Donkey-hide gelatin solid beverage and preparation method thereof

Abstract

The invention provides a donkey-hide gelatin solid beverage and a preparation method thereof, the preparation method comprises the following steps: adding 8 times by mass of water into rhizoma polygonati, Chinese wolfberry, astragalus membranaceus, codonopsis pilosula, red dates, angelica sinensis and orange peel, soaking for 0.5 h, extracting for 2 h for the first time, adding 6 times by mass of water for extracting for 1.5 h for the second time, combining filtrates, and concentrating until the relative density is 1.23 g / cm < 3 > to obtain a water extraction concentrated solution; mixing the water extraction concentrated solution with maltodextrin, and drying to obtain an extract; and adding auxiliary materials into the extract and the donkey-hide gelatin, and molding to obtain the donkey-hide gelatin solid beverage. In the extraction step, proper soaking time, water adding amount and extraction time are combined, so that the ferulic acid content, the total polysaccharide content, the hesperidin content and the calycosin-7-glucoside content in the concentrated solution are all higher. And on the basis, subsequent drying and forming are carried out, so that the final donkey-hide gelatin solid beverage also has relatively high content of the components, and the content in each batch of products is stable.

Description

Technical Field

[0001] The invention relates to the field of solid preparations, in particular to a donkey-hide gelatin solid beverage and a preparation method thereof. Background Art

[0002] Donkey-hide gelatin solid beverage is a solid beverage made by mixing donkey-hide gelatin with other ingredients. It combines the nourishing effect of donkey-hide gelatin with the convenience of beverage. Donkey-hide gelatin solid beverage usually has the effect of nourishing blood and yin, moistening dryness and stopping bleeding. It is suitable for various symptoms caused by blood deficiency, such as pale complexion, dizziness, palpitations, insomnia, irregular menstruation and other symptoms.

[0003] Donkey hide gelatin solid beverage is usually made by mixing donkey hide gelatin and other effective ingredients, and then processed, mixed, granulated, dried, granulated, etc. However, the quality of donkey hide gelatin solid beverage prepared by conventional process is unstable, and the content of ferulic acid and total polysaccharide fluctuates. Summary of the invention

[0004] The main purpose of the present invention is to provide a donkey-hide gelatin solid beverage and a preparation method thereof, so as to solve the technical problems that the donkey-hide gelatin solid beverage prepared by conventional processes has unstable quality and fluctuates in ferulic acid content and total polysaccharide content.

[0005] To achieve the above object, the present invention provides a method for preparing a donkey-hide gelatin solid beverage, comprising the following steps:

[0006] Prepare the raw materials of donkey-hide gelatin solid beverage, wherein the raw materials of the donkey-hide gelatin solid beverage include, by weight, 120 parts of donkey-hide gelatin, 68 parts of polygonatum, 58 parts of wolfberry, 58 parts of astragalus, 58 parts of codonopsis, 46 parts of red dates, 22 parts of angelica, and 22 parts of orange peel.

[0007] Add 8 times the mass of water to polygonatum, wolfberry, astragalus, codonopsis, red dates, angelica and tangerine peel, soak for 0.5 h, extract for 2 h for the first time, add 6 times the mass of water for the second time to extract for 1.5 h, combine the filtrate, concentrate, and obtain a water extract concentrate.

[0008] The water extract concentrate is mixed with maltodextrin and dried to obtain an extract.

[0009] The extract and the donkey-hide gelatin are added into auxiliary materials for molding to obtain a donkey-hide gelatin solid beverage.

[0010] According to an embodiment of the present application, the step of mixing the water extract concentrate with maltodextrin and drying to obtain an extract comprises:

[0011] The water extract concentrate is mixed with maltodextrin and heated at an air inlet speed of 0.4 to 0.5 m / s. 3The extract is obtained by spray drying under the conditions of 1000 g / min, 130-140°C inlet air temperature, 7.5-10 mL / min injection speed, 0.3-0.4 MPa spray gun pressure, and 60-70°C liquid temperature. The concentration of the water extract concentrate is 0.25 g / mL, and the amount of maltodextrin added is 5.0 g / 100 mL.

[0012] According to an embodiment of the present application, the step of mixing the water extract concentrate with maltodextrin and drying to obtain an extract comprises:

[0013] The water extract concentrate is mixed with maltodextrin and heated at an inlet wind speed of 0.41 m / s. 3 The extract was obtained by spray drying under the conditions of 100 mL / min, 140°C inlet air temperature, 10 mL / min injection speed, 0.4 MPa spray gun pressure and 60°C liquid temperature.

[0014] According to an embodiment of the present application, the step of mixing the water extract concentrate with maltodextrin and drying to obtain an extract comprises:

[0015] The maltodextrin is added to the water extract concentrate, and stirred in a water bath at 80-90° C. until dissolved.

[0016] Dilute in a container, dry under reduced pressure at 65°C and -0.65MPa for 1-2 days, then lower the temperature to 55°C and continue drying for 2-3 days to obtain an extract. The relative density of the water extract concentrate is 1.23 g / cm 3 The mass of the maltodextrin is 12.5% ​​of the crude drug amount.

[0017] According to an embodiment of the present application, the step of adding the extract and the donkey-hide gelatin to auxiliary materials for molding comprises:

[0018] Ethanol is added to a mixture of extract powder obtained from extract, donkey-hide gelatin powder obtained from donkey-hide gelatin, brown sugar powder, maltodextrin and erythritol to obtain a soft material, which is then granulated. The mass ratio of the extract powder, donkey-hide gelatin powder, brown sugar powder, maltodextrin and erythritol is 5250:3620:39300:11030:800.

[0019] The obtained granules are dried and sized.

[0020] According to the implementation of the present application, after mixing the extract powder obtained from the extract, the donkey-hide gelatin powder obtained from the donkey-hide gelatin, brown sugar powder, maltodextrin and erythritol, ethanol is added to obtain a soft material, and in the step of granulation:

[0021] The granulation is carried out under the conditions of an ambient temperature of 15-25° C. and an ambient humidity of less than 50%. The amount of ethanol added is 18%-20% of the mass of the mixed material, and the concentration of ethanol is 86-88%.

[0022] According to the implementation of the present application, after mixing the extract powder obtained from the extract, the donkey-hide gelatin powder obtained from the donkey-hide gelatin, brown sugar powder, maltodextrin and erythritol, ethanol is added to obtain a soft material, and in the step of granulation:

[0023] The granulation is carried out under the conditions of an ambient temperature of less than 10° C. and an ambient humidity of less than 50%. The amount of ethanol added is 20% to 24% of the mass of the mixed material, and the concentration of the ethanol is 85 to 86%.

[0024] According to an embodiment of the present application, in the step of drying and granulating the obtained granules:

[0025] The obtained granules were dried at 55°C for 2-3 h, turning them over halfway.

[0026] The dried granules were sized into 10 mesh and then dried for 0.5 to 1.0 h.

[0027] According to an embodiment of the present application, the filtrate is concentrated under reduced pressure at a temperature of 58 to 60° C. and a vacuum degree of -0.065 MPa.

[0028] The present application also provides a donkey-hide gelatin solid beverage prepared by the above-mentioned method for preparing the donkey-hide gelatin solid beverage.

[0029] In the preparation method of the above-mentioned donkey-hide gelatin solid beverage, in the extraction step, a suitable combination of soaking time, water addition amount and extraction time is used, so that the content of ferulic acid, total polysaccharide content, hesperidin content and calycosin glucoside content in the concentrated solution are all high. On this basis, after subsequent drying and molding, the final donkey-hide gelatin solid beverage also has a high content of the above components, and the content is stable in each batch of products. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the structures shown in these drawings without paying creative work.

[0031] Figure 1 This is a chromatogram of the high performance liquid phase content determination of calycosin glucoside and hesperidin according to one embodiment of the present application;

[0032] Figure 2This is a standard curve chart for determining the content of calycosin isoflavone glucoside in the donkey-hide gelatin solid beverage according to one embodiment of the present application;

[0033] Figure 3 This is a standard curve diagram for determining the hesperidin content of donkey-hide gelatin solid beverage according to one embodiment of the present application;

[0034] Figure 4 It is a moisture absorption curve diagram of the medicinal powder and donkey-hide gelatin solid beverage according to one embodiment of the present application;

[0035] Figure 5 This is a result diagram of the critical relative humidity of the donkey-hide gelatin solid beverage according to one embodiment of the present application.

[0036] The realization of the purpose, functional features and advantages of the present invention will be further explained in conjunction with the implementation methods and with reference to the accompanying drawings. DETAILED DESCRIPTION

[0037] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0038] It should be noted that all directional indications (such as up, down, etc.) in the embodiments of the present invention are only used to explain the relative position relationship, movement status, etc. between the components under a certain specific posture (as shown in the accompanying drawings). If the specific posture changes, the directional indication will also change accordingly.

[0039] In addition, in the present invention, the descriptions of "first", "second", etc. are only used for descriptive purposes and cannot be understood as indicating or implying their relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" or "second" may explicitly or implicitly include at least one of the features.

[0040] Furthermore, the technical solutions between the various embodiments of the present invention may be combined with each other, but this must be based on the fact that they can be implemented by ordinary technicians in the field. When the combination of technical solutions is mutually contradictory or cannot be implemented, it should be deemed that such combination of technical solutions does not exist and is not within the scope of protection required by the present invention.

[0041] To achieve the above object, the present invention provides a method for preparing a donkey-hide gelatin solid beverage, comprising the following steps:

[0042] S100: preparing raw materials for donkey-hide gelatin solid beverage, wherein the raw materials for the donkey-hide gelatin solid beverage include, by mass, 120 parts of donkey-hide gelatin, 68 parts of polygonatum, 58 parts of wolfberry, 58 parts of astragalus, 58 parts of codonopsis, 46 parts of red dates, 22 parts of angelica, and 22 parts of orange peel.

[0043] The raw materials in donkey-hide gelatin solid beverage are prepared according to the principle of compatibility of monarch, minister, assistant and envoy. Among them:

[0044] Main medicine: donkey-hide gelatin (nourishes yin and replenishes blood). Assistant medicine: polygonatum, wolfberry (tonifies kidney and replenishes essence).

[0045] Auxiliary drugs: Codonopsis pilosula, Astragalus membranaceus, and red dates (tonify qi and produce blood).

[0046] Enabling drugs: Angelica sinensis, tangerine peel (Angelica sinensis: replenishes blood and activates blood circulation, tangerine peel: regulates qi and strengthens the spleen, replenishes and promotes circulation, replenishes without stagnation. Donkey-hide gelatin, Polygonatum sibiricum, and wolfberry are greasy in nature and hinder digestion. Adding Angelica sinensis and tangerine peel can prevent the above drugs from being greasy and hindering the stomach.)

[0047] Donkey-hide gelatin solid beverages use a lot of donkey-hide gelatin to nourish yin and blood, moisturize dryness and nourish the skin, and are combined with polygonatum and wolfberry to nourish the kidney and essence, improve eyesight and darken hair; dangshen and astragalus are used to nourish the spleen and lungs, replenish qi and produce blood, and red dates are used to strengthen the spleen and stomach, replenish blood and nourish the skin; angelica is added to replenish blood and activate blood circulation, and tangerine peel is added to regulate qi and strengthen the spleen, which can replenish and nourish without stagnation. The whole formula can nourish blood and nourish yin, moisturize the skin and nourish the skin. Taking it can replenish yin and blood, produce body fluids, regulate the body's defense system, and improve the complexion.

[0048] S200: Add 8 times the mass of water to polygonatum, wolfberry, astragalus, codonopsis, red dates, angelica and tangerine peel, soak for 0.5h, extract for 2h for the first time, and add 6 times the mass of water for the second time to extract for 1.5h, combine the filtrate, concentrate, and obtain a water extract concentrate.

[0049] In this step, the first extraction is performed by adding 8 times the mass of water, which is 8 times the total mass of polygonatum, wolfberry, astragalus, codonopsis, red dates, angelica and orange peel. After the first extraction, the filtrate is separated, which is the first filtrate. Referring to the first extraction, 6 times the mass of water is added to extract for 1.5 hours, and the filtrate is separated, which is the second filtrate. The first filtrate and the second filtrate are combined.

[0050] In the extraction step, the soaking time, the amount of water added, and the extraction time will affect the ferulic acid content, the hesperidin content, the total polysaccharide content and the extract yield. Therefore, the above indicators in this application are evaluation indicators, and the orthogonal test is used to optimize the extraction process, and finally the process parameters in S200 are determined.

[0051] S300: mixing the water extract concentrate with maltodextrin, and drying the mixture to obtain an extract.

[0052] In this step, drying methods include spray drying and reduced pressure drying.

[0053] Spray drying is performed by spray drying. Reduced pressure drying is performed by reduced pressure drying equipment. There are no specific requirements for the specific drying method. The drying method is selected according to the actual situation such as the equipment conditions.

[0054] S400: adding the extract and the donkey-hide gelatin into auxiliary materials for molding to obtain a donkey-hide gelatin solid beverage.

[0055] In the preparation method of the above-mentioned donkey-hide gelatin solid beverage, in the extraction step, a suitable combination of soaking time, water addition amount and extraction time is used, so that the content of ferulic acid, total polysaccharide content, hesperidin content and calycosin glucoside content in the concentrated solution are all high. On this basis, after subsequent drying and molding, the final donkey-hide gelatin solid beverage also has a high content of the above components, and the content is stable in each batch of products.

[0056] In some embodiments, the step of mixing the water extract concentrate with maltodextrin and drying to obtain an extract comprises:

[0057] The water extract concentrate is mixed with maltodextrin and heated at an air inlet speed of 0.4 to 0.5 m / s. 3 The extract is obtained by spray drying under the conditions of 1000 g / min, 130-140°C inlet air temperature, 7.5-10 mL / min injection speed, 0.3-0.4 MPa spray gun pressure, and 60-70°C liquid temperature. The concentration of the water extract concentrate is 0.25 g / mL, and the amount of maltodextrin added is 5.0 g / 100 mL.

[0058] In this embodiment, step S200 is performed by spray drying.

[0059] Preliminary experimental results show that directly spray drying the extract of donkey-hide gelatin solid beverage will cause sticking to the wall and it is impossible to obtain a dry extract powder, so it is considered to add a certain amount of auxiliary materials to the solution.

[0060] Maltodextrin, resistant dextrin, α-lactose, mannitol, soluble starch, and microcrystalline cellulose were selected as the objects of spray drying process auxiliary materials. Among them, microcrystalline cellulose is insoluble in water, and the addition will cause the injection tube to be directly blocked, so it is excluded; when mannitol is sprayed under the current conditions, a powder similar to that after hygroscopic absorption will appear on the cyclone separator, and there is no powdery solid in the collector after all the injections, which is all hygroscopic powder, so it is excluded; soluble starch is insoluble in cold water, but soluble in boiling water. Based on the existing liquid temperature of 70°C, the extract yield after spray drying is only 11%, and there is undissolved white matter at the bottom of the beaker.

[0061] Therefore, this time, maltodextrin, resistant dextrin and α-lactose were spray dried. When maltodextrin was added, the extract yield was the highest at 43.83%; after adding α-lactose, the water content was the lowest at 3.67%, but its price was higher. Therefore, maltodextrin was selected as the best auxiliary material.

[0062] The temperature of the liquid medicine can improve the viscosity of the liquid medicine to a certain extent. When the temperature of the liquid medicine is increased, the viscosity of the liquid medicine decreases. The air inlet velocity affects the separation effect of the cyclone separator and thus affects the results of spray drying. The spray gun pressure can affect the results of spray drying by affecting the particle size of the extract powder. In addition, the injection concentration, inlet temperature, and injection speed will also affect the results of spray drying, and ultimately affect the powder yield, the transfer rate of calycosin isoflavone glucoside, the transfer rate of total polysaccharides, the transfer rate of hesperidin, the water content and other indicators of donkey-hide gelatin solid beverage. Therefore, the Box-Behnken test was used to optimize the drying process and determine the optimal spray drying experimental conditions.

[0063] In some embodiments, the step of mixing the water extract concentrate with maltodextrin and drying to obtain an extract comprises:

[0064] The water extract concentrate is mixed with maltodextrin and heated at an inlet wind speed of 0.41 m / s. 3 The extract was obtained by spray drying under the conditions of 100 mL / min, 140°C inlet air temperature, 10 mL / min injection speed, 0.4 MPa spray gun pressure and 60°C liquid temperature.

[0065] The process conditions are the optimal spray drying process parameters. The average powder yield, calycosin glucoside transfer rate, hesperidin transfer rate, total polysaccharide transfer rate and moisture content were measured to be 88.48%, 69.22%, 72.22%, 60.36% and 4.17%, respectively, indicating that the process is stable and reliable.

[0066] In some embodiments, the step of mixing the water extract concentrate with maltodextrin and drying to obtain an extract comprises:

[0067] The maltodextrin is added to the water extract concentrate, and stirred in a water bath at 80-90° C. until dissolved.

[0068] Dilute in a container, dry under reduced pressure at 65°C and -0.65MPa for 1-2 days, then lower the temperature to 55°C and continue drying for 2-3 days to obtain an extract. The relative density of the water extract concentrate is 1.23 g / cm 3 The mass of the maltodextrin is 12.5% ​​of the crude drug amount.

[0069] The amount of crude drugs refers to the mass of all raw materials of donkey-hide gelatin solid beverage. Exemplarily, 1.25 kg of maltodextrin with a crude drug amount of 12.5% ​​is added to the concentrate, and stirred in a water bath at 80-90°C until dissolved. Spread thinly on a square plate with a plastic film on the bottom, dry under reduced pressure (-0.65MPa) at 65°C for 1-2 days, then lower the temperature to 55°C and continue drying for 2-3 days to prevent coking, to obtain an extract. After drying, crush the extract, take it out of the plate, bag it, weigh it, and set it aside (pay attention to moisture-proof). About 4100 g of extract was obtained, and the extract yield was about 41%.

[0070] In some embodiments, the step of adding the extract and the donkey-hide gelatin to auxiliary materials for molding comprises:

[0071] Ethanol is added to a mixture of extract powder obtained from extract, donkey-hide gelatin powder obtained from donkey-hide gelatin, brown sugar powder, maltodextrin and erythritol to obtain a soft material, which is then granulated. The mass ratio of the extract powder, donkey-hide gelatin powder, brown sugar powder, maltodextrin and erythritol is 5250:3620:39300:11030:800.

[0072] The obtained granules are dried and sized.

[0073] In some embodiments, after mixing the extract powder obtained from the extract, the donkey-hide gelatin powder obtained from the donkey-hide gelatin, brown sugar powder, maltodextrin and erythritol, ethanol is added to obtain a soft material, and in the step of granulating:

[0074] The granulation is carried out under the conditions of an ambient temperature of 15-25° C. and an ambient humidity of less than 50%. The amount of ethanol added is 18%-20% of the mass of the mixed material, and the concentration of ethanol is 86-88%.

[0075] In some embodiments, after mixing the extract powder obtained from the extract, the donkey-hide gelatin powder obtained from the donkey-hide gelatin, brown sugar powder, maltodextrin and erythritol, ethanol is added to obtain a soft material, and in the step of granulating:

[0076] The granulation is carried out under the conditions of an ambient temperature of less than 10° C. and an ambient humidity of less than 50%. The amount of ethanol added is 20% to 24% of the mass of the mixed material, and the concentration of the ethanol is 85 to 86%.

[0077] In some embodiments, during the step of drying and sizing the prepared granules:

[0078] The obtained granules were dried at 55°C for 2-3 h, turning them over halfway.

[0079] The dried granules were sized into 10 mesh and then dried for 0.5 to 1.0 h.

[0080] In some embodiments, the filtrate is concentrated under reduced pressure at a temperature of 58-60° C. and a vacuum degree of -0.065 MPa.

[0081] The present application also provides a donkey-hide gelatin solid beverage prepared by the above-mentioned method for preparing the donkey-hide gelatin solid beverage.

[0082] The technical solution of the present application is described below in conjunction with specific embodiments.

[0083] The evaluation indexes are determined as follows:

[0084] Extract yield determination: Accurately measure 10 mL of the water extract concentrate in an evaporating dish that has been dried to constant weight, and dry it at 70°C under reduced pressure to constant weight. The extract yield (%) is calculated based on the lost weight. Extract yield = (MM0) / m×100%, where M1 is the total mass of the dry extract and the evaporating dish, M0 is the net mass of the evaporating dish dried to a constant mass, and m is the amount of crude drug in 10 mL of the drug solution.

[0085] Determination of powder yield after spray drying: (total mass of powder after spray drying / total mass of material before spray drying) × 100%

[0086] Ferulic acid content determination: Prepare ferulic acid reference substance, and measure ferulic acid in water extract concentrate based on liquid chromatography. Specific chromatographic conditions:

[0087] Instrument: Agilent HPLC-UV detector (1200), ZorbaxC 18 (250mm×4.6mm.5.0μm), mobile phase: acetonitrile-0.085% phosphoric acid water = 17:83, column temperature 30°C,

[0088] The volume flow rate was 1.0 mL / min and the injection volume was 10 μL.

[0089] Determination of hesperidin content: Prepare hesperidin reference substance and measure hesperidin in water extract concentrate based on liquid chromatography. Chromatographic conditions:

[0090] Instrument: Agilent HPLC-UV detector (1200), chromatographic column: ZorbaxC 18 (250mm×4.6mm.5.0μm), acetonitrile-pure water as the mobile phase, gradient elution program, detection wavelength of 283nm, column temperature of 30℃, volume flow rate of 1.0mL / min, injection volume of 10μL.

[0091] Determination of the content of calycosin isoflavone glucoside: Prepare calycosin isoflavone glucoside reference substance, and measure the hesperidin in the water extract concentrate based on liquid chromatography. Chromatographic conditions:

[0092] Instrument: Agilent high performance liquid chromatograph-UV detector (1200), chromatographic column: Kromasil C18 (250 mm×4.6 mm.5.0 μm), mobile phase: acetonitrile-0.2% formic acid water, column temperature of 30°C, volume flow rate of 1.0 mL / min, injection volume of 10 μL, detection wavelength of 260 nm.

[0093] Determination of total polysaccharide content: D-anhydrous glucose reference substance was prepared, and the absorbance was measured at a wavelength of 492 nm using an ultraviolet spectrophotometer to obtain the total polysaccharide content in the water extract concentrate.

[0094] Example 1 Extraction process study

[0095] 1.1 Investigation of soaking time

[0096] Weigh the prescribed amount of medicinal materials, crush them into coarse powder, add 8 times the amount of water, soak for 0h, 0.5h, 1h and 2h respectively, extract for 2h for the first time, add 6 times the amount of water for the second time, extract for 1.5h, combine the two extracts, concentrate at 70℃ under reduced pressure to a crude drug concentration of 0.25g / mL, and repeat three times. The ferulic acid content, total polysaccharide content, extract yield and hesperidin content were used as evaluation indicators, and the comprehensive score was calculated by AHP-entropy weight method. The results are shown in Table 1.

[0097] 1.2 Investigation of water addition

[0098] Weigh the prescribed amount of medicinal materials, crush them into coarse powder, add 6, 8, 10 and 12 times the amount of water, soak for 0.5h, extract for 2h for the first time, add 4, 6, 8 and 10 times the amount of water for the second time, extract for 1.5h, combine the two extracts, concentrate at 70℃ under reduced pressure to a crude drug concentration of 0.25g / mL, and repeat three times. The ferulic acid content, hesperidin content, total polysaccharide content and extract yield were used as evaluation indicators, and the comprehensive score was calculated by AHP-entropy weight method. The results are shown in Table 1.

[0099] 1.3 Extraction time investigation

[0100] Weigh the prescribed amount of medicinal materials, crush them into coarse powder, add 8 (6) times the amount of water, soak for 0.5h, and extract

[0101] The extracts were concentrated at 1.0 (0.5) h, 1.5 (1.0) h, 2.0 (1.5) h and 2.5 (2.0) h, and the two extracts were combined and concentrated under reduced pressure at 70 °C to a crude drug concentration of 0.25 g / mL. The extracts were repeated three times. The ferulic acid content, hesperidin content, total polysaccharide content and extract yield were used as evaluation indicators. The comprehensive score was calculated using the AHP-entropy weight method. The results are shown in Table 1.

[0102] Table 1 Results of single factor investigation on extraction process

[0103]

[0104] 1.4 Orthogonal test to optimize the extraction process

[0105] 1.4.1 Orthogonal Experimental Design Results and Analysis

[0106] On the basis of the single factor experiment, soaking time (A), water addition (B) and extraction time (C) were selected as the investigation factors, ferulic acid content, total polysaccharide content, extract yield and hesperidin content were selected as the investigation indicators, the orthogonal method was used for experimental design, and the AHP-entropy weight method was used for comprehensive evaluation to select the best extraction process. The factor level table is shown in Table 2. The orthogonal experimental design and results of the extraction process are shown in Table 3, and the variance analysis of the extraction process is shown in Table 4.

[0107] Table 2 Extraction process orthogonal design factor level table

[0108]

[0109] Table 3 Orthogonal experimental design schedule and results of extraction process

[0110]

[0111] Table 4 Variance analysis table of orthogonal test of extraction process

[0112]

[0113] Note F 0.05(2,2) =19.0, F 0.01(2,2) =99.0

[0114] Through range analysis, it was found that the influencing factors of ferulic acid content were C>A>B, the influencing factors of total polysaccharide content were A>C>B, the influencing factors of extract yield were A>C>B, the influencing factors of hesperidin content were C>A>B, and the influencing factors of comprehensive score were A>C>B. According to the comprehensive scoring results of AHP-entropy weight method, the process with the highest score was A1B3C3, but because there was no significant difference in the levels of different factors, considering the economic cost comprehensively, the process combination A1B2C2 with a relatively high score was selected, that is: soak for 0.5h, add 10 times water to extract for 2h for the first time, add 8 times water to extract for 1.5h for the second time, combine the two extracts, and evaporate at 70℃ under reduced pressure to a crude drug concentration of 0.25g / mL to obtain the water-extracted concentrate of donkey-hide gelatin solid beverage.

[0115] 1.5 Confirmatory tests

[0116] Weigh the prescribed amount of medicinal materials, and prepare the water extract concentrate of donkey-hide gelatin solid beverage according to the optimal result A1B3C3 process. Prepare three copies in parallel, and determine the ferulic acid content, total polysaccharide content, extract yield and hesperidin content. The results are shown in Table 5. The average ferulic acid content, total polysaccharide content, extract yield and hesperidin content are 0.1947 mg / g, 0.4668 g / g, 57.48%,

[0117] 1.9916 mg / g, and the RSD values ​​were 1.45%, 1.92%, 1.53% and 2.48% respectively. It can be seen that the extraction process is stable and feasible, and can be used for the extraction process of donkey-hide gelatin solid beverage.

[0118] Table 5 Extraction process validation test

[0119]

[0120] Example 2 Spray Drying Process Study

[0121] 2.1 Single factor investigation

[0122] 2.1.1 Investigation of auxiliary materials

[0123] The results of the preliminary experiment showed that the direct spray drying of the extract of donkey-hide gelatin solid beverage would cause wall adhesion and fail to obtain dry extract powder, so it was considered to add a certain amount of auxiliary materials to the liquid medicine. Maltodextrin, resistant dextrin, α-lactose, mannitol, soluble starch, and microcrystalline cellulose were selected as the objects of spray drying process auxiliary materials. Among them, microcrystalline cellulose is insoluble in water, and the addition will cause the injection tube to be directly blocked, so it is excluded; when mannitol is sprayed under the current conditions, a powder similar to that after hygroscopic absorption will appear on the cyclone separator, and there is no powdered solid in the collector after all the injections, all of which are hygroscopic powders, so it is excluded; soluble starch is insoluble in cold water, but soluble in boiling water. Based on the existing liquid temperature of 70°C, the extract yield after spray drying is only 11%, and there is undissolved white matter at the bottom of the beaker. Therefore, the three auxiliary materials of maltodextrin, resistant dextrin and α-lactose were spray dried. After the donkey-hide gelatin solid beverage was extracted to a concentration of 0.25g / mL, 6g / 100mL of auxiliary materials were added, and the instrument parameters were set to an inlet air temperature of 130℃ and an inlet air speed of 0.5m 3 / min, the spray gun pressure was 0.5Mpa, the liquid temperature was controlled at 70℃, the sample was injected at a speed of 5mL / min, and 180mL was injected each time for spray drying. The results are shown in Table 6. When maltodextrin was added, the extract yield was the highest at 43.83%; after adding α-lactose, the water content was the lowest at 3.67%, but its price was relatively high. Therefore, maltodextrin was selected as the auxiliary material for subsequent investigation.

[0124] Table 6 Investigation of auxiliary materials

[0125]

[0126] 2.1.2 Investigation of the amount of auxiliary materials added

[0127] Different amounts of excipients added to the liquid medicine have different effects on the spray drying results. After the donkey-hide gelatin solid beverage is extracted to a concentration of 0.25 g / mL, a certain amount of maltodextrin is added, and the instrument parameters are set to an inlet air temperature of 130 °C and an inlet air speed of 0.5 m 3 / min, the spray gun pressure was 0.5Mpa, the liquid temperature was controlled at 70℃, the sample was injected at a speed of 5mL / min, and 180mL was injected each time for spray drying. The effect of the addition amount of excipients on spray drying was investigated at 0, 1, 2, 3, 4, 5, 6, 7, and 8g / 100mL. With the increase of the addition amount of excipients, the sticking condition of spray drying was significantly improved. When the addition amount of excipients was less than 4g / 100mL, the sticking state of spray drying was more serious, and the extract powder could not be collected. When the addition amount of excipients was 6g / 100mL, the extract yield was the highest at 46.50%; when the addition amount of excipients was 8g / 100mL, the water content was the lowest at 5.61%. The results are shown in Table 7. Taking the extract yield and water content as indicators, combined with the principle of reducing the addition amount of excipients, the addition amount of excipients is 6g / 100mL.

[0128] Table 7 Investigation of the amount of excipients added to the liquid medicine

[0129]

[0130] 2.1.3 Investigation of liquid temperature

[0131] The temperature of the liquid medicine can improve the viscosity of the liquid medicine to a certain extent. When the temperature of the liquid medicine is increased, the viscosity of the liquid medicine decreases. After the donkey-hide gelatin solid beverage is extracted to a concentration of 0.25g / mL, 6g / 100mL of maltodextrin is added, and the instrument parameters are set to an inlet air temperature of 130℃ and an inlet air speed of 0.5m 3 / min, the spray gun pressure was 0.5Mpa, the liquid temperature was controlled at 25, 40, 50, 60, 70℃, the sample was injected at a speed of 5mL / min, and 180mL was injected each time for spray drying. The effect of liquid temperature on spray drying was investigated. As the liquid temperature increased, its wall adhesion gradually decreased. When the liquid temperature was 70℃, its wall adhesion was improved to the greatest extent. The extract yield and water content were used as evaluation indicators, and combined with its wall adhesion state, the effect of liquid temperature on the spray drying of Ejiao Zaoqi prescription was investigated. The results are shown in Table 8. When the liquid temperature was 70℃, the extract yield was the highest at 44.23% and the water content of the extract was the lowest at 6.67%. The best liquid temperature was 70℃.

[0132] Table 8 Results of spray drying liquid temperature investigation

[0133]

[0134] 2.1.4 Investigation of air inlet speed

[0135] The inlet air speed affects the separation effect of the cyclone separator and thus the result of spray drying. After the donkey-hide gelatin solid beverage formula was extracted to a concentration of 0.25g / mL, 6g / 100mL of maltodextrin was added, and the instrument parameters were set to an inlet air temperature of 130℃ and an inlet air speed of 0.3, 0.35, 0.4, 0.45, and 0.5m 3 / min, the spray gun pressure was 0.5Mpa, the liquid temperature was controlled at 70℃, the sample was injected at a speed of 5mL / min, and 180mL was injected each time for spray drying. The effect of wind speed on spray drying was investigated. When the wind speed was 0.5m 3 / min, the extract powder does not stick to the wall. The extract yield and water content after sampling at different wind speeds are shown in Table 9. As the wind speed increases, the extract yield also increases. When the wind speed is 0.5m 3 / min is the largest, which is 44.23%; the moisture content increases with the increase of wind speed, and the wind speed is 0.3m 3 / min, the lowest moisture content is 5.38%, wind speed is 0.4m 3 / min~0.5m 3 / min, the difference in water content is not big; taking the extract yield and water content as evaluation indexes, combined with its wall adhesion state, and the inlet wind speed of 0.5m 3 / min is better.

[0136] Table 9 Investigation results of spray drying inlet air velocity

[0137]

[0138] 2.1.5 Inspection of spray gun pressure

[0139] The spray gun pressure can affect the results of spray drying by affecting the particle size of the extract powder. After the donkey-hide gelatin solid beverage is extracted to a concentration of 0.25g / mL, 6g / 100mL of maltodextrin is added, and the instrument parameters are set to an inlet air temperature of 130℃ and an inlet air speed of 0.5m 3 / min, the spray gun pressure was 0.2, 0.3, 0.4, 0.5Mpa, the liquid temperature was controlled at 70℃, the sample was injected at a speed of 5mL / min, and 180mL was injected each time for spray drying. The effect of the spray gun pressure on spray drying was investigated. The results of the spray gun pressure investigation are shown in Table 10. No obvious wall adhesion phenomenon was observed in the cyclone separator; when the spray gun pressure was 0.2Mpa, the extract yield was the highest at 47.51%; when the spray gun pressure was 0.5Mpa, the water content was the lowest at 7.06%, as shown in Table 10. Comprehensively considering the extract yield and water content indicators, the spray gun pressure was determined to be 0.4Mpa.

[0140] Table 10 Spray drying gun pressure investigation results

[0141]

[0142] 2.1.6 Injection concentration investigation

[0143] After the raw materials of donkey-hide gelatin solid beverage were extracted to concentrations of 0.33, 0.29, 0.25, 0.22, and 0.20 g / mL, 6 g / 100 mL of maltodextrin was added and the instrument parameters were set to an inlet air temperature of 130 °C and an inlet air speed of 0.5 m / s. 3 / min, the spray gun pressure was 0.5Mpa, the liquid temperature was controlled at 70℃, the sample was injected at a speed of 5mL / min, and 180mL was injected each time for spray drying. The effect of injection concentration on spray drying was investigated. The concentration of 0.33g / mL had slight wall adhesion, and the other concentrations did not stick to the wall. When the liquid concentration was 0.29g / mL, the highest extract yield was 43.04%, and the lowest water content was 5.79%. The results are shown in Table 11. Combined with the wall adhesion state and the maximum benefit, the injection concentration of 0.29g / mL is the best.

[0144] Table 11 Spray drying injection concentration investigation results

[0145]

[0146] 2.1.7 Inlet temperature investigation

[0147] After the donkey-hide gelatin solid beverage was extracted to a concentration of 0.25 g / mL, 6 g / 100 mL of maltodextrin was added, and the instrument parameters were set to inlet temperature of 130, 140, 150, 160 °C and air velocity of 0.5 m 3 / min, the spray gun pressure was 0.5Mpa, the liquid temperature was controlled at 70℃, the sample was injected at a speed of 5mL / min, and 180mL was injected each time for spray drying. The effect of inlet temperature on spray drying was investigated. When the inlet temperature was 160℃, the spray drying result was severely sticky to the wall, while the other temperatures were not sticky to the wall; when the inlet temperature was 140℃, the extract yield was the highest at 43.29% and the water content was the lowest at 4.75%. The results are shown in Table 12, so the inlet temperature was determined to be 140℃.

[0148] Table 12 Investigation results of spray drying inlet temperature

[0149]

[0150] 2.1.8 Injection speed investigation

[0151] After the donkey-hide gelatin solid beverage was extracted to a concentration of 0.25 g / mL, 6 g / 100 mL of maltodextrin was added and the instrument parameters were set to an inlet air temperature of 130 °C and an inlet air speed of 0.5 m / s. 3 / min, the spray gun pressure was 0.5Mpa, the liquid temperature was controlled at 70℃, the injection speed was 5.0, 7.5, 10.0, 12.5mL / min, and 180mL was injected each time for spray drying. The effect of injection speed on spray drying was investigated. When the injection speed was 12.5mL / min, the liquid in the spray-dried tank was not completely dried, and the other properties were good. When the injection speed was 7.5mL / min, the extract yield was the highest at 44.22%; when the injection speed was 5.0mL / min, the water content was the lowest at 5.24%. The results are shown in Table 13. Taking the extract yield and water content as evaluation indicators, combined with the wall adhesion state and maximum benefit, 10mL / min was selected as the injection speed.

[0152] Table 13 Spray drying injection speed investigation results

[0153]

[0154]

[0155] 2.2 Box-Behnken test to optimize drying process

[0156] 2.2.1Plackett-Burman design (PBD) experimental design

[0157] On the basis of the single factor investigation results, the comprehensive score Y of powder yield y1, transfer rate of calycosin isoflavone glucoside y2, transfer rate of hesperidin y3, transfer rate of total polysaccharides y4, and moisture content y5 was used as the evaluation index. The PBD experimental design was used to investigate the seven influencing factors of the spray drying process, including the concentration of crude drug in the liquid medicine X1, air inlet temperature X2, injection speed X3, amount of auxiliary materials (dextrin) added X4, air inlet speed X5, liquid temperature X6, and spray gun pressure X7. Each factor was set at the lowest (-1) and the highest (+1) levels. The subjective weights W of the five indicators of powder yield y1, transfer rate of calycosin isoflavone glucoside y2, transfer rate of hesperidin y3, transfer rate of total polysaccharides y4, and moisture content y5 were assigned by the analytic hierarchy process. AHP They are 0.3651, 0.2221, 0.2221, 0.1351, and 0.0555 respectively, and CR = 0.009 < 0.10, indicating that the weights of each indicator are consistent. The objective weight W is obtained by using the entropy weight method. 熵权 They are 0.1559, 0.1392, 0.1268, 0.3892, and 0.189 respectively. The combined weight of AHP-entropy weight method W 组合They were 0.3178, 0.1726, 0.1527, 0.2937, and 0.0586, respectively. The comprehensive score Y of the five evaluation indicators was used as the response value for factor screening. The PBD test design and results, and the variance analysis results are shown in Tables 14 and 15. The variance analysis results showed that only the injection concentration of the drug solution, the injection speed, and the inlet wind speed had a statistically significant effect on the comprehensive score value (P<0.05), so the range of the above three factors was further optimized, and the parameters of other factors were fixed according to the experimental results as follows: inlet air temperature 140℃, auxiliary material addition amount 5g / 100mL, drug solution temperature 60℃, and spray gun pressure 0.4MPa.

[0158] Table 14 Plackett-Burman test design and results

[0159]

[0160] Table 15: Analysis of variance for Plackett-Burman test

[0161]

[0162] 2.2.2 Box-Behnken (BBD) response surface design

[0163] On the basis of PBD experiment, the comprehensive score Y of powder yield y1, transfer rate of calycosin isoflavone glucoside y2, transfer rate of hesperidin y3, transfer rate of total polysaccharides y4 and water content y5 was used as evaluation index, and the Box-Behnken response surface design was applied to further optimize the three significant influencing factors of drug concentration in solution (X1), injection speed (X2) and air inlet speed (X3). Each factor was set at three levels: low (-1), medium (0) and high (+1).

[0164] The combined weight of each indicator W 组合 The comprehensive scores Y of the five evaluation indicators were used as the response value for factor screening. The BBD test design and results are shown in Table 16. The quadratic regression equation was fitted to X1, X2, and X3 using the comprehensive score Y. The regression equation was Y = 89.042-2.42X1+8.11X2+8.5675X3-7.045X1X2-2.845X1X3-5.31X2X3-12.1535X1 2 -11.3935X2 2 -16.5685X3 2. The results of variance analysis showed that the regression model P < 0.001, and the level of lack of fit was not significant (P > 0.05), indicating that the model fit was good. The injection speed (X2) and the air inlet speed (X3) had a significant effect on Y (P < 0.05), and the interaction between the factors was not significant (P > 0.05), see Table 17. Under the premise of ensuring that Y and the degree of fit were the highest, the optimal parameters of the above three factors were determined by software screening: the concentration of the crude drug in the liquid was 0.259 g / mL, the injection speed was 11.539 mL / min, and the air inlet speed was 0.412 m 3 / min, combined with the actual equipment conditions, the final determination was: the drug concentration of the liquid was 0.25g / mL, the injection speed was 10mL / min, and the air speed was 0.41m 3 / min.

[0165] Table 16 Box-Behnken test design and results

[0166]

[0167] Table 17 Box-Behnken test variance analysis

[0168]

[0169]

[0170] 2.3 Confirmatory test

[0171] In summary, the optimal spray drying process parameters are: drug concentration of 0.25g / mL, auxiliary material addition amount of 5.0g / 100mL, air inlet speed of 0.41m 3 / min, air inlet temperature 140℃, injection speed 10mL / min, spray gun pressure 0.4Mpa, liquid temperature 60℃. Three batches of verification tests were carried out according to the above optimized process, and the average powder yield, calycosin glucoside transfer rate, hesperidin transfer rate, total polysaccharide transfer rate, and water content were measured to be 88.48%, 69.22%, 72.22%, 60.36%, and 4.17%, respectively. The average comprehensive score Y value was 90.81 (n=3), which was close to the predicted value Y=90.69, indicating that the process was stable and reliable.

[0172] Embodiment 3 Research on the molding process of donkey-hide gelatin solid beverage

[0173] 3.1 Determination method of evaluation indicators

[0174] 3.1.1 Particle yield

[0175] The particle yield is the ratio of the amount of qualified particles after sorting to the amount of material input.

[0176] Particle yield (%) = (particle weight between 10 mesh and 60 mesh) / (total weight of drug powder + excipients) × 100%

[0177] 3.1.2 Forming rate

[0178] The forming rate is the ratio of the weight of qualified particles obtained after drying to the total weight of dry particles, indicating the proportion of qualified particles with a particle size between 1 and 60 mesh.

[0179] Forming rate (%) = weight of particles between 10 mesh and 60 mesh / total weight of dry particles × 100%

[0180] 3.1.3 Particle size distribution

[0181] Pass the particles through 10-mesh, 30-mesh, 50-mesh and 60-mesh sieves respectively, weigh the particles in each sieve, and calculate the distribution ratio of particles in the range of 10-mesh to 30-mesh, 30-mesh to 50-mesh and 50-mesh to 60-mesh.

[0182] 3.2 Orthogonal design to investigate the concentration and dosage of wetting agent ethanol

[0183] The comprehensive score of yield, forming rate and particle size distribution was used as the evaluation index, and the ethanol concentration and ethanol addition amount were used as the influencing factors to optimize the preparation process of donkey-hide gelatin solid beverage, so as to determine its optimal preparation process and provide a basis for its industrial production. The main factors affecting the extraction, ethanol concentration and ethanol addition, were selected as two factors, with 3 levels for each factor, and L9 (3 4 ) Orthogonal table design, factor level table is shown in Table 18, and orthogonal experimental design is shown in Table 19. Wetting agent selected 86%, 87%, 88% ethanol solution, the dosage is 10%, 12%, 14% respectively, weighed according to the prescription ratio and placed in a stainless steel basin, mixed evenly, sprayed with ethanol in small amounts in batches to make soft material, mixed until "kneaded into a ball, lightly squeezed and scattered", squeezed through a 10 mesh sieve, dried at 60 ° C, sieved through 10 and 60 mesh sieves, and comprehensively evaluated the soft material, granulation and granule properties during the granule preparation process with granule yield, forming rate and particle size distribution. The experimental results are shown in Table 20. It can be seen that the solid beverages prepared in Groups 1, 5, and 7 have good properties. In the pilot experiment, adjustments can be made within this range according to specific environmental conditions.

[0184] Table 18 Factor level table

[0185]

[0186] Table 19 Orthogonal experimental design

[0187]

[0188] Table 20 Investigation results of mixed ethanol dosage and concentration

[0189]

[0190]

[0191] Example 4 Pilot stage

[0192] 4.1. Prescription: 2.05kg of polygonatum, 1.66kg of astragalus, 1.75kg of codonopsis, 1.75kg of wolfberry, 1.39kg of red dates, 0.66kg of tangerine peel, and 0.57kg of angelica, a total of 10.0kg.

[0193] 4.2. Preparation process

[0194] 4.2.1 Extraction and concentration process

[0195] Weigh according to the prescription ratio, add 8 times the amount of water (80kg) to 10kg of the slices and soak for 0.5h, then heat with hot steam until slightly boiling and start timing, the first extraction is 2h; the second extraction is 6 times the amount of water (60kg) for 1.5h, and the two extractions are combined after filtering with 100 mesh double-layer gauze to obtain a water extract. Heat the above water extract with hot steam, control the temperature at 58-60℃ and concentrate under reduced pressure (vacuum degree -0.065MPa) to a crude drug concentration of about 0.25g / ml (relative density 1.23g / cm 3 To obtain the concentrated solution.

[0196] 4.2.2 Drying process

[0197] Combined with the existing production conditions of the enterprise, it was finally determined that the drying method was to use vacuum drying. 1.25 kg of maltodextrin with a crude drug content of 12.5% ​​was added to the concentrate, and stirred in a water bath at 80-90°C until dissolved. Spread thinly on a square plate with a plastic film on the bottom, dry at 65°C under reduced pressure (-0.65MPa) for 1-2 days, then lower the temperature to 55°C and continue drying for 2-3 days to prevent coking, and obtain the extract. After drying, the extract was crushed, taken out of the plate, bagged, weighed, and set aside (pay attention to moisture-proof). About 4100 g of extract was collected, and the extract yield was about 41%.

[0198] 4.2.3 Molding process

[0199] Based on the company's original process and laboratory experimental results, the material input amount was determined to be: 5250g extract powder (including 1150kg maltodextrin), 3620g donkey-hide gelatin powder, 39300g brown sugar powder, 11030g maltodextrin, 800g erythritol, and the total weight of molding process materials is 60kg.

[0200] 4.2.3.1 Granulation

[0201] Pilot studies have shown that the temperature and humidity of different production environments have a great influence on the properties of the material during granulation, so the concentration and dosage of the wetting agent are different. When the temperature is low, the material is not sticky enough, and the product is not easy to agglomerate into granules. Low concentration of ethanol is required for granulation, and the dosage of ethanol needs to be increased; when the temperature is high, the material is easy to become sticky due to heat, adsorbed into clumps, and ethanol is easy to volatilize. The concentration of ethanol used for granulation needs to be increased and the dosage needs to be reduced.

[0202] Therefore, it is recommended to turn on the air conditioner and dehumidifier in advance during production, and control the temperature at 15-25℃, and the humidity is preferably <50%. If the temperature of the production environment is difficult to control in winter, it is recommended to make appropriate adjustments according to the range in Table 21. (Note: In winter, even if the ambient temperature shows a certain temperature, the overall temperature of the materials may not reach the corresponding temperature due to the large amount of materials and material accumulation.)

[0203] Table 21 Alcohol concentration and dosage for wet granulation

[0204]

[0205] 4.2.3.2 Drying and granulation

[0206] The obtained granules are evenly spread on an iron plate, placed in an oven, and dried at 55°C for 2-3 hours, turning over several times in the middle. The dried granules are placed in a swing granulator for 10-mesh granulation, and the granules are further dried for 0.5-1.0 hours. The granules after granulation and drying are weighed, and the yield is calculated. The yield of the granules is measured to be in the range of 95-98%.

[0207] Example 5 Determination of the content of donkey-hide gelatin solid beverage

[0208] The donkey-hide gelatin solid beverage prepared in Example 4 was tested for its calycosin glucoside content, hesperidin content, nitrogen content, hygroscopicity of the solid beverage, and critical relative humidity content.

[0209] 5.1 Study on the Determination Method of the Content of Calycosin Glucoside and Hesperidin

[0210] 5.1.1 Chromatographic conditions

[0211] Instrument: Agilent high performance liquid chromatograph-UV detector (1200), chromatographic column: Kromasil C18 (250 mm×4.6 mm.5.0 μm), mobile phase: acetonitrile-0.2% formic acid water, column temperature of 30°C, volume flow rate of 1.0 mL / min, injection volume of 10 μL, detection wavelength of 260 nm, gradient elution program see Table 22.

[0212] Table 22 Gradient elution program and detection wavelength program

[0213]

[0214] 5.1.2 Preparation of test solution

[0215] Weigh 5.0 g of donkey-hide gelatin solid beverage into a stoppered conical flask, add 30 mL of methanol, stopper it, accurately weigh it, ultrasonicate it for 45 minutes, make up the lost weight with methanol, and pass it through a membrane to obtain it.

[0216] 5.1.3 Preparation of mixed reference solution

[0217] Accurately weigh a certain amount of calycosin glucoside and hesperidin, add methanol to make up to 100 mL, and obtain 47.2 μg / mL and 130.8 μg / mL of calycosin glucoside and hesperidin mixed reference solutions.

[0218] 5.1.4 Preparation of negative sample solution

[0219] Weigh the medicinal materials lacking astragalus and tangerine peel according to the prescribed amount, prepare the negative sample granules lacking astragalus and tangerine peel according to the test sample preparation method, take 5.0 g of the negative sample granules into a stoppered conical bottle, prepare the negative sample solution according to the test sample preparation method, and obtain the negative sample solution lacking astragalus and the negative sample solution lacking tangerine peel.

[0220] 5.1.5 Specificity inspection

[0221] Accurately pipette the mixed reference solution of calycosin glucoside and hesperidin, the test solution and the negative sample solution, and inject under the above chromatographic conditions. The separation degree of calycosin glucoside and hesperidin is good (greater than 1.5), the theoretical plate number is not less than 4000, and there is no interference with the negative. The results are shown in Figure 1 .

[0222] Figure 1 This is a chromatogram of the HPLC content determination of calycosin isoflavone glucoside and hesperidin; wherein, A. calycosin isoflavone glucoside and hesperidin mixed reference substance; B. donkey-hide gelatin solid beverage test sample; C. negative sample lacking astragalus; D. negative sample lacking tangerine peel; 1. calycosin isoflavone glucoside; 2. hesperidin.

[0223] 5.1.6 Linear Investigation

[0224] Take the mixed reference of calycosin glucoside and hesperidin, add methanol to dilute to the concentration of calycosin glucoside is 4.72, 9.44, 18.88, 28.32, 37.76, 47.20μg / mL, hesperidin concentration is 13.08, 26.16, 52.32, 78.48, 104.64, 130.80μg / mL. Each concentration is injected twice in parallel according to the chromatographic conditions, and the regression equation of the peak area and concentration of calycosin glucoside and hesperidin is: Y = 13.105X, R 2=0.9991; Y = 4.7523X, R 2 =0.9993. It can be seen that the linear relationship between the peak area and the calycosin glucoside and hesperidin is good within a certain concentration range. The results are shown in Table 23. Figure 2 and Figure 3 .

[0225] Table 23 Investigation of the linear relationship between calycosin glucoside and hesperidin

[0226]

[0227] 5.1.7 Assay

[0228] 5.0 g of three different batches of donkey-hide gelatin solid beverage were weighed into a stoppered conical flask, 30 mL of methanol was added, the flask was sealed, and accurate weighing was performed. After ultrasonication for 45 min, methanol was used to make up the lost weight, the flask was passed through a membrane, and the samples were tested according to chromatographic conditions to determine the contents of calycosin glucoside and hesperidin. The results are shown in Table 24.

[0229] Table 24 Determination of the contents of calycosin glucoside and hesperidin in three batches of donkey-hide gelatin solid beverages

[0230]

[0231] 5.2 Determination of nitrogen content in donkey-hide gelatin solid beverage

[0232] The nitrogen content in donkey-hide gelatin solid beverage was determined by Kjeldahl method, and a method for determining the nitrogen content was established.

[0233] 5.2.1 Solution preparation

[0234] 5.2.1.1 Sodium hydroxide solution

[0235] Weigh an appropriate amount of sodium hydroxide solid powder into a beaker, add purified water to dissolve, cool to room temperature, and dilute to volume in a 1000mL volumetric flask to obtain a 0.4g / mL sodium hydroxide solution.

[0236] 5.2.1.2 Methyl red and bromocresol green mixed indicator solution

[0237] Weigh 0.1 g of methyl red and bromocresol green solid powders respectively into two 100 mL volumetric flasks, add appropriate amount of 95% ethanol to dissolve and make up to volume, mix methyl red and bromocresol green solution in a ratio of 1:5 as a mixed indicator.

[0238] 5.2.1.3 Boric acid solution

[0239] Weigh 20.00 g of boric acid, dissolve it in purified water and dilute it to a 1000 mL volumetric flask, add 10 mL of mixed indicator to adjust the pH so that the solution turns light purple, shake well, and transfer to a reagent bottle.

[0240] 5.2.1.4 Preparation of standard titrated acid solution

[0241] Take 2.08 mL of 12 mol / L hydrochloric acid (mass fraction 36-38%) and dilute to a 250 mL volumetric flask to obtain a 0.1 mol / L standard titrated acid solution.

[0242] 5.2.2 Digestion

[0243] Weigh 1.00 g of the sample into a digestive tube, add 10 g of potassium sulfate and 0.5 g of copper sulfate powder in sequence, then slowly add 20 mL of concentrated sulfuric acid along the wall of the Kjeldahl flask, place a small funnel at the mouth of the Kjeldahl flask and tilt the flask at 45 degrees, slowly heat with direct fire to keep the temperature of the solution below the boiling point, wait for the solution to stop bubbling, heat strongly to boiling, and when the solution turns clear green, continue heating for 30 minutes and let cool.

[0244] 5.2.3 Semi-automatic Kjeldahl nitrogen analyzer reaction conditions

[0245] After the digestion tube has cooled, the sample rack was placed in the sampler of the semi-automatic Kjeldahl nitrogen analyzer, and 10 mL of dilution water, 30 mL of boric acid, 80 mL of alkali, 5 min of distillation time, and 10 mL of elution water were input.

[0246] 5.2.4 Titration

[0247] After the reaction is completed, the receiving bottle is taken out and titrated with standard titrating acid (0.1 mol / L) until the blue color disappears.

[0248] 5.2.5 Calculation

[0249]

[0250] Where W(N) is the nitrogen content (%), V is the standard acid consumption of the sample, unit is mL, V0 is the standard titration acid consumption of the blank sample (10 g potassium sulfate, 0.5 g copper sulfate powder), unit is mL; m is the sample mass.

[0251] 5.2.6 Precision test

[0252] Weigh six portions of sample granules from the same batch, each weighing 1 g, and determine the nitrogen content according to the above method. Calculate the average nitrogen content and RSD value. The results are shown in Table 25. The average nitrogen content of the granules is 8.86 mg / g, and the RSD value of the content is 1.29%.

[0253] Table 25 Investigation on the precision of nitrogen content determination

[0254]

[0255] 5.2.7 Sample recovery test

[0256] Accurately weigh 0.5 g of high-grade pure ammonium sulfate reagent, add 0.5 g of sample particles, and determine the nitrogen content according to the above method, with 6 replicates. The average sample recovery and RSD results are shown in Table 26. The average sample recovery is 99.82% and the RSD value is 1.14%.

[0257] Table 26 Nitrogen content determination sample recovery test

[0258]

[0259] 5.2.8 Content determination

[0260] Weigh 10g of potassium sulfate and 0.5g of copper sulfate powder as blank samples, and measure the standard acid consumption of the blank sample to be 0.1mL. Weigh 1g of donkey-hide gelatin solid beverage as the test sample, and make three replicates. Then weigh 1.0g of negative granules without donkey-hide gelatin. Place the above samples in Kjeldahl flasks respectively, and slowly add 20mL of sulfuric acid along the wall. After digestion, perform Kjeldahl nitrogen analyzer reaction. The results of determination according to the above method are shown in Table 27. The nitrogen content of the negative sample granules without donkey-hide gelatin is 0.96mg / g, the average nitrogen content of the test sample granules is 8.85mg / g, and the RSD value of the three batches of test samples is 2.28%.

[0261] Table 27 Determination of nitrogen content in negative samples of donkey-hide gelatin and three batches of test products

[0262]

[0263] 5.3 Determination of hygroscopicity of donkey-hide gelatin solid beverage

[0264] 5.3.1 Constant weight of weighing bottle

[0265] Take 6 weighing bottles (40×25 specifications), number them, place them at 105℃ to dry for 5h, cool them in a desiccator for 30min, weigh them quickly, dry them for another hour, cool them in a desiccator for 30min, weigh them again, until constant weight is reached (the difference between two consecutive drying masses shall not exceed 0.0003g).

[0266] 5.3.2 Constant weight of the test sample

[0267] Weigh appropriate amounts of powder and granules respectively and place them in two large weighing bottles. Dry them in a phosphorus pentoxide desiccator for 72 hours. Take them out and weigh them accurately. Dry them for another 24 hours and weigh them accurately again until constant weight is achieved.

[0268] 5.3.3 75% relative humidity environment manufacturing

[0269] Take a desiccator, add the prepared supersaturated sodium chloride solution (weigh 100g of sodium chloride solution and dissolve it in 200mL of water), cover it, and place it in a constant temperature incubator at 25°C for 24 hours. At this time, the relative humidity in the desiccator is 75%.

[0270] 5.3.4 Determination of hygroscopicity

[0271] Place 2 g of ungranulated drug powder or granules with a thickness of about 2 mm at the bottom of a weighing bottle (40×25 specification) with constant weight. Prepare 3 parallel portions, weigh them accurately (contents + weighing bottle), place them in a glass desiccator (with the weighing bottle lid open), and store them at 25°C. Weigh them at 0, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, and 156 h, respectively, and record the data. The results are shown in Table 28. Calculate the moisture absorption percentage using the formula: Moisture absorption percentage = (measured weight - initial weight) / initial weight * 100%, and plot the moisture absorption percentage against time. The results are shown in Figure 4 At 156 h, the moisture absorption rates of the powder and granules were 26.28% and 23.28%, respectively, indicating that the moisture absorption rate can be effectively reduced by granulation.

[0272] Table 28 Hygroscopicity of medicinal powder and donkey-hide gelatin solid beverage

[0273]

[0274] 5.4 Determination of critical relative humidity of donkey-hide gelatin solid beverage

[0275] Water-soluble drugs have different hygroscopicity in different humidity environments. When the drug is in a low relative humidity environment, the hygroscopicity is small and almost non-hygroscopic. As the humidity of the environment in which the drug is located continues to increase, when it reaches a certain value, the hygroscopicity increases sharply. The humidity at which the hygroscopicity of the drug increases sharply is called the critical relative humidity. The critical relative humidity can provide a theoretical basis for the control of humidity in the production, transportation, and storage of drugs.

[0276] 5.4.1 Constant weight of weighing bottle

[0277] Take 21 weighing bottles (25×25 specifications), number them, place them at 105℃ to dry for 5 hours, cool them in a desiccator for 30 minutes, weigh them quickly, dry them for another hour, cool them in a desiccator for 30 minutes, and weigh them again until constant weight is reached (the difference between two consecutive drying masses shall not exceed 0.0003g).

[0278] 5.4.2 Constant weight of the test article

[0279] Take an appropriate amount of granules and place them in a large weighing bottle. Put it into a phosphorus pentoxide desiccator and dry it for 72 hours. Take it out and weigh it accurately. Dry it for another 24 hours and weigh it accurately until the weight is constant.

[0280] 5.4.3 Creating different relative humidity environments

[0281] Take 7 desiccators, add sufficient amount of potassium acetate, magnesium chloride, potassium carbonate, sodium bromide, sodium chloride, potassium chloride and potassium nitrate in turn, add water to dissolve to make them all supersaturated solutions, seal them, and put them in a 25°C constant temperature incubator for 24 hours. At this time, the relative humidity of the corresponding desiccators is 22.50%, 32.80%, 43.20%, 57.60%, 75.30%, 84.30% and 93.60% in turn.

[0282] 5.4.4 Determination of hygroscopicity

[0283] Put about 0.5g of 2mm thick particles at the bottom of a weighing bottle (25×25 specification) that has been weighed to a constant weight, and place them in 21 parallel portions. Open the cover and place them in a dryer under different relative humidity conditions, and place them in a 25℃ constant temperature incubator for 7 days. Then weigh them accurately. The results are shown in Table 29. The moisture absorption percentage is calculated using the formula: moisture absorption percentage = (measured weight - initial weight) / initial weight * 100%. A curve is drawn from relative humidity - moisture absorption percentage, and two tangent lines are drawn. The intersection of the two tangent lines is the critical relative humidity (CRH), and the value is calculated by Figure 5 It can be seen that the critical relative humidity of particles is about 68%.

[0284] Table 29 Hygroscopicity of donkey-hide gelatin solid beverage at different humidity

[0285]

[0286] The above technical solutions of the present invention are only preferred embodiments of the present invention, and the patent scope of the present invention is not limited thereto. All equivalent structural changes made by using the contents of the present invention specification and drawings under the technical concept of the present invention, or directly / indirectly applied in other related technical fields are included in the patent protection scope of the present invention.

Claims

1. A method for preparing donkey-hide gelatin solid beverage, characterized in that: The following steps are involved: Prepare raw materials for donkey-hide gelatin solid beverage; wherein the raw materials of the donkey-hide gelatin solid beverage include, by mass, 120 parts of donkey-hide gelatin, 68 parts of polygonatum, 58 parts of wolfberry, 58 parts of astragalus, 58 parts of codonopsis, 46 parts of red dates, 22 parts of angelica, and 22 parts of tangerine peel; Add 8 times the mass of water to polygonatum, wolfberry, astragalus, codonopsis, red dates, angelica and tangerine peel, soak for 0.5h, extract for 2h for the first time, add 6 times the mass of water for the second time to extract for 1.5h, combine the filtrate, concentrate, and obtain a water extract concentrate; The water extract concentrate is mixed with maltodextrin and dried to obtain an extract; The extract and the donkey-hide gelatin are added into auxiliary materials for molding to obtain a donkey-hide gelatin solid beverage.

2. The method for preparing the donkey-hide gelatin solid beverage according to claim 1, characterized in that: The step of mixing the water extract concentrate with maltodextrin and drying to obtain an extract comprises: The water extract concentrate is mixed with maltodextrin and heated at an air inlet speed of 0.4 to 0.5 m / s. 3 / min, inlet air temperature 130-140°C, injection speed 7.5-10mL / min, spray gun pressure 0.3-0.4Mpa, and liquid temperature 60-70°C to obtain the extract; wherein the concentration of the water extract concentrate is 0.25g / mL, and the amount of maltodextrin added is 5.0g / 100mL.

3. The method for preparing the donkey-hide gelatin solid beverage according to claim 2, characterized in that: The step of mixing the water extract concentrate with maltodextrin and drying to obtain an extract comprises: The water extract concentrate is mixed with maltodextrin and heated at an inlet wind speed of 0.41 m / s. 3 The extract was obtained by spray drying under the following conditions: 1.5 mL / min, 2.5 mL / min air inlet temperature, 140°C sample injection speed, 10 mL / min spray gun pressure, 0.4 MPa, and liquid medicine temperature of 60°C.

4. The method for preparing the donkey-hide gelatin solid beverage according to claim 1, characterized in that: The step of mixing the water extract concentrate with maltodextrin and drying to obtain an extract comprises: Adding the maltodextrin to the water extract concentrate, stirring in a water bath at 80-90° C. until dissolved; Dilute in a container, dry under reduced pressure at 65°C and -0.65MPa for 1 to 2 days, then lower the temperature to 55°C and continue drying for 2 to 3 days to obtain an extract; wherein the relative density of the water extract concentrate is 1.23 g / cm 3 The mass of the maltodextrin is 12.5% ​​of the crude drug amount.

5. The method for preparing donkey-hide gelatin solid beverage according to claim 1, characterized in that: The step of adding the extract and the donkey-hide gelatin into auxiliary materials for molding comprises: Add ethanol to a mixture of extract powder obtained from extract, donkey-hide gelatin powder obtained from donkey-hide gelatin, brown sugar powder, maltodextrin and erythritol to obtain a soft material, and granulate the mixture; the mass ratio of the extract powder, donkey-hide gelatin powder, brown sugar powder, maltodextrin and erythritol is 5250:3620:39300:11030:800; The obtained granules are dried and sized.

6. The method for preparing the donkey-hide gelatin solid beverage according to claim 5, characterized in that: After mixing the extract powder obtained from the extract, the donkey-hide gelatin powder obtained from the donkey-hide gelatin, brown sugar powder, maltodextrin and erythritol, ethanol is added to obtain a soft material, and granulation is performed: The granulation is carried out under the conditions of an ambient temperature of 15-25° C. and an ambient humidity of less than 50%. The amount of ethanol added is 18%-20% of the mass of the mixed material, and the concentration of ethanol is 86-88%.

7. The method for preparing donkey-hide gelatin solid beverage according to claim 5, characterized in that: After mixing the extract powder obtained from the extract, the donkey-hide gelatin powder obtained from the donkey-hide gelatin, brown sugar powder, maltodextrin and erythritol, ethanol is added to obtain a soft material, and granulation is performed: The granulation is carried out under the conditions of an ambient temperature of less than 10° C. and an ambient humidity of less than 50%. The amount of ethanol added is 20% to 24% of the mass of the mixed material, and the concentration of the ethanol is 85 to 86%.

8. The method for preparing donkey-hide gelatin solid beverage according to claim 5, characterized in that: In the step of drying and granulating the obtained granules: Dry the obtained granules at 55°C for 2-3h, turning them over halfway; The dried granules were sized into 10 mesh and then dried for 0.5 to 1.0 h.

9. The method for preparing donkey-hide gelatin solid beverage according to claim 5, characterized in that: The filtrate is concentrated under reduced pressure at a temperature of 58-60° C. and a vacuum degree of -0.065 MPa.

10. A donkey-hide gelatin solid beverage prepared by the method for preparing the donkey-hide gelatin solid beverage according to any one of claims 1 to 8.

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