Biological breeding soybean feed formula for evaluating reproductive development safety of experimental monkeys

By designing a nutritionally balanced experimental monkey reproductive development safety evaluation formula for biological breeding soybean feed, the problem of assessment of the safety of biological breeding products for non-human primate reproduction and offspring development is solved, and the nutritional needs and safety guarantee of experimental monkeys during reproductive development is achieved.

CN119949426APending Publication Date: 2025-05-09INST OF MEDICAL BIOLOGY CHINESE ACAD OF MEDICAL SCI
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Patent Information

Application Number
CN202510147416.4
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-02-11
Publication Date
2025-05-09

AI Technical Summary

Technical Problem

The prior art is difficult to effectively evaluate the safety of biological breeding products for the reproduction and development of offspring in non-human primates, especially in the case of long-term consumption.

Method used

A biological breeding soybean feed formula for evaluation of reproductive development safety of experimental monkeys was designed. By selecting raw materials such as corn, casein, soybeans, flour, etc., the nutrients in the feed are balanced, and high oleic acid soybeans are used to meet the growth needs of experimental monkeys.

Benefits of technology

This feed formula can meet the nutritional needs of experimental monkeys during reproductive development, ensure long-term consumption safety, and ensure nutritional balance and safety through testing.

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Abstract

The invention discloses a biological breeding soybean feed formula for evaluating the reproductive development safety of experimental monkeys, and relates to the field of animal feeds, and the biological breeding soybean feed formula comprises the following raw materials in parts by weight: 52.5 parts of corn, 4 parts of casein, 30 parts of soybeans, 5 parts of flour, 1.8 parts of calcium hydrophosphate, 2 parts of fish meal, 1.3 parts of stone powder, 1 part of yeast powder, 1 part of a 1% premix, 0.5 part of table salt, 0.4 part of vitamin C, 0.2 part of methionine and 0.3 part of lysine. Protein, fat, vitamins and other nutrients in the feed formula meet GB14924 requirements through detection and analysis, the characteristics of the biologically bred soybeans and the factors of the proportion of the biologically bred soybeans in the dietary composition of people are also considered, the feed formula is balanced in nutrition, and the nutritional requirements of the experimental monkeys in the reproductive development process after being eaten for a long time can be met. According to the present invention, the biological breeding soybean is adopted as the raw material, the nutrition is balanced through development, the maximum amount (30%) of the biological breeding soybean can be doped in the feed, the bran is not added in the formula, and the problem of overhigh cellulose content of the feed due to the soybean hull doping is avoided;
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Description

Technical Field

[0001] The invention relates to animal feed technology, and in particular to a biological breeding soybean feed formula for evaluating the reproductive development safety of experimental monkeys. Background Art

[0002] In recent years, with the development of agricultural biotechnology and the change in people's livelihood needs, the research and development of new biological breeding products has entered the early stage of industrialization. The use of strategies such as RNAi, gene editing, and transgenics will be important means of biological breeding in the future, which has brought greater challenges to the edible and feeding evaluation of biological breeding products. It is of great significance to establish a non-human primate (NHPs) animal model for long-term consumption of biological breeding products and complete the long-term consumption of biological breeding products with new transgenic and gene editing technologies for the reproductive and offspring development safety of NHPs animals.

[0003] Studies have shown that genistein in soy isoflavones is a low-toxic substance. Its toxicity is mainly manifested as estrogen-like effects, which can cause reproductive toxicity such as precocious puberty, pseudopregnancy, placental absorption, stillbirth, miscarriage and infertility in experimental animals, as well as a decrease in body weight and organ weight. Extremely large doses can cause animal death.

[0004] Since primates are closely related to humans, consuming an appropriate amount of soy isoflavones will not cause changes in the levels of estrogen and androgen in the body, leading to endocrine dysfunction, and may even affect sexual desire and sperm production. Messina M. et al.'s study (Messina M.'s article Soybean isoflavone exposure does not have feminizing effects on men: a critical examination of the clinical evidence. published in Fertil Steril) showed that neither isoflavone supplements nor isoflavone-rich soybeans affect total testosterone (T) or free testosterone levels, and there is little evidence that isoflavone exposure affects circulating estrogen levels in men. Clinical evidence also shows that isoflavones have no effect on sperm or semen parameters. Although animal experimental studies on mice have found that a large amount of isoflavone intake increases the risk of erectile dysfunction, due to the differences in isoflavone metabolism between rodents and humans, there is no evidence that soy isoflavones affect the estrogen levels of male experimental monkeys, sperm or semen parameters, or erectile dysfunction in experimental monkeys.

[0005] For the experimental design of safety evaluation, the original sample can be considered for administration of the test substance. If the original sample cannot be used, the test substance should be properly handled according to the test substance handling principle: the test substance can be processed into powder and mixed into the feed formula to make customized feed. The dosage of biological breeding products is to mix the maximum amount into the feed under the premise of ensuring nutritional balance to make customized feed, and meet the daily complete nutrition feed standard GB 14924.3 for non-human primates. The customized feed must be tested by a third party and meet the relevant requirements of amino acids, vitamins, minerals, etc. in addition to the conventional nutrients of experimental monkeys. For the long-term safety evaluation experiment of NHPs, the maximum amount of crushed feed should be mixed into the feed first, and customized feed should be made for daily feeding. The test substance can be used as a feed raw material to ensure the stability and uniformity of the test substance preparation, and the principle is not to affect the animal's feeding, nutritional balance and water intake. It is recommended to produce customized feed according to the national standard GB 14924 for the nutritional requirements of NHPs animals, and the nutrient content of customized feed should comply with GB 14924. At the same time, the main nutrient content of the feed should be tested.

[0006] According to the recommendations of the "Dietary Guidelines for Chinese Residents (2022)", each person consumes 200-300g of cereal food per day, including 50-150g of whole grains and beans and 50-100g of potatoes. Calculated based on the content of soy isoflavones in soybeans of 0.8mg / g, assuming the recommended upper limit of 150g of soybeans, it contains 120mg of soy isoflavones. Calculated based on the dose per unit body weight, the equivalent dose of experimental monkeys is equivalent to 1.05 times that of humans, and the recommended amount of soy isoflavones they consume is ≤126mg. The feed produced by the formula contains 171.9mg / kg of soy isoflavones. Based on the feed intake of each experimental monkey of 200g / day, each experimental monkey obtains 34.38mg / day of soy isoflavones from the feed, which is in line with the recommended intake in the dietary guidelines.

[0007] As important experimental animals in scientific research, experimental monkeys play an irreplaceable role in vaccine development, drug screening, and reproductive development research. Summary of the invention

[0008] The purpose of the present invention is to provide a biological breeding soybean feed formula for evaluating the reproductive development safety of experimental monkeys.

[0009] In order to achieve the above-mentioned purpose, the present invention provides the following technical scheme: a biological breeding soybean feed formula for evaluating the reproductive development safety of experimental monkeys, wherein the raw materials include, by weight: 52.5 parts of corn, 4 parts of casein, 30 parts of soybeans, 5 parts of flour, 1.8 parts of calcium hydrogen phosphate, 2 parts of fish meal, 1.3 parts of stone powder, 1 part of yeast powder, 1 part of 1% premix, 0.5 parts of salt, 0.4 parts of vitamin C, 0.2 parts of methionine and 0.3 parts of lysine.

[0010] Furthermore, the 1% premix is ​​a mixture of copper, iron, zinc, manganese and vitamins.

[0011] Furthermore, the soybeans are biologically bred soybeans, and the biologically bred soybeans are high oleic acid soybeans.

[0012] The present invention also discloses a method for preparing a biological breeding soybean feed for evaluating the reproductive development safety of experimental monkeys, and the preparation method specifically comprises the following steps:

[0013] S1. Select corn, casein, soybean, flour, calcium hydrogen phosphate, fish meal, stone powder, yeast powder, 1% premix, salt, vitamin C, methionine and lysine according to the selected weight, place them separately and keep them for later use;

[0014] S2, then washing and drying the corn and soybeans, putting the dried soybeans into a steaming and frying pan for high temperature and high pressure treatment to obtain pretreated soybeans and dried corn;

[0015] S3, putting the pretreated soybeans and dried corns in S2 into a grinder for grinding, and after the grinding, cooling to room temperature to obtain crushed soybeans and powdered corns;

[0016] S4, adding the crushed soybeans and powdered corn cooled in S3 into a stirring device, and then sequentially adding casein, flour, calcium hydrogen phosphate, fish meal, stone powder, yeast powder, 1% premix, salt, methionine and lysine, and stirring with the stirring device. After the stirring is completed, adding vitamin C, and mixing again to obtain feed powder;

[0017] S5, pouring the feed powder mixed evenly in S4 into a pellet machine for processing to make feed pellets;

[0018] S6, putting the feed particles in S5 into a dryer to dry, and obtaining a biological breeding soybean feed for evaluating the reproductive development safety of experimental monkeys;

[0019] S7. The biological breeding soybean feed obtained for the reproductive development safety evaluation of experimental monkeys is bagged to ensure that the weight of each bag of feed is consistent, and the feed is vacuumed, packed in cartons, and irradiated with CO60. The feed is stored in a dry, cool, well-ventilated warehouse to avoid direct sunlight and high temperature environment.

[0020] Compared with the prior art, the biological breeding soybean feed formula for evaluating the reproductive development safety of experimental monkeys provided by the present invention is designed based on the conventional basic feed formula of non-human primates. The nutrients such as protein, fat, carbohydrates, vitamins and minerals in the feed meet the growth needs of experimental monkeys and meet the requirements of GB14924 after testing and analysis. The biological breeding soybean varieties and characteristics and the proportion of them in the dietary composition of the population are also considered. The feed formula is nutritionally balanced and can meet the nutritional needs of experimental monkeys in the reproductive development process during long-term consumption. Biological breeding soybeans are used as raw materials. After research, the test-biological breeding soybeans can be added to the feed on the basis of nutritional balance. The formula does not add bran, avoiding the problem of excessive cellulose in the feed due to the addition of soybean hulls, and meeting the nutritional needs of experimental monkeys in the reproductive development process during long-term consumption. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments recorded in the present invention. For ordinary technicians in this field, other drawings can also be obtained based on these drawings.

[0022] Figure 1 The present invention provides a flow chart of the preparation process. DETAILED DESCRIPTION

[0023] In order to enable those skilled in the art to better understand the technical solution of the present invention, the present invention will be further described in detail below with reference to the accompanying drawings.

[0024] Embodiment 1:

[0025] See also Figure 1 A biological breeding soybean feed formula for evaluating the reproductive development safety of experimental monkeys, the raw materials of which include by weight: 52.5 parts of corn, 4 parts of casein, 30 parts of soybeans, 5 parts of flour, 1.8 parts of calcium hydrogen phosphate, 2 parts of fish meal, 1.3 parts of stone powder, 1 part of yeast powder, 1 part of 1% premix, 0.5 parts of salt, 0.4 parts of vitamin C, 0.2 parts of methionine and 0.3 parts of lysine.

[0026] The 1% premix is ​​a mixture of copper, iron, zinc, manganese and vitamins. The weight ratio of copper, iron, zinc and manganese is 1:8:10:10, and the vitamin mixture includes vitamin A 100000-200000 IU / G, vitamin D3 20000 IU / G, vitamin E 60-80 IU / G, vitamin K3 10 mg / g, vitamin B1 20 mg / g, vitamin B2 40 mg / g, vitamin B6 30 mg / g, vitamin B12 0.1 mg / g, niacin 160 mg / g, pantothenic acid 40 mg / g, folic acid 5 mg / g, biotin 0.5 mg / g and choline 500 mg / g.

[0027] The soybeans are biologically bred soybeans, and biologically bred soybeans are high oleic soybeans. High oleic soybeans are a biologically bred crop with complex traits. Compared with traditional soybeans, high oleic soybeans are rich in monounsaturated fatty acids and low in unsaturated fatty acids, which help lower blood cholesterol levels and are beneficial to cardiovascular health. The oil produced by pressing does not contain trans fatty acids, which is beneficial to the health of experimental monkeys.

[0028] Compared with traditional feed preparation, this formula does not contain bran, thus avoiding the problem of excessive cellulose in the feed due to the incorporation of soybean hulls.

[0029] A biological breeding soybean feed formula for evaluating the reproductive development safety of experimental monkeys, wherein the preparation method thereof specifically comprises the following steps:

[0030] S1. Select corn, casein, soybean, flour, calcium hydrogen phosphate, fish meal, stone powder, yeast powder, 1% premix, salt, vitamin C, methionine and lysine according to the selected weight, place them separately and keep them for later use;

[0031] S2, then washing and drying the corn and soybeans, putting the dried soybeans into a steaming and frying pan for high temperature and high pressure treatment to obtain pretreated soybeans and dried corn;

[0032] S3, putting the pretreated soybeans and dried corns in S2 into a grinder for grinding, and after the grinding, cooling to room temperature to obtain crushed soybeans and powdered corns;

[0033] S4, adding the crushed soybeans and powdered corn cooled in S3 into a stirring device, and then sequentially adding casein, flour, calcium hydrogen phosphate, fish meal, stone powder, yeast powder, 1% premix, salt, methionine and lysine, and stirring with the stirring device. After the stirring is completed, adding vitamin C, and mixing again to obtain feed powder;

[0034] S5, pouring the feed powder mixed evenly in S4 into a pellet machine for processing to make feed pellets;

[0035] S6, putting the feed particles in S5 into a dryer to dry, and obtaining a biological breeding soybean feed for evaluating the reproductive development safety of experimental monkeys;

[0036] S7. The biological breeding soybean feed obtained for the reproductive development safety evaluation of experimental monkeys is bagged to ensure that the weight of each bag of feed is consistent, and the feed is vacuumed, packed in cartons, and irradiated with CO60. The feed is stored in a dry, cool, well-ventilated warehouse to avoid direct sunlight and high temperature environment.

[0037] The specific implementation method is as follows: according to the given weight points, the following raw materials are accurately selected: 52.5 parts of corn, 4 parts of casein, 30 parts of soybeans, 5 parts of flour, 1.8 parts of calcium hydrogen phosphate, 2 parts of fish meal, 1.3 parts of stone powder, 1 part of yeast powder, 1 part of 1% premix, 0.5 parts of salt, 0.4 parts of vitamin C, 0.2 parts of methionine and 0.3 parts of lysine. All the selected raw materials are placed separately to ensure that they are dry and pollution-free, and are reserved for later use. The selected gene-edited high-oleic soybeans are treated with high temperature and high pressure, and then placed in a grinder after drying for crushing. After the crushing is completed, the crushed soybeans are allowed to cool naturally to room temperature to prevent the loss of nutrients caused by high temperature. The cooled crushed soybeans are added to the stirring device, and the corn is also crushed and dried, and then casein, flour, calcium hydrogen phosphate, fish meal, Stone powder, yeast powder, 1% premix, salt, methionine and lysine are fully stirred with a stirring device to ensure that all raw materials are evenly mixed. After all other raw materials are evenly mixed, vitamin C is added and mixed again with a stirring device to ensure that vitamin C is evenly distributed in the feed powder. The evenly mixed feed powder is put into a pellet machine to make feed pellets. The prepared feed pellets are poured into clean feed bags to ensure that the weight of each bag of feed is consistent (10kg). The packaging bags are vacuumed and the packaged feed is packed in cartons. Feed information such as name, production date and batch number are posted or printed on the cartons. Feed is irradiated with CO60 and stored in a dry, cool and well-ventilated warehouse to avoid direct sunlight and high temperature environment to ensure the quality and shelf life of the feed.

[0038] The feed formula uses a variety of raw materials, including corn, casein, soybeans, especially genetically edited high oleic soybeans, flour, etc. These raw materials provide rich carbohydrates, protein and fat, ensuring the nutritional balance of the feed. By adding calcium hydrogen phosphate, fish meal, stone powder, yeast powder and 1% premix (containing copper, iron, zinc, manganese and vitamins), etc., the feed provides the experimental monkeys with essential minerals and vitamins, which helps to maintain their normal physiological functions. The soybeans are crushed to make the particles smaller, which is easier for the experimental monkeys to digest and absorb.

[0039] The above description is only by way of illustration of certain exemplary embodiments of the present invention. It is undoubted that those skilled in the art can modify the described embodiments in various ways without departing from the spirit and scope of the present invention. Therefore, the above drawings and descriptions are illustrative in nature and should not be construed as limiting the scope of protection of the claims of the present invention.

Claims

1. A biological breeding soybean feed formula for evaluating the reproductive development safety of experimental monkeys, characterized in that: The raw materials include, by weight: 52.5 parts of corn, 4 parts of casein, 30 parts of soybeans, 5 parts of flour, 1.8 parts of calcium hydrogen phosphate, 2 parts of fish meal, 1.3 parts of stone powder, 1 part of yeast powder, 1 part of 1% premix, 0.5 parts of salt, 0.4 parts of vitamin C, 0.2 parts of methionine and 0.3 parts of lysine.

2. The biological breeding soybean feed formula for evaluating the reproductive development safety of experimental monkeys according to claim 1, characterized in that: The 1% premix is ​​a mixture of copper, iron, zinc, manganese and vitamins.

3. The biological breeding soybean feed formula for evaluating the reproductive development safety of experimental monkeys according to claim 1, characterized in that: The soybeans are biologically bred soybeans, and the biologically bred soybeans are high oleic acid soybeans.

4. A biological breeding soybean feed formula for evaluating the reproductive development safety of experimental monkeys according to any one of claims 1 to 3, characterized in that: The preparation method specifically comprises the following steps: S1. Select corn, casein, soybean, flour, calcium hydrogen phosphate, fish meal, stone powder, yeast powder, 1% premix, salt, vitamin C, methionine and lysine according to the selected weight, place them separately and keep them for later use; S2, then washing and drying the corn and soybeans, putting the dried soybeans into a steaming and frying pan for high temperature and high pressure treatment to obtain pretreated soybeans and dried corn; S3, putting the pretreated soybeans and dried corns in S2 into a grinder for grinding, and after the grinding, cooling to room temperature to obtain crushed soybeans and powdered corns; S4, adding the crushed soybeans and powdered corn cooled in S3 into a stirring device, and then sequentially adding casein, flour, calcium hydrogen phosphate, fish meal, stone powder, yeast powder, 1% premix, salt, methionine and lysine, and stirring with the stirring device. After the stirring is completed, adding vitamin C, and mixing again to obtain feed powder; S5, pouring the feed powder mixed evenly in S4 into a pellet machine for processing to make feed pellets; S6, putting the feed particles in S5 into a dryer to dry, and obtaining a biological breeding soybean feed for evaluating the reproductive development safety of experimental monkeys; S7. The biological breeding soybean feed obtained for the reproductive development safety evaluation of experimental monkeys is bagged to ensure that the weight of each bag of feed is consistent, and the feed is vacuumed, packed in cartons, and irradiated with CO60. The feed is stored in a dry, cool, well-ventilated warehouse to avoid direct sunlight and high temperature environment.