-0.00001, Culture medium DMEM F12 rest.