HK1082680B - Compositions for preventing or treating pollenosis, allergic nephritis, atopic dermatitits, asthma or urticaria - Google Patents

Description

Composition for preventing or treating pollinosis, allergic rhinitis, atopic dermatitis, asthma or urticaria

Technical Field

The present invention relates to a composition, a health food or a functional food for preventing or treating pollinosis, allergic rhinitis, atopic dermatitis, asthma or urticaria, which comprises 2 kinds of crude drugs including pumpkin seed and safflower as active ingredients.

Background

In recent years, patients suffering from pollinosis have been rapidly growing with pollen of plants such as cedar pollen, ambrosia americana, cocksfoot (カモガヤ), timothy grass, and birch as an allergen. The pollinosis is a disease in which chemical transfer substances such as histamine and leukotriene and various enzymes are released from mast cells and basophils due to the invasion of pollen, and causes symptoms in the nose and eyes, allergic conjunctivitis, allergic rhinitis (nasal discharge, nasal obstruction, sneeze), and the like.

Furthermore, not only pollen, but also allergic rhinitis (page 16th, 326-327), atopic dermatitis (page 16th, 2409-2410), asthma (page 16th, 652), urticaria (page 16th, 322-323) and THE like caused by indoor dust, mites and THE like as allergens tend to increase gradually.

The current therapeutic measures include preventive treatment with an antiallergic agent, oral administration such as various antagonists of chemical transfer substances including the next-generation antihistamines having less side effects such as sedative action and inhibitors of release of chemical transfer substances, symptomatic treatment with a steroid agent having a rapid drug action and a quick-acting nasal drop of an antihistamine having a strong action, allergy-reducing treatment, and the like. However, there are no Chinese herbal medicines or antiallergic medicines that have been developed to achieve a satisfactory therapeutic effect as preventive therapy, and antihistamines and steroid preparations used for symptomatic therapy have frequently been problematic in that they have side effects. In the treatment, there are also reports of the current situation where patient satisfaction is significantly reduced. On the other hand, allergy-reducing therapies are being newly recognized and the recognition thereof is becoming more and more clear.

It has been reported that, in the case of pumpkin seeds, safflower, plantain seeds and honeysuckle flowers, for example, by adding one or more (particularly three kinds of crude drugs) of pumpkin seeds, plantain seeds and honeysuckle flowers to a feed, the natural infection with parasites, bacteria and viruses is prevented, the defense of the organism is enhanced, and the meat quality and egg quality are improved. Further, it has been revealed that a laying hen fed with a feed containing 4 kinds of crude drugs including pumpkin seed, plantain seed, honeysuckle flower and safflower has an effect of inhibiting leucocytozoosis, an effect of inhibiting Newcastle disease of quail, and an effect of inhibiting intestinal coccidiosis and the number of staphylococci, because the health state, survival rate and egg quality of the laying hen are improved (see, for example, patent document 1).

Further, a method for producing an interferon inducer from a cucurbitaceae plant such as japanese pumpkin has been disclosed (for example, see patent document 2). Interferon inducers extracted from safflower have antiviral activity and antitumor activity (see, for example, patent document 3). Furthermore, the interferon inducer extracted from honeysuckle flower, plantain herb or the like can be used for the prevention and treatment of viral infection in humans and animals (see, for example, patent document 4). Macrophage activators are prepared from 2 crude drugs including pumpkin seed and safflower (see, for example, patent document 5). Neutrophil activators are prepared from 4 crude drugs of pumpkin seed, safflower, plantain and honeysuckle (see, for example, patent document 6).

The above documents disclose interferon-inducing activity, macrophage activation activity, neutrophil activation activity, IgE antibody production-inhibiting activity, and the like for a crude drug combination as an active ingredient of the present invention, but neither mention nor suggest the effect of preventing or treating human diseases.

[ patent document 1 ] specification of U.S. Pat. No. 5,882,672

[ patent document 2 ] specification of U.S. Pat. No. 4,421,746

[ patent document 3 ] specification of U.S. Pat. No. 4,456,597

[ patent document 4 ] specification of U.S. Pat. No. 4,469,685

[ patent document 5 ] Japanese patent laid-open No. Hei 11-116498

[ patent document 6 ] Japanese patent application laid-open No. 2000-281584

Disclosure of The Invention

The present inventors have conducted intensive studies with a view to finding more specific applications from plant-derived crude drugs, particularly crude drugs such as pumpkin seeds, safflower, plantain, and honeysuckle. As a result, it has been found that the combination of crude drugs of the present invention, at least pumpkin seed and safflower can significantly improve the symptoms of diseases or prevent the symptoms from occurring in patients suffering from pollinosis, allergic rhinitis, atopic dermatitis, asthma or urticaria. Furthermore, the crude drug combination of the present invention is extremely safe and causes no side effects even after long-term administration for 6 years, and therefore, it can be administered for a long period of time as not only a therapeutic agent but also a prophylactic agent, a health food or a functional food.

That is, the crude drug combination of the present invention is a combination of 2 crude drugs of pumpkin seed and safflower and at least one crude drug selected from the group consisting of plantain, honeysuckle flower, licorice root, coix seed, dried ginger, turmeric, zedoary and mugwort.

The present invention is as follows.

1. A composition for preventing or treating pollinosis, allergic rhinitis, atopic dermatitis, asthma or urticaria comprises 2 kinds of crude drugs selected from semen Cucurbitae and Carthami flos and at least one crude drug selected from herba plantaginis, flos Lonicerae, Glycyrrhrizae radix, Coicis semen, Zingiberis rhizoma, Curcuma rhizome, Curcumae rhizoma and folium Artemisiae Argyi as effective components.

2. The composition according to the foregoing 1, which is used for preventing or treating allergic rhinitis, asthma or urticaria.

3. The composition for preventing or treating according to 1 or 2, wherein 4 kinds of crude drugs selected from pumpkin seed, safflower, plantain seed and honeysuckle flower are used as effective ingredients.

4. A composition for preventing pollinosis is prepared from semen Cucurbitae, Carthami flos 2 crude drugs, and at least one crude drug selected from herba plantaginis, flos Lonicerae, Glycyrrhrizae radix, Coicis semen, Zingiberis rhizoma, Curcuma rhizome, Curcumae rhizoma and folium Artemisiae Argyi.

5. The prophylactic composition as described in the above 4, wherein the composition comprises 4 kinds of crude drugs selected from pumpkin seed, safflower, plantain seed and honeysuckle flower as active ingredients.

6. The composition for preventing pollinosis according to claim 4 or 5, wherein said mammal is human.

7. A composition for preventing or treating pollinosis, allergic rhinitis, atopic dermatitis, asthma or urticaria is prepared from semen Cucurbitae, Carthami flos 2 crude drugs and at least one crude drug selected from herba plantaginis, flos Lonicerae, Glycyrrhrizae radix, Coicis semen, Zingiberis rhizoma, Curcuma rhizome, Curcumae rhizoma and folium Artemisiae Argyi.

8. A method for preparing a composition for preventing pollinosis comprises administering semen Cucurbitae, Carthami flos 2 crude drugs and at least one crude drug selected from herba plantaginis, flos Lonicerae, Glycyrrhrizae radix, Coicis semen, Zingiberis rhizoma, Curcuma rhizome, Curcumae rhizoma and folium Artemisiae Argyi to patients with pollinosis all year round from season ago.

9. A health food or functional food for preventing pollinosis, allergic rhinitis, atopic dermatitis, asthma or urticaria, or improving or alleviating symptoms thereof, comprises 2 kinds of crude drugs including pumpkin seed and safflower, and at least one crude drug selected from plantain, honeysuckle flower, licorice root, coix seed, dried ginger, turmeric, zedoary and mugwort as effective components.

10. The health food or functional food according to the above 9, which comprises 4 kinds of crude drugs selected from pumpkin seed, safflower, plantain seed and honeysuckle flower as effective ingredients.

11. The composition according to 9 or 10, which is used for preventing allergic rhinitis, asthma or urticaria, or ameliorating or alleviating symptoms thereof.

12. A health food or functional food for preventing pollinosis is prepared from semen Cucurbitae, Carthami flos 2 crude drugs and at least one crude drug selected from herba plantaginis, flos Lonicerae, Glycyrrhrizae radix, Coicis semen, Zingiberis rhizoma, Curcuma rhizome, Curcumae rhizoma and folium Artemisiae Argyi.

13. The health food or functional food as described in the above 12, which comprises 4 kinds of crude drugs selected from pumpkin seed, safflower, plantain seed and honeysuckle flower as effective ingredients.

14. A health food or functional food for animals for preventing pollinosis, allergic rhinitis, atopic dermatitis, asthma or urticaria, or improving or relieving symptoms thereof comprises 2 kinds of crude drugs including semen Cucurbitae and Carthami flos and at least one crude drug selected from herba plantaginis, flos Lonicerae, Glycyrrhrizae radix, Coicis semen, Zingiberis rhizoma, Curcuma rhizome, Curcumae rhizoma and folium Artemisiae Argyi as effective components.

15. The composition, health food or functional food according to any one of the items 1 to 14, wherein the composition comprises 2 kinds of crude drugs including 20 to 60 wt% of pumpkin seeds and 10 to 40 wt% of safflower, and 5 to 50 wt% of at least one crude drug selected from the group consisting of plantain seeds, honeysuckle flowers, licorice roots, coix seeds, dried ginger, turmeric, zedoary and mugwort.

16. The composition, health food or functional food of the above 15, which is prepared from pumpkin seeds 30-50 wt%, safflower 10-30 wt%, plantain seeds 5-30 wt% and honeysuckle flower 5-30 wt%.

17. A method for preventing or treating pollinosis, allergic rhinitis, atopic dermatitis, asthma or urticaria comprises administering to a patient effective amounts of semen Cucurbitae and Carthami flos 2 crude drugs and at least one crude drug selected from herba plantaginis, flos Lonicerae, Glycyrrhrizae radix, Coicis semen, Zingiberis rhizoma, Curcuma rhizome, Curcumae rhizoma and folium Artemisiae Argyi.

18. A method for preventing or treating pollinosis, allergic rhinitis, atopic dermatitis, asthma or urticaria comprises administering to a patient an effective amount of pumpkin seed, safflower, plantain seed and honeysuckle flower.

19. The method for the prophylaxis or treatment according to the aforementioned 17 or 18, which is applied to the prophylaxis or treatment of allergic rhinitis, asthma or urticaria.

20. Use of pumpkin seed and safflower 2 crude drugs and at least one crude drug selected from plantain, honeysuckle flower, licorice root, coix seed, dried ginger, turmeric, zedoary and mugwort as effective components in preparing preventive or therapeutic agent for pollinosis, allergic rhinitis, atopic dermatitis, asthma or urticaria.

21. The use as described in the aforementioned 20, a prophylactic or therapeutic agent produced for the prophylaxis or treatment of allergic rhinitis, asthma or urticaria.

22. The use of 20 or 21, wherein the prophylactic or therapeutic agent comprises 4 kinds of crude drugs selected from pumpkin seed, safflower, plantain seed and honeysuckle flower as effective components.

The present invention can be used not only for the known pollinosis, allergic rhinitis, atopic dermatitis, asthma or urticaria, but also for the combined use with other therapeutic agents for diseases other than those mentioned above without adverse effect, and therefore, it is considered that the present invention can be used in combination with the existing therapeutic agents as an auxiliary.

The present invention will be described in more detail below.

First, the crude drugs used in the present invention will be described.

The pumpkin seeds are seeds of a plant of Cucurbitaceae, pumpkin (Japanese pumpkin: Cucurbita moschata Duch), and the present invention includes seeds of its related plant for the purpose of the present invention. The semen Cucurbitae can be raw, but dried semen Cucurbitae can be used as medicinal product and health food for easy preservation, and only seed coat can be used. The ingredients comprise cucurbitine, protein, and vitamin A, B₁、B₂C, carotene, and the like.

Safflower (Carthamus tinctorius L.) is a dried product of tubular flower of Chrysanthemum family plant. The composition comprises carthamin, xylan, and sterol. Can be used for treating blood circulation disorder such as gynecological diseases, cold syndrome and climacteric disorder.

Plantago asiatica (Plantago asiatica L.) uses seeds (Plantago asiatica) or whole plants (Plantago asiatica) matured in Plantago. It comprises polysaccharides, Plantnolic acid, succinic acid, adenine, aucubin, plantaginin, vitamin A and vitamin B₁And the like. When used as a medicine, it is used as an anti-inflammatory, diuretic and antidiarrheal medicine.

Flos Lonicerae (Lonicera japonica Thunb.) is prepared from flower or flower bud (flos Lonicerae), leaf, stem or whole plant (Lonicera japonica Thunb) of Caprifoliaceae. The components comprise waxy substances, inositol, tannic acid, saponin, loniceraside, etc. When used as a medicine, it is used as antipyretic, antidotal, diuretic and anti-inflammatory agent.

Glycyrrhiza uralensis Fisch (Glycyrrhiza uralensis Fisch.) is a dried root and rhizome of Leguminosae. The main component of the medicine is glycyrrhizin. When used as a medicine, it is used as a soothing, relieving, cough-relieving, pain-relieving and phlegm-eliminating medicine.

Coix seed (Coixlachryma-jobi L. var. ma-yuen Stapf.) was used as a seed kernel of the family Oryzaceae. The components of the oil comprise fatty oil, wherein the oil mainly comprises coixenolide, coixol, amino acid, vitamin B1 and glucide. When administered, it can be used as cancer cell inhibitor, antipyretic, analgesic, sedative and hypoglycemic.

Dried rhizome of Zingiber officinale Rose is used. In the stage of raw rhizoma Zingiberis, its crude drug name is rhizoma Zingiberis recens, and the effect is the same when rhizoma Zingiberis is used, but rhizoma Zingiberis, which is a dried product, is useful as a pharmaceutical product and a health food for preservation. The composition comprises essential oil and gingerol. When administered, it can be used for improving blood circulation, increasing blood pressure, exciting blood vessel motor center, and exciting sympathetic nerve.

Curcuma longa L (Curcuma longa L.) uses rhizomes of plants of Zingiberaceae. The composition comprises curcumin and essential oil (containing turmerone as main ingredient). When used as a medicine, the medicine is used as a cholagogue, antihypertensive, antibacterial and analgesic medicine.

Curcumae rhizoma (Curcuma zedoaria (Berg.)) is prepared from rhizome of Zingiberaceae plant. The components include curcumin and essential oil (main component is セキテルペン type). When used as a medicine, the composition is used as an anti-tumor, antibacterial and stomach-invigorating medicine.

Artemisia argyi Levl. et Vant uses dried leaves of Compositae plant (Artemisia argyi). It comprises essential oil (main components including cineol, limonone and betaterpenes), vitamins A, B, C and D. When used as medicine, has the functions of resisting bacteria, shortening bleeding and blood coagulation time, relieving cough, eliminating phlegm, diminishing inflammation, stimulating appetite, etc.

The patient is a mammal, preferably a group of animals such as an income group or an ape, a dog or a cat (companion animals).

In the present invention, when the crude drug is used as a raw material, the crude drug is used as a fresh, dried in the shade or dried product, and used as a fine powder or a powder. The crude drugs can be used as water or organic solvent extract. That is, it can be used as a raw material, a solvent preparation, a powder, a forming agent, an extraction agent, or the like. Ethanol or acetone may be used as the organic solvent, and these may be used in combination with water or 2 or more kinds of organic solvents. The extraction is to add solvent in an amount of several times the amount of crude drug, and to perform extraction or extraction at normal temperature or even at elevated temperature. Can be used for preparing single extract of each crude drug, or extracting the raw materials mixed with various crude drugs in advance to obtain extract.

The crude drug material or water or organic solvent extract can be used as health food, functional food (supplement) or medicine directly or in various forms by known method.

For example, a pharmaceutical product or a functional food (supplement) is provided as an oral tablet, powder, granule, capsule, pill, or syrup by a usual preparation method. To form a formulation, an excipient, a binder, a disintegrant, a lubricant, a buffer, a flavoring agent, a stabilizer, or the like may be added as necessary. May be mixed with at least one inert diluent, such as lactose, mannitol, glucose, hydroxypropyl cellulose, microcrystalline cellulose, starch, polyvinylpyrrolidone or magnesium aluminosilicate. The composition may further contain additives other than inert diluents according to conventional methods, for example, lubricants such as magnesium stearate, starch, and talc, disintegrating agents such as calcium cellulose glycolate, stabilizers such as lactose, and solubilizing agents such as glutamic acid and aspartic acid. The tablet or pill can be coated with sugar coating such as sucrose, gelatin, agar, pectin, hydroxypropyl cellulose or hydroxypropyl methylcellulose phthalate, or film of gastric or enteric soluble substance.

In addition, caffeine and vitamin B can be added without affecting the crude drug as the active ingredient of the present invention₁Vitamin B₂Vitamin B₆Water-soluble vitamins such as vitamin B12, vitamin C, biotin, carnitine, pantothenic acid, nicotinic acid or derivatives thereof, fat-soluble vitamins such as vitamin A, vitamin E or derivatives thereof, and amino acids such as taurine and arginine. In addition, the composition can be formulated into DONGYANG herbal medicine (Glycyrrhrizae radix, semen Ginkgo, herba Taraxaci, flos Chrysanthemi, Ginseng radix or cortex Cinnamomi Japonici, etc.) or western herbal medicine (Serenoa repens, herba Hyperici perforati, Echinacea purpurea, Pimpinella Brachycarpa, etc.) in auxiliary mannerCamomile (camomile), rosemary, mint, eucalyptus, lavender, rose, hibiscus or aloe, etc.). Perilla frutescens (FOOD Style 21, 2(4), 50-54, 1998) which has been reported to be effective for pollinosis, allergic rhinitis or atopic dermatitis can also be formulated supplementarily.

Oral liquid compositions include pharmaceutically acceptable opacifiers, solutions, suspensions, syrups or elixirs and the like, including inert diluents commonly used, such as purified water or ethanol. The composition may contain, in addition to the inert diluent, adjuvants such as wetting agents and suspending agents, sweetening, flavoring, perfuming or preservative agents.

The food is provided as a health food or a functional food in the form of a food such as a beverage, a jelly, a biscuit, a cake, or a candy.

The present invention contains pumpkin seed, safflower 2 kinds of crude drugs and at least one crude drug selected from plantain, honeysuckle flower, licorice root, coix seed, dried ginger, turmeric, zedoary and mugwort as effective components, wherein the pumpkin seed is preferably 20-60 wt%, the safflower is preferably 10-40 wt%, the other crude drugs are 5-50 wt%, the preferable mixture ratio is 20-50 wt%, the safflower is 10-40 wt% and the other crude drugs are 5-50 wt%. More preferably, the mixture ratio is 20-60 wt% of pumpkin seed, 10-40 wt% of safflower, 5-50 wt% of plantain seed and 5-50 wt% of honeysuckle flower (the total of pumpkin seed, safflower, plantain seed and honeysuckle flower is 100 wt%).

The best mixture ratio is 30-50 wt% of pumpkin seeds, 10-30 wt% of safflower, 5-30 wt% of plantain and 5-30 wt% of honeysuckle.

The crude drug combination of the present invention can be suitably adjusted depending on the age, sex, etc. of the subject to be administered, and the total amount of crude drugs administered per 60kg per day for an adult is usually 0.5 to 2g, preferably 1g, and the desired therapeutic or prophylactic effect can be exhibited without any side effect.

The time for administering the crude drug of the present invention to a mammal suffering from a pollinosis all year round before season can be determined according to the pollen scattering time of various patients, and various plants of rice such as fir, cypress, dactylophora, timothy and the like, chrysanthemum such as ambrosia americana, mugwort and the like, and birch and the like. For example, cedar pollen causes symptoms to appear in months 2 to 4, so the administration time is from 12 to 2, preferably 1 to 2.

The crude drug combination of the present invention can be used not only as a prophylactic and therapeutic agent and a health food for humans, but also as a therapeutic agent for skirt animals such as dogs and cats and a health food for ameliorating and relieving symptoms.

Brief description of the drawings

FIG. 1 shows the amount of total IgE antibodies against cedar pollen in the blood of mice orally or intraperitoneally inoculated with the hot water extract of formula A of production example 1.

FIG. 2 shows the evaluation of symptom improvement of patients with pollens who took the hot water extract of formula A of production example 1.

FIG. 3 shows the evaluation of symptom improvement of patients with pollens who took the hot water extract of formula B of production example 1.

Fig. 4 shows the improvement rate of symptoms that did not occur during the test period among symptoms that occurred all year round after taking the hot water extract of formula a of production example 1.

Fig. 5 shows the improvement rate of symptoms that did not occur during the test period among symptoms that occurred all year round after taking the hot water extract of formula B of production example 1.

FIG. 6 shows the degree of improvement in the symptoms before onset of pollinosis by starting ingestion of the hot water extract of formula B of production example 1.

FIG. 7 shows the degree of improvement in the symptoms after onset of pollinosis by starting ingestion of the hot water extract of formula B of production example 1.

FIG. 8 shows the degree of improvement of a male patient who ingested the hot water extract of formula B of production example 1.

FIG. 9 shows the degree of improvement of a female patient who ingested the hot water extract of formula B of production example 1.

Best Mode for Carrying Out The Invention

The present invention will be described in more detail below based on production examples and examples, but the present invention is not limited thereto.

Production example 1

Preparing crude drug raw materials of the following formula A or formula B, extracting with 10 times of water at 95 + -5 deg.C for 30 min, filtering the extractive solution, concentrating, adding excipient such as reducing maltose, lactose and starch, and perfume, and granulating.

Prescription A: the components (proportion) are as follows: pumpkin seed (50%), safflower (20%), plantain seed (15%) and honeysuckle flower (15%)

And a prescription B: the components (proportion) are as follows: pumpkin seed (40%), safflower (20%), coix seed (20%) and perilla (20%)

Production example 2

The pumpkin seeds 5.0g, the safflower 3.0g, the plantain 1.0g, the honeysuckle 3.0g, the lactose 67g and the starch 16g are put into a vertical mixer to be uniformly mixed, the mixture is mixed with a mixed solvent in which 2g of hydroxypropyl cellulose and 5g of capric triglyceride are dissolved in 40g of 85% ethanol in advance, after mixing, the mixture is put into a basket type granulator (screen diameter is 1mm) to be granulated, and then the granulated mixture passes through a sieve with 14 meshes, and then the granulated mixture is dried to obtain cylindrical granules. The above components were uniformly mixed with mannitol, hydroxypropylcellulose, magnesium aluminosilicate, aspartame and a flavor to obtain granules 12 (see Japanese patent laid-open No. 2000-231584).

Hereinafter, compositions in various proportions (wt%) can be prepared in the same manner as in production example 2.

TABLE 1

Prescription example	Pumpkin seed	Safflower	Front of vehicle	Honeysuckle
					1	60	20	10	10
2	50	20	15	15
					3	50	10	25	15
4	45	20	30	5
					5	42	25	8	25
6	40	30	20	10
					7	25	10	40	25
8	25	15	38	22
					9	25	25	25	25
10	25	25	5	45
					11	20	40	20	20
12	20	10	60	10
					13	25	15	38	22
14	25	25	25	25
					15	25	25	2	45
16	20	40	20	20
					17	20	10	60	10

Production example 3

Preparing crude drug materials of semen Cucurbitae, Carthami flos, herba plantaginis and flos Lonicerae, extracting with 10 times of water at 95 + -5 deg.C for 30 min, filtering the extractive solution, concentrating, adding excipient such as reduced maltose, lactose and starch, and perfume, and granulating to obtain fine granule [ Interpunch ] (registered trademark, manufactured by Sanwell corporation). The following table shows the compositions.

TABLE 2 Nutrition ingredients in 2 packets of Interpunch (1.5 g. times.2)

Example 1 inhibition of blood Total IgE antibody production in mice allergic to cedar pollen

Changes may be made as appropriate according to representative assays (allergy, 42(1), 74-80 (1993)).

The inhibitory effect of total IgE antibody production in blood against Cedar Pollen (Cedar Pollen Extract-Cj (LSLCO., LTD)) when the hot water Extract of formulation A of production example 1 was orally or intraperitoneally inoculated was examined using 12-15 week-old BALB/cCrSlc female mice. The extract for oral administration is obtained by adding 10 times of water to the crude drug of formula A, extracting at 95 + -5 deg.C for 30 min, continuously centrifuging at 900 × g, centrifuging the supernatant at 10,000 × g, collecting the supernatant, and extracting. The extract for intraabdominal inoculation is obtained by adding 10 times of water to the crude drug of formula A, extracting at 95 + -5 deg.C for 30 min, continuously centrifuging at 900 Xg, centrifuging the supernatant at 10,000 Xg, collecting the supernatant, dialyzing the supernatant, collecting the fraction with molecular weight of 14000 or more, filtering and sterilizing with 0.45MY filter (Fuji Film, microfilter, lot No. 16555970436), and extracting. The experimental groups are as follows.

Group 1: no treatment control (negative control group).

And 2, group: group with only pollen taken intraperitoneally.

And 3, group: the group ingested pollen and extract (0.3ml) in the abdominal cavity (1 time of the extract of formula A on day 13 after the first immunization).

4 groups are as follows: the group ingested pollen and orally administered extract (0.6ml) intraperitoneally (0.1 ml/day orally administered from 7 th to 12 th day after the first immunization, and 5mg of cedar pollen and 4mg of aluminum hydroxide were intraperitoneally injected on 13 th day).

The total IgE antibody measurement method comprises collecting whole blood under anesthesia, separating serum from the sample, storing at-80 deg.C until the antibody titer is measured, and measuring total IgE antibody by sandwich (sandwich) ELISA method according to the conventional method.

The results of the measurement of total IgE antibodies are shown in fig. 1. No significant differences were confirmed between groups before dosing, at week 1 and week 2. At week 3, the antibody amount increased to 1474.2ng/ml in the group ingested only with pollen (group 2), and the increase was significantly suppressed in the intraperitoneal administration group of formula A (group 3) (866.97ng/ml) and the oral administration group of formula A (group 4) (1036.24ng/ml) as compared with the group ingested only with pollen (group 2) (P <0.05 in parent' st-test). In addition, no significant difference was observed in comparison between the intraperitoneal administration group (3 groups) of the formula a and the oral administration group (4 groups) of the formula a.

From the above results, it was confirmed that the health food of the present invention can suppress the production of IgE antibodies in blood of mice allergic to cedar pollen and can suppress allergy.

Example 2 preventive or therapeutic effects on patients with Japanese cedar pollen disease

In order to examine the effectiveness and safety of the health food of the present invention against cedar pollinosis, clinical trials were conducted on hot water extracts of formula a and formula B of production example 1, for adult male and female pollinosis patients. Prescription A has 20 patients with pollinosis (10 each for male and female), and prescription B has 72 subjects with pollinosis. The test was started in the first ten days of 2 months, and the administration was started at will for 90 days. The patient is asked to fill out a questionnaire before starting and at the end, from which a comparison is made for decision. During the test, 1.0g of hot water extract was taken daily as the crude drug, and the intake was recorded daily on recording paper. The subject who had discontinued administration or had irregular ingestion is excluded from the effect determination.

After the test, the degree of improvement compared with the symptoms of the year was obtained from the subjects as 8 grades of results of complete cure, great improvement, slight improvement, no change, slight deterioration, great deterioration. As a result, the symptoms of patients who took prescription a and prescription B improved significantly more than half of the way, and slightly improved more than 80% (fig. 2 and 3).

The results of comparison of the past symptoms and the symptoms of the present year in subjects who took the hot water extract of formula a showed that the symptoms were improved in the order of nasal obstruction, nasal discharge, sneezing, itchy eyes, lacrimation, itchy nose, hoarseness, sleep disturbance, improvement in symptoms, headache, itching of mouth and throat, itching of skin, unpleasantness, nausea, dyspnea, sore throat, muscle pain, or discomfort in the mouth (fig. 4).

The results of comparison of the past symptoms and the symptoms of the present year with those of the subjects who took the hot water extract of formula B showed that the symptoms of urticaria, asthma, rash, dysentery, myalgia, constipation, and congestion of eyes were improved by 100%, and the symptoms of mouth and throat itching, cough, eczema, sleep disorder, unpleasantness, vomiting, cutaneous pruritus, rhinocnesmus, headache, nasal obstruction, lacrimation, sneezing, itchy eyes, dry eyes, or rhinorrhea were improved in this order (fig. 5).

From the correlation analysis of the intake start time and the evaluation degree of symptom improvement of the subject who took the hot water extract of formula B, it was concluded that the ratio of the intake before the onset of symptoms (beginning of 2 months) to the intake after the onset of symptoms was more than the improvement in symptoms of the intake after the onset of symptoms was larger (fig. 6 and 7).

Therefore, it was confirmed that the crude drug composition of the present invention had a preventive therapeutic effect.

The degree of improvement of the subjects who took the hot water extract of formula B was not different depending on the sex (fig. 8 and 9).

The combination of the doctor's treatment, the use of the medicine or other health foods is improved to almost the same degree as the case of the use of the health foods alone, and therefore, it is considered that the use together with other products does not have any adverse effect. No influence on the degree of improvement due to differences in body type was observed.

From the above results, it was confirmed that the health food of the present invention is effective for improving symptoms of patients with pollinosis, and particularly, the health food can suppress the occurrence of symptoms when taken prophylactically from pre-season.

Example 3 preventive Effect against patients with pollinosis

The improvement of symptoms was observed in a 66-year-old female pollen disease patient who consumed the health food of formula A of production example 1 (1 g/day as raw material) during 2 months from the beginning of 3 months. Ambroxol hydrochloride (ambroxol hydrochloride) and progesterone have been used together as a pharmaceutical for years, which is afflicted with nasal discharge and itchy eyes, but symptoms of pollinosis do not appear when the health food of the present invention is consumed.

Example 4 therapeutic Effect on allergic rhinitis patients

In order to examine the effectiveness and safety of the health food of the present invention against allergic rhinitis, a single-blind (single-blind) comparative test was conducted on the health food of formula B of production example 1 (genuine drug) and a placebo (fake drug) having the same appearance and taste, for a patient suffering from allergic rhinitis for a long time. The method is performed on 53 patients with indoor dust (HD) allergic rhinitis all year round (if the patients are more than 18 years old, the patients cannot be used together). The diagnosis was carried out by taking the guidelines for allergic rhinitis diagnosis (the guidelines for allergic rhinitis diagnosis-perennial rhinitis and pollinosis-revised 3 rd edition (1999) -manufactured by the institute of allergic rhinitis diagnosis, Committee), and taking patients who had sneezing, nasal discharge, nasal congestion symptoms and who were positive for nasal discharge eosinophil examination, HD intradermal reaction, HD RAST values in blood, and HD intranasal induction examination, as perennial HD allergic rhinitis patients. During the administration period, patients who were afraid of the effects of pollinosis were removed. In the classification of mild and severe symptoms, 25 patients with mild symptoms, 28 patients with moderate symptoms and 8 patients with severe symptoms are treated. After a control observation period of 1 week, the patients were administered the true or false drug 2 times a day (1.0g per equivalent of the crude drug) for 4 weeks, and the development of symptoms was judged from the allergy diary of the patients. Peripheral blood test, liver/biliary tract system, renal function test and urine test were performed before and after administration, and the presence or absence of side effects was evaluated. 18 patients administered at 12 months were collected from peripheral blood before and after administration, red blood cells were removed, and the resultant was stimulated with mite antigen (10ng/ml) in a 24-well plate, and IL-5 and IFN γ in the culture supernatant after 7 days were measured by ELISA, and the amounts of production of HD-stimulated IL-5 and IFN γ were compared with IL-5 and IFN γ in the culture supernatant without stimulation.

As a result, no patient left the test after eating the health food, and the study was conducted on 30 genuine drugs and 23 fake drugs. No difference in classification of disease severity was found in genuine and sham groups. The improvement in the ratio from the judgment of allergy diary was sneezing onset: 20.0% of genuine drug group, 30.4% of fake drug group, and nasal discharge frequency: 16.6% of genuine drug group, 39.1% of fake drug group, nasal obstruction: 20.0% of genuine drug group and 30.4% of fake drug group, and the degree of disorder brought to daily life is as follows: the genuine drug group was 6.60% and the sham drug group was 13.0%, which revealed excellent results regardless of the genuine drug groups. In addition, no specific side effects such as gastrointestinal diseases are found in the genuine drug group and the fake drug group. Also, no abnormal value was found in the conventional blood test.

The production of cytokines by peripheral blood was investigated for IFN γ by 11 true drug groups and 7 pseudodrug groups, and for IL-5 by 6 true drug groups and 6 pseudodrug groups, respectively. The production of IFN γ by HD stimulation was significantly increased after dosing in the authentic group compared to before dosing (p <0.05), with no significant change in the sham group. IL-5 production by HD stimulation was significantly reduced after administration in the true drug group (p <0.05), and not even to a minimal extent in the sham group. Therefore, it is apparent that the health food of the present invention has a Th1 cytokine-promoting effect and a Th2 cytokine-suppressing effect.

From the above results, it was confirmed that the health food of the present invention is safe and effective for improving symptoms of allergic rhinitis patients. Therefore, the main effect of the present invention is to improve the balance by regulating the abnormal balance of Th1/Th2 cytokines, which is the cause of type I allergy.

Example 5 therapeutic Effect on patients with perennial allergic rhinitis

The health food of formula A of production example 1 (1 g/day as raw material) was administered to a 4-year-old male patient suffering from allergic rhinitis all year round, and the improvement of symptoms was observed. At first, nasal obstruction is serious, but after eating the product, nasal discharge is gradually discharged, and the nose is smooth and good. After 1 week, the food is stopped, and nasal obstruction begins again.

Example 6 therapeutic Effect on atopic dermatitis

A female patient with atopic dermatitis who was 27 years old was administered the health food of the formula A of production example 1 (1 g/day as raw material conversion), and the improvement of skin symptoms was observed. The patients have been treated with the medicine before and eat other healthy foods, but the symptom improvement has no obvious effect. The product is observed after about 1 month, and has reduced skin redness, exudation, and pruritus, and the pruritus is rapidly improved.

From the above results, it was confirmed that the health food of the present invention is effective for ameliorating the symptoms of atopic dermatitis.

Example 7 therapeutic Effect on infantile asthma

A7-year-old asthmatic boy and child patient were fed the health food (1.5 g/day as raw material) of the formula A of preparation example 1 and observed to have improved symptoms. Although the medicine is also used for treatment in the past, asthma symptoms appear immediately after the medicine is exposed to dust, cough is relieved after the medicine is eaten, and nasal obstruction is greatly improved.

Example 8 therapeutic Effect on urticaria

After the pregnancy was terminated half a year before 23 years old women, a map-like urticaria appeared in the soft part of the skin around the abdomen, hands and feet every night, and the symptom was observed to improve for 6 months by eating the health food of formula a of production example 1 (1 g × 3 times/day as raw materials), and gradually improved during the eating period.

Example 9 confirmation test of safety

The safety of recipe a and recipe B of production example 1 to humans was investigated.

Healthy adult men 7 were ingested 2 times a day (1 equivalent to 1.0G of crude drug), blood was collected before and after the start of ingestion for 2 weeks, at 1 week and 2 weeks, and subjected to routine clinical examinations (hematological examinations (white blood cell count, red blood cell count, hemoglobin amount, hematocrit value, MCV, MCH, MCHC, platelet count, white blood cell image), hematochemcological examinations (total protein, albumin, a/G, total bilirubin, MCV, MCH, MCHC, GOT, GPT, alkaline phosphatase, γ -GTP, total cholesterol, neutral fat, urea nitrogen, uric acid, creatinine) and immunochemical examinations (nonspecific IgE, nonspecific IgG, iron transfer protein)), and physiological examinations (body temperature, pulse, blood pressure) by doctors. As a result, during the 2-week ingestion test, no problem was found in the safety of the healthy food of production example 1, and the safety of formula a and formula B, because no problem was found to occur in subjective symptoms, external observation, and each test including clinical test values of immunochemical tests.

Example 10 safety as a health food

The healthy adult male has eaten the health food for 6 years. Consumption began at 31 years of age. The raw materials of the formula A were ingested in the first 2 years, and the average daily dose was 1g, and then the health food of formula A was consumed in an amount of 1g in terms of raw materials per day. As a result, the general blood properties and health conditions are not adversely affected during the eating period.

Example 11 safety of use during pregnancy

A29-year-old female in pregnancy in which the health status was not adversely affected until the prognosis of delivery or after delivery was fed the prescription example B of production example 1. Moreover, the born boy is also free from abnormalities and thereafter grows healthily.

Example 12 therapeutic efficacy on animal dermatitis

22 dogs suffering from dermatitis having positive IgE antibodies in animal hospitals (age: half year after the year-14 years, sex: 5 males, 17 females, breed: 5 hamabouts, 3 fagoets, 3 equisetics, 3 crossbred dogs, 2 lions, 1 crammed beagles, 1 boston dog, 1 japanese beagles, 1 small short leg beagles, 1 french beagles, and 1 labrador beagles) were administered with tablets (4 tablets containing 1.0g of the raw material) or granules (1.0g of the raw material contained in the granules), which were processed according to the prescription A of production example 1, for 1 month, to study the effect of the drugs on alleviating dermatitis. The standard amount of 1 day intake is 5kg or less, 5-10kg or 10-20kg body weight, 2, 4 or 8 tablets in case of tablet, or 0.5g, 1.0g or 2.0g in case of granule. Evaluation items were 1. erythema, 2. dryness and desquamation, 3. pimple and 4. itching, and evaluation was performed on 5 grades of 1 to 5. From these ratings the veterinarian determines the total disease status of the dogs into 6 grades, which are: 1. disappearance of symptoms, 2 significant improvement, 3 improvement, 4 slight improvement, 5 no change, 6 worsening. The health food of the present invention was not taken together with a drug alone, and 12 dogs were observed and the disease was judged, and as a result, the number of dogs was significantly improved to 2, slightly improved to 6, unchanged to 2, and no deterioration was observed. In addition, 10 dogs treated with a drug such as a steroid agent in combination with the health food of the present invention showed a marked improvement of 2, 1, a slight improvement of 3, and no change of 4, and no deterioration. All of the 4 symptoms of the evaluation item were improved. In the case of using the combination drug, the effect of reducing the dosage of the drug by half is obtained. The above results show that the present invention has a good alleviation effect on dog allergic dermatitis.

Possibility of industrial applicability

The present invention provides a therapeutic agent which is a composition containing a crude drug and has a safe and excellent therapeutic effect on pollinosis, allergic rhinitis, atopic dermatitis, asthma or urticaria, which have not been known in the past, in humans or animals of the same group. In particular, for pollinosis, the composition can be used as a prophylactic agent because the symptom can be suppressed by taking the composition from the season ago. Further, since there is no side effect, it can be used not only as a pharmaceutical product but also as a functional food or a health food for a long period of time.

Claims (5)

1. The application of a composition in preparing a medicine for preventing or treating pollinosis, allergic rhinitis, atopic dermatitis, asthma or urticaria is characterized in that the composition comprises 30-50 wt% of pumpkin seeds, 10-30 wt% of safflower, 5-30 wt% of plantain seeds and 5-30 wt% of honeysuckle.

2. The use according to claim 1, for the prevention or treatment of allergic rhinitis, asthma or urticaria.

3. Use of a composition for the preparation of a health food or a functional food for preventing pollinosis, allergic rhinitis, atopic dermatitis, asthma or urticaria, or for ameliorating or alleviating the symptoms thereof, wherein the composition comprises 30-50 wt% of pumpkin seeds, 10-30 wt% of safflower, 5-30 wt% of plantain seeds and 5-30 wt% of honeysuckle flowers.

4. The use according to claim 3, for preventing allergic rhinitis, asthma or urticaria or ameliorating or alleviating the symptoms thereof.

5. The use according to claim 3, wherein the food product is a health food for animals or a functional food for animals.