Turbid dissolving and detoxification traditional Chinese medicine composition for improving insulin resistance and preparation method of turbidity dissolving and detoxification traditional Chinese medicine composition

Abstract

The invention discloses a turbidity-dissolving and detoxifying traditional Chinese medicine composition for improving insulin resistance and a preparation method. The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 20-40 parts of herba eupatorii, 20-40 parts of ramulus euonymi, 20-40 parts of ramulus mori, 10-30 parts of poria cocos, 10-20 parts of cassia twig, 10-20 parts of rhizoma atractylodis macrocephalae, 10-20 parts of rhizoma atractylodis, 8-12 parts of pericarpium citri reticulatae, 8-12 parts of bombyx batryticatus and 5-7 parts of liquorice root. The invention provides a new medicine choice for treating diabetes mellitus, the medicine takes a unique detoxification and turbidity dissolving method as a formula principle, and clinical and animal experiments prove that the medicine can obviously improve insulin resistance, has a remarkable curative effect on diabetes mellitus, especially type 2 diabetes mellitus and chronic complications thereof, and has a good application prospect.

Description

Technical Field

[0001] The invention relates to a Chinese medicine composition for preventing and treating diabetes, in particular to a turbidity-clearing and detoxifying Chinese medicine composition for improving insulin resistance and a preparation method thereof, belonging to the technical field of traditional Chinese medicine. Background Art

[0002] Insulin resistance is the central link and pathophysiological basis of the onset of type 2 diabetes. Turbidity and turbidity are closely related to insulin resistance. Turbidity and yin are the key to the development of diabetes in patients and the core of diabetes and its complications. The detoxification and turbidity removal method can significantly improve insulin sensitivity and improve insulin resistance. Treating from the perspective of turbidity and turbidity is an important rule for improving insulin resistance. The detoxification and turbidity removal method is an effective method for improving insulin resistance and treating type 2 diabetes (T2DM). However, there is currently no Chinese medicine preparation for the treatment of type 2 diabetes on the market that uses the detoxification and turbidity removal method as the formulation principle. Summary of the invention

[0003] The technical problem to be solved by the present invention is to provide a turbidity-clearing and detoxifying Chinese medicine composition for improving insulin resistance and a preparation method thereof, thereby providing a new drug option for patients with type 2 diabetes.

[0004] In order to solve the above technical problems, the technical solution adopted by the present invention is as follows:

[0005] A turbidity-clearing and detoxifying Chinese medicinal composition for improving insulin resistance is prepared from the following raw materials in parts by weight: 20-40 parts of perilla, 20-40 parts of euphorbia pulex, 20-40 parts of mulberry branches, 10-30 parts of tuckahoe, 10-20 parts of cassia twig, 10-20 parts of atractylodes, 10-20 parts of atractylodes, 8-12 parts of tangerine peel, 8-12 parts of bombyx batryticatus, and 5-7 parts of liquorice.

[0006] As a preferred embodiment, the optimal weight of the raw materials is: 30g of Perilla frutescens, 30g of Phellodendron chinense, 30g of Morus alba, 20g of Poria cocos, 15g of Cinnamon twig, 15g of Atractylodes macrocephala, 15g of Atractylodes lancea, 10g of Tangerine peel, 10g of Bombyx batryticatus, and 6g of Licorice.

[0007] The preparation method of the above-mentioned turbidity-clearing and detoxifying Chinese medicine composition for improving insulin resistance comprises the following steps: weighing medicinal materials such as Perilla frutescens, Psoralea corylifolia, Morus alba, Poria cocos, Cinnamon twig, Atractylodes macrocephala, Atractylodes lancea, Tangerine peel, Bombyx batryticatus, and Licorice, soaking the above-mentioned medicinal materials in 5 times the mass of pure water for 2 hours, boiling them with high heat at 150-220°C and then decocting them with low heat at 80-120°C for 30 minutes, collecting the decoction after filtering; adding 2 times the mass of pure water to the filter residue and decocting it for 20 minutes, collecting the decoction after filtering; mixing the two decoctions and concentrating them to a Chinese medicine concentration of 2.5 g / ml to obtain the Chinese medicine composition of the present invention.

[0008] As a preferred embodiment, the above-mentioned Chinese medicine composition for clearing turbidity and detoxifying for improving insulin resistance can be made into a pharmaceutical preparation, which is made of the following raw materials in parts by weight: 20-40 parts of Perilla frutescens, 20-40 parts of Phellodendron chinense, 20-40 parts of Morus alba, 10-30 parts of Poria cocos, 10-20 parts of Cassia twig, 10-20 parts of Atractylodes macrocephala, 10-20 parts of Atractylodes lancea, 8-12 parts of Citrus reticulata, 8-12 parts of Bombyx batryticatus, 5-7 parts of Licorice, and pharmaceutically acceptable excipients.

[0009] As a preference, the pharmaceutical preparation includes injection, oral solution, pill, powder, paste, tablet, granule, powder or capsule.

[0010] Beneficial effects: Compared with the prior art, the present invention provides a new drug option for treating diabetes. The drug is formulated based on the principle of detoxification and turbidity removal. Clinical and animal experiments have shown that the drug can significantly improve insulin resistance and has a significant effect on the treatment of diabetes, especially type 2 diabetes and its chronic complications. The drug of the present invention is formulated based on the principle of detoxification and turbidity removal. The applicant has found through clinical studies that the drug has a good effect on the treatment of diabetes and its chronic complications, and its mechanism may be related to improving insulin resistance.

[0011] The formula of the present invention is composed of eleven medicinal materials, including perilla, euphorbia obesa, mulberry twig, poria, cassia twig, atractylodes, atractylodes, tangerine peel, bombyx batryticatus and liquorice. The formula is composed of perilla, a representative drug for detoxification and turbidity removal, combined with Lingguishugan decoction with additions and subtractions. Perilla is used for detoxification and turbidity removal, and is the main drug; Lingguishugan decoction is used for dampness removal and turbidity removal, and is the assistant drug; perilla and mulberry twig are used for promoting blood circulation and removing blood stasis, bombyx batryticatus is used for removing phlegm and dispersing nodules, and tangerine peel is used for regulating qi and removing phlegm, which respectively remove blood stasis and phlegm turbidity, which are precursors of turbidity and toxin generation, and prevent and treat turbidity and toxin generation, and are all adjuvant drugs; liquorice is used for harmonizing various drugs as a guiding drug, and the whole formula has the effects of detoxification and turbidity removal.

[0012] Based on the clinical research, the applicant further conducted animal experiments on the drug of the present invention to improve insulin resistance. The experimental results show that the drug of the present invention can significantly improve the insulin resistance level of experimental rats.

[0013] The following are relevant experimental data:

[0014] 1. Clinical Trials

[0015] 1. Clinical data

[0016] 1.1 Diagnostic criteria

[0017] The diagnostic criteria for type 2 diabetes mellitus (T2DM) were based on the 1999 WHO criteria, and the diagnostic criteria for diabetic bladder were developed with reference to the Diagnosis and Treatment of Diabetic Neuropathy: (1) meeting the diagnostic criteria for type 2 diabetes; (2) the presence of symptoms and signs of autonomic neuropathy; and (3) bladder residual urine volume (BRU) > 50 ml.

[0018] Inclusion criteria: (1) meeting the diagnostic criteria for T2DM and DCP; (2) aged 18-70 years; (3) glycosylated hemoglobin (HbA1c) ≤ 7.5%; (4) discontinuation of the original medication for DCP for more than 2 weeks.

[0019] Exclusion criteria: patients with severe heart, liver, kidney and hematopoietic system diseases and increased bladder residual urine volume due to other reasons.

[0020] 1.2 General Information

[0021] The 100 patients who met the criteria were outpatients and inpatients in the Department of Endocrinology of the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from November 2019 to October 2022. They were divided into a treatment group of the Chinese medicine composition of the present invention and a methylcobalamin control group according to a random number table. The treatment group had 53 cases, including 30 males and 23 females, aged 64.3±8.8 years, a course of diabetes of 174.8±55.7 months, a course of bladder lesions of 65.7±16.7 months, and HbA1c (%) of 6.9±0.6. The control group had 47 cases, including 27 males and 20 females, aged 63.9±8.3 years, a course of diabetes of 171.7±56.7 months, a course of bladder lesions of 62.9±13.4 months, and HbA1c (%) of 6.8±0.6. Gender composition was compared using χ 2 The t-test was used to compare age, disease course, and glycosylated hemoglobin. Statistical analysis showed that there were no significant differences in gender, age, disease course, and glycosylated hemoglobin between the two groups (P>0.05).

[0022] 2 Methods

[0023] 2.1 Treatment

[0024] Control group: Oral hypoglycemic drugs or insulin were used to control blood sugar, and no other drugs were used. The patients were observed for 3 months.

[0025] Treatment group: Oral hypoglycemic drugs or insulin were used to control blood sugar, so that blood sugar was controlled stably, and the Chinese medicine composition of the present invention was given, the drug composition: 30g of Perilla frutescens, 30g of Radix Angelicae Pubescentis, 30g of Morus alba, 20g of Poria, 15g of Cinnamon Twig, 15g of Atractylodes macrocephala, 15g of Atractylodes macrocephala, 10g of Chenpi, 10g of Bombyx batryticatus, 6g of Licorice, the medicinal materials were soaked in 5 times the mass of pure water for 2 hours, boiled with high heat (150-220℃), and then decocted with low heat (80-120℃) for 30min, and the decoction was collected after filtration; the filter residue was added with 2 times the mass of pure water and decocted for 20min, and the decoction was filtered; the two decoctions were mixed and concentrated to 300ml, 1 dose per day, 100ml each time, and warmed for 3 times. The experimental drugs were prepared by the preparation room of the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine. The control group was given methylcobalamin tablets (produced by Japan Eisai Co., Ltd., specification: 500ug / tablet), orally, 500ug each time, 3 times a day, and treated for 3 months.

[0026] 2.2 Observation items

[0027] The clinical manifestation score, insulin resistance index HOMA-IR and other indicators were observed before and after medication.

[0028] 2.3 Detection methods

[0029] The quantification standard for clinical manifestation grading was formulated with reference to the quantification standard for diabetes symptom grading. Clinical manifestations were graded into none, mild, moderate, and severe, with none scoring 0 points, mild scoring 1 point, moderate scoring 2 points, and severe scoring 3 points (dysuria, weak urination, terminal dribbling, change in urine volume, change in urination frequency × 1.0, urinary incontinence, orthostatic hypotension, resting tachycardia × 2.0). The reduction rate of clinical manifestation score was calculated using the nimodipine method, and the calculation formula was: [(pre-treatment score-post-treatment score) ÷ pre-treatment score] × 100%; the insulin resistance index HOMA-IR was the product of fasting plasma insulin (μU / ml) and fasting plasma glucose (mmol / L) divided by 22.5.

[0030] 2.4 Statistical methods

[0031] SPSS 16.0 statistical software was used for statistical analysis, and quantitative data were analyzed using The t-test was used to compare the two groups, and P < 0.05 was considered to be significantly different.

[0032] 3 Results

[0033] 3.1 Comparison of clinical manifestation scores between the two groups before and after treatment

[0034] There was no significant difference in clinical performance scores between the two groups before treatment (P>0.05); compared with before treatment, the clinical performance scores of the two groups after treatment were significantly reduced, and the difference was statistically significant (P 0.000<0.01); compared with the control group, the clinical performance scores of the treatment group after treatment were significantly reduced, and the difference was statistically significant (P=0.0007<0.01). (See Table 1).

[0035] Table 1 Clinical manifestation scores of the two groups before and after treatment

[0036]

[0037] Note: Compared with before treatment, ** P<0.01; compared with the control group, △△ P<0.01

[0038] 3.2 Comparison of insulin resistance index HOMA-IR between the two groups before and after treatment

[0039] There was no significant difference in HOMA-IR between the two groups before treatment (P>0.05); compared with before treatment, there was no significant difference in HOMA-IR in the control group after treatment (P>0.05), and the HOMA-IR in the treatment group was significantly lower than that before treatment, with a statistically significant difference (P=0.001<0.01); compared with the control group, the HOMA-IR in the treatment group was significantly lower after treatment, with a statistically significant difference (P=0.005<0.01). (See Table 2)

[0040] Table 2 HOMA-IR in the two groups before and after treatment

[0041]

[0042] Note: Compared with before treatment, ** P<0.01; compared with the control group, △△ P<0.01.

[0043] 2. Animal Testing

[0044] 1. Materials

[0045] 1.1 Animals

[0046] Forty SPF male 6-week-old spontaneous type 2 diabetic db / db mice and ten normal male db / m mice of the same age, weighing 28-35 g, were purchased from Changzhou Cavens Experimental Animal Co., Ltd. (certificate number: NO.201826879). This experiment was reviewed and approved by the Ethics Committee of the Institute of Experimental Animals of Guizhou University of Traditional Chinese Medicine.

[0047] 1.2 Drugs and reagents

[0048] The Chinese medicine composition of the present invention is prepared by the pharmacy of the Second Affiliated Hospital of Guizhou University of Chinese Medicine; rosiglitazone (ROS) (Chengdu Hengrui Pharmaceutical Co., Ltd., approval number: H20030569); hematoxylin, histochemical primary antibody diluent, DAB color development kit, enhanced enzyme-labeled goat anti-mouse / rabbit IgG polymer, horseradish enzyme-labeled goat anti-rabbit IgG (H+L) (Beijing Zhongshan Jinqiao Biotechnology Co., Ltd., batch numbers: ZLI-9610, ZLI-9030, ZLI-9018, PV-9001, ZB-2301 respectively), Anti-TLR4, Anti-NFκBp65, Anti-IκK alpha, Anti-IκB alpha antibody (Abcam, batch numbers: ab22048, 14220-1-AP, ab32041, ab32518); Insulin kit (Nanjing Jiancheng Biological Research Institute, batch number: H203-1-2), Protein Maker, reverse transcription kit, BCA protein concentration determination kit (Thermo Fisher Scientific, batch numbers: 26616, A25742, P0100), WB primary antibody diluent (Beyotime, batch number: P0023A-500ml).

[0049] 1.3 Instruments

[0050] BBS-DDC clean bench (Jinan Xinbeisi Biotechnology Co., Ltd.), centrifugal oscillator, S1010E centrifuge (Labnet, USA), low-speed centrifuge (Hunan Xiangyi Laboratory Instrument Development Co., Ltd.), fluorescence quantitative PCR instrument, electrotransfer instrument, electrophoresis tank, Bio-rad680 microplate reader (Bio-Rad, USA), 4℃, -20℃ refrigerator (Qingdao Haier Co., Ltd.), -80℃ ultra-low temperature freezer (Zhongke Meiling Cryogenic Technology Co., Ltd.), TS-8 horizontal shaker (Jiangsu Haimen Qilin Bell Instrument Manufacturing Co., Ltd.), developer (Azure, USA), slicer (Leica, Germany), TB-718E embedding machine (Hubei Taiwei Technology Industry Co., Ltd.), blood glucose meter and test strips (Roche integrated blood glucose meter, Germany).

[0051] 2. Methods

[0052] 2.1 Drug preparation

[0053] The Chinese medicine composition of the present invention comprises the following medicinal materials: 30g of Perilla frutescens, 30g of Psoralea corylifolia, 30g of Morus alba, 20g of Poria cocos, 15g of Cinnamomum cassia, 15g of Atractylodes macrocephala, 15g of Atractylodes lancea, 10g of Tangerine peel, 10g of Bombyx batryticatus and 6g of Licorice root, the medicinal materials are soaked in 5 times the mass of pure water for 2 hours, boiled with high fire (150-220 DEG C) and then decocted with low fire (80-120 DEG C) for 30min, and the decoction is collected after filtering; the filter residue is added with 2 times the mass of pure water and decocted for 20min, and the decoction is filtered to obtain the decoction; all the decoctions are mixed and concentrated to a Chinese medicine concentration of 2.5g / ml to obtain the Chinese medicine composition of the present invention.

[0054] Rosiglitazone, specification 4mg / tablet. The above medicinal materials are purchased and prepared by the pharmacy of the Second Affiliated Hospital of Guizhou University of Chinese Medicine.

[0055] 2.2 Grouping and drug administration of experimental animals

[0056] 40 SPF male 6-week-old spontaneous type 2 diabetes db / db mice and 10 male normal db / m mice of the same age, weighing 28-35g, were randomly divided into 4 groups after adaptive feeding for 1 week, including model group (MOD), low-dose group of the Chinese medicine composition of the present invention (TDQL), high-dose group of the Chinese medicine composition of the present invention (TDQH) and rosiglitazone group (ROS), with 10 mice in each group, and normal db / m mice were set as blank control group (CON). The mice were intragastrically administered daily for 8 consecutive weeks, wherein MOD and CON were intragastrically administered with distilled water, and the dosage was 5ml / kg / d; the dosage of TDQL was 10.15g / kg.d, the dosage of TDQH was 20.30g / kg.d, and the dosage of ROS was 4mg / kg.d.

[0057] 2.3 Index detection

[0058] 2.3.1AUC

[0059] Mice were gavaged until the end of the 8th week. All mice were fasted for 12 hours but not water. Blood was collected from the tail tip of the next morning to test the fasting blood glucose of each mouse, and the blood glucose value was recorded as 0min blood glucose value. After recording, 2g / kg / 10ml 50% glucose was gavaged, and blood glucose was measured at the tail tip 30min, 60min and 120min after gavage. The blood glucose level curve of each group of mice at each time point was drawn, and the AUC was calculated.

[0060] 2.3.2 HOMA-IR and QUICKI

[0061] HOMA-IR=FBG×FINS / 22.5; QUICKI=1 / (LogFBG+LogFINS) (fasting blood glucose (FBG), fasting insulin (FINS).

[0062] 3. Results

[0063] 3.1 Area under the oral glucose tolerance curve (AUC)

[0064] Compared with the model group, the AUC of mice in the low-dose and high-dose groups of the Chinese medicine composition of the present invention and the rosiglitazone group was significantly reduced (P<0.05); compared with the rosiglitazone group, there was no significant difference in the area under the curve between the low-dose and high-dose groups of the Chinese medicine composition of the present invention (P>0.05); there was no significant difference between the low-dose and high-dose groups of the Chinese medicine composition of the present invention (P>0.05). The results are shown in Table 3:

[0065] Table 3 Comparison of the area under the curve of oral glucose tolerance test in each group of mice

[0066]

[0067] Note: Compared with the MOD group, * P<0.05.

[0068] 3.2HOME-IR, QUICKI level

[0069] Compared with the model group, the FINS and HOME-IR levels of mice in the low-dose and high-dose groups of the Chinese medicine composition of the present invention and the rosiglitazone group were significantly reduced (P<0.05), and QUICKI was increased (P<0.05); compared with the rosiglitazone group, the FINS and HOMA-IR of the low-dose group of the Chinese medicine composition of the present invention were increased (P<0.05), and QUICKI was decreased (P<0.05), and there was no significant difference in FINS, HOMA-IR, and QUICKI in the high-dose group of the Chinese medicine composition of the present invention (P>0.05); compared with the low-dose group, the FINS and HOMA-IR of the high-dose group of the Chinese medicine composition of the present invention were decreased (P<0.05), and QUICKI was increased (P<0.05). The results are shown in Table 4:

[0070] Table 4 Comparison of FINS, HOMA-IR and QUICKI in each group of db / db mice

[0071]

[0072] Note: Compared with MOD, * P<0.05; compared with ROS, # P<0.005; compared with TDQL △ P<0.05. Experiments have shown that the drug of the present invention can significantly improve the insulin resistance level of experimental rats.

Claims

1. A turbidity-clearing and detoxifying Chinese medicine composition for improving insulin resistance, characterized in that: The invention is prepared from the following raw materials in parts by weight: 20-40 parts of perilla, 20-40 parts of euphorbia obesa, 20-40 parts of mulberry branches, 10-30 parts of tuckahoe, 10-20 parts of cassia twigs, 10-20 parts of atractylodes macrocephala, 10-20 parts of atractylodes lancea, 8-12 parts of tangerine peel, 8-12 parts of bombyx batryticatus and 5-7 parts of liquorice.

2. The turbidity-clearing and detoxifying Chinese medicine composition for improving insulin resistance according to claim 1, characterized in that: The weight of the raw materials is: 30g of Perilla frutescens, 30g of Phellodendron chinense, 30g of Morus alba, 20g of Poria cocos, 15g of Cassia twig, 15g of Atractylodes macrocephala, 15g of Atractylodes lancea, 10g of Tangerine peel, 10g of Bombyx batryticatus, and 6g 3. The method for preparing the turbidity-clearing and detoxifying Chinese medicine composition for improving insulin resistance according to claim 1 or 2, characterized in that: Weigh the medicinal materials of Perilla frutescens, Radix Phellodendri, Morus alba, Poria cocos, Cassia twig, Atractylodes macrocephala, Atractylodes lancea, Tangerine peel, Bombyx batryticatus and Licorice, soak the above medicinal materials in 5 times the weight of pure water for 2 hours, boil them with high heat at 150-220° C. and then decocted with low heat at 80-120° C. for 30 minutes, collect the decoction after filtering; add 2 times the weight of pure water to the filter residue and decoct for 20 minutes, collect the decoction after filtering; mix the two decoctions and concentrate them to a Chinese medicine concentration of 2.5 g / ml to obtain the Chinese medicine composition of the present invention.

4. The turbidity-clearing and detoxifying Chinese medicine composition for improving insulin resistance according to claim 1, characterized in that: The pharmaceutical preparation is made from the following raw materials in parts by weight: 20-40 parts of Perilla frutescens, 20-40 parts of Psoralea corylifolia, 20-40 parts of Morus alba, 10-30 parts of Poria cocos, 10-20 parts of Cassia twig, 10-20 parts of Atractylodes macrocephala, 10-20 parts of Atractylodes lancea, 8-12 parts of Citrus reticulatae, 8-12 parts of Bombyx batryticatus, 5-7 parts of Licorice, and pharmaceutically acceptable excipients.

5. The turbidity-clearing and detoxifying Chinese medicine composition for improving insulin resistance according to claim 4, characterized in that: The pharmaceutical preparations include injections, oral liquids, pills, powders, pastes, tablets, granules, powders or capsules.

Images