A traditional Chinese medicine gel for treating or improving postoperative hypertrophic scars in plastic surgery and a preparation method thereof

Abstract

The application provides a traditional Chinese medicine gel for treating or improving postoperative hypertrophic scars of plastic surgery and a preparation method thereof, and relates to the technical field of biological medicine.The traditional Chinese medicine gel is prepared by taking traditional Chinese medicine powder prepared from millipede, semen eurycoryadi, herba lophatheri, herba sanguicarpae, radix scrophulariae, and rhizoma curcumae as main active substances, and each traditional Chinese medicine ingredient is indispensable for mutual assistance and synergistic effect, and the drugs are used together to achieve the effects of breaking blood and removing blood stasis, clearing heat and resolving toxins, promoting dampness and swelling, promoting qi and resolving masses, and jointly playing the pharmacological effects of dissipating scar induration, reducing local redness and pain, and inhibiting abnormal proliferation of scars.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, specifically to a traditional Chinese medicine gel for treating or improving hypertrophic scars after plastic surgery and its preparation method. Background Technology

[0002] Hypertrophic scars (HS) are a pathological phenomenon of abnormal repair after skin tissue injury. Clinically, they appear as purplish-red or flushed red scars with a relatively hard texture. They not only affect the patient's appearance but can also cause a series of problems such as pain, itching, and functional impairment. With the improvement of people's living standards and the increasing pursuit of beauty, the prevention and treatment of scars has gradually become a focus of public and medical attention. Although various scar treatments are now available, such as surgical excision, laser therapy, drug therapy, and radiotherapy, certain risks and adverse reactions exist. For example, hormone injections may lead to skin atrophy and vasodilation; simple surgical excision has a high recurrence rate and often needs to be combined with other treatment methods to improve the effect; and radiotherapy may cause radiation dermatitis or hypopigmentation, increasing treatment costs and causing pain to patients. Therefore, finding a practical and feasible treatment method for HS remains an urgent problem to be solved.

[0003] Studies have shown that certain traditional Chinese medicines can not only improve the antibacterial ability of skin wounds and enhance local blood circulation and immune function, but also promote wound healing and inhibit the growth of hypertrophic scars by regulating cytokines. This invention aims to provide a traditional Chinese medicine gel based on herbal extracts that can be used to prevent and treat hypertrophic scars after plastic surgery, offering a new approach to the treatment of HS (hypertrophic scarring). Summary of the Invention

[0004] (a) Technical problems to be solved

[0005] To address the shortcomings of existing technologies, this invention provides a traditional Chinese medicine gel for treating or improving hypertrophic scars after plastic surgery, and its preparation method.

[0006] (II) Technical Solution

[0007] To achieve the above objectives, the present invention provides the following technical solution:

[0008] In a first aspect, the present invention provides a traditional Chinese medicine gel for treating or improving hypertrophic scars after plastic surgery. The gel is made from the following raw materials in parts by weight per 100 parts: 20-40 parts of traditional Chinese medicine powder, 0.7-1.8 parts of carbomer 980, 0.4-1.2 parts of hydroxypropyl methylcellulose (HPMC) E50, 0.3-1.0 parts of polyvinylpyrrolidone (PVP) K30, 1.0-2.8 parts of triethanolamine, 0.08-0.3 parts of citric acid, 0.08-0.3 parts of sodium citrate, 4.0-10.0 parts of propylene glycol, 3.0-9.0 parts of glycerin, 2.0-6.0 parts of polyethylene glycol 400, 0.3-1.2 parts of medical-grade light liquid paraffin, 2.5-6.5 parts of anhydrous ethanol, and Tween 80. 0.2-0.7 parts, 0.04-0.18 parts, vitamin E succinate 0.05-0.25 parts, phenoxyethanol 0.25-0.75 parts, ethylhexylglycerin 0.08-0.25 parts, and the remainder purified water to make up to 100 parts by weight.

[0009] Further, each 100 parts by weight of the herbal gel is made from the following raw materials in parts by weight: 30-40 parts of herbal powder, 0.7-1.8 parts of carbomer 980, 0.4-1.2 parts of hydroxypropyl methylcellulose HPMC E50, 0.3-1.0 parts of polyvinylpyrrolidone, 1.0-2.8 parts of triethanolamine, 0.08-0.3 parts of citric acid, 0.08-0.3 parts of sodium citrate, 4.0-10.0 parts of propylene glycol, 3.0-9.0 parts of glycerin, 2.0-6.0 parts of polyethylene glycol 400, 0.3-1.2 parts of medical light liquid paraffin, 2.5-6.5 parts of anhydrous ethanol, and Tween 80. 0.2-0.7 parts, 0.04-0.18 parts, vitamin E succinate 0.05-0.25 parts, phenoxyethanol 0.25-0.75 parts, ethylhexylglycerin 0.08-0.25 parts, and the remainder purified water to make up to 100 parts by weight.

[0010] Further, each 100 parts by weight of the herbal gel is made from the following raw materials in parts by weight: 35 parts of herbal powder, 0.7-1.8 parts of carbomer 980, 0.4-1.2 parts of hydroxypropyl methylcellulose HPMC E50, 0.3-1.0 parts of polyvinylpyrrolidone, 1.0-2.8 parts of triethanolamine, 0.08-0.3 parts of citric acid, 0.08-0.3 parts of sodium citrate, 4.0-10.0 parts of propylene glycol, 3.0-9.0 parts of glycerin, 2.0-6.0 parts of polyethylene glycol 400, 0.3-1.2 parts of medical light liquid paraffin, 2.5-6.5 parts of anhydrous ethanol, and Tween 80. 0.2-0.7 parts, 0.04-0.18 parts, vitamin E succinate 0.05-0.25 parts, phenoxyethanol 0.25-0.75 parts, ethylhexylglycerin 0.08-0.25 parts, and the remainder purified water to make up to 100 parts by weight.

[0011] Furthermore, the Chinese medicine powder is made from the following Chinese medicinal materials in parts by weight: 20-40 parts of woodlice, 10-30 parts of senna powder, 20-40 parts of Scutellaria barbata, 20-40 parts of Saururus chinensis, 10-30 parts of Angelica dahurica, and 10-30 parts of turmeric.

[0012] Furthermore, the Chinese medicine powder is made from the following Chinese medicinal materials in parts by weight: 25-40 parts of woodlice, 15-30 parts of senna powder, 25-40 parts of Scutellaria barbata, 25-40 parts of Saururus chinensis, 15-30 parts of Angelica dahurica, and 15-30 parts of turmeric.

[0013] Furthermore, the Chinese medicine powder is made from the following Chinese medicinal materials in parts by weight: 35 parts of woodlice, 20 parts of senna powder, 30 parts of Scutellaria barbata, 35 parts of Saururus chinensis, 25 parts of Angelica dahurica, and 20 parts of turmeric.

[0014] Furthermore, the medicinal powder contains the dried whole body of *Armadillidium vulgare* (Latreille), an animal belonging to the genus *Armadillidium* of the family Solitaireceae, or *Porcellio scaber Latreille*, an animal belonging to the genus *Porcellio* of the family Solitaireceae. It possesses the effects of breaking up blood stasis and eliminating masses, promoting menstruation, diuresis, detoxification, and relieving pain. It is mainly used to treat abdominal masses, malaria, amenorrhea due to blood stasis, urinary retention, infantile convulsions with tinnitus, toothache, and thrush. The woodlice mainly contain sterols, alkaloids, organic acids, and lipids. Modern pharmacological studies have shown that it has analgesic and anti-inflammatory effects, antibacterial activity, anticoagulant function, antitumor activity, and pharmacological effects on the proliferation and migration of vascular smooth muscle cells.

[0015] Furthermore, among the aforementioned traditional Chinese medicine powders, Qianjinzi Shuang is a processed product of the dried, mature seeds (Qianjinzi) of Euphorbia lathyris L., a plant of the Euphorbiaceae family. It possesses the effects of purging and promoting diuresis, breaking up blood stasis and eliminating masses; externally, it is effective in treating tinea and warts. It is commonly used for constipation, edema, phlegm retention, abdominal distension due to stagnation, blood stasis and amenorrhea; externally, it is used to treat stubborn tinea, warts, and other ailments. Its main components include diterpenoid alcohols and their esters, sterols, coumarins, flavonoids, volatile oils, fatty oils, and other compounds. Modern pharmacological studies have shown that it has anti-tumor, anti-pulmonary fibrosis, and intestinal motility-promoting pharmacological effects.

[0016] Furthermore, in the aforementioned Chinese herbal powder, *Scutellaria barbata* D. Don, a plant of the Lamiaceae family, is the dried whole herb. It possesses the effects of clearing heat and detoxifying, resolving blood stasis, and promoting diuresis. It is mainly used to treat boils and carbuncles, sore throat, traumatic injuries, edema, jaundice, and snake and insect bites. Flavonoids, terpenes, polysaccharides, and volatile oils are the active ingredients that contribute to the medicinal effects of *Scutellaria barbata*. Modern pharmacological research shows that anti-tumor and anti-inflammatory effects are its main pharmacological effects. In addition, *Scutellaria barbata* also has antibacterial, antiviral, antioxidant, and hepatoprotective effects.

[0017] Furthermore, in the aforementioned Chinese herbal powder, Saururus chinensis (Lour.) Baill. is a plant of the Saururaceae family, and its rhizome or whole herb is usually used medicinally; it has the effects of clearing heat and detoxifying, promoting diuresis and reducing swelling. Saururus chinensis contains a variety of active chemical components such as lignans, flavonoids, terpenes, and steroids, and also has a wide range of pharmacological activities such as anti-inflammatory, anti-tumor, liver protection, and hypoglycemic effects.

[0018] Furthermore, in the aforementioned traditional Chinese medicine powder, *Peucedanum decursivum* is the dried root of the plant *Peucedanum decursivum* (Miq.) Maxim. (family Apiaceae); it has the effects of lowering qi and resolving phlegm, dispelling wind and clearing heat. It is mainly used to treat phlegm-heat wheezing, thick yellow phlegm, and wind-heat cough with excessive phlegm. The pharmacological effects of *Peucedanum decursivum* are mainly anticoagulant, expectorant, antiasthmatic, and antitumor; its main active ingredients are linear furanocoumarins, specifically *Peucedanum decursivum* glycoside and *Peucedanum decursivum* aglycone.

[0019] Furthermore, in the aforementioned traditional Chinese medicine powder, turmeric is the dried rhizome of Curcuma longa L., a plant belonging to the genus Curcuma in the ginger family (Zingiberaceae). It has the effects of promoting blood circulation, regulating qi, and relieving pain; it is mainly used to treat chest and rib pain, angina pectoris, dysmenorrhea, amenorrhea, abdominal masses, rheumatic shoulder and arm pain, and swelling and pain from falls and injuries. The main active components of turmeric are curcumin and volatile oil. Modern pharmacological studies have shown that turmeric has pharmacological effects such as antioxidant, antibacterial, anti-inflammatory, analgesic, antitumor, antimicrobial, hepatoprotective, choleretic, lipid-lowering, blood pressure-lowering, blood sugar-lowering, and nervous system-regulating and protective effects.

[0020] Secondly, the present invention provides a method for preparing a traditional Chinese medicine gel for treating or improving hypertrophic scars after plastic surgery, wherein the traditional Chinese medicine gel is prepared according to the following steps:

[0021] S1: Preparation of Traditional Chinese Medicine Powder

[0022] (1) Weigh out the woodlice, scutellaria barbata, scutellaria barbata, scutellaria barbata, angelica dahurica, and turmeric according to the above weight proportions, clean them, crush them, pass them through a 40-60 mesh sieve, and mix them evenly to obtain raw material coarse powder;

[0023] (2) Add 8-10 times the amount of purified water to the raw material powder, soak for more than 1.5 hours, then heat to 90-100℃, reflux the extract for more than 2 hours, and then collect the first extract; add 6-8 times the amount of purified water to the residue, then heat to 85-95℃, reflux the extract for more than 2 hours, filter, and collect the second extract; combine the two extracts, filter finely, remove fine residue impurities, and obtain Chinese medicine filtrate;

[0024] (3) Concentrate the Chinese herbal filtrate under reduced pressure to a clear Chinese herbal extract with a relative density of 1.15-1.25. Then, bring the clear Chinese herbal extract to room temperature and slowly add 95% ethanol while stirring, so that the volume fraction of ethanol in the system reaches 65-70%. Then, refrigerate and let stand for more than 12 hours, remove the upper alcohol liquid, and then filter it with a filter screen of 300 mesh or higher to remove precipitated impurities and obtain alcohol extract. Recover the ethanol from the alcohol extract under reduced pressure until there is no alcohol smell to obtain a purified and concentrated extract. Perform vacuum freeze-drying on the extract, pulverize it through a 150-200 mesh sieve to obtain Chinese herbal powder.

[0025] S2 Preparation of Gel Matrix

[0026] Take 60-65% of total purified water, evenly sprinkle in carbomer 980 powder, stir at room temperature at 80-120 r / min for 25-30 min, and let it stand in a sealed container for 14-16 h to swell, obtaining a transparent carbomer sol; separately take a small amount of purified water and heat to 40-45℃ to dissolve HPMC E50 and PVP K30, stirring until there are no particles, then slowly add the carbomer sol, continue stirring, mix evenly, then add citric acid and sodium citrate, stir to dissolve, and obtain a gel matrix for later use;

[0027] S3 Preparation of drug-loaded dispersion

[0028] Propylene glycol, glycerin, polyethylene glycol 400, and anhydrous ethanol were mixed and stirred. Then Tween 80 was added, and stirring was continued for 10-15 minutes. Menthol and vitamin E succinate were then added and stirred until completely dissolved. Medical light liquid paraffin was then added, and the mixture was stirred at 700-800 rpm for 15-20 minutes to obtain an emulsion for enhanced penetration. Subsequently, the Chinese herbal medicine powder was added to the emulsion for enhanced penetration in 3-5 portions, and homogenized at high speed at 15000-20000 rpm for 35-40 minutes until there were no drug residues or lumps, resulting in a uniform drug-loaded dispersion for later use.

[0029] S4 Preparation of Traditional Chinese Medicine Gel

[0030] The drug-loaded dispersion was poured into the gel matrix at a uniform speed and stirred at 300-500 rpm for at least 30 minutes. Then, it was homogenized and emulsified at high speed for 12-20 minutes to ensure complete integration and no precipitation. The pH of the system was then adjusted to 5.2-6.4 with triethanolamine. Phenoxyethanol and ethylhexylglycerin were then added and stirred for at least 10 minutes. Purified water was added to bring the total weight to 100 parts by weight and stirred until homogeneous. Vacuum degassing was then performed, and the mixture was allowed to stand at room temperature in the dark for at least 30 hours. After maturation, the mixture was aseptically filtered through a 120-150 mesh sieve, sterilized, and dispensed to obtain the traditional Chinese medicine gel.

[0031] (III) Beneficial Effects

[0032] This invention uses a powder made from woodlice, *Euphorbia lathyris*, *Scutellaria barbata*, *Saururus chinensis*, *Peucedanum praeruptorum*, and turmeric as the main active ingredients to prepare a herbal gel. Each herbal component complements and enhances the effect; none can be omitted. Woodlice, *Euphorbia lathyris*, and turmeric all have the function of breaking up blood stasis. Woodlice excels at breaking up blood stasis and eliminating masses, *Euphorbia lathyris* is good at eliminating masses and dispersing nodules, and turmeric can both break up blood stasis and promote qi circulation. The combination of these three herbs breaks up blood stasis and promotes the smooth flow of qi, thus treating the root cause. *Scutellaria barbata* and *Saururus chinensis* both have the functions of clearing heat and detoxifying, and promoting diuresis. Their cold and cooling properties can balance the warming and drying effects of woodlice, *Euphorbia lathyris*, and turmeric, making the entire formula neither too harsh nor too drying. Simultaneously, for postoperative local damp-heat accumulation, redness, swelling, and pain, clearing heat and eliminating dampness are combined; once heat is cleared and dampness is removed, swelling and pain subside, thus treating the symptoms. The purple-flowered Peucedanum praeruptorum disperses wind and regulates qi, acting as a guide for blood-activating herbs to prevent stagnation and aid in their blood-breaking effects. The combined effects of these herbs address both the root cause and the symptoms, possessing the functions of breaking up blood stasis, clearing heat and detoxifying, promoting diuresis and reducing swelling, and regulating qi and dispersing stagnation. Together, they work to dissipate scar nodules, reduce local redness, swelling, and pain, and inhibit abnormal scar proliferation.

[0033] Furthermore, using a rabbit ear hypertrophic scar pathological model as the research object, this invention comprehensively evaluated the therapeutic effect of the herbal gel of this invention in treating or improving hypertrophic scars. Experimental results showed that the herbal gel of this invention can significantly reduce the number of fibroblasts in scar tissue, reduce collagen cell deposition, promote the metabolism of collagen Col I and Col III in scar tissue, inhibit the expression of inflammatory factors, and downregulate the expression of TGF-β1 and VEGF in scar tissue. Through multiple target pathways such as anti-inflammatory, anti-fibrotic, and anti-angiogenic effects, it achieves a therapeutic effect on hypertrophic scars. The herbal gel provided by this invention has strong clinical practical value. Attached Figure Description

[0034] Figure 1 The effects of different drugs on the proliferation (A) and apoptosis (B) of fibroblasts in hypertrophic scars; * P<0.05, ** P<0.01.

[0035] Figure 2 The results of the detection of scar hyperplasia index (A), fibroblast number (B), collagen fiber areal density (C), TNF-α (D), IL-6 (E), Col I (F), Col III (G), TGF-β1 (H), and VEGF (I) in each group of wounds were as follows: * P<0.05, ** P<0.01. Detailed Implementation

[0036] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0037] Example 1

[0038] A traditional Chinese medicine gel for treating or improving hypertrophic scars after plastic surgery, wherein every 100 parts by weight of the gel is made from the following raw materials in parts by weight: 35 parts of traditional Chinese medicine powder, 1.2 parts of carbomer 980, 0.8 parts of hydroxypropyl methylcellulose HPMC E50, 0.6 parts of polyvinylpyrrolidone PVP K30, 1.3 parts of triethanolamine, 0.15 parts of citric acid, 0.2 parts of sodium citrate, 8 parts of propylene glycol, 8 parts of glycerin, 3.5 parts of polyethylene glycol 400, 0.8 parts of medical-grade light liquid paraffin, 4.5 parts of anhydrous ethanol, and Tween 80. 0.5 parts, 0.08 parts, vitamin E succinate 0.15 parts, phenoxyethanol 0.50 parts, ethylhexylglycerin 0.15 parts, and the remainder purified water to make up to 100 parts by weight; wherein, the Chinese medicine powder is made from the following Chinese medicinal materials in parts by weight: 35 parts of woodlice, 20 parts of *Euphorbia lathyris*, 30 parts of *Scutellaria barbata*, 35 parts of *Saururus chinensis*, 25 parts of *Peucedanum praeruptorum*, and 20 parts of turmeric.

[0039] Specifically, the traditional Chinese medicine gel is prepared according to the following steps:

[0040] S1: Preparation of Traditional Chinese Medicine Powder

[0041] (1) Weigh out the woodlice, scutellaria barbata, scutellaria barbata, scutellaria barbata, angelica dahurica, and turmeric according to the above weight proportions, clean them, crush them, pass them through a 40-60 mesh sieve, and mix them evenly to obtain raw material coarse powder;

[0042] (2) Add 10 times the amount of purified water to the raw material powder, soak for more than 1.5 hours, then heat to 95°C, reflux the extract for more than 2 hours, and then collect the first extract; add 8 times the amount of purified water to the residue, then heat to 90°C, reflux the extract for more than 2 hours, filter, and collect the second extract; combine the two extracts, filter finely, remove fine residue impurities, and obtain Chinese medicine filtrate;

[0043] (3) Concentrate the Chinese herbal filtrate under reduced pressure to a clear Chinese herbal extract with a relative density of 1.15-1.25. Then, bring the clear Chinese herbal extract to room temperature and slowly add 95% ethanol while stirring, so that the volume fraction of ethanol in the system reaches 70%. Then, refrigerate and let stand for more than 12 hours, remove the upper alcohol liquid, and then filter it with a filter screen of 300 mesh or higher to remove precipitated impurities and obtain alcohol extract. Recover the ethanol from the alcohol extract under reduced pressure until there is no alcohol smell to obtain a purified and concentrated extract. Perform vacuum freeze-drying on the extract, pulverize it through a 150-200 mesh sieve, and obtain Chinese herbal powder.

[0044] S2 Preparation of Gel Matrix

[0045] Take 60% of the total purified water, evenly sprinkle in carbomer 980 powder, stir at room temperature at 100 r / min for 25 min, and let it stand in a sealed container for 16 h to swell, to obtain a transparent carbomer sol; separately take a small amount of purified water, heat to 40℃ to dissolve HPMC E50 and PVP K30, stir until there are no particles, then slowly add the carbomer sol, continue stirring, mix evenly, then add citric acid and sodium citrate, stir to dissolve, to obtain a gel matrix, for later use;

[0046] S3 Preparation of drug-loaded dispersion

[0047] Propylene glycol, glycerin, polyethylene glycol 400, and anhydrous ethanol were mixed and stirred. Then Tween 80 was added, and stirring was continued for 15 minutes. Menthol and vitamin E succinate were then added and stirred until completely dissolved. Medical light liquid paraffin was then added, and the mixture was stirred at 800 rpm for 20 minutes to obtain an emulsion for enhanced penetration. Subsequently, the Chinese herbal medicine powder was added to the emulsion for enhanced penetration in 3-5 portions, and homogenized at high speed at 15,000 rpm for 40 minutes until there were no drug residues or lumps, resulting in a uniform drug-loaded dispersion for later use.

[0048] S4 Preparation of Traditional Chinese Medicine Gel

[0049] The drug-loaded dispersion was poured into the gel matrix at a uniform speed and stirred at 500 rpm for at least 30 minutes. Then, it was homogenized and emulsified at high speed for 20 minutes to ensure complete integration and no precipitation. The pH of the system was then adjusted to 5.2-6.4 with triethanolamine. Phenoxyethanol and ethylhexylglycerin were then added and stirred for at least 10 minutes. Purified water was added to bring the total weight to 100 parts by weight and stirred until homogeneous. Vacuum degassing was then performed, and the mixture was allowed to stand at room temperature in the dark for at least 30 hours. After maturation, the mixture was aseptically filtered through a 120-150 mesh sieve, sterilized, and dispensed to obtain the traditional Chinese medicine gel.

[0050] Example 2

[0051] The difference between this embodiment and Embodiment 1 is that each 100 parts by weight of the traditional Chinese medicine gel is made from the following raw materials: 20 parts of traditional Chinese medicine powder, 1.6 parts of carbomer 980, 1.0 part of hydroxypropyl methylcellulose HPMC E50, 0.8 parts of polyvinylpyrrolidone PVP K30, 1.8 parts of triethanolamine, 0.2 parts of citric acid, 0.25 parts of sodium citrate, 8 parts of propylene glycol, 7.5 parts of glycerin, 5.0 parts of polyethylene glycol 400, 1 part of medical light liquid paraffin, 5 parts of anhydrous ethanol, 0.6 parts of Tween 80, 0.06 parts of menthol, 0.08 parts of vitamin E succinate, 0.6 parts of phenoxyethanol, 0.12 parts of ethylhexylglycerin, and the remainder purified water to make up to 100 parts by weight.

[0052] Example 3

[0053] The difference between this embodiment and Embodiment 1 is that each 100 parts by weight of the traditional Chinese medicine gel is made from the following raw materials: 40 parts of traditional Chinese medicine powder, 1.5 parts of carbomer 980, 1.4 parts of hydroxypropyl methylcellulose HPMC E50, 0.6 parts of polyvinylpyrrolidone PVP K30, 2.2 parts of triethanolamine, 0.25 parts of citric acid, 0.25 parts of sodium citrate, 5.0 parts of propylene glycol, 6.0 parts of glycerin, 4.5 parts of polyethylene glycol 400, 0.8 parts of medical light liquid paraffin, 4 parts of anhydrous ethanol, 0.7 parts of Tween 80, 0.12 parts of menthol, 0.12 parts of vitamin E succinate, 0.4 parts of phenoxyethanol, 0.2 parts of ethylhexylglycerin, and the remainder purified water to make up to 100 parts by weight.

[0054] Example 4

[0055] The difference between this embodiment and Embodiment 1 is that the Chinese medicine powder in the Chinese medicine gel is made from the following Chinese medicinal materials in parts by weight: 20 parts of woodlice, 10 parts of scutellaria barbata, 20 parts of scutellaria barbata, 20 parts of angelica dahurica, 10 parts of turmeric.

[0056] Example 5

[0057] The difference between this embodiment and Embodiment 1 is that the Chinese medicine powder in the Chinese medicine gel is made from the following Chinese medicinal materials in parts by weight: 40 parts of woodlice, 30 parts of scutellaria barbata, 40 parts of scutellaria barbata, 40 parts of angelica dahurica, 30 parts of turmeric.

[0058] Example 6

[0059] The difference between this embodiment and Embodiment 1 is that the Chinese medicine powder in the Chinese medicine gel is made from the following Chinese medicinal materials in parts by weight: 22 parts of woodlice, 12 parts of scutellaria barbata, 20 parts of Scutellaria barbata, 24 parts of Saururus chinensis, 14 parts of Angelica dahurica, and 12 parts of turmeric.

[0060] Example 7

[0061] The difference between this embodiment and Embodiment 1 is that the traditional Chinese medicine powder in the herbal gel is made from the following parts by weight of traditional Chinese medicinal materials: 25 parts of woodlice, 15 parts of scutellaria barbata, 25 parts of scutellaria barbata, 25 parts of angelica dahurica, 15 parts of turmeric.

[0062] Example 8

[0063] The difference between this embodiment and Embodiment 1 is that the Chinese medicine powder in the Chinese medicine gel is made from the following Chinese medicinal materials in parts by weight: 30 parts of woodlice, 20 parts of senna powder, 35 parts of Scutellaria barbata, 20 parts of Saururus chinensis, 20 parts of Angelica dahurica, and 20 parts of Curcuma longa.

[0064] Example 9

[0065] The difference between this embodiment and Embodiment 1 is that the Chinese medicine powder in the Chinese medicine gel is made from the following Chinese medicinal materials in parts by weight: 36 parts of woodlice, 24 parts of senna powder, 32 parts of Scutellaria barbata, 36 parts of Saururus chinensis, 28 parts of Angelica dahurica, and 26 parts of turmeric.

[0066] Experimental Example 1

[0067] The effects of the main active ingredient, a traditional Chinese medicine powder, on the proliferation and apoptosis of hypertrophic scar fibroblasts (HSF) in this invention.

[0068] 1. Isolation and culture of hypertrophic scar fibroblasts

[0069] Surgically excised hypertrophic scar tissue was collected, and subcutaneous adipose tissue and blood vessels were removed in a clean bench. The scar tissue was then cut into small pieces and added to 0.3% Diapase II enzyme solution, and refrigerated overnight. Afterward, the scar tissue was minced, and 0.25% type I collagenase was added. The mixture was then digested in a 37°C shaker for 3-4 h. The mixture was then filtered, and the filtrate was centrifuged at 1500 r / min for 5 min. The supernatant was discarded, and the tissue was resuspended in culture medium containing 10% FBS and cultured in an incubator. This was marked as generation 0. The tissue was then passaged, and generations 3-5 were used for subsequent experiments.

[0070] 2 Experimental drugs

[0071] Drug 1: 35 parts woodlice, 20 parts powdered jujube seeds, 30 parts Scutellaria barbata, 35 parts Saururus chinensis, 25 parts Angelica dahurica, 20 parts Curcuma longa.

[0072] Drug 2: 20 parts of *Euphorbia lathyris* powder, 30 parts of *Scutellaria barbata*, 25 parts of *Peucedanum praeruptorum*, and 20 parts of turmeric.

[0073] Drug 3: Leech 35 parts, Thousand Golden Seeds Powder 20 parts, Scutellaria barbata 30 parts, Sophora flavescens 35 parts, Peucedanum praeruptorum 25 parts, Curcuma longa 20 parts

[0074] Drug 4: 35 parts woodlice, 20 parts stir-fried morning glory seeds, 30 parts prunella vulgaris, 35 parts white sage, 25 parts angelica dahurica, 20 parts turmeric.

[0075] Drug 5: 35 parts woodlice, 20 parts powdered jujube seeds, 30 parts Scutellaria barbata, 35 parts Saururus chinensis, 25 parts Angelica dahurica, 20 parts Curcuma longa.

[0076] The above-mentioned drug powder was prepared according to the method for preparing traditional Chinese medicine powder described in Example 1. Each part by weight is 0.5g. When used, the drug-containing medium is prepared with serum-free DMEM medium to the corresponding concentration.

[0077] 3. MTT assay for cell proliferation

[0078] HSF cells in the logarithmic growth phase were seeded into 96-well plates at a seeding density of 5 × 10⁶ cells / well. 3 Cells were randomly divided into a control group, drug groups 1-5, and a blank control group without cells. Each group was repeated in 6 replicates. After cell attachment, the culture medium was discarded. Blank culture medium was added to the control group (NC), and 20 μg / mL of drug-containing culture medium was added to drug groups 1-5 (M1-M5). After culturing for 24 h, the culture medium was discarded, and 100 μL of culture medium containing 10% MTT solution was added to each well. The cells were incubated at 37°C in the dark for 4 h. The supernatant was discarded, and DMSO was added to dissolve the cells. The optical density (OD) was measured at 490 nm using a microplate reader, and the cell proliferation rate was calculated.

[0079] 4. Flow cytometry to detect apoptosis levels

[0080] Cells were seeded in 6-well plates at a seeding density of 1 × 10⁶ cells / well. 5Cells were randomly divided into a control group and drug groups 1-5, with six replicates per group. After cell attachment, the culture medium was discarded. Blank culture medium was added to the control group (NC), and drug groups 1-5 (M1-M5) were added with 20 μg / mL of drug-containing medium. After culturing for 24 h, cells were washed with PBS and then treated with trypsin to detach them from the culture plate. Cells were collected and centrifuged to precipitate the cells. 500 μL of binding buffer was added to resuspend the cells. Annexin V and PI reagent were added according to the apoptosis kit instructions, and the cells were incubated for 15 min. Flow cytometry was used to detect apoptosis.

[0081] 5 Results

[0082] Figure 1 The results showed that, compared with the control group, drugs 1-5 significantly inhibited the proliferation of hypertrophic scar fibroblasts (P<0.01) and significantly promoted apoptosis of hypertrophic scar fibroblasts (P<0.01). Among them, drug 1 had a significantly better inhibitory effect on the proliferation of hypertrophic scar fibroblasts and apoptosis-promoting effect than drugs 2-5 (P<0.01).

[0083] The above results indicate that the traditional Chinese medicine powder (drug 1) provided by this invention can inhibit the growth of hypertrophic scar fibroblasts to achieve the pharmacological effect of inhibiting hypertrophic scars. Importantly, the deletion or replacement of some medicinal ingredients in the traditional Chinese medicine powder significantly affects the aforementioned pharmacological effect. The components of the traditional Chinese medicine powder of this invention complement each other and synergistically enhance the effect; their fixed formulation is a necessary technical means to achieve the technical effect of this invention. Each component is indispensable and cannot be arbitrarily replaced or deleted.

[0084] Experimental Example 2

[0085] The effects and functions of the herbal gel of this invention on hypertrophic scars in rabbit ears

[0086] 1. Preparation of rabbit ear skin scar model

[0087] Twenty healthy New Zealand White rabbits, of average grade, half male and half female, weighing (2.2±0.3) kg, were selected and acclimatized for one week before the experiment. Four rabbits were randomly selected as the control group (NC), and the remaining 16 rabbits were used for modeling. The specific method was as follows: after anesthetizing the rabbits by injecting 20% ​​urethane solution at a dose of 5 mL / kg along the marginal ear vein, four circular areas with a diameter of about 1 cm were marked on the ventral side of the rabbit ears. The circular marked wounds were imprinted with a punch, and the full thickness of skin and perichondrium were removed with a scalpel, avoiding blood vessels, with adjacent wounds spaced about 1 cm apart, to form a rabbit ear skin injury model.

[0088] 2. Grouping and Processing

[0089] Sixteen rabbits with wound formation were randomly divided into four groups of four. The control group and the model group were treated with saline solution. The traditional Chinese medicine gel group was treated with the traditional Chinese medicine gel prepared in Example 1. The scar antipruritic ointment group was treated with scar antipruritic softening cream. The Centella asiatica group was treated with Centella asiatica cream ointment. The application amount was 0.1g per scar, twice a day. Each group was treated for 28 consecutive days.

[0090] 3 detection indicators

[0091] 3.1 Scar hyperplasia index

[0092] During the administration period, the scar hyperplasia of rabbit ears was observed. After the administration was completed, the thickness of the scar was measured with calipers and the scar elevation index (SEI) was calculated. The scar elevation index = thickness from the scar protrusion to the cartilage surface / thickness of the surrounding normal skin to the cartilage surface.

[0093] 3.2 Calculation of fibroblast number and collagen fiber areal density

[0094] After drug administration, normal rabbit ear tissue and scar tissue from each group of rabbit ears were collected and routinely fixed, dehydrated, embedded in paraffin, sectioned, stained with hematoxylin and eosin (HE), and stained with Mosson's stain. HE-stained specimens were examined under low magnification to identify areas with abundant fibroblasts, and then four fields of view were selected under high magnification for fibroblast counting. For Mosson's stained specimens, ten rectangular fields of view were taken from the center and sides of the scar, and collagen fiber areal density was determined using pathological image analysis software.

[0095] 3.3 ELISA detection of scar tissue

[0096] Normal rabbit ear tissue and rabbit ear scar tissue from each group were washed, ground, and homogenized with PBS solution. The tissue homogenates were centrifuged, and the supernatant was collected. The levels of TNF-α and IL-6 in the rabbit ear tissue of each group were detected using an ELISA kit. The operation method was in accordance with the kit instructions.

[0097] 3.4 Western blot analysis of scar tissue

[0098] Western blot was used to detect the protein expression of type I collagen (Col I), type III collagen (Col III), TGF-β1, and vascular endothelial growth factor (VEGF) in scar tissue. 100 mg of rabbit ear scar tissue was collected, washed with pre-chilled PBS buffer, and 500 μL of tissue lysis buffer was added. The tissue was homogenized on ice for 30 s, centrifuged at 4°C for 10 min, and used for total protein extraction. The protein content was determined using the BCA method. Take 20 μL of sample and add it to the loading buffer. Boil in water for 5–10 min and perform SDS-PAGE gel electrophoresis. Transfer the protein to a PVDF membrane, gently vortex and rinse 3 times with TBST, and block with blocking buffer at room temperature for 2 h. Incubate with primary antibody at 4°C overnight and rinse 3 times with TBST. Decolorize with secondary antibody at room temperature and incubate on a shaker for 2 h, and rinse 3 times with TBST. After reacting in ECL reagent at room temperature in the dark for 5 min, expose the film in a dark room, develop and fix it, and quantitatively analyze the optical density value (OD value) of the target band using a gel imaging system to calculate the relative protein expression level.

[0099] 4 Data Processing Methods

[0100] All experimental data are expressed as mean ± standard deviation. One-way ANOVA was performed using SPSS 22.0 statistical software. P < 0.05 was considered statistically significant.

[0101] 5 Results

[0102] Compared with the control group, the model group showed a significant increase in the scar hyperplasia index, fibroblast count, and collagen fiber areal density of the rabbit ear wound (P<0.01), indicating that the hypertrophic scar model was successfully established. Furthermore, compared with the control group, the model group showed a significant increase in the levels of inflammatory factors TNF-α and IL-6 in the rabbit ear scar tissue (P<0.01), and a significant increase in the relative protein expression levels of Col I, Col III, TGF-β1, and VEGF (P<0.01).

[0103] After treatment with different drugs, compared with the model group, the scar hyperplasia index of rabbit ear wounds in the traditional Chinese medicine gel group, scar antipruritic ointment group, and centella asiatica group were significantly reduced, as were the number of fibroblasts and the areal density of collagen fibers. At the same time, the levels of inflammatory factors TNF-α and IL-6, and the relative protein expression of Col I, Col III, TGF-β1 and VEGF in the rabbit ear scar tissue of the three drug treatment groups were significantly reduced compared with the model group (P<0.01).

[0104] Furthermore, the scar hyperplasia index, fibroblast count, and collagen fiber areal density of the rabbit ear wound in the traditional Chinese medicine gel group were significantly lower than those in the scar antipruritic ointment group and the centella asiatica group (P<0.01); the levels of inflammatory factors TNF-α and IL-6, and the relative protein expression levels of Col I, Col III, TGF-β1, and VEGF in the rabbit ear scar tissue of the traditional Chinese medicine gel group were significantly lower than those in the scar antipruritic ointment group and the centella asiatica group (P<0.05, P<0.01). These results are as follows. Figure 2 As shown.

[0105] Currently, the pathogenesis of hypertrophic scars is not fully understood. Traditional Chinese medicine (TCM) preparations with good efficacy, low cost, and few side effects have broad clinical application prospects for scar treatment. In the early stages, this invention conducted extensive screening and verification of TCM ingredients, ultimately selecting a TCM gel prepared from a powder made from woodlice, *Euphorbia lathyris*, *Scutellaria barbata*, *Saururus chinensis*, *Peucedanum praeruptorum*, and turmeric as the main active ingredients. This gel possesses the effects of breaking up blood stasis, clearing heat and detoxifying, promoting diuresis and reducing swelling, and regulating qi and dispersing stagnation. This experimental case uses a rabbit ear hypertrophic scar pathological model as the research object to comprehensively evaluate the therapeutic effect of the TCM gel of this invention in treating or improving hypertrophic scars. Experimental results show that the herbal gel of this invention can significantly reduce the number of fibroblasts in scar tissue, reduce collagen cell deposition, promote the metabolism of collagen Col I and Col III in scar tissue, inhibit the expression of inflammatory factors, and downregulate the expression of TGF-β1 and VEGF in scar tissue. It achieves a therapeutic effect on hypertrophic scars through multiple target pathways, including anti-inflammatory, anti-fibrotic, and anti-angiogenic effects. It is worth noting that the herbal gel of this invention has advantages over scar antipruritic ointment and Centella asiatica cream in the treatment of hypertrophic scars.

[0106] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A traditional Chinese medicine gel for treating or improving postoperative hypertrophic scar in orthopedic surgery, characterized in that, The herbal gel is made from the following raw materials in parts by weight per 100 parts: 20-40 parts herbal powder, 0.7-1.8 parts carbomer 980, 0.4-1.2 parts hydroxypropyl methylcellulose HPMC E50, 0.3-1.0 parts polyvinylpyrrolidone PVP K30, 1.0-2.8 parts triethanolamine, 0.08-0.3 parts citric acid, 0.08-0.3 parts sodium citrate, 4.0-10.0 parts propylene glycol, 3.0-9.0 parts glycerin, 2.0-6.0 parts polyethylene glycol 400, 0.3-1.2 parts medical light liquid paraffin, 2.5-6.5 parts anhydrous ethanol, and Tween 80. 0.2-0.7 parts, 0.04-0.18 parts, vitamin E succinate 0.05-0.25 parts, phenoxyethanol 0.25-0.75 parts, ethylhexylglycerin 0.08-0.25 parts, and the remainder purified water to make up to 100 parts by weight.

2. The traditional Chinese medicine gel for treating or improving postoperative hypertrophic scars in orthopedic surgery according to claim 1, characterized in that, The herbal gel is made from the following raw materials in parts by weight per 100 parts: 30-40 parts herbal powder, 0.7-1.8 parts carbomer 980, 0.4-1.2 parts hydroxypropyl methylcellulose HPMC E50, 0.3-1.0 parts polyvinylpyrrolidone, 1.0-2.8 parts triethanolamine, 0.08-0.3 parts citric acid, 0.08-0.3 parts sodium citrate, 4.0-10.0 parts propylene glycol, 3.0-9.0 parts glycerin, 2.0-6.0 parts polyethylene glycol 400, 0.3-1.2 parts medical light liquid paraffin, 2.5-6.5 parts anhydrous ethanol, and Tween 80. 0.2-0.7 parts, 0.04-0.18 parts, vitamin E succinate 0.05-0.25 parts, phenoxyethanol 0.25-0.75 parts, ethylhexylglycerin 0.08-0.25 parts, and the remainder purified water to make up to 100 parts by weight.

3. The traditional Chinese medicine gel according to claim 1 for treating or improving hypertrophic scars after plastic surgery, characterized in that, The herbal gel is made from the following raw materials in parts by weight per 100 parts: 35 parts herbal powder, 0.7-1.8 parts carbomer 980, 0.4-1.2 parts hydroxypropyl methylcellulose HPMC E50, 0.3-1.0 parts polyvinylpyrrolidone, 1.0-2.8 parts triethanolamine, 0.08-0.3 parts citric acid, 0.08-0.3 parts sodium citrate, 4.0-10.0 parts propylene glycol, 3.0-9.0 parts glycerin, 2.0-6.0 parts polyethylene glycol 400, 0.3-1.2 parts medical light liquid paraffin, 2.5-6.5 parts anhydrous ethanol, and Tween 80. 0.2-0.7 parts, 0.04-0.18 parts, vitamin E succinate 0.05-0.25 parts, phenoxyethanol 0.25-0.75 parts, ethylhexylglycerin 0.08-0.25 parts, and the remainder purified water to make up to 100 parts by weight.

4. A traditional Chinese medicine gel for treating or improving hypertrophic scars after plastic surgery, as described in any one of claims 1 to 3, characterized in that... The herbal powder is made from the following parts by weight of Chinese medicinal materials: 20-40 parts of woodlice, 10-30 parts of scutellaria barbata, 20-40 parts of scutellaria barbata, 20-40 parts of angelica dahurica, 10-30 parts of turmeric.

5. A traditional Chinese medicine gel for treating or improving hypertrophic scars after plastic surgery, as described in any one of claims 1 to 3, characterized in that... The herbal powder is made from the following parts by weight of Chinese medicinal materials: 25-40 parts of woodlice, 15-30 parts of scutellaria barbata, 25-40 parts of scutellaria barbata, 25-40 parts of angelica dahurica, 15-30 parts of turmeric.

6. A traditional Chinese medicine gel for treating or improving hypertrophic scars after plastic surgery, according to any one of claims 1 to 3, characterized in that, The Chinese medicine powder is made from the following Chinese medicinal materials in parts by weight: 35 parts woodlice, 20 parts scutellaria barbata, 30 parts scutellaria barbata, 35 parts scutellaria barbata, 25 parts angelica dahurica, and 20 parts turmeric.

7. A method for preparing a traditional Chinese medicine gel for treating or improving hypertrophic scars after plastic surgery, as described in any one of claims 1 to 6, characterized in that, The herbal gel is prepared according to the following steps: S1: Preparation of Traditional Chinese Medicine Powder (1) Weigh out the woodlice, scutellaria barbata, scutellaria barbata, scutellaria barbata, angelica dahurica, and turmeric according to the weight parts mentioned above. After cleaning, crush them, pass them through a 40-60 mesh sieve, and mix them evenly to obtain raw material coarse powder. (2) Add 8-10 times the amount of purified water to the raw material powder, soak for more than 1.5 hours, then heat to 90-100℃, reflux the extract for more than 2 hours, and then collect the first extract; add 6-8 times the amount of purified water to the residue, then heat to 85-95℃, reflux the extract for more than 2 hours, filter, and collect the second extract; combine the two extracts, filter finely, remove fine residue impurities, and obtain Chinese medicine filtrate; (3) Concentrate the Chinese herbal filtrate under reduced pressure to a clear Chinese herbal extract with a relative density of 1.15-1.

25. Then, bring the clear Chinese herbal extract to room temperature and slowly add 95% ethanol while stirring, so that the volume fraction of ethanol in the system reaches 65-70%. Then, refrigerate and let stand for more than 12 hours, remove the upper alcohol liquid, and then filter it with a filter screen of 300 mesh or higher to remove precipitated impurities and obtain alcohol extract. Recover the ethanol from the alcohol extract under reduced pressure until there is no alcohol smell to obtain a purified and concentrated extract. Perform vacuum freeze-drying on the extract, pulverize it through a 150-200 mesh sieve to obtain Chinese herbal powder. S2 Preparation of Gel Matrix Take 60-65% of total purified water, evenly sprinkle in carbomer 980 powder, stir at room temperature at 80-120 r / min for 25-30 min, and let it stand in a sealed container for 14-16 h to swell, to obtain a transparent carbomer sol; separately take a small amount of purified water and heat it to 40-45℃ to dissolve HPMC E50 and PVPK30, stir until there are no particles, then slowly add the carbomer sol, continue stirring, mix evenly, then add citric acid and sodium citrate, stir to dissolve, to obtain a gel matrix, for later use; S3 Preparation of drug-loaded dispersion Propylene glycol, glycerin, polyethylene glycol 400, and anhydrous ethanol were mixed and stirred. Then Tween 80 was added, and stirring was continued for 10-15 minutes. Menthol and vitamin E succinate were then added and stirred until completely dissolved. Medical light liquid paraffin was then added, and the mixture was stirred at 700-800 rpm for 15-20 minutes to obtain an emulsion for enhanced penetration. Subsequently, the Chinese herbal medicine powder was added to the emulsion for enhanced penetration in 3-5 portions, and homogenized at high speed at 15000-20000 rpm for 35-40 minutes until there were no drug residues or lumps, resulting in a uniform drug-loaded dispersion for later use. S4 Preparation of Traditional Chinese Medicine Gel The drug-loaded dispersion was poured into the gel matrix at a uniform speed and stirred at 300-500 rpm for at least 30 minutes. Then, it was homogenized and emulsified at high speed for 12-20 minutes to ensure complete integration and no precipitation. The pH of the system was then adjusted to 5.2-6.4 with triethanolamine. Phenoxyethanol and ethylhexylglycerin were then added and stirred for at least 10 minutes. Purified water was added to bring the total weight to 100 parts by weight and stirred until homogeneous. Vacuum degassing was then performed, and the mixture was allowed to stand at room temperature in the dark for at least 30 hours. After maturation, the mixture was aseptically filtered through a 120-150 mesh sieve, sterilized, and dispensed to obtain the traditional Chinese medicine gel.

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