A method for preparing low-sensitivity cereal antigen powder

Abstract

This invention relates to the field of medical biological antigen processing technology, and discloses a method for preparing low-sensitivity cereal antigen powder, comprising the following steps: washing and draining cereal raw materials with sterile purified water, followed by sequential ethanol soaking for desensitization, ozone water oxidation for desensitization, and auxiliary shaping treatment; then rinsing multiple times with sterile purified water, constant temperature and ventilation drying, sterile pulverization, and grading and sieving to obtain low-sensitivity cereal antigen powder; and finally, individually aseptically packaging the low-sensitivity cereal antigen powder. This invention uses rice, millet, and corn as cereal raw materials, and through a progressive combination of ethanol soaking for desensitization, ozone water oxidation for desensitization, and auxiliary shaping treatment, it modifies natural cereals to reduce their allergenicity, expanding the application of natural cereal raw materials in the preparation of low-sensitivity cereal antigen powder; it can reduce the allergenicity of cereals while retaining the immune-activating effect of natural cereal antigens.

Description

Technical Field

[0001] This invention relates to the field of medical biological antigen processing technology, and in particular to a method for preparing low-sensitivity cereal antigen powder. Background Technology

[0002] Antigens are substances that can stimulate the human immune system to produce an immune response. Antigens come from a wide range of sources, including allogeneic blood, animal blood, animal tissues, various plant proteins, insect proteins, and drug-derived proteins, all of which possess certain antigenic characteristics and can be applied to diagnosis and treatment related to immune regulation.

[0003] However, various antigens still have unavoidable drawbacks in practical clinical applications, making it difficult to meet the needs of safe, stable, and routine diagnosis and treatment. Allogeneic blood antigens are subject to medical ethics constraints and pose risks of blood contamination, cross-infection, and pathogen transmission, hindering their widespread use. Animal tissue and insect protein antigens have complex compositions and a high proportion of sensitizing components, easily inducing allergic reactions, resulting in fluctuating treatment effects and poor controllability. Common plant and vegetable antigens have significant individual differences in suitability and are prone to adverse reactions. Drug-based antigens have certain toxic side effects, and long-term use may affect human organ function, limiting their applicability to certain populations.

[0004] Rice, millet, and corn are staple foods for most people, and allergic reactions are rare with long-term oral consumption, making them relatively safe to eat. However, these grains contain specific protein components that possess a certain ability to stimulate antigens. If they are directly processed into preparations for injection in their original state, they can easily induce allergic immune reactions, posing a medical safety risk.

[0005] Current applications of cereal-based immunotherapy have significant limitations. In China, cereal antigen-related technologies are mainly used for oral desensitization, skin allergy testing, and surface irritation. Internationally, rice-based immunotherapy products often rely on transgenic technology to express exogenous antigens and are typically limited to oral use. In Europe and America, cereals are primarily used for allergy screening and oral desensitization. Currently, there is a lack of mature technologies for producing injectable immunoantigens from natural rice, millet, and corn after desensitization modification.

[0006] Furthermore, conventional single desensitization methods have limited effects on modifying cereal raw materials, making it difficult to simultaneously reduce sensitization and retain antigen activity. The industry also lacks mature, stable, and mass-producible multi-stage desensitization processes for natural cereals. Therefore, there is an urgent need for a method to prepare low-sensitivity cereal antigen powder that can reduce the risk of allergic reactions from natural cereals, retain their antigenic stimulating ability, and is suitable for standardized production. This would address the issues of easy allergic reactions when natural cereals are directly applied, the lack of unified medical processing standards, and the insufficient safety and compatibility of existing antigen sources. Summary of the Invention

[0007] The purpose of this invention is to address the shortcomings of existing technologies by proposing a method for preparing low-sensitivity grain antigen powder.

[0008] To achieve the above objectives, the present invention adopts the following technical solution:

[0009] A method for preparing a low-sensitivity cereal antigen powder includes the following steps:

[0010] After washing and draining the grain raw materials with sterile purified water, the grain raw materials were subjected to ethanol soaking for desensitization, ozone water oxidation for desensitization, and auxiliary shaping treatment in sequence.

[0011] Then, the powder is repeatedly rinsed with sterile purified water, dried under constant temperature and ventilation, aseptically pulverized and graded to obtain low-sensitivity cereal antigen powder of 100-500 mesh.

[0012] The low-sensitivity cereal antigen powder is individually aseptically packaged, with a single-dose package weight of 0.05g~2g;

[0013] The grain raw materials include at least one of rice, millet, and corn.

[0014] Preferably, the grain raw material is a clean grain raw material that is free from mold, insects, and pollution; when the grain raw material is corn, the peeled and clean corn endosperm is selected, and coarse fiber impurities are removed.

[0015] Preferably, the ethanol immersion desensitization uses a 90% medical ethanol solution, the immersion time is 40 minutes, and the stirring speed during the immersion process is 30~50 r / min.

[0016] Preferably, the ozone water oxidation desensitization uses a sterile ozone aqueous solution with an ozone concentration of 5 mg / L, and is treated at room temperature in a sealed environment for 30 minutes.

[0017] Preferably, the auxiliary shaping treatment is set after ozone water oxidation and desensitization and before constant temperature ventilation drying. The pH value of the treatment system is 6.8~7.2, the treatment temperature is 38℃~40℃, the stirring speed is 25~30r / min, and the continuous shaping and soaking time is 25min.

[0018] Preferably, the particle size of the low-sensitivity cereal antigen powder is 300 mesh.

[0019] Preferably, the weight of the single-agent encapsulation is 0.2g.

[0020] Preferably, the temperature for constant temperature ventilation drying is 50°C.

[0021] A hypoallergenic cereal antigen product includes hypoallergenic cereal antigen powder prepared by the above preparation method, wherein the hypoallergenic cereal antigen powder is packaged in an independent aseptic package with a single package weight of 0.05g to 2g.

[0022] The beneficial effects of this invention are as follows:

[0023] This invention uses rice, millet, and corn as grain raw materials. Through a progressive combination of processes including ethanol soaking for desensitization, ozone water oxidation for desensitization, and auxiliary shaping treatment, natural grains are modified to reduce their sensitivity, thus expanding the application of natural grain raw materials in the preparation of low-sensitivity grain antigen powders.

[0024] In this invention, ethanol soaking desensitizes the alcohol-soluble allergenic proteins, ozone water oxidation desensitizes the proteins, and auxiliary shaping treatment regularizes the spatial configuration of the cereal proteins, locks in effective antigen sites, eliminates residual trace allergenic groups, and prevents protein structure rebound and resensitization during constant temperature and ventilation drying. These three processes work synergistically to achieve deep desensitization of the cereal raw materials.

[0025] This invention can reduce the allergenicity of grains while preserving the immune-activating effect of natural grain antigens. Testing showed that after treatment using the method of this invention, the overall allergenicity of grains decreased by no less than 80%, and the effective immune activity retention rate was no less than 96.1%, thus improving upon the problem that single desensitization methods often fail to simultaneously achieve both low allergenicity and antigen activity.

[0026] The preparation method of the present invention is applicable to three types of grain raw materials: rice, millet, and corn. The three types of grain raw materials can share the same preparation process and process parameters, which has good process versatility and facilitates standardized production.

[0027] This invention limits the particle size of the low-sensitivity cereal antigen powder to 100-500 mesh and the single-dose packaging weight to 0.05g-2g, which helps to improve the consistency of finished product specifications and ease of use.

[0028] The low-sensitivity cereal antigen powder prepared by this invention can be used as a supporting raw material for immune awakening systems. Low-sensitivity cereal antigen powders made from rice, millet, or corn can be used alternately to utilize the differences in epitopes of different cereal antigens to form diversified immune stimulation and reduce the risk of immune tolerance that may occur with long-term use of a single raw material. Detailed Implementation

[0029] To provide a clearer understanding of the technical features, objectives, and beneficial effects of this invention, the technical solution of this invention is described in detail below, but this should not be construed as limiting the scope of implementation of this invention. Unless otherwise specified, the raw materials, reagents, or equipment used in this invention can all be commercially available products conventional in the art.

[0030] In one embodiment, the present invention provides a method for preparing low-sensitivity cereal antigen powder, comprising the following steps:

[0031] After washing and draining the grain raw materials with sterile purified water, the grain raw materials were subjected to ethanol soaking for desensitization, ozone water oxidation for desensitization, and auxiliary shaping treatment in sequence.

[0032] Then, the powder is repeatedly rinsed with sterile purified water, dried under constant temperature and ventilation, aseptically pulverized and graded to obtain low-sensitivity cereal antigen powder of 100-500 mesh.

[0033] The low-sensitivity cereal antigen powder is individually aseptically packaged, with a single-dose package weight of 0.05g~2g;

[0034] The grain raw materials include at least one of rice, millet, and corn.

[0035] In a preferred embodiment of the present invention, the grain raw material is a clean grain raw material that is free from mold, insects, and pollution; when the grain raw material is corn, the peeled and clean corn endosperm is selected, and coarse fiber impurities are removed.

[0036] In a preferred embodiment of the present invention, the ethanol soaking desensitization uses a 90% medical ethanol solution, the soaking time is 40 minutes, and the stirring speed during the soaking process is 30~50 r / min.

[0037] In a preferred embodiment of the present invention, the ozone water oxidation desensitization uses a sterile ozone aqueous solution with an ozone concentration of 5 mg / L, and is treated at room temperature in a sealed environment for 30 minutes.

[0038] In a preferred embodiment of the present invention, the auxiliary shaping treatment is performed after ozone water oxidation and desensitization and before constant temperature ventilation drying. The pH value of the treatment system is 6.8~7.2, the treatment temperature is 38℃~40℃, the stirring speed is 25~30r / min, and the continuous shaping and soaking time is 25min.

[0039] In a preferred embodiment of the present invention, the particle size of the low-sensitivity cereal antigen powder is 300 mesh.

[0040] In a preferred embodiment of the present invention, the weight of the single-agent encapsulation is 0.2g.

[0041] In a preferred embodiment of the present invention, the temperature for constant temperature ventilation drying is 50°C.

[0042] In another embodiment, the present invention provides a low-sensitivity cereal antigen product, comprising low-sensitivity cereal antigen powder prepared by the above preparation method, wherein the low-sensitivity cereal antigen powder is packaged in an independent aseptic package, with a single package weight of 0.05g to 2g.

[0043] This invention provides a method for preparing low-sensitivity cereal antigen powder. Using at least one of rice, millet and corn as cereal raw materials, a multi-step desensitization process system is formed through ethanol soaking desensitization, ozone water oxidation desensitization and auxiliary shaping treatment. This system removes the sensitizing active substances in the cereal raw materials in layers, while preserving the immune-activating effect of the natural cereal antigens as much as possible.

[0044] Specifically, after washing and draining the grain raw materials with sterile purified water, they are first desensitized by ethanol soaking, then desensitized by ozone water oxidation, and finally subjected to auxiliary shaping treatment. Ethanol soaking desensitization, ozone water oxidation desensitization, and auxiliary shaping treatment are performed sequentially, working synergistically to achieve deep antigen modification of the grain raw materials. Ethanol soaking desensitization is mainly used to dissolve alcohol-soluble allergenic proteins in the grain raw materials, reducing their allergenic activity; ozone water oxidation desensitization is mainly used to oxidatively desensitize and modify the allergenic proteins; auxiliary shaping treatment is mainly used to regulate the spatial configuration of grain proteins, lock in effective antigenic sites with immune-activating effects, further eliminate residual trace allergenic groups, stabilize the physicochemical properties of the finished product, and prevent protein structure rebound and resensitization during the subsequent constant temperature and ventilation drying process.

[0045] In the ethanol immersion desensitization process, the grain raw materials were soaked in a 90% medical ethanol solution for 40 minutes, with a stirring speed of 30-50 rpm during the soaking process. The 90% medical ethanol solution can dissolve alcohol-soluble allergenic proteins in the grain raw materials and affect the spatial structure of allergens, thereby reducing the allergenic activity of the grain raw materials.

[0046] In the ozone water oxidation desensitization process, a sterile ozone solution with an ozone concentration of 5 mg / L is used to treat the ethanol-soaked and desensitized grain raw materials at room temperature in a sealed environment for 30 minutes. Ozone water oxidation desensitization can act on the amino acid residues, disulfide bond structure, and IgE specific recognition sites of the grain allergenic proteins, disrupting the spatial conformation of the allergenic proteins and reducing the possibility of the allergenic sites binding to human immune cells. After the ozone reaction, it ultimately decomposes into oxygen, producing no harmful residues, making it a suitable desensitization processing method for grain raw materials.

[0047] The auxiliary shaping treatment is performed after ozone water oxidation desensitization and before constant temperature and ventilation drying. The auxiliary shaping treatment uses a sterile purified water system, maintaining a pH of 6.8–7.2, a temperature of 38–40°C, a stirring speed of 25–30 r / min, and a continuous shaping soaking time of 25 min. Through this auxiliary shaping treatment, after ethanol soaking desensitization and ozone water oxidation desensitization, the spatial configuration of the cereal protein can be further regularized, preserving effective antigenic sites with immune-activating effects and further eliminating residual trace sensitizing groups, thereby achieving a balance between desensitization effect and antigen activity retention.

[0048] Ethanol soaking desensitization, ozone water oxidation desensitization, and auxiliary shaping treatment work synergistically in a fixed order, rather than being a simple superposition of individual processes. Ethanol soaking desensitization is used to initially reduce the sensitizing activity in grain raw materials, ozone water oxidation desensitization is used for further oxidative desensitization modification, and auxiliary shaping treatment is used to stabilize the grain protein structure after desensitization. The three work together to ensure that the grain raw materials retain their immune-activating ability while reducing sensitization.

[0049] After auxiliary shaping treatment, the grain raw materials are rinsed multiple times with sterile purified water to remove surface residues and free allergenic proteins. Following rinsing, the grain raw materials are dried at a constant temperature and ventilation of 50°C. The dried grain raw materials are then aseptically pulverized and graded by sieving to obtain low-allergenic grain antigen powder with a particle size of 100-500 mesh. Subsequently, the low-allergenic grain antigen powder is individually aseptically packaged.

[0050] In the preparation method of this invention, rice, millet, and corn can be prepared using the same set of processes: ethanol soaking for desensitization, ozone water oxidation for desensitization, auxiliary shaping treatment, multiple rinsing with sterile purified water, constant temperature and ventilation drying, sterile pulverization and grading sieving, and independent sterile packaging. When the grain raw material is rice, clean rice is selected as the raw material; when the grain raw material is millet, clean millet is selected as the raw material; when the grain raw material is corn, peeled and clean corn endosperm is selected, and coarse fiber impurities are removed. Through this universal process, low-sensitivity grain antigen powders of rice, millet, or corn can be obtained respectively.

[0051] Testing showed that after treatment using the preparation method of this invention, the overall allergenicity of the grains decreased by more than 80%, and the antigen activity retention rate was not less than 96.1%. This result indicates that the preparation method of this invention can reduce the allergenicity of grain raw materials while retaining the immune-activating effect of natural grain antigens, thus providing the low-allergenic grain antigen powder with the foundation to serve as a supporting raw material for immune awakening systems.

[0052] The hypoallergenic cereal antigen powder prepared by this invention can be used as a supporting raw material for immune awakening systems. In practical applications, hypoallergenic cereal antigen powders made from rice, millet, or corn can be selected as needed, or hypoallergenic cereal antigen powders made from different cereal raw materials can be used alternately to utilize the differences in epitopes of different cereal antigens to form diversified immune stimulation. Autologous blood and medical immune stimulation solutions are common and conventional materials and are not protected by this invention.

[0053] The hypoallergenic cereal antigen powder prepared by this invention undergoes ethanol soaking for desensitization, ozone water oxidation for desensitization, and auxiliary shaping treatment, significantly reducing the risk of sensitization. However, trace amounts of natural antigen activity are still retained, leading to individual differences in tolerance. Therefore, when using this product, it should be handled in accordance with standard medical operating procedures, including conducting skin allergy tests before use, and should be operated by qualified medical personnel.

[0054] The specific implementation of the present invention will be described in detail below with reference to specific embodiments.

[0055] Example 1: Preparation of low-sensitivity rice cereal antigen powder. High-quality, impurity-free refined rice was selected as the cereal raw material. After washing off surface impurities with sterile purified water, the rice was drained at room temperature. The drained rice was then immersed in a 90% medical ethanol solution for ethanol desensitization for 40 minutes, with low-speed stirring at 30-50 r / min during the soaking process.

[0056] After ethanol soaking for desensitization, the rice was rinsed to remove residual ethanol; then it was placed in a sterile ozone solution with an ozone concentration of 5 mg / L for ozone water oxidation desensitization, and treated at room temperature in a sealed environment for 30 minutes.

[0057] After ozone water oxidation and desensitization are completed, an auxiliary shaping treatment is immediately carried out. The pH value of the auxiliary shaping treatment system is 6.8~7.2, the treatment temperature is 38℃~40℃, the stirring speed is 25~30 r / min, and the continuous shaping and soaking time is 25 min.

[0058] After the auxiliary shaping process, the rice was rinsed multiple times with sterile purified water and then placed in a constant-temperature, ventilated environment at 50°C for drying. After drying, the rice was aseptically pulverized and graded by sieving to obtain a uniform, low-sensitivity cereal antigen powder of 300 mesh. Subsequently, the low-sensitivity cereal antigen powder was individually aseptically packaged at a single-dose packaging weight of 0.2g.

[0059] Testing showed that the allergenic protein removal rate of the rice low-sensitivity cereal antigen powder prepared in this embodiment was 81.2%, and the immune activity retention rate was 96.2%.

[0060] Example 2: Preparation of low-sensitivity millet grain antigen powder. High-quality millet free from mold and impurities was selected as the grain raw material. After washing away surface impurities with sterile purified water, the millet was drained at room temperature. The drained millet was then immersed in a 90% (w / w) medical ethanol solution for ethanol desensitization for 40 minutes, with low-speed stirring at 30-50 rpm during the soaking process.

[0061] After ethanol soaking for desensitization, the millet was rinsed to remove residual ethanol; then it was placed in a sterile ozone solution with an ozone concentration of 5 mg / L for ozone water oxidation desensitization and treated at room temperature in a sealed environment for 30 minutes.

[0062] After ozone water oxidation and desensitization are completed, an auxiliary shaping treatment is immediately carried out. The pH value of the auxiliary shaping treatment system is 6.8~7.2, the treatment temperature is 38℃~40℃, the stirring speed is 25~30 r / min, and the continuous shaping and soaking time is 25 min.

[0063] After the auxiliary shaping process, the millet was rinsed multiple times with sterile purified water and then placed in a constant-temperature, ventilated environment at 50°C for drying. After drying, the millet was aseptically pulverized and graded by sieving to obtain a uniform, low-sensitivity cereal antigen powder of 300 mesh. Subsequently, the low-sensitivity cereal antigen powder was individually aseptically packaged at a single-dose packaging weight of 0.2g.

[0064] Testing showed that the allergenic protein removal rate of the millet hypoallergenic cereal antigen powder prepared in this embodiment was 81.5%, and the immune activity retention rate was 96.5%. The physicochemical properties, hypoallergenic effect, and immune activation performance of the product were consistent with those of the rice hypoallergenic cereal antigen powder prepared in Example 1.

[0065] Example 3: Preparation of low-sensitivity corn cereal antigen powder. Peeled and cleaned corn endosperm was selected as the cereal raw material, and coarse fiber impurities were removed. After washing the surface impurities with sterile purified water, the endosperm was drained at room temperature. The drained corn endosperm was then immersed in a 90% (w / w) medical ethanol solution for ethanol desensitization for 40 minutes, with low-speed stirring at 30-50 rpm during the immersion process.

[0066] After ethanol soaking for desensitization, the corn endosperm was rinsed to remove residual ethanol; then it was placed in a sterile ozone solution with an ozone concentration of 5 mg / L for ozone water oxidation desensitization and treated at room temperature in a sealed environment for 30 minutes.

[0067] After ozone water oxidation and desensitization are completed, an auxiliary shaping treatment is immediately carried out. The pH value of the auxiliary shaping treatment system is 6.8~7.2, the treatment temperature is 38℃~40℃, the stirring speed is 25~30 r / min, and the continuous shaping and soaking time is 25 min.

[0068] After the auxiliary shaping treatment, the corn endosperm was rinsed multiple times with sterile purified water and then placed in a constant temperature and ventilation environment at 50°C for drying. After drying, the corn endosperm was aseptically pulverized and graded by sieving to obtain a uniform low-sensitivity cereal antigen powder of 300 mesh. Subsequently, the low-sensitivity cereal antigen powder was individually aseptically packaged at a single-dose packaging weight of 0.2g.

[0069] Testing showed that the removal rate of allergenic proteins in the corn hypoallergenic cereal antigen powder prepared in this embodiment was 80.9%, and the retention rate of immune activity was 96.1%.

[0070] The desensitization effect of grain samples before and after treatment using the method of this invention was tested. Three detection methods were used: in vitro IgE affinity binding assay, protein electrophoresis sensitization band grayscale analysis, and mast cell degranulation assay, to comprehensively evaluate the desensitization effect of the low-sensitivity grain antigen powder.

[0071] Testing revealed that, after treatment using the method of this invention, the overall removal rate of allergenic proteins was no less than 80.9%; the specific binding rate of proteins to human IgE decreased by no less than 80.7%; and the degranulation rate of mast cells decreased from 42.6% in the original grain sample to less than 6.9%. Based on the above test results, the overall allergenicity of grains treated using the method of this invention decreased by no less than 80%.

[0072] Furthermore, the immunological activity retention of grain samples before and after treatment using the method of this invention was tested. During the test, antigen activity was detected by a lymphocyte proliferation and transformation assay, with the Stimulation Index (SI) used as the evaluation criterion.

[0073] The SI value of the native cereal protein was 1.82, and the SI value of the low-sensitivity cereal antigen powder obtained by modification using the method of this invention was 1.75. Based on these SI values, the effective immune activity retention rate after treatment using the method of this invention is no less than 96.1%, indicating that the low-sensitivity cereal antigen powder obtained after ethanol soaking desensitization, ozone water oxidation desensitization, and auxiliary shaping treatment retains its immune-activating ability while reducing sensitization.

[0074] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A method for preparing a low-sensitivity cereal antigen powder, characterized in that, Includes the following steps: After washing and draining the grain raw materials with sterile purified water, the grain raw materials were subjected to ethanol soaking for desensitization, ozone water oxidation for desensitization, and auxiliary shaping treatment in sequence. Then, the powder is repeatedly rinsed with sterile purified water, dried under constant temperature and ventilation, aseptically pulverized and graded to obtain low-sensitivity cereal antigen powder of 100-500 mesh. The low-sensitivity cereal antigen powder is individually aseptically packaged, with a single-dose package weight of 0.05g~2g; The grain raw materials include at least one of rice, millet, and corn.

2. The method for preparing a low-sensitivity cereal antigen powder according to claim 1, characterized in that, The grain raw material is a clean grain raw material that is free from mold, insects, and pollution; when the grain raw material is corn, the peeled and clean corn endosperm is selected, and coarse fiber impurities are removed.

3. The method for preparing a low-sensitivity cereal antigen powder according to claim 1, characterized in that, The ethanol immersion desensitization uses a 90% medical ethanol solution, with an immersion time of 40 minutes and a stirring speed of 30-50 r / min during the immersion process.

4. The method for preparing a low-sensitivity cereal antigen powder according to claim 1, characterized in that, The ozone water oxidation desensitization process uses a sterile ozone aqueous solution with an ozone concentration of 5 mg / L, and is treated at room temperature in a sealed environment for 30 minutes.

5. The method for preparing a low-sensitivity cereal antigen powder according to claim 1, characterized in that, The auxiliary shaping treatment is set after ozone water oxidation and desensitization and before constant temperature ventilation drying. The pH value of the treatment system is 6.8~7.2, the treatment temperature is 38℃~40℃, the stirring speed is 25~30r / min, and the continuous shaping and soaking time is 25min.

6. The method for preparing a low-sensitivity cereal antigen powder according to claim 1, characterized in that, The particle size of the low-sensitivity cereal antigen powder is 300 mesh.

7. The method for preparing a low-sensitivity cereal antigen powder according to claim 1, characterized in that, The weight of the single-agent encapsulation is 0.2g.

8. The method for preparing a low-sensitivity cereal antigen powder according to claim 1, characterized in that, The temperature for constant temperature ventilation drying is 50℃.

9. A low-sensitivity cereal antigen product, characterized in that, The preparation includes low-sensitivity cereal antigen powder prepared by any of the preparation methods described in claims 1-8, wherein the low-sensitivity cereal antigen powder is packaged in an individual aseptic package with a single package weight of 0.05g to 2g.