A traditional Chinese medicine composition containing cicerbitia extract and kalimeris indica extract, application and medicine thereof

Abstract

The application belongs to the technical field of natural product application, and particularly relates to a traditional Chinese medicine composition containing Cirsium japonicum extract and Trichosanthes kirilowii extract and application and medicine thereof. The traditional Chinese medicine composition comprises Cirsium japonicum extract and Trichosanthes kirilowii extract in a mass ratio of (1-31):(1-19). The traditional Chinese medicine composition is obtained by extracting and processing Cirsium japonicum and Trichosanthes kirilowii, and the optimal compounding ratio is obtained by optimizing the dosages of Cirsium japonicum extract and Trichosanthes kirilowii extract. The traditional Chinese medicine composition has a significantly stronger inhibitory effect on lipase than single extract, has high safety, does not cause gastrointestinal adverse reactions such as diarrhea, can be used for a long time, has high patient compliance, can replace orlistat as a new type of high-efficiency lipase inhibitor, and is suitable for obese patients who need to reduce weight.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of natural product application, and particularly relates to a traditional Chinese medicine composition containing Cirsium japonicum extract and Trichosanthes rosthornii extract and application and medicine thereof. BACKGROUND

[0002] Long-term excessive obesity can cause a series of complications, such as type 2 diabetes, hypertension, osteoarthritis, non-alcoholic fatty liver disease, gout, obstructive sleep apnea, and the like, and the prevalence and mortality of obese people suffering from cardiovascular diseases are also much higher than those of normal people.

[0003] The FDA-approved drugs for treating obesity mainly include naltrexone, lorcaserin, phentermine, orlistat and liraglutide. However, at present, the drug approved by the State Drug Administration of China is only orlistat. Orlistat is a selective, long-acting and reversible lipase inhibitor, which can inhibit the lipase activity of pancreas and gastrointestinal tract, reduce the absorption of dietary fat by intestinal mucosa, and can promote 30%-35% of the intake of fat to be discharged from the body. Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist, which can inhibit appetite, increase satiety and delay gastric emptying by acting on the GLP-1 receptor in multiple central nervous system regions such as brainstem and hypothalamus. In China, liraglutide can be used for patients with BMI>25kg / m 2 with at least one obesity complication, or patients with simple obesity with BMI>30kg / m 2 , and can be used beyond the instructions.

[0004] The safety of weight loss drugs is the main reason for limiting their wide application. For example, sibutramine approved by FDA has the risk of increasing cardiovascular diseases, and rimonabant has strong nervous system side effects, such as seizures, depression, anxiety and suicidal tendency, and finally is declared to be withdrawn from the market. Orlistat, which is currently used the most, also has many side effects, and its main adverse reactions are gastrointestinal discomfort, increased gastrointestinal gas, oily spots, fatty stools, diarrhea and the like, and can cause severe rhabdomyolysis and liver damage. In the face of the increasing number of overweight and obese patients, the drugs that can be applied to obesity are very limited, and the demand for drug use is obviously not met, so it is an urgent problem to develop weight loss drugs that are safer and more effective and have fewer side effects.

[0005] Cirsium japonicum is the dry whole plant of Cirsium japonicum DC. of the family Compositae, with sweet taste and cool nature. It is mainly distributed in Inner Mongolia, Jilin, Liaoning, Heilongjiang, Shanxi, Ningxia and Xinjiang. Cirsium japonicum is a characteristic Mongolian medicine listed in the Standards of Ministry of Public Health of the People's Republic of China (Mongolian Medicine Volume), and is used for treating lung abscess, phthisis, sputum and saliva dysfunction, cough, skin disease, liver heat and sore, etc. Malotus repandus is a plant of the genus Malotus in the family Araliaceae, and its root, root bark, stem bark, branch and leaf are used as medicine. Malotus repandus is often used in modern ethnic medicine for treating chronic nephritis, prostatitis, edema and rheumatic arthralgia, etc. and good effects have been achieved. At present, the modern Chinese medicine research on Cirsium japonicum and Malotus repandus is still in the initial stage, and no report has been made on the lipase inhibitory activity of Cirsium japonicum and Malotus repandus. SUMMARY

[0006] In order to solve the problems in the prior art, the present application provides a traditional Chinese medicine composition containing Cirsium japonicum extract and Malotus repandus extract, and application and medicine thereof. The traditional Chinese medicine composition provided by the present application is a safe and efficient lipase inhibitor with low toxic and side effects, which can be used for reducing the weight of obese patients, avoiding gastrointestinal side effects on human body, and allowing long-term use by obese patients.

[0007] The technical scheme provided by the present application is as follows:

[0008] The present application provides a traditional Chinese medicine composition containing Cirsium japonicum extract.

[0009] The traditional Chinese medicine composition containing Cirsium japonicum extract provided by the above technical scheme can be used as a safe and efficient lipase inhibitor to inhibit the absorption of fat in the intestinal tract and reduce the weight of obese patients.

[0010] The present application provides a traditional Chinese medicine composition containing Malotus repandus extract.

[0011] The traditional Chinese medicine composition containing Malotus repandus extract provided by the above technical scheme can be used as a safe and efficient lipase inhibitor to inhibit the absorption of fat in the intestinal tract and reduce the weight of obese patients.

[0012] The present application provides a traditional Chinese medicine composition containing Cirsium japonicum extract and Malotus repandus extract, and the mass ratio of the Cirsium japonicum extract and the Malotus repandus extract is (1-31):(1-19).

[0013] The traditional Chinese medicine composition containing Cirsium japonicum extract and Malotus repandus extract provided by the above technical scheme can be used as a safe and efficient lipase inhibitor to inhibit the activity of enzyme by combining with pancreatic lipase, thereby inhibiting the absorption of fat in the intestinal tract and reducing the weight of obese patients.

[0014] On the basis of the above technical scheme, the present application can be further improved as follows.

[0015] Preferably, the mass ratio of the Cirsium japonicum extract and the Trichosanthes kirilowii extract is 18:7.

[0016] The beneficial effect of the above further scheme is that the Cirsium japonicum extract and the Trichosanthes kirilowii extract in the combination of the traditional Chinese medicine composition have the strongest synergistic effect, and the inhibitory effect on the lipase activity is significantly stronger than that of the single extract.

[0017] Specifically, the Cirsium japonicum extract is prepared by the following steps:

[0018] 1) Cirsium japonicum whole plant is decocted with water, and then filtered to obtain a Cirsium japonicum water extract;

[0019] 2) The Cirsium japonicum water extract is decolorized, filtered, and vacuum dried to obtain the Cirsium japonicum extract.

[0020] The beneficial effect of the above further scheme is that the extract obtained by the above method has a higher content of effective components and the best inhibitory effect on the lipase activity after repeated tests.

[0021] Preferably, the decoction process parameters include that the mass ratio of the Cirsium japonicum whole plant and water is 1:(8-12), and the decoction time is 80-100 min.

[0022] Preferably, the decolorization method of the Cirsium japonicum water extract is that the Cirsium japonicum water extract and the pretreated decolorization resin are mixed according to a mass ratio of 1:(0.7-1.0), and then decolorized at 40-45℃ for 6-10 h.

[0023] Preferably, the vacuum drying process parameters of the Cirsium japonicum water extract include that the gas flow rate is 1400-1600 mL / h, the feeding speed is 20-30 mL / min, the drying temperature is 37-42℃, and the water content of the Cirsium japonicum extract after drying is 0.14%-0.18%.

[0024] Preferably, the decolorization resin can be D392 macroporous resin, D301 weakly basic anion exchange resin, D900 weakly basic anion exchange resin, HPD-907A macroporous adsorption resin, ADS-5 macroporous adsorption resin, etc.

[0025] The beneficial effect of the above further scheme is that the extract obtained under the above parameters has a higher content of effective components and the best inhibitory effect on the lipase activity.

[0026] Specifically, the Trichosanthes kirilowii extract is prepared by the following steps:

[0027] 1) Trichosanthes kirilowii rhizomes are heated and refluxed with an ethanol solution for extraction to obtain a Trichosanthes kirilowii crude extract;

[0028] 2) vacuum concentration, decolorization, vacuum distillation and drying of the crude extract of Trichosanthes kirilowii Maxim to obtain Trichosanthes kirilowii Maxim extract.

[0029] The beneficial effect of the above further scheme is that the effective component content of the extract obtained under the above parameters is higher, and the inhibitory effect on lipase activity is the best.

[0030] Preferably, the process parameters of the heating reflux extraction include that the volume concentration of the ethanol solution is 85-95 v / v %, the mass ratio of the Trichosanthes kirilowii Maxim rhizome to the ethanol solution is 1:(7-10), the extraction temperature is 75-80 ℃, the extraction times are 3-6 times, and the extraction time of each time is 50-70 min.

[0031] Preferably, the product mass obtained by the vacuum concentration is 18-22 % of the mass before the concentration.

[0032] Preferably, the decolorization is that the Trichosanthes kirilowii Maxim concentrated solution after the vacuum concentration and the pretreated decolorization resin are mixed according to the mass ratio of 1:(0.6-0.8), and then decolorized at 45-55 ℃ for 5-8 h.

[0033] Preferably, the process parameters of the vacuum distillation include that the rotation speed condition is 120-160 r / min, and the distillation temperature is 25-30 ℃.

[0034] Preferably, the process parameters of the drying include that the drying temperature is 55-65 ℃, and the water content of the Trichosanthes kirilowii Maxim extract after the drying is 0.14 %-0.18 %.

[0035] Preferably, the decolorization resin can be D392 macroporous resin, D301 weakly basic anion exchange resin, D900 weakly basic anion exchange resin, HPD-907A macroporous adsorption resin, ADS-5 macroporous adsorption resin, etc.

[0036] The beneficial effect of the above further scheme is that the effective component content of the extract obtained under the above parameters is higher, and the inhibitory effect on lipase activity is the best. The product obtained after the vacuum concentration is not completely dried, which is convenient for the subsequent decolorization process.

[0037] On the other hand, the present application provides an application of a traditional Chinese medicine composition containing Trichosanthes kirilowii Maxim extract and Trichosanthes kirilowii Maxim extract in preparing a medicine for reducing the body weight of obese patients, an application of a traditional Chinese medicine composition containing Trichosanthes kirilowii Maxim extract in preparing a medicine for reducing the body weight of obese patients, and an application of a traditional Chinese medicine composition of Trichosanthes kirilowii Maxim extract in preparing a medicine for reducing the body weight of obese patients.

[0038] Specifically, the rat dosage of the traditional Chinese medicine composition is 0-3.0 g / kg·bw (not including zero), and preferably 1.5-3.0 g / kg·bw.

[0039] In another aspect, the present application provides a medicine for reducing the weight of an obese patient, wherein the medicine further comprises a combination of one or more of pharmaceutically acceptable fillers, binders, disintegrants, lubricants, and surfactants.

[0040] Specifically, the medicine is any one of a compound tablet, a compound capsule, or a compound powder.

[0041] Preferably, the tablet of the traditional Chinese medicine composition is composed of the following components by mass: Cirsium japonicum extract 20-40 g, Mallotus repandus extract 10-20 g, microcrystalline cellulose 5 g, magnesium stearate 2 g, cross-linked polyvinylpyrrolidone 1.5 g, carboxymethyl cellulose 1.5 g, and starch 10 g, and the tablet size is 0.5-1 g / tablet.

[0042] Preferably, the capsule of the traditional Chinese medicine composition is composed of the following components by mass: Cirsium japonicum extract 30-55 g, Mallotus repandus extract 20-40 g, starch paste 5 g, sodium carboxymethyl starch 3 g, micronized silica gel 3 g, polyvinyl alcohol 4 g, and starch 25 g, and the filling amount is 0.5-1 g / capsule.

[0043] Preferably, the powder of the traditional Chinese medicine composition is composed of the following components by mass: Cirsium japonicum extract 10-30 g, Mallotus repandus extract 8-15 g, polyethylene glycol 6000 2 g, micronized silica gel 1.5 g, talc 3 g, hydroxypropyl methyl cellulose 3 g, and starch 14 g, and the powder specification is 2-4 g / pack.

[0044] The present application has the following beneficial effects:

[0045] The traditional Chinese medicine composition of the present application is obtained by extraction and processing from Cirsium japonicum and Mallotus repandus, and the optimal compound ratio is obtained by optimizing the use amount of Cirsium japonicum extract and Mallotus repandus extract. The traditional Chinese medicine composition of the present application has a significantly stronger inhibitory effect on lipase than a single extract. Animal acute toxicity tests and animal long-term toxicity tests prove that the traditional Chinese medicine extract composition of the present application has high safety, can be used for a long time, and does not cause gastrointestinal adverse reactions such as diarrhea. Animal fat reduction tests prove that the traditional Chinese medicine composition of the present application has a better fat reduction effect than orlistat at medium and high doses, and can be used as a new type of efficient lipase inhibitor, and is suitable for obese patients who need to reduce weight. DETAILED DESCRIPTION

[0046] The principles and characteristics of the present application are described below, and the examples are used only to explain the present application, and are not used to limit the scope of the present application. If a specific technology or condition is not specified in the examples, the technology or condition is performed according to the technology or condition described in the literature in the art, or according to the product instruction. If the reagent or instrument is not specified by the manufacturer, it is a conventional product that can be commercially available through a regular channel.

[0047] Example 1

[0048] A traditional Chinese medicine composition containing a Cirsium japonicum extract and a Mallotus paniculatus extract and a preparation method thereof, comprising:

[0049] (1) Preparation of the Cirsium japonicum extract:

[0050] 2 kg of Cirsium japonicum whole plant was purchased and washed with water, then crushed in a crusher. The crushed Cirsium japonicum rhizome and water were decocted at a mass ratio of 1:10 for 90 min, then filtered with a vacuum filter to obtain a Cirsium japonicum water extract;

[0051] The D392 macroporous resin was soaked in deionized water to remove residual dirt, then soaked in an ethanol solution with a volume concentration of 75% for 10 h, washed with deionized water until no white turbidity was observed to remove trace amounts of ethanol-soluble substances, then transferred to a 7% NaOH solution to stand for 12 h to remove the pore-forming agent remaining in the pores of the macroporous resin. Finally, the D392 macroporous resin was washed to neutral and dried at room temperature to obtain the pretreated macroporous resin;

[0052] The Cirsium japonicum water extract and the pretreated macroporous resin were mixed at a mass ratio of 1:0.9, then placed in a shaking bed under the conditions of a temperature of 42°C and a rotation speed of 170 r / min for 8 h of decolorization. After decolorization, the D392 macroporous resin was removed by filtration to obtain a decolorized Cirsium japonicum water extract;

[0053] The decolorized Cirsium japonicum water extract was cooled to room temperature, then filtered and the precipitate was discarded. The filtered Cirsium japonicum water extract was vacuum concentrated and dried with a vacuum spray dryer to a water content of 0.16%, with a gas flow rate of 1500 mL / h, a feeding speed of 25 mL / min, and a drying temperature of 40°C to obtain the Cirsium japonicum extract.

[0054] (2) Preparation of the Mallotus paniculatus extract:

[0055] 2 kg of Mallotus paniculatus rhizome was purchased and washed with water multiple times, then placed in a vacuum condensation tank after being soaked in 90% (v / v) ethanol at a mass ratio of 1:9. The mixture was heated and refluxed for 4 times at a temperature of 78°C, with each refluxing time being 60 min. The precipitate was filtered out with a vacuum filter to obtain a Mallotus paniculatus crude extract;

[0056] The Mallotus paniculatus crude extract was transferred to a vacuum condensation tank and cooled at room temperature. Under the conditions of a vacuum degree of -0.12 MPa and a steam pressure of 0.02 MPa, the Mallotus paniculatus crude extract was vacuum concentrated to 19% of the mass of the Mallotus paniculatus crude extract before concentration to obtain a Mallotus paniculatus concentrated solution;

[0057] The D392 macroporous resin was soaked in deionized water to remove residual dirt, and after washing, it was soaked in an ethanol solution with a volume concentration of 75% for 10 h, and then washed with deionized water until no white turbidity was observed to remove trace amounts of ethanol-soluble substances. Then, the D392 macroporous resin was transferred to a 7% NaOH solution and left to stand for 12 h to remove the pore-forming agent remaining in the pores of the macroporous resin. Finally, the D392 macroporous resin was washed to neutral and dried at room temperature to obtain the pretreated macroporous resin;

[0058] The concentrated Acanthopanax giraldii Harms solution and the pretreated macroporous resin were mixed at a mass ratio of 1:0.7, and then placed in a shaking table with a temperature of 50°C and a rotation speed of 170 r / min for 6 h. After decolorization, the D392 macroporous resin was removed by centrifugation to obtain the decolorized Acanthopanax giraldii Harms concentrated solution.

[0059] The decolorized Acanthopanax giraldii Harms concentrated solution was placed in a rotary evaporator and distilled under reduced pressure, with a rotation speed of 150 r / min, a temperature of 28°C, and a vacuum degree of -0.09 MPa. Subsequently, it was dried at 60°C until the moisture content was 0.15% to obtain the Acanthopanax giraldii Harms extract.

[0060] (3) Preparation of a traditional Chinese medicine composition containing a Cirsium japonicum extract and an Acanthopanax giraldii Harms extract:

[0061] The Cirsium japonicum extract and the Acanthopanax giraldii Harms extract prepared in steps (1) and (2) were mixed at a mass ratio of 17:3 to obtain a traditional Chinese medicine extract composition.

[0062] Example 2

[0063] The Cirsium japonicum extract and the Acanthopanax giraldii Harms extract prepared in Example 1 were mixed at a mass ratio of 13:7 to obtain a traditional Chinese medicine extract composition.

[0064] Example 3

[0065] The Cirsium japonicum extract and the Acanthopanax giraldii Harms extract prepared in Example 1 were mixed at a mass ratio of 1:1 to obtain a traditional Chinese medicine extract composition.

[0066] Example 4

[0067] The Cirsium japonicum extract and the Acanthopanax giraldii Harms extract prepared in Example 1 were mixed at a mass ratio of 7:13 to obtain a traditional Chinese medicine extract composition.

[0068] Example 5

[0069] The Cirsium japonicum extract and the Acanthopanax giraldii Harms extract prepared in Example 1 were mixed at a mass ratio of 3:17 to obtain a traditional Chinese medicine extract composition.

[0070] Example 6

[0071] The Sempervivum tectorum extract and the Mallotus repandulatus extract prepared in Example 1 were mixed uniformly at a mass ratio of 4:1 to obtain a traditional Chinese medicine extract composition.

[0072] Example 7

[0073] The Sempervivum tectorum extract and the Mallotus repandulatus extract prepared in Example 1 were mixed uniformly at a mass ratio of 19:6 to obtain a traditional Chinese medicine extract composition.

[0074] Example 8

[0075] The Sempervivum tectorum extract and the Mallotus repandulatus extract prepared in Example 1 were mixed uniformly at a mass ratio of 18:7 to obtain a traditional Chinese medicine extract composition.

[0076] Example 9

[0077] The Sempervivum tectorum extract and the Mallotus repandulatus extract prepared in Example 1 were mixed uniformly at a mass ratio of 17:8 to obtain a traditional Chinese medicine extract composition.

[0078] Example 10

[0079] The Sempervivum tectorum extract and the Mallotus repandulatus extract prepared in Example 1 were mixed uniformly at a mass ratio of 31:19 to obtain a traditional Chinese medicine extract composition.

[0080] Example 11

[0081] The Sempervivum tectorum extract and the Mallotus repandulatus extract prepared in Example 1 were mixed uniformly at a mass ratio of 11:9 to obtain a traditional Chinese medicine extract composition.

[0082] Experiment 1

[0083] Lipase inhibitory activity detection of Sempervivum tectorum extract, Mallotus repandulatus extract and traditional Chinese medicine extract compositions with different proportions:

[0084] The detection method and specific steps are as follows:

[0085] (1) Preparation of Tris-HCl buffer solution: 1.8 g of Tris, 0.439 g of NaCl and 0.333 g of CaCl2 were weighed into ultrapure water, and the volume was made up to 300 mL. Hydrochloric acid was added to adjust the pH value to 8.0 to obtain a 50 mmol / L Tris-HCl buffer solution;

[0086] (2) Preparation of lipase solution: 0.5 g of pancrelipase freeze-dried powder was dissolved in 50 mL of Tris-HCl buffer solution, centrifuged at 12000 r / min for 5 min, and the supernatant was transferred to a new 50 mL centrifuge tube to obtain a 10 mg / mL pancrelipase solution;

[0087] (3) Preparation of p-nitrophenyl palmitate (p-NPP) solution: 15.1 mg of p-NPP was accurately weighed, 250 μL of Triton X-100 solution, 5 mL of isopropyl alcohol and an appropriate amount of Tris-HCl buffer solution were added, respectively, after fully mixed and dissolved, the Tris-HCl buffer solution was used to make up to 50 mL, and 0.8 mmol / L of p-NPP solution was obtained.

[0088] (4) Preparation of extract solution and traditional Chinese medicine composition solution: 9 portions of each of the Cirsium japonicum extract, Mallotus repandus extract and traditional Chinese medicine composition in Example 1 were taken, respectively, and each of the extracts or traditional Chinese medicine compositions was prepared into 0.05 mg / mL, 0.1 mg / mL, 0.2 mg / mL, 0.5 mg / mL, 1 mg / mL, 2 mg / mL, 5 mg / mL, 10 mg / mL and 20 mg / mL drug solutions by adding water, respectively, and was ready for use.

[0089] (5) Preparation of orlistat solution: 9 portions of orlistat powder were taken, respectively, and 0.05 mg / mL, 0.1 mg / mL, 0.2 mg / mL, 0.5 mg / mL, 1 mg / mL, 2 mg / mL, 5 mg / mL, 10 mg / mL and 20 mg / mL orlistat solutions were prepared by adding DMSO, respectively, and were ready for use.

[0090] (6) Lipase activity determination: the test group was mixed according to the reaction system by adding Tris-HCl buffer, different concentrations of drug solution and pancreatic lipase solution into the 96-well plate, and was incubated at 37℃ for 10 min, then 80 μL of p-NPP solution was added, and was incubated at 37℃ for another 30 min; the blank group was mixed according to the reaction system by adding Tris-HCl buffer and different concentrations of drug solution, and the negative control blank group used Tris-HCl buffer instead of the same volume of drug solution, and the determination method was the same, each test was repeated for 3 times. The total reaction system is shown in Table 1:

[0091] Table 1 Lipase activity detection reaction system

[0092]

[0093] The absorbance value was determined at 405 nm wavelength by using an enzyme marker, and the lipase activity inhibition rate was calculated.

[0094] Lipase activity inhibition rate (%) = [1-(Ac-A d ) / (A a -A b )]x100%, wherein A a is the absorbance value of the negative control test group; A bAbsorbance of negative control blank group; Ac is absorbance of sample test group / orlistat group; A d Absorbance of sample blank group.

[0095] (7) Lipase inhibition activity detection results:

[0096] The inhibition of lipase activity of C. rotundus extract, T. wilfordii extract, and the compositions of different ratios in Examples 1-5 and orlistat was determined according to the above method, and the determination results were calculated by GraphPad Prism 8 statistical analysis software to obtain the half maximal inhibitory concentration IC 50 value. The lower the IC 50 value, the stronger the inhibition of the drug on lipase, and the higher the IC 50 value, the weaker the inhibition of the drug on lipase. The detection results are shown in Table 2:

[0097] Table 2 Half maximal inhibitory concentration (IC 50 ) of C. rotundus extract, T. wilfordii extract, and the composition of different ratios of traditional Chinese medicine extracts and orlistat on lipase activity

[0098]

[0099] According to the experimental results in Table 2, C. rotundus extract and T. wilfordii extract have strong inhibitory effect on pancreatic lipase activity, and the combination of the two can produce synergistic lipase inhibition. In the traditional Chinese medicine composition in Example 2, when the mass ratio of C. rotundus extract and T. wilfordii extract is 13:7, the traditional Chinese medicine composition has the strongest inhibitory effect on lipase activity, and the inhibitory effect is significantly stronger than that of single extract.

[0100] According to the above experimental results, the mass ratio of C. rotundus extract and T. wilfordii extract that produces better synergistic effect is determined. In order to determine the mass ratio of the extracts that can produce the best synergistic effect, the inhibition of lipase activity of the traditional Chinese medicine compositions in Examples 6-11 and orlistat was also determined according to the above method, and the determination results were calculated to represent the half maximal inhibitory concentration IC 50 . The results are shown in Table 3: Table 3 Half maximal inhibitory concentration (IC 50 ) of the traditional Chinese medicine extract composition with optimized ratio and orlistat on lipase activity

[0101]

[0102]

[0103] According to the experimental results in Table 3, the mass ratio of the Cirsium japonicum extract and the Mallotus philippinensis extract in the traditional Chinese medicine composition in Example 8 is 18:7, and the traditional Chinese medicine composition has the strongest inhibitory effect on the activity of lipase, and the inhibitory effect is significantly stronger than that of the single extract and the traditional Chinese medicine composition in other examples.

[0104] Experiment 2

[0105] Animal acute toxicity experiment and animal long-term toxicity experiment of the optimal ratio of traditional Chinese medicine extract composition:

[0106] The specific steps of the acute toxicity experiment are as follows:

[0107] (1) Sample: The sample selected in this experiment is the traditional Chinese medicine extract composition in Example 8, which is used at room temperature.

[0108] (2) Test animals: 20 healthy adult SPF level SD rats, half male and half female, with a body weight of 180-200g, purchased from Guangdong Medical Laboratory Animal Center.

[0109] (3) Test method: The traditional Chinese medicine extract composition in Example 8 is dissolved in ultrapure water, and the intragastric dose is 20g / kg·bw, which is given twice with an interval of 4 hours. After administration, normal diet is given, and the rats are observed for 14 days, and the poisoning performance and death of the rats are recorded. The body weight is measured once on the 0th day, the 7th day and the 14th day. After the observation period, the organs of the rats are pathologically examined.

[0110] (4) Test results: As shown in Table 4, none of the 20 SD rats died, and no organ lesions were found.

[0111] Table 4 Effect of the traditional Chinese medicine extract composition in Example 8 on the acute toxicity of rats

[0112]

[0113]

[0114] The specific steps of the long-term toxicity experiment are as follows:

[0115] (1) Sample: The sample selected in this experiment is the extract composition in Example 8, which is used at room temperature.

[0116] (2) Test animals: 60 SPF level healthy weaned SD rats, half male and half female, with a body weight of 80-100g, purchased from Guangdong Medical Laboratory Animal Center.

[0117] (3) Test method: 60 rats were randomly divided into 3 groups, namely blank control group, low-dose treatment group and high-dose treatment group, 20 rats in each group, half male and half female, and the rats were given drugs by gavage. The traditional Chinese medicine extract composition in Example 8 was dissolved in ultrapure water, and the rats in the low-dose treatment group and the high-dose treatment group were given the traditional Chinese medicine extract composition solution, the gavage dose of the low-dose treatment group was 1.5 g / kg·bw, and the gavage dose of the high-dose treatment group was 3 g / kg·bw, and the rats in the blank control group were given the same volume of purified water. Gavage twice a day, and weigh twice a week. After 28 days of continuous gavage, weigh each rat, record the poisoning performance and death of the rats, and perform hematology index examination and organ pathological examination on the rats.

[0118] (4) Test results:

[0119] Table 5 Effect of traditional Chinese medicine extract composition in Example 8 on long-term toxicity of rats

[0120]

[0121] Table 6 Effect of traditional Chinese medicine extract composition in Example 8 on hematology indexes of rats

[0122]

[0123] Table 7 Effect of traditional Chinese medicine extract composition in Example 8 on organ pathology indexes of rats

[0124]

[0125]

[0126] As shown in Table 5, no obvious abnormalities, no poisoning performance and no death were observed in the animals of each group. Compared with the blank control group, the body weight of the rats in the low-dose treatment group and the high-dose treatment group decreased, indicating that the traditional Chinese medicine extract composition of Example 8 of the present application can inhibit the activity of gastrointestinal lipase of rats, reduce the absorption of intestinal fat, and thus reduce the body weight of rats. As shown in Tables 6 and 7, the hematology indexes of rats in the blank control group, the low-dose treatment group and the high-dose treatment group were within the normal range, and the organs of rats in each group had no pathological changes, indicating that the traditional Chinese medicine extract composition of Example 8 of the present application had almost no toxic and side effects on rats, had high safety, and could be used for a long time.

[0127] Experiment 3

[0128] Animal fat-reducing function test of the optimal proportion traditional Chinese medicine extract composition:

[0129] (1) Sample: The sample selected in this test is the traditional Chinese medicine extract composition in Example 8, which is used at room temperature.

[0130] (2) Test animals: 70 healthy male SPF-grade SD rats were purchased from Guangdong Provincial Medical Experimental Animal Center.

[0131] (3) Establishing a rat obesity model:

[0132] Seventy rats were randomly divided into two groups according to their body weight. Ten rats were given a standard maintenance diet as a blank control group, while 60 rats were given a high-calorie model diet. After two weeks of feeding, the 60 rats given the high-calorie diet were ranked according to their weight gain, and the 10 obese resistant rats with the lowest weight gain were eliminated. The 50 obese sensitive rats selected were then given a high-calorie diet for another 6 weeks, while the blank control group was given a maintenance diet at the same time.

[0133] (4) Test methods:

[0134] After the modeling period, 50 obese-sensitive rats were randomly divided into 5 groups based on their body weight: a model control group, a positive control group, and low-, medium-, and high-dose treatment groups, with 10 rats in each group. Administering the medication was done via gavage. The herbal extract composition from Example 8 was dissolved in ultrapure water. Rats in the low-, medium-, and high-dose treatment groups were given the herbal extract composition solution. The gavage dose for the low-dose treatment group was 100 mg / kg body weight (bw), for the medium-dose treatment group it was 200 mg / kg bw, and for the high-dose treatment group it was 400 mg / kg bw. Rats in the positive control group were given orlistat at a gavage dose of 40 mg / kg bw. Rats in the blank control group and the model control group were given an equal volume of purified water. Administration was twice daily for 4 weeks. During this period, the model control group, positive control group, and low-, medium-, and high-dose treatment groups were given a high-calorie model diet, while the blank control group was given a maintenance diet. Feed intake, spilled feed, and uneaten feed were recorded weekly, and body weight was measured once a week.

[0135] After the experiment, the rats were weighed, and the fat around the kidneys and testes was dissected and weighed to calculate the body fat percentage. Body fat percentage (%) = Total weight of kidney and testicular fat (g) / Rat body weight (g) × 100%

[0136] (5) Experimental results:

[0137] Table 8. Effects of the herbal extract composition in Example 8 on body weight and diet in obese rats.

[0138]

[0139] Table 9. Effects of the herbal extract composition in Example 8 on body fat content in obese rats.

[0140]

[0141] As shown in Table 8 and Table 9, after the rats were given the traditional Chinese medicine extract composition in Example 8 of the present application, the body weight, daily food intake, total weight of kidney and testicular fat, and body fat ratio of the rats in the low, medium and high dose treatment groups were significantly reduced, and there was a significant difference (p<0.05) compared with the model control group, indicating that the traditional Chinese medicine extract composition in Example 8 of the present application can inhibit the activity of gastrointestinal lipase in obese rats, reduce fat absorption, and reduce the daily food intake of obese rats to the normal value range, thereby reducing the body weight of obese rats. After the rats were given the traditional Chinese medicine composition at a medium dose and a high dose for 4 weeks, the body weight of the rats was lower than that of the positive control group, indicating that the traditional Chinese medicine extract composition of the present application has a better fat-reducing effect than orlistat when taken at a medium dose and a high dose. The daily food intake and defecation frequency of the rats were stable during the administration period, and there was no diarrhea and adverse reactions in the gastrointestinal tract, indicating that the traditional Chinese medicine extract composition of the present application has no toxic side effects on rats and has high safety.

[0142] Example 12

[0143] Preparation of traditional Chinese medicine composition tablets containing Cirsium japonicum extract and Hippophae rhamnoides extract

[0144] Table 10 Formulation of traditional Chinese medicine composition tablets containing Cirsium japonicum extract and Hippophae rhamnoides extract

[0145]

[0146] According to the formulation amount, 20-40 g of Cirsium japonicum extract and 10-20 g of Hippophae rhamnoides extract were weighed, and 5 g of microcrystalline cellulose, 2 g of magnesium stearate, 1.5 g of cross-linked polyvinylpyrrolidone, 1.5 g of carboxymethyl cellulose, and 10 g of starch were added. The extract and excipients were mixed uniformly using a high-speed mixer, and then one-step tabletting was performed using a tablet press to obtain traditional Chinese medicine composition tablets containing Cirsium japonicum extract and Hippophae rhamnoides extract, with a tablet size of 0.5-1 g / tablet.

[0147] Example 13

[0148] Preparation of traditional Chinese medicine composition capsules containing Cirsium japonicum extract and Hippophae rhamnoides extract

[0149] Table 11 Formulation of traditional Chinese medicine composition capsules containing Cirsium japonicum extract and Hippophae rhamnoides extract

[0150]

[0151]

[0152] The 30-55 g of S. japonica extract and 20-40 g of T. chinensis extract are weighed according to the prescription amount, 5 g of starch paste, 3 g of carboxymethyl starch sodium, 3 g of micro-silica gel, 4 g of polyvinyl alcohol and 25 g of starch are added respectively, the extract and the excipients are mixed uniformly by using a high-speed mixer, and then the Chinese medicinal composition capsules containing S. japonica extract and T. chinensis extract are prepared by using a capsule filling machine, and the filling amount is 0.5-1 g / capsule.

[0153] Example 14

[0154] Preparation of the Chinese medicinal composition powder containing S. japonica extract and T. chinensis extract

[0155] Table 12 Prescription of the Chinese medicinal composition powder containing S. japonica extract and T. chinensis extract

[0156]

[0157] The 10-30 g of S. japonica extract and 8-15 g of T. chinensis extract are weighed according to the prescription amount, 2 g of polyethylene glycol 6000, 1.5 g of micro-silica gel, 3 g of talc, 3 g of hydroxypropyl methyl cellulose and 14 g of starch are added respectively, the extract and the excipients are mixed uniformly by using a high-speed mixer, the material is separated according to the particle size by using a vibrating screen, and then the material is sent into a packaging machine for packaging. The powder specification is 2-4 g / pack.

[0158] The above only describes the preferred embodiments of the present application and is not used to limit the present application, and any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application should be included in the protection scope of the present application.

Claims

1. A traditional Chinese medicine composition for reducing the body weight of an obese patient, characterized in that: consists of a Cirsium maackii extract and a Mallotus repandulatus extract, and a mass ratio of the Cirsium maackii extract to the Mallotus repandulatus extract is 18:7; ​ the Cirsium maackii extract is prepared by the following steps: 1) decocting Cirsium maackii whole plant with water and filtering to obtain a Cirsium maackii water extract; 2) decolorizing, filtering and vacuum drying the Cirsium maackii water extract to obtain the Cirsium maackii extract; the Mallotus repandulatus extract is prepared by the following steps: 1) heating refluxing and extracting Mallotus repandulatus rhizome with an ethanol solution to obtain a Mallotus repandulatus crude extract; 2) vacuum concentrating, decolorizing, vacuum distilling and drying the Mallotus repandulatus crude extract to obtain the Mallotus repandulatus extract.

2. The Chinese medicine composition for reducing the weight of obese patients according to claim 1, characterized in that, in the preparation method of the Cirsium maackii extract: in step 1), the process parameters of decocting include: a mass ratio of Cirsium maackii whole plant to water is 1:8-12, and a decocting time is 80-100 min; and / or in step 2), the decolorizing manner of the Cirsium maackii water extract is that the Cirsium maackii water extract and pretreated decolorizing resin are mixed according to a mass ratio of 1:0.7-1.0, and then decolorized at 40-45 ℃ for 6-10 h; and / or in step 2), the process parameters of vacuum drying of the Cirsium maackii water extract include: a gas flow rate is 1400-1600 mL / h, a feeding speed is 20-30 mL / min, a drying temperature is 37-42 ℃, and a water content of the Cirsium maackii extract after drying is 0.14%-0.18%.

3. The Chinese medicine composition for reducing the weight of obese patients according to claim 1, characterized in that, in the preparation method of the Mallotus repandulatus extract: in step 1), the process parameters of heating refluxing and extracting include: a volume concentration of the ethanol solution is 85-95 v / v%, a mass ratio of the Mallotus repandulatus to the ethanol solution is 1:7-10, an extraction temperature is 75-80 ℃, the extraction is performed for 3-6 times, and an extraction time of each time is 50-70 min; and / or in step 2), a product mass obtained by vacuum concentration is 18-22% of that before concentration; and / or in step 2), the decolorizing is that the Mallotus repandulatus concentrated solution after vacuum concentration and pretreated decolorizing resin are mixed according to a mass ratio of 1:0.6-0.8, and then decolorized at 45-55 ℃ for 5-8 h; and / or in step 2), the process parameters of vacuum distilling include: a rotating speed condition is 120-160 r / min, and a distilling temperature is 25-30 ℃; and / or in step 2), the process parameters of drying include: a drying temperature is 55-65 ℃, and a water content of the Mallotus repandulatus extract after drying is 0.14%-0.18%.

4. The use of the traditional Chinese medicine composition for reducing the weight of obese patients according to any one of claims 1 to 3, characterized in that: a medicine for reducing body weight of an obese patient.

5. A medicament for reducing body weight in obese patients, characterized by, comprises: a traditional Chinese medicine composition of the Cirsium maackii extract and the Mallotus repandulatus extract according to any one of claims 1-3; and a combination of one or more of a pharmaceutically acceptable filler, a binder, a disintegrant, a lubricant or a surface active agent.

6. The drug for alleviating obesity in a patient according to claim 5, wherein: the medicine is any one of a compound tablet, a compound capsule or a compound powder.

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