Background
Acne is a common chronic inflammatory disease of pilosebaceous glands, the course of disease is long-lasting and slow to cure, the disease is easy to repeat, abscess is caused in severe cases, and scars are left after healing.
The external medicine for treating acne comprises vitamin A acid medicine and antibiotic medicine, such as lincomycin, clindamycin, benzoyl peroxide, etc. Compared with lincomycin, the antibacterial activity of clindamycin is enhanced by 4-8 times, and adverse reactions are low. Clindamycin hydrochloride (Clindamycin hydrochloride) is also called Clindamycin hydrochloride, has a chemical name of 6- (1-methyl-trans-4-propyl-L-2-pyrrolidine formamido) -1-sulfo-7-chloro-6, 7, 8-trideoxy-L-threo-alpha-D-galactopyranoside hydrochloride, and has a molecular formula as follows: c18H33ClN2O5S & HCl is a semi-synthetic derivative of lincomycin hydrochloride, namely the lincomycin hydrochloride is formed by replacing hydroxyl on C7 position of the lincomycin hydrochloride with chlorine atom after structural modification. Clindamycin phosphate is a semi-synthetic derivative of clindamycin, the chemical name of which is (2S-trans) -6- (1-methyl-4-propyl-2-pyrrolidine carbonamide) -1-thio-methyl-7-chloro-6, 7, 8-trideoxy-L-threo-alpha-D-galactopyranoside-2-dihydrophosphate, which has no antibacterial activity in vitro but is fat-soluble, is easier to be absorbed transdermally than clindamycin, is rapidly hydrolyzed into clindamycin in vivo to show antibacterial activity, and the action mechanism is to inhibit early synthesis of bacterial protein, thereby inhibiting propionibacterium acnes and eliminating inflammation.
Hyaluronic acid is a macromolecular chain polysaccharide consisting of glucuronic acid and N-acetylglucosamine. With the continuous and intensive research, hyaluronic acid and salts thereof are widely applied to the industries of medicines, cosmetics, foods and the like. Research shows that exogenous high-concentration and high-molecular-weight hyaluronic acid can loosen the structure of wound tissue and is beneficial to repair cells such as macrophages and fibroblasts to enter the wound tissue, so that the covering of epithelial cells on the wound surface is accelerated, and the healing process of the wound tissue is promoted. In addition, the content of type III collagen in the wound surface is obviously increased, the diameter of collagen fiber is reduced, and the collagen fiber is arranged loosely and orderly, so that the scar formation in the wound surface healing process is reduced.
Ergothioneine is a natural amino acid occurring in the natural world, which is not synthesized in animals by themselves but can be accumulated in the body by ingestion. It is an effective antioxidant, and can effectively remove active oxygen free radicals, especially hydroxyl free radicals, generated by Propionibacterium acnes metabolism, prevent cells from forming color spots due to peroxidation, increase cell activity, and promote repair.
The existing clindamycin-containing products for treating acne mainly comprise gels, creams and dressings with anti-inflammatory and bacteriostatic effects. Compared with the cream, the gel has the advantages that the gel has good spreadability, is fresh and cool, has no greasy feeling, is easy to clean, and has higher transdermal absorption speed than the cream; compared with external dressing, the gel has certain adhesiveness, is beneficial to the release and absorption of the medicine, and is convenient to use and carry. In terms of therapeutic efficacy, the existing clindamycin-containing products mainly have the effects of inhibiting propionibacterium acnes, eliminating inflammation and promoting wound healing, but do not consider skin cell repair and prevent and reduce scar formation, and the scar formation is usually accompanied by pruritus, stabbing pain and possible later hyperplasia, thereby causing great pain to patients.
Content of application
Aiming at the defects of the prior art, the invention aims to provide a novel clindamycin gel and a preparation method thereof, and the novel gel can inhibit bacteria, diminish inflammation, resist oxidation, relieve the damage of ultraviolet rays to the fragile skin of an affected part, promote wound healing and prevent or reduce the formation of scars in the aspect of treating inflammatory acne. The technical scheme of the application is as follows:
the present application provides a gel composition for treating inflammatory acne, characterized in that said gel composition comprises:
clindamycin or clindamycin hydrochloride or clindamycin phosphate,
hyaluronic acid having a molecular weight of 100kDa-1200kDa or a salt thereof, and
ergothioneine.
2. The gel composition of claim 1, wherein the hyaluronic acid or salt thereof has a molecular weight of 600kDa to 700 kDa.
3. The gel composition according to item 1 or 2, characterized in that it comprises, based on the total weight of the gel composition:
0.2-2% by weight of clindamycin or clindamycin hydrochloride or clindamycin phosphate,
1-10% by weight of hyaluronic acid or a salt thereof, and
0.01-5% by weight of ergothioneine.
4. The gel composition according to any one of items 1 to 3, wherein the gel composition comprises, based on the total weight of the gel composition:
0.8-1.2% by weight of clindamycin or clindamycin hydrochloride or clindamycin phosphate,
1.5-5% by weight of hyaluronic acid or a salt thereof, and
0.04-1.5% by weight of ergothioneine.
5. The gel composition of any of claims 1-4, wherein the gel composition comprises, based on the total weight of the gel composition:
0.8-1.2% by weight of clindamycin or clindamycin hydrochloride or clindamycin phosphate,
1.7-2.5% by weight of hyaluronic acid or a salt thereof, and
0.04-0.07 wt% ergothioneine.
6. The gel composition of any one of claims 1-5, further comprising: thickening agent, humectant and preservative.
7. The gel composition of any of claims 1-6, further comprising, based on the total weight of the gel composition: 0.3-3 wt% of thickening agent, 5-30 wt% of humectant and 0.1-2 wt% of preservative.
8. The gel composition of item 6 or 7, wherein the thickener is carbomer, the humectant is glycerin, and the preservative is methylparaben.
9. The gel composition according to any one of claims 1 to 8, characterized in that it comprises: clindamycin phosphate.
10. The gel composition of any one of claims 1-9, further comprising a pH adjusting agent.
11. The gel composition of any of claims 1-10, wherein the pH adjusting agent is triethanolamine.
12. A method of preparing a gel composition for treating inflammatory acne, comprising the steps of:
dissolving clindamycin or clindamycin hydrochloride or clindamycin phosphate, hyaluronic acid or salt thereof and ergothioneine in water;
adding humectant and antiseptic, and stirring to dissolve;
adding the thickening agent, and stirring to uniformly disperse the thickening agent;
adding a pH regulator, and regulating the pH to 6-7.5;
and (4) supplementing the balance with water, and uniformly stirring to obtain the gel composition.
13. The method of claim 12, wherein the molecular weight of the hyaluronic acid or salt thereof is 600kDa to 700 kDa.
14. The method of item 12 or 13, wherein the gel composition comprises, based on the total weight of the gel composition:
0.2-2% by weight of clindamycin or clindamycin hydrochloride or clindamycin phosphate,
1-10% by weight of hyaluronic acid or a salt thereof, and
0.01-5% by weight of ergothioneine.
15. The method of any one of claims 12-14, wherein the gel composition comprises, based on the total weight of the gel composition:
0.8-1.2% by weight of clindamycin or clindamycin hydrochloride or clindamycin phosphate,
1.5-5% by weight of hyaluronic acid or a salt thereof, and
0.04-1.5% by weight of ergothioneine.
16. The method of any one of claims 12-15, wherein the gel composition comprises, based on the total weight of the gel composition:
0.8-1.2% by weight of clindamycin or clindamycin hydrochloride or clindamycin phosphate,
1.7-2.5% by weight of hyaluronic acid or a salt thereof, and
0.04-0.07 wt% ergothioneine.
17. The method of any one of claims 12-16, wherein the gel composition further comprises: thickening agent, humectant and preservative.
18. The method of any one of claims 12-17, wherein the gel composition further comprises, based on the total weight of the gel composition: 0.3-3 wt% of thickening agent, 5-30 wt% of humectant and 0.1-2 wt% of preservative.
19. The method of claim 17 or 18, wherein the thickening agent is carbomer, the humectant is glycerin, and the preservative is methylparaben.
20. The method of any one of claims 12-19, wherein the gel composition comprises: clindamycin phosphate.
21. The method of any one of claims 12-20, wherein the gel composition further comprises a pH adjusting agent.
22. The method of any one of claims 12-21, wherein the pH adjusting agent is triethanolamine.
Effect of application
The novel gel composition containing clindamycin or clindamycin hydrochloride or clindamycin phosphate is added with hyaluronic acid or salt thereof with the molecular weight of 100kDa-1200kDa and ergothioneine, so that the gel composition can inhibit propionibacterium acnes, eliminate inflammation, remove oxygen free radicals in cells, prevent skin damage cells from keratinizing, improve cell activity, repair cell barriers, play a role in promoting wound healing and preventing and reducing scar formation on inflammatory acne with wounds and even skin injuries, and achieve a better healing effect.
The gel composition for treating inflammatory acne comprises clindamycin or clindamycin hydrochloride or clindamycin phosphate, hyaluronic acid or salt thereof and ergothioneine in the proportion, so that the gel composition has more excellent effect of treating inflammatory acne.
Detailed Description
The following detailed description illustrates and describes embodiments of the present application with reference to specific examples, but the following description should not be construed as limiting the present application in any way.
The present application provides a gel composition for treating inflammatory acne, characterized in that said gel composition comprises:
clindamycin or clindamycin hydrochloride or clindamycin phosphate,
hyaluronic acid having a molecular weight of 100kDa-1200kDa or a salt thereof, and
ergothioneine.
Clindamycin is called clindamycin, belongs to lincomycin medicines, is an artificial semi-synthetic antibiotic, and mainly plays a role by inhibiting the synthesis of bacterial protein. Clindamycin has stronger action and less side effect than lincomycin. Clinically, clindamycin hydrochloride and clindamycin phosphate are used in many forms.
The hyaluronate may be any salt of hyaluronic acid disclosed in the prior art, such as sodium hyaluronate, zinc hyaluronate, silver hyaluronate, calcium hyaluronate, gold hyaluronate, or potassium hyaluronate, preferably sodium hyaluronate.
The molecular weight of the hyaluronic acid or a salt thereof may specifically be 100kDa, 150kDa, 200kDa, 250kDa, 300kDa, 350kDa, 400kDa, 450kDa, 500kDa, 550kDa, 600kDa, 650kDa, 700kDa, 750kDa, 800kDa, 850kDa, 900kDa, 950kDa, 1000kDa, 1050kDa, 1100kDa, 1150kDa, 1200kDa, or the like. In a preferred embodiment, the molecular weight of the hyaluronic acid or salt thereof is between 600kDa and 700 kDa.
In a preferred embodiment, the gel composition includes clindamycin phosphate, which is more readily absorbed transdermally than clindamycin and produces less of an adverse reaction than clindamycin hydrochloride.
In one embodiment, the gel composition comprises, based on the total weight of the gel composition:
0.2 to 2% by weight, preferably 0.8 to 1.2% by weight of clindamycin or clindamycin hydrochloride or clindamycin phosphate, specifically 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2% by weight or the like of clindamycin or clindamycin hydrochloride or clindamycin phosphate;
1 to 10% by weight, preferably 1.5 to 5% by weight, more preferably 1.7 to 2.5% by weight of hyaluronic acid or a hyaluronic acid salt, specifically 1%, 1.5%, 1.6%, 1.7%, 1.8%, 1.9%, 2%, 2.1%, 2.2%, 2.3%, 2.4%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, 10% by weight or the like of hyaluronic acid or a hyaluronic acid salt; and
0.01 to 5% by weight, preferably 0.04 to 1.5% by weight, more preferably 0.04 to 0.07% by weight, of ergothioneine, and specifically may be 0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.5%, 0.7%, 1%, 1.3%, 1.5%, 1.7%, 2%, 2.3%, 2.5%, 2.7%, 3%, 3.2%, 3.5%, 3.7%, 4%, 4.2%, 4.5%, 4.7%, 5% by weight, or the like.
In one embodiment, the gel composition comprises, based on the total weight of the gel composition: 0.2-2 wt% of clindamycin or clindamycin hydrochloride or clindamycin phosphate, 1.7-2.5 wt% of hyaluronic acid or a salt thereof, and 0.01-5 wt% of ergothioneine.
In one embodiment, the gel composition comprises, based on the total weight of the gel composition: 0.2-2 wt% of clindamycin or clindamycin hydrochloride or clindamycin phosphate, 1.7-2.5 wt% of hyaluronic acid or a salt thereof, and 0.04-1.5 wt% of ergothioneine.
In one embodiment, the gel composition comprises, based on the total weight of the gel composition: 0.8-1.2 wt% of clindamycin or clindamycin hydrochloride or clindamycin phosphate, 1.5-5 wt% of hyaluronic acid or a salt thereof, and 0.04-0.07 wt% of ergothioneine.
In one embodiment, the gel composition further comprises: thickening agent, humectant and preservative. As the thickener, for example, carbomer, carboxymethylcellulose, poloxamer, etc. can be used. As the humectant, for example, glycerin, propylene glycol, polyethylene glycol, and the like can be used. As the preservative, for example, methylparaben, sorbic acid, chlorocresol, and the like can be used.
In one embodiment, the gel composition further comprises, based on the total weight of the gel composition: 0.3 to 3% by weight of a thickener, specifically 0.3%, 0.5%, 0.8%, 1%, 1.3%, 1.6%, 1.9%, 2.1%, 2.5%, 2.8%, 3.0% by weight; 5 to 30% by weight, and specifically 5%, 7%, 8%, 9%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30% by weight, and the like; and 0.1 to 2% by weight of a preservative, specifically 0.1%, 0.3%, 0.5%, 0.7%, 0.8%, 1%, 1.2%, 1.4%, 1.6%, 1.8%, 2% by weight or the like.
In one embodiment, the gel composition further comprises, based on the total weight of the gel composition: 0.3-1.2% by weight of carbomer, 8-15% by weight of glycerol, and 0.1-0.5% by weight of methylparaben.
In one embodiment, the gel composition further comprises a pH adjuster, which may be triethanolamine, 2% NaOH solution, or the like.
In one embodiment, the gel composition consists of clindamycin or clindamycin hydrochloride or clindamycin phosphate, hyaluronic acid or a salt thereof, ergothioneine, a thickening agent, a humectant, a preservative, a pH adjusting agent, and water.
The application also provides a preparation method of the gel composition for treating inflammatory acne, which is characterized by comprising the following steps:
dissolving clindamycin or clindamycin hydrochloride or clindamycin phosphate, hyaluronic acid or salt thereof and ergothioneine in water;
step two, adding a humectant and a preservative into the solution obtained in the step one, and stirring to dissolve the humectant and the preservative;
step three, adding a thickening agent into the solution obtained in the step two, and stirring to uniformly disperse the thickening agent;
step four, adding a pH regulator into the product obtained in the step three, and regulating the pH to 6-7.5;
and step five, supplementing the balance of water, and uniformly stirring to obtain the gel composition.
In a specific embodiment, in the fourth step, the pH may be specifically adjusted to 6, 6.2, 6.4, 6.6, 6.8, 7, 7.2, 7.4, 7.5, etc., preferably to 7.
In one embodiment, only a small amount of water is added for replenishment in step five, and after replenishment with water, the pH of the gel composition changes very little, between 5.9 and 7.6, preferably between 6 and 7.5, relative to the pH of the product obtained in step four.
In one embodiment, in the third step, the thickener is added into the solution obtained in the second step, and the mixture is stirred for 30 to 60min to uniformly disperse the thickener, preferably for 40 min.
According to the application, hyaluronic acid or salt thereof and ergothioneine are simultaneously added into clindamycin or clindamycin hydrochloride or clindamycin phosphate, the molecular weight of the hyaluronic acid or salt thereof is limited to be 100kDa-1200kDa, and the obtained gel composition can better prevent and reduce scar formation and achieve a better healing effect. Clindamycin or clindamycin hydrochloride or clindamycin phosphate, hyaluronic acid or salt thereof and ergothioneine are added in the content defined in the application, and the pH of the gel composition is further controlled, so that inflammatory acne can be better treated, and scar hyperplasia can be prevented.
Examples
The content of the present application is further illustrated by the following examples. The technical means used in the examples are conventional means well known to those skilled in the art and commercially available common instruments, unless otherwise specified.
The preparation and the effects of the present invention will now be further described by the following examples, which are provided for illustration only and are not intended to limit the contents of the present invention. The protection scope of the present invention is subject to the claims.
The preparation of the gel compositions of examples 1 to 8 and comparative examples 1 to 3 were carried out according to the formulations in table 1, respectively:
TABLE 1
Example 1
The preparation method comprises the following steps:
(1) dissolving 1.0g of clindamycin phosphate, 2.0g of sodium hyaluronate with the molecular weight of 600-700kDa and 0.05g of ergothioneine in water;
(2) adding 10g of glycerol and 0.15g of methyl p-hydroxybenzoate into the solution obtained in the step (1), and stirring to dissolve the glycerol and the methyl p-hydroxybenzoate;
(3) adding 0.3g of carbomer-940 into the solution obtained in the step (2), and stirring for 40min to make the solution uniform;
(4) and (4) uniformly stirring the product obtained in the step (3), adding triethanolamine, stirring, adjusting the pH value to 7.0, supplementing the balance of the formula with water, uniformly stirring, canning and sterilizing to obtain the gel.
Example 2
Example 2 differs from example 1 in that clindamycin phosphate content is 0.4g, sodium hyaluronate content is 1.5g, and ergothioneine content is 0.02 g. The preparation method is as in example 1.
Example 3
Example 3 differs from example 1 in that clindamycin phosphate content is 1.8g, sodium hyaluronate content is 9g, and ergothioneine content is 4.5 g. The preparation method is as in example 1.
Example 4
Example 4 differs from example 1 in that clindamycin phosphate content is 0.8g, sodium hyaluronate content is 3.5g, and ergothioneine content is 1.2 g. The preparation method is as in example 1.
Example 5
Example 5 differs from example 2 in that sodium hyaluronate has a molecular weight of 200-400 kDa. The preparation method is as in example 2.
Example 6
Example 6 differs from example 2 in that sodium hyaluronate has a molecular weight of 1000-1200 kDa. The preparation method is as in example 2.
Example 7
Example 7 differs from example 2 in that the ergothioneine content was 5.5 g. The preparation method is as in example 2.
Example 8
Example 8 differs from example 2 in that the pH is adjusted to 5.5. The preparation method is as in example 2.
Example 9
Example 9 differs from example 2 in that the amount of carbomer-940 was 2g and the amount of glycerol was 7 g. The preparation method is as in example 2.
Comparative example 1
Comparative example 1 differs from example 2 in that sodium hyaluronate was not included. The preparation method is as in example 2.
Comparative example 2
Comparative example 2 differs from example 2 in that sodium hyaluronate has a molecular weight of 50-70 kDa. The preparation method is as in example 2.
Comparative example 3
Comparative example 3 differs from example 2 in that it does not contain ergothioneine. The preparation method is as in example 2.
Test examples
Test example 1
65 healthy white rabbits with the weight of 2.0kg-2.3kg are selected. The opening of the ear canal on the inner side of the ear of each rabbit is coated with coal tar for two weeks for 1 time every day, 0.5mL each time, so as to establish an acne model for testing. After two weeks, the rabbit ears coated with coal tar have scab and acne, the thickness of the rabbit ears is increased, the hardness is increased compared with the rabbit ears, and the bulge of the hair follicle is in a papule shape, so that an acne model is formed.
65 rabbits were randomly divided into 13 test groups, i.e., group 1, group 2, group 3, group 4, group 5, group 6, group 7, group 8, group 9, group 10, group 11, group 12, group 13, each group consisting of 5 rabbits, and then equally raised conditions were continued for 3 weeks, the gel compositions obtained in examples 1, 2, 3, 4, 5, 6,7,8, 9 were used for groups 1, 2, 3, 4, 5, 6,7,8, 9, respectively, the gel compositions of comparative examples 1, 2, 3, 12, and 13 were used for groups 10, 11, 12, and 13, respectively, and a commercially available clindamycin phosphate gel (containing 1.0g of clindamycin phosphate based on 100g of the total weight, and carbomer, triethanolamine, propylene glycol, isopropyl alcohol as an adjuvant), and were administered once a day during the treatment period and skin changes were recorded.
After one week of administration, the skin acne symptoms of the rabbit ears in each group began to be reduced, and the hair follicle cornification protrusions of the rabbit ears were slightly reduced and began to be softened. After two weeks, the acne models are recovered obviously, wherein the recovery conditions of the 1 st to 4 th groups are good, the cornification bulges are obviously flat, and the skin damage area is reduced; groups 5-9 had a slight degree of keratinization or bulging, with the acne models in groups 10-13 taking effect slowly and being associated with desquamation.
After three weeks of administration, the acne models in the groups 1-9 are totally recovered, wherein the group 1 has the best effect, the original skin lesions of 4 rabbits are well recovered, the keratinized bulges of hair follicles are basically disappeared, the skin is smooth, erythema and scars do not exist, and only a small amount of epidermis keratinization phenomenon exists; the effects of the groups 2 and 3 are similar, one rabbit in each group recovers well, the original skin lesion is healed without scars and red spots, the hair follicle keratosis of the two rabbit models is obvious, and the pore is large; the two rabbits recovered better in the acne model, only a small amount of keratinized epidermis remained, and the hair follicle opening slightly enlarged; the 4 th group is next to the 1 st group, the skin lesions of three rabbits are well recovered, the hair follicle keratosis disappears, no scar and erythema are left, one rabbit still has slight skin keratosis, and the hair follicle opening is enlarged and the keratosis is obvious after the original skin lesion is healed; after the group 5 is treated, the three rabbits have good treatment effect, less skin keratosis exists after healing, and hair follicle keratosis is obvious after two rabbits heal; after the group 6 treatment, two rabbits recovered well, the skin keratosis was light after the skin lesion healed, the hair follicle opening was slightly enlarged, and the hair follicle keratosis was more obvious and enlarged after three rabbits healed; in the 7 th group, one rabbit is recovered to be normal, one rabbit has slight keratinization, and the hair follicle keratinization of three rabbits is obvious; group 8, three rabbits had less keratosis with slightly enlarged follicular orifices; after the treatment of the 9 th group, two rabbits healed better, hair follicles keratinized are less, hair follicles of the two rabbits are more obvious keratinized, and one hair follicle mouth is obvious keratinized to form raised scars, so that the skin is thickened. The skin lesions of the ears of the rabbits in the 10 th group to the 13 th group still have slight dandruff shedding, and compared with the rabbits in the 1 st group to the 9 th group, the hair follicle keratosis scar bulges with obvious erythema in different degrees after the medicine is applied, wherein after the skin lesions of the acne model in the 13 th group heal, the hair follicle keratosis of the rabbits is serious, and the epidermis bulges and thickens to form red scars, which is the most obvious group in the 13 th group.
According to the thickening of the rabbit ear epidermis, the keratinization of hair follicles and the expansion degree of hair follicle mouths, an acne model is divided into 4 grades: "-" is normal; "+/-" refers to less cornification, and the hair follicle opening is slightly enlarged; "+" indicates that the hair follicle is more sharply keratinized and the hair follicle opening is enlarged; "+ +" indicates that the hair follicle mouth is cornified and obviously causes slight convex scar and the skin is thickened; the hair follicle is severely keratinized, the epidermis is raised, the skin is thickened, and red scars are obvious. The results of each test group are shown in table 1 below.
TABLE 1
Test example 2
Acne patients 130 aged 18-35 years were selected and divided into 13 groups of 10 people each. The first, second, third, fourth, fifth, sixth, seventh, eighth, ninth, tenth, eleventh, twelfth, thirteenth groups were treated with the gel composition of examples 1, 2, 3, 4, 5, 6,7,8, 9, the gel composition of comparative examples 1, 2, 3, the commercially available clindamycin phosphate gel, respectively; subjects in the 13 groups were treated with the indicated gel compositions daily, twice daily in the morning and evening for a total of three weeks.
The treatment results are shown in table 2.
TABLE 2
As can be seen from the treatment evaluation results in table 2, the gels obtained in the examples of the present invention have a good treatment effect on acne, and the first group used example 1 was the most effective example. Compared with clindamycin phosphate gel in the prior art, the invention has the advantages of promoting wound healing and preventing scar hyperplasia.