Application of combination of quercetin and curcumin in preparation of anti-allergic drug

Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to application of quercetin combined with curcumin in preparation of an anti-allergic reaction medicine. Through a large number of researches, the inventor finds that combined administration of quercetin and curcumin with a specific concentration can effectively inhibit mast cell degranulation, and the inhibition rate of mast cell degranulation reaches 90% or more, so that I-type anaphylaxis mediated by immune globulin E is inhibited, especially systemic anaphylaxis, and the curative effect is good. The compound can be used for preparing anti-anaphylaxis drugs. The drug combination scheme provided by the invention has important significance and wide application prospect in drugs for treating or preventing anaphylactic reactions.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and more specifically, relates to the application of quercetin combined with curcumin in the preparation of anti-allergic drugs. Background Art

[0002] Allergic reactions not only affect the patient's physical health and quality of life, but also bring heavy burdens to family, medical and public health management. Therefore, the development of safe and effective anti-allergic products has important practical significance and broad market prospects.

[0003] Allergic reaction is a manifestation of the body's immune system's overreaction to foreign substances (such as pollen, dust mites, food, etc.). When these substances enter the human body, the immune system will mistake them for harmful substances, produce an immune response, and release a large number of inflammatory mediators, such as histamine, leukotrienes, etc., thereby triggering allergic symptoms. Common allergic symptoms include itchy skin, redness and swelling, sneezing, runny nose, coughing, asthma, etc. Severe allergic reactions may even lead to shock and death. The occurrence of allergic reactions not only brings physical discomfort to patients, but may also affect their mental health, leading to emotional problems such as anxiety and depression.

[0004] At present, anti-allergic products on the market are mainly divided into two categories: drug treatment and physical protection. In terms of drug treatment, although commonly used antihistamines and glucocorticoids can relieve allergic symptoms to a certain extent, long-term use may cause side effects, such as drowsiness, dry mouth, gastrointestinal discomfort, etc., and may even lead to drug dependence. In terms of physical protection, such as masks and protective clothing, although they can effectively block contact with allergens, long-term wearing may cause skin discomfort, breathing problems, etc., and cannot fundamentally solve allergic reactions.

[0005] In recent years, studies have found that some natural medicines have significant anti-allergic effects when applied topically. However, the anti-allergic effects of these medicines when taken orally have not been fully studied and applied.

[0006] In recent years, the research on natural anti-allergic ingredients has attracted much attention. Curcumin and quercetin, as natural active ingredients, have been proven to have significant anti-allergic effects when applied topically. For example, a Chinese patent application discloses the use of curcumin in anti-sensitive cosmetics, which works by scavenging free radicals and inhibiting inflammatory factors; a Chinese patent application proposes that the combination of quercetin and turmeric extract can relieve mask face symptoms. In addition, a Chinese patent application discloses an anti-allergic deodorant containing curcumin and quercetin. The combination of the anti-allergic agent and the deodorant can greatly reduce the allergy rate of the skin when the product is used. However, the application of the two in the prior art is limited to topical use, and there has been no research or report showing that the drug can exert an anti-allergic effect through oral administration. In addition, topical drugs have limitations in the treatment of systemic allergic reactions (such as allergic rhinitis, asthma, etc.) and cannot effectively act on the whole body.

[0007] Therefore, it is urgent to develop a new, safe and effective anti-allergic product that can be taken orally. Summary of the invention

[0008] The technical problem to be solved by the present invention is to overcome the defects and shortcomings of the prior art that the application of curcumin and quercetin is mainly concentrated in the field of local external use, such as anti-sensitive cosmetics, anti-allergic deodorants, etc. The scope of action of these external products is limited, and they can only target local skin allergy symptoms and cannot effectively treat systemic allergic reactions. The present invention provides the application of quercetin combined with curcumin in the preparation of a drug for treating or preventing allergic reactions through oral administration.

[0009] Another object of the present invention is to provide an oral antiallergic composition.

[0010] The above-mentioned purpose of the present invention is achieved through the following technical solutions:

[0011] The present invention protects the use of quercetin combined with curcumin in the preparation of a drug for treating or preventing allergic reactions through oral administration. The quercetin includes quercetin and its pharmaceutically acceptable salts or esters; the curcumin includes curcumin and its pharmaceutically acceptable salts or esters; wherein the concentration of the quercetin for cell administration is ≥8 μM, and the concentration of the curcumin for cell administration is greater than ≥0.8 μM.

[0012] Topical drugs mainly exert their therapeutic effects through local effects, and their range of action is usually limited to the site of medication. Oral drugs need to be absorbed through the digestive tract to enter the blood circulation and can only take effect after being distributed throughout the body. In this process, they will be affected by multiple factors such as gastrointestinal absorption efficiency, liver first-pass effect and metabolic transformation. Due to the significant differences in the action pathways and metabolic processes of the two types of drugs, the specific therapeutic effects of topical drugs cannot guarantee the same effect when they are changed to oral administration. In the prior art, the application of curcumin and quercetin is mainly concentrated on local external use to exert anti-allergic effects. After a lot of research, the inventors found that the combined administration of quercetin and curcumin at a specific concentration can effectively inhibit mast cell degranulation (referring to preventing mast cells from releasing their internal granule contents through intervention means), thereby inhibiting the occurrence of type I allergic reactions mediated by immunoglobulin E (IgE), especially systemic allergic reactions, and can be used to prepare drugs for anti-allergic reactions.

[0013] Preferably, the concentration of quercetin administered to cells is ≥10 μM, and the concentration of curcumin administered to cells is greater than ≥1 μM.

[0014] Preferably, the mass ratio of curcumin to quercetin is 1:(1-20).

[0015] Furthermore, the allergic reaction is a type I allergic reaction. Type I allergic reaction, also known as immediate allergic reaction or IgE-mediated allergic reaction, is an immune response mediated by IgE antibodies.

[0016] Furthermore, the type I allergic reaction includes one or more of allergic rhinitis, asthma, urticaria, anaphylactic shock, and allergic conjunctivitis.

[0017] Furthermore, the treatment or prevention of allergic reaction is to inhibit mast cell degranulation.

[0018] Furthermore, the treatment or prevention of allergic reaction is to inhibit IgE-mediated serum histamine release.

[0019] Furthermore, the treatment or prevention of allergic reaction is to inhibit the release of β-hexosaminidase mediated by IgE.

[0020] Furthermore, the treatment or prevention of allergic reactions is to inhibit IgE-mediated prostaglandin D 2 release.

[0021] Furthermore, the treatment or prevention of allergic reactions is to inhibit IgE-mediated leukotriene C4 (LTC4) release.

[0022] Furthermore, the oral administration includes gastrointestinal administration.

[0023] The present invention also protects an oral antiallergic composition, comprising quercetin and curcumin, wherein the quercetin comprises quercetin and its pharmaceutically acceptable salts or esters; the curcumin comprises curcumin and its pharmaceutically acceptable salts or esters; wherein the concentration of the quercetin is ≥8 μM, and the concentration of the curcumin is greater than ≥0.8 μM.

[0024] Preferably, the concentration of quercetin is ≥10 μM, and the concentration of curcumin is greater than ≥1 μM.

[0025] Preferably, the mass ratio of curcumin to quercetin is 1:(1-20).

[0026] Furthermore, a pharmaceutically acceptable carrier is also included.

[0027] Furthermore, the oral antiallergic composition is in the form of tablets, powders, capsules, granules, oral liquids or syrups.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] The inventors have found through extensive research that the combined administration of quercetin and curcumin at a specific concentration can effectively inhibit mast cell degranulation (referring to preventing mast cells from releasing their internal granule contents through intervention means), and the inhibition rate of mast cell degranulation reaches 90% or more, thereby inhibiting the occurrence of type I allergic reactions mediated by IgE, especially systemic allergic reactions, and can be used to prepare drugs for anti-allergic reactions. The combined drug regimen of the present invention has important significance and broad application prospects in drugs for treating or preventing allergic reactions. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 Statistical graph showing the cytotoxicity of the combined use of quercetin and curcumin.

[0031] Figure 2 Statistical graph of Western blot data of different quercetin concentrations.

[0032] Figure 3 Statistical graph of Western blot data of quercetin at different administration time.

[0033] Figure 4 The data statistics of Western blot of quercetin combined with curcumin are shown in Figure 2.

[0034] Figure 5 PGD ​​for the combined use of quercetin and curcumin 2 Statistical graph of data (* indicates P < 0.05, ** indicates P < 0.01, *** indicates P < 0.001).

[0035] Figure 6This is a statistical chart of histamine data for the combined use of quercetin and curcumin (* indicates P<0.05, ** indicates P<0.01, *** indicates P<0.001).

[0036] Figure 7 This is a statistical chart of the LTC4 data of quercetin combined with curcumin (* indicates P<0.05, ** indicates P<0.01, *** indicates P<0.001). DETAILED DESCRIPTION

[0037] The present invention is further described below in conjunction with the accompanying drawings and specific examples, but the examples do not limit the present invention in any form. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the art.

[0038] Unless otherwise specified, the reagents and materials used in the following examples are commercially available.

[0039] Oral gavage is a common oral administration method, especially in animal experiments. Oral gavage simulates the effect of oral administration by injecting the drug directly into the stomach. Therefore, oral gavage can be regarded as a specific implementation method of oral administration.

[0040] Example 1 Verification of cytotoxicity of combined administration of quercetin and curcumin

[0041] 1. Experimental methods

[0042] When bone marrow-derived mast cells (BMMCs) are in the logarithmic growth phase, transfer them from the T75 culture flask to a centrifuge tube and centrifuge at 1200 rpm / min for 4 min. Discard the supernatant, wash with sterile PBS 2-3 times, add RPMI-1640 complete medium to resuspend the cells, gently pipette and mix, count, and adjust the cell density to 5×10 4 cells / mL, gently blow and mix repeatedly, inoculate into 96-well plates, 100 μL per well, add 0.5 μL of DMSO to each well of the control group, and add 0.5 μL of different final drug concentrations in the experimental group according to the concentration gradient (Q10, C10, Q10+C10, Q100, C100, Q100+C100 μM, where Q10 represents quercetin administration, the drug concentration is 10 μM; C10 represents curcumin administration, the drug concentration is 10 μM; Q10+C10 represents quercetin and curcumin co-administration, each concentration is 10 μM, and other drug concentrations are analogous). Set up three replicate wells for each concentration, add 100 μL of PBS buffer to the edge well to reduce evaporation. Place in 37°C, 5% CO 2 After 8 h of incubation in the incubator, 10 μL of CCK-8 solution was added to each well and placed in a 37°C, 5% CO 2After incubation in the incubator for 1 hour, the absorbance of each well was measured at a wavelength of 450 nm using an ELISA reader, and the measured data was saved. The proliferation inhibition experiment of BMMCs was set up in the following three groups:

[0043] Blank group (Ab): culture medium and CCK-8 solution were added, without cells and drugs.

[0044] Control group (Ac): culture medium containing cells and CCK-8 solution were added, but no drug was included.

[0045] Experimental group (As): culture medium containing cells, drugs and CCK-8 solution were added.

[0046] The absorbance of each well was obtained by using an ELISA instrument. The cell viability was the difference between the absorbance of the experimental well and the blank well divided by the difference between the control well and the blank well. The formula is as follows:

[0047] Cell viability = [(OD As -OD Ab ) / (OD Ac -OD Ab )]×100%

[0048] 2. Experimental results

[0049] Before studying the effect of combined administration on mast cell activation, the cytotoxicity of quercetin and curcumin combined was first evaluated by CCK-8 assay in BMMCs cells. Figure 1 It can be seen that when the combined drug administration concentration reaches 100 μM, the cell survival rate is basically not affected. Therefore, this experiment proves that the cytotoxicity of combined drug administration is very small and highly safe.

[0050] Example 2 Combined administration of quercetin and curcumin inhibits mast cell degranulation

[0051] (1) Exploration of quercetin administration concentration and administration time and combined administration of quercetin and curcumin to inhibit mast cell degranulation

[0052] 1. Experimental methods

[0053] 1.1 Isolation of bone marrow cells from mouse bone marrow:

[0054] 1.1.1 Six-week-old BALB / C male mice were killed by cervical dislocation. The mice were soaked in 75% alcohol for 30 seconds. The mice were taken out and the skin on both legs was cut open with surgical scissors. The leg bones on both sides were cut off from the hip joint. The muscles attached to the femur and tibia were carefully removed. The joint surface was not damaged and the bone marrow cavity was not exposed.

[0055] Remove the fur and tissue from the hind legs and place them on a cell culture dish for later use;

[0056] Use surgical scissors to gently cut open the two ends of the femur or tibia, then use a 5mL sterile syringe to absorb RPMI1640 culture medium and flush out the bone marrow tissue fluid in the bone marrow into a 50mL centrifuge tube;

[0057] Centrifuge at 1200 rpm / min at room temperature for 3 min, discard the supernatant, add 10 mL of new RPMI1640 medium, resuspend the cells by pipetting, count the cells with a cell counting plate under a microscope, and set aside.

[0058] 1.2. Cultivate the bone marrow cells obtained in step 1.1;

[0059] 1.2.1 After cell counting, add 10% FBS + 1% double antibody + 1% HEPES Solution + Mem non-essential amino acid solution (100×) and other nutrients to RPMI1640, and then adjust the cell density to 1×10 6 cell / mL;

[0060] 1.2.2 After bone marrow stem cells are completely differentiated into mast cells, subsequent experiments can be performed;

[0061] 1.2.3 Collect mast cells, transfer to centrifuge tubes, centrifuge at 1200 rpm for 4 min, discard supernatant, wash the tubes three times with 2 mL PBS, and spread them into 60 mm cell culture dishes with a ratio of culture medium to IgE antibody of 2000:1, and treat overnight;

[0062] 1.2.4 Collect the cells treated in 1.2.3 into a centrifuge tube and centrifuge at 1200 rpm for 4 min, leaving the cells at the bottom, wash with PBS three times, discard the supernatant, add HBSS and mix by pipetting.

[0063] 1.2.5 Add cell suspension to 96-well plate, 200 μL per well.

[0064] 1.2.6 Concentration dependence experiment: Different concentrations of quercetin (1, 5, 10, 20 μmoL / mL) were added to the culture system and incubated for 1 h;

[0065] Time-dependent experiment: 10 μmoL / mL quercetin was added to the culture system and incubated for 1, 2, and 6 h at different times;

[0066] Combined administration experiment: 10μmoL / mL quercetin and 10μmoL / mL curcumin were added to the culture system for combined administration, the total volume of the combined administration was 2.5μL, and incubated for 1h; in addition, a single drug administration group was set up, in which the single drug administration doses of quercetin and curcumin were 20μmoL / mL and 2.5μL, respectively, and incubated for 1h; DMSO was used as a blank control, AICAR (using a concentration of 4moL / mL; AICAR (also known as acadexin) as an AMPK activator, which can inhibit the release of mast cell granules and inflammatory factors by inhibiting downstream protein expression) was used as a positive control, and the dosage was 2.5μL.

[0067] 1.2.7 Add DNP-HSA antigen to the above samples, 50 μmoL, add 1 μL to each well, and do not add antigen to the blank group. Treat for 15 minutes.

[0068] 1.2.8 Transfer the treated cells to EP tubes, centrifuge at 3500 rpm for 4 min at 4°C, remove all PBS from each well, and add 40 μL WBIP lysis buffer to each EP tube.

[0069] 1.2.9WBIP lysis buffer: protease inhibitor (PMSF): phosphatase inhibitor (A, B) is 100:1:1.

[0070] 1.2.10 Prepare 250 μL lysis buffer, lyse on ice for 15 min, then incubate at 4°C, 12,000 rpm, for 15 min, transfer 40 μL supernatant to a new EP tube, and add 10 μL loading buffer.

[0071] 1.2.11 Load 15 μL of protein into each well and run at 60 V for 30 min. Then switch to 120 V and run until bromophenol blue reaches the bottom of the gel and stop electrophoresis.

[0072] 1.2.12 After electrophoresis, transfer the membrane at 100 V for 70 min, then block the PVDF membrane with blocking solution for 2 h, wash it with TBST 3 times for 10 min each time, and cut out the target band;

[0073] 1.2.13 After washing the membrane, incubate it with primary antibody overnight.

[0074] 1.2.14 On the second day, remove the target band after incubation, wash it 3 times with TBST, 10 min each time, then incubate it with secondary antibody for 1 hour, then repeat washing 3 times and develop.

[0075] 2. Experimental results

[0076] The concentration-dependent results were as follows Figure 2As shown in Figure 2, the optimal dosing concentration of quercetin is 10-20 μM (μmoL / mL); the time-dependent results are shown in Figure 2. Figure 3 As shown in the results, the optimal administration time of quercetin is 2h.

[0077] The results of combined administration of quercetin and curcumin are as follows Figure 4 As shown, the combination of quercetin and curcumin can inhibit the activation of mast cells and inhibit the degranulation effect. The combined administration of the two can further and more effectively inhibit mast cell degranulation, thereby inhibiting type I allergic reactions mediated by mast cells.

[0078] (2) Different combined concentrations of quercetin and curcumin inhibit mast cell degranulation

[0079] 1. Experimental methods

[0080] After the cells in the dish were treated with antibodies, the cells were washed with HBSS buffer. A 96-well plate was taken and the cells were treated with drugs according to the following groups (C10+C20; C10+Q10; C10+Q5; C5+Q20; C5+Q10; C5+Q5; C1+Q20; C1+Q10; C1+Q5), with 3 replicate wells in each group. After the cells were divided into groups, 0.125μL of drug was added to every 100μL of cell suspension and treated for 1 hour. Then, 2μL of antigen was added to each well per 100μL of cell suspension and incubated at 37°C for 15 minutes. After the incubation, the cells were transferred to EP tubes respectively; centrifuged, the supernatant was taken, and the supernatant was transferred to a new 96-well plate, 50 μL of substrate (β-HEX) and 25 μL of supernatant were added to each well, incubated at 37°C for 1 hour, and then 175 μL of stop solution was added. The absorbance was measured at a wavelength of 405 nm using an ELISA reader. The results are shown in Table 1.

[0081] 2. Experimental results

[0082] Table 1 Effects of different combined concentrations of quercetin and curcumin on inhibiting mast cell degranulation

[0083]

[0084]

[0085] Note: quercetin represents quercetin, represented by Q; curcumin represents curcumin, represented by C; such as C10 is 10μM curcumin concentration, Q10 is 10μM quercetin concentration; β-hex represents β-hexosaminidase; DB.G represents the absorbance value measured by the microplate reader, minus the value of the bottom of the 96-well plate; BG represents the absorbance of the bottom of the 96-well plate; N / C represents the blank group; P / D represents the absorbance value of artificial degranulation, that is, the model group. β-hex realease = DBG / 1.88; Inhibition = 1-(β-hex realease-blank group β-hex realease) / (model group β-hexrealease-blank group β-hexrealease).

[0086] The results of the inhibition rate are shown in Table 1. When the concentration of quercetin is ≥10 μM and the concentration of curcumin is greater than ≥1 μM, the combined use of quercetin and curcumin has a better inhibition rate on mast cell degranulation caused by allergies, both ≥90%.

[0087] Example 3 Combination of quercetin and curcumin to inhibit systemic allergic reactions in mice

[0088] 1. Experimental methods

[0089] 1.1 Take 6-week-old ICR mice for use.

[0090] 1.2 Dissolve the IGE antibody in physiological saline to a concentration of 20 μg / mL.

[0091] 1.3 Each ICR mouse was injected with dissolved IgE antibody and treated with antibody overnight.

[0092] 1.4 Preparation of single-dose quercetin and curcumin doses were both 5 mg / mL and 2.5 mg / mL for combined administration of quercetin and curcumin.

[0093] 1.5 Quercetin and curcumin were administered by oral gavage 1 hour before antigen challenge, 0.3 mL per mouse.

[0094] 1.6 After 1 hour, inject 0.2 mL of antigen DNP-HSA.

[0095] 1.7 After 15 minutes, blood was collected from the eyeball.

[0096] 1.8 After the blood has coagulated for 2 hours, centrifuge to obtain serum.

[0097] 1.9 Dilute the obtained serum and add it to different ELISA kits for determination. Determine PGD according to the instructions of the ELISA kits.2 , LCT4 and histamine content.

[0098] 1.10 Take out the required strips from the aluminum foil bag after equilibration at room temperature for 20 minutes, and seal the remaining strips in a ziplock bag and return them to 4°C.

[0099] 1.11 Set up standard wells and sample wells, and add 50 μL of different concentrations to each standard well.

[0100] 1.12 First add 10μl of the sample to be tested to the sample well, and then add 40μl of sample diluent; do not add to the blank well.

[0101] 1.13 Except for the blank wells, add 100 μL of horseradish peroxidase (HRP)-labeled antibody to each of the standard wells and sample wells, seal the reaction wells with a sealing plate, and incubate in a 37°C water bath or incubator for 60 min.

[0102] 1.14 Discard the liquid, pat dry on absorbent paper, fill each well with washing solution, let stand for 1 minute, shake off the washing solution, pat dry on absorbent paper, and repeat this washing process 5 times.

[0103] 1.15 Add 50 μL of substrate A and B to each well and incubate at 37°C in the dark for 15 min.

[0104] 1.16 Add 50 μL of stop solution to each well, measure the OD value of each well at a wavelength of 450 nm using an ELISA reader within 15 minutes, substitute the OD value measured by the ELISA reader into the conversion formula provided by the kit to obtain the PGD 2 , LCT4 and histamine mass concentrations.

[0105] 2. Experimental results

[0106] The data obtained by processing Graphpad Prism in the mouse systemic allergy experiment (Fexo represents the positive drug fexofenadine) are as follows Figures 5 to 7 As shown, the combination of quercetin and curcumin can effectively inhibit PGD 2 , LCT4 and histamine release, the effect is better than any single drug, especially the amount of prostaglandins and histamine in mouse serum is significantly less than that in the positive drug group, the effect is better than the positive drug. This shows that the combined administration of quercetin and curcumin to mice 15 minutes before the onset of allergy can significantly inhibit the systemic allergic reaction of mice.

[0107] The above results indicate that the combined administration of quercetin and curcumin can more effectively and thoroughly inhibit mast cell degranulation, thereby inhibiting the systemic allergic reaction of mice (the above mouse allergy model is created by injecting antibodies and antigens into the tail vein, which are transmitted to the whole body through the blood, and the allergy caused is systemic allergy), and can be used to prepare specific drugs for the treatment of type I allergic reactions.

[0108] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. Use of quercetin combined with curcumin in the preparation of a medicament for treating or preventing allergic reactions by oral administration, characterized in that: The quercetin includes quercetin and its pharmaceutically acceptable salts or esters; the curcumin includes curcumin and its pharmaceutically acceptable salts or esters; wherein the concentration of the quercetin for cell administration is ≥8 μM, and the concentration of the curcumin for cell administration is greater than ≥0.8 μM.

2. The application according to claim 1, characterized in that: The allergic reaction is a type I allergic reaction.

3. The use according to claim 1 or 2, characterized in that: The treatment or prevention of allergic reactions is to inhibit mast cell degranulation.

4. The use according to claim 1 or 2, characterized in that: The treatment or prevention of allergic reactions is to inhibit IgE-mediated serum histamine release.

5. The use according to claim 1 or 2, characterized in that: The treatment or prevention of allergic reactions is to inhibit the release of β-hexosaminidase mediated by IgE.

6. The use according to claim 1 or 2, characterized in that: The treatment or prevention of allergic reactions is to inhibit the release of prostaglandin D2 mediated by IgE.

7. The use according to claim 1 or 2, characterized in that: The method for treating or preventing allergic reactions is to inhibit the release of leukotriene C4 mediated by IgE.

8. An oral antiallergic composition, characterized in that: It includes quercetin and curcumin, wherein the quercetin includes quercetin and its pharmaceutically acceptable salts or esters; the curcumin includes curcumin and its pharmaceutically acceptable salts or esters; wherein the concentration of the quercetin is ≥8 μM, and the concentration of the curcumin is greater than ≥0.8 μM.

9. The oral antiallergic composition according to claim 8, characterized in that: Also included are pharmaceutically acceptable carriers.

10. The oral antiallergic composition according to claim 8, characterized in that: The oral antiallergic composition is in the form of tablets, powders, capsules, granules, oral liquids or syrups.

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