A scar repair softening cream and its preparation method and application

Abstract

This invention belongs to the field of pharmaceutical preparation technology, specifically relating to a scar repair and softening cream, its preparation method, and its application. The raw materials of the scar repair and softening cream include active ingredients, matrix, stabilizer, hardness modifier, and emulsifier; the emulsifier contains at least a phospholipid derivative. The preparation of the scar repair and softening cream includes: (1) taking the matrix, hardness modifier, and emulsifier, heating and stirring them, then adding the stabilizer and mixing them to form the cream matrix. (2) taking camphor, methyl salicylate, and menthol to prepare a mixed solution. (3) cooling, adding borneol, stirring, then adding the mixed solution from step (2) to step (1), mixing, then adding compound gallnut extract and mixing, vacuuming, and homogenizing. (4) cooling and filling to obtain the product. The cream of this invention is easy to apply and disperse, has better stability and transdermal properties, and has a more significant scar repair effect, showing good application prospects.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical preparation technology, specifically relating to a scar repair and softening cream, its preparation method, and its application. Background Technology

[0002] Skin, one of the largest organs in the human body, forms a protective barrier between the natural environment and the internal environment, safeguarding the body and protecting it from external aggressors. Scars are a form of repair resulting from incomplete histological regeneration after injury, where connective tissue replaces the damaged tissue. Essentially, scars are abnormal and incomplete tissue lacking normal skin structure and function. Burns, scalds, and surgical procedures are the main causes of hypertrophic scars; additionally, factors such as collagen metabolism imbalance, myofibroblast contraction, or changes in the composition of the extracellular matrix in the dermis can also lead to hypertrophic scars.

[0003] Clinically, antibiotics and local surgery are commonly used treatments, with Western medicine being a common approach due to its ability to quickly control and alleviate symptoms. Wound care and psychological support during the repair process serve as adjunctive therapies, achieving good therapeutic results. However, patients often experience slow wound healing, scarring, drug resistance, liver and kidney damage, and decreased immune function, severely impacting their long-term mental and physical health. Furthermore, wound infection is a common complication of burns. Sudden external injury breaches the skin's protective barrier in a short time, and the formation of a large amount of necrotic tissue and cells at the wound site easily leads to bacterial infection.

[0004] Chinese invention patent application CN200410029929.3 discloses a traditional Chinese medicine ointment for treating scars and its quality control method. The ointment is prepared by heating glycerin, stearic acid, triethanolamine, etc., to melt them, adding water to emulsify and form a base, then adding compound gallnut extract, borneol, menthol, camphor, and methyl salicylate, mixing, and stirring. The preparation made using this traditional Chinese medicine ointment and its quality control method has definite curative effect and controllable quality.

[0005] Another Chinese invention patent application, CN202310852166.5, discloses a scar repair cream composition, its preparation method, and its application. This composition is a cream, but it is easy to apply, non-greasy, and does not easily fall off. After application, it forms a breathable but waterproof and stable silicone protective layer on the skin surface. The moisturizer and active ingredients in the inner layer maintain the moisture content of sub-healthy skin while absorbing a small amount of exudate. The double-layer membrane structure formed after application effectively inhibits scar formation while reducing irritation to the skin during the recovery period, promoting the orderly and rapid growth of skin fibroblasts, and effectively preventing scar formation.

[0006] Another Chinese invention patent application, CN201980098673.6, discloses a novel antioxidant composition for wound healing, specifically relating to a novel composition with antioxidant and hydrating activities for topical application, which can be used to promote wound healing and is suitable for therapeutic and / or cosmetic treatment and prevention of skin lesions. This novel composition introduces certain agents and ingredients, including galactomannan and carotenoids, which improve the healing and remedial activity of extensive wounds occurring in the presence of reactive oxygen species.

[0007] The existing technologies have explored scar repair preparations to some extent and achieved certain results. However, the scar repair effect of these topical preparations still needs to be further improved, and the stability, application sensory effects, and transdermal absorption of these preparations also need to be further enhanced. Summary of the Invention

[0008] To address the shortcomings of existing technologies, this invention provides a scar repair and softening cream, its preparation method, and its application.

[0009] To achieve the objectives of this invention, the following technical solution is adopted: In a first aspect, the present invention provides a scar repair and softening cream, wherein the raw materials of the scar repair and softening cream include active ingredients, a matrix, a stabilizer, a hardness modifier, and an emulsifier; The active ingredients include compound gallnut extract, borneol, menthol, camphor, and methyl salicylate; The emulsifier contains at least a phospholipid derivative.

[0010] In one embodiment of the present invention, the phospholipid derivative is selected from one or more combinations of soybean lecithin, egg yolk lecithin, hydrogenated soybean lecithin, dipalmitoylphosphatidylcholine and distearate phosphatidylcholine, preferably at least one of soybean lecithin and hydrogenated soybean lecithin.

[0011] In one embodiment of the present invention, the emulsifier further includes fatty acid sorbitans.

[0012] As one embodiment of the present invention, the fatty acid sorbitan is selected from one or more combinations of sorbitan trioleate, sorbitan lauryl, sorbitan oleate, sorbitan palmitate and sorbitan stearate, preferably sorbitan stearate.

[0013] Preferably, the emulsifier is selected from a mixture of phospholipid derivatives and fatty acid sorbitans.

[0014] More preferably, the mass ratio of the phospholipid derivative to the fatty acid sorbitan is 1-3:1.

[0015] In one embodiment of the present invention, the matrix is ​​selected from white petrolatum.

[0016] In one embodiment of the present invention, the stabilizer is a starch ester derivative, preferably one or a combination of several of the following: aluminum starch octenyl succinate, sodium starch octenyl succinate, sodium starch octadecenyl succinate, aluminum starch decenyl succinate, aluminum starch dodecenyl succinate, starch laurate, starch myristate, starch palmitate, and starch octanoate.

[0017] Preferably, the stabilizer is selected from one or two of aluminum starch octenyl succinate and sodium starch octenyl succinate.

[0018] In one embodiment of the present invention, the hardness modifier is selected from one or a combination of several of the following: white beeswax, beeswax, paraffin wax, Japanese wax, carnauba wax, shellac wax, rice wax, cork wax, ceresin wax, montan wax, lanolin wax, and microcrystalline wax.

[0019] Preferably, the hardness modifier includes one or more of white beeswax and beeswax.

[0020] More preferably, the hardness modifier is selected from white beeswax.

[0021] As one embodiment of the present invention, the raw materials of the scar repair and softening cream also include an antibacterial agent.

[0022] Preferably, the antibacterial agent is selected from one or a combination of several of methylparaben, ethylparaben, propylparaben, and butylparaben.

[0023] Preferably, the amount of the antibacterial agent is 1-10 parts by weight, more preferably 2-4 parts.

[0024] Preferably, the antibacterial agent is selected from ethylparaben and propylparaben, with a mass ratio of 1-2:1.

[0025] In one embodiment of the present invention, the scar repair and softening cream comprises, by weight, 100-150 parts of compound gallnut extract, 30-50 parts of borneol, 20-40 parts of menthol, 20-40 parts of camphor, 20-30 parts of methyl salicylate, 550-640 parts of matrix, 50-120 parts of stabilizer, 40-60 parts of hardness modifier, and 10-20 parts of emulsifier.

[0026] Secondly, the present invention provides a method for preparing the above-mentioned scar repair and softening cream, comprising the following steps: (1) Take the base, hardness modifier and emulsifier, mix them, heat until melted, mix well, then add the stabilizer and mix well to make the cream base; (2) Mix camphor, methyl salicylate, and menthol to prepare mixed solution A; (3) Cool down the cream base from step (1), add borneol and mix well, then add the mixed solution A from step (2) and mix well, and finally add the compound gallnut extract and mix well to obtain mixture B; (4) After cooling mixture B, scar repair and softening cream is obtained.

[0027] or: (1) Take the base, hardness modifier and emulsifier, mix them, heat until melted, mix well, then add the stabilizer and mix well to make the cream base; (2) Mix camphor, methyl salicylate, menthol, and antibacterial agent to prepare mixed solution A; (3) Cool down the cream base from step (1), add borneol and mix well, then add the mixed solution A from step (2) and mix well, and finally add the compound gallnut extract and mix well to obtain mixture B; (4) After cooling mixture B, scar repair and softening cream is obtained.

[0028] In step (2), methyl salicylate is used as a solvent, and camphor and menthol can form a mixed solution with methyl salicylate under stirring.

[0029] In this invention, compound gallnut extract is used as the aqueous phase, and after being mixed evenly with other ingredients, it is emulsified to obtain a softening cream.

[0030] In one embodiment of the present invention, the heating temperature in step (1) is 70-85°C.

[0031] In one embodiment of the present invention, the temperature after cooling in step (3) is 55-65℃.

[0032] As one embodiment of the present invention, the specific operation of adding compound gallnut extract and mixing in step (3) is as follows: vacuum to -0.02~-0.04MPa and homogenize for 15-25 minutes.

[0033] As one embodiment of the present invention, the temperature after cooling in step (4) is 25-35°C.

[0034] In a preferred embodiment of the present invention, the preparation method includes the following steps: (1) Take the base, hardness modifier and emulsifier, heat to 70-85℃ to melt, stir evenly, then add stabilizer and mix evenly to make cream base; (2) Take camphor, methyl salicylate, and menthol, with or without adding antibacterial agents, and mix them to prepare mixed solution A; (3) Cool the cream base to 55-65℃, add borneol, then add the mixed solution A from step (2), mix, then add the compound gallnut extract and mix, vacuum to -0.02~-0.04MPa, homogenize for 15-25 minutes; (4) Cooling water is introduced to lower the temperature, and the mixture is stirred to lower the temperature to 25-35℃. The mixture is then filled into containers.

[0035] Thirdly, the present invention provides the use of the above-mentioned scar repair and softening cream or the scar repair and softening cream prepared by the above-mentioned preparation method in the preparation of medicaments for the prevention and / or repair of scars.

[0036] In one embodiment of the present invention, the scar is a proliferative scar.

[0037] In a preferred embodiment of the present invention, the proliferative scar is caused by burns or surgery, such as flame burns, hot liquid burns, chemical burns, electric shocks, surgery, or trauma.

[0038] Compared with the prior art, the beneficial effects of the present invention are as follows: (1) The present invention optimizes the excipients and uses specific emulsifiers and other matrices that are easy to coat and disperse, have good stability, and synergistically promote drug stability, coating sensory effect and improve scar repair effect; (2) The present invention optimizes the preparation method and adopts a specific preparation method to maintain the high temperature stability of the cream. Detailed Implementation

[0039] The present invention will be further described below with reference to specific embodiments. All the raw materials listed below are commercially available conventional raw materials.

[0040] The compound gallnut extracts used in the following examples and comparative examples were prepared in-house. The specific preparation process followed the drug standards issued by the Ministry of Health (Volume 6 of Traditional Chinese Medicine Compound Preparations): Scar Relief and Softening Ointment, standard number: WS3-B-1296-92. The prescription and preparation method of the compound gallnut extract are described below: [Prescription] Gallnut 500g, Clematis chinensis 500g, Moutan bark 250g, Lycopus lucidus 250g.

[0041]

Preparation

[0042] The specific ingredients and dosages of the creams in Examples 1-5 and Comparative Examples 1-6 are shown in Tables 1-2 below. Table 1 Prescriptions for Examples 1-5

[0043] Table 2 Comparative Examples 1-6 Prescriptions

[0044] The preparation methods of scar repair and softening creams in Examples 1 and 4-5 are as follows: (1) Take the base, hardness modifier and emulsifier, mix them, heat to 80°C to melt, stir evenly, then add the stabilizer and mix evenly to make the cream base; (2) Prepare a mixed solution by taking camphor, methyl salicylate, menthol and antibacterial agent; (3) Cool down to 60℃, add borneol, then add the mixed solution from step (2) to step (1), mix, then add compound gallnut extract and mix, vacuum to -0.02MPa, homogenize for 25 minutes; (4) Cooling water is introduced to lower the temperature, and the mixture is stirred to lower the temperature to 30°C. The mixture is then filled into containers.

[0045] Example 2: Preparation method of scar repair and softening cream, the steps are as follows: (1) Mix the base, hardness modifier and emulsifier, heat to 85°C to melt, stir evenly, then add stabilizer and mix evenly to make cream base; (2) Prepare a mixed solution by taking camphor, methyl salicylate, menthol and antibacterial agent; (3) Cool down to 65℃, add borneol, then add the mixed solution from step (2) to step (1), mix, then add compound gallnut extract and mix, vacuum to -0.03MPa, homogenize for 15 minutes; (4) Cooling water is introduced to lower the temperature, and the mixture is stirred to lower the temperature to 25°C. The mixture is then filled into containers.

[0046] Example 3: Preparation method of scar repair and softening cream, the steps are as follows: (1) Mix the base, hardness modifier and emulsifier, heat to 70°C to melt, stir evenly, then add stabilizer and mix evenly to make cream base; (2) Prepare a mixed solution by taking camphor, methyl salicylate, menthol and antibacterial agent; (3) Cool down to 55℃, add borneol and stir well. Then add the mixed solution from step (2) to step (1), mix, then add compound gallnut extract and mix. Vacuum up to -0.04MPa and homogenize for 20 minutes. (4) Cooling water is introduced to lower the temperature, and the mixture is stirred to lower the temperature to 35°C. The mixture is then filled into containers.

[0047] Comparative Examples 1-2: Scar Repair and Softening Creams were prepared according to the preparation method of Example 1.

[0048] Comparative Examples 3-6: Scar Repair and Softening Creams were prepared according to the preparation method of Example 2.

[0049] Comparative Example 7 The only difference from Example 2 is the preparation method of the scar repair and softening cream, as follows: (1) Mix the base, hardness modifier and emulsifier, heat to 85°C to melt, stir evenly, then add stabilizer and mix evenly to make cream base; (2) Prepare a mixed solution by adding camphor, methyl salicylate, menthol, antibacterial agent, borneol and 43g ethanol; (3) Cool down to 65℃, add the mixed solution from step (2) to step (1), and mix. Then add the compound gallnut extract and mix, vacuum to -0.03MPa, and homogenize for 15 minutes; (4) Cooling water is introduced to lower the temperature, and the mixture is stirred to lower the temperature to 25°C. The mixture is then filled into containers.

[0050] Comparative Example 8 The ointment was prepared according to Chinese Invention Patent Publication No. CN1319516C. The composition, dosage, and preparation method are shown below: Compound Gallnut Extract 120g, Borneol 43g, Menthol 34g, Camphor 34g, Methyl Salicylate 26g.

[0051] Take 50g of glycerin, 30g of stearic acid, 20g of triethanolamine, 20g of lanolin, 200g of petrolatum, 20g of liquid paraffin, 2g of ethylparaben, and 2g of propylparaben. Heat (80℃) to melt them. Add 399g of water and emulsify for 10 minutes to form a matrix. When the temperature drops to 55℃, add compound gallnut extract, borneol, menthol, camphor, and methyl salicylate and mix. Stir for 10 minutes, then dispense into containers to obtain the final product.

[0052] I. Stability Testing 1.1 The cream products prepared in Examples 1-5 and Comparative Examples 1-8 were centrifuged at 3500 rpm for 30 minutes to examine the centrifugal stability of the creams. Then, another batch of cream products was added to 10 mL sealed vials and placed in a 40℃ hot air oven for 3 days to examine the properties of the creams. The results are shown in Table 3.

[0053] 1.2 The creams prepared in Examples 1-5 and Comparative Examples 1-8 were placed at 30℃±2℃ and RH65%±5% for 12 months and various indicators were tested. The results are shown in Table 3 below.

[0054] Table 3. Stability Test Results

[0055] II. Efficacy Test 2.1 Sixty subjects with mild to moderate proliferative scars of similar age were selected and divided into 10 groups. Each group underwent efficacy testing using a product with relatively good stability. The groups were, in order: Examples 1-5, Comparative Examples 1, 3, 5, 6, and 8, with 6 subjects in each group. The treatment lasted for 3 months. All participants were enrolled approximately one week after complete wound healing. Scar test data within each group was kept similar before the test. There were no statistically significant differences in general characteristics among the 10 groups (p > 0.05), indicating comparability. Product usage: Clean and dry the scar area. Apply an appropriate amount of the test sample to the scar gently three times daily.

[0056] 2.2 The Vancouver Scar Score (VSS) in Table 4 was used for quantification. Based on the scoring criteria in the table, scores ranging from 0 to 5 points were assigned from low to high. The VSS score was used to assess the scar condition of both groups of patients before and after treatment. The assessment focused on four aspects: color (3 points), thickness (4 points), vascular distribution (3 points), and softness (5 points). The total score was 15 points, with higher scores indicating more severe scarring.

[0057] Table 4. Vancouver Scar Scoring Quantification Table

[0058] 2.3 Based on the observation of the scar repair of the subjects, 6 volunteers (3 males and 3 females) with good physical and mental health and healthy skin were selected as the experimental subjects. The cream was evenly applied to the back of each subject's hand with fingers. The sensory evaluation of the cream was based on three aspects: spreadability, smoothness of skin feel, and oiliness / viscosity. The specific scoring criteria are shown in Table 5.

[0059] Table 5 Sensory Evaluation Criteria for Coating Exhibition

[0060] 2.4 Experimental Results (1) The VSS scale scores were recorded as average values, and the results for each group are shown in Table 6. There was no significant difference in VSS scores among the groups before treatment (p>0.05).

[0061] Table 6 Comparison of VSS scores before and after treatment in subjects

[0062] Note: Lowercase letters a, b, and c are labels for uniform subsets. The same letter indicates no significant difference (p > 0.05), and different letters indicate significant difference (p < 0.05).

[0063] In Table 6, the comparison between the treatment results and the pre-treatment results of each group showed a significant difference (p < 0.05). The inter-group comparison showed that each example and comparative example belonged to a different uniform subset, and the overall average score of the example group was significantly lower than that of the comparative example group, indicating that the treatment effect of each example group was significantly better than that of each comparative example group (p < 0.05). The cream of each example group of the present invention has better efficacy in improving scars and its excipients are better. Within each example group, Example 5 and Example 4 had the best efficacy (lowest average score) and showed a significant difference compared with the efficacy of Example 1 (p < 0.05), indicating that Example 4-Example 5 further optimized the emulsifier composition and significantly improved the efficacy.

[0064] (2) The sensory evaluation results of each group of creams are shown in Table 7 below.

[0065] Table 7 Summary of Average Sensory Scores for Coating Exhibition

[0066] Results Analysis: In Table 7, Examples 1-5 showed the best spreadability, while the other samples exhibited varying degrees of decline in spreadability. The formulation of Comparative Example 1 was affected by the type of emulsifier; the formulation of Comparative Example 3 was affected by the amount of emulsifier; the formulation of Comparative Example 5 lacked a hardness modifier; the formulation of Comparative Example 6 lacked a stabilizer; and the cream prepared using the published patent in Comparative Example 8 had a poor skin feel.

Claims

1. A scar repair and softening cream, characterized in that, The raw materials of the scar repair and softening cream include active ingredients, emulsifiers, matrix, stabilizers, and hardness modifiers; The active ingredients include compound gallnut extract, borneol, menthol, camphor, and methyl salicylate; The emulsifier contains at least a phospholipid derivative.

2. The scar repair and softening cream according to claim 1, characterized in that, The phospholipid derivative is selected from one or a combination of several of soybean lecithin, egg yolk lecithin, hydrogenated soybean lecithin, dipalmitoylphosphatidylcholine, and distearate phosphatidylcholine.

3. The scar repair and softening cream according to claim 1, characterized in that, The emulsifiers also include sorbitan fatty acids.

4. The scar repair and softening cream according to claim 3, characterized in that, The fatty acid sorbitans are selected from one or more of sorbitan trioleate, sorbitan lauryl, sorbitan oleate, sorbitan palmitate, and sorbitan stearate.

5. The scar repair and softening cream according to claim 3, characterized in that, The mass ratio of the phospholipid derivative to the fatty acid sorbitan is 1-3:

1.

6. The scar repair and softening cream according to claim 1, characterized in that, The matrix is ​​selected from white petrolatum.

7. The scar repair and softening cream according to claim 1, characterized in that, The stabilizer is selected from starch sugar ester derivatives.

8. The scar repair and softening cream according to claim 7, characterized in that, The starch ester derivative is selected from one or a combination of several of the following: octenyl succinate aluminum starch, octenyl succinate sodium starch, octadecenyl succinate sodium starch, decenyl succinate aluminum starch, dodecenyl succinate aluminum starch, laurate starch ester, myristate starch ester, palmitic starch ester, and caprylic starch ester.

9. The scar repair and softening cream according to claim 1, characterized in that, The hardness modifier is selected from one or a combination of several of the following: white beeswax, beeswax, paraffin wax, Japanese wax, carnauba wax, shellac wax, rice wax, cork wax, ceresin wax, montan wax, lanolin wax, and microcrystalline wax.

10. The scar repair and softening cream according to claim 1, characterized in that, By weight, the scar repair and softening cream comprises 100-150 parts of compound gallnut extract, 30-50 parts of borneol, 20-40 parts of menthol, 20-40 parts of camphor, 20-30 parts of methyl salicylate, 10-20 parts of emulsifier, 550-640 parts of matrix, 50-120 parts of stabilizer, and 40-60 parts of hardness modifier.

11. The scar repair and softening cream according to any one of claims 1-10, characterized in that, The ingredients of the scar repair and softening cream also include antibacterial agents.

12. The scar repair and softening cream according to claim 11, characterized in that, The antibacterial agent is selected from one or a combination of several of methylparaben, ethylparaben, propylparaben, and butylparaben.

13. The scar repair and softening cream according to claim 12, characterized in that, The antibacterial agent is selected from ethyl paraben and propyl paraben, with a mass ratio of 1-2:

1.

14. The scar repair and softening cream according to claim 11, characterized in that, The amount of the antibacterial agent is 1-10 parts by weight, preferably 2-4 parts.

15. A method for preparing a scar repair and softening cream according to any one of claims 1-14, characterized in that, Includes the following steps: (1) Take the base, hardness modifier and emulsifier, mix them, heat until melted, mix well, then add the stabilizer and mix well to make the cream base; (2) Mix camphor, methyl salicylate and menthol, with or without adding antibacterial agents, to prepare mixed solution A; (3) Cool down the cream base from step (1), add borneol and mix well, then add the mixed solution A from step (2) and mix well, and finally add the compound gallnut extract and mix well to obtain mixture B; (4) After cooling mixture B, scar repair and softening cream is obtained.

16. The preparation method according to claim 15, characterized in that, The heating temperature in step (1) is 70-85℃; and / or the temperature after cooling in step (3) is 55-65℃; and / or the specific operation of adding compound gallnut extract and mixing in step (3) is: vacuuming to -0.02~-0.04MPa and homogenizing for 15-25 minutes; and / or cooling mixture B in step (4) to 25-35℃ to obtain scar repair and softening cream.

17. The use of a scar repair and softening cream according to any one of claims 1-14 or a scar repair and softening cream prepared by the preparation method according to any one of claims 15-16 in the preparation of a medicament for preventing and / or repairing scars.

18. The application according to claim 17, characterized in that, The scar is a proliferative scar.

19. The application according to claim 18, characterized in that, The proliferative scars are caused by burns or surgery.

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