JP3450080B2 - Health foods and pharmaceuticals containing procyanidin - Google Patents

Description

Detailed Description of the Invention

[0001]

The present invention relates to the treatment of allergic diseases.
The present invention relates to an antiallergic agent for the purpose of improvement .

[0002]

2. Description of the Related Art Epigallocatechin gallate, epigallocatechin,
Epicatechin gallate and epicatechin are known. Among these, the use of catechins as antiallergic agents is disclosed in JP-A-3-157330, which is epigallocatechin gallate.

[0003]

So far, we have investigated antiallergic components in tea leaves using histamine release inhibitory action as an index. In addition to the above catechins, catechins represented by the following general formula (1) We found that histamine release was suppressed in the polymer procyanidins.

[Chemical 1] Further, procyanidin is more stable than other catechins such as epigallocatechin gallate, and thus the present invention has been accomplished as an antiallergic agent of procyanidin.

[0004]

The present invention is an antiallergic agent characterized by containing procyanidins.
Procyanidin is a polymer of (+) catechin or (−) epicatechin, and procyanidins B-1 and B-
2, B-3, B-4, B-5, B-6, B-7 and B-
8 and the like, and those isolated and purified from oolong stem tea, green tea, oolong tea, black tea leaves and the like can be used. For the purification method, see Chemica.
l & Pharmaceutical Bullet
In, 31, 3906-3914, (1983) can be referred to. That is, green tea, oolong stem tea,
A procyanidin can be obtained by adding a solvent to oolong tea, black tea or the like, extracting the mixture, and subjecting the extract to chromatography. Examples of the solvent used for the extraction include water, ethanol, methanol, acetone, ethyl acetate, n-butanol or a mixed solvent thereof, and the extraction may be performed at room temperature. The obtained extract may be directly subjected to chromatography, or it may be dissolved in water and then fractionated by partition extraction with ethyl acetate or n-butanol. Liquid chromatography is often used as the chromatography, and examples of the packing material include ion exchange resins, silica gel, octadecyl silica gel and the like.

The antiallergic agents mentioned in the present invention include candy, drops, confectionery, chewing gum, capsules,
Beverages are included. In addition, the anti-allergy referred to in the present invention
The drug can be administered orally, intramuscularly, intracutaneously, subcutaneously, intravenously,
It is administered by parenteral administration to the lower body cavity or the skin. Furthermore, in order to formulate the antiallergic agent of the present invention ,
Dosage forms such as tablets, granules, powders, capsules, syrups, eye drops, troches, injections, suppositories, ointments and the like can be adopted by a conventional method in the technical field of formulation. That is, when preparing a solid preparation for oral use, an excipient, and if necessary, a binder, a lubricant, a colorant, a flavoring agent, etc. are added to the main drug, and then tablets, granules, Powders, capsules, lozenges, etc.

Procyanidin is an antiallergic agent of the present invention
In total amount, 0.005 wt%, preferably, 0.0
It is added in an amount of 1 to 0.5% by weight. 0.
If the amount is less than 005% by weight, the effect is poor, and if the amount exceeds 1% by weight, the effect cannot be expected to increase. The dose of the antiallergic agent varies depending on the symptoms of the disease, the age of the patient, etc., but is usually 30 to 100 mg, preferably about 50 mg per day for an adult. In an acute toxicity test using mice, both oral, subcutaneous and intravenous administration were 2 g / k
No deaths were observed in g. Moreover, no abnormalities were found in all organs in autopsy findings.

[0007]

EXAMPLES Next, typical examples will be given to explain the present invention in detail, but the present invention is not limited thereto. Moreover, a part shows a weight part. Production Example-1 Purified Procyanidin To oolong stem tea was added 50 times the amount of water, heated at 90 to 95 ° C for 1 hour and filtered, and the filtrate was concentrated and freeze-dried to obtain a hot water extract. 1 Kg of this hot water extract was dissolved in 5 L of water, and the mixture was extracted with 2 volumes of ethyl acetate three times to obtain 40 g of ethyl acetate fraction.
Obtained. This ethyl acetate fraction was dissolved in water and subjected to Sephadex LH-20 (Pharmacia) column chromatography (eluent: 0-100% methanol aqueous solution). The obtained catechin fraction was lyophilized, then dissolved again in water and subjected to MCI gel (manufactured by Mitsubishi Kasei Co., Ltd.) column chromatography (eluent: 0-100% methanol aqueous solution). Elution of catechins was performed by TLC analysis (plate: silica gel 60, developing solvent: benzene / ethyl formate / formic acid (2: 7: 1), chromogenic agent:
Anisaldehyde or ferric chloride)
Fractions giving one spot were collected, concentrated and lyophilized to obtain 250 mg of procyanidin B-1 in which the 8-position of (+) catechin and the 4-position of (−) epicatechin were bonded. Also, in the same way,
825 mg of procyanidin B-4 in which the 4-position of (+) catechin and the 8-position of (-) epicatechin were bonded was obtained. Each structure was identified by measuring specific rotation and NMR spectrum and comparing with literature values.

Example-1 Candy maltitol 48.0 parts Starch saccharified product 20.0 Procyanidin 0.1 [Production Method] The raw materials are heated and melted at 120 to 170 ° C and solidified in a mold.

Example-2 Drop Sugar 81.0 parts D-Glucose 16.5 Citric acid 1.1 Fragrance Appropriate amount Colorant Appropriate amount procyanidin 0.1 [Production Method] The raw materials are heated and melted at 100 to 120 ° C and solidified in a mold.

[0010]   Example-3 Tablet confectionery     White sugar (fine powder) 100.0 parts     Gum arabic (fine powder) 7.0     Procyanidins 0.2     Mint extract 0.1     Proper amount of water [Production method] The raw materials are mixed well and compressed to produce.

[0011]   Example-4 chewing gum     Gum base 20.0 parts     Sugar 78.5     Procyanidins 0.1     Mint extract 1.0     Proper amount of water [Manufacturing method] The raw materials are well mixed and manufactured by a conventional method.

Example-5 Beverage Procyanidin 0.1 part Sodium benzoate 0.1 Fructose 1.0 Fragrance Appropriate amount Dye Appropriate amount Purified water 100.0 [Production method] Raw materials are added to purified water to dissolve, and the total amount is adjusted to 100.0 parts.

Example-6 Tablets Procyanidin 1.0 part Lactose 99.0 Dry cornstarch 2.0 Talc 1.8 Calcium stearate 0.2 or more Blended to give 200 tablets. Weight of one tablet 0.52 g [Production method] Lactose and dried cornstarch are added to procyanidin for sizing, and a lubricant such as talc and calcium stearate is added and mixed, and the mixture is tableted. Run the mixer for 10 minutes.

Example 7 Granules Procyanidin 0.1 part Lactose 5.0 Gum arabic powder 1.0 Single syrup Admixed in appropriate amount or more 200 granules are prepared. [Production method] Put procyanidin in a mortar, dissolve in a small amount of water, immediately add lactose to this, grind evenly, then add gum arabic powder, and finally add an appropriate amount of syrup little by little and knead with a pestle to make a hard mixture. It is made into a plastic mass, and this is granulated by a granulator.

Example-8 Powders Procyanidin 0.1 part Lactose 9.0 or more Admixture 12 powders. [Production method] Put procyanidins in a mortar, dissolve in a small amount of water, add lactose and grind until even, then dry and grind to give fine powder.

Example-9 Capsule Preparation Procyanidin 0.1 part Microcrystalline Cellulose 8.5 Corn Starch 2.0 Lactose 2.2 Polyvinylpyrrolidone 0.3 or more Blended into 30 capsules. [Production Method] Procyanidin, microcrystalline cellulose, corn starch and lactose were mixed, polyvinylpyrrolidone was added as a binder, and the mixture was granulated by a conventional method and then filled into a gelatin hard capsule.

Example-10 Lozenge Agent Procyanidin 0.1 part Glucose 100.0 Sodium hydrogencarbonate 2.0 White sugar powder 4.0 Gum arabic 3.0 Dextrin 1.0 or more 20 troches mixed with each other. [Manufacturing method] Grind all drugs into fine powder, add water or simple syrup little by little, and pour this into a mold to divide into 20 pieces. Sucrose powder is used as the clothing.

Example-11 Eye Drops Procyanidin 0.1 part Chlorobutanol 0.1 Sodium Chloride Suitable amount Purified water 30.0 [Production Method] Procyanidin, chlorobutanol and sodium chloride were weighed and dissolved in suitable amount of purified water to obtain the total amount.
30 copies.

Example-12 Syrup Agent Procyanidin 1.0 part Carboxymethylcellulose 2.0 Single syrup Total 100.0 [Production Method] First, carboxymethylcellulose is weighed and ground in a mortar until it becomes a fine powder. Next, take a portion of the simple syrup, add little by little, and grind well to make it even. Gradually add procyanidin to the mixture and grind it, and finally add the remaining single syrup to make a uniform viscous liquid.

Example-13 Injection Procyanidin 0.5 parts Chlorobutanol 0.5 Sodium chloride 0.9 Distilled water for injection All 100.0 [Production Method] Distilled water was dissolved by dissolving warm chlorobutanol, and sodium chloride and procyanidin were added to the solution. Is added to make the total amount 100.0 parts. Filter, put in a vial, seal, and sterilize at 121 ° C for 15 minutes.

Example-14 Suppository Procyanidin 1.0 part Carbowax 4000 20.0 Carbowax 1500 90.0 or more 70 suppositories are used. [Production method] Procyanidin is placed in a mortar, made into fine powder, and the melted and mixed carbowax is added little by little to be ground and poured into a suppository mold.

Example-15 Ointment Procyanidin 1.0 part Liquid paraffin 10.0 White petrolatum 100.0 [Production method] Procyanidin is ground with liquid paraffin to form a mud, and white petrolatum is mixed and kneaded to prepare a homogeneous product.

Example-16 Candy Maltitol 48.0 parts Starch saccharified product 20.0 Procyanidin B-1 0.1 [Production Method] The raw materials are heated and melted at 120 to 170 ° C and solidified in a mold.

Example-17 Drop Sugar 81.0 parts D-Glucose 16.5 Citric acid 1.1 Fragrance Appropriate amount Dye Appropriate amount Procyanidin B-1 0.1 [Production Method] The raw materials are heated and dissolved at 100 to 120 ° C. and solidified in a mold.

[0025]   Example-18 Tablet confectionery     White sugar (fine powder) 100.0 parts     Gum arabic (fine powder) 7.0     Procyanidin B-1 0.2     Mint extract 0.1     Proper amount of water [Production method] The raw materials are mixed well and compressed to produce.

[0026]   Example-19 Chewing gum     Gum base 20.0 parts     Sugar 78.5     Procyanidin B-1 0.1     Mint extract 1.0     Proper amount of water [Manufacturing method] The raw materials are well mixed and manufactured by a conventional method.

Example-20 Beverage Procyanidin B-1 0.1 part Sodium benzoate 0.1 Fructose 1.0 Fragrance Suitable amount Colorant Suitable amount Purified water 100.0 [Production Method] Raw materials were added to purified water to dissolve, and total amount was 100.0 parts To do.

Example-21 Tablet Procyanidin B-1 1.0 part Lactose 99.0 Dry cornstarch 2.0 Talc 1.8 Calcium stearate 0.2 or more Blend 200 tablets. Weight of one tablet 0.52 g [Production method] Lactose and dried cornstarch are added to procyanidin B-1 for sizing, and a lubricant such as talc and calcium stearate is added, mixed, and compressed. Run the mixer for 10 minutes.

Example-22 Granules Procyanidin B-1 0.1 part Lactose 5.0 Gum arabic powder 1.0 Single syrup Admixed in appropriate amount or more 200 granules are prepared. [Manufacturing method] Put procyanidin B-1 in a mortar, dissolve in a small amount of water, immediately add lactose to this, and polish uniformly.
Then add gum arabic powder, and finally add an appropriate amount of syrup little by little and knead with a pestle to make a hard plastic mass,
This is put into a granulator and sized.

Example-23 Powder Procyanidin B-1 0.1 part Lactose 9.0 or more Admixture 12 powder mixture. [Production method] Put procyanidin B-1 in a mortar, dissolve in a small amount of water, add lactose and grind until uniform, dry and grind to give fine powder.

Example-24 Capsule Preparation Procyanidin B-1 0.1 Part Microcrystalline Cellulose 8.5 Corn Starch 2.0 Lactose 2.2 Polyvinylpyrrolidone 0.3 or more Mixture 30 capsules are prepared. [Production Method] Procyanidin B-1, microcrystalline cellulose, corn starch and lactose were mixed, polyvinylpyrrolidone was added as a binder, and the mixture was granulated by a conventional method and then filled into a gelatin hard capsule.

Example-25 Lozenge Agent Procyanidin B-1 0.1 part Glucose 100.0 Sodium hydrogencarbonate 2.0 White sugar powder 4.0 Gum arabic 3.0 Dextrin 1.0 or more 20 troches mixed with each other are used. [Manufacturing method] Grind all drugs into fine powder, add water or simple syrup little by little, and pour this into a mold to divide into 20 pieces. Sucrose powder is used as the clothing.

Example-26 Eye Drops Procyanidin B-1 0.1 part Chlorobutanol 0.1 Sodium chloride suitable amount Purified water 30.0 [Production Method] Procyanidin B-1, chlorobutanol and sodium chloride were weighed and dissolved in appropriate amount of purified water. The total amount is 30 copies.

Example-27 Syrup Agent Procyanidin B-1 1.0 part Carboxymethylcellulose 2.0 Single syrup Total 100.0 [Production Method] First, carboxymethylcellulose is weighed and ground in a mortar until it becomes a fine powder. Next, take a portion of the simple syrup, add little by little, and grind well to make it even. Gradually add procyanidin B-1 to this,
Finally, add the remaining single syrup to make a uniform viscous liquid.

Example-28 Injectable preparation Procyanidin B-1 0.5 part Chlorobutanol 0.5 Sodium chloride 0.9 Distilled water for injection Total 100.0 [Production Method] Distilled water was warmed to dissolve chlorobutanol, and sodium chloride and procyanidin B-1 were added thereto. In addition, dissolve and add distilled water to make the total volume 100.0 parts.
Filter, put in a vial, seal, and sterilize at 121 ° C for 15 minutes.

Example-29 Suppository Procyanidin B-1 1.0 part Carbowax 4000 20.0 Carbowax 1500 90.0 More than 70 suppositories. [Production Method] Procyanidin B-1 is placed in a mortar, made into fine powder, and the carbowax which is melted and mixed is added little by little to be ground and poured into a suppository mold.

Example-30 Ointment Procyanidin B-1 1.0 part Liquid paraffin 10.0 White petrolatum 100.0 [Production method] Procyanidin B-1 was ground with liquid paraffin to form a mud, and white petrolatum was kneaded and kneaded to prepare a homogeneous product. .

According to the present invention, procyanidin is the main component.
It is possible to provide an antiallergic agent having a strong effect of Since this ingredient is mainly obtained from tea and is used daily, it is highly safe. Further, procyanidins were superior in stability to other catechins and were easy to formulate. Next, in order to explain the effect of the present invention in detail, an experimental example will be given.

Experimental Example 1 Histamine Release Inhibitory Effect The histamine release inhibitory effect was examined using mast cells collected from the abdominal cavity of Sprague-Dawley male rats. That is, the isolated mast cells were sensitized with an IgE antibody, and the amount of histamine released by ovalbumin stimulation was measured.
Mast cells are derived from the method of Sullivan et al. (J. Immunology, 114 (5),
1473-1479, 1975), and histamine was quantified by the method of May et al. (J. Allergy, 46, 12-20, 1970). As shown in Table 1, procyanidins showed a strong histamine release inhibitory effect, and procyanidin B-1 showed a higher inhibitory rate than epigallocatechin gallate. Margin below

[0040]

[Table 1] Experimental Example-2 Usage Test A usage test of the candy of Example-16 was conducted on 52 subjects suffering from allergic rhinitis or hay fever. The test subject was the candy of Example-16, and eight other subjects were candy obtained by removing procyanidin B-1 from Example-16 (Comparative Example-1) for 3 to 1 day each.
Five meals were eaten and the degree of improvement was examined 2 months later. As a result, in Comparative Example-1, improvement was observed in 1 out of 8 persons (12.5%), whereas in Example-16, 38 out of 52 persons (7
Improvement of symptoms was observed in 3.1%).

Experimental Example-3 Use Test The use test of the troche of Example-25 was conducted on 61 subjects suffering from allergic rhinitis or hay fever. To the subject, the lozenge of Example-25 was eaten, and to another 8 persons, 3 to 5 lozenges (Comparative Example-2) excluding procyanidin B-1 from Example-25 were eaten per day. After 2 months, the degree of improvement was examined. As a result, in Comparative Example-2, no improvement was observed, whereas in Example-25, 43 of 61 (70.5%) showed improvement in symptoms.

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Claims (2)

(57) [Claims] 1. A composition containing procyanidins.
Anti-allergic agent. 2. A method which comprises procyanidin B-1.
Antiallergic agent to be taken.