Multi-effect compound scar-removing gel for repairing sensitive muscle scars and preparation method of multi-effect compound scar-removing gel

Abstract

The invention discloses a multi-effect compound scar-removing gel for repairing sensitive muscle scars and a preparation method of the multi-effect compound scar-removing gel, and belongs to the technical field of preparation of medical preparations for skin. The multi-effect compound scar-removing gel is prepared from the following raw materials in percentage by weight: 0.05 percent to 0.08 percent of recombinant III type humanized collagen, 0.63 percent to 0.66 percent of carbomer, 0.18 percent to 0.21 percent of sodium phosphosilicate calcium, 0.09 percent to 0.11 percent of gamma-polyglutamic acid, 1.6 percent to 2.2 percent of levodopa-amino silicon oil mixed liquid, 0.8 percent to 1.1 percent of oxidized ganoderma lucidum polysaccharide and the balance of deionized water. The preparation method comprises the following steps: mixing and dispersing recombinant III-type humanized collagen, carbomer, calcium sodium phosphosilicate, polyglutamic acid, a levodopa-amino silicon oil mixed solution, oxidized ganoderan and deionized water to form a dispersion solution; then, the dispersion liquid is adjusted to be in a weakly alkaline environment for cross-linking and then is adjusted to be neutral for standing and gelation, and the obtained multi-effect compound scar-removing gel is effective and good in scar repair and does not have a red and swollen irritation phenomenon.

Description

Technical Field

[0001] The present invention belongs to the technical field of the preparation of pharmaceutical preparations for skin, and particularly relates to a multi-effect compound scar-removing gel for sensitive muscle scar repair and a preparation method thereof. Background Art

[0002] The skin, as the largest organ of the human body, is composed of three layers: the epidermis, the dermis, and the subcutaneous tissue. The skin has a protective function and can form a physical protective barrier between the external environment and the internal environment, thus defending against the invasion of harmful substances such as external physical, chemical, and microbial substances, and playing a role in preventing the loss of water and electrolytes and maintaining the stability of the internal environment. Moreover, the skin also has a sensory function. Because the nerve endings of sensory nerves and motor nerves and special receptors are widely distributed in the epidermis, dermis, and subcutaneous tissue, various stimuli inside and outside the body can be sensed, various sensations can be generated, and corresponding nerve reflexes can be caused. The skin is in direct contact with the external environment and is the first line of defense for the body to resist external injuries. As a powerful biological barrier, it can protect the body from the invasion of external bacteria, prevent the massive loss of body water, regulate the normal body temperature of the human body, and maintain the stability of the internal environment. When the skin is damaged by physical, biological, chemical and other factors and wounds appear, situations such as a large amount of loss of water and protein, damage to the immune system, and infection may occur, resulting in serious damage to the skin soft tissue and inability to completely repair itself normally. At this time, during the healing process of the skin wound surface, fibrous tissue will replace and repair, but scars will also be produced. Scars are a general term for the appearance and histopathological changes of normal skin tissue caused by various traumas, and they are an inevitable product in the process of human body trauma repair. When the growth of scars exceeds a certain limit, various complications will occur, such as damage to the appearance and dysfunction of activities, bringing great physical and mental pain to patients, especially the scars left after burns, scalds, and serious external injuries. The scar population is a large group. In daily life, the vast majority of people will leave scars of varying degrees due to inevitable bumps or surgical operations, etc. At present, the number of the scar population is large and the market capacity is large, and the multiple harms caused by scars, such as physiological and psychological harms, are serious. The existing treatment means and methods have their own advantages and some defects. Especially, surgical treatment requires relatively high costs and the pain during the operation, and it will also increase secondary injuries and cause new scars, and surgical treatment is not convenient.

[0003] Patent CN105709266A discloses a human-like collagen scar repair silicone gel. This invention mixes and stirs human-like collagen, silicon dioxide, cyclopentasiloxane, polydimethylsiloxanol, water, and polydimethylsiloxane to prepare a scar repair silicone gel.

[0004] Patent CN106983784A discloses a scar-removing silicone gel and its preparation method. In this invention, dimethyl silicone oil, hexamethyldisiloxane, polydimethylsiloxane self-crosslinking polymer, natural plant antibacterial agent, and antipruritic agent are used as raw materials and mixed and stirred. Under the action of hexamethyldisiloxane, dimethyl silicone oil and polydimethylsiloxane self-crosslinking polymer can quickly crosslink and combine with other components. Moreover, hexamethyldisiloxane has strong volatility and can quickly promote the formation of a thin film after the crosslinking and combination of various substances, which can fit tightly with the epidermis well, ensure the hydration of the skin, and has the effect of smoothing and softening scars caused by various external factors, thereby achieving the improvement effect on scars.

[0005] A large number of silicone products such as organosilicon oxides are used above. In the actual use process, silicone scar gels may cause slight irritation to the skin around the scars, manifested as slight redness or discomfort of the skin, and silicone scar gels are easily scratched off by external forces and have weak water resistance, thus resulting in limited repair effects.

[0006] Therefore, it is of great significance to design a scar-removing gel that reduces the use of organosilicon oxides to reduce irritation to the skin and has a good repair effect on scars at the same time. Summary of the Invention

[0007] According to the deficiencies of the prior art, in this invention, recombinant type III humanized collagen, carbomer, calcium phosphosilicate, polyglutamic acid, levodopa-aminosilicone oil mixture, oxidized ganoderma lucidum polysaccharide, and deionized water are mixed and dispersed to form a dispersion liquid, and then the dispersion liquid is adjusted to a weakly alkaline environment for crosslinking and then adjusted to neutral for static gelation to obtain a multi-effect compound scar-removing gel, thus solving the technical problems proposed in the background art. Specifically, the technical solution of this invention includes the following contents:

[0008] A multi-effect compound scar-removing gel for sensitive muscle scar repair, and the multi-effect compound scar-removing gel contains the following raw materials in weight percentages:

[0009] 0.05% - 0.08% of recombinant type III humanized collagen, 0.63% - 0.66% of carbomer, 0.18 - 0.21% of calcium phosphosilicate, 0.09% - 0.11% of γ-polyglutamic acid, 1.6% - 2.2% of levodopa-aminosilicone oil mixture, 0.8% - 1.1% of oxidized ganoderma lucidum polysaccharide, and the balance is made up to 100% with deionized water.

[0010] Further, the multi-effect compound scar-removing gel contains the following raw materials in weight percentages:

[0011] 0.07% recombinant type III humanized collagen, 0.65% carbomer, 0.2% calcium phosphosilicate, 0.1% γ-polyglutamic acid, 2% levodopa-aminosilicone oil mixture, 1% oxidized ganoderma polysaccharide, and 95.98 deionized water.

[0012] Furthermore, the preparation method of the levodopa-aminosilicone oil mixture includes the following steps:

[0013] Levodopa, aminosilicone oil, EDC hydrochloride, N-hydroxysuccinimide, and acetone are mixed and ultrasonically dispersed to form a dispersion, and the dispersion is adjusted to pH 5.0 - 5.5 and then stirred and reacted to obtain the levodopa-aminosilicone oil mixture.

[0014] Furthermore, the weight ratio of levodopa: aminosilicone oil: EDC hydrochloride: N-hydroxysuccinimide: acetone is 1: 5 - 10: 1 - 1.5: 1 - 1.5: 20 - 30.

[0015] Furthermore, the conditions of the ultrasonic dispersion include an ultrasonic power of 400W - 500W and an ultrasonic time of 10min - 15min.

[0016] Furthermore, the stirring reaction includes a reaction temperature of 20°C - 25°C and a reaction time of 12h - 15h.

[0017] Furthermore, the preparation method of the oxidized ganoderma polysaccharide includes the following steps:

[0018] Ganoderma lucidum fruit body powder, deionized water, and a complex enzyme solution are mixed and then heated and enzymatically hydrolyzed to obtain an enzymolysis solution;

[0019] The enzymolysis solution is sequentially subjected to high-temperature inactivation and decolorization treatment to obtain a ganoderma polysaccharide dispersion;

[0020] The ganoderma polysaccharide dispersion and sodium periodate are mixed and oxidized in a light-shielded environment to obtain the oxidized ganoderma polysaccharide.

[0021] Furthermore, the complex enzyme solution is obtained by mixing cellulase and papain in a weight ratio of 2:1.

[0022] Furthermore, the weight ratio of the ganoderma lucidum fruit body powder: deionized water: complex enzyme solution is 1: 20 - 30: 0.005 - 0.01.

[0023] Furthermore, the conditions of the heating enzymolysis include an enzymolysis pH of 5.0 - 5.5, an enzymolysis temperature of 40°C - 50°C, and an enzymolysis time of 1.5h - 2h.

[0024] Furthermore, the conditions of the high-temperature inactivation include an inactivation temperature of 80°C - 90°C and an inactivation time of 5min - 10min.

[0025] Further, the operation steps of the decolorization treatment include adding activated carbon according to 1% of the total weight of the enzymatic hydrolysate and stirring for 20 min to 30 min.

[0026] Further, the weight ratio of the ganoderma lucidum polysaccharide dispersion to sodium periodate is 1:0.1 to 0.2.

[0027] Further, the conditions for the oxidation treatment in the light-proof environment include an oxidation temperature of 25°C to 30°C and an oxidation time of 5 h to 6 h.

[0028] Further, the preparation method includes the following steps:

[0029] Add deionized water and carbomer to an emulsifying pan and stir until homogeneous, then add oxidized ganoderma lucidum polysaccharide and mix and heat to 80°C to 90°C for homogenization treatment for 5 min to 8 min, and then cool to 50°C to 60°C for heat preservation. In this heat preservation temperature environment, add calcium phosphosilicate and γ-polyglutamic acid for homogenization treatment for 2 min to 3 min, and then cool to 30°C to 35°C for heat preservation. Then add the recombinant type III humanized collagen and levodopa-aminosilicone oil mixture and stir to form a dispersion;

[0030] Adjust the dispersion to an alkaline environment and let it stand until a turbid gel solution appears, and finally adjust it to neutral and let it stand to form hydrogelation, obtaining the multi-effect compound scar-removing gel.

[0031] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0032] (1) In the present invention, levodopa and amino silicone oil are first mixed and reacted to obtain a levodopa-amino silicone oil mixture. Using the levodopa-amino silicone oil mixture with amino groups and oxidized ganoderma lucidum polysaccharide with aldehyde functional groups as the inclusion structure, then recombinant type III humanized collagen, carbomer, calcium sodium phosphosilicate, polyglutamic acid, the levodopa-amino silicone oil mixture and oxidized ganoderma lucidum polysaccharide are mixed and dispersed to form a dispersion. Then, the dispersion is adjusted to a weakly alkaline environment for crosslinking and then adjusted to neutral for static gelation to obtain a multi-effect compound scar-removing gel. Recombinant type III humanized collagen has the functions of promoting cell growth and migration to improve the healing speed and quality, inhibiting the activity of tyrosinase to reduce melanin production to achieve the effect of whitening the skin, and promoting the growth and proliferation of epithelial cells and fibroblasts to accelerate the repair and regeneration of damaged tissues; Ganoderma lucidum polysaccharide has strong antioxidant effects. The adjacent dihydroxy groups on its structure are broken to generate aldehyde groups, which are crosslinked with the levodopa-amino silicone oil mixture with amino groups, thereby realizing the encapsulation of recombinant type III humanized collagen and simultaneously synergistically improving the antioxidant ability with recombinant type III humanized collagen, and further reducing the influence of scar pigmentation. The role of levodopa is that under the use of a low dose of amino silicone oil, it can form a poly-levodopa structure with an adhesion effect through base-catalyzed self-polymerization, improving the adhesion of the multi-effect compound scar-removing gel to the skin and preventing shedding.

[0033] (2) Carbomer can play an emulsifying and stabilizing role in oil or water phases, helping the product texture to be more uniform and delicate, and improving the stability and skin feel of the product. Calcium sodium phosphosilicate stimulates the growth of growth factors during in vivo degradation, repairs damaged cells and tissues, and has anti-inflammatory and bactericidal effects. It can repair, replace and regenerate body tissues and form a bonding effect with tissues. Polyglutamic acid has extremely strong moisturizing effects, can combine with the moisture in the stratum corneum to form a protective film, reduce water loss, and thus play a moisturizing role. Detailed implementation mode

[0034] The technical solutions of the present invention will be clearly and completely described below through the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative efforts fall within the protection scope of the present invention.

[0035] Unless otherwise specified, the raw materials and reagents used in the present invention below are all commercially available products or can be prepared by known methods.

[0036] Preparation example 1:

[0037] A preparation method of a levodopa-amino silicone oil mixture specifically includes the following process:

[0038] Add 1 part by weight of levodopa and 5 parts by weight of amino silicone oil to 20 parts by weight of anhydrous acetone and heat to 40 °C for mixing and stirring to form a mixed solution. Subsequently, add 1 part by weight of EDC hydrochloride and 1 part by weight of N-hydroxysuccinimide to the mixed solution and place it in an ultrasonic disperser. Control the ultrasonic power at 400 W, and then time the ultrasonic treatment for 10 min. After the ultrasonic dispersion ends, take out the dispersion liquid, adjust the pH to 5.0 with dilute hydrochloric acid, place it in a water bath, control the temperature of the water bath at 20 °C, and then carry out magnetic stirring for a reaction time of 12 h. After the reaction ends, pour it into a dialysis bag with a molecular weight cut-off of 3500 kDa, dialyze with 0.1 mol / L sodium chloride for 1 day, then dialyze with anhydrous ethanol for 1 day, and finally dialyze with deionized water for 1 day to obtain a levodopa-amino silicone oil mixed solution.

[0039] Preparation Example 2:

[0040] A method for preparing a levodopa-amino silicone oil mixed solution, specifically including the following process:

[0041] Add 1 part by weight of levodopa and 7 parts by weight of amino silicone oil to 24 parts by weight of anhydrous acetone and heat to 40 °C for mixing and stirring to form a mixed solution. Subsequently, add 1.2 parts by weight of EDC hydrochloride and 1.2 parts by weight of N-hydroxysuccinimide to the mixed solution and place it in an ultrasonic disperser. Control the ultrasonic power at 400 W, and then time the ultrasonic treatment for 12 min. After the ultrasonic dispersion ends, take out the dispersion liquid, adjust the pH to 5.0 with dilute hydrochloric acid, place it in a water bath, control the temperature of the water bath at 20 °C, and then carry out magnetic stirring for a reaction time of 13 h. After the reaction ends, pour it into a dialysis bag with a molecular weight cut-off of 500 Da, dialyze with 0.1 mol / L sodium chloride for 1 day, then dialyze with anhydrous ethanol for 1 day, and finally dialyze with deionized water for 1 day to obtain a levodopa-amino silicone oil mixed solution.

[0042] Preparation Example 3:

[0043] A method for preparing a levodopa-amino silicone oil mixed solution, specifically including the following process:

[0044] Add 1 part by weight of levodopa and 9 parts by weight of amino silicone oil into 28 parts by weight of anhydrous acetone and heat to 40 °C for mixing and stirring to form a mixed solution. Subsequently, add 1.4 parts by weight of EDC hydrochloride and 1.4 parts by weight of N-hydroxysuccinimide into the mixed solution and place it in an ultrasonic disperser. Control the ultrasonic power at 500 W, and then time the ultrasonic treatment for 14 min. After the ultrasonic dispersion ends, take out the dispersion liquid, adjust the pH to 5.5 with dilute hydrochloric acid, then place it in a water bath pot, control the temperature of the water bath pot at 25 °C, and then carry out magnetic stirring for a reaction time of 14 h. After the reaction ends, pour it into a dialysis bag with a molecular weight cut-off of 500 Da, dialyze with 0.1 mol / L sodium chloride for 1 day first, then dialyze with anhydrous ethanol for 1 day, and finally dialyze with deionized water for 1 day to obtain a levodopa-amino silicone oil mixed solution.

[0045] Preparation Example 4:

[0046] A preparation method of a levodopa-amino silicone oil mixed solution specifically includes the following process:

[0047] Add 1 part by weight of levodopa and 10 parts by weight of amino silicone oil into 30 parts by weight of anhydrous acetone and heat to 40 °C for mixing and stirring to form a mixed solution. Subsequently, add 1.5 parts by weight of EDC hydrochloride and 1.5 parts by weight of N-hydroxysuccinimide into the mixed solution and place it in an ultrasonic disperser. Control the ultrasonic power at 500 W, and then time the ultrasonic treatment for 15 min. After the ultrasonic dispersion ends, take out the dispersion liquid, adjust the pH to 5.5 with dilute hydrochloric acid, then place it in a water bath pot, control the temperature of the water bath pot at 25 °C, and then carry out magnetic stirring for a reaction time of 15 h. After the reaction ends, pour it into a dialysis bag with a molecular weight cut-off of 500 Da, dialyze with 0.1 mol / L sodium chloride for 1 day first, then dialyze with anhydrous ethanol for 1 day, and finally dialyze with deionized water for 1 day to obtain a levodopa-amino silicone oil mixed solution.

[0048] Preparation Example 5:

[0049] A preparation method of a dopamine hydrochloride-amino silicone oil mixed solution specifically includes the following process:

[0050] Add 1 part by weight of dopamine hydrochloride and 10 parts by weight of amino silicone oil to 30 parts by weight of anhydrous acetone and heat to 40 °C for mixing and stirring to form a mixed solution. Subsequently, add 1.5 parts by weight of EDC hydrochloride and 1.5 parts by weight of N-hydroxysuccinimide to the mixed solution and place it in an ultrasonic disperser. Control the ultrasonic power at 500 W, and then time the ultrasonic treatment for 15 min. After the ultrasonic dispersion is completed, take out the dispersion liquid, adjust the pH to 5.5 with dilute hydrochloric acid, then place it in a water bath, control the temperature of the water bath at 25 °C, and then react for 15 h by magnetic stirring. After the reaction is completed, pour it into a dialysis bag with a molecular weight cut-off of 500 Da, dialyze with 0.1 mol / L sodium chloride for 1 day, then dialyze with anhydrous ethanol for 1 day, and finally dialyze with deionized water for 1 day to obtain a dopamine hydrochloride-amino silicone oil mixed solution.

[0051] Preparation Example 6:

[0052] A method for preparing oxidized ganoderma polysaccharide specifically includes the following process:

[0053] Clean the ganoderma fruiting body with clean water, and then put it into an oven at 55 °C and dry it to a constant weight. Crush the dried ganoderma fruiting body with a pulverizer and pass it through a sieve with 100 mesh to obtain ganoderma fruiting body powder. Subsequently, take 1 part by weight of ganoderma fruiting body powder and add it to 20 parts by weight of deionized water and stir until completely dispersed. Then, use a pipette to aspirate 0.005 part by weight of a composite enzyme solution (composed of cellulase and papain mixed in a weight ratio of 2:1) and inject it into the aqueous dispersion of ganoderma fruiting body powder, adjust the pH value to 5.0, then place it in a water bath, control the temperature at 40 °C, and time the enzymatic hydrolysis for 1.5 h. After the enzymatic hydrolysis is completed, continue to raise the temperature of the enzymatic hydrolysis solution to 80 °C in the water bath and time the inactivation treatment for 5 min. After the inactivation is completed, naturally cool it to room temperature, add activated carbon according to 1% of the weight of the enzymatic hydrolysis solution and stir for decolorization treatment for 20 min. After the decolorization treatment is completed, filter to remove the activated carbon to obtain a ganoderma polysaccharide dispersion. Take 1 part by weight of the ganoderma polysaccharide dispersion and 0.1 part by weight of sodium periodate and mix and stir, then place it in a dark environment, control the temperature at 25 °C, and time the oxidation treatment for 5 h. After the oxidation treatment is completed, immediately add ethylene glycol with twice the weight of sodium periodate for quenching treatment to obtain a reaction solution. Then pour the reaction solution into a dialysis bag with a molecular weight cut-off of 1000 Da to obtain oxidized ganoderma polysaccharide powder.

[0054] Preparation Example 7:

[0055] A method for preparing oxidized ganoderma polysaccharide specifically includes the following process:

[0056] Clean the Ganoderma lucidum fruiting body with clear water, and then place it in an oven at 55 °C to dry to a constant weight. Crush the dried Ganoderma lucidum fruiting body with a pulverizer and pass it through a sieve with 100 mesh to obtain Ganoderma lucidum fruiting body powder. Subsequently, take 1 part by weight of Ganoderma lucidum fruiting body powder and add it to 24 parts by weight of deionized water, stir until completely dispersed, and then use a pipette to aspirate 0.007 part by weight of a composite enzyme solution (composed of cellulase and papain mixed in a weight ratio of 2:1) and inject it into the aqueous dispersion of Ganoderma lucidum fruiting body powder. Adjust the pH value to 5.0, then place it in a water bath, control the temperature at 45 °C, and time the enzymatic hydrolysis for 1.5 h. After the enzymatic hydrolysis is completed, continue to heat the enzymatic hydrolysis solution in the water bath to 85 °C and time the inactivation treatment for 7 min. After the inactivation is completed, naturally cool it to room temperature, add activated carbon according to 1% of the weight of the enzymatic hydrolysis solution and stir for decolorization treatment for 25 min. After the decolorization treatment is completed, filter to remove the activated carbon to obtain a Ganoderma lucidum polysaccharide dispersion. Take 1 part by weight of Ganoderma lucidum polysaccharide dispersion and 0.14 part by weight of sodium periodate, mix and stir, and then place it in a dark environment, control the temperature at 25 °C, and time the oxidation treatment for 5.5 h. After the oxidation treatment is completed, immediately add ethylene glycol with twice the weight of sodium periodate for quenching treatment to obtain a reaction solution. Then pour the reaction solution into an oxidation Ganoderma lucidum polysaccharide powder with a molecular weight cut-off of 1000 Da.

[0057] Preparation Example 8:

[0058] A method for preparing oxidized Ganoderma lucidum polysaccharide specifically includes the following process:

[0059] Clean the Ganoderma lucidum fruiting body with clear water, and then place it in an oven at 55 °C to dry to a constant weight. Crush the dried Ganoderma lucidum fruiting body with a pulverizer and pass it through a sieve with 100 mesh to obtain Ganoderma lucidum fruiting body powder. Subsequently, take 1 part by weight of Ganoderma lucidum fruiting body powder and add it to 28 parts by weight of deionized water, stir until completely dispersed, and then use a pipette to aspirate 0.009 part by weight of a composite enzyme solution (composed of cellulase and papain mixed in a weight ratio of 2:1) and inject it into the aqueous dispersion of Ganoderma lucidum fruiting body powder. Adjust the pH value to 5.5, then place it in a water bath, control the temperature at 50 °C, and time the enzymatic hydrolysis for 2 h. After the enzymatic hydrolysis is completed, continue to heat the enzymatic hydrolysis solution in the water bath to 85 °C and time the inactivation treatment for 10 min. After the inactivation is completed, naturally cool it to room temperature, add activated carbon according to 1% of the weight of the enzymatic hydrolysis solution and stir for decolorization treatment for 30 min. After the decolorization treatment is completed, filter to remove the activated carbon to obtain a Ganoderma lucidum polysaccharide dispersion. Take 1 part by weight of Ganoderma lucidum polysaccharide dispersion and 0.18 part by weight of sodium periodate, mix and stir, and then place it in a dark environment, control the temperature at 30 °C, and time the oxidation treatment for 5.5 h. After the oxidation treatment is completed, immediately add ethylene glycol with twice the weight of sodium periodate for quenching treatment to obtain a reaction solution. Then pour the reaction solution into an oxidation Ganoderma lucidum polysaccharide powder with a molecular weight cut-off of 1000 Da.

[0060] Preparation Example 9:

[0061] Preparation method of oxidized Ganoderma lucidum polysaccharide, specifically including the following process:

[0062] Clean the Ganoderma lucidum fruit body with clear water, and then put it into an oven at 55 °C to dry to a constant weight. Crush the dried Ganoderma lucidum fruit body with a pulverizer, and pass it through a sieve with a mesh size of 100 meshes to obtain Ganoderma lucidum fruit body powder. Subsequently, take 1 part by weight of Ganoderma lucidum fruit body powder and add it to 30 parts by weight of deionized water and stir until completely dispersed. Then, use a pipette to aspirate 0.01 part by weight of the composite enzyme solution (composed of cellulase and papain mixed in a weight ratio of 2:1) and inject it into the aqueous dispersion of Ganoderma lucidum fruit body powder, adjust the pH value to 5.5, then place it in a water bath, control the temperature at 50 °C, and time the enzyme hydrolysis for 2 h. After the enzyme hydrolysis is completed, the enzyme hydrolysis solution is further heated to 90 °C in the water bath and timed for inactivation treatment for 10 min. After the inactivation is completed, it is naturally cooled to room temperature, and 1% of the weight of the enzyme hydrolysis solution is added with activated carbon and stirred for decolorization treatment for 30 min. After the decolorization treatment is completed, filter to remove the activated carbon to obtain Ganoderma lucidum polysaccharide dispersion. Take 1 part by weight of Ganoderma lucidum polysaccharide dispersion and mix it with 0.2 part by weight of sodium periodate and stir, then place it in a dark environment, control the temperature at 30 °C, and time the oxidation treatment for 6 h. After the oxidation treatment is completed, immediately add ethylene glycol with twice the weight of sodium periodate for quenching treatment to obtain a reaction solution. Then pour the reaction solution into an oxidized Ganoderma lucidum polysaccharide powder with a cut-off molecular weight of 1000 Da.

[0063] Preparation Example 10:

[0064] Preparation method of oxidized Ganoderma lucidum polysaccharide, specifically including the following process:

[0065] Clean the Ganoderma lucidum fruit body with clear water, and then put it into an oven at 55 °C to dry to a constant weight. Crush the dried Ganoderma lucidum fruit body with a pulverizer, and pass it through a sieve with a mesh size of 100 meshes to obtain Ganoderma lucidum fruit body powder. Subsequently, take 1 part by weight of Ganoderma lucidum fruit body powder and add it to 30 parts by weight of deionized water and stir until completely dispersed. Then, use a pipette to aspirate 0.01 part by weight of cellulase and inject it into the aqueous dispersion of Ganoderma lucidum fruit body powder, adjust the pH value to 5.5, then place it in a water bath, control the temperature at 50 °C, and time the enzyme hydrolysis for 2 h. After the enzyme hydrolysis is completed, the enzyme hydrolysis solution is further heated to 90 °C in the water bath and timed for inactivation treatment for 10 min. After the inactivation is completed, it is naturally cooled to room temperature, and 1% of the weight of the enzyme hydrolysis solution is added with activated carbon and stirred for decolorization treatment for 30 min. After the decolorization treatment is completed, filter to remove the activated carbon to obtain Ganoderma lucidum polysaccharide dispersion. Take 1 part by weight of Ganoderma lucidum polysaccharide dispersion and mix it with 0.2 part by weight of sodium periodate and stir, then place it in a dark environment, control the temperature at 30 °C, and time the oxidation treatment for 6 h. After the oxidation treatment is completed, immediately add ethylene glycol with twice the weight of sodium periodate for quenching treatment to obtain a reaction solution. Then pour the reaction solution into an oxidized Ganoderma lucidum polysaccharide powder with a cut-off molecular weight of 1000 Da.

[0066] Preparation Example 11:

[0067] A method for preparing oxidized Ganoderma lucidum polysaccharide, specifically including the following process:

[0068] Clean the Ganoderma lucidum fruiting body with clean water, and then place it in an oven at 55 °C to dry to a constant weight. Crush the dried Ganoderma lucidum fruiting body with a pulverizer and pass it through a 100-mesh sieve to obtain Ganoderma lucidum fruiting body powder. Subsequently, take 1 part by weight of Ganoderma lucidum fruiting body powder and add it to 30 parts by weight of deionized water and stir until completely dispersed. Then, use a pipette to aspirate 0.01 part by weight of a composite enzyme solution (composed of cellulase and papain mixed in a weight ratio of 2:1) and inject it into the aqueous dispersion of Ganoderma lucidum fruiting body powder, adjust the pH value to 5.5, then place it in a water bath, control the temperature at 50 °C, and time the enzyme treatment for 2 h. After the enzyme treatment is completed, the enzyme solution is further heated to 90 °C in the water bath and timed for inactivation treatment for 10 min. After the inactivation is completed, it is naturally cooled to room temperature, and 1% of activated carbon based on the weight of the enzyme solution is added and stirred for decolorization treatment for 30 min. After the decolorization treatment is completed, the activated carbon is removed by filtration to obtain a Ganoderma lucidum polysaccharide dispersion. Take 1 part by weight of Ganoderma lucidum polysaccharide dispersion and mix it with 0.5 part by weight of sodium periodate and stir, then place it in a dark environment, control the temperature at 30 °C, and time the oxidation treatment for 6 h. After the oxidation treatment is completed, immediately add ethylene glycol with twice the weight of sodium periodate for quenching treatment to obtain a reaction solution. Then, pour the reaction solution into an oxidized Ganoderma lucidum polysaccharide powder with a molecular weight cut-off of 1000 Da.

[0069] Example 1:

[0070] A method for preparing a multi-effect compound scar-removing gel for sensitive muscle scar repair, specifically including the following process:

[0071] According to the weight percentage, add 96.65% deionized water and 0.63% carbomer to an emulsifying pot and stir until uniform, then add 0.8% of the oxidized Ganoderma lucidum polysaccharide obtained in Preparation Example 6, mix and heat to 80 °C, homogenize for 5 min, and then cool to 50 °C for heat preservation. In this heat preservation temperature environment, add 0.18% calcium phosphosilicate and 0.09% γ-polyglutamic acid, homogenize for 2 min, and then cool to 30 °C for heat preservation. Then add 0.05% recombinant type III humanized collagen and 1.6% of the levodopa-aminosilicone oil mixture obtained in Preparation Example 1 and stir to form a dispersion;

[0072] Adjust the dispersion to an alkaline environment with a pH value of 8.0 and let it stand at room temperature for a period of time until a turbid gel solution appears, then immediately adjust the pH to neutral, and then continue to stand to produce hydrogelation to complete the preparation of the multi-effect compound scar-removing gel.

[0073] Example 2:

[0074] A preparation method of a multi - effect compound scar - removing gel for sensitive muscle scar repair specifically includes the following process:

[0075] By weight percentage, add 96.32% ionic water and 0.64% carbomer into an emulsifying pot and stir until uniform. Then add 0.9% of the oxidized ganoderma lucidum polysaccharide obtained in Preparation Example 7, mix and heat to 85°C, homogenize for 6 min, and then cool to 55°C for heat preservation. In this heat - preservation temperature environment, add 0.19% calcium phosphosilicate and 0.09% γ - polyglutamic acid, homogenize for 2 min, and then cool to 30°C for heat preservation. Then add 0.06% recombinant type III humanized collagen and 1.8% of the levodopa - amino silicone oil mixture obtained in Preparation Example 2 and stir to form a dispersion;

[0076] Adjust the dispersion to an alkaline environment with a pH value of 8.0, let it stand at room temperature for a period of time until a turbid gel solution appears, then immediately adjust the pH to neutral, and then continue to stand to produce hydrogelation, thus completing the preparation of the multi - effect compound scar - removing gel.

[0077] Example 3:

[0078] A preparation method of a multi - effect compound scar - removing gel for sensitive muscle scar repair specifically includes the following process:

[0079] By weight percentage, add 96.09% deionized water and 0.65% carbomer into an emulsifying pot and stir until uniform. Then add 0.9% of the oxidized ganoderma lucidum polysaccharide obtained in Preparation Example 8, mix and heat to 90°C, homogenize for 7 min, and then cool to 60°C for heat preservation. In this heat - preservation temperature environment, add 0.19% calcium phosphosilicate and 0.1% γ - polyglutamic acid, homogenize for 3 min, and then cool to 35°C for heat preservation. Then add 0.07% recombinant type III humanized collagen and 2% of the levodopa - amino silicone oil mixture obtained in Preparation Example 3 and stir to form a dispersion;

[0080] Adjust the dispersion to an alkaline environment with a pH value of 8.0, let it stand at room temperature for a period of time until a turbid gel solution appears, then immediately adjust the pH to neutral, and then continue to stand to produce hydrogelation, thus completing the preparation of the multi - effect compound scar - removing gel.

[0081] Example 4:

[0082] A preparation method of a multi - effect compound scar - removing gel for sensitive muscle scar repair specifically includes the following process:

[0083] According to the weight percentage, 95.64% deionized water and 0.66% carbomer were added to an emulsifying pot and stirred until uniform. Then, 1.1% of the oxidized Ganoderma lucidum polysaccharide obtained in Preparation Example 9 was added, and the mixture was heated to 90 °C, homogenized for 8 min, and then cooled to 60 °C for heat preservation. In this heat preservation temperature environment, 0.21% calcium phosphosilicate and 0.11% γ-polyglutamic acid were added, homogenized for 3 min, and then cooled to 35 °C for heat preservation. Then, 0.08% recombinant type III humanized collagen and 2.2% of the levodopa-aminosilicone oil mixture obtained in Preparation Example 4 were added and stirred to form a dispersion;

[0084] The dispersion was adjusted to an alkaline environment with a pH value of 8.0 and left to stand in a room temperature environment for a period of time until a turbid gel solution appeared. Then, the pH was immediately adjusted to neutral, and then left to stand continuously to produce hydrogelation, completing the preparation of the multi-effect compound scar-removing gel.

[0085] Comparative Example 1:

[0086] A preparation method of a multi-effect compound scar-removing gel for sensitive muscle scar repair specifically includes the following process:

[0087] The levodopa-aminosilicone oil mixture in Example 3 was replaced with the levodopa-aminosilicone oil mixture obtained in Preparation Example 5, and the other conditions were the same as those in Example 3.

[0088] Comparative Example 2:

[0089] A preparation method of a multi-effect compound scar-removing gel for sensitive muscle scar repair specifically includes the following process:

[0090] The oxidized Ganoderma lucidum polysaccharide in Example 3 was replaced with the oxidized Ganoderma lucidum polysaccharide obtained in Preparation Example 10, and the other conditions were the same as those in Example 3.

[0091] Comparative Example 3:

[0092] A preparation method of a multi-effect compound scar-removing gel for sensitive muscle scar repair specifically includes the following process:

[0093] The oxidized Ganoderma lucidum polysaccharide in Example 3 was replaced with the oxidized Ganoderma lucidum polysaccharide obtained in Preparation Example 11, and the other conditions were the same as those in Example 3.

[0094] Comparative Example 4:

[0095] A preparation method of a multi-effect compound scar-removing gel for sensitive muscle scar repair specifically includes the following process:

[0096] 0.9% of the oxidized Ganoderma lucidum polysaccharide in Example 3 was replaced with 0.8% sodium alginate and 0.1% calcium chloride solution (the mass concentration of the calcium chloride solution was 10%), and the other conditions were the same as those in Example 3.

[0097] Verification of scar treatment effect:

[0098] After anesthetizing the rats, the hair on their backs was removed, and then the skin area where the hair was removed was disinfected with iodophor. Then, a disposable biopsy punch was used to artificially create a damaged skin with a diameter of 20 mm. Then, the broken skin was treated with normal disinfection and care, and waited for it to heal naturally to form a scar. The area of the scar after natural healing was recorded. Then, the multi-effect compound scar-removing gel prepared in Examples 1-4 and Comparative Examples 1-4 was applied to the scar, once in the morning and once in the evening for 30 consecutive days. At 10 minutes after the application was completed, wear gloves and rub the multi-effect compound scar-removing gel. Record whether it is easy to fall off. The results are shown in Table 1. On the 31st day, record the area of the scar after treatment. The scar removal rate = (the area of the scar after natural healing - the area of the scar after treatment) / the area of the scar after natural healing × 100%. The blank group was not treated with anything. The results are shown in Table 1 below.

[0099] Table 1 Scar treatment effect

[0100]

[0101] The following conclusions can be drawn from Table 1 above:

[0102] (1) It can be found from Examples 1-4 that the multi-effect compound scar-removing gel obtained by mixing and dispersing recombinant type III humanized collagen, carbomer, calcium phosphosilicate, polyglutamic acid, levodopa-aminosilicone oil mixture, oxidized ganoderma polysaccharide and deionized water in the present invention, then adjusting the dispersion to a weakly alkaline environment for cross-linking and then adjusting to neutral for static gelation has good effectiveness in scar repair and does not show redness or other irritating phenomena.

[0103] (2) It can be found from Comparative Example 1 that the prepared multi-effect compound scar-removing gel has poor adhesion. This may be because in this system, although dopamine hydrochloride can polymerize to form sticky polydopamine and achieve the same adhesion effect as levodopa, since dopamine hydrochloride does not have a functional group carboxyl that can react with the amino group on the aminosilicone oil, dopamine hydrochloride and aminosilicone oil cannot react. When dialysis treatment is carried out, dopamine hydrochloride is removed by dialysis, and only aminosilicone oil remains. Under the formula of this system, the adhesion is poor and it is easy to fall off, which is not conducive to actual use.

[0104] (3) It can be found from Comparative Example 2 that the prepared multi-effect compound scar-removing gel shows poor performance in scar pigmentation. This may be because in this system, when cellulase is used alone for enzymatic hydrolysis, cellulase mainly plays a role in hydrolyzing the cell wall structure, thereby promoting the release of substances inside the cells. However, due to the interference of the proteins contained in Ganoderma lucidum fruiting bodies, the enzymatic hydrolysis efficiency may be low. At the dosage used in this system, the content of Ganoderma lucidum polysaccharide may be low, and the decrease in the content of Ganoderma lucidum polysaccharide makes the overall antioxidant performance of the multi-effect compound scar-removing gel poor and prone to pigmentation, thus affecting the scar repair effect.

[0105] (4) It can be found from Comparative Example 3 that the prepared multi-effect compound scar-removing gel shows poor adhesion. This may be because in this system, the dosage of sodium periodate is too high, resulting in too strong oxidation intensity, so that the aldehyde group content of the oxidized Ganoderma lucidum polysaccharide is high. During the mixing preparation, due to the cross-linking of the relatively high content of aldehyde groups and amino groups, the gelation may be too high, thus hindering the process of levodopa polymerization to form poly-levodopa, and further resulting in poor adhesion of the multi-effect compound scar-removing gel.

[0106] (5) It can be found from Comparative Example 4 that although sodium alginate can achieve gelation through the metal coordination of calcium ions, due to the low adhesion after gelation and the lack of antioxidant ability of sodium alginate, the scar repair effect is poor.

[0107] The above-described embodiments have detailed the technical solutions and beneficial effects of the present invention. It should be understood that the above is only the specific embodiments of the present invention and is not used to limit the present invention. Without departing from the spirit and scope of the present invention, the present invention will have various changes and improvements, and these changes and improvements all fall within the scope of the present invention claimed.

Claims

1. A multi-effect compound scar removal gel for sensitive skin scar repair, characterized in that: The multi-effect compound scar removal gel comprises the following raw materials in percentage by weight: 0.05% to 0.08% recombinant humanized type III collagen, 0.63% to 0.66% carbomer, 0.18% to 0.21% sodium calcium phosphosilicate, 0.09% to 0.11% γ-polyglutamic acid, 1.6% to 2.2% L-dopa-amino silicone oil mixture, 0.8% to 1.1% oxidized Ganoderma lucidum polysaccharide, and the balance is made up to 100% with deionized water.

2. The multi-effect compound scar removal gel for sensitive skin scar repair according to claim 1, characterized in that: The preparation method of the levodopa-amino silicone oil mixed solution comprises the following steps: Levodopa, amino silicone oil, EDC hydrochloride, N-hydroxysuccinimide and acetone are mixed and dispersed by ultrasonication to form a dispersion liquid. The dispersion liquid is adjusted to pH 5.0-5.5 and then stirred for reaction to obtain the levodopa-amino silicone oil mixed liquid.

3. The multi-effect compound scar removal gel for sensitive skin scar repair according to claim 2, characterized in that: The weight ratio of levodopa: amino silicone oil: EDC hydrochloride: N-hydroxysuccinimide: acetone is 1:5-10:1-1.5:1-1.5:20-30.

4. The multi-effect compound scar removal gel for sensitive skin scar repair according to claim 1, characterized in that: The preparation method of the oxidized Ganoderma lucidum polysaccharide comprises the following steps: Ganoderma lucidum fruiting body powder, deionized water and compound enzyme solution are mixed, and then heated and enzymolyzed to obtain enzymolysis solution; The enzymatic hydrolysate is sequentially subjected to high temperature inactivation and decolorization treatments to obtain a Ganoderma lucidum polysaccharide dispersion; The ganoderma lucidum polysaccharide dispersion and sodium periodate are mixed and oxidized in a light-proof environment to obtain the oxidized ganoderma lucidum polysaccharide.

5. The multi-effect compound scar removal gel for sensitive skin scar repair according to claim 4, characterized in that: The complex enzyme solution is obtained by mixing cellulase and papain in a weight ratio of 2:

1.

6. The multi-effect compound scar removal gel for sensitive skin scar repair according to claim 4, characterized in that: The weight ratio of the ganoderma lucidum fruiting body powder: deionized water: complex enzyme solution is 1:20-30:0.005-0.

01.

7. The multi-effect compound scar removal gel for sensitive skin scar repair according to claim 4, characterized in that: The conditions for the heating enzymolysis include an enzymolysis pH of 5.0 to 5.5, an enzymolysis temperature of 40° C. to 50° C., and an enzymolysis time of 1.5 h to 2 h.

8. The multi-effect compound scar removal gel for sensitive skin scar repair according to claim 4, characterized in that: The weight ratio of the ganoderma lucidum polysaccharide dispersion to sodium periodate is 1:0.1-0.

2.

9. A method for preparing a multi-effect compound scar removal gel for sensitive skin scar repair as claimed in any one of claims 1 to 8, characterized in that: The preparation method comprises the following steps: Deionized water and carbomer are added to an emulsifier and stirred until uniform, then oxidized Ganoderma lucidum polysaccharide is added, the mixture is heated to 80°C to 90°C and homogenized for 5min to 8min, then the temperature is reduced to 50°C to 60°C for insulation, sodium calcium phosphosilicate and γ-polyglutamic acid are added in this insulation temperature environment and homogenized for 2min to 3min, then the temperature is reduced to 30°C to 35°C for insulation, and then recombinant type III humanized collagen and L-dopa-amino silicone oil mixture are added and stirred to form a dispersion; The dispersion is adjusted to an alkaline environment and then allowed to stand until a turbid gel appears. Finally, the dispersion is adjusted to a neutral environment and allowed to stand to form a hydrogel to obtain a multi-effect compound scar removal gel.

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