Application of traditional Chinese medicine composition in preparation of medicine for promoting wound healing

Abstract

The invention provides application of a traditional Chinese medicine composition in preparation of a medicine for promoting wound healing. The experimental process finds that within the dosage range, the ointment has an obvious promoting effect on healing of scalded skin wounds and also has a certain improving effect on healing of frostbite skin wounds.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine, and particularly relates to application of a traditional Chinese medicine composition in preparation of a medicine for promoting wound healing. BACKGROUND

[0002] Wound healing, also known as wound healing, is a series of repair processes in which local tissues fill, connect or replace damaged and missing tissues through regeneration and proliferation after the action of injury factors on the body. The injury factors of the wound include high temperature, low temperature, electric current, radiation, acid, alkali, toxic gas, mosquito bites, etc. Among them, potential heat sources such as hot water, hot oil, steam and heating elements are everywhere, so high-temperature scald is one of the most common types of trauma in daily life. Although frostbite caused by low temperature and cold invasion is much less frequent due to geographical and seasonal limitations, the high rate of disability undoubtedly greatly affects the quality of life of patients.

[0003] Wound healing can be divided into physiological healing and pathological healing. Physiological healing can be divided into hemostasis period, inflammation period, cell proliferation period and maturation period, and finally shows wound remodeling and maturation, while pathological healing lacks the necessary conditions for healing, and shows stagnation in the hemostasis period, inflammation period or cell proliferation period. In terms of treatment, according to the different severity of the wound, the anti-infective drugs and biological agents used in Western medicine play different roles, but Western medicine often has single action and lacks comprehensive efficacy, which is difficult to adapt to the abnormal complexity of wound healing. Traditional Chinese medicine preparations are constantly being updated, traditional Chinese medicine prescriptions and preparation processes are constantly being optimized, and gradually showing great advantages in external treatment of wound healing. SUMMARY

[0004] The main purpose of the embodiments of the present application is to propose the application of the traditional Chinese medicine composition in the preparation of the medicine for promoting wound healing.

[0005] To achieve the above-mentioned purpose, the first aspect of the present application proposes the application of the traditional Chinese medicine composition in the preparation of the medicine for promoting wound healing, and the raw materials of the active ingredients of the traditional Chinese medicine composition include notoginseng, astragalus, ginseng and radix puerariae or pueraria.

[0006] In some embodiments of the present application, the wound includes a wound caused by at least one of physical, chemical and biological factors.

[0007] In some embodiments of the present application, the wound caused by the physical factor includes one or more of temperature (such as high temperature, low temperature), electric current, radiation, external force (including surgery or other sharp and blunt instruments, firearms), light, sound, air pressure, etc.

[0008] In some embodiments of the present application, the chemical factor includes one or more of acid, alkali, toxic gas, drug, etc.

[0009] In some embodiments of the application, the biological factor comprises a wound surface caused by at least one of an autogenous factor (such as local blood supply disorder), an allogenic factor (such as a bite).

[0010] In some embodiments of the application, the wound surface comprises a wound surface of at least one of a frostbite, a burn.

[0011] In some embodiments of the application, the frostbite comprises a first degree frostbite, a second degree frostbite, a third degree frostbite, a fourth degree frostbite.

[0012] In some embodiments of the application, the burn comprises a first degree burn, a second degree burn (superficial second degree burn, deep second degree burn), a third degree burn.

[0013] In some embodiments of the application, promoting wound healing comprises reducing the wound area.

[0014] In some embodiments of the application, promoting wound healing comprises increasing the expression of at least one of vascular endothelial growth factor (vEGF), collagen in the wound surface.

[0015] In some embodiments of the application, the collagen comprises at least one of collagen type 1, collagen type 2, collagen type 3.

[0016] In some embodiments of the application, the wound surface comprises at least one of a skin wound surface, a mucosal wound surface.

[0017] In some embodiments of the application, the mucosal wound surface comprises at least one of an oral mucosal wound surface, a digestive tract mucosal wound surface, a respiratory tract mucosal wound surface, a genital tract mucosal wound surface, etc.

[0018] In some embodiments of the application, the wound surface is a wound surface of at least one of a Carnivora (such as a dog, a cat), a Perissodactyla (such as a horse, a donkey), an Even-toed ungulate (such as a sheep, a goat, a camel, a cow, a pig), a Rodentia (such as a mouse, a rat, a hamster, a guinea pig), a Lagomorpha (such as a rabbit), a Primates (such as a monkey, a gorilla, a chimpanzee, a human).

[0019] In some embodiments of the application, the wound surface is a wound surface of at least one of a dog, a cat, a pig, a sheep, a cow, a horse, a rabbit, a mouse, a monkey, a chimpanzee, a gorilla, a human, etc.

[0020] The term "active ingredient" refers to the functional ingredient in the traditional Chinese medicine composition that is capable of bringing clinical benefits to the subject after administration, including at least partially alleviating, controlling and / or improving the disease or its symptoms.

[0021] Sanqi refers to the dried root and rhizome of Panax notoginseng (Burk.) F.H.Chen of the Araliaceae family. It is sweet and slightly bitter in nature, and warm in property. It belongs to the liver and stomach meridians. It has the functions of stopping bleeding, removing blood stasis, and relieving swelling and pain. It is used for hemoptysis, hematemesis, epistaxis, hematochezia, metrorrhagia, external trauma bleeding, chest and abdominal pain, and contusion pain.

[0022] Huangqi is the dried root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge. of the Leguminosae family. It is sweet in nature and warm in property. It belongs to the lung and spleen meridians. Huangqi has the functions of tonifying qi and ascending yang, consolidating the exterior and stopping sweating, promoting water and relieving swelling, generating fluid and nourishing blood, removing stagnation and relieving arthralgia, promoting pus discharge, and promoting healing and tissue regeneration. It is used for qi deficiency and debilitation, poor appetite and loose stools, middle-qi collapse, chronic diarrhea and prolapse of the anus, hematochezia and metrorrhagia, exterior deficiency and spontaneous sweating, qi deficiency and edema, internal heat and diabetes, blood deficiency and emaciation, hemiplegia, arthralgia and numbness, and ulcer and non-healing.

[0023] Renshen is the dried root and rhizome of Panax ginseng C.A.Mey. of the Araliaceae family. It is sweet and slightly bitter in nature, and warm in property. It belongs to the spleen, lung, heart, and kidney meridians. Renshen has the functions of tonifying primordial qi, restoring pulse and preventing collapse, tonifying the spleen and lung, generating fluid and nourishing blood, and calming the mind and improving intelligence. It is used for body weakness and collapse, cold limbs and weak pulse, spleen deficiency and poor appetite, lung deficiency and cough, fluid deficiency and thirst, internal heat and diabetes, qi and blood deficiency, chronic disease and emaciation, palpitation and insomnia, and impotence and cold hands and feet.

[0024] Gegen is the dried root of Pueraria lobata (Willd.) Ohwi of the Leguminosae family. It is sweet and pungent in nature, and cool in property. It belongs to the spleen, stomach, and lung meridians. Gegen has the functions of relieving the exterior and reducing fever, generating fluid and relieving thirst, promoting rash, ascending yang and stopping diarrhea, promoting meridians and activating collaterals, and resolving alcohol toxicity. It is used for external heat and headache, neck and back pain, thirst, diabetes, measles without rash, dysentery, diarrhea, dizziness and headache, stroke and hemiplegia, chest pain, and alcohol toxicity.

[0025] Puheng is the dried root of Pueraria thomsonii Benth. of Leguminosae. It is sweet and acrid in nature and cool in property. It is associated with the spleen and stomach meridians. Puheng also has the functions of relieving the exterior and reducing fever, generating fluid and relieving thirst, promoting eruption, ascending yang and stopping diarrhea, promoting blood circulation and removing blood stasis, and removing alcohol toxicity. It is also used for treating external invasion of pathogenic factors with fever, headache, stiff neck, thirst, diabetes, measles without eruption, dysentery, diarrhea, dizziness, headache, hemiplegia, chest pain, alcohol toxicity. However, there are differences in the contents of starch, puerarin, flavonoids and other substances between Puheng and Gegen, so Gegen is more focused on promoting blood circulation and removing blood stasis and relieving the exterior and reducing fever, while Puheng is more focused on generating fluid and relieving thirst and ascending yang and stopping diarrhea.

[0026] In some embodiments of the present application, the active ingredients of the traditional Chinese medicine composition are made from raw materials containing the following mass parts: 100-500 parts of Sanqi, 300-900 parts of Huangqi, 50-200 parts of Renshen, 50-150 parts of Gegen or Puheng; for example, it can be 100, 150, 200, 250, 300, 350, 400, 450, 500 parts of Sanqi, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900 parts of Huangqi, 50, 100, 150, 200 parts of Renshen, 50, 100, 150 parts of Gegen or Puheng.

[0027] In some embodiments of the present application, the traditional Chinese medicine composition comprises at least one of a water extract, an alcohol extract of Radix Astragali, Panax Notoginseng, Radix et Rhizoma Ginseng, Pueraria lobata or Pueraria montana. In some embodiments, the traditional Chinese medicine composition comprises a1-a4: a1. at least one of a water extract and an alcohol extract of Radix Astragali, a2. at least one of a water extract and an alcohol extract of Panax Notoginseng, a3. at least one of a water extract and an alcohol extract of Radix et Rhizoma Ginseng, a4. at least one of a water extract and an alcohol extract of Pueraria lobata or Pueraria montana. In some embodiments, the traditional Chinese medicine composition comprises an alcohol extract of Radix Astragali, an alcohol extract of Panax Notoginseng, an alcohol extract of Radix et Rhizoma Ginseng, an alcohol extract of Pueraria lobata or Pueraria montana. In some embodiments, the traditional Chinese medicine composition comprises a water extract of Radix Astragali, an alcohol extract of Panax Notoginseng, an alcohol extract of Radix et Rhizoma Ginseng, an alcohol extract of Pueraria lobata or Pueraria montana. In some embodiments, the traditional Chinese medicine composition comprises an alcohol extract of Radix Astragali, an alcohol extract of Panax Notoginseng, an alcohol extract of Radix et Rhizoma Ginseng, an alcohol extract of Pueraria lobata or Pueraria montana. In some embodiments, the traditional Chinese medicine composition comprises an alcohol extract of Radix Astragali, an alcohol extract of Panax Notoginseng, a water extract of Radix et Rhizoma Ginseng, an alcohol extract of Pueraria lobata or Pueraria montana. In some embodiments, the traditional Chinese medicine composition comprises an alcohol extract of Radix Astragali, an alcohol extract of Panax Notoginseng, an alcohol extract of Radix et Rhizoma Ginseng, a water extract of Pueraria lobata or Pueraria montana. In some embodiments, the traditional Chinese medicine composition comprises a water extract of Radix Astragali, an alcohol extract of Panax Notoginseng, an alcohol extract of Radix et Rhizoma Ginseng, an alcohol extract of Pueraria lobata or Pueraria montana. In some embodiments, the traditional Chinese medicine composition comprises a water extract of Radix Astragali, an alcohol extract of Panax Notoginseng, a water extract of Radix et Rhizoma Ginseng, an alcohol extract of Pueraria lobata or Pueraria montana. In some embodiments, the traditional Chinese medicine composition comprises a water extract of Radix Astragali, an alcohol extract of Panax Notoginseng, a water extract of Radix et Rhizoma Ginseng, a water extract of Pueraria lobata or Pueraria montana. In some embodiments, the traditional Chinese medicine composition comprises a water extract of Radix Astragali, an alcohol extract of Panax Notoginseng, a water extract of Radix et Rhizoma Ginseng, a water extract of Pueraria lobata or Pueraria montana. In some embodiments, the traditional Chinese medicine composition comprises a water extract of Radix Astragali, an alcohol extract of Panax Notoginseng, a water extract of Radix et Rhizoma Ginseng, a water extract of Pueraria lobata or Pueraria montana.

[0028] In some embodiments of the present application, the preparation of the water extract of Astragalus includes decocting Astragalus with water for 1-3 times, filtering to obtain the filtrate, and obtaining the water extract. In some embodiments, each decoction is for 1-2 hours. In some embodiments, the water extract is further concentrated. In some embodiments, the concentration is such that the relative density of the concentrated water extract is 1.05-1.30 (e.g., it can be 1.05, 1.10, 1.15, 1.20, 1.25, 1.30), wherein the reference for the relative density is the density of pure water at 4℃, i.e., 1.0 g / cm3. In some embodiments, the measurement of the relative density is performed at 40-90℃ (e.g., it can be 40℃, 45℃, 50℃, 55℃, 60℃, 65℃, 70℃, 75℃, 80℃, 85℃, 90℃). In some embodiments, the water extract is further subjected to alcohol precipitation to remove impurities. In some embodiments, the alcohol precipitation uses ethanol. In some embodiments, the alcohol precipitation includes adding ethanol to the concentrated water extract such that the alcohol content is 40-90% (e.g., 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%), standing, filtering, and recovering the ethanol from the filtrate. In some embodiments, the preparation of the water extract of Astragalus includes decocting Astragalus with water for 1-3 times, each for 1-2 hours, concentrating the filtrate to a relative density of 1.05-1.20 (at 75℃), adding ethanol once, standing, filtering, recovering the ethanol from the filtrate, and further concentrating to a relative density of 1.18-1.30 (at 60℃), adding ethanol twice, standing, filtering, recovering the ethanol from the filtrate, and concentrating, to obtain the water extract of Astragalus. In some embodiments, the alcohol content in the first addition of ethanol is 50-70%. In some embodiments, the alcohol content in the second addition of ethanol is 70-90%.

[0029] In some embodiments of the present application, the preparation of the water extract of Panax includes decocting Panax with water for 1-3 times, filtering to obtain the filtrate, and obtaining the water extract. In some embodiments, each decoction is for 1-2 hours. In some embodiments, the water extract is further concentrated. In some embodiments, the water extract is further subjected to alcohol precipitation to remove impurities. In some embodiments, the alcohol precipitation uses ethanol. In some embodiments, the alcohol precipitation includes adding ethanol to the concentrated water extract such that the alcohol content is 40-90% (e.g., 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%), standing, filtering, and recovering the ethanol from the filtrate. In some embodiments, the preparation of the water extract of Panax includes decocting Panax with water for 1-3 times, each for 1-2 hours, concentrating the filtrate to a relative density of 1.13-1.23 (at 80℃), adding ethanol such that the alcohol content is 60-80%, standing, filtering, recovering the ethanol from the filtrate, and concentrating, to obtain the water extract of Panax.

[0030] In some embodiments of the present application, the dosage form of the traditional Chinese medicine composition is any one of powder, granules, tablets, capsules, gels, suspensions, drops, dripping pills, injections, oral liquids, ointments, emulsions, and enemas.

[0031] In some embodiments of the present application, the traditional Chinese medicine composition further comprises a pharmaceutically acceptable excipient.

[0032] The term "pharmaceutically acceptable" means a substance or material that is, within the scope of sound medical judgment, suitable for contact with the tissues of a subject, such as a human, without excessive toxicity, irritation, allergic response, or other problem, commensurate with a reasonable benefit / risk ratio.

[0033] In some embodiments of the present application, the excipient comprises at least one of a carrier, a lubricant, a wetting agent, a binder, an emulsifier, a suspension stabilizer, a solubilizer, a preservative, a sweetener, and a flavoring agent.

[0034] The carrier can also be referred to as an excipient or a diluent. The carrier can be selected according to the intended dosage form of the composition, such as different carriers can be selected for different dosage forms of powder, granules, tablets, capsules, gels, suspensions, drops, dripping pills, injections, oral liquids, ointments, emulsions, and enemas, and the like. Specifically, at least one of lactose, starch, glucose, sucrose, cellulose, methyl cellulose, microcrystalline cellulose, magnesium stearate, mannitol, sorbitol, acacia, calcium phosphate, alginate, tragacanth, gelatin, calcium silicate, polyvinylpyrrolidone, sugar syrup, ethanol, glycerol, and water can be selected. Lubricants such as sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, talc, mineral oil, polyethylene glycol, sodium lauryl sulfate, and the like; wetting agents such as starch paste, sugar syrup, glycerol, liquid glucose, acacia mucilage, gelatin mucilage, and the like; binders such as starch, gelatin, sodium carboxymethyl cellulose, hydroxypropyl methyl cellulose, povidone, natural sugars, and natural or synthetic gum, and the like; emulsifiers such as polysorbate, polyoxyethylene fatty acid ester, acacia, lecithin, and the like; suspension stabilizers such as sodium carboxymethyl cellulose, hydroxypropyl methyl cellulose, magnesium aluminum silicate, thixotropic agents, and the like; solubilizers such as polysorbate, polyoxyethylene castor oil, poloxamer, dodecyl sulfate, and the like; preservatives include benzoic acid and its salts, sorbic acid and its salts, p-hydroxybenzoic acid esters, quaternary ammonium salts, nitromide esters, and the like.

[0035] In some embodiments of the present application, the traditional Chinese medicine composition is at least one of Qixuekang oral liquid, Qixuekang capsules, and Qixuekang tablets.

[0036] The main components of Qixuekang oral liquid are notoginseng (fresh), astragalus, ginseng, and radix puerariae, and the excipients are honey, sucrose, and sodium benzoate.

[0037] The main components of Qixuekang tablets are notoginseng, astragalus, ginseng, and radix puerariae.

[0038] The main components of Qixuekang capsules are notoginseng, astragalus, ginseng, and radix puerariae.

[0039] In some embodiments of the present application, the daily administration dose of Qixuekang oral liquid for adults is 0.5-5 mL / kg bw, for example, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, 5 mL / kg·bw.

[0040] In some embodiments of the present application, the daily administration dose of the traditional Chinese medicine composition for adults is 0.05-1 g / kg bw of crude drug, for example, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.15, 0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.55, 0.6, 0.65, 0.7, 0.75, 0.8, 0.85, 0.9, 0.95, 1 g / kg bw.

[0041] The beneficial effects of the present application are:

[0042] It is found in the experimental process that the above-mentioned composition has obvious promoting effect on the healing of scalded skin wounds, and also has certain improvement effect on the healing of frozen skin wounds. BRIEF DESCRIPTION OF DRAWINGS

[0043] Figure 1 is the photo of the 0th day of the influence result of Qixuekang oral liquid on the healing of scalded rat skin in the examples of the present application.

[0044] Figure 2 is the photo of the 4th day of the influence result of Qixuekang oral liquid on the healing of scalded rat skin in the examples of the present application.

[0045] Figure 3 is the photo of the 9th day of the influence result of Qixuekang oral liquid on the healing of scalded rat skin in the examples of the present application.

[0046] Figure 4 is the photo of the 14th day of the influence result of Qixuekang oral liquid on the healing of scalded rat skin in the examples of the present application.

[0047] Figure 5Figure 1 is a photo of the result of the influence of Qixuekang oral liquid on the skin healing of the frozen rats on day 0 in the embodiment of the present application.

[0048] Figure 6 Figure 2 is a photo of the result of the influence of Qixuekang oral liquid on the skin healing of the frozen rats on day 4 in the embodiment of the present application.

[0049] Figure 7 Figure 3 is a photo of the result of the influence of Qixuekang oral liquid on the skin healing of the frozen rats on day 9 in the embodiment of the present application.

[0050] Figure 8 Figure 4 is a photo of the result of the influence of Qixuekang oral liquid on the skin healing of the frozen rats on day 14 in the embodiment of the present application. DETAILED DESCRIPTION

[0051] In order to make the objects, technical solutions and advantages of the present application clearer, the present application will be further described in detail below with reference to the drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application and not intended to limit the present application. The terms "first", "second" and the like are used to distinguish similar objects, and do not necessarily describe a specific order or sequence. "At least one" means one or more, and "multiple" means two or more.

[0052] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present application belongs. The terms used herein are only for the purpose of describing the embodiments of the present application and are not intended to limit the present application.

[0053] The embodiments described in the embodiments of the present application are for the purpose of more clearly illustrating the technical solutions of the embodiments of the present application, and do not constitute a limitation on the technical solutions provided by the embodiments of the present application. Those skilled in the art can know that, with the evolution of technology and the appearance of new application scenarios, the technical solutions provided by the embodiments of the present application are also applicable to similar technical problems.

[0054] The content of the present application will be further described in detail through specific embodiments. It should be understood that these embodiments are only used to illustrate the present application and not used to limit the scope of the present application.

[0055] The samples, reagents, instruments, equipment and model animals involved in the following embodiments are described as follows:

[0056] (1) Experimental materials

[0057] Tested sample

[0058] Tested sample information

[0059] Qixuekang oral liquid, 30 mL / branch (equivalent to crude drug 5.37 g), batch number: WFF2403, produced by Yunnan Baiyuan Group Wensan Seven Flowers Co., Ltd., keep away from light, at room temperature.

[0060] Dose design

[0061] The human clinical oral dose of Qixuekang oral liquid is 30 mL / time, 2 times / day, that is, the daily use dose of an adult (adult body weight is calculated as 70 kg) is 30 mL x 2 ÷ 70 kg = 0.8571 mL / kg, and the equivalent dose of rats is 0.8571 mL / kg x 6.3 = 5.40 mL / kg. In this embodiment, the rat dose of Qixuekang oral liquid is set as 5 mL / kg, 10 mL / kg, and 20 mL / kg, which is equivalent to 0.93 times, 1.85 times, and 3.7 times of the human clinical equivalent dose, respectively.

[0062] (2) Positive drug

[0063] Recombinant bovine basic fibroblast growth factor gel for external use (hereinafter referred to as "rb-bFGF"), batch number: 042409A04, produced by Zhuhai Yisheng Biopharmaceutical Co., Ltd., and an appropriate amount (about 100 mg per mouse) is applied to the affected area during the experiment.

[0064] (3) Experimental reagents

[0065] 0.9% sodium chloride injection, produced by Kunming Nanjiang Pharmaceutical Co., Ltd., batch number: A23111301B;

[0066] Isoflurane, produced by Jiangsu Zhongmu Beikang Pharmaceutical Co., Ltd., batch number: 20240326;

[0067] Vascular endothelial growth factor (VEGF) ELISA kit, produced by Yoke Life Science Technology (Hangzhou) Co., Ltd., item number: ER0008, batch number: ER00080002;

[0068] Collagen I (Collagen I) ELISA kit, produced by Wuhan Elyra Biotech Co., Ltd., item number: E-EL-R3008, batch number: WL044X64V7924;

[0069] Collagen III (Collagen III) ELISA kit, produced by Wuhan Elyra Biotech Co., Ltd., item number: E-EL-R0235, batch number: WL03FV8204798.

[0070] (4) Experimental instruments and equipment

[0071] JJ-2000 electronic balance, produced by Jiangsu Changshu Shuangjie Testing Instrument Factory;

[0072] Practum224 SQP electronic balance, produced by Sartorius Science Instruments (Beijing) Co., Ltd.;

[0073] ELGA LA 613 ultrapure water machine, produced by ELGA LabWater / VWS (UK) Ltd;

[0074] MSS-4 respiratory anesthesia machine, produced by Medical Supplies & Services INT. LTD;

[0075] JXFSTPRP-CLN-48 freeze grinder, produced by Shanghai Jingxin Industrial Development Co., Ltd.;

[0076] 3K15 table type refrigerated high-speed centrifuge, produced by Sigma, Germany;

[0077] Refrigerator (4 ℃, -20 ℃), produced by Hefei Midea Co., Ltd.;

[0078] Multiskan GO full-wavelength microplate reader, produced by Thermo, USA;

[0079] BPX-52 electric heating constant temperature incubator, produced by Shanghai Boyuntong Medical Biological Instrument Co., Ltd.

[0080] (5) Experimental system

[0081] SPF SD rats were purchased from Beijing Huafukang Biotechnology Co., Ltd., and the environmental conditions and feeding management met the requirements of the People's Republic of China National Standard “Experimental Animal Environment and Facilities GB14925-2023”. The experimental animals were quarantined and adaptively fed for 5 days, and all were normal. All were used for experiments.

[0082] Example 1: Promoting effect of Qixuekang oral liquid on wound healing of frostbite

[0083] The experimental method is as follows:

[0084] Fifty SPF SD rats, half male and half female, weighing 200-220 g, were randomly divided into 5 groups: model control group, rb-bFGF group, Qixuekang oral liquid 5 mL / kg group, Qixuekang oral liquid 10 mL / kg group, and Qixuekang oral liquid 20 mL / kg group.

[0085] The rats in each group were subjected to back region depilation treatment one day before the experiment, and the depilation area was about 3 cm x 3 cm. The rats were anesthetized by inhaling isoflurane, and the skin of the depilation area was sterilized with 75% ethanol for modeling. A 2 cm diameter iron rod was immersed in liquid nitrogen for 15 min, cooled sufficiently, taken out, and immediately attached to the skin of the rat modeling part for 30 s to prepare a Ⅱ degree frostbite model (the model is consistent with clinical degree ≥ 90%). After the animal modeling, 10 mL / kg volume of physiological saline was injected into the abdominal cavity to resist shock. After the animals woke up, the drug administration began, and the Qifuxiakang oral liquid in each dose group was administered by gavage according to the corresponding dose, and the rb-bFGF group was evenly applied to the wound (about 100 mg). The model control group was administered with pure water by gavage at a volume of 10 mL / kg, once a day, for 14 days of continuous administration.

[0086] Before administration and on the 4th, 9th, and 14th days of administration, the animal wounds were photographed using a microscope, and the wound area was analyzed using ImageMeasuring Software Version 6.0 pathological analysis software and the wound healing rate was calculated according to the following formula:

[0087]

[0088] Wherein, S0 is the skin wound area before administration; St is the skin wound area after administration.

[0089] After the last wound photographing was completed, the rats were euthanized by CO2 asphyxiation, and about 50 mg of rat wound skin tissue was taken, rinsed in pre-cooled physiological saline, blood was removed, dried with filter paper, accurately weighed, placed in a pre-cooled freezing grinding tube, 1 mL / 50 mg of tissue lysis solution (containing 1x protease inhibitor cocktail) was added, and 3 magnetic grinding beads (one large and two small) were added. The sample was ground in a pre-cooled freezing grinder at 65 HZ, 30 s, interval 20 s, -20 ℃ for 46 times, centrifuged at 4 ℃, 12000 rpm for 15 min, and the supernatant was reserved for use. The contents of VEGF, Collagen I, and Collagen III in the tissue were detected by ELISA kit.

[0090] The experimental results were expressed as mean ± standard deviation, and statistical analysis was performed. When the data met the normal distribution and homogeneity of variance, single factor analysis of variance was used for statistics. When the data did not meet the normal distribution and homogeneity of variance, rank sum test was used for analysis.

[0091] The experimental results are as follows:

[0092] 1. Effect on the healing rate of frostbite rat skin

[0093] Reference Figures 1-4and Table 1. Compared with the model control group, the positive control rb-bFGF had no significant effect on the wound healing rate of the frostbite rats (P>0.05); compared with the model control group, Qixuekang Oral Liquid at a dose of 20 mL / kg had a certain promoting effect on the wound healing rate of the frostbite rats, but the statistical result showed that there was no significant difference between the two (P>0.05).

[0094] Table 1. Effect of Qixuekang Oral Liquid on the wound healing rate of frostbite rats

[0095]

[0096] 2. Effect on the content of related proteins in the wound tissue of frostbite rats

[0097] The results are shown in Table 2. Compared with the model control group, Qixuekang Oral Liquid at a dose of 20 mg / kg significantly increased the content of Collagen I protein in the wound tissue of the scalded rats (P<0.01), and doses of 5 mg / kg, 10 mg / kg and 20 mg / kg significantly increased the content of Collagen III protein (P<0.05 or P<0.01).

[0098] Table 2. Effect of Qixuekang Oral Liquid on the content of related proteins in the wound tissue of frostbite rats

[0099]

[0100] Note: Compared with the model control group, *P<0.05, **P<0.01.

[0101] Example 2: Effect of Qixuekang Oral Liquid on the skin healing of scalded rats

[0102] The experimental method is referred to Example 1, and the modeling process is as follows:

[0103] The rats in each group were subjected to depilation treatment on the back area one day before the experiment, and the depilation area was about 3 cm x 3 cm. The rats were anesthetized by inhaling isoflurane, and the depilation area skin was disinfected with 75% ethanol to prepare for modeling. A flat-bottom glass bottle with a diameter of 2 cm was used, which was filled with water to a constant height, and placed in an electric kettle containing water. After the water temperature was heated to boiling (about 94 ℃), it was quickly wiped dry, and the bottom was placed vertically on the skin of the rat operation area for 25 s. The pressure and temperature of the scalded area of each rat were consistent. After modeling, the local skin was white and edematous, indicating that a deep Ⅱ degree scald model was successfully established. After modeling, the animals were injected with 10 mL / kg of normal saline intraperitoneally to prevent shock.

[0104] The administration and index determination were the same as in Example 1.

[0105] The experimental results are as follows:

[0106] 1. Effect on skin healing rate of scalded rats

[0107] Reference Figures 5-8 And Table 3, compared with the model control group, the positive control rb-bFGF group and Qixuekang oral liquid 5 mg / kg, 10 mg / kg, 20 mg / kg dose group of rats in the 4th day, 9th day after administration, the wound healing rate was significantly increased (P<0.05 or P<0.01 or P<0.001).

[0108] Table 3. Effect of Qixuekang oral liquid on wound healing rate of scalded rats

[0109]

[0110] Note: compared with the model control group, *P<0.05, **P<0.01, ***P<0.001.

[0111] 2. Effect on the content of related proteins in the wound tissue of scalded rats

[0112] Compared with the model control group, the positive control rb-bFGF could significantly increase the content of Collagen I and Collagen III proteins in the wound tissue of scalded rats (P<0.05); Qixuekang oral liquid 5 mg / kg, 10 mg / kg, 20 mg / kg dose could significantly increase the content of vEGF and Collagen III proteins in the wound tissue of scalded rats (P<0.05 or P<0.001). See Table 4.

[0113] Table 4. Effect of Qixuekang oral liquid on the content of related proteins in the wound tissue of scalded rats

[0114]

[0115] Note: compared with the model control group, *P<0.05, ***P<0.001.

[0116] Based on the above results, Qixuekang oral liquid can significantly improve the skin wound healing rate of scalded rats, and increase the content of vEGF and Collagen III proteins in the skin tissue, indicating that Qixuekang oral liquid can effectively promote the wound healing caused by scald.

[0117] Qixuekang oral liquid 20 mL / kg dose can improve the skin wound healing rate of frozen rats, and can significantly increase the content of Collagen I and Collagen III proteins in the skin tissue, indicating that Qixuekang oral liquid has a certain improvement effect on the wound healing caused by frostbite.

[0118] Therefore, in the experimental condition and the used dose range, Qixuekang oral liquid has obvious promoting effect on the healing of the skin wound of the scalded rats, and also has certain improvement effect on the healing of the skin wound of the frozen rats.

[0119] The above examples are the preferred embodiments of the present application, but the embodiments of the present application are not limited to the above examples, and any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present application should be equivalent replacement methods, and are all included in the protection scope of the present application.

Claims

1. The application of a traditional Chinese medicine composition in the preparation of a drug that promotes wound healing, characterized in that, The active ingredients of the traditional Chinese medicine composition include Panax notoginseng, Astragalus membranaceus, ginseng, and kudzu root or kudzu powder.

2. The application according to claim 1, characterized in that, The wound includes wounds caused by at least one physical, chemical, or biological factor.

3. The application according to claim 2, characterized in that, The wound includes at least one of the following: first-degree frostbite, second-degree frostbite, third-degree frostbite, fourth-degree frostbite, first-degree burn, second-degree burn, and third-degree burn.

4. The application according to claim 1, characterized in that, Promoting wound healing includes reducing the wound area.

5. The application according to claim 1, characterized in that, The promotion of wound healing includes increasing the expression of at least one of vascular endothelial growth factor and collagen in the wound.

6. The application according to claim 5, characterized in that, The collagen includes at least one of collagen type 1, collagen type 2, and collagen type 3.

7. The application according to claim 1, characterized in that, The wound includes at least one of skin wounds and mucosal wounds.

8. The application according to claim 1, characterized in that, The active ingredients of the traditional Chinese medicine composition are made from raw materials comprising the following parts by weight: 100-500 parts Panax notoginseng, 300-900 parts Astragalus membranaceus, 50-200 parts Panax ginseng, and 50-150 parts Pueraria lobata or Pueraria lobata root.

9. The application according to claim 1, characterized in that, The traditional Chinese medicine composition is at least one of Qi Xue Kang oral liquid, Qi Xue Kang capsules, and Qi Xue Kang tablets.

10. The application according to claim 9, characterized in that, The daily adult dosage of the Qi Xue Kang oral liquid is 0.5~5 mL / kg bw.

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