CN112057523A

CN112057523A - Cistanche granule and preparation method and application thereof

Info

Publication number: CN112057523A
Application number: CN202011069402.9A
Authority: CN
Inventors: 赵萍; 刘冰; 罗玉全; 丁德; 杨倩倩; 芮文静; 皮文洁; 李沛; 张喆; 张仪君; 沙会宁
Original assignee: Lanzhou University of Technology
Current assignee: Lanzhou University of Technology
Priority date: 2020-09-30
Filing date: 2020-09-30
Publication date: 2020-12-11

Abstract

The invention provides cistanche granules and a preparation method and application thereof, belonging to the technical field of traditional Chinese medicine preparations, wherein the cistanche granules comprise the following raw materials in parts by weight: 50-80 parts of cistanche alcohol extract, 15-25 parts of momordica grosvenori, 5-25 parts of medlar water extract, 5-25 parts of hawthorn water extract, 80-200 parts of excipient and 50-100 parts of wetting agent. The preparation method comprises the steps of mixing and concentrating the medlar water extract and the hawthorn water extract to obtain an extract, mixing the extract with a cistanche alcohol extract and momordica grosvenori to obtain a dry extract, crushing the dry extract, mixing the dry extract with an excipient and a wetting agent, and carrying out wet granulation to obtain cistanche particles. The cistanche granule has the characteristics of good granulation performance, wear resistance and attractive appearance. The experimental results show that: the cistanche particles have the effects of reducing blood sugar and blood fat.

Description

Cistanche granule and preparation method and application thereof

Technical Field

The invention belongs to the technical field of traditional Chinese medicine preparations, and particularly relates to cistanche particles as well as a preparation method and application thereof.

Background

With the development of socioeconomic, the lifestyle and diet are changed greatly, so that the diseases caused by the change are remarkably changed, and hyperglycemia and hyperlipidemia are one of the diseases which occur most frequently in modern people. Diabetes is a group of metabolic diseases characterized by hyperglycemia. Hyperglycemia is caused by a defect in insulin secretion or an impaired biological action, or both. Hyperglycemia occurring in the long term of diabetes results in chronic damage to, and dysfunction of, various tissues, particularly the eyes, kidneys, heart, blood vessels, nerves. Hyperlipidemia is strictly defined as metabolic disorder of blood lipid or structural and disorientation disorder of blood lipid, and refers to a chronic disease with high blood lipid level such as phospholipid, cholesterol triglyceride and unesterified fatty acid in blood plasma, which mainly causes many complications such as complications of arteriosclerosis, heart problems, cerebrovascular problems and liver dysfunction. Hyperglycemia and hyperlipidemia have gradually developed important global health problems.

At present, various chemical blood sugar and blood fat reducing medicines exist in the market, but due to obvious toxic and side effects, the long-term administration of the medicines has great harm to human bodies, such as hepatitis, kidney stone, pancreatitis, anorexia, insomnia, diarrhea, flatulence, abdominal distension and the like, and further influences the clinical use. Therefore, the selection of a natural medicine with good effect, safety and no side effect to reduce blood sugar and blood fat is an inevitable direction for market development.

Disclosure of Invention

In view of the above, the invention aims to provide cistanche granules with the effects of reducing blood sugar and blood fat, and the granules have the characteristics of good granulation property, wear resistance and attractive appearance.

In order to achieve the above purpose, the invention provides the following technical scheme:

the invention provides cistanche granules, which comprise the following raw materials in parts by weight: 50-80 parts of cistanche alcohol extract, 15-25 parts of momordica grosvenori, 5-25 parts of medlar water extract, 5-25 parts of hawthorn water extract, 80-200 parts of excipient and 50-100 parts of wetting agent; the cistanche alcohol extract comprises total cistanche glycosides and total cistanche flavones, and the mass ratio of the total cistanche glycosides to the total cistanche flavones is (2-5): (5-8).

Preferably, the excipients include soluble starch and maltodextrin.

Preferably, the weight ratio of the soluble starch to the maltodextrin is (3-5): 1.

Preferably, the wetting agent comprises an ethanol solution with the volume fraction of 70-80%.

Preferably, the extraction method of the total cistanchis glycosides comprises the following steps: pulverizing herba cistanches to obtain pulverized material, and extracting with ethanol solution to obtain herba cistanches total glycosides;

preferably, the extraction time is 0.5-2 h, and the volume ratio of the mass of the crushed material to the volume of the ethanol solution is 1g: 35-45 mL; the volume percentage content of the ethanol solution is 45-55%; the extraction temperature is 65-75 ℃.

Preferably, the extraction method of total flavonoids from cistanche deserticola comprises the following steps: crushing cistanche to obtain crushed substances, and extracting the crushed substances with ethanol solution to obtain total flavonoids of cistanche;

preferably, the extraction time is 1-3 h, and the volume ratio of the mass of the crushed material to the ethanol solution is 1g: 10-20 mL; the volume percentage content of the ethanol solution is 65-75%; the extraction temperature is 75-85 ℃.

Preferably, the extraction method of the medlar water extract comprises the following steps: mixing fructus Lycii with water, and extracting to obtain fructus Lycii water extractive solution; the extraction time is 0.5-2 h, and the mass-to-water volume ratio of the medlar is 1g: 5-18 mL; the extraction temperature is 65-75 ℃;

preferably, the extraction method of the hawthorn water extracting solution comprises the following steps: mixing fructus crataegi with water, and extracting to obtain fructus crataegi water extractive solution; the extraction time is 2-3 h, and the mass-to-water volume ratio of the hawthorn is 1g: 5-25 mL; the extraction temperature is 65-75 ℃;

the invention also provides a preparation method of the cistanche granule in the technical scheme, which comprises the following steps: mixing the fructus Lycii water extractive solution and fructus crataegi water extractive solution, concentrating to obtain extract, mixing the extract with Cistanchis herba alcohol extract and fructus Siraitiae Grosvenorii to obtain dry extract, pulverizing the dry extract, mixing with excipient and wetting agent, and granulating to obtain Cistanchis herba granule.

Preferably, the granulation comprises wet granulation.

The invention also provides application of the cistanche granule in the technical scheme in preparation of hypoglycemic and/or hypolipidemic drugs.

The cistanche alcohol extract in the cistanche granules comprises total cistanche glycosides and total cistanche flavones, wherein the total cistanche glycosides have the functions of tonifying kidney and benefiting marrow, and strengthening brain and improving intelligence, and the total cistanche flavones have the functions of resisting oxidation and enhancing immunity; the fructus momordicae not only can provide effective components and improve the blood sugar and blood fat reducing effects of the cistanche particles, but also has a better taste modifying effect and improves the taste of the cistanche particles; the excipient adopts soluble starch and maltodextrin, so that the obtained cistanche granule has the characteristics of high granule yield and good hygroscopicity; the ethanol solution is used as a wetting agent, so that the cistanche particles are not easy to be adhered and agglomerated in the preparation process; the wet granulation adopted in the preparation process has the characteristics of high granulation property, simple operation, auxiliary material saving and relatively good appearance. The cistanche granules obtained by the preparation method have the characteristics of good granulation property, wear resistance and attractive appearance.

The experimental results show that: the cistanche granule of the invention has IC of alpha-amylase and alpha-glucosidase₅₀The value and the maximum inhibition effect are respectively 11mg/mL and 68.9 percent; 6.2mg/mL, 71.3%; the combining ability of the cholate is ranked as 87.7 percent of the maximum sodium taurocholate, 43.8 percent of the sodium glycocholate and 22.6 percent of the minimum sodium cholate, and the in vitro test of the cistanche granule shows that the developed cistanche granule has certain effects of reducing blood sugar and blood fat.

Drawings

FIG. 1 is a full wavelength scan of the to-be-detected liquid of cistanche salsa;

FIG. 2 shows the inhibition effect of granule solutions of cistanche deserticola with different concentrations on alpha-amylase;

FIG. 3 shows the inhibition effect of granule solutions of cistanche deserticola with different concentrations on alpha-glucosidase;

FIG. 4 is a full wavelength scan of cholate;

FIG. 5 is a standard graph of cholate;

FIG. 6 is a graph of the stability of the cholate assay process;

FIG. 7 is a graph of the adsorption efficiency of cholate;

FIG. 8 is a cholate adsorption energy diagram;

FIG. 9 is a Freundlich fitting graph of isothermal curve of adsorption capacity of Cistanchis herba particles to cholate;

FIG. 10 is a Langmuir fitting graph of isothermal curve of cistanche granule vs. cholate adsorption capacity;

FIG. 11 is a graph showing the effect of cistanche granules on the adsorption of bile acid salts;

FIG. 12 is a graph showing the adsorption effect of simvastatin on cholate.

Detailed Description

The invention provides cistanche granules, which comprise the following raw materials in parts by weight: 50-80 parts of cistanche alcohol extract, 15-25 parts of momordica grosvenori, 5-25 parts of medlar water extract, 5-25 parts of hawthorn water extract, 80-200 parts of excipient and 50-100 parts of wetting agent; preferably, 60-70 parts of cistanche alcohol extract, 18-22 parts of momordica grosvenori, 15-18 parts of medlar water extract, 15-18 parts of hawthorn water extract, 90-180 parts of excipient and 60-90 parts of wetting agent, more preferably 65 parts of cistanche alcohol extract, 20 parts of momordica grosvenori, 15 parts of medlar water extract, 15 parts of hawthorn water extract, 150 parts of excipient and 80 parts of wetting agent; the cistanche alcohol extract comprises total cistanche glycosides and total cistanche flavones, and the mass ratio of the total cistanche glycosides to the total cistanche flavones is (2-5) - (5-8), and preferably 3: 7.

In the present invention, the luo han guo preferably includes luo han guo fine powder, and the preparation method of the luo han guo fine powder preferably includes: the raw material of the momordica grosvenori is crushed and sieved by a 65-mesh sieve to obtain momordica grosvenori fine powder. The fructus momordicae can provide effective components, has a good taste-modifying effect and improves the taste of the cistanche particles.

In the invention, the excipient preferably comprises soluble starch and maltodextrin, and the weight ratio of the soluble starch to the maltodextrin is preferably (3-5): 1, and more preferably 4: 1. The invention selects soluble starch and maltodextrin as excipient, and limits specific proportion, which can ensure the obtained cistanche granule has the characteristics of high yield and good hygroscopicity.

In the invention, the wetting agent preferably comprises an ethanol solution, and the volume fraction of the ethanol solution is preferably 70-80%, and more preferably 75%. The ethanol solution is a semi-polar wetting agent, and is not easy to be adhered and agglomerated in the preparation process of the cistanche particles.

In the present invention, the extraction method of total cistanchis glycosides preferably comprises: pulverizing herba cistanches to obtain pulverized material, and extracting with ethanol solution to obtain herba cistanches total glycosides; the extraction time is preferably 0.5-2 h, more preferably 1h, and the ratio of the mass of the crushed material to the volume of the ethanol solution is preferably 1g: 35-45 mL, more preferably 1g:40 mL; the volume percentage content of the ethanol solution is preferably 45-55%, and more preferably 50%; the extraction temperature is preferably 65-75 ℃, and more preferably 70 ℃.

In the present invention, the extraction method of total flavonoids from cistanche deserticola preferably comprises: crushing cistanche to obtain crushed substances, and extracting the crushed substances with ethanol solution to obtain total flavonoids of cistanche; preferably, the extraction time is 1-3 h, more preferably 2h, and the ratio of the mass of the crushed material to the volume of the ethanol solution is 1g: 10-20 mL, more preferably 1g:15 mL; the volume percentage content of the ethanol solution is preferably 65-75%, and more preferably 70%; the extraction temperature is preferably 75-85 ℃, and more preferably 80 ℃.

In the present invention, the method for extracting the aqueous extract of lycium barbarum preferably comprises: mixing fructus Lycii with water, and extracting to obtain fructus Lycii water extractive solution; the extraction time is preferably 0.5-2 h, more preferably 1h, and the volume ratio of the mass of the medlar to the volume of water is preferably 1g: 5-18 mL, more preferably 10 mL; the extraction temperature is preferably 65-75 ℃, and more preferably 70 ℃.

In the present invention, the extraction method of the hawthorn water extract preferably includes: mixing fructus crataegi with water, and extracting to obtain fructus crataegi water extractive solution; the extraction time is preferably 2-3 h, more preferably 2.5h, and the volume ratio of the mass of the hawthorn to the volume of water is preferably 1g: 15-25 mL, more preferably 20 mL; the extraction temperature is preferably 65-75 ℃, and more preferably 70 ℃.

In the invention, the granulation comprises wet granulation, and the wet granulation adopted by the invention has the characteristics of high granulation performance, simple operation, auxiliary material saving and relatively good appearance.

The invention has no special limitation on the type of the cistanche granule formulation, the content of active ingredients and auxiliary materials, and adopts the conventional mode in the field.

The source of the raw materials is not particularly limited in the invention, and the raw materials can be obtained by adopting conventional commercial products.

The apparatus used in the process of preparing cistanche granules according to the present invention is shown in table 1.

TABLE 1 summary of the laboratory instruments

The technical solutions provided by the present invention are described in detail below with reference to examples, but they should not be construed as limiting the scope of the present invention.

Example 1

The extraction method of the total cistanchis glycosides comprises the following steps: crushing cistanche, sieving with a 65-mesh sieve to obtain crushed substances, mixing with 45 vol% ethanol solution, wherein the volume ratio of the mass of the crushed substances to the ethanol solution is 1g:35mL, and extracting at 75 ℃ for 0.5h to obtain total glucosides of cistanche, wherein the yield of the total glucosides of cistanche is 3.92%.

The extraction method of the total flavone from the desertliving cistanche comprises the following steps: crushing cistanche, sieving with a 65-mesh sieve to obtain crushed substances, mixing with 65 volume percent ethanol solution, wherein the volume ratio of the mass of the crushed substances to the ethanol solution is 1g to 10mL, and extracting at 85 ℃ for 1h to obtain total flavonoids of cistanche, wherein the yield of the total flavonoids of cistanche is 6.42%.

The preparation method of the fine powder of the momordica grosvenori comprises the following steps: the raw material of the momordica grosvenori is crushed and sieved by a 65-mesh sieve to obtain momordica grosvenori fine powder.

The extraction method of the medlar water extract comprises the following steps: mixing the wolfberry fruit and water according to the volume ratio of 1g to 18mL, and extracting at 65 ℃ for 0.5h to obtain a wolfberry fruit water extracting solution.

The extraction method of the hawthorn water extract comprises the following steps: mixing the mass of the hawthorn and the volume ratio of water of 1g:15mL, and extracting at 65 ℃ for 3h to obtain hawthorn water extract.

Accurately weighing raw materials:

50g of cistanche alcohol extract, 15g of momordica grosvenori, 5g of medlar water extract, 5g of hawthorn water extract, 80g of excipient and 50g of ethanol solution with volume fraction of 70%; the mass ratio of total cistanchis glycosides to total cistanchis flavones in the cistanche alcohol extract is 2: 8, the mass ratio of the soluble starch to the maltodextrin in the excipient is 3: 1.

Mixing the fructus Lycii water extractive solution and fructus crataegi water extractive solution, concentrating to obtain extract, mixing the extract with Cistanchis herba alcohol extract and fructus Siraitiae Grosvenorii to obtain dry extract, pulverizing the dry extract, mixing with excipient and wetting agent, and wet granulating to obtain Cistanchis herba granule.

Example 2

The extraction method of the total cistanchis glycosides comprises the following steps: crushing cistanche, sieving with a 65-mesh sieve to obtain crushed substances, mixing with 55 volume percent ethanol solution, wherein the volume ratio of the mass of the crushed substances to the ethanol solution is 1g:45mL, and extracting at 65 ℃ for 2h to obtain total glucosides of cistanche, wherein the yield of the total glucosides of cistanche is 4.05%.

The extraction method of the total flavone from the desertliving cistanche comprises the following steps: crushing cistanche, sieving with a 65-mesh sieve to obtain crushed substances, mixing with 75% by volume of ethanol solution, wherein the volume ratio of the mass of the crushed substances to the volume of the ethanol solution is 1g to 20mL, and extracting at 85 ℃ for 3h to obtain total flavonoids of cistanche, wherein the yield of the total flavonoids of cistanche is 6.56%.

The extraction method of the medlar water extract comprises the following steps: mixing the wolfberry fruit and water according to the volume ratio of 1g to 10mL, and extracting at 75 ℃ for 2h to obtain a wolfberry fruit water extracting solution.

The extraction method of the hawthorn water extract comprises the following steps: mixing the mass of the hawthorn and the volume ratio of water of 1g:25mL, and extracting at 75 ℃ for 2h to obtain hawthorn water extract.

Accurately weighing raw materials:

80g of cistanche alcohol extract, 25g of momordica grosvenori, 25g of medlar water extract, 25g of hawthorn water extract, 200g of excipient and 100g of ethanol solution with volume fraction of 80%; the mass ratio of total cistanches glycosides to total cistanches flavones in the alcohol extract of cistanche deserticola is 1:1, and the mass ratio of soluble starch to maltodextrin in the excipient is 5: 1.

Example 3

The extraction method of the total cistanchis glycosides comprises the following steps: crushing cistanche, sieving with a 65-mesh sieve to obtain crushed substances, mixing with 50% by volume of ethanol solution, wherein the volume ratio of the mass of the crushed substances to the volume of the ethanol solution is 1g to 40mL, and extracting at 70 ℃ for 1h to obtain total glucosides of cistanche, wherein the yield of the total glucosides of cistanche is 4.11%.

The extraction method of the total flavone from the desertliving cistanche comprises the following steps: crushing cistanche, sieving with a 65-mesh sieve to obtain crushed substances, mixing with 70% ethanol solution by volume percentage, wherein the volume ratio of the mass of the crushed substances to the ethanol solution is 1g:15mL, and extracting at 85 ℃ for 2h to obtain total flavonoids of cistanche, wherein the yield of the total flavonoids of cistanche is 6.87%.

The extraction method of the medlar water extract comprises the following steps: mixing the wolfberry fruit and water according to the volume ratio of 1g:15mL, and extracting at 70 ℃ for 1h to obtain a wolfberry fruit water extracting solution.

The extraction method of the hawthorn water extract comprises the following steps: mixing fructus crataegi at a volume ratio of fructus crataegi to water of 1g:20mL, and extracting at 70 deg.C for 2.5h to obtain fructus crataegi water extractive solution.

Accurately weighing raw materials:

65g of cistanche alcohol extract, 20g of momordica grosvenori, 15g of medlar water extract, 15g of hawthorn water extract, 150g of excipient and 80g of ethanol solution with volume fraction of 75%; the mass ratio of total cistanches glycosides to total cistanches flavones in the alcohol extract of cistanche deserticola is 3:7, and the mass ratio of soluble starch to maltodextrin in the excipient is 4: 1.

Example 4

Yield determination of total glycosides and total flavonoids in cistanche

4.1 determination of yield of Total glycosides in Cistanchis herba

The extraction and determination of the total glycoside content adopts a single-factor and orthogonal analysis method, takes the yield of the phenylethanoid glycoside and the echinacoside as indexes, and researches the content of the phenylethanoid glycoside in the cistanche and the optimal extraction process parameters. The method comprises the following specific steps:

(1) taking 1g of cistanche deserticola powder, precisely weighing, placing in a 150mL round bottom flask, precisely adding a certain amount of ethanol-water solution, sealing, weighing, soaking for 30min, heating and refluxing in a water bath at 70 ℃ for a certain time, taking out, placing to room temperature, weighing again, complementing weight loss with ethanol, shaking up, and filtering. Precisely measuring 1mL of the subsequent filtrate, placing the subsequent filtrate in a 10mL volumetric flask, adding ethanol to dilute to a scale, and shaking up to obtain the product. The filtrate was placed in a brown bottle for further use.

(2) The maximum absorption peaks of the echinacoside standard product and the cistanche medicinal material are both near 333nm in the selection of the detection wavelength, so 333nm is selected as the detection wavelength of the phenylethanoid glycoside in the experiment.

(3) Drawing a standard curve, respectively sucking 0.0mL, 0.2 mL, 0.4mL, 0.6mL, 0.8 mL and 1.0mL of echinacoside reference substance solution, placing in a 10mL measuring flask, diluting with 50% ethanol to scale, and shaking uniformly. Taking distilled water as a blank, taking 1mL of each of a reference solution and a sample solution and a blank tube, volatilizing the solvent, adding 0.4mL of a newly prepared 5% vanillin-glacial acetic acid solution and 0.6mL of perchloric acid, shaking up, heating in a 70 ℃ water bath for 30min, taking out, immediately cooling in the ice water bath for 5min, adding 10mL of glacial acetic acid, shaking up, and measuring the ultraviolet absorbance of standard solutions with different concentrations at 333 nm.

(4) According to the standard curve making method, measuring the absorbance of the total cistanchis glycosides in the examples 1-3, and calculating the total glycoside yield. Calculated, the yield of the total cistanchis glycosides in example 1 is 3.92%, the yield of the total cistanchis glycosides in example 2 is 4.05%, and the yield of the total cistanchis glycosides in example 3 is 4.11%.

4.2 determination of yield of Total Flavonoids in Cistanchis herba

The extraction process of cistanche flavone is characterized by taking ethanol as a solvent, carrying out reflux extraction according to the following set conditions (material-liquid ratio, ethanol concentration and extraction time), and exploring the extraction process of total cistanche flavone by using a single-factor and orthogonal experiment, and comprises the following specific steps of:

(1) using NaNO₂-Al(NO₃)₃-NaOH colorimetry. Accurately weighing 10mg of rutin standard substance, placing in a 50mL volumetric flask, adding 50% ethanol for dissolving and diluting to scale, and preparing the rutin standard solution with the concentration of 0.2 mg/mL.

(2) Drawing a standard curve, namely respectively filling 0.0mL, 0.2 mL, 0.5mL, 1.0mL, 2.0 mL, 3.0 mL and 4.0mL of prepared rutin standard solution into a 10mL volumetric flask, adding 0.4mL of 5% sodium nitrite, standing for 6min, then adding 0.4mL of 10% aluminum nitrate, standing for 6min, then adding 4mL of 4% sodium hydroxide solution, adding water to the scale, shaking uniformly, standing for 15min, measuring the absorbance under the wavelength of 505nm, wherein the regression relationship between the absorbance value Y and the concentration X (mg/mL) of the rutin standard solution is as follows: 6.1268X +0.0185, R²＝0.9974。

(3) And (5) according to the preparation method of the standard curve, measuring the absorbance of the sample, and calculating the yield of the total flavone. Calculated, the yield of the total flavone from the desertliving cistanche in the example 1 is 6.42 percent, the yield of the total flavone from the desertliving cistanche in the example 2 is 6.56 percent, and the yield of the total flavone from the desertliving cistanche in the example 3 is 6.87 percent.

Example 5

Selection of excipients

5.1 selection of excipient type

5.1.1 method for evaluating moisture absorption

And (3) putting supersaturated NaOH solution into the glass dryer, standing for 24 hours, and ensuring that the dryer has better humidity. Accurately weighing 3g of granules, putting the granules into a constant-temperature drying box for constant weight, uniformly paving the granules with constant weight in a constant-weight weighing bottle, putting the bottles into a supersaturated NaCl solution dryer, opening a weighing bottle cap, standing at room temperature for 12 hours, 24 hours, 36 hours and 48 hours, respectively taking out the granules, accurately weighing, and calculating the moisture absorption percentage. The calculation method of the moisture absorption rate comprises the following steps:

5.1.2 method for determining particle yield by test

The measurement was carried out according to the method of appendix XI B of the year 2015 version of Chinese pharmacopoeia. The granules which can pass through the first sieve and can not pass through the fifth sieve are qualified granules.

5.1.3 selection of excipients

The results of the above 2 measurements were obtained by separately granulating 4 different excipients, soluble starch, maltodextrin, lactose, powdered sugar, and the like, and are shown in Table 2.

Table 24 excipient alone granulation findings

As can be seen from Table 2, the hygroscopicity and the yield of the granules prepared by using 4 excipients of soluble starch, maltodextrin, lactose and powdered sugar alone can be in accordance with the requirements of pharmacopoeia. The hygroscopicity effect is from small to large: maltodextrin, powdered sugar, soluble starch, lactose; but the final qualified yield of the granules is from large to small: maltodextrin, soluble starch, sugar powder and lactose. The least hygroscopic is maltodextrin, followed by powdered sugar and soluble starch, and the most hygroscopic is lactose; wherein the hygroscopicity of powdered sugar and soluble starch is very small in value. The final yield in the granules goes from large to small: maltodextrin, soluble starch, sugar powder and lactose. Therefore, during the wet granulation process of cistanche granules, the maltodextrin is best in the aspects of hygroscopicity and granule yield, the data of soluble starch and powdered sugar are close to each other to a great extent, and lactose is not suitable for being used as an auxiliary material of the granules compared with the former three excipients, but the price of the maltodextrin and the powdered sugar is high, so the wet granulation is carried out after the soluble starch and the maltodextrin are mixed according to the proportion.

5.1.4 selection of the proportions of the composite excipients

The proportion of the excipient has great influence on the granulating process in the preparation process, and the invention inspects the proportion of the soluble starch and the maltodextrin and determines the optimal mixing proportion. The dry paste crushed material (about 5g) of a single prescription amount is weighed according to the medicine proportion, 2 times of mixed excipient is weighed according to the proportion in the following table 3, and 75% ethanol is added as a main wetting agent for wet granulation. The raw material softwood and sieved aspects of soluble starch and maltodextrin in different mass ratios are shown in table 3.

Table 3 examination results of excipient mixing ratio

As can be seen from Table 3, when the mass ratio of soluble starch to maltodextrin is 4:1, the soft material has uniform particle size, hardly blocks and is not sticky to the sieve, so the soluble starch is selected in the invention: the mass ratio of maltodextrin was 4: 1.

Example 6

Hypoglycemic effect of cistanche granules

Diabetes can be achieved by inhibiting carbohydrate hydrolyzing enzymes such as alpha-amylase and alpha-glucosidase. Alpha-glucosidase and alpha-amylase are important enzymes involved in carbohydrate digestion. Alpha-amylases are involved in the breakdown of long-chain carbohydrates, and alpha-glucosidases break down starch and disaccharides into glucose. They are the main digestive enzymes and contribute to intestinal absorption. Alpha-amylase and alpha-glucosidase inhibitors are potential targets for the development of lead compounds for the treatment of diabetes. Therefore, the effect of the cistanche granules on reducing blood sugar is verified by the effect of the cistanche granules on alpha-amylase and alpha-glucosidase inhibitors.

6.1 materials and apparatus

5.1.1 materials and reagents

Cistanche granule: cistanche granules obtained according to example 3 were prepared.

The main reagents are as follows: acarbose, alpha-glucosidase, p-nitrophenyl-beta-D-galactopyranoside (PNPG), glutathione (all purchased from Meclin Biotechnology Co., Ltd., Shanghai), porcine pancreatic alpha-amylase, soluble starch, sodium carbonate, sodium dihydrogen phosphate, disodium hydrogen phosphate and the like are all analytical pure reagents purchased in laboratories.

6.1.2 instruments and devices

Table 4 Instrument and Equipment List

6.2 test methods

6.2.1 alpha-Amylase Activity inhibition assay

The effect of cistanche granules of the present invention on alpha-amylase inhibition was determined by DNS (dinitrosalicylic acid) method.

6.2.1.1 configuration of Primary test reagents

Reagent: pH6.8 phosphate buffer (buffer configuration reference 2015 edition pharmacopoeia); 5% soluble starch; 1% alpha-amylase solution; DNS agent.

Preparing a phosphate buffer solution (0.1mol/L, pH6.8): 30.20g NaH was weighed₂PO₄·2H₂O and 35.60gNa₂HPO₄·2H₂And O, respectively adding distilled water to a constant volume of 1000 mL. Absorb 510.0mL NaH respectively₂PO₄·2H₂O solution, 490.0mLNa₂HPO₄·2H₂And O is metered to 1000 mL. Mixing, and storing at room temperature.

Configuration of DNS reagents:

1) liquid A: 6.9g of crystalline phenol was dissolved in 15.2mL of 10% sodium hydroxide solution and diluted to 69mL, and 6.9g of sodium hydrogen sulfite was added to this solution to dissolve it.

2) B, liquid B: 255g of potassium sodium tartrate is weighed and added into 300mL of 10 percent sodium hydroxide solution, 880mL of 1 percent 3.5-dinitrosalicylic acid solution is added after dissolution, and the mixture is evenly mixed to obtain the potassium sodium tartrate-sodium solid solution.

Preparing a cistanche deserticola solution to be tested:

dissolving a certain amount of cistanche granule preparation in distilled water to obtain a certain amount of cistanche granule solution, centrifuging to remove protein, and diluting the supernatant solution by 2, 4, 8, 16 and 32 times respectively to obtain solutions to be detected with various concentrations.

6.2.1.2 full wavelength scanning of cistanche salsa to be tested solution

Taking a proper amount of cistanche granule sample solution, adding 2mL of phosphate buffer solution, adding 1mL of alpha-amylase solution, and shaking up. Preheating in 37 deg.C water bath for 20min, activating amylase, adding 1mL starch solution, standing in 37 deg.C water bath for 10min, adding 4mL DNS solution, placing in boiling water bath for 20min to stop reaction, cooling with ice water for 10min to stabilize, and scanning with full wavelength in spectrophotometer.

As can be seen from the full wavelength scanning chart of the cistanche salsa to-be-detected liquid in fig. 1, the cistanche salsa particle to-be-detected liquid has a large absorption peak at a wavelength of lambda 540 nm.

6.2.1.3 method for determining alpha-amylase activity inhibition

(1) Sample experimental group: taking a certain amount of cistanche deserticola particles, adding 2mL of phosphate buffer solution, adding 1mL of alpha-amylase solution, and shaking up. Preheating in 37 deg.C water bath for 20min, activating amylase, adding 1mL soluble starch solution, standing in 37 deg.C water bath for 10min, adding 4mL of solution of LDNS, placing in boiling water bath for 5min to stop reaction, and measuring absorbance at wavelength lambda 540 nm.

(2) Sample blank group: the same test was carried out with phosphate buffer solution instead of the solution of alpha-amylase in the sample experimental group, and the absorbance value at wavelength lambda 540nm was measured with a spectrophotometer.

(3) Control experimental group: adding 2mL of phosphate buffer solution, adding 1mL of alpha-amylase solution, and shaking up. Preheating in 37 deg.C water bath for 20min, activating amylase, adding 1mL soluble starch solution, standing in 37 deg.C water bath for 10min, adding 4mL of solution of LDNS, placing in boiling water bath for 5min to stop reaction, and measuring absorbance at wavelength lambda 540 nm.

(4) Control blank group: the same test was carried out using a phosphate buffer solution instead of the alpha-amylase solution in the control test group, and the absorbance value at a wavelength of lambda 540nm was measured using a spectrophotometer.

(5) The inhibition rate was calculated according to the following formula:

each concentration was repeated three times during each experiment. IC (integrated circuit)₅₀The concentration of inhibitor at which the enzyme activity is inhibited by half (i.e., 50%).

As can be seen from FIG. 2, the aqueous solution of the granule formulation of cistanche deserticola has a certain inhibition effect on the activity of alpha-amylase and has a good dose-effect relationship. In the concentration gradient range of the test, the highest inhibition rate of the cistanche granule aqueous solution on the activity of the alpha-amylase is 71.3 percent, and the IC of the cistanche granule aqueous solution is under the condition₅₀The value was 0.011 g/mL.

From the comparison of acarbose and cistanche granule formulation curves in fig. 2, it can be further found that the cistanche granules of the present invention have an inhibitory effect on α -amylase activity equivalent to acarbose at higher concentrations. However, with the dilution of the concentration, the inhibition effect of the sample on the activity of the alpha-amylase is obviously reduced, and the phenomenon of very low inhibition activity is shown, so that the requirement of the dosage of the medicament can be reflected.

6.2.2 alpha-glucosidase Activity inhibition assay

The inhibition effect of the cistanche granule aqueous solution on alpha-glucosidase is measured by taking PNPG as a substrate.

6.2.2.1 preparation of Primary test reagents

Reagent: phosphate buffered saline (0.1mol/L, pH 6.8); alpha-glucosidase (1U/mL); glutathione solution (3 mmol/L); p-nitrobenzene-beta-D-galactopyranoside solution ((PNPG)10 mmol/L); sodium carbonate solution (0.1 mol/L).

Preparing a phosphate buffer solution (0.1mol/L, pH6.8): 30.20g NaH was weighed₂PO₄·2H₂O and 35.60g Na₂HPO₄·2H₂And O, respectively adding distilled water to a constant volume of 1000 mL. Absorb 510.0mL NaH respectively₂PO₄·2H₂O solution, 490.0mL Na₂HPO₄·2H₂And O is metered to 1000 mL. Mixing, and storing at room temperature.

α -glucosidase (1.0U/mL): accurately weighing a certain amount of alpha-glucosidase phosphate buffer solution for dissolution, and preparing the concentration of the mother liquor to be 100.0U/mL. After subpackaging, the mixture is preserved at the temperature of minus 4 ℃ to avoid repeated freeze thawing. When in use, 1.0mL of the mother solution is sucked, and the volume of the phosphoric acid buffer solution is adjusted to 100.0 mL.

PNPG solution (10mmol/L) preparation: weighing 0.3013g of PNPG, dissolving in phosphoric acid buffer solution, and fixing the volume to 100 mL.

Preparing a cistanche granule solution: the cistanche granules prepared in the embodiment 3 of the invention are accurately weighed and dissolved in a certain amount of distilled water.

6.2.2.2 full-wavelength scanning of to-be-detected liquid of cistanche

Dissolving 0.5g of cistanche granule sample solution into 2mL of phosphate buffer solution, adding 1mL of alpha-glucosidase, mixing uniformly, incubating at 37 ℃ for 10min, and activating enzyme. Then, 1mL of glutathione solution was added, and 0.5mL of p-nitrophenyl-beta-D-galactopyranoside (PNPG) was reacted. After reacting for 20min in 37 ℃ water bath, 2mL of Na is added₂CO₃The solution terminates the reaction progress and a full wavelength scan is performed in an ultraviolet visible spectrophotometer.

The full wavelength scanning graph of the cistanche granule solution to be detected shows that the cistanche granule solution to be detected has a large absorption peak at the lambda 400nm wavelength.

6.2.2.3 method for determining activity of inhibiting alpha-glucosidase

(1) Sample experimental group: adding 1mL of cistanche granule solution into 2mL of phosphate buffer solution, adding 1mL of alpha-glucosidase, mixing, incubating at 37 deg.C for 10min, and activating enzyme. Then 1mL glutathione solution was addedThe reaction was started with 0.5mL p-nitrophenyl-beta-D-galactopyranoside (PNPG). Reacting for 20min under the condition of 37 ℃ water bath, and adding 2mLNa₂CO₃The solution stops the reaction, and the absorbance value of the solution to be detected at the wavelength lambda 400nm is measured.

(2) Sample blank group: the same test was carried out using a phosphate buffer solution instead of the sample test group α -glucosidase solution, and the absorbance value at a wavelength of λ 400nm was measured using a spectrophotometer.

(3) Control experimental group: the same test was carried out by replacing the sample test group cistanche solution with phosphate buffer solution, and the absorbance value at wavelength λ 400nm was measured with a spectrophotometer.

(4) Control blank group: the same test procedure was carried out using a buffer solution instead of the control test group α -glucosidase solution, and the absorbance value at a wavelength of λ 400nm was measured using a spectrophotometer.

The following formula was used for calculation:

Fig. 3 shows that the effect of cistanche granules with different concentrations on inhibiting the activity of alpha-glucosidase is different. The cistanche granule water solutions with different concentrations have certain inhibition effect on the activity of alpha-glucosidase, and have a relatively obvious dose-effect relationship. Under the test condition, the highest inhibition rate of the cistanche granule aqueous solution on the activity of the alpha-glucosidase is 68.9 percent, and the IC of the cistanche granule aqueous solution is₅₀The value was 0.0062 g/mL.

Example 7

Cistanche granule with blood fat reducing effect

7.1 materials and reagents

Cistanche granule: the cistanche granules prepared in embodiment 3 of the invention.

The main reagents are as follows: sodium taurocholate, sodium glycocholate, sodium cholate, pancreatin, simvastatin (all purchased from Shanghai Michelin Biochemical technology Co., Ltd.), sodium dihydrogen phosphate and disodium hydrogen phosphate are all analytical pure reagents purchased in laboratories.

7.2 instruments and devices

TABLE 5 Instrument and Equipment List

7.3 Experimental methods

7.3.1 in vitro lipid-lowering test

Observing the adsorption efficiency of the cistanche particles on cholate and the adsorption property under the isothermal condition, preliminarily judging the property and the capability of the cistanche particles in reaction with the cholate, and further preliminarily reflecting the effect of reducing blood fat.

7.3.2 preparation of Primary test reagents

Reagent: phosphate buffer (pH 6.3) (buffer formulation reference 2015 edition pharmacopoeia), sodium taurocholate, sodium glycocholate, sodium cholate solution, pancreatin solution.

Preparing a phosphate buffer solution (0.1mol/L, pH6.3): 17.50g NaH was weighed₂PO₄·2H₂O and 13.80gNa₂HPO₄·2H₂And O, respectively adding distilled water to a constant volume of 1000 mL. 224.0mL of NaH were sucked in respectively₂PO₄·2H₂O solution, 776.0mLNa₂HPO₄·2H₂And O is metered to 1000 mL. Mixing, and storing at room temperature.

Sodium taurocholate solution (0.3 mmol/L): 0.016g of sodium taurocholate was accurately weighed and dissolved in 100mL of buffered saline solution.

Sodium glycocholate (0.3 mmol/L): 0.0146g of sodium glycocholate was accurately weighed out and dissolved in 100mL of buffered salt solution.

Sodium cholate (0.3 mmol/L): 0.013g of sodium cholate was weighed accurately and dissolved in 100mL of buffered salt solution.

Pancreatin solution (10mg/mL (2500U/g)): 0.1g of pancreatin was precisely weighed and dissolved in 100mL of a buffer solution.

7.3.3 cholate Standard Curve

And (3) respectively adding the sodium taurocholate, the sodium glycocholate and the sodium cholate solution into 50mL of colorimetric tubes, adding a phosphoric acid buffer solution (pH 6.3) to the volume of 2.5mL, adding 7.5mL of a concentrated sulfuric acid solution with the mass fraction of 60%, carrying out water bath at 70 ℃ for 20min, taking out the solution in the ice bath for 10min, and measuring the absorbance at the position of the wavelength lambda 540 nm. The absorbance was measured as a function of cholate and a standard curve was plotted.

As can be seen from fig. 5, the standard curves of the three cholates have a relatively good linear relationship, and the regression equations are:

sodium taurocholate: y-18.029 x-0.0269, R²＝0.9927；

Sodium glycocholate: 15.453x-0.0156, R²＝0.9918；

Sodium cholate: 11.705x-0.0166, R²＝0.9915。

7.3.4 maximum absorption wavelength of cholate

And respectively taking three cholate to be correspondingly concentrated to carry out full-wave-band scanning, and recording the numerical value of the absorption wavelength corresponding to the maximum absorbance position.

As is clear from FIG. 4, the maximum absorption wavelengths of all three cholates are λ 386. + -.1 nm, and therefore λ 368nm is selected as the maximum absorption wavelength.

7.3.5 stability of cholate assay

And (3) optionally selecting a cholic acid solution in the solution to be detected of 0.05mmol/L for determination, processing according to a 6.3.3 method, determining the absorbance time interval for multiple times for 20min, and recording the numerical value. The absorbance results of the cholate assay are shown in Table 6.

TABLE 6 stability of cholate assay procedure

As can be seen from table 6, the cholate measurement process has a stable data detection effect, and the RDS values of sodium taurocholate, sodium glycocholate, and sodium cholate were 0.092%, 0.097%, and 0.130%, respectively, in 6 measurement processes of 2 hours, which indicates a stable test result.

7.3.6 test of adsorption efficiency of cistanche granule on cholate

Respectively weighing a certain amount of cistanche particles into 50mL colorimetric test tubes, adding 1mL of 0.01mol/L hydrochloric acid solution to simulate gastric acid digestion, carrying out oscillatory digestion for 1h in a 37 ℃ constant temperature oscillation box, raising the pH value of a solution to be tested to 6.3 by using 0.1mol/L NaOH solution after the digestion is finished, then adding 5mL of 10mg/mL pancreatin solution to simulate a link of liver and intestine circulation, and carrying out oscillatory digestion for 1h in the 37 ℃ constant temperature oscillation box. After completion, 4mL of the cholic acid salt solution was added to each sample, and the mixture was shaken at 37 ℃ for 10, 30, 50, 70, 90 and 110 min. Transferring the obtained solution to be tested into centrifuge tubes respectively, and centrifuging at 3900r/min for 25 min. Taking out the supernatant, diluting phosphate to proper concentration, and measuring the cholate content in the supernatant.

From fig. 7, the following two conclusions can be drawn: firstly, the aqueous solution of cholate and cistanche granules has a fast binding speed: the binding rate is basically stable in about 30min, and the calculation shows that the binding rate reaches over 95 percent when the binding equilibrium is reached already at 30 min. And secondly, the combination rate of sodium taurocholate is higher than that of sodium glycocholate, and the combination rate of the sodium taurocholate and the sodium glycocholate is higher than that of the sodium cholate by about 20 percent, and the main reason is probably that the carboxyl at the tail end of the main side chain of the structure of the sodium taurocholate and the sodium glycocholate is easier to ionize than the carboxyl at the tail end of the side chain of the sodium cholate, which is more favorable for the exposure of active groups under a neutral condition, so that the combination of the sodium taurocholate and cistanche can be accelerated.

7.3.7 Desertliving cistanche granule adsorption capacity test for cholate

Respectively weighing the same amount of cistanche particles into 50mL colorimetric test tubes, adding 1mL of 0.01mol/L HCl solution, carrying out constant-temperature oscillation digestion at 37 ℃ for 1h, raising the pH value of a solution to be tested to 6.3 by using 0.1mol/L NaOH solution after the digestion is finished, then adding 5mL of 10mg/mL pancreatin solution to simulate a link of liver and intestine circulation, and carrying out constant-temperature oscillation digestion in a constant-temperature oscillation box at 37 ℃ for 1 h. After the end, 4mL of cholate solution is added into each sample, the mixture is shaken at constant temperature of 37 ℃ for 1h, the obtained solution to be detected is respectively transferred into a centrifuge tube, and the centrifuge is carried out for 25min at 3900 r/min. Taking out the supernatant, diluting phosphate to proper concentration, and measuring the cholate content in the supernatant.

As can be seen from fig. 8: (1) when the concentration of cholate is low, the absorption rate of cholate is higher; when the concentration of the cholate is increased continuously, the absorption rate of the cholate is reduced continuously until a stable maximum value is reached, and the absorption effects of the three cholates keep a relatively similar change trend; (2) the cistanche granule has high adsorption rate on sodium taurocholate relative to sodium glycocholate and sodium cholate, so that the combination capacity of the sodium taurocholate and the cistanche granule is stronger, and the maximum adsorption capacity of the sodium taurocholate of the cistanche granule is larger than that of the sodium glycocholate and the sodium cholate along with the increase of time.

The data of FIG. 8 were fitted with Freundiich (1) and Langmuir (2) isotherms, which are expressed as:

wherein: y is the adsorption capacity (mmol/0.1g cistanche particles)

a, b, c are constants associated with the adsorbent and the adsorbate itself.

Isothermal adsorption curve Langmuir fitting parameters of cistanche to cholate are detailed in table 7.

TABLE 7 isothermal adsorption Curve Langmuir fitting parameters of cistanche deserticola on cholate

The isothermal adsorption curve Freundlich fitting parameters of cistanche to cholate are detailed in Table 8.

TABLE 8 isothermal adsorption Curve Freundlich fitting parameters of cistanche deserticola to cholate

As can be seen from tables 7 and 8, the equations obtained by the two isotherm fitting curves have good correlation, and the correlation coefficient r is greater than 0.94, which can better reflect the adsorption and binding behavior of cistanche particles to cholate. In addition, by analyzing the above two curves, the following conclusions can be drawn, respectively.

After the Freundlich curve is fitted to the experimental data, the balance value of the adsorption capacity of the cistanche granule aqueous solution to cholate can be obtained by referring to the type of the parameter, when the concentration of the cholate is low, the binding capacities of the cholate to the cholate are similar from large to small, and the data difference among glycocholic acid, sodium taurocholate and sodium cholate is small; but the maximum absorption capacity of the equilibrium concentration is gradually increased along with the increase of the concentration, wherein the maximum equilibrium binding capacity of the cistanche granule aqueous solution to cholate is in the following sequence from large to small: sodium taurocholate, sodium glycocholate, sodium cholate.

After Langmuir curve fitting is carried out on the experimental data, the parameter types are referred, and the absorption amount of the aqueous solution of cistanche particles to taurine sodium cholate is the largest, the sodium glycinate is the second largest and the absorption amount of the sodium cholate is the smallest in the absorption process of the aqueous solution of cistanche particles to various cholates from high to low. The maximum adsorption capacity of the sodium glycocholate and the sodium taurocholate can be presumed to be influenced by the structure of the sodium glycocholate, and the reference shows that the sodium glycocholate and the sodium taurocholate both belong to the combined cholate, and the two substances are different from each other in the maximum point that: the final end group of the side chain of sodium taurocholate is a sulfonic acid group, and the final end group of the side chain of sodium glycinate is a carboxyl group of glycine in amino acid. It is possible that the sulfonic group has a relatively high polarity in the structural arrangement, while the carboxyl group has a relatively low structural polarity; the sulfonic group with larger polarity is easier to dissociate, so that the active site which is easy to react is easier to expose, and reacts with the active function of the cistanche, so that the cholate is adsorbed in the active function of the cistanche. However, in the whole process, the maximum equilibrium adsorption amount of the sodium cholate is the lowest, which is consistent with each test result, the structure of the sodium cholate is formed, the tail end of the side chain is still carboxyl, the polarity is relatively small, the sodium cholate is not easy to dissociate, so that the active functional reaction with the cistanche occurs, and the binding amount of the sodium cholate is reduced. In addition, from the format of the paper, the value of the absorption Y is always larger than zero in the calculation process, which can further illustrate that the combination of cistanche and cholate is relatively easy, basically belongs to spontaneous reaction, and does not need external energy to participate.

From fig. 11, it can be derived that: (1) with the addition of the cistanche granule, the residual quantity of cholate in a test tube added with the same amount of cholate content is gradually reduced, and finally the three cholate contents all tend to stable contents, when the stable contents are reached, the content of sodium taurocholate is the lowest, the content of sodium glycocholate is the next lowest, and the balance content of sodium cholate is the highest. (2) In the adsorption process of a reference simvastatin on cistanche, the maximum adsorption amount is that the blood fat reducing effect of sodium taurocholate can reach 43.8% of that of the reference simvastatin; the blood fat reducing effect of the sodium glycocholate can reach 87.7 percent of that of a reference substance; the blood fat reducing effect of the sodium cholate can reach 22.6 percent of that of a reference substance. Therefore, at the maximum adsorption amount, the adsorption effect of cholate is not significant enough. Finally, when the content of the cistanche is measured at 0.005g/mL, the content of cholate shows a relatively large downward trend, and it can be further presumed that the cholate is relatively high in adsorption efficiency at this time, and the cistanche particles are relatively good in adsorption efficiency, so that the method can be further applied to guidance of later-stage drug dosage, is convenient to find out the optimal drug dosage, and maximally reduces the side effect of the drug in the use process.

Example 8

Stability study of cistanche granule

The principle of accelerated testing of the shelf life of a drug is to quantify the influence of external factors such as temperature, humidity, air pressure, light and the like on the deterioration reaction by using chemical kinetics. By controlling the drug to be in an environment where one or more external factors are above normal levels, the rate of deterioration will be accelerated or accelerated, and it can be determined whether the product is deteriorated in a time shorter than normal. Since the extrinsic factors affecting deterioration can be quantified and the degree of acceleration can also be calculated, the actual shelf life of the product under normal storage conditions can be estimated.

Accelerated tests prove that the effective quality guarantee period of the cistanche granules in a cool and dry place is 2 years.

In conclusion, the inhibition effects of the cistanche granules with different contents and acarbose on alpha-amylase and alpha-glucosidase are compared in an in-vitro simulated human digestion environment; the combination ability of the cistanche granule aqueous solution with different concentrations to cholate in vitro is compared by taking simvastatin as a contrast drug for reducing blood fat. IC of cistanche granule to alpha-amylase and alpha-glucosidase₅₀The values and maximum inhibitory effect were respectively: 11mg/mL, 68.9%; 6.2mg/mL, 71.3%; the combining ability of the cholate is ranked as 87.7 percent of the maximum sodium taurocholate, 43.8 percent of the sodium glycocholate and 22.6 percent of the minimum sodium cholate, and the in vitro test of the cistanche granule shows that the developed cistanche granule has certain effects of reducing blood sugar and blood fat.

The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.

Claims

1. The cistanche granule is characterized by comprising the following raw materials in parts by weight: 50-80 parts of cistanche alcohol extract, 15-25 parts of momordica grosvenori, 5-25 parts of medlar water extract, 5-25 parts of hawthorn water extract, 80-200 parts of excipient and 50-100 parts of wetting agent;

the cistanche alcohol extract comprises total cistanche glycosides and total cistanche flavones, and the mass ratio of the total cistanche glycosides to the total cistanche flavones is (2-5) to (5-8).

2. The cistanche granule according to claim 1, wherein the excipient comprises soluble starch and maltodextrin.

3. The cistanche granule according to claim 2, wherein the weight ratio of the soluble starch to the maltodextrin is (3-5): 1.

4. The cistanche granule according to claim 1, wherein the wetting agent comprises an ethanol solution with a volume fraction of 70-80%.

5. The cistanche granule according to claim 1, wherein the extraction method of total cistanche glycosides comprises: pulverizing herba cistanches to obtain pulverized material, and extracting with ethanol solution to obtain herba cistanches total glycosides;

the extraction time is 0.5-2 h, and the volume ratio of the mass of the crushed material to the volume of the ethanol solution is 1g: 35-45 mL; the volume percentage content of the ethanol solution is 45-55%; the extraction temperature is 65-75 ℃.

6. The cistanche granule as claimed in claim 1, wherein the extraction method of total cistanche flavonoids comprises: crushing cistanche to obtain crushed substances, and extracting the crushed substances with ethanol solution to obtain total flavonoids of cistanche;

the extraction time is 1-3 h, and the ratio of the mass of the crushed material to the volume of the ethanol solution is 1g: 10-20 mL; the volume percentage content of the ethanol solution is 65-75%; the extraction temperature is 75-85 ℃.

7. The cistanche granule as claimed in claim 1, wherein the extraction method of the aqueous extract of lycium barbarum comprises: mixing fructus Lycii with water, and extracting to obtain fructus Lycii water extractive solution; the extraction time is 0.5-2 h, and the mass-to-water volume ratio of the medlar is 1g: 5-18 mL; the extraction temperature is 65-75 ℃;

the extraction method of the hawthorn water extracting solution comprises the following steps: mixing fructus crataegi with water, and extracting to obtain fructus crataegi water extractive solution; the extraction time is 2-3 h, and the mass-to-water volume ratio of the hawthorn is 1g: 15-25 mL; the extraction temperature is 65-75 ℃.

8. The method for preparing cistanche granule according to any one of claims 1 to 7, comprising: mixing the fructus Lycii water extractive solution and fructus crataegi water extractive solution, concentrating to obtain extract, mixing the extract with Cistanchis herba alcohol extract and fructus Siraitiae Grosvenorii to obtain dry extract, pulverizing the dry extract, mixing with excipient and wetting agent, and granulating to obtain Cistanchis herba granule.

9. The method of claim 8, wherein said granulating comprises wet granulating.

10. Use of cistanche granules according to any one of claims 1 to 7 for the preparation of a hypoglycemic and/or hypolipidemic agent.