A wild ginseng freeze-dried powder and deer product extract composite paste pill preparation and a preparation method thereof

Abstract

This invention relates to the field of nutritional food and ointment / pill formulation technology, and discloses a compound ointment / pill formulation of wild ginseng freeze-dried powder and deer product extract, and its preparation method. The formulation includes wild ginseng freeze-dried powder, deer product extract composed of enzymatic hydrolysis extracts of deer antler and deer blood, β-cyclodextrin, soybean lecithin, honey, isomaltooligosaccharide syrup, maltitol, glycerol, and ascorbic acid; the deer product extract contains at least 65% polypeptides with a mass of 500–3000 Da. The preparation employs vacuum freeze-drying of wild ginseng, compound enzymatic hydrolysis and membrane fractionation of deer products, cyclodextrin-phospholipid synergistic inclusion, vacuum low-temperature concentration of the ointment / pill matrix, and low-temperature pelleting. This invention can reduce the loss of heat-sensitive components, improve the degree of polypeptide fractionation, material dispersion uniformity, and storage stability.

Description

Technical Field

[0001] This invention relates to the field of nutritional food and ointment / pill preparation technology, specifically to a compound ointment / pill preparation of wild ginseng freeze-dried powder and deer product extract and its preparation method. Background Technology

[0002] Wild ginseng contains various substances such as ginsenosides, polysaccharides, amino acids, and volatile components. However, some components of wild ginseng are quite sensitive to temperature, oxygen, and moisture. Traditional ginseng products are usually processed by slicing and drying, decocting and concentrating, or directly pulverizing. Prolonged heating can easily lead to the loss of heat-sensitive components. Ordinary pulverization results in larger particle sizes, which can easily cause uneven dispersion of raw materials inside the paste or pill, a rough texture, and unstable release rates of active ingredients.

[0003] Deer products such as deer antler and deer blood contain proteins, polypeptides, amino acids, and minerals. Current deer product processing methods typically involve boiling, alcohol extraction, or single enzymatic hydrolysis to obtain extracts. These methods suffer from problems such as incomplete protein hydrolysis, a wide molecular weight distribution of the resulting polypeptides, a pronounced fishy odor, and insufficient compatibility with plant-based powders. In particular, when deer product extracts are directly mixed with pastes such as ginseng powder and honey, hydrophilic polypeptides are prone to aggregation, sedimentation, or localized enrichment with hydrophobic or poorly soluble ginseng components.

[0004] Existing compound ointments typically use honey, syrup, or sugar alcohol as a binding matrix, directly mixing various powders or extracts before forming the pills. While this method is simple, the preparation process often involves high-temperature boiling and concentration, which can easily lead to the loss of heat-sensitive components in wild ginseng and deer product extracts. Furthermore, moisture migration within the ointments can cause problems during storage, such as surface dampness, internal hardening, pill adhesion, or decreased microbial stability.

[0005] In addition, existing technologies lack coordinated control over the specific raw material composition, enzymatic hydrolysis conditions, target polypeptide molecular weight, wild ginseng freeze-drying conditions, and moisture and water activity after pill formation of deer product extracts, making it difficult to simultaneously ensure the retention rate of active ingredients, uniform dispersion of raw materials, pill formation and storage stability.

[0006] Therefore, it is necessary to provide a compound paste pill formulation of wild ginseng freeze-dried powder and deer product extract and its preparation method. Through low-temperature freeze-drying and pulverization, compound enzymatic hydrolysis, membrane classification, inclusion dispersion and low-temperature pill forming process, the wild ginseng freeze-dried powder and deer product small molecule peptide extract are uniformly compounded, and the water content and water activity of the paste pill are controlled, thereby improving the component stability, dispersion uniformity and storage stability of the compound paste pill. Summary of the Invention

[0007] In order to overcome the shortcomings of the prior art, the present invention aims to provide a compound ointment preparation of wild ginseng freeze-dried powder and deer product extract with high active ingredient retention rate, uniform material dispersion and stable storage, and the preparation method thereof.

[0008] To achieve the above objectives, the present invention provides the following technical solution: a compound paste / pill preparation of wild ginseng freeze-dried powder and deer product extract, comprising the following raw materials by weight:

[0009] Wild ginseng freeze-dried powder 6-12 parts, deer product extract 10-20 parts, β-cyclodextrin 2-5 parts, soybean lecithin 0.5-2 parts, honey 25-40 parts, isomaltooligosaccharide syrup 10-25 parts, maltitol 4-12 parts, glycerin 1-4 parts, and ascorbic acid 0.05-0.20 parts;

[0010] The deer product extract is composed of deer antler enzymatic hydrolysis extract and deer blood enzymatic hydrolysis extract, and the polypeptides with a molecular weight of 500-3000 Da account for more than 65% of the total mass of polypeptides in the deer product extract.

[0011] The compound ointment preparation has a water content of 6% to 12% and a water activity of 0.45 to 0.65.

[0012] Furthermore, the mass ratio of the deer antler enzymatic hydrolysate to the deer blood enzymatic hydrolysate is 1:0.3 to 0.8, and the total peptide content of the deer product extract on a dry basis is not less than 70%.

[0013] Furthermore, the honey, isomaltooligosaccharide syrup, maltitol, and glycerin together constitute the ointment matrix, and the soluble solids content of the ointment matrix before mixing with the freeze-dried wild ginseng powder and deer product extract is 78% to 84%.

[0014] Furthermore, it includes the following steps:

[0015] S1. After cleaning, slicing and pre-freezing the wild ginseng, vacuum freeze-dry it and then pulverize it under the condition that the material temperature does not exceed 15℃ to obtain freeze-dried wild ginseng powder.

[0016] S2. Add water to deer antler raw material and deer blood raw material to prepare raw material solution, and enzymatically hydrolyze them with neutral protease and papain in sequence. After inactivating the enzyme and separating the solid and liquid in the obtained enzymatic hydrolysate, ultrafiltration and nanofiltration are performed in sequence to collect polypeptide components with molecular weight of 500-3000 Da. After concentration and freeze drying, deer antler enzymatic hydrolysate extract and deer blood enzymatic hydrolysate extract are obtained respectively. Mix the two to obtain deer product extract.

[0017] S3. Add β-cyclodextrin to water to prepare an inclusion solution, add soybean lecithin for shear dispersion, then add wild ginseng freeze-dried powder, deer product extract and ascorbic acid, and homogenize and include under vacuum conditions to obtain composite active material.

[0018] S4. Mix honey, isomaltooligosaccharide syrup, maltitol and glycerin, and concentrate them at low temperature under vacuum to obtain the ointment matrix.

[0019] S5. Cool the paste matrix to no higher than 45°C, add the composite active material, and then perform vacuum mixing, pelleting and low-temperature drying to obtain the composite paste preparation of wild ginseng freeze-dried powder and deer product extract.

[0020] Further, in step S1, the wild ginseng is cut into thin slices with a thickness of 1-3 mm, pre-frozen at -45 to -35°C for 4-8 hours, and then freeze-dried under vacuum conditions of 20-80 Pa. The vacuum freeze-drying process includes sublimation drying at -25 to -15°C, desorption drying at -10 to 5°C, and final drying at 15 to 25°C until the moisture content of the wild ginseng is no higher than 5%.

[0021] Further, in step S2, water of 8 to 15 times the weight of the raw materials is added to the raw materials of deer antler and deer blood respectively, the pH is adjusted to 6.5 to 7.5, and neutral protease is added first at 45 to 55°C for 1 to 3 hours of enzymatic hydrolysis, and then papain is added for 1 to 3 hours of enzymatic hydrolysis.

[0022] The amount of neutral protease added is 1500-3000 U / g of raw material, and the amount of papain added is 500-1500 U / g of raw material;

[0023] After enzymatic hydrolysis, the enzyme is inactivated at 85–95°C for 10–20 min. The enzymatic hydrolysate obtained from solid-liquid separation is passed through an ultrafiltration membrane with a molecular weight cutoff of 3000 Da to collect the ultrafiltration permeate. The ultrafiltration permeate is then passed through a nanofiltration membrane with a molecular weight cutoff of 500 Da to collect the nanofiltration retentate.

[0024] Further, in step S3, the mass concentration of β-cyclodextrin in the inclusion solution is 10% to 25%. After adding soybean lecithin, it is sheared and dispersed at 6000 to 10000 r / min for 5 to 15 min. After adding wild ginseng freeze-dried powder, deer product extract and ascorbic acid, it is homogenized and included for 15 to 40 min at a temperature of 35 to 45°C and a vacuum degree of -0.06 to -0.09 MPa.

[0025] Further, in step S4, the vacuum low-temperature concentration temperature is 50-65°C until the soluble solids content of the obtained ointment matrix is ​​78%-84%.

[0026] In step S5, the mixture is kneaded for 10 to 30 minutes under a vacuum of -0.06 to -0.09 MPa. The kneaded material is then made into pills with a single pill weight of 1 to 5 g and dried at 35 to 45°C until the moisture content is 6% to 12% and the water activity is 0.45 to 0.65.

[0027] Compared with the prior art, the present invention has the following beneficial technical effects:

[0028] This invention employs vacuum freeze-drying and low-temperature pulverization to process wild ginseng, avoiding the loss of ginsenosides and other heat-sensitive components caused by prolonged high-temperature drying. Neutral protease and papain are used to sequentially enzymatically hydrolyze deer antler and deer blood, and the extract is then directionally fractionated using a 3000Da ultrafiltration membrane and a 500Da nanofiltration membrane. This ensures that the polypeptides in the deer product extract are mainly concentrated in the 500-3000Da range, which helps reduce the residue of large molecular proteins and the fishy smell of the raw materials.

[0029] This invention utilizes the inclusion effect of β-cyclodextrin and the interfacial dispersion effect of soybean lecithin to synergistically disperse wild ginseng freeze-dried powder and deer product extract, reducing the aggregation and local enrichment of composite active materials in high-viscosity paste matrix, and improving the uniformity of active ingredient content among different pastes.

[0030] This invention uses vacuum low-temperature concentration, low-temperature mixing, and water activity control to produce ointments with suitable flexibility and hardness, and reduces moisture absorption, adhesion, hardening, and attenuation of active ingredients during storage, thereby improving the forming quality and storage stability of the ointments. Detailed Implementation

[0031] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention are described clearly and completely. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0032] The β-cyclodextrin used in the following examples is CAVAMAX® W7FOOD type food-grade β-cyclodextrin, manufactured by Wacker Chemie AG, Germany; the soybean lecithin is Yelkin® TS type food-grade soybean lecithin, product code 700160, manufactured by Archer Daniels Midland Company (ADM); the neutral protease is Neutrase® type food-grade neutral protease with an enzyme activity of 0.8 AU-N / g, manufactured by Novonesis A / S; the papain is food-grade papain, conforming to GB1886.174 requirements, manufactured by Sunson Enzymes; the isomaltooligosaccharide syrup is IMO-50 type syrup, manufactured by Baolingbao Biotechnology Co., Ltd.; the maltitol is SWEETPEARL® P200 type, manufactured by Roquette Frères; and the ascorbic acid is Quali®-C type food-grade L-ascorbic acid, manufactured by dsm-firmenich.

[0033] Example 1

[0034] The ingredients are prepared as follows: 1 part by weight = 10g, consisting of 6 parts of freeze-dried wild ginseng powder, 10 parts of deer product extract, 2 parts of β-cyclodextrin, 0.5 parts of soybean lecithin, 25 parts of honey, 10 parts of isomaltooligosaccharide syrup, 4 parts of maltitol, 1 part of glycerin and 0.05 parts of ascorbic acid.

[0035] S1. After cleaning the wild ginseng, cut it into thin slices with a thickness of 1 mm, pre-freeze it at -45℃ for 4 hours, and then successively sublimate it at -25℃ for 8 hours, desorption it at -10℃ for 4 hours, and finally dry it at 15℃ for 2 hours under a vacuum of 20 Pa. Then, pulverize it under the condition that the material temperature does not exceed 15℃ to obtain freeze-dried wild ginseng powder with a moisture content of 4.3% and a particle size D90 of 38.6 μm.

[0036] S2. Take 100g each of deer antler raw material and deer blood raw material, add 800g of water to each, adjust the pH to 6.5, add 1500U / g of neutral protease of raw material at 45℃ for 1h, then add 500U / g of papain of raw material for 1h, inactivate enzyme at 85℃ for 10min, centrifuge at 5000r / min for 15min, pass the obtained supernatant through an ultrafiltration membrane with a molecular weight cutoff of 3000Da and collect the permeate, then pass it through a nanofiltration membrane with a molecular weight cutoff of 500Da and collect the retentate, concentrate the retentate under vacuum at 45℃ to a solid content of 20% and freeze dry, mix the obtained deer antler enzymatic hydrolysis extract and deer blood enzymatic hydrolysis extract at a mass ratio of 1:0.3 to obtain deer product extract.

[0037] S3. Add β-cyclodextrin to water to prepare an inclusion solution with a mass concentration of 10%. Add soybean lecithin and shear at 6000 r / min for 5 min. Then add wild ginseng freeze-dried powder, deer product extract and ascorbic acid. Homogenize and include at 35℃ and -0.06 MPa for 15 min to obtain the composite active material.

[0038] S4. Mix honey, isomaltooligosaccharide syrup, maltitol, and glycerin, and concentrate under vacuum at 50°C until the soluble solids content is 78.3% to obtain the paste matrix. S5. Cool the paste matrix to 43°C, add the composite active material, and mix at -0.06 MPa for 10 minutes to form paste pills with a single pill weight of 2g. Dry at 35°C until the water content is 8.7% and the water activity is 0.55, and then seal and package to obtain the composite paste preparation.

[0039] Example 2

[0040] The ingredients are prepared as follows: 1 part by weight = 10g, consisting of 9 parts of freeze-dried wild ginseng powder, 15 parts of deer product extract, 3.5 parts of β-cyclodextrin, 1.2 parts of soybean lecithin, 32.5 parts of honey, 17.5 parts of isomaltooligosaccharide syrup, 8 parts of maltitol, 2.5 parts of glycerin and 0.12 parts of ascorbic acid.

[0041] S1. After cleaning the wild ginseng, cut it into thin slices with a thickness of 2 mm, pre-freeze it at -40℃ for 6 hours, and then successively sublimate it at -20℃ for 10 hours, desorption it at -2℃ for 5 hours, and finally dry it at 20℃ for 3 hours under a vacuum of 50 Pa. Then, pulverize it under the condition that the material temperature does not exceed 15℃ to obtain freeze-dried wild ginseng powder with a moisture content of 4.1% and a particle size D90 of 36.9 μm.

[0042] S2. Take 100g each of deer antler raw material and deer blood raw material, add 1000g of water to each, adjust the pH to 7.0, add 2250U / g of neutral protease of raw material at 50℃ for 2h, then add 1000U / g of papain of raw material for 2h, inactivate enzyme at 90℃ for 15min, centrifuge at 5000r / min for 15min, and fractionate by using an ultrafiltration membrane with a molecular weight cutoff of 3000Da and a nanofiltration membrane with a molecular weight cutoff of 500Da. Concentrate the nanofiltration retentate under vacuum at 45℃ to a solid content of 20% and freeze dry. Mix the deer antler enzymatic hydrolysis extract and deer blood enzymatic hydrolysis extract at a mass ratio of 1:0.55 to obtain deer product extract.

[0043] S3. Add β-cyclodextrin to water to prepare an inclusion solution with a mass concentration of 17.5%. Add soybean lecithin and shear at 8000 r / min for 10 min. Then add wild ginseng freeze-dried powder, deer product extract and ascorbic acid. Homogenize and include at 40℃ and -0.075 MPa for 25 min to obtain the composite active material.

[0044] S4. Mix honey, isomaltooligosaccharide syrup, maltitol and glycerin, and concentrate under vacuum at 58°C until the soluble solids content is 81.0% to obtain the paste matrix.

[0045] S5. Cool the paste matrix to 42℃, add the composite active material, and mix at -0.075MPa for 20 minutes to make paste pills with a single pill weight of 3g. Dry at 40℃ until the water content is 8.3% and the water activity is 0.54. After sealing and packaging, the composite paste pill preparation is obtained.

[0046] Example 3

[0047] The ingredients are prepared as follows: 1 part by weight = 10g, consisting of 12 parts of freeze-dried wild ginseng powder, 20 parts of deer product extract, 5 parts of β-cyclodextrin, 2 parts of soybean lecithin, 40 parts of honey, 25 parts of isomaltooligosaccharide syrup, 12 parts of maltitol, 4 parts of glycerin and 0.20 parts of ascorbic acid.

[0048] S1. After cleaning the wild ginseng, cut it into thin slices with a thickness of 3 mm, pre-freeze it at -35℃ for 8 hours, and then successively sublimate it at -15℃ for 12 hours, desorption it at 5℃ for 6 hours, and final it at 25℃ for 4 hours under a vacuum of 80 Pa. Finally, pulverize it under the condition that the material temperature does not exceed 15℃ to obtain freeze-dried wild ginseng powder with a moisture content of 4.5% and a particle size D90 of 39.2 μm.

[0049] S2. Take 100g each of deer antler raw material and deer blood raw material, add 1500g of water to each, adjust the pH to 7.5, add 3000U / g of neutral protease of raw material at 55℃ for 3h, then add 1500U / g of papain of raw material for 3h, inactivate enzyme at 95℃ for 20min, centrifuge at 5000r / min for 15min, and fractionate by using an ultrafiltration membrane with a molecular weight cutoff of 3000Da and a nanofiltration membrane with a molecular weight cutoff of 500Da. Concentrate the nanofiltration retentate under vacuum at 45℃ until the solid content is 20% and freeze dry. Mix the deer antler enzymatic hydrolysis extract and deer blood enzymatic hydrolysis extract at a mass ratio of 1:0.8 to obtain deer product extract.

[0050] S3. Add β-cyclodextrin to water to prepare an inclusion solution with a mass concentration of 25%. Add soybean lecithin and shear at 10000 r / min for 15 min. Then add wild ginseng freeze-dried powder, deer product extract and ascorbic acid. Homogenize and include at 45℃ and -0.09 MPa for 40 min to obtain the composite active material.

[0051] S4. Mix honey, isomaltooligosaccharide syrup, maltitol and glycerin, and concentrate under vacuum at 65°C until the soluble solids content is 83.8% to obtain the paste matrix.

[0052] S5. Cool the paste matrix to 44℃, add the composite active material, and mix at -0.09MPa for 30 minutes to make paste pills with a single pill weight of 5g. Dry at 45℃ until the water content is 7.9% and the water activity is 0.53. After sealing and packaging, the composite paste pill preparation is obtained.

[0053] Comparative Example 1

[0054] This comparative example is based on Example 2, except that in step S2, the enzymatic hydrolysate is not subjected to 3000Da ultrafiltration and 500Da nanofiltration fractionation, but is directly concentrated under vacuum and freeze-dried. The resulting deer antler enzymatic hydrolysate and deer blood enzymatic hydrolysate are still mixed at a ratio of 1:0.55. The amount of other raw materials and preparation conditions are the same as in Example 2.

[0055] Comparative Example 2

[0056] This comparative example is based on Example 2, except that β-cyclodextrin and soybean lecithin are not added in step S3, and the solids are supplemented with an equal mass of maltodextrin. Wild ginseng freeze-dried powder, deer product extract and ascorbic acid are directly added to the ointment matrix and mixed. The amount of other raw materials and preparation conditions are the same as in Example 2.

[0057] Comparative Example 3

[0058] This comparative example is based on Example 2, except that the wild ginseng is dried with hot air at 70°C for 10 hours and then pulverized at room temperature. In step S4, the paste matrix is ​​heated and concentrated at 85°C under normal pressure, and the composite active material is mixed with the paste matrix at 70°C. The remaining raw material amounts and preparation conditions are the same as in Example 2.

[0059] Performance testing

[0060] To evaluate the retention of active ingredients, dispersion uniformity, molding quality, and storage stability of the compound ointment pills of the present invention, the samples prepared in Examples 1-3 and Comparative Examples 1-3 were subjected to the following tests; three parallel samples were set for each physicochemical test, and the average value of the results was taken; 10 pills were randomly selected for the content uniformity test; and three independent packages were used for each group in the accelerated storage test.

[0061] 1. Moisture content test

[0062] The method was performed according to the second method of vacuum drying in GB5009.3-2016 "National Food Safety Standard - Determination of Moisture in Food". The sample was chopped and mixed thoroughly, and 2.000–5.000 g was weighed into a pre-weighed weighing dish. The sample was dried in a vacuum drying oven at 70℃±2℃ and a vacuum degree of 40–53 kPa for 5 hours. After drying, the sample was removed and cooled in a desiccator for 30 minutes, then weighed again. This process was repeated for 1 hour each time until the difference in weight between two drying cycles did not exceed 2 mg. The moisture content was calculated as a percentage of the sample mass lost during drying.

[0063] 2. Water activity test

[0064] The determination of water activity in food was performed according to the water activity meter method in GB5009.238-2016, "National Food Safety Standard - Determination of Water Activity in Food". The sample was cut into small pieces no larger than 3 mm and spread to the bottom of the sample dish. The dish was sealed and equilibrated for 30 min. The water activity was measured at 25℃±1℃. The water activity was recorded when the instrument reading changed by no more than 0.003 within 5 min. Each sample was measured in triplicate.

[0065] 3. Test of soluble solids in the ointment / pill matrix

[0066] The analysis was performed according to the refractometer method in GB / T12143-2008 "General Analytical Methods for Beverages". Approximately 5g of the paste matrix obtained in step S4 was diluted with an equal mass of distilled water and thoroughly mixed. The soluble solids content was measured using a digital refractometer at 20℃±0.5℃. The soluble solids mass fraction was calculated based on the dilution factor. The instrument was zeroed with distilled water before use.

[0067] 4. Test of total peptide content in deer product extracts

[0068] The peptide content determination method was performed according to Appendix B of GB / T22492-2008 "Soybean Peptide Powder". A 1% (w / w) sample solution of deer product extract was prepared, and an equal volume of 10% trichloroacetic acid solution was added. After mixing, the solution was allowed to stand for 10 min and then centrifuged at 10000 r / min for 10 min. The acid-soluble protein content and free amino acid content in the supernatant were determined. The peptide content was obtained by subtracting the free amino acid content from the acid-soluble protein content and converted to a dry basis mass fraction.

[0069] 5. Polypeptide molecular weight distribution test

[0070] High-performance gel filtration chromatography (HPLC) was performed according to Appendix A of GB / T22492-2008. A TSK gel G2000SWXL column (7.8 mm × 300 mm, 5 μm) was used. The mobile phase consisted of acetonitrile, water, and trifluoroacetic acid in a volume ratio of 45:55:0.1. The flow rate was 0.5 mL / min, the column temperature was 30 °C, the detection wavelength was 220 nm, and the injection volume was 10 μL. Calibration curves of retention time versus logarithm of molecular weight were established using cytochrome C, aprotinin, bacitracin, tetrapeptide, and tripeptide. The mass percentage of peptides in the 500–3000 Da range was calculated using the peak area normalization method.

[0071] 6. Ginsenoside Retention Rate Test

[0072] The method was determined by high performance liquid chromatography (HPLC) according to General Chapter 0512 of Part IV of the 2025 edition of the Chinese Pharmacopoeia, combined with the content determination method under the Ginseng section of Part I. 2.0 g of the pulverized paste sample was weighed, 50 mL of 70% methanol was added, and the sample was ultrasonically extracted for 45 min. After cooling, the weight loss was made up, and the sample was filtered through a 0.45 μm filter membrane. A C18 column (4.6 mm × 250 mm, 5 μm) was used with acetonitrile-water gradient elution at a flow rate of 1.0 mL / min, a column temperature of 30 ℃, and a detection wavelength of 203 nm. External standards were used for quantification of ginsenosides Rg1, Re, and Rb1. The retention rate of ginsenosides was the ratio of the total measured amount of Rg1, Re, and Rb1 in the finished product to the theoretical total amount calculated based on the added wild ginseng freeze-dried powder.

[0073] 7. Test for uniformity of content between pellets

[0074] Ten pills were randomly selected from each group, weighed, and crushed. The total peptide content and total amounts of Rg1, Re, and Rb1 in each pill were determined according to the above methods for determining total peptides and ginsenosides. The relative standard deviation (RSD) of the results of the 10 pills was calculated. The smaller the RSD, the better the uniformity of the dispersion of the compound active material in the pill.

[0075] 8. Hardness test

[0076] Compression tests were conducted using a texture analyzer with a cylindrical flat-bottomed probe of 36 mm in diameter. The speeds were 1.0 mm / s before testing, 0.5 mm / s during testing, and 1.0 mm / s after testing. The trigger force was 5 g, and the compression deformation was 30% of the diameter of the pill. Ten pills were randomly measured in each group, and the peak force of the first compression was taken as the hardness of the pill, and the average value was calculated.

[0077] 9. Accelerated storage stability testing

[0078] Samples were individually sealed in moisture-barrier composite film and placed at 40℃±2℃ and 75%±5% relative humidity for 90 days. The total ginsenoside content, total peptide content, water activity, and hardness were measured before and after 90 days. The retention rate of ginsenosides and total peptides was the ratio of the measured value at 90 days to the initial value, and the change rate of hardness was the percentage of the difference between the hardness at 90 days and the initial hardness to the initial hardness. Total bacterial count was determined according to GB4789.2-2022. 25g of sample was added to 225mL of sterile phosphate buffer and homogenized. The sample was then poured onto a suitable dilution of pour plate counting agar medium and incubated at 36℃±1℃ for 48h±2h before counting.

[0079] Table 1: Initial quality index test results for each group of samples

[0080] Test Project Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Comparative Example 3 Moisture content / % 8.7 8.3 7.9 8.5 9.8 8.9 water activity 0.55 0.54 0.53 0.56 0.62 0.58 Matrix soluble solids / % 78.3 81.0 83.8 81.1 81.0 82.4 Total peptides from deer product extracts / % (dry basis) 72.8 74.1 73.5 68.2 74.0 72.4 Percentage of peptides with a daily limit of 500–3000 Da 68.4 70.2 69.3 47.6 70.0 68.9 Ginsenoside retention rate / % 94.3 95.1 94.6 93.8 94.0 78.7 RSD / % between ginsenoside pills 2.8 2.4 2.6 3.1 8.7 4.9 Total peptide inter-particle RSD / % 2.6 2.2 2.4 3.3 7.9 4.5 Hardness of ointment / N 20.8 21.4 21.9 21.6 24.9 25.7

[0081] As shown in Table 1, the data for Examples 1-3 show minimal differences, indicating that composite pills with suitable water content, water activity, and hardness can be stably prepared within the defined range of raw material dosage and process parameters. In Examples 1-3, the total peptide content of the deer product extract was 72.8%-74.1%, the proportion of 500-3000 Da polypeptides was 68.4%-70.2%, the ginsenoside retention rate was 94.3%-95.1%, and the RSD between ginsenosides and total peptides in the pills was no higher than 2.8%.

[0082] Comparative Example 1, without membrane fractionation, showed that the proportion of peptides in the 500–3000 Da range decreased to 47.6%, indicating that the combination of ultrafiltration and nanofiltration can effectively narrow the molecular weight distribution of peptides in deer products. Comparative Example 2, without the synergistic dispersion of β-cyclodextrin and soybean lecithin, showed that the RSD of ginsenosides and total peptides between pills increased to 8.7% and 7.9%, respectively, while water activity and hardness also increased. Comparative Example 3, using high-temperature drying, concentration, and mixing, showed that the ginsenoside retention rate decreased to 78.7%, and the hardness of the pills increased significantly.

[0083] Table 2: Stability test results of each group of samples after 90 days of accelerated storage:

[0084] Test Project Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Comparative Example 3 Ginsenoside retention rate / % 93.5 94.2 93.8 88.7 84.8 79.4 Total peptide retention rate / % 95.2 96.0 95.6 90.5 88.9 86.6 90d water activity 0.59 0.57 0.56 0.63 0.71 0.66 Hardness change rate / % +8.5 +7.4 +8.0 +16.9 +28.4 +24.8 Total bacterial count (CFU / g) 95 80 90 230 1.8×10³ 660 Appearance Surface dry, no sticking Surface dry, no sticking Surface dry, no sticking Slightly hardened Moisture buildup, localized adhesions Darker in color and noticeably harder

[0085] As shown in Table 2, after 90 days of accelerated storage, the ginsenoside retention rate of Examples 1-3 remained at 93.5%-94.2%, the total peptide retention rate at 95.2%-96.0%, the water activity at no higher than 0.59, the hardness change rate at no higher than 8.5%, and the sample surface remained dry without significant adhesion. In contrast, Comparative Example 1 showed a decrease in both active ingredient retention and textural stability due to its wider polypeptide molecular weight distribution; Comparative Example 2, lacking a cyclodextrin-phospholipid synergistic dispersion system, experienced a rise in water activity to 0.71 and exhibited re-adhesion after storage; Comparative Example 3 showed significant initial loss and storage degradation of active ingredients after high-temperature treatment. These results indicate that the membrane fractionation, synergistic inclusion dispersion, and low-temperature processing techniques of the present invention have a synergistic effect, simultaneously improving the retention of active ingredients, content uniformity, and storage stability of the composite ointment.

[0086] It should be noted that, in this document, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Unless otherwise specified, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes said element.

[0087] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

[0088] Those skilled in the art should understand that the above descriptions are merely several specific embodiments of the present invention, and not all embodiments.

Claims

1. A compound paste / pill preparation of wild ginseng freeze-dried powder and deer product extract, characterized in that, By weight, it includes the following ingredients: Wild ginseng freeze-dried powder 6-12 parts, deer product extract 10-20 parts, β-cyclodextrin 2-5 parts, soybean lecithin 0.5-2 parts, honey 25-40 parts, isomaltooligosaccharide syrup 10-25 parts, maltitol 4-12 parts, glycerin 1-4 parts, and ascorbic acid 0.05-0.20 parts; The deer product extract is composed of deer antler enzymatic hydrolysis extract and deer blood enzymatic hydrolysis extract, and the polypeptides with a molecular weight of 500-3000 Da account for more than 65% of the total mass of polypeptides in the deer product extract. The moisture content of the compound ointment preparation is 6% to 12%.

2. The compound paste / pill preparation of wild ginseng freeze-dried powder and deer product extract according to claim 1, characterized in that, The mass ratio of the deer antler enzymatic hydrolysate to the deer blood enzymatic hydrolysate is 1:0.3 to 0.8, and the total peptide content of the deer product extract, on a dry basis, is not less than 70%.

3. The compound paste / pill preparation of wild ginseng freeze-dried powder and deer product extract according to claim 1, characterized in that, The honey, isomaltooligosaccharide syrup, maltitol, and glycerin together constitute the ointment matrix, and the soluble solids content of the ointment matrix before being mixed with wild ginseng freeze-dried powder and deer product extract is 78% to 84%.

4. A method for preparing a compound paste / pill formulation of wild ginseng freeze-dried powder and deer product extract as described in any one of claims 1 to 3, characterized in that, Includes the following steps: S1. After cleaning, slicing and pre-freezing the wild ginseng, vacuum freeze-dry it and then pulverize it under the condition that the material temperature is not higher than 15℃ to obtain wild ginseng freeze-dried powder. S2. Add water to deer antler raw material and deer blood raw material to prepare raw material solution, and enzymatically hydrolyze them with neutral protease and papain in sequence. After inactivating the enzyme and separating the solid and liquid in the obtained enzymatic hydrolysate, ultrafiltration and nanofiltration are performed in sequence to collect polypeptide components with molecular weight of 500-3000 Da. After concentration and freeze drying, deer antler enzymatic hydrolysate extract and deer blood enzymatic hydrolysate extract are obtained respectively. Mix the two to obtain deer product extract. S3. Add β-cyclodextrin to water to prepare an inclusion solution, add soybean lecithin for shear dispersion, then add wild ginseng freeze-dried powder, deer product extract and ascorbic acid, and homogenize and include under vacuum conditions to obtain composite active material. S4. Mix honey, isomaltooligosaccharide syrup, maltitol and glycerin, and concentrate them at low temperature under vacuum to obtain the ointment matrix. S5. Cool the paste matrix to no higher than 45°C, add the composite active material, and then perform vacuum mixing, pelleting and low-temperature drying to obtain the composite paste preparation of wild ginseng freeze-dried powder and deer product extract.

5. The preparation method according to claim 4, characterized in that, In step S1, the wild ginseng is cut into thin slices with a thickness of 1-3 mm, pre-frozen at -45 to -35°C for 4-8 hours, and then freeze-dried under vacuum conditions of 20-80 Pa. The vacuum freeze drying process includes sublimation drying at -25 to -15°C, desorption drying at -10 to 5°C, and final drying at 15 to 25°C, until the moisture content of the wild ginseng is no higher than 5%.

6. The preparation method according to claim 4, characterized in that, In step S2, water of 8 to 15 times the weight of the raw materials is added to the raw materials of deer antler and deer blood respectively, the pH is adjusted to 6.5 to 7.5, and neutral protease is added at 45 to 55°C for 1 to 3 hours for enzymatic hydrolysis, followed by papain hydrolysis for 1 to 3 hours. The amount of neutral protease added is 1500-3000 U / g of raw material, and the amount of papain added is 500-1500 U / g of raw material; After enzymatic hydrolysis, the enzyme is inactivated at 85–95°C for 10–20 min. The enzymatic hydrolysate obtained from solid-liquid separation is passed through an ultrafiltration membrane with a molecular weight cutoff of 3000 Da to collect the ultrafiltration permeate. The ultrafiltration permeate is then passed through a nanofiltration membrane with a molecular weight cutoff of 500 Da to collect the nanofiltration retentate.

7. The preparation method according to claim 4, characterized in that, In step S3, the mass concentration of β-cyclodextrin in the inclusion solution is 10% to 25%. After adding soybean lecithin, the mixture is sheared and dispersed at 6000 to 10000 r / min for 5 to 15 min. After adding wild ginseng freeze-dried powder, deer product extract and ascorbic acid, the mixture is homogenized and included for 15 to 40 min at a temperature of 35 to 45°C and a vacuum degree of -0.06 to -0.09 MPa.

8. The preparation method according to claim 4, characterized in that, In step S4, the vacuum low-temperature concentration temperature is 50-65°C until the soluble solids content of the obtained ointment matrix is ​​78%-84%. In step S5, the mixture is kneaded for 10 to 30 minutes under a vacuum of -0.06 to -0.09 MPa. The kneaded material is then made into pills with a single pill weight of 1 to 5 g and dried at 35 to 45°C until the moisture content is 6% to 12% and the water activity is 0.45 to 0.65.