WO2024074159A1 - 小分子阿胶多肽制品的制备方法 - Google Patents

小分子阿胶多肽制品的制备方法 Download PDF

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WO2024074159A1
WO2024074159A1 PCT/CN2023/136381 CN2023136381W WO2024074159A1 WO 2024074159 A1 WO2024074159 A1 WO 2024074159A1 CN 2023136381 W CN2023136381 W CN 2023136381W WO 2024074159 A1 WO2024074159 A1 WO 2024074159A1
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donkey
hide gelatin
ass
hide glue
preparing
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PCT/CN2023/136381
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French (fr)
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王超
赵强
宋文路
安筱雅
王毅恒
韩舒阳
张一诺
朱明月
史瑞瑞
冯磊
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济宁学院
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/18—Peptides; Protein hydrolysates
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/14—Extraction; Separation; Purification
    • C07K1/34—Extraction; Separation; Purification by filtration, ultrafiltration or reverse osmosis
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P21/00—Preparation of peptides or proteins
    • C12P21/06—Preparation of peptides or proteins produced by the hydrolysis of a peptide bond, e.g. hydrolysate products
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the invention belongs to the technical field of functional foods, and in particular relates to a method for preparing a small molecule donkey-hide gelatin polypeptide product.
  • donkey-hide gelatin The main component of donkey-hide gelatin is protein, with a content of about 60%-80%, mainly including collagen, serum albumin and other proteins with large molecular weight. Therefore, donkey-hide gelatin is not easily absorbed by the human body directly, and direct consumption will cause the problem of "greasy and stomach-inhibiting", reducing the health care effect of donkey-hide gelatin.
  • the macromolecular proteins in donkey-hide gelatin will form donkey-hide gelatin polypeptides with a molecular weight of less than 3kDa after being degraded by biological enzymes such as pepsin and trypsin, which are easily absorbed by the human body and play an important role in immune regulation, blood tonic and white blood cell raising.
  • the technical problem to be solved by the present invention is to provide a method for preparing a small molecule donkey-hide gelatin polypeptide product, which has strong operability, high preparation efficiency, and is easy to industrialize.
  • the prepared donkey-hide gelatin polypeptide product has good quality.
  • the method for preparing the small molecule donkey-hide gelatin polypeptide product of the present invention comprises the following steps:
  • enzymatic hydrolysis of donkey-hide gelatin adjusting the pH of the donkey-hide gelatin solution to 5.5, adding papain, and inactivating the enzyme after the enzymatic hydrolysis reaction; then adjusting the solution pH to 6.0, adding a composite biological enzyme, and inactivating the enzyme after the enzymatic hydrolysis reaction to obtain an enzymatic hydrolyzed donkey-hide gelatin solution;
  • excipient processing crushing the excipient and then extracting it with alcohol to obtain an alcohol extract; extracting the remaining drug residue after the alcohol extraction of the excipient with water to obtain a water extract; distilling the alcohol extract and the water extract under reduced pressure to obtain an alcohol extract concentrate and a water extract concentrate, combining and drying to obtain an excipient fluid extract;
  • the donkey-hide gelatin polypeptide complex and auxiliary material fluid extract are prepared into a solid oral preparation with a pharmaceutically acceptable carrier, namely the small molecule donkey-hide gelatin polypeptide product.
  • the amount of water used is 9-10 times the mass of the donkey-hide gelatin block.
  • the composite biological enzyme includes bromelain, ficin, pepsin and flavor protease, and the mass ratio thereof is 3:(2-4):(5-7):1;
  • the mass ratio of raw material donkey-hide gelatin block: papain: composite biological enzyme is 50: (1-5): (1-5);
  • the temperature of papain enzymolysis reaction is 38-42°C and the time is 2-2.5h;
  • the temperature of the compound biological enzyme hydrolysis reaction is 48-52°C and the time is 2-2.5h;
  • the enzyme inactivation temperature is 95°C and the enzyme inactivation time is 10 min.
  • step S3 the donkey-hide gelatin enzymatic hydrolysate is filtered using a plate-and-frame filter press, and activated carbon is used to remove odor;
  • Drying treatment of donkey-hide gelatin hydrolysate Use a freeze dryer, set oil temperatures 1 and 2 to 90-100°C and 60-70°C respectively, the cold trap temperature to -30- -20°C, and the drying time to 10-12h.
  • the auxiliary materials include 5-6 parts of red dates, 5-6 parts of walnuts, 3-4 parts of wolfberries, and 9-10 parts of black sesame seeds in terms of dry weight;
  • the solvent used in the alcohol extraction treatment was 75% medicinal ethanol, and the extraction was performed twice;
  • the solvent used in the water extraction treatment was deionized water, and the extraction was performed twice.
  • step S5 the mass ratio of the donkey-hide gelatin polypeptide complex to the auxiliary material fluid extract is 1:(3-6);
  • the pharmaceutically acceptable carrier includes dextrin, ethyl cellulose and micro-powder silica gel, and the mass ratio of the carrier to the donkey-hide gelatin polypeptide complex is 1:1.
  • the pulverizing operation uses a ball mill.
  • the present invention has the following beneficial effects:
  • the present invention adopts a specific combination of biological enzymes, optimizes the types and dosages of biological enzymes, improves the enzymatic hydrolysis efficiency and degree of donkey-hide gelatin, produces donkey-hide gelatin polypeptide molecules that are smaller and easier to absorb, and the types and quantities of active ingredients in the donkey-hide gelatin polypeptide complex obtained after enzymatic hydrolysis are large;
  • the small molecule donkey-hide gelatin polypeptide product of the present invention has a strong effect of nourishing blood and raising white blood cells, and improving immunity.
  • the use of auxiliary materials further improves the nutritional and nourishing effects of donkey-hide gelatin polypeptide;
  • the preparation method of the present invention has high preparation efficiency, strong operability and is easy to industrialize.
  • the method for preparing the small molecule donkey-hide gelatin polypeptide product of the present invention comprises the following steps:
  • enzymatic hydrolysis of donkey-hide gelatin adjust the pH of the donkey-hide gelatin solution to 5.5, add papain, react at 40°C for 2h, heat to 95°C, and inactivate the enzyme for 10min; then cool the donkey-hide gelatin solution to 50°C, adjust the pH of the solution to 6.0, add composite biological enzyme, hydrolyze for 2h, heat to 95°C, and inactivate the enzyme for 10min to obtain donkey-hide gelatin enzymatic hydrolyzate;
  • the composite biological enzyme includes bromelain, ficin, pepsin and flavor protease in a mass ratio of 3:2:5:1; the mass ratio of raw material donkey-hide gelatin block: papain: composite biological enzyme is 50:1:1;
  • drying treatment using a freeze dryer, oil temperature 1 and 2 are set to 100°C and 70°C respectively, cold trap temperature is -30°C, and drying time is 12h;
  • excipient treatment crush the excipient and use 75% medicinal ethanol to extract twice to obtain an alcohol extract; use deionized water to extract the remaining residue after the excipient is extracted twice to obtain a water extract; the alcohol extract and the water extract are respectively subjected to reduced pressure distillation to obtain an alcohol extract concentrate and a water extract concentrate, which are combined and dried to obtain an excipient fluid extract;
  • the auxiliary materials calculated by dry weight, include 5 parts of red dates, 5 parts of walnuts, 3 parts of wolfberries, and 10 parts of black sesame seeds, which are ground using a ball mill;
  • the donkey-hide gelatin polypeptide complex and auxiliary material fluid extract are prepared into granules with a pharmaceutically acceptable carrier by a granulator, which is the small molecule donkey-hide gelatin polypeptide product;
  • the pharmaceutically acceptable carrier includes dextrin, ethyl cellulose and micro-powdered silica gel, and the mass ratio of the three is 2:1:1;
  • the mass ratio of donkey-hide gelatin polypeptide complex: auxiliary material fluid extract: carrier is 1:3:1.
  • the preparation method of the small molecule donkey-hide gelatin polypeptide product described in this embodiment refers to Example 1, except that the composite biological enzyme includes bromelain, ficin, pepsin and flavor protease in a mass ratio of 3:4:7:1; the mass ratio of the raw material donkey-hide gelatin block: papain: composite biological enzyme is 10:1:1.
  • the preparation method of the small molecule donkey-hide gelatin polypeptide product described in this embodiment refers to Example 1, except that the composite biological enzyme includes bromelain, ficin, pepsin and flavor protease in a mass ratio of 3:3:6:1; the mass ratio of the raw material donkey-hide gelatin block: papain: composite biological enzyme is 25:2:1.
  • the preparation method is similar to that of Example 1, except that no composite biological enzyme is used.
  • the preparation method is as in Example 1, except that papain is not used.
  • the preparation method is similar to that of Example 1, except that no enzymatic treatment is performed.
  • the HPLC method was used to determine the content of the small molecule donkey-hide gelatin polypeptide, with three replicates in each group. The results are shown in Table 1. From the comparison results, it can be seen that the content of the small molecule donkey-hide gelatin polypeptide prepared by the method of the present invention is significantly higher than that of comparative examples 1-3.
  • mice of similar age and weight were divided into groups with 10 mice in each group. All mice were anesthetized with ether and blood was collected through the heart to make an anemic mouse model. The amount of blood loss was 30% of the mouse blood volume. 24 hours after blood loss, 0.02 mL of blood was collected from the tip of the tail, and red blood cell diluent was added to 4 mL, shaken well, and the red blood cell count was counted as the red blood cell count before administration, and the hemoglobin content was detected.
  • mice The drug was dissolved in water and administered to mice by gavage (0.10 mL/mouse) once a day for 15 consecutive days. After the experiment, all mice were again bled through the tail to count the number of red blood cells and test the hemoglobin content. The results are shown in Tables 2 and 3.
  • Experimental groups 1, 2 and 3 were intragastrically administered with the donkey-hide gelatin products of Example 1, Example 2 and Example 3, respectively;
  • Control group The blank group was gavaged with normal saline, and control group 1, control group 2, and control group 3 were gavaged with the donkey-hide gelatin products of comparison example 1, comparison example 2, and comparison example 3, respectively.

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Abstract

一种小分子阿胶多肽制品的制备方法，包括以下步骤：S1、阿胶预处理：将原料阿胶块粉碎，加水溶解，离心去除上层油脂，过滤得到阿胶溶液；S2、阿胶酶解处理：调节阿胶溶液pH至5.5，加入木瓜蛋白酶，酶解反应结束后灭酶；再调节溶液pH至6.0，加入复合生物酶，酶解反应结束后灭酶，得到阿胶酶解液；S3、阿胶后处理：将阿胶酶解液依次进行过滤，去异味，干燥粉碎处理，得到阿胶多肽复合物，备用；S4、辅料处理：将辅料粉碎后进行醇提，得到醇提液；将辅料醇提后剩余的药渣进行水提，得到水提液；将醇提液和水提液分别经减压蒸馏后，得到醇提浓缩液和水提浓缩液，合并烘干，得到辅料流浸膏；S5、制品：将阿胶多肽复合物和辅料流浸膏，与药学上可接受的载体制成固体口服制剂，即为所述小分子阿胶多肽制品。上述制备方法制备效率高，可操作性强，易于产业化。

Description

小分子阿胶多肽制品的制备方法 技术领域
本发明属于功能性食品技术领域，具体涉及小分子阿胶多肽制品的制备方法。
 背景技术
阿胶中主要成分是蛋白质，含量约为60%-80%，主要包括胶原蛋白、血清白蛋白等分子量较大的蛋白质。因此，阿胶不易被人体直接吸收，直接食用会产生“滋腻碍胃”的问题，降低了阿胶的保健效果。但是，有研究发现，阿胶中的大分子蛋白质经胃蛋白酶、胰蛋白酶等生物酶降解后会形成分子量小于3kDa的阿胶多肽，其易被人体吸收，在免疫调节、补血升白等方面具有重要的作用。然而，研究使用的胃蛋白酶和胰蛋白酶价格昂贵，不适用阿胶多肽的大规模工业生产。另外，由于缺乏对阿胶组成蛋白序列系统的研究，选择成本合适且能应用于生产的生物酶，并研发相应的加工工艺，成为阿胶多肽研发和生产的关键共性技术问题。
 发明内容
本发明要解决的技术问题是，提供了小分子阿胶多肽制品的制备方法，可操作性强，制备效率高，易于产业化，制备得到的阿胶多肽制品的品质好。
本发明所述的小分子阿胶多肽制品的制备方法，包括以下步骤：
S1、阿胶预处理：将原料阿胶块粉碎，加水溶解，离心去除上层油脂，过滤得到阿胶溶液；
S2、阿胶酶解处理：调节阿胶溶液pH至5.5，加入木瓜蛋白酶，酶解反应结束后灭酶；再调节溶液pH至6.0，加入复合生物酶，酶解反应结束后灭酶，得到阿胶酶解液；
S3、阿胶后处理：将阿胶酶解液依次进行过滤，去异味，干燥粉碎处理，得到阿胶多肽复合物，备用；
S4、辅料处理：将辅料粉碎后进行醇提，得到醇提液；将辅料醇提后剩余的药渣进行水提，得到水提液；将醇提液和水提液分别经减压蒸馏后，得到醇提浓缩液和水提浓缩液，合并烘干，得到辅料流浸膏；
S5、制品：将阿胶多肽复合物和辅料流浸膏，与药学上可接受的载体制成固体口服制剂，即为所述小分子阿胶多肽制品。
优选的，步骤S1中，水的用量为阿胶块质量的9-10倍。
优选的，步骤S2中，复合生物酶包括菠萝蛋白酶、无花果蛋白酶、胃蛋白酶和风味蛋白酶，其质量比为3:(2-4):(5-7):1；
原料阿胶块：木瓜蛋白酶：复合生物酶的质量比为50:(1-5):(1-5)；
木瓜蛋白酶酶解反应的温度为38-42℃，时间为2-2.5h；
复合生物酶酶解反应的温度为48-52℃，时间为2-2.5h；
灭酶温度为95℃，灭酶时间为10min。
优选的，步骤S3中，使用板框压滤机对阿胶酶解液进行过滤，使用活性炭去异味；
阿胶酶解液的干燥处理：使用冷冻干燥机，油温1和2分别设置为90-100℃和60-70℃，冷阱温度为-30- -20℃，干燥时间为10-12h。
优选的，步骤S4中，辅料以干重的重量份数计包括红枣5-6份、核桃5-6份、枸杞3-4份、黑芝麻9-10份；
醇提处理使用的溶剂为75％的药用乙醇，提取2次；
水提处理使用的溶剂为去离子水，提取2次。
优选的，步骤S5中，阿胶多肽复合物和辅料流浸膏的质量比为1:(3-6)；
药学上可接受的载体包括糊精、乙基纤维素、微粉硅胶，载体：阿胶多肽复合物的质量比为1:1。
优选的，粉碎操作使用球磨机。
与现有技术相比，本发明具备以下有益效果：
1、本发明采用特定的生物酶组合，优化了生物酶的种类和用量，提高了阿胶的酶解效率和酶解程度，产生的阿胶多肽分子更小，更容易被吸收，并且，酶解后得到的阿胶多肽复合物中活性成分的种类和数量多；
2、本发明的小分子阿胶多肽制品具有较强的补血升白，提高免疫力的作用，同时，辅料的使用进一步提高了阿胶多肽的营养和滋补效果；
3、本发明制备方法制备效率高，可操作性强，易于产业化。
 本发明的实施方式
为使本发明实施例的技术方案和优点更加清楚，下面将结合具体实施例对本发明的技术方案进行进一步阐述，此实施例仅为本发明的一部分，不可理解为对发明保护权利的限制，熟悉该领域的技术人员根据本发明所作出的非本质、非创造性的改进与调整，仍属于本发明的保护范围。实施例中用到的所有原料除特殊说明外，均为市购。
实施例1
本发明所述的小分子阿胶多肽制品的制备方法，包括以下步骤：
S1、阿胶预处理：将原料阿胶块粉碎，加原料阿胶块9倍重量的水溶解，离心去除上层油脂，过滤得到阿胶溶液；
S2、阿胶酶解处理：调节阿胶溶液pH至5.5，加入木瓜蛋白酶，40℃反应2h后，升温至95℃，灭酶10min；然后阿胶溶液冷却至50℃，再调节溶液pH至6.0，加入复合生物酶，酶解2h后，升温至95℃，灭酶10min，得到阿胶酶解液；
其中，复合生物酶包括菠萝蛋白酶、无花果蛋白酶、胃蛋白酶和风味蛋白酶，其质量比为3:2:5:1；原料阿胶块：木瓜蛋白酶：复合生物酶的质量比为50:1:1；
S3、阿胶后处理：将阿胶酶解液使用板框压滤机进行过滤，使用活性炭去异味，而后干燥粉碎，得到阿胶多肽复合物，备用；
其中，干燥处理：使用冷冻干燥机，油温1和2分别设置为100℃和70℃，冷阱温度为-30℃，干燥时间为12h；
S4、辅料处理：将辅料粉碎后使用75％的药用乙醇，醇提2次，得到醇提液；将辅料醇提后剩余的药渣使用去离子水，水提2次，得到水提液；将醇提液和水提液分别经减压蒸馏后，得到醇提浓缩液和水提浓缩液，合并烘干，得到辅料流浸膏；
其中，辅料以干重的重量份数计包括红枣5份、核桃5份、枸杞3份、黑芝麻10份，使用球磨机粉碎；
S5、制品：将阿胶多肽复合物和辅料流浸膏，与药学上可接受的载体，用制粒机制备成颗粒剂，即为所述小分子阿胶多肽制品；
其中，药学上可接受的载体包括糊精、乙基纤维素、微粉硅胶，三者质量比为2:1:1；
阿胶多肽复合物：辅料流浸膏：载体的质量比为1:3:1。
实施例2
本实施例所述的小分子阿胶多肽制品的制备方法参考实施例1，不同的是：复合生物酶包括菠萝蛋白酶、无花果蛋白酶、胃蛋白酶和风味蛋白酶，其质量比为3:4:7:1；原料阿胶块：木瓜蛋白酶：复合生物酶的质量比为10:1:1。
实施例3
本实施例所述的小分子阿胶多肽制品的制备方法参考实施例1，不同的是：复合生物酶包括菠萝蛋白酶、无花果蛋白酶、胃蛋白酶和风味蛋白酶，其质量比为3:3:6:1；原料阿胶块：木瓜蛋白酶：复合生物酶的质量比为25:2:1。
对比例1
制备方法参考实施例1，不同的是：未使用复合生物酶。
对比例2
制备方法参考实施例1，不同的是：未使用木瓜蛋白酶。
对比例3
制备方法参考实施例1，不同的是：未进行酶解处理。
将上述实施例1-3和对比例1-3制备得到的阿胶多肽制品，进行如下检测。
小分子阿胶多肽含量测定
采用HPLC法，测定其小分子阿胶多肽含量，每组三个重复，结果见表1，从对比结果可以看出，本发明方法制备得到的小分子阿胶多肽含量显著高于对比例1-3。
表1样品小分子阿胶多肽含量数据表
2.保健效果试验
取日龄、体重相近的小鼠60只，分为组，每组10只小鼠，全部小鼠用乙醚麻醉，经心脏采血，制作贫血小鼠模型，失血量为小鼠血量的30％，失血后24h，尾尖取血0.02mL，加入红细胞稀释液至4mL，摇匀，计红细胞数，作为给药前的红细胞数，并检测血红蛋白含量。
将药品用水溶解，对小鼠进行灌胃（0.10mL/只），每天一次，连续给药15天，试验结束后，所有小鼠再次经尾部取血，计红细胞数，并检测血红蛋白含量，结果见表2和表3。
分组和处理如下：
实验组：实验组1、实验组2、实验组3分别灌胃实施例1、实施例2、实施例3的阿胶制品；
对照组：空白组灌胃生理盐水，对照组1、对照组2、对照组3分别灌胃对比例1、对比例2、对比例3的阿胶制品。
表2贫血小鼠给药前后红细胞数（RBC）
表3贫血小鼠给药前后血红蛋白含量（Hb）
从对比结果可以看出，与对照组相比，灌胃实施例1-3的阿胶多肽制品后小鼠的红细胞数和血红蛋白含量显著提高，对照组1-3相比于空白组小鼠的红细胞数和血红蛋白含量也有一定量的提高。说明，通过本发明所述方法制备的小分子阿胶多肽制品具有较强的补血作用，对于贫血具有很好改善作用。

Claims (10)

  1. 一种小分子阿胶多肽制品的制备方法，其特征在于：包括以下步骤：
    S1、阿胶预处理：将原料阿胶块粉碎，加水溶解，离心去除上层油脂，过滤得到阿胶溶液；
    S2、阿胶酶解处理：调节阿胶溶液pH至5.5，加入木瓜蛋白酶，酶解反应结束后灭酶；再调节溶液pH至6.0，加入复合生物酶，酶解反应结束后灭酶，得到阿胶酶解液；
    S3、阿胶后处理：将阿胶酶解液依次进行过滤，去异味，干燥粉碎处理，得到阿胶多肽复合物，备用；
    S4、辅料处理：将辅料粉碎后进行醇提，得到醇提液；将辅料醇提后剩余的药渣进行水提，得到水提液；将醇提液和水提液分别经减压蒸馏后，得到醇提浓缩液和水提浓缩液，合并烘干，得到辅料流浸膏；
    S5、制品：将阿胶多肽复合物和辅料流浸膏，与药学上可接受的载体制成固体口服制剂，即为所述小分子阿胶多肽制品。
  2. 根据权利要求1所述的小分子阿胶多肽制品的制备方法，其特征在于：步骤S1中，水的用量为阿胶块质量的9-10倍。
  3. 根据权利要求1所述的小分子阿胶多肽制品的制备方法，其特征在于：步骤S2中，复合生物酶包括菠萝蛋白酶、无花果蛋白酶、胃蛋白酶和风味蛋白酶，其质量比为3:(2-4):(5-7):1。
  4. 根据权利要求1所述的小分子阿胶多肽制品的制备方法，其特征在于：原料阿胶块：木瓜蛋白酶：复合生物酶的质量比为50:(1-5):(1-5)。
  5. 根据权利要求1所述的小分子阿胶多肽制品的制备方法，其特征在于：步骤S2中，木瓜蛋白酶酶解反应的温度为38-42℃，时间为2-2.5h。
  6. 根据权利要求1所述的小分子阿胶多肽制品的制备方法，其特征在于：步骤S2中，复合生物酶酶解反应的温度为48-52℃，时间为2-2.5h。
  7. 根据权利要求1所述的小分子阿胶多肽制品的制备方法，其特征在于：步骤S3中，阿胶酶解液的干燥处理：使用冷冻干燥机，油温1和2分别设置为90-100℃和60-70℃，冷阱温度为-30- -20℃，干燥时间为10-12h。
  8. 根据权利要求1所述的小分子阿胶多肽制品的制备方法，其特征在于：步骤S4中，辅料以干重的重量份数计包括红枣5-6份、核桃5-6份、枸杞3-4份、黑芝麻9-10份。
  9. 根据权利要求1所述的小分子阿胶多肽制品的制备方法，其特征在于：步骤S5中，阿胶多肽复合物和辅料流浸膏的质量比为1:(3-6)。
  10. 根据权利要求1所述的小分子阿胶多肽制品的制备方法，其特征在于：步骤S5中，药学上可接受的载体包括糊精、乙基纤维素、微粉硅胶。
PCT/CN2023/136381 2023-04-11 2023-12-05 小分子阿胶多肽制品的制备方法 WO2024074159A1 (zh)

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