JP2007308428A - Feeding deterrent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a feeding deterrent composition, and to provide a feeding deterrent in the form of a medicament having feeding deterrent effect. <P>SOLUTION: The feeding deterrent composition contains equol as active ingredient. The feeding deterrent comprises equol, wherein the equol is (+)-equal and/or (-)-equol. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to an antifeedant.

In the present age of satiety, obesity and the accompanying deterioration of appearance, increased mental stress, decreased social evaluation and self-evaluation, etc., are the causes of lowering the QOL of obese people. In addition, according to the results of epidemiological surveys, it has been clarified that obese people are reduced not only to the person themselves but also to other people's appreciation. The first cause of obesity is excessive intake of energy, and it is difficult to properly control the amount of food intake especially in obese people.
For obesity and social and mental problems associated with it, obesity needs to be improved. Dietary therapy that lowers dietary energy intake is the primary choice, but the amount consumed is appropriate. It is difficult to control, and so-called rebound occurs. In order to solve this situation, drugs that suppress eating are being developed. As drugs having anorectic effect, the effects of amphetamine and methamphetamine used as stimulants are known, but they are not suitable for clinical use because of their excitability and dependence. Moreover, as a thing with the same effect, the invention (patent document 1: Unexamined-Japanese-Patent No. 2000-143506) which discovered that the psychotropic drug phenylalkylamine derivative has an appetite suppression effect, N-piperonyl-1,2, Appetite suppressant containing 3,4-tetrahydrobenzo [b] thieno [2,3-C] pyridine-3-carboxamide as an active ingredient (Patent Document 2: Japanese Patent Laid-Open No. 7-145054), separated from hiratake historical entity An appetite suppressant that utilizes such ingredients (Patent Document 3: Japanese Patent No. 2965284). However, these effects are still not sufficient.

JP 2000-143506 A JP 7-145054 A Japanese Patent No. 2965284 JP 2005-232074 A

  An object of the present invention is to develop a drug having an antifeedant action.

  The present inventors have completed the present invention by finding that the amount of food intake can be effectively reduced when an equol, an isoflavan, is orally ingested.

The main configuration of the present invention is as follows.
(1) An eating inhibitor comprising equol as an active ingredient.
(2) The equol is (+) equol and / or (−) equol.
(3) The antifeedant according to (1) or (2), which is an oral or enteral administration agent.
(4) The feeding inhibitor according to any one of (1) to (3), wherein equol is contained in an amount of 0.015% by weight or more per solid weight.
(5) Animal feed to which an antifeedant according to any one of (1) to (4) is added.

  It was confirmed that the amount of food intake was reduced by administration of equol. Therefore, this invention has an antifeeding action and can provide an antifeedant. In addition, as a form of oral intake, it can be used as human and veterinary drugs, or quasi drugs, food additives, and animal feed additives. Moreover, it can utilize as an enteral nutrient as one form of enteral ingestion.

Ecole is a kind of isoflavan and is a compound represented by Chemical Formula 1. This is known to be produced by intestinal bacteria and used by humans when humans ingest daidzein, a kind of isoflavone. However, so-called equol producers, in which equol is detected in the blood when ingesting daidzein or its glycoside derivatives, etc., are about 50% of Japanese, and in non-equol producers daidzein or its Ingestion of derivatives does not produce equol. That is, taking equol from the outside is the only means of taking equol.
Conventionally, it has been known that a specific equol content is effective as a preventive and / or therapeutic agent for osteoporosis (Patent Document 4: JP 2005-232074 A). However, it has not been known that when equol is ingested orally, it has an antifeedant effect.

（化学式１）

(Chemical formula 1)

Ecole is a compound having optical activity. In the present invention, any of (+) equol, (−) equol, racemate, and a mixture thereof can be used.
In addition, the origin of equol used in the present invention is not particularly limited, and all of the commonly used chemical synthesis methods, enzyme synthesis methods, microbial synthesis methods, extraction from natural products, and the like can be used. As a method using chemical synthesis, for example, it can be produced by the following method. By reducing the aldol condensate of 4-hydroxyphenyllactic acid and 2,4-hydroxybenzaldehyde, only the benzyl position of the resulting diol is hydrolyzed selectively, and this is subjected to an intramolecular ring-closing reaction (± ) Synthesize equol. In addition, (+) equol and (-) equol are synthesized by conducting an asymmetric aldol reaction in which Evans's asymmetric inducer is introduced into 4-hydroxyphenyl lactic acid. Moreover, as a method using the microorganism synthesis method, there is a method shown in JP-T-2006-504409. That is, the first composition containing an isoflavone that can be converted to (−) equol is cultured for a sufficient time with a microorganism that can be converted to (−) equol, and the microorganism is selectively inactivated to (−) equol. Can be manufactured.

The present invention is an antifeedant containing equol as an active ingredient. As for equol, (+) equol and (−) equol are particularly effective. It is preferable that equol contains 0.015% by weight or more as an active ingredient per solid weight.
The antifeedant of the present invention can be used for human and veterinary drugs, quasi drugs, and food additives. Or it can be set as the additive for animal feed.
When used as a medicine, there is no limitation as long as it is in a form that can be absorbed from the digestive tract, mainly the intestinal tract, such as a medicine intended for oral intake for humans, pets, and livestock animals, or enteral nutrition. . For example, the administration route of the present invention may be processed into a form such as tablet, syrup, granule, powder, soft capsule, hard capsule, enteral nutrition, etc. The method is not limited. These various preparations are usually used in the pharmaceutical preparation technical field such as excipients, binders, disintegrants, lubricants, flavoring agents, solubilizers, suspension agents, coating agents, etc. Can be formulated using known adjuvants.
The amount used varies depending on symptoms, age, body weight, and dosage form, but it is usually desirable to administer 30-50 mg per day for oral administration to adults. The content of the active ingredient is not particularly limited, but it is preferable to contain equol as an active ingredient in an amount of 0.015% by weight or more per solid weight.

The effect is confirmed by the following test, and an Example is shown. The present invention will be described in more detail by way of examples, but the present invention is not limited to these examples.
Twenty-four 6-week-old female SD rats obtained from Japan SLC Co., Ltd. are individually stored in a stainless steel gauge in a 12-hour light / dark cycle (light period 3: 00-15: 00) at room temperature 23 ± 1 ° C. Raised.
After the experimental animals were brought in, they were fed with a commercial solid feed for 2 days, acclimated to the breeding environment, and then subjected to ovariectomy (OVX) under Nembutal anesthesia (Pentobarbital Sodium Salt; Abbot Laboratories, North Chicago, USA) After the operation, a commercial chow was given for 5 days. After confirming sufficient recovery, the 6 animals were divided into 3 groups each fed with a control feed (group C), (+) equol feed (E + group), and (−) equol (E− group) feed. Feed and drinking water were given ad libitum and raised for 4 weeks. Dissection was performed on the 28th day of breeding. Food intake and body weight were measured daily during the breeding period.
Table 1 shows the feed composition.

Fig. 1 shows the amount of food consumed by OVX rats fed each feed.
As shown in FIG. 1, the intake of (+) equol and (−) equol effectively reduced food intake.

FIG. 2 shows the weight gain of OVX rats fed each diet.
As shown in FIG. 2, ingestion of (+) equol and (−) equol effectively suppressed body weight gain.

Twenty-four 6-week-old female SD rats obtained from Japan SLC Co., Ltd. are individually stored in a stainless steel gauge in a 12-hour light / dark cycle (light period 3: 00-15: 00) at room temperature 23 ± 1 ° C. Raised. After the experimental animals were introduced, they were fed with a commercially available solid feed for 7 days and acclimated to the breeding environment. E-group) Divided into 4 groups fed feed. Feed and drinking water were given ad libitum and raised for 4 weeks. Dissection was performed on the 28th day of breeding. Food intake and body weight were measured daily during the breeding period.
Table 1 shows the feed composition.

Fig. 3 shows the amount of food consumed by normal rats fed each feed.
As shown in FIG. 3, ingestion of (+) equol and (−) equol effectively reduced food intake.

FIG. 4 shows the weight gain of normal rats ingesting each diet.
As shown in FIG. 4, ingestion of (+) equol and (−) equol effectively suppressed body weight gain.
Next, in order to verify whether or not the above test result is due to the influence of rat preference (taste), the following test was performed.

  Twenty-four 6-week-old female Wistar rats obtained from Japan SLC Co., Ltd., individually in a stainless steel gauge at room temperature 23 ± 1 ° C and 12 hours light / dark cycle (light period 3: 00-15: 00) Raised. After carrying in the experimental animals, the animals were bred with control feeds and acclimated to the breeding environment, and then divided into 2 groups, each containing 9 control feeds (Group C) and (±) equol feed (Group E). Feed and drinking water were ad libitum, reared for 3 days and habituated to the taste of each feed. Thereafter, a control feed and an equol feed were simultaneously given to each group and allowed to freely ingest, and the intake of each feed was measured for 3 days. Note that (±) equol, (+) equol, and (−) equol affect the taste.

Table 2 shows the feed composition.

FIG. 5 shows the intake of each diet for 3 days after the rats were accustomed to the control and equol diets.
When the rats were accustomed to the control diet (comparison between black circles and white circles), the intake of the equol diet after 3 days was almost the same as that of the control diet.
Even when rats were accustomed to the equol diet (comparison between black triangle and white triangle), the intake of the equol diet after 3 days exceeded the control diet.
From this, it became clear that the suppression of eating by equol is not due to the taste of equol.

The average value of the amount of food intake in each week of OVX rats fed each diet is shown. Diamonds indicate control, black triangles indicate (+) equol, and white triangles indicate (−) equol. Moreover, the alphabet in a graph shows that there exists a significant difference by the multiple comparison method of Tukey between the groups which do not have the same symbol. It represents the weight gain of OVX rats fed each diet. C represents control, E (+) represents (+) equol, and E (-) represents (-) equol. Moreover, the alphabet in a graph shows that there exists a significant difference by the multiple comparison method of Tukey between the groups which do not have the same symbol. The average value of the amount of food intake of each normal rat fed each diet is shown. Diamonds indicate control, black triangles indicate (+) equol, and white triangles indicate (−) equol. Moreover, the alphabet in a graph shows that there exists a significant difference by the multiple comparison method of Tukey between the groups which do not have the same symbol. It represents the weight gain of normal rats fed each diet. C represents control, E (+) represents (+) equol, and E (-) represents (-) equol. Moreover, the alphabet in a graph shows that there exists a significant difference by the multiple comparison method of Tukey between the groups which do not have the same symbol. It represents the intake of each diet for 3 days after the rats are accustomed to the control and equol diets. (A) The black circle is the intake of the control feed after the acclimation of the control feed, (b) The white circle is the intake of the equol feed after the acclimation of the control feed, (c) The black triangle is the intake of the control feed after the acclimation of the equol feed, (D) White triangles indicate the intake of equol feed after acclimatization. The “*” mark indicates that there is a significant difference by the Tukey multiple comparison method with respect to the control feed intake (black circle) after acclimatization of the control feed.

Claims (5)

An antifeedant comprising equol as an active ingredient. The eating inhibitor according to claim 1, wherein the equol is (+) equol and / or (-) equol. 3. The antifeedant according to claim 1 or 2, which is an oral or enteral administration agent. The feeding inhibitor according to any one of claims 1 to 3, comprising 0.015% by weight or more of equol per solid weight. Animal feed to which an antifeedant according to any one of claims 1 to 4 is added.

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