RU2469704C1 - Regenerin serum for external application with anti-inflammatory and regenerative effect - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: serum for external application with anti-inflammatory and regenerative effect containing a biologically active additive presented by a noisome suspension of size up to 100 nm with included a swine placenta extract, hyaluronic acid, propylene glycol extract of Callisia fragrans and Calendula officinalis in relation 1:1; and a base contains Cyclomethicone DC 345, preserving agent Kathon CG and purified water in certain proportions.

EFFECT: agent described above is able to penetrate in deep skin layers having an effect on keratinocytes.

2 tbl, 2 ex

Description

The invention relates to medicine, in particular to medical cosmetology. The serum is intended for external use, it has a pronounced anti-inflammatory and regenerative effect on the skin with the help of biologically active substances (BAS), which are included in the transdermal carriers - niosomes.

Transdermal products contain components that enhance the permeability of the skin, the so-called enhancers (from the English. Enhance - increase, increase) and the "delivery system", which is a nano-vesicle-niosomes.

Enhancers are the basis of serum for external use (hereinafter referred to as serum) and solve a difficult problem: they must ensure the penetration of biologically active substances (BAS) into the skin and at the same time not cause an allergic skin reaction.

Vegetable oils, fatty acids, organic solvents (ethanol, propylene glycol), surfactants (cationic, anionic and nonionic surfactants) (carboxylic acids and their salts, film-forming compounds (hyaluronic acid) and hygroscopic substances (glycerol) are usually used as enhancers.

Some surfactants are able to form bimolecular layers in oil / water systems due to their amphiphilic properties (the content of water and fat soluble parts in one molecule). Phospholipids and some organosilicon compounds, dimethicone copolyols (esters of alcohols and polydimethylsiloxane), possess such properties. One of these compounds is PEG-12 Dimethicone, capable of forming vesicles, which are an effective delivery system for a wide range of biologically active substances.

Known bactericidal and anti-inflammatory agent in the form of ointments (RF Patent No. 2240780, publ. 11/27/2004), containing: iodine 1,0-2,0; anestezin 0.8-0.9%; beeswax 8.0-9.0; lanolin 17.0-20.0; dimexide 9.0-10.0; fir oil 2.5-3.0 and petroleum jelly - the rest. It has a high anti-inflammatory, bactericidal and regenerative effect in the treatment of a wide range of diseases. The invention provides a quick healing effect.

However, the above agent contains lanolin, a well-known potential allergen that also increases the stickiness of the formulation and impairs the skin's oxygen supply.

Also known is an ointment with a phytocomplex that has anti-inflammatory and wound healing effects (RF Patent No. 2317098, publ. 02.20.2008), containing sea buckthorn oil, arborvitae oil, tincture of calendula, Kalanchoe juice, oil extracts of onion and garlic, aerosil, T emulsifier ₂ , taken in a certain ratio. An ointment with a phytocomplex exhibits a pronounced wound healing, anti-burn and anti-inflammatory effect in combination with the ability to reduce the accumulation of exudate in the focus of inflammation and delay the formation of granulation-fibrous tissue that forms in the second phase of inflammation, which determines the possibility of using the developed dosage form in the field of minor surgery and traumatology.

However, the ointment does not have sufficient transdermal activity due to the lack of transdermal carriers of biologically active substances and does not contain auxiliary components to improve rheological characteristics (increase fluidity, eliminate stickiness).

Closest to the claimed invention is an anti-inflammatory drug for external use and a method for its production (RF Patent No. 2236844, publ. 09/27/2004), containing an 18-20% suspension of liposomes in 0.01 M phosphate buffer pH 7.5 from phospholipids and lipids of animal and plant origin with the included chloroform extract of laurel and sweet clover with a weight ratio of 2: 2: 1, while the chloroform extract of herbs contains an extract from a mixture of laurel and sweet clover in equal amounts in a ratio with chloroform equal to 1:20, and base includes ammonium I am a salt of a rare crosslinked copolymer of acrylic acid and polyallyl esters of pentaerythritol, triethanolamine, glycerin, methyl and propyl esters of paraoxybenzoic acid, laurel oil and water, with a certain ratio of components, wt.%. The invention provides a prolonged action of the drug.

However, a significant drawback of the anti-inflammatory agent is the presence of parabens - preservatives that contribute to skin cancer and are not effective against gram-positive and gram-negative bacteria. In world practice, there is a tendency to replace parabens with safer preservatives.

Positive is the presence of transdermal transporters of biologically active substances-liposomes, which give sufficient transdermal activity. However, the phospholipids that form the liposome membrane are unstable in time due to oxidative processes that continuously occur in any agent in the form of an ointment. Also, the manufacture of a suspension of liposomes is a technologically complex and long-term process.

The purpose of the invention is the anti-inflammatory and regenerative effect of serum on the skin with biologically active substances included in the transdermal carriers - niosomes.

Niosomes are vesicles consisting of a shell in the form of a water-insoluble double layer of a nonionic emulsifier (surfactant), which is a group of dimethicone copolyols substances that are esters of a polyethylene glycol and a polydimethylsiloxane base and a biologically active substance enclosed inside a capsule.

The goal is achieved due to the fact that the biologically active substances included in the vesicles - niosomes, are able to penetrate the deepest layers of the skin, affecting keratinocytes.

In relation to the prototype in composition, the claimed serum has the following distinctive features.

The use of niosomes as transdermal carriers of biologically active substances inside the skin cells has several advantages: biological compatibility with the human body, the absence of allergic, toxic, pyrogenic effects of transported components, prolonged action of substances introduced into the skin cells, reduction in the amount of drugs introduced into the skin cells while maintaining the effect their effects, the possibility of including several biologically active substances in the membrane and the internal contents of niosomes.

To penetrate into the deeper layers of the skin, you have to use workarounds, which are the intercellular spaces and excretory ducts of the skin glands. For the transfer of active substances into the epidermis, transdermal carriers are used - niosomes, which are complexes of amphiphilic PEG-12 Dimethicone molecules (INCI: PEG-12 Dimethicone) surrounding the active components. Paving their way through the epidermal barrier, carriers are pulling biologically active substances. All serum biologically active substances are included in niosomes.

Polyethylene glycol, which is part of the PEG-12 Dimethicone molecule, also contributes to a decrease in the resistance of the stratum corneum due to its hygroscopicity. Hydration occurs, i.e. swelling of the stratum corneum due to increased moisture content. Polyethylene glycol is embedded in the domains of the liquid crystal structure of intercellular lipid layers. As a result, they swell, while along with polyethylene glycol a certain amount of water penetrates into them, which further increases the permeability. When applied to the skin, as well as during prolonged occlusion, the formation of aqueous microchannels in the intercellular lipid layers occurs. This, in turn, facilitates the penetration of additional quantities of polyethylene glycol. This statement is confirmed by the facts of increased penetration of various biologically active substances when using polyethylene glycol in transdermal systems.

It was established that CH ₃ - (methyl) groups form a “cloud” around the S1 atoms (dimethicone part of the molecule) and create reaction sites for interaction with hydrophobic biologically active substances.

The Si — O bond length in organosilicon compounds is 1.6 angstroms, in contrast to phospholipids, in which the C — C bond is 1.4 angstroms. Also, the Si-O-Si bond angle is 130 degrees, in contrast to 109 degrees of the C-C-C bond.

Thus, the Si – O bond length is longer than the С – С bond and the bond angle is larger; therefore, the PEG-12 Dimethicone molecule is more elastic than the phospholipids used in liposome formation and is able to form vesicles without significant energy efforts.

The presence of a polydimethylsiloxane base allows one to obtain vesicles capable of withstanding a wide range of solvents such as ethyl alcohol, isopropyl palmitate, etc. Thus, unlike other vesicles, nano-vesicles-niosomes can be used in alcohol-containing formulations.

The reaction properties of dimethicone and polyethylene glycol make it possible to use nano vesicles-niosomes for interstitial (transdermal) delivery of a wide range of biologically active substances with hydrophilic and hydrophobic properties.

As a biologically active substance, pig placenta extract and hyaluronic acid are used in the gel. Also used is the propylene glycolic extract of Callisia fragrans and Calendula officinalis (Calendula officinalis) in a 1: 1 ratio.

Studies of pig placenta extract have led to the conclusion that there are valuable biologically active components of growth factors, cytokines, cytamines and other substances that contribute to the regeneration and proliferation of skin cells. Using the extract as the main biologically active substance in serum will enhance its effect: accelerate the renewal of skin cells due to cell division of collagen, elastin and keratinocytes. The action of the stem cell extract is based not on the external effect on the skin cells, but on the effect on the signaling mechanisms of intercellular interaction. We can say that the process is "from the inside."

To maximize the cosmetic effect, the serum was supplemented with propylene glycol extract of fragrant callisia (Callisia fragrans) and calendula (Calendula officinalis) in a 1: 1 ratio, which contains carotenoids (terpenes, terpenoids), pectins, tannins (tannins), kakhetins, flavonoids, carbohydrates , vitamins C, A, minerals in the form of metal complexes with organic substances.

Currently, special attention is paid to tactile sensations when applying a cosmetic product to the skin surface, therefore, cyclomethicone DC 345 (INCI: Cyclomethicone) is introduced to give a feeling of silkiness to the skin and improve the spreadability of serum on the skin surface and maintain the moisturizing effect. Cyclomethicone is a mixture of cyclic polydimethylsiloxanes having a low heat of vaporization from the skin surface, which guarantees the absence of a “cooling” effect when using the gel at low temperatures.

Serum contains hyaluronic acid, which is known for its hygroscopic properties: one molecule of hyaluronic acid is able to bind about a hundred molecules of water. Hyaluronic acid is a component of the natural moisturizing factor (NMF).

Serum protection is done by adding the water-soluble preservative Kathon CG (INCI: 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one, Rohm and Haas ^® ). The use of a water-soluble preservative allows better protection of serum than the use of a fat-soluble preservative (for example, parabens) due to the high content of the aqueous phase and the ability of microorganisms to reproduce precisely in the aqueous phase and at the interface.

The possibility of carrying out the claimed invention is confirmed by examples of specific performance.

Example 1

Serum "Regenerin" contains as a biologically active additive 10.0 wt.% Suspension of niosomes up to 100 Nm in size with pig placenta extract, hyaluronic acid, propylene glycol extract of fragrant callisia (Callisia fragrans) and calendula (Calendula officinalis) in a ratio of 1 : 1, and the basis includes cyclomethicone DC 345 - 20.0 wt.%, The preservative Kathon CG - 0.04 wt.% And purified water up to 100 wt.%. The phases of preparation and formulation of serum are presented in table 1.

Phase A is prepared at room temperature by mechanically mixing the components in a mixer. Phase B, containing a suspension of niosomes up to 100 Nm in size, is manufactured separately and introduced into phase A with vigorous stirring.

The prepared serum was applied to previously cleansed face skin 1 time a day before bedtime. After 10 days of serum use, the degree of keratinization and moisture were evaluated. The maximum increase in the degree of keratinization was 14% and the moisture content was 7% with a niosome content of 10.0 wt.%.

Example 2. It is carried out analogously to example 1, only a suspension of niosomes is introduced in an amount of 20 wt.%, Which includes extract of pig placenta, propylene glycol extract of fragrant callisia (Callisia fragrans) and calendula (Calendula officinalis) in a ratio of 1: 1, hyaluronic acid. The maximum increase in the degree of keratinization was 38% and the degree of moisture 35% of the initial values.

Example 3. It is carried out analogously to example 1, only a suspension of niosomes is introduced in an amount of 30 wt.%, Which includes extracts of pig placenta, propylene glycolic extract of callis aromatic and calendula in a ratio of 1: 1, and hyaluronic acid. The maximum increase in the degree of keratinization was 39% and the moisture content was 37% of the initial values.

Thus, the optimal delivery system is a suspension of niosomes in an amount of 20.0 wt.% With a content of pig placenta extract, hyaluronic acid and propylene glycol extract of fragrant callisia and calendula in a ratio of 1: 1 (example 2). A further increase in the percentage of niosomes did not lead to a significant increase in the degree of keratinization and hydration of the skin.

Serum "Regenerin" passed preclinical tests in the regional dermatovenerological dispensary and at the Department of Dermatovenerology and Cosmetology of the Stavropol State Medical Academy.

As a result of the studies, the optimal percentage ratio of niosomes in serum was selected, which allows to obtain the maximum increase in the degree of keratinization and skin hydration (table 2).

The claimed content of all components in the serum formulation optimally ensures the achievement of the desired effect, which is mainly achieved due to the content of transdermal carriers - niosomes and penetration enhancers of biologically active substances.

Thus, the claimed serum "Regenerin" has anti-inflammatory and regenerative effects on the skin.

Table 1 Preparation phases and formulation of Regenerin Serum with anti-inflammatory and regenerative effect No. p / p Name of ingredient Content in% (by weight) Phase A one Purified water up to 100.0 2 Preservative (Kathon CG) 0.04-0.06 3 Cyclomethicone (DC 345) 20.0-25.0 Phase B four Niosome suspension containing propylene glycol extract of fragrant callisia (Callisia fragrans) and calendula (Calendula officinalis) in a 1: 1 ratio, pig placenta extract, hyaluronic acid 10.0-40.0

table 2 Dependence of the degree of keratinization and skin hydration on the content of niosome suspension when using Regenerin serum with anti-inflammatory and regenerating effect for 10 days Examples one 2 3 Niosome suspension containing propylene glycol extract of fragrant callisia (Callisia fragrans) and calendula (Calendula officinalis) in a 1: 1 ratio, pig placenta extract, hyaluronic acid (% gel) 10 twenty thirty Humidity (% increase from baseline) 7 35 37 The degree of keratinization (% increase from the initial value) fourteen 38 39

Claims (1)

1. Serum for external use with anti-inflammatory and regenerating effect, containing biologically active substances, a preservative, water, characterized in that it contains as a biologically active additive a suspension of nios in sizes up to 100 Nm with the included pig placenta extract, hyaluronic acid, propylene glycol extract fragrant callisia (Callisia fragrans) and calendula (Calendula officinalis) in a ratio of 1: 1, and the base includes Cyclomethicone DC 345, Kathon CG preservative and purified water with the following components, wt.%:
Niosome suspension containing fragrant propylene glycolic callisia extract (Callisia fragrans) and calendula (Calendula officinalis) in a ratio of 1: 1, pig placenta extract, hyaluronic acid 10.0-40.0 Cyclomethicone DC 345 20.0-25.0 Preservative Kathon CG 0.04-0.06 Purified water up to 100.0