JP2009102270A - Fat metabolism inhibitor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a highly safe fat metabolism inhibitor having excellent fat metabolism-inhibiting activities for solving the problems wherein, although 50-150 mg/dl of the neutral fat is present in the blood at a fasting time in a case of a healthy adult, and the value becomes maximum on 3-5 hr after eating, when the neutral fat exceeds a normal value, the fat is accumulated under the skin or around the internal organs to cause fatness and accumulation in the liver to cause fatty liver, and also VLDL is a cause of arteriosclerosis. <P>SOLUTION: The fat metabolism inhibitor contains Lactobacillus paracasei KW3110 strain or a variant of the Lactobacillus paracasei KW3110 strain having the fat metabolism-inhibiting effects as an active ingredient. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a fat metabolism inhibitor.

Neutral fat is found in healthy adults at 50 to 150 mg / dL in the blood on an empty stomach and reaches its maximum 3 to 5 hours after meals. May accumulate under the skin or around the internal organs and become obese, or may accumulate in the liver and become fatty liver. VLDL is a factor causing arteriosclerosis.
In recent years, obesity, fatty liver, and hyperlipidemia caused by the westernization of food and lack of exercise have become a problem. Typical treatment methods for these symptoms include diet restriction therapy and pharmaceutical administration.
However, the former method often has a negative effect on daily life, and the latter method cannot avoid the problem of side effects.
On the other hand, lipid metabolism improving agents derived from natural products have been proposed. For example, many lipid metabolism improving agents have been proposed, such as a fat accumulation inhibitor containing methylated catechins (Patent Document 1) and a body fat reducing agent containing sesamin as an active ingredient (Patent Document 2).

On the other hand, lactic acid bacteria are known to have an intestinal regulating action, a cholesterol lowering action, a blood pressure lowering action, etc., and are known to have antiallergic activity in the KW3110 strain in the present invention described below (Patent Document 3). . However, it is not known that the KW3110 strain has a very excellent fat metabolism inhibitory effect.
JP 2006-298792 A Japanese Patent No. 3305315 Japanese Patent No. 3585487

  An object of the present invention is to provide a fat metabolism inhibitor containing the KW3110 strain, having high safety and having an excellent fat metabolism inhibitory action.

  The present invention provides a fat metabolism inhibitor comprising as an active ingredient a Lactobacillus paracasei KW3110 strain or a mutant strain of Lactobacillus paracasei KW3110 strain having a fat metabolism inhibitory effect.

  ADVANTAGE OF THE INVENTION According to this invention, while containing KW3110 strain | stump | stock, the safety | security high and the fat metabolism inhibitor which has the outstanding fat metabolism inhibitory effect can be provided.

The lactic acid bacterium which is an active ingredient of the present invention is a composition containing the lactic acid bacterium and containing the lactic acid bacterium as an active ingredient, and a carrier, excipient and / or other auxiliary agent is added to the lactic acid bacterium. It is also possible to formulate and use.
The fat metabolism inhibitor of the present invention can be administered orally by use in foods and beverages and formulation. L. The paracasei KW3110 strain is a lactic acid bacterium that is resistant to digestive juice and highly adherent to the intestinal tract, and exhibits particularly excellent effects when taken orally.

L. used as an active ingredient in the present invention. The paracasei KW3110 strain can be obtained from the Japan Dairy Industry Association as the L.casei L14 strain. L. The paracasei KW3110 strain is further deposited as FERM BP-08634 at the Patent Organism Depositary, National Institute of Advanced Industrial Science and Technology, which is an international depositary authority, based on the Budapest Treaty for the Deposit of Patent Microorganisms.
Moreover, the mutant strain of the strain can be easily obtained by mutating the strain by a known mutation treatment and selecting a strain having an effect of inhibiting fat metabolism from the strain subjected to the mutation treatment. it can.
In addition, L. used as an active ingredient in the present invention. Examples of the strain exhibiting the same effect as the paracasei KW3110 strain include Lactobacillus plantarum KW4110 strain, Lactobacillus paracasei KW3925 strain, Lactobacillus paracasei KW3926 strain, or Streptococcus salivarius KW3210. L. plantarum KW4110 strain plantarum JCM1149 strain, The paracasei KW3926 strain Paracasei JCM8132 strain can be obtained from JCM (RIKEN Microbial System Storage Facility). paracasei KW3925 strain It can be obtained from NRIC (Tokyo University of Agriculture) as paracasei NRIC1917.

  L. The paracasei KW3110 strain is R. S. (De Man, Rogosa, Sharpe) After appropriately growing in a culture medium for lactic acid bacteria known to those skilled in the art, such as culture medium, sterilize with live bacteria or, if necessary, freeze-dry or spray-dry to make powder It can be used as an active ingredient of food and drink.

  In the present invention, L.P. Strains with different traits generated from paracasei KW3110 strain can be selected and used as a derivative strain.

  The fat metabolism inhibitor of the present invention can be formulated and used by mixing with a physiologically acceptable carrier, excipient, binder, diluent and the like. The fat metabolism inhibitor of the present invention can be administered orally or parenterally. Oral preparations include granules, powders, tablets (including sugar-coated tablets), pills, capsules, syrups, emulsions, and suspensions. Examples of parenteral preparations include injections (for example, subcutaneous injections, intravenous injections, intramuscular injections, intraperitoneal injections), drops, and external preparations (for example, nasal preparations, transdermal preparations, ointments) ), Suppositories (for example, rectal suppositories, vaginal suppositories). These preparations can be formulated together with pharmaceutically acceptable excipients and additives by techniques commonly used in the art. In formulating, the fat metabolism inhibitor of the present invention can exert its function in a living body in a timely and effective manner, that is, the elution start time is controlled, or a function as a bitter taste masking agent is added. , Obtained by increasing the stability against oxygen and humidity, for example, by encapsulating with a soft capsule or a hard capsule according to a coating treatment product coated with a coating agent mainly composed of a yeast cell wall described in Japanese Patent No. 3334977 Both capsules can be preferably used in fields such as pharmaceutical preparations and health foods. Examples of pharmaceutically acceptable excipients and additives include carriers, binders, fragrances, buffers, thickeners, colorants, stabilizers, emulsifiers, dispersants, suspending agents, preservatives, and the like. It is done. Examples of the pharmaceutically acceptable carrier include magnesium carbonate, magnesium stearate, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, a low melting wax, cocoa butter and the like. It is done.

  The preparation can be produced, for example, as follows. That is, oral preparations are active ingredients such as excipients (eg, lactose, sucrose, starch, mannitol), disintegrants (eg, calcium carbonate, carboxymethylcellulose calcium), binders (eg, pregelatinized starch, gum arabic). , Carboxymethylcellulose, polyvinylpyrrolidone, hydroxypropylcellulose) or lubricant (eg, talc, magnesium stearate, polyethylene glycol 6000) and then compression molded, then taste masking, enteric or persistent as needed For this purpose, it can be produced by coating by a method known per se. As the coating agent, for example, ethyl cellulose, hydroxymethyl cellulose, polyoxyethylene glycol, cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate and Eudragit (Rohm, Germany, methacrylic acid / acrylic acid copolymer) can be used.

  An injection comprises an active ingredient as a dispersant (for example, Tween 80 (manufactured by Atlas Powder, USA), HCO 60 (manufactured by Nikko Chemicals), polyethylene glycol, carboxymethylcellulose, sodium alginate, etc.), a preservative (for example, Methylparaben, propylparaben, benzyl alcohol, chlorobutanol, phenol), isotonic agents (for example, sodium chloride, glycerin, sorbitol, glucose, invert sugar) and aqueous solvents (for example, distilled water, physiological saline, Ringer's solution, etc.) ) Or an oil-based solvent (for example, olive oil, sesame oil, cottonseed oil, vegetable oil such as corn oil, propylene glycol) or the like. At this time, if desired, additives such as a solubilizing agent (for example, sodium salicylate, sodium acetate), a stabilizer (for example, human serum albumin), a soothing agent (for example, benzalkonium chloride, procaine hydrochloride) are added. Also good.

  The external preparation can be produced by making the active ingredient into a solid, semi-solid or liquid composition. For example, the solid composition is prepared by using the active ingredient as it is, or an excipient (eg, lactose, mannitol, starch, microcrystalline cellulose, sucrose), a thickener (eg, natural gums, cellulose derivatives, acrylic acid). Polymer) and the like can be added and mixed to form a powder. The liquid composition can be produced in almost the same manner as in the case of an injection. The semi-solid composition is preferably an aqueous or oily gel or a cartilage. In addition, these compositions are all pH adjusters (for example, carbonic acid, phosphoric acid, citric acid, hydrochloric acid, sodium hydroxide), preservatives (for example, p-hydroxybenzoates, chlorobutanol, benzalkonium chloride). Etc. may be included. Suppositories can be produced by making the active ingredient into an oily or aqueous solid, semi-solid or liquid composition. Examples of the oily base used in the composition include higher fatty acid glycerides [for example, cacao butter, witepsols (manufactured by Dynamite Nobel)], intermediate fatty acids [for example, miglyols (manufactured by Dynamite Nobel)], or vegetable oils (for example, , Sesame oil, soybean oil, cottonseed oil). Examples of the aqueous base include polyethylene glycols and propylene glycol. Examples of the aqueous gel base include natural gums, cellulose derivatives, vinyl polymers, and acrylic acid polymers.

  The fat metabolism inhibitor of the present invention can be used as a food or drink. In order to mix and use the fat metabolism inhibitor of the present invention in foods and drinks, an effective amount of the active ingredient is added and blended at the production raw material stage of the food or drinks or the stage of the manufactured products. Here, the “effective amount of the active ingredient” refers to a content that allows the active ingredient to be ingested in the following range when the amount normally eaten in each food or drink is ingested.

That is, the dose or intake of an effective amount of the active ingredient in the food or drink in the present invention depends on the recipient, the age and weight of the recipient, symptoms, administration time, dosage form, administration method, combination of drugs, and the like. Can be determined. For example, when the active ingredient according to the present invention is orally administered as a medicine, 0.1 to 100 mg / kg body weight (preferably 1 to 10 mg / kg body weight) per adult, and 0.01 to 10 mg when administered parenterally. / Kg body weight (preferably 0.1-1 mg / kg body weight) can be administered in 1 to 3 divided doses per day. Drugs having other mechanisms of action used in combination with the active ingredient according to the present invention can also be appropriately determined based on the clinically used dose. When the dose or intake of an effective amount of the active ingredient in the present invention is expressed as the number of lactic acid bacteria, the daily intake is preferably 5 × 10 ⁹ or more, more preferably 1 per day. It is preferable to ingest 10 × 10 ¹⁰ or more, more preferably 5 × 10 ¹⁰ or more. Therefore, the number of lactic acid bacteria to be contained in each food is determined according to the amount of food or drink that is usually ingested per day. For example, when ingested as a food (yogurt), the active ingredient according to the present invention can be added to the food so that the amount of intake per adult is in the range of 50 to 500 g per day, preferably in the range of 60 to 200 g.

  In this invention, the active ingredient of the fat metabolism inhibitor of this invention can be mix | blended with food-drinks as it is or the form of the above preparations. More specifically, the food / beverage products of the present invention are prepared by appropriately blending the active ingredient of the present invention with a base material and directly prepared as food / beverage products, or various proteins, sugars, fats, trace elements, vitamins, etc. Various usage forms such as those further blended, those in liquid, semi-liquid or solid form, and those added and blended with general foods and beverages can be adopted.

  Conventionally, in the field of foods and drinks using lactic acid bacteria, the utilization classification is roughly divided into dairy products, meats, breads, beverages, and vegetables. As a lactic acid bacterium in the production of foods and beverages using these lactic acid bacteria or a part thereof, or as an additive of the produced foods and beverages, the lactic acid bacteria in the fat metabolism inhibitor of the present invention are used to inhibit fat metabolism in the food and beverage An effect can be imparted.

  As another embodiment of the present invention, when lactic acid bacteria as an active ingredient are added to a food or drink, the fermentation of the lactic acid bacteria itself is not required, and when maintaining the flavor of the food or drink itself, For example, it is particularly preferable to use after sterilization by a treatment such as heat sterilization. Moreover, it is preferable that the food / beverage products in this invention are manufactured with the form of sealed container-packed food / beverage products in order to prevent mixing of another microorganism and a foreign material, and to maintain the quality of the content.

  The food in the present invention can be prepared as health food, functional food, food for specified health use, or food for the sick. Moreover, it is not specifically limited to the form of food, The form of a drink may be sufficient.

  As the health food and functional food in the present invention, various foods can be mentioned, but regarding the production of the health food and functional food, in addition to the commonly used food materials and food additives, shaping In the form of food and beverage products using adjuvants such as additives, extenders, binders, disintegrants, lubricants, dispersants, preservatives, wetting agents, solubilizers, preservatives, stabilizers, capsule bases, etc. Can be used. Specific examples of the adjuvant include lactose, fructose, glucose, starch, gelatin, magnesium carbonate, synthetic magnesium silicate, talc, magnesium stearate, calcium carbonate, methylcellulose, carboxymethylcellulose, or a salt thereof, gum arabic , Polyethylene glycol, syrup, petrolatum, glycerin, ethanol, propylene glycol, citric acid, sodium chloride, sodium sulfite, sodium phosphate, pullulan, carrageenan, dextrin, reduced palatinose, sorbitol, xylitol, stevia, synthetic sweetener, citric acid Ascorbic acid, acidulant, baking soda, sucrose ester, hardened vegetable oil, potassium chloride, safflower oil, beeswax, soybean lecithin, flavor, and the like can be blended. Regarding the production of such health foods and functional foods, reference books for pharmaceutical preparations such as “Japanese Pharmacopoeia Manual (General Rules for Preparations)” (Yodogawa Shoten) can be referred to.

  In addition, as food and drink in the present invention, specifically, pudding, cookies, crackers, potato chips, biscuits, bread, cakes, chocolate, donuts, jelly and other Western confectionery, rice crackers, sheep crab, Daifuku, ohagi, other buns, castella Japanese confectionery such as frozen confectionery (boiled rice cakes), bread and confectionery such as chewing gum, noodles such as udon, soba and kishimen, fish paste products such as kamaboko, ham and fish sausage, ham, sausage, hamburger, corn beef, etc. Meat products, seasonings such as salt, pepper, miso, soy sauce, sauce, dressing, mayonnaise, ketchup, sweetener, spicy seasoning, teppanyaki foods such as Akashiyaki, takoyaki, monjayaki, okonomiyaki, yakisoba, fried udon Dairy products such as cheese, hard yogurt, natto, deep fried, tofu, Various dishes such as nyak, dumplings, pickles, boiled dumplings, dumplings, shumai, croquettes, sandwiches, pizzas, burgers, salads, etc., various livestock products such as beef, pork, chicken, marine products such as shrimp, scallops, salmon, kelp , Vegetables / fruits, plants, yeast, algae, etc.), oils and fragrances (vanilla, citrus fruits, bonito, etc.) and powdered foods and drinks (instant coffee, instant tea, instant milk, instant) Various foods such as soup, miso soup, etc. can be mentioned, but are not particularly limited thereto.

  In particular, when the active ingredient according to the present invention is contained in a dairy product, the active ingredient according to the present invention is added as a living bacterium to a milk raw material to carry out bacterial growth / fermentation to obtain a fermented lactic acid bacteria food and drink such as yogurt.

  The fat metabolism inhibitor of the present invention can be used continuously, particularly in the form of a beverage, and can be taken continuously every day.

When the lactic acid bacterium in the present invention is blended into a beverage, the blending amount of the lactic acid bacterium can be determined as appropriate, but the effective dose or intake of the active ingredient in the present invention is determined by the number of lactic acid bacteria. When displayed, the daily intake is preferably 5 × 10 ⁹ or more, more preferably 1 × 10 ¹⁰ or more, and even more preferably 5 × 10 ¹⁰ or more per day. Therefore, the number of lactic acid bacteria to be contained in each beverage is determined by the above index according to the amount of beverage that is usually consumed per day. For example, if 100 g of beverage is ingested per day, it is preferable to add 10 ⁹ or more bacteria per 100 g of beverage. On the other hand, the addition of lactic acid bacteria, considering the range not impairing the flavor or appearance of the beverage, preferably 10 ¹¹ or less. Furthermore, 5 × 10 ¹⁰ or less is more preferable. Particularly preferred are those in the range of 10 ⁹ to 10 ¹¹ per 100 g of beverage. Regarding the relationship between the number of lactic acid bacteria and the weight of dry bacteria, see, for example, L. In paracasei KW3110 strain, 10 ¹² cells correspond to 1 g of dry cell weight.

  Examples of the beverage in the present invention include various beverages such as alcoholic beverages (whiskey, bourbon, spirits, liqueur, wine, fruit liquor, sake, Chinese sake, shochu, beer, alcohol content of 1% or less. Non-alcoholic beer, happoshu, strawberry high, etc.) and non-alcoholic beverages (drink-type yogurt, apples, mandarin oranges, grapes, bananas, pears, ume, watermelon and other fruit juices, tomatoes, carrots, celery, cucumbers and other vegetable juices, Soft drinks, milk, soy milk, coffee, cocoa, black tea, green tea, barley tea, brown rice tea, sencha, gyokuro tea, roasted tea, oolong tea, turmeric tea, puer tea, rooibo tea, rose tea, chrysanthemum tea, mint tea, jasmine tea And various herbal teas, sports drinks, mineral water, energy drinks, etc.) .

  In the present invention, when a beverage is commercialized, the beverage can be appropriately sterilized according to the method defined in the Food Sanitation Law. As the sterilization method, pasteur sterilization, hot pack sterilization, UHT sterilization, retort sterilization and the like can be properly used depending on the pH of the beverage.

  Furthermore, as a product form, the form of the drink with a sealed container currently normally used for the product form of a drink is especially preferable, and any form of a can, a bottle, PET, and a paper container may be sufficient as this sealed container. In addition, there is no particular limitation on the volume, but generally, in consideration of the amount consumed by consumers as a drink on a daily basis, the number of lactic acid bacteria and the number of bacteria required per day, as appropriate, Can be determined.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further, this invention is not restrict | limited to the following example.

Example 1
Lactobacillus paracasei KW3110 strain R. S. What was cultured in (de Man, Rogosa, Sharpe) medium (OXOID) for 48 hours was washed three times with sterile water and suspended in sterile water.

  Orbital blood collection was performed from 7-week-old male ddY mice (9 mice per group) fasted for 20 hours, and 10 mL / kg of salad oil was orally administered. Immediately after that, 10 mL / kg of water or the above-mentioned sterilized suspension of KW3110 was suspended. Water was administered orally. The dosage of the KW3110 strain is 500 μg / kg. After 60 minutes, 120 minutes, and 180 minutes, orbital blood was collected again, and plasma was separated to measure the neutral fat concentration. By administration of the KW3110 strain, an increase in plasma triglyceride level after loading with salad oil was remarkably suppressed, and the KW3110 strain was found to have an effect of inhibiting neutral fat absorption (Table 1).

Comparative Example 1
Example 1 was repeated except that the KW3110 strain was changed to Lactobacillus casei. The results are shown in Table 2.

Example 2
Next, the metabolic control effect of serum neutral fat of the KW3110 strain was examined by clinical trials.

Twelve healthy test subjects (20-65-year-old males) with serum total triglycerides of 150 mg / dL or less were divided into two groups. The first group contained 100 g of the following sports drink 1 (control group), In the second group, 100 g of the following sports drink 2 (test group) was added to 200 g of commercially available corn cream potage soup (“Sujata Plenty of Corn Cream Potage Nama” (trade name, manufactured by Nagoya Dairy Co., Ltd.)). 17 g of Snow Brand Milk Products Co., Ltd.) and 14 g of Snow Brand Lard (Yuki Brand Milk Products Co., Ltd.) were added and dissolved by heating. Serum total neutral fat level (TG) of the test subjects was measured. As a result, the serum total triglyceride level (TG) of the second group after 3 hours decreased to about 60% of the first group. In addition, no abnormality was observed from various blood tests.
(Sport drink 1)
Formulation liquid containing granulated sugar 4.5% by weight, citric acid 0.2% by weight, sodium citrate 0.05% by weight, and fragrance 0.1% by weight.
(Sport drink 2)
0.0143 wt% of lactic acid bacteria KW3110 strain (100 g of product) with respect to a preparation containing 4.5 wt% granulated sugar, 0.2 wt% citric acid, 0.05 wt% sodium citrate and 0.1 wt% fragrance 1.5 × 10 ¹⁰ per unit) was added.

Comparative Example 2
Example 2 was repeated except that the KW3110 strain was changed to Lactobacillus casei in the test group. As a result, there was no difference in serum total triglyceride level (TG) between the control group and the test group.

Example 3
(Manufacture of tea-based beverages)
Deionized water was added so that the tea leaf usage rate was 0.8% by weight with respect to the extract of oolong tea, black tea, green tea, hoji tea and jasmine tea extracted with hot water at 85 ° C. At that time, ascorbic acid was added so that it might become 0.025 weight%, and then it adjusted to pH which was easy to drink using baking soda. Furthermore, after adding lactic acid bacteria KW3110 strain so that the number of bacteria becomes 1.5 × 10 ¹⁰ and 3 × 10 ¹⁰ per 100 g of the prepared solution, UHT sterilization is performed as usual, and 350 ml PET bottles are added. Filled.

Example 4
(Manufacture of beverages containing fruit juice)
Add a predetermined amount of lactic acid bacteria to 900 g of turbid apple juice and 1 g of fragrance, add deionized water to make a total of 1 kg, and then perform hot pack filling in a 180 ml glass bottle as usual. A juice-containing beverage was prepared. The lactic acid bacteria KW3110 strain was added so that the number of bacteria was 2 × 10 ¹⁰ or 4 × 10 ¹⁰ with respect to 100 g of the preparation.

Example 5
(Manufacture of yogurt)
Raw materials containing milk (milk, skim milk powder, cream, sugar liquid sugar, stabilizer, fragrance, water) are uniformly mixed, sterilized by heating at 128 ° C for 15 seconds, cooled to 40 ° C or lower, and then lactic acid bacteria starter KW3110 And the fermentation was started in a fermentation tank maintained at 37 ° C. Lactic acid bacteria KW3110 decomposed the lactose in the mixed solution to produce lactic acid, and the pH reached 4.6 after about 18 hours. When gelation became stable due to isoelectric point aggregation of the milk protein, the mixture was stirred and cooled. The yogurt made into a paste by stirring was filled in a paper container, sealed, and stored in a refrigerator at 10 ° C. or lower. After cooling, it was confirmed by sensory inspection that the yogurt has proper taste and physical properties.

Claims (1)

  A fat metabolism inhibitor comprising, as an active ingredient, a Lactobacillus paracasei KW3110 strain or a mutant strain of Lactobacillus paracasei KW3110 strain having an effect of inhibiting fat metabolism.