JPH1192552A - Orally administrative polyhydroxycarboxylic acid - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a polyhydroxycarboxylic acid having an intestine conditioning action and a specified weight-average molecular weight and being capable of lowering the pH in the intestinal tract. SOLUTION: There is provided a polyhydroxycarboxylic acid having a weight- average molecular weight of 1,000-50,000 and obtained by polymerizing an α- hydroxycarboxylic acid selected among L-lactic acid, D-lactic acid, a mixture thereof, glycolic acid, etc., and having an intestine conditioning action. This is mixed with an extender, a coagulant, a gelling agent, a texturing agent, etc., to form a medicine for intestine diseases in the form of tablets, capsules, a powder, granules, a liquid, a jelly, a suppository or the like. The daily dosage is abut 0.1 mg to 1 g/kg body weight in the case where it is used in the form a medicine for intestinal diseases or a food additive. It is desirable that such a medicine or additive is taken periodically every day or every several days. The polyhydroxycarboxylic acid is produced under conditions in which the kind of the solvent used, the kind of the catalyst used, the amount of the catalyst, the reaction temperature, and the reaction time are suitably selected. After the synthesis, it is purified by an operation such as recrystallization, reprecipitation, extraction or deaeration.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The technical field to which the invention pertains relates to polyhydroxycarboxylic acids.

[0002]

2. Description of the Related Art With regard to human intestinal regulation, conventionally useful intestinal bacteria such as lactic acid bacteria and bifidobacteria generate organic acids such as lactic acid and acetic acid in the intestinal tract of a host to acidify the pH in the intestinal tract. It has been reported that the growth of harmful bacteria in the intestinal tract represented by Escherichia coli and Proteus bacteria is suppressed. In addition, if the pH in the intestinal tract is tilted toward the acidic side, it suppresses the absorption of ammonia and amines from the intestinal tract, further promotes intestinal peristalsis, and promotes bowel movements. Although it is known to reduce the risk of the occurrence of lactic acid, direct ingestion of lactic acid and the like is absorbed in the upper intestine and does not lower the pH in the lower intestine. For this reason, many lactic acid bacteria preparations and preparations containing oligosaccharides for the purpose of growing useful bacteria in the intestinal tract have been developed.
There is no known substance having a bowel-regulating action for the purpose of lowering blood pressure.

[0003]

SUMMARY OF THE INVENTION The present invention relates to constipation caused by the growth of harmful bacteria in the intestinal tract and the absorption of ammonia and amine produced from the harmful bacteria by directly lowering the pH in the intestinal tract. It is an object of the present invention to provide a substance for oral ingestion having an intestinal action that improves symptoms such as abdominal bloating and loose stool. It is another object of the present invention to provide a food additive containing the substance as an active ingredient for intestinal regulation. Moreover, it aims at providing the foodstuff which added the said food additive. Moreover, it aims at providing the drink which added the said food additive. It is another object of the present invention to provide a feed to which the food additive has been added. It is another object of the present invention to provide an intestinal medicine containing the substance as an active ingredient for intestinal action.

[0004]

Means for Solving the Problems The present inventors directly reduce the pH in the intestinal tract, that is, the intestinal flora (flora).
As a result of diligent studies using the index of lowering the pH of feces, which reflects the pH of intestinal digestions and intestinal digestions, when polyhydroxycarboxylic acid is ingested orally, it lowers the pH of the intestinal tract, resulting in excellent intestinal control. It was newly found that the action was exhibited, and based on this finding, the present invention was completed. The present invention is specified by the following items [1] to [10].

[1] An orally ingestible polyhydroxycarboxylic acid having an intestinal action. [2] The weight average molecular weight is 1,000 to 50,000
Polyhydroxycarboxylic acid for oral ingestion according to [1]. [3] The polyhydroxycarboxylic acid for oral ingestion according to [1] or [2], which comprises at least a part of a polymer obtained by polymerizing an α-hydroxycarboxylic acid.

[4] The polyhydroxycarboxylic acid for oral ingestion according to [1] or [2], comprising a polymer obtained by polymerizing a hydroxycarboxylic acid containing at least a part of an α-hydroxycarboxylic acid. [5] The polyhydroxycarboxylic acid for oral ingestion according to [3] or [4], wherein the α-hydroxycarboxylic acid is lactic acid. [6] A food additive comprising the polyhydroxycarboxylic acid for oral ingestion according to any one of [1] to [5] as an active ingredient for intestinal regulation.

[7] A food to which the food additive according to [6] is added. [8] A beverage to which the food additive according to [6] is added. [9] A feed to which the food additive according to [6] is added. [10] An intestinal preparation comprising the polyhydroxycarboxylic acid for oral ingestion according to any one of [1] to [5] as an active ingredient for intestinal action.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The hydroxycarboxylic acid, which is a raw material of the polyhydroxycarboxylic acid used in the present invention, is not particularly limited. Preferred examples thereof include α-hydroxycarboxylic acids such as glycolic acid and lactic acid. Among these, lactic acid is particularly advantageous. As lactic acid, L-lactic acid, D-lactic acid, and a mixture thereof can be used.

The weight-average molecular weight of the polyhydroxycarboxylic acid used in the present invention is not limited as long as it can be ingested. Usually, when the weight-average molecular weight is small, it becomes syrupy and can be handled as powder. It can be difficult. In general, when the weight average molecular weight is too large, the hydrolysis rate may be reduced, and at the same time, it may be difficult to pulverize by a treatment such as pulverization. Therefore, the weight average molecular weight is usually 300 to 100,0.
00 is preferable, and 1,000 to 50,000 is more preferable.

The method for producing the polyhydroxycarboxylic acid used in the present invention is not particularly limited. Examples thereof include a method of directly dehydrating and condensing hydroxycarboxylic acid as a raw material and a method of ring-opening polymerization of a cyclic ester of hydroxycarboxylic acid. There is. Weight average molecular weight of polyhydroxycarboxylic acid,
The molecular weight distribution can be controlled to a desired value by appropriately selecting conditions such as the type of the solvent, the type of the catalyst and the amount, the reaction temperature and the reaction time in the polymerization method. In general, it is preferable that no impurities such as a catalyst are contained, and it is preferable to select a synthesis method suitable for this purpose. After the polyhydroxycarboxylic acid is synthesized, the polyhydroxycarboxylic acid can be purified and used by a method such as recrystallization, reprecipitation, extraction, and degassing.

The polyhydroxycarboxylic acid for oral ingestion according to the present invention can be used by adding it to foods, drinks and the like. The form to be added is not particularly limited, but is usually preferably in a powder form. Foods to be added are not particularly limited, but include, for example, ice cream, jelly, pudding, frozen desserts such as bavarois, yogurt, butter, dairy products such as cheese, short cakes, cakes such as cheese cakes, tangerines, peaches. Processed fruits, biscuits, cookies, etc.
Baked confectionery such as rice crackers and other confectionery such as candy, caramel, chocolate and the like. Other specific examples of the food to be added include, for example, foods such as cooked rice, pasta, noodles, bread, and the like, and processed foods of meats, vegetables, seafood, and the like. Other specific examples of foods to be added include instant foods prepared by freeze-drying and the like, and other processed foods such as retort foods and frozen foods. Usually, among the foods to be added, preferred foods are those that are taken daily or regularly every few days, and specific examples thereof include, for example, frozen desserts, dairy products, cakes, and fruit processing Dessert foods such as products.

The interval of ingestion of foods and drinks to which the polyhydroxycarboxylic acid for oral ingestion according to the present invention is added is not particularly limited, but it is preferable to ingest it daily or periodically every few days. The majority of people can ingest without resistance, as well as foods and beverages to which the polyhydroxycarboxylic acid for oral ingestion according to the present invention is not added. In particular, it is preferably used in combination with a food containing dietary fiber, oligosaccharide, mannan, etc. having an intestinal action.

The beverage to which the polyhydroxycarboxylic acid for oral ingestion according to the present invention is added is not particularly limited, and specific examples thereof include, for example, fruit juice,
Juices such as vegetable juices, coffee, black tea, green tea,
Preferred drinks such as oolong tea, carbonated drinks such as cola and cider, health drinks such as sports drinks, nutritional drinks and diet drinks, and soups such as corn soup and consommé soup. Usually, it can be preferably added to health drinks.

The polyhydroxycarboxylic acid for oral ingestion according to the present invention can be used as an active ingredient as an intestinal medicine. The dosage form is not particularly limited, and examples thereof include tablets, capsules, powders, granules, liquids, jellies, suppositories, and the like. Can also be used.

The polyhydroxycarboxylic acid for oral ingestion according to the present invention can be added to foods, beverages and feeds as an active ingredient for intestinal regulation, or used as an intestinal preparation, by using a bulking agent, a flocculant, a gelling agent, and a texture. An agent can be added. Specific examples of these additives include, for example, animal protein, vegetable protein, milk protein, fiber, carboxymethylcellulose, hydroxypropylmethylcellulose, cyclodextrin, gum arabic, shellac, gelatin, casein, starch, matsutodextrin , Lactose, carbohydrate syrup and the like.

Further, a sweetener, a sour agent and a stabilizer may be added to the polyhydroxycarboxylic acid for oral ingestion according to the present invention. Specific examples of sweeteners include, for example, dipeptide sweeteners such as aspartame, sucrose, fructose, glucose, liquid sugar, isomerized sugar, stevioside, sodium glycyrrhizinate, sodium saccharin, xylitol,
Sorbitol, mannitol, acesulfame K, alitame, sodium cyclamate, dihydrochalcone, thaumatin, monelin, glyciridine and the like can be mentioned. In addition to vitamins and additives such as taurine,
Conventionally known lactic acid bacteria, dry cells such as lactic acid bacteria, yeasts and chlorella, and intestinal agents such as tannin and bismuth may be added in combination.

In the case of humans, the amount of intake or dose is
Usually, about 0.1 mg to 1 g / kg of body weight per day is preferable. The behavior of the polyhydroxycarboxylic acid for oral administration according to the present invention in the intestinal tract and the mechanism of excellent intestinal regulation are not always clear, but in the intestinal tract, lactic acid and the like generated by decomposition by intestinal bacteria and the like are included. But,
It is considered to promote a decrease in pH in the intestinal tract (particularly, in the lower intestinal tract such as the large intestine). The concept of the word "oral" of the "polyhydroxycarboxylic acid for oral ingestion" according to the present invention is defined as "oral → esophagus → stomach → duodenum → small intestine → large intestine → rectum →
Includes the concept of transfer to the digestive system or intestinal system of the "anus" and includes not only the usual "oral" but also via the anus (for example, the route of administration by suppository or endoscope), nasal, transesophageal, etc. It also encompasses concepts. In the specification of the present application, "intestinal action"
The concept of at least includes the following effects of: The action of acidifying the pH in the intestinal tract, the action of suppressing the absorption of toxic substances (eg, ammonia, amines, etc.) from the intestinal tract. Promotes intestinal peristalsis and promotes bowel movements. Action to reduce the risk of carcinogenesis in the intestinal tract and the occurrence of adult diseases.

[0018]

【Example】

[Example 1] pH lowering action of polylactic acid in the intestinal tract Weight average molecular weight 500, 1,330, 2,700, 5,
300 and 11,600 polylactic acids were added in 5
% (W / V) of a polylactic acid solution suspended in a physiological saline solution and human feces suspended in a physiological saline solution of 10% (W / V) in equal amounts of 1 ml each. Mix,
After adjusting the pH to 6 to 6.3, each sample solution was incubated at 37 ° C. for 24 hours under nitrogen gas. After the incubation, the pH of each sample solution was measured (Table 1). In all of the sample solutions to which polylactic acid was added, a decrease in pH was observed.

Example 2 Weight average molecular weight 1,330
100 g of each of 2,700, 5,300, and 11,600 polylactic acids, 100 g of lactose as an excipient,
And 0.5 g of magnesium stearate as a lubricant
Are added, and the mixture is stirred and mixed, and then tableted.
0 pieces were obtained.

Example 2 Weight average molecular weight 1,330
0.1 g of magnesium stearate as a lubricant was added to 100 g of each of 2,700, 5,300, and 11,600 polylactic acids, and after stirring and mixing, 1 capsule was added to the Japanese Pharmacopoeia capsule (# 1). Each capsule was filled with 0.4 g to obtain 250 capsules.

[0021]

[Table 1] * Physiological saline

[0022]

EFFECT OF THE INVENTION The polyhydroxycarboxylic acid for oral ingestion according to the present invention has an excellent direct intestinal pH lowering action, acidifies the pH of intestinal flora (microflora) and intestinal digestion, It is considered to have an effect of suppressing the growth of intestinal harmful bacteria such as Escherichia coli and Proteus bacteria. The polyhydroxycarboxylic acid for oral ingestion according to the present invention, when taken orally, makes the pH in the intestinal tract acidic, suppresses the absorption of toxic substances (eg, ammonia, amines, etc.) from the intestinal tract, and further intestinal peristalsis. Is also considered to have the effect of reducing the risk of carcinogenesis in the intestinal tract and the like and the occurrence of adult diseases by promoting bowel movement.

In contrast to the case where lactic acid which is a known intestinal medicine is taken, it is absorbed in the upper part of the intestine and cannot reach the lower part of the intestine. It reaches the lower intestine as a polymer or an oligomer, and is decomposed by intestinal bacteria and the like into lactic acid for the first time in the lower intestine, and is considered to have an effect of promoting a decrease in pH of the lower intestine such as the large intestine.

[0024] Various lactic acid bacteria preparations and oligosaccharide preparations which are known intestinal preparations are in contrast to having only an indirect action of promoting the useful bacteria in the intestinal tract and increasing the amount of lactic acid secreted by the useful bacteria. In addition, the polyhydroxycarboxylic acid for oral ingestion according to the present invention has a direct effect of directly producing lactic acid in the intestinal tract and lowering the pH in the intestinal tract. As described above, the polyhydroxycarboxylic acid for oral ingestion according to the present invention has an excellent intestinal action, is highly safe, and contributes to health promotion and disease prevention for a comfortable life. is there.

Claims (10)

[Claims] 1. A polyhydroxycarboxylic acid for oral ingestion, which has an intestinal action. 2. A weight average molecular weight of 1,000 to 50,
2. The polyhydroxycarboxylic acid for oral ingestion according to claim 1, which is 000. 3. The polyhydroxycarboxylic acid for oral ingestion according to claim 1, which comprises at least a part of a polymer obtained by polymerizing an α-hydroxycarboxylic acid. 4. The polyhydroxycarboxylic acid for oral ingestion according to claim 1, comprising a polymer obtained by polymerizing a hydroxycarboxylic acid containing at least a part of α-hydroxycarboxylic acid. 5. The polyhydroxycarboxylic acid for oral ingestion according to claim 3, wherein the α-hydroxycarboxylic acid is lactic acid. 6. A food additive comprising the polyhydroxycarboxylic acid for oral ingestion according to claim 1 as an active ingredient for intestinal regulation. 7. A food to which the food additive according to claim 6 is added. 8. A beverage to which the food additive according to claim 6 is added. 9. A feed to which the food additive according to claim 6 is added. 10. An intestinal preparation comprising the polyhydroxycarboxylic acid for oral ingestion according to claim 1 as an active ingredient for intestinal action.