WO2006003750A1 - Inflammation preventive/antiinflammatory agent, pharmaceutical product, food or beverage, and perfume or cosmetic - Google Patents

Abstract

[PROBLEMS] To provide an inflammation preventive/antiinflammatory agent that is useful for treatment or prevention of the inflammatory symptoms of rhinitises, such as perennial allergic rhinitis, pollenosis and allergic sinusitis, and that can be safely administered for a prolonged period of time, ensuring reduced side effects as compared with those of drugs. [MEANS FOR SOLVING PROBLEMS] There is provided an inflammation preventive/antiinflammatory agent capable of inflammation prevention and having an antiinflammatory potency, characterized in that a polyphenol derived from apples is contained as an active ingredient.

Description

 Specification

 Inflammation prevention * Anti-inflammatory agents, pharmaceuticals, food and drinks and cosmetics

 Technical field

 [0001] The present invention relates to a natural product-derived inflammation preventive 'anti-inflammatory agent, and further relates to a medicament, a food and drink, and a cosmetic containing an inflammation preventive' anti-inflammatory agent.

 Background art

 [0002] Allergic rhinitis with inflammatory symptoms is a typical type I allergy, characterized by three major characteristics: sneezing, nasal discharge, and nasal congestion. These symptoms are caused by re-exposure of nasal tissue sensitized by repeated inhalation of antigens such as cedar pollen and house dust. (Non-patent document 1).

 [0003] Allergic rhinitis began to increase in the latter half of 1965 in inverse proportion to the decrease in chronic sinusitis, which began in the first half of 1960, and became milder. ing. The recent increase is remarkable in Japanese cedar pollinosis, and indoor dust allergy is still on the rise in the power town village where the plateau has become somewhat plateau. Recent data suggest that there are between 18 and 23 million patients with allergic rhinitis, and the cost of medical treatment is estimated to be between 120 and 150 billion yen (1994). (Non-patent document 2)

 [0004] Human allergic rhinitis occurs as a result of complex intertwined biological reactions, many of which have various chemical mediators released from mast cells and basophils triggered by antigen-antibody reactions. It is thought to cause inflammation by increasing the permeability of peripheral blood vessels.

 [0005] Currently, desensitization therapy, which is the only treatment that can be expected to be cured, is a method in which a doctor examines and identifies the causative antigen and injects the antigen component artificially. It's like “vaccination” to follow. However, it usually takes three to four years before the effect appears, and the percentage of people who are completely cured remains below 60%, and there is still room for improvement.

[0006] In addition, there is a prophylactic method to use antiallergic drugs before the symptoms of hay fever appear, and the symptom can be reduced by using the front force for about 2 weeks. But It can be done. This method is considered a “run-up” to increase the effectiveness of the drug during the season and should be used at a hospital or clinic and in accordance with the doctor's guidance and drug prescription.

 Under such circumstances, antihistamines and steroids are currently being developed and used as drugs. These drugs have side effects such as worsening of symptoms due to long-term administration, drowsiness by acting on the central nervous system, effects on the endocrine system, and strong pharmacological effects, so it is necessary to use them under the supervision of a doctor. is there. On the other hand, among the conventional foods, those having anti-inflammatory effects have been searched, and development as food materials has been attempted.

 [0007] For example, there is a persimmon tea extract (Patent Document 1) extracted with hot water from tea leaves of persimmon tea, and a perilla leaf extract (Patent Document 2 and Patent Document 3) extracted with hot water. However, there was a problem with the flavor, so there were naturally restrictions on its use as food and drink, and no mention was made of its preventive effect.

 [0008] In addition, there is a conventional technique (Patent Document 4) that uses polyphenol derived from immature fruit of the Rosaceae fruit as an allergy inhibitor or the like. However, Patent Document 4 reports on the hyaluronan-tase inhibitory action and histamine release inhibitory action on polyphenols derived from immature fruit of the Rosaceae fruit, but it has a preventive action against rhinitis. Not mentioned at all.

 [0009] Therefore, it can be used as a safe and effective pharmaceutical, and it is incorporated into the foods and drinks used daily, and used in cosmetics, and is effective in preventing inflammation and preventing inflammation. Development was desired.

 Non-patent document 1: Nasal allergy basics and clinical practice, Kei Okuda, Medicinal Journal, 1999 Non-patent document 2: Nasal allergy clinical practice guideline 2002 edition, nasal allergy clinical practice guideline compilation committee (2002), life science Company

 Patent Document 1: JP-A-6-192114

 Patent Document 2: JP-A-1 121217

 Patent Document 3: Japanese Patent Laid-Open No. 7-215884

 Patent Document 4: Japanese Patent Laid-Open No. 7-285876

Disclosure of the invention Problems to be solved by the invention

 [0010] The problem to be solved by the present invention is useful for the prevention and treatment of inflammatory symptoms of rhinitis such as perennial allergic rhinitis, hay fever and allergic sinusitis, and has fewer side effects than drugs. Inflammation prevention / anti-inflammation agent and inflammation prevention 'medicine, food and drink, cosmetics and the like containing anti-inflammatories are safe even after long-term use.

 Means for solving the problem

 [0011] In view of such circumstances, the present inventors have found that they have an anti-inflammatory and anti-inflammatory action including inflammation derived from apple-derived polyphenola sneezing, and to complete the present invention. It came.

 That is, the gist of the present invention is as follows.

 (1) An anti-inflammatory and anti-inflammatory agent that prevents inflammation and has an anti-inflammatory action, characterized by containing polyphenol derived from apple as an active ingredient.

 (2) The inflammation preventive anti-inflammatory agent according to (1), wherein the inflammation is rhinitis.

(3) A inflammation-preventing “anti-inflammatory drug comprising the anti-inflammatory agent according to (1)”.

 (4) An inflammation prevention anti-inflammatory food or drink characterized by containing the inflammation prevention 'anti-inflammatory agent according to (1).

 (5) A inflammation-preventing anti-inflammatory cosmetic comprising the anti-inflammatory agent according to (1).

 The invention's effect

[0013] The anti-inflammatory agent according to the present invention has an effect of improving or preventing inflammation, for example, sneezing and nasal discharge, which are the main symptoms of allergic rhinitis, and has no side effects, so it can be used safely. Can be taken for a period. Therefore, the inflammation prevention 'anti-inflammatory agent of the present invention can be suitably used not only as an active ingredient of a pharmaceutical agent but also in foods and beverages and cosmetics in anticipation of inflammation prevention' anti-inflammation. And can provide an anti-inflammatory effect. In addition, since it exhibits an antiallergic action by inhibiting inflammation, it is possible to improve symptoms of nasal inflammation such as perennial allergic rhinitis, hay fever and allergic sinusitis. Brief Description of Drawings

 [0014] FIG. 1 is a graph showing the dose-dependent anti-inflammatory effect of polyphenol derived from apples against sneezing induced by antigen nasal nasal dysfunction using an allergic rhinitis model prepared by active sensitization.

 [Fig. 2] A graph showing anti-inflammatory and preventive effects due to differences in the pre-administration effect of apple-derived polyphenol against sneezing induced by antigen nose using an allergic rhinitis model prepared by active sensitization. .

 Explanation of symbols

 [0015] (0: Apple-derived polyphenol test group in which inhalation sensitization was performed twice and the period until the first sensitization was induced was 28 days.

 (ii): Apple-derived polyphenol test group with inhalation sensitization 4 times and initial sensitization time up to 28 days.

 (iii): Apple-derived polyphenol test group in which antigen immunization was induced by inhalation sensitization twice and antigen solution administered intranasally for 8 days 14 days after the first inhalation sensitization

 BEST MODE FOR CARRYING OUT THE INVENTION

 [0016] The active ingredient of the anti-inflammatory agent according to the present invention is an apple-derived polyphenol.

 [0017] The apple-derived polyphenol in the present invention is a polyphenol fraction extracted and purified from apple fruit or immature fruit.

 [0018] As the polyphenol fraction, firstly, a juice obtained by squeezing raw fruit or an extract extracted with an organic solvent such as water or ethanol can be used. The extract from which the juice juice or organic solvent has been removed can be used as it is, but if necessary, it is clarified with an enzyme such as a vectorase and subjected to a normal separation process such as centrifugation or filtration. A clear fruit juice or extract is obtained. The clear fruit juice or extract containing the polyphenol fraction is further purified as a polyphenol fraction using an ion exchange resin synthetic adsorbent resin, an adsorbent such as silica gel, a gel filter agent, or the like.

[0019] Polyphenola derived from apples The ability to prevent inflammation and especially allergic rhinitis and its effectiveness in the treatment of its onset is unknown. Stabilization of mast cells and basophils (Biosci. Biotech. Biochem., 62, 1284, 1998) and oral tolerance (Japan Pharmaceutical Association 2004 Conference) The contribution of is reported.

 [0020] Next, the polyphenol fraction can be concentrated in the following manner to obtain a liquid formulation, and further, a powder formulation can be obtained by spray drying or freeze-drying the concentrated solution. For liquid preparations, organic solvents such as ethanol and organic acids such as citrate can be used. For powder preparations, dextrin, saccharides and the like can be used as excipients.

 [0021] Apple-derived polyphenols are preferred because of their high polyphenol concentration. As the fruit, both mature and immature fruits can be used, but immature fruits are particularly preferred because they contain more polyphenols and many active ingredients having a wide range of physiological functions. .

 [0022] The anti-inflammatory agent according to the present invention is effective for the prevention and treatment of inflammation including rhinitis such as perennial allergic rhinitis, hay fever and allergic sinusitis.

 [0023] Since the anti-inflammatory agent of the present invention has an inflammation-preventing effect, it may be used prophylactically before the onset of inflammation and also has a therapeutic action for inflammation. It may be used as an anti-inflammatory agent.

 [0024] The dosage in the case of using the anti-inflammatory agent described in the present invention as an oral preparation varies depending on the purpose of administration, sex, age, weight, health status, etc. of the subject of administration, but is a dry polyphenol. The fraction can be administered in the range of lmgZkg body weight to lOOmgZkg body weight.

 [0025] The polyphenol fraction obtained as described above includes caffeic acid derivatives (esters) such as chlorogenic acid, P-tamaric acid derivatives, flavan 3-ols (catechins), flavonols such as quercetin glycosides, etc. It is composed of chalcones such as phloretin glycosides, and polyphenols such as procyanines such as procyanin B-2, among which procyanines are the main components.

[0026] The medicament of the present invention is prepared by formulating the apple extract as it is or with a known pharmaceutical carrier. The medicament of the present invention is a medicament having an anti-inflammatory effect on inflammation prevention. The medicament of the present invention may be an oral preparation such as a tablet, granule, powder, syrup or the like, or a parenteral preparation such as a suppository or an external preparation. [0027] In addition, apple-derived polyphenols may be blended in food and drink. Examples of the food and drink include candies, troches, gums, yognoreto, ice cream, pudding, jelly, chicken pox, coffee drinks, juice, carbonated drinks, soft drinks, milk, milky drinks and lactic acid bacteria drinks. . Prevention of inflammation and anti-inflammatory action can be expected by ingesting foods and drinks containing apple-derived polyphenols.

 [0028] In addition, apple-derived polyphenols may be blended in cosmetics. The cosmetic product in the present invention means a series of products applied to the human body such as cosmetics, body cleaning agents, oral preparations, bathing agents and the like. Examples of the cosmetics include lying lotion, cosmetic cream, milky lotion, foundation, funny, lipstick, hair conditioner, hair tonic, hair restorer, hair rinse and the like. Examples of body cleansing agents include face wash, shampoo, body soap and the like. Examples of the oral preparation include toothpaste and mouthwash. Prevention of inflammation and anti-inflammatory action can be expected by using cosmetics containing apple polyphenol.

 [0029] As the pharmaceutical carrier that can be used for the preparation of the medicament of the present invention, there are no particular restrictions, and those that are usually used can be used. Examples thereof include starch, lactose, sucrose, Solid carriers such as mannitol, carboxymethylcellulose, corn starch and inorganic salts, distilled water, physiological saline, aqueous glucose 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 fins and waxes.

[0030] In addition, in order to produce the above-mentioned food and drink or cosmetic using the anti-inflammatory agent of the present invention, an appropriate ingredient usually used according to the type of the product is blended. I can do it. For example, when preparing food and drinks, glucose, fructose, sucrose, maltose, sorbitol, stepioside, rubusoside, corn syrup, lactose, citrate, tartaric acid, phosphonic acid, succinic acid, lactic acid, L- Ascorbic acid, a-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, gum arabic, carrageenan, casein, gelatin, pectin, agar, vitamin B, nicotinamide , Calcium pantothenate, amino acids, calcium salts, pigments, fragrances, preservatives, etc. can do.

 [0031] Furthermore, when preparing cosmetics, oils and fats such as vegetable oils, mouths such as lanolin and beeswax, hydrocarbons, fatty acids, higher alcohols, esters, various surfactants, dyes, It can be produced by appropriately blending those used as usual cosmetic raw materials such as fragrances, vitamins, plants, animal extract components, ultraviolet absorbers, antioxidants, antiseptics and fungicides.

 [0032] Since apple is a fruit with a long eating experience that has been eaten all over the world since ancient times, it has been confirmed that it is safe even in toxicity tests using animals and cells. The extract used in is very safe.

[0033] Next, in order to facilitate understanding of the present invention, examples and test examples will be given, but it goes without saying that the present invention is not limited thereto.

 Example 1

 [0034] 300 kg of apple fruit from Aomori Prefecture was crushed and pressed to obtain 210 kg of fruit juice. The obtained fruit juice is clarified with 30 ppm of pectinase, and after centrifugation, diatomaceous earth (silica 300S, manufactured by Chuo Silica)

 ) Clarification by filtration!

[0035] The clarified fruit juice was passed through an adsorption column (Separbeads SP-850, manufactured by Mitsubishi Chemical Corporation) to adsorb polyphenols. Subsequently, pure water was passed through to remove non-adsorbed substances (saccharides, organic acids, etc.) in the column, and then eluted with 80% alcohol.

[0036] The resulting fractional force alcohol was concentrated under reduced pressure to prepare about 2 kg of an extracted powder product.

[0037] When the extracted powder product was tested using reversed-phase high performance liquid chromatography, chlorogenic acids (about 20%), phloretin glycosides (about 5%), flavonols (about 15%), proanthocyana -Gins (about 50%) and other browning substances (about 10%) were confirmed. Furthermore, these proanthocyanidins are also analyzed by a matrix-assisted laser ionic-time-of-flight mass spectrometer (MALDHTOF / MS, manufactured by Applied Systems), and as a result, the flavonols, such as force catechin epicatechin force, are also constructed. It was confirmed to be an oligomer or polymer from dimer to 15-mer. (M.

Ohnishi—Kameyama et al., Mass spectrometry, 11, 31—36, 1997). [0038] Test Example 1

 Using an allergic rhinitis model prepared by active sensitization, the effect of the polyphenol derived from apple obtained in Example 1 on the combing induced by antigen nose was examined. Kud: Hartley's male guinea pig (6 weeks old, n = 8Z group) was actively sensitized by inhalation of ovalbumin and antigen-antibody reaction was induced by intranasal administration of antigen solution (ovalbumin solution). An average of 16.0 sneezes was observed in 15 minutes after the induction of antigen solution. The sneezes in the groups that were orally administered for 18 consecutive days from the strength of 3 days before the start of sensitization to the day of antigen challenge at doses of 10, 100, and lOOOOmgZkg of phospho-derived polyphenols averaged 8.9, 7.6, and 3. Five times, the occurrence of sneezing was significantly suppressed at doses of 100 and lOOOOmgZkg compared to the vehicle control group. The average sneezing in the group that received ketotifen, which was used as a comparative control substance, at the dose of lmg Zkg orally 1 hour before antigen challenge, was significantly suppressed compared to the vehicle control group. . Apple-derived polyphenols suppressed sneezing in a dose-dependent manner in an allergic rhinitis model.

The results are shown in FIG.

[0040] Test Example 2

 We investigated the creation of a basic model that can be administered continuously after the sensitization. Kud: Hartley male guinea pig (6 weeks old, n = 4Z group) was actively sensitized by inhalation of ovalbumin, and antigen-antibody reaction was induced by intranasal administration of antigen solution (ovalbumin solution)

[0041] Test group (i) in which inhalation sensitization was performed twice and the period until the first sensitization was performed for 28 days (i) and inhalation sensitization was performed four times. The average number of sneezes for 15 minutes after intranasal administration of the antigen solution of test group (ii) with a period of 28 days was 4.0 and 3.0. The inhalation sensitization was performed twice, and 14 days after the first inhalation sensitization, the test group (iii) in which the antigen solution was administered into the nasal cavity for 8 consecutive days and induced the antigen-antibody reaction, the maximum number of sneezes for 15 minutes Eight times (1st day of induction), at least 1.6 times (6th day of induction). In addition, the test group (iv), in which the antigen solution was administered intranasally for 8 consecutive days 21 days after the first inhalation sensitization, caused sneezes for 15 minutes at a maximum of 8.4 times. Day), at least 1.6 times (day 6). In the test groups (iii) and (iv), sneezing reactions with a cycle of 2 to 3 days Was recognized. In particular, the 14th day of the test group (iii) is the same as the test system of Test Example 1.Since the reactivity of sneezing was strong, the reactivity was maintained if it was erected continuously at intervals of 2 to 3 days. It became clear that it can be applied to continuous administration tests of substances.

[0042] Test Example 3

 Using an allergic rhinitis model created by active sensitization, which is equivalent to a preventive action verification test, the pre-administration effect of polyphenol derived from apple obtained in Example 1 on sneezing induced by antigen nose was examined. .

[0043] Kud: Hartley male guinea pigs (6 weeks old, n = 8Z group) were sensitized by inhalation of ovalbumin, and antigen-antibody reaction was induced by intranasal administration of antigen solution (ovalbumin solution). Invocations were performed 3 times in succession every 4 days (4 times in total), and the number of sneezes for 15 minutes after induction was measured.

 [0044] As a result, the vehicle control group showed an average of 9.1 sneezing times in the first invocation. As the number of invocations increased, the number of sneezes decreased, with an average of 6.4 to 4.4 in three invocations thereafter. In addition, the total number of sneezing 4 times was 24.4 on average.

 [0045] Induction of the apple-derived polyphenol (i) group obtained in Example 1 that started administration from the beginning of the first induction The average number of sneezes in the first one was 4.0, and then three times Average 1. 9-4. The total number of sneezes was 13.5 on average. Compared to the vehicle control group, significant suppression of sneezing was observed at the first, second, third, and total.

 [0046] Induction of the polyphenol GO group derived from apple obtained in Example 1 that started administration from the end of sensitization. The average number of sneezes in the first round was 4.1. After that, the average of 2.4 to 4.5 times was shown in the 3 invocations. In addition, the total number of sneezes that occurred 4 times averaged 13.4. Compared to the vehicle control group, significant suppression of sneezing was observed at the first, fourth and total number of evoked events.

[0047] In the polyphenol (iii) group derived from apple obtained in Example 1 which started administration after the end of the first sensitization, the average number of sneezes for the first time was 2.5. After that, the average of 1.6 to 4.0 times was shown in the three invocations. In addition, the total number of sneezing four times was 9.8 on average. Compared with the vehicle control group, significant suppression of sneezing was observed at the first, second, fourth, and total. In addition, compared with the apple-derived polyphenol (i) group, Compared to the phenol GO group, a significant suppression of combing was observed at the second induction. From the above, it has been clarified that the polyphenol derived from apple obtained in Example 1 shows an inhibitory action on the sneezing reaction in the guinea pig allergic rhinitis model no matter what timing is started. In addition, the longer the pre-administration period before induction, the stronger the tendency to suppress sneezing, demonstrating the preventive effect.

 The results are shown in FIG.

 Comparative Example 1

[0049] (Beverage 1)

 Add 1000 kg of sweetened glucose liquid sugar 200 kg, apple transparent concentrated fruit juice 8.5 kg, maltodextrin 1.5 kg, trisodium citrate 1.2 kg, ascorbic acid 0.3 kg, citrate anhydrous 2.7 kg Adjusted soft drinks. In the preparation of soft drinks, flavor ingredients can be added as appropriate. For example, fruit juice, dairy products, alcohol or the like may be added. Example 2

[0050] (Beverage 2)

 Polyphenol derived from apple obtained in Example 1 in 1000 L of water 1.4 kg, sweetened grape sugar liquid sugar 200 kg, apple transparent concentrated fruit juice 8.5 kg, maltodextrin 1.5 kg, trisodium citrate 1.2 kg, ascorbine A soft drink was prepared by mixing 0.3 kg of acid and 2.7 kg of citrate anhydride. In the preparation of soft drinks, flavor raw materials can be added as appropriate. For example, fruit juice, dairy products, alcohol or the like may be added.

 Example 3

[0051] (Beverage 3)

 Polyphenols derived from apple obtained in Example 1 in 1000 L of water 3.5 kg, sweetened grape sugar liquid sugar 200 kg, apple transparent concentrated fruit juice 8.5 kg, maltodextrin 1.5 kg, trisodium citrate 1.2 kg, ascorbine A soft drink was prepared by mixing 0.3 kg of acid and 2.7 kg of citrate anhydride. In the preparation of soft drinks, flavor raw materials can be added as appropriate. For example, fruit juice, dairy products, alcohol or the like may be added.

[0052] Test Example 4

Permanent allergic rhinitis with moderate severity for mites with a severity of 3 years or more Beverages prepared in Comparative Example 1 and Examples 1-2 as test foods for 33 men and women aged 15-65 years with allergies as described above (control group (apple-derived polyphenols obtained in Example 1 Omg: 11), low-dose group (apple-derived polyphenol 200 mg obtained in Example 1: 11), high-dose group (apple-derived polyphenol 500 mg obtained in Example 1: 11)) 1 1 bottle (150ml) once a day for 4 weeks.

 [0053] With regard to nasal symptoms, significant improvement was observed before and after ingestion of sneezing attacks and nasal discharge in the high-dose group (p <0. 05, p <0. 01). There was also a significant improvement in comb and seizures in the low-dose group (p <0. 05). Furthermore, the improvement of nasal symptoms was confirmed to be more effective than the control group in sneezing attacks and nasal discharge in the treated group, and the improvement in nasal findings was found in the swelling of the lower turbinate mucosa. It was confirmed that the effect beyond the improvement was greater in the administration group. In addition, various blood tests and urine tests showed no abnormalities. During the drinking period, no complaining complaints were found.

 [0054] Test Example 5

 Using the drink obtained in Example 2, 12 adult panelists (8 men and 4 women) were allowed to taste each, and the ease of drinking and the taste were judged by the following criteria. For comparison, a beverage was prepared by adding strawberry tea extract or perilla extract instead of apple-derived polyphenol in Example 2. Table 1 below summarizes the average judgment results of the above 12 adult panelists.

[0055] {Criteria for ease of drinking)

 1 After drinking, I feel uncomfortable and difficult to drink.

 2 After drinking, I feel a little uncomfortable and a little difficult to drink.

 3 After drinking, you may feel a little uncomfortable, but you can drink.

 4 After drinking, you can drink well without feeling uncomfortable.

 5 After drinking, it is comfortable and comfortable to drink.

 {Decision criteria for deliciousness]

 1 The smell is strong.

 2 I'm worried about the smell, and the mouth feels bad.

3 It feels a little odory, and the mouth feels slightly bad, but you can drink it. You don't have to worry about the smell, you can drink it deliciously without feeling bad over the mouth.

 Smells, mouthfeel and throat are good.

実施例 4

Example 4

[0057] (nasal drops)

 Polyphenol 500 mg, sorbitol 50 g and methyl paraoxybenzoate 20 mg obtained in Example 1 were dissolved in distilled water for injection, the pH was adjusted to 6.5 with a phosphate buffer, and the total volume was 1000 ml. It was. After filtration through a 0.45 m membrane filter, the filtrate was aseptically dispensed into a nasal bottle to give a nasal drop.

 Example 5

[0058] (Tablet)

 50 g of apple-derived polyphenol obtained in Example 1, 90 g of ratatoose and 17 g of corn starch were mixed together, and the mixture was crushed and granulated with a paste prepared from 70 g of corn starch. The obtained granules were mixed with magnesium stearate lg and mixed well, and the mixture was tableted with a tableting machine to produce 1000 tablets.

 Example 6

[0059] (Candy)

 After adding water to 300 g of sucrose and 250 g of syrup, the mixture was boiled in a flat pan to 150 ° C to obtain a candy base with a moisture content of 2.5%. The candy base was cooled to a temperature of 130 ° C, and 1.2 g of apple-derived polyphenol obtained in Example 1, 5 g of taenic acid, fragrance lg, and pigment lg were added in a pan. Kneaded until uniform. This kneaded product was molded using a stamping molding machine to obtain a candy.

 Example 7

[0060] (cream) Mix the oil phase components of petrolatum 30g, liquid paraffin 20g, «Raffin 7g, lanolin 4g, and dissolve by heating at 75 ° C. On the other hand, 4 g of sorbitan sesquioleate, 2.5 g of propylene glycol, 0.2 g of magnesium sulfate, 0.2 g of methyl parabenzoate and 31.7 g of purified water were mixed and dissolved by heating at 75 ° C. To this, 0.2 g of a fragrance was added and dispersed uniformly with a homomixer. The oil phase component was added to the aqueous phase component and milked with a homomixer. After the emulsification, cooling was started, and 0.2 g of the apple-derived polyphenol obtained in Example 1 was obtained at 40 ° C. and mixed uniformly.

 Example 8

[0061] (Lotion)

 10 g of ethyl alcohol, 0.2 g of polyphenol derived from apple, 6 g of 1,3-butylene glycol, 5 g of glycerin, polyoxyethylene sorbitan monolaurate (20E.O.) lg, 0.2 g of methyl noraoxybenzoate, fragrance 0 Dissolve 2g. After dissolution, 77.39 g of purified water and 0. Olg of citrate were sequentially added, and the mixture was sufficiently stirred and mixed uniformly.

 Example 9

[0062] (Bath bath)

 3 g of polyphenol derived from apple obtained in Example 1, 55 g of sodium hydrogen carbonate, 40 g of sodium sulfate, dye lg, and fragrance lg were uniformly mixed.

 Example 10

[0063] {14-day repeated dose toxicity study)

 Male and female SD rats (Japanese chilis livelihood) were divided into 3 each, and the polyphenol derived from the ring obtained in Example 1 was administered in 2000, 3000 mgZkg, stomach tube for 14 days. . No abnormalities were found in the general condition and body weight at the time of the experiment, and no abnormalities were found in the general blood tests and anatomical findings after the experiment.

[0064] {90-day repeated dose toxicity study}

The male and female of SD rats (Japanese chilis river) are divided into 10 males and the positive phenols derived from Lingo obtained in Example 1 are administered in doses of 500, 1000, 2000 mg / kg for 90 days with gastric sonde. Went. No abnormalities were observed in the general condition and body weight at the time of the experiment, and there were no abnormalities in the general blood test and anatomical findings after the experiment. [0065] {Mutagenicity test)

 Males of SD rats (Japanese chilis river) were divided into 5 animals, and the positive phenols derived from apples obtained in Example 1 were administered in amounts of 500, 1000, 2000 mg / kg in gastric sonde. There was no abnormality in general condition and body weight, and there was no significant difference in the appearance frequency of polychromatic erythrocytes and polychromatic erythrocytes with micronuclei compared to the negative control group. o

 Industrial applicability

 [0066] The anti-inflammatory agent of the present invention has the effect of improving or preventing sneezing and nasal discharge, which are the main symptoms of allergic rhinitis, and has no side effects, so it can be taken safely for a long time. Can do. Therefore, the anti-inflammatory agent of the present invention can be suitably used not only as a pharmaceutical ingredient but also in foods and drinks, cosmetics, etc., and can be imparted with an anti-inflammatory action and an inflammation-preventing action, which are extremely useful. It is.

 [0067] Further, since anti-allergic action is exhibited by inhibiting inflammation, it is possible to improve nasal inflammation such as perennial allergic rhinitis, hay fever and allergic sinusitis.

Claims

The scope of the claims  [1] An anti-inflammatory agent for preventing inflammation and having an anti-inflammatory action, characterized by comprising polyphenol derived from apple as an active ingredient.  [2] The inflammation prevention 'anti-inflammatory agent according to claim 1, wherein the inflammation is rhinitis. [3] The inflammation prevention 'anti-inflammatory drug according to claim 1, comprising an anti-inflammatory agent according to claim 1'.  [4] The inflammation prevention according to claim 1, comprising an anti-inflammatory agent, and a food and drink for anti-inflammation.  [5] An inflammation prevention composition according to claim 1, comprising an anti-inflammatory agent, and an anti-inflammation cosmetic product.