Composition for dissolving turbidity and relieving itching as well as preparation method and application thereof

Abstract

The invention provides a turbid-dissolving and itching-relieving composition as well as a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicine compositions. The turbidity-dissolving and itching-relieving composition provided by the invention is prepared from the following raw materials in parts by weight: 5 to 15 parts of cortex moutan, 15 to 25 parts of semen coicis, 10 to 20 parts of radix cynanchi paniculati, 5 to 15 parts of radix rehmanniae, 5 to 15 parts of fructus cnidii, 5 to 15 parts of fructus kochiae, 15 to 25 parts of cortex lycii radicis and 5 to 15 parts of liquorice root. The composition for dissolving turbidity and relieving itching provided by the invention is reasonable in whole formula compatibility, can dissolve turbidity and clear damp to treat pruritic dermatosis, dispel wind and relieve itching to treat pruritic dermatosis, nourish yin and moisten dryness to prevent long-term damage of yin, treat both symptoms and root causes, can be used for treating various types of pruritic dermatosis, and has no obvious adverse reaction.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine composition technology, specifically relating to a composition for relieving turbidity and itching, its preparation method, and its application. Background Technology

[0002] Pruritus is a group of diseases with varying causes and pathological changes in the skin, characterized primarily by itching. Currently, there are diverse treatment options for pruritus. In Western medicine, antihistamines are a common choice. They relieve symptoms by blocking the binding of histamine to receptors, reducing histamine-mediated itch signaling. However, these drugs often have significant limitations. For example, some patients experience adverse reactions such as drowsiness, dry mouth, and dizziness, affecting their normal work and life. Long-term use may also lead to drug resistance, gradually reducing the drug's effectiveness. Corticosteroids are also commonly used for anti-inflammatory and anti-allergic purposes, but long-term use may cause side effects such as skin atrophy, telangiectasia, and pigmentation, especially on the face and other areas with thin, delicate skin. There is also a risk of rebound after discontinuation. Dermatitis, eczema, urticaria, and pruritus are all common pruritus diseases in clinical practice, and their causes are multifaceted and complex.

[0003] Traditional Chinese medicine (TCM) has a long history of treating pruritic skin diseases, and some TCM compound formulas or single herbs have been proven to be effective. For example, certain TCM herbs with heat-clearing, detoxifying, wind-dispelling, and itch-relieving properties have a positive effect on improving symptoms. However, traditional TCM treatment also faces many challenges. The components of TCM are complex, the mechanisms of action are unclear, quality control is difficult, and the efficacy of different batches of drugs may vary. Furthermore, the extraction and preparation processes of some TCM herbs are relatively outdated, making it difficult to accurately extract the effective components, resulting in unstable drug efficacy.

[0004] Among physical therapy methods, phototherapy (such as ultraviolet irradiation) can be used to treat some pruritic skin diseases by modulating the skin's immune response. However, phototherapy equipment is expensive, the treatment process requires professional operation, and there are potential risks such as inducing skin cancer. In addition, there are topical antipruritic agents, such as preparations containing menthol and camphor, which can temporarily relieve itching, but the effect is short-lived, and some patients may be allergic to these ingredients.

[0005] Overall, existing methods for treating pruritic skin diseases have varying degrees of shortcomings in terms of efficacy, safety, and stability, making it difficult to meet clinical treatment needs. Developing a safe, effective drug or composition with a clearly defined mechanism of action and good stability for treating pruritic skin diseases is of significant practical importance. This would not only help improve patients' treatment outcomes and quality of life but also fill some gaps in current clinical treatment. Summary of the Invention

[0006] In view of this, the purpose of this invention is to provide a composition for clearing turbidity and relieving itching. The composition is rationally formulated and can be used to treat the root cause of pruritus by clearing turbidity and removing dampness, to treat the symptoms of pruritus by dispelling wind and relieving itching, and to nourish yin and moisten dryness to prevent yin damage from prolonged illness. It treats both the root cause and the symptoms and can be used to treat various types of pruritus.

[0007] To achieve the above-mentioned objectives, the present invention provides the following technical solution: The present invention provides a composition for relieving turbidity and itching, comprising the following raw materials in parts by weight: 5-15 parts of peony bark, 15-25 parts of coix seed, 10-20 parts of Cynanchum paniculatum, 5-15 parts of Rehmannia glutinosa, 5-15 parts of Cnidium monnieri, 5-15 parts of Kochia scoparia, 15-25 parts of Lycium chinense root bark, and 5-15 parts of licorice.

[0008] The present invention also provides a method for preparing the above-mentioned antipruritic and anti-itch composition, comprising the following steps: mixing the raw materials to obtain a mixture; mixing the mixture with water for soaking, boiling, filtering and obtaining the filtrate; spray drying to obtain spray-dried powder; mixing the spray-dried powder with dextrin and ethanol solution to form a soft material, and then granulating it.

[0009] Preferably, the soaking time is 0.5 hours.

[0010] Preferably, the mass ratio of the mixture to water is 1:10.

[0011] Preferably, the decoction is performed twice. The first decoction lasts for 2.5 hours. After the first decoction, the filtrate and residue are collected by filtration. The residue is then mixed with water for a second decoction, which lasts for 1.5 hours.

[0012] Preferably, during the second boiling, the mass of water is 8 times the mass of the mixture.

[0013] Preferably, the method further includes a step of concentrating the filtrate to a relative density of 1.10 to 1.15; the concentration method includes vacuum concentration, wherein the pressure of vacuum concentration is 0.15 MPa, the vacuum degree is -0.06 MPa, and the temperature is 80°C.

[0014] Preferably, the inlet air temperature of the spray dryer is 200°C, the outlet air temperature is 100°C, and the pressure is 0.4 MPa.

[0015] Preferably, the mass ratio of the spray-dried powder to dextrin is 1:3, the volume fraction of the ethanol solution is 55%, and the mass ratio of the spray-dried powder to the ethanol solution is 1:0.35.

[0016] The present invention also provides the application of the above-mentioned antipruritic composition or the above-mentioned preparation method in the preparation of medicaments for treating pruritic skin diseases.

[0017] The beneficial effects of this invention are: The antipruritic and turbidity-resolving composition provided by this invention has a reasonable overall formula. It resolves turbidity and dampness to treat the root cause of pruritus, dispels wind and relieves itching to treat the symptoms of pruritus, and nourishes yin and moistens dryness to prevent yin damage from prolonged illness. It treats both the root cause and the symptoms and can be used to treat various types of pruritus without significant adverse reactions. Attached Figure Description

[0018] Figure 1 This is a flowchart of the preparation method of the present invention.

[0019] Figure 2 This is a chromatogram of a mixed reference standard, a test sample, and a negative control. In the mixed reference standard, 1 represents gallic acid, 2 represents glycyrrhizic acid, and 3 represents osthol. Detailed Implementation

[0020] The present invention provides a composition for relieving turbidity and itching, comprising the following raw materials in parts by weight: 5-15 parts of peony bark, 15-25 parts of coix seed, 10-20 parts of Cynanchum paniculatum, 5-15 parts of Rehmannia glutinosa, 5-15 parts of Cnidium monnieri, 5-15 parts of Kochia scoparia, 15-25 parts of Lycium chinense root bark, and 5-15 parts of licorice.

[0021] In this invention, the preferred amount of peony bark is 7-13 parts, more preferably 9-11 parts; the preferred amount of coix seed is 17-23 parts, more preferably 19-21 parts; the preferred amount of Cynanchum paniculatum is 12-18 parts, more preferably 14-16 parts; the preferred amount of Rehmannia glutinosa is 7-13 parts, more preferably 9-11 parts; the preferred amount of Cnidium monnieri is 7-13 parts, more preferably 8-11 parts; the preferred amount of Kochia scoparia is 7-13 parts, more preferably 9-11 parts; the preferred amount of Lycium chinense root bark is 17-23 parts, more preferably 18-21 parts; and the preferred amount of licorice root is 7-13 parts, more preferably 9-11 parts. This invention does not have any special limitations on the specific source of the above-mentioned raw materials; conventional commercially available products in the art can be used.

[0022] This invention's turbidity-resolving and antipruritic composition is a drug developed based on the "turbidity-toxin theory" of Traditional Chinese Medicine. As a newly emerging theory in Traditional Chinese Medicine, the turbidity-toxin theory explores the impact of changes in the contemporary ecological environment and human health on diet, emotions, and lifestyle through a holistic approach that emphasizes the unity of man and nature and syndrome differentiation. Turbidity-toxin is both a pathogenic factor that can severely damage the body's organs, meridians, qi, blood, yin, and yang, and a pathological product that cannot be eliminated from the body due to various reasons. This invention, based on the turbidity-toxin theory, treats related skin diseases through syndrome differentiation, has many years of clinical experience, and has achieved good clinical efficacy. In this invention's turbidity-resolving and antipruritic composition, the principal ingredient is Coix seed, which is sweet, bland, and slightly cold in nature, and enters the spleen, stomach, and lung meridians. It has the functions of promoting diuresis and eliminating dampness, strengthening the spleen and stopping diarrhea, relieving numbness, draining pus, and detoxifying and dispersing nodules. In this formula, its ability to resolve turbidity and eliminate dampness is the principal ingredient, targeting the main pathogenesis of internal dampness and turbidity. The assistant herbs are Cnidium monnieri and Kochia scoparia, both of which can dispel wind and relieve itching. Cnidium monnieri is warm in nature and can dry dampness and dispel wind; Kochia scoparia is cold in nature and can clear heat, promote diuresis, and dispel wind. Together, they enhance the effect of dispelling wind and relieving itching, assisting the principal herb in dispelling dampness and relieving itching. The adjuvant herbs are Paeonia suffruticosa, Rehmannia glutinosa, and Lycium chinense. Paeonia suffruticosa clears heat and cools the blood, invigorates blood and removes blood stasis; Rehmannia glutinosa nourishes yin and clears heat, nourishes blood and moistens dryness; Lycium chinense cools the blood and eliminates steaming heat, clears the lungs and reduces fire. These three herbs nourish yin and cool the blood, moisten dryness and eliminate steaming heat, treating yin deficiency and blood dryness caused by prolonged illness, while also restraining the warming and drying properties of the principal and assistant herbs. The guiding herbs are Cynanchum paniculatum, which dispels wind, relieves pain, and stops itching; and Glycyrrhiza uralensis, which harmonizes the herbs and clears heat and detoxifies. Glycyrrhiza uralensis has the effect of harmonizing the properties of the herbs, making the whole formula more coordinated. In summary, the formula is rationally formulated, addressing the root cause of pruritus by clearing away turbidity and dampness, relieving wind and itching to address the symptoms of pruritus, and nourishing yin and moistening dryness to prevent yin damage from prolonged illness. It treats both the root cause and the symptoms and can be used to treat various types of pruritus.

[0023] The present invention also provides a method for preparing the above-mentioned antipruritic and anti-itch composition, comprising the following steps: mixing the raw materials to obtain a mixture; mixing the mixture with water for soaking, boiling, filtering and obtaining the filtrate; spray drying to obtain spray-dried powder; mixing the spray-dried powder with dextrin and ethanol solution to form a soft material, and then granulating it.

[0024] In this invention, the soaking time is preferably 0.5 hours. The mass ratio of the mixture to water is preferably 1:10. The decoction is preferably performed twice, with the first decoction preferably lasting 2.5 hours. After the first decoction, the filtrate and residue are collected by filtration. The residue is mixed with water for a second decoction, which is preferably lasting 1.5 hours. During the second decoction, the mass of water is preferably 8 times the mass of the mixture. In the preparation method of this invention, a step of concentrating the filtrate is preferred, wherein the concentration is to a relative density of 1.10~1.15 (measured at 60°C). The concentration method preferably includes vacuum concentration, wherein the pressure of the vacuum concentration is preferably 0.15 MPa, the vacuum degree of the vacuum concentration is preferably -0.06 MPa, and the temperature of the vacuum concentration is preferably 80°C. In this invention, the inlet air temperature of the spray drying is preferably 200°C, the outlet air temperature is preferably 100°C, and the pressure is preferably 0.4 MPa. In this invention, the preferred mass ratio of the spray-dried powder to dextrin is 1:3, the preferred volume fraction of the ethanol solution is 55%, and the preferred mass ratio of the spray-dried powder to the ethanol solution is 1:0.35. In the preparation method of this invention, after granulation, the method preferably further includes steps of granulation, drying into granules, and then packaging into finished products. The flow chart of the above preparation method of this invention is as follows: Figure 1 As shown. In this invention, after the purging and antipruritic composition is made into a granule formulation, it is preferred that each bag contains 10g (each bag contains Cnidium monnieri with osthol (C 15 H 16 (Calculated as O3, not less than 0.35mg). The preferred dosage is 1-2 sachets taken with warm water, 2-3 times daily. The purgative and antipruritic granules of this invention are brown granules; they have a slight odor and a bland taste.

[0025] The active ingredients in the antipruritic and turbidity-reducing composition of this invention include triterpenoids (glycyrrhetinic acid, oleanolic acid, glycyrrhizic acid, glycyrrhizin, etc.), flavonoids (paeoniflorin, scutellarin, apigenin, etc.), coumarins (ostrichol, imperatorin, etc.), and iridoid glycosides (rehinoside A, rehinoside B, rehinoside C, etc.). These components are easily soluble in hot water and are stable and not easily destroyed. Traditional decoctions, however, suffer from drawbacks such as large dosages, inconvenient portability, difficulty in quality control, and susceptibility to mold and spoilage upon prolonged storage. This invention prepares the antipruritic and turbidity-reducing composition into granules with a large drug loading capacity. Granules are a solid dosage form that retains the rapid absorption and efficacy of decoctions while also offering advantages such as accurate dosage, stable properties, ease of control, convenient storage and transportation, convenient portability and administration, and good taste. This invention employs a process of whole-formula water extraction → spray drying → wet granulation, minimizing the dosage while ensuring the quality of the preparation.

[0026] This invention also provides the application of the above-described antipruritic composition or the above-described preparation method in the preparation of a medicament for treating pruritic skin diseases. In this invention, the pruritic skin diseases preferably include dermatitis, eczema, urticaria, and / or pruritus.

[0027] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0028] Unless otherwise specified, the following embodiments are all conventional methods.

[0029] Unless otherwise specified, all materials and reagents used in the following examples are commercially available.

[0030] The peony bark, coix seed, cynanchum paniculatum, rehmannia root, cnidium fruit, kochia fruit, and licorice root used in the following examples were purchased from Anguo Yikang Pharmaceutical Co., Ltd., and lycium bark was purchased from Hebei Anguo Zhenyu Pharmaceutical Co., Ltd.

[0031] Example 1 A composition for relieving turbidity and itching (also known as turbidity-relieving and itching-relieving granules) is made from the following raw materials in parts by weight: 5g of peony bark, 15g of coix seed, 10g of Cynanchum paniculatum, 5g of Rehmannia glutinosa, 5g of Cnidium monnieri, 5g of Kochia scoparia, 15g of Lycium chinense root bark, and 5g of licorice.

[0032] The preparation method is as follows: Peony bark, coix seed, Cynanchum paniculatum, Rehmannia glutinosa, Cnidium monnieri, Kochia scoparia, Lycium chinense root bark, and licorice are mixed to obtain a mixture; the mixture is mixed with water at a mass ratio of 1:10, soaked for 0.5 hours, and then decocted for 2.5 hours, filtered to obtain filtrate 1; the residue is mixed with water at a mass ratio of 8 times that of the mixture, decocted for 1.5 hours, and filtered to obtain filtrate 2; filtrate 1 and filtrate 2 are mixed and concentrated under reduced pressure at a pressure of 0.15 MPa, a vacuum degree of -0.06 MPa, and a temperature of 80℃ to a relative density of 1.10 (measured at 60℃), and then spray-dried under conditions of an inlet air temperature of 200℃, an outlet air temperature of 100℃, and a pressure of 0.4 MPa to obtain spray-dried powder; the spray-dried powder, dextrin, and a 55% ethanol solution are mixed at a mass ratio of 1:3:0.35 to form a soft mass, which is then granulated, sized, and dried to obtain turbidity-relieving and itch-relieving granules.

[0033] Example 2 A composition for relieving turbidity and itching (also known as turbidity-relieving and itching-relieving granules) is made from the following raw materials in parts by weight: 15g of peony bark, 25g of coix seed, 20g of Cynanchum paniculatum, 15g of Rehmannia glutinosa, 15g of Cnidium monnieri, 15g of Kochia scoparia, 25g of Lycium chinense root bark, and 15g of licorice.

[0034] The preparation method is as follows: Peony bark, coix seed, Cynanchum paniculatum, Rehmannia glutinosa, Cnidium monnieri, Kochia scoparia, Lycium chinense root bark, and licorice are mixed to obtain a mixture; the mixture is mixed with water at a mass ratio of 1:10, soaked for 0.5 hours, and then decocted for 2.5 hours, filtered to obtain filtrate 1; the residue is mixed with water at a mass ratio of 8 times that of the mixture, decocted for 1.5 hours, and filtered to obtain filtrate 2; filtrate 1 and filtrate 2 are mixed and concentrated under reduced pressure at a pressure of 0.15 MPa, a vacuum degree of -0.06 MPa, and a temperature of 80℃ to a relative density of 1.15 (measured at 60℃), and then spray-dried under conditions of an inlet air temperature of 200℃, an outlet air temperature of 100℃, and a pressure of 0.4 MPa to obtain spray-dried powder; the spray-dried powder, dextrin, and a 55% ethanol solution are mixed at a mass ratio of 1:3:0.35 to form a soft mass, which is then granulated, sized, and dried to obtain turbidity-relieving and itch-relieving granules.

[0035] Example 3 A composition for relieving turbidity and itching (also known as turbidity-relieving and itching-relieving granules) is made from the following raw materials in parts by weight: 210g of peony bark, 420g of coix seed, 315g of Cynanchum paniculatum, 210g of Rehmannia glutinosa, 210g of Cnidium monnieri, 210g of Kochia scoparia, 420g of Lycium chinense root bark, and 210g of licorice.

[0036] The preparation method is as follows: Peony bark, coix seed, Cynanchum paniculatum, Rehmannia glutinosa, Cnidium monnieri, Kochia scoparia, Lycium chinense root bark, and licorice are mixed to obtain a mixture; the mixture is mixed with water at a mass ratio of 1:10, soaked for 0.5 hours, and then decocted for 2.5 hours, filtered to obtain filtrate 1; the residue is mixed with water at a mass ratio of 8 times that of the mixture, decocted for 1.5 hours, and filtered to obtain filtrate 2; filtrate 1 and filtrate 2 are mixed and concentrated under reduced pressure at a pressure of 0.15 MPa, a vacuum degree of -0.06 MPa, and a temperature of 80℃ to a relative density of 1.13 (measured at 60℃), and then spray-dried under conditions of an inlet air temperature of 200℃, an outlet air temperature of 100℃, and a pressure of 0.4 MPa to obtain spray-dried powder; the spray-dried powder, dextrin, and a 55% ethanol solution are mixed at a mass ratio of 1:3:0.35 to form a soft mass, which is then granulated, sized, and dried to obtain turbidity-relieving and itch-relieving granules.

[0037] Example 4 The inspection was conducted in accordance with the relevant provisions of the 2020 edition of the Chinese Pharmacopoeia.

[0038] (1) Particle size inspection According to the particle size distribution determination method (General Rule 0982, Method 2, Double Sieve Method), the total percentage of particles that cannot pass through sieve No. 1 and those that can pass through sieve No. 5 shall not exceed 15%, which shall comply with the regulations.

[0039] Double sieving method: Take the purging and antipruritic granules obtained in Examples 1 to 3, weigh them, and place them in the upper layer (No. 1 sieve) of the dosage form specified below (the lower sieve is equipped with a sealed receiving container). Keep the sieve horizontal and sieve back and forth, tapping the granules while sieving for 3 minutes. Take the granules and powder that cannot pass through the No. 1 sieve and those that can pass through the No. 5 sieve, weigh them, and calculate their proportion (%). The results are shown in Table 1. According to the particle size distribution determination method, the average proportion of the purging and antipruritic granules that cannot pass through the No. 1 sieve and those that can pass through the No. 5 sieve is 1.70%, which does not exceed 15% and meets the requirements.

[0040] Table 1. Results of particle size determination for Huazhuo Zhiyang granules

[0041] (2) Moisture content test According to the second method (drying method) for moisture determination (General Rule 0832), the moisture content shall not exceed 8.0% and shall comply with the regulations.

[0042] Determination Method: Take 5 g of each of the Huazhuo Zhiyang granules obtained in Examples 1-3, spread them evenly in a flat weighing bottle dried to constant weight, with a thickness not exceeding 5 mm, and for loose samples not exceeding 10 mm. Accurately weigh the contents, open the bottle cap and dry at 105℃ for 5 h. Close the bottle cap, transfer it to a desiccator, cool for 30 min, accurately weigh the contents, and then dry at the above temperature for another hour. Cool and weigh the contents again until the difference between two consecutive weighings does not exceed 5 mg. Calculate the water content (%) in the sample based on the weight loss. The results are shown in Table 2. According to the second method (drying method) for moisture determination, the average water content of the Huazhuo Zhiyang granules is 2.22%, which does not exceed 8.0% and meets the requirements.

[0043] Table 2. Moisture content determination results of different groups of Huazhuo Zhiyang granules

[0044] (3) Solubility test For granules, the solubility should meet the requirements as specified in the following tests.

[0045] Soluble particle test method: Take the anti-itch and anti-turbidity granules obtained in Examples 1 to 3 respectively, add 200mL of hot water, stir for 5 minutes, and observe immediately. The soluble particles should be completely dissolved or slightly turbid.

[0046] Test results: The Huazhuo Zhiyang Granules were tested according to the soluble particle test method. They showed slight turbidity, which meets the requirements.

[0047] (4) Microbial limit test Granules made from non-monomer components derived from plants were tested according to the microbial limit test for non-sterile products: microbial count method (Chinese Pharmacopoeia, Part IV, General Chapter 1105) and control bacteria test method (Chinese Pharmacopoeia, Part IV, General Chapter 1106) and the microbial limit standard for non-sterile drugs (Chinese Pharmacopoeia, Part IV, General Chapter 1107), and met the requirements.

[0048] Huazhuo Zhiyang Granules are a non-sterile oral solid dosage form of traditional Chinese medicine that does not contain raw medicinal powder. The total aerobic bacteria count must not exceed 10. 3 CFU / g, and the total number of molds and yeasts must not exceed 10. 2 CFU / g; Escherichia coli (1g or 1 mL) and Salmonella (10g or 10 mL) were not detected, which meets the requirements. The antipruritic granules obtained in Examples 1 to 3 all meet the requirements.

[0049] Example 5 Extraction process research The water extraction process was selected, and the process study mainly investigated the effects of three factors on extraction efficiency: water volume, extraction time, and number of extractions. To maximize the extraction of the effective components from each raw material in the composition and ensure the clinical efficacy of the formulation, the content of gallic acid, glycyrrhizic acid, and osthol, as well as the yield of extract, were used as evaluation indicators. An orthogonal experiment was conducted to screen for the optimal process, the specific method of which is as follows: The comprehensive score M was calculated using the water addition ratio, extraction times, and extraction time as the main influencing factors, and the contents of gallic acid, glycyrrhizic acid, and osthol, as well as the yield of extract, as evaluation indicators. The entropy weight method was used to calculate M. An orthogonal experimental design was adopted, and the levels of the experimental design factors are shown in Table 3. The extraction time in Table 3 is the total time, and the water addition ratio is the water addition ratio of the last extraction.

[0050] Table 3 Factors and Levels

[0051] Determination of the weights of each indicator and overall scoring: Establish the original evaluation matrix (P). Based on the results of "gallic acid, glycyrrhizic acid, osthol content, and extract yield," establish the original evaluation index matrix (P). X ). Calculate P according to formula (1). ij The original evaluation matrix is ​​transformed into a "probability" matrix (P).

[0052] (1) Calculate information entropy ( H i ). Calculate the information entropy of each indicator according to formula (2). H i The result isH i =[0.968, 0.943, 0.917, 0.979].

[0053] (2) Calculate the weighting coefficients of each indicator ( W i The weights are calculated according to formula (3). W i =[0.164, 0.297, 0.430, 0.109]. After normalizing the data, the comprehensive index M was calculated (M = gallic acid content / Max). （没食子酸含量） ×0.164 + glycyrrhizic acid content / Max （甘草酸含量） ×0.297+ Osthol content / Max （蛇床子素含量） ×0.430 + Ointment Yield / Max （出膏率） ×0.109)×100%.

[0054] (3) The method for determining the yield of extract is as follows: the extract is concentrated under reduced pressure to form a thick extract, placed in an evaporating dish, evaporated to dryness in a water bath, dried at 105℃ to constant weight, cooled in a desiccator for 30 min, accurately weighed, and the yield of extract is calculated by the weight reduction method.

[0055] Determination of the content of components in the extraction process: (1) High performance liquid chromatography conditions Column: QYRH AQ-C 18 (2.1 mm × 100 mm, 1.7 μm); using A (acetonitrile)-B (0.1% formic acid aqueous solution) as the mobile phase, gradient elution: 0–20 min, 5% → 15% A; 20–28 min, 15% → 17% A; 28–38 min, 17% → 27% A; 38–65 min, 27% → 48% A. Column temperature: 30℃, flow rate: 1.0 mL / min. Detection wavelength: 248 nm, injection volume: 10 μL. HPLC chromatogram is shown below. Figure 2 .

[0056] (2) Solution preparation method: 2.1 Preparation of the test solution: Weigh out 52.5 g of each raw material according to the proportion of the composition in Example 3, place it in a 1000 mL round-bottom flask, add 10 times the amount of water and soak for 0.5 h, extract twice, the first time for 2.5 h, the second time add 8 times the amount of water and extract for 1.5 h, combine the filtrates, take 1 mL and place it in a 10 mL volumetric flask, dilute to volume with methanol, shake thoroughly, let stand, take the supernatant and filter it through a 0.22 μm microporous membrane to obtain the test solution.

[0057] 2.2 Preparation of the reference solution: Accurately weigh appropriate amounts of gallic acid, glycyrrhizic acid, and osthol reference standards, and place them separately in volumetric flasks. Dilute to volume with methanol to obtain single reference standard solutions with mass concentrations of 0.628, 0.511, and 0.170 mg / mL, respectively. Take appropriate amounts of each reference standard solution and place them in volumetric flasks to obtain a mixed reference standard solution.

[0058] 2.3 Preparation of negative solution: According to the prescription ratio described in Example 3, the three herbs, peony bark, licorice root, and cnidium fruit, were removed respectively and prepared into negative test samples of the three herbs according to the preparation method. The negative test sample solution was prepared using the same test sample solution preparation method.

[0059] Examining linear relationships: The reference solution was serially diluted to obtain a series of reference solutions with different concentration gradients. HPLC was used for detection, and the peak area was recorded. Linear regression was performed with peak area as the ordinate (y) and reference concentration as the abscissa (x, μg / mL). The results are shown in Table 4.

[0060] Table 4. Linear regression equation for the control sample, R0 2 and linear range

[0061] Inject the test solution once under the above chromatographic conditions, record the peak area, and calculate the contents of gallic acid, glycyrrhizic acid and osthol according to the linear regression equation in Table 4.

[0062] The results of the orthogonal experiment on the extraction process are shown in Table 5.

[0063] Table 5. Orthogonal experimental design and results of extraction process

[0064] Table 5 shows that, based on the R-values, the order of influence of each factor on M is C>A>B, i.e., extraction times > water addition ratio > extraction time. Statistical results indicate that the number of extractions has the most significant impact on M. Analysis shows that the optimal extraction conditions for Huazhuo Zhiyang Granules are: A2B2C2, water addition ratio 8 times, extraction times 2 times, and a total extraction time of 4 hours. Specifically, the first extraction uses 10 times the amount of water (2 times the water absorption rate) for 2.5 hours, and the second extraction uses 8 times the amount of water for 1.5 hours.

[0065] Example 6 Concentration process research Reduced pressure concentration can improve concentration efficiency while saving costs. Based on the preparation method described in Example 3, the experiment used a single-factor approach to explore the effect of different temperatures on the concentration process. The key parameter mainly examined was the concentration temperature. The concentration pressure was controlled at 0.15 MPa and the vacuum degree at -0.06 MPa. Different concentration temperatures were set, and an original evaluation index matrix was established based on the results of "gallic acid, glycyrrhizic acid, and osthol content (determination method as in Example 5)". X ). Calculate according to formula (1) P ij Transform the original evaluation matrix into a "probability" matrix. P ); calculate the information entropy of each indicator according to formula (2). H i The result is H i =[0.997, 0.998, 0.997]; according to formula (3), the weights are calculated. W i =[0.351, 0.307, 0.342]. After normalizing the data, the comprehensive index Y (Y = gallic acid content / Max) was calculated. （没食子酸含量） ×0.351+glycyrrhizic acid content / Max （甘草酸含量） ×0.307+ Osthol content / Max （蛇床子素含量） (×0.342)×100%, the experimental results are shown in Table 6. The comprehensive score is the highest when the concentration temperature is 80℃.

[0066] Table 6. Effect of Concentration Temperature on Overall Score

[0067] Example 7 Drying process research Spray drying has the advantages of fast drying speed, short material heating time, simple production process and uniform product texture. Therefore, spray drying process is selected based on existing production equipment.

[0068] Spray drying test: Raw materials sufficient to prepare 1000g of medicine were weighed according to the raw material ratio in Example 3. Extraction was performed according to the process determined in Example 3. The density after vacuum concentration was investigated through single-factor experiments. Based on the single-factor experiments, orthogonal design was used to screen the three optimal operating conditions of the spray drying equipment (inlet air temperature: 180~200℃, outlet air temperature: 85~105℃, pressure: 0.4MPa), and the optimal spray drying conditions were selected. (Yield = Amount of extract obtained after vacuum concentration / Amount of raw material × 100%). The effect of density after vacuum concentration on yield is shown in Table 7, the factor level design of spray drying conditions is shown in Table 8, and the results of orthogonal experiments and design are shown in Table 9.

[0069] Table 7 Effect of density on yield from vacuum concentration

[0070] Table 8. Levels of factors in spray drying

[0071] Table 9 Orthogonal Experiment and Design of Spray Drying Process

[0072] Table 9 shows that, according to the R-values, the order of influence of each factor on the yield is A>C>B, i.e., inlet temperature > steam pressure > outlet temperature; the P-values ​​indicate that the inlet temperature has the most significant impact on the yield. The analysis results show that the optimal spray drying process conditions for the Huazhuo Zhiyang Granules are: A3B2C2, i.e., after extraction according to the decoction process in Example 3, the extract is concentrated under reduced pressure to a relative density of 1.10~1.15 (measured at 60℃). Based on the optimal operating conditions of the spray drying equipment and the material properties, the spray drying conditions (inlet temperature 200℃, outlet temperature 100℃, and pressure 0.4 MPa) were set, and three batches of process verification were conducted. The results showed that there was little wall adhesion during the drying process, and a dry and loose spray powder was obtained, with good results and a stable and feasible process.

[0073] Example 8 Molding process research 1. Evaluation index determination 1.1 Molding rate The formability of the particles is characterized, and a higher formability rate is better. The particle size and particle size distribution were determined according to the 2020 edition of the Chinese Pharmacopoeia, Part IV (General Chapter 0982, Double Sieve Method). Particles passing through a No. 1 sieve (10 mesh) and those not passing through a No. 5 sieve (80 mesh) were collected, weighed, and the formability rate was calculated. Formability rate (%) = (Total weight of qualified particles / Total weight of particles) × 100.

[0074] 1.2 Moisture absorption rate Accurately weigh approximately 2g of granules, divide into three equal portions, and place each portion into a dry, constant-weight weighing bottle. Spread the portions evenly and place them in a desiccator containing a supersaturated sodium chloride solution, which has been kept at room temperature for 24 hours (temperature: 25℃, relative humidity: 75%). Seal the bottles and accurately weigh them after 48 hours. Calculate the moisture absorption rate. Moisture absorption rate = (weight of granules after moisture absorption - weight of granules before moisture absorption) / weight of granules before moisture absorption × 100. The lower the moisture absorption rate of the granules, the better.

[0075] 1.3 Melting rate A higher solubility is better. Accurately weigh approximately 1 g of granules and place them in a centrifuge tube. Add 20 mL of boiling water, stir and shake for 5 min, then centrifuge for 5 min (3500 r / min). Place the residue in a 60℃ forced-air drying oven until constant weight, weigh it, and calculate the solubility. Solubility = (Total granule weight - Residue weight) / Total granule weight × 100.

[0076] 1.4 Angle of repose To characterize the accuracy of particle dosage, a smaller angle of repose indicates better particle flowability. The angle of repose was determined using the fixed funnel method. The funnel was fixed at a height of 1 cm (H) on a horizontally placed graph paper. Particles were slowly poured into the funnel along its wall until the resulting cone of particles touched the final opening of the funnel. The diameter of the cone (2R) was measured, and the angle of repose α was calculated. Angle of repose (α) = arctanH / R, where H = 1 cm. Each sample was measured three times, and the average value was taken.

[0077] 1.5 bulk density Bulk density affects the dosage and characterizes the compactness of the granules. Because traditional Chinese medicine is consumed in large quantities, a higher bulk density is better. Take a 10 mL graduated cylinder that has been dried to constant weight, slowly pour the granules along the cylinder wall, and record the volume when the surface of the granules is level with the graduation line. Weigh the granules and calculate the bulk density. Bulk density (ρ) = Granule mass / Granule volume.

[0078] 2. Preparation of granules Based on the raw materials and preparation method described in Example 3, the ratio of dextrin to spray-dried powder, the ratio of spray-dried powder to ethanol, and the ethanol concentration were used as the main influencing factors. The overall score Y was calculated using the granulation rate, moisture absorption rate, solubility rate, angle of repose, and bulk density as evaluation indicators. An original evaluation matrix (P) was established using the relevant formulas from Example 5, and the information entropy of each indicator was calculated. H i Y was calculated using the entropy weight method. The information entropy of the molding rate, moisture absorption rate, melting rate, angle of repose, and bulk density was calculated. H i The weighting coefficients are 0.9989, 0.9987, 0.9999, 0.9997, and 0.9956, respectively. Wi The values ​​are 0.1491, 0.1743, 0.0204, 0.0461, and 0.6101, respectively. The overall score is calculated as follows: (0.1491 × molding rate / molding rate max + 0.1743 × moisture absorption rate min / moisture absorption rate + 0.0204 × melting rate / melting rate max + 0.0461 × angle of repose min / angle of repose + 0.6101 × bulk density / bulk density max) × 100.

[0079] Design L9 (3) 4The optimal molding process parameters for the Huazhuo Zhiqi granules were screened using orthogonal experiments. The factor levels are shown in Table 10. The results of the orthogonal experiments were recorded in the orthogonal table, as shown in Table 11.

[0080] Table 10. Factors related to particle forming process.

[0081] Table 11 Orthogonal Experiment and Design of Particle Molding Process

[0082] Table 11 shows that, according to the R-values, the order of influence of each factor on Y is A>C>B, i.e., the ratio of spray-dried powder to dextrin > ethanol concentration > ethanol dosage. The P-values ​​indicate that the ratio of spray-dried powder to dextrin has the most significant impact on Y. The analysis results show that the optimal molding process conditions for the Huazhuo Zhiqi granules are: A2B1C1. Raw materials sufficient to prepare 1000 g of granules are weighed, extracted according to the determined process, concentrated under reduced pressure to an extract with a relative density of 1.12 (measured at 60℃), and spray-dried. Three batches of granules were used to verify the molding process. The results show that the granules are loose, have a high molding rate, and the overall score Y-value RSD is less than 3%, indicating that the process is stable and feasible.

[0083] Example 9 From January 2021 to December 2023, the Huazhuo Zhiyang granules obtained in Example 3 were used to treat 60 cases of pruritic skin diseases, achieving good results. The summary is as follows: Clinical Data: General Information: 60 cases, 24 males and 36 females. Among them, 12 cases had dermatitis (5 males and 7 females), aged 16-45 years, with a mean age of 31.3±14.0 years; 22 cases had eczema (9 males and 13 females), aged 19-58 years, with a mean age of 39.5±13.1 years; 11 cases had urticaria (5 males and 6 females), aged 16-55 years, with a mean age of 33.1±12.3 years; and 15 cases had pruritus (5 males and 10 females), aged 35-70 years, with a mean age of 51.0±13.6 years. All patients had not used antihistamines or topical corticosteroids within the past 4 weeks.

[0084] Administration: The antipruritic granules obtained in Example 3 should be taken half an hour after breakfast and half an hour after dinner, one sachet at a time, 10g per sachet, twice a day, for 14 days as one course of treatment. During the medication period, alcohol, spicy and irritating foods, and fishy and pungent foods should be avoided. Before and on the 14th day of medication, the changes in skin lesions, subjective symptoms, and adverse reactions should be carefully observed and recorded.

[0085] Efficacy Evaluation: Scoring Criteria: Six indicators—pruritus, erythema, papules, vesicles, exudation, and lichenification—were graded, with 0 = none, 1 = mild, 2 = moderate, and 3 = severe. Scoring was performed before and after treatment. Cure: Itching eliminated, with a total score reduction rate ≥90%; Significantly Effective: Itching significantly reduced, with a total score reduction rate of 60% ≤ <90%; Effective: Itching reduced, with a total score reduction rate of 30% ≤ <60%; Ineffective: Itching remained the same or worsened, with a total score reduction rate of less than 30%. Total score reduction rate = Pre-treatment score - Post-treatment score / Pre-treatment score; Effective rate = (Number of cured cases + Number of significantly effective cases) / Total number of treated cases * 100%.

[0086] Results: Clinical efficacy is shown in Table 12. The overall effective rate for 60 cases of pruritic skin diseases was 85%, with dermatitis at 83.33%, eczema at 86.36%, urticaria at 81.82%, and pruritus at 86.67%. No significant adverse reactions were observed during the observation period, and all patients completed the treatment course. This indicates that the Huazhuo Zhiyang Granules of this invention can be used to treat pruritic skin diseases with good efficacy and few side effects, and can be used to treat dermatitis, eczema, urticaria, pruritus, and other skin diseases characterized by itching.

[0087] Table 12 Results of treating 60 cases of pruritic skin diseases with Huazhuo Zhiyang Granules

[0088] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A composition for relieving turbidity and itching, characterized in that, The ingredients include the following raw materials by weight: 5-15 parts of peony bark, 15-25 parts of coix seed, 10-20 parts of cynanchum paniculatum, 5-15 parts of rehmannia root, 5-15 parts of cnidium fruit, 5-15 parts of kochia fruit, 15-25 parts of lycium bark, and 5-15 parts of licorice root.

2. The method for preparing the antipruritic and turbidity-reducing composition according to claim 1, characterized in that, The process includes the following steps: mixing the raw materials to obtain a mixture; soaking the mixture in water, boiling it, filtering it to obtain the filtrate; spray drying it to obtain spray-dried powder; mixing the spray-dried powder with dextrin and ethanol solution to form a soft mass, and then granulating it.

3. The preparation method according to claim 2, characterized in that, The soaking time is 0.5 hours.

4. The preparation method according to claim 2, characterized in that, The mass ratio of the mixture to water is 1:

10.

5. The preparation method according to claim 2, characterized in that, The decoction process includes two cycles. The first decoction lasts for 2.5 hours. After the first decoction, the filtrate and residue are collected by filtration. The residue is then mixed with water for a second decoction, which lasts for 1.5 hours.

6. The preparation method according to claim 5, characterized in that, During the second boiling, the mass of water was 8 times the mass of the mixture.

7. The preparation method according to claim 2, characterized in that, It also includes a step of concentrating the filtrate to a relative density of 1.10 to 1.15; the concentration method includes vacuum concentration, wherein the pressure of vacuum concentration is 0.15 MPa, the vacuum degree is -0.06 MPa, and the temperature is 80°C.

8. The preparation method according to claim 2, characterized in that, The spray dryer has an inlet air temperature of 200°C, an outlet air temperature of 100°C, and a pressure of 0.4 MPa.

9. The preparation method according to claim 2, characterized in that, The mass ratio of the spray-dried powder to dextrin is 1:3, the volume fraction of the ethanol solution is 55%, and the mass ratio of the spray-dried powder to the ethanol solution is 1:0.

35.

10. The use of the antipruritic composition of claim 1 or the preparation method of any one of claims 1 to 9 in the preparation of a medicament for treating pruritic skin diseases.

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