Effect of collateral dredging preparation on type 2 diabetes mellitus with visceral fat deposition

Abstract

The invention provides application of a traditional Chinese medicine composition in preparing a medicine for treating fat deposition, and relates to the technical field of traditional Chinese medicines. The traditional Chinese medicine composition consists of astragalus membranaceus, honeysuckle, golden cypress, rhizoma atractylodis, semen coicis, radix scrophulariae, angelica sinensis, radix paeoniae alba, liquorice, leech, centipede and scorpio, has the effects of reducing fat deposition in a body and improving insulin resistance, and particularly has the best effect of preventing and treating visceral fat deposition accompanied by type II diabetes.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, in particular to the technical field of a drug for treating fat deposition, and specifically to the effect of Mailuo Shutong preparation on type 2 diabetes with visceral fat deposition. Background Art

[0002] As living standards improve, obesity is becoming more and more common among the population, especially abdominal obesity, which is an important member of metabolic syndrome and an important risk factor for many diseases such as T2DM, IR, coronary heart disease, and hyperlipidemia. Visceral fat area (VFA) refers to the accumulation of a large amount of adipose tissue around the internal organs, and the visceral fat area is large. The abnormal accumulation of visceral fat tissue is an important risk factor for type 2 diabetes and has been proven to be more harmful to the human body than fat accumulated in other parts of the body. The visceral fat index is positively correlated with the risk of type 2 diabetes. When the visceral fat content exceeds a certain critical value, the higher the visceral fat content, the higher the risk faced by patients with type 2 diabetes. When fat deposition gradually decreases, diabetes can be effectively improved.

[0003] Diabetes is an epidemic disease that affects the health of all mankind. It is a metabolic disorder characterized by defects in the body's regulation of blood sugar and insulin homeostasis. Type 2 diabetes mellitus (T2DM) is the most common type of diabetes in adults, characterized by persistent and slow hyperglycemia. It is an endocrine disease caused by insulin resistance or pancreatic β-cell dysfunction, with high morbidity and mortality rates worldwide. The pancreatic β-cell function of patients with type 2 diabetes decreases at an average rate of 2% per year. If blood sugar is not well controlled, it can cause a series of complications such as visceral fat deposition, which brings great distress to the lives of patients with diabetes. Studies have shown that more than 1 million patients die from diabetes and its complications every year worldwide. The World Health Organization (WHO) stated that by 2030, T2DM will become the seventh leading cause of death in the world.

[0004] In order to alleviate the deposition of visceral fat in patients, Western medicine generally uses diet pills, which reduce the deposition of visceral fat by reducing overall body fat.

[0005] The prior art "Study on the Effects of High-content DHA / EPA Triglycerides on Regulating Lipid Metabolism and Improving Insulin Resistance" (Zhu Yuzhe et al., published on June 9, 2013) records that high-content DHA / EPA triglycerides in fish oil can effectively regulate lipid metabolism in rats with fatty liver and significantly improve insulin resistance in model mice.

[0006] However, existing technologies show that fish oil can interfere with the body's blood coagulation mechanism, increase the risk of bleeding, cause indigestion, cause palpitations, chest tightness, and increase the risk of atrial fibrillation. Researchers from Sun Yat-sen University published "Regular use of fish oil supplements and course of cardiovascular diseases: prospective cohort study" in BMJ Medicine, revealing the different effects of fish oil supplements on people at different stages of cardiovascular health. Regular use of fish oil supplements by people with good cardiovascular health may increase the risk of first-time heart disease and stroke, atrial fibrillation by 13%, and stroke by 5%; women and non-smokers who use fish oil supplements have a 6% higher risk of developing heart disease, stroke, or heart failure. Therefore, in the face of such risks, safer and more appropriate drugs are needed to meet patients' medication needs.

[0007] After developing and experimentally verifying new uses for the existing product, the Coriolus Tong preparation, the inventors found that the Coriolus Tong preparation can regulate lipid metabolism and improve insulin resistance. At the same time, compared with fish oil, it has lower production costs and lower risks, and has already been industrialized in reality.

[0008] Therefore, the present invention provides a use of a Mailuoshutong preparation in the preparation of a drug for preventing and treating fat deposition, which uses traditional Chinese herbal medicines as raw materials, conforms to the theory of traditional Chinese medicine, has significant efficacy, higher safety, and lower production costs than the existing technology and has been realized in production, providing more medication options for patients with fat deposition. Summary of the invention

[0009] In view of the deficiencies in the prior art, the present invention provides a new use of a Mailuoshutong preparation based on the clinical application feedback of the marketed product "Mailuoshutong". Pharmacological experiments have confirmed that the Mailuoshutong preparation has excellent efficacy in preventing and treating fat deposition, especially in treating visceral fat deposition associated with type II diabetes, and the production cost is lower than that of the prior art, and industrialized production has been achieved.

[0010] One of the purposes of the present invention is to provide a new use of a Mailuoshutong preparation. The use described in the present invention is based on the clinical application of the marketed products "Mailuoshutong Pills" and "Mailuoshutong Granules", but the use of the present invention is not limited to the above products. The preparations obtained by adopting the following technical solutions of the present invention can achieve the same or similar therapeutic effects.

[0011] The technical purpose of the present invention is achieved by the following technical solutions:

[0012] A Mailuoshutong preparation is composed of a traditional Chinese medicine composition and a pharmaceutically acceptable excipient. The traditional Chinese medicine composition is composed of astragalus, honeysuckle, phellodendron, atractylodes, scrophularia, angelica, white peony root, liquorice, centipede, scorpion, coix seed and leech, and the weight percentage is:

[0013]

[0014] Furthermore, preferably, the Chinese medicine composition is made of the following components:

[0015]

[0016]

[0017] The pharmaceutically acceptable excipients are fillers, binders, surfactants and lubricants.

[0018] The percentage of the excipients in the Mailuoshutong preparation is: 30-45% of filler, 5-10% of binder, 5-10% of surfactant, and 1-2% of lubricant.

[0019] Furthermore, preferably, the percentage of the excipients in the Channeloshutong preparation is: filler 35%, binder 8%, surfactant 8%, lubricant 2%.

[0020] The filler is white clay, powdered cellulose or pectin; the binder is low-substituted hydroxypropyl methylcellulose or hydroxyethyl methylcellulose; the surfactant is sucrose stearate, sorbitan sesquioleate or glyceryl monooleate; and the lubricant is magnesium stearate, sodium stearyl fumarate and talc.

[0021] The second purpose of the present invention is to provide pharmaceutical uses of the Mailuo Shutong preparation. The various Chinese medicinal materials of the Mailuo Shutong preparation of the present invention synergize and enhance the efficacy. Pharmacology and clinical cases show that the Chinese medicine composition of the present invention can regulate lipid metabolism, improve insulin resistance, improve fat deposition, and has a high total effective rate, high safety, and low production cost.

[0022] Specifically, the Mailuoshutong preparation has the effect of preventing and treating fat deposition, especially visceral fat deposition.

[0023] Furthermore, the visceral fat deposition is visceral fat deposition associated with type II diabetes.

[0024] In addition, the Mailuoshutong preparation has the effect of improving insulin resistance and can be used in the preparation or treatment of diabetes drugs. Preferably, the diabetes is type 1 diabetes or type 2 diabetes, preferably type 2 diabetes.

[0025] The third aspect of the present invention provides a preparation of the above-mentioned traditional Chinese medicine composition, wherein the dosage form of the Mailuo Shutong preparation is an oral preparation.

[0026] Furthermore, the oral preparation is a pill, a tablet, a mixture, a capsule, a granule, a powder or a paste; preferably, the clinically acceptable dosage form is a pill or a granule.

[0027] Furthermore, the Mailuoshutong preparation provided by the present invention relies on the clinical feedback of the marketed varieties "Mailuoshutong Pills" and "Mailuoshutong Granules". Therefore, the product is preferably Mailuoshutong Pills or Mailuoshutong Granules, but the product of the present invention is not limited to this variety.

[0028] The present invention also provides a method for preparing the Mailuoshutong preparation, comprising the following steps:

[0029] A. Take leeches, centipedes and scorpions and crush them into particles less than 100 μm;

[0030] B. Phellodendron amurense, coix seed, Scrophularia ningpoensis, and white peony root are extracted with ethanol, and then extracted with water. After the ethanol extract is recovered, it is concentrated into an alcohol extract, and the water extract is filtered for later use;

[0031] C. Extract volatile oil from honeysuckle, atractylodes, angelica, astragalus and liquorice with water, add 1 / 2 amount of leech, centipede and scorpion to the remaining liquid and residue, decoct with water, filter, and concentrate the filtrate and the water extract in step B into an extract;

[0032] D. Evenly mix the remaining 1 / 2 amount of leeches, centipedes and scorpions with the alcohol extract of step B and the water extract of step C, and prepare a clinically acceptable dosage form directly or by adding a pharmaceutically acceptable excipient through conventional procedures.

[0033] Compared with the prior art, the present invention has the following outstanding advantages:

[0034] 1. In the prescription of the present invention, astragalus invigorates qi and nourishes blood, honeysuckle clears away heat and detoxifies, Scrophularia nourishes yin and reduces fire, coix seed promotes diuresis and reduces swelling, scorpion and leech dredge meridians. The Chinese medicinal components complement each other, integrating qi invigoration and yin nourishing, blood nourishing and collateral dredging, and heat clearing and detoxification, demonstrating the characteristics of Chinese medicine components emphasizing the whole, dynamic adjustment, harmonizing yin and yang, and increasing efficacy and reducing toxicity, thereby improving the effectiveness and safety of drugs.

[0035] 2. The present invention develops a new use of the Mailuoshutong preparation in the preparation of drugs for preventing and treating fat deposition. The Mailuoshutong preparation can significantly reduce the lipid content in the liver, reduce visceral fat deposition, and can also reduce serum insulin and improve insulin resistance. It has the beneficial effect of preventing and treating visceral fat deposition, especially visceral fat deposition in patients with type 2 diabetes. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1is the fasting blood glucose concentration of rats in each group (compared with the blank group##P<0.01; compared with the model group&&P<0.01,&P<0.05);

[0037] Figure 2 is the serum TC and TG concentrations of rats in each group (compared with the blank group##P<0.01; compared with the model group&&P<0.01,&P<0.05);

[0038] Figure 3 is the serum FFA concentration of rats in each group (compared with the blank group##P<0.01; compared with the model group&&P<0.01,&P<0.05);

[0039] Figure 4 is the visceral fat mass and fat body ratio of rats in each group (compared with the blank group##P<0.01; compared with the model group&&P<0.01,&P<0.05);

[0040] Figure 5 The fasting serum insulin content and insulin resistance index of each group (compared with the blank group ##P<0.01; compared with the model group &&P<0.01, &P<0.05). DETAILED DESCRIPTION

[0041] The following specific implementation modes are listed to further illustrate the present invention, but do not limit the scope of the present invention in any way. Those skilled in the art can make various modifications or improvements based on the basic idea of ​​the present invention, but as long as they do not deviate from the basic idea of ​​the present invention, they are all within the scope of the present invention.

[0042] Example 1 Mailuo Shutong Pills

[0043] Chinese medicine formula:

[0044]

[0045]

[0046] Preparation method:

[0047] A. Take leeches, centipedes and scorpions and crush them into particles less than 100 μm;

[0048] B. Phellodendron amurense, coix seed, Scrophularia ningpoensis, and white peony root are extracted with ethanol, and then extracted with water. After the ethanol extract is recovered, it is concentrated into an alcohol extract, and the water extract is filtered for later use;

[0049] C. Extract volatile oil from honeysuckle, atractylodes, angelica, astragalus and liquorice with water, add 1 / 2 amount of leech, centipede and scorpion to the remaining liquid and residue, decoct with water, filter, and concentrate the filtrate and the water extract in step B into an extract;

[0050] D. Evenly mix the remaining 1 / 2 amount of leeches, centipedes and scorpions with the alcohol extract of step B and the water extract of step C, and prepare pills directly or by adding pharmaceutically acceptable excipients through conventional procedures.

[0051] Example 2 Mailuo Shutong Granules

[0052] Chinese medicine formula:

[0053]

[0054] Preparation method:

[0055] A. Take leeches, centipedes and scorpions and crush them into particles less than 100 μm;

[0056] B. Phellodendron amurense, coix seed, Scrophularia ningpoensis, and white peony root are extracted with ethanol, and then extracted with water. After the ethanol extract is recovered, it is concentrated into an alcohol extract, and the water extract is filtered for later use;

[0057] C. Extract volatile oil from honeysuckle, atractylodes, angelica, astragalus and liquorice with water, add 1 / 2 amount of leech, centipede and scorpion to the remaining liquid and residue, decoct with water, filter, and concentrate the filtrate and the water extract in step B into an extract;

[0058] D. Mix the remaining 1 / 2 amount of leeches, centipedes and scorpions with the alcohol extract of step B and the water extract of step C, and prepare granules directly or by adding pharmaceutically acceptable excipients through conventional procedures.

[0059] Example 3 Mailuo Shutong Pills

[0060] Chinese medicine formula:

[0061]

[0062] The preparation method is the same as Example 1.

[0063] Embodiment 4 Mailuo Shutong Pills

[0064] Chinese medicine formula:

[0065]

[0066] The preparation method is the same as Example 1.

[0067] Example 5 Mailuo Shutong Pills

[0068] Chinese medicine formula:

[0069]

[0070] The preparation method is the same as Example 1.

[0071] Embodiment 6 Mailuo Shutong granules Chinese medicine prescription:

[0072]

[0073] The preparation method is the same as Example 2.

[0074] Comparative Example 1 Mailuo Shutong Pills Chinese medicine formula:

[0075]

[0076] The preparation method is the same as Example 1.

[0077] Comparative Example 2 Mailuo Shutong Granules

[0078] Chinese medicine formula:

[0079]

[0080] The preparation method is the same as Example 2.

[0081] 1. Experimental Example 1: Effects of Mailuo Shutong preparation on liver lipid content, body fat ratio, fasting blood glucose and fasting serum insulin content in rats.

[0082] 1. Materials

[0083] 1.1 Experimental animals

[0084] After 2 weeks of routine adaptive feeding, healthy male 8-week-old SPF Wistar rats weighing 180-200 g were obtained, and the animal license number was SYXK (Lu) 2023-0023.

[0085] 1.2 Experimental drugs

[0086] Mailuo Shutong Pills (National Medicine Standard Z20090636), produced by Lunan Houpu Pharmaceutical Co., Ltd.; Example 1 pills, Example 2 granules, Comparative Example 1 pills, Comparative Example 2 granules; Atorvastatin calcium tablets; Ethyl ester fish oil. The medicinal materials and preparations used are all commercially available, and the product quality meets national regulations.

[0087] 2. Methods

[0088] 2.1 Modeling

[0089] Healthy rats were fasted for 12 hours but not water, and the model was established. Streptozotocin was dissolved in 0.1 mol / L citrate buffer (pH 4.2) to prepare a 1% solution, and a single intraperitoneal injection of 60 mg / kg was given. Blood was collected from the tail vein 72 hours after the first injection of streptozotocin, and blood sugar levels were tested for 2 consecutive weeks. Rats with blood sugar levels above 16.7 mmol / L were considered to have successfully established the model.

[0090] 2.2 Grouping

[0091] The rats with successful modeling were randomly divided into a model group, a Mailuo Shutong Pills group, an Example 1 group, an Example 2 group, a Comparative Example 1 group, a Comparative Example 2 group, an atorvastatin calcium tablet group, and an ethyl fish oil group, with 10 rats in each group.

[0092] Blank group: 10 healthy rats.

[0093] 2.3 Experimental methods

[0094] (1) Drug intervention: The Mailuo Shutong Pills group, Example 1 group, Example 2 group, Comparative Example 1 group, and Comparative Example 2 group were given a daily dose of 12.50 g / kg, once a day; the positive control drug was atorvastatin calcium 0.60 g / kg aqueous solution by intragastric administration, once a day; the ethyl ester fish oil group was 1.48 g / kg by intragastric administration, once a day; the blank group and the model group were given 12.50 g / kg of normal saline by intragastric administration, once a day; the medication lasted for 6 weeks.

[0095] (2) Detection of fasting blood glucose concentration in rats: After the last administration, the rats were fasted but not watered for 12 h. Venous blood was collected from the rats to detect fasting blood glucose concentration.

[0096] (3) Determination of fasting serum insulin content and lipid concentration in rats: After the last administration, the rats were fasted but not watered for 12 hours. After the rats were anesthetized, blood was collected from the abdominal aorta to detect serum insulin content, total cholesterol (TC), triglyceride (TG), and free fatty acid (FFA) concentrations. HOMA-IR (insulin resistance index) = fasting blood glucose concentration × fasting serum insulin content / 22.5.

[0097] (4) Determination of fat body ratio of rats: After the last blood collection, the rats were euthanized, and the adipose tissue of the visceral parts (mesentery, perirenal, inguinal, genital, etc.) was quickly removed, rinsed with ice saline, and then blotted with filter paper, weighed with an electronic analytical balance, and the fat body ratio was calculated. Fat body ratio (%) = visceral fat mass / body mass × 100%.

[0098] 2.4 Statistical processing of experimental data

[0099] SPSS22.0 software was used to perform statistical analysis on the data obtained. P<0.05 indicated a significant difference, and P<0.01 indicated a very significant difference.

[0100] 3. Results

[0101] 3.1 Fasting blood glucose concentration of rats in each group

[0102] like Figure 1As shown, after modeling, compared with the blank group rats, the fasting blood glucose levels of the model group and the drug administration group rats were significantly increased (##P<0.01). After drug administration, the blood glucose levels of the drug administration group rats were reduced to varying degrees at each period. After 6 weeks of drug administration, compared with the model group, the fasting blood glucose levels of the rats in the Mailuo Shutong Pills group, Example 1 group, and Example 2 group were significantly reduced && (P<0.01), and the fasting blood glucose levels of the rats in the atorvastatin calcium tablets group and the ethyl ester fish oil group were significantly reduced (&P<0.05), and the fasting blood glucose levels of the rats in the comparative example 1 group and the comparative example 2 group were reduced to a lesser extent. Therefore, the Mailuo Shutong Pills group and Examples 1 and 2 can effectively reduce the fasting blood glucose levels of diabetic rats and have a good hypoglycemic effect.

[0103] 3.2 Serum lipid concentrations of rats in each group

[0104] like Figure 2 , 3 As shown, after modeling, compared with the blank group rats, the TC, TG, and FFA contents of the model group and the drug administration group rats were significantly increased (##P﹤0.01). After administration, compared with the model group, the TC, TG, and FFA contents of the rats in the Mailuo Shutong Pills group, Example 1 group, and Example 2 group were significantly reduced (&&P﹤0.01), and the TC, TG, and FFA contents of the rats in the atorvastatin calcium tablets group and the ethyl ester fish oil group were significantly reduced (&P﹤0.05), and the TC, TG, and FFA contents of the rats in the comparative example 1 group and the comparative example 2 group were reduced to a lesser extent.

[0105] 3.3 Liposome ratio of rats in each group

[0106] like Figure 4 As shown, after modeling, compared with the blank group, the body weight, visceral fat mass and fat body ratio of the model group rats were significantly increased (##P﹤0.01). After administration, compared with the model group, the body weight, visceral fat mass and fat body ratio of the rats in the Mailuo Shutong Pills group, Example 1 group and Example 2 group were significantly reduced (&&P﹤0.01), the body weight, visceral fat mass and fat body ratio of the rats in the atorvastatin calcium tablets group and the ethyl ester fish oil group were reduced, and the reduction degree of the rats in the comparative example 1 group and the comparative example 2 group was smaller.

[0107] Therefore, Mailuo Shutong Pills, Example 1 and Example 2 can significantly reduce liver fat accumulation, and the effect is obviously better than atorvastatin calcium tablets and fish oil.

[0108] 3.4 Fasting serum insulin levels in rats of each group

[0109] like Figure 5As shown, after modeling, compared with the blank group rats, the insulin content of the model group and the drug administration group rats increased significantly (##P﹤0.01). After administration, compared with the model group, the fasting insulin content of the rats in the Mailuo Shutong Pills group, Example 1 group, and Example 2 group decreased significantly (&&P﹤0.01), the HOMA-IR index decreased, and the insulin content in the serum of the rats in the atorvastatin calcium tablets group and the ethyl ester fish oil group decreased significantly (&P﹤0.05); but the reduction in the insulin content in the serum of the rats in the comparative example 1 group and the comparative example 2 group was smaller.

[0110] Therefore, Mailuo Shutong Pills, Example 1 and Example 2 have the best effects in reducing serum insulin and improving insulin resistance.

Claims

1. Use of a Mailuoshutong preparation in preparing a drug for preventing and treating fat deposition.

2. The use according to claim 1, characterized in that The Mailuoshutong preparation is composed of a traditional Chinese medicine composition and a pharmaceutically acceptable excipient; the traditional Chinese medicine composition is made of the following components: Astragalus 550-850 weight parts Honeysuckle 520-850 weight parts Coix seeds 520-850 weight parts Atractylodes lancea 300-430 parts by weight Scrophularia 520-850 parts by weight Scorpio 60-150 parts by weight White peony root 300-480 parts by weight Cortex Phellodendri 300-430 parts by weight Scolopendra subspinipes 17-40 parts by weight 300-480 parts by weight of Chinese Angelicae Sinensis 60-150 parts by weight of Licorice 260-500 parts by weight of Leech; Preferably, the Chinese medicine composition is made from the following components: 830 parts by weight of Astragalus Root 830 parts by weight of Honeysuckle 830 parts by weight of Coix Seed 830 parts by weight 420 parts by weight of Atractylodes lancea 830 parts by weight of Scrophularia ningpoensis 130 parts by weight of Scorpio 420 parts by weight of white peony root 420 parts by weight of Phellodendron chinense 30 parts by weight 420 parts by weight of Angelica sinensis, 130 parts by weight of Licorice, and 420 parts by weight of Leech.

3. The use according to claim 1, characterized in that The fat deposits are visceral fat deposits.

4. The use according to claim 1, characterized in that The fat deposits are visceral fat deposits associated with type 2 diabetes.

5. The use according to claim 1, characterized in that The pharmaceutically acceptable excipients are fillers, binders, surfactants and lubricants.

6. The use according to claim 5, characterized in that The percentage of the excipients in the Coriolis Pain Relief Preparation is: 30-45% filler, 5-10% binder, 5-10% surfactant, and 1-2% lubricant; preferably, the percentage of the excipients in the Coriolis Pain Relief Preparation is: 35% filler, 8% binder, 8% surfactant, and 2% lubricant.

7. The use according to claim 1, characterized in that The dosage form of the Mailuoshutong preparation is an oral preparation.

8. The use according to claim 7, characterized in that The oral preparation is a pill, a tablet, a mixture, a capsule, a granule, a powder or an ointment; preferably, the clinically acceptable dosage form is a pill or a granule.

9. The use according to claim 1, characterized in that The Mailuoshutong preparation is Mailuoshutong granules or Mailuoshutong pills.

10. The use according to claim 1, characterized in that The preparation method of the Mailuoshutong preparation comprises the following steps: A. Take leeches, centipedes and scorpions and crush them into particles less than 100 μm; B. Phellodendron amurense, coix seed, Scrophularia ningpoensis, and white peony root are extracted with ethanol, and then extracted with water. After the ethanol extract is recovered, it is concentrated into an alcohol extract, and the water extract is filtered for later use; C. Extract volatile oil from honeysuckle, atractylodes, angelica, astragalus and liquorice with water, add 1 / 2 amount of leech, centipede and scorpion to the remaining liquid and residue, decoct with water, filter, and concentrate the filtrate and the water extract in step B into an extract; D. Evenly mix the remaining 1 / 2 amount of leeches, centipedes and scorpions with the alcohol extract of step B and the water extract of step C, and prepare a clinically acceptable dosage form directly or by adding a pharmaceutically acceptable excipient through conventional procedures.

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