A traditional Chinese medicine composition for treating cholestatic pruritus, and its preparation method and use

Abstract

The invention discloses a Chinese medicine composition for treating cholestatic pruritus and its preparation method and use, and relates to the technical field of Chinese medicine. The Chinese medicine composition described in the present invention is composed of Sophora flavescens, Scutellaria baicalensis, Bupleurum chinense, Artemisia capillaris, Kochia scoparia, Dictamni cortex, Campsis creeper, Tribulus terrestris, Periostracum cicada and Radix Clematidis. The Chinese medicine composition is made up of the following components in parts by weight: 6-9 parts of Sophora flavescens, 6-9 parts of Scutellaria baicalensis, 6-12 parts of Bupleurum chinense, 6-15 parts of Artemisia capillaris, 5-9 parts of Kochia scoparia, 3-6 parts of Dictamni cortex, 7-9 parts of Campsis creeper, 5-8 parts of Tribulus terrestris, 3-5 parts of Periostracum cicada and 5-8 parts of Radix Clematidis. The Chinese medicine composition of the present invention can effectively alleviate cholestatic pruritus, has significant efficacy, is highly safe, and long-term use will not produce serious adverse reactions. It has good application prospects in treating cholestatic pruritus.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to a traditional Chinese medicine composition for treating cholestatic pruritus, a preparation method thereof and uses thereof. Background Art

[0002] Cholestasis refers to a pathological condition in which bile formation, secretion, and excretion are impaired due to various factors both inside and outside the liver, preventing bile from flowing normally into the duodenum and entering the bloodstream. Hepatobiliary diseases characterized by cholestasis as the primary manifestation of liver disease due to various factors, such as progressive liver and gallbladder disease and medication use, are collectively referred to as cholestatic liver disease. Regional clinical observational studies suggest that cholestasis is prevalent in hospitalized patients with chronic liver disease, with an increasing trend with age. Epidemiological surveys indicate that common cholestatic liver diseases include primary sclerosing cholangitis, primary biliary cholangitis, liver tumors, and drug-induced liver disease.

[0003] Pruritus is a common clinical manifestation of cholestatic liver disease, with a high incidence in patients with primary sclerosing cholangitis and intrahepatic cholestasis of pregnancy. Clinically, cholestatic pruritus can exhibit a circadian rhythm, worsening at night, severely impacting patients' quality of life and causing physiological and psychological impairments. The precise pathophysiological mechanisms of cholestatic pruritus remain unclear, with current theories linking abnormal nerve fiber stimulation, abnormal bile excretion, and progesterone metabolism, with abnormal bile excretion being the most widely accepted.

[0004] Currently, the primary treatment for cholestatic pruritus is still to improve cholestasis. The main therapeutic drugs include ursodeoxycholic acid, S-adenosylmethionine, cholestyramine, fibrates and obeticholic acid. However, the above drugs have disadvantages such as heavy liver and kidney burden, limited clinical response rate and insufficient effectiveness in improving pruritus symptoms. Antihistamines or hormone drugs given for pruritus symptoms can only improve symptoms in the short term but cannot improve the cause.

[0005] Traditional Chinese Medicine (TCM) treatments primarily include acupuncture and cold compresses. Acupuncture at points such as Quchi, Xuehai, Geshu, and Baichongwo can cool blood, invigorate blood circulation, dispel wind, and relieve itching, making it an effective treatment for pruritus secondary to cholestatic liver disease. External application of traditional Chinese medicine powders utilizes the principles of Chinese medicine meridian regulation, delivering medications directly through the skin to the affected area, thereby dispelling wind, relieving itching, and dissolving dampness and toxins. Modern TCM believes that the pathogenesis of pruritus secondary to cholestatic liver disease is primarily due to poor bile excretion, resulting in its accumulation and overflow into the skin; accumulation of damp-heat and fire toxins in the skin, which cannot be dissipated; blood deficiency and liver hyperactivity, which generate wind and dryness, leading to skin malnutrition; or blood stasis blocking the collaterals, resulting in blocked blood vessels and a lack of nourishment to the skin, leading to symptoms such as itching, dryness, and desquamation. Clinically, soothing the liver and promoting bile secretion, clearing heat and dampness, and dispelling wind and relieving itching are common treatments. Commonly used prescriptions include Longdan Xiegan Decoction and Xiaofeng San. Traditional Chinese medicine still has great therapeutic potential in improving the treatment of cholestatic pruritus.

[0006] Therefore, it is necessary to develop a Chinese medicine composition that is highly acceptable to patients, has few toxic and side effects, is highly safe, has significant efficacy, and can treat both the symptoms and the root cause. Summary of the Invention

[0007] The present invention aims to provide a traditional Chinese medicine composition for treating cholestatic pruritus, a preparation method thereof and use thereof.

[0008] In order to achieve the above-mentioned object of the invention, the technical solution of the present invention is as follows:

[0009] In one aspect, the present invention provides a traditional Chinese medicine composition, which consists of Sophora flavescens, Scutellaria baicalensis, Bupleurum chinense, Artemisia capillaris, Kochia scoparia, Dictamni bark, Campsis creeper, Tribulus terrestris, Periostracum cicada and Clematis chinensis.

[0010] Specifically, the traditional Chinese medicine composition is made of the following components by weight: 6-9 parts of Sophora flavescens, 6-9 parts of Scutellaria baicalensis, 6-12 parts of Bupleurum chinense, 6-15 parts of Artemisia capillaris, 5-9 parts of Kochia scoparia, 3-6 parts of Dictamni cortex, 7-9 parts of Campsis creeper, 5-8 parts of Tribulus terrestris, 3-5 parts of Cicada slough and 5-8 parts of Clematis chinensis.

[0011] Furthermore, the Chinese medicine composition is made of the following components in parts by weight: 9 parts of Sophora flavescens, 6 parts of Scutellaria baicalensis, 10 parts of Bupleurum chinense, 15 parts of Artemisia capillaris, 5 parts of Kochia scoparia, 3 parts of Dictamni cortex, 7 parts of Campsis creeper, 6 parts of Tribulus terrestris, 5 parts of Periostracum cicada and 6 parts of Clematidis.

[0012] Furthermore, the Chinese medicine composition is made of the following components in parts by weight: 6 parts of Sophora flavescens, 9 parts of Scutellaria baicalensis, 6 parts of Bupleurum chinense, 12 parts of Artemisia capillaris, 9 parts of Kochia scoparia, 6 parts of Dictamni cortex, 9 parts of Campsis creeper, 6 parts of Tribulus terrestris, 3 parts of Periostracum cicada and 6 parts of Clematidis.

[0013] Furthermore, the Chinese medicine composition is made of the following components in parts by weight: 8 parts of Sophora flavescens, 7 parts of Scutellaria baicalensis, 10 parts of Bupleurum chinense, 15 parts of Artemisia capillaris, 5 parts of Kochia scoparia, 3 parts of Dictamni cortex, 7 parts of Campsis creeper, 6 parts of Tribulus terrestris, 5 parts of Periostracum cicada and 6 parts of Clematidis.

[0014] Furthermore, the Chinese medicine composition is made of the following components in parts by weight: 8 parts of Sophora flavescens, 7 parts of Scutellaria baicalensis, 12 parts of Bupleurum chinense, 6 parts of Artemisia capillaris, 9 parts of Kochia scoparia, 6 parts of Dictamni cortex, 8 parts of Campsis creeper, 6 parts of Tribulus terrestris, 4 parts of Periostracum cicada and 6 parts of Clematidis.

[0015] Furthermore, the Chinese medicine composition is made of the following components in parts by weight: 6 parts of Sophora flavescens, 9 parts of Scutellaria baicalensis, 10 parts of Bupleurum chinense, 10 parts of Artemisia capillaris, 5 parts of Kochia scoparia, 6 parts of Dictamni cortex, 9 parts of Campsis creeper, 6 parts of Tribulus terrestris, 5 parts of Periostracum cicada and 6 parts of Clematidis.

[0016] Furthermore, the Chinese medicine composition is made of the following components in parts by weight: 9 parts of Sophora flavescens, 6 parts of Scutellaria baicalensis, 12 parts of Bupleurum chinense, 6 parts of Artemisia capillaris, 9 parts of Kochia scoparia, 6 parts of Dictamni cortex, 8 parts of Campsis creeper, 6 parts of Tribulus terrestris, 4 parts of Periostracum cicada and 6 parts of Clematidis.

[0017] In another aspect, the present invention provides a method for preparing the above-mentioned Chinese medicine composition, comprising the following steps:

[0018] S1. Weigh each raw material according to the weight ratio, add water to the raw material and boil it 1-3 times, and filter the decoction;

[0019] S2. The filtrate is concentrated to obtain an extract, which is then centrifuged and dried.

[0020] Specifically, the amount of water added in step S1 is 7-10 times the total mass of the medicinal materials;

[0021] Furthermore, when water is added for decocting three times in step S1, the amount of water added is 10 times, 7 times, and 7 times the total mass of the medicinal materials, respectively.

[0022] Specifically, the boiling time of each time adding water in step S1 is 1-3 hours;

[0023] Furthermore, in step S1, water is added and boiled for 3 times, each time for 1 hour.

[0024] Specifically, in step S2, the density of the extract is 1.20-1.30, and the preferred temperature is below 80°C.

[0025] In another aspect, the present invention provides a pharmaceutical preparation comprising the above-mentioned traditional Chinese medicine composition and pharmaceutically acceptable excipients.

[0026] Furthermore, the pharmaceutically acceptable excipients are selected from any one or more of stabilizers, pH regulators, protective agents, antibacterial agents, excipients, solubilizers, flavoring agents, diluents, and buffers.

[0027] Specifically, the dosage form of the pharmaceutical preparation is granules, capsules, oral liquids, syrups, extracts, pills, powders, teas, pills, wines, dews, gels, soft capsules, micropills, microcapsules, effervescents, oral suspensions, oral emulsions, chewable tablets, orally disintegrating tablets, lozenges, sublingual tablets, oral lyophilized powders, liposome oral liquids, nanosuspensions, self-emulsifying preparations, solid dispersions, gels, oral microspheres, sustained-release or controlled-release tablets / capsules, enteric-coated tablets, oral osmotic pump tablets, oral adhesive tablets, oral films or inhalation powders.

[0028] In another aspect, the present invention provides use of the aforementioned traditional Chinese medicine composition or the aforementioned pharmaceutical preparation in the preparation of a medicament for treating cholestatic pruritus.

[0029] Specifically, the medicine also includes pharmaceutically acceptable excipients.

[0030] Furthermore, the pharmaceutically acceptable excipients are selected from any one or more of stabilizers, pH regulators, protective agents, antibacterial agents, excipients, solubilizers, flavoring agents, diluents, and buffers.

[0031] Specifically, the dosage form of the pharmaceutical preparation is granules, capsules, oral liquids, syrups, extracts, pills, powders, teas, pills, wines, dews, gels, soft capsules, micropills, microcapsules, effervescents, oral suspensions, oral emulsions, chewable tablets, orally disintegrating tablets, lozenges, sublingual tablets, oral lyophilized powders, liposome oral liquids, nanosuspensions, self-emulsifying preparations, solid dispersions, gels, oral microspheres, sustained-release or controlled-release tablets / capsules, enteric-coated tablets, oral osmotic pump tablets, oral adhesive tablets, oral films or inhalation powders.

[0032] Specifically, the drug has at least one of the following effects:

[0033] (1) Reduce the duration of itching;

[0034] (2) Increased itch threshold;

[0035] (3) Reduce the levels of total bilirubin and direct bilirubin.

[0036] The traditional Chinese medicine composition of the present invention is prepared by combining ten herbs: Sophora flavescens, Scutellaria baicalensis, Bupleurum chinense, Artemisia capillaris, Kochia scoparia, Dictamnus chinensis, Campsis creeper, Tribulus terrestris, Periostracum cicadae, and Radix Clematis chinensis. Sophora flavescens and Scutellaria baicalensis are monarch herbs, clearing away heat and dampness, purging fire and detoxifying, and dispelling wind and relieving itching. Bupleurum chinense, which soothes the liver and clears the exterior, works in conjunction with Scutellaria baicalensis to harmonize the exterior and interior, and reconcile the Shaoyang meridians, thereby regulating the liver and gallbladder qi and dissipating dampness and heat. Artemisia capillaris belongs to the liver and gallbladder meridians. According to the "Medical Records of Chinese and Western Medicine," "Artemisia capillaris is good at clearing heat from the liver and gallbladder, and regulating liver and gallbladder stagnation, dispelling heat and stagnation, and unblocking the bile's passage into the small intestine." Kochia scoparia and Dictamnus chinensis are damp-removing and relieving itching. These four herbs are minister herbs, assisting the monarch herbs in dispelling wind, removing dampness, and relieving itching. Campsis creeper is cold in nature, dispelling heat, cooling blood and dispelling wind. Together with Tribulus terrestris and Periostracum Cicadae, it guides the herbs into the liver meridian, calming the liver, relieving wind and relieving itching, promoting qi circulation, relieving depression and dispersing stagnation, while Clematidis expel wind and dredges the meridians, acting as adjuvants. The combined effects of these herbs, which soothe the interior and exterior, dispel wind and relieve itching, clear away heat and dampness, and cool blood and resolve blood stasis, are used for cholestatic pruritus and damp-heat syndrome.

[0037] The beneficial effects of the present invention are:

[0038] (1) The Chinese medicine composition of the present invention can significantly shorten the duration of itch in mice induced by dextran, significantly increase the itch threshold in the histamine-induced itch model of rats with extrahepatic cholestasis after bile duct ligation, and significantly reduce the levels of total bilirubin and direct bilirubin in the rat model of extrahepatic cholestasis after bile duct ligation. The composition is reasonable and has significant therapeutic effects.

[0039] (2) This prescription is exquisitely formulated, with all the main, secondary, adjuvant and guiding ingredients complete, in line with the principles of traditional Chinese medicine; the medicinal properties of each ingredient are harmoniously matched, with appropriate weights and degrees, and high safety, and no serious adverse reactions will occur even with long-term use; the prescription is targeted at the syndrome differentiation and treatment of cholestatic pruritus, with the prescription corresponding to the syndrome, taking both the symptoms and the root cause into consideration, and has significant efficacy, and has good application prospects in the treatment and improvement of cholestatic pruritus. DETAILED DESCRIPTION

[0040] In order to make the technical means, creative features, purpose and efficacy of the present invention easy to understand, the present invention is further illustrated below in conjunction with specific examples, but the following examples are only preferred embodiments of the present invention, not all. Based on the examples in the implementation manner, other embodiments obtained by those skilled in the art without making creative work are all within the scope of protection of the present invention. In the following examples, unless otherwise specified, the operating methods used are all conventional operating methods, the equipment used are all conventional equipment, and the equipment and materials used in each embodiment are all the same.

[0041] Unless otherwise indicated, all percentages, ratios, proportions or % are by weight.

[0042] Example 1

[0043] The Chinese medicine composition is:

[0044] Sophora flavescens 9g, Scutellaria baicalensis 6g, Bupleurum 10g, Artemisia capillaris 15g, Dictamni bark 3g, Kochia scoparia 5g, Periostracum cicada 5g, Campsis creeper 7g, Tribulus terrestris 6g, Clemati radix 6g.

[0045] The preparation method of the Chinese medicine composition is as follows: the Chinese medicine is decocted with water three times (the amount of water is 10 times, 7 times and 7 times the weight of the medicinal materials respectively), each decoction is decocted for 1 hour, filtered, and the filtrate is concentrated under reduced pressure to a thick paste with a relative density of 1.20-1.30, and dried to obtain a dry paste powder for later use.

[0046] Example 2

[0047] The Chinese medicine composition is:

[0048] Sophora flavescens 6g, Scutellaria baicalensis 9g, Bupleurum 6g, Artemisia capillaris 12g, Dictamni cortex 6g, Kochia scoparia 9g, Periostracum cicadae 3g, Campsis creeper 9g, Tribulus terrestris 6g, Clemati radix 6g, the preparation method is the same as that in Example 1.

[0049] Example 3

[0050] The Chinese medicine composition is:

[0051] Sophora flavescens 8g, Scutellaria baicalensis 7g, Bupleurum 10g, Artemisia capillaris 15g, Dictamni cortex 3g, Kochia scoparia 5g, Periostracum cicadae 5g, Campsis creeper 7g, Tribulus terrestris 6g, Clematidis 6g, the preparation method is the same as that in Example 1.

[0052] Example 4

[0053] The Chinese medicine composition is:

[0054] Sophora flavescens 8g, Scutellaria baicalensis 7g, Bupleurum 12g, Artemisia capillaris 6g, Dictamni cortex 6g, Kochia scoparia 9g, Periostracum cicadae 4g, Campsis creeper 8g, Tribulus terrestris 6g, Clematidis 6g, the preparation method is the same as that in Example 1.

[0055] Example 5

[0056] The Chinese medicine composition is:

[0057] Sophora flavescens 6g, Scutellaria baicalensis 9g, Bupleurum 10g, Artemisia capillaris 10g, Dictamni cortex 6g, Kochia scoparia 5g, Periostracum cicadae 5g, Campsis creeper 9g, Tribulus terrestris 6g, Clematidis 6g, the preparation method is the same as that in Example 1.

[0058] Example 6

[0059] The Chinese medicine composition is:

[0060] Sophora flavescens 9g, Scutellaria baicalensis 6g, Bupleurum 12g, Artemisia capillaris 6g, Dictamni cortex 6g, Kochia scoparia 9g, Periostracum cicadae 4g, Campsis creeper 8g, Tribulus terrestris 6g, Clematidis 6g, the preparation method is the same as that in Example 1.

[0061] Comparative Example 1

[0062] The Chinese medicine composition is:

[0063] Sophora flavescens 9g, Bupleurum 10g, Artemisia capillaris 15g, Dictamni bark 3g, Kochia scoparia 5g, Periostracum cicada 5g, Campsis creeper 7g, Tribulus terrestris 6g, Clemati radix 6g.

[0064] The difference from Example 1 is that one of the main drugs, Scutellaria baicalensis, is deleted, and the preparation method is the same as that of Example 1.

[0065] Comparative Example 2

[0066] Sophora flavescens 9g, Scutellaria baicalensis 6g, Artemisia capillaris 15g, Dictamni cortex 3g, Kochia scoparia 5g, Periostracum cicada 5g, Campsis creeper 7g, Tribulus terrestris 6g, Clemati radix 6g.

[0067] The difference from Example 1 is that one of the ministerial drugs, Radix Bupleuri, is deleted, and the preparation method is the same as that of Example 1.

[0068] Comparative Example 3

[0069] Sophora flavescens 9g, Scutellaria baicalensis 6g, Bupleurum 10g, Artemisia capillaris 15g, Dictamni bark 3g, Kochia scoparia 5g, Periostracum cicada 5g, Tribulus terrestris 6g, Clemati radix 6g.

[0070] The difference from Example 1 is that one of the adjuvant drugs, Campsis glomerata, is deleted, and the preparation method is the same as that of Example 1.

[0071] Comparative Example 4

[0072] The Chinese medicine composition is:

[0073] Sophora flavescens 5g, Scutellaria baicalensis 10g, Bupleurum 13g, Artemisia capillaris 16g, Kochia scoparia 4g, Dictamni cortex 2g, Campsis creeper 6g, Tribulus terrestris 4g, Periostracum cicada 2g, Clematidis 4g, the preparation method is the same as that in Example 1.

[0074] Experimental Example 1 Effect of a Chinese herbal composition on dextran-induced pruritus

[0075] 1 Animal grouping, modeling, and drug administration

[0076] Several 6-week-old SPF-grade ICR mice, half male and half female, weighing 20-30 g, were randomly selected after one week of adaptive feeding as normal control group animals. The remaining qualified animals were divided into model control group, positive control group, Example 1-6 groups, and Comparative Example 1-4 groups, with 8 animals in each group. The specific dosing information is as follows:

[0077] Table 1

[0078]

[0079] Note: * is calculated based on the content of chlorpheniramine maleate; # is calculated based on the amount of decoction pieces.

[0080] The positive control group received chlorpheniramine maleate tablets (purchased from Guangdong Sancai Shiqi Pharmaceutical Co., Ltd., batch number 231201) once daily. The remaining groups received chlorpheniramine maleate tablets twice daily for 15 consecutive days. Ten minutes after the last dose, mice in all groups, except the normal control group, received a tail vein injection of 0.025% dextran 40 solution (1.25 mg / kg). The number of scratching attempts and the cumulative duration of scratching were observed within 30 minutes after injection.

[0081] 2 Data Statistics and Processing

[0082] The data results of the inspection and observation need to be recorded manually on appropriate forms or directly collected by computers.

[0083] All data were entered into EXCEL for statistical analysis. The measured data of each group were calculated as x±s. Before comparing the experimental groups, an analysis of variance (F-test) was performed between the groups. When the variances between the groups were equal, the Student-T test (unpaired T test) was used for statistical analysis. When the variances between the groups were unequal, the corrected Student-T test was used for statistical analysis. The results are shown in the following table:

[0084] Table 2

[0085]

[0086] Note: Compared with the normal control group: ##p<0.01; compared with the model control group: **p<0.01; compared with the Example 1 group, &p<0.05, &&p<0.01.

[0087] Compared with the normal control group, the duration of pruritus in the model control group was significantly prolonged (P < 0.01), indicating that the pruritus model was successfully established. Compared with the model control group, the cumulative duration of pruritus in the groups of Examples 1-6 was significantly reduced (P < 0.01), and the differences were statistically significant, indicating that the Chinese medicine compositions of the present invention are effective in treating pruritus. There were no significant differences between the comparative examples and the model control group, indicating that the comparative examples were less effective in treating pruritus, and were significantly worse than the therapeutic effect of Example 1 (P < 0.01).

[0088] Experimental Example 2 Effect of a Chinese herbal composition on histamine-induced pruritus caused by extrahepatic cholestasis after bile duct ligation

[0089] 1 Animal grouping, modeling, and drug administration

[0090] Several 6-8 week old SPF grade SD male rats weighing 180-220 g were randomly selected as sham operation group animals after one week of adaptive feeding, and the remaining qualified animals were reserved for subsequent other groups.

[0091] Extrahepatic cholestasis was modeled in rats using bile duct ligation. After anesthesia, the rats were skin-secured on the operating table, and the surgical area was disinfected with 75% alcohol. At the midline of the abdomen, approximately 1 cm above the perineum, the skin and muscle layers were incised, and the incision was extended upward to approximately 0.5 cm above the xiphoid process to expose the liver. Sterile cotton swabs were used to gently part the liver lobes and stomach. The common bile duct, approximately 1-2 mm in diameter and accompanying the portal vein, was identified and isolated. Two sutures were passed beneath the common bile duct and ligated 0.5-0.8 cm apart. The bile duct was then severed between the ligatures. The abdominal lining muscle (continuous lockstitch) and skin (nodular suture) were then sutured separately. The animals were placed on a heating platform to maintain a rectal temperature of 37 ± 0.5°C. In the sham-operated group, only the common bile duct was isolated after laparotomy. After repositioning other organs, sutures were performed. Once the animals regained consciousness, they were returned to clean cages and the housing room. Animal health and mortality were regularly observed and recorded.

[0092] After bile duct ligation, the animals were divided into groups. Twelve qualified sham-operated animals were selected as the sham-operated group. Rats that developed yellowing of the skin around the eyes and ears after bile duct ligation were screened and divided into a model control group, a positive control group (administered with ursodeoxycholic acid, purchased from Sigma-Aldrich, catalog number U5127), Example groups 1-6, and Comparative Example groups 1-4, with 12 animals in each group.

[0093] The positive control group was given the drug once a day, and the other groups were given the drug twice a day by gavage according to the following table:

[0094] Table 3

[0095]

[0096] Note: * is calculated based on ursodeoxycholic acid content; # is calculated based on the amount of decoction pieces.

[0097] Pruritus threshold tests were performed before oral administration (D0), on the 7th day after oral administration (D7), and on the 14th day after oral administration (D14). The skin was prepared the day before testing, using a hair shaver to remove hair from the dorsum of the right hind paw. During the test, 50 μL of histamine solution was applied sequentially (from low to high concentrations), with 3-minute intervals between each application. The histamine concentration at the first paw lick was recorded and used as the pruritus threshold. If no paw licking occurred within 5 minutes after application of 1 mg / mL histamine, the pruritus threshold was recorded as 1 mg / mL.

[0098] 2. Detection of total bilirubin, direct bilirubin, liver pathology, and pruritus duration

[0099] At the end of the experiment, all animals were anesthetized and euthanized by blood sampling from the abdominal aorta. After anesthesia, blood was collected from the abdominal aorta and the animals were sacrificed. Whole blood was centrifuged at 3000 rpm for 10 minutes at 4°C to separate serum. Total bilirubin (TBIL) and direct bilirubin (DBIL) were measured using an automated blood biochemical analyzer. Liver samples were collected, fixed in 4% paraformaldehyde for 48 hours, dehydrated, embedded in paraffin, and routinely sectioned. Hematoxylin and eosin (HE) staining was performed, and liver pathological changes were observed under a microscope.

[0100] 3 Data Statistics and Processing

[0101] The data results of the inspection and observation need to be recorded manually on appropriate forms or directly collected by computers.

[0102] All data were input into EXCEL for statistical analysis. The measured data of each group were calculated as x±s. Before the inter-group comparison of each experimental group, the inter-group variance analysis (F-test) was performed. When the inter-group variances were equal, the inter-group comparison was performed using the Student-T test (unpaired T test). When the inter-group variances were unequal, the corrected Student-T test was used for statistical analysis.

[0103] 4 Experimental Results

[0104] 4.1 Liver Histopathology and Itch Threshold

[0105] The results are as follows:

[0106] Table 4

[0107]

[0108] Note: Compared with the sham operation group: ##p<0.01; compared with the model control group: *p<0.05; **p<0.01; compared with the Example 1 group, &p<0.05, &&p<0.01.

[0109] In terms of liver tissue pathology, compared with the sham operation group, animals in other groups showed partial liver tissue hepatocellular necrosis, bile duct hyperplasia, bile duct dilatation, fibrous tissue hyperplasia, inflammatory cell infiltration, bleeding, etc., indicating that the cholestasis model was successfully established.

[0110] In terms of pruritus threshold, compared with the model control group, the pruritus thresholds of Example 1 and Example 4 groups were significantly increased after 7 days of administration, with statistically significant increases (P < 0.05 or P < 0.01). After 14 days of administration, the pruritus thresholds of the positive control group and Examples 1-6 groups were significantly increased compared with the model control group (P < 0.01), indicating that the compositions prepared in Examples 1-6 have a significant antipruritic effect. However, the pruritus thresholds of the compositions of Comparative Examples 1-4 groups were not significantly different from those of the model control group after 14 days of administration, nor were they significantly different from those of Example 1, indicating that the therapeutic effect of the compositions is poor when the components are outside the scope of protection of the present invention.

[0111] 4.2 Total bilirubin and direct bilirubin

[0112] The results are as follows:

[0113] Table 5

[0114]

[0115] Note: Compared with the sham operation group: ##p<0.01; compared with the model control group: **p<0.01; compared with the Example 1 group, &&p<0.01.

[0116] In terms of blood biochemical levels, compared with the sham operation group, the total bilirubin and direct bilirubin in the model control group were significantly increased ( P <0.01), indicating that the bile stasis model was successfully established.

[0117] Compared with the model control group, the total bilirubin and direct bilirubin in the Example 1-6 groups were significantly reduced ( P <0.01), indicating that the composition of the present invention can antagonize the increase of total bilirubin and direct bilirubin in rats caused by bile duct ligation, while there is no significant change in the comparative example 1-4 groups compared with the model control group; and compared with the example 1 group, the comparative example 1-4 groups have significant differences, indicating that the effect of the composition of the example 1-4 groups in antagonizing the increase of bilirubin in rats with cholestasis is significantly better than that of the comparative example 1-4 groups.

[0118] The composition of the present invention can significantly shorten the duration of itch in mice induced by dextran, significantly increase the itch threshold in a rat model of itch with bile duct ligation and extrahepatic cholestasis induced by histamine, and significantly reduce the levels of total bilirubin and direct bilirubin in a rat model of extrahepatic cholestasis induced by bile duct ligation, and the differences are statistically significant ( P <0.05 or P <0.01), and reducing the monarch drug (Comparative Example 1), reducing the ministerial drug (Comparative Example 2), reducing the adjuvant drug (Comparative Example 3), and the prescription ratio outside the scope of protection claimed in the present invention (Comparative Example 4) all failed to achieve the same effect, indicating that the prescription of the present invention is reasonable and has significant therapeutic effect.

[0119] This prescription is exquisitely formulated, with all the main, secondary, adjuvant and guiding ingredients complete, in line with the principles of traditional Chinese medicine; the medicinal properties of each ingredient are harmoniously matched, the severity is appropriate, and it is highly safe, and no serious adverse reactions will occur even with long-term use; the prescription is targeted at the syndrome differentiation and treatment of cholestatic pruritus, with the prescription corresponding to the syndrome, taking both the symptoms and the root cause into consideration, and has significant efficacy, and has good application prospects in the treatment and improvement of cholestatic pruritus.

[0120] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A Chinese medicine composition for treating cholestatic pruritus, characterized in that: The traditional Chinese medicine composition is prepared from the following components by weight: 6-9 parts of sophora flavescens, 6-9 parts of scutellaria baicalensis, 6-12 parts of bupleurum, 6-15 parts of capillaries, 5-9 parts of kochia scoparia, 3-6 parts of dittany, 7-9 parts of campsis, 5-8 parts of tribulus terrestris, 3-5 parts of cicada slough and 5-8 parts of clematis.

2. The Chinese medicine composition according to claim 1, characterized in that The traditional Chinese medicine composition is prepared from the following components by weight: 9 parts of sophora flavescens, 6 parts of scutellaria baicalensis, 10 parts of bupleurum, 15 parts of capillaries, 5 parts of kochia scoparia, 3 parts of difficile cortex, 7 parts of campsis, 6 parts of tribulus terrestris, 5 parts of cicada slough and 6 parts of clematis.

3. The method for preparing the Chinese medicine composition according to any one of claims 1 to 2, characterized in that: The following steps are involved: S1. Weigh each raw material according to the weight ratio, add water to the raw material and boil it 1-3 times, and filter the decoction; S2. The filtrate is concentrated to obtain an extract, which is then centrifuged and dried.

4. The preparation method according to claim 3, characterized in that The amount of water added in step S1 is 7-10 times the total mass of the medicinal materials, and the decoction time for each addition of water in step S1 is 1-3 hours.

5. A pharmaceutical preparation, characterized in that The pharmaceutical preparation is composed of the traditional Chinese medicine composition according to any one of claims 1 to 2 and pharmaceutically acceptable excipients.

6. The pharmaceutical preparation according to claim 5, characterized in that The pharmaceutically acceptable excipients are selected from any one or more of stabilizers, pH regulators, protective agents, antibacterial agents, excipients, cosolvents, flavoring agents, diluents, and buffers.

7. The pharmaceutical preparation according to claim 5, characterized in that The dosage form of the pharmaceutical preparation is granules, capsules, oral liquids, syrups, extracts, pills, powders, teas, pills, wines, dews, gels, soft capsules, micropills, microcapsules, effervescents, oral suspensions, oral emulsions, chewable tablets, orally disintegrating tablets, lozenges, sublingual tablets, oral lyophilized powders, liposome oral liquids, nanosuspensions, self-emulsifying preparations, gels, oral microspheres, enteric-coated tablets, oral osmotic pump tablets, oral adhesive tablets, oral films or inhalation powders.

8. Use of the traditional Chinese medicine composition according to any one of claims 1 to 2 or the pharmaceutical preparation according to any one of claims 5 to 7 in the preparation of a medicament for treating cholestatic pruritus.

9. The use according to claim 8, characterized in that The drug has at least one of the following effects: (1) Reduce the duration of itching; (2) Increased itch threshold; (3) Reduce the levels of total bilirubin and direct bilirubin.

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