Traditional Chinese medicine composition as well as preparation method and application thereof

Abstract

The invention provides a traditional Chinese medicine composition as well as a preparation method and application thereof. The traditional Chinese medicine composition is prepared from the following medicinal raw materials: radix angelicae sinensis, radix rehmanniae preparata, rhizoma atractylodis macrocephalae, radix saposhnikoviae, radix astragali seu hedysari, radix polygoni multiflori, rhizoma gastrodiae, cortex dictamni, herba schizonepetae and radix glycyrrhizae. The traditional Chinese medicine composition and the traditional Chinese medicine preparation provided by the invention can remarkably relieve neurodermatitis and symptoms such as pruritus or edema caused by neurodermatitis, adopt pure natural plant raw materials, have no obvious adverse reaction in the use process of a patient, and can be used as a candidate medicine for treating neurodermatitis.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of medicine, and particularly relates to a traditional Chinese medicine composition and a preparation method and use thereof. BACKGROUND

[0002] Neurodermatitis, also known as chronic simple lichen in medicine, is a common chronic inflammatory skin disease characterized by paroxysmal severe itching and skin lichenoid change, and is divided into localized and disseminated. Of course, there are also views that part of neurodermatitis may be a skin manifestation of atopic dermatitis. Localized neurodermatitis is prone to occur in the neck side, nape, elbow fossa, waist, inner thigh, perineum, scrotum and other folded parts of young and middle-aged people. It is manifested as normal skin color, light red, brown yellow flat papules of pinhead size or slightly larger, smooth surface or a small amount of scales, most of which are densely packed into patches, showing lichenoid change or pigmentation. The skin of the affected part is dry, infiltrated and thickened, and there may be scratches, blood scabs and mild pigmentation on the surface, and the patient feels paroxysmal itching. Disseminated neurodermatitis is prone to occur in adults and the elderly, and in addition to the above-mentioned parts, it can also involve eyelids, scalp, trunk and limbs, and is manifested as paroxysmal severe itching, more obvious at night, long-term difficult to heal, and easy to relapse, and can also secondary folliculitis and lymphadenitis.

[0003] Neurodermatitis is related to the disorder of brain cortex excitation and inhibition, and often occurs in people with symptoms of neurasthenia such as dizziness, insomnia, irritability, anxiety and the like. In addition, endocrine disorders, gastrointestinal dysfunction, infectious foci, excessive fatigue, mental stress and scratching, sun exposure, drinking, mechanical and physical stimulation and the like can trigger the disease and aggravate the condition.

[0004] The common methods for treating neurodermatitis at present are as follows: 1. Topical external use of glucocorticoid, and the effect can be enhanced by sealing after external use. 2. Local injection of glucocorticoid into skin lesions. 3. Application of tranquilizers and antihistamines. 4. Shallow X-ray, ultraviolet, helium-neon laser irradiation, photochemical therapy and the like can be used as the auxiliary treatment of neurodermatitis. However, the treatment cost of the above treatment methods is relatively high, and patients can only receive effective treatment in hospitals with good medical conditions in cities. In rural areas, especially in some villages far away from towns, people with neurodermatitis often do not go to see a doctor due to low family income, poor life, lack of medical conditions in the local area, and high cost of treatment and medicine. Some patients thus delay the treatment opportunity. At present, there are some Chinese medicine prescriptions with certain treatment effect on neurodermatitis, for example, a Chinese medicine prescription composed of cortex dictamni, sophora flavescens, cnidium monnieri and fructus kochiae, which can significantly reduce the treatment cost, but these Chinese medicine prescriptions often have the problems of poor treatment effect and long treatment cycle. Therefore, there is still a lack of a neurodermatitis treatment method or product which can balance low treatment cost and excellent treatment effect. Therefore, it is of great significance to provide a Chinese medicine composition for treating neurodermatitis. SUMMARY

[0005] The present application aims to at least solve one of the above technical problems in the prior art. To this end, the object of the present application is to provide a Chinese medicine composition and a preparation method and use thereof, in particular a Chinese medicine composition for treating neurodermatitis, which has the effects of nourishing blood, activating blood, dispelling wind and relieving itching, and can significantly relieve the symptoms of neurodermatitis, itching and edema caused by neurodermatitis and the like.

[0006] In a first aspect of the present application, a Chinese medicine composition is provided, which comprises the following medicinal material raw materials: angelica, prepared rehmannia, atractylodes, wind-preventing plant, milkvetch root, radix falcaliae, gastrodia, cortex dictamni, schizonepeta and licorice.

[0007] In some embodiments of the present application, the Chinese medicine composition comprises the following medicinal material raw materials in parts by mass: angelica 5-30 parts, prepared rehmannia 5-25 parts, atractylodes 5-20 parts, wind-preventing plant 2-18 parts, milkvetch root 12-30 parts, radix falcaliae 5-20 parts, gastrodia 1-12 parts, cortex dictamni 15-30 parts, schizonepeta 5-15 parts, and licorice 1-20 parts.

[0008] In some embodiments of the present application, the Chinese medicine composition comprises the following medicinal material raw materials by mass fraction: Angelica 5-20 parts, Radix Rehmanniae Preparata 10-25 parts, Atractylodes 5-20 parts, Saposhnikovia 2-18 parts, Astragalus 12-30 parts, Polygoni Multiflori 5-15 parts, Gastrodia 1-12 parts, Dictamnus 15-30 parts, Schizonepeta 5-15 parts, and Glycyrrhiza 1-15 parts.

[0009] In some embodiments of the present application, the Chinese medicine composition comprises the following medicinal material raw materials by mass fraction: Angelica 5-20 parts, Radix Rehmanniae Preparata 10-25 parts, Atractylodes 5-20 parts, Saposhnikovia 5-15 parts, Astragalus 15-30 parts, Polygoni Multiflori 5-15 parts, Gastrodia 1-10 parts, Dictamnus 15-30 parts, Schizonepeta 5-15 parts, and Glycyrrhiza 1-10 parts.

[0010] In some embodiments of the present application, the Chinese medicine composition comprises the following medicinal material raw materials by mass fraction: Angelica 5-15 parts, Radix Rehmanniae Preparata 10-20 parts, Atractylodes 5-15 parts, Saposhnikovia 5-15 parts, Astragalus 15-30 parts, Polygoni Multiflori 5-15 parts, Gastrodia 1-10 parts, Dictamnus 15-30 parts, Schizonepeta 5-15 parts, and Glycyrrhiza 1-10 parts.

[0011] In the second aspect of the present application, a Chinese medicine preparation is provided, wherein the active ingredient of the Chinese medicine preparation comprises the Chinese medicine composition of the first aspect of the present application.

[0012] In some embodiments of the present application, the active ingredient is the water extract of the Chinese medicine composition of the first aspect of the present application.

[0013] In some embodiments of the present application, the preparation method of the water extract of the Chinese medicine composition comprises the following steps: decocting the medicinal material raw materials with water, filtering, and obtaining the Chinese medicine water extract.

[0014] In some embodiments of the present application, the preparation method of the water extract of the Chinese medicine composition further comprises the following step: crushing the medicinal material raw materials before decocting with water.

[0015] In some embodiments of the present application, the Chinese medicine preparation further comprises a pharmaceutical excipient.

[0016] In some embodiments of the present application, the pharmaceutical excipient comprises at least one of a solvent, a propellant, a solubilizer, a co-solvent, an emulsifier, a colorant, a binder, a disintegrant, a filler, a lubricant, a wetting agent, an osmotic pressure regulator, a stabilizer, a glidant, a flavoring agent, a preservative, a suspending agent, a coating material, an aromatic agent, an anti-adhesion agent, an integrating agent, a penetration enhancer, a pH regulator, a buffer, a plasticizer, a surfactant, a foaming agent, an antifoaming agent, a thickening agent, a complexing agent, a humectant, an absorbent, a diluent, a flocculating agent and a deflocculating agent, a filtering aid, a release retardant, and a carrier.

[0017] In some embodiments of the present application, the flavoring agent includes, but is not limited to, honey, sucrose, sodium saccharin, aspartame, acesulfame potassium, sucralose or steviol glycosides.

[0018] In some embodiments of the present application, the preservative includes, but is not limited to, sorbic acid and its potassium salt, benzoic acid and its sodium salt, dehydroacetic acid and its sodium salt or parabens.

[0019] In some embodiments of the present application, the filler includes, but is not limited to, starch or microcrystalline cellulose.

[0020] In some embodiments of the present application, the binder includes, but is not limited to, starch, sucrose, gelatin or gum arabic.

[0021] In some embodiments of the present application, the wetting agent includes ethanol or water.

[0022] In some embodiments of the present application, the dosage form of the traditional Chinese medicine preparation includes ointment, hard capsule, tablet, granule, pill, oral liquid, syrup, powder, suspension, solution, injection, lyophilized powder for injection, injection, suppository, cream, spray and patch.

[0023] In some embodiments of the present application, the unit dose of the traditional Chinese medicine preparation contains 200-500 mg of medicinal materials, and the rest is pharmaceutical excipients.

[0024] According to the definition in the Chinese Pharmacopoeia 2025 edition, unit dose refers to the content of medicinal ingredients in a single dose packaging or the content of medicinal ingredients in a preparation unit that can be independently administered in a multiple dose packaging. Unit dose is expressed in metric weight units (g / mg).

[0025] In the third aspect of the present application, a preparation method of the traditional Chinese medicine preparation of the second aspect of the present application is provided, which comprises the following steps: decocting medicinal material raw materials in the traditional Chinese medicine composition of the first aspect of the present application with water, filtering to obtain water extract of the traditional Chinese medicine composition.

[0026] In some embodiments of the present application, the preparation method of the traditional Chinese medicine preparation further comprises: concentrating the water extract of the traditional Chinese medicine composition into extract, and mixing the extract with pharmaceutical excipients to prepare the traditional Chinese medicine preparation.

[0027] In some embodiments of the present application, when the traditional Chinese medicine preparation is an ointment, the preparation method comprises the following steps: a1) decocting medicinal material raw materials in the traditional Chinese medicine composition of the first aspect of the present application with water, filtering to obtain water extract of the traditional Chinese medicine; b1) concentrating the water extract of the traditional Chinese medicine of step a1 into extract; c1) heating and mixing the extract of step b1 with honey, and concentrating to obtain a paste.

[0028] In some embodiments of the present application, step c1 further comprises adding sucrose and heating and mixing.

[0029] In some embodiments of the present application, step c1 further comprises adding potassium sorbate and heating and mixing.

[0030] In some embodiments of the present application, when the traditional Chinese medicine preparation is a hard capsule, the preparation method comprises the following steps: a2) decocting the medicinal material raw materials in the traditional Chinese medicine composition of the first aspect of the present application with water, filtering, and obtaining a traditional Chinese medicine water extract; b2) concentrating the traditional Chinese medicine water extract of step a2 into an extract; c2) drying the extract of step b2 under reduced pressure to obtain a dry extract; d2) crushing the dry extract of step c2 and then adding starch to mix to obtain a mixture; e2) granulating the mixture of step d2 with ethanol, drying, sizing, and filling into capsules to obtain a hard capsule.

[0031] In some embodiments of the present application, when the traditional Chinese medicine preparation is an oral liquid, the preparation method comprises the following steps: a3) decocting the medicinal material raw materials in the traditional Chinese medicine composition of the first aspect of the present application with water, filtering, and obtaining a traditional Chinese medicine water extract; b3) concentrating the traditional Chinese medicine water extract of step a3 into an extract and refining; c3) dissolving a proper amount of sucrose in boiling water, filtering, and preparing a monosaccharide syrup; d3) adding the monosaccharide syrup obtained in step c3 to the extract obtained in step b3, and then adding purified water; e3) adding potassium sorbate to the mixture obtained in step d3, mixing uniformly, filtering, and filling to obtain an oral liquid.

[0032] In some embodiments of the present application, when the traditional Chinese medicine preparation is a granule, the preparation method comprises the following steps: a4) decocting the medicinal material raw materials in the traditional Chinese medicine composition of the first aspect of the present application with water, filtering, and obtaining a traditional Chinese medicine water extract; b4) concentrating the traditional Chinese medicine water extract of step a4 into an extract; c4) adding sucrose powder to the extract obtained in step b4, mixing uniformly, granulating, drying, and sizing to obtain a granule.

[0033] In some embodiments of the present application, the preparation method of the traditional Chinese medicine preparation further comprises: crushing the medicinal material raw materials before decocting with water.

[0034] In some embodiments of the present application, the relative density of the extract is 1.10-1.15.

[0035] In the fourth aspect of the present application, the use of the traditional Chinese medicine composition of the first aspect of the present application or the traditional Chinese medicine preparation of the second aspect of the present application in the preparation of a drug for at least one of the following purposes is provided: 1) preventing and / or treating neurodermatitis; 2) relieving and improving the clinical symptoms caused by neurodermatitis.

[0036] In some embodiments of the present application, the clinical symptoms caused by neurodermatitis include itching and edema.

[0037] The pharmacology of each component of the medicinal material raw material in the present application is as follows: The combination of various drugs in the formula has the effects of tonifying blood, invigorating spleen and dispelling wind. According to the strict formula of Chinese medicine, angelica sinensis and prepared rehmannia are used as the monarch drug to fill essence, tonify blood and activate blood, astragalus membranaceus and radix falcaliae multiflorae are used as the ministerial drug to tonify blood and dispel wind, atractylodes macrocephala, saposhnikovia divaricata, cortex meliae and schizonepeta tenuifolia are used as the auxiliary drug to invigorate spleen, clear heat and dry dampness, and licorice root is used as the ministerial drug to harmonize the properties of various drugs.

[0038] The beneficial effects of the present application are: In view of the core pathogenesis of neurodermatitis "blood deficiency causing wind and dryness" (symptoms of pale skin, severe itching at night, dizziness and palpitations), the present application uses prepared rehmannia and angelica sinensis as the monarch drug to tonify blood deficiency, and the structure of monarch, minister and auxiliary is completely reconstructed in view of the root of blood deficiency and wind dryness, establishing a new system of "tonifying blood as the monarch + invigorating spleen and dispelling wind as the minister and auxiliary". The newly added atractylodes macrocephala is used as the key auxiliary drug to solve the problem of tonifying drugs being greasy and to help the formation of blood and qi at the same time; gastrodia elata is used as the ministerial drug to calm the liver and dispel wind, directly attacking the symptoms of blood deficiency causing wind, and aiming at the core symptoms (edema and itching) of neurodermatitis, the two form a synergistic effect of "invigorating spleen and assisting transportation + dispelling wind and relieving itching" in the angelica sinensis-prepared rehmannia blood tonifying system.

[0039] The traditional Chinese medicine composition and the traditional Chinese medicine preparation provided by the present application can significantly relieve neurodermatitis and symptoms such as itching or edema caused by neurodermatitis, and use pure natural plant raw materials, and no obvious adverse reactions occur during the use of patients, which can be used as a candidate drug for treating neurodermatitis; the preparation method steps of the ointment, capsule and oral liquid dosage forms are simple and operable, and are suitable for actual production. BRIEF DESCRIPTION OF DRAWINGS

[0040] Figure 1 The synergistic effect of the traditional Chinese medicine composition of the embodiment on the treatment of acute ear swelling caused by dimethylbenzene in mice is verified by the Bliss model.

[0041] Figure 2The synergistic effect of the traditional Chinese medicine composition of the embodiment verified by the Bliss model on treating local skin itching of guinea pigs is shown.

[0042] Figure 3 The synergistic effect of the traditional Chinese medicine composition of the embodiment verified by the Bliss model on improving the skin lesion condition is shown.

[0043] Figure 4 The synergistic effect of the traditional Chinese medicine composition of the embodiment verified by the Bliss model on reducing the number of inflammatory cells in the dermis is shown. DETAILED DESCRIPTION

[0044] In order to make the personnel in the technical field better understand the present application scheme, the technical scheme of the present application will be further described in detail below in combination with the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by the person skilled in the art without making creative efforts shall belong to the protection scope of the present application. It should be noted that the embodiments in the present application and the features in the embodiments can be combined with each other without conflict. The present application will be described in detail below in combination with the embodiments.

[0045] Embodiment 1 A traditional Chinese medicine composition for treating neurodermatitis, which is composed of the following medicinal raw materials: Angelica 10g, Prepared Rehmannia 15g, Atractylodes 10g, Saposhnikovia 12g, Astragalus 20g, Polygonum multiflorum 10g, Gastrodia 6g, Dictamnus 20g, Schizonepeta 10g, and Licorice 6g.

[0046] Embodiment 2 A traditional Chinese medicine composition for treating neurodermatitis, which is composed of the following medicinal raw materials: Angelica 5g, Prepared Rehmannia 10g, Atractylodes 5g, Saposhnikovia 5g, Astragalus 15g, Polygonum multiflorum 5g, Gastrodia 1g, Dictamnus 15g, Schizonepeta 5g, and Licorice 1g.

[0047] Embodiment 3 A traditional Chinese medicine composition for treating neurodermatitis, which is composed of the following medicinal raw materials: Angelica 15g, Prepared Rehmannia 20g, Atractylodes 15g, Saposhnikovia 15g, Astragalus 30g, Polygonum multiflorum 15g, Gastrodia 10g, Dictamnus 30g, Schizonepeta 15g, and Licorice 10g.

[0048] Comparative Example 1 A traditional Chinese medicine composition for treating neurodermatitis, which is composed of the following medicinal raw materials: Angelica 15g, Prepared Rehmannia 20g, Saposhnikovia 15g, Astragalus 30g, Polygonum multiflorum 15g, Dictamnus 30g, Schizonepeta 15g, and Licorice 10g.

[0049] Comparative Example 2 A traditional Chinese medicine composition for treating neurodermatitis is composed of the following medicinal material raw materials: 15g of angelica, 20g of prepared rehmannia, 15g of siler, 30g of milkvetch root, 15g of radix falcaliae, 10g of gastrodia, 30g of cortex meliae, 15g of schizonepeta, and 10g of licorice.

[0050] Comparative Example 3 A traditional Chinese medicine composition for treating neurodermatitis is composed of the following medicinal material raw materials: 15g of angelica, 20g of prepared rehmannia, 15g of atractylodes, 15g of siler, 30g of milkvetch root, 15g of radix falcaliae, 30g of cortex meliae, 15g of schizonepeta, and 10g of licorice.

[0051] Comparative Example 4 A traditional Chinese medicine composition for treating neurodermatitis is composed of the following medicinal material raw materials: 15g of angelica, 20g of prepared rehmannia, 15g of atractylodes, and 15g of siler.

[0052] Comparative Example 5 A traditional Chinese medicine composition for treating neurodermatitis is composed of the following medicinal material raw materials: 15g of angelica, 20g of prepared rehmannia, and 10g of gastrodia.

[0053] On the basis of the medicinal material raw materials provided in the above Examples 1-3, medicinal adjuvants are added to prepare a paste, a hard capsule, an oral liquid, and granules, respectively, according to the following methods: Preparation method of the paste: The medicinal materials are weighed according to the prescription, and are crushed into coarse powder. All the medicinal materials are mixed and decocted for 3 times, the first time for 3 hours with 12 times the amount of water, the second time for 2 hours with 8 times the amount of water, and the third time for 0.5 hours with 6 times the amount of water. The decoction is filtered and combined, and is concentrated into an extract with a relative density of 1.10-1.15 at 60-65℃. Then, 50% of honey by mass of the extract is added, and is mixed and heated. The paste is concentrated to a relative density of 1.2-1.25 at 60-65℃, and is obtained.

[0054] Preparation method of the hard capsule: The medicinal materials are weighed according to the prescription, and are crushed into coarse powder. All the medicinal materials are mixed and decocted for 3 times, the first time for 3 hours with 12 times the amount of water, the second time for 2 hours with 8 times the amount of water, and the third time for 0.5 hours with 6 times the amount of water. The decoction is filtered and combined, and is concentrated into an extract with a relative density of 1.10-1.15 at 80℃. The extract is dried under reduced pressure at 70℃ into a dry extract, which is crushed and mixed with 10% of starch by mass. The mixture is granulated with 70% ethanol, dried, and filled into capsules, and is obtained.

[0055] Preparation method of the oral liquid: The prescription amount of each medicinal material is weighed, and the medicinal materials are crushed into coarse powder. All the medicinal materials are mixed and decocted for 3 times. The first time is decocted for 3 hours with 12 times the amount of water, the second time is decocted for 2 hours with 8 times the amount of water, and the third time is decocted for 0.5 hours with 6 times the amount of water. Filtration is performed, and the decoction is combined and concentrated into an extract with a relative density of 1.10-1.15 at 80°C. Sucrose is taken and added into boiled water to be uniformly dissolved. Filtration is performed, and the monosaccharide syrup is prepared. The monosaccharide syrup is added into the above-mentioned medicinal filtrate to make the final sugar content 20-60% (w / w). Purified water is added to 500 mL. Potassium sorbate with a preparation amount of 0.2% is added, and mixing is uniformly performed. Filling is performed to obtain the oral liquid.

[0056] The preparation method of the granules is as follows: The prescription amount of each medicinal material is weighed, and the medicinal materials are crushed into coarse powder. All the medicinal materials are mixed and decocted for 3 times. The first time is decocted for 3 hours with 12 times the amount of water, the second time is decocted for 2 hours with 8 times the amount of water, and the third time is decocted for 0.5 hours with 6 times the amount of water. Filtration is performed, and the decoction is combined and concentrated into an extract with a relative density of 1.10-1.15 at 80°C. 4 times the amount of sucrose powder is added according to the weight of the extract, and mixing is uniformly performed. Granulation, drying, and whole-grain processing are performed to obtain the granules.

[0057] Test Example 1 Acute toxicity experiment 40 Kunming mice, half of each sex, with a body weight of 18-22 g, are taken and divided into 4 groups, 10 mice in each group. Three groups are respectively given by gavage the traditional Chinese medicine compositions prepared in Examples 1-3, wherein the traditional Chinese medicine composition is the extract in the process of preparing the paste. The gavage amount is 20 mL / (kg·d). The control group is given by gavage distilled water, and the gavage amount is 20 mL / kg. The animals are given by gavage 3 times a day. The reaction conditions of the animals are observed immediately after the administration, including the appearance, behavior, mental state, appetite, excretion and its color, fur, nose, eyes, mouth, and abnormal secretions, and death. The animals are observed every 30 min to 1 h on the first day of administration, and then observed and weighed once a day. The observation is continuously performed for 14 days. The toxicity reaction and death distribution of the animals, the body weight change, and the reaction condition are recorded. The results show that the mice are normal in activity, feeding, and excretion, grow well, have bright fur, and have weight gain without death within 14 days after the administration. Therefore, the LD50 is not measured. The average body weight of the mice is increased with the prolongation of the test time, which is the same as that of the control group at the corresponding time. The animals are killed and observed for organ changes after the end of the observation period. The results show that the mice in the administration group and the control group have no abnormal changes in organs.

[0058] Test Example 2 Long-term toxicity experiment Forty guinea pigs, half male and half female, weighing 250-300 g, were selected and divided into 4 groups, 10 guinea pigs in each group. One group of guinea pigs was a blank control group, and the other three groups were respectively given the traditional Chinese medicine composition prepared in Examples 1-3 by gavage, in which the traditional Chinese medicine composition was the extract during the preparation process of the paste. The gavage amount was 50 mL / (kg·d), and the guinea pigs were continuously given drugs for 90 days. The blank control group was given an equal amount of distilled water. During the experiment, the appearance and behavior of the animals were observed, the body weight was recorded, and after 12 h of fasting after the 90th day of administration, blood routine examination, routine examination of stool and urine, and determination of serum glutamic-pyruvic transaminase (SGPT) and urea nitrogen (BUN) were performed. Finally, the animals were sacrificed by excessive anesthesia with 3% sodium pentobarbital, and the heart, liver, and kidney were removed for pathological examination. The results showed that there were no abnormal changes in the above observation indexes, and no animal death occurred. The results of macroscopic observation are as follows: there was no exudation in the chest and abdominal cavity, and there was no significant difference in color, size, shape, etc. of the organs such as heart, liver, and kidney between the drug administration groups and the control group. The results of histological observation are as follows: the heart, liver, and kidney tissue structure of the drug administration groups was normal, and no obvious pathological changes were found compared with the control group.

[0059] Test Example 3 Therapeutic effect of traditional Chinese medicine composition on acute ear swelling caused by xylene in mice Animals Two hundred and twenty Kunming mice, half female, weighing 18-22 g, were taken and immediately divided into 11 groups, 20 mice in each group, for observing the influence on xylene-induced mouse auricle swelling, which were blank control group, model control group, positive control group, treatment group 1 to treatment group 3, and efficacy control group 1 to efficacy control group 5, respectively.

[0060] Reagents Xylene was provided by Qingdao Hobon Chemical Industry Co., Ltd.

[0061] Dosage regimen The mice in treatment groups 1-3 were respectively orally administered with the traditional Chinese medicine compositions prepared in Examples 1-3, and the mice in pharmacodynamic control groups 1-5 were respectively orally administered with the traditional Chinese medicine compositions prepared in Comparative Examples 1-5. The traditional Chinese medicine compositions were dissolved in distilled water, wherein the traditional Chinese medicine compositions were extracts obtained in the preparation process of the pastes, and were heated to 30°C until completely dissolved to obtain a solution with a crude drug concentration (the total mass of the original monarch drug corresponding to each milliliter of the solution) of 1 g / mL. The converted crude drug concentration (g / mL) = total mass of the monarch drug in the extract (g) / total mass of the extract (g) x total mass of the extract (g) / final volume (mL). The solution was used to orally administer the mice, and the oral administration amount was 0.0096 mL / (g·d), which was equivalent to 10 times the adult drug amount. The positive control group was administered with loratadine: 0.01 mg / (g·d) (equivalent to 10 times the adult drug amount). The model control group and the blank control group were given the same volume of normal saline. The administration was performed once a day for 7 consecutive days. After the last administration, the right ears of the mice in each group were inflamed by applying 50 μL of xylene on both sides of the right ear of the mice in the model control group and the blank control group, and the mice were sacrificed after 1 h. The left and right ears of the mice were punched at the same position by using a puncher (pore diameter: 8 mm), and the weights of the left and right ear pieces were measured. The difference between the weights of the two ear pieces was taken as the swelling degree, and the swelling degrees of the groups were calculated for statistical processing. The measurement data was represented by χ2test, and all data was processed by using SPSS 12.0 statistical software. The results are shown in Table 1.

[0062] Table 1. Therapeutic effect of the traditional Chinese medicine compositions on acute ear swelling of mice caused by xylene

[0063] As shown in Table 1, the traditional Chinese medicine compositions of Examples 1-3 had a significant inhibitory effect on the ear swelling of mice caused by xylene, and the inhibitory effect was significantly better than that of the whole formula Baizhu / Tianma single-drug deletion group (Comparative Examples 2 and 3) and the Buxue drugs (Angelica and Prepared Rehmannia) single-added Baizhu / Tianma group (Comparative Examples 4 and 5). Based on the ear swelling degree of the model control group, the inhibition rate of each group relative to the model control group was calculated, and the formula was: inhibition rate = (model group ear swelling degree The ear swelling degree of the experimental group) / model group ear swelling degree x 100%, wherein the experimental group was the average value of the positive control group, the pharmacodynamic control group, or the treatment groups 1-3. The results showed that, compared with Examples 1-3, the inhibitory effect decreased by 90.7% after removing Baizhu and Tianma from the whole formula (Comparative Example 1), the inhibition rate of Angelica-Prepared Rehmannia-Baizhu was 28.0%, the inhibition rate of Angelica-Prepared Rehmannia-Tianma was 38.3%, and the combination effect predicted by the Bliss model was 55.6% ( E pred = 28.0% + 38.3% (28.0% x 38.3%) ≈ 55.6%), while the actual combination inhibition rate was 79.4%, significantly higher than the predicted value, suggesting that the two had significant synergistic effect in inhibiting ear swelling (see Figure 1 The Bliss model verified that in the inhibition of edema index, the atractylodes and gastrodia in the angelica and radix lactifiae system had synergistic effect.

[0064] Test Example 4 Therapeutic effect of traditional Chinese medicine composition on local skin itching of guinea pigs Reagents Histamine phosphate was provided by Shanghai Jin Sui Biological Technology Co., Ltd.

[0065] 100 healthy guinea pigs, half male and half female, weighing 250-300 g, were randomly divided into 10 groups according to body weight, 10 in each group. Model control group, positive control group, treatment group 4 to treatment group 6, efficacy control group 1 to efficacy control group 5, guinea pigs in treatment groups 4-6 were respectively orally administered with traditional Chinese medicine compositions prepared in examples 1-3, guinea pigs in efficacy control groups 1-5 were respectively orally administered with traditional Chinese medicine compositions prepared in comparative examples 1-5, the traditional Chinese medicine compositions were dissolved in distilled water, the traditional Chinese medicine composition was extract paste in the preparation process of the ointment, heated to 30℃, dissolved completely, to obtain a solution with a crude drug concentration of 1 g / mL (each milliliter of solution corresponds to the total mass of the original monarch drug), the conversion of crude drug concentration (g / mL) = total mass of monarch drug in extract paste (g) / total mass of extract paste (g) x total mass of extract paste (g) / final volume (mL). The solution was used to gavage the mice, the gavage amount was 0.0036 mL / (g·d), equivalent to 10 times the adult drug amount, the positive control group took loratadine: 0.00375 mg / (g·d) (equivalent to 10 times the adult drug amount), the model control group was given the same volume of normal saline. Each group was gavaged once a day for 7 consecutive days. 1 h after the last administration on the 7th day, the right hind foot of each group of guinea pigs was shaved, the positive control group was smeared with fluocinolone acetonide ointment, and the right hind foot of each group of guinea pigs was shaved. 10 min later, 0.01% histamine phosphate solution was dropped on the wound, 0.05 mL per mouse, and then 0.02%, 0.03%, 0.04% and other increasing concentrations were added every 3 min, each time 0.05 mL per mouse, until the guinea pigs turned their heads to lick the back of the right hind foot. The total amount of histamine phosphate given when the guinea pigs turned their heads to lick the back of the right hind foot was recorded as the itching threshold. The itching thresholds of each group were recorded and compared, and the results were statistically processed. The results are shown in Table 2.

[0066] Table 2. Therapeutic effect of traditional Chinese medicine composition on local skin itching of guinea pigs

[0067] Table 2 shows that the herbal compositions used in Examples 1-3 have excellent antipruritic effects, with significantly better inhibitory effects than the groups lacking the single herb combination of Atractylodes macrocephala / Gastrodia elata (Comparative Examples 2 and 3) and the groups containing blood-tonifying herbs (Angelica sinensis and Rehmannia glutinosa) plus Atractylodes macrocephala / Gastrodia elata (Comparative Examples 4 and 5). Using the itch threshold of the model control group as a benchmark, the relative inhibition rate of each group relative to the model control group was calculated using the formula: Relative inhibition rate = (Itch threshold of experimental group) / (Itch threshold of experimental group) The itch threshold of the model control group was divided into the itch threshold of the model control group and the itch threshold of the model control group. The experimental group was the average of the positive control group, the efficacy control group, or the treatment group (4-6). The results showed that compared with Examples 1-3, after removing Atractylodes macrocephala and Gastrodia elata from the whole formula (Comparative Example 1), the inhibitory effect decreased by 72%. The relative inhibition rate of Angelica sinensis-Rehmannia glutinosa-Atractylodes macrocephala was 1.753; the relative inhibition rate of Angelica sinensis-Rehmannia glutinosa-Gastrodia elata was 1.966. The combined effect predicted by the Bliss model was 0.273 (E0.05). pred =1.753+1.966 (1.753×1.966)≈0.273), while the measured relative inhibition rate was 3.236, significantly higher than the predicted value, suggesting that the two have a significant synergistic effect in relieving itching (see [reference needed]). Figure 2 The Bliss model was used to verify that Atractylodes macrocephala and Gastrodia elata in the Angelica sinensis-Rehmannia glutinosa system have a synergistic effect on the inhibition of pruritus.

[0068] Experimental Example 5 Clinical observation of the treatment of neurodermatitis reagents 2,4-Dinitrochlorobenzene (DNCB) and acetone were both provided by Qingdao Hebang Chemical Co., Ltd.; 7% (v / v) 2,4-dinitrochlorobenzene (DNCB) acetone solution and 1% (v / v) 2,4-dinitrochlorobenzene (DNCB) solution were prepared for the experiment.

[0069] Modeling One hundred healthy guinea pigs (provided by Qingdao Experimental Animal and Animal Experimentation Center), half male and half female, were used. The hair on both sides of the back was shaved one day before the experiment, covering an area of ​​3cm × 3cm. On the day of the experiment, 25μL of 7% (v / v) DNCB acetone solution was applied topically to the shaved area to sensitize it. Two weeks later, 1% (v / v) DNCB solution was applied topically to the shaved area for induction, followed by 100μL of acetone solution for challenge. Topical application was repeated once a week for four consecutive weeks. The presence of erythema, scaling, edema, scratch marks, etc., within 48 hours after the last challenge indicated successful model establishment.

[0070] Experimental drug administration and grouping The guinea pigs were randomly divided into 10 groups according to body weight, 10 in each group, half male and half female. The model control group, the positive control group, the treatment group 7 to the treatment group 9, the pharmacodynamic control group 1 to the pharmacodynamic control group 5 were set. The guinea pigs in the treatment group 7 to 9 were respectively orally administered with the traditional Chinese medicine compositions prepared in Examples 1 to 3, and the guinea pigs in the pharmacodynamic control group 1 to 5 were respectively orally administered with the traditional Chinese medicine compositions prepared in Comparative Examples 1 to 5. The traditional Chinese medicine composition was the extract in the preparation process of the paste. The traditional Chinese medicine composition was dissolved in distilled water and heated to 30°C until completely dissolved to obtain a solution with a crude drug concentration (the total mass of the original monarch drug corresponding to each milliliter of the solution) of 1 g / mL. The conversion of the crude drug concentration (g / mL) = the total mass of the monarch drug in the extract (g) / the total mass of the extract (g) x the total mass of the extract (g) / the final volume (mL). The solution was used to orally administer the mice, and the oral administration amount was 0.0036 mL / (g·d), which was equivalent to 10 times of the adult drug amount. The positive control group was administered with loratadine: 0.00375 mg / (g·d) (equivalent to 10 times of the adult drug amount), and at the same time, was smeared with fluocinolone acetonide ointment, and the smearing amount was 0.05 g per guinea pig. The model control group was given the same volume of normal saline, and the administration was continuously performed for 21 days.

[0071] Therapeutic effect evaluation Erythema: 0 point for no, 1 point for slight, 2 points for obvious erythema without scab, 3 points for moderate erythema with mild to moderate scab, and 4 points for severe erythema with severe scab; edema: 0 point for no, 1 point for mild, 2 points for moderate, and 3 points for severe; scratch marks: 0 point for no, 1 point for slight, and 2 points for severe. The integral after treatment was divided by the integral before treatment, and then the therapeutic index was obtained.

[0072] Histological observation At two time points of 48 h after the last antigen stimulation and 21 days after treatment and 1 day after drug withdrawal, the guinea pigs in each group were anesthetized with 2% sodium pentobarbital intraperitoneally, and 10 mm x 1-2 mm skin biopsy was taken. After being fixed in 10% formalin solution, 4 μm paraffin sections were obtained and HE staining was performed, and then the pathological sections were observed under an optical microscope, and the number of inflammatory cells in the dermis was counted in 10 high power fields (HPF), and the average value was obtained.

[0073] Statistical method Measurement data was expressed, and χ2test was used for comparison between groups. All data were processed by SPSS 12.0 statistical software.

[0074] Results Lesion condition At 48 hours after modeling, the guinea pigs in each group showed different degrees of diffuse edematous erythema on the back skin, with unclear boundaries, skin infiltration, a large number of scales, obvious scratch marks with blood scabs, and a small number of papules. After 12 days of treatment, the treatment groups 7 to 9 showed a significant reduction in erythema and edema, no scratch marks and papules, and the positive control group showed reduced erythema, mild edema, and a few papules the size of mung beans to soybeans, reduced scratch marks, and a small amount of scales. The model control group still had obvious erythema, papules, unclear boundaries, mild swelling, and a large number of scales and scratch marks. After 21 days of treatment, the treatment groups 7 to 9 showed that the erythema and edema had basically subsided, the scratch marks had disappeared, and there were no scales, and the skin had basically returned to normal. The positive control group showed mild erythema and mild edema, and the model control group still had partial redness and edema, with a few scales and a small amount of scratch marks. The lesion score results are shown in Table 3.

[0075] Table 3. Comparison of symptom scores before and after treatment

[0076] As can be seen from Table 3, the traditional Chinese medicine compositions of Examples 1-3 can significantly improve the skin lesion condition, and the skin repair effect is significantly better than that of the single-drug omission groups of the whole prescription (Comparative Examples 2 and 3) and the single addition of blood tonics (Angelica and Prepared Rehmannia) and white atractylodes / rhizoma gastrodia (Comparative Examples 4 and 5). Taking the efficacy index of the model control group as the benchmark, the relative effect value of each group relative to the model control group was calculated, and the formula was: relative effect value = (efficacy index of the experimental group efficacy index of the model control group) / (100% efficacy index of the model control group), wherein the experimental group was the average value of the positive control group, the pharmacodynamic control group, or the treatment groups 7-9. The results showed that, compared with Examples 1-3, the skin repair effect decreased by 92.4% after removing white atractylodes and rhizoma gastrodia from the whole prescription (Comparative Example 1), the relative effect value of Angelica-Prepared Rehmannia-White Atractylodes was 0.375, and the relative effect value of Angelica-Prepared Rehmannia-Rhizoma Gastrodia was 0.429. The combination effect predicted by the Bliss model was 0.643 (E pred = 0.375 + 0.429 (0.375 x 0.429) ≈ 0.643), and the actual combination effect value was 0.754, which was significantly higher than the predicted value, indicating that the two had significant synergistic effect in skin repair (see Figure 3 ). The Bliss model verified that white atractylodes and rhizoma gastrodia in the Angelica-Prepared Rehmannia system had synergistic effect on skin repair indicators.

[0077] The histopathological manifestations of the guinea pigs with neurodermatitis before treatment (48 hours after modeling): hyperkeratosis with parakeratosis, the epidermis thickened from 2-3 layers of cells in normal skin to 6-8 layers, the stratum spinosum thickened, intercellular edema, epidermal processes lengthened and widened, a large number of lymphocytes and histiocytes infiltrated in the superficial dermis, and obvious expansion and hyperemia of the dermal small blood vessels; the histopathological manifestations after 21 days of treatment and 1 day of drug withdrawal: the epidermis of the treatment group 7 to the treatment group 9 returned to 2-3 layers of normal cells, a small amount of lymphocytes infiltrated in the dermis, no expansion and hyperemia of the dermal small blood vessels, and the tissue structure was basically the same as that of the normal tissue section; the stratum spinosum of the model control group was thickened, intercellular edema, epidermal processes lengthened and widened, and a large number of lymphocytes infiltrated in the superficial dermis.

[0078] The comparison results of the number of inflammatory cell infiltrations in the dermis are shown in Table 4.

[0079] Table 4. Comparison of the number of inflammatory cell infiltrations in the dermis

[0080] As can be seen from Table 4, the traditional Chinese medicine composition of Examples 1-3 can significantly reduce the number of inflammatory cells in the dermis, and the effect of reducing the number of inflammatory cells in the dermis is significantly better than that of the whole prescription without atractylodes rhizome / gastrodium (Comparative Examples 2 and 3) and the addition of atractylodes rhizome / gastrodium to blood tonics (angelica and prepared rehmannia) (Comparative Examples 4 and 5). Taking the number of inflammatory cells in the dermis of the model control group as a benchmark, the inhibition rate of each group relative to the model control group was calculated, and the formula was: inhibition rate = (number of inflammatory cells in the dermis of the model group / number of inflammatory cells in the dermis of the model group) x 100%, wherein the experimental group was the average value of the positive control group, the pharmacodynamic control group, or the treatment groups 7-9. The results showed that, compared with Examples 1-3, the removal of atractylodes rhizome and gastrodium from the whole prescription (Comparative Example 1) reduced the number of inflammatory cells in the dermis by 85.2%, and the inhibition rate of angelica-prepared rehmannia-atractylodes rhizome was 30.0%; the inhibition rate of angelica-prepared rehmannia-gastrodium was 20.2%, and the combination effect predicted by the Bliss model was 44.1% (pred=30.0%+20.2%). (30.0% x 20.2%) ≈ 44.1%), the actual combination inhibition rate was 68.1%, which was significantly higher than the predicted value, indicating that atractylodes rhizome and gastrodium in the angelica-prepared rehmannia system had significant synergistic effects in reducing inflammatory cell infiltration (see E ). Figure 4 The Bliss model verified that atractylodes rhizome and gastrodium in the angelica-prepared rehmannia system had synergistic effects in reducing the number of inflammatory cells in the dermis.

[0081] As can be seen from the animal experiments of Test Examples 3-5, the traditional Chinese medicine composition of the present application can significantly improve the inflammation and itching conditions, improve the skin lesions, and reduce the number of inflammatory cells in the dermis, thereby effectively treating neurodermatitis.​

[0082] The application is directed to the core pathogenesis of neurodermatitis "blood deficiency generating wind and dryness", with radix rehmanniae and angelica sinensis as the monarch tonifying blood deficiency, aiming at the root of blood deficiency wind and dryness, the monarch, minister and assistant structure is completely reconstructed, and a new system of "tonifying blood as the monarch + invigorating the spleen and relieving wind as the minister and assistant" is established. The newly added atractylodes rhizome is used as a key assistant medicine, which solves the problem of tonifying medicine being greasy by invigorating the spleen to prevent stagnation, and at the same time, helps blood and qi to be transformed; Gastrodia as a ministerial medicine, calming liver wind and directly attacking the symptoms of blood deficiency generating wind, aiming at the core symptoms of neurodermatitis, the two form a synergistic effect of "invigorating the spleen and assisting transportation + relieving wind and itching" in the angelica sinensis-radix rehmanniae blood tonifying system. The traditional Chinese medicine composition and traditional Chinese medicine preparation provided by the application can significantly relieve the symptoms of neurodermatitis and itching or edema caused by neurodermatitis, and use pure natural plant raw materials, and no obvious adverse reactions occur in the use process of patients, and can be used as a candidate drug for treating neurodermatitis.

[0083] The above examples are preferred embodiments of the application, but the embodiments of the application are not limited by the above examples, and any changes, modifications, substitutions, combinations and simplifications made without departing from the spirit and principles of the application shall be equivalent replacement methods and shall be within the scope of protection of the application.

Claims

1. A traditional Chinese medicine composition, characterized in that, The Chinese medicine composition comprises the following medicinal raw materials: Angelica sinensis, Radix Rehmanniae Preparata, Atractylodes macrocephala, Saposhnikovia divaricata, Astragalus membranaceus, Polygonum multiflorum, Gastrodia elata, Dictamnus dasycarpus, Schizonepeta tenuifolia and Glycyrrhiza uralensis.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The Chinese medicine composition comprises the following medicinal raw materials: Angelica sinensis 5-30 parts, Radix Rehmanniae Preparata 5-25 parts, Atractylodes macrocephala 5-20 parts, Saposhnikovia divaricata 2-18 parts, Astragalus membranaceus 12-30 parts, Polygonum multiflorum 5-20 parts, Gastrodia elata 1-12 parts, Dictamnus dasycarpus 15-30 parts, Schizonepeta tenuifolia 5-15 parts, and Glycyrrhiza uralensis 1-20 parts.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The Chinese medicine composition comprises the following medicinal raw materials: Angelica sinensis 5-20 parts, Radix Rehmanniae Preparata 10-25 parts, Atractylodes macrocephala 5-20 parts, Saposhnikovia divaricata 2-18 parts, Astragalus membranaceus 12-30 parts, Polygonum multiflorum 5-15 parts, Gastrodia elata 1-12 parts, Dictamnus dasycarpus 15-30 parts, Schizonepeta tenuifolia 5-15 parts, and Glycyrrhiza uralensis 1-15 parts.

4. A Chinese medicine preparation, wherein the active ingredient comprises the Chinese medicine composition according to any one of claims 1-3.

5. The traditional Chinese medicine preparation according to claim 4, characterized in that, The active ingredient is the water extract of the Chinese medicine composition according to any one of claims 1-3.

6. The traditional Chinese medicine preparation according to claim 4, characterized in that, The Chinese medicine preparation further comprises pharmaceutical adjuvants.

7. The traditional Chinese medicine preparation according to any one of claims 4-6, characterized in that, The dosage form of the Chinese medicine preparation comprises ointment, hard capsule, tablet, granule, pill, oral liquid, syrup, powder, suspension, solution, injection, freeze-dried powder injection, injection, suppository, cream, spray or patch.

8. A method for preparing the traditional Chinese medicine preparation according to any one of claims 4-7, characterized in that, The method comprises the following steps: decocting the medicinal raw materials of the Chinese medicine composition according to any one of claims 1-3 with water, filtering, and obtaining the water extract of the Chinese medicine composition.

9. The production method according to claim 8, characterized by, The method further comprises the following steps: concentrating the water extract of the Chinese medicine composition into extract, and mixing the extract with pharmaceutical adjuvants to prepare the Chinese medicine preparation.

10. Use of the Chinese medicine composition according to any one of claims 1-3, or the Chinese medicine preparation according to any one of claims 4-7 in the preparation of a medicament for at least one of the following purposes: 1) preventing and / or treating neurodermatitis; 2) relieving and improving the clinical symptoms caused by neurodermatitis.

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