Application of traditional Chinese medicine composition in preparation of lipid-lowering and liver-protecting medicine

Abstract

The invention discloses application of a traditional Chinese medicine composition in preparation of lipid-lowering and liver-protecting medicines. The traditional Chinese medicine composition is prepared from pseudo-ginseng and red yeast rice. Researches find that by compounding the pseudo-ginseng and the red yeast rice, the lipid-lowering effect can be remarkably improved, cholesterol, triglyceride and low-density lipoprotein of a patient are reduced, and meanwhile, the influence of the red yeast rice on the liver function is also relieved. Compared with the prior art, the GGT, ALP and TBIL levels of patients are basically unchanged. Therefore, the traditional Chinese medicine composition provided by the invention has the effects of lowering lipid, protecting the liver, activating blood, removing turbidity and resisting atherosclerosis, can be used for treating patients with hyperlipidemia, and has a wide application prospect in clinical guidance of medication.

Description

Technical Field

[0001] The present invention relates to the technical field of Chinese medicine compositions, and more specifically, to the use of a Chinese medicine composition in the preparation of lipid-lowering and liver-protecting drugs. Background Art

[0002] Panax notoginseng is a traditional Chinese medicine commonly used in clinical practice. It has the effects of stopping bleeding, dispersing blood stasis, reducing swelling, relieving pain, replenishing deficiency, and strengthening. Saponins are the main physiologically active ingredients of Panax notoginseng, which have the effects of lowering blood lipids, reducing blood viscosity, resisting thrombosis, and improving microcirculation. The Chinese medicine red yeast rice is rich in natural statins, and its main ingredient is Monacolin-K, also known as lovastatin. The reason why red yeast rice can play a lipid-lowering role is directly related to Monacolin-K. Under the action of this active substance, it can competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase in the body, thereby inhibiting cholesterol synthesis, thereby achieving the purpose of blood lipid regulation.

[0003] However, clinical medication has found that drug-induced liver injury accounts for 57% of adverse reactions caused by statins, and the incidence rate in the total population taking statins is 1.2 / 100,000. Lovastatin is metabolized by cytochrome P450 oxidase (CYP450 enzyme). The results of network meta-analysis showed that the incidence of CYP450 liver function abnormalities was higher than that of placebo, and the difference was statistically significant. At present, in clinical research reports, patients taking Xuezhikang (the main active ingredient is red yeast rice) are prone to elevated γ-glutamyl transferase (GGT), alkaline phosphatase (ALP), and total bilirubin (TBIL). Therefore, it is urgent to solve the problem of liver function affected by lipid-lowering treatment with drugs containing red yeast rice ingredients. Summary of the invention

[0004] To solve the above problems, the object of the present invention is to provide a Chinese medicine composition for use in the preparation of lipid-lowering and liver-protecting drugs. The compound use of Panax notoginseng and red yeast rice can significantly improve the lipid-lowering effect, reduce the patient's cholesterol, triglycerides and low-density lipoprotein, and also alleviate the influence of red yeast rice on liver function. Compared with before taking the medicine, the patient's gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), and total bilirubin (TBIL) levels are basically unchanged. Therefore, the Chinese medicine composition provided by the present invention has the effects of lipid-lowering and liver-protecting, promoting blood circulation and removing turbidity, and resisting atherosclerosis, and can treat hyperlipidemia patients with phlegm and blood stasis syndrome.

[0005] In order to achieve the above object, the present invention adopts the following technical solutions:

[0006] The invention discloses application of a traditional Chinese medicine composition in preparing a lipid-lowering and liver-protecting medicine. The raw materials of the traditional Chinese medicine composition include notoginseng and red yeast rice.

[0007] The Panax notoginseng in the prescription is warm in nature and slightly bitter in taste. It enters the liver and stomach meridians and has the effects of promoting blood circulation and removing blood stasis, reducing swelling and relieving pain, and replenishing blood and qi. Red yeast rice is light in taste and slightly sweet. It enters the liver, spleen, and stomach meridians and has the effects of removing turbidity and lowering fat, promoting blood circulation and removing blood stasis, and strengthening the spleen and digestion. The two medicines are matched to reduce fat and remove turbidity, promote blood circulation and remove blood stasis, remove blood stasis and turbidity without hurting the body, and replenish qi, strengthen the spleen and replenish deficiency.

[0008] Through animal experiments and clinical case studies, this research group found that compared with taking Panax notoginseng or red yeast rice alone, the Chinese medicine composition provided by the present invention can significantly reduce the cholesterol, triglycerides, and low-density lipoprotein of the subject, wherein the efficacy of taking red yeast rice alone in reducing the cholesterol and triglycerides of the subject is slightly better than that of taking Panax notoginseng alone, but not as good as the combination of Panax notoginseng and red yeast rice. After taking the Chinese medicine red yeast rice alone, some subjects had increased γ-glutamyl transferase (GGT), alkaline phosphatase (ALP), and total bilirubin (TBIL) compared with before taking the medicine, while when Panax notoginseng and red yeast rice were used in combination, the levels of γ-glutamyl transferase (GGT), alkaline phosphatase (ALP), and total bilirubin (TBIL) of the subjects were unchanged compared with before taking the medicine, indicating that the Chinese medicine composition provided by the present invention has the effect of protecting liver function while reducing lipids, indicating that the combination of Panax notoginseng and red yeast rice can solve the problem of red yeast rice affecting liver function, which is very important for clinical guidance of medication.

[0009] Furthermore, the raw materials of the traditional Chinese medicine composition include 2-5 parts of Panax notoginseng and 2-6 parts of red yeast rice by weight.

[0010] The study found that when the mass ratio of Panax notoginseng to red yeast rice was 3:4-2:1, the liver protection function was significant, and there was no statistical difference in the patients' γ-glutamyl transferase (GGT), alkaline phosphatase (ALP), and total bilirubin (TBIL) levels compared with before taking the medicine.

[0011] Furthermore, in terms of weight, the raw materials of the traditional Chinese medicine composition include 3 parts of Panax notoginseng and 4 parts of red yeast rice.

[0012] Furthermore, in terms of weight, the raw materials of the traditional Chinese medicine composition include 3 parts of Panax notoginseng and 3 parts of red yeast rice.

[0013] Furthermore, in terms of weight, the raw materials of the traditional Chinese medicine composition include 4 parts of Panax notoginseng and 3 parts of red yeast rice.

[0014] Furthermore, in terms of weight, the raw materials of the traditional Chinese medicine composition include 4 parts of Panax notoginseng and 2 parts of red yeast rice.

[0015] Furthermore, in terms of weight, the raw materials of the traditional Chinese medicine composition include 4 parts of Panax notoginseng and 5 parts of red yeast rice.

[0016] Furthermore, in terms of weight, the raw materials of the traditional Chinese medicine composition include 5 parts of Panax notoginseng and 4 parts of red yeast rice.

[0017] Furthermore, in terms of weight, the raw materials of the traditional Chinese medicine composition include 5 parts of Panax notoginseng and 3 parts of red yeast rice.

[0018] Furthermore, in terms of weight, the raw materials of the traditional Chinese medicine composition include 5 parts of Panax notoginseng and 6 parts of red yeast rice.

[0019] Further, in terms of a single dose, the Chinese medicine composition includes 2-5g of Panax notoginseng and 2-6g of red yeast rice, twice a day. Exemplarily, in terms of a single dose, the Chinese medicine composition includes 3g of Panax notoginseng and 4g of red yeast rice, twice a day; or in terms of a single dose, the Chinese medicine composition includes 3g of Panax notoginseng and 3g of red yeast rice, twice a day; or in terms of a single dose, the Chinese medicine composition includes 4g of Panax notoginseng and 3g of red yeast rice, twice a day; or in terms of a single dose, the Chinese medicine composition includes 4g of Panax notoginseng and 2g of red yeast rice, twice a day; or in terms of a single dose, the Chinese medicine composition includes 4g of Panax notoginseng and 5g of red yeast rice, twice a day; or in terms of a single dose, the Chinese medicine composition includes 5g of Panax notoginseng and 4g of red yeast rice, twice a day; or in terms of a single dose, the Chinese medicine composition includes 5g of Panax notoginseng and 3g of red yeast rice, twice a day; or in terms of a single dose, the Chinese medicine composition includes 5g of Panax notoginseng and 6g of red yeast rice, twice a day, and so on.

[0020] Furthermore, the Chinese medicine composition is prepared according to the following steps:

[0021] The raw materials of the traditional Chinese medicine composition are crushed and mixed uniformly to obtain the traditional Chinese medicine composition; or

[0022] Extracting the active ingredients from the raw materials of the Chinese medicine composition to obtain an extract; or

[0023] The active ingredients in the raw materials of the traditional Chinese medicine composition are extracted to obtain extracts, which are then prepared into preparations.

[0024] Furthermore, the extraction method is selected from conventional extraction methods such as immersion extraction, decoction extraction, reflux extraction, ultrasonic extraction, etc. Each extract is generally a water extract or an ethanol extract of each raw material drug.

[0025] Furthermore, the preparation is selected from tablets, granules, capsules, oral liquids, and powders.

[0026] Furthermore, the preparation also includes pharmaceutically acceptable excipients, such as disintegrants, lubricants, fillers, suspending agents, binders, preservatives, sweeteners, flavoring agents, and the like.

[0027] The beneficial effects of the present invention are as follows:

[0028] The present invention discloses an application of a Chinese medicine composition in the preparation of a lipid-lowering and liver-protecting drug. The raw materials of the Chinese medicine composition include Panax notoginseng and red yeast rice. Studies have found that the compound use of Panax notoginseng and red yeast rice can significantly improve the lipid-lowering effect, reduce the patient's cholesterol, triglycerides and low-density lipoprotein, and also alleviate the influence of red yeast rice on liver function. Compared with before taking the medicine, the patient's γ-glutamyl transferase (GGT), alkaline phosphatase (ALP), and total bilirubin (TBIL) levels are basically unchanged. Therefore, the Chinese medicine composition provided by the present invention has the effects of lowering lipids and protecting the liver, promoting blood circulation and removing turbidity, and resisting atherosclerosis, and can treat patients with hyperlipidemia with phlegm and blood stasis syndrome, and has broad application prospects in clinical guidance of medication. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] The specific implementation modes of the present invention are further described in detail below in conjunction with the accompanying drawings.

[0030] Figure 1 Shown is a comparison chart of blood lipid indicators of each group of mice in the animal experiment.

[0031] Figure 2 Shown is a comparison chart of liver function indicators of each group of mice in the animal experiment.

[0032] Figure 3 A comparison chart of safety indicators of each group of mice in the animal experiment is shown.

[0033] Figure 4 Shown is a comparison of changes in LDL-C, TC, TG, and HDL-C levels before and after treatment in clinical trials.

[0034] Figure 5 Shows a comparison of changes in liver function-related indicators before and after treatment in clinical trials. DETAILED DESCRIPTION

[0035] In order to explain the present invention more clearly, the present invention is further described below in conjunction with preferred embodiments and drawings. It should be understood by those skilled in the art that the content described below is illustrative rather than restrictive, and should not be used to limit the scope of protection of the present invention.

[0036] Unless otherwise specified, the raw materials and reagents used in the following examples are commercially available or can be prepared by known methods.

[0037] Example 1

[0038] The invention provides a traditional Chinese medicine composition with lipid-lowering and liver-protecting effects. The raw materials of the traditional Chinese medicine composition include 3g of Panax notoginseng and 4g of red yeast rice.

[0039] The preparation method comprises the following steps: crushing the prescribed amount of Panax notoginseng and red yeast rice, and mixing them uniformly to obtain the traditional Chinese medicine composition.

[0040] Example 2

[0041] The invention provides a traditional Chinese medicine composition with lipid-lowering and liver-protecting effects. The raw materials of the traditional Chinese medicine composition include 3g of Panax notoginseng and 3g of red yeast rice.

[0042] The preparation method is the same as Example 1.

[0043] Example 3

[0044] The invention provides a traditional Chinese medicine composition with lipid-lowering and liver-protecting effects. The raw materials of the traditional Chinese medicine composition include 4g of Panax notoginseng and 3g of red yeast rice.

[0045] The preparation method is the same as Example 1.

[0046] Example 4

[0047] The invention provides a traditional Chinese medicine composition with lipid-lowering and liver-protecting effects. The raw materials of the traditional Chinese medicine composition include 4g of Panax notoginseng and 2g of red yeast rice.

[0048] The preparation method is the same as Example 1.

[0049] Example 5

[0050] The invention provides a traditional Chinese medicine composition with lipid-lowering and liver-protecting effects. The raw materials of the traditional Chinese medicine composition include 4g of Panax notoginseng and 5g of red yeast rice.

[0051] The preparation method is the same as Example 1.

[0052] Example 6

[0053] The invention provides a traditional Chinese medicine composition with lipid-lowering and liver-protecting effects. The raw materials of the traditional Chinese medicine composition include 5g of Panax notoginseng and 4g of red yeast rice.

[0054] The preparation method is the same as Example 1.

[0055] Example 7

[0056] The invention provides a traditional Chinese medicine composition with lipid-lowering and liver-protecting effects. The raw materials of the traditional Chinese medicine composition include 5g of Panax notoginseng and 3g of red yeast rice.

[0057] The preparation method is the same as Example 1.

[0058] Example 8

[0059] The invention provides a traditional Chinese medicine composition with lipid-lowering and liver-protecting effects. The raw materials of the traditional Chinese medicine composition include 5g of Panax notoginseng and 6g of red yeast rice.

[0060] The preparation method is the same as Example 1.

[0061] Example 9

[0062] The formula of the Chinese medicine composition is the same as that of Example 1, and the preparation method is as follows:

[0063] Add the formulated amount of Panax notoginseng and red yeast rice to 8-10 times the amount of water, boil for 30-60 minutes, filter, add 8-10 times the amount of water to the residue, boil for 30-60 minutes, combine the two filtrates, and concentrate.

[0064] Example 10

[0065] The formula of the Chinese medicine composition is the same as that of Example 1, and the preparation method is as follows:

[0066] Use ethanol to extract the formulated amount of Panax notoginseng and red yeast rice to obtain an extract, and then concentrate it.

[0067] Comparative Example 1

[0068] The invention provides a traditional Chinese medicine composition with lipid-lowering and liver-protecting effects. The raw materials of the traditional Chinese medicine composition include 1g of Panax notoginseng and 4g of red yeast rice.

[0069] The preparation method is the same as Example 1.

[0070] Comparative Example 2

[0071] The invention provides a traditional Chinese medicine composition with lipid-lowering and liver-protecting effects. The raw materials of the traditional Chinese medicine composition include 10g of hawthorn and 4g of red yeast rice.

[0072] The preparation method is the same as Example 1.

[0073] 1 Animal experiments

[0074] 1.1 Experimental animals and drugs

[0075] In this experiment, 7-week-old male SPF grade APOE - / - Mice were used as a hyperlipidemia model, and male non-transgenic C57BL / 6 mice of the same age and genetic background were used as blank controls. All mice were purchased from Beijing Huafukang Laboratory Animal Technology Co., Ltd. [Animal License No.: SCXK (Beijing) 2019-0008] and raised at the Guang'anmen Medical Animal Experimental Center. APOE - / -Mice were fed with a high-fat diet [License No.: SCXK (Beijing) 2019-0008] (high-fat diet refers to the Technical Specifications for Inspection and Evaluation of Health Foods issued in 2003, provided by Beijing Huafukang Experimental Animal Co., Ltd.: processing formula: 1.2% cholesterol, 0.2% bile acid, 1.6% cellulose, 20% sucrose, 2.2% mixed minerals, 15% lard and 59.8% standard mouse maintenance feed, etc.), and C57BL / 6 mice were fed with a standard mouse maintenance feed. The temperature of the breeding environment was 25±2%℃, the humidity was 55±10%, the indoor lighting was artificially controlled, and the light rhythm was 12L:12D (6:00-18:00) alternating cycles. Mice were free to eat and drink. Chinese medicine Panax notoginseng was provided by Yunnan Qidan Pharmaceutical Co., Ltd. (Batch No.: YPZGF2018-03), and red yeast rice powder was provided by Luoyang Wokang Pharmaceutical Co., Ltd. (Batch No.: Yu 20170304).

[0076] 1.2 Experimental methods

[0077] 1.2.1APOE - / - Establishment of mouse hyperlipidemia model

[0078] After the mice were adapted to feeding for one week, 50 male APOE - / - Mice were used as the high-fat group, and 12 male C57BL / 6 mice of the same age and genetic background were used as the normal group. The normal group was fed with a standard maintenance diet for mice, and the high-fat group was fed with a high-fat diet to establish a hyperlipidemia model. At the end of the 12th week of modeling, C57BL / 6 mice and APOE - / - Six mice were used to test the establishment of hyperlipidemia model. The operation was as follows:

[0079] The mice were weighed after fasting and deprivation of water overnight, and anesthetized by intraperitoneal injection of 2% pentobarbital solution at a ratio of 0.45 mg / 10 g injection volume / body weight. After anesthesia, about 0.5-0.7 ml of blood was collected from each mouse's retroorbital vein, and centrifuged at 10000 rpm and 4°C for 10 min after standing at room temperature for 1.5 h. After centrifugation, the supernatant was taken into a 1.5 ml enzyme-free EP tube and stored in a 4°C refrigerator. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), γ-glutamyl transferase (GGT), alkaline phosphatase (ALP), and total bilirubin (TBIL) were detected using an automatic biochemical analyzer.

[0080] 1.2.2 Intervention medication

[0081] APOE - / -The hyperlipidemia model mice were classified and given Panax notoginseng, red yeast rice, Panax notoginseng red yeast rice dosage 1, Panax notoginseng red yeast rice dosage 2, and Hawthorn red yeast rice gavage, twice a day for 3 weeks, and were divided into Panax notoginseng group, red yeast rice group, Panax notoginseng + red yeast rice group 1, Panax notoginseng + red yeast rice group 2, and Hawthorn + red yeast rice group, with 10 mice in each group. During the administration period, the normal group was fed with standard maintenance feed for mice, and the other groups were still fed with high-fat feed. The mice were free to eat and drink water, and the weight of mice in each group was monitored once a week to adjust the gavage dose in time.

[0082] The oral dose is based on the "mg / kg dose conversion table for standard weight animals (±20%)" in "Pharmacological Experimental Methodology", and the daily oral drug dose conversion coefficient R for adults and mice is ab =12.33. The dosage for an average adult is calculated as follows: Panax notoginseng 3g / time, twice a day; red yeast rice 4g / time, twice a day; pure hawthorn (powdered) 10g / time, twice a day.

[0083] ① Panax notoginseng:

[0084] A) Drug concentration is 3g / 60kg=50mg / kg.

[0085] According to R ab =12.33 coefficient converted into drug concentration for mice: 12.33×50=616.5mg / kg≈6.2mg / 10g.

[0086] B) The drug concentration is 1 g / 60 kg = 16.70 mg / kg.

[0087] According to R ab =12.33 coefficient converted into drug concentration for mice: 12.33×16.7=205.9mg / kg≈2.1mg / 10g.

[0088] ② Red yeast rice: drug concentration is 4g / 60kg=66.7mg / kg.

[0089] According to R ab =12.33 coefficient converted into drug concentration for mice: 12.33×66.7=822.4mg / kg≈8.2mg / 10g.

[0090] ③Hawthorn: drug concentration is 10g / 60kg=166.7mg / kg.

[0091] According to R ab =12.33 coefficient converted into drug concentration in mice: 12.33×166.7=2055mg / kg≈20.6mg / 10g.

[0092] 0.5% edible sodium carboxymethyl cellulose (CMC) solution was selected as the solvent, and the converted Panax notoginseng, red yeast rice, and hawthorn were dispersed and gavaged. The volume of the drug solution for gavage of mice was calculated based on 0.1 ml / 10 g of mouse body weight. Among them, the Panax notoginseng group was gavaged with 6.2 mg / 10 g of Panax notoginseng, the red yeast rice group was gavaged with 8.2 mg / 10 g of red yeast rice, the Panax notoginseng + red yeast rice group 1 was gavaged with 6.2 mg / 10 g of Panax notoginseng + 8.2 mg / 10 g of red yeast rice, the Panax notoginseng + red yeast rice group 2 was gavaged with 2.1 mg / 10 g of Panax notoginseng + 8.2 mg / 10 g of red yeast rice, and the hawthorn + red yeast rice group was gavaged with 20.6 mg / 10 g of hawthorn + 8.2 mg / 10 g of red yeast rice. The model group was gavaged with an equal amount of normal saline according to body weight.

[0093] 1.2.3 Sample Collection

[0094] At the end of the third week after gavage, mice in each group were fasted and deprived of water overnight, and blood samples were collected.

[0095] Blood collection: Grab the mouse neck scalp, gently press the eye skin, fully expose the mouse eyeball and congestion, fix the mouse and cut the mouse whiskers. Grasp the eyeball with ophthalmic curved forceps and quickly remove it, allowing the blood to flow into the 1ml enzyme-free EP tube. When the blood is flowing slowly and slowly, gently squeeze the mouse heart, and kill the mouse by cervical dislocation after no blood flows out. After marking the blood, let it stand at room temperature for 1.5-2h, and centrifuge it at 10000rpm and 4℃ for 10min. After centrifugation, take the supernatant and package it. Take 300μl of serum into a 1ml enzyme-free EP tube within 2h:

[0096] ① Blood lipid indicators: total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C);

[0097] ② Liver function indicators: detection of γ-glutamyl transferase (GGT), alkaline phosphatase (ALP), and total bilirubin (TBIL);

[0098] ③Safety indicators: white blood cells (WBC), hemoglobin (HGB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood creatinine (Scr), urea nitrogen (BUN), and blood uric acid (UA).

[0099] 1.3 Experimental Results

[0100] 1.3.1 Blood lipid indexes of mice in each group

[0101] See also Figure 1Compared with the model group, the plasma TC, TG, and LDL-C levels of the Panax notoginseng group, the red yeast rice group, the Panax notoginseng + red yeast rice group 1, the Panax notoginseng + red yeast rice group 2, and the hawthorn + red yeast rice group were all decreased, and the differences were statistically significant (P<0.05); the plasma HDL-C levels were all increased, and the differences among the Panax notoginseng group, the Panax notoginseng + red yeast rice group 2, and the hawthorn + red yeast rice group were statistically significant (P<0.05). This shows that the Panax notoginseng group, the Panax notoginseng + red yeast rice group 1, the Panax notoginseng + red yeast rice group 2, and the hawthorn + red yeast rice group can all reduce the TC, TG, and LDL-C blood lipid indicators, thereby regulating blood lipids; compared with the Panax notoginseng group, the Panax notoginseng + red yeast rice group 1, the red yeast rice group, and the hawthorn + red yeast rice group have more significant effects on reducing the levels of TC and TG.

[0102] 1.3.2 Liver function indexes of mice in each group

[0103] See also Figure 2 Compared with the model group, the AST, ALT, TBIL, and GGT of the Panax notoginseng group and Panax notoginseng + red yeast group 1 were not significantly different from those of the model group (P>0.05); the plasma AST, ALT, TBIL, and GGT of the red yeast group, Panax notoginseng + red yeast group 2, and hawthorn + red yeast group were all increased, and the difference was statistically significant (P<0.05). The results showed that the red yeast group, Panax notoginseng + red yeast group 2, and hawthorn + red yeast group had effects on AST, ALT, TBIL, and GGT liver function; compared with the red yeast group and hawthorn + red yeast group, the Panax notoginseng group and Panax notoginseng + red yeast group 1 had no effect on AST, ALT, TBIL, and GGT liver function.

[0104] In summary, the combination of hawthorn + red yeast rice, Panax notoginseng + red yeast rice group 1 and Panax notoginseng + red yeast rice group 2 can reduce TC, TG, and LDL-C blood lipid indicators, but the combination of Panax notoginseng + red yeast rice group 1 has no effect on AST, ALT, TBIL, and GGT liver function indicators on the basis of reducing TC, TG, and LDL-C blood lipid indicators, and has the dual effects of lipid-lowering and liver protection. However, the combination of Panax notoginseng + red yeast rice with low Panax notoginseng content and the combination of hawthorn and red yeast rice, which also have liver protection effects, have poor liver protection performance.

[0105] 1.3.3 Safety indicators of mice in each group

[0106] See also Figure 3 Compared with the model group, there was no statistically significant difference in the changes of blood routine (WBC, HGB) and renal function (Scr, BUN, UA) indicators of mice in each group (P>0.05), indicating that each group was safe.

[0107] 2 Clinical trials

[0108] 2.1 Research subjects

[0109] 40 subjects with hyperlipidemia (phlegm and blood stasis syndrome) who visited Guang'anmen Hospital of China Academy of Chinese Medical Sciences from May 2022 to July 2023 were selected. The researchers fully explained the project situation and informed consent requirements to the subjects before enrollment, including possible adverse reactions during the study. After the subjects signed the informed consent and biological sample donation consent, they officially entered the clinical trial.

[0110] 2.2 Diagnostic criteria

[0111] (1) Western medicine diagnostic criteria: Refer to the clinical classification of dyslipidemia and the lipid level stratification criteria in the "Guidelines for the Prevention and Treatment of Dyslipidemia in Chinese Adults" (revised in 2016), that is, meeting one of the following criteria: LDL-C ≥ 3.37 mmol / L, TG ≥ 1.70 mmol / L, TC ≥ 5.18 mmol / L, HDL-C < 1.04 mmol / L.

[0112] (2) Syndrome differentiation of phlegm and blood stasis in traditional Chinese medicine: The syndrome differentiation of phlegm and blood stasis is formulated with reference to the 2002 edition of "Guidelines for Clinical Research of New Chinese Medicines for the Treatment of Hyperlipidemia". That is, the patient has one symptom each of any two of the following main symptoms ①②③, and one symptom each of any two of the following secondary symptoms ①②③, and the diagnosis can be made in combination with the tongue and pulse.

[0113] Main symptoms: ① shortness of breath, fatigue, and weakness; ② dizziness and palpitations; ③ chest and abdominal distension.

[0114] Secondary symptoms: ① spontaneous sweating and laziness to speak; ② heaviness in the head and vomiting of phlegm; ③ numbness of limbs.

[0115] Tongue appearance: pale tongue, or dark purple tongue, or with petechiae or ecchymosis; tongue coating is white, thick and greasy or white and greasy.

[0116] Pulse: deep and fine, or stringy and slippery, or astringent.

[0117] 2.3 Inclusion criteria

[0118] (1) Those who meet the diagnostic criteria of traditional Chinese and Western medicine;

[0119] (2) Aged 25-65;

[0120] (3) Any gender;

[0121] (4) Subjects follow the principle of voluntariness and sign informed consent and biological sample donation consent.

[0122] 2.4 Exclusion criteria

[0123] (1) Those who have participated in or are currently participating in other clinical trials in the past three months.

[0124] (2) Those with secondary hyperlipidemia or those taking drugs that affect blood lipid metabolism;

[0125] (3) Patients with severe primary diseases of the cardiovascular, cerebrovascular and hematopoietic systems;

[0126] (4) Patients with severe hypertension, type 1 diabetes, or type 2 diabetes (fasting blood glucose ≥ 11.0 mmol / L after hypoglycemic treatment);

[0127] (5) Abnormal renal function, creatinine > upper limit of reference value;

[0128] (6) Those who are allergic to the known ingredients of the drugs used in this study or have allergic constitution;

[0129] (7) Those who are pregnant, breastfeeding or planning to have children in the near future;

[0130] (8) Patients with malignant tumors, chronic alcoholism, drug addiction or mental illness; or those who are judged by the researchers to be unsuitable for participation in clinical trials.

[0131] 2.5 Shedding Standard

[0132] (1) Subjects experience serious adverse events;

[0133] (2) Those with poor compliance, withdrawal midway, or not using any trial drugs for various reasons after inclusion;

[0134] (3) patients who dropped out without reason or were lost to follow-up;

[0135] (4) Violation of the trial medication requirements;

[0136] (5) Subjects withdraw their informed consent or the blind is unblinded for any reason during the trial;

[0137] (6) Death of the subject.

[0138] 2.6 Intervention measures

[0139] After enrollment, the subjects took Panax notoginseng powder (provided by Yunnan Qidan Pharmaceutical Co., Ltd., batch number: YPZGF2018-03) 3g / time alone, red yeast rice powder (provided by Luoyang Wokang Pharmaceutical Co., Ltd., batch number: Yu 20170304) 4g / time alone, and a combination of Panax notoginseng powder 3g / time + red yeast rice powder 4g / time, twice a day for 3 consecutive weeks. The lead-in period was 1 week. During the lead-in period, the subjects stopped taking health products and medicines with the effect of regulating blood lipids. During the entire observation period, the subjects were prohibited from taking drugs with similar effects outside this trial protocol. The researchers followed up in time and counted the number of drugs to determine the subjects' treatment compliance.

[0140] 2.7 Collection and processing of plasma samples from clinical subjects

[0141] 4 ml of peripheral blood was collected from the subjects before and after treatment and placed in EDTA vacuum anticoagulation tubes at 3000 r·min. -1, centrifuge at 4°C for 10 min, transfer the upper plasma to a 1.5 ml cryotube, and store in a -80°C refrigerator until detection.

[0142] Efficacy indicators: Plasma LDL-C, TC, TG, and HDL-C levels of subjects before and after treatment were measured using ThermoScientific TM Indiko TM Detected by fully automatic biochemical analyzer.

[0143] 2.8 Safety indicators

[0144] The subjects' blood routine, urine routine, liver function (ALT, AST, ALP, TBIL, DBIL, γ-GT), renal function (BUN, Cr) and other safety indicators were tested before and after treatment.

[0145] 2.9 Efficacy evaluation criteria

[0146] Refer to the clinical research guidelines for the treatment of hyperlipidemia in the "Guidelines for Clinical Research of New Chinese Medicines" as the efficacy evaluation standard.

[0147] (1) Clinical control: All laboratory tests returned to normal.

[0148] (2) Significant effect: blood lipid test results show any of the following: LDL-C decrease ≥ 20%, TC decrease ≥ 20%, TG decrease ≥ 40%, HDL-C increase ≥ 0.26 mmol / L (10 mg / dl).

[0149] (3) Effective: Those whose blood lipid test results meet any of the following criteria: LDL-C decrease ≥10% but <20%, TC decrease ≥10% but <20%, TG decrease ≥20% but <40%, HDL-C increase ≥0.104mmol / L (4mg / dl) but <0.26mmol / L (10mg / dl).

[0150] (4) Invalid: Those whose blood lipid test did not meet the above standards.

[0151] 2.10 Statistical methods

[0152] IBM SPSS Statistics 22.0 software was used for analysis. Measurement data that conformed to normal distribution or approximate normal distribution were expressed as mean ± standard deviation. If the measurement data conformed to normal distribution and had equal variance, paired t test was used for intra-group comparison before and after treatment; nonparametric test was used for data that did not conform to normal distribution; chi-square test was used for count data. 2 All statistical tests were two-sided, and P < 0.05 indicated statistically significant differences.

[0153] 2.11 Research Results

[0154] (1) Changes in LDL-C, TC, TG, and HDL-C levels before and after treatment

[0155] See also Figure 4 After treatment, the subjects' LDL-C, TC, and TG were significantly reduced compared with those before treatment, and HDL-C increased to a certain extent, with statistically significant differences (P<0.05). The results showed that Panax notoginseng, red yeast rice, and Panax notoginseng + red yeast rice combination had significant clinical lipid-lowering effects.

[0156] (2) Changes in liver function-related indicators before and after treatment

[0157] See also Figure 5 The liver function indicators (GGT), alkaline phosphatase (ALP), and total bilirubin (TBIL) of some subjects in the red yeast rice group were higher than before taking the medicine, while the GGT, ALP, and TBIL levels of the subjects in the Panax notoginseng + red yeast rice group remained unchanged compared with before taking the medicine, proving that the traditional Chinese medicine combination of Panax notoginseng + red yeast rice has a significant lipid-lowering effect and a protective effect on liver function.

[0158] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not limitations on the implementation methods of the present invention. For ordinary technicians in the relevant field, other different forms of changes or modifications can be made based on the above description. It is impossible to list all the implementation methods here. All obvious changes or modifications derived from the technical solution of the present invention are still within the protection scope of the present invention.

Claims

1. Use of a Chinese medicine composition in the preparation of a lipid-lowering and liver-protecting drug, characterized in that: The raw materials of the traditional Chinese medicine composition include Panax notoginseng and red yeast rice.

2. The use according to claim 1, characterized in that: By weight, the raw materials of the traditional Chinese medicine composition include 2-5 parts of Panax notoginseng and 2-6 parts of red yeast rice.

3. The use according to claim 1, characterized in that: The mass ratio of Panax notoginseng to red yeast rice is 3:4-2:

1.

4. The use according to claim 1, characterized in that: By weight, the raw materials of the traditional Chinese medicine composition include 3 parts of Panax notoginseng and 4 parts of red yeast rice.

5. The use according to claim 1, characterized in that: By weight, the raw materials of the traditional Chinese medicine composition include 3 parts of Panax notoginseng and 3 parts of red yeast rice.

6. The use according to claim 1, characterized in that: By weight, the raw materials of the traditional Chinese medicine composition include 4 parts of Panax notoginseng and 3 parts of red yeast rice.

7. The use according to claim 1, characterized in that: By weight, the raw materials of the traditional Chinese medicine composition include 4 parts of Panax notoginseng and 2 parts of red yeast rice.

8. The use according to claim 1, characterized in that: Based on a single dosage, the Chinese medicine composition includes 2-5g of Panax notoginseng and 2-6g of red yeast rice, twice a day.

9. The use according to claim 1, characterized in that: The Chinese medicine composition is prepared according to the following steps: The raw materials of the traditional Chinese medicine composition are crushed and mixed evenly to obtain the traditional Chinese medicine composition; or Extracting the active ingredients from the raw materials of the traditional Chinese medicine composition to obtain an extract; or The active ingredients in the raw materials of the traditional Chinese medicine composition are extracted to obtain extracts, which are then prepared into preparations.

10. The use according to claim 9, characterized in that: The preparation is selected from tablets, granules, capsules, oral liquids and powders.

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