A traditional Chinese medicine composition for treating eczema, its preparation method and uses

Abstract

This application relates to a traditional Chinese medicine composition for treating eczema, its preparation method and uses. The traditional Chinese medicine composition of the present invention is derived from inheriting the classic ancient formula "Xiaofeng Powder" and combining with the traditional Chinese medicine theory of "tonifying the earth", which conforms to the traditional Chinese medicine theory, and is mainly used for treating eczema, especially acute eczema. The traditional Chinese medicine composition of the present invention can play an obvious anti-eczema effect on the eczema model of Balb / c mice, and the effect increases with the increase of the dose. The curative effect on erythema, epidermal exfoliation and lichenification of the eczema model animals is significantly better than that of the commonly used proprietary Chinese medicine Xiaofeng Zhiyang Granule for this indication.

Description

Technical Field

[0001] The invention belongs to the technical field of Chinese patent medicines, and particularly relates to a Chinese medicine composition for treating eczema, a preparation method thereof and uses thereof. Background Art

[0002] Eczema is a delayed allergic reaction caused by internal and external stimuli. It is also a common and frequently-occurring disease in dermatology. The prevalence rate in the general population in my country is about 7.5%. Modern medicine believes that the occurrence of eczema is related to type I immediate and type IV delayed allergic reactions, and is divided into three stages: acute, subacute, and chronic. Traditional Chinese medicine believes that it is related to the weakness of vital energy and the invasion of external evils such as wind, dampness, and heat. It is divided into damp-heat infiltration type, spleen deficiency and dampness accumulation type, blood deficiency and wind dryness type, etc. Clinically, it has the characteristics of diverse skin lesions, symmetrical distribution, severe itching, repeated attacks, and a long course of disease, which can directly or indirectly affect the patient's physical and mental health.

[0003] At present, the treatment of eczema is still mainly based on topical medication, and the main drugs are mainly glucocorticoids for external use in Western medicine. However, long-term use of such drugs can lead to multiple side effects such as skin atrophy, and it is very easy to relapse after stopping the drug. Most of the traditional Chinese medicine external preparations have the disadvantages of being heavier or greasy in color, affecting the appearance after rubbing, and being easy to stain clothes and not easy to clean. However, the operation of therapies such as fumigation and soaking is relatively complicated, the conditions are limited, the patients are inconvenient to use, the acceptance is not high, and the compliance is poor. In addition, the single prescription of traditional Chinese medicine for the treatment of eczema is mainly based on the theory of clearing heat and removing dampness, which is very easy to consume yin fluid, which is not conducive to the treatment of syndrome differentiation. Therefore, it is of practical significance to develop a drug that can give play to the clinical advantages of traditional Chinese medicine, embody the characteristics of prescription compatibility, can replace hormone drugs and has little side effects, is not easy to relapse after treatment, and can solve the shortcomings of external use of traditional Chinese medicine for the treatment of skin eczema.

[0004] The root of red stinking peony is a common medicinal material used by Xishuangbanna Dai medicine. It is not commonly used in clinical Chinese medicine, but it is a commonly used prescription medicinal material in the preparations of Xishuangbanna Autonomous Prefecture Dai Medicine Hospital. It has the effects of nourishing the earth and strengthening the stomach, clearing away heat and detoxifying, removing wind and relieving pain, and promoting blood circulation and stopping bleeding. To this end, we conducted in-depth research and obtained very ideal results through reasonable prescription. Eczema is caused by three evil qi, wind evil, damp evil and heat evil, which invade the human body, soak the blood vessels, and cannot be discharged from the inside and cannot penetrate from the outside, and are blocked in the skin. The itching of the rash is caused by wind evil, because "itching comes from the wind"; after scratching, the exudation of body fluid is a sign of damp evil; occasionally the skin rash is red, which is actually a sign of the descending of heat evil; if damp evil is too strong, the tongue coating will be white and greasy, and if heat evil is too strong, the tongue coating will be yellow, and the floating pulse is mainly wind and heat. It is suitable for removing dampness and clearing heat, dispersing wind and stopping itching.

[0005] Traditional Chinese medicine prescriptions represented by the classic ancient prescription "Xiaofengsan" mainly treat eczema by clearing away heat, promoting dampness and relieving itching. They are insufficient in treating symptoms such as the stickiness of dampness that easily obstructs Qi and blood. Therefore, although it is clinically effective, it is prone to relapse.

[0006] In the Medical Records. Dampness, it is believed that "dampness diseases have different external and internal causes", and it says: "It can be seen that the symptoms of internal injury and exogenous infection are all caused by the weakness of the original qi, which causes dampness to develop inside and attack outside. The Classic says: The strong will be fine if the qi flows, but the weak will become sick. When the spleen is healthy and functioning, the essence will be dispersed to the lungs and the skin will be firm, so there is no way for external dampness to enter; when the kidney qi is full, the yin and yang will be harmonized and rise and fall in moderation, so how can internal dampness arise?" Therefore, spleen and stomach deficiency can be said to be the common premise for the onset of exogenous and internal injury dampness diseases. In the Clinical Guide Medical Cases. Dampness and the Complete Collection of Ancient and Modern Medicines, dampness diseases are mostly caused by spleen deficiency, and both emphasize the key role of the spleen and stomach in the onset of the disease. In the discussion of the overall treatment principle of dampness diseases, the Syndrome and Treatment Collection. Dampness Diseases specifically emphasizes that dampness should be treated with spleen strengthening: "Therefore, if you treat dampness without knowing how to regulate the spleen, it is not the right treatment." This shows the importance of tonifying the spleen and stomach in the treatment of dampness diseases. Li Gao, one of the four famous doctors in the Jin and Yuan dynasties, proposed the view that "internal injury of the spleen and stomach will cause all kinds of diseases." Modern research has found that the incidence of eczema is getting higher and higher, covering the entire age group, and the incidence is higher in the old and young (relatively poor spleen and stomach function), and it is very easy to relapse after treatment. This is directly related to the diet and living habits of modern society. Excessive intake of high-fat, high-protein, high-calorie foods, coupled with insufficient exercise, has long-term burdens on the spleen and stomach, and has caused "dampness" over time. Compared with ancient people, modern people with weak spleen and stomach are more serious. Eczema caused by internal injury of the spleen and stomach is the most lingering and difficult to cure, and recurs repeatedly.

[0007] The Chinese patent document with application publication number CN 101214345B discloses a Chinese medicine preparation for treating various pruritic skin diseases such as eczema, dermatitis, urticaria, etc. The preparation is made of the following medicines in parts by weight: 8-15 parts of angelica sinensis, 8-15 parts of raw rehmannia, 8-15 parts of pericarp of cicada, 8-15 parts of rhizoma anemarrhenae, 8-15 parts of sophora flavescens, 8-15 parts of sesame seeds, 8-15 parts of schizonepeta, 8-15 parts of atractylodes, 8-15 parts of burdock seeds, 8-15 parts of gypsum, 3-8 parts of liquorice, 3-8 parts of akebia, 8-15 parts of ebony, 10-20 parts of lithospermum officinale, 8-15 parts of cnidium monnieri, and 8-15 parts of duckweed.

[0008] Xiaofeng Zhiyang Granules are made from 11 kinds of herbs, including Saposhnikovia divaricata, Chanchu, Digupi, Rhizoma Atractylodis Macrocephalae, Linseed, Angelica sinensis, Rehmannia glutinosa, Akebia, Nepeta tenuifolia, Gypsum, and Licorice. It has the effects of eliminating wind and clearing heat, removing dampness and relieving itching. It is mainly used for papular urticaria, eczema, and skin pruritus. It is a commonly used Chinese patent medicine for the clinical treatment of eczema. Summary of the invention

[0009] The traditional Chinese medicine composition of the invention is composed of safflower clover root, sophora flavescens, fried burdock fruit, siler, schizonepeta, cicada shell, rhizome of anemarrhena, canna seed, yew bark and camphor root.

[0010] Preferably, the Chinese medicine composition described in the present application is made of the following raw materials in the following weight proportions: 18-20 parts of red peony root, 6-8 parts of sophora flavescens, 8-10 parts of stir-fried burdock seeds, 8-10 parts of siler, 8-10 parts of schizonepeta, 4-6 parts of cicada shells, 8-10 parts of anemarrhena, 6-8 parts of hemp seed, 5-7 parts of yew bark, and 13-15 parts of camphor tree root.

[0011] Preferably, the Chinese medicine composition described in the present application is made of the following raw materials in the following weight proportions: 18 parts of red peony root, 6 parts of sophora flavescens, 8 parts of stir-fried burdock seeds, 8 parts of siler, 8 parts of schizonepeta, 4 parts of cicada shells, 8 parts of anemarrhena, 6 parts of hemp seed, 5 parts of yew bark, and 13 parts of camphor tree root.

[0012] Preferably, the Chinese medicine composition described in the present application is made of the following raw materials in the following weight proportions: 20 parts of red peony root, 8 parts of sophora flavescens, 10 parts of stir-fried burdock seeds, 10 parts of siler, 10 parts of schizonepeta, 6 parts of cicada shells, 10 parts of anemarrhena, 8 parts of hemp seed, 7 parts of yew bark, and 15 parts of camphor tree root.

[0013] Preferably, the Chinese medicine composition described in the present application is made of the following raw materials in the following weight proportions: 19 parts of red peony root, 7 parts of sophora flavescens, 9 parts of stir-fried burdock seeds, 9 parts of siler, 9 parts of schizonepeta, 5 parts of cicada shells, 9 parts of anemarrhena, 7 parts of hemp seed, 6 parts of yew bark, and 14 parts of camphor tree root.

[0014] Preferably, the Chinese medicine composition described in the present application is made of the following raw materials in the following weight proportions: 20 parts of red peony root, 8 parts of sophora flavescens, 8 parts of stir-fried burdock seeds, 9 parts of siler, 10 parts of schizonepeta, 6 parts of cicada shells, 8 parts of anemarrhena asphodeloides, 8 parts of hemp seed, 7 parts of taxus bark, and 14 parts of camphor tree root.

[0015] Secondly, the present application discloses a method for preparing the above-mentioned Chinese medicine composition, as follows:

[0016] Step 1) according to the raw material ratio of the composition, add water and boil twice, each time for 1 to 2 hours, filter and combine the filtrate;

[0017] Step 2) taking the filtrate obtained in step 1) and concentrating it under reduced pressure at 60-80° C. to obtain an extract concentrate;

[0018] Step 3) Take the extract obtained in step 2), dry it under reduced pressure at 60-80°C to obtain a dry paste, grind it, add appropriate amount of auxiliary materials and adhesives to granulate, and dry it.

[0019] The auxiliary material is dextrin, and its usage amount is the same as the weight of the crushed dry paste.

[0020] The adhesive is 70% to 95% ethanol.

[0021] The granules obtained by the above process are yellow-brown or brown, fragrant, slightly bitter, and the particle size meets the requirements of the granules in the general rules for preparations of Part IV of the 2020 edition of the Chinese Pharmacopoeia.

[0022] Each gram of granules contains not less than 0.5 mg of Sophora flavescens in terms of matrine, and not less than 0.4 mg of Saposhnikovia divaricata in terms of the total amount of cimicifuga glycosides and 5-O-methylvisaminoid glycosides.

[0023] The above-mentioned particles can be further added with pharmaceutically acceptable excipients to be further prepared into capsules, tablets, granules, pastes and the like.

[0024] Finally, the present application discloses the use of the above-mentioned Chinese medicine composition for preparing a medicine for treating eczema.

[0025] The functions and indications of each Chinese herbal medicine in the above composition are as follows:

[0026] Red flower stinking peony root, fragrant, slightly sweet, cool; in water, soil, wind tower; replenishes soil and strengthens the stomach, clears heat and detoxifies, removes wind and relieves pain, activates blood circulation and stops bleeding;

[0027] Sophora flavescens, bitter, cold; clears heat and dries dampness, diuretic;

[0028] Fried burdock seeds are pungent, bitter, and cold; they can dispel wind-heat, clear the lungs and relieve rashes, and detoxify and relieve sore throats.

[0029] Fangfeng, pungent, sweet, slightly warm; dispel wind and relieve exterior symptoms, overcome dampness and relieve pain;

[0030] Schizonepeta, pungent, slightly warm; dispels wind, clears rashes, and eliminates sores;

[0031] Anemarrhena, bitter, sweet, cold; clears heat and purges fire, nourishes yin and moistens dryness;

[0032] Hemp seed, sweet, flat; moisturizes the intestines and promotes bowel movements;

[0033] Cicada slough, sweet, cold; dispel wind-heat, relieve sore throat, and promote rash;

[0034] Taxus bark, slightly sweet, bitter, neutral; regulates menstruation and promotes urination;

[0035] Camphor tree root is pungent and warm; it can dispel rheumatism, benefit joints, and promote qi and blood circulation.

[0036] In the Chinese medicine composition of the present invention, the root of red flower stinking peony root can promote blood circulation and stop bleeding, dispel wind and relieve pain, clear away heat and detoxify, and also nourish the spleen and strengthen the stomach, so as to eliminate evil without hurting the body; the bitter taste of sophora flavescens is cold in nature, clears away heat, dries dampness and relieves itching, and is an important medicine for treating skin diseases caused by damp heat; the burdock seed is bitter and cold, can expel heat and toxins, dispel wind and relieve itching, and can be fried to slightly reduce the bitter, cold and laxative properties, and the three are combined and serve as the main medicine;

[0037] Schizonepeta and Saposhnikovia are the assistant herbs. They are pungent and warm in nature, and can dispel wind evil on the surface. They are combined with Sophora flavescens and Arctium lappa, and are used with both pungent and warm properties, and pungent and cool properties, to dispel wind and expel evil, open the pores, and have the effect of dispelling wind and relieving itching.

[0038] When wind evil invades the human body, it cannot be vented inside and cannot penetrate outside, which is easy to turn into heat, so Zhimu is used to clear heat and nourish Yin; wind-heat or rheumatism infiltrates the blood vessels and damages Yin blood, Wuhuo Ma Ren is moist and fat-rich, moistens the intestines and promotes bowel movements, facilitates the intestines and viscera to help the lungs and guard against the spread of qi, and nourishes and replenishes deficiency; cicada slough is used to disperse and release hair, and is used to disperse wind-heat, clear rashes and relieve itching; and camphor tree roots, which are slightly warm and spicy, are used to dispel wind and cold, promote blood circulation and remove blood stasis, and relieve pain. The above five flavors are used as adjuvants;

[0039] The bark of Taxus chinensis can reduce swelling and resolve nodules, and also has the function of guiding drugs to the skin, so it is called a guiding drug.

[0040] The combination of these medicines, bitter, dry, pungent, dispersing, sweet and moistening, has the effect of dispersing, activating, clearing and facilitating, while also nourishing, and together they have the effect of dispersing wind and dampness, clearing away heat and activating blood circulation.

[0041] The Chinese medicine composition of the present invention inherits the classic ancient prescription "Xiaofengsan" and combines it with the traditional Chinese medicine "butu" theory, conforms to the theory of traditional Chinese medicine, and is mainly used to treat eczema, especially acute eczema.

[0042] The Chinese medicine composition of the present invention, on the basis of "tonifying earth" to strengthen the spleen and promote blood circulation, can dispel wind and dampness, clear away heat and promote blood circulation, and achieves the goal of treating both the symptoms and the root causes of eczema. The curative effect is clear and the disease is not likely to relapse after drug withdrawal, which fundamentally solves the problem of repeated attacks of eczema caused by weak spleen and stomach in patients.

[0043] The Chinese medicine composition of the present invention can have an obvious anti-eczema effect on the Balb / c mouse eczema model, and the effect increases with the increase of the dosage. The therapeutic effect on erythema, epidermal exfoliation and lichenification of eczema model animals is significantly better than the commonly used Chinese patent medicine Xiaofeng Zhiyang granules for this indication.

[0044] The Chinese medicine composition provided by the present invention was clinically observed for efficacy on 43 outpatients with acute eczema at Hangzhou Boruitang TCM Clinic and Hangzhou Lin'an District TCM Hospital. The patients took one dose a day, twice a day, morning and evening, for a course of treatment of 10 days, and 3 to 4 courses of treatment from the date of treatment were the duration. As a result, 28 cases were cured, 9 cases were markedly effective, 5 cases were effective, and 1 case was ineffective; the total effective rate reached 97.6%, of which the cure rate was 65.1%. DETAILED DESCRIPTION

[0045] The present invention is further described in detail by way of examples below. The following examples are explanations of the present invention, but the examples do not limit the present invention in any form. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the art.

[0046] Comparative Example 1 A medicinal material mixed powder sample was prepared with reference to Example 2 of Chinese invention patent application CN101214345B, which is the Comparative Example 1 sample.

[0047] Example 1 Preparation of Chinese medicine composition

[0048] Each dose includes the following raw materials in weight ratio:

[0049] 18 parts of red flower stinking peony root, 6 parts of sophora flavescens, 8 parts of fried burdock seeds, 8 parts of siler, 8 parts of schizonepeta, 4 parts of pericarp of cicada, 8 parts of rhizoma anemarrhenae, 6 parts of fructus hemp, 5 parts of bark of taxus, and 13 parts of camphor tree roots.

[0050] Preparation method:

[0051] The above raw material pieces are decocted with water for 2 times, the first time for 2 hours, filtered, the residue is added with water, decocted for another hour, filtered, the filtrate is combined, and concentrated to obtain an extract. The obtained extract is dried under reduced pressure at 60-80°C, crushed through an 80-mesh sieve, an equal amount of dextrin is added, wet granulated with 70%-95% ethanol, dried under reduced pressure at 55-80°C, and granulated through a 10-mesh sieve.

[0052] Each gram of granules contains 1.65 mg of matrine and a total of 0.82 mg of cimicifuga glycosides and 5-O-methylvisaminol glycosides from fangfeng.

[0053] Example 2 Preparation of Chinese medicine composition

[0054] Each dose includes the following raw materials in weight ratio:

[0055] 20 parts of red flower stinking peony root, 8 parts of sophora flavescens, 10 parts of fried burdock fruits, 10 parts of siler, 10 parts of schizonepeta, 6 parts of pericarp of cicada, 10 parts of rhizoma anemarrhenae, 8 parts of fructus hemp, 7 parts of bark of taxus, and 15 parts of camphor tree roots.

[0056] Preparation method:

[0057] The above raw material pieces are decocted with water for 2 times, the first time for 2 hours, filtered, the residue is added with water, decocted for another hour, filtered, the filtrate is combined, and concentrated to obtain an extract. The obtained extract is dried under reduced pressure at 60-80°C, crushed through an 80-mesh sieve, an equal amount of dextrin is added, wet granulated with 70%-95% ethanol, dried under reduced pressure at 55-80°C, and granulated through a 10-mesh sieve.

[0058] Each gram of granules contains 2.21 mg of matrine and a total of 1.02 mg of cimicifuga glycosides and 5-O-methylvisaminoid glycosides from fangfeng.

[0059] Example 3 Preparation of Chinese medicine composition

[0060] Each dose includes the following raw materials in weight ratio:

[0061] 19 parts of red flower stinking peony root, 7 parts of sophora flavescens, 9 parts of fried burdock seeds, 9 parts of siler, 9 parts of schizonepeta, 5 parts of cicada shells, 9 parts of anemarrhena, 7 parts of canna seed, 6 parts of taxus bark, and 14 parts of camphor tree root.

[0062] Preparation method:

[0063] The above raw material pieces are decocted with water for 2 times, the first time for 2 hours, filtered, the residue is added with water, decocted for another hour, filtered, the filtrate is combined, and concentrated to obtain an extract. The obtained extract is dried under reduced pressure at 60-80°C, crushed through an 80-mesh sieve, an equal amount of dextrin is added, wet granulated with 70%-95% ethanol, dried under reduced pressure at 55-80°C, and granulated through a 10-mesh sieve.

[0064] Each gram of granules contains 1.93 mg of matrine and a total of 0.90 mg of cimicifuga glycosides and 5-O-methylvisaminol glycosides from fangfeng.

[0065] Example 4 Preparation of Chinese medicine composition

[0066] Each dose includes the following raw materials in weight ratio:

[0067] 20 parts of red flower stinking peony root, 8 parts of sophora flavescens, 8 parts of fried burdock seeds, 9 parts of siler, 10 parts of schizonepeta, 6 parts of pericarp of cicada, 8 parts of rhizoma anemarrhenae, 8 parts of fructus hemp, 7 parts of bark of taxus, and 14 parts of camphor tree roots.

[0068] Preparation method:

[0069] The above raw material pieces are decocted with water for 2 times, the first time for 2 hours, filtered, the residue is added with water, decocted for another hour, filtered, the filtrate is combined, and concentrated to obtain an extract. The obtained extract is dried under reduced pressure at 60-80°C, crushed through an 80-mesh sieve, an equal amount of dextrin is added, wet granulated with 70%-95% ethanol, dried under reduced pressure at 55-80°C, and granulated through a 10-mesh sieve.

[0070] Each gram of granules contains 2.2 mg of matrine and a total of 0.92 mg of cimicifuga glycosides and 5-O-methylvisaminol glycosides from fangfeng.

[0071] Example 5 Toxicity test in SD rats by intragastric administration

[0072] The toxicity of the granule sample obtained in Example 4 was investigated after being intragastrically administered to SD rats for four consecutive weeks.

[0073] 1. Methods:

[0074] 40 SD rats that passed the quarantine were randomly divided into a vehicle control group (pure water) and low, medium and high dose groups (3, 6, 12 g / kg / day), 10 rats in each group, half male and half female, and gavaged with the corresponding drug preparation at a volume of 15 mL / kg, twice a day (5 h ± 30 min interval), for 28 consecutive days. The first day of administration was defined as the first day of the experiment (D1).

[0075] During the experiment, clinical observation was performed every day, and body weight and food intake were measured twice a week. After the administration, all animals were subjected to hematology, coagulation and serum biochemical tests, as well as gross observation, organ weighing and histopathological examination.

[0076] 2. Materials and Instruments

[0077] 2.1 Experimental animals and feeding

[0078] 44 SPF SD rats, half male and half female, were purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd. After 5 days of adaptive feeding, the animals were grouped. The weight range of the animals at the time of grouping was 180.3g-206.2g for females and 219.7g-241.5g for males. The age at the start of drug administration was 41-54 days old. During the animal experiment, the animals were allowed to drink water and eat freely unless otherwise specified.

[0079] After purchase, the animals were kept in the SPF animal room on the fourth floor of the New Drug Evaluation Center of Shandong Academy of Pharmaceutical Sciences. The experimental institution use license number is: SYKX (Lu) 20180031. The animals were kept in rat breeding boxes, and males and females were kept separately, with 5 rats in each cage.

[0080] 2.2 Trial drug ZY21007

[0081] 2.3 Main reagents and instruments

[0082] 50(France Virbac Co., Ltd.)

[0083] Xylazine Hydrochloride Injection (Changsha Beit Biotechnology Research Institute Co., Ltd.)

[0084] UW2200H electronic balance (Shimadzu, Japan)

[0085] 7180 fully automatic biochemical analyzer (Hitachi High-Tech Co., Ltd., Japan)

[0086] SYSMEX CA1500 fully automatic coagulation analyzer (Sysmex, Japan)

[0087] SYSMEX XT-2000iv fully automatic blood analyzer (Sysmex, Japan)

[0088] 3. Test methods

[0089] 3.1 Animal grouping

[0090] The Provantis built-in grouping module was used to allocate the 40 qualified animals to 4 groups according to gender and weight. The specific grouping information is shown in Table 1. The weight difference of the animals did not exceed 20% of their respective average weights.

[0091] Table 1 Animal grouping and identification

[0092]

[0093] Note: The animal number is 4 digits. The thousands digit represents the group number. The hundreds digit represents the sex of the animal. “1” represents female and “2” represents male. The last two digits represent the sequence number of the sex of the animal in the group.

[0094] 3.2 Dosage design

[0095] The proposed clinical dosage of this product is to be taken orally once a day in the morning and evening, which is equivalent to 98g of crude drug. Each 1g of dry powder is equivalent to 7.6g of crude drug, and each 2g of granules is approximately equivalent to 7.6g of crude drug. The proposed clinical dosage of dry powder is 0.18g / kg / day, calculated based on an adult body weight of 70kg. After preliminary concentration exploration, the maximum feasible concentration of 0.4g / mL was explored using the TFEP-003 2.5*75mm disposable gavage device.

[0096] Based on the above information, this trial was designed to administer the drug twice a day, with a high dose of 12g / kg / day, a medium dose of 6g / kg / day, and a low dose of 3g / kg / day, respectively, and a dosing volume of 15mL / kg / time, which are approximately 67 times, 33 times, and 17 times the intended clinical dose, respectively. A solvent control group (pure water) was also set up.

[0097] Table 2 Dosage design table

[0098]

[0099] 3.3 Administration

[0100] Route of administration: oral administration.

[0101] Dosage frequency: 2 times a day, with an interval of 5h±30min.

[0102] Dosage cycle: Continuous administration for 28 days.

[0103] Dosing volume: 15mL / kg.

[0104] The dosage was calculated based on the latest animal weight. The test group drug preparation was stirred in an appropriate amount of pure water at room temperature for at least 10 minutes before administration and visually observed to be uniformly suspended. Stirring was required during administration.

[0105] 3.4 Observation indicators and detection methods

[0106] 3.4.1 Clinical observation

[0107] During the dosing period, clinical observations of the animals were conducted once before dosing in the morning and once after dosing in the afternoon, including but not limited to appearance, physical signs, behavioral activities, glandular secretions, respiration, fecal characteristics, death, etc.

[0108] 3.4.2 Weight

[0109] The body weight of the animals was measured twice a week (D3, D6, D10, D13, D17, D20, D24, and D27).

[0110] 3.4.3 Food intake

[0111] The food intake of animals was measured twice a week (D2, D5, D9, D12, D16, D19, D23, and D26).

[0112] 3.4.4 Clinical pathological examination

[0113] Each group planned to dissect the animals on D29 to collect blood samples from the abdominal aorta. All animals were fasted overnight (12h-18h) before sample collection, but water was not prohibited. Sample testing parameters are as follows:

[0114] Table 3 Hematological indicators

[0115]

[0116] Table 4 Blood coagulation index

[0117]

[0118]

[0119] Table 5 Serum biochemical indexes

[0120]

[0121] 3.4.5 Animal autopsy and pathological examination

[0122] All animals were dissected on D29. The body surface of the animals was observed grossly during the dissection. The organs listed in Table 6 were weighed and the organ system coefficient and organ-brain coefficient were calculated. The heart, liver, spleen, lung, kidney, and thymus of the animals in each group were fixed in 10% neutral formalin and subjected to histopathological examination.

[0123] Table 6 Organ weights

[0124]

[0125] 4. Test results

[0126] 4.1 Clinical observation

[0127] During the test, no animal died / moribund in any group. No abnormalities were observed in the clinical observation of male and female animals in the vehicle control group; male and female animals in the 3, 6, and 12 g / kg / day dose groups showed salivation after about 2 weeks of administration, which lasted until the end of administration; male and female animals in the 12 g / kg / day dose group showed fecal discoloration (drug-like color) from D3, which lasted until the end of administration. In addition, no abnormal manifestations related to the test product were observed in the animals in each group.

[0128] 4.2 Weight

[0129] During the test, the body weights of male and female animals in the vehicle control group increased normally. Compared with the vehicle control group, the body weight of male rats D6 in the 12g / kg / day dose group decreased (P<0.05). Considering that the changes were only at individual time points without obvious time relationship, it was considered to have no toxicological significance. In addition, there was no statistical difference in the body weights of male and female animals in each dose group compared with the vehicle control group (P>0.05).

[0130] 4.3 Food intake

[0131] During the test, no obvious abnormality was observed in the food intake of male and female animals in the vehicle control group; compared with the vehicle control group, the food intake of D2 of female rats in the 3, 6, and 12g / kg / day dose groups decreased, the food intake of D2 of male rats in the 6g / kg / day dose group, and the food intake of D2 and D5 of male rats in the 12g / kg / day dose group decreased; considering that the above changes in food intake were transient and had no obvious time relationship, they were considered to have no toxicological significance. In addition, the food intake of male and female animals in each dose group at each time point did not fluctuate much compared with the vehicle control group.

[0132] 4.4 Hematological indicators

[0133] At the end of the administration, the hematological indicators of the animals were tested. The results showed that compared with the vehicle control group, the HGB of male rats in the 12g / kg / day dose group decreased and RET% increased, and the difference was statistically significant (P<0.05); although there was no statistically significant decrease in RBC of male rats and RBC and HGB of female rats, a decreasing trend was observed. Although RBC and HGB of the above indicators were within the background data range of this institution, it still suggests that the changes in red blood cell indicators should be paid attention to in subsequent repeated administration trials.

[0134] The specific changes are as follows:

[0135]

[0136] Note: * indicates comparison with the vehicle control group, P < 0.05; ↓ indicates decrease, ↑ indicates increase.

[0137] 4.5 Coagulation index

[0138] At the end of administration, the blood coagulation indexes of the animals were tested, and the results showed that compared with the solvent control group, there were no abnormal changes in PT, APTT, TT, and FIB of male and female animals in each group.

[0139] 4.6 Serum biochemical indexes

[0140] At the end of the administration, the serum biochemical indexes of the animals were tested. The results showed that compared with the vehicle control group, the Urea of ​​male rats in the 12g / kg / day dose group increased (P<0.05), but no relevant pathological changes were found in the kidneys by histopathological examination. In addition, the TC of female rats in the 3, 6, and 12g / kg / day dose groups increased (P<0.05). In addition, although the individual indexes of each dose group showed statistical differences compared with the vehicle control group (P<0.05), the changes were small and all within the background data range of this institution, and were considered to have no toxicological significance.

[0141] The specific changes are as follows:

[0142]

[0143] Note: * indicates comparison with the vehicle control group, P < 0.05; ↑ indicates increase.

[0144] 4.7 Organ weight and coefficient

[0145] At the end of the administration, the weight and coefficient of the animals' organs were measured. The results showed that compared with the vehicle control group, the liver weight and organ coefficient of male and female animals in the 12g / kg / day dose group increased (P<0.05). In addition, although the weight and coefficient of individual organs of animals in each group were statistically different from those in the vehicle control group (P<0.05), no relevant pathological changes were observed, and it was considered to have no toxicological significance.

[0146] The specific changes are as follows:

[0147]

[0148] Note: * indicates P < 0.05 compared with the vehicle control group; ↓ indicates a decrease.

[0149] 4.8 Gross Observation and Histopathological Examination

[0150] At the end of drug administration, gross anatomical observations were performed on the animals in each group, and no macroscopic morphological changes related to the test article were observed.

[0151] The results of histopathological examination showed that no pathological changes related to the test article were found in male and female animals in the 3 and 6 g / kg / day dose groups. Obvious pathological changes in the livers of male and female animals in the 12 g / kg / day dose group were manifested as diffuse hypertrophy of central lobular hepatocytes. The degree of lesions was mild and the incidence rate was high, which was considered to be related to the test article. Combined with the analysis that no abnormalities were found in liver function-related indicators, it was considered that this mild lesion related to the test article was not an adverse reaction, but it still suggested that the effect of the test article on liver function should be focused on in subsequent long-term toxicity tests.

[0152] 5. Experimental conclusion

[0153] Under the conditions of this experiment, SD rats were gavaged with 3, 6, and 12 g / kg / day of the granule sample of Example 4 of the present application, twice a day, for 28 consecutive days, and the no observed adverse effect level (NOAEL) was 12 g / kg / day.

[0154] Example 6 Effect of Chinese medicine composition on eczema mouse model

[0155] 1. Methods:

[0156] 1.1 Animal grouping

[0157] 100 Balb / c mice were selected and divided into a normal control group, a model control group, a Xiaofeng Zhiyang granule 11.7 g / kg control group, a sample group of comparative example 1 (1.25 g / kg), high-dose groups of Example 1, Example 2, and Example 3 of the present invention (6.8 g / kg), and low-, medium-, and high-dose groups of the Chinese medicine composition of Example 4 (2.4 g / kg, 3.4 g / kg, and 6.8 g / kg), with a total of 10 groups, each with 10 animals, half of which were male and half were female.

[0158] 1.2 Basis for dosage design

[0159] The clinical daily dosage of the prescription of the present invention is 98g of crude drug. 2g of the granule sample of Example 4 is approximately equivalent to 7.6g of crude drug, and the human dosage of the granule sample of Example 4 is approximately 25.78g / day / person, and the equivalent dose for mice is: 25.78×0.0026÷0.02≈3.36g / kg.

[0160] Each capsule of the sample of comparative example 1 contains 0.5-0.8g of crude drug, and the clinical daily dosage is 4 capsules each time, 3 times a day. According to this calculation, the daily clinical dosage of the sample of comparative example 1 is 6.0g-9.6g of crude drug (according to the description of paragraphs 0010-0011 of the specification of CN101214345B). Here, 9.6g of crude drug is used. The equivalent dose for mice is converted to: 9.6×0.0026÷0.02≈1.25g / kg.

[0161] Xiaofeng Zhiyang Granules eliminate wind, clear heat, remove dampness and stop itching. It is mainly used to treat papular urticaria, and is also used for eczema and skin pruritus. It is a commonly used Chinese patent medicine for the clinical treatment of eczema. The clinical human dosage is 6 bags per day, each bag is 15g, and is taken in 2 to 3 times. Based on 90g / person per day, the equivalent dose for mice is: 90×0.0026÷0.02=11.7g / kg.

[0162] According to the above usage and dosage and taking into account the convenience of preparation, the low dose of the granule sample in Example 4 is designed to be 2.40 g / kg, the medium dose is 3.40 g / kg, and the high dose is 6.80 g / kg. The dose of Xiaofeng Zhiyang Granules is 11.70 g / kg. At the same time, in order to prove the efficacy, the granule samples of Examples 1-3 are designed to be administered at a high dose (6.80 g / kg).

[0163] 1.3 Sample preparation

[0164] Low-dose group of the granule sample of Example 4: 4.80 g of the granule sample of Example 4 was weighed and diluted to 40 mL with pure water to prepare a low-dose suspension of the granule sample of Example 4 with a concentration of 0.120 g / mL.

[0165] Medium dose group of the granule sample of Example 4: 6.80 g of the granule sample of Example 4 was weighed and diluted to 40 mL with pure water to prepare a medium dose suspension of the granule sample of Example 4 with a concentration of 0.170 g / mL.

[0166] High-dose group of the granule sample of Example 4: 13.60 g of the granule sample of Example 4 was weighed and diluted to 40 mL with pure water to prepare a high-dose suspension of the granule sample of Example 4 with a concentration of 0.340 g / mL.

[0167] High-dose group of the granule sample of Example 1: 13.60 g of the granule sample of Example 1 was weighed and diluted to 40 mL with pure water to prepare a high-dose suspension of the granule sample of Example 1 with a concentration of 0.340 g / mL.

[0168] High-dose group of the granule sample of Example 2: 13.60 g of the granule sample of Example 2 was weighed and diluted to 40 mL with pure water to prepare a high-dose suspension of the granule sample of Example 2 with a concentration of 0.340 g / mL.

[0169] High-dose group of the granule sample of Example 3: 13.60 g of the granule sample of Example 3 was weighed and diluted to 40 mL with pure water to prepare a high-dose suspension of the granule sample of Example 3 with a concentration of 0.340 g / mL.

[0170] Xiaofeng Zhiyang Granule Control Group: Weigh 15.21 g of Xiaofeng Zhiyang Granule and dilute it to 26 mL with pure water to prepare a Xiaofeng Zhiyang Granule Control Group suspension with a concentration of 0.585 g / mL.

[0171] Comparative Example 1 sample: Weigh 2.5 g of the comparative example 1 sample and dilute it to 40 mL with pure water to prepare a high-dose suspension of the mixed powder sample of comparative example 1 with a concentration of 0.0625 g / mL.

[0172] 1.4 Model preparation

[0173] One day before sensitization (D0), All the hair on the abdomen of the mice was removed, and the depilated area was about 3cm×3cm. During sensitization, 25μL of acetone solution was applied to the depilated area on the abdomen of the animals in the normal control group, and 25μL of 7% 2,4-dinitrochlorobenzene solution was applied to the depilated area on the abdomen of the animals in the other groups for the first sensitization, and the same method was used to strengthen it once more on the second day.

[0174] Use on the 4th day after the first sensitization All the hair on the back of the mice was removed, and the depilated area was about 5cm×3cm. The next day, the first stimulation was performed. The normal control group was smeared with 20μL of acetone solution on the depilated area on the back of the mice, and the other groups of mice were smeared with 20μL of 1% 2,4-dinitrochlorobenzene solution on the depilated area on the back for stimulation. The smearing area was about 2cm×2cm, and it was performed once every 3 days for a total of 4 times.

[0175] 1.5 Administration

[0176] Gavage administration began on the day of the first sensitization. The normal control group and the model control group were given pure water, and the Xiaofeng Zhiyang granule control group and the test article groups were given the corresponding test article solution / suspension. The administration volume was 20 mL / kg, and it was given continuously until the last stimulation day, for a total of 18 days.

[0177] 2 Observation and scoring of animal sensitization and stimulation areas

[0178] The skin reactions at the sensitized sites of the animals were observed and recorded daily during the sensitization period. The skin reactions at the sensitized sites of the animals in each group were observed and recorded by taking photos 24 hours after each stimulation.

[0179] After each challenge, the EASI scoring method was used to classify and score the symptoms of erythema (E), hard swelling (edema) / papule (I), epidermal exfoliation (Ex), lichenification (L), exudation / scab (S) at the challenge site of the mouse as described in Tables 1 and 2. The score should be judged by three trained testers, and the average score of the three people was used as the final score of the animal. Each animal was scored four times in total.

[0180] Table 7 Evaluation of eczema skin symptoms

[0181]

[0182] Table 8 Scoring criteria for eczema skin symptoms

[0183]

[0184] Note: Half a grade, i.e. 0.5, can be recorded between various symptom scores. EASI score = E+I+Ex+L+S.

[0185] The EASI scores of animals in each group are summarized in Table 9.

[0186] Table 9 Summary of animal EASI scores ( n=10)

[0187]

[0188]

[0189] Note: #P<0.05, ##P<0.01 each group compared with the model control group; ★P<0.05 the medium dose group of the granule sample of Example 4 compared with the Xiaofeng Zhiyang granule control group.

[0190] 3. Results and Conclusions

[0191] The skin lesions of the modeling sites on the backs of the animals in each group of the granule samples of Examples 1-4 were observed with naked eyes better than those in the model control group, and the EASI scores were lower than those in the model control group of the same period (P < 0.05 or P < 0.01). Compared with the control group of Xiaofeng Zhiyang granules in the same period, the granule samples of Examples 1-4 took effect more quickly, as shown in the second and third scoring, the scores of the high-dose group of the granule samples of Examples 1-3, and the medium and high-dose groups of the granule samples of Example 4 were better than those of the control group of Xiaofeng Zhiyang granules, especially the high-dose group of Examples 1-4.

[0192] At the same time, since the medicinal materials Sophora flavescens, Nepeta tenuifolia, Fructus arctii, Periostracum cicadae and Rhizoma Anemarrhenae used in the sample of Comparative Example 1 are also used in the Chinese medicine composition of the present application. Therefore, it is used as a comparative example to further illustrate the efficacy of the Chinese medicine composition of the present application. Experiments have shown that the sample of Comparative Example 1 does have a certain effect in the treatment of eczema in model animals, which is basically equivalent to Xiaofeng Zhiyang Granules, and is even slightly better than Xiaofeng Zhiyang Granules, which is specifically manifested in that the second and third scores of the sample of Comparative Example 1 are slightly lower than those of Xiaofeng Zhiyang Granules.

[0193] However, compared with the Chinese medicine composition of the present application, the second and third scores of the sample in Comparative Example 1 are significantly higher than the high-dose group in Examples 1-3 of the present application and the high-dose group in Example 4, proving that the Chinese medicine composition described in the present application has better therapeutic effects on eczema model animals at medium and high dose levels than Comparative Example 1. This proves that although the Chinese medicine composition described in the present application and Comparative Example 1 have the same five medicinal materials, the difference in their therapeutic effects is caused by the differentiated medicinal material composition of the Chinese medicine composition described in the present application and Comparative Example 1. Ultimately, the Chinese medicine composition described in the present application has a better therapeutic effect on eczema than Comparative Example 1.

[0194] The above invention contents and embodiments describe the basic principles and main features of the patent application of the present invention and the advantages of the patent application of the present invention. Those skilled in the art should understand that the patent application of the present invention is not limited by the above embodiments. The above embodiments and the specification only describe the optimal technical solutions of the patent application of the present invention. Without departing from the spirit and scope of the patent application of the present invention, the patent application of the present invention may have various changes and improvements, that is, the Chinese medicine composition composed of the various medicinal materials described in this application and the use thereof for preparing eczema treatment drugs are within the scope of the patent application of the present invention, and the scope of protection claimed in the patent application of the present invention is defined by the attached claims and their equivalents.

Claims

1. A Chinese medicine composition for treating eczema, characterized in that: The Chinese medicine composition is prepared from the following raw materials in proportion by weight: 18-20 parts of safflower clover root, 6-8 parts of sophora flavescens, 8-10 parts of stir-fried burdock seeds, 8-10 parts of siler, 8-10 parts of schizonepeta tenuifolia, 4-6 parts of cicada slough, 8-10 parts of anemarrhena asphodeloides, 6-8 parts of hemp seeds, 5-7 parts of yew bark, and 13-15 parts of camphor tree roots.

2. The Chinese medicine composition according to claim 1, characterized in that The Chinese medicine composition is prepared from the following raw materials in proportion by weight: 18 parts of red clover root, 6 parts of sophora flavescens, 8 parts of fried burdock seeds, 8 parts of siler, 8 parts of schizonepeta, 4 parts of cicada shells, 8 parts of anemarrhena, 6 parts of hemp seeds, 5 parts of yew bark, and 13 parts of camphor tree roots.

3. The Chinese medicine composition according to claim 1, characterized in that: The Chinese medicine composition is prepared from the following raw materials in proportion by weight: 20 parts of safflower peony root, 8 parts of sophora flavescens, 10 parts of stir-fried burdock seeds, 10 parts of siler, 10 parts of schizonepeta tenuifolia, 6 parts of cicada shells, 10 parts of anemarrhena asphodeloides, 8 parts of hemp seeds, 7 parts of yew barks and 15 parts of camphor tree roots.

4. The Chinese medicine composition according to claim 1, characterized in that: The Chinese medicine composition is prepared from the following raw materials in proportion by weight: 19 parts of safflower peony root, 7 parts of sophora flavescens, 9 parts of fried burdock seeds, 9 parts of siler, 9 parts of schizonepeta tenuifolia, 5 parts of cicada shells, 9 parts of anemarrhena asphodeloides, 7 parts of hemp seeds, 6 parts of yew bark, and 14 parts of camphor tree roots.

5. The Chinese medicine composition according to claim 1, characterized in that: The traditional Chinese medicine composition is prepared from the following raw materials in proportion by weight: 20 parts of safflower peony root, 8 parts of sophora flavescens, 8 parts of fried burdock seeds, 9 parts of siler, 10 parts of schizonepeta, 6 parts of cicada shells, 8 parts of anemarrhena, 8 parts of hemp seeds, 7 parts of yew bark and 14 parts of camphor tree roots.

6. The Chinese medicine composition according to any one of claims 1 to 5, characterized in that: The preparation method is as follows: Step 1) according to the raw material ratio of the composition, add water and boil twice, each time for 1 to 2 hours, filter and combine the filtrate; Step 2) taking the filtrate obtained in step 1), concentrating under reduced pressure at 60-80° C. to obtain an extract concentrate; Step 3) The extract obtained in step 2) is dried under reduced pressure at 60-80°C to obtain a dry paste, which is crushed, granulated with dextrin and 70%-95% ethanol, and dried; The amount of dextrin used is the same as the weight of the crushed dry paste.

7. The Chinese medicine composition according to claim 6, characterized in that: The Chinese medicine composition contains no less than 0.5 mg of Sophora flavescens in terms of matrine per gram of granules, and no less than 0.4 mg of Saposhnikovia divaricata in terms of the total amount of cimicifuga glycosides and 5-O-methylvisaminol glycosides.

8. Use of the Chinese medicine composition according to any one of claims 1 to 5 in the preparation of a medicament for treating eczema.

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