JP2011236239A - Gip secretion inhibitor - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a GIP (gastric inhibitory polypeptide) secretion inhibitor useful for medicines or foods.SOLUTION: A postprandial GIP secretion inhibitor having a hydroxypropylated starch as an active ingredient is provided.

Description

  The present invention relates to a GIP secretion inhibitor useful as a medicine or food.

  Gastric inhibitory polypeptide (GIP) is a gastrointestinal hormone having gastric acid secretion inhibitory action and gastric motility inhibitory action, and it is known that its secretion is enhanced by dietary lipids and the like during feeding (non-patent) Literatures 1-3). Therefore, it is considered that a substance that inhibits GIP secretion is useful for promoting digestion and improving stomach sag. As a result of research so far, 3-bromo-5-methyl-2-phenylpyrazolo [1,5-a] pyrimidin-7-ol (BMPP) is known as a substance that inhibits the function of GIP. Gua gum etc. are known as what suppresses the secretion of (patent document 1, nonpatent literatures 4-9). However, the former substance has not been confirmed to have an inhibitory effect on GIP function in vivo, and the latter substance has a problem that the effect of suppressing GIP secretion upon intake of lipids has not been studied. However, it is not necessarily sufficient in terms of the above.

Alginate, on the other hand, is a high molecular acidic polysaccharide (molecular weight: tens of thousands to hundreds of thousands) composed mainly of uronic acid (D-mannuronic acid and L-guluronic acid) distributed as an intercellular substance in all brown algae. As its physiological action, cholesterol lowering action, postprandial blood glucose rise inhibiting action, constipation improving action and the like have been reported (Non-Patent Documents 10 to 13). Further, hydroxypropylated starch is known to have an anti-obesity effect, an effect of improving constipation, and the like, in addition to being used as, for example, a texture improving agent (Patent Documents 2, 3, and 4).
However, the relationship between these substances and GIP has not been known.

International Publication No. 01/87341 Pamphlet JP 2004-315405 A JP 2004-269458 A JP 2005-27643 A

J.C.Brown et al., Canadian J Physiol Pharmacol 47: 113-114, 1969 J. M. Falko et al., J Clin Endocrinol Metab 41 (2): 260-265, 1975 Toshiji Oda et al., Gastrointestinal function and pathology, 1981, Chugai Medical, P205-216 Gagenby S J et al., Diabet Med. 1996 Apr; 13 (4): 358-64 Ellis PR et al., Br J Nutr. 1995 Oct; 74 (4): 539-56 Simoes Nunes C et al., Reprod Nutr Dev. 1992; 32 (1): 11-20 Morgan LM et al., Br J Nutr. 1990 Jul; 64 (1): 103-10 Requejo F et al., Diabet Med. 1990 Jul; 7 (6): 515-20 Morgan et al., Br J Nutr. 1985 May; 53 (3): 467-75 Seal, C.J., et al., Br J Nutr. 2001; 85: 317-324. Ohta, A. et al., Int J Vitam Nutr Res 1997; 67 (1): 55-61 Torsdottir, I. et al., J Nutr 1991; 121: 795-799 Anderson, D.M., et al., Food Addit Contam. 1991; 8: 237-48

  An object of the present invention is to provide a GIP secretion inhibitor useful as a medicine or food.

  The present inventors have found that alginates and hydroxypropylated starch used in foods and the like remarkably suppress postprandial GIP secretion and are useful for promoting digestion and improving stomach sag.

  That is, the present invention provides a postprandial GIP secretion inhibitor containing alginic acid or a salt thereof or hydroxypropylated starch as an active ingredient.

  The present invention also provides a food with a label indicating that alginic acid or a salt thereof or hydroxypropylated starch is used as an active ingredient for promoting digestion or improving stomach sag.

  If the GIP secretion inhibitor of this invention is used, GIP after a meal can be reduced, digestion absorption can be accelerated | stimulated and the improvement of stomach sag can be aimed at.

The hydroxypropylated starch of the present invention can be obtained by hydroxypropylating starch or modified starch by a conventional method. Specifically, it can be obtained by reacting propylene oxide with starch.
National Frigex (from tapioca, National Starch and Chemical), National 1658 (from Corn, National Starch and Chemical), Therm Flow (from Waxy Corn, National Starch and Chemical), Thermtex (from Waxy Corn, National Commercial products such as Starch and Chemical Co.) can also be used.

  Examples of the raw material starch include waxy corn starch, corn starch, wheat starch, rice starch, glutinous rice starch, potato starch, sweet potato starch, tapioca starch, and sago starch, and the amylopectin content is 70% by weight or more, preferably 75. It is more preferable that the content is -100%, more preferably 90-100%, because the paste liquid has high transparency, and when applied to foods and drinks, its appearance is not impaired and the application range is widened. Among these, waxy corn starch and tapioca starch are preferable as the raw material starch.

  The “hydroxypropylated starch” in the present invention includes a hydroxypropylated starch obtained by combining other processing treatments. Processing that can be combined includes esterification of acetic acid, octenyl succinic acid, phosphoric acid, etc., etherification by carboxymethyl etherification other than hydroxypropylation, trimetaphosphate, hexametaphosphate, phosphorus oxychloride, adipic acid , Epichlorohydrin and the like, crosslinking treatment using a conventional crosslinking agent, oxidation treatment, acid treatment, bleaching treatment, wet heat treatment, heat treatment, enzyme treatment, etc. may be mentioned, of which one or more of them may be combined good. Of these, esterification treatment is preferred, and phosphorylation treatment, particularly phosphoric acid crosslinking treatment is preferred. As the degree of phosphorylation treatment, the bound phosphorus content is in the range of 0.0001 to 2%, preferably 0.0001 to 0.5%, more preferably 0.0001 to 0.2%. Is preferred.

  As the degree of hydroxypropylation, the degree of substitution (number of hydroxypropyl groups per anhydroglucose residue in starch) is preferably 0.001 to 1, more preferably 0.05 to 0.5. Yes, and preferably 0.1 to 0.3.

  The hydroxypropylated starch can be produced from starch with high purity and relatively low cost by a simple process. Moreover, it is highly safe and has no sense of incongruity when used in various foods, medicines, pet foods, etc., as compared with conventional dietary fiber and resistant starch. Moreover, since it is excellent in refrigeration resistance, it can have the advantage that alteration by thaw is unlikely to occur.

  Examples of the salt of alginic acid or a salt thereof (hereinafter referred to as alginic acid) used in the postprandial GIP secretion inhibitor of the present invention include alkali metal salts such as sodium salt and potassium salt, and sodium salt is particularly preferable. Alginic acids preferably have a weight average molecular weight measured by a high performance liquid chromatography (HPLC) method of 200,000 or less, preferably 100,000 or less, particularly 40,000 to 80,000.

  And since the hydroxypropylated starch or alginic acid or a salt thereof has a GIP secretion inhibitory effect that there is little GIP in blood after simultaneous intake of saccharides, lipids, and proteins, as shown in Examples below, It can exert effects such as reducing GIP after meals and promoting digestion and absorption. Therefore, the hydroxypropylated starch or alginic acid or a salt thereof of the present invention can be a food or pharmaceutical material for humans or animals as a postprandial GIP secretion inhibitor.

  The postprandial GIP secretion inhibitor of the present invention can be administered to one or more hydroxypropylated starches or alginic acid or a salt thereof alone to humans and animals, and ingested in various foods, medicines, pet foods, etc. Can do. As the food, it can be applied to foods such as beauty foods, foods for sick people, foods for specified health use, etc., which are used for improvement of gastric acid secretion suppression, digestion promotion, stomach sag improvement and the like. When used as a pharmaceutical, for example, oral solid preparations such as tablets and granules, and oral liquid preparations such as oral liquids and syrups can be used.

  When preparing an oral solid preparation, the hydroxypropylated starch of the present invention, alginic acid or a salt thereof, an excipient, and if necessary, a binder, a disintegrant, a lubricant, a colorant, and a corrigent. After adding a flavoring agent, tablets, coated tablets, granules, powders, capsules and the like can be produced by conventional methods. Moreover, when preparing a liquid preparation for oral use, a liquid preparation, a syrup, an elixir, etc. can be manufactured by a conventional method by adding a corrigent, a buffer, a stabilizer, a corrigent and the like.

  The blending amount of the hydroxypropylated starch to be blended in each of the above-mentioned preparations is usually 0.1-100% by weight, preferably 1-80% by weight, more preferably 5-50% by weight. .

  The blending amount of alginic acid or a salt thereof to be blended in each of the above preparations is usually 0.01-100% by weight, preferably 0.1-80% by weight, more preferably 1-50% by weight. .

  The dose (effective intake) of the postprandial GIP secretion inhibitor or food of the present invention is preferably 0.001 g / kg body weight or more per day as alginic acid or a salt thereof, particularly 0.01 g / kg body weight or more, Further, it is preferably 0.05 g / kg body weight or more, and as hydroxypropylated starch, it is preferably 0.01 g / kg body weight or more per day, particularly 0.1 g / kg body weight or more, further 0.4 g / kg. It is preferable to be over body weight.

Test Example 1 GIP Secretion Inhibiting Action of Hydroxypropylated Starch As a hydroxypropylated starch, a commercially available National Frigex (derived from Tapioca, National Starch and Chemical Co.) was used. As a starch to be compared, high amylose corn starch (Phibose, Nissho Chemical Co., Ltd.) was used.
The above starch was suspended in distilled water to 50% by weight, autoclaved (wet heat treatment) at 120 ° C. for 15 minutes, and then freeze-dried to prepare a test starch that was pregelatinized.
Mice (C57BL / 6J male, 6 weeks old) were 8 per group, and using various pregelatinized starch, 2 g of distilled water was added to 1 g of powdered feed prepared with the formulation shown in Table 1 and well dispersed. Mice fasted for 16 hours were orally administered with 0.3 g / 10 g body weight of the dispersion using a sonde needle. After 5 minutes, blood was collected from the abdominal vena cava and plasma was prepared. GIP in plasma was measured by ELISA (General Protocol For EIA Kit, Phoenix Pharmaceuticals Inc.). The blood GIP of mice that were fasted for 16 hours and were not orally administered was determined, and the increase in blood GIP after oral administration was calculated. A similar test was performed again and the results for 16 animals per group are shown in Table 2.

  From the results shown in Table 2, the mice that ingested a diet containing 10% of hydroxypropylated starch (derived from tapioca) had less blood GIP than the mice ingested the diet formulated with high amylose corn starch. It can be seen that a postprandial GIP secretion inhibitory effect is observed.

Test Example 2 GIP secretion inhibitory action of Na alginate Na alginate was obtained from Wako Pure Chemical Industries, Ltd. Mice (C57BL / 6J male, 6 weeks old) were assigned to 9 mice per group, and 2 g of distilled water was added to 1 g of powdered feed prepared with the formulation shown in Table 3 and dispersed well. Mice fasted for 16 hours were orally administered with 0.3 g / 10 g body weight of the dispersion using a sonde needle. After 15 minutes, blood was collected from the abdominal vena cava and plasma was prepared. GIP in plasma was measured by ELISA (General Protocol For EIA Kit, Phoenix Pharmaceuticals Inc.). The results are shown in Table 4.

From the results shown in Table 4, it can be seen that in mice fed with a diet containing 5% Na alginate, there was less GIP in the blood and a postprandial GIP secretion inhibitory effect was observed compared to mice fed a diet containing no alginate Na. Recognize.

Claims (1)

  A postprandial GIP secretion inhibitor comprising hydroxypropylated starch as an active ingredient.