Preparation method of chemically modified high-activity cholla horn protease microcapsule anti-allergic agent
By chemically modifying the combination of highly active bell keratosin, carboxymethylcellulose and sodium alginate, microcapsules are prepared by atomizing and drying mechanism, the problems of insufficient anti-allergicity and high irritation of traditional anti-allergic agents are solved, and the problem of insufficient anti-allergicity and great irritation of traditional anti-allergic agents is achieved. It has efficient and long-term anti-allergic effects.
Patent Information
- Application Number
- CN202411444209.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-16
- Publication Date
- 2025-01-10
AI Technical Summary
Traditional anti-allergic agents are not strong in environmental prevention and treatment, cannot achieve controlled release and inactivation, and are highly irritating to hair and skin, unable to deeply moisturize hair, and cannot achieve long-lasting and long-lasting anti-allergic effects.
Microcapsules are prepared through atomization and drying mechanism to form chemically modified high-active bell keratoplastase microcapsules, carboxymethylcellulose and sodium alginate to form chemically modified high-active bell keratoplastase microcapsules anti-allergic agents.
It significantly improves the activity and retention time, stability and delivery efficiency of anti-allergic agents, achieves deep moisturizing of hair and skin, avoids irritation, and provides a long-lasting and long-lasting anti-allergic effect.
Smart Images
Figure CN119280186A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the field of antiallergic agents, and in particular relates to a method for preparing a chemically modified high-activity bell-like protease microcapsule antiallergic agent. Background Art
[0002] Allergic diseases include allergic rhinitis, allergic bronchial asthma, atopic dermatitis, food allergies and other diseases. Allergic diseases affect 40% of the population. Globally, about 400 million people suffer from allergic rhinitis, 300 million people suffer from asthma, and 250 million people have food allergies. Allergic diseases have been listed by the WHO as one of the six most common chronic diseases and have become a disease that needs to be studied and prevented in the 21st century. Allergic diseases not only affect the quality of life, but may also endanger life and bring heavy economic burdens to families and society. In recent years, the prevalence of allergic diseases in my country has shown a rapid upward trend, gradually approaching or even exceeding that of Western developed countries. Multiple allergic diseases may occur in the same patient at the same time, posing serious challenges to diagnosis, treatment and prevention.
[0003] The occurrence of allergic reactions is divided into three stages. The first stage is the sensitization stage. In this stage, the target cells in the body grasp the allergens and produce an allergic reaction. After the allergic reaction, bioactive mediators are produced, which put the body in a sensitized state. If there is no contact with allergens for a long time, the sensitized state will disappear. The second stage is the excitation stage. In this stage, the same allergen enters the body again, and the release of bioactive mediators increases, causing smooth muscle contraction and increased capillary permeability. The third stage is the effect stage. In this stage, various discomforts induced by allergic reactions occur. The above-mentioned released bioactive substances act on the target organs of the body, causing skin discomfort symptoms or gastrointestinal discomfort symptoms.
[0004] The prevention and treatment of allergic diseases can also be mainly divided into two categories: drug treatment and environmental prevention. Among them, drug treatment is aimed at the body itself; environmental prevention refers to reducing the incidence of the disease by avoiding factors that induce allergies. There are four common allergens, including dust mites, pollen, cat hair, and dog hair. Traditional anti-allergic agents are not strong in anti-allergic properties during environmental prevention, and cannot achieve controlled release and inactivation. How to prepare a product that can significantly improve the activity of anti-allergic agents and is non-irritating to hair and skin, deeply moisturizes hair, and has long-lasting anti-allergic properties is a problem that needs to be solved urgently in the existing market. Summary of the invention
[0005] In view of the existing problems, the present invention discloses a method for preparing a chemically modified high-activity Bell's protease microcapsule antiallergic agent, which uses chemically modified high-activity Bell's protease as a raw material and adopts an atomizing dryer to perform microencapsulation treatment to prepare the antiallergic agent.
[0006] The present invention discloses a method for preparing a chemically modified high-activity bell-shaped hornwort protease microcapsule antiallergic agent, and the preparation method mainly comprises the following steps:
[0007] (1) subjecting the protease to chemical modification with a chemical modifier of a certain concentration according to a certain volume ratio to obtain a chemically modified protease;
[0008] (2) subjecting a Bell's protease promoter to an enzymatic reaction with a chemically modified Bell's protease to obtain a chemically modified highly active Bell's protease;
[0009] (3) A certain mass fraction of carboxymethyl cellulose solution, sodium alginate solution and chemically modified high-activity C. bellii protease are uniformly mixed, and microencapsulated in a certain manner to obtain chemically modified high-activity C. bellii protease microcapsules.
[0010] The certain concentration described in step (1) is 100 μg / mL-200 μg / mL; preferably 120-180 μg / mL.
[0011] The chemical modifier described in step (1) is one or more of dextran, polyethylene glycol, and heparin; preferably dextran and polyethylene glycol.
[0012] The certain volume ratio described in step (1) is to add 5-10 mL of the chemical modifier to 40-50 mL of a 5 mg / mL-10 mg / mL Bell's hornwort protease solution; preferably, 5-8 mL of the chemical modifier is added to 40-45 mL of a 8 mg / mL-10 mg / mL Bell's hornwort protease solution.
[0013] The chemical modification reaction conditions in step (1) are stirring at 25-30° C. for 1-2 hours.
[0014] The bell-type hornwort protease promoter described in step (2) is 8-((4-(2,4-dimethoxyphenyl)piperazine-1-yl)methyl)-5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-benzopyran-4-one.
[0015] The amount of the protease promoter added in step (2) is 2-4% of the mass of the protease; preferably 3-4%.
[0016] The enzymatic reaction conditions in step (2) are as follows: pH value is 6.3-6.5, enzymatic temperature is 20-30° C., and enzymatic time is 2-2.5 h.
[0017] The certain mass fraction described in step (3) is that the concentration of carboxymethyl cellulose solution is 80-100 g / L, the concentration of trehalose solution is 20-40 g / L, and the concentration of chemically modified high-activity Bell's protease solution is 30-40 g / L; preferably, the concentration of carboxymethyl cellulose solution is 90-100 g / L, the concentration of trehalose solution is 30-40 g / L, and the concentration of chemically modified high-activity Bell's protease solution is 30-40 g / L.
[0018] The certain volume ratio in step (3) refers to the carboxymethyl cellulose solution: trehalose solution: chemically modified high-activity hornwort protease solution of 3:4:2.
[0019] The certain method described in step (3) is to use an atomizing dryer to carry out microencapsulation treatment.
[0020] Carboxymethyl cellulose Carboxymethyl cellulose Carboxymethyl cellulose The present invention uses highly active Bell's hornwort protease after chemical modification and enzymatic reaction as raw materials, and adopts atomizing dryer for microencapsulation to prepare antiallergic agent. The antiallergic agent prepared by the method of the present invention can significantly improve the retention time, stability and delivery efficiency of chemically modified highly active Bell's hornwort protease, and the microcapsules are easy to manufacture and use, and can effectively solve the problems of controlled release and inactivation that cannot be solved by traditional processes, thereby achieving good antiallergic properties. BRIEF DESCRIPTION OF THE DRAWINGS
[0021] Figure 1 This is a graph showing the anti-allergic performance of the anti-allergic agents with different proportions in Examples 1-5 of the present invention against the house dust mite allergen protein Der p 1;
[0022] Figure 2 This is a graph showing the anti-allergic performance of the anti-allergic agents with different proportions in Examples 1-5 of the present invention against the house dust mite allergen protein Der f1;
[0023] Figure 3 This is a graph showing the anti-allergic performance of the anti-allergic agents with different proportions in Examples 1-5 of the present invention against cat dander allergen protein Fel d1;
[0024] Figure 4 This is a graph showing the anti-allergic performance of the anti-allergic agents in different proportions in Examples 1-5 of the present invention against the dog dander allergen protein Can f1. DETAILED DESCRIPTION
[0025] The method of the present invention is described in detail below in conjunction with specific embodiments. This embodiment is implemented based on the technical solution of the present invention, but the protection scope of the present invention is not limited to the following embodiments.
[0026] Example 1
[0027] (1) 40 mL of 10 mg / mL Bell's hornwort protease and 5 mL of 180 μg / mL dextran were mixed evenly, and stirred at 25-30° C. for 1-2 hours to perform a chemical modification reaction to obtain a chemically modified Bell's hornwort protease;
[0028] (2) 4 g of 8-((4-(2,4-dimethoxyphenyl)piperazine-1-yl)methyl)-5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-benzopyran-4-one and 100 g of the above-mentioned chemically modified bell-shaped protease are subjected to an enzymatic reaction, and the enzymatic reaction conditions are pH 6.3-6.5, enzymatic temperature 20-30° C., and enzymatic time 2-2.5 h to obtain a chemically modified high-activity bell-shaped protease;
[0029] (3) 30 mL of 90 g / L carboxymethyl cellulose solution, 40 mL of 40 g / L trehalose solution and 20 mL of 20 g / L chemically modified high-activity Camphora protease were mixed evenly, and microencapsulated using an atomizing dryer to obtain chemically modified high-activity Camphora protease microcapsules.
[0030] Carboxymethyl cellulose Example 2
[0031] (1) 40 mL of 10 mg / mL Bell's hornwort protease and 5 mL of 160 μg / mL dextran were mixed evenly, and stirred at 25-30° C. for 1-2 hours to perform a chemical modification reaction to obtain a chemically modified Bell's hornwort protease;
[0032] (2) 4 g of 8-((4-(2,4-dimethoxyphenyl)piperazine-1-yl)methyl)-5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-benzopyran-4-one and 100 g of the above-mentioned chemically modified bell-shaped protease are subjected to an enzymatic reaction, and the enzymatic reaction conditions are pH 6.3-6.5, enzymatic temperature 20-30° C., and enzymatic time 2-2.5 h to obtain a chemically modified high-activity bell-shaped protease;
[0033] (3) 30 mL of 90 g / L carboxymethyl cellulose solution, 40 mL of 40 g / L trehalose solution and 20 mL of 20 g / L chemically modified high-activity Camphora protease were mixed evenly, and microencapsulated using an atomizing dryer to obtain chemically modified high-activity Camphora protease microcapsules.
[0034] Carboxymethyl cellulose Example 3
[0035] (1) 40 mL of 10 mg / mL Bell's hornwort protease and 5 mL of 140 μg / mL dextran were mixed evenly, and stirred at 25-30° C. for 1-2 hours to perform a chemical modification reaction to obtain a chemically modified Bell's hornwort protease;
[0036] (2) 4 g of 8-((4-(2,4-dimethoxyphenyl)piperazine-1-yl)methyl)-5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-benzopyran-4-one and 100 g of the above-mentioned chemically modified bell-shaped protease are subjected to an enzymatic reaction, and the enzymatic reaction conditions are pH 6.3-6.5, enzymatic temperature 20-30° C., and enzymatic time 2-2.5 h to obtain a chemically modified high-activity bell-shaped protease;
[0037] (3) 30 mL of 90 g / L carboxymethyl cellulose solution, 40 mL of 40 g / L trehalose solution and 20 mL of 20 g / L chemically modified high-activity Camphora protease were mixed evenly, and microencapsulated using an atomizing dryer to obtain chemically modified high-activity Camphora protease microcapsules.
[0038] Carboxymethyl cellulose Example 4
[0039] (1) 40 mL of 10 mg / mL Bell's hornwort protease and 5 mL of 120 μg / mL dextran were mixed evenly, and stirred at 25-30° C. for 1-2 hours to perform a chemical modification reaction to obtain a chemically modified Bell's hornwort protease;
[0040] (2) 4 g of 8-((4-(2,4-dimethoxyphenyl)piperazine-1-yl)methyl)-5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-benzopyran-4-one and 100 g of the above-mentioned chemically modified bell-shaped protease are subjected to an enzymatic reaction, and the enzymatic reaction conditions are pH 6.3-6.5, enzymatic temperature 20-30° C., and enzymatic time 2-2.5 h to obtain a chemically modified high-activity bell-shaped protease;
[0041] (3) 30 mL of 90 g / L carboxymethyl cellulose solution, 40 mL of 40 g / L trehalose solution and 20 mL of 20 g / L chemically modified high-activity Camphora protease were mixed evenly, and microencapsulated using an atomizing dryer to obtain chemically modified high-activity Camphora protease microcapsules.
[0042] Carboxymethyl cellulose Example 5
[0043] (1) 40 mL of 10 mg / mL C. ceratospermum protease and 5 mL of 180 μg / mL polyethylene glycol were mixed evenly, and stirred at 25-30° C. for 1-2 hours to perform a chemical modification reaction to obtain a chemically modified C. ceratospermum protease;
[0044] (2) 4 g of 8-((4-(2,4-dimethoxyphenyl)piperazine-1-yl)methyl)-5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-benzopyran-4-one and 100 g of the above-mentioned chemically modified bell-shaped protease are subjected to an enzymatic reaction, and the enzymatic reaction conditions are pH 6.3-6.5, enzymatic temperature 20-30° C., and enzymatic time 2-2.5 h to obtain a chemically modified high-activity bell-shaped protease;
[0045] (3) 30 mL of 90 g / L carboxymethyl cellulose solution, 40 mL of 40 g / L trehalose solution and 20 mL of 20 g / L chemically modified high-activity Camphora protease were mixed evenly, and microencapsulated using an atomizing dryer to obtain chemically modified high-activity Camphora protease microcapsules.
[0046] Carboxymethyl cellulose
[0047] Test method: using Methods To detect the anti-allergic effect.
Claims
1. A method for preparing a chemically modified highly active hornwort protease microcapsule antiallergic agent, characterized in that: The preparation method mainly comprises the following steps: (1) subjecting the protease to chemical modification with a chemical modifier of a certain concentration according to a certain volume ratio to obtain a chemically modified protease; (2) subjecting a Bell's protease promoter to an enzymatic reaction with a chemically modified Bell's protease to obtain a chemically modified highly active Bell's protease; (3) A certain mass fraction of carboxymethyl cellulose solution, a sodium alginate solution and a chemically modified high-activity Bell's protease are uniformly mixed according to a certain volume fraction, and microencapsulated in a certain manner to obtain chemically modified high-activity Bell's protease microcapsules.
2. The method for preparing a chemically modified highly active hornwort protease microcapsule antiallergic agent according to claim 1, characterized in that: The certain concentration described in step (1) is 100 μg / mL-200 μg / mL.
3. The method for preparing a chemically modified highly active hornwort protease microcapsule antiallergic agent according to claim 1, characterized in that: The chemical modifier described in step (1) is one or more of dextran, polyethylene glycol, and heparin.
4. The method for preparing a chemically modified highly active hornwort protease microcapsule antiallergic agent according to claim 1, characterized in that: The certain volume ratio described in step (1) is to add 5-10 mL of the chemical modifier into 40-50 mL of a 5 mg / mL-10 mg / mL solution of C.
5. The method for preparing a chemically modified highly active hornwort protease microcapsule antiallergic agent according to claim 1, characterized in that: The chemical modification reaction conditions in step (1) are stirring at 25-30° C. for 1-2 hours.
6. The method for preparing a chemically modified highly active hornwort protease microcapsule antiallergic agent according to claim 1, characterized in that: The bell-type hornwort protease promoter described in step (2) is 8-((4-(2,4-dimethoxyphenyl)piperazine-1-yl)methyl)-5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-benzopyran-4-one.
7. The method for preparing a chemically modified highly active Ceratitis protease microcapsule antiallergic agent according to claim 1, characterized in that: The amount of the protease promoter added in step (2) is 2-4% of the mass of the protease.
8. The method for preparing a chemically modified highly active Ceratitis protease microcapsule antiallergic agent according to claim 1, characterized in that: The enzymatic reaction conditions in step (2) are as follows: pH value is 6.3-6.5, enzymatic temperature is 20-30° C., and enzymatic time is 2-2.5 h.
9. The method for preparing a chemically modified highly active Ceratitis protease microcapsule antiallergic agent according to claim 1, characterized in that: The certain mass fraction described in step (3) is that the concentration of carboxymethyl cellulose solution is 80-100 g / L, the concentration of trehalose solution is 20-40 g / L, and the concentration of chemically modified highly active Bell's protease solution is 30-40 g / L; the certain volume ratio refers to the carboxymethyl cellulose solution: trehalose solution: chemically modified highly active Bell's protease solution is 3:4:
2.
10. The method for preparing a chemically modified highly active Ceratitis protease microcapsule antiallergic agent according to claim 1, characterized in that: The certain method described in step (3) is to carry out microcapsule treatment using an atomizing dryer.