A traditional Chinese medicine composition and external preparation for treating chloasma

Abstract

The application relates to a traditional Chinese medicine composition for treating chloasma and an external preparation. At present, the treatment of chloasma by western medicine has obvious adverse reactions, and traditional Chinese medicine believes that the formation of chloasma is mainly due to liver and kidney malnutrition, the application takes nourishing essence-blood, promoting blood circulation to remove blood stasis, regulating qi and phlegm, and removing freckles and whitening as the prescription principle, provides a traditional Chinese medicine composition with chloasma treatment effect, which comprises 30-100 parts of dark plum, 20-80 parts of angelica, 2-8 parts of notoginseng and 2-6 parts of white muscardine moth, and further provides an external preparation of the composition. It is verified that the external preparation can effectively treat various types of chloasma, has a remarkable lifting effect on facial conditions, and has a simple preparation process, no obvious side effects and a good market prospect.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine compositions, and in particular to a traditional 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 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 those skilled in the art.

[0003] Melasma, also known in Traditional Chinese Medicine as "liver spots" or "black spots," is a common facial pigmentation disorder characterized by the appearance of light brown or yellowish-brown patches of varying sizes and shapes. According to statistics, melasma is most common in Asian women aged 30-40. Because it often occurs on the face, it can affect patients' facial aesthetics and, in severe cases, their psychological well-being and reduce their quality of life. Therefore, the onset and treatment of melasma have become a topic of concern in both the medical and cosmetic communities.

[0004] The main Western medical treatments for melasma include tyrosinase inhibitors, phototherapy, antifibrinolytics, topical depigmenting agents, and chemical peels. First-line treatments include hydroquinone cream, tretinoin, tranexamic acid, azelaic acid, niacinamide, and arbutin cream. While these treatments have some efficacy, they are prone to recurrence and come with numerous drawbacks, including adverse reactions such as redness, pain, scaling, itching, and ulceration. These treatments can damage the skin barrier and, in some cases, can lead to permanent damage or even life-threatening consequences. Consequently, these medications are clinically controversial and have even been banned.

[0005] External treatments in Traditional Chinese Medicine (TCM) have a long history and consistently adhere to the fundamental principle of syndrome differentiation and treatment. Prescriptions are modified based on the underlying etiology and symptoms. This approach not only offers remarkable efficacy with minimal adverse reactions, but also avoids first-pass effects on the liver and gastrointestinal tract. Chloasma is caused by localized qi stagnation, blood stasis, and phlegm accumulation in the skin, leading to a lack of proper qi and blood nourishment, resulting in freckles. Traditional Chinese medicine believes that "what goes on inside manifests itself externally." While chloasma is a skin disease, its core pathogenesis lies in liver and kidney dysfunction. The liver and kidney share a common origin, and deficiencies in liver and kidney essence and blood, leading to weak essence and blood, result in skin malnutrition and freckles. Qi is the leader of blood, and its flow distributes body fluids. Kidney essence deficiency prevents liver nourishment, while liver blood deficiency prevents the transformation and nourishment of qi, leading to liver qi stagnation. Alternatively, emotional stimulation can lead to liver qi stagnation, resulting in poor qi flow, qi stagnation, blood stasis, and phlegm accumulation. This deprives the skin of qi and blood nourishment, leading to freckles. Using TCM external treatment theory to guide the application of topical Chinese medicine to improve or treat chloasma holds promise for achieving a treatment approach with fewer side effects. Summary of the Invention

[0006] In response to the problems existing in the existing technology, the inventors, based on their many years of clinical experience, have screened out a core formula that has good therapeutic effects on the vast majority of chloasma patients by adding, subtracting, and modifying the basic formula for different clinical cases. They provide a traditional Chinese medicine composition for treating chloasma and a corresponding external preparation, and provide the following technical solutions:

[0007] In a first aspect, the present invention provides a traditional Chinese medicine composition for treating chloasma, wherein the composition comprises the following medicinal ingredients in parts by weight:

[0008] 10-100 parts of black plums, 10-100 parts of Chinese angelica, 1-10 parts of Panax notoginseng, and 1-10 parts of Bombyx batryticatus.

[0009] The origins and effects of the above-mentioned medicinal flavors are as follows:

[0010] Black plum:

[0011] Prunus mume Prunus mume The dried nearly ripe fruits of (Sieb.) Sieb. et Zucc. are harvested in summer when they are nearly ripe, dried at low temperature and then steamed until they turn black.

[0012] Preparation method: remove impurities, wash and dry.

[0013] Nature and flavor: sour, astringent, neutral. Enters the liver, spleen, lung, large intestine, and kidney meridians.

[0014] Functions and indications: Astringes the liver and lungs, astringes the intestines and promotes the production of body fluids, and calms ascaris. It is used for chronic cough due to lung deficiency, chronic diarrhea and dysentery, deficiency-heat and thirst, ascariasis-induced vomiting and abdominal pain, and treats black spots on the skin and numbness.

[0015] Angelica:

[0016] 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 has evaporated slightly, they are bundled into small bundles, hung on a shed, and slowly smoked dry with smoke.

[0017] Processing: Remove impurities, wash, soak thoroughly, cut into thin slices, dry in the sun or at low temperature.

[0018] Nature and flavor: sweet, pungent, warm. Enters the liver, heart, and spleen meridians.

[0019] Functions and indications: Nourishes blood and invigorates blood circulation, regulates menstruation and relieves pain, and moistens the intestines and promotes bowel movements. It is used for sallow complexion due to blood deficiency, dizziness and palpitations, irregular menstruation, amenorrhea and dysmenorrhea, abdominal pain due to deficiency and cold, rheumatic pain, injuries from falls, carbuncles and ulcers, and constipation due to dry intestines. 37:

[0021] Radix et Rhizoma Notoginseng is the dried root and rhizome of Panax notoginseng (Burk.) F. H. Chen. The root and rhizome are dug in autumn before flowering, washed, separated into main roots, branch roots and rhizomes, and dried. The branch roots are commonly known as "Jin Tiao", and the rhizomes are commonly known as "Cai Kou".

[0022] Processing: Commonly used powder, take Sanqi, wash, dry, and grind into fine powder.

[0023] Flavor and meridian distribution: sweet, bitter, and warm. It belongs to the liver and stomach meridians.

[0024] Function and indication: dispersing blood stasis, stopping bleeding, removing swelling and relieving pain. It is used for hemoptysis, hematemesis, metrorrhagia, uterine bleeding, external injury, chest and abdominal pain, and contusion.

[0025] White bionic silkworm:

[0026] Also known as Juecang, it is the dried body of the silkworm Bombyx mori Linnaeus 4-5 age larvae infected (or artificially inoculated) with Beauveria bassiana (Bals.) Vuillant and died. Beauveria bassiana

[0027] Processing: After washing, dry and remove impurities.

[0028] Flavor and meridian distribution: salty, pungent, and flat. It belongs to the liver, lung and stomach meridians.

[0029] Function and indication: calming wind and stopping convulsion, expelling wind and relieving pain, resolving phlegm and removing mass. It is used for liver wind combined with phlegm, convulsion, infantile convulsion, tetanus, stroke, wind-dry mouth, wind-heat headache, red eyes and sore throat, wind-itch and scabies, and mumps.

[0030] The present application provides a traditional Chinese medicine composition for treating chloasma. The idea of the above medicine composition is mainly derived from the following aspects:

[0031] (1) "Lingshuo: Disease Form of Pathogenic Qi and Zangfu Organs" says: "The twelve meridians and three hundred and sixty-five collaterals, their blood and qi all rise to the face." "Hailun" says: "The twelve meridians belong to the internal organs and are connected to the limbs and skin." The meridians are the channels that connect the internal organs, connect the skin and skin orifices, communicate the inside and outside, and run the blood and body fluid. When the internal organs function normally and the body has sufficient essence, blood and body fluid, the essence, blood and body fluid run through the meridians to the skin and face, and the skin and face are nourished, so the face is red and shiny. When the internal organs function abnormally and the body lacks essence, blood and body fluid, the blood and body fluid run through the meridians is not smooth, and the blood and body fluid are blocked, so the skin is not nourished and dark spots appear.

[0032] ​(2) Chloasma is closely related to liver and kidney dysfunction. According to the theory of Zangfu, liver is responsible for the dispersion of Qi and the promotion of the movement of blood and body fluid. Kidney is the source of the essence, blood and body fluid. For example, it is stated in the book of Three Factors and One Disease that 'depression and anger can damage the liver and kidney, respectively. Liver and kidney are closely related. The patient is deficient in essence and blood, and his face is dark. '

[0033] (3) According to the theory of Yeteinshi, liver is the source of women. Chloasma is more common in women, and the treatment of chloasma from the liver is of great importance. According to the theory of traditional Chinese medicine, liver is responsible for the dispersion of Qi and the regulation of emotions. At present, due to the fast pace of work, high tension and great life pressure, etc., it is easy to lead to the stagnation of liver-Qi. In addition, staying up late, eating spicy food and drinking coffee can easily consume kidney essence, and kidney essence deficiency can not nourish the liver, leading to the stagnation of liver-Qi. According to the theory of traditional Chinese medicine, liver opens into the eyes, and excessive dependence on electronic products can easily damage liver blood, and liver blood deficiency can not nourish liver-Qi, leading to the stagnation of liver-Qi. Qi is the leader of blood, and Qi moves body fluid. The stagnation of liver-Qi, the dispersion of liver, the unsmoothness of Qi, the influence of Qi and blood and body fluid, the stagnation of blood and phlegm, the deficiency of skin in nourishment, and the dark complexion of chloasma.

[0034] (4) According to the book of Five Views and Five Messengers, 'kidney disease is the blackness of cheeks and face. Kidney deficiency is the main cause of chloasma. According to the book of Women's Face Black Spots, 'water deficiency can not regulate fire, blood weakness can not beautify meat, leading to the formation of black spots by fire and dryness, and the color of the skin is dark and dull. According to the book of Kidney Theory, 'dark complexion is a symptom of kidney deficiency. It is closely related to the formation of chloasma. Chloasma caused by kidney deficiency is more common in kidney deficiency, blood deficiency and skin deficiency. Kidney deficiency can not nourish the liver, leading to the stagnation of liver-Qi, the unsmoothness of blood and the stagnation of blood. According to the book of Yeteinshi Medical Records, 'external pathogens have been left for years, and Qi and blood have been damaged. The blood is mixed with phlegm in the meridians. After years of Qi deficiency, the patient is abandoned and the tumor is formed. It can be seen that the stagnation of phlegm and blood in the skin is also an important mechanism of chloasma.

[0035] (5) There are records of traditional Chinese medicine for the treatment of chloasma in ancient books, such as Yuyong Powder and Meirong Ointment recorded in the books of Puji Fang and Medical Canon of Golden Prescriptions, which have been used until now. Because the human body is an organic whole, according to the book of Sea Theory, 'the twelve meridians belong to Zangfu internally and are connected with limbs externally. The external use of traditional Chinese medicine can act on the skin, and can be absorbed into the collaterals through the skin, pores and conduits, and can directly reach the parts of chloasma caused by the stagnation of Qi, blood and phlegm. At the same time, it can also improve the function of internal Zangfu such as liver and kidney through the transmission of skin meridians, and then strengthen the movement of Qi and blood to achieve the purpose of treating chloasma by activating blood and resolving phlegm.

[0036] Based on the above-mentioned research ideas for treating chloasma, the traditional Chinese medicine composition of the first aspect is guided by the theory of deficiency of liver and kidney essence and blood, stagnation of qi and blood stasis, and blockage of phlegm, and is based on the principle of nourishing essence and blood, promoting blood circulation to remove blood stasis, regulating qi and resolving phlegm, and removing chloasma and whitening. Among them, Fructus Mume and Angelica sinensis are the monarch drugs, and Panax notoginseng and Bombyx Batryticatus are the ministerial drugs. Fructus Mume and Angelica sinensis jointly play the role of nourishing liver and kidney essence and blood, Angelica sinensis and Panax notoginseng supplement blood and promote blood circulation to remove blood stasis, and Bombyx Batryticatus regulates qi and resolves phlegm, and the above-mentioned components jointly play the role of removing chloasma and whitening.

[0037] In the preferred scheme of the above-mentioned traditional Chinese medicine composition, the weight parts of each medicinal ingredient are as follows: Fructus Mume 10-100 parts, Angelica sinensis 10-100 parts, Panax notoginseng 1-10 parts, and Bombyx Batryticatus 1-10 parts.

[0038] In one embodiment, the traditional Chinese medicine composition has the following medicinal ingredients and proportions: Fructus Mume 100 parts, Angelica sinensis 80 parts, Panax notoginseng 8 parts, and Bombyx Batryticatus 6 parts.

[0039] In another embodiment, the traditional Chinese medicine composition has the following medicinal ingredients and proportions: Fructus Mume 60 parts, Angelica sinensis 70 parts, Panax notoginseng 8 parts, and Bombyx Batryticatus 6 parts.

[0040] In another embodiment, the traditional Chinese medicine composition has the following medicinal ingredients and proportions: Fructus Mume 40 parts, Angelica sinensis 80 parts, Panax notoginseng 4 parts, and Bombyx Batryticatus 6 parts.

[0041] In another embodiment, the traditional Chinese medicine composition has the following medicinal ingredients and proportions: Fructus Mume 40 parts, Angelica sinensis 20 parts, Panax notoginseng 2 parts, and Bombyx Batryticatus 2 parts.

[0042] In another embodiment, the traditional Chinese medicine composition has the following medicinal ingredients and proportions: Fructus Mume 50 parts, Angelica sinensis 30 parts, Panax notoginseng 2 parts, and Bombyx Batryticatus 5 parts.

[0043] In a preferred embodiment of the present application with good effects, the traditional Chinese medicine composition has the following medicinal ingredients and proportions: Fructus Mume 30 parts, Angelica sinensis 20 parts, Panax notoginseng 3 parts, and Bombyx Batryticatus 2 parts.

[0044] The above-mentioned composition has been fully investigated for toxicity before being applied in clinical practice, and rat and mouse toxicity tests have confirmed that the drug combination with the above-mentioned proportions does not show toxicity to the body. In the subsequent clinical treatment application, no adverse reactions have been found.

[0045] The application form of the above-mentioned traditional Chinese medicine composition includes but is not limited to the following forms:

[0046] The above-mentioned medicinal ingredients are in the form of whole medicinal materials, such as Fructus Mume, Angelica sinensis, Panax notoginseng, and Bombyx Batryticatus, which are mixed after being powdered; or the above-mentioned medicinal ingredients are in the form of extracts, including but not limited to water extracts, alcohol extracts, or extracts of other organic reagents. The second aspect of the present application provides a functional product for preventing, improving, or treating chloasma, and the preparation raw material of the functional product comprises the composition of the first aspect.

[0047] The functional product can be a medicine, a functional food, a washing and caring product, the medicine including but not limited to an injection, an oral preparation or a transdermal preparation, and more preferably a transdermal preparation such as a microneedle, a patch, a paste, a cream or a gel.

[0048] The washing and caring product is preferably a mask, an aqueous preparation, a cream or a paste which is applied by smearing.

[0049] In a third aspect, the present application provides an external preparation for treating chloasma, which comprises a traditional Chinese medicine extract and a base, wherein the traditional Chinese medicine extract is prepared from the traditional Chinese medicine composition of the first aspect.

[0050] The traditional Chinese medicine extract is prepared by mixing the extract of Fructus Mume, the extract of Angelica sinensis, the extract of Panax notoginseng and the extract of White Muscardine Moth, and then concentrating the mixture.

[0051] The extract of Fructus Mume is prepared by adding Fructus Mume into a sodium bicarbonate solution and extracting at room temperature, with a ratio of 1g:8-12mL, an extraction time of 1.5-2.5h and a concentration of the sodium bicarbonate solution of 4-7%, and then centrifuging to reserve the solution part as the extract of Fructus Mume.

[0052] The extract of Angelica sinensis is prepared by adding Angelica sinensis into an ethanol solution and refluxing, with a ratio of 1g:6-10mL, a concentration of the ethanol solution of 65-75% (volume fraction), and repeating the extraction for two to three times, and then combining the extraction solutions, with an extraction time of 1-2h each time.

[0053] The extract of Panax notoginseng is prepared by adding Panax notoginseng into an ethanol solution and refluxing, with a ratio of 1g:7-10mL, a concentration of the ethanol solution of 65-75% (volume fraction), and repeating the extraction for two to three times, and then combining the extraction solutions, with an extraction time of 1-2h each time.

[0054] The extract of White Muscardine Moth is prepared by adding White Muscardine Moth into water and refluxing, with a ratio of 1g:8-12mL, and repeating the extraction for two to three times, and then combining the extraction solutions, with an extraction time of 1-2h each time.

[0055] The concentration is performed by combining the four kinds of extracts, heating to remove alcohol from the solution by rotary evaporation, and further concentrating the solution to a volume ratio of 1:1 between the removed water and the remaining solution.

[0056] The above-mentioned matrix is mainly used as a carrier of traditional Chinese medicine extract, preferably a matrix suitable for external use on skin, such as an aqueous preparation, an emulsion, a cream or a paste, etc., which includes lipid, soap, ester matrix components, and other functional agents, such as moisturizing agents, flavoring agents or preservatives, etc.

[0057] In one embodiment of the present application, the above-mentioned external preparation is a paste, which includes the following ingredients by weight:

[0058] 4-6 parts of traditional Chinese medicine extract, 1-3 parts of cetyl stearyl alcohol, 5-7 parts of oil, 0.5-1.5 parts of glycerol stearate, 1-3 parts of C12-20 acid PEG-8 ester, 45-55 parts of deionized water, 7-9 parts of amino acid moisturizing agent, 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 (ester) / C10-30 alkanol acrylate cross-linked polymer, 0.05-0.15 parts of carbomer, 0.3-0.5 parts of arginine, 0.2-0.4 parts of preservative, and 0.3-0.7 parts of vanillyl butyl ether.

[0059] The preparation method of the above-mentioned paste is as follows:

[0060] (1) Put phase A into a beaker and heat to 80-85℃ in a water bath; stir evenly, wherein phase A is: cetyl stearyl alcohol, oil, glycerol stearate and C12-20 acid PEG-8 ester;

[0061] (2) Put phase B into a beaker and heat to 80-85℃ to uniformly disperse the components, and add phase B to phase A in a fine stream under stirring, gradually increase the amount and stir, wherein phase B is: deionized water, amino acid moisturizing agent, disodium EDTA, allantoin, sodium polyacrylate, potassium cetyl phosphate, acrylic acid (ester) / C10-30 alkanol acrylate cross-linked polymer and carbomer;

[0062] (3) Continue to add traditional Chinese medicine extract, stir evenly, then reduce to 60-70℃, add arginine, cool to 40-50℃, then add amino acid moisturizing agent, preservative and vanillyl butyl ether, stir evenly, cool to 30-40℃, stir evenly, and discharge.

[0063] In the fourth aspect of the present application, a method for preventing, improving or treating chloasma is provided, which comprises applying the functional product of the second aspect or the external preparation of the third aspect to the area in need of prevention, improvement or treatment.

[0064] Compared with the prior art, the present application has the following advantages:

[0065] 1、The traditional Chinese medicine composition has small irritability, can be used as an external medicine, and is safe.

[0066] 2、The traditional Chinese medicine composition has definite curative effect, is easy to obtain, and is economical and practical.

[0067] 3、The traditional Chinese medicine composition has the following curative effects: pigmentation is reduced or completely disappears; skin antioxidant capacity is improved; tyrosinase activity is reduced, and melanin production is reduced; and the depigmentation effect is long-term effective. BRIEF DESCRIPTION OF DRAWINGS

[0068] The drawings constituting a part of the specification of the present application are used to provide further understanding of the present application, and the illustrative embodiments of the present application and the description thereof are used to explain the present application, and do not constitute improper limitation on the present application.

[0069] Figure 1 Apparent experimental results of the chloasma model group and the traditional Chinese medicine extract group;

[0070] Figure 1 A is the apparent condition of the chloasma of the back of the chloasma model rat;

[0071] Figure 1 B is the apparent condition of the skin of the back of the rat after administration of the traditional Chinese medicine extract;

[0072] Figure 2 Effect of the traditional Chinese medicine extract on the TYR activity in the serum, liver and skin of the rats in each group;

[0073] Figure 2 A is the TYR activity in the serum of the rats in each group;

[0074] Figure 2 B is the TYR activity in the liver of the rats in each group;

[0075] Figure 2 C is the TYR activity in the skin of the rats in each group;

[0076] Figure 3 Effect of the traditional Chinese medicine extract on the SOD activity in the serum, liver and skin of the rats in each group;

[0077] Figure 3 A is the SOD activity in the serum of the rats in each group;

[0078] Figure 3 B is the SOD activity in the liver of the rats in each group;

[0079] Figure 3 C is the SOD activity in the skin of the rats in each group

[0080] Figure 4The effect of the traditional Chinese medicine extract on the SOD activity in the serum, liver and skin of each group of rats;

[0081] Figure 4 A is the MDA activity in the serum of each group of rats;

[0082] Figure 4 B is the MDA activity in the liver of each group of rats;

[0083] Figure 4 C is the MDA activity in the skin of each group of rats;

[0084] The above Figures 2-4 The "Qubanfang" shown in the horizontal coordinate is the traditional Chinese medicine extract prepared in Example 3;

[0085] Figure 5 The effect of the traditional Chinese medicine extract on the histopathological changes of the skin tissue of each group of rats;

[0086] Figure 5 A is the blank group;

[0087] Figure 5 B is the model group;

[0088] Figure 5 C is the positive drug group;

[0089] Figure 5 D is the low-dose traditional Chinese medicine extract group;

[0090] Figure 5 E is the medium-dose traditional Chinese medicine extract group;

[0091] Figure 5 F is the high-dose traditional Chinese medicine extract group;

[0092] Figure 5 In A-5F, the yellow arrow indicates parakeratosis, the black arrow indicates hyperkeratosis, the blue arrow indicates sweat gland duct, and the red arrow indicates inflammatory cell infiltration;

[0093] Figure 6 The clinical treatment results of 27 cases; DETAILED DESCRIPTION

[0094] It should be noted that the following detailed description is exemplary and is intended to provide further explanation of the application. 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 this application belongs.

[0095] It is to be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of example embodiments in accordance with the present application. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms "comprises" and / or "comprising," when used in this specification, specify the presence of stated features, steps, operations, elements, components, and / or groups thereof, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and / or groups thereof.

[0096] Terminology:

[0097] Traditional Chinese medicine composition: refers to two or more than two traditional Chinese medicine or traditional Chinese medicine extract mixture according to a certain proportion, with certain properties and purposes. The traditional Chinese medicine composition in the file in this application refers to the mixture of four medicinal materials of Fructus Mume, Angelica sinensis, Panax notoginseng and White Muscardine after mixing according to the dosage ratio of 10-100:10-100:1-10:1-10, or the mixture of extracts of the above medicinal materials. The mixture has the effect of preventing, improving, lightening or treating chloasma. The "traditional Chinese medicine extract", "traditional Chinese medicine composition" and "anti-chloasma prescription" in this application all refer to the above substances.

[0098] In order to enable those skilled in the art to more clearly understand the technical solutions of the present application, the technical solutions of the present application will be described in detail below in combination with specific examples.

[0099] The raw materials involved in the following examples are as follows:

[0100] Fructus Mume, Angelica sinensis, Panax notoginseng and White Muscardine and arbutin ointment are purchased from Shuyu Common People's Drugstore.

[0101] Example 1

[0102] A traditional Chinese medicine extract for treating chloasma, the preparation raw materials of the extract include the following weight parts of medicinal materials: Fructus Mume 100 parts, Angelica sinensis 80 parts, Panax notoginseng 8 parts, White Muscardine 6 parts.

[0103] The preparation method of the extract includes the following steps:

[0104] (1) Preparation of Fructus Mume extract: Fructus Mume is mixed with 5% sodium bicarbonate aqueous solution (1g:10mL) and extracted at room temperature, the extraction time is 2h, and the solution part is reserved after centrifugation, which is the Fructus Mume extract.

[0105] (2) Preparation of Angelica sinensis extract: Angelica sinensis is mixed with 70% ethanol aqueous solution (1g:8mL) and then refluxed, filtered, and the original medicinal material is mixed with 70% ethanol aqueous solution again and then heated and refluxed, a total of 2 times (soaking for 30 minutes before the first extraction), each time for 1h, and the solution part is reserved after centrifugation, and the alcohol extract of the two extractions is combined to obtain the extract of Angelica sinensis.

[0106] (3) Preparation of the extract of Panax notoginseng: Panax notoginseng was mixed with 70% ethanol aqueous solution (1 g: 8 mL) and then subjected to reflux extraction, filtered, and the original medicinal material was mixed with 70% ethanol aqueous solution again and then subjected to reflux extraction, totally for 2 times (the original medicinal material was soaked for 30 minutes before the first extraction), and each time of extraction lasted for 1 h. The solution part was reserved by centrifugation, and the alcohol extractives of the two times of extraction were combined to obtain the extract of Panax notoginseng.

[0107] (4) Preparation of the extract of Musca domestica L: Musca domestica L was mixed with deionized water (1 g: 10 mL) and then subjected to reflux extraction, filtered, and the original medicinal material was mixed with water again and then subjected to reflux extraction, totally for 2 times (the original medicinal material was soaked for 30 minutes before the first extraction), and each time of extraction lasted for 1 h. The residue was separated by centrifugation, and the water extractives were combined to obtain the extract of Musca domestica L.

[0108] (5) The above extract of Fructus mume, extract of Angelica sinensis, extract of Panax notoginseng and extract of Musca domestica L were mixed and heated to recover ethanol and concentrate the medicinal liquid to a concentration of 1:1 to obtain the traditional Chinese medicine extract.

[0109] Example 2

[0110] A traditional Chinese medicine extract for treating chloasma, the preparation raw material of the extract comprises the following medicinal ingredients in parts by weight: Fructus mume 60 parts, Angelica sinensis 70 parts, Panax notoginseng 8 parts, and Musca domestica L 6 parts.

[0111] The preparation method of the traditional Chinese medicine extract is as follows:

[0112] (1) Preparation of the extract of Fructus mume: Fructus mume was mixed with 5% sodium bicarbonate aqueous solution (1 g: 8 mL) and then extracted at room temperature, and the extraction time lasted for 2.5 h. The solution part was reserved by centrifugation to obtain the extract of Fructus mume.

[0113] (2) Preparation of the extract of Angelica sinensis: Angelica sinensis was mixed with 70% ethanol (1 g: 6 mL) and then subjected to reflux extraction, filtered, and the original medicinal material was mixed with 70% ethanol again (1 g: 5 mL) and then subjected to reflux extraction, totally for 2 times (the original medicinal material was soaked for 30 minutes before the first extraction), and each time of extraction lasted for 1.5 h. The solution part was reserved by centrifugation, and the alcohol extractives of the two times of extraction were combined to obtain the extract of Angelica sinensis.

[0114] (3) Preparation of the extract of Panax notoginseng: Panax notoginseng was mixed with 70% ethanol (1 g: 7 mL) and then subjected to reflux extraction, filtered, and the original medicinal material was mixed with 70% ethanol again (1 g: 5 mL) and then subjected to reflux extraction, totally for 2 times (the original medicinal material was soaked for 30 minutes before the first extraction), and each time of extraction lasted for 2 h. The solution part was reserved by centrifugation, and the alcohol extractives of the two times of extraction were combined to obtain the extract of Panax notoginseng.

[0115] (4) Preparation of the extract of white muscardine: white muscardine was mixed with deionized water (1 g: 8 mL) and then subjected to reflux extraction, filtered, and the original medicinal material was mixed with water (1 g: 6 mL) again and then subjected to reflux extraction, a total of 2 times (soaked for 30 minutes before the first extraction), and each time for 2 h. The dregs were separated by centrifugation, and the water extracts were combined to obtain the extract of white muscardine.

[0116] (5) The above extract of Fructus Mume, extract of Angelica sinensis, extract of Panax notoginseng, and extract of white muscardine were mixed, heated, and concentrated to a concentration of 1:1 to obtain the traditional Chinese medicine extract.

[0117] Example 3

[0118] A traditional Chinese medicine extract for treating chloasma, the preparation of which comprises the following medicinal materials in parts by weight: Fructus Mume 30 parts, Angelica sinensis 20 parts, Panax notoginseng 3 parts, and white muscardine 2 parts.

[0119] The preparation method of the traditional Chinese medicine extract is as follows:

[0120] (1) Preparation of the extract of Fructus Mume: Fructus Mume was mixed with 4% sodium bicarbonate aqueous solution (1 g: 12 mL) and then extracted at room temperature for 1.5 h. The solution was separated by centrifugation to obtain the extract of Fructus Mume.

[0121] (2) Preparation of the extract of Angelica sinensis: Angelica sinensis was mixed with 70% ethanol (1 g: 10 mL) and then subjected to reflux extraction, filtered, and the original medicinal material was mixed with 75% ethanol (1 g: 7 mL) again and then subjected to reflux extraction, a total of 2 times (soaked for 30 minutes before the first extraction), and each time for 2 h. The solution was separated by centrifugation, and the alcohol extracts of the two extractions were combined to obtain the extract of Angelica sinensis.

[0122] (3) Preparation of the extract of Panax notoginseng: Panax notoginseng was mixed with 70% ethanol (1 g: 10 mL) and then subjected to reflux extraction, filtered, and the original medicinal material was mixed with 70% ethanol aqueous solution (1 g: 8 mL) again and then subjected to reflux extraction, a total of 2 times (soaked for 30 minutes before the first extraction), and each time for 1 h. The solution was separated by centrifugation, and the alcohol extracts of the two extractions were combined to obtain the extract of Panax notoginseng.

[0123] (4) Preparation of the extract of white muscardine: white muscardine was mixed with deionized water (1 g: 12 mL) and then subjected to reflux extraction, filtered, and the original medicinal material was mixed with water (1 g: 10 mL) again and then subjected to reflux extraction, a total of 2 times (soaked for 30 minutes before the first extraction), and each time for 1.5 h. The dregs were separated by centrifugation, and the water extracts were combined to obtain the extract of white muscardine.

[0124] (5) the above-mentioned extract of Fructus Mume, extract of Angelica sinensis, extract of Panax notoginseng and extract of White Muscardine are mixed, heated and concentrated to 1:1 concentration to obtain the traditional Chinese medicine extract.

[0125] Example 4

[0126] A traditional Chinese medicine composition for treating chloasma, the preparation raw material of the extract includes the following weight parts of medicinal ingredients: Fructus Mume 40 parts, Angelica sinensis 80 parts, Panax notoginseng 4 parts, White Muscardine 6 parts.

[0127] The preparation method of the traditional Chinese medicine extract is as follows:

[0128] (1) Preparation of extract of Fructus Mume: Fructus Mume is mixed with 5% sodium bicarbonate aqueous solution (1g:10mL) and extracted at room temperature, the extraction time is 2h, and the solution part is reserved after centrifugation to obtain the extract of Fructus Mume.

[0129] (2) Preparation of extract of Angelica sinensis: Angelica sinensis is mixed with 65% ethanol (1g:9mL) and reflux extracted, filtered, the original medicinal material is added with 70% ethanol (1g:7mL) again and reflux extracted, a total of 2 times (soaked for 30 minutes before the first extraction), the extraction time is 1h each time, the solution part is reserved after centrifugation, and the alcohol extractives of the two times of extraction are combined to obtain the extract of Angelica sinensis.

[0130] (3) Preparation of extract of Panax notoginseng: Panax notoginseng is mixed with 70% ethanol (1g:7mL) and reflux extracted, filtered, the original medicinal material is added with 70% ethanol (1g:5mL) again and reflux extracted, a total of 2 times (soaked for 30 minutes before the first extraction), the extraction time is 2h each time, the solution part is reserved after centrifugation, and the alcohol extractives of the two times of extraction are combined to obtain the extract of Panax notoginseng.

[0131] (4) Preparation of extract of White Muscardine: White Muscardine is mixed with deionized water (1g:11mL) and reflux extracted, filtered, the original medicinal material is added with water (1g:8mL) again and reflux extracted, a total of 2 times (soaked for 30 minutes before the first extraction), the extraction time is 1h each time, the residue is separated by centrifugation, and the water extractives are combined to obtain the extract of White Muscardine.

[0132] (5) The above-mentioned extract of Fructus Mume, extract of Angelica sinensis, extract of Panax notoginseng and extract of White Muscardine are mixed, heated and concentrated to 1:1 concentration to obtain the traditional Chinese medicine extract.

[0133] Example 5

[0134] A traditional Chinese medicine composition for treating chloasma, the preparation raw material of the extract includes the following weight parts of medicinal ingredients: Fructus Mume 40 parts, Angelica sinensis 80 parts, Panax notoginseng 4 parts, White Muscardine 6 parts.

[0135] The preparation method of the traditional Chinese medicine extract is as follows:

[0136] (1) Preparation of the extract of Fructus Mume: Fructus Mume is mixed with 6% sodium bicarbonate aqueous solution (1 g: 9 mL) and extracted at room temperature, and the extraction time is 2 h. The solution part is reserved after centrifugation, and the extract of Fructus Mume is obtained.

[0137] (2) Preparation of the extract of Angelica sinensis: Angelica sinensis is mixed with 72% ethanol (1 g: 8 mL) and reflux extracted. The filtrate is obtained, and the original medicinal material is added with 70% ethanol (1 g: 6 mL) and reflux extracted again. The extraction is performed twice (the original medicinal material is soaked for 30 minutes before the first extraction), and the extraction time is 1 h each time. The solution part is reserved after centrifugation, and the extract of Angelica sinensis is obtained.

[0138] (3) Preparation of the extract of Panax notoginseng: Panax notoginseng is mixed with 70% ethanol (1 g: 8 mL) and reflux extracted. The filtrate is obtained, and the original medicinal material is added with 70% ethanol (1 g: 6 mL) and reflux extracted again. The extraction is performed twice (the original medicinal material is soaked for 30 minutes before the first extraction), and the extraction time is 1.5 h each time. The solution part is reserved after centrifugation, and the extract of Panax notoginseng is obtained.

[0139] (4) Preparation of the extract of Bombyx Batryticatus: Bombyx Batryticatus is mixed with deionized water (1 g: 10 mL) and reflux extracted. The filtrate is obtained, and the original medicinal material is added with water (1 g: 8 mL) and reflux extracted again. The extraction is performed twice (the original medicinal material is soaked for 30 minutes before the first extraction), and the extraction time is 2 h each time. The residue is separated by centrifugation, and the extract of Bombyx Batryticatus is obtained.

[0140] (5) The extract of Fructus Mume, the extract of Angelica sinensis, the extract of Panax notoginseng and the extract of Bombyx Batryticatus are mixed, heated to recover ethanol, and concentrated to 1:1 concentration to obtain the traditional Chinese medicine extract.

[0141] Example 6

[0142] A traditional Chinese medicine composition for treating chloasma, the preparation raw material of the extract includes the following ingredients by weight: Fructus Mume 50 parts, Angelica sinensis 30 parts, Panax notoginseng 2 parts, and Bombyx Batryticatus 5 parts.

[0143] The preparation method of the traditional Chinese medicine extract is as follows:

[0144] (1) Preparation of the extract of Fructus Mume: Fructus Mume is mixed with 6% sodium bicarbonate aqueous solution (1 g: 9 mL) and extracted at room temperature, and the extraction time is 2 h. The solution part is reserved after centrifugation, and the extract of Fructus Mume is obtained.

[0145] (2) Preparation of Angelica extract: Angelica was mixed with 70% ethanol (1 g:8 mL) and reflux extracted, filtered, and the original medicinal material was mixed with 70% ethanol (1 g:6 mL) again and reflux extracted, a total of 2 times (soaked for 30 minutes before the first extraction), each time for 1 h, the solution was reserved by centrifugation, and the alcohol extracts of the two times were combined to obtain the Angelica extract.

[0146] (3) Preparation of Panax notoginseng extract: Panax notoginseng was mixed with 70% ethanol (1 g:8 mL) and reflux extracted, filtered, and the original medicinal material was mixed with 70% ethanol (1 g:6 mL) again and reflux extracted, a total of 2 times (soaked for 30 minutes before the first extraction), each time for 2 h, the solution was reserved by centrifugation, and the alcohol extracts of the two times were combined to obtain the Panax notoginseng extract.

[0147] (4) Preparation of Musca domestica extract: Musca domestica was mixed with deionized water (1 g:10 mL) and reflux extracted, filtered, and the original medicinal material was mixed with water (1 g:8 mL) again and reflux extracted, a total of 2 times (soaked for 30 minutes before the first extraction), each time for 2 h, the residue was separated by centrifugation, and the water extracts were combined to obtain the Musca domestica extract.

[0148] (5) The above Fructus Mume extract, Angelica extract, Panax notoginseng extract and Musca domestica extract were mixed and heated to recover ethanol to concentrate the medicinal liquid to 1:1 concentration to obtain the traditional Chinese medicine extract.

[0149] Example 7

[0150] In this embodiment, a traditional Chinese medicine ointment for treating chloasma is provided, which comprises the following raw materials: 5 parts of the traditional Chinese medicine extract prepared in any one of Examples 1-6, 2 parts of cetostearyl 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 moisturizing agent, 0.05 part of disodium EDTA, 0.15 part of allantoin, 0.3 part of sodium polyacrylate, 0.15 part of cetyl alcohol phosphate potassium, 0.4 part of acrylic acid (ester) / C10-30 alkanol acrylate cross-linked polymer, 0.1 part of carbomer, 0.45 part of arginine, 0.3 part of preservative, and 0.5 part of eugenyl buty ether.

[0151] The preparation method of the traditional Chinese medicine ointment comprises the following steps:

[0152] (1) The A phase was put into a beaker and heated to 80-85°C in a water bath; and stirred uniformly, wherein the A phase is: cetostearyl alcohol, oil, glyceryl stearate and C12-20 acid PEG-8 ester.

[0153] (2) Add phase B into a beaker and stir for 5 minutes until the powder is dispersed. Stir and heat to 80-85℃ and stir evenly until there are no lumps or powders. Add phase B to phase A in a thin stream, gradually adding and stirring. Phase B consists of: deionized water, amino acid moisturizer, disodium EDTA, allantoin, sodium polyacrylate, potassium cetyl phosphate, acrylic acid (esters) / C10-30 alkyl acrylate crosspolymer and carbomer.

[0154] (3) Add the Chinese herbal extract and stir evenly for 15 minutes. Then cool to 65°C and add arginine. Cool to 45°C and add amino acid moisturizer, preservative, and vanillyl butyl ether in sequence. Stir evenly. Cool to 35°C, stir evenly, and discharge.

[0155] The Chinese herbal extracts and ointments in Examples 1-7 have been verified by acute and chronic toxicity experiments and have good safety when applied to organisms.

[0156] 1. Pharmacodynamic Verification

[0157] (I) Preparation of chloasma rat model and drug administration method

[0158] 1. Experimental Animals

[0159] Table 1 Experimental animal information

[0160]

[0161] 2. Preparation of Chloasma Rat Model

[0162] Table 2 Dosage Table

[0163]

[0164] After all rats were acclimated to the laboratory for one week, 72 Wistar rats were randomly divided according to body weight into a blank group, a model group, a low-dose Chinese herbal extract group, a medium-dose Chinese herbal extract group, a high-dose Chinese herbal extract group, and a positive drug group, with 12 rats in each group. Based on literature reports, this example used ultraviolet irradiation and progesterone injection to establish a chloasma rat model. The back hair of the model rats was shaved with a razor, and the hair on the skin was carefully removed with a depilatory cream, leaving an area of ​​approximately 4 x 4 cm exposed. Hair removal was performed every three days. Following hair removal, the model rats were irradiated daily with a 311 nm ultraviolet lamp for one hour, with the rat skin approximately 50 cm from the lamp source. Following UV irradiation, the model rats received an intramuscular injection of progesterone (20 mg / kg) at 5:00 PM daily. The modeling lasted for 30 days. The blank group received no intervention and was housed normally. Skin changes in the rats were photographed during the modeling process.

[0165] 3. Administration method

[0166] The rats in group 2 were administered with the traditional Chinese medicine extract prepared by the method of Example 3 above, and the administration area of each rat was 3x3 cm 2 The low dose was 0.04 mL each time, recorded as the low-dose Quzhifang group, the medium dose was 0.12 mL, recorded as the medium-dose Quzhifang group, and the high dose was 0.36 mL, recorded as the high-dose Quzhifang group. The rats were administered with the traditional Chinese medicine extract by cotton swab and applied on the skin of the depilated area on the back of the rats. The positive drug group was administered with arbutin cream. The blank group was normally fed without any intervention. See Table 2.

[0167] (B) Pharmacodynamic experiment results of extract of Fructus Mume, Angelica sinensis, Panax notoginseng, and White Muscardine

[0168] 1. Apparent evaluation results

[0169] The model of rats with chloasma was successfully prepared by ultraviolet irradiation combined with intramuscular injection of progesterone. From the apparent index, the yellow-brown patches on the back of the rats in the model group were consistent with the clinical manifestations of patients with chloasma. The results of this example showed that after 30 days of administration, the chloasma in the low-, medium-, and high-dose groups of the traditional Chinese medicine extract was significantly eliminated, indicating that the traditional Chinese medicine extract could achieve the effect of whitening and removing spots.

[0170] 2. Microscopic index experiment results

[0171] 2.1 Results of changes in the content of tyrosinase (TYR) in serum, liver, and skin

[0172] It has been proved that the incidence of chloasma is closely related to the increase in the activity of tyrosinase. In melanocytes, tyrosine forms melanin under the catalysis of tyrosinase, and finally floats to the surface to form chloasma. When the activity of tyrosinase increases, the amount of melanin synthesis increases, which promotes the incidence of chloasma. The results of this example showed that after 30 days of administration, the TYR in the serum of the rats in the low-, medium-, and high-dose groups of the traditional Chinese medicine 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 traditional Chinese medicine extract of Example 3 could reduce the rate of melanin synthesis. Figure 2

[0173] 2.2 Results of changes in the content of SOD in serum, liver, and skin

[0174] Oxidative stress is also an important index for evaluating the efficacy of spot-removing drugs. It has been found that SOD is a natural oxygen free radical scavenger in the body. When the body is in a state of imbalance between oxidation and antioxidant, it is in oxidative stress. The results of this example showed that after 30 days of administration, the SOD in the serum of the rats in the low-, medium-, and high-dose groups of the traditional Chinese medicine extract was significantly higher than that in the model group (****P<0.0001, ***P<0.001, **P<0.01, *P<0.05), indicating that the traditional Chinese medicine extract of Example 3 could improve the body's antioxidant capacity. Figure 3 ​It is shown that after 30 days of administration, the SOD in serum, liver and skin of rats in the low-dose group of the traditional Chinese medicine extract is significantly higher than that in the model group (***P<0.001); the SOD in liver and skin of rats in the medium-dose group of the traditional Chinese medicine extract is significantly higher than that in the model group (***P<0.001); the SOD in liver of rats in the high-dose group of the traditional Chinese medicine extract is significantly higher than that in the model group (***P<0.001), indicating that the traditional Chinese medicine extract of Example 3 can improve the antioxidant capacity of the body.

[0175] 2.3 Changes in the contents of MDA in serum, liver and skin

[0176] Oxidative stress causes a large number of free radicals in the body to be produced, which damages cells and tissues to form pigmentation, and MDA is the most harmful lipid peroxide in this process. The results of this example are as follows: Figure 4 It is shown that after 30 days of administration, the contents of MDA in serum, liver and skin of rats in the low-, medium- and high-dose groups of the traditional Chinese medicine extract are significantly lower than those in the model group (***P<0.001, **P<0.01, *P<0.05), indicating that the traditional Chinese medicine extract of Example 3 has the effect of reducing lipid peroxidation damage.

[0177] 2.4 HE staining results of rat skin

[0178] The results of this example are as follows: Figure 5 It is shown that the skin tissue of rats in the blank group is arranged in order, the epidermis is uniform in thickness, inflammatory cell infiltration is occasionally observed in the superficial dermis, and sebaceous gland hyperplasia is not observed. Compared with the blank group, the skin tissue of rats in the model group is arranged in disorder, the epidermis is obviously thickened and uneven in thickness, the keratin layer has hyperkeratosis and parakeratosis, the spinous layer is thickened, the sweat gland duct is expanded, the sebaceous gland is hyperplastic, the number of blood vessels is increased, a large number of inflammatory cells are observed in the superficial dermis and the spinous layer, and the fibrous tissue in the dermis is arranged in disorder. Compared with the model group, the epidermis of rats in each administration group is thinner and the tissue arrangement is more orderly, among which: the epidermis of rats in the low-dose group of the traditional Chinese medicine extract is uniform in thickness and arranged in order, the keratin layer has slight hyperkeratosis and parakeratosis, a small amount of inflammatory cell infiltration is observed in the dermis, and the sebaceous gland and sweat gland duct are expanded; the epidermis of rats in the medium-dose group of the traditional Chinese medicine extract is uniform in thickness and has hyperkeratosis, the dermis is arranged in order and the cell structure is complete, and a small amount of sweat gland duct is expanded, which is close to the blank group; the epidermis of rats in the high-dose group of the traditional Chinese medicine extract is uniform in thickness and has hyperkeratosis and parakeratosis, and compared with the medium-dose group, more inflammatory cell infiltration is observed; the hyperkeratosis of the skin of rats in the positive drug group is reduced, the epidermis is relatively uniform in thickness, a large number of sweat gland ducts are observed in the dermis, and inflammatory cell infiltration is observed around the blood vessel wall. However, compared with the low-, medium- and high-dose groups of the traditional Chinese medicine extract, the epidermis is increased in thickness.

[0179] 2.4 Immunohistochemical results of rat skin

[0180] 2.4.1 Melan-A expression results

[0181] The experimental example results are shown in Table 3. The skin of the blank group rats was labeled with Melan-A as a positive control to mark melanin particles, and a few melanin particles were observed to be scattered in the epidermis. The Melan-A label of the model group rats showed clustered melanin particles in the basal layer of the epidermis, and a large number of melanin particles were also observed in the prickle cell layer, showing a strong positive reaction. The Melan-A label of the low-dose traditional Chinese medicine extract group rats showed scattered melanin particles in the basal layer and prickle cell layer of the epidermis, and the reaction was close to that of the blank group. The Melan-A label of the medium-dose traditional Chinese medicine extract group rats showed scattered single melanin particles in the epidermis, and the pigment depth was lower than that of the model group. The Melan-A label of the high-dose traditional Chinese medicine extract group rats showed scattered melanin particles in the basal layer of the epidermis, and the pigment depth was higher than that of the blank group. The basal layer melanin cells of the positive drug group were scattered, and the number and density were lower than those of the model group.

[0182] Table 3 Melan-A positive area and average optical density of rat skin in each group

[0183]

[0184] Note: compared with the model group, ### P<0.0001, ## P<0.001, # P<0.01

[0185] The experimental example results are shown in Table 3. After 30 days of administration, the Melan-A positive cell area of the low-dose and medium-dose traditional Chinese medicine extract groups was significantly smaller than that of the model group. The average optical density of the low-dose traditional Chinese medicine extract group was significantly lower than that of the model group ( ### P<0.0001, ## P<0.001, # P<0.01).

[0186] 2.4.1 Tyrosinase (TYR) expression results

[0187] The experimental example results are shown in Table 4. After 30 days of administration, the TYR positive area of the low-dose, medium-dose and high-dose traditional Chinese medicine extract groups was significantly smaller than that of the model group. The average optical density of the low-dose traditional Chinese medicine extract group was significantly lower than that of the model group (****P<0.0001, ***P<0.001, **P<0.01).

[0188] Table 4 TYR positive area and average optical density of rat skin in each group

[0189]

[0190] Note: compared with the model group, *** P<0.001, ** P<0.01

[0191] Summary:

[0192] In summary, the chloasma model animals before and after administration, compared with the rats in the control group, whether from the apparent skin, or in the micro indicators (serum, liver, skin hormone content, epithelial cells, key gene expression, etc.) can better simulate the pathological symptoms of chloasma patients in clinic. After administration of drugs, compared with the model group, the TYR activity and MDA content in the skin, liver and serum of rats in each administration group were significantly reduced (P<0.0001, P<0.001, P<0.01, P<0.05), and the SOD activity was significantly increased (P<0.0001, P<0.001, P<0.01, P<0.05); HE staining results showed that, compared with the model group, the epidermal proliferation degree of rats in the administration group was reduced, the inflammatory cells were reduced, 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 traditional Chinese medicine extract was significantly smaller than that in the model group; the average optical density number of the skin of rats in the low-dose group of traditional Chinese medicine 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 traditional Chinese medicine extract was significantly smaller than that in the model group; the average optical density number of TYR in the skin of rats in the low-dose group of traditional Chinese medicine extract was significantly lower than that in the model group (P<0.0001, P<0.001, P<0.01). And in addition to the traditional Chinese medicine extract in Example 3, the traditional Chinese medicine extract in Examples 1-2 or 4-6 can also play the same treatment level.

[0193] II. Clinical verification

[0194] 1. Treatment group

[0195] Before and after treatment, control.

[0196] Treatment group: transdermal administration of the traditional Chinese medicine composition of Example 3, 1 mL each time, 2-3 times a day;

[0197] After treatment, 28-40 days of treatment per course. After completing one course of observation, the changes of clinical symptoms (skin lesions) of patients before and after treatment were observed.

[0198] 2. Inclusion criteria of this study:

[0199] (1) Patients aged 20-60 years old.

[0200] (2) Voluntarily participate in this study and sign the treatment consent form, and can comply with the doctor's advice during the treatment process.

[0201] (3) Meet the clinical diagnostic criteria for chloasma:

[0202] ① There are clear patches of light to dark brown on the face, usually symmetrical distribution, no inflammatory manifestations and scales.

[0203] ② No obvious subjective symptoms.

[0204] ③ More common in women, mainly occurring after puberty.

[0205] ④ The disease may have seasonal changes, often heavier in summer and lighter in winter.

[0206] ⑤ Exclude other diseases (such as Riehl melanosis and pigmentary photodermatosis) caused by pigmentation.

[0207] 3. Efficacy evaluation criteria:

[0208] Before treatment, the MASI (Melasma Area and Severity Index) was used to evaluate the area and severity of melasma. After the application of the traditional Chinese medicine extract of Example 3, the efficacy of melasma area and severity was evaluated every 2 weeks. Before and after treatment, digital cameras or high-pixel mobile phones were used to take photos of the lesion area for archiving and numbering, and the lesion improvement level score was scored by a dermatologist who did not participate in the treatment.

[0209] Table 5 MASI (Melasma Area and Severity Index) for evaluating the severity of chloasma

[0210]

[0211] Forehead score = 0.3 * (D + H) * A

[0212] Right cheek score = 0.3 * (D + H) * A

[0213] Left cheek score = 0.3 * (D + H) * A

[0214] Chin score = 0.1 * (D + H) * A

[0215] MASI total score = total of the above scores

[0216] The lesion improvement level score was scored by a dermatologist who did not participate in the treatment, and the clinical efficacy was divided into 5 levels according to the efficacy index: recovery (> 75%), significant improvement (51% ~ 75%), moderate improvement (26% ~ 50%), mild improvement (≤25%), and no improvement (≤0%).

[0217] Efficacy index = (pre-treatment score - post-treatment score) / pre-treatment score x 100%.

[0218] 4. Clinical efficacy observation results

[0219] In this study, 27 cases of chloasma patients were collected, including 26 female and 1 male, aged 26-60 years, with a disease course of 6 months to 20 years. According to the lesion type, 3 cases (11.11%) were butterfly type, 7 cases (25.93%) were upper facial type, and 17 cases (62.96%) were generalized type. All patients were informed of the purpose, risk and potential complications of the treatment before entering the group, and signed the informed consent form. Before and after treatment, digital camera or high-pixel mobile phone was used to take photos of the lesion area for archiving and numbering, and the lesion improvement level was scored by a doctor who did not participate in the treatment before and after treatment.

[0220] According to the MASI scale, the clinical efficacy was divided into recovery (>75%), significant improvement (50%-75%), moderate improvement (26%-49%), and mild improvement (<25%). The results showed that among the 27 cases, 1 case (3.70%) was cured, 5 cases (18.52%) were significantly improved, 10 cases (37.04%) were moderately improved, and 11 cases (40.74%) were mildly improved (see Table 1). Figure 6

[0221] This example screened 10 typical cases, as follows:

[0222] Case 1

[0223] Lü, female, 36 years old, admitted to hospital on March 4, 2021, with a disease course of 12 years. Symptoms: facial patches were dark brown, with clear boundaries, symmetrical distribution, no inflammatory manifestations or scales, no obvious subjective symptoms, pale red tongue with thin white fur, and normal urination and defecation. Diagnosed as butterfly type chloasma. The following formula of traditional Chinese medicine composition was used for transdermal administration treatment. Treatment method: external application to the patch area, massaging with the palm of the hand for 2-3 minutes, 2-3 times a day, for 40 days of treatment, the butterfly type chloasma was significantly improved.

[0224] Case 2

[0225] Gong, male, 37 years old, admitted to hospital on July 4, 2022, with a disease course of 6 years and a half. Symptoms: patches on the cheeks and forehead were dark brown, with clear boundaries, symmetrical distribution, no inflammatory manifestations or scales, no obvious subjective symptoms, pale red tongue with thin white fur, and normal urination and defecation. Diagnosed as generalized chloasma. The following formula of traditional Chinese medicine composition was used for transdermal administration treatment. Treatment method: external application to the patch area, massaging with the palm of the hand for 2-3 minutes, 2-3 times a day, for 30 days of treatment, the generalized chloasma was significantly improved.

[0226] Case 3 ​

[0227] Gao Moumou, female, 45 years old, diagnosed on February 4, 2021, disease course 6 years. Symptoms: The facial cheek patch is dark brown, the boundary is clear, the distribution is symmetrical, there is no inflammation and scales, and there is no obvious subjective symptoms. The tongue is light red with thin yellow fur, and the two excrements are adjusted. Diagnosed as facial upper type chloasma. The following prescription of traditional Chinese medicine composition is used for transdermal administration treatment. Treatment method: externally apply the patch, massage with the palm of the hand for 2-3 minutes, 2-3 times a day, treat for 40 days, and the facial upper type chloasma is significantly improved.

[0228] Case 4

[0229] Wangmoumou, female, 50 years old, diagnosed on May 18, 2022, disease course 12 years. Symptoms: The facial cheek patch is light brown, the boundary is clear, the distribution is symmetrical, there is no inflammation and scales, and there is no obvious subjective symptoms. The tongue is light red with thin yellow fur, and the two excrements are adjusted. Diagnosed as butterfly type chloasma. The following prescription of traditional Chinese medicine composition is used for transdermal administration treatment, treatment method: externally apply the patch, massage with the palm of the hand for 2-3 minutes, 2-3 times a day, treat for 35 days, and the butterfly type chloasma is cured.

[0230] Case 5

[0231] Zhangmoumou, female, 60 years old, diagnosed on March 22, 2021, disease course 10 years. Symptoms: The facial cheek and mandibular patch is dark brown, the boundary is clear, the distribution is symmetrical, there is no inflammation and scales, and there is no obvious subjective symptoms. The tongue is light red with thin white fur, and the two excrements are adjusted. Diagnosed as generalized chloasma. The following prescription of traditional Chinese medicine composition is used for transdermal administration treatment, treatment method: externally apply the patch, massage with the palm of the hand for 2-3 minutes, 2-3 times a day, treat for 28 days, and the generalized chloasma has significant effect.

[0232] Case 6

[0233] Guomoumou, female, 47 years old, diagnosed on June 22, 2021, disease course 10 years, summer exacerbation. Symptoms: The facial cheek patch is dark brown, the boundary is clear, the distribution is symmetrical, there is no inflammation and scales, and the skin has slight allergy. The tongue is light with thin white fur, and the two excrements are adjusted. Diagnosed as butterfly type chloasma. The following prescription of traditional Chinese medicine composition is used for transdermal administration treatment, treatment method: externally apply the patch, massage with the palm of the hand for 2-3 minutes, 2-3 times a day, treat for 40 days, and the butterfly type chloasma has significant effect.

[0234] Case 7

[0235] Li, female, 48 years old, April 15, 2021, course of disease 4 years. Symptoms: The patch on the cheeks is dark brown, the boundary is clear, the distribution is symmetrical, there is no inflammatory performance and scales, there is no obvious subjective symptoms, the tongue is light red with thin white fur, and the two excrements are adjusted. Diagnosed as facial upper type chloasma. The following prescription of traditional Chinese medicine composition is used for transdermal drug delivery treatment, treatment method: external application on the patch, massage with finger palm for 2-3 minutes, 2-3 times a day, treatment for 40 days, the effect of facial upper type chloasma is remarkable.

[0236] Case 8

[0237] Li, female, 48 years old, April 15, 2021, course of disease 5 years. Symptoms: The patch on the cheeks is dark brown, the boundary is clear, the distribution is symmetrical, there is no inflammatory performance and scales, there is no obvious subjective symptoms, the tongue is light red with thin white fur, and the two excrements are adjusted. Diagnosed as facial upper type chloasma. The following prescription of traditional Chinese medicine composition is used for transdermal drug delivery treatment, treatment method: external application on the patch, massage with finger palm for 2-3 minutes, 2-3 times a day, treatment for 30 days, the effect of facial upper type chloasma is remarkable.

[0238] Case 9

[0239] Hao, female, 35 years old, June 18, 2022, course of disease 3 years, aggravated with seasons, especially in summer. Symptoms: The patch on the cheeks is dark brown, the boundary is clear, the distribution is symmetrical, there is no obvious subjective symptoms, there is no inflammatory performance and scales, the tongue is light red with thin yellow fur, and the two excrements are adjusted. Diagnosed as facial upper type chloasma. The following prescription of traditional Chinese medicine composition is used for transdermal drug delivery treatment, treatment method: external application on the patch, massage with finger palm for 2-3 minutes, 2-3 times a day, treatment for 40 days, the effect of facial upper type chloasma is remarkable.

[0240] Case 10

[0241] Dong, female, 33 years old, August 17, 2022, course of disease 3 years, onset after childbirth, aggravated in summer. Symptoms: The patch on the cheeks is dark brown, the boundary is clear, the distribution is symmetrical, there is no obvious subjective symptoms, there is no inflammatory performance and scales, the tongue is light red with thin yellow fur, and the two excrements are adjusted. Diagnosed as generalized chloasma. The following prescription of traditional Chinese medicine composition is used for transdermal drug delivery treatment, treatment method: external application on the patch, massage with finger palm for 2-3 minutes, 2-3 times a day, treatment for 30 days, the effect of generalized chloasma is remarkable.

[0242] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. For those skilled in the art, the present application can have various modifications and changes. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A Chinese medicine composition for treating chloasma, characterized in that: The traditional Chinese medicine composition is composed of 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, wherein 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, wherein 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 Chinese angelica, 2 parts of Panax notoginseng, 5 parts of white silkworm; Or, 30 parts of black plums, 20 parts of Chinese angelica, 3 parts of Panax notoginseng, and 2 parts of white silkworm.

4. The Chinese medicine composition according to any one of claims 1 to 3, wherein The application form of the traditional Chinese medicine composition includes the whole medicinal material form of the medicinal flavor or a combination of extracts of each medicinal flavor, and the extract is selected from water extract, alcohol extract or other organic reagent extract.

5. A functional product for preventing, improving or treating chloasma, characterized in that: The raw materials for preparing the functional product include the Chinese medicine composition according to any one of claims 1 to 4; The functional product is selected from medicines and toiletries, and the medicine is selected from injections, oral preparations or transdermal preparations; The toiletries are selected from facial masks, lotions, emulsions or ointments.

6. The functional product for preventing, improving or treating chloasma according to claim 5, characterized in that: The drug is a transdermal preparation.

7. 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 Chinese herbal medicine composition according to any one of claims 1 to 4 as a raw material.

8. The external preparation according to claim 7, wherein 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 them and concentrating them to obtain the traditional Chinese medicine extract.

9. The external preparation according to claim 8, wherein in, The preparation method of the black plum extract is as follows: adding black plum to a sodium bicarbonate solution at room temperature for extraction, 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 portion retained after 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 at a ratio of 1 g: 6-10 mL, wherein the concentration of the ethanol solution is 65-75%, and the extraction is repeated two to three times and the extracts are combined, and each extraction time is 1-2 hours; The preparation method of the Panax notoginseng extract is as follows: adding Panax notoginseng to an ethanol solution for reflux extraction at a ratio of 1 g: 7-10 mL, wherein the concentration of the ethanol solution is 65-75%, repeating the extraction two to three times and combining the extracts, each extraction time being 1-2 hours; The preparation method of the Bombyx batryticatus extract is as follows: adding Bombyx batryticatus to water for reflux extraction, with a ratio of 1 g: 8-12 mL, repeating the extraction two to three times and combining the extracts, each extraction time being 1-2 hours; The concentration operation is as follows: combining the above four extracts, heating to remove alcohol in the solution to obtain a medicinal solution, and further concentrating the medicinal solution until the volume ratio of the evaporated water to the remaining medicinal solution is 1:

1.

10. The external preparation according to claim 7, wherein The external preparation is an ointment, 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 crosspolymer, 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.

11. The external preparation according to claim 10, wherein The preparation method of the ointment is as follows: (1) Put phase A into a beaker and heat it in a water bath to 80-85°C; stir evenly. Phase A consists of: 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 adding and stirring. Phase B consists of: 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 medicine 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.

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