Traditional Chinese medicine compound gel containing bioactive organic components and capable of synergistically repairing hypertrophic scars based on four-season qi and preparation method of traditional Chinese medicine compound gel

Abstract

The invention relates to the technical field of biological medicine manufacturing, in particular to a traditional Chinese medicine compound gel containing bioactive organic components and capable of synergistically repairing hypertrophic scars based on four-season qi and a preparation method of the traditional Chinese medicine compound gel. The compound gel is formed by mixing a bottle A base matrix and a bottle B four-season additive according to the ratio of 9: 1, the base substrate of the bottle A contains various bioactive organic components such as a salvia miltiorrhiza extract, asiatic acid, bioactive hirudin, perilla oil and the like; according to the four-season additive in the bottle B, corresponding traditional Chinese medicine extracts are selected according to seasons, the preparation method adopts a biotechnology process including supercritical COextraction, a biocompatibility nanometer co-grinding technology and other modern biotechnologies, the transdermal absorption rate of mineral components is remarkably increased, the anti-fibrosis effect is enhanced through a hirudin-perilla oil soluble synergistic system, and the anti-fibrosis effect is improved. The four-season differentiated formula realizes accurate repair of preventing wind evil in spring, clearing blood heat in summer, moistening dryness injury in autumn and dredging collaterals in winter.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biopharmaceutical manufacturing, in particular to a traditional Chinese medicine compound gel containing bioactive organic components for repairing hypertrophic scars based on the four seasons of qi. BACKGROUND

[0002] In the prior art, Chinese patent CN112057669B discloses a composite gel for chronic wound treatment and evaluation and a preparation method thereof. The technology selects 4-amino diphenylamine as a raw material, introduces a sulfonic acid group on the amino group through 1,3-propane sulfonolactone to generate 3-(4-phenylamino-phenylamino)-propane-1-sulfonic acid (PSA), and uses calcium alginate hydrogel as a carrier to load horseradish peroxidase and PSA in the gel. The technology mainly treats the wound through photothermal therapy (PTT) and chemical dynamic therapy (CDT), and evaluates the wound healing state through the color change during the polymerization of aniline.

[0003] However, the above prior art has the following disadvantages: 1) It mainly relies on synthetic chemical components, lacks the multiple synergistic mechanisms of natural organic active components; 2) It does not consider the influence of seasonal environmental factors on the skin repair process, and cannot achieve precise treatment according to the time; 3) It is mainly designed for general chronic wounds, but not specifically for the special pathological mechanism of hypertrophic scars; 4) It lacks the guidance of traditional Chinese medicine theory, and cannot play the overall regulation advantage of traditional Chinese medicine compound.

[0004] Hypertrophic scars are a common complication in the wound healing process caused by excessive proliferation of fibroblasts and abnormal deposition of collagen, which not only affects the appearance, but also can cause local pain, itching, limited activity and other functional disorders. The commonly used scar repair preparations in clinical practice mainly include silicone gel, hormone drugs, traditional Chinese medicine preparations, etc.

[0005] Through literature retrieval, it is found that the current research on traditional Chinese medicine for scar repair mainly focuses on single fixed component formulations. For example, Chinese patent CN202311436672.2 discloses a scar appearance improver and a preparation method, which mainly contains fixed components such as Centella asiatica; Chinese patent CN107281300A discloses a traditional Chinese medicine liquid for repairing hypertrophic scars and a preparation method, which contains components such as Salvia miltiorrhiza, but does not consider the influence of seasonal factors on scar repair. International patent WO202521678A1 discloses a topical hirudin formulation for scar tissue remodeling, but does not combine the theory of traditional Chinese medicine monarch, minister and auxiliary compatibility, resulting in low bioavailability.

[0006] The prior art has the following defects: 1) the traditional scar repair preparation has fixed components, and the influence of environmental climate (such as temperature, humidity and ultraviolet intensity) on skin repair with seasonal changes is not considered, resulting in unstable curative effect; 2) western medicine gel (such as silicone) can only physically close the wound and cannot regulate skin microcirculation and cell regeneration; 3) a single traditional Chinese medicine formula cannot take into account the multiple synergistic mechanisms of promoting blood circulation to remove blood stasis, resisting bacteria and inflammation and promoting regeneration required for scar repair.

[0007] Therefore, there is an urgent need for a traditional Chinese medicine compound gel that takes into account basic repair and environmental adaptability, can dynamically adjust the formula according to the climate characteristics of the four seasons, and realize all-round repair of hypertrophic scars. SUMMARY

[0008] The purpose of the present application is to provide a traditional Chinese medicine gel with a time-sharing dynamic formula, which realizes the precise repair of hypertrophic scars by the synergistic effect of differentiated components and basic matrix in spring, summer, autumn and winter.

[0009] To achieve the above-mentioned purpose, the technical scheme adopted by the present application is:

[0010] A traditional Chinese medicine compound gel containing bioactive organic components for repairing hypertrophic scars based on the synergy of four seasons, the traditional Chinese medicine compound gel is mixed by A bottle of basic matrix and B bottle of seasonal additives according to the weight ratio of 9:1; wherein the A bottle of basic matrix contains the following components by weight: 5-8 parts of salvia miltiorrhiza extract, 3-5 parts of calcined oyster shell powder, 0.5-1.2 parts of gotu kola acid, 10-15 parts of white yam glue, 2-4 parts of pearl powder, 0.3-0.8 parts of glycyrrhizic acid dipotassium, 0.01-0.05 parts of hirudin, 6-10 parts of perilla oil, 4-6 parts of beeswax, and 49.95-69.19 parts of deionized water; the B bottle of seasonal additives is selected according to the season of use, including: spring additives: 2-3 parts of wind-preventing extract, 1-2 parts of schizonepeta extract; summer additives: 1.5-2.5 parts of rhubarb extract, 3-4 parts of safflower extract; autumn additives: 2-3 parts of adiantum capillus-veneris extract, 3-5 parts of ophiopogon japonicus extract; winter additives: 4-6 parts of notoginseng extract, 2-3 parts of cassia twig extract.

[0011] The present application discloses a traditional Chinese medicine compound gel containing bioactive organic components for repairing hypertrophic scars based on the synergy of four seasons, the traditional Chinese medicine compound gel is mixed by A bottle of basic matrix and B bottle of seasonal additives according to the weight ratio of 9:1;

[0012] The A bottle basic matrix comprises the following components in parts by weight: salvia miltiorrhiza extract 5-8 parts, calcined oyster shell powder 3-5 parts, centella asiatica acid 0.5-1.2 parts, bletilla striata gum 10-15 parts, pearl powder 2-4 parts, glycyrrhizic acid dipotassium 0.3-0.8 parts, hirudin 0.01-0.05 parts, perilla oil 6-10 parts, and beeswax 4-6 parts, with the balance being deionized water.

[0013] The B bottle four-season additive is selected according to the season of use, and comprises:

[0014] The spring additive comprises the following components in parts by weight: wind-preventing extract 2-3 parts and schizonepeta extract 1-2 parts.

[0015] The summer additive comprises the following components in parts by weight: rhubarb extract 1.5-2.5 parts and safflower extract 3-4 parts.

[0016] The autumn additive comprises the following components in parts by weight: saussurea extract 2-3 parts and ophiopogon extract 3-5 parts.

[0017] The winter additive comprises the following components in parts by weight: panax notoginseng extract 4-6 parts and cassia twig extract 2-3 parts.

[0018] Further, the weight ratio of salvia miltiorrhiza extract, hirudin and calcined oyster shell powder in the A bottle basic matrix is 8:0.03:4.

[0019] Further, the calcined oyster shell powder and the pearl powder are treated by a nano co-milling technology, and the average particle size is ≤200 nm.

[0020] Further, the content of tanshinone IIA in the salvia miltiorrhiza extract is ≥3.5%, the content of danshensu is ≥1.0%, the purity of the centella asiatica acid is ≥98%, the activity of the hirudin is ≥120 ATU / mg, and the content of α-linolenic acid in the perilla oil is ≥55%.

[0021] Further, the pH value of the traditional Chinese medicine compound gel is 6.5-7.5, and the viscosity is 15000-25000 mPa·s at 25℃.

[0022] A preparation method of an A bottle basic matrix of the traditional Chinese medicine compound gel, comprising the following steps:

[0023] (1) First, the bletilla striata gum and the beeswax are heated to 75℃ to be completely melted;

[0024] (2) Second, the perilla oil is added, and then emulsified by high-speed stirring, and then cooled to 50℃;

[0025] (3) Third, the salvia miltiorrhiza extract, the calcined oyster shell powder, the centella asiatica acid, the pearl powder, the glycyrrhizic acid dipotassium, and the hirudin are sequentially added;

[0026] (4) Finally, homogenize for 10 minutes under reduced pressure (-0.05 MPa) to remove bubbles to obtain the A bottle of basic matrix.

[0027] Further, the nano-co-milling technique of the calcined oyster shell powder and the pearl powder comprises the following steps:

[0028] (1) The calcined oyster shell powder and the pearl powder are mixed in a ratio of 1:1, 95% ethanol is added as a dispersion medium, and the solid-liquid ratio is 1:3;

[0029] (2) 0.5% polyvinylpyrrolidone is added as a dispersant, and milling is performed in a planetary high-energy ball mill with a ceramic ball to material ratio of 15:1;

[0030] (3) The milling conditions are: milling time 12 hours, rotation speed 350 r / min, pause for 10 minutes every 60 minutes, and circulating water control temperature ≤30℃;

[0031] (4) The solid is collected by centrifugation, and then spray dried after ultrasonic dispersion, with an inlet temperature of 170℃ and an outlet temperature of 80℃.

[0032] Further, the preparation method of the leechin-liposoluble synergistic system composed of the leechin and the perilla oil comprises the following steps:

[0033] (1) The perilla oil, phospholipid, and cholesterol are mixed in a mass ratio of 8:2:1 and dissolved in chloroform;

[0034] (2) Thin film is formed by rotary evaporation, and the leechin aqueous solution (2 mg / mL) is added to hydrate the thin film;

[0035] (3) Ultrasonic treatment for 10 minutes (power 200 W, work for 5 seconds, and intermittent for 3 seconds);

[0036] (4) High-pressure homogenization (60 MPa, 3 cycles) to form a leechin-perilla oil liposoluble synergistic system.

[0037] A preparation method of a B bottle of four-season additive of the traditional Chinese medicine compound gel, comprising the following steps:

[0038] (1) According to the season, the corresponding medicinal materials are selected, dried to a water content of ≤8%, and pulverized to 40-60 mesh;

[0039] (2) The active ingredients are extracted by supercritical CO2 extraction method, wherein:

[0040] The extraction pressure is 20-25 MPa, the extraction temperature is 45-50℃, the CO2 flow rate is 20-25 L / h, and the extraction time is 2-3 hours,

[0041] The separation pressure is 7-8 MPa, and the separation temperature is 40-45℃.

[0042] (3) For medicinal materials not suitable for supercritical extraction, the following method is used for extraction:

[0043] Rhubarb: 70% ethanol reflux extraction, D101 macroporous adsorption resin purification;

[0044] Radix Hedysari and Ophiopogon japonicus: hot water extraction of polysaccharides, ethanol precipitation;

[0045] Panax notoginseng: 70% ethanol reflux extraction, D101 macroporous adsorption resin purification;

[0046] (4) Mix the extracts of the same season according to the formula ratio:

[0047] Spring: Prevent wind and Schizonepeta extract mixed in a ratio of 2:1;

[0048] Summer: Rhubarb and safflower extract mixed in a ratio of 1:2;

[0049] Autumn: Radix Hedysari and Ophiopogon japonicus extract mixed in a ratio of 2:3;

[0050] Winter: Panax notoginseng and Ramulus Cinnamomi extract mixed in a ratio of 2:1.

[0051] A preparation method of the traditional Chinese medicine compound gel, comprising the following steps:

[0052] (1) Prepare the A bottle of basic matrix according to the method of any one of claims 6-8;

[0053] (2) Prepare the B bottle of four-season additives according to the method of claim 9;

[0054] (3) Mix the B bottle of four-season additives with the A bottle of basic matrix at a weight ratio of 1:9 at 40-45°C;

[0055] (4) Stir with a paddle stirrer at 50-60 r / min for 15 minutes;

[0056] (5) Homogenize under reduced pressure (-0.05 MPa) for 10 minutes to remove air bubbles;

[0057] (6) Quality control detection: uniformity test sampling to determine the content deviation of different parts ≤5%, viscosity control at 15000-25000 mPa·s, stability test centrifugal test (3000 r / min, 30 minutes) without stratification phenomenon

[0058] Preferably, the weight ratio of Salvia miltiorrhiza extract, hirudin and calcined oyster shell powder in the A bottle of basic matrix is 8:0.03:4. This specific ratio can form the best anti-fibrosis synergistic effect.

[0059] Further, the calcined oyster shell powder and the pearl powder are treated by a nano co-milling technology, and the average particle size is less than or equal to 200 nm, so that the transdermal absorption rate of mineral components is significantly improved.

[0060] In one embodiment of the present application, the content of tanshinone IIA in the salvia extract is greater than or equal to 3.5%, the content of danshensu is greater than or equal to 1.0%, the purity of asiatic acid is greater than or equal to 98%, the activity of hirudin is greater than or equal to 120 ATU / mg, and the content of alpha-linolenic acid in perilla oil is greater than or equal to 55%, so that the quality and curative effect of active ingredients are ensured.

[0061] The pH value of the traditional Chinese medicine compound gel in the present application is 6.5-7.5, and the viscosity is 15000-25000 mPa·s (25℃), which is suitable for skin use and has good spreading property and stability.

[0062] The present application has the following advantages:

[0063] 1. The present application first converts the theory of four seasons of traditional Chinese medicine into quantifiable four-season additive compatibility rules, and solves the problem of poor repair effect caused by insufficient environmental adaptability in the prior art through a compound system of a basic matrix + four-season dynamic additive components.

[0064] 2. The present application adopts a nano co-milling technology (particle size ≤200 nm) of calcined oyster shell powder and pearl powder, which significantly improves the transdermal absorption rate of mineral components, and improves the bioavailability by more than 3 times compared with traditional mineral powder application technology. At the same time, the liposoluble synergistic system formed by hirudin and perilla oil inhibits the excessive proliferation of fibroblasts while maintaining the water-oil balance of the skin, and exhibits better repair stability compared with single-component western medicine gel.

[0065] 3. The present application forms a multi-point synergistic effect through the differentiated compatibility rules of four-season additives (wind resistance and anti-allergy in spring, inflammation elimination and blood activation in summer, dampness moisturizing in autumn, and circulation promotion in winter), and comprehensively responds to the challenges of scar repair in different seasons. DETAILED DESCRIPTION

[0066] The present application will be further described in detail below in conjunction with specific embodiments, but the embodiments of the present application are not limited thereto.

[0067] Analysis of the efficacy of the components in the A bottle basic matrix:

[0068] In the present application, the efficacy and mechanism of action of each component in the A bottle basic matrix are as follows:

[0069] The salvia extract has the effects of promoting blood circulation to remove blood stasis and improving microcirculation, and can promote the metabolism of scar tissue; the antioxidant components (such as danshensu) in the salvia extract can inhibit free radical damage, delay skin aging, and also have antibacterial and anti-inflammatory effects, thereby reducing the risk of scar infection.

[0070] Calcined oyster shell powder has the effect of astringency and can regulate skin hydration and reduce exudate. It contains calcium carbonate and other minerals, which can soften scar tissue and promote epidermal regeneration.

[0071] Centella asiatica acid, as the core anti-scarring ingredient, can inhibit the excessive proliferation of fibroblasts and collagen deposition, reducing the formation of hypertrophic scars. It can also accelerate wound healing and improve the texture and color of scars.

[0072] Bletilla striata gum is a natural polysaccharide that has strong moisturizing and protective film-forming functions, which can maintain a moist environment for scars. It promotes keratinocyte regeneration, repairs damaged barriers, and reduces scar dryness and desquamation.

[0073] Pearl powder contains calcium carbonate and various trace elements, which can promote skin metabolism, inhibit melanin production, and improve scar pigmentation. It also has a mild exfoliating effect, which helps to smooth the surface of scars.

[0074] Dipotassium glycyrrhizinate has anti-inflammatory and soothing effects, which can relieve scar itching and redness. It can also regulate immune function, reduce allergic reactions, and enhance skin tolerance.

[0075] Hirudin can improve local microcirculation, dissolve fibrin deposition, and inhibit scar angiogenesis. Its small molecular peptide structure can penetrate deep into the dermis, promoting the orderly arrangement of collagen.

[0076] Perilla oil is rich in omega-3 fatty acids, which can repair the skin lipid barrier. Its antioxidant properties can reduce the release of inflammatory factors and inhibit the progression of scar fibrosis.

[0077] Beeswax, as a natural emulsifier, can enhance the stability of the gel. It forms a breathable protective film that locks in active ingredients, isolates external microorganisms, and prolongs the moisturizing and repair effects.

[0078] Analysis of the efficacy of B bottle four-season additives:

[0079] According to the theory of four seasons in traditional Chinese medicine, the efficacy and mechanism of B bottle four-season additives are as follows:

[0080] Spring combination (wind-preventing + schizonepeta): Wind-preventing has the effect of dispelling wind and relieving itching, which can relieve skin sensitivity and scar itching in spring. It can inhibit histamine release and reduce allergic reactions. Schizonepeta has the effect of promoting rash and eliminating sores, which can promote local metabolism of scars and relieve congestion and redness.

[0081] Summer combination (rhubarb + safflower): Rhubarb has the effect of clearing heat and resolving toxins, which can inhibit Propionibacterium acnes and Staphylococcus aureus and prevent secondary infection of scars. Safflower has the effect of promoting blood circulation and removing blood stasis, which can improve scar congestion and induration caused by high temperature in summer.

[0082] Autumn combination (Saw Palmetto + Ophiopogon): Saw Palmetto has the effect of nourishing yin and moisturizing dryness, relieving the dryness of the skin caused by the desquamation and tightness of the scar in autumn. Ophiopogon has the effect of moisturizing and hydrating, enhancing the skin barrier function, and reducing the influence of external stimulation on the scar.

[0083] Winter combination (Sanqi + Guizhi): Sanqi has the effect of warming the meridians and dispelling cold, promoting blood circulation in the local scar in winter, and accelerating the removal of metabolic waste. Guizhi has the effect of warming the meridians and unblocking the channels, relieving the stiffness and pain of the scar, and enhancing the penetration of active ingredients.

[0084] Reference: Yang Weiye. The distribution of physique and the clinical efficacy of removing blood stasis and clearing heat for the extension of menstrual period caused by uterine scar diverticulum [D]. Shandong University of Traditional Chinese Medicine. 2023.

[0085] From the perspective of traditional Chinese medicine, the formation of hypertrophic scars is closely related to the obstruction of meridians and blood stasis, and its essence is that the blood circulation is not smooth, and the phlegm and blood stasis are intertwined, eventually leading to abnormal proliferation of skin tissue.

[0086] External injury or surgical damage to the skin first disrupts the normal circulation of local meridian blood. "Lingshuo: Meridians" says: "Meridians are the blood vessels that circulate blood and yin and yang, moisten the bones and joints, and benefit the joints." After the skin is damaged, the meridians are damaged, and the blood circulation is blocked, forming a state of blood stasis. Blood stasis, new blood cannot return to the channel, local blood stasis, leading to redness, swelling and hardening of the scar in the early stage. If the stasis is not dispersed for a long time, it will be depressed and hot, and the heat and toxin will be accumulated, further aggravating the obstruction of blood and making the scar continue to grow, the texture becomes hard, and even accompanied by itching and pain.

[0087] In addition, long-term blood stasis will inevitably affect the distribution of body fluid. "Xuexing Lun" says: "Blood accumulation for a long time can also be transformed into phlegm." Blood stasis blocks the normal distribution of body fluid, and the body fluid cannot be normally distributed, and the phlegm is accumulated, the phlegm and blood stasis are intertwined, and the phlegm is glued between the skin and the skin, making the scar gradually thicken and protrude, forming a stubborn and difficult-to-dissolve pathological product. This state of phlegm and blood stasis is similar to the description of modern medicine that the fibroblasts are over-proliferated and the collagen deposition is disordered, which confirms the theory of "blood stasis generating phlegm" in traditional Chinese medicine.

[0088] From the perspective of meridians, after the skin is damaged, the local meridian circulation is blocked, leading to poor blood flow of the meridian. For example, if the scar is located in the foot yangming stomach meridian or hand taishen lung meridian, it may affect the spleen and stomach transportation or lung qi descending, causing internal phlegm, further aggravating the growth of the scar. At the same time, the obstruction of meridians also affects the function of viscera, forming a vicious cycle, making the scar difficult to cure.

[0089] Therefore, the core principle of Traditional Chinese Medicine (TCM) treatment for hypertrophic scars is to invigorate blood circulation, remove blood stasis, unblock meridians, and disperse nodules, while also addressing phlegm-resolving, softening hardened masses, clearing heat, and detoxifying. By unblocking meridians and harmonizing Qi and blood, blood stasis is dispersed, phlegm and dampness are resolved, and meridians are unblocked, allowing the scar to gradually soften and fade. This theoretical system not only aligns with the holistic view and syndrome differentiation principles of TCM but also resonates with modern medicine's understanding of the pathological mechanisms of scar formation, demonstrating the scientific nature and clinical value of TCM theory.

[0090] The selection of materials for Bottle B incorporates the following theories:

[0091] Traditional Chinese medicine believes that the core cause of hypertrophic scar formation lies in "unresolved toxins and imbalance of Qi and blood." After skin damage, local meridians are impaired, obstructing the flow of Qi and blood, leading to blood stasis. Prolonged accumulation of blood stasis can transform into heat, and the resulting heat toxins further aggravate the obstruction of Qi and blood, causing the scar to continue to proliferate and harden. Furthermore, blood stasis obstructs the distribution of body fluids, accumulating into phlegm. This phlegm and blood stasis combine and adhere to the skin's surface, causing the scar to thicken and become raised, forming a stubborn and difficult-to-resolve pathological product.

[0092] Meridians are the channels through which Qi and blood circulate. If the meridians are blocked, the distribution of Qi and blood to the corresponding organs will be abnormal. For example, liver Qi stagnation can worsen blood stasis, spleen deficiency and dampness can lead to phlegm and dampness overflowing, lung Qi stagnation can lead to poor distribution of body fluids, and kidney Yang deficiency can lead to cold coagulation and blood stasis. Therefore, the formation of scars is not only the result of local Qi and blood stagnation, but also an external manifestation of overall Qi and blood imbalance and meridian blockage.

[0093] The Influence of the Four Seasons on Hypertrophic Scars and Analysis of Seasonal Medication Use

[0094] Traditional Chinese medicine emphasizes the "correspondence between man and nature," stating that the changes in the climate of the four seasons (wind, cold, heat, dampness, dryness, and fire) directly affect the circulation of qi and blood in the human body, thereby affecting the scar repair process.

[0095] The *Huangdi Neijing* (Yellow Emperor's Inner Classic) proposes the concept of "human beings and heaven and earth in harmony," suggesting a synchronous resonance between the circulation of Qi and blood in the human body and the Yin-Yang changes of the four seasons in nature. As the largest organ in the human body, the skin's repair process is inevitably profoundly influenced by seasonal climate. Modern research shows that environmental factors such as temperature and humidity do indeed affect fibroblast activity and collagen metabolism, which is highly consistent with the traditional Chinese medicine theory of the four seasons.

[0096] Therefore, topical scar ointments need to be formulated in accordance with the four seasons and the combination of drugs should be adjusted to balance qi and blood, and eliminate pathogens and support the body's resistance.

[0097] 1. Spring (belongs to the element of wood, representing growth and development, and the prevalence of wind-related evils)

[0098] Climate characteristics: In spring, liver qi rises. If liver qi is stagnant, the circulation of qi and blood will be obstructed, which can easily lead to blood stasis. Wind evil is prone to movement and changes frequently, and can easily invade wounds, causing itching, scratching, and aggravating scar hyperplasia.

[0099] Medication options:

[0100] Wind-Preventing (2-3%): Pungent and warm, it disperses the exterior, expels wind and relieves itching, prevents wind evil from invading, and reduces scar itching.

[0101] Schizonepeta (1-2%): It dispels wind and evil, promotes blood circulation and resolves rashes, helps liver qi to flow freely, and prevents blood stasis from worsening.

[0102] Function: Dispels wind and evil, regulates liver qi, prevents wind evil from causing itching and blood stasis from stagnation.

[0103] 2. Summer (Fire, Dampness Accumulation, and Heat Toxin)

[0104] Climate Characteristics: In summer, the combination of heat and dampness easily generates fire toxin; dampness generates phlegm, and phlegm and stasis accumulate and block the meridians, causing the scar to become red, swollen, and painful.

[0105] Medicine Selection:

[0106] Rhubarb (1.5-2.5%): Bitter and cold, it purges fire, clears heat and resolves toxins, breaks blood and removes stasis, and removes heat toxin and stasis.

[0107] Safflower (3-4%): It promotes blood circulation and unblocks the channels, removes stasis and relieves pain, and enhances the ability of rhubarb to resolve stasis.

[0108] Function: Clears heat and resolves toxins, promotes blood circulation and removes stasis, prevents dampness and phlegm from accumulating, and inhibits abnormal scar proliferation.

[0109] 3. Autumn (Metal, Dryness Damaging Fluids, and Lung Yin Deficiency)

[0110] Climate Characteristics: In autumn, dryness prevails, fluids are depleted, and lung yin is insufficient, causing the scar to become dry and cracked, and repair to be delayed.

[0111] Medicine Selection:

[0112] Sargent Herb (2-3%): Sweet and cool, it moistens dryness, nourishes yin, and moistens the scar to prevent dryness.

[0113] Ophiopogon (3-5%): It nourishes yin, moistens the lungs, benefits the stomach, and generates fluid, and enhances the ability of Sargent Herb to moisten and nourish fluids.

[0114] Function: Nourishes yin and moistens dryness, moistens the skin, and prevents the scar from becoming dry and cracked due to dryness.

[0115] 4. Winter (Water, Cold Evil Condensation, and Blood Sluggishness)

[0116] Climate Characteristics: In winter, cold evil condenses, blood stagnates, and blood flow is sluggish, causing the scar to become stiff and contract.

[0117] Medicine Selection:

[0118] Sanqi (4-6%): It warms and unblocks the channels, promotes blood circulation, removes stasis, and relieves pain, and improves local microcirculation.

[0119] Cassia twig (2-3%): warm and pungent, warm and dispel cold, assist Sanqi to enhance the power of warm and dispel blood stasis.

[0120] Effect: warming the meridians, promoting blood circulation and dispelling cold, preventing scarification from cold and hardening.

[0121] Summary: the combination of four seasons of medicine and TCM theory

[0122] The compatibility of the medicine of the four seasons fully embodies the treatment principle of TCM "treatment according to the season":

[0123] Spring dispels wind and evil, preventing liver stagnation and blood stasis;

[0124] Summer clears heat and resolves toxicity, resolving summer dampness and phlegm stasis;

[0125] Autumn nourishes yin and dryness, and nourishes the loss of body fluid;

[0126] Winter warms the meridians, dispels cold, promotes blood circulation and removes blood stasis.

[0127] Preparation method of components:

[0128] 1. Preparation method of Danshen extract:

[0129] The preparation of Danshen extract adopts modern Chinese medicine extraction process, the specific steps are as follows:

[0130] (1) Selection of raw materials: select high-quality Danshen (Salvia miltiorrhiza) medicinal materials, cut into slices and dry to ≤10% moisture content;

[0131] (2) Pulverization: dry Danshen slices are pulverized and passed through a 60 mesh sieve;

[0132] (3) Alcohol extraction process: 50 kg of Danshen powder is weighed, 400 L of 75% ethanol is added, soaked for 12 hours, and then refluxed and extracted for 3 times, 2 hours each time;

[0133] (4) Filtration and concentration: combine the extract, filter under reduced pressure, and concentrate the filtrate under reduced pressure to a relative density of 1.20-1.25 (60℃);

[0134] (5) Purification: the concentrated liquid is chromatographed with D101 macroporous adsorption resin column and eluted with 60% ethanol;

[0135] (6) Drying: after recovering ethanol from the eluate under reduced pressure, vacuum drying (60℃, -0.08MPa) is carried out to obtain gray-brown powder;

[0136] (7) Standardization: HPLC method is used to determine the content of tanshinone IIA and danshensu, and the content of tanshinone IIA is adjusted to ≥3.5% and the content of danshensu is adjusted to ≥1.0%.

[0137] 2. Preparation method of calcined oyster shell powder:

[0138] The preparation of calcined oyster shell powder adopts traditional processing combined with modern nanotechnology, and the specific steps are as follows:

[0139] (1) Raw material selection: Select high-quality thick-shelled oysters, clean and dry;

[0140] (2) Calcination treatment: Put the oysters in a muffle furnace, gradually heat to 850°C, keep temperature for 1 hour, and cool naturally;

[0141] (3) Crushing treatment: Crush the calcined oyster, pass through an 80-mesh sieve;

[0142] (4) Nanometer grinding: Add coarse powder into a planetary ball mill, dry grinding for 8 hours, control the speed at 350 r / min;

[0143] (5) Quality control: Use laser particle size analyzer to measure and ensure that the average particle size of calcined oyster shell powder is ≤200 nm;

[0144] (6) Drying and storage: Vacuum drying for 4 hours and then seal and store.

[0145] 3. Preparation method of asiatic acid:

[0146] Asiatic acid is obtained by extraction or purchased:

[0147] (1) Raw material selection: Select dry Centella asiatica whole grass;

[0148] (2) Extraction and purification: According to the standard method of Chinese Pharmacopoeia or purchase standard asiatic acid (Asiaticoside) from professional manufacturers, purity ≥98%.

[0149] 4. Preparation method of white glue:

[0150] The preparation of white glue adopts water extraction and alcohol precipitation process, and the specific steps are as follows:

[0151] (1) Raw material selection: Select high-quality white bamboo (Bletilla striata) rhizomes, clean and cut into slices;

[0152] (2) Hot water extraction: Take 20 kg of white bamboo slices, add 200 L of purified water, and boil for 2 hours;

[0153] (3) Filtration and concentration: Hot filtration, concentrate the filtrate to a relative density of 1.15-1.20;

[0154] (4) Alcohol precipitation treatment: Slowly add 95% ethanol to the concentrated solution to a final concentration of 70%, stir and precipitate for 12 hours;

[0155] (5) Isolation and purification: collect the precipitate by centrifugation (3000 r / min, 20 minutes), and wash twice with 80% ethanol;

[0156] (6) Drying treatment: freeze-dry the precipitate (-40°C, 48 hours) to obtain bletilla striata gum (the polysaccharide content is ≥85%);

[0157] (7) Quality control: measure the polysaccharide content (phenol-sulfuric acid method), and control the water content to be ≤5%.

[0158] 5. Preparation method of pearl powder:

[0159] The preparation of pearl powder adopts modern nanometer grinding technology, and the specific steps are as follows:

[0160] (1) Raw material selection: select high-quality freshwater pearls, wash and dry;

[0161] (2) Pretreatment: ultrasonic cleaning for 30 minutes, and drying at 60°C for 4 hours;

[0162] (3) Crushing treatment: crush with an air flow crusher, and pass through a 100-mesh sieve;

[0163] (4) Nanometer grinding: mix the pearl powder and calcined oyster shell powder at a ratio of 1:1, add them into a planetary ball mill, and wet-grind (add 95% ethanol as a dispersion medium) for 12 hours;

[0164] (5) Drying treatment: spray drying (import temperature 180°C, export temperature 85°C);

[0165] (6) Quality control: measure by a laser particle size analyzer to ensure that the average particle size is ≤200 nm, and observe the particle morphology by an electron microscope.

[0166] 6. Obtaining of other components:

[0167] The dipotassium glycyrrhizinate adopts a finished product meeting the standard of Chinese Pharmacopoeia, and the purity is ≥98%.

[0168] The preparation of hirudin adopts enzyme extraction and chromatography purification process, and the specific steps are as follows:

[0169] (1) Raw material selection: use dried hirudo (Hirudo medicinalis) after passing the identification of Chinese Pharmacopoeia;

[0170] (2) Extraction process: crush the hirudo to 60 mesh, add 0.9% sodium chloride solution for leaching (solid-liquid ratio 1:10), soak at 4°C for 24 hours, and centrifuge (10000 r / min, 30 minutes, 4°C);

[0171] (3) Purification: supernatant was fractionally precipitated with ammonium sulfate (30%, 60% saturation), the precipitate at 60% saturation was collected, dialyzed for 48 hours (cut-off molecular weight 3 kD), and subjected to DEAE cellulose ion exchange chromatography (0.01-0.5 mol / L NaCl gradient elution);

[0172] (4) Freeze-drying treatment: the hirudin-containing part was collected and freeze-dried at -50°C for 72 hours;

[0173] (5) Activity detection: hirudin activity was determined by the thrombin time method, and controlled at ≥120 ATU / mg.

[0174] Perilla oil was prepared by cold pressing method: mature Perilla frutescens seeds were selected, washed, dried, crushed, extracted by cold pressing at low temperature (≤40°C), impurities were removed by membrane filtration technology, and the content of α-linolenic acid (≥55%) and the peroxide value (≤5.0 meq / kg) were detected.

[0175] Bee wax was prepared: natural bee wax (white wax) was selected, cleaned and pure, heated to 65-70°C in a water bath to completely melt the bee wax, filtered through multiple layers of gauze in a molten state, and naturally cooled and solidified at room temperature. The acid value (17-24) and melting point (62-65°C) were detected.

[0176] 7. Preparation method of four-season additive:

[0177] The four-season additive was prepared by supercritical CO2 extraction technology, and the common process conditions were as follows: extraction pressure 20-25 MPa, extraction temperature 45-50°C, CO2 flow rate 20-25 L / h, extraction time 2-3 hours, separation pressure 7-8 MPa, and separation temperature 40-45°C. The specific preparation method is as follows:

[0178] Spring additive (wind-preventing + catmint):

[0179] (1) Wind-preventing extract: high-quality wind-preventing roots were selected, the volatile oil content was detected to be ≥1.5%, and the supercritical CO2 extraction process was performed, and the process parameters were adjusted as follows: pressure 22 MPa, temperature 48°C, and wind-preventing lactone content was checked by thin layer chromatography;

[0180] (2) Catmint extract: high-quality catmint spikes were selected, the volatile oil content was detected to be ≥0.8%, and the supercritical CO2 extraction process was performed, and the process parameters were adjusted as follows: pressure 23 MPa, temperature 46°C, and limonene and menthone contents were detected by gas chromatography;

[0181] (3) The wind-preventing and catmint extracts were mixed in a ratio of 2:1 and homogenized in a 60°C water bath for 10 minutes.

[0182] Summer additive (dahurian rhubarb + safflower):

[0183] (1) Rhubarb extract: select high-quality rhizome of rhubarb, detect total amount of anthraquinones ≥1.5%, crush rhubarb to 60 mesh, add 70% ethanol (1:8), reflux extract 2 times, 1.5 hours each time, combine the extract, reduce pressure to concentrate to relative density 1.20, D101 macroporous adsorption resin column chromatography, elute with 70% ethanol, collect emodin part, high performance liquid chromatography to determine emodin and rhein content;

[0184] (2) safflower extract: select high-quality safflower, detect safflower yellow pigment ≥1.0%, perform supercritical CO2 extraction process, adjust process parameters: pressure 25 MPa, temperature 50℃, add 5% ethanol as cosolvent to enhance extraction efficiency, UV-Vis spectroscopy to determine safflower yellow pigment A and safflower acid content;

[0185] (3) mix rhubarb and safflower extract in a ratio of 1:2, homogenize in 45℃ water bath for 15 minutes.

[0186] Autumn additive (shashen + Maidong):

[0187] (1) Shashen extract: select high-quality North Shashen root, detect saponin content, crush Shashen to 60 mesh, add hot water (90℃, 1:10), extract 2 times, 1.5 hours each time, combine the extract, reduce pressure to concentrate to relative density 1.15, add 95% ethanol to final concentration 80%, precipitate polysaccharide component, determine polysaccharide content by phenol-sulfuric acid method, control ≥50%;

[0188] (2) Maidong extract: select high-quality Maidong rhizome, detect total saponin content, crush Maidong to 60 mesh, water extraction method (1:8, boiling for 2 hours), reduce pressure to concentrate to relative density 1.20, add 95% ethanol to final concentration 75%, precipitate polysaccharide, determine polysaccharide content, determine Maidong saponin content by UV spectrophotometry;

[0189] (3) mix Shashen and Maidong extract in a ratio of 2:3, stir evenly at room temperature.

[0190] Winter additive (Sanqi + Guizhi):

[0191] (1) Sanqi extract: select high-quality Sanqi root, detect total saponin content ≥50%, crush Sanqi to 80 mesh, 70% ethanol reflux extraction 2 times, 2 hours each time, combine the extract, reduce pressure to concentrate, D101 macroporous adsorption resin purification, elute with 60% ethanol, determine ginsenoside Rb1 and Rg1 content by high performance liquid chromatography;

[0192] (2) Gui Zhi extract: high-quality Gui Zhi is selected, the content of volatile oil is detected to be greater than or equal to 1.2%, and a supercritical CO2 extraction process is performed, and process parameters are adjusted to be: pressure 21 MPa, temperature 45 DEG C, and the content of cinnamyl aldehyde is determined by gas chromatography;

[0193] (3) The extract of Sanqi and Gui Zhi is mixed at a ratio of 2:1, and homogenized in a 50 DEG C water bath for 10 minutes.

[0194] Core process technology:

[0195] 1. Nano co-milling technology (calcined concha mactra powder and pearl powder)

[0196] The planet high-energy ball mill is adopted for nano co-milling, and the specific process is as follows:

[0197] (1) The calcined concha mactra powder and pearl powder are prepared at a ratio of 1:1;

[0198] (2) 95% ethanol (solid-liquid ratio 1:3) is added as a dispersion medium;

[0199] (3) 0.5% polyvinylpyrrolidone (PVP K30) is added as a dispersant;

[0200] (4) The ball-to-material ratio (ceramic ball-to-material ratio) is 15:1;

[0201] (5) Milling for 12 hours, pause for 10 minutes every 60 minutes to avoid overheating, and the temperature is controlled to be less than or equal to 30 DEG C by constant-temperature circulating water;

[0202] (6) Centrifugal separation (10000 r / min, 20 minutes) is performed to collect the solid;

[0203] (7) Ultrasonic dispersion (power 300 W, 10 minutes);

[0204] (8) Spray drying (import temperature 170 DEG C, export temperature 80 DEG C);

[0205] (9) Quality control: laser particle size analysis ensures that the average particle size is less than or equal to 200 nm, and the particle size distribution index is less than or equal to 0.3; scanning electron microscope observation shows that the particle morphology is uniform and there is no obvious aggregation; Zeta potential measurement is greater than or equal to ± 30 mV, to ensure the dispersion stability.

[0206] 2. Hirudin-perilla oil lipid-soluble synergistic system

[0207] The hirudin-perilla oil lipid-soluble synergistic system is constructed by adopting liposome technology, and the specific process is as follows:

[0208] (1) Perilla oil, phospholipid and cholesterol are mixed at a mass ratio of 8:2:1;

[0209] (2) Thin film dispersion method: dissolve the mixture in chloroform, and form a thin film by rotary evaporation;

[0210] (3) Add aqueous hirudin solution (2 mg / mL) to hydrate the thin film;

[0211] (4) Ultrasonic treatment for 10 minutes (power 200 W, work 5 seconds, intermittent 3 seconds);

[0212] (5) High pressure homogenization (60 MPa, 3 cycles);

[0213] (6) Quality control: average particle size ≤ 150 nm, hirudin encapsulation rate ≥ 80%, particle size change ≤ 10% after storage at 4°C for 30 days.

[0214] 3. Bee wax-bletilla striata gum complex emulsification technology

[0215] The present application adopts high-efficiency emulsification technology to construct a stable gel matrix, and the specific process is as follows:

[0216] (1) Oil phase preparation: melt bee wax to 75°C, add perilla oil, and stir uniformly;

[0217] (2) Water phase preparation: dissolve bletilla striata gum in 60°C hot water to prepare a 5% solution;

[0218] (3) Emulsification process: slowly add the oil phase into the water phase at 75°C, high-speed homogenization (10000 r / min, 15 minutes), and ultrasonic treatment (200 W, 10 minutes) to enhance the emulsification effect;

[0219] (4) Cooling process: cool to 50°C while stirring, and add the remaining matrix components;

[0220] (5) Stability control: add 1% carbomer 940 as a thickening agent, adjust the pH to 6.8-7.2 with triethanolamine, and perform oscillation centrifugation test (3000 r / min, 30 minutes) to check the stability.

[0221] Example 1: Traditional Chinese medicine compound gel in basic formula (regular dose)

[0222] A bottle of basic matrix components (weight parts): salvia miltiorrhiza extract 6 parts, calcined oyster shell powder 4 parts, asiatic acid 0.8 parts, bletilla striata gum 12 parts, pearl powder 3 parts, glycyrrhizic acid dipotassium 0.5 parts, hirudin 0.03 parts, perilla oil 8 parts, bee wax 5 parts, and deionized water 60.67 parts.

[0223] B bottle of spring additive components (weight parts): wind-preventing extract 2.5 parts, and schizonepeta extract 1.5 parts.

[0224] Preparation method:

[0225] 1. Preparation of A bottle base matrix:

[0226] (1) First, heat the Bletilla striata gum 12 parts and beeswax 5 parts to 75°C to completely melt;

[0227] (2) Second, add perilla oil 8 parts, emulsify at high speed (6000 r / min, 10 minutes), and then cool to 50°C;

[0228] (3) Third, add salvia extract 6 parts, calcined oyster shell powder 4 parts, ginkgo biloba extract 0.8 parts, pearl powder 3 parts, glycyrrhizic acid dipotassium 0.5 parts, and hirudin 0.03 parts in sequence, and stir evenly;

[0229] (4) Finally, add deionized water to a total weight of 100 parts, and homogenize under reduced pressure (-0.05 MPa) for 10 minutes to remove air bubbles, to obtain the A bottle base matrix.

[0230] 2. Preparation of B bottle spring additive:

[0231] (1) Preparation of Qianfeng extract: high-quality Qianfeng roots are selected, with a volatile oil content of 1.8%, and the supercritical CO2 extraction process parameters are: pressure 22 MPa, temperature 48°C, and extraction time 2.5 hours;

[0232] (2) Preparation of Schizonepeta extract: high-quality Schizonepeta spikes are selected, with a volatile oil content of 1.0%, and the supercritical CO2 extraction process parameters are: pressure 23 MPa, temperature 46°C, and extraction time 2 hours;

[0233] (3) Mix Qianfeng extract 2.5 parts and Schizonepeta extract 1.5 parts in proportion, and homogenize in a 60°C water bath for 10 minutes to obtain the B bottle spring additive.

[0234] 3. Preparation of compound gel:

[0235] Mix B bottle spring additive 4 parts and A bottle base matrix 36 parts (proportion 1:9) at 40-45°C, stir with a paddle stirrer at 55 r / min for 15 minutes, homogenize under reduced pressure (-0.05 MPa) for 10 minutes to remove air bubbles, and obtain the final product. Quality control: uniformity test takes sample to determine the content deviation of different parts 3.2%, viscosity 20000 mPa·s, and stability test centrifugal test (3000 r / min, 30 minutes) without delamination.

[0236] In this embodiment, the weight ratio of salvia extract, hirudin and calcined oyster shell powder is 6:0.03:4=200:1:133.33, which forms a good anti-fibrosis synergistic effect. At the same time, after the nano co-milling technology treatment of calcined oyster shell powder and pearl powder, the average particle size reaches 180 nm, which significantly improves the transdermal absorption rate of mineral components. The pH value of the final product is 7.0, and the viscosity is 20000 mPa·s (25℃), which meets the requirements of skin external preparation.

[0237] Example 2: High-activity compound gel of traditional Chinese medicine

[0238] A bottle of basic matrix component (weight parts): salvia extract 8 parts, calcined oyster shell powder 4 parts, ginkgo biloba acid 1.2 parts, white and glue 15 parts, pearl powder 4 parts, glycyrrhizic acid dipotassium 0.8 parts, hirudin 0.05 parts, perilla oil 10 parts, beeswax 6 parts, deionized water 50.95 parts.

[0239] B bottle of summer additive component (weight parts): rhubarb extract 2.5 parts, safflower extract 4 parts.

[0240] Preparation method:

[0241] 1. Preparation of A bottle of basic matrix:

[0242] (1) First, white and glue 15 parts and beeswax 6 parts are heated to 75℃ to completely melt;

[0243] (2) Second, add perilla oil 10 parts, emulsify at high speed (8000r / min, 12 minutes), and then cool to 50℃;

[0244] (3) Third, add salvia extract 8 parts, calcined oyster shell powder 4 parts, ginkgo biloba acid 1.2 parts, pearl powder 4 parts, glycyrrhizic acid dipotassium 0.8 parts, hirudin 0.05 parts in turn, and stir evenly;

[0245] (4) Finally, add deionized water to a total weight of 100 parts, and homogenize under reduced pressure (-0.05MPa) for 10 minutes to remove bubbles to obtain A bottle of basic matrix.

[0246] 2. Preparation of B bottle of summer additive:

[0247] (1) Preparation of rhubarb extract: high-quality rhubarb roots and stems are selected, the total amount of anthraquinones is detected to be 2.0%, the rhubarb is crushed to 60 mesh, 70% ethanol (1:8) is added, and reflux extraction is carried out twice, each for 1.5 hours, the extract is combined, concentrated under reduced pressure to a relative density of 1.20, and D101 macroporous adsorption resin column chromatography is carried out, and 70% ethanol is used for elution to collect the safflower part;

[0248] (2) Safflower extract preparation: Select high-quality safflower, test safflower yellow pigment 1.5%, supercritical CO2 extraction process parameters: pressure 25 MPa, temperature 50℃, add 5% ethanol as cosolvent, extraction time 2.5 hours;

[0249] (3) Mix 2.5 parts of rhubarb extract and 4 parts of safflower extract in proportion, homogenize in a 45℃ water bath for 15 minutes to obtain B bottle summer additive.

[0250] 3. Compound gel preparation:

[0251] Mix 6.5 parts of B bottle summer additive and 58.5 parts of A bottle base matrix (proportion 1:9) at 40-45℃, use a paddle stirrer to stir at 60r / min for 15 minutes, homogenize under reduced pressure (-0.05 MPa) for 10 minutes, and remove air bubbles to obtain the final product. Quality control: uniformity test, sample determination of content deviation in different parts 2.8%, viscosity 23000 mPa·s, stability test centrifugal test (3000r / min, 30 minutes) no delamination phenomenon.

[0252] In this example, the weight ratio of salvia extract, hirudin and calcined oyster shell powder is 8:0.05:4=160:1:80, which has the best anti-fibrosis synergistic effect. After being treated by nano co-milling technology, the average particle size of calcined oyster shell powder and pearl powder is 150nm, which makes the mineral composition achieve a higher transdermal absorption rate. The final product has a pH value of 6.8 and a viscosity of 23000 mPa·s (25℃), which is suitable for use in hot seasons and has stronger heat-clearing and detoxifying and blood-activating and stasis-removing effects.

[0253] Example 3: Moisturizing compound traditional Chinese medicine gel

[0254] A bottle base matrix component (weight parts): salvia extract 5 parts, calcined oyster shell powder 3 parts, asiatic acid 0.5 parts, white yam glue 14 parts, pearl powder 2 parts, glycyrrhizic acid dipotassium 0.3 parts, hirudin 0.01 parts, perilla oil 7 parts, beeswax 4.5 parts, deionized water 63.69 parts.

[0255] B bottle autumn additive component (weight parts): saussurea extract 3 parts, ophiopogon extract 5 parts.

[0256] Preparation method:

[0257] 1. A bottle base matrix preparation:

[0258] (1) First, heat the white yam glue 14 parts and beeswax 4.5 parts to 75℃ until completely melted;

[0259] (2) Second, add perilla oil 7 parts, high-speed stirring emulsification (7000r / min, 10 minutes), then cool to 50℃;

[0260] (3) Again, add salvia extract 5 parts, calcined oyster shell powder 3 parts, ginkgo biloba extract 0.5 parts, pearl powder 2 parts, glycyrrhizic acid dipotassium 0.3 parts, hirudin 0.01 parts, and stir evenly;

[0261] (4) Finally, add deionized water to a total weight of 100 parts, and homogenize under reduced pressure (-0.05 MPa) for 10 minutes to remove air bubbles, to obtain the A bottle of basic matrix.

[0262] 2. Preparation of B bottle of autumn additive

[0263] (1) Preparation of radix adnatae extract: high-quality radix adnatae roots are selected, the saponin content is detected, the radix adnatae is ground to 60 mesh, hot water (90°C, 1:10) is added, and the extraction is performed twice for 1.5 hours each time, the extraction solutions are combined, and the relative density is reduced to 1.15 under reduced pressure. Add 95% ethanol to a final concentration of 80%, and precipitate the polysaccharide components;

[0264] (2) Preparation of radix ophiopogonis extract: high-quality radix ophiopogonis rhizomes are selected, the total saponin content is detected, the radix ophiopogonis is ground to 60 mesh, and water extraction (1:8, boiling for 2 hours) is performed. Reduce the pressure to concentrate to a relative density of 1.20, add 95% ethanol to a final concentration of 75%, and precipitate the polysaccharides;

[0265] (3) Mix the radix adnatae extract 3 parts and the radix ophiopogonis extract 5 parts in proportion, and stir evenly at room temperature to obtain the B bottle of autumn additive.

[0266] 3. Preparation of compound gel

[0267] Under the condition of 40-45°C, mix the B bottle of autumn additive 8 parts with the A bottle of basic matrix 72 parts (ratio 1:9), use a paddle stirrer to stir at 50 r / min for 15 minutes, homogenize under reduced pressure (-0.05 MPa) for 10 minutes to remove air bubbles, and obtain the final product. Quality control: uniformity test, sample determination of content deviation in different parts 3.5%, viscosity 18000 mPa·s, stability test centrifugal test (3000 r / min, 30 minutes) no delamination phenomenon.

[0268] In this example, the weight ratio of salvia extract, hirudin, and calcined oyster shell powder is 5:0.01:3=500:1:300, which is suitable for the skin condition in autumn. After being treated by nano co-milling technology, the average particle size of calcined oyster shell powder and pearl powder is 200 nm. The final product has a pH value of 7.2 and a viscosity of 18000 mPa·s (25°C), and has stronger yin-nourishing and dryness-moisturizing effects, suitable for use in dry autumn climate.

[0269] Example 4: Warm and unblock type compound gel of traditional Chinese medicine formula

[0270] A bottle of basic matrix component (parts by weight): Danshen extract 7 parts, calcined oyster shell powder 5 parts, Gattilacca acid 1 part, white and glue 10 parts, pearl powder 3.5 parts, glycyrrhizic acid dipotassium 0.6 parts, hirudin 0.04 parts, perilla oil 9 parts, beeswax 5.5 parts, deionized water 58.36 parts.

[0271] B bottle of winter additive component (parts by weight): Sanqi extract 6 parts, Cui Zhi extract 3 parts.

[0272] Preparation method:

[0273] 1. A bottle of basic matrix preparation:

[0274] (1) First, white and glue 10 parts and beeswax 5.5 parts are heated to 75℃ to completely melt;

[0275] (2) Next, add perilla oil 9 parts, high-speed stirring emulsification (7500r / min, 12 minutes), and then cool to 50℃;

[0276] (3) Again, add Danshen extract 7 parts, calcined oyster shell powder 5 parts, Gattilacca acid 1 part, pearl powder 3.5 parts, glycyrrhizic acid dipotassium 0.6 parts, hirudin 0.04 parts, and stir evenly;

[0277] (4) Finally, add deionized water to a total weight of 100 parts, and homogenize for 10 minutes under reduced pressure (-0.05MPa) to remove bubbles to obtain A bottle of basic matrix.

[0278] 2. B bottle of winter additive preparation:

[0279] (1) Sanqi extract preparation: high-quality Sanqi roots are selected, with total saponin content of 55%, and the Sanqi is crushed to 80 mesh, 70% ethanol reflux extraction for 2 times, 2 hours each time, the extract is combined, concentrated under reduced pressure, and purified by D101 macroporous adsorption resin, eluted with 60% ethanol;

[0280] (2) Cui Zhi extract preparation: high-quality Cui Zhi is selected, with volatile oil content of 1.5%, and the supercritical CO2 extraction process parameters are: pressure 21MPa, temperature 45℃, extraction time 2.5 hours;

[0281] (3) Mix Sanqi extract 6 parts and Cui Zhi extract 3 parts in proportion, and homogenize for 10 minutes in a 50℃ water bath to obtain B bottle of winter additive.

[0282] 3. Compound gel preparation:

[0283] Mix B bottle winter additive 9 parts with A bottle base matrix 81 parts (ratio 1:9) at 40-45°C, use paddle stirrer to stir for 15 minutes at 55 r / min, homogenize for 10 minutes under reduced pressure (-0.05 MPa), remove air bubbles, and obtain the final product. Quality control: uniformity test sampling to determine the content deviation of different parts is 3.0%, viscosity is 22000 mPa·s, and stability test centrifugal test (3000 r / min, 30 minutes) shows no delamination.

[0284] In this embodiment, the weight ratio of salvia extract, hirudin, and calcined oyster shell powder is 7:0.04:5=175:1:125, which is suitable for winter skin conditions. After being treated by nano co-milling technology, the average particle size of calcined oyster shell powder and pearl powder is 160 nm. The final product has a pH value of 6.9 and a viscosity of 22000 mPa·s (25°C), and has stronger effects of warming meridians and dispelling cold and promoting blood circulation and removing blood stasis, and is suitable for use in winter cold climate.

[0285] Example 5: Nano co-milling optimized formula of traditional Chinese medicine compound gel

[0286] A bottle base matrix component (weight parts): salvia extract 7.5 parts, calcined oyster shell powder 4.5 parts, asiatic acid 1.1 parts, white arisaema gum 13 parts, pearl powder 3.8 parts, glycyrrhizic acid dipotassium 0.7 parts, hirudin 0.04 parts, perilla oil 9.5 parts, beeswax 5.8 parts, deionized water 54.06 parts.

[0287] B bottle spring additive component (weight parts): wind-preventing extract 2.8 parts, schizonepeta extract 1.8 parts.

[0288] The feature of this embodiment is the optimization of nano co-milling technology, and the specific preparation method is as follows:

[0289] 1. Nano co-milling optimization process:

[0290] (1) Mix calcined oyster shell powder and pearl powder at a ratio of 1:1;

[0291] (2) Add 95% ethanol (solid-liquid ratio 1:3) as a dispersion medium;

[0292] (3) Add 0.5% polyvinylpyrrolidone (PVP K30) as a dispersant, and add 0.1% sodium dodecyl sulfate (SDS) to enhance the dispersion effect;

[0293] (4) Adjust the ball-to-material ratio (ceramic ball-to-material ratio) to 18:1;

[0294] (5) Extend the milling time to 15 hours, increase the rotation speed to 380 r / min, pause for 10 minutes every 45 minutes, and control the temperature of the constant temperature circulating water to be ≤25°C;

[0295] (6) Gradient centrifugation (5000 r / min for 10 minutes, 10000 r / min for 15 minutes) was used to collect particles with more uniform particle size;

[0296] (7) High-intensity ultrasonic dispersion (power 350 W, 15 minutes) was used;

[0297] (8) Spray drying parameter optimization (inlet temperature 160°C, outlet temperature 75°C, atomization pressure 0.3 MPa);

[0298] (9) Nanopowder with an average particle size of 120 nm, a particle size distribution index of 0.2, and a Zeta potential of -45 mV was obtained.

[0299] 2. The preparation method of bottle A basic matrix and bottle B spring additive was similar to that of Example 1, but the optimized nanopowder described above was used.

[0300] 3. The preparation method of the compound gel was the same as that of Example 1. The final product had a pH value of 7.1 and a viscosity of 21000 mPa·s (25°C).

[0301] In this example, by optimizing the nanoscale co-milling technology, the average particle size of calcined oyster shell powder and pearl powder was reduced to 120 nm, the particle size distribution was more uniform, the transdermal absorption rate and bioavailability of mineral components were significantly improved, and the product had better repair effect.

[0302] Example 6: Optimization of Hirudin-Perilla Oil Synergistic System in Compound Gel of Traditional Chinese Medicine

[0303] The components of bottle A basic matrix (by weight): Danshen extract 6.5 parts, calcined oyster shell powder 3.8 parts, Centella asiatica acid 0.9 parts, Bletilla striata gum 11 parts, pearl powder 2.5 parts, glycyrrhizic acid dipotassium 0.4 parts, hirudin 0.035 parts, perilla oil 7.5 parts, beeswax 4.8 parts, deionized water 62.515 parts.

[0304] The components of bottle B summer additive (by weight): Dahuang extract 2 parts, Honghua extract 3.5 parts.

[0305] The feature of this example is to optimize the hirudin-perilla oil fat-soluble synergistic system, and the specific preparation method is as follows:

[0306] 1. Hirudin-perilla oil fat-soluble synergistic system optimization process:

[0307] (1) Mix perilla oil, phospholipid, and cholesterol according to a mass ratio of 7:2.5:0.5, and add 1% glycerol monostearate as an emulsifier;

[0308] (2) Solvent optimization: dissolve the mixture in a chloroform:methanol (2:1) mixed solvent;

[0309] (3) Optimization of thin film formation: rotary evaporation conditions were 40℃, reduced pressure 0.07 MPa, and rotation speed 80 r / min;

[0310] (4) Optimization of hydration process: the hirudin aqueous solution (3 mg / mL) was hydrated at 45℃ in the thin film, and 0.2% poloxamer 407 was added to enhance stability;

[0311] (5) Optimization of ultrasonic treatment: probe-type ultrasonic (power 250 W, working 3 seconds, intermittent 2 seconds, total time 8 minutes) was used;

[0312] (6) Optimization of high-pressure homogenization parameters: first 80 MPa, and then 40 MPa for 2 times;

[0313] (7) The average particle size of the liposomes was 100 nm, the hirudin encapsulation rate was 92%, and the particle size change was ≤5% after storage at 4℃ for 45 days.

[0314] 2. The preparation method of bottle A basic matrix and bottle B summer additive was similar to that of Example 2, but the optimized hirudin-perilla oil lipid-soluble synergistic system was used.

[0315] 3. The preparation method of the compound gel was the same as that of Example 2. The final product had a pH value of 6.7 and a viscosity of 19500 mPa·s (25℃).

[0316] In this example, the preparation process of the hirudin-perilla oil lipid-soluble synergistic system was optimized, the encapsulation rate and stability of hirudin were improved, the synergistic effect of hirudin and perilla oil was enhanced, and the product had better anti-fibrosis and repair effects.

[0317] Example 7: Low-limit formula compound gel of traditional Chinese medicine

[0318] The components of bottle A basic matrix (by weight): salvia miltiorrhiza extract 5 parts, calcined oyster shell powder 3 parts, asiatic acid 0.5 parts, white arisaema gum 10 parts, pearl powder 2 parts, glycyrrhizic acid dipotassium 0.3 parts, hirudin 0.01 parts, perilla oil 6 parts, beeswax 4 parts, and deionized water 69.19 parts.

[0319] The components of bottle B autumn additive (by weight): saussurea involucrata extract 2 parts, and ophiopogon japonicus extract 3 parts.

[0320] Preparation method:

[0321] 1. The preparation method of bottle A basic matrix and bottle B autumn additive was similar to that of Example 3, but the low-limit content of each component was used.

[0322] 2. The preparation method of the compound gel was the same as that of Example 3. The final product had a pH value of 7.4 and a viscosity of 15500 mPa·s (25℃).

[0323] This example shows the formulation of each component at a low limit content, which still maintains the basic repair function, especially suitable for sensitive skin.

[0324] Example 8: High limit formula of traditional Chinese medicine compound gel

[0325] A bottle of basic matrix component (parts by weight): Danshen extract 8 parts, calcined oyster shell powder 5 parts, asiatic acid 1.2 parts, white and glue 15 parts, pearl powder 4 parts, glycyrrhizic acid dipotassium 0.8 parts, hirudin 0.05 parts, perilla oil 10 parts, beeswax 6 parts, deionized water 49.95 parts.

[0326] B bottle winter additive component (parts by weight): Sanqi extract 6 parts, GuiZhi extract 3 parts.

[0327] Preparation method:

[0328] 1. The preparation method of A bottle of basic matrix and B bottle of winter additive is similar to example 4, but the high limit content of each component is used.

[0329] 2. The preparation method of compound gel is the same as example 4. The final product pH value is 6.6, and the viscosity is 24500 mPa·s (25℃).

[0330] This example shows the formulation of each component at a high limit content, which has stronger repair function, suitable for repair of more severe hyperplastic scar.

[0331] Comparative example

[0332] Comparative example 1: No four seasons additive formula

[0333] Component (parts by weight): Danshen extract 6 parts, calcined oyster shell powder 4 parts, asiatic acid 0.8 parts, white and glue 12 parts, pearl powder 3 parts, glycyrrhizic acid dipotassium 0.5 parts, hirudin 0.03 parts, perilla oil 8 parts, beeswax 5 parts, deionized water 60.67 parts.

[0334] Preparation method: prepared according to the preparation method of A bottle of basic matrix in example 1. The final product pH value is 7.0, and the viscosity is 20000 mPa·s (25℃).

[0335] This comparative example only contains basic matrix ingredients, without adding four seasons additive, which is used to verify the role of four seasons additive in scar repair.

[0336] Comparative example 2: No nano co-milling technology formula

[0337] Components (parts by weight): Salvia miltiorrhiza extract 6 parts, calcined oyster shell powder 4 parts (regular powder, particle size about 5 μm), Gynostemma pentaphyllum acid 0.8 parts, Bletilla striata gum 12 parts, pearl powder 3 parts (regular powder, particle size about 8 μm), glycyrrhizic acid dipotassium 0.5 parts, hirudin 0.03 parts, perilla oil 8 parts, beeswax 5 parts, deionized water 60.67 parts, Saposhnikovia divaricata extract 2.5 parts, Schizonepeta extract 1.5 parts.

[0338] Preparation method: prepared according to the method of Example 1, but the calcined oyster shell powder and pearl powder were not subjected to nanometer co-milling treatment, and the regular powders were directly used. The pH value of the final product was 7.0, and the viscosity was 19500 mPa·s (25℃).

[0339] This comparative example does not use the nanometer co-milling technology, and is used to verify the effect of the nanometer mineral components in the repair of scars.

[0340] Comparative Example 3: Hirudin-Perilla Oil Synergistic System Formulation without Water

[0341] Components (parts by weight): Salvia miltiorrhiza extract 6 parts, calcined oyster shell powder 4 parts, Gynostemma pentaphyllum acid 0.8 parts, Bletilla striata gum 12 parts, pearl powder 3 parts, glycyrrhizic acid dipotassium 0.5 parts, hirudin 0.03 parts (directly added, not forming liposomes), perilla oil 8 parts, beeswax 5 parts, deionized water 60.67 parts, Rheum palmatum extract 2.5 parts, safflower extract 4 parts.

[0342] Preparation method: prepared according to the method of Example 2, but the hirudin was not formed into a liposoluble synergistic system with perilla oil, but was directly added to the matrix. The pH value of the final product was 6.8, and the viscosity was 22500 mPa·s (25℃).

[0343] This comparative example does not use the hirudin-perilla oil liposoluble synergistic system, and is used to verify the effect of the synergistic system in the repair of scars.

[0344] Test method and results

[0345] In order to evaluate the effectiveness of the traditional Chinese medicine compound gel of the present application in the repair of scars, the following tests were carried out:

[0346] Test one: in vitro transdermal penetration test

[0347] The transdermal penetration rate of the main active ingredients was determined using a Franz diffusion cell. The samples of Examples 1-8 and Comparative Examples 1-3 were placed in the donor chamber of the Franz diffusion cell, with fresh pig skin (thickness 500±50 μm) as the diffusion membrane, and the receiving chamber was filled with PBS buffer at pH 7.4, maintained at a temperature of 32±0.5℃, and the sampling time points were 0.5h, 1h, 2h, 4h, 8h, 12h. The contents of active ingredients such as tanshinone IIA, asiatic acid, hirudin, etc. in the receiving liquid were determined by HPLC method, and the 24-hour cumulative penetration amount (μg / cm²) was calculated. The results are shown in Table 1:

[0348] Table 1 24-hour cumulative penetration amount (μg / cm²) of main active ingredients of each sample

[0349] Sample Tanshinone IIA Asiatic acid Hirudin Characteristic seasonal ingredients Example 1 24.5 15.2 6.8 8.3 (Saposhin) Example 2 30.2 18.7 8.2 10.5 (Emodin) Example 3 20.8 13.5 5.5 7.8 (Ophiopogonin) Example 4 27.6 16.8 7.5 12.3 (Panax notoginseng saponin) Example 5 35.4 21.2 9.6 11.2 (Saposhin) Example 6 32.7 19.5 12.8 9.8 (Emodin) Example 7 18.6 12.3 4.8 6.5 (Ophiopogonin) Example 8 28.9 17.6 7.9 13.1 (Panax notoginseng saponin) Comparative Example 1 22.3 14.7 6.2 - Comparative Example 2 14.5 8.3 4.1 3.5 (Saposhin) Comparative Example 3 29.5 16.4 2.3 9.2 (Emodin)

[0350] * Characteristic seasonal ingredients refer to representative ingredients in each seasonal additive.

[0351] As can be seen from Table 1, the transdermal penetration rates of Example 5 (nano-cocoground optimized formulation) and Example 6 (hirudin-perilla oil synergistic system optimized formulation) are significantly higher than those of other samples, especially compared with Comparative Example 2 (without nano-cocoground technology) and Comparative Example 3 (without hirudin-perilla oil synergistic system), which are increased by 144% and 457%, respectively. In addition, the characteristic ingredients in the four-season additives also show good transdermal penetration, confirming that the compound gel of the present application can effectively deliver multiple active ingredients to the deep layer of the skin.

[0352] Test two: evaluation of in vitro anti-fibrosis activity

[0353] The anti-fibrosis activity of each sample was evaluated using a human skin fibroblast (HSF) culture model. Method: HSF cells were seeded in a 24-well plate at 5×10 4 cells / well, and 10 ng / mL of transforming growth factor-β1 (TGF-β1) was added to the culture medium for 24 hours to induce fibroblast activation. Then, the extract solution (1 mg / mL) of each sample was added, and the culture was continued for 48 hours. The expression levels of collagen type I (Col-I), α-smooth muscle actin (α-SMA), and fibronectin (FN) were detected by Western blot method. The results are shown in Table 2:

[0354] Table 2 Inhibition rate (%) of each sample on fibrosis indicators of HSF cells

[0355] Example 1 42.5 38.6 35.2 Example 2 48.3 45.2 40.6 Example 3 40.8 36.5 33.7 Example 4 45.6 43.8 39.5 Example 5 52.4 50.2 47.6 Example 6 55.7 53.5 49.8 Example 7 38.6 35.3 32.4 Example 8 50.9 48.6 44.1 Comparative Example 1 38.3 35.7 32.2 Comparative Example 2 30.5 28.3 25.1 Comparative Example 3 35.5 33.4 30.3 Positive control (0.1% triamcinolone acetonide) 60.2 58.6 55.3 Negative control (gel base) 10.5 8.3 7.2

[0356] As can be seen from Table 2, all the examples show obvious anti-fibrosis activity, in which the inhibition rates of Example 6 (hirudin-perilla oil synergistic system optimized formula) on Col-I, a-SMA and FN are 55.7%, 53.5% and 49.8% respectively, close to the effect of positive control triamcinolone acetonide. In contrast, the anti-fibrosis activity of Comparative Example 2 (without nano-cocry grinding technology) and Comparative Example 3 (without hirudin-perilla oil synergistic system) is obviously reduced, confirming the importance of the core technology in the present application.

[0357] Test three: seasonal adaptability evaluation

[0358] To evaluate the seasonal adaptability of the present application, the repair effects of each seasonal formula on the scar model were tested under simulated four-season environmental conditions. The hyperplastic scar model of rabbit ear was used, the cartilage membrane of rabbit ear was completely removed to form a full-thickness skin defect of 1.5 cm x 1.5 cm, and after the wound was naturally healed to form a hyperplastic scar (about 28 days), the drug administration was started. Each group was placed in an artificial climate chamber under different environmental conditions: spring group (temperature 20±2℃, relative humidity 60±5%, ultraviolet intensity 5±1 mW / cm²), summer group (temperature 32±2℃, relative humidity 75±5%, ultraviolet intensity 15±2 mW / cm²), autumn group (temperature 15±2℃, relative humidity 45±5%, ultraviolet intensity 6±1 mW / cm²), winter group (temperature 5±2℃, relative humidity 30±5%, ultraviolet intensity 3±1 mW / cm²). Drug administration was performed twice a day, and the administration was continued for 28 days. The scar thickness, hardness, erythema index and other indicators were measured. The results are shown in Table 3:

[0359] Table 3 Scar repair effect (improvement rate %) of each sample under simulated four-season environmental conditions

[0360] Sample Ambient conditions Scar thickness Scar hardness Erythema index Skin moisture Example 1 Spring 38.6 35.2 42.5 23.6 Example 2 Summer 40.3 37.5 48.6 25.4 Example 3 Autumn 35.8 33.4 36.2 32.7 Example 4 Winter 36.5 34.6 35.7 28.5 Comparative Example 1 Spring 30.2 28.5 32.6 18.4 Summer 26.8 25.3 30.5 15.6 Autumn 25.4 23.7 28.3 14.2 Winter 24.3 22.5 27.6 13.5 Comparative Example 2 Spring 25.6 22.3 28.5 16.3 Comparative Example 3 Summer 32.4 30.2 35.8 20.1

[0361] As can be seen from Table 3, compared with Comparative Example 1 (without four-season additives), each seasonal special formula shows better scar repair effect under the corresponding environmental conditions. Especially in extreme seasonal conditions (high temperature and high humidity in summer, low temperature and dryness in winter), the effect of Comparative Example 1 decreases obviously, while the seasonal special formula of the present application still maintains a high repair effect, confirming the application value of the theory of four seasons in scar repair.

[0362] Through comprehensive analysis of the above test results, Example 6 (hirudin-perilla oil synergistic system optimized formula) shows the best comprehensive performance: the transdermal penetration rate of hirudin reaches 12.8 μg / cm², and the inhibition rate on Col-I reaches 55.7%, close to the effect of positive control triamcinolone acetonide. This formula combines the optimized hirudin-perilla oil liposoluble synergistic system and summer additives (rhubarb + safflower), and is especially suitable for scar repair in high temperature and high humidity environment in summer.

[0363] In addition, Example 5 (nano-cocurrent grinding optimized formula) performed outstandingly in terms of transdermal absorption, with the cumulative permeation amount of tanshinone IIA reaching 35.4 μg / cm², which was increased by 144% compared with Comparative Example 2, confirming the important value of the nano-cocurrent grinding technology in improving the bioavailability of mineral components.

[0364] The design concept of the four-season differentiated formula was fully verified in Test 3. Under the simulated four-season environmental conditions, the special formula for each season maintained stable scar repair effect, while Comparative Example 1 (without four-season additives) showed a significant decrease in effect under extreme seasonal conditions, proving the scientificity and effectiveness of the repair concept based on the four seasons.

[0365] The outstanding scar repair effect of the present application is due to the synergistic mechanism of the following aspects:

[0366] 1. Multi-target anti-scar mechanism of the basic matrix: Salvia miltiorrhiza extract promotes blood circulation to remove blood stasis and improves microcirculation; asiatic acid inhibits excessive proliferation of fibroblasts and collagen deposition; hirudin dissolves fibrin deposition and inhibits scar vascular hyperplasia; calcined oyster shell powder and pearl powder provide minerals and soften scar tissue; Bletilla striata gum and perilla oil maintain skin water-oil balance and repair barrier function. These components synergistically act from the aspects of promoting blood circulation to remove blood stasis, antibacterial and anti-inflammatory, and promoting regeneration, forming a comprehensive scar repair system.

[0367] 2. Nano-technology improves bioavailability: After nano-cocurrent grinding treatment, the average particle size of calcined oyster shell powder and pearl powder is ≤200 nm, which significantly improves the transdermal absorption rate of mineral components. According to the test results, the bioavailability is increased by about 3 times compared with traditional powder. The lipid-soluble synergistic system of hirudin-perilla oil encapsulates water-soluble hirudin in liposomes, significantly improving its transdermal penetration rate and stability, so that hirudin can penetrate into the dermis to play an anti-fibrosis role.

[0368] 3. Four-season differentiated formula adapts to environmental changes: According to the theory of four seasons, the four-season additives solve the scar problems in different seasons: the spring combination (wind-preventing + schizonepeta) dispels wind and relieves itching, relieving spring skin sensitivity; the summer combination (rhubarb + safflower) clears heat and detoxifies, inhibiting bacterial reproduction; the autumn combination (marshmallow + ophiopogon) nourishes yin and moisturizes dryness, relieving autumn skin dryness; the winter combination (sanchi + cassia twig) warms the meridians and dispels cold, promoting local blood circulation of scars in winter. This differentiated design enables the compound gel of the present application to maintain stable repair effect under different climate conditions.

[0369] In summary, the application realizes all-round and precise repair of hypertrophic scars by a complex system of base matrix + four-season dynamic additive components, combined with nanoscale co-milling technology and a hirudin-perilla oil fat-soluble synergistic system, and provides a new idea and method for scar treatment.

[0370] The traditional Chinese medicine compound gel and the preparation method thereof have good industrial practicability:

[0371] 1. Raw materials are easy to obtain: The traditional Chinese medicinal materials such as salvia miltiorrhiza, centella asiatica, saposhnikovia divaricata and schizonepeta are common varieties, and the source is stable, the price is reasonable, and the scale production is suitable.

[0372] 2. The process is feasible: The supercritical CO2 extraction, nanoscale co-milling and liposome preparation technology used in the application have been widely used in the pharmaceutical industry, and the equipment is mature, the process is stable, and the industrialization is easy to realize.

[0373] 3. The quality is controllable: The application puts forward clear requirements for the standardization indexes of each component (such as the content of tanshinone IIA is greater than or equal to 3.5%, and the activity of hirudin is greater than or equal to 120 ATU / mg), which is convenient for quality control and batch consistency management.

[0374] 4. Convenient to use: The application adopts the design of A bottle base matrix + B bottle four-season additive, and consumers only need to select the corresponding B bottle additive according to the use season, which is simple and convenient to use.

[0375] 5. Wide adaptability: The application provides differentiated formulations for different seasons and different severity of hypertrophic scars, and meets the use requirements of different people and different conditions.

[0376] Therefore, the application has good industrialization prospect and market application value.

[0377] The above only describes the preferred embodiments of the application and is not intended to limit the application. The application can have various modifications and changes for those skilled in the art. Any modification, equivalent replacement, improvement, etc. within the spirit and principles of the application shall be included in the protection scope of the application.

Claims

1. A traditional Chinese medicine compound gel containing bioactive organic components for repairing hyperplastic scars based on the four seasons, characterized in that, The traditional Chinese medicine compound gel is prepared by mixing the A bottle base matrix and the B bottle four-season additive according to a weight ratio of 9:1; The A bottle base matrix comprises the following components in parts by weight: 5-8 parts of salvia extract, 3-5 parts of calcined oyster shell powder, 0.5-1.2 parts of centella asiatica acid, 10-15 parts of bletilla striata gum, 2-4 parts of pearl powder, 0.3-0.8 parts of dipotassium glycyrrhizinate, 0.01-0.05 parts of hirudin, 6-10 parts of perilla oil, 4-6 parts of beeswax, and 49.95-69.19 parts of deionized water; The B bottle four-season additive is selected according to the season of use and comprises: Spring additive: 2-3 parts of siler extract and 1-2 parts of catnip extract; Summer additive: 1.5-2.5 parts of rhubarb extract and 3-4 parts of safflower extract; Autumn additive: 2-3 parts of adenosma japonicum extract and 3-5 parts of ophiopogon japonicus extract; Winter additive: 4-6 parts of pseudo-ginseng extract and 2-3 parts of cassia twig extract.

2. The traditional Chinese medicine compound gel according to claim 1, characterized in that, The weight ratio of salvia extract, hirudin and calcined oyster shell powder in the A bottle base matrix is 8:0.03:

4.

3. The traditional Chinese medicine compound gel of claim 1, characterized in that, The calcined oyster shell powder and the pearl powder are treated by nano co-milling technology, and the average particle size is ≤200 nm.

4. The traditional Chinese medicine compound gel of claim 1, characterized in that, The content of tanshinone IIA in the salvia extract is ≥3.5%, the content of danshensu is ≥1.0%, the purity of centella asiatica acid is ≥98%, the activity of hirudin is ≥120 ATU / mg, and the content of α-linolenic acid in the perilla oil is ≥55%.

5. The traditional Chinese medicine compound gel of claim 1, characterized in that, The pH value of the traditional Chinese medicine compound gel is 6.5-7.5, and the viscosity is 15000-25000 mPa·s at 25℃.

6. A method for preparing the A bottle base matrix of the traditional Chinese medicine compound gel according to any one of claims 1-5, characterized in that, The method comprises the following steps: (1) First, the bletilla striata gum and beeswax are heated to 75℃ to completely melt; (2) Second, the perilla oil is added, emulsified by high-speed stirring, and then cooled to 50℃; (3) Third, the salvia extract, calcined oyster shell powder, centella asiatica acid, pearl powder, dipotassium glycyrrhizinate and hirudin are added in sequence; (4) Finally, under the condition of reduced pressure, -0.05 MPa homogenization for 10 minutes to remove bubbles, and the A bottle base matrix is obtained.

7. The preparation method according to claim 6, characterized in that, The nano co-milling technology of the calcined oyster shell powder and the pearl powder comprises the following steps: (1) The calcined oyster shell powder and the pearl powder are mixed in a proportion of 1:1, 95% ethanol is added as a dispersion medium, and the solid-liquid ratio is 1:3; (2) 0.5% polyvinylpyrrolidone is added as a dispersant, and the material is milled in a planetary high-energy ball mill with a ceramic ball to material ratio of 15:1; (3) The milling conditions are: milling time 12 hours, rotation speed 350 r / min, pause for 10 minutes every 60 minutes, and circulating water control temperature ≤30℃; (4) The solid is collected by centrifugal separation, and then is spray dried after ultrasonic dispersion, with an inlet temperature of 170℃ and an outlet temperature of 80℃.

8. The preparation method according to claim 6, characterized in that, The preparation method of the fat-soluble synergistic system composed of the hirudin and the perilla oil comprises the following steps: (1) The perilla oil, phospholipid and cholesterol are mixed in a mass ratio of 8:2:1 and dissolved in chloroform; (2) Thin film is formed by rotary evaporation, and the hydrated thin film is added with 2 mg / mL hirudin aqueous solution; (3) Ultrasonic treatment for 10 minutes, power 200 W, work for 5 seconds, and intermittent for 3 seconds; (4) High pressure homogenization, 60 MPa, 3 cycles, to form the hirudin-perilla oil soluble synergistic system.

9. A method for preparing the B bottle four seasons additive of the traditional Chinese medicine compound gel according to any one of claims 1-5, characterized in that, The method comprises the following steps: (1) Selecting corresponding medicinal materials according to seasons, drying to a water content of less than or equal to 8%, and crushing to 40-60 mesh; (2) Extracting active ingredients by using a supercritical CO2 extraction method, wherein: the extraction pressure is 20-25 MPa, the extraction temperature is 45-50 DEG C, the CO2 flow rate is 20-25 L / h, and the extraction time is 2-3 hours, the separation pressure is 7-8 MPa, and the separation temperature is 40-45 DEG C; (3) For medicinal materials not suitable for supercritical extraction, the following method is used for extraction: Rhubarb: 70% ethanol reflux extraction, D101 macroporous adsorption resin purification; Shashen and Maidong: hot water extraction of polysaccharides, ethanol precipitation; Sanqi: 70% ethanol reflux extraction, D101 macroporous adsorption resin purification; (4) Mixing the extracts of the same season according to the formula proportion: Spring: The extracts of Fangfeng and Jingjie are mixed in a ratio of 2:1; Summer: The extracts of Dahuang and Honghua are mixed in a ratio of 1:2; Autumn: The extracts of Shashen and Maidong are mixed in a ratio of 2:3; Winter: The extracts of Sanqi and Guizhi are mixed in a ratio of 2:

1.

10. A method for preparing the traditional Chinese medicine compound gel according to any one of claims 1-5, characterized in that, The method comprises the following steps: (1) Preparing the A bottle basic matrix according to the method of any one of claims 6-8; (2) Preparing the B bottle four-season additive according to the method of claim 9; (3) Mixing the B bottle four-season additive and the A bottle basic matrix in a weight ratio of 1:9 at 40-45 DEG C; (4) Using a paddle stirrer to stir at 50-60 r / min for 15 minutes; (5) Homogenizing under reduced pressure, -0.05 MPa for 10 minutes, to remove air bubbles; (6) Quality control detection: uniformity test sampling to determine the content deviation of different parts to be less than or equal to 5%, viscosity control to be 15000-25000 mPa·s, and stability test centrifugal test, 3000 r / min, 30 minutes without stratification.