Traditional Chinese medicine composition for treating chloasma and external preparation

Abstract

The invention particularly relates to a traditional Chinese medicine composition for treating chloasma and an external preparation. At present, the mode of treating chloasma by western medicine has obvious adverse reaction, the traditional Chinese medicine believes that the formation of chloasma mainly lies in liver and kidney malnutrition, the invention provides a traditional Chinese medicine composition with chloasma treatment effect on the basis of formula principles of nourishing essence and blood, promoting blood circulation to remove blood stasis, regulating qi-flowing for eliminating phlegm, removing freckles and whitening, and the traditional Chinese medicine composition comprises 30-100 parts of dark plum, 20-80 parts of Chinese angelica and 2-8 parts of pseudo-ginseng. The invention further provides an external preparation of the composition. Through verification, the external preparation can be used for effectively treating various types of chloasma, has a remarkable improvement effect on the facial state, is simple in preparation process and free of obvious side effects, and has a good market prospect.

Description

Technical Field

[0001] The present invention relates to the technical field of Chinese medicine compositions, and in particular to a Chinese medicine composition and an external preparation for treating chloasma. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance the understanding of the overall background of the invention, and should not necessarily be regarded as an admission or any form of suggestion that the information constitutes the prior art already known to a person skilled in the art.

[0003] Chloasma, also known as "liver spots" or "black spots" in traditional Chinese medicine, is a common facial pigmentation skin disease, clinically manifested by the appearance of light brown and yellow-brown patches of varying sizes and irregular shapes on the face. According to statistics, chloasma is more common in Asian women aged 30-40. Because it often occurs on the face, it affects the patient's facial beauty. In severe cases, it affects the patient's mental health and reduces the patient's quality of life. Therefore, the incidence and treatment of chloasma has gradually become a topic of common concern in the medical and beauty industries.

[0004] The main methods of Western medicine for treating melasma are the use of tyrosinase inhibitors, photoelectric therapy, antifibrinolytic agents, topical depigmenting agents, chemical peels, etc. The first-line treatment drugs mainly include hydroquinone cream, retinoic acid, tranexamic acid, azelaic acid, niacinamide, arbutin cream, etc. Although they have certain efficacy, they are prone to recurrence and have many problems. For example, after use, the skin will have adverse reactions such as redness, pain, desquamation, itching, ulceration, etc., which damage the skin barrier structure, and even cause permanent damage or life-threatening. Therefore, these drugs are controversial in clinical practice and have even been banned.

[0005] External treatment in traditional Chinese medicine has a long history and always follows the basic principle of syndrome differentiation and treatment. Prescriptions are added or subtracted according to the etiology and syndrome. It not only has significant efficacy and few adverse reactions, but also avoids the first-pass effect of the liver and gastrointestinal tract. The formation of chloasma is caused by local qi stagnation, blood stasis and phlegm obstruction in the skin, and the skin loses the normal qi and blood nourishment and forms spots. Traditional Chinese medicine believes that "what is inside will be reflected outside". Although chloasma is a skin disease, its core pathogenesis lies in liver and kidney dysfunction. The liver and kidney are of the same origin. If the liver and kidney are deficient in essence and blood, the essence is deficient and the blood is weak, the skin loses nourishment and forms spots; Qi is the leader of blood, and the flow of Qi causes the distribution of body fluid. Kidney essence deficiency cannot nourish the liver, and liver blood deficiency cannot transform qi and nourish qi, resulting in liver qi stagnation, or emotional stimulation leads to liver failure to release, poor qi movement, qi stagnation and blood circulation, and stagnation of body fluid, forming qi stagnation, blood stasis and phlegm obstruction, and the skin loses the nourishment of qi and blood and forms spots. Using the theory of external treatment in traditional Chinese medicine to guide the external use of traditional Chinese medicine to improve or treat chloasma is expected to achieve a treatment method with fewer side effects. Summary of the invention

[0006] In view of the problems existing in the prior art, the inventors, based on their many years of clinical experience, screened out a core formula that has good therapeutic effects on the vast majority of chloasma patients in the process of adding, subtracting and modifying the basic formula for different clinical cases, and provided a traditional Chinese medicine composition for treating chloasma and a corresponding external preparation, and provided the following technical solutions: In a first aspect, the present invention provides a Chinese medicine composition for treating chloasma, wherein the composition comprises the following medicinal ingredients in parts by weight: 10-100 parts of black plums, 10-100 parts of angelica sinensis, 1-10 parts of Panax notoginseng, and 1-10 parts of Bombyx batryticatus.

[0007] The sources and effects of the above medicinal flavors are as follows: Ume: Prunus mume Prunus mume Dried nearly ripe fruits of (Sieb.) Sieb.etZucc. The fruits are harvested in summer when they are nearly ripe, dried at low temperature and then steamed until they turn black.

[0008] Processing method: remove impurities, wash and dry.

[0009] Nature and flavor: sour, astringent, neutral. Enters the liver, spleen, lung, large intestine, and kidney meridians.

[0010] Functions and indications: It can astringe the liver and lungs, astringe the intestines and promote the production of body fluids, and calm ascaris. It is used for chronic cough due to lung deficiency, chronic diarrhea and dysentery, deficiency heat and thirst, ascariasis and vomiting and abdominal pain, black spots on the skin, and paralysis.

[0011] Angelica: Angelica sinensis Angelica sinensis The dried roots of Oliv. Diels are dug up in late autumn, the fibrous roots and sand are removed, and after the water evaporates slightly, they are tied into small bundles, put on a shed, and slowly dried with fireworks.

[0012] Processing: Remove impurities, wash, soak, cut into thin slices, dry in the sun or at low temperature.

[0013] Nature and flavor: sweet, pungent, warm. Enters the liver, heart and spleen meridians.

[0014] Functions and indications: replenishing blood and activating blood circulation, regulating menstruation and relieving pain, moistening intestines and relieving constipation. Used for sallow complexion due to blood deficiency, dizziness and palpitations, irregular menstruation, amenorrhea and dysmenorrhea, abdominal pain due to deficiency and cold, rheumatic arthralgia, injuries due to falls, carbuncle, ulcers, and constipation due to dry intestines. 37: It is the dried root and rhizome of Panax notoginseng (Burk.) FH Chen of the Araliaceae family. It is dug up in autumn before the flowers bloom, washed, separated from the main root, lateral roots and rhizome, and dried. The lateral roots are commonly known as "tendons" and the rhizome is commonly known as "cut mouth".

[0016] Preparation: For common powders, take Panax notoginseng, wash, dry and grind into fine powder.

[0017] Nature and flavor: sweet, slightly bitter, warm. Enters the liver and stomach meridians.

[0018] Functions and indications: dissipate blood stasis and stop bleeding, reduce swelling and relieve pain. Used for hemoptysis, hematemesis, epistaxis, bloody stool, metrorrhagia, bleeding from trauma, stabbing pain in the chest and abdomen, and swelling and pain from falls.

[0019] White silkworm: Also known as silkworm, it is an insect of the family Bombyx mori Bombyx mori Linnaeus Larvae of the 4th to 5th instar are infected (or artificially inoculated) with Beauveria bassiana Beauveria bassiana The dried bodies of silkworms that died of Beauveria bassiana are usually produced in spring and autumn, and the bodies are dried after the silkworms were infected with Beauveria bassiana and died.

[0020] Processing: Wash and dry to remove impurities.

[0021] Nature and flavor: salty, pungent, neutral. Enters the liver, lung and stomach meridians.

[0022] Functions and indications: calming wind and stopping spasms, dispelling wind and relieving pain, resolving phlegm and dispersing stagnation. Used for liver wind with phlegm, convulsions and convulsions, acute convulsions in children, tetanus, stroke and mouth ulcers, wind-heat headache, red eyes and sore throat, pruritus caused by urticaria, and mumps.

[0023] The present invention is designed to provide a Chinese medicine composition for treating chloasma. The ideas for the above-mentioned medicinal formula mainly include the following aspects: (1) The "Lingshu·Evil Qi Zangfu Disease Form" states: "The twelve meridians and three hundred and sixty-five collaterals, all of which are on the face." The "Lingshu·Hai Lun" states: "The twelve meridians belong to the internal organs and collaterals to the limbs." The meridians are channels that connect the internal organs and collaterals to the skin and pores of the limbs, communicate the inside and the outside, and circulate qi, blood, and body fluids. When the internal organs function normally, the body's essence, qi, blood, and body fluids are sufficient, and they are transported to the skin and face through the meridians. When the facial skin and pores are nourished, the complexion is rosy and shiny. However, when the internal organs function abnormally, the body's essence, qi, blood, and body fluids are insufficient, the meridians qi and blood flow poorly, qi stagnation, blood stasis, and phlegm blockage occur, and the skin is not nourished, then it becomes dark and spots appear.

[0024] (2) The occurrence of chloasma is closely related to liver and kidney dysfunction. According to the theory of viscera in traditional Chinese medicine, the liver is responsible for regulating qi and promoting the circulation of essence, blood, body fluids, and body fluids; the kidney is the innate foundation and the source of power for the generation and circulation of essence, qi, blood, and body fluids of the five internal organs. For example, the "Three Causes of Disease and Symptoms: Internal Causes of Lumbar Pain" states: "Loss of will hurts the kidney, depression and anger hurt the liver... The liver and kidney are of the same system... This syndrome is characterized by weakness and insufficiency, and a dark complexion." (3) Ye Tianshi proposed the view that "women are born with liver". Chloasma is more common in women, so the liver plays an important role in treating chloasma. According to TCM theory, the liver is responsible for regulating emotions and promoting the flow of qi throughout the body. At present, due to factors such as the accelerated work pace, high tension and high life pressure, it is easy to cause liver qi stagnation. Staying up late, eating spicy food and drinking a lot of coffee can easily damage kidney essence. Kidney essence deficiency cannot nourish the liver, leading to liver qi stagnation. According to TCM theory, the liver opens to the eyes. Excessive dependence on electronic products can easily damage liver blood. Liver blood deficiency cannot nourish liver qi and also leads to liver qi stagnation. Qi is the leader of blood. Qi circulates and distributes body fluids. When liver qi is stagnant, the liver fails to vent and the qi flow is not smooth, which affects the distribution of qi, blood and body fluids, leading to qi stagnation, blood stasis and phlegm obstruction, skin loss of moisture and nourishment, dark complexion and spots.

[0025] (4) Lingshu Wuyue Wushi says: "People with kidney disease have dark cheekbones and complexion." Kidney deficiency is the main cause of chloasma. The 95th chapter of the Authentic Surgery says: "Dark spots are caused by water deficiency that cannot control fire, and blood deficiency that cannot nourish the flesh, which results in dry fire forming dark spots and dull color." Taiping Shenghui Fang Shenshen Lun says: "Dark complexion...is a sign of kidney deficiency," which directly states that kidney deficiency is closely related to the formation of chloasma. Chloasma caused by kidney deficiency is often seen in cases where kidney deficiency leads to a lack of body fluid and blood, poor blood circulation, and poor nourishment of the skin and veins; kidney deficiency leads to a lack of body fluid and dry fire, which burns the blood vessels and causes blood stasis; kidney deficiency cannot nourish the liver, which results in liver qi stagnation and poor blood circulation, causing blood stasis. "The Essence of Ye Tianshi's Medical Cases" said: "Over the years, the external evil has remained, and both Qi and blood have been damaged... It has caused blood stasis and turbid phlegm, which are mixed in the meridians... Over the years, Qi has been weakened, leading to the death of a carbuncle." It can be seen that the condensation of phlegm and blood stasis in the skin is also an important mechanism leading to chloasma.

[0026] (5) The use of Chinese medicine for external treatment of chloasma has been recorded in ancient books, such as the Yurong Powder and Beauty Cream recorded in Puji Fang and Yi Zong Jin Jian, which are still in use today. Because the human body is an organic whole, Lingshu Hai Lun states: "The twelve meridians belong to the internal organs and are connected to the limbs externally." Chinese medicine for external use acts on the skin, penetrates into the collaterals through the skin, pores, and can directly reach the site of chloasma where qi stagnation, blood stasis, and phlegm are blocked to exert a therapeutic effect; at the same time, it can also improve the circulation of qi and blood in the meridians through the conduction of the skin meridians, regulate the functions of the internal organs such as the liver and kidneys, and by improving the functions of the internal organs, further strengthen the circulation of qi, blood, and body fluids to achieve the purpose of promoting blood circulation and removing blood stasis, regulating qi and removing phlegm to treat chloasma.

[0027] Based on the above research ideas for the treatment of chloasma, the Chinese medicine composition described in the first aspect of the present invention is guided by the theories of liver and kidney essence and blood deficiency, qi stagnation, blood stasis and phlegm obstruction, and skin malnutrition, and is formulated with the principles of nourishing essence and blood, promoting blood circulation and removing blood stasis, regulating qi and removing phlegm, and removing spots and whitening. Among them, black plum and angelica are the main drugs, and Panax notoginseng and Bombyx batryticatus are the secondary drugs. Black plum and angelica work together to nourish the liver and kidney essence and blood, while angelica and Panax notoginseng replenish blood, promote blood circulation and remove blood stasis, and Bombyx batryticatus regulates qi and removes phlegm. The above components work together to remove spots and whiten the skin.

[0028] In the preferred embodiment of the above-mentioned Chinese medicine composition, the weight proportions of each medicinal ingredient are as follows: 10-100 parts of black plum, 10-100 parts of angelica, 1-10 parts of Panax notoginseng, and 1-10 parts of Bombyx batryticatus.

[0029] In one embodiment, the medicinal ingredients and proportions of the traditional Chinese medicine composition are as follows: 100 parts of black plums, 80 parts of angelica sinensis, 8 parts of Panax notoginseng, and 6 parts of Bombyx batryticatus.

[0030] In another embodiment, the medicinal ingredients and proportions of the Chinese medicine composition are as follows: 60 parts of black plum, 70 parts of angelica, 8 parts of Panax notoginseng, and 6 parts of Bombyx batryticatus.

[0031] In another embodiment, the medicinal ingredients and proportions of the traditional Chinese medicine composition are as follows: 40 parts of black plum, 80 parts of angelica, 4 parts of Panax notoginseng, and 6 parts of Bombyx batryticatus.

[0032] In another embodiment, the medicinal ingredients and proportions of the Chinese medicine composition are as follows: 40 parts of black plum, 20 parts of angelica, 2 parts of Panax notoginseng, and 2 parts of Bombyx batryticatus.

[0033] In another embodiment, the medicinal ingredients and proportions of the Chinese medicine composition are as follows: 50 parts of black plum, 30 parts of angelica, 2 parts of Panax notoginseng, and 5 parts of Bombyx batryticatus.

[0034] In an embodiment of the present invention with better effect, the medicinal ingredients and proportions of the Chinese medicine composition are as follows: 30 parts of black plums, 20 parts of angelica sinensis, 3 parts of Panax notoginseng, and 2 parts of Bombyx batryticatus.

[0035] The above formula was fully tested for toxicity before clinical application, and rat and mouse toxicity tests confirmed that the above drug combination showed no toxicity to the body. No adverse reactions were observed in subsequent clinical treatment applications.

[0036] The application forms of the above-mentioned Chinese medicine composition include but are not limited to the following: The whole medicinal material form of the above medicinal flavors, such as the powdered drug parts of black plum, angelica, Panax notoginseng, and white silkworm, are mixed for use; the combination of the extracts of the above medicinal flavors, the extracts include but are not limited to water extracts, alcohol extracts or other organic reagent extracts. In the second aspect of the present invention, a functional product for preventing, improving or treating chloasma is provided, and the raw materials for preparing the functional product include the composition described in the first aspect.

[0037] The functional products can be medicines, functional foods, toiletries, and the medicines include but are not limited to injections, oral preparations or transdermal preparations, more preferably transdermal preparations, such as microneedles, patches, ointments, emulsions or gels.

[0038] The cleaning and care product is preferably a product for external use such as a facial mask, lotion, emulsion or ointment.

[0039] The third aspect of the present invention provides an external preparation for treating chloasma, wherein the external preparation comprises a Chinese medicine extract and a matrix, and the Chinese medicine extract is prepared using the Chinese medicine composition described in the first aspect as a raw material.

[0040] The preparation method of the above-mentioned Chinese medicine extract is as follows: obtain a black plum extract, an angelica extract, a Panax notoginseng extract, and a Bombyx batryticatus extract respectively, mix them, and then concentrate them to obtain the Chinese medicine extract; The preparation method of black plum extract is as follows: add black plum to sodium bicarbonate solution and extract at room temperature, the ratio is 1g:8~12mL, the extraction time is 1.5~2.5h, the concentration of sodium bicarbonate solution is 4~7%, and the solution retained by centrifugation is the black plum extract.

[0041] The preparation method of the angelica extract is as follows: adding angelica to an ethanol solution for reflux extraction, the ratio is 1g:6-10mL, the concentration of the ethanol solution is 65-75% (volume fraction), the extraction is repeated two to three times and the extract is combined, and the extraction time each time is 1-2h.

[0042] The preparation method of the Panax notoginseng extract is as follows: add Panax notoginseng to ethanol solution for reflux extraction, the ratio is 1g:7~10mL, the concentration of the ethanol solution is 65~75% (volume fraction), the extraction is repeated two to three times to combine the extracts, and the extraction time each time is 1~2h.

[0043] The preparation method of the Bombyx batryticatus extract is as follows: adding the Bombyx batryticatus into water for reflux extraction, the ratio is 1g:8-12mL, repeating the extraction two to three times to combine the extracts, and the extraction time each time is 1-2h.

[0044] The concentration operation is as follows: the above four extracts are combined, and the alcohol in the solution is removed by heating through rotary evaporation or the like to obtain a medicinal solution, and the medicinal solution is further concentrated until the volume ratio of the evaporated water to the remaining medicinal solution is 1:1.

[0045] The above-mentioned matrix is ​​mainly used as a carrier of Chinese medicine extracts, and is preferably suitable for the matrix of skin external preparations, such as aqueous solutions, emulsions, ointments or pastes, etc. The matrix includes lipid, soap, ester matrix components, and also includes other functional agents, such as moisturizers, fragrances or preservatives.

[0046] In one embodiment of the present invention with better effects, the above-mentioned external preparation is a paste, comprising the following raw materials in parts by weight: 4-6 parts of Chinese herbal medicine extract, 1-3 parts of cetearyl alcohol, 5-7 parts of oils and fats, 0.5-1.5 parts of glyceryl stearate, 1-3 parts of C12-20 acid PEG-8 ester, 45-55 parts of deionized water, 7-9 parts of amino acid moisturizer, 0.02-0.1 parts of disodium EDTA, 0.1-0.2 parts of allantoin, 0.2-0.5 parts of sodium polyacrylate, 0.1-0.2 parts of potassium cetyl phosphate, 0.3-0.5 parts of acrylic acid (esters) / C10-30 alkyl acrylate crosslinked polymer, 0.05-0.15 parts of carbomer, 0.3-0.5 parts of arginine, 0.2-0.4 parts of preservatives, and 0.3-0.7 parts of vanillyl butyl ether.

[0047] The preparation method of the above-mentioned ointment is as follows: (1) Place phase A in a beaker and heat in a water bath to 80-85°C; stir evenly. Phase A comprises: cetearyl alcohol, oil, glyceryl stearate and C12-20 acid PEG-8 ester; (2) Put phase B into a beaker and heat it to 80-85°C to evenly disperse the ingredients. Add phase B to phase A in a thin stream while stirring. Gradually add the amount and stir. Phase B is: deionized water, amino acid moisturizer, disodium EDTA, allantoin, sodium polyacrylate, potassium cetyl phosphate, acrylic acid (esters) / C10-30 alkyl acrylate crosspolymer and carbomer. (3) Continue to add Chinese herbal extract, stir evenly, then cool to 60~70℃, add arginine, cool to 40~50℃, then add amino acid moisturizer, preservative and vanillyl butyl ether, stir evenly, cool to 30~40℃, stir evenly, and discharge.

[0048] A fourth aspect of the present invention provides a method for preventing, improving or treating chloasma, comprising applying the functional product of the second aspect or the external preparation of the third aspect to an area requiring prevention, improvement or treatment.

[0049] Compared with the prior art, the present invention has the following beneficial effects: 1. The Chinese medicine composition of the present invention has low irritation, can be used as an external medicine, and has high safety. Compared with traditional freckle-removing external preparations, it is not easy to cause redness, allergies, heavy metals, etc.

[0050] 2. The Chinese medicine composition of the present invention has definite curative effect, is easy to obtain, and is economical and practical.

[0051] 3. The therapeutic effects of the Chinese medicine composition of the present invention: pigmentation is reduced or completely eliminated; the skin's antioxidant capacity is improved; tyrosinase activity is reduced, and melanin production is reduced; the freckle removal effect is long-term and effective. BRIEF DESCRIPTION OF THE DRAWINGS

[0052] The accompanying drawings in the specification, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0053] Figure 1 The apparent experimental results of the chloasma model group and the Chinese herbal medicine extract group; Figure 1 A is the appearance of chloasma on the back of rats with chloasma model; Figure 1 B is the appearance of the back skin of rats after administration of the Chinese medicine extract group; Figure 2 The effect of Chinese herbal extract on TYR activity in serum, liver and skin of rats in each group; Figure 2 A is the TYR activity in the serum of rats in each group; Figure 2 B is the TYR activity in the liver of rats in each group; Figure 2 C is the TYR activity in the skin of rats in each group; Figure 3 The effect of Chinese herbal extract on SOD activity in serum, liver and skin of rats in each group; Figure 3 A is the SOD activity in the serum of rats in each group; Figure 3 B is the SOD activity in the liver of rats in each group; Figure 3 C is the SOD activity in the skin of rats in each group Figure 4 The effect of Chinese herbal extract on SOD activity in serum, liver and skin of rats in each group; Figure 4 A is the MDA activity in the serum of rats in each group; Figure 4 B is the MDA activity in the liver of rats in each group; Figure 4 C is the MDA activity in the skin of rats in each group; Above Figure 2-Figure 4 The "freckle removal prescription" shown on the middle horizontal axis is the Chinese herbal extract prepared in Example 3; Figure 5 The effects of Chinese herbal extracts on the pathological changes of skin tissues in each group of rats; Figure 5 A is the blank group; Figure 5 B is the model group; Figure 5 C is the positive drug group; Figure 5 D is the low-dose group of Chinese herbal extract; Figure 5 E is the medium-dose group of Chinese herbal medicine extracts; Figure 5 F is the high-dose group of Chinese herbal extracts; Figure 5 In A-5F, the yellow arrow indicates parakeratosis, the black arrow indicates hyperkeratosis, the blue arrow indicates the sweat gland duct, and the red arrow indicates inflammatory cell infiltration; Figure 6 These are the clinical treatment results of 27 cases. DETAILED DESCRIPTION

[0054] It should be noted that the following detailed descriptions are all illustrative and intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used herein have the same meanings as those commonly understood by those skilled in the art to which the present invention belongs.

[0055] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit exemplary embodiments according to the present invention. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "comprising" and / or "including" are used in this specification, it indicates the presence of features, steps, operations, devices, components and / or combinations thereof.

[0056] Terminology explanation: Chinese medicine composition: refers to a mixture of two or more Chinese medicinal materials or Chinese medicinal material extracts in a certain proportion, with certain properties and uses. The Chinese medicine composition referred to in the document of this application refers to a mixture of four medicinal materials, namely, black plum, angelica, Panax notoginseng, and Bombyx batryticatus, in a dosage ratio of 10-100 parts: 10-100 parts: 1-10 parts: 1-10 parts, or a mixture of the extracts of the above medicinal materials, which has the effect of preventing, improving, fading or treating chloasma. The "Chinese medicine extract", "Chinese medicine composition" and "freckle removal prescription" referred to in this application all refer to the above substances.

[0057] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below in conjunction with specific embodiments.

[0058] The sources of the raw materials involved in the following examples are as follows: Wumei, angelica, Panax notoginseng, Bombyx batryticatus and arbutin ointment were purchased from Shuyu Pingmin Pharmacy.

[0059] Example 1 A Chinese medicinal extract for treating chloasma. The raw materials for preparing the extract include the following medicinal ingredients in parts by weight: 100 parts of black plum, 80 parts of angelica, 8 parts of Panax notoginseng, and 6 parts of Bombyx batryticatus.

[0060] The preparation method of the extract comprises the following steps: (1) Preparation of black plum extract: Mix black plum with 5% sodium bicarbonate aqueous solution (1 g: 10 mL) and extract at room temperature for 2 h. The solution retained by centrifugation is the black plum extract. (2) Preparation of Angelica sinensis extract: Angelica sinensis was mixed with a 70% ethanol aqueous solution (1 g: 8 mL) and subjected to reflux extraction. The mixture was filtered and the original material was again mixed with a 70% ethanol aqueous solution and subjected to heating reflux extraction. The reflux extraction was performed twice (soaked for 30 minutes before the first extraction). Each extraction time was 1 h. The solution was retained by centrifugation and the alcohol extracts from the two extractions were combined to obtain the Angelica sinensis extract. (3) Preparation of Panax notoginseng extract: Panax notoginseng was mixed with 70% ethanol aqueous solution (1 g: 8 mL) and subjected to reflux extraction. The mixture was filtered and the original medicinal material was again mixed with 70% ethanol aqueous solution and subjected to reflux extraction. The reflux extraction was performed twice (soaked for 30 minutes before the first extraction). Each extraction time was 1 h. The solution was retained by centrifugation and the alcohol extracts from the two extractions were combined to obtain the Panax notoginseng extract.

[0061] (4) Preparation of Bombyx batryticatus extract: Bombyx batryticatus was mixed with deionized water (1 g: 10 mL) and subjected to reflux extraction. The mixture was filtered and water (1 g: 8 mL) was added to the original medicinal material again and mixed and subjected to reflux extraction. The reflux extraction was performed twice (soaked for 30 minutes before the first extraction). Each extraction time was 1 hour. The residue was separated by centrifugation and the aqueous extracts were combined to obtain the Bombyx batryticatus extract.

[0062] (5) The above-mentioned black plum extract, angelica extract, Panax notoginseng extract and Bombyx batryticatus extract are mixed, heated and recovered to concentrate the ethanol solution to a concentration of 1:1 to obtain the Chinese herbal medicine extract.

[0063] Example 2 A Chinese medicinal extract for treating chloasma. The raw materials for preparing the extract include the following medicinal ingredients in parts by weight: 60 parts of black plum, 70 parts of angelica, 8 parts of Panax notoginseng, and 6 parts of Bombyx batryticatus.

[0064] The preparation method of the Chinese herbal medicine extract is as follows: (1) Preparation of black plum extract: Mix black plum with 5% sodium bicarbonate aqueous solution (1 g: 8 mL) and extract at room temperature for 2.5 h. The solution retained by centrifugation is the black plum extract. (2) Preparation of Angelica extract: Angelica was mixed with 70% ethanol (1 g: 6 mL) by volume and subjected to reflux extraction. The mixture was filtered and the original material was again mixed with 70% ethanol (1 g: 5 mL) and subjected to reflux extraction. The reflux extraction was performed twice (soaked for 30 minutes before the first extraction). Each extraction time was 1.5 h. The solution was retained by centrifugation and the alcohol extracts from the two extractions were combined to obtain the Angelica extract. (3) Preparation of Panax notoginseng extract: Panax notoginseng was mixed with 70% ethanol (1 g: 7 mL) by volume and subjected to reflux extraction. The mixture was filtered and the original medicinal material was again mixed with 70% ethanol (1 g: 5 mL) and subjected to reflux extraction. The reflux extraction was performed twice (soaked for 30 minutes before the first extraction). Each extraction time was 2 h. The solution was retained by centrifugation and the alcohol extracts from the two extractions were combined to obtain the Panax notoginseng extract.

[0065] (4) Preparation of Bombyx batryticatus extract: Bombyx batryticatus was mixed with deionized water (1 g: 8 mL) and subjected to reflux extraction. The mixture was filtered and water (1 g: 6 mL) was added to the original medicinal material again and mixed and subjected to reflux extraction. The reflux extraction was performed twice (soaked for 30 minutes before the first extraction). Each extraction time was 2 h. The residue was separated by centrifugation and the aqueous extracts were combined to obtain the Bombyx batryticatus extract.

[0066] (5) The above-mentioned black plum extract, angelica extract, Panax notoginseng extract and Bombyx batryticatus extract are mixed, heated and recovered to concentrate the ethanol solution to a concentration of 1:1 to obtain the Chinese herbal medicine extract.

[0067] Example 3 A Chinese medicinal extract for treating chloasma. The raw materials for preparing the extract include the following medicinal ingredients in parts by weight: 30 parts of black plum, 20 parts of angelica, 3 parts of Panax notoginseng, and 2 parts of Bombyx batryticatus.

[0068] The preparation method of the Chinese herbal medicine extract is as follows: (1) Preparation of black plum extract: Mix black plum with 4% sodium bicarbonate aqueous solution (1 g: 12 mL) and extract at room temperature for 1.5 h. The solution retained by centrifugation is the black plum extract. (2) Preparation of Angelica sinensis extract: Angelica sinensis was mixed with 70% ethanol (1 g: 10 mL) by volume and subjected to reflux extraction. The mixture was filtered and the original material was again mixed with 75% ethanol (1 g: 7 mL) and subjected to reflux extraction. The reflux extraction was performed twice (soaked for 30 minutes before the first extraction). Each extraction time was 2 h. The solution was retained by centrifugation and the alcohol extracts from the two extractions were combined to obtain the Angelica sinensis extract. (3) Preparation of Panax notoginseng extract: Panax notoginseng was mixed with 70% ethanol (1 g: 10 mL) by volume and then subjected to reflux extraction. The mixture was filtered and the original medicinal material was again mixed with 70% ethanol aqueous solution (1 g: 8 mL) and then subjected to reflux extraction. The reflux extraction was performed twice (soaked for 30 minutes before the first extraction). Each extraction time was 1 h. The solution was retained by centrifugation and the alcohol extracts from the two extractions were combined to obtain the Panax notoginseng extract.

[0069] (4) Preparation of Bombyx batryticatus extract: Bombyx batryticatus was mixed with deionized water (1 g: 12 mL) and subjected to reflux extraction. The mixture was filtered and water (1 g: 10 mL) was added to the original medicinal material again and mixed and subjected to reflux extraction. The reflux extraction was performed twice (soaked for 30 minutes before the first extraction). Each extraction time was 1.5 h. The residue was separated by centrifugation and the aqueous extracts were combined to obtain the Bombyx batryticatus extract.

[0070] (5) The above-mentioned black plum extract, angelica extract, Panax notoginseng extract and Bombyx batryticatus extract are mixed, heated and recovered to concentrate the ethanol solution to a concentration of 1:1 to obtain the Chinese herbal medicine extract.

[0071] Example 4 A Chinese medicinal composition for treating chloasma. The raw materials for preparing the extract include the following medicinal ingredients in parts by weight: 40 parts of black plum, 80 parts of angelica, 4 parts of Panax notoginseng, and 6 parts of Bombyx batryticatus.

[0072] The preparation method of the Chinese herbal medicine extract is as follows: (1) Preparation of black plum extract: Mix black plum with 5% sodium bicarbonate aqueous solution (1 g: 10 mL) and extract at room temperature for 2 h. The solution retained by centrifugation is the black plum extract. (2) Preparation of Angelica sinensis extract: Angelica sinensis was mixed with 65% ethanol (1 g: 9 mL) by volume and subjected to reflux extraction. The mixture was filtered and the original material was again mixed with 70% ethanol (1 g: 7 mL) and subjected to reflux extraction. The reflux extraction was performed twice (soaked for 30 minutes before the first extraction). Each extraction time was 1 h. The solution was retained by centrifugation and the alcohol extracts from the two extractions were combined to obtain the Angelica sinensis extract. (3) Preparation of Panax notoginseng extract: Panax notoginseng was mixed with 70% ethanol (1 g: 7 mL) by volume and subjected to reflux extraction. The mixture was filtered and the original medicinal material was again mixed with 70% ethanol (1 g: 5 mL) and subjected to reflux extraction. The reflux extraction was performed twice (soaked for 30 minutes before the first extraction). Each extraction time was 2 h. The solution was retained by centrifugation and the alcohol extracts from the two extractions were combined to obtain the Panax notoginseng extract.

[0073] (4) Preparation of Bombyx batryticatus extract: Bombyx batryticatus was mixed with deionized water (1 g: 11 mL) and subjected to reflux extraction. The mixture was filtered and water (1 g: 8 mL) was added to the original medicinal material again and mixed and subjected to reflux extraction. The reflux extraction was performed twice (soaked for 30 minutes before the first extraction). Each extraction time was 1 h. The residue was separated by centrifugation and the aqueous extracts were combined to obtain the Bombyx batryticatus extract.

[0074] (5) The above-mentioned black plum extract, angelica extract, Panax notoginseng extract and Bombyx batryticatus extract are mixed, heated and recovered to concentrate the ethanol solution to a concentration of 1:1 to obtain the Chinese herbal medicine extract.

[0075] Example 5 A Chinese medicinal composition for treating chloasma. The raw materials for preparing the extract include the following medicinal ingredients in parts by weight: 40 parts of black plum, 20 parts of angelica, 2 parts of Panax notoginseng, and 2 parts of Bombyx batryticatus.

[0076] The preparation method of the Chinese herbal medicine extract is as follows: (1) Preparation of black plum extract: Mix black plum with 6% sodium bicarbonate aqueous solution (1 g: 9 mL) and extract at room temperature for 2 h. The solution retained by centrifugation is the black plum extract. (2) Preparation of Angelica sinensis extract: Angelica sinensis was mixed with 72% ethanol (1 g: 8 mL) by volume and subjected to reflux extraction. The mixture was filtered and the original material was again mixed with 70% ethanol (1 g: 6 mL) and subjected to reflux extraction. The reflux extraction was performed twice (soaked for 30 minutes before the first extraction). Each extraction time was 1 h. The solution was retained by centrifugation and the alcohol extracts from the two extractions were combined to obtain the Angelica sinensis extract. (3) Preparation of Panax notoginseng extract: Panax notoginseng was mixed with 70% ethanol (1 g: 8 mL) by volume and subjected to reflux extraction. The mixture was filtered and the original medicinal material was again mixed with 70% ethanol (1 g: 6 mL) and subjected to reflux extraction. The reflux extraction was performed twice (soaked for 30 minutes before the first extraction). Each extraction time was 1.5 h. The solution was retained by centrifugation and the alcohol extracts from the two extractions were combined to obtain the Panax notoginseng extract.

[0077] (4) Preparation of Bombyx batryticatus extract: Bombyx batryticatus was mixed with deionized water (1 g: 10 mL) and subjected to reflux extraction. The mixture was filtered and water (1 g: 8 mL) was added to the original medicinal material again and mixed and subjected to reflux extraction. The reflux extraction was performed twice (soaked for 30 minutes before the first extraction). Each extraction time was 2 h. The residue was separated by centrifugation and the aqueous extracts were combined to obtain the Bombyx batryticatus extract.

[0078] (5) The above-mentioned black plum extract, angelica extract, Panax notoginseng extract and Bombyx batryticatus extract are mixed, heated and recovered to concentrate the ethanol solution to a concentration of 1:1 to obtain the Chinese herbal medicine extract.

[0079] Example 6 A Chinese medicinal composition for treating chloasma. The raw materials for preparing the extract include the following medicinal ingredients in parts by weight: 50 parts of black plum, 30 parts of angelica, 2 parts of Panax notoginseng, and 5 parts of Bombyx batryticatus.

[0080] The preparation method of the Chinese herbal medicine extract is as follows: (1) Preparation of black plum extract: Mix black plum with 7% sodium bicarbonate aqueous solution (1 g: 10 mL) and extract at room temperature for 2 h. The solution retained by centrifugation is the black plum extract.

[0081] (2) Preparation of Angelica sinensis extract: Angelica sinensis was mixed with 70% ethanol (1 g: 8 mL) by volume and subjected to reflux extraction. The mixture was filtered and the original material was again mixed with 70% ethanol (1 g: 6 mL) and subjected to reflux extraction. The reflux extraction was performed twice (soaked for 30 minutes before the first extraction). Each extraction time was 1 h. The solution was retained by centrifugation and the alcohol extracts from the two extractions were combined to obtain the Angelica sinensis extract. (3) Preparation of Panax notoginseng extract: Panax notoginseng was mixed with 70% ethanol (1 g: 8 mL) by volume and subjected to reflux extraction. The mixture was filtered and the original medicinal material was again mixed with 70% ethanol (1 g: 6 mL) and subjected to reflux extraction. The reflux extraction was performed twice (soaked for 30 minutes before the first extraction). Each extraction time was 2 h. The solution was retained by centrifugation and the alcohol extracts from the two extractions were combined to obtain the Panax notoginseng extract.

[0082] (4) Preparation of Bombyx batryticatus extract: Bombyx batryticatus was mixed with deionized water (1 g: 10 mL) and subjected to reflux extraction. The mixture was filtered and water (1 g: 8 mL) was added to the original medicinal material again and mixed and subjected to reflux extraction. The reflux extraction was performed twice (soaked for 30 minutes before the first extraction). Each extraction time was 2 h. The residue was separated by centrifugation and the aqueous extracts were combined to obtain the Bombyx batryticatus extract.

[0083] (5) The above-mentioned black plum extract, angelica extract, Panax notoginseng extract and Bombyx batryticatus extract are mixed, heated and recovered to concentrate the ethanol solution to a concentration of 1:1 to obtain the Chinese herbal medicine extract.

[0084] Example 7 In the present embodiment, a traditional Chinese medicine ointment for treating chloasma is provided, comprising the following raw materials: 5 parts of the traditional Chinese medicine extract prepared in any one of Examples 1-6, 2 parts of cetearyl alcohol, 6 parts of oil, 1 part of glyceryl stearate, 2 parts of C12-20 acid PEG-8 ester, 50 parts of deionized water, 8 parts of amino acid moisturizer, 0.05 parts of disodium EDTA, 0.15 parts of allantoin, 0.3 parts of sodium polyacrylate, 0.15 parts of potassium cetyl phosphate, 0.4 parts of acrylic acid (ester) / C10-30 alkyl acrylate cross-linked polymer, 0.1 parts of carbomer, 0.45 parts of arginine, 0.3 parts of preservatives, and 0.5 parts of vanillyl butyl ether.

[0085] The preparation method of the above-mentioned Chinese medicine ointment comprises the following steps: (1) Place phase A in a beaker and heat in a water bath to 80-85°C; stir evenly. Phase A comprises: cetearyl alcohol, oil, glyceryl stearate and C12-20 acid PEG-8 ester.

[0086] (2) Add phase B into a beaker, stir for 5 minutes until the powder is dispersed, heat to 80-85°C, stir evenly, and there is no lumps or powder. Add phase B to phase A in a stream, gradually add and stir, where phase B is: deionized water, amino acid moisturizer, disodium EDTA, allantoin, sodium polyacrylate, potassium cetyl phosphate, acrylic acid (ester) / C10-30 alkyl acrylate crosspolymer and carbomer.

[0087] (3) Add the Chinese herbal extract, stir evenly for 15 minutes, then cool to 65°C and add arginine. Cool to 45°C, add amino acid moisturizer, preservative and vanillyl butyl ether in sequence and stir evenly. Cool to 35°C, stir evenly and discharge.

[0088] The Chinese herbal extracts and ointments in the above Examples 1-7 have been verified by acute and chronic toxicity experiments and have good safety when applied to organisms.

[0089] 1. Pharmacodynamic Verification 1. Preparation and administration method of chloasma model rat 1. Experimental Animals Table 1 Experimental animal information 2. Preparation of Chloasma Rat Model Table 2 Dosage Table After all rats were adaptively fed for one week after entering the laboratory, 72 Wistar rats were randomly divided into a blank group, a model group, a low-dose group of Chinese herbal extracts, a medium-dose group of Chinese herbal extracts, a high-dose group of Chinese herbal extracts, and a positive drug group according to their weight, with 12 rats in each group. Combined with literature reports, this embodiment uses ultraviolet irradiation and progesterone injection to prepare a chloasma rat model. The hair on the back of the rats in the model group was shaved with a razor, and the hair on the skin was carefully removed with a depilatory cream to expose a skin area of ​​about 4x4cm. Hair removal was performed every three days. After the model group rats were depilated, ultraviolet light was irradiated every day with a wavelength of 311nm, 1h per day, and the rat skin was about 50cm away from the light source; after the ultraviolet light irradiation was completed, the model group rats were injected with progesterone (20mg / kg) at 17:00 every day, and the injection method was intramuscular injection. The modeling time was 30 days, and the blank group was not given any intervention and was raised normally. During the modeling process, photos were taken to record the changes in the rat skin.

[0090] 3. Dosage method The rats in the two groups were given drugs, and the drug was the Chinese herbal extract prepared by the method of Example 3 above. The drug administration area of ​​each mouse was 3×3 cm 2 The low dose was 0.04 mL each time, recorded as the low dose group of Quban Fang, the medium dose was 0.12 mL, recorded as the medium dose group of Quban Fang, and the high dose was 0.36 mL, recorded as the high dose group of Quban Fang. The rats were respectively dipped with cotton swabs and smeared on the depilated skin on the back of the rats. The positive drug group was smeared with arbutin cream, and the blank group was fed normally without any intervention, see Table 2.

[0091] (II) Pharmacodynamics experimental results of the combination preparation of black plum, angelica, Panax notoginseng and Bombyx batryticatus extracts 1. Appearance evaluation results The study successfully prepared a chloasma rat model using ultraviolet irradiation combined with progesterone intramuscular injection. From the apparent indicators, the yellow-brown patches on the back of the model group rats were consistent with the clinical manifestations of chloasma patients. The results of this example showed that after 30 days of administration, the chloasma in the low, medium and high dose groups of the Chinese herbal extract was significantly eliminated, indicating that the Chinese herbal extract can achieve the effect of whitening and removing spots.

[0092] 2. Micro-indicator experimental results 2.1 Results of changes in serum, liver, and skin tyrosinase (TYR) levels It has been confirmed that the onset of chloasma is closely related to the increase of tyrosinase activity. In melanocytes, tyrosine forms melanin under the catalysis of tyrosinase, and finally floats to the surface to form chloasma. That is, when tyrosinase activity increases, the amount of melanin synthesis increases, promoting the onset of chloasma. The results of this example are shown in Figure 2The results showed that after 30 days of administration, the serum TYR of rats in the low, medium and high dose groups of the Chinese herbal extract was significantly lower than that in the model group (****P<0.0001, ***P<0.001, **P<0.01, *P<0.05), indicating that the Chinese herbal extract of Example 3 can reduce the rate of melanin synthesis.

[0093] 2.2 Results of changes in serum, liver, and skin SOD levels Oxidative stress is also an important indicator for evaluating the efficacy of freckle-removing drugs. Studies have found that SOD is a natural oxygen free radical scavenger in the body. When the body is in an unbalanced state between oxidation and anti-oxidation, it is oxidative stress. Figure 3 The results showed that after 30 days of administration, the SOD in the serum, liver and skin of rats in the low-dose group of Chinese herbal extract was significantly higher than that in the model group (*** P<0.001); the SOD in the liver and skin of rats in the medium-dose group of Chinese herbal extract was significantly higher than that in the model group (*** P<0.001); the SOD in the liver of rats in the high-dose group of Chinese herbal extract was significantly higher than that in the model group (*** P<0.001), indicating that the Chinese herbal extract in Example 3 can improve the body's antioxidant capacity.

[0094] 2.3 Results of changes in serum, liver, and skin MDA levels During oxidative stress, a large number of free radicals are produced in the body, causing damage to cells and tissues and forming pigmentation. MDA is the most harmful lipid peroxide in this process. Figure 4 The results showed that after 30 days of administration, the MDA content in the serum, liver and skin of rats in the low, medium and high dose groups of the Chinese herbal extract was significantly lower than that in the model group (*** P<0.001, ** P<0.01, * P<0.05), indicating that the Chinese herbal extract of Example 3 has the effect of reducing lipid peroxidation damage.

[0095] 2.4 Results of HE staining of rat skin The results of this experiment are as follows Figure 5The results showed that the skin tissue of the rats in the blank group was arranged in an orderly manner, the thickness of the epidermis was uniform, inflammatory cells were occasionally infiltrated in the superficial dermis, and no sebaceous gland hyperplasia was observed. Compared with the rats in the blank group, the skin tissue of the rats in the model group was arranged in a disordered manner, the epidermis was significantly thickened and the thickness was uneven, there was hyperkeratosis and parakeratosis in the stratum corneum, hypertrophy of the stratum spinosum, dilation of the sweat gland duct, hyperplasia of the sebaceous glands, an increase in the number of blood vessels, a large number of inflammatory cells infiltrated in the superficial dermis and stratum spinosum, and the fibrous tissue in the dermis was arranged in a disordered manner. Compared with the model group, the epidermis of each drug-treated group was thinner and the tissues were arranged more neatly. The epidermis of the rats in the low-dose group of Chinese herbal extract was uniform in thickness, the tissues were arranged neatly, the stratum corneum showed slight hyperkeratosis and incomplete keratosis, a small amount of inflammatory cell infiltration was seen in the dermis, and the sebaceous glands and sweat gland ducts were dilated; the epidermis of the rats in the medium-dose group of Chinese herbal extract was uniform in thickness, hyperkeratosis was present, the dermis tissue was arranged neatly, the cell structure was intact, and a small amount of sweat gland duct dilation was seen, which was close to the blank group; the epidermis of the high-dose group of Chinese herbal extract was uniform in thickness, hyperkeratosis and incomplete keratosis appeared, and there were more inflammatory cell infiltrations compared with the medium-dose group; the skin hyperkeratosis of the rats in the positive drug group was reduced, the epidermis thickness was relatively uniform, a large number of sweat gland duct dilations were seen in the dermis, and inflammatory cell infiltration was seen around the vascular wall. However, the epidermis thickness increased compared with the low, medium and high-dose groups of Chinese herbal extract.

[0096] 2.4 Rat skin immunohistochemistry results 2.4.1 Melanocyte (Melan-A) expression results The results of this experimental example are shown in Table 3. Melan-A was used as a positive control to label melanin granules in the skin of rats in the blank group, and a few melanin granules were scattered in the epidermis. Melan-A labeling showed clustered melanin granules in the basal layer of the epidermis, and a large number of melanin granules were also seen in the spinous cell layer of the rats in the model group, showing a strong positive reaction. Melan-A labeling showed scattered melanin granules in the basal layer and spinous cell layer of the epidermis of rats in the low-dose group of Chinese herbal extract, and its reaction was close to that of the blank group. Scattered single melanin granules were seen in the epidermis of rats in the medium-dose group of Chinese herbal extract, and the pigment depth was lower than that of the model group. Melan-A labeled melanin granules were scattered in the basal layer of the epidermis of rats in the high-dose group of Chinese herbal extract, and the pigment depth was higher than that of the blank group. Melanocytes in the basal layer of the positive drug group were scattered, and their number and density were lower than those of the model group.

[0097] Table 3 Melan-A positive area and average optical density of rat skin in each group Note: Compared with the model group, ### P < 0.0001, ## P < 0.001, # P<0.01 The results of this experiment are shown in Table 3. After 30 days of administration, the Melan-A positive cell area in the skin of rats in the low-dose and medium-dose groups of Chinese herbal extracts was significantly smaller than that in the model group; the average optical density of the skin of rats in the low-dose group of Chinese herbal extracts was significantly lower than that in the model group ( ### P<0.0001, ## P<0.001, # P<0.01).

[0098] 2.4.1 Tyrosinase (TYR) expression results The results of this experiment are shown in Table 4. After 30 days of administration, the TYR-positive area of ​​the skin of rats in the low-dose, medium-dose and high-dose groups of Chinese herbal extract was significantly smaller than that in the model group; the average optical density of TYR in the skin of rats in the low-dose group of Chinese herbal extract was significantly lower than that in the model group (****P<0.0001, ***P<0.001, **P<0.01).

[0099] Table 4 TYR positive area and average optical density of skin in rats of each group Note: Compared with the model group, *** P<0.001, ** P<0.01 summary: In summary, before and after drug treatment, compared with the rats in the control group, the chloasma model animals were able to better simulate the pathological symptoms of clinical chloasma patients in terms of both the skin appearance and the microscopic indicators (serum, liver, hormone content in skin, epithelial cells, key gene expression, etc.). After drug treatment, compared with the model group, the TYR activity and MDA content in the skin, liver and serum of the rats in each drug group were significantly reduced (P<0.0001, P<0.001, P<0.01, P<0.05), and the SOD HE staining results showed that compared with the model group, the degree of epidermal hyperplasia of rats in the drug-treated groups was reduced, the number of inflammatory cells decreased, and the sebaceous gland hyperplasia was improved; Melan-A immunohistochemical staining results showed that the Melan-A positive cell area in the skin of rats in the low-dose and medium-dose groups of Chinese herbal extract was significantly smaller than that in the model group; the average optical density of the skin of rats with low-dose Chinese herbal extract was significantly lower than that in the model group (P<0.0001, P<0.001, P<0.01); TYR immunohistochemical staining results showed that the TYR positive area of ​​the skin of rats in the low-dose, medium-dose and high-dose groups of Chinese herbal extract was significantly smaller than that in the model group; the average optical density of the skin of rats with low-dose Chinese herbal extract was significantly lower than that in the model group (P<0.0001, P<0.001, P<0.01). Furthermore, except for the Chinese herbal extracts in the above-mentioned Example 3, the Chinese herbal extracts in Examples 1-2 or 4-6 can all exert the same therapeutic level.

[0100] 2. Clinical Validation 1. Treatment Group Comparison was performed before and after treatment.

[0101] Treatment group: The Chinese medicine composition of Example 3 was administered percutaneously, 2-3 times a day, 1 mL each time; After treatment, one course of treatment lasts 28-40 days. After one course of treatment, the changes in the patient's clinical symptoms (skin lesions) before and after treatment were observed.

[0102] 2. Inclusion criteria of this study: (1) Patients aged 20 to 60 years old.

[0103] (2) Voluntarily participate in this study and sign the treatment consent form, and be able to follow the doctor's instructions during the treatment process.

[0104] (3) Meet the clinical diagnostic criteria for melasma: ① Light brown to dark brown, clearly defined patches on the face, usually symmetrically distributed, with no signs of inflammation or scaling.

[0105] ② No obvious subjective symptoms.

[0106] ③It is more common in females, mainly occurring after puberty.

[0107] ④The condition may be seasonal, often more severe in summer and milder in winter.

[0108] ⑤Exclude pigmentation caused by other diseases (such as malar nevus, Riehl's melanosis and pigmented actinic lichen planus).

[0109] 3. Efficacy evaluation criteria: Before treatment, the melasma area and severity score (MASI) was used to evaluate the area and severity of melasma. After the Chinese herbal extract of Example 3 was used, the efficacy of the melasma area and severity was evaluated every 2 weeks. Before and after treatment, photos of the lesions were taken with a digital camera or a high-pixel mobile phone and numbered for archiving. A dermatologist who was not involved in the treatment scored the improvement level of the lesions before and after treatment.

[0110] Table 5 Melasma Area and Severity Score (MASI) is used to evaluate the severity of melasma Forehead score = 0.3*(D+H)*A Right zygomatic score = 0.3*(D+H)*A Left zygomatic score = 0.3*(D+H)*A Chin score = 0.1*(D+H)*A MASI total score = sum of the above scores A dermatologist who was not involved in the treatment scored the improvement level of skin lesions before and after treatment. The clinical efficacy was divided into 5 levels according to the efficacy index: cure (>75%), significant improvement (51%~75%), moderate improvement (26%~50%), slight improvement (≤25%), and no improvement (≤0%).

[0111] Efficacy index = (pre-treatment score - post-treatment score) / pre-treatment score × 100%.

[0112] 4. Clinical efficacy observation results A total of 27 patients with melasma were collected in this study, including 26 females and 1 male, aged 26 to 60 years, with a disease course of 6 months to 20 years. According to the skin lesion classification of the 27 patients, 3 cases (11.11%) were butterfly type, 7 cases (25.93%) were facial type, and 17 cases (62.96%) were generalized. All patients were informed of the purpose, risks and potential complications of treatment before enrollment and signed informed consent. Before and after treatment, photos of the lesions were taken with a digital camera or a high-pixel mobile phone and the photos were filed and numbered. The doctors who did not participate in the treatment compared the improvement level of the lesions before and after treatment using the MASI scale.

[0113] According to the MASI efficacy index, the clinical efficacy was divided into cure (>75%), significant improvement (50%-75%), moderate improvement (26%-49%), and mild improvement (≤25%). The results showed that among the 27 cases, 1 case was cured (3.70%), 5 cases were significantly improved (18.52%), 10 cases were moderately improved (37.04%), and 11 cases were mildly improved (40.74%) (see Figure 6 ).

[0114] This example selects 10 typical cases, and the situations are as follows: Case 1 Lv, female, 36 years old, was diagnosed on March 4, 2021, with a course of 12 years. Symptoms: Facial patches are dark brown, with clear boundaries and symmetrical distribution, no inflammation and scaling, no obvious subjective symptoms, pale red tongue with thin white fur, and regular bowel movements. Diagnosed as butterfly-shaped chloasma. The following Chinese medicine composition was used for transdermal administration. Treatment method: Apply externally to the patches, massage with the fingertips for 2-3 minutes, 2-3 times a day, and treat for 40 days, and the butterfly-shaped chloasma is significantly improved.

[0115] Case 2 Gong, male, 37 years old, was diagnosed on July 4, 2022, with a course of 6 and a half years. Symptoms: The cheeks and forehead patches are dark brown, with clear boundaries and symmetrical distribution, no inflammation and scaling, no obvious subjective symptoms, pale red tongue with thin white fur, and normal bowel movements. Diagnosed as generalized chloasma. The following Chinese medicine composition was used for transdermal administration. Treatment method: Apply externally to the patches, massage with the fingertips for 2-3 minutes, 2-3 times a day, and treat for 30 days, and the generalized chloasma is significantly improved.

[0116] Case 3 Gao, female, 45 years old, was diagnosed on February 4, 2021, with a course of 6 years. Symptoms: The cheek patches are dark brown, with clear boundaries and symmetrical distribution, no inflammation and scaling, no obvious subjective symptoms, pale red tongue with thin yellow fur, and normal bowel movements. Diagnosed as upper facial melasma. The following Chinese medicine composition was used for transdermal administration. Treatment method: Apply externally to the patches, massage with the fingertips for 2-3 minutes, 2-3 times a day, and treat for 40 days, and the upper facial melasma is significantly improved.

[0117] Case 4 Wang, female, 50 years old, was diagnosed on May 18, 2022, with a course of 12 years. Symptoms: The cheek patches are light brown, with clear boundaries and symmetrical distribution, no inflammation and scaling, no obvious subjective symptoms, light red tongue with thin yellow fur, and normal bowel movements. Diagnosed as butterfly-shaped chloasma. The following Chinese medicine composition was used for transdermal administration. The treatment method was: apply externally to the patches, massage with the fingertips for 2-3 minutes, 2-3 times a day, and the butterfly-shaped chloasma was cured after 35 days of treatment.

[0118] Case 5 Zhang, female, 60 years old, was diagnosed on March 22, 2021, with a course of 10 years. Symptoms: The cheek and mandibular patches are dark brown, with clear boundaries and symmetrical distribution, no inflammation and scaling, no obvious subjective symptoms, pale red tongue with thin white fur, and normal bowel movements. Diagnosed as generalized chloasma. The following Chinese medicine composition was used for transdermal administration. The treatment method was: apply externally to the patches, massage with the fingertips for 2-3 minutes, 2-3 times a day, and treat for 28 days. The generalized chloasma had a significant effect.

[0119] Case 6 Guo Moumou, female, 47 years old, was diagnosed on June 22, 2021. The disease lasted for 10 years and worsened in summer. Symptoms: The cheek patches were dark brown, with clear boundaries and symmetrical distribution, no inflammation and scaling, mild skin allergies, pale tongue with thin white fur, and regular bowel movements. Diagnosed as butterfly-shaped chloasma. The following Chinese medicine composition was used for transdermal administration. The treatment method was: apply externally to the patches, massage with the fingertips for 2-3 minutes, 2-3 times a day, and treat for 40 days. The effect of butterfly-shaped chloasma was significant.

[0120] Case 7 Li, female, 48 years old, was diagnosed on April 15, 2021, with a course of 4 years. Symptoms: The cheek patches are dark brown, with clear boundaries and symmetrical distribution, no inflammation and scaling, no obvious subjective symptoms, pale red tongue with thin white fur, and normal bowel movements. Diagnosed as upper facial melasma. The following Chinese medicine composition was used for transdermal administration. The treatment method was: apply externally to the patches, massage with the fingertips for 2-3 minutes, 2-3 times a day, and treat for 40 days. The upper facial melasma had a significant effect.

[0121] Case 8 Li, female, 48 years old, visited the hospital on April 15, 2021, with a course of 5 years. Symptoms: The cheek patches are dark brown, with clear boundaries and symmetrical distribution, no inflammation and scaling, no obvious subjective symptoms, pale red tongue with thin white fur, and normal bowel movements. Diagnosed as upper facial melasma. The following Chinese medicine composition was used for transdermal administration. The treatment method was: apply externally to the patches, massage with the fingertips for 2-3 minutes, 2-3 times a day, and treat for 30 days. The upper facial melasma had a significant effect.

[0122] Case 9 Hao Moumou, female, 35 years old, was diagnosed on June 18, 2022. The course of the disease is 3 years, which worsens with the seasons, especially in summer. Symptoms: The cheek patches are dark brown, with clear boundaries and symmetrical distribution, no obvious subjective symptoms, no inflammatory manifestations and scaling, pale red tongue with thin yellow fur, and regular bowel movements. Diagnosed as upper facial type chloasma. The following formula of Chinese medicine composition is used for transdermal administration. The treatment method is: apply the patches externally, massage with the fingertips for 2-3 minutes, 2-3 times a day, and treat for 40 days. The upper facial type chloasma has a significant effect.

[0123] Case 10 Dong Moumou, female, 33 years old, was diagnosed on August 17, 2022. The course of disease is 3 years. The disease occurred after childbirth and worsened in summer. Symptoms: The cheek patches are dark brown, with clear boundaries and symmetrical distribution. There are no obvious subjective symptoms, no inflammatory manifestations and scaling. The tongue is light red with thin yellow fur, and the bowel movements are normal. Diagnosed as generalized chloasma. The Chinese medicine composition with the following formula is used for transdermal administration. The treatment method is: apply the patches externally, massage with the fingertips for 2-3 minutes, 2-3 times a day, and treat for 30 days. The generalized chloasma has a significant effect.

[0124] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A Chinese medicine composition for treating chloasma, characterized in that: The composition comprises the following medicinal ingredients in parts by weight: 30-100 parts of black plum, 20-80 parts of angelica, 1-10 parts of Panax notoginseng and 1-10 parts of Bombyx batryticatus.

2. The Chinese medicine composition according to claim 1, characterized in that The weight proportions of the various medicinal ingredients are as follows: 30-100 parts of black plum, 20-80 parts of angelica, 2-8 parts of Panax notoginseng, and 2-6 parts of white silkworm.

3. The Chinese medicine composition according to claim 2, characterized in that: The medicinal ingredients and proportions of the Chinese medicine composition are as follows: 100 parts of black plum, 80 parts of angelica, 8 parts of Panax notoginseng, and 6 parts of white silkworm; Or, 60 parts of Prunus mume, 70 parts of Angelica sinensis, 8 parts of Panax notoginseng, and 6 parts of Bombyx batryticatus; Or, 40 parts of Prunus mume, 80 parts of Angelica sinensis, 4 parts of Panax notoginseng, and 6 parts of Bombyx batryticatus; Or, 40 parts of black plum, 20 parts of angelica, 2 parts of Panax notoginseng, 2 parts of Bombyx batryticatus; Or, 50 parts of black plum, 30 parts of angelica, 2 parts of Panax notoginseng, 5 parts of Bombyx batryticatus; Or, 30 parts of ebony, 20 parts of angelica, 3 parts of Panax notoginseng, and 2 parts of Bombyx batryticatus.

4. The Chinese medicine composition according to any one of claims 1 to 3, characterized in that: The application form of the pharmaceutical composition includes the whole medicinal material form of the medicinal flavor or a combination of extracts of various medicinal flavors, and the extracts include but are not limited to water extracts, alcohol extracts or other organic agent extracts.

5. A functional product for preventing, improving or treating chloasma, characterized in that: The raw materials for preparing the functional product include the composition according to any one of claims 1 to 4; The functional product is selected from medicines, functional foods, and toiletries, and the medicines include but are not limited to injections, oral preparations, or transdermal preparations, more preferably transdermal preparations; The cleaning product is preferably a facial mask, lotion, emulsion or cream.

6. An external preparation for treating chloasma, characterized in that: The external preparation comprises a Chinese herbal medicine extract and a matrix, and the Chinese herbal medicine extract is prepared using the composition according to any one of claims 1 to 4 as a raw material. The external preparation according to claim 6 is characterized in that the preparation method of the traditional Chinese medicine extract is as follows: obtaining black plum extract, angelica extract, Panax notoginseng extract, and Bombyx batryticatus extract respectively, mixing and concentrating to obtain the traditional Chinese medicine extract.

7. The external preparation according to claim 6, characterized in that in, The preparation method of the black plum extract is as follows: adding black plum to a sodium bicarbonate solution for extraction at room temperature, the ratio is 1g: 8-12mL, the extraction time is 1.5-2.5h, the concentration of the sodium bicarbonate solution is 4-7%, and the solution retained by centrifugation is the black plum extract; The preparation method of the angelica extract is as follows: adding angelica to an ethanol solution for reflux extraction, the ratio is 1g: 6-10mL, the concentration of the ethanol solution is 65-75%, the extraction is repeated two to three times and the extract is combined, and the extraction time each time is 1-2h; The preparation method of the Panax notoginseng extract is as follows: adding Panax notoginseng to an ethanol solution for reflux extraction, the ratio is 1g:7-10mL, the concentration of the ethanol solution is 65-75%, the extraction is repeated two to three times and the extract is combined, and the extraction time for each time is 1-2h; The preparation method of the Bombyx batryticatus extract is as follows: adding Bombyx batryticatus to water for reflux extraction, the ratio is 1g: 8-12mL, repeating the extraction two to three times to combine the extracts, and the extraction time for each time is 1-2h; The concentration operation is as follows: combine the above four extracts, heat to remove the alcohol in the solution to obtain a medicinal solution, and further concentrate the medicinal solution until the volume ratio of the evaporated water and the remaining medicinal solution is 1:

1.

8. The external preparation according to claim 6, characterized in that The external preparation is a paste, comprising the following raw materials in parts by weight: 4-6 parts of Chinese herbal medicine extract, 1-3 parts of cetearyl alcohol, 5-7 parts of oils and fats, 0.5-1.5 parts of glyceryl stearate, 1-3 parts of C12-20 acid PEG-8 ester, 45-55 parts of deionized water, 7-9 parts of amino acid moisturizer, 0.02-0.1 parts of disodium EDTA, 0.1-0.2 parts of allantoin, 0.2-0.5 parts of sodium polyacrylate, 0.1-0.2 parts of potassium cetyl phosphate, 0.3-0.5 parts of acrylic acid (esters) / C10-30 alkyl acrylate crosslinked polymer, 0.05-0.15 parts of carbomer, 0.3-0.5 parts of arginine, 0.2-0.4 parts of preservatives, and 0.3-0.7 parts of vanillyl butyl ether.

9. The external preparation according to claim 6, characterized in that The preparation method of the ointment is as follows: (1) Place phase A in a beaker and heat in a water bath to 80-85°C; stir evenly. Phase A comprises: cetearyl alcohol, oil, glyceryl stearate and C12-20 acid PEG-8 ester; (2) Put phase B into a beaker and heat it to 80-85°C to evenly disperse the ingredients. Add phase B to phase A in a thin stream while stirring. Gradually add the amount and stir. Phase B is: deionized water, amino acid moisturizer, disodium EDTA, allantoin, sodium polyacrylate, potassium cetyl phosphate, acrylic acid (esters) / C10-30 alkyl acrylate crosspolymer and carbomer. (3) Continue to add Chinese herbal extract, stir evenly, then cool to 60~70℃, add arginine, cool to 40~50℃, then add amino acid moisturizer, preservative and vanillyl butyl ether, stir evenly, cool to 30~40℃, stir evenly, and discharge.

10. A method for preventing, improving or treating chloasma, characterized in that: The method comprises applying the functional product according to claim 5 or the external preparation according to any one of claims 6 to 9 to an area requiring prevention, improvement or treatment.

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