Pericarpium citri reticulatae traditional Chinese medicine formula granular preparation and preparation method thereof

Abstract

The invention provides a pericarpium citri reticulatae traditional Chinese medicine formula granular preparation and a preparation method thereof, and belongs to the technical field of traditional Chinese medicine granular preparations. The preparation method comprises the following steps: preparing modified porous starch; preparing secondary modified porous starch; preparing first mixed powder; preparing composite medicine carrying powder; and preparing the traditional Chinese medicine granular preparation. The preparation method comprises the following steps: dissolving chitosan in an acetic acid solution, mixing the solution with an aqueous suspension of porous starch, adding citric acid, carrying out a cross-linking modification reaction to form modified porous starch with a stable three-dimensional network structure, and carrying out secondary modification on the modified porous starch by using octenyl succinic anhydride so as to obtain the modified porous starch with a stable three-dimensional network structure. After water-soluble components and indissolvable components in the traditional Chinese medicine raw materials are respectively loaded by utilizing the secondary modified porous starch, the water solubility of the indissolvable components can be effectively improved, and the bioavailability of the traditional Chinese medicine raw materials is further improved.

Description

Technical Field

[0001] The invention relates to the technical field of Chinese medicine granule preparations, and in particular to a tangerine peel Chinese medicine formula granule preparation and a preparation method thereof. Background Art

[0002] Chinese medicine granule preparation is an important direction for the development of modern Chinese medicine. It overcomes the problems of inconvenience in decocting and carrying traditional Chinese medicine, and improves the convenience of using Chinese medicine and patient compliance. As one of the traditional Chinese medicines, tangerine peel has the effects of regulating qi and strengthening the spleen, drying dampness and resolving phlegm, and is widely used to treat cough, indigestion and other diseases.

[0003] At present, most of the existing granule preparations are prepared by decocting Chinese medicine with water, extracting the active ingredients in the Chinese medicine by water extraction, concentrating the water extract and drying it into powder, and then extruding it into granules by a granulator. However, this method can only extract water-soluble active ingredients in Chinese medicine, but cannot extract other water-insoluble active ingredients in Chinese medicine, and cannot make full use of the insoluble components in the Chinese medicine raw materials, resulting in a great waste of Chinese medicine raw materials. Moreover, the granule preparations prepared by this method have poor moisture resistance and are prone to moisture absorption and agglomeration during storage, affecting the stability and quality of the medicine.

[0004] Therefore, it is necessary to propose a tangerine peel Chinese medicine granule preparation and a preparation method thereof that can fully utilize raw materials and has good moisture resistance. Summary of the invention

[0005] In view of the deficiencies in the prior art, the object of the present invention is to provide a Chinese medicinal formula granule preparation of dried tangerine peel and a preparation method thereof.

[0006] A method for preparing a tangerine peel Chinese medicine granule preparation comprises the following steps:

[0007] S1: Preparation of modified porous starch

[0008] The wheat starch is dispersed in an acetic acid-sodium acetate buffer, and then a composite enzyme is added for enzymolysis to obtain porous starch, and then the porous starch and chitosan are respectively prepared into a porous starch suspension and a chitosan solution, which are mixed and citric acid is added for reaction to obtain a modified porous starch;

[0009] S2: Preparation of secondary modified porous starch

[0010] The modified porous starch is dispersed in deionized water, and then an ethanol solution of octenyl succinic anhydride is added to react to obtain a secondary modified porous starch;

[0011] S3: Preparation of the first mixed powder

[0012] The Chinese medicine raw material is decocted twice with water, the two extracts are combined, the secondary modified porous starch is added, the mixture is evenly mixed, and then freeze-dried to obtain a first mixed powder, and then the secondary mixed drug residue obtained after the second decoction is added to an ethanol solution for heating and reflux extraction to obtain a third extract;

[0013] S4: Preparation of composite drug-loaded powder

[0014] The three extracts are concentrated to prepare insoluble extract powders, which are then dissolved in anhydrous ethanol to prepare extract solutions. The secondary modified porous starch is then dispersed in n-hexane and added to the extract solutions for ultrasonic loading to prepare second mixed powders, which are then uniformly mixed with the first mixed powders to obtain composite drug-loaded powders.

[0015] S5: Preparation of Chinese medicine granules

[0016] The polyethylene glycol-polylactic acid-glycolic acid block copolymer and the above-mentioned composite drug-loaded powder are respectively prepared into a copolymer solution and a composite drug-loaded solution, and then the composite drug-loaded solution is added to the copolymer solution to prepare a mixed drug-loaded emulsion, and then the genipin solution is added to react to prepare drug-loaded nanoparticle powder, which is granulated by a dry granulator to obtain a traditional Chinese medicine granule preparation.

[0017] Furthermore, S1 specifically includes the following steps:

[0018] S1.1: Add wheat starch to acetic acid-sodium acetate buffer at a solid-liquid ratio of 1 g: (20-30) mL, ultrasonically treat for 10-20 min, heat at 35-40°C for 20-30 min and keep warm to obtain wheat starch solution;

[0019] S1.2: Add complex enzyme to the above wheat starch solution, keep warm and stir for enzymolysis for 10-12 hours, inactivate the enzyme, centrifuge at a rate of 3000-4000 r / min for 8-10 minutes, wash the precipitate, freeze-dry in vacuum, crush and sieve to obtain porous starch;

[0020] S1.3: Add chitosan to 1% acetic acid solution at a solid-liquid ratio of 1 g: (40-50) mL, stir and dissolve to obtain a chitosan solution;

[0021] S1.4: Add the porous starch into deionized water at a solid-liquid ratio of 1 g: (60-70) mL, stir and disperse to obtain a porous starch suspension;

[0022] S1.5: After the chitosan solution and the porous starch suspension are stirred and mixed evenly in a volume ratio of 1:(6-8), citric acid is added while stirring, and then heated and stirred at 40-50°C for 2-4h. After centrifugation, filtration, washing and drying, modified porous starch is obtained.

[0023] Furthermore, S2 specifically includes the following steps:

[0024] S2.1: adding the modified porous starch obtained in step S1.5 into deionized water, stirring and dispersing the mixture, and then adding 3% sodium hydroxide solution to adjust the pH to 8-9 to obtain a modified porous starch dispersion;

[0025] S2.2: Add octenyl succinic anhydride to anhydrous ethanol at a solid-liquid ratio of 1 g: (30-40) mL, stir thoroughly to dissolve, and obtain an octenyl succinic anhydride solution;

[0026] S2.3: Add the above octenylsuccinic anhydride solution to the above modified porous starch dispersion while stirring, heat and stir at 30-40°C for 1-2h, then adjust the pH to 6-7 with 3% hydrochloric acid, centrifuge, filter, wash, dry, grind and sieve to obtain a secondary modified porous starch.

[0027] Furthermore, S3 specifically includes the following steps:

[0028] S3.1: Add the Chinese medicine raw materials into 8-10 times the mass of water, heat and boil for 1-2 hours, and filter to obtain a primary extract and a primary mixed residue;

[0029] S3.2: Add the primary mixed residue to 4-6 times the mass of water, continue heating and boiling for 1-2 hours, and filter to obtain a secondary extract and secondary mixed residue;

[0030] S3.3: Add the secondary mixed medicinal residue to 75% ethanol solution at a solid-liquid ratio of 1 g: (20-30) mL, heat and reflux at 70-80°C for 2-3 hours, and filter to obtain a tertiary extract;

[0031] S3.4: Combine the primary extract and the secondary extract, and then add the secondary modified porous starch obtained in step S2.3 at a solid-liquid ratio of 1g:(8-12)mL. After stirring and mixing evenly, place in a freeze dryer for freeze drying. After grinding and sieving, a first mixed powder is obtained.

[0032] Furthermore, S4 specifically includes the following steps:

[0033] S4.1: placing the tertiary extracts obtained in step S3.3 in a concentrator, heating and concentrating, condensing and recovering ethanol, and then continuing to concentrate until evaporated to dryness to obtain a poorly soluble extract powder;

[0034] S4.1: Add the above-mentioned poorly soluble extraction powder into anhydrous ethanol at a solid-liquid ratio of 1 g: (80-100) mL, stir thoroughly to dissolve, and obtain an extract solution;

[0035] S4.2: Add the secondary modified porous starch obtained in step S2.3 to n-hexane at a solid-liquid ratio of 1 g: (35-45) mL, and ultrasonically disperse for 20-30 min to obtain a modified porous starch dispersion;

[0036] S4.3: adding the modified porous starch dispersion to the extract solution in a volume ratio of 1:(18-20), subjecting to ultrasonic loading for 1-2 hours, centrifuging and drying the precipitate in an oven for 10-12 hours, grinding and sieving to obtain a second mixed powder;

[0037] S4.4: Place the first mixed powder obtained in step S3.4 and the second mixed powder in a dry mixer, mix them thoroughly and evenly, and then compound the drug-loaded powder.

[0038] Furthermore, S5 specifically includes the following steps:

[0039] S5.1: adding polyethylene glycol-polylactic acid-glycolic acid block copolymer to acetone at a solid-liquid ratio of 1 g:(50-60) mL, stirring and mixing thoroughly to obtain a copolymer solution, wherein the mass ratio of polyethylene glycol to polylactic acid-glycolic acid copolymer in the polyethylene glycol-polylactic acid-glycolic acid block copolymer is 1:(3.4-3.6);

[0040] S5.2: Add the composite drug-loaded powder obtained in step S4.4 into distilled water at a solid-liquid ratio of 1 g: (75-85) mL, and stir and mix thoroughly to obtain a composite drug-loaded solution;

[0041] S5.3: adding the composite drug-loaded solution to the copolymer solution in a volume ratio of 1:(8-10), and ultrasonically treating for 20-30 min to obtain a mixed drug-loaded emulsion;

[0042] S5.4: Dissolve genipin in deionized water at a solid-liquid ratio of 1:(200-300) mL to obtain a genipin solution;

[0043] S5.5: adding the genipin solution to the mixed drug-loaded emulsion at a volume ratio of 1:(8-10) while stirring, stirring for 1-2 hours, cooling in an ice-water bath at 0°C, performing vacuum rotary evaporation, centrifugal separation, washing and vacuum freeze drying to obtain drug-loaded nanoparticle powder;

[0044] S5.6: Place the above-mentioned drug-loaded nanoparticle powder in a dry granulator and extrude it into granules to obtain a Chinese medicine granule preparation.

[0045] Furthermore, the compound enzyme is prepared by mixing α-amylase and saccharifying enzyme in a mass ratio of 1:4, and the added amount of the compound enzyme is 2-3% of the mass of wheat starch.

[0046] Furthermore, the solid-liquid ratio of citric acid to porous starch suspension is 1 g: (100-120) mL.

[0047] Furthermore, in terms of weight, the Chinese medicinal raw materials include: 30 parts of dried tangerine peel, 10 parts of pinellia, 10 parts of platycodon, 5 parts of magnolia bark, 5 parts of schizonepeta, 5 parts of aster, 3 parts of stemona, 3 parts of scutellaria, 3 parts of coltsfoot and 1 part of asarum.

[0048] A tangerine peel Chinese medicine formula granule preparation is prepared by any of the above-mentioned preparation methods of tangerine peel Chinese medicine formula granule preparations.

[0049] Compared with the prior art, the present invention has the following beneficial effects:

[0050] 1. The present invention dissolves chitosan in an acetic acid solution, mixes the mixture with an aqueous suspension of porous starch, adds citric acid for cross-linking modification, and makes three carboxyl groups in the citric acid molecule react with amino groups in the chitosan molecule and hydroxyl groups in the porous starch molecule, respectively. The chitosan and the porous starch are connected together by citric acid to form a modified porous starch with a stable three-dimensional network structure, thereby increasing the specific surface area and adsorption sites of the porous starch and improving its drug loading capacity. The modified porous starch is then subjected to secondary modification by octenyl succinic anhydride to introduce hydrophilic carboxyl groups into the modified porous starch molecules and improve the water solubility of the modified porous starch. Therefore, after the water-soluble components and the insoluble components in the Chinese medicine raw materials are loaded respectively by the secondary modified porous starch, the solubility of the insoluble components can be effectively improved, thereby improving the bioavailability of the Chinese medicine raw materials.

[0051] 2. The present invention is characterized in that after dissolving the polyethylene glycol-polylactic acid-glycolic acid block copolymer and the composite drug-loaded powder respectively, the composite drug-loaded solution is added to the polyethylene glycol-polylactic acid-glycolic acid block copolymer solution to prepare a mixed drug-loaded emulsion, and then genipin is added as a cross-linking agent to carry out a cross-linking reaction to obtain a drug-loaded nanoparticle powder, so that the polyethylene glycol-polylactic acid-glycolic acid block copolymer is coated on the surface of the composite drug-loaded powder, thereby improving the moisture resistance of the composite drug-loaded powder, preventing the particles from absorbing moisture and agglomerating, and improving the stability of the drug. In addition, by coating the polyethylene glycol-polylactic acid-glycolic acid block copolymer on the surface of the composite drug-loaded powder through the cross-linking reaction, the release rate of the drug can be more accurately controlled, the sustained-release effect of the drug can be improved, the drug effect can be prolonged, and the polyethylene glycol-polylactic acid-glycolic acid block copolymer and the composite drug-loaded powder can be prevented from being rapidly released in a short time due to weak binding force, resulting in insufficient drug absorption and reduced drug effect.

[0052] 3. The present invention uses a polyethylene glycol-polylactic acid-glycolic acid block copolymer with a mass ratio of polyethylene glycol to polylactic acid-glycolic acid copolymer of 1: (3.4-3.6) to coat the composite drug-loaded powder, thereby improving the water solubility of the polylactic acid-glycolic acid copolymer without affecting the moisture resistance of the prepared traditional Chinese medicine granule preparation, thereby not affecting the bioavailability of the drug, and achieving a balance between water solubility and moisture resistance. BRIEF DESCRIPTION OF THE DRAWINGS

[0053] The accompanying drawings, which are incorporated herein and constitute a part of the specification, illustrate embodiments of the present disclosure and, together with the description, further serve to explain the principles of the present disclosure and to enable those skilled in the relevant art to make and use the present disclosure.

[0054] Figure 1 A flow chart of the preparation method of the dried tangerine peel Chinese medicine granule preparation adopted in the embodiment of the present invention;

[0055] Figure 2 It is a cumulative drug release rate curve diagram of Example 1 of the present invention and Comparative Example 4. DETAILED DESCRIPTION

[0056] Below in conjunction with specific embodiment, a kind of dried orange peel Chinese medicine formula granule preparation and preparation method thereof provided by the present invention are described in detail.At the same time, what is described here is that, in order to make the embodiment more detailed, the following embodiment is the best, preferred embodiment, and other alternatives can also be adopted by those skilled in the art to implement for some known technologies.

[0057] Example 1

[0058] A method for preparing a tangerine peel Chinese medicine granule preparation comprises the following steps:

[0059] S1: Preparation of modified porous starch

[0060] S1.1: Add wheat starch to acetic acid-sodium acetate buffer at a solid-liquid ratio of 1 g:20 mL, ultrasonically treat for 10 min, heat at 35 °C for 20 min and keep warm to obtain wheat starch solution;

[0061] S1.2: Adding a composite enzyme to the above wheat starch solution, stirring and enzymolyzing for 10 hours, inactivating the enzyme, and centrifuging at a rate of 3000r / min for 8 minutes, washing the precipitate, vacuum freeze-drying, crushing and sieving to obtain porous starch, wherein the composite enzyme is prepared by mixing α-amylase and saccharifying enzyme in a mass ratio of 1:4, and the amount of the composite enzyme added is 2% of the mass of the wheat starch;

[0062] S1.3: Add chitosan to 1% acetic acid solution at a solid-liquid ratio of 1 g:40 mL, stir and dissolve to obtain a chitosan solution;

[0063] S1.4: Add the porous starch into deionized water at a solid-liquid ratio of 1 g:60 mL, stir and disperse to obtain a porous starch suspension;

[0064] S1.5: After the chitosan solution and the porous starch suspension are stirred and mixed uniformly at a volume ratio of 1:6, citric acid is added while stirring, and then heated and stirred at 40°C for 2 hours, and then centrifuged, filtered, washed and dried to obtain modified porous starch, wherein the solid-liquid ratio of citric acid to porous starch suspension is 1g:100mL;

[0065] S2: Preparation of secondary modified porous starch

[0066] S2.1: adding the modified porous starch obtained in step S1.5 into deionized water, stirring and dispersing the mixture, and then adding 3% sodium hydroxide solution to adjust the pH to 8 to obtain a modified porous starch dispersion;

[0067] S2.2: Add octenyl succinic anhydride to anhydrous ethanol at a solid-liquid ratio of 1 g:30 mL, stir thoroughly to dissolve, and obtain an octenyl succinic anhydride solution;

[0068] S2.3: adding the octenyl succinic anhydride solution to the modified porous starch dispersion while stirring, heating and stirring at 30° C. for 1 h, adjusting the pH to 6 with 3% hydrochloric acid, centrifuging, filtering, washing, drying, grinding and sieving to obtain a secondary modified porous starch;

[0069] S3: Preparation of the first mixed powder

[0070] S3.1: Add the Chinese medicinal raw materials into 8 times the weight of water, heat and boil for 1 hour, filter, and obtain a primary extract and a primary mixed medicinal residue, wherein, by weight, the Chinese medicinal raw materials include: 30 parts of dried orange peel, 10 parts of pinellia, 10 parts of platycodon, 5 parts of magnolia bark, 5 parts of schizonepeta, 5 parts of aster, 3 parts of stemon, 3 parts of radix scutellariae, 3 parts of coltsfoot and 1 part of asarum;

[0071] S3.2: Add the primary mixed residue to 4 times the mass of water, continue heating and boiling for 1 hour, and filter to obtain the secondary extract and secondary mixed residue;

[0072] S3.3: Add the secondary mixed drug residue to 75% ethanol solution at a solid-liquid ratio of 1g:20mL, heat and reflux at 70°C for 2h, and filter to obtain a tertiary extract;

[0073] S3.4: Combine the primary extract and the secondary extract, add the secondary modified porous starch obtained in step S2.3 at a solid-liquid ratio of 1 g:8 mL, stir and mix evenly, place in a freeze dryer, freeze dry, grind and sieve to obtain a first mixed powder;

[0074] S4: Preparation of composite drug-loaded powder

[0075] S4.1: placing the tertiary extracts obtained in step S3.3 in a concentrator, heating and concentrating, condensing and recovering ethanol, and then continuing to concentrate until evaporated to dryness to obtain a poorly soluble extract powder;

[0076] S4.1: Add the above-mentioned poorly soluble extract powder into anhydrous ethanol at a solid-liquid ratio of 1g:80mL, stir thoroughly to dissolve, and obtain an extract solution;

[0077] S4.2: Add the secondary modified porous starch obtained in step S2.3 into n-hexane at a solid-liquid ratio of 1 g:35 mL, and disperse by ultrasonic for 20 min to obtain a modified porous starch dispersion;

[0078] S4.3: adding the modified porous starch dispersion to the extract solution at a volume ratio of 1:18, subjecting the solution to ultrasonic loading for 1 hour, centrifugation filtration is performed, and the precipitate is dried in an oven for 10 hours, and then ground and sieved to obtain a second mixed powder;

[0079] S4.4: placing the first mixed powder obtained in step S3.4 and the second mixed powder in a dry mixer, and mixing them sufficiently and evenly to obtain a composite drug-loaded powder;

[0080] S5: Preparation of Chinese medicine granules

[0081] S5.1: adding polyethylene glycol-polylactic acid-glycolic acid block copolymer to acetone at a solid-liquid ratio of 1 g:50 mL, and stirring and mixing to obtain a copolymer solution, wherein the mass ratio of polyethylene glycol to polylactic acid-glycolic acid copolymer in the polyethylene glycol-polylactic acid-glycolic acid block copolymer is 1:3.4;

[0082] S5.2: Add the composite drug-loaded powder obtained in step S4.4 into distilled water at a solid-liquid ratio of 1 g:75 mL, and stir and mix thoroughly to obtain a composite drug-loaded solution;

[0083] S5.3: adding the composite drug-loaded solution to the copolymer solution at a volume ratio of 1:8, and ultrasonically treating for 20 min to obtain a mixed drug-loaded emulsion;

[0084] S5.4: Dissolve genipin in deionized water at a solid-liquid ratio of 1:200 mL to obtain a genipin solution;

[0085] S5.5: adding the genipin solution to the mixed drug-loaded emulsion at a volume ratio of 1:8 while stirring, stirring for 1 hour, cooling in an ice-water bath at 0°C, performing vacuum rotary evaporation, centrifugal separation, washing and vacuum freeze drying to obtain drug-loaded nanoparticle powder;

[0086] S5.6: Place the above-mentioned drug-loaded nanoparticle powder in a dry granulator and extrude it into granules to obtain a Chinese medicine granule preparation.

[0087] Example 2

[0088] A method for preparing a tangerine peel Chinese medicine granule preparation comprises the following steps:

[0089] S1: Preparation of modified porous starch

[0090] S1.1: Add wheat starch to acetic acid-sodium acetate buffer at a solid-liquid ratio of 1 g:25 mL, ultrasonically treat for 15 min, heat at 38 °C for 25 min and keep warm to obtain wheat starch solution;

[0091] S1.2: Adding a composite enzyme to the above wheat starch solution, stirring and enzymolyzing for 11 hours, inactivating the enzyme, and centrifuging at a rate of 3500r / min for 9 minutes, washing the precipitate, vacuum freeze-drying, crushing and sieving to obtain porous starch, wherein the composite enzyme is prepared by mixing α-amylase and saccharifying enzyme in a mass ratio of 1:4, and the amount of the composite enzyme added is 2.5% of the mass of the wheat starch;

[0092] S1.3: Add chitosan to 1% acetic acid solution at a solid-liquid ratio of 1 g:45 mL, stir and dissolve to obtain a chitosan solution;

[0093] S1.4: Add the porous starch into deionized water at a solid-liquid ratio of 1 g:65 mL, stir and disperse to obtain a porous starch suspension;

[0094] S1.5: After the chitosan solution and the porous starch suspension are stirred and mixed evenly at a volume ratio of 1:7, citric acid is added while stirring, and then heated and stirred at 45°C for 3 hours, and then centrifuged, filtered, washed and dried to obtain modified porous starch, wherein the solid-liquid ratio of citric acid to porous starch suspension is 1g:110mL;

[0095] S2: Preparation of secondary modified porous starch

[0096] S2.1: adding the modified porous starch obtained in step S1.5 into deionized water, stirring and dispersing the mixture, and then adding 3% sodium hydroxide solution to adjust the pH to 8.5 to obtain a modified porous starch dispersion;

[0097] S2.2: Add octenyl succinic anhydride to anhydrous ethanol at a solid-liquid ratio of 1 g:35 mL, stir thoroughly to dissolve, and obtain an octenyl succinic anhydride solution;

[0098] S2.3: adding the octenyl succinic anhydride solution to the modified porous starch dispersion while stirring, heating and stirring at 35° C. for 1.5 h, adjusting the pH to 6.5 with 3% hydrochloric acid, centrifuging, filtering, washing, drying, grinding and sieving to obtain a secondary modified porous starch;

[0099] S3: Preparation of the first mixed powder

[0100] S3.1: Add the Chinese medicinal raw materials into 9 times the weight of water, heat and boil for 1.5 hours, and filter to obtain an extract and a mixed medicine residue, wherein the Chinese medicinal raw materials include, by weight: 30 parts of dried orange peel, 10 parts of pinellia, 10 parts of platycodon, 5 parts of magnolia bark, 5 parts of schizonepeta, 5 parts of aster, 3 parts of stemon, 3 parts of radix scutellariae, 3 parts of coltsfoot and 1 part of asarum;

[0101] S3.2: Add the primary mixed residue to 5 times the mass of water, continue heating and boiling for 1.5 hours, and filter to obtain a secondary extract and secondary mixed residue;

[0102] S3.3: Add the secondary mixed medicinal residue to 75% ethanol solution at a solid-liquid ratio of 1g:25mL, heat and reflux at 75°C for 2.5h, and filter to obtain a tertiary extract;

[0103] S3.4: Combine the primary extract and the secondary extract, add the secondary modified porous starch obtained in step S2.3 at a solid-liquid ratio of 1 g:10 mL, stir and mix evenly, place in a freeze dryer, freeze dry, grind and sieve to obtain a first mixed powder;

[0104] S4: Preparation of composite drug-loaded powder

[0105] S4.1: placing the tertiary extracts obtained in step S3.3 in a concentrator, heating and concentrating, condensing and recovering ethanol, and then continuing to concentrate until evaporated to dryness to obtain a poorly soluble extract powder;

[0106] S4.1: Add the above-mentioned poorly soluble extract powder into anhydrous ethanol at a solid-liquid ratio of 1g:90mL, stir thoroughly to dissolve, and obtain an extract solution;

[0107] S4.2: Add the secondary modified porous starch obtained in step S2.3 into n-hexane at a solid-liquid ratio of 1 g:40 mL, and disperse by ultrasonic for 25 min to obtain a modified porous starch dispersion;

[0108] S4.3: adding the modified porous starch dispersion to the extract solution at a volume ratio of 1:19, subjecting to ultrasonic loading for 1.5 hours, centrifugation filtration is performed, and the precipitate is placed in an oven to dry for 11 hours, and then ground and sieved to obtain a second mixed powder;

[0109] S4.4: placing the first mixed powder obtained in step S3.4 and the second mixed powder in a dry mixer, and mixing them sufficiently and evenly to obtain a composite drug-loaded powder;

[0110] S5: Preparation of Chinese medicine granules

[0111] S5.1: adding polyethylene glycol-polylactic acid-glycolic acid block copolymer to acetone at a solid-liquid ratio of 1 g:40 mL, stirring and mixing thoroughly to obtain a copolymer solution, wherein the mass ratio of polyethylene glycol to polylactic acid-glycolic acid copolymer in the polyethylene glycol-polylactic acid-glycolic acid block copolymer is 1:3.5;

[0112] S5.2: Add the composite drug-loaded powder obtained in step S4.4 into distilled water at a solid-liquid ratio of 1 g:80 mL, and stir and mix thoroughly to obtain a composite drug-loaded solution;

[0113] S5.3: adding the composite drug-loaded solution to the copolymer solution at a volume ratio of 1:9, and ultrasonically treating for 25 min to obtain a mixed drug-loaded emulsion;

[0114] S5.4: Dissolve genipin in deionized water at a solid-to-liquid ratio of 1:250 mL to obtain a genipin solution;

[0115] S5.5: adding the genipin solution to the mixed drug-loaded emulsion at a volume ratio of 1:9 while stirring, stirring for 1.5 hours, cooling in an ice-water bath at 0°C, performing vacuum rotary evaporation, centrifugal separation, washing and vacuum freeze drying to obtain drug-loaded nanoparticle powder;

[0116] S5.6: Place the above-mentioned drug-loaded nanoparticle powder in a dry granulator and extrude it into granules to obtain a Chinese medicine granule preparation.

[0117] Example 3

[0118] A method for preparing a tangerine peel Chinese medicine granule preparation comprises the following steps:

[0119] S1: Preparation of modified porous starch

[0120] S1.1: Add wheat starch to acetic acid-sodium acetate buffer at a solid-liquid ratio of 1 g:30 mL, ultrasonically treat for 20 min, heat at 40 °C for 30 min and keep warm to obtain wheat starch solution;

[0121] S1.2: Adding a composite enzyme to the above wheat starch solution, stirring and enzymolyzing for 12 hours, inactivating the enzyme, and centrifuging at a rate of 4000r / min for 10 minutes, washing the precipitate, vacuum freeze-drying, crushing and sieving to obtain porous starch, wherein the composite enzyme is prepared by mixing α-amylase and saccharifying enzyme in a mass ratio of 1:4, and the amount of the composite enzyme added is 3% of the mass of the wheat starch;

[0122] S1.3: Add chitosan to 1% acetic acid solution at a solid-liquid ratio of 1 g:50 mL, stir and dissolve to obtain a chitosan solution;

[0123] S1.4: Add the porous starch into deionized water at a solid-liquid ratio of 1 g:70 mL, stir and disperse to obtain a porous starch suspension;

[0124] S1.5: After the chitosan solution and the porous starch suspension are stirred and mixed evenly at a volume ratio of 1:8, citric acid is added while stirring, and then heated and stirred at 50°C for 4 hours, and then centrifuged, filtered, washed and dried to obtain modified porous starch, wherein the solid-liquid ratio of citric acid to porous starch suspension is 1g:120mL;

[0125] S2: Preparation of secondary modified porous starch

[0126] S2.1: adding the modified porous starch obtained in step S1.5 into deionized water, stirring and dispersing the mixture, and then adding 3% sodium hydroxide solution to adjust the pH to 9 to obtain a modified porous starch dispersion;

[0127] S2.2: Add octenyl succinic anhydride to anhydrous ethanol at a solid-liquid ratio of 1 g:40 mL, stir thoroughly to dissolve, and obtain an octenyl succinic anhydride solution;

[0128] S2.3: adding the octenyl succinic anhydride solution to the modified porous starch dispersion while stirring, heating and stirring at 40° C. for 2 h, adjusting the pH to 7 with 3% hydrochloric acid, centrifuging, filtering, washing, drying, grinding and sieving to obtain a secondary modified porous starch;

[0129] S3: Preparation of the first mixed powder

[0130] S3.1: Add the Chinese medicinal raw materials into 10 times the weight of water, heat and boil for 2 hours, and filter to obtain an extract and a mixed medicine residue, wherein the Chinese medicinal raw materials include, by weight: 30 parts of dried orange peel, 10 parts of pinellia, 10 parts of platycodon, 5 parts of magnolia bark, 5 parts of schizonepeta, 5 parts of aster, 3 parts of stemon, 3 parts of radix scutellariae, 3 parts of coltsfoot and 1 part of asarum;

[0131] S3.2: Add the primary mixed residue to 6 times the mass of water, continue heating and boiling for 2 hours, and filter to obtain a secondary extract and secondary mixed residue;

[0132] S3.3: Add the secondary mixed drug residue to 75% ethanol solution at a solid-liquid ratio of 1g:30mL, heat and reflux at 80°C for 3h, and filter to obtain a tertiary extract;

[0133] S3.4: Combine the primary extract and the secondary extract, add the secondary modified porous starch obtained in step S2.3 at a solid-liquid ratio of 1 g:12 mL, stir and mix evenly, place in a freeze dryer, freeze dry, grind and sieve to obtain a first mixed powder;

[0134] S4: Preparation of composite drug-loaded powder

[0135] S4.1: placing the tertiary extracts obtained in step S3.3 in a concentrator, heating and concentrating, condensing and recovering ethanol, and then continuing to concentrate until evaporated to dryness to obtain a poorly soluble extract powder;

[0136] S4.1: Add the above-mentioned poorly soluble extraction powder into anhydrous ethanol at a solid-liquid ratio of 1g:100mL, stir thoroughly to dissolve, and obtain an extract solution;

[0137] S4.2: Add the secondary modified porous starch obtained in step S2.3 into n-hexane at a solid-liquid ratio of 1 g:45 mL, and disperse by ultrasonic for 30 min to obtain a modified porous starch dispersion;

[0138] S4.3: adding the modified porous starch dispersion to the extract solution at a volume ratio of 1:20, subjecting to ultrasonic loading for 2 hours, centrifugation filtration is performed, and the precipitate is placed in an oven to dry for 12 hours, and then ground and sieved to obtain a second mixed powder;

[0139] S4.4: placing the first mixed powder obtained in step S3.4 and the second mixed powder in a dry mixer, and mixing them sufficiently and evenly to obtain a composite drug-loaded powder;

[0140] S5: Preparation of Chinese medicine granules

[0141] S5.1: adding polyethylene glycol-polylactic acid-glycolic acid block copolymer to acetone at a solid-liquid ratio of 1 g:60 mL, and stirring and mixing to obtain a copolymer solution, wherein the mass ratio of polyethylene glycol to polylactic acid-glycolic acid copolymer in the polyethylene glycol-polylactic acid-glycolic acid block copolymer is 1:3.6;

[0142] S5.2: Add the composite drug-loaded powder obtained in step S4.4 into distilled water at a solid-liquid ratio of 1 g:85 mL, and stir and mix thoroughly to obtain a composite drug-loaded solution;

[0143] S5.3: adding the composite drug-loaded solution to the copolymer solution at a volume ratio of 1:10, and ultrasonically treating for 20-30 min to obtain a mixed drug-loaded emulsion;

[0144] S5.4: Dissolve genipin in deionized water at a solid-liquid ratio of 1:300 mL to obtain a genipin solution;

[0145] S5.5: adding the genipin solution to the mixed drug-loaded emulsion at a volume ratio of 1:10 while stirring, stirring for 2 hours, cooling in an ice-water bath at 0°C, performing vacuum rotary evaporation, centrifugal separation, washing and vacuum freeze drying to obtain drug-loaded nanoparticle powder;

[0146] S5.6: Place the above-mentioned drug-loaded nanoparticle powder in a dry granulator and extrude it into granules to obtain a Chinese medicine granule preparation.

[0147] Comparative Example 1

[0148] The difference between Comparative Example 1 and Example 1 is that steps S1.3-1.5 are removed, and the modified porous starch in step S2.1 is replaced by an equal amount of the porous starch prepared in step S1.

[0149] Comparative Example 2

[0150] The difference between Comparative Example 2 and Example 1 is that step S2 is removed, and the secondary modified porous starch in steps S3.4 and S4.2 is replaced by the modified porous starch obtained in step S1.5, that is, the modified porous starch is not subjected to secondary modification.

[0151] Comparative Example 3

[0152] The difference between Comparative Example 3 and Example 1 is that step S5 is removed, and the composite drug-loaded powder obtained in step S4.4 is directly prepared into a Chinese medicine granule preparation by dry granulation.

[0153] Comparative Example 4

[0154] The difference between this comparative example 4 and example 1 is that the cross-linking reaction is removed, and specifically step S5 is modified as follows:

[0155] The polyethylene glycol-polylactic acid-glycolic acid block copolymer is added to acetone at a solid-liquid ratio of 1g:50mL, and the mixture is stirred thoroughly to obtain a copolymer solution, wherein the mass ratio of polyethylene glycol to polylactic acid-glycolic acid copolymer in the polyethylene glycol-polylactic acid-glycolic acid block copolymer is 1:3.4; then, the composite drug-loaded powder prepared in step S4.4 is added to distilled water at a solid-liquid ratio of 1g:75mL, and the mixture is stirred thoroughly to obtain a composite drug-loaded solution; then, the composite drug-loaded solution is added to the copolymer solution at a volume ratio of 1:8, and ultrasonic treatment is performed for 20 minutes to obtain a drug-loaded primary emulsion; and then, the composite drug-loaded powder is added to the copolymer solution at a volume ratio of 1:3 The drug-loaded primary emulsion is added to an aqueous solution of poloxamer 188 with a mass concentration of 0.5%, and stirred at a rate of 800 r / min for 1 hour to obtain a drug-loaded double emulsion. The drug-loaded double emulsion is added to an aqueous solution of 1% poloxamer 188 at a volume ratio of 1:10, and stirred at a rate of 800 r / min for 30 minutes. The drug-loaded nanoparticle powder is obtained by reduced pressure rotary evaporation and vacuum freeze drying. Finally, the drug-loaded nanoparticle powder is placed in a dry granulator and extruded into granules to obtain a traditional Chinese medicine granule preparation, that is, the polyethylene glycol-polylactic acid-glycolic acid block copolymer is directly physically coated on the surface of the composite drug-loaded powder.

[0156] Comparative Example 5

[0157] The difference between Comparative Example 5 and Example 1 is that the mass ratio of polyethylene glycol to polylactic acid-glycolic acid copolymer in the polyethylene glycol-polylactic acid-glycolic acid block copolymer in step S5 is replaced from 1:3.4 to 1:3.

[0158] Comparative Example 6

[0159] The difference between Comparative Example 6 and Example 1 is that the mass ratio of polyethylene glycol to polylactic acid-glycolic acid copolymer in the polyethylene glycol-polylactic acid-glycolic acid block copolymer in step S5 is replaced from 1:3.4 to 1:4.

[0160] Performance Testing

[0161] Test 1: The mass concentration of the insoluble extraction powder in the filtrate after centrifugal filtration in step S4.3 of Examples 1-3 and Comparative Example 1 was detected by high performance liquid chromatography. The loading rate of the insoluble extraction powder in the secondary modified porous starch was calculated as follows:

[0162] R(%)=[(m0-C e ×V e ) / m0]×100%;

[0163] Where R is the load factor, C e is the mass concentration of the insoluble extraction powder in the filtrate, V e is the volume of the filtrate, and m0 is the initial mass of the poorly soluble extraction powder. The results are shown in Table 1.

[0164] Table 1: Comparison of the load rate results of Examples 1-3 and Comparative Example 1

[0165] Example 1 Example 2 Example 3 Comparative Example 1 Load rate (%) 83.35 82.96 83.43 71.79

[0166] Test 2: 60 SD rats, half male and half female, were randomly divided into 6 groups, 10 rats in each group, and were respectively gavaged with the Chinese medicine granule preparations prepared in Examples 1-3 and Comparative Examples 2, 5, and 6. Fasting was performed for 12 hours before gavage, and sufficient water was ensured. The gavage concentration of the 6 groups of rats was 50 mg / kg (calculated according to the content of the effective ingredients of the Chinese medicine). Recording began after intragastric administration. Blood samples were obtained by orbital venous sinus puncture at 0.5h, 1.0h, 2.0h, 4.0h, 6.0h, 8.0h, 10.0h, 12.0h, and 24.0h, respectively. The blood samples were immediately centrifuged at 3000r / min for 10min. Then 20μL of serum sample was accurately drawn and extracted with 100μL of anhydrous ethanol. The extraction system was shaken on a vortex agitator for 1min and then centrifuged at 10000r / min for 10min. Finally, the supernatant was taken for HPLC detection to determine the concentration of the active ingredient of the Chinese medicine granule preparation in each sample. The blood drug concentration data were model fitted and analyzed by using the software DAS2.0. The blood drug peak concentration and the area under the drug-time curve were used as bioavailability parameters. The results are shown in Table 2.

[0167] Table 2: Comparison of bioavailability parameters of Examples 1-3 and Comparative Examples 2 and 4-5

[0168] Peak blood concentration (μg / mL) Area under the drug-time curve Example 1 5.23 98.57 Example 2 5.19 98.45 Example 3 5.24 98.55 Comparative Example 2 4.42 76.53 Comparative Example 5 5.22 98.48 Comparative Example 6 4.87 88.16

[0169] As can be seen from Table 1 and Table 2, in Comparative Example 1, when the porous starch is not subjected to the first modification but directly subjected to the second modification, the drug loading rate of the porous starch is about 71.79%, which is less than that of Examples 1-3, while in Comparative Example 2, when the porous starch is not subjected to the second modification, the peak blood drug concentration and the area under the drug-time curve of the prepared Chinese medicine granule preparation are both less than those of Examples 1-3, that is, the bioavailability of the Chinese medicine granule preparation prepared in Comparative Example 2 is lower than that of Examples 1-3. It can be seen that by first dissolving chitosan in an acetic acid solution, then mixing it with an aqueous suspension of porous starch, and adding citric acid for cross-linking modification reaction, the three carboxyl groups in the citric acid molecule are respectively cross-linked with chitosan. The amino group in the molecule reacts with the hydroxyl group in the porous starch molecule, and citric acid is used to connect chitosan and porous starch together to form a modified porous starch with a stable three-dimensional network structure, thereby increasing the specific surface area and adsorption sites of the porous starch, thereby improving its drug loading capacity, and then using octenyl succinic anhydride to perform secondary modification on the modified porous starch, introducing hydrophilic carboxyl groups into the modified porous starch molecules, thereby improving the water solubility of the modified porous starch. Therefore, after the water-soluble components and the insoluble components in the traditional Chinese medicine raw materials are loaded separately by the secondary modified porous starch, the solubility of the insoluble components can be effectively improved, thereby improving the bioavailability of the traditional Chinese medicine raw materials.

[0170] Test 3: Place a desiccator with a supersaturated sodium chloride solution at the bottom at 25°C for 48 hours to make the relative humidity inside it about 75%. Accurately weigh the weighing bottle containing the Chinese medicine granule preparations prepared in Examples 1-3, Comparative Example 3, Comparative Example 5, and Comparative Example 6 and place it in the desiccator (with the weighing bottle cover open). Accurately weigh the bottle and the Chinese medicine granule preparation after 120 hours. The moisture resistance is calculated as follows:

[0171] Moisture proof rate = 1 - [(mass of Chinese herbal medicine granule preparation after moisture absorption - mass of Chinese herbal medicine granule preparation before moisture absorption) / mass of Chinese herbal medicine granule preparation before moisture absorption] × 100%. The results are shown in Table 3.

[0172] Table 3: Comparison of moisture resistance results of Examples 1-3 and Comparative Examples 3-5

[0173] Moisture resistance (%) Example 1 99.36 Example 2 99.32 Example 3 99.34 Comparative Example 3 62.48 Comparative Example 5 80.26 Comparative Example 6 99.43

[0174] As can be seen from Table 3, after the composite drug-loaded powder is directly made into the Chinese medicine granule preparation in Comparative Example 3, its moisture resistance is about 62.48%, which is much lower than that of Examples 1-3. It can be seen that by dissolving the polyethylene glycol-polylactic acid-glycolic acid block copolymer and the composite drug-loaded powder respectively, adding the composite drug-loaded solution to the polyethylene glycol-polylactic acid-glycolic acid block copolymer solution to prepare a mixed drug-loaded emulsion, and then adding genipin as a cross-linking agent to carry out a cross-linking reaction to obtain a drug-loaded nanoparticle powder, the polyethylene glycol-polylactic acid-glycolic acid block copolymer is coated on the surface of the composite drug-loaded powder, thereby improving the moisture resistance of the composite drug-loaded powder, preventing the particles from absorbing moisture and agglomerating, and improving the stability of the drug.

[0175] In addition, it can be seen from Tables 2 and 3 that when the polyethylene glycol content in the polyethylene glycol-polylactic acid-glycolic acid block copolymer used in Comparative Example 5 is increased compared to that in Examples 1-3, the water solubility of the prepared Chinese medicine granule preparation is improved, although it will not affect its bioavailability, but its moisture resistance is reduced. When the polyethylene glycol content in the polyethylene glycol-polylactic acid-glycolic acid block copolymer used in Comparative Example 6 is reduced compared to that in Examples 1-3, the water solubility of the prepared Chinese medicine preparation is reduced, although it will not affect its moisture resistance, but its bioavailability is reduced. It can be seen that by using a polyethylene glycol-polylactic acid-glycolic acid block copolymer with a mass ratio of polyethylene glycol to polylactic acid-glycolic acid copolymer of 1: (3.4-3.6) to coat the composite drug-loaded powder, it is possible to improve the water solubility of the polylactic acid-glycolic acid copolymer without affecting the moisture resistance of the prepared Chinese medicine granule preparation, thereby not affecting the bioavailability of the drug, and achieving a balance between water solubility and moisture resistance.

[0176] Test 4: Weigh 50 mg of the Chinese medicine granule preparations prepared in Example 1 and Comparative Example 4 respectively, put them into dialysis bags, place them in a beaker containing 60 mL of phosphate buffer with a pH of 7.4, and oscillate them in a constant temperature oscillating box at 37°C. Then, take 3 mL of the solution every 1 hour, measure its absorbance, calculate the cumulative drug release, and add 3 mL of blank phosphate buffer to the beaker to keep the solution constant. The results are as follows: Figure 2 shown.

[0177] from Figure 2 It can be seen that the drug release rate in Comparative Example 4 is faster than that in Example 1. It can be seen that by coating the polyethylene glycol-polylactic acid-glycolic acid block copolymer on the surface of the composite drug-loaded powder through a cross-linking reaction, the drug release rate can be more accurately controlled, the sustained-release effect of the drug can be improved, and the drug effect can be prolonged, thereby preventing the polyethylene glycol-polylactic acid-glycolic acid block copolymer from being rapidly released in a short time due to weak binding force with the composite drug-loaded powder, resulting in insufficient drug absorption and reduced drug efficacy.

[0178] The above embodiments are merely illustrative of the principles and effects of the present invention, and are not intended to limit the present invention. Anyone familiar with the art may modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by a person of ordinary skill in the art without departing from the spirit and technical concept disclosed by the present invention shall still be covered by the claims of the present invention.

Claims

1. A method for preparing a Chinese medicinal granule preparation of dried orange peel, characterized in that: The steps include: S1: Preparation of modified porous starch The wheat starch is dispersed in an acetic acid-sodium acetate buffer, and then a composite enzyme is added for enzymolysis to obtain porous starch, and then the porous starch and chitosan are respectively prepared into a porous starch suspension and a chitosan solution, which are mixed and citric acid is added for reaction to obtain a modified porous starch; S2: Preparation of secondary modified porous starch The modified porous starch is dispersed in deionized water, and then an ethanol solution of octenyl succinic anhydride is added to react to obtain a secondary modified porous starch; S3: Preparation of the first mixed powder The Chinese medicine raw material is decocted twice with water, the two extracts are combined, the secondary modified porous starch is added, the mixture is evenly mixed, and then freeze-dried to obtain a first mixed powder, and then the secondary mixed drug residue obtained after the second decoction is added to an ethanol solution for heating and reflux extraction to obtain a third extract; S4: Preparation of composite drug-loaded powder The three extracts are concentrated to prepare insoluble extract powders, which are then dissolved in anhydrous ethanol to prepare extract solutions. The secondary modified porous starch is then dispersed in n-hexane and added to the extract solutions for ultrasonic loading to prepare second mixed powders, which are then uniformly mixed with the first mixed powders to obtain composite drug-loaded powders. S5: Preparation of Chinese medicine granules The polyethylene glycol-polylactic acid-glycolic acid block copolymer and the above-mentioned composite drug-loaded powder are respectively prepared into a copolymer solution and a composite drug-loaded solution, and then the composite drug-loaded solution is added to the copolymer solution to prepare a mixed drug-loaded emulsion, and then the genipin solution is added to react to prepare drug-loaded nanoparticle powder, which is granulated by a dry granulator to obtain a traditional Chinese medicine granule preparation.

2. The method for preparing a tangerine peel Chinese medicine granule preparation according to claim 1, wherein: S1 specifically includes the following steps: S1.1: Add wheat starch to acetic acid-sodium acetate buffer at a solid-liquid ratio of 1 g: (20-30) mL, ultrasonically treat for 10-20 min, heat at 35-40°C for 20-30 min and keep warm to obtain wheat starch solution; S1.2: Add complex enzyme to the above wheat starch solution, keep warm and stir for enzymolysis for 10-12 hours, inactivate the enzyme, centrifuge at a rate of 3000-4000 r / min for 8-10 minutes, wash the precipitate, freeze-dry in vacuum, crush and sieve to obtain porous starch; S1.3: Add chitosan to 1% acetic acid solution at a solid-liquid ratio of 1 g: (40-50) mL, stir and dissolve to obtain a chitosan solution; S1.4: Add the porous starch into deionized water at a solid-liquid ratio of 1 g: (60-70) mL, stir and disperse to obtain a porous starch suspension; S1.5: After the chitosan solution and the porous starch suspension are stirred and mixed evenly in a volume ratio of 1:(6-8), citric acid is added while stirring, and then heated and stirred at 40-50°C for 2-4h. After centrifugation, filtration, washing and drying, modified porous starch is obtained.

3. The method for preparing a tangerine peel Chinese medicine granule preparation according to claim 2, wherein: S2 specifically includes the following steps: S2.1: adding the modified porous starch obtained in step S1.5 into deionized water, stirring and dispersing the mixture, and then adding 3% sodium hydroxide solution to adjust the pH to 8-9 to obtain a modified porous starch dispersion; S2.2: Add octenyl succinic anhydride to anhydrous ethanol at a solid-liquid ratio of 1 g: (30-40) mL, stir thoroughly to dissolve, and obtain an octenyl succinic anhydride solution; S2.3: Add the above octenylsuccinic anhydride solution to the above modified porous starch dispersion while stirring, heat and stir at 30-40°C for 1-2h, then adjust the pH to 6-7 with 3% hydrochloric acid, centrifuge, filter, wash, dry, grind and sieve to obtain a secondary modified porous starch.

4. The method for preparing a tangerine peel Chinese medicine granule preparation according to claim 3, wherein: S3 specifically includes the following steps: S3.1: Add the Chinese medicine raw materials into 8-10 times the mass of water, heat and boil for 1-2 hours, and filter to obtain a primary extract and a primary mixed residue; S3.2: Add the primary mixed residue to 4-6 times the mass of water, continue heating and boiling for 1-2 hours, and filter to obtain a secondary extract and secondary mixed residue; S3.3: Add the secondary mixed medicinal residue to 75% ethanol solution at a solid-liquid ratio of 1 g: (20-30) mL, heat and reflux at 70-80°C for 2-3 hours, and filter to obtain a tertiary extract; S3.4: Combine the primary extract and the secondary extract, and then add the secondary modified porous starch obtained in step S2.3 at a solid-liquid ratio of 1g:(8-12)mL. After stirring and mixing evenly, place in a freeze dryer for freeze drying. After grinding and sieving, a first mixed powder is obtained.

5. The method for preparing a tangerine peel Chinese medicine granule preparation according to claim 4, wherein: S4 specifically includes the following steps: S4.1: placing the tertiary extracts obtained in step S3.3 in a concentrator, heating and concentrating, condensing and recovering ethanol, and then continuing to concentrate until evaporated to dryness to obtain a poorly soluble extract powder; S4.1: Add the above-mentioned poorly soluble extraction powder into anhydrous ethanol at a solid-liquid ratio of 1 g: (80-100) mL, stir thoroughly to dissolve, and obtain an extract solution; S4.2: Add the secondary modified porous starch obtained in step S2.3 to n-hexane at a solid-liquid ratio of 1 g: (35-45) mL, and ultrasonically disperse for 20-30 min to obtain a modified porous starch dispersion; S4.3: adding the modified porous starch dispersion to the extract solution in a volume ratio of 1:(18-20), subjecting to ultrasonic loading for 1-2 hours, centrifuging and drying the precipitate in an oven for 10-12 hours, grinding and sieving to obtain a second mixed powder; S4.4: Place the first mixed powder obtained in step S3.4 and the second mixed powder in a dry mixer, mix them thoroughly and evenly, and then compound the drug-loaded powder.

6. The method for preparing a tangerine peel Chinese medicine granule preparation according to claim 5, characterized in that: S5 specifically includes the following steps: S5.1: adding polyethylene glycol-polylactic acid-glycolic acid block copolymer to acetone at a solid-liquid ratio of 1 g:(50-60) mL, stirring and mixing thoroughly to obtain a copolymer solution, wherein the mass ratio of polyethylene glycol to polylactic acid-glycolic acid copolymer in the polyethylene glycol-polylactic acid-glycolic acid block copolymer is 1:(3.4-3.6); S5.2: Add the composite drug-loaded powder obtained in step S4.4 into distilled water at a solid-liquid ratio of 1 g: (75-85) mL, and stir and mix thoroughly to obtain a composite drug-loaded solution; S5.3: adding the composite drug-loaded solution to the copolymer solution in a volume ratio of 1:(8-10), and ultrasonically treating for 20-30 min to obtain a mixed drug-loaded emulsion; S5.4: Dissolve genipin in deionized water at a solid-liquid ratio of 1:(200-300) mL to obtain a genipin solution; S5.5: adding the genipin solution to the mixed drug-loaded emulsion at a volume ratio of 1:(8-10) while stirring, stirring for 1-2 hours, cooling in an ice-water bath at 0°C, performing vacuum rotary evaporation, centrifugal separation, washing and vacuum freeze drying to obtain drug-loaded nanoparticle powder; S5.6: Place the above-mentioned drug-loaded nanoparticle powder in a dry granulator and extrude it into granules to obtain a Chinese medicine granule preparation.

7. The method for preparing a tangerine peel Chinese medicine granule preparation according to claim 2, wherein: The compound enzyme is prepared by mixing alpha-amylase and saccharifying enzyme in a mass ratio of 1:4, and the added amount of the compound enzyme is 2-3% of the mass of wheat starch.

8. The method for preparing a tangerine peel Chinese medicine granule preparation according to claim 2, characterized in that: The solid-liquid ratio of citric acid to porous starch suspension is 1 g: (100-120) mL.

9. The method for preparing a tangerine peel Chinese medicine granule preparation according to claim 4, characterized in that: In terms of weight, the Chinese medicinal raw materials include: 30 parts of dried tangerine peel, 10 parts of pinellia, 10 parts of platycodon, 5 parts of magnolia bark, 5 parts of schizonepeta, 5 parts of aster, 3 parts of stemona, 3 parts of scutellaria, 3 parts of coltsfoot and 1 part of asarum.

10. A Chinese medicinal granule preparation of dried tangerine peel, characterized in that: The granule preparation is prepared by the method for preparing the tangerine peel Chinese medicine formula granule preparation described in any one of claims 1 to 9.

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