JPH0853360A - Histamine liberation inhibitor and cosmetic and food product containing the same - Google Patents

Abstract

PURPOSE:To obtain a histamine liberation inhibitor which comprises an extract from a specific plant as a main component and shows a strong inhibitory action on hyaluronidase and histamine liberation, thus is useful as a raw material for cosmetics and food products having anti-inflammatory or antiallergic activity. CONSTITUTION:This inhibitor comprises, as an active ingredient, an extract of a plant, for example, Jambosa vulgaris, Piper aduncum, Anacardium occidantale, Smilax japecanga, Hymenaea courbaril, Anchietea salutaris, Piptadenia peregrina, Stryphnodendron barbatimao or the like. The plant is extracted with 5-100 pts.wt. of a solvent such as water, ethanol or the like per 1 pt.wt. of the plant. The daily oral dose of this active ingredient is preferably 5-500mg based on the dry weight.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a histamine release inhibitor containing a plant extract as an active ingredient, more specifically, as an anti-inflammatory or antiallergic agent, or inflammation and throat swelling associated with a cold, Prevention and improvement of hay fever, cough, etc.,
The present invention relates to a histamine release inhibitor incorporated into cosmetics or foods for the purpose of improving itching and pain of the skin and imparting moisturizing properties to the skin.

[0002]

BACKGROUND ART It is known that histamine is involved in the development of inflammation and allergies, and it is said that hyaluronidase is involved when histamine is released from mast cells. This hyaluronidase further destroys the connective tissue matrix and promotes the infiltration of cells of the inflammatory system into tissues and the permeability of blood vessels.Therefore, inhibition of the enzyme suppresses inflammation and allergic reactions. Expected to be done. In fact, it is also known that sodium cromoglycate and tranilast, which are known as antiallergic agent components, are inhibitors of hyaluronidase.

Although many studies have been conducted on anti-inflammatory and anti-allergic properties of pharmaceutical ingredients, licorice extract and the like are used only for the food materials having anti-inflammatory or anti-allergic activity. The current situation. In addition, various cosmetic raw materials having anti-inflammatory or antiallergic activity have been searched, but safe and promising ones have not been obtained yet.

[0004]

[Problems to be Solved by the Invention] For the 21st century, there is a growing demand for prevention rather than treatment of diseases. For example, inflammation and allergies may be considered to be an overreaction of the resistance of the human body, but when thinking about the suffering at the onset of illness,
Some precautionary measures are needed. It is desirable to take this measure for foods and cosmetics that are ingested or used on a daily basis, but no useful food material or cosmetic raw material having anti-inflammatory or anti-allergic activity has been obtained. The provision of such materials and raw materials remains an issue.

In addition, maintaining the hyaluronic acid content of the living body,
The need to increase is not just a skin issue. The water retention structure by hyaluronic acid also plays an important role in the aorta and joint fluid. As aging is accompanied by a decrease in the hyaluronic acid content of the human body, it is expected that the need to maintain the water content retained by hyaluronic acid in the skin and blood vessels will increase more and more toward an aging society. However, at present, attention is paid only to hyaluronic acid that is externally used as a moisturizer for cosmetics, and there are almost no attempts to maintain the hyaluronic acid content in the human body and thus the water content, which remains an important issue.

[0006]

Means for Solving the Problems The present inventor has focused on the relationship between hyaluronidase, which is a hyaluronic acid hydrolase, and histamine release from mast cells, and suppresses the release of histamine by inhibiting hyaluronidase. We carried out an intensive search to find a natural product that could be produced.
And as a result, in particular, the extract of a certain plant produced in South America has a strong hyaluronidase inhibitory action and histamine release inhibitory action, and found that it can be used as a histamine release inhibitor to complete the present invention. I arrived.

That is, the first object of the present invention is Jambosa vulgaris, Piper aduncum, Anacardium occidentale, Smilax.
Smilax japecanga, Hymenaea courbaril, Anchietea salutaris, Piptadenia peregrina, Stryphnodendron barbatimao, Stryphnodendron barbatima
Arctium lappa, Periandra dulcis, Eucalyptus globulus, Myrcia sphaerocarpa, Coccoloba uvifera, eira Schin aloe ), Guazuma ulmifolia, Arctostaphylos
Uva Urushi (Arctostaphylos uva-ursi), Cestrum pseudo-quina, Ferraria purgans and Aniva
Cannilla (Aniba canelilla), Adiantum capillus veneris (Adiantum capillus-veneris),
Erythroxylum catua
ba), Pithecolobium to
rtum), Hamamelis virginiana (Hamamelis vi
rginiana), Cariniana legali
s), Fevillea tril
obata), Curatella ameri
cana), Hedychium coro
narium) and Remijia fe
The present invention provides a histamine release inhibitor containing an extract of at least one plant selected from the group consisting of rruginea) as an active ingredient.

A second object of the present invention is to provide cosmetics and foods containing the histamine release inhibitor.

The active ingredient of the histamine release inhibitor of the present invention comprises whole plants, bark, heartwood, leaves, flowers, seeds,
It is obtained by extracting stems, roots, etc. by a conventional method.

The plant used for extraction has been used as a crude drug for a long time in South America and the like. The main ones are Jambosa vulgaris (Jambo-amarelo). (The name of the plant is given in parentheses after the scientific name of the plant. The same applies to the following.), Piper Adungkam (Aperta Luang) [Pi
per aduncum (Aperta-ruao)], Anacardium
Occidental (Cajueiro) [Anacardium occiden
tale (Cajueiro)], Smilax japecanga (Japecanga) [Smilax japecanga (Japecanga)], Himenaea courbir (Jatoba) [Hymenaea courb]
aril (Jatoba)], Anchietea salutaris (Cipo-suma)], Piptadenia peregrina (Anjico) [Piptadenia pereg
rina (Angico)], Strifnodendron Barbatimao (Stryphnodendron barbatimao)
(Barbatimao)], Arctium lappa (Bardana) [Arctium lappa (Bardana)], Periandra dulcis (Alcatus) [Periandra dulcis (Alcacu
z)], Eucalyptus globulus (Eucalyptus globulus)
(Eucalipto)], Myrcia sphaerocarpa (Pedra-u)
me-caa)], Coccoloba uvifera (Uva-do-mato)], Sinus
Aloeira (Schinus aroeira (Aroeir
a)], Guazma Ulmifolia (Mutamba) [Guazu
ma ulmifolia (Mutamba)], Arctostaphylos
Uva Urushi (Uva Urushina, Azaleaaceae, Urawa Urushi)
[Arctostaphylos uva-ursi (Uva-ursina)], Sestrum Pseudo Kina (Quina do Mat) [Cestrum
pseudo-quina (Quina-do-mato)], Ferraria purgans (Ruibarvo do Campo)
(Ruibarbo-do-campo)], Aniba canelilla (Casca-precios)
a)], Adiantum capillus venellis (Avenca Cabello de Venus) [Adiantum capil
lus-veneris (Avenca-cabello-de-Venus)], Erythrooxyl Katuaaba (Erythroxyl)
um catuaba (Catuaba)], Pisecorobium tortum (Jurema),
Hamamelis Virginiana [Hamame]
lis virginiana (Hamamelis)], Carinianalegalis (Je
quitiba-rosa)], Fevillea trilobata (Cipo-jat)
oba)], Kraterra Americana (Reseira) [Cur
atella americana (Lixeira)], Hedychium coronarium (Napoleon)
leao)] and Remigia Ferruginea (Quina-da-serra)
And the like.

As the solvent used for extracting these plants,
It may be any of a single solvent selected from the group consisting of water, alcohols such as methanol or ethanol, or ketones such as acetone, or an arbitrary mixed solvent of two or more solvents, but the extract is finally a food product or the like. In view of safety, it is preferable to use water, ethanol, or a mixed solvent thereof, from the viewpoint of safety.

The ratio of the plant to the solvent at the time of extraction is not particularly limited, but the solvent is 2 to 100 per 1 plant.
It is preferably 0 times by weight, particularly 5 to 100 times by weight in terms of extraction operation and efficiency. The extraction temperature is conveniently in the range of room temperature-boiling point of the solvent under normal pressure, and the extraction time is preferably in the range of 2 hours to 2 weeks, although it varies depending on the extraction temperature and the like.

If necessary, the plant extract thus obtained may be subjected to column chromatography or the like to give a fraction. Specifically, the plant extract is dissolved in a small amount of water, a solvent such as methanol or ethanol, or a mixed solvent thereof, and Sephadex LH-20 (manufactured by Pharmacia), Diaion HP20 (manufactured by Mitsubishi Kasei Co., Ltd.), Sepabeads. HP1MG (manufactured by Mitsubishi Kasei),
After adsorbing to a column such as Toyopearl HW40F (manufactured by Toyo Soda Kogyo Co., Ltd.), it may be washed sufficiently with water and eluted with a hydrophilic solvent such as methanol, ethanol, acetone or a mixed solvent thereof.

Further, these extracts and fractions can be made into dried products by removing the solvent from them, and those in this state are preferable from the viewpoint of storability and easy handling.

To prepare a histamine release inhibitor using the plant extract obtained as described above, or a fraction thereof or a dried product thereof, the extract or the like may be used as it is or a known pharmaceutical carrier. Alternatively, it may be formulated together with a carrier for addition to cosmetics and foods. Upon formulation, two or more kinds of plant extracts and the like may be mixed.

The pharmaceutical carrier that can be used in the preparation of the histamine release inhibitor is not particularly limited, and those commonly used can be used, but preferred examples are starch, lactose, sucrose, Solid carriers such as mannitol, carboxymethyl cellulose, corn starch, and inorganic salts; distilled water, physiological saline, glucose aqueous solution, alcohols such as ethanol, liquid carriers such as propylene glycol and polyethylene glycol, various animal and vegetable oils, white petrolatum, paraffin, Examples thereof include oily carriers such as wax.

The dosage form of the histamine release inhibitor includes oral agents such as tablets, granules, powders and syrups, parenteral agents such as suppositories and external preparations, and additions to cosmetics and foods. An agent can be mentioned.

The histamine release inhibitor of the present invention has a histamine release inhibitory action, whereby diseases caused by allergic inflammation such as allergic rhinitis and allergic dermatitis caused by cedar pollen, house dust, etc. and allergic asthma, foods. It can be widely used as a medicine for treating / preventing allergic diseases such as allergies, and since it also has a hyaluronidase inhibitory activity, it is a powerful hyaluronic acid decomposition inhibitor for the skin, arterial wall, joint cavity, etc. It suppresses the decrease in the content of hyaluronic acid contained, enhances the moisture retention and flexibility of the skin, prevents arteriosclerosis with aging, and contributes to the improvement of arthritis.

The dose of the plant extract when used as a medicine varies greatly depending on the type of plant used, the degree of production, the age and symptoms of the patient, etc. The range is 5 to 500 mg / day.

The foods and cosmetics of the present invention can be produced by blending appropriate components usually used according to the purpose and the histamine release inhibitor.

For example, the food of the present invention includes glucose, fructose, sucrose, maltose, sorbitol, stevioside, rubusoside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid, in addition to the histamine release inhibitor. , Lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, gum arabic, carrageenan , Casein, gelatin, pectin, agar, vitamin Bs, nicotinamide, calcium pantothenate, amino acids, calcium salts, pigments, flavors, preservatives, etc. The produced by appropriately blending, it is possible to obtain candies, chewing gum, milk, yogurt, whey beverages, lactic acid bacteria beverages, juices, beverages, ice cream, pudding, water jelly like.

In addition to the histamine release inhibitor, the cosmetics of the present invention include oils and fats such as vegetable oils, waxes such as lanolin and beeswax, hydrocarbons, fatty acids, higher alcohols, esters and various interfaces. It can be produced by appropriately blending active ingredients, pigments, fragrances, vitamins, plant / animal extract components, ultraviolet absorbers, antioxidants, antiseptic / bactericides, etc. which are commonly used as raw materials for cosmetics. , Other anti-inflammatory / anti-allergic cosmetic raw materials, such as licorice extract components (especially glycyrrhetinic acid), diphenhydramine hydrochloride, azulene, dl-α-tocopherol and its derivatives, vitamins B ₂ and B _{6 and the} like,
Further, the effect can be enhanced.

Furthermore, in the case of producing the cosmetic of the present invention, the moisturizing effect can be further enhanced by using the histamine release inhibitor in combination with hyaluronic acid and the like.

That is, since the histamine release inhibitor of the present invention also has a hyaluronidase inhibitory activity, it indirectly has a moisturizing / skinning effect by inhibiting the decomposition of hyaluronic acid in the skin. , Other moisturizing / skin-care cosmetic ingredients such as hyaluronic acid, for example, elastin, collagen, lecithin, squalene, placenta liquid (placenta extract), glycerins, glycols, fermentation metabolites, lactic acid bacterium culture fluid, vitamins A and C, sodium chondroitin sulfate, 2-pyrrolidone-
The moisturizing effect can be further enhanced by using it together with a plant polysaccharide such as sodium 5-carboxylate (PCA-Na) and Bakumondou mucilage polysaccharide.

The cosmetics containing the histamine release inhibitor of the present invention can be used in lotions, cosmetic creams, emulsions, foundations, lipsticks, hair styling agents, hair tonics, hair restoration agents, toothpaste, mouthwashes, etc. It can also be in the form of shampoo, conditioner, bath salt or the like.

The plant of the present invention has been used as a crude drug for a long time in South America and the like, and extracts or fractions thereof have no problem in safety. However, when added to foods and cosmetics, the concentration range of 0.0001 to 5% in terms of dry weight of the plant extract or its fraction is obtained in terms of its effect, fragrance when added, and color tone. Is desirable.

[0027]

In the plant extract used in the present invention, the histamine release inhibitor has a potent inhibitory activity on histamine release from mast cells and a strong hyaluronidase inhibitory activity. The plant, which is a raw material, has been used as a crude drug in South America since ancient times, and the extract or the like thereof has no problem in terms of safety. Therefore, the histamine release inhibitor of the present invention is useful as a drug having an anti-inflammatory action and an anti-allergic action.

The histamine release inhibitor of the present invention is
Since it also has a hyaluronidase inhibitory effect, it suppresses the decrease in the content of hyaluronic acid contained in the skin, arterial wall, joint space, etc., enhances the moisturizing properties and flexibility of the skin, prevents arteriosclerosis with age, improves arthritis, etc. It has the potential to be used as a drug.

Further, by ingesting the food containing the histamine release inhibitor on a daily basis, inflammation and sore throat, hay fever, cough and the like associated with the cold can be prevented and improved. Similarly, since this histamine release inhibitor also has a hyaluronidase inhibitory activity, the use of cosmetics containing it improves skin itchiness and pain due to allergic symptoms and inflammation, and imparts moisturizing properties to the skin. It is possible.

[0030]

EXAMPLES Next, the present invention will be described in more detail with reference to Examples of the method for producing a histamine release inhibitor of the present invention, a hyaluronidase inhibitory or histamine release inhibitory test, and production of anti-inflammatory agents, antiallergic agents, foods and cosmetics. As will be seen, the invention is in no way limited to these examples.

Example 1 Production of plant extract: 100 g of dried product of specific part of plant
Was immersed in 1000 ml of 50% by volume ethanol at room temperature for 7 days, and the supernatant was filtered. The obtained extract was concentrated to dryness under reduced pressure to obtain a dried product. The extraction sites and extract yields for each plant are shown in Table 1.

[0032]

Example 2 Preparation of plant extract: 100 dry plant products shown in Table 2.
g was immersed in 1000 ml of 50% by volume ethanol at room temperature for 7 days, and the supernatant was filtered. The obtained extract was concentrated to dryness under reduced pressure to obtain a dried product. The yield of extract of each plant is also shown in Table 2.

[0034]

Example 3 Assay of Hyaluronidase Inhibitory Activity (1): The hyaluronidase inhibitory activity of the plant extracts shown in Table 1 of Example 1 was measured by the method described below. The results are shown in Table 3.
Shown in

(Measurement method) Using a hyaluronidase derived from beef testis (Sigma, Type IV), the inhibitory action of the compound 48/80 on the activation step of the inactive enzyme was mainly measured. The enzymatic activity was measured by colorimetrically quantifying the increase in the reducing power of the tetrasaccharide having N-acetylhexosamine, which is produced by hydrolysis of hyaluronic acid, as a reducing end by A ₅₈₅ (Yumie Maeda et al. , 31
Vol. 233-237, 1990).

That is, an appropriate amount of the test sample was dissolved in 100 μl of 0.1 M acetate buffer (pH 4.0) and placed in a test tube, and 0.10 mg (1 of enzyme) dissolved in 50 μl of the same buffer.
00NF units) and incubate at 37 ° C. for 20 minutes. Then, compound 48/80 (50 μg) dissolved in 100 μl of the same buffer is added, and the mixture is further incubated at 37 ° C. for 20 minutes. Furthermore, hyaluronic acid sodium salt (2
00 μg, derived from a microorganism) and then incubated at 37 ° C. for 40 minutes. Finally, 0.4 N NaOH 100
After adding μl and cooling with ice, borate buffer (pH 9.1) 10
Add 0 μl and boil for 3 minutes, cool with ice, add 3 ml of p-dimethylaminobenzaldehyde reagent solution, and add 2 at 37 ° C.
After incubating for 0 minutes, A ₅₈₅ was measured.

As a control, the acetate buffer was used instead of the sample solution. Further, as each blank, the above-mentioned acetate buffer was used instead of the enzyme solution. The inhibitory activity was represented by the inhibition rate calculated from the following formula.

[0039] A: Control solution A ₅₈₅ B: Control solution blank A ₅₈₅ C: Sample solution A ₅₈₅ D: Sample solution blank A ₅₈₅

[0040]

Example 4 Assay of Hyaluronidase Inhibitory Activity (2): For the plant extracts shown in Table 2 of Example 2, the hyaluronidase inhibitory activity was measured in the same manner as in Example 3. The results are shown in Table 4.
Shown in

[0042]

Example 5 Assay of inhibitory activity against histamine release from rat peritoneal mast cells (1): For plant extracts shown in Table 1 of Example 1,
The inhibitory activity against histamine release was measured by the following method. The results are shown in Tables 5 and 6.

(Test animal) Weight 272-349g
5 male Wistar rats (Japan SLC)
It was used after acclimatization for more than one day. Temperature 20 ~ 25 ℃,
Humidity 40-70%, lighting 12 hours / day (7 o'clock lighting, 19
It was bred under the environment (lights off when turned off). Solid feed M during breeding
After filtering with F (Oriental Yeast Co., Ltd.) and a filter of 5 μm, tap water irradiated with ultraviolet rays was freely taken.

(Isolation of Rat Peritoneal Mast Cells) MCM solution (140 mM NaC was injected into the peritoneal cavity of a rat exsanguinated by exsanguination).
1, 2.5 mM KCl, 1.0 mM CaCl ₂ , 1.2
1 mM of MgCl ₂ , 5 mM glucose and 0.1% BSA (6.7 mM phosphate buffer, pH 7.1).
11 ml was injected per animal, the abdomen was massaged for 3 minutes, the peritoneal exudate was collected, and mast cells were isolated by the Ficoll gradient method. The obtained cells were washed twice with MCM solution and then 2.5 × 10 ⁴ cells /
A cell suspension was prepared by suspending the cells in an MCM solution at 0.5 ml / tube.

(Histamine release inhibition test) 2.5 × 1
0 ⁴ cells / 0.5 ml / tube of cell suspension at 37 ℃
After preincubation for 0 minutes, 10 μl of a test sample solution dissolved or suspended in 50% methanol at an appropriate concentration was added and left at 37 ° C. for 10 minutes. Compound 48/80 (25 μg / ml) as a degranulation inducer
10 μl was added and the mixture was reacted at 37 ° C. for 10 minutes (final concentration of compound 48/80 was 0.5 μg / ml). After the reaction, 0.5 ml of ice-cooled MCM solution was added, and the amount of histamine released in the supernatant after centrifugation (420 × g, 5 minutes, 4 ° C.) was measured using OPT (O-ph) such as Shore.
tal-aldehyde) Fluorescence method (JPET, 127,182-186,1959) according to the centrifugal general-purpose automatic analyzer (COBAS R FARAII, Baxter). From the measured amount of free histamine, the histamine release inhibition rate was calculated by the following formula.

[0047] C: amount of histamine released from control cells to which no inducer was added R: amount of histamine released from cells when an inducer was added SR: released from cells when an inducer was added in the presence of the test sample Amount of histamine

[0048] (Note) The final concentration of all test samples in the reaction solution was 200 μg / ml.

[0049] * IC ₈₅ : concentration that suppresses histamine release by 85%

Example 6 Assay of inhibitory activity against histamine release from rat peritoneal mast cells (2): For plant extracts shown in Table 2 of Example 2,
The inhibitory activity against histamine release was measured by the following method. The results are shown in Table 7.

(Test animals) Acclimation for 7 days or more 9-
12-week-old male Wistar rats (CLEA Japan, Inc.) were used. The animals were raised in an environment of a temperature of 23.5 ± 2 ° C., a humidity of 55 ± 10%, and an illumination time of 12 hours (lights on at 7:00, lights off at 19:00). During the breeding, the solid feed CE2 (CLEA Japan, Inc.) and tap water were freely ingested.

(Isolation of Rat Peritoneal Mast Cells) Tyrode's solution (PBS) containing 2 (V / V)% fetal calf serum (hereinafter, 2% FCS) was intraperitoneally injected in exsanguinated rats.
About 15 ml of 0.5 (W / V) sucrose was added to (+), and the abdominal wall was lightly massaged, and the peritoneal exudate was collected. Further, the same operation was repeated once. The peritoneal exudate thus obtained was placed at 4 ° C., 100 g, 10 g.
The precipitated cells were collected by centrifugation for minutes. This is 2m
1% of Tyrode's solution containing 2% FCS
For S-containing Tyrode's solution, metrizamide (metrizam
ide) in a solution of 22.5 (W / V)% and overlaid 3
Mast cells were isolated by centrifugation at 50 g for 15 minutes at room temperature. Mast cells obtained in this way are 2% FCS
Suspend in the contained Tyrode solution, 4 ℃, 100g, 10
It was washed by centrifuging for a minute. After washing twice, 2.5% 10 ⁴ pieces / 0.5 ml 2% FCS
It was suspended in the contained Tyrode's solution.

(Histamine release inhibition test) 2.5 × 1
0 ⁴ cells / 0.5 ml / tube of cell suspension at 37 ℃
After pre-incubating for 0 minutes, 5 μl of a test sample solution dissolved or suspended in 25% ethanol at an appropriate concentration was added and left at 37 ° C. for 10 minutes. Compound 48/84 solution (25 μg / ml) as a degranulation inducer 1
0 μl was added and the reaction was carried out at 37 ° C. for 20 minutes.

After the reaction, 0.5 ml of ice-cooled Tyrode's solution containing 2% FCS was added, followed by centrifugation (4 ° C., 150 g, 1
Histamine in the supernatant (0 min) was separated by high performance liquid chromatography, and the O-phthalaldehyde fluorescence method (JPET, 127, 128 to 186, such as Shore) was used.
1959). From the measured amount of free histamine, the histamine release inhibition rate was calculated by the following formula,
C ₅₀ (concentration that inhibits histamine release by 50%) was determined.

[0055] C: amount of histamine released from control cells to which no inducer was added R: amount of histamine released from cells when the inducer was added SR: released from cells when the inducer was added in the presence of the test sample Amount of histamine

[0056]

Example 7 Tablets: 150 g of Smilax japecanga (japecanga) extract obtained by the same method as in Example 1 was mixed with the same amount of lactose and 5 g of magnesium stearate.
The resulting mixture was tabletted with a single-shot tableting machine to give a diameter of 10
mm tablets with a weight of 300 mg were produced. By taking these tablets 2 times a day for 1 week, symptoms such as itching of the eyes and excessive nasal discharge of hay fever were significantly reduced.

Example 8 Condyle Granules: The tablets obtained in Example 7 were crushed, sized, and sieved to obtain 20-50 mesh granules. Example 9 Large-scale extraction of Hamamelis virginiana: In accordance with the method of Example, 1 kg of Hamamelis virginiana 1
Extract 2 with 0 liters of 50% ethanol by volume
05 g was obtained.

Example 10 Tablets: 150 g of Hamamelis virginiana extract of Example 9 was mixed with the same amount of lactose and 5 g of magnesium stearate. The obtained mixture was tabletted with a single-shot tableting machine to produce tablets having a diameter of 10 mm and a weight of 300 mg.

Example 11 Condyle Granules: The tablets obtained in Example 10 were crushed and sized,
Sieve to obtain 20-50 mesh granules.

Example 12 Candy: Using the Anchithea sultalis (Sipoh suma) extract of Example 1, a candy having the following composition was produced. The taste was good without bitterness.

(Composition) (Composition%) Granulose Sugar 55.0 Syrup 43.5 Quenoic acid 1.0 Perfume 0.2 Chromium 0.2 Anchietea sartalis extract 0.2 1

Example 13 Chocolate: Guazuma ulmifolia (mutamba) extract of Example 1 was used to produce chocolate having the following composition.

(Composition) (Composition%) Bitter chocolate 18.0 Cocoa butter 16.85 Powdered sugar 40.0 Whole fat powdered milk 20.0 Lecithin 5.0 Perfume 0.1 Guazma ulmifolia Extract 0.05

Example 14 Juice: Using the extract of Smilax japecanga (japecanga) of Example 1, juice having the following composition was produced. The extract did not affect the taste or color of the juice.

(Composition) (Composition%) Frozen concentrated Unshu mandarin orange juice 5.0 Fructose dextrose liquid sugar 11.0 Quenoic acid 0.2 L-Ascorbic acid 0.02 Perfume 0.2 Chromium 0.2 1 Sumilux japecanga extract 0.2 Water 83.28

Example 15 Coffee Drink: A coffee drink having the following composition was produced using the extract of guazuma ulmifolia (mutambar) of Example 1.

(Composition) (Composition%) Granu-sugar 8.0 Degreased milk 5.0 5.0 Caramel 0.2 Coffee extract 2.0 Perfume 0.1 Polyglycerin fatty acid ester 0.05 Food salt 0.05 Guazuma ulmifolia extract 0.1 Water 84.5

Example 16 Candy: A candy having the following composition was produced using the extract of Carina naregalis (Jequitiva rosa) of Example 2.

(Composition) (Composition%) Granulose Sugar 55.0 Syringe starch 43.5 Quenoic acid 1.0 Fragrance 0.2 Chromium 0.2 Cariniana regalis extract 0.2 1

Example 17 Chocolate: The Erythrozyme Katuauba (Katuaba) extract of Example 2 was used to produce a chocolate having the following composition.

[0072]

Example 18 Juice: Adiantum Capillus venellis of Example 2 (Avenca Capello de Venus)
The extract was used to produce a juice having the following composition.

[0074]

Example 19 Coffee Beverage: Using the extract of Carina naregalis (Jequitiva rosa) of Example 2, a coffee beverage having the following composition was produced.

(Composition) (Composition%) Granuy sugar 8.0 Degreased milk 5.0 5.0 Caramel 0.2 Coffee extract 2.0 Fragrance 0.1 Polyglycerin fatty acid ester 0.05 Food salt 0.05 Carina na Regalis extract 0.1 Water 84.5

Example 20 Emollient Cream: An emollient cream having the following composition was produced using the Smilax japecanga extract (japecanga) extract of Example 1.

[0078]

Example 21 Emollient Lotion: Using the Anchietea sartalis (Sipho Suma) extract of Example 1, an emollient lotion having the following composition was produced.

[0080]

Example 22 Shampoo: Using the extract of guazuma ulmifolia (mutamuba) of Example 1, a shampoo having the following composition was produced.

(Composition) (Composition%) Lauryl polyoxyethylene (3 mol) sulfuric acid ester triethanolamine salt (40% aqueous solution) 30.0 Lauryl polyoxyethylene (3 mol) sulfuric acid ester sodium salt (40% aqueous solution) ) 20.0 Lauroyldiethanolamide 4.0 Guazma ulmifolia extract 0.1 Purified water 45.9

Example 23 Toothpaste A dentifrice having the following composition was prepared using the extract of Smilax japecanga (japecanga) of Example 1.

(Composition) (Composition%) Calcium phosphate dihydrate 42.0 Glycerin 18.0 Carrageenan 0.9 Sodium lauryl sulfate 1.2 Sodium saccharin 0.1 Butyl paraoxybenzoate 0.005 Smilax japekanga extract Product 0.05 Perfume 1.0 Purified water 36.745

Example 24 Emollient Cream: An emollient cream having the following composition was produced using the Pisecorobium tortum (Julema) extract of Example 2.

[0086]

Example 25 Emollient Lotion: Using the extract of Kraterella americana (Liceira) of Example 2, an emollient lotion having the following composition was produced.

[0088]

Example 26 Shampoo: The Hamamelis virginiana (Hamamelis) extract of Example 2 was used to prepare a shampoo having the following composition.

(Composition) (Composition%) Lauryl polyoxyethylene (3 mol) sulfuric acid ester triethanolamine salt (40% aqueous solution) 30.0 Lauryl polyoxyethylene (3 mol) sulfuric acid ester sodium salt (40% aqueous solution) ) 20.0 Lauroyldiethanolamide 4.0 Hamamelis virginiana extract 0.1 Purified water 45.9

Example 27 Toothpaste Hedychium coronarium (Napoleon) of Example 2
The extract was used to produce a dentifrice having the following composition.

(Composition) (composition%) Calcium phosphate dihydrate 42.0 Glycerin 18.0 Carrageenan 0.9 Sodium lauryl sulfate 1.2 Saccharin sodium 0.1 Butyl paraoxybenzoate 0.005 Hedidium coronium extract 0.05 Perfume 1.0 Pure water 36.745 and above

Continuation of front page (51) Int.Cl. ⁶ Identification number Office reference number FI technical display location // C12N 9/99

Claims (5)

[Claims] 1. A Jambosa vulg.
aris), Piper aduncum, Anacardium occiden
tale), Smilax japecanga
ga), Hymenaea courbari
l), Anchietea salutari
s), Piptadenia peregrin
a), Strifno Dendron Barbatimao (Stryphn
odendron barbatimao), Arctium Rappa (Arc
tium lappa), Periandra Dulcis (Periandra)
dulcis), Eucalyptus globulus (Eucalyptus)
globulus), Myrcia sphaerocarpa (Myrcia sp
haerocarpa), Coccoloba uv
ifera), Schinus aroeira, Guazuma ulmifolia, Arctostaphylos uva
-ursi), Cestrum pseud
o-quina), Ferraria purgans
s), Aniba canelilla, Adiantum capillus
-Veneris), Erythrosailm Katuaba (Eryth
roxylum catuaba), Pisecorobium tortum (Pit
hecolobium tortum), Hamamelis virginiana, Calineana regalis (Ca
riniana legalis), Fevillea trilobata, Curatella americana, Hedychium coronarium and Remijia ferruginea. A histamine release inhibitor as an active ingredient. 2. The histamine release inhibitor according to claim 1, which has a hyaluronidase inhibitory activity. 3. The histamine release inhibitor according to claim 1 or 2, which is an anti-inflammatory agent or an anti-allergic agent. 4. A cosmetic containing the histamine release inhibitor according to claim 1 or 2. 5. A food containing the histamine release inhibitor according to claim 1 or 2.