WO2020244507A1 - Use of nicotinamide mononucleotide and/or nicotinamide mononucleotide salt - Google Patents

Abstract

The present invention relates to the field of medicament and health food research and development, and in particular to use of a nicotinamide mononucleotide and/or a nicotinamide mononucleotide salt. Provided is use of a nicotinamide mononucleotide or a nicotinamide mononucleotide salt in preparation of anti-allergic medicaments and/or anti-allergic health care products. In the technical solution, using the nicotinamide mononucleotide or the nicotinamide mononucleotide salt can induce Treg cells to secrete immunosuppressive cytokines IL10, TGF-β and the like, so as to inhibit the immune response of TH2, blood basicytes and tissue mast cells, reduce sIgE synthesis, increase sIgG and sIgA synthesis at the same time, and finally alleviate allergic symptoms. Further, it can be found through experiments that after using the nicotinamide mononucleotide and/or the nicotinamide mononucleotide salt, there are fewer adverse reactions and allergy recurrence rate is reduced. Provided is use of the nicotinamide mononucleotide and/or the nicotinamide mononucleotide salt for solving the technical defects in the prior art that antiallergic medicament have some adverse reactions and need to be used repeatedly and allergies tend to recur.

Description

Application of nicotinamide mononucleotide and/or nicotinamide mononucleotide salt Technical field

This application belongs to the field of medicine and health food research and development, and in particular relates to an application of nicotinamide mononucleotide and/or nicotinamide mononucleotide salt.

Background technique

Allergies are a series of hypersensitivity phenomena caused by human body contacting some of the allergic factors in the environment that have little effect on ordinary people, that is, the phenomenon of excessive immunity of the human body to certain foreign substances. Allergies include: immediate allergic reactions (also known as IgE-mediated allergic reactions), antibody-dependent and cytotoxic allergic reactions, immune complex-mediated allergic reactions, and delayed allergic reactions.

In the prior art, common anti-allergic drugs include: antihistamines, glucocorticoids, anti-leukotrienes, intranasal decongestants, etc., all of which have certain adverse reactions and require repeated medication to control symptoms. Allergies are easy to recur.

Therefore, an application of nicotinamide mononucleotide and/or nicotinamide mononucleotide salt has been developed to solve the technology in the prior art that has some adverse reactions to anti-allergic drugs, the need for repeated medication, and the recurrence of allergies. Defects have become an urgent problem for those skilled in the art.

Application content

In view of this, this application provides an application of nicotinamide mononucleotide and/or nicotinamide mononucleotide salt, which is used to solve the problems of anti-allergic drugs in the prior art, which require repeated medication and allergies. Technical defects that are prone to relapse.

The application provides an application of nicotinamide mononucleotide and/or nicotinamide mononucleotide salt in anti-allergic drugs and/or anti-allergic health products.

Preferably, a nicotinamide mononucleotide and nicotinamide mononucleotide salt are used in anti-allergic drugs and/or anti-allergic health products.

Preferably, the allergic reaction of the anti-allergic drug and/or anti-allergic health care product is selected from any one of allergic asthma, allergic rhinitis, allergic conjunctivitis, drug allergy, food allergy, pollen allergy and oral allergy Or multiple.

Preferably, in the composition, the mass ratio of nicotinamide mononucleotide and nicotinamide mononucleotide salt is (1-10):(1-10).

Preferably, the allergic reaction of the anti-allergic drug and/or anti-allergic health product is selected from: IL10, TGF-β, and IFN-γ immunosuppressive cytokine protein expression.

Preferably, the dosage form of the anti-allergic drug and/or anti-allergic health care product is oral or injection.

Preferably, the oral agent is selected from any one or more of tablets, powders, capsules, granules, pills, suspensions, syrups, mixtures, powders, oral liquids and dripping pills.

Preferably, the injection is selected from: solution injection, suspension injection, emulsion injection and sterile powder for injection, and the injection method is selected from intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, spinal injection and joint injection Internal injection.

Preferably, the anti-allergic drug and/or the auxiliary material of the anti-allergic health product is selected from: mannitol, microcrystalline cellulose, magnesium stearate, carboxymethyl cellulose, calcium hydrogen phosphate, starch, sucrose, dextrin, Lactose, calcium sulfate, talc, micronized silica gel, methyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, sodium alginate, polyethylene glycol, magnesium aluminum silicate, polyvinylpyrrolidone, carboxymethyl Sodium starch, low-substituted hydroxypropyl fiber, sodium bicarbonate, citric acid, tartaric acid, stearic acid, calcium stearate, hydrogenated vegetable oil, purified water, water for injection, oil for injection (sesame oil, tea oil), ethanol, Any one or more of glycerin, propylene glycol, polyethylene glycol, benzyl benzoate, dimethylacetamide, ethyl oleate, and ethyl lactate.

Preferably, the oral dose of nicotinamide mononucleotide or nicotinamide mononucleotide salt is 2-30 mg/kg;

The injection dose of the nicotinamide mononucleotide or nicotinamide mononucleotide salt is 5-10 mg/kg.

Preferably, the anti-allergic drugs and/or anti-allergic health products do not contain other anti-allergic active ingredients except for nicotinamide mononucleotide and/or nicotinamide mononucleotide salt.

In summary, the application provides an application of nicotinamide mononucleotide or nicotinamide mononucleotide salt in anti-allergic drugs and/or anti-allergic health products. In the technical solution provided in this application, the use of nicotinamide mononucleotide or nicotinamide mononucleotide salt can induce Treg cells to secrete immunosuppressive cytokines IL10, TGF-β, etc., thereby inhibiting TH2, blood basophilic and Organize the immune response of mast cells, reduce the synthesis of sIgE, and increase the synthesis of sIgG and sIgA at the same time, and ultimately reduce allergic symptoms; further, experimentally determined that the use of nicotinamide mononucleotide or nicotinamide mononucleotide salt is not good The reaction is less and the allergy recurrence rate is reduced. This application provides an application of nicotinamide mononucleotide and/or nicotinamide mononucleotide salt, which is used to solve the technology of anti-allergic drugs in the prior art that have some adverse reactions, need to be used repeatedly, and allergies are prone to recurrence. defect.

Detailed ways

The embodiment of the application provides an application of nicotinamide mononucleotide and/or nicotinamide mononucleotide salt, which is used to solve the problems of antiallergic drugs in the prior art, the need for repeated medication, and the recurrence of allergies. Technical defects.

The technical solutions in the embodiments of the present application will be described clearly and completely below. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in this application, all other embodiments obtained by those of ordinary skill in the art without creative work shall fall within the protection scope of this application.

In order to explain this application in more detail, the application of a nicotinamide mononucleotide and/or nicotinamide mononucleotide salt provided in this application will be specifically described below in conjunction with examples.

The application provides an application of nicotinamide mononucleotide or nicotinamide mononucleotide salt in anti-allergic drugs and/or anti-allergic health products.

In the technical solution provided in this application, the use of nicotinamide mononucleotide or nicotinamide mononucleotide salt can induce Treg cells to secrete immunosuppressive cytokines IL10, TGF-β, etc., thereby inhibiting TH2, blood basophilic and Organize the immune response of mast cells, reduce the synthesis of sIgE, and increase the synthesis of sIgG and sIgA, ultimately reducing allergic symptoms.

At the same time, further combining with Examples 1 to 3, it can be concluded that nicotinamide mononucleotide or nicotinamide mononucleotide salt has a good inhibitory and therapeutic effect on allergic reactions.

According to experimental statistics, in the technical solution provided in this application, the allergic reactions of anti-allergic drugs and/or anti-allergic health products prepared from nicotinamide mononucleotide or nicotinamide mononucleotide salt are selected from: allergic Any one or more of asthma, allergic rhinitis, allergic conjunctivitis, drug allergy, food allergy, pollen allergy, and oral allergy.

Further, according to the target of action of nicotinamide mononucleotide or nicotinamide mononucleotide salt, in the technical solution provided in the embodiments of this application, the allergic reaction of the anti-allergic drug and/or anti-allergic health care product is selected from: IL10, The expression of proteins composed of TGF-β and IFN-γ immunosuppressive cytokines.

In the actual application process, in order to better specifically target secondary allergic reactions, effectively improve the therapeutic effect on allergic reactions, prolong the action time, and reduce the occurrence of repeated medications, in the technical solutions provided in the embodiments of this application, The prepared anti-allergic drug and/or anti-allergic health care product has a dosage form of oral or injection.

Further, the dosage form of the oral agent is selected from: any one or more of tablets, injections, powders, capsules, granules, pills, suspensions, syrups, mixtures, powders, oral liquids, and dripping pills .

Further, the injection is selected from: solution injection, suspension injection, emulsion injection and sterile powder for injection, and the injection method is selected from intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection, spinal injection and intraarticular injection .

In order to effectively prevent nicotinamide mononucleotide or nicotinamide mononucleotide salt from being unstable and easy to decompose in gastric acid, its bioavailability decreases after decomposition, and to effectively improve bioavailability, the technical solutions provided in the embodiments of this application include The coating of the coated tablet is an acid stable coating.

In order to ensure that NMN products can maintain a better shape, be convenient to take, and improve the design requirements of the product shelf life, in the technical solutions provided in the embodiments of this application, the anti-allergic drugs and/or anti-allergic health care products are selected from: mannitol, Microcrystalline cellulose, magnesium stearate, carboxymethyl cellulose, calcium hydrogen phosphate, starch, sucrose, dextrin, lactose, calcium sulfate, talc, micronized silica gel, methyl cellulose, hydroxypropyl methyl cellulose , Ethyl cellulose, sodium alginate, polyethylene glycol, magnesium aluminum silicate, polyvinylpyrrolidone, sodium carboxymethyl starch, low-substituted hydroxypropyl fiber, sodium bicarbonate, citric acid, tartaric acid, stearic acid , Calcium stearate, hydrogenated vegetable oil, purified water, water for injection, oil for injection (sesame oil, tea oil), ethanol, glycerin, propylene glycol, polyethylene glycol, benzyl benzoate, dimethylacetamide, ethyl oleate Any one or more of ester and ethyl lactate.

According to the results of clinical experiments, taking into account the good anti-allergic effect and low adverse reactions, in the technical solution provided in the embodiments of this application, the appropriate daily oral dosage of nicotinamide mononucleotide or nicotinamide mononucleotide salt is 2-30mg/kg, the more optimized daily oral dose is 2-10mg/kg; the injection dose of nicotinamide mononucleotide or nicotinamide mononucleotide salt is 5-10mg/kg.

Example 1

In this example, C3H/HeJ peanut allergic mice were prepared by the following method: 6-week-old female C3H/HeJ mice were purchased from Shanghai Experimental Animal Center. The test animals were reared in a room with an average temperature of 21°C to 23°C and a relative humidity of 40% to 70% under specific non-pathogenic conditions, and a 12-hour light/dark cycle. The mice in the sensitized group were given intraperitoneal injection (ip) of 30 mg CPE (peanut extract) per day by intraperitoneal injection (ip) of peanut homogenate (80 mg/each) every day. Rats, pups that have never been exposed to peanuts were used as negative controls. Then, through skin tests and allergic reactions (by measuring vascular leakage, monitoring clinical symptoms, rectal temperature, respiratory rate and measuring serum mast cell protease-1 (mmcp-1)-a specific marker of mast cell degranulation) The test confirms the successful establishment of the sensitized mouse model.

1.1 Animals and experimental reagents:

6-week-old C3H/HeJ female mice (strain: C3H/HeJ, purchased from Shanghai Experimental Animal Center), IL10, TGF-β, IFN-γ and IgE antibodies (purchased by Sigma-aldrich), nicotinamide mononucleotide or smoke Amide mononucleotide salt (purchase).

1.2 Experimental method

Randomly take 6 wild-type mice and 24 peanut-sensitized mice and randomly divide the peanut-sensitized mice into 4 groups, each with 6 mice. The grouping is as follows:

① Blank group: C3H/HeJ wild-type mice (injection of physiological saline 10mg/kg body weight);

②. Treatment group 1: C3H/HeJ peanut allergic mice (injected nicotinamide mononucleotide or nicotinamide mononucleotide salt 1 mg/kg body weight);

③. Treatment group 2: C3H/HeJ peanut allergic mice (injected nicotinamide mononucleotide or nicotinamide mononucleotide salt 5mg/kg body weight);

④ Treatment group 3: C3H/HeJ peanut allergic mice (injected nicotinamide mononucleotide or nicotinamide mononucleotide salt 10mg/kg body weight);

⑤. Control group 4: C3H/HeJ peanut allergic mice (injection of physiological saline 10 mg/kg body weight).

C3H/HeJ wild-type mice and C3H/HeJ peanut allergic mice were injected intraperitoneally with 30mg CPE (peanut extract)/mouse after sensitization. The blank control group was injected with physiological saline 10 mg/kg body weight, and the treatment groups 1-3 were injected with nicotinamide mononucleotide or nicotinamide mononucleotide salt 1 mg/kg body weight, 5 mg/kg body weight, and 10 mg/kg body weight respectively. 4Inject normal saline 10mg/kg body weight.

16 hours after the medication, the intracanthal venous blood of each group of mice was taken to detect the contents of the cellular immunosuppressive factors IL10, TGF-β, IFN-γ and IgE in the peripheral blood serum of the mice.

1.3 Results

C3H/HeJ peanut allergic mice treated with different concentrations of nicotinamide mononucleotide or nicotinamide mononucleotide salt can increase the levels of cellular immunosuppressive factors IL10, TGF-β and IFN-γ in peripheral blood to varying degrees. Reduce the content of allergenic protein IgE.

ELISA plates coated with 5 μg/mL recombinant protein overnight, and then blocked with 2% BSA (98% PBS). The serum samples were diluted 1:500 in 1% BSA, and then serially diluted 1:3. To detect IgE, the serum was treated with agarose-protein G (Thermo Fisher Scientific, Rockford, IL) for 50 minutes, and then the 1:20 diluted sample was loaded onto the ELISA plate, and the sample was detected with the corresponding antibody.

The reaction was performed with SureBlue TMB substrate (KPL, Gaithersburg, MD), and the reaction was terminated with TMB stop solution (KPL, Gaithersburg, MD). Use Epoch ELISA reader (BioTek, Winooski, VT) to read the results. Compared with the control group, C3H/HeJ peanut allergic mice treated with different concentrations of nicotinamide mononucleotide or nicotinamide mononucleotide salt can increase the peripheral blood cellular immunosuppressive factors IL10, TGF-β, IFN to varying degrees -γ content and reduce the content of allergenic protein IgE are shown in Table 1.

Table 1 is a numerical table for the injection of nicotinamide mononucleotide or nicotinamide mononucleotide salt to increase the levels of cellular immunosuppressive factors IL10, TGF-β and IFN-γ and reduce the level of IgE antibodies in allergic mouse models.

Table 1

Grouping	IFN-γ	TGF-β	IL-10	IgE
Blank group	429±1.82pg/ml	42.16±3.64pg/ml	12.03±1.11pg/ml	2.16±0.29KU/L
Control group	259±2.23pg/ml	20.39±3.08pg/ml	5.94±0.89pg/ml	7.01±0.71KU/L
Treatment group 1	365±2.66pg/ml	30.98±4.22pg/ml	7.64±0.92pg/ml	5.44±0.37KU/L
Treatment group 2	359±4.18pg/ml	33.45±2.58pg/ml	10.67±0.25pg/ml	3.58±0.52KU/L
Treatment group 3	434±3.32pg/ml	44.86±1.59pg/ml	11.42±0.61pg/ml	2.26±0.32KU/L

Example 2

The C3H/HeJ peanut allergic mice in the test example of this application were prepared by the following method: 6-week-old female C3H/HeJ mice were purchased from Shanghai Experimental Animal Center. The test animals were reared in a room with an average temperature of 21°C to 23°C and a relative humidity of 40% to 70% under specific non-pathogenic conditions, and a 12-hour light/dark cycle. The mice in the sensitized group were given intraperitoneal injection (ip) of 30 mg CPE (peanut extract) per day by intraperitoneal injection (ip) of peanut homogenate (80 mg/each) every day. Rats, pups that have never been exposed to peanuts were used as negative controls. Then, through skin tests and allergic reactions (by measuring vascular leakage, monitoring clinical symptoms, rectal temperature, respiratory rate and measuring serum mast cell protease-1 (mmcp-1)-a specific marker of mast cell degranulation) The test confirms the successful establishment of the sensitized mouse model.

2.1 Animals and experimental reagents:

6-week-old C3H/HeJ female mice (strain: C3H/HeJ, purchased from Shanghai Experimental Animal Center), IL10, TGF-β, IFN-γ and IgE antibodies (purchased by Sigma-aldrich), nicotinamide mononucleotide or smoke Amide mononucleotide salt (purchase).

2.2 Experimental method

Six wild-type mice and 24 peanut-sensitized mice were randomly selected, and the peanut-sensitized mice were randomly divided into 4 groups with 6 mice in each group. The grouping is as follows:

① Blank group: C3H/HeJ wild-type mice (given general diet);

②. Treatment group 1: C3H/HeJ peanut allergic mice (in the course of sensitization, they are given a general diet and orally supplemented with nicotinamide mononucleotide or nicotinamide mononucleotide salt 1mg/kg body weight (including excipients);

③ Treatment group 2: C3H/HeJ peanut allergic mice (during the sensitization process, they were given a general diet and orally supplemented with nicotinamide mononucleotide or nicotinamide mononucleotide salt 10mg/kg body weight (including excipients);

④ Treatment group 3: C3H/HeJ peanut allergic mice (in the course of sensitization, they were given a general diet and supplemented with nicotinamide mononucleotide or nicotinamide mononucleotide salt 20mg/kg body weight (including excipients);

⑤ Control group: C3H/HeJ peanut allergic mice (during the sensitization process, given the general diet and the same amount of excipients as the treatment group 3)

C3H/HeJ wild-type mice (given a general diet) and C3H/HeJ mice were supplemented with different concentrations of nicotinamide mononucleotide or nicotinamide mononucleotide salt during the peanut sensitization process, and the mice in each group were raised for 21 days , Mice in each group were sensitized by intraperitoneal injection of 30mg CPE (peanut extract)/mouse.

After injection of CPE sensitization, blood from the intracanthal veins of each group of mice was taken, and the serum levels of cytoimmune inhibitory factors IL10, TGF-β, IFN-γ and IgE in the peripheral blood serum of the mice were detected.

2.3 Results

C3H/HeJ peanut allergic mice treated with different concentrations of nicotinamide mononucleotide or nicotinamide mononucleotide salt can increase the levels of cellular immunosuppressive factors IL10, TGF-β and IFN-γ in peripheral blood to varying degrees. Reduce the content of allergenic protein IgE.

ELISA plates coated with 5 μg/mL recombinant protein overnight, and then blocked with 2% BSA (98% PBS). The serum samples were diluted 1:500 in 1% BSA, and then serially diluted 1:3. To detect IgE, the serum was treated with agarose-protein G (Thermo Fisher Scientific, Rockford, IL) for 50 minutes, and then the 1:20 diluted sample was loaded onto the ELISA plate, and the sample was detected with the corresponding antibody.

The reaction was performed with SureBlue TMB substrate (KPL, Gaithersburg, MD), and the reaction was terminated with TMB stop solution (KPL, Gaithersburg, MD). Use Epoch ELISA reader (BioTek, Winooski, VT) to read the results. Compared with the control group, C3H/HeJ peanut allergic mice treated with different concentrations of nicotinamide mononucleotide or nicotinamide mononucleotide salt can increase the peripheral blood cellular immunosuppressive factors IL10, TGF-β, IFN to varying degrees -γ content and reduce the allergenic protein IgE content results are shown in Table 2.

Table 2 is a numerical table for oral administration of nicotinamide mononucleotide or nicotinamide mononucleotide salt to increase the levels of cellular immunosuppressive factors IL10, TGF-β and IFN-γ and decrease the level of IgE antibodies in the allergic mouse model.

Table 2

Grouping	IFN-γ	TGF-β	IL-10	IgE
Blank group	416±4.1pg/ml	38.92±3.7pg/ml	11.25±0.68pg/ml	2.44±0.39KU/L
Control group	248±4.56pg/ml	18.23±4.58pg/ml	5.82±0.76pg/ml	5.99±0.21KU/L
Treatment group 1	294±6.25pg/ml	28.22±3.13pg/ml	6.59±1.24pg/ml	4.35±0.60KU/L
Treatment group 2	341±2.97pg/ml	40.77±2.01pg/ml	9.08±0.66pg/ml	3.28±0.48KU/L
Treatment group 3	430±3.11pg/ml	39.43±8.01pg/ml	12.06±1.34pg/ml	2.77±0.52KU/L

Example 3

3.1 Experimental materials and experimental reagents:

Peripheral blood of healthy children of the same age and peripheral blood of children with food allergy (PBMC), from Shenzhen Children's Hospital. IL10, TGF-β, IFN-γ and IgE antibodies (purchased by Sigma-aldrich), nicotinamide mononucleotide or nicotinamide mononucleotide salt (purchase).

3.2 Experimental method

Randomly take the peripheral blood of healthy children and the peripheral blood (PBMC) of children with food allergies. Suspend the PBMC in a medium with 10% autologous plasma (RPMI-1640; Mediatech) and place it in a 37°C, 5% CO2 cell incubator The training groups are as follows:

①. Healthy group: PBMC (10^7/ml) of healthy children were suspended and cultured in the medium (with 0.2mg/ml normal saline added to the medium);

② Blank group: PBMC (10^7/ml) of children with food allergies were suspended and cultured in the medium (normal saline 0.2mg/ml was added to the medium);

③ Treatment group 1: PBMC (10^7/ml) of children with food allergies were suspended and cultured in the medium (with nicotinamide mononucleotide or nicotinamide mononucleotide salt 0.02mg/ml);

④. Treatment group 2: PBMC (10^7/ml) of children with food allergies were suspended and cultured in the medium (the medium was added with nicotinamide mononucleotide or nicotinamide mononucleotide salt 0.1mg/ml);

⑤ Treatment group 3: PBMC (10^7/ml) of children with food allergies were suspended and cultured in the culture medium (Nicotinamide mononucleotide or nicotinamide mononucleotide salt 0.2mg/ml was added to the medium)

Different concentrations of nicotinamide mononucleotide or nicotinamide mononucleotide salt were added to the culture medium of each group of PBMC and cultured in vitro for 72 hours. The serum levels of IgE, IL-10, IFN-γ and IgE in the peripheral blood of the 5 groups were detected by ELISA. The content of TGF-β.

3.3 Results

PBMC treated with different concentrations of nicotinamide mononucleotide or nicotinamide mononucleotide salt can increase the levels of cellular immunosuppressive factors IL10, TGF-β, and IFN-γ in peripheral blood to varying degrees and reduce the allergenic protein IgE. content;

ELISA plates coated with 5 μg/mL recombinant protein overnight, and then blocked with 2% BSA (98% PBS). The medium supernatant was diluted 1:500 in 1% BSA, and then serially diluted 1:3. To detect IgE, the serum was treated with agarose-protein G (Thermo Fisher Scientific, Rockford, IL) for 50 minutes, and then the 1:20 diluted sample was loaded onto the ELISA plate. Test the sample with the corresponding antibody. The reaction was performed with SureBlue TMB substrate (KPL, Gaithersburg, MD), and the reaction was terminated with TMB termination solution (KPL, Gaithersburg, MD). Use Epoch ELISA reader (BioTek, Winooski, VT) to read the results. Compared with the control group, the PBMC of children with food allergies treated with different concentrations of nicotinamide mononucleotide or nicotinamide mononucleotide salt can increase the peripheral blood cellular immunosuppressive factors IL10, TGF-β, IFN- to varying degrees The content of γ and reduce the content of allergenic protein IgE are shown in Table 3.

Table 3 shows the addition of nicotinamide mononucleotide or nicotinamide mononucleotide salt to culture the peripheral blood (PBMC) of children with food allergies to increase the immunosuppressive factors IL10, TGF-β and IFN-γ of PBMC cells in children with food allergy Table of levels and reduction of IgE antibody levels.

table 3

Example 4

30 cases of allergic asthma and 30 cases of allergic rhinitis. There were 20 males, 20 females, and 20 children under 12 years of age. The cause of the disease was diagnosed as delayed allergy caused by chemical contact, respiratory tract inhalation, etc. Non-allergic cases such as organic disease and trauma have been excluded. Randomly divided into 2 groups, namely the control group and the experimental group (10 mg nicotinamide mononucleotide or nicotinamide mononucleotide salt). The gender, age, and disease course of each group were statistically processed, and there was no significant difference Meaning and comparability.

The control group was given loratadine tablets (10 mg/tablet), which was used according to the drug instructions for one month.

Experiment 1 group was given 10 mg of nicotinamide mononucleotide or nicotinamide mononucleotide salt, once a day on an empty stomach in the morning for 1 month.

Diagnostic criteria

Ineffective: The patient's symptoms have not improved at all, and there are signs of aggravation;

Significantly effective: The patient's symptoms have been significantly improved, but they have not completely disappeared;

Effective: The patient's symptoms disappeared completely.

Side effects: drowsiness, dizziness, lack of concentration, etc.

Treatment results:

The total effective rate (%) of each treatment group and the recurrence rate (%) at 1 month, 3 months, and 6 months after stopping the drug were investigated. The results are shown in Table 4.

Table 4

It can be seen from the results in the above table that compared with the control group, the experimental group 1 of this application has the same therapeutic effect on allergic rhinitis and allergic asthma as that of loratadine, which proves that nicotinamide mononucleotide or nicotinamide mononucleotide Nucleotide salts can effectively treat delayed-onset allergic diseases. In terms of the recurrence rate, the recurrence rate after 6 months was all lower than 25%, which was much lower than 76.6% in the control group, which proved that nicotinamide mononucleotide or nicotinamide mononucleotide salt can significantly reduce the risk of allergic diseases. Recurrence rate.

During the treatment, 15 cases of side effects occurred in the control group, while no side effects occurred in the experimental group.

In summary, the application provides an application of nicotinamide mononucleotide or nicotinamide mononucleotide salt in anti-allergic drugs and/or anti-allergic health products. In the technical solution provided in this application, the use of nicotinamide mononucleotide or nicotinamide mononucleotide salt can induce Treg cells to secrete immunosuppressive cytokines IL10, TGF-β, etc., thereby inhibiting TH2, blood basophilic and Organize the immune response of mast cells, reduce the synthesis of sIgE, and increase the synthesis of sIgG and sIgA at the same time, and ultimately reduce allergic symptoms; further, experimentally determined that the use of nicotinamide mononucleotide or nicotinamide mononucleotide salt is not good The reaction is less and the allergy recurrence rate is reduced. This application provides an application of nicotinamide mononucleotide and/or nicotinamide mononucleotide salt, which is used to solve the technology of anti-allergic drugs in the prior art that have some adverse reactions, need to be used repeatedly, and allergies are prone to recurrence. defect.

The above are only the preferred embodiments of this application. It should be pointed out that for those of ordinary skill in the art, without departing from the principle of this application, several improvements and modifications can be made, and these improvements and modifications are also Should be regarded as the scope of protection of this application.

Claims (10)

1. An application of nicotinamide mononucleotide and/or nicotinamide mononucleotide salt in anti-allergic drugs and/or anti-allergic health products.
2. The application according to claim 1, characterized in that a combination of nicotinamide mononucleotide and nicotinamide mononucleotide salt is used in anti-allergic drugs and/or anti-allergic health products.
3. The application according to claim 1, characterized in that the allergic reaction of the anti-allergic drug and/or anti-allergic health care product is selected from: allergic asthma, allergic rhinitis, allergic conjunctivitis, drug allergy, food allergy, Any one or more of pollen allergy and oral allergy.
4. The application according to claim 2, wherein the mass ratio of nicotinamide mononucleotide to nicotinamide mononucleotide salt in the composition is (1-10):(1-10).
5. The application according to claim 1 or 2, characterized in that the allergic reaction of the anti-allergic drug and/or anti-allergic health care product is selected from the group consisting of: IL10, TGF-β, and IFN-γ immunosuppressive cytokine protein expression.
6. The application according to claim 1 or 2, characterized in that the dosage form of the anti-allergic drug and/or anti-allergic health care product is oral or injection.
7. The application according to claim 6, wherein the oral agent is selected from the group consisting of: tablets, powders, capsules, granules, pills, suspensions, syrups, mixtures, powders, oral liquids and dripping pills Any one or more of; the injection is selected from: solution injection, suspension injection, emulsion injection and sterile powder for injection, and the injection method is selected from intradermal injection, subcutaneous injection, intramuscular injection, intravenous injection , Spinal injection and intra-articular injection.
8. The application according to claim 4, wherein the anti-allergic drugs and/or anti-allergic health products are selected from the group consisting of: mannitol, microcrystalline cellulose, magnesium stearate, carboxymethyl cellulose, phosphoric acid Calcium hydrogen, starch, sucrose, dextrin, lactose, calcium sulfate, talc, micronized silica gel, methyl cellulose, hydroxypropyl methyl cellulose, ethyl cellulose, sodium alginate, polyethylene glycol, silicic acid Magnesium aluminum, polyvinylpyrrolidone, sodium carboxymethyl starch, low-substituted hydroxypropyl fiber, sodium bicarbonate, citric acid, tartaric acid, stearic acid, calcium stearate, hydrogenated vegetable oil, purified water, water for injection, for injection Any one or more of oil (sesame oil, tea oil), ethanol, glycerin, propylene glycol, polyethylene glycol, benzyl benzoate, dimethylacetamide, ethyl oleate, and ethyl lactate.
9. The application according to claim 1, wherein the oral dose of nicotinamide mononucleotide or nicotinamide mononucleotide salt is 2-30 mg/kg;

   The injection dose of the nicotinamide mononucleotide or nicotinamide mononucleotide salt is 5-10 mg/kg.
10. The application according to claim 1, wherein the anti-allergic drugs and/or anti-allergic health products contain no other anti-allergic drugs except nicotinamide mononucleotide and/or nicotinamide mononucleotide salt. Active ingredient.