CN108686260B

CN108686260B - Preparation method of compound scar-proof emulsion biological dressing

Info

Publication number: CN108686260B
Application number: CN201810505384.0A
Authority: CN
Inventors: 沈静飞
Original assignee: Hainan Phoenix Medical Instrument Co Ltd
Current assignee: Hainan Phoenix Medical Instrument Co Ltd
Priority date: 2018-05-24
Filing date: 2018-05-24
Publication date: 2020-02-28
Anticipated expiration: 2038-05-24
Also published as: CN108686260A

Abstract

The invention discloses a preparation method of a compound scar-proof emulsion biological dressing. The preparation method comprises the following steps: 1) preparing hyaluronic acid and water into solution A; 2) preparing growth factor, glycerol and water into solution B; 3) preparing compound active peptide, hydroxyethyl cellulose, glyceryl stearate, xanthan gum, tridecanol, phenoxyethanol, hamamelis extract, Scutellariae radix extract, Rubi fructus extract, radix Sangusorbae extract, Bulbus Allii Cepae extract and water into solution C; 4) and uniformly mixing the solution A, the solution B and the solution C, and filling to obtain the compound scar-proof emulsion biological dressing. The compound anti-scar emulsion biological dressing prepared by the invention can fully exert all effects of the active components in the aspects of skin repair, protection and nursing by compounding the active components such as gradient hyaluronic acid, small molecular active peptide, growth factor, plant extract and the like, ensure the effect stability of the product, and can promote wound healing, prevent and reduce scar formation.

Description

Preparation method of compound scar-proof emulsion biological dressing

Technical Field

The invention relates to a preparation method of a compound scar-proof emulsion biological dressing.

Background

The skin of a human body is an organ directly exposed to the external environment, is often injured and eroded by various external factors to cause wound or defect of skin tissues, and needs an ideal product for repair and nursing. The current dressing products mainly pay attention to the links of protecting the wound environment, promoting wound healing and preventing wound infection, although the dressing products play a good role in wound treatment, the prevention and the reduction of scar formation are not involved, the generation of scars not only affects the beauty, but also can generate symptoms of unsmooth perspiration, serious itching and the like, and great pain is caused to patients.

With the development of molecular biology, the application of biomaterials in medical dressings has been increasingly researched, and a great deal of results have been obtained, such as collagen, growth factors, hyaluronic acid, chitosan, alginate and the like. CN1337270A discloses a wound dressing and a preparation method thereof, wherein collagen and hyaluronic acid are coated or adhered on a substrate surface as a wound dressing. CN1228338A discloses a multilayer composite dressing containing collagen and growth factors for promoting wound tissue repair. CN1335135A discloses an artificial skin powder containing sodium hyaluronate and its preparation method, wherein the powder is prepared from sodium hyaluronate and pharmacologically active substances (heparin, chondroitin sulfate, epidermal growth factor, etc.) and is used for treating burn and scald. CN1380109A discloses a chitosan, collagen and calcium alginate composite sponge biological dressing and a preparation process thereof, the method comprises the steps of compounding and crosslinking the substances, neutralizing the substances with a buffer solution until the PH value is 5-7, emulsifying, pre-freezing, and freeze-drying to obtain the chitosan collagen sponge biological dressing. CN1379146A discloses a compound (Ag + Ag)₂O) a production process of the silver-containing antibacterial fabric, and the dressing with antibacterial effect can be produced.

In 1971, professor Berrington, university of Colorado, USA, found that the wound of skin tissue of a fetus is quickly healed without scars, and the theory of 'scar-free healing of the fetus' is provided, so that the professor attracts extensive attention in academic circles; the more intensive research result shows that compared with adults, the fetal skin wound is rich in various growth factors represented by hyaluronic acid and EGF, is the main reason of scar-free healing, and guides the research of the scar-proof dressing.

Hyaluronic acid, also known as uronic acid, is a high molecular acidic mucopolysaccharide formed by repeating connection of N-acetylglucosamine and D-glucuronic acid disaccharide units, and is widely present in extracellular matrices of connective tissues of animals and humans. Hyaluronic acid has wide physicochemical properties and rich biological functions, and is particularly suitable for repairing, protecting and nursing skin. Hyaluronic acid is widely applied in the field of skin products (external medicines, medical instruments and cosmetics), but most hyaluronic acid with a molecular weight within a certain range is only used, has partial characteristics of hyaluronic acid and exerts all effects of hyaluronic acid, and products with the same name have obvious differences in performance and effects among different enterprises and even among different batches of the same enterprise.

Disclosure of Invention

The invention aims to provide a preparation method of a compound scar-proof emulsion biological dressing, and the emulsion can promote wound healing and prevent and reduce scar formation.

The technical scheme adopted by the invention is as follows:

a preparation method of a compound scar-proof emulsion biological dressing comprises the following steps:

1) mixing high molecular weight hyaluronic acid with the molecular weight Mr more than or equal to 200 ten thousand, medium molecular weight hyaluronic acid with the molecular weight Mr more than or equal to 20 ten thousand and less than 200 ten thousand, low molecular weight hyaluronic acid with the molecular weight Mr more than or equal to 1 ten thousand and oligomeric hyaluronic acid with the molecular weight Mr less than 1 ten thousand with water, and uniformly stirring to obtain solution A;

2) mixing epidermal growth factor, keratinocyte growth factor, fibroblast growth factor, glycerol and water, and stirring to obtain solution B;

3) mixing compound active peptide, hydroxyethyl cellulose, glyceryl stearate, xanthan gum, tridecanol, phenoxyethanol, hamamelis extract, Scutellariae radix extract, Rubi fructus extract, radix Sangusorbae extract, Bulbus Allii Cepae extract and water, and stirring to obtain solution C;

4) and uniformly mixing the solution A, the solution B and the solution C, and filling to obtain the compound scar-proof emulsion biological dressing.

In the step 1), the mass percentage of each hyaluronic acid in the solution A is as follows: 1% -5% of high molecular weight hyaluronic acid; 0.2 to 2 percent of hyaluronic acid with medium molecular weight; 0.5 to 5 percent of low molecular weight hyaluronic acid; 0.1 to 1 percent of oligomeric hyaluronic acid.

In the step 2), the liquid B comprises the following raw materials in percentage by mass: 0.01 to 0.1 percent of epidermal growth factor, 0.01 to 0.05 percent of keratinocyte growth factor, 0.01 to 0.05 percent of fibroblast growth factor, 20 to 40 percent of glycerol and the balance of water.

In the step 3), the mass percentages of the raw materials in the solution C are as follows: 0.3 to 1 percent of compound active peptide, 0.1 to 5 percent of hydroxyethyl cellulose, 0.5 to 3 percent of glyceryl stearate, 0.1 to 0.5 percent of xanthan gum, 1 to 5 percent of tridecanol, 0.1 to 0.5 percent of phenoxyethanol, 0.01 to 0.1 percent of witch hazel extract, 0.1 to 0.5 percent of radix scutellariae extract, 0.05 to 0.3 percent of raspberry extract, 0.02 to 0.1 percent of sanguisorba extract, 0.05 to 0.2 percent of onion extract and the balance of water.

In the step 3), the composite active peptide comprises a short-chain peptide consisting of 3-10 amino acids.

In the step 3), the compound active peptide is composed of at least five of copper tripeptide-1, palmitoyl tripeptide-5, palmitoyl tetrapeptide-7, acetyl tetrapeptide-9, tetrapeptide-30, pentapeptide-3, pentapeptide-18, hexapeptide-2, hexapeptide-9, hexapeptide-10, nonapeptide-1 and decapeptide-12.

In the step 4), the volume ratio of the solution A to the solution B to the solution C is 1: 1: (7-9).

The invention has the beneficial effects that:

the compound anti-scar emulsion biological dressing prepared by the invention can fully exert all effects of the active components in the aspects of skin repair, protection and nursing by compounding the active components such as gradient hyaluronic acid, small molecular active peptide, growth factor, plant extract and the like, ensure the effect stability of the product, and can promote wound healing, prevent and reduce scar formation.

Specifically, the method comprises the following steps:

1) according to the invention, hyaluronic acid with different molecular weights is scientifically proportioned to form a gradient hyaluronic acid system, so that the hyaluronic acid has more various performances and effects than hyaluronic acid with a single molecular weight, can fully exert all effects of hyaluronic acid in the aspects of skin repair, protection and nursing, and ensure the effect stability of related products;

2) the invention selects a plurality of small molecule active peptides with the functions of promoting repair and protecting skin as main components, and the small molecule active peptides can be directly absorbed by skin to play the effect in the modes of epithelial cell and intercellular space passive diffusion, carrier transmembrane transport, endocytosis and the like, and can generate good repair and protection effects on skin inflammation, superficial injury and sub-health skin.

3) The selected growth factor has obvious effects of promoting healing, preventing and reducing scar formation on skin wounds, and can be used for treating and nursing various body surface wounds and problem skins.

4) The Hamamelis virginiana extract has the effects of moisturizing, whitening, promoting blood circulation, balancing skin pH value and grease secretion and repairing damaged skin, the radix scutellariae extract is a flavonoid extract and has the effects of inhibiting bacteria, resisting inflammation and removing free radicals, so that scar skin can be repaired and scar formation can be prevented, the raspberry extract contains a large amount of organic acid, saccharide, vitamin C and β -sitosterol, wherein the important nutrient component β -sitosterol has high permeability to the skin, so that moisture on the surface of the skin can be kept, skin metabolism is promoted, skin inflammation is inhibited, the auxiliary extensibility is good, smoothness and non-stickiness are achieved, tannin and triterpenoid saponin in the radix sanguisorbae extract can relax muscles and tendons, promote tissue regeneration and relieve pain, no scar is left in a skin wound, collagen can be promoted, the skin is completely and smooth and has no scar, the onion extract can be used for remarkably improving the symptoms and the appearance of structural tissues of the scar, promoting the recovery of hyperplastic erythema, pruritus and tissue texture of the scar, so that the beauty of the skin scar can be remarkably repaired, the better scar and the tender scar and the skin hardness of the scar tissue can be quickly removed.

Detailed Description

Preferably, in the step 1), the mass percentage of each hyaluronic acid in the solution a is as follows: 1% -5% of high molecular weight hyaluronic acid; 0.2 to 2 percent of hyaluronic acid with medium molecular weight; 0.5 to 5 percent of low molecular weight hyaluronic acid; 0.1 to 1 percent of oligomeric hyaluronic acid.

Preferably, in the step 2), the mass percentages of the raw materials in the solution B are as follows: 0.01-0.1% of Epidermal Growth Factor (EGF), 0.01-0.05% of Keratinocyte Growth Factor (KGF), 0.01-0.05% of Fibroblast Growth Factor (FGF), 20-40% of glycerol and the balance of water.

Preferably, in the step 3), the mass percentages of the raw materials in the solution C are as follows: 0.3 to 1 percent of compound active peptide, 0.1 to 5 percent of hydroxyethyl cellulose, 0.5 to 3 percent of glyceryl stearate, 0.1 to 0.5 percent of xanthan gum, 1 to 5 percent of tridecanol, 0.1 to 0.5 percent of phenoxyethanol, 0.01 to 0.1 percent of witch hazel extract, 0.1 to 0.5 percent of radix scutellariae extract, 0.05 to 0.3 percent of raspberry extract, 0.02 to 0.1 percent of sanguisorba extract, 0.05 to 0.2 percent of onion extract and the balance of water.

Preferably, in the step 3), the composite active peptide comprises a short-chain peptide consisting of 3-10 amino acids.

Further preferably, in step 3), the complex active peptide is composed of at least five of copper tripeptide-1, palmitoyl tripeptide-5, palmitoyl tetrapeptide-7, acetyl tetrapeptide-9, tetrapeptide-30, pentapeptide-3, pentapeptide-18, hexapeptide-2, hexapeptide-9, hexapeptide-10, nonapeptide-1, and decapeptide-12.

Preferably, in the step 4), the volume ratio of the solution A to the solution B to the solution C is 1: 1: (7-9); more preferably, in the step 4), the volume ratio of the solution a to the solution B to the solution C is 1: 1: 8.

the present invention will be described in further detail with reference to specific examples. The starting materials used in the examples are, unless otherwise specified, commercially available from conventional sources.

Example 1:

example 1 a method for preparing a compound anti-scarring emulsion biological dressing comprises the following steps:

1) weighing 25g of high molecular weight hyaluronic acid, 5g of medium molecular weight hyaluronic acid, 15g of low molecular weight hyaluronic acid and 5g of oligomeric hyaluronic acid, adding 1000mL of ultrapure water, heating, stirring and dissolving to obtain solution A;

2) weighing 0.5g of EGF, 0.25g of KGF, 0.25g of FGF, 300g of glycerol and 1000mL of ultrapure water, and uniformly mixing and stirring to obtain solution B;

3) weighing 5g of copper tripeptide-1, 20g of palmitoyl tetrapeptide-7, 10g of acetyl tetrapeptide-9, 5g of pentapeptide-3, 5g of hexapeptide-10, 5g of nonapeptide-1, 20g of hydroxyethyl cellulose, 150g of glyceryl stearate, 30g of xanthan gum, 200g of tridecanol, 20g of phenoxyethanol, 5g of witch hazel extract, 20g of scutellaria baicalensis root extract, 10g of raspberry extract, 5g of sanguisorba officinalis extract, 10g of onion extract and 8000mL of ultrapure water, mixing, and uniformly stirring to obtain solution C;

4) and mixing the A, B, C solutions, stirring uniformly, and filling to obtain the compound scar-proof emulsion biological dressing of the embodiment 1.

Example 2:

embodiment 2 a method for preparing a compound anti-scar emulsion biological dressing, comprising the following steps:

1) weighing 20g of high molecular weight hyaluronic acid, 10g of medium molecular weight hyaluronic acid, 10g of low molecular weight hyaluronic acid and 10g of oligomeric hyaluronic acid, adding 1000mL of ultrapure water, heating, stirring and dissolving to obtain solution A;

2) weighing 0.5g of EGF, 0.25g of KGF, 0.25g of FGF, 200g of glycerol and 1000mL of ultrapure water, and uniformly mixing and stirring to obtain solution B;

3) weighing 5g of palmitoyl tripeptide-5, 5g of palmitoyl tetrapeptide-7, 15g of acetyl tetrapeptide-9, 5g of tetrapeptide-30, 5g of pentapeptide-3, 5g of hexapeptide-9, 5g of hexapeptide-10, 5g of decapeptide-12, 20g of hydroxyethyl cellulose, 150g of glyceryl stearate, 30g of xanthan gum, 180g of tridecanol, 20g of phenoxyethanol, 5g of witch hazel extract, 20g of scutellaria baicalensis root extract, 10g of raspberry extract, 5g of sanguisorba officinalis extract, 10g of onion extract and 8000mL of ultrapure water, mixing, and stirring uniformly to obtain solution C;

4) and mixing the A, B, C solutions, stirring uniformly, and filling to obtain the compound scar-proof emulsion biological dressing of the embodiment 2.

Example 3:

example 3 a method of preparing a compounded anti-scarring emulsion biological dressing includes the following steps:

1) weighing 25g of high molecular weight hyaluronic acid, 10g of medium molecular weight hyaluronic acid, 10g of low molecular weight hyaluronic acid and 5g of oligomeric hyaluronic acid, adding 1000mL of ultrapure water, heating, stirring and dissolving to obtain solution A;

2) weighing 0.5g of EGF, 0.25g of KGF, 0.25g of FGF, 250g of glycerol and 1000mL of ultrapure water, and uniformly mixing and stirring to obtain solution B;

3) weighing 5g of copper tripeptide-1, 20g of palmitoyl tripeptide-5, 5g of tetrapeptide-30, 5g of pentapeptide-3, 5g of pentapeptide-18, 5g of hexapeptide-2, 5g of nonapeptide-1, 20g of hydroxyethyl cellulose, 100g of glyceryl stearate, 30g of xanthan gum, 150g of tridecanol, 20g of phenoxyethanol, 5g of witch hazel extract, 20g of scutellaria root extract, 10g of raspberry extract, 5g of sanguisorba extract, 10g of onion extract and 8000mL of ultrapure water, mixing uniformly, and stirring to obtain solution C;

4) and mixing the A, B, C solutions, stirring uniformly, and filling to obtain the compound scar-proof emulsion biological dressing of the embodiment 3. Comparative example 1:

comparative example 1 in preparing the solution a, 50g of high molecular weight hyaluronic acid was used to prepare the solution a, and the rest was the same as that of example 2, thereby obtaining the anti-scarring emulsion biological dressing of comparative example 1.

Comparative example 2:

comparative example 2 the same biological dressing as that of example 2 was obtained without adding the ingredient of the composite active peptide when preparing solution C, thereby obtaining the anti-scarring emulsion biological dressing of comparative example 2.

Comparative example 3:

comparative example 3 at the time of preparation, liquid B was not prepared, and only liquid a and liquid C were used, and the rest was the same as that of example 2, thereby obtaining the anti-scarring emulsion biological dressing of comparative example 3.

Performance evaluation:

mono-super pulse CO₂Dot matrix laser postoperative repair

Finding the depressed scar after mild to severe acne and receiving super-pulse CO₂70 patients treated by dot matrix laser, wherein 28 males and 42 females are aged 18-40 years. The test was randomly divided into seven groups of 10 persons each, of which three groups were volunteer tested in examples 1-3, three groups were tested in comparative examples 1-3, and the last group was tested as a comparative example. After operation, the emulsion biological dressings in examples 1-3 are respectively adopted in three groups of examples, the emulsion biological dressings in comparative examples 1-3 are respectively adopted in three groups of comparative examples, and the dressing is externally applied for 1 time in the morning and evening of each day for 10 days continuously. Meanwhile, a self-made cold water ice bag is selected for cold compress as a comparison example, and the cold water ice bag is externally applied once in the morning and at night every day for 10 days continuously. During the test period, the patients are required to be strictly sun-protected after the operation, and the aureomycin hydrochloride eye ointment is normally used for external use for 2 times/day for three days in each group.

Scoring according to inflammatory reaction on the 5 th day of the test, scoring according to the degree from 1 to 5, wherein 1 indicates no erythema, edema and burning sensation; score 5 indicates marked erythema, edema, burning and burning pain. The results are shown in Table 1, with scores shown as the average of 10 people per group.

TABLE 1 inflammatory response score

Test group	Example 1	Example 2	Example 3	Comparative example 1	Comparative example 2	Comparative example 3	Comparative example
								Average score	2.4	2.2	2.3	2.5	2.6	2.9	3.3

Volunteers were instructed to record the time to wound scab, the time to first scab exfoliation and the time to total scab exfoliation, the average of the times (days) being shown in table 2.

TABLE 2 average escharosis and decrustation times

Second, repairing acne scar

70 acne patients were collected and tested for scar repair, 21 men and 49 women aged 18-32 years. The test was randomly divided into seven groups of 10 persons each, of which three groups were volunteer tested in examples 1-3, three groups were tested in comparative examples 1-3, and the last group was tested as a comparative example. The three groups of the embodiment respectively adopt the emulsion biological dressings of the embodiments 1 to 3, and the three groups of the comparative example respectively adopt the emulsion biological dressings of the comparative examples 1 to 3, and the dressing is externally applied once every morning and evening for continuous use for 15 days; in the control example, a commercially available common dressing is externally applied for 15 days in the morning and at night.

The volunteers are scored according to the skin lesion forms, and are scored according to the degree of erythema/pigmentation from 0 to 5, wherein 0 represents observation under natural light and no macroscopic erythema/pigmentation; score 3 indicates moderate erythema/pigmentation, reddish/tan in color, observed under natural light; score 5 indicates severe erythema/pigmentation, bright red/dark lift observed under natural light.

The results of the scoring for acne scar repair are shown in table 3, and the scores are the average scores.

TABLE 3 acne scar repair Effect score

Test group	Example 1	Example 2	Example 3	Comparative example 1	Comparative example 2	Comparative example 3	Comparative example
								Before treatment	4.5	4.5	4.4	4.4	4.5	4.4	4.6
Treatment day 5	3.5	3.3	3.6	3.8	3.7	3.9	4.2
								Day 10 of treatment	2.7	2.2	2.6	2.7	2.8	2.8	3.5
Treatment day 15	1.6	1.1	1.5	1.6	1.8	1.9	3.0

From the above performance evaluation results, it is understood that the dressing of the present invention can promote wound healing, prevent and reduce scar formation.

Claims

1. A preparation method of a compound scar-proof emulsion biological dressing is characterized by comprising the following steps: the method comprises the following steps:

4) uniformly mixing the solution A, the solution B and the solution C, and filling to obtain the compound scar-proof emulsion biological dressing;

in the step 1), the mass percentage of each hyaluronic acid in the solution A is as follows: 1% -5% of high molecular weight hyaluronic acid; 0.2 to 2 percent of hyaluronic acid with medium molecular weight; 0.5 to 5 percent of low molecular weight hyaluronic acid; 0.1 to 1 percent of oligomeric hyaluronic acid;

in the step 2), the liquid B comprises the following raw materials in percentage by mass: 0.01-0.1% of epidermal growth factor, 0.01-0.05% of keratinocyte growth factor, 0.01-0.05% of fibroblast growth factor, 20-40% of glycerol and the balance of water;

in the step 3), the mass percentages of the raw materials in the solution C are as follows: 0.3 to 1 percent of compound active peptide, 0.1 to 5 percent of hydroxyethyl cellulose, 0.5 to 3 percent of glyceryl stearate, 0.1 to 0.5 percent of xanthan gum, 1 to 5 percent of tridecanol, 0.1 to 0.5 percent of phenoxyethanol, 0.01 to 0.1 percent of witch hazel extract, 0.1 to 0.5 percent of radix scutellariae extract, 0.05 to 0.3 percent of raspberry extract, 0.02 to 0.1 percent of sanguisorba extract, 0.05 to 0.2 percent of onion extract and the balance of water;

in the step 3), the compound active peptide consists of at least five of copper tripeptide-1, palmitoyl tripeptide-5, palmitoyl tetrapeptide-7, acetyl tetrapeptide-9, tetrapeptide-30, pentapeptide-3, pentapeptide-18, hexapeptide-2, hexapeptide-9, hexapeptide-10, nonapeptide-1 and decapeptide-12;