WO2015172608A1 - Capsule for assisting in reducing blood fat and preparation method therefor - Google Patents

Abstract

Disclosed are a capsule for assisting in reducing blood fat and a preparation method thereof. The contents of the capsule comprise the following components in parts by weight: 5-10 parts of freeze-dried natto powder, 4-8 parts of Crataegus pinnatifida extract, 1-5 parts of Radix puerariae extract, 1-5 parts of Ligusticum wallichii extract, 1-5 parts of Auricularia auricula extract, and 0.1-0.5 parts of microcrystalline cellulose; magnesium stearate and silicon dioxide are also added into the contents, wherein the addition amount of the magnesium stearate accounts for 0.5-1.5 percent of the total weight of the contents, and the addition amount of the silicon dioxide accounts for 0.5-1.5 percent of the total weight of the contents.

Description

[Name of invention established by ISA according to Rule 37.2] Capsule for assisting blood fat reduction and preparation method thereof Technical field

The invention relates to the technical field of health care products, in particular to a natto hawthorn capsule with auxiliary blood fat lowering function and a preparation method thereof.

Background technique

In the "three high" symptoms, high blood fat is often neglected, many people may talk about high blood lipids to head, but little is known about what is harmful to high blood fat and high blood lipids. Hyperlipidemia usually means that the content of one or more lipids or lipoproteins such as cholesterol and triglycerides in the blood exceeds a high limit. The formation of hyperlipidemia requires a long process, most of which have no clinical symptoms at the beginning, which is an important reason why many people do not pay attention to early diagnosis and early treatment. Because these vascular damage processes are mostly insidious and gradual, hyperlipidemia is also known as the "silent killer."

Epidemiological statistics show that the current population of hyperlipidemia is growing rapidly and the age distribution is further advanced. The results of serum biochemical examination and liver B-ultrasound examination of 1514 occupational groups were compared. Results: In this group of people, 471 cases of high blood lipids (31.11%), 432 cases of fatty liver (28.53%), including 358 cases of hyperlipidemia and fatty liver, 74 cases of normal blood lipids (7.10%), high blood lipids were significantly higher than Normal blood lipids. Among the 921 medical examiners in a city, the prevalence of hypertension was 21.61% and the high blood lipid was 51.36%. According to data from a large health check-up center, almost one out of every five young people in the physical examination had excess blood lipids. Urban white-collar workers have a fast pace of life, high work pressure, irregular diet, lack of exercise, and about 40% of people are hyperlipidemia.

Studies have shown that the rejuvenation of hyperlipidemia, in addition to genetic factors, and unhealthy working methods with young people (work stress, long-term meditation, nervousness, anxiety, etc.), unhealthy lifestyle (less movement, long staying up late, etc.) ) and unreasonable eating habits (excessive consumption of high-fat foods, alcohol, smoking, etc.) and other factors. Dietary nutritional imbalances such as excessive intake of saturated fatty acids, insufficient intake of trace elements and vitamins, coupled with smoking, drinking and other adverse diets and lifestyles lead to thick blood and high blood lipids; busy work, making physical exercise less and less , physical weakness; and high mental stress or excessive anxiety, often cause or aggravate the development of hyperlipidemia.

Hyperlipidemia is an important risk factor for cardiovascular and cerebrovascular diseases such as cerebral hemorrhage, cerebral infarction and coronary heart disease. Flow The pathological investigation and experimental research have proved that the dietary composition is closely related to the blood lipid level. Through the dietary intake of a large amount of saturated fatty acids, monosaccharides, cholesterol, etc., it is easy to produce hyperlipidemia, causing atherosclerosis, and finally inducing the heart. Vascular disease. Therefore, controlling hyperlipidemia, lowering cholesterol, triglycerides and low-density lipoprotein, and increasing high-density lipoprotein are important for preventing cardiovascular and cerebrovascular diseases caused by hyperlipidemia.

At present, from the website of the State Food and Drug Administration, a total of 312 health foods with approved hypolipidemic functions have been inquired. The raw materials are made of raw materials such as propolis, Chinese herbal medicine, tea, red yeast, lecithin, fish oil and natto. Health food, this product is made of natto lyophilized powder, hawthorn extract, puerarin extract, Chuanxiong extract, black fungus extract as effective raw materials, made of microcrystalline cellulose, magnesium stearate, silica as auxiliary materials. A health food that uses hard capsules as a dosage form. The hard capsule has the characteristics of convenient eating, no bad taste, hygienic, easy to carry, simple production process and low cost. It is suitable for daily eating at home, and is more suitable for people to go out for vacation and travel.

Summary of the invention

The object of the present invention is to provide a natto hawthorn capsule having an auxiliary hypolipidemic function and a preparation method thereof, in order to overcome the defects of the prior art described above.

The object of the present invention can be achieved by the following technical solution: a natto hawthorn capsule having an auxiliary hypolipidemic function, consisting of a content and a capsule, wherein the raw material of the content comprises, by weight: Natto lyophilized powder 5-10, hawthorn extract 4-8, puerarin extract 1-5, Chuanxiong extract 1-5, black fungus extract 1-5, microcrystalline cellulose 0.1-0.5; Magnesium stearate and silica are also added, and magnesium stearate is added in an amount of 0.5 to 1.5% by weight based on the total amount of the content, and silica is added in an amount of 0.5 to 1.5% by weight based on the total amount of the contents.

The raw materials of the contents are: natto lyophilized powder 6.6, hawthorn extract 5.25, pueraria extract 3.75, chuanxiong extract 3.24, black fungus extract 3, microcrystalline cellulose 0.168; Magnesium stearate and silica were also added to the contents, and magnesium stearate was added in an amount of 1% by weight based on the total weight of the contents, and silica was added in an amount of 1% by weight based on the total weight of the contents.

A preparation method of natto hawthorn capsule with auxiliary blood fat lowering function, comprising the following steps:

(1) Weighed hawthorn extract, puerarin extract, Chuanxiong extract, black wood Mixing ear, microcrystalline cellulose, making soft material, granulating, drying, granulating, to obtain a mixture a;

(2) weighed natto lyophilized powder, silica, magnesium stearate by weight to obtain a mixture b;

(3) Mixture a and mixture b were stirred and mixed in a mixer for 20 minutes, and then filled in a hard capsule, and polished to obtain a product.

The sieved particle size described in the step (1) is an 80 mesh standard sieve.

The specific step of the soft material according to the step (1) is: weigh the hawthorn extract, the kudzu extract, the extract of Rhizoma Chuanxiong, the extract of black fungus, and the microcrystalline cellulose according to the weight, and add 95%. The ethanol is soft.

The granulation described in the step (1) is extrusion granulation in a twin-screw extruder, and the obtained granules are 20 mesh standard sieves.

The drying temperature in the step (1) is 55-60 ° C, and the whole granule refers to passing the dried material through a 40-mesh standard sieve.

The sieved particle size described in the step (2) is: a 60 mesh standard sieve.

The filling content described in the step (3) is controlled between 380 mg and 420 mg, and is polished until the surface of the capsule has no powder.

The product of the invention comprises natto lyophilized powder, hawthorn extract, puerarin extract, Chuanxiong extract and black fungus extract as effective raw materials, microcrystalline cellulose, magnesium stearate and silicon dioxide as auxiliary materials, and hawthorn, Gegen and Chuanxiong are the "Notice of the Ministry of Health on Further Regulating the Management of Raw Materials for Health Foods" (Wei Jian Jian Fa [2002] No. 51), "List of Items Available for Health Foods", "List of Foods and Drugs" The medicine in the natto is a traditional soybean fermented food, and the black fungus can be eaten as a common food. Modern pharmacological studies have proved that the above raw materials have the function of assisting blood fat lowering, and the quality standards of the above raw material extracts are in accordance with Appendix B of the enterprise standard. Excipients microcrystalline cellulose as a filler, magnesium stearate, silica as a flow aid, and the above-mentioned excipients are the raw materials allowed in GB2760, the quality standards meet the appendix C of the enterprise standard.

The efficacy, dosage and impact on the safety of the selected materials of the present invention:

1, natto lyophilized powder

Natto is a traditional soybean fermented food. It has a history of more than 2,000 years. It is simple in production, unique in flavor and low in price. Natto is made from soybeans and is fermented by Bacillus natto. The nutritional value of each of the 100 grams of natto containing protein 31.2g, fat l9.9g, carbohydrate 22.8g, calcium 331mg, iron 13.7mg a large number of studies confirmed that natto's various health functions are closely related to human health, Regular consumption can play a role in strengthening the body and preventing diseases. Duan Zhichang et al., in the study of the effect of natto freeze-dried powder on experimental hyperlipidemia, established an experimental hyperlipidemia rabbit model to observe the effects of natto freeze-dried powder on the body's antioxidant and blood lipid levels. the result shows. At the 8th week of model establishment, the TC, TG, LDL-C, MDA, and AL values of the natto freeze-dried powder group were 39.88% (p<0.05), 44.54% (p<0.05), and 48.84%, respectively, compared with the model group. P<0.05), 48.25% (p<0.01), 70.20%, and HDL-C and SOD values increased by 75.81% (p<0.01) and 38.32% (p<0.01), respectively. The conclusion indicates that natto lyophilized powder can be obtained. Reduce blood lipid levels. By raising HDL-C and lowering LDL-C to regulate lipid metabolism, it has anti-lipid peroxidation and can prevent the formation of atherosclerosis. Han Yanbin et al. In the study of Natto Capsule on the regulation of blood lipids in hyperlipidemia model rats, the effects of Natto Capsule on blood lipid levels in hyperlipidemia model rats were investigated. This experiment was to feed rats with high fat diet. A high-fat rat model was established, and the rats with hyperlipidemia were continuously administrated for 30 days with 235, 470, 940 mg/kg BW (5, 10, and 20 times doses of natto capsules respectively recommended by the human body, respectively). The blood samples were collected at the end of the experiment to determine the contents of TC, TG and HDL-C. The results showed that the Natto capsule can reduce the serum total cholesterol (TC) and triglyceride (TG) levels in high-fat model rats and increase their serum levels. The content of density lipoprotein cholesterol (HDL-C) had no significant effect on the weight gain of rats, suggesting that the sample has an auxiliary hypolipidemic function. Thereby delaying or reducing the occurrence and development of atherosclerosis. Yang Qing et al. in the "Natto Capsule Toxicity and Regulation of Blood Lipids in Rats", the daily recommended dose of human body is 2.7g/person, for acute oral toxicity test, mouse bone marrow polychromatic erythrocyte micronucleus test, mouse sperm The malformation test, the Ames test and the auxiliary hypolipidemic function test were carried out using a two-stage toxicity test method and a health food functional evaluation program and a test method 2003 to assist in the regulation of blood lipids. Results The acute oral toxicity test of mice was actual non-toxic grade. The mouse bone marrow polychromatic erythrocyte micronucleus test, mouse sperm abnormality test and Ames test were negative. And has the effect of lowering blood fat.

2, hawthorn extract

Hawthorn acid, sweet, lukewarm. Return to the spleen, stomach, liver. It has the functions of digestion and stomach, qi and phlegm, turbidity and lipid-lowering. Modern pharmacological studies have shown that hawthorn has the function of helping to lower blood fat. Xiao Ting et al. explored the effect of hawthorn on the protective effect of hawthorn on blood lipids and blood vessels in hyperlipidemic rats. Methods: The experiment was divided into normal control group, hyperlipidemia model group, and simva Heding group, mountain 楂 low dose group, hawthorn middle dose group, hawthorn high dose group, 30 days after administration of the corresponding drugs, blood was taken from the abdominal aorta and aortic blood vessels were taken to detect serum total cholesterol, triglyceride, high density lipoprotein and vascular peroxidation. Dismutase activity, malondialdehyde content. RESULTS: All the doses of hawthorn significantly reduced serum total cholesterol and triglyceride levels, increased vascular malondialdehyde activity, and decreased vascular MDA content. Conclusion: Hawthorn can effectively reduce the serum total cholesterol and triglyceride levels in experimental hyperlipidemic rat models, and it can protect blood vessels. Gu Jianren reviewed the hypolipidemic effects and pharmaceutical preparations of Shanzhi and its compound preparations in recent years in the research progress of hypolipidemic effects and preparations of hawthorn and its compound preparations. In the clinical application, Zhu Guang said that in the discussion of the "Danxi Heart Law" Zhongbao Pill in the representative method of the elimination method, it is believed that the mountain glutinous rice eliminates the greasy product of meat and has the effect of dilating phlegm and has good curative effect on lipid-lowering. Wang Xiaoming believes that in the process of Shenqi Huoxue Decoction in the treatment of angina pectoris, hyperlipidemia should be added to the hawthorn. Huang Liping treated 31 cases of hyperlipidemia with Jiangzhi Decoction, and believed that hawthorn had the effect of reducing TC and TG. Cao Wuzhen and other treatments for fatty liver with Zhiganling are better than Western medicine group, and it is believed that hawthorn has the effect of promoting the oxidative degradation of fat in the liver. Guanxinning tablets (each containing 3.1g of red probiotics in the mountain) served 3 times a day, 5 tablets each time, treating 104 patients with hypercholesterolemia. After 1 month and a half, 77 cases of cholesterol decreased to normal, 15 cases decreased by 20mg%. One patient increased; 21 patients with hypertriglyceridemia, 17 patients with TG decreased to normal after one and a half months of treatment; 59 patients with high β-lipoproteinemia decreased from an average of 473 mg% to 361.8 mg% after taking the drug. In the study of hyperlipidemia and coronary heart disease, Wang Xiangkang believes that the level of blood lipids is positively correlated with various symptoms of coronary heart disease. Controlling blood lipid levels can control the onset of angina pectoris and is of great significance in preventing myocardial infarction. Zheng Yiming treated 89 cases of cerebral thrombosis, and believed that hawthorn contains total flavonoids, lipolytic enzymes, etc., which can lower blood fat, expand blood vessels and improve myocardial and brain cell metabolism. In the discussion of the prescription of compound Chinese medicine for the treatment of hyperlipidemia, Wang Liang screened 47 kinds of traditional Chinese medicine compound for classification, quantified the treatment of Chinese medicine with higher frequency, and discharged 17 kinds of traditional Chinese medicine, of which Shan Zhi was the first one. Hawthorn should be the first choice when treating hyperlipidemia. Gao Ying et al. observed the effects of hawthorn flavonoids and hawthorn juice on serum lipid and liver lipid levels in rats with hyperlipidemia in the study of the effects of hawthorn and hawthorn flavonoid extracts on regulating blood lipids in rats. Rat high fat diet contains 1% cholesterol, 10% lard, 10% egg yolk powder and 79% basal feed. The results showed that at the end of the fifth weekend, hawthorn flavonoids and hawthorn juice significantly decreased serum triglyceride and liver triglyceride in hyperlipidemia rats (P<0.05). Hawthorn flavonoids and hawthorn juice significantly reduced liver cholesterol (P<0.05). <0.05), but neither of the test substances lowered serum cholesterol. This study suggests that hawthorn and hawthorn flavone can improve the triglyceride metabolism in hyperlipidemia rats, and the effect on cholesterol metabolism needs further study.

3, Pueraria extract

Gegen Gan, Xin, cool. Return to the spleen, stomach, lungs. It has the functions of relieving muscle fever, thirst, diarrhea, sunburn and diarrhea, and it is effective in relieving alcohol and hangover. Modern pharmacological studies have shown that Pueraria has the function of helping to lower blood fat. Liu Yaming [8] and etc. in the experimental study of the effect of Fufang Kugen Capsule on blood sugar and blood lipid in experimental diabetes and hyperlipidemia model, the compound Kudzu capsule consisting of the radix puerarin extract and the glucose tolerance factor of yeast extract Hypoglycemic and lipid-lowering effects in experimental diabetic mice and hyperlipidemia rats. METHODS: The diabetic mice model and the high-fat diet were used to replicate the hyperlipidemia rat model. The effects of Fufang Kugen Capsule on the blood lipid levels in rats with fasting blood glucose, glucose tolerance and hyperlipidemia were observed. RESULTS: Fufang Kugen Capsule can significantly reduce the level of hyperglycemia induced by alloxan in mice and improve the glucose tolerance of alloxan-induced diabetic mice. At the same time, the drug can significantly reduce TG, TC and HDL-C, HDL/TC. The role. Conclusion: Fufang Kudzu Capsule has obvious hypoglycemic and lipid-lowering effects. Zheng Youli in the "Caogen Jiangzhi Decoction for the Treatment of Hyperlipidemia" in order to observe the clinical efficacy of self-made Gegen Jiangzhi Decoction in the treatment of hyperlipidemia, 182 patients were randomly divided into treatment group 130 cases (with Gegen lipid-lowering soup) Treatment) and control group of 52 patients (treated with lipids). RESULTS: The treatment group was superior to the control group in terms of clinical efficacy, lipid-lowering effect and improvement of blood lipid index (P<0.05). Compared with the control group, the tongue and tongue coatings were significantly improved before and after treatment. , P < 0.05. Tip: Gegen Jiangzhi Decoction can be effectively used in the treatment of hyperlipidemia. Mu Yadong et al. observed the effects of extracts of Radix Puerariae, Hawthorn and Shouwu on the hypolipidemic effect of experimental hyperlipidemia rats in the study of the effects of extracts from Pueraria lobata, Hawthorn and Shouwu. METHODS: Rats were fed a high-fat diet to induce hyperlipidemia in rats. The extracts of Radix Puerariae, Hawthorn and Shouwu were administered continuously for 25 days, and their effects on TC, TG and HD-C in hyperlipidemic rats were observed and added. The drug group of pearl powder was compared. RESULTS: The pure extracts of Radix Puerariae, Hawthorn and Shouwu had a significant effect on the content of blood lipids (TC, TG), and had a significant effect on HDL-C. There was no significant difference in the hypolipidemic effect between the group in which the pearl powder was added and the group that was not added. Conclusion: The extracts of Radix Puerariae, Hawthorn and Shouwu have good hypolipidemic effects on experimental hyperlipidemia rats.

4, Chuanxiong extract

Chuanxiong Xin, Wen. Return to the liver, biliary pericardium. It has a blood circulation, hurricane and pain relief function. Modern pharmacological studies have shown that Chuanxiong has the function of assisting blood fat reduction. Gao Guangwei et al. observed the effect of Jiawei Chuandu Duliang Pill on high-fat rats in the pharmacological effects of Jiawei Chuandu Duliang Pill on high-fat rats. METHODS: A rat model of hyperlipidemia was established to determine the blood lipids and blood flow in the serum of high-fat rats after administration of Jiawei Chuandu Duliang Pill suspension. Changes in the changes, and measuring the amount of thrombosis after administration of the drug in normal rats, were set in the control group. RESULTS: After administration, the contents of TC, TG and LDL in high-fat rats were significantly decreased, HDL/TC increased, blood viscosity (ratio) decreased significantly, and thrombus formation decreased significantly. Conclusion: Jiawei Chuandu Duliang Pill has the effect of significantly lowering blood lipid, lowering blood viscosity and resisting thrombosis. Sun Shengmei et al. In the effect of Chuanxiong on the changes of blood lipids in mice caused by aircraft noise, the relationship between noise and blood lipids and arteriosclerosis was studied by observing the influence of aircraft noise on blood cholesterol and blood triglyceride levels in mice. After the change of blood lipid content in mice affected by aircraft noise, a substance that enhances the anti-noise ability of the body to prevent adverse effects on blood lipids and cardiovascular system is obtained. As a result, Chuanxiong has the effect of counteracting the increase of blood lipid caused by noise, and increases the anti-noise of the body. Ability to eliminate its adverse effects on the heart and tube system.

5, black fungus extract

Black fungus belongs to the genus Basidiomycetes, Basidiomycetes, Auricularia, Fungi, and Fungus, aliased as fungus, black fungus, fine fungus. It is a kind of both food and medicine, and it is also a traditional food and export trade food in China. It has the dual value of medicine and food, and it has the effect of nourishing and strengthening the body and strengthening the body. Zhou Guohua et al. In the study of extracting, purifying and lowering blood lipids of polysaccharides from Auricularia auricula, different concentrations of Auricularia auricular polysaccharide were tested in high-fat model mice to study the triglyceride (TG) of high-fat model mice. , the effects of total cholesterol (TC), high density lipoprotein (HDL-C) and low density lipoprotein (LDL-C). The results showed that the serum triglyceride (TG), total cholesterol (TC) and low density lipoprotein (LDL-C) of the Auricularia auricular polysaccharide group were lower than the high fat model group, while the high density lipoprotein (HDL). -C) is extremely significantly higher than the high-fat model group, suggesting that the black fungus polysaccharide has a significant hypolipidemic effect. Wang Peng et al. selected 50 patients with clinical hyperlipidemia in the clinical study of anti-thrombotic antihypertupemia in black fungus. Serum total cholesterol (TC) was at 6.50 mMol/l, and β-lipoprotein (β-LP) was More than 6.00g / L, the patient is divided into two groups, the first group of 30, 15 grams of dry black fungus daily for one month, the second group of 20, 5 grams of dry black fungus for one and a half months. Both will be black fungus After soaking, cook for cooking. Do not take any lipid-lowering and anticoagulant during the observation period. As a result, it was found that the blood lipid was markedly lowered, the thrombus formation was remarkably reduced, and the platelet aggregation rate was decreased more significantly. This shows that black fungus does have a variety of effects such as lowering blood fat, anti-thrombosis and inhibition of platelet aggregation. Han Chunran et al. extracted the polysaccharide of Auricularia auricula in the extraction, purification and hypolipidemic effect of Auricularia auricula, and purified it by column chromatography. The purified Auricularia auricula polysaccharide was fed. Rats were examined for their ability to lower blood lipids. Two kinds of Auricularia auricula polysaccharides, APE I and APE II, were obtained by experiment. Each dose of APE I had no significant effect on rat body weight; APE I at 100 mg/kg body weight and above could significantly reduce TG in serum of high-fat rats. TC, LDL-C levels, increase its HDL-C level; the effect of 200mg/kg body weight of Auricularia auricular polysaccharide on TG, TC, LDL-C and HDL-C in serum of high-fat rats and 70mg/kg body weight of lipid There was no significant difference in the effect and the HDL-C/TC levels in hyperlipidemic rats were significantly increased. Auricularia auricula (APE I) has hypolipidemic function, has a certain preventive effect on the occurrence of hyperlipidemia, and also has a certain preventive effect on coronary heart disease and atherosclerosis.

Compared with the prior art, the present invention selects hard capsules, which can mask the unpleasant taste and odor of the raw materials, has a neat appearance and is easy to swallow, and the hard capsules are different from tablets and pills, and can be prepared without pressure, so In the gastrointestinal tract, the explanation is quick, the absorption effect is good, the taking is convenient and hygienic, the carrying is convenient, the storage period is long, and the production process is simple and the cost is low. Therefore, this product chooses a hard capsule preparation.

detailed description

The invention will now be described in detail in connection with specific embodiments.

Example 1

First, the formula:

The natto hawthorn capsule with auxiliary hypolipidemic function is composed of a content and a capsule. The raw materials of the content include: natto lyophilized powder 6.6, hawthorn extract 5.25, puerarin extract 3.75, Chuanxiong Extract 3.24, black fungus extract 3, microcrystalline cellulose 0.168; magnesium stearate and silica are also added to the content, and magnesium stearate is added in an amount of 1% by weight of the total content. The silica was added in an amount of 1% by weight based on the total weight of the contents.

Second, the preparation method:

The preparation method of the above natto hawthorn capsule comprises the following steps:

(1) Weighing hawthorn extract, Pueraria lobata extract, Ligusticum chuanxiong extract, black fungus extract, and microcrystalline cellulose sifted through 80 mesh standard sieve by weight, and adding 95% ethanol to obtain soft material. Extrusion granulation in a twin-screw extruder, the obtained particle size is 20 mesh standard sieve, dried, granulated to obtain a mixture a;

(2) weighed 60 parts of standard sieve natto lyophilized powder, silica, magnesium stearate mixed to obtain a mixture b;

(3) Mixture a and mixture b are stirred and mixed in a mixer for 20 minutes, then filled, and the contents are controlled between 380 mg and 420 mg, and polished to the surface of the capsule without powder.

Third, performance

Daily consumption of 0.66g of natto lyophilized powder has the health-care function of assisting blood fat reduction, and it is safe; daily consumption of hawthorn extract 0.525g, hawthorn extract extraction ratio of 10 to 1, equivalent to hawthorn crude drug amount 5.25g, China The People's Republic of China Pharmacopoeia recommends that the daily dose of hawthorn is 9-12g, so this product has the health-care function of assisting blood fat reduction, and it is safe. Daily consumption of Radix Puerariae extract 0.375g, Pueraria extract extract ratio of 10 to 1, equivalent to Pueraria crude drug dosage 3.75g, the People's Republic of China Pharmacopoeia recommended Pueraria daily dosage of 10-15g, so this product has a health-care function to help reduce blood fat, and It is safe. Daily consumption of Chuanxiong extract 0.324g, Chuanxiong extract extraction ratio of 10 to 1, equivalent to Chuanxiong raw drug amount 3.24g, the People's Republic of China Pharmacopoeia recommended Chuanxiong daily dosage of 3-10g, so this product has a health-care function to help reduce blood fat, and It is safe. Daily consumption of black fungus extract 0.3g, black fungus extract extraction ratio of 10 to 1, equivalent to dry black fungus 3g, so this product has a health-care function to help reduce blood fat, and is safe.

Microcrystalline cellulose: as a filler. The GB2760 stipulates that it can be used in various types of foods according to the production needs. The amount of this product is 28g/1000 tablets.

Silica and magnesium stearate are flow aids and lubricants. The addition of the above auxiliary materials can make the contents of the capsule have good fluidity, ensure that the powder is quickly filled into the capsule, and ensure the stability of the difference in the amount of the preparation.

The main factor affecting the normal operation and the accuracy of the filling of the hard capsule filling is the fluidity of the filling, and the simplest method of evaluating the fluidity is represented by the angle of repose. The smaller the angle of repose, the smaller the friction, the better the fluidity, and the easier it is to fill the capsule. Generally, the angle of repose α ≤ 40 ° can meet the demand for fluidity in the capsule filling production process. The angle of repose was measured with or without the addition of magnesium stearate and silica described above. The results are as follows:

Group	The amount in the formula (silica, magnesium stearate)	Angle of repose alpha value	fluidity
				A group	Content	46.7	not good
Two groups	1% silica + content	42.3°	not good
				Three groups	1% magnesium stearate + content	41.5°	not good
Four groups	1% silica + 1% magnesium stearate + content	37.2°	it is good

It can be seen from the above experimental results that 1% of silica and 1% of magnesium stearate are added to the formulation, and the angle of repose α is less than 40°, and the fluidity of the material is good, and the powder can be quickly filled into the capsule, and the preparation is ensured. The stability of the quantitative difference.

In order to verify the above experimental results, the capsule filling machine was continuously filled for 30 minutes, randomly sampled 3 times, and the difference in the amount of the test was detected. Each time 10 samples were taken, and the difference in the amount of the test was detected. The results are as follows:

It can be seen from the above results that the loading is stable.

It is determined that the iconic component of the product is total saponin: the raw materials are mixed in a mixer, and the mixing time is set to 10 minutes, 20 minutes, and 30 minutes, respectively, and sampled 3 times, 100 g each time, and the total saponin content of the iconic component is measured. as follows:

From the results of the above RSD indicators, the mixture is mixed for 20 minutes and mixed for 30 minutes, and the RSD value is close. In order to save energy, it is determined that the mixing time is 20 minutes, that is, the purpose of mixing can be achieved.

Fourth, animal experiments

1 Materials and methods

1.1 Sample: Provided by Shanghai Chunzhitang Biological Products Co., Ltd., the recommended dose for oral administration is 3 times a day, 2 capsules per time, and the adult weight is calculated as 60kg, and the equivalent dose is 0.04g/kg.bw.

1.2 Experimental animals and environmental conditions: 40 SPF male SD rats and feed were provided by Dongchuang Experimental Animal Science and Technology Service Department of Kaifu District, Changsha City. The experimental animal production license number was SCXK (Xiang) 2009-0012. The experimental conditions are the barrier environment. During the experiment, the experimental environment temperature is 22 ° C ~ 24 ° C, and the humidity is 52% ~ 56%. The experimental animal use license number is SYXK (Xiang) 2010~0010.

1.3 Main instruments, equipment and reagents: OLYMPUS AU400 automatic biochemical analyzer, etc.; CHOL and TG kits were purchased from Shanghai Fosun Long March Medical Science Co., Ltd.; HDL cholesterol (HDL) -C) The kit was purchased from Ningbo Meikang Biotechnology Co., Ltd.

1.4 High fat diet: 78.8% basic feed, 1% cholesterol, 10% egg yolk powder, 10% lard, 0.2% bile salt.

1.5 Experimental methods:

1.5.1 Dosage design: set low, medium and high doses of 0.20g/kg.bw, 0.40g/kg.bw, 1.20g/kg.bw (5, 10, 30 times of the recommended amount of human body respectively) When the test substance was prepared, the contents of Chunzhitang brand Nadoushan plant capsules were taken 4.00g, 8.00g, 24.00g and distilled water to 200ml, respectively, and administered to the test animals once a day, the volume of the gavage was l. 0 ml/100 g.bw for 30 consecutive days, the control group was given an equal volume of distilled water.

1.5.2 Animal grouping: Rats were fed with basal diet for one week, fasted for 16 hours, tail blood was taken, and serum total cholesterol (TC), glycerol three (TG), and high were measured by OLYMPUS AU400 automatic biochemical analyzer. Density lipoprotein cholesterol (HDL-C), animals were randomly divided into 4 groups according to Tc level and TG: high-fat control group and low, medium and high test subjects. From the beginning of the formal test, each group of animals switched to high-fat diet, and at the same time, according to the dose of 1.5.1, the animals in each group were intragastrically administered.

1.5.3 Determination of indicators: Weigh once a week, fasting for 16 hours at the end of the experiment, and taking eyeballs to measure serum TC, TG, HDL-C.

1.6 data processing

The data was statistically analyzed using Excel2003 and Spssl1.0 software. First, the data were tested for homogeneity of variance. If the variances were homogeneous, one-way analysis of variance was used for overall comparison. It was found that the difference was compared with the Dunnett method for the comparison between the multiple dose groups and the average of one control group. If the variance is not uniform, the appropriate data is transformed into the original data, and after the homogeneity test of the variance is satisfied, the converted data is used for statistics; if the variance is not reached after the variable is converted, the rank sum test is used for statistics. If the overall comparison is found to be different, the Tamhane's TZ test, which does not require homogeneity of variance, is used for the pairwise comparison.

1.7 result determination

1.7.1, the results of assisted hypolipidemic function determination: in the serum total cholesterol, glycerol three, high-density lipoprotein cholesterol test, serum total cholesterol, glycerol three cool two indicators positive, can be determined that the test sample assisted blood lipids Functional animal experiments were positive.

1.7.2 Auxiliary reduction of glycerol triacetate results: 1 glycerol three cool two dose group results positive; 2 glycerol three vinegar one dose group results positive, while high density lipoprotein cholesterol was significantly higher than the control group, can determine the sample The product assisted in reducing the glycerol triacetate animal test results were positive.

1.7.3 Auxiliary reduction of serum total cholesterol results: 1 serum total cholesterol in two dose groups was positive; 2 serum total cholesterol in one dose group was positive, and high-density lipoprotein cholesterol was significantly higher than the control group, the sample can be determined Product-assisted reduction of serum total cholesterol was positive in animal experiments.

2. Results

2.1 The effect of sample on rat body weight

Table 1 Effect of sample on rat body weight x±s: (g)

See Table 1: Before and after the experiment, the body weight of the test group and the weight gain during the experiment were not significantly different from the high-fat control group (P>0.05).

2.2 Effect of sample on serum TC, TG and HDL-C in rats

Table 2 Serum TC levels in rats before and after the experiment

Table 3 Serum TG levels in rats before and after the experiment

Table 4 Serum HDL-C of rats in each group before and after the experiment

See Tables 2 to 4. After the experiment, the serum TC and TG of the high-fat control group were significantly increased. Compared with the experiment, the difference was significant (P<0.05), indicating successful modeling. High-dose group can significantly reduce serum triglyceride levels and total cholesterol levels in rats, compared with high-fat control group, the difference was significant (P<0.05), and each dose had no significant effect on serum high-density lipoprotein cholesterol level in rats. (P>0.05).

3 summary

Under the laboratory conditions, the contents of Chunzhitang brand Nadoushan plant capsules at a dose of 0.20g/kg.bw, 0.40g/kg.bw, and 1.20g/kg.bw were administered to SD rats for 30 days. Compared with the high-fat control group, the dose of 1.20g/kg.bw significantly decreased the serum triglyceride level and total cholesterol level of rats fed with high fat diet (P<0.05). It is suggested that the sample to be tested has an auxiliary hypolipidemic function for the animal.

V. Human experiment

1 Materials and methods

1.1 sample

Chunzhitang Brand Nadoushan Capsules No.1 and No.2 are provided by Shanghai Chunzhitang Biological Products Co., Ltd., and their appearance and taste are basically the same. One of them is Chunzhitang brand Nadoushan plant capsule, and the other is comfort. Agent. The recommended oral dose is 3 times a day, 2 capsules each time.

1.2 subject selection

1.2.1 Inclusion criteria: Subjects are not limited in gender, age 18-65 years. Blood was collected twice within half a year, and serum total cholesterol was ≥5.2mmol/L or serum triglyceride≥1.65mmol/L. Simple dyslipidemia, no obvious brain, heart, liver, lung, kidney, blood disease, no long-term medication History, voluntary test to ensure cooperation.

1.2.2 Subject exclusion criteria: pregnant or lactating women, those who are allergic to health foods: patients with serious diseases such as heart, liver, kidney and hematopoietic system; taking items related to the test function in a short period of time, affecting the results Judgment; does not meet the inclusion criteria, does not consume the test sample as specified, can not determine the work Ineffectiveness or incomplete data affects efficacy or safety judges.

1.3 Experimental design and grouping

Both self and inter-group control designs were used. According to the blood lipid level of the subjects, they were randomly divided into the Chunzhitang brand Nadoushan plant capsule test group and the placebo control group. The main factors affecting the results such as age, sex, diet, etc. were considered as much as possible to ensure the balance test to ensure Comparability between groups. The test was conducted in a double-blind manner.

1.4 Test methods

Subjects took samples at recommended doses daily for 45 days. During the test, the original eating habits were not changed and the normal diet was used.

2 observation indicators

Each observation was measured at the beginning and end of the test.

2.1 Safety indicators

2.1.1 General physical examination: Before the trial, ask in detail and understand the subjects' mental, sleep, diet, urine and so on, and measure changes in body weight, blood pressure and heart rate before and after the test.

2.1.2 blood routine: red blood cell count, white blood cell count and classification, hemoglobin content determination.

2.1.3 urine routine: pH, white blood cells, urine sugar, etc.

2.1.4 stool routine.

2.1.5 Abdominal B-ultrasound, electrocardiogram, X-ray chest fluoroscopy (measured once before the start of the test).

2.1.6 Blood biochemical indicators: serum total protein (TP), albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid (UA), urea nitrogen (BUN), muscle intoxication (Cr) , blood glucose (GLU) and other measurements.

2.1.7 Observation of adverse reactions.

2.2 efficacy indicators: serum total cholesterol (CHOL), triglyceride (TG), high density lipoprotein cholesterol (HDL-C).

3. Result determination

3.1 CHOL decreased by >10%; TG decreased by >15%; HDL-C increased by >0.104mmol/L: the efficacy of each indicator was compared before and after the test, and the comparison between the groups was statistically significant. ;

3.2 serum total cholesterol, triglyceride two indicators positive, high-density lipoprotein cholesterol is not significantly lower than the control group, can be determined that the test sample has an auxiliary hypolipidemic function; serum total cholesterol, glycerol One of the three lipids was positive, and high-density lipoprotein cholesterol was not significantly lower than the control group. It can be determined that the test sample has the effect of lowering serum total cholesterol or assisting in lowering triglyceride.

4. Statistical processing

The results were expressed as mean ± standard deviation. The paired t test was used for the paired data. The comparison between the test group and the control group was based on the variance of the variance. The mean was compared using the group t test. Otherwise, the variables were transformed to satisfy the variance. Using the t test, if the variance is still not uniform, the rank sum test is used.

5. Results

The double-blind observation ended: the person who took the No. 1 was a placebo, and the person who took the No. 2 was Chunzhitang Natangshan Plant Capsule.

5.1 Security observation

5.1.1 General: 52 cases in the control group and 52 cases in the test group. Before and after the test, the subjects' mental, sleep, diet, and bowel movements were not abnormal. The control group: male/female 22/30, age 51.63±9.24 years old; test group: male/female 22/30, The age is 51.87 ± 8.52 years old.

5.1.2 Abdominal B-ultrasound, electrocardiogram, X-ray chest fluoroscopy: all in the normal range.

5.1.3 Changes in body weight, blood pressure, heart rate, urine routine, stool routine, and blood routine indicators

See Table 1. There were no obvious abnormal changes in body weight, blood pressure and heart rate before and after the test sample, and urine routine, stool routine and blood routine were within the normal range.

Table 1 Changes in body weight, blood pressure, heart rate, urine routine, stool routine and blood routine before and after the test (x s)

5.1.5 No obvious adverse reactions were observed during the test.

5.2 efficacy observation

See Tables 3, 4, and 5. The blood was collected twice within half a year, and the blood lipid data before the test and before the test, respectively, were grouped and statistically processed according to the pre-test 2 blood lipid levels of the test samples. There was no significant difference in serum CHOL and TG levels between the control group and the test group before the test (P>0.05), suggesting that the two groups were comparable. After the test, the CHOL and TG were significantly different from those before the test and after the test, the difference was significant (P<0.05). There was no significant change in HDL-C level before and after the test (P>0.05)

Table 3 Serum CHOL, TG, HDL-C levels before the test (x s)

Table 4 Serum CHOL, TG, HDL-C levels after the test (x s)

Table 5 Changes of serum CHOL, TG and HDL-C before and after the test

index	Control group	Test group
			TG reduction rate (%)	1.10	17.41
CHOL reduction rate (%)	1.02	10.70
			HDL-C elevation value (mmol/L)	0.02	0.09

5.3 Loss rate

After 45 days of testing, 0 subjects in the control group were unable to judge the effect of screening because of intermittent use of the test article; 0 subjects in the test group were unable to judge the effect of being screened out due to intermittent use of the test article. Finally, 52 patients in the control group and 52 patients in the test group. See Table 6.

Table 6 Test loss rate

Group	Control group	Test group
			Before the test	52	52
Number of lost	0	0
			Loss rate	0.00%	0.00%

6. Summary

Using self-control and inter-group control method, volunteers who met the test conditions were selected to take the test substance for 45 days. The results showed that: taking the CHG, TG and the test before the test group of the Chunqitang brand Nadoushan plant capsules The comparison decreased by 10.70% and 17.41% respectively. After the test, the CHOL and TG of the test group were compared with those before the test and after the test. The difference was significant (P<0.05). After the test, the HDL-C and the control group were compared with the control. There was no significant difference in group comparison (P>0.05). No obvious adverse reactions were observed during the test. According to the "Technical Specification for Health Food Inspection and Evaluation" (2003 edition) evaluation criteria, it is suggested that the test sample has an auxiliary hypolipidemic function.

Example 2

A natto hawthorn capsule having an auxiliary hypolipidemic function, consisting of a content and a capsule, the raw materials of the contents comprising: natto lyophilized powder 5, hawthorn extract 4, puerarin extract 1 , Chuanxiong extract 1, black fungus extract 1, microcrystalline cellulose 0.1; magnesium stearate and silica are also added to the content, magnesium stearate is added in an amount of 0.5 of the total weight of the contents %, silica was added in an amount of 0.5% by weight based on the total weight of the contents. The rest are the same as in the first embodiment.

Example 3

A natto hawthorn capsule with auxiliary hypolipidemic function, consisting of a content and a capsule, the raw materials of the content comprising: natto lyophilized powder 10, hawthorn extract 8, pueraria extract 5 , Chuanxiong extract 5, black fungus extract 5, microcrystalline cellulose 0.5; magnesium stearate and silica are also added to the content, magnesium stearate is added in an amount of 1.5 of the total weight of the contents %, silica was added in an amount of 1.5% by weight based on the total weight of the contents. The rest are the same as in the first embodiment.

Claims (9)

1. A natto hawthorn capsule having an auxiliary hypolipidemic function, comprising a content and a capsule, wherein the raw material of the content comprises: natto lyophilized powder 5-10, hawthorn extract 4-8, Pueraria lobata extract 1-5, Chuanxiong extract 1-5, black fungus extract 1-5, microcrystalline cellulose 0.1-0.5; magnesium stearate and dioxide are added to the content Silicon, magnesium stearate is added in an amount of from 0.5 to 1.5% by weight based on the total weight of the content, and silica is added in an amount of from 0.5 to 1.5% by weight based on the total weight of the contents.
2. The natto hawthorn capsule with the auxiliary hypolipidemic function according to claim 1, wherein the raw material of the content is: natto lyophilized powder 6.6, hawthorn extract 5.25, puerarin Extract 3.75, Chuanxiong extract 3.24, Black fungus extract 3, microcrystalline cellulose 0.168; magnesium stearate and silica were also added to the content, and the amount of magnesium stearate added was the total content. 1% by weight, silica is added in an amount of 1% by weight based on the total weight of the contents.
3. A method for preparing a natto hawthorn capsule having an auxiliary hypolipidemic function according to any one of claims 1 to 2, characterized in that it comprises the following steps:

   (1) Weighing the hawthorn extract, Pueraria extract, Ligusticum chuanxiong extract, black fungus extract, and microcrystalline cellulose by weight, making soft materials, granulating, drying, and granulating to obtain a mixture ;

   (2) weighed natto lyophilized powder, silica, magnesium stearate by weight to obtain a mixture b;

   (3) Mixture a and mixture b were stirred and mixed in a mixer for 20 minutes, and then filled in a hard capsule, and polished to obtain a product.
4. The method for preparing a natto hawthorn capsule having an auxiliary hypolipidemic function according to claim 3, wherein the sieved particle size in the step (1) is an 80 mesh standard sieve.
5. The method for preparing a natto hawthorn capsule with an auxiliary hypolipidemic function according to claim 3, wherein the specific step of the soft material according to the step (1) is: after sieving by weight Hawthorn extract, Pueraria lobata extract, Chuanxiong extract, black fungus extract, microcrystalline cellulose were mixed, and 95% ethanol was added to obtain a soft material.
6. Preparation of natto hawthorn capsule with auxiliary hypolipidemic function according to claim 3 The method is characterized in that the granulation described in the step (1) is extrusion granulation in a twin-screw extruder, and the obtained particle size is a 20-mesh standard sieve.
7. The method for preparing a natto hawthorn capsule having an auxiliary hypolipidemic function according to claim 3, wherein the drying temperature in the step (1) is 55-60 ° C, and the whole granule refers to : The dried material is passed through a 40 mesh standard sieve.
8. The method for preparing a natto hawthorn capsule having an auxiliary hypolipidemic function according to claim 3, wherein the sieved particle size in the step (2) is a 60 mesh standard sieve.
9. The method for preparing a natto hawthorn capsule with an auxiliary hypolipidemic function according to claim 3, wherein the filling content in the step (3) is controlled between 380 mg and 420 mg, and is polished to a capsule. There is no powder on the surface.