JP2004026839A - Composition for inhibiting ulcerative colitis - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain an ulcerative colitis-inhibiting composition including high amylose starch (HAS) as an effective ingredient because HAS inhibits incidence of ulcerative colitis and has therapeutic effects. <P>SOLUTION: This chronic ulcerative colitis-inhibiting composition comprises the high amylose starch (HAS) as an effective ingredient. The high amylose starch content is preferably 10-50 wt.% based on the composition and the composition is used preferably in the form of a stick or wafer food. The composition is continuously taken at a dose of 10-70 g/day for an adult. The high amylose starch has better palatability and taste than dietary fibers and can be much ingested continuously and can prevent and treat ulcerative colitis. <P>COPYRIGHT: (C)2004,JPO

Description

The present invention relates to a composition capable of suppressing ulcerative colitis, particularly a food composition. In the present invention, high amylose starch (hereinafter, referred to as “HAS”) is contained as an active ingredient capable of suppressing ulcerative colitis.

An inflammatory disorder of the large intestine of unknown origin is ulcerative colitis, which mainly affects its mucous membrane diffusely and is often accompanied by numerous erosions and ulcers. This ulcerative colitis has been a relatively common disease in Europe and the United States, but has recently been increasing gradually in Japan. The cause may be related to changes in diet and lifestyle, but has not yet been confirmed.
Therefore, treatment of ulcerative colitis is performed with conservative therapy rather than with causative therapy. In general, conservative therapy consists in sedating the acute activity phase as soon as possible and maintaining a stable phase. In most cases, conservative therapy is the first principle.

It is said that it is better to give a low-residue diet as much as possible during the acute activity period, paying attention to nutrition. Until now, nutritional management for inflammatory bowel diseases such as ulcerative colitis has been mainly performed by central parenteral nutrition, and component nutrition or low-residue diet has been encouraged as enteral nutrition. However, when the inflammatory bowel disease enters a stable period, it is necessary to determine whether a low-residue diet is effective as an enteral nutrition or whether a diet supplemented with dietary fiber is good for suppressing recurrence. The effect on the colonic mucosa differs depending on the type of intestine, and it has not yet been determined which dietary fiber is better (Non-Patent Document 1).
At present, the intake of dietary fiber is decreasing with changes in dietary habits, but recently, the influence of dietary fiber on the digestive tract and metabolism is being reviewed. However, dietary fiber has different physiological actions depending on its type, and not only does not provide the expected effect, but also worsens in some cases. In addition, it may be necessary to consume a large amount in order to show the effect, and it is not preferred by the user because the texture, taste and color are inferior, and it is difficult to take for a long time because the quality as food is low There are also problems.

On the other hand, recently, starch having a high amylose content called HAS has been developed and attracted attention. So-called HAS is known to impart desirable properties to various compositions such as films, foods, and industrial products. For example, it is known that HAS is used as a sausage skin, sugar confectionery, food with increased gel strength, a film having excellent gas barrier properties when laminated with a polymer such as polyethylene vinyl alcohol, and the like (Patent Document 1). ). Further, it has been proposed to mix HAS with ordinary starch and extrude and granulate it into a low-protein rice-like food for kidney patients and the like who require foods from which protein has been removed as much as possible. (Patent Document 2).
WO 94/03049 JP-A-64-37262 Journal of Japanese Society for Parenteral and Enteral Nutrition Vol. 8, February 1993

In view of the above-mentioned present state of colitis therapy, the present inventors have searched for an ulcerative colitis inhibitor, and have also studied HAS, which inhibits and treats ulcerative colitis. It has an effect. Therefore, an object of the present invention is to provide a composition for suppressing ulcerative colitis.

That is, the present invention relates to an ulcerative colitis inhibitory composition obtained by blending HAS with various materials, particularly food materials, as an active ingredient for suppressing the development of ulcerative colitis and treating it. The composition of the present invention can be formed into various forms and eaten easily on a daily basis.
Hereinafter, the present invention will be described in detail.

HAS is a general term for starch having a high amylose content, and HAS containing amylose in an amount of 40 to 90% by weight, preferably 50 to 90% by weight, and more preferably 70 to 90% by weight is used. In addition, HAS is a different substance from dietary fiber, and the total dietary fiber quantification method of Prosky et al., Which is used as one of the methods for quantifying dietary fiber, is the journal of Association of Official Analytical Chemistry. Analytical chemists 71 , (5), 1017 (1988)), and HAS which shows 25 to 40% by weight when an indigestible component is obtained is preferred. The raw material of such HAS is not particularly limited, and examples thereof include raw plant starch such as corn, potato, rice, wheat, and beans, starch decomposed products, and mixtures thereof. It originally contains starch with a high amylose content as well as mutants. Further, it can be preferably produced from hybrid corn as described in WO 94/03049 (Patent Document 1).
HAS is known to impart desirable physical properties to various industrial products as described above, but it has not been known that HAS has an ulcerative colitis inhibitory action.
However, according to the study of the present inventors, a food composition in which the above-mentioned HAS is blended with other food materials, and HAS accounts for 10 to 50% by weight, preferably 20 to 40% by weight of the ingestible food. It has been found that when the adult is continuously taken 10 to 70 g, preferably 20 to 40 g per day, onset, suppression, and therapeutic effect of ulcerative colitis are observed.
In the present invention, the food material in which HAS is blended is not particularly limited, and other sugars, lipids, proteins, and if necessary, other additives such as vitamins and minerals are added to the HAS-containing food material. It can be a food composition.
Such well if HAS-containing composition is easy to intake form, usually of food form as is, for example, cookies, breads, cakes, block confectionery such as Calorie Mate ^TM, wafer confectionery, sticks confectionery, dairy products, drink And various foods such as miso, etc., and into a so-called health food form in the form of tablets, lumps, liquids, syrups, granules, and powders using, for example, appropriate fillers and excipients. I can do it.
HAS is superior in texture, taste, color, and the like to dietary fiber, so that a composition containing the same can be ingested in large amounts for a long period of time, and suppresses and treats the development of ulcerative colitis. be able to.

潰 The ulcerative colitis inhibitory effect of HAS in the present invention will be described in detail based on test examples.

Test example 1

Sprague-Dawley male rats (7 weeks old) were preliminarily reared for 7 days on a standard diet using carbohydrate as a source of normal corn starch (hereinafter, referred to as CS). Each group consisted of 12 animals.
The HAS used was Hi-Maize ^™ (manufactured by Starch Australasia, with an amylose content of about 70% by weight).
The rats were transanally administered with 30 mg of 2,4,6-trinitrobenzenesulfonic acid (TNB) dissolved in 0.25 ml of 50% by weight ethanol to induce colitis (Gastroenterology 96, 795-803 (1989). )). The untreated group received only 0.25 ml of physiological saline instead of TNB.
From the day after the administration of TNB, 15% by weight or 30% by weight of HAS was added to the CS diet, or 8.3% by weight of beet dietary fiber was added to the CS diet.
fiber) (hereinafter, referred to as BDF) was allowed to freely ingest BDF feed with water for 2 weeks.
The untreated group was fed a standard feed. Table 1 shows the composition of the standard feed HAS feed and the BDF feed.

* AIN-76組成（ジャアナル オブ ニュートリション(Journal of Nutrition 107 、1340)) に準じた。

* Based on AIN-76 composition (Journal of Nutrition 107 , 1340).

Each sample was sacrificed 2 weeks after TNB administration, and each sample was examined for macroscopic findings (macro score 1-5) of colon tissue at necropsy, total myeloperoxidase activity in colon tissue, and serum transglutaminase activity. . Macroscopic observation of colon tissue was performed according to the method of Morris et al. (Gastroenterology 96 , 795 (1989)), and myeloperoxidase activity was determined by Krawisz et al. (Gastroenterology 87 , 1344, (1984)). The serum transglutaminase activity was measured according to the method of Jaanal of Clinical Gastroenterology 12 , 400, (1990) Student's t-test was used for the significance test.
(1) Macroscopic findings As shown in FIG. 1, evaluation was performed according to the following macro score criteria. As a result, the ulcer of the colon tissue at the time of necropsy was improved by about 35% in the 30% HAS diet group compared to the standard diet group. And a statistically significant difference (p <0.05) was observed between the two groups.
Macroscopic score evaluation criteria 0 No abnormality 1 Local hyperemia (no ulcer) is observed 2 Linear ulcer (no obvious inflammatory reaction) is observed 3 Ulcer with inflammatory reaction is observed only in one place Yes 4 Ulcers or inflamed areas are observed in 2 or more places 5 Both ulcers and inflammation are observed in a relatively large area in 2 or more places or large ulcers extending 1 cm or more along the longitudinal direction of the rectum In addition, as shown in Table 2 and FIG. 2, the body weight gain and feed intake of rats after ingestion of each test feed for 2 weeks are significantly higher in the untreated group, as shown in Table 2 and FIG. Although values were shown, no difference was observed in the amount of increase in body weight and feed intake between the test groups to which TNB was administered.

(2) ミエロペルオキシダーゼ活性
　炎症マーカーである全大腸組織中のミエロペルオキシダーゼ活性量は、図３に示されるようにＴＮＢ無処置群を除き、３０重量％ＨＡＳ飼料群で最も低値（ＣＳ飼料群に対し約４０％の減少、ｐ＜０．０５）を示した。また、１５重量％ＨＡＳおよび８．３重量％ＢＤＦ飼料群においてもＣＳ飼料群に対し、それぞれ約１８％および２２％の活性量の低下が認められた。
(3) 血清中のトランスグルタミナーゼ活性
　D'Argenio らは血清中のトランスグルタミナーゼ活性と潰瘍性大腸炎による傷害の程度との間には明らかな逆相関関係が認められると報告している（ジャアナル・オブ・クリニカル・ガストロエンテロロジイ(J.Clin.Gastroenterology 12 400 (1990) およびスカンジナビアン・ジャアナル・オブ・ガストロエンテッロジイ(Scand.J.Gastroenterol) 27、111 (1992)）。従って、血清中のトランスグルタミナーゼ活性は、潰瘍性大腸炎の状態を把握する上でよい指標になり得るものと考えられる。
　結果は図４に示すように、３０重量％ＨＡＳ飼料群の活性はＣＳ飼料群に比べ約１．８倍上昇しており、両群間の活性には差が認められた（ｐ＜０．０５）。また３０重量％ＨＡＳ飼料群とＴＮＢ無処置群間の活性に差はなかった。一方、１５重量％ＨＡＳおよび８．３重量％ＢＤＦ飼料群の血清トランスグルタミナーゼ活性においてもＣＳ飼料群に対し、それぞれ1.5 倍、1.4 倍の活性値の上昇が認められた。　これらの実験結果から、ＨＡＳは潰瘍性大腸炎に対し組織学的な改善作用を示すだけでなく、炎症の抑制作用、また潰瘍性大腸炎の診断マーカーとなりうる血清トランスグルタミナーゼ値の改善作用をも有することが明らかになった。一方、食物繊維であるＢＤＦには改善作用は認められず、炎症マーカー、血清トランスグルタミナーゼ値においても有意な改善効果は認められなかった。

(2) Myeloperoxidase activity The myeloperoxidase activity in the whole colon tissue, which is an inflammatory marker, was the lowest in the 30 wt% HAS diet group (except for the CS diet group), except for the TNB untreated group, as shown in FIG. About 40% reduction, p <0.05). Also, in the 15 wt% HAS and 8.3 wt% BDF feed groups, the activity levels were reduced by about 18% and 22%, respectively, compared to the CS feed group.
(3) Serum transglutaminase activity D'Argenio et al. Reported that there was a clear inverse correlation between serum transglutaminase activity and the degree of injury caused by ulcerative colitis (Janar, J. Clin. Gastroenterology 12 400 (1990) and Scandinavian Juanal of Gastroenterolii (Scand. J. Gastroenterol) 27 , 111 (1992). It is thought that the transglutaminase activity of can be a good index for understanding the state of ulcerative colitis.
As shown in FIG. 4, the activity of the 30% by weight HAS diet group was about 1.8 times higher than that of the CS diet group, and a difference was observed in the activity between the two groups (p <0. 05). In addition, there was no difference in the activity between the 30% by weight HAS diet group and the TNB untreated group. On the other hand, the serum transglutaminase activity of the 15 wt% HAS and 8.3 wt% BDF feed groups also showed 1.5-fold and 1.4-fold increase in the activity value compared to the CS feed group, respectively. From these experimental results, HAS not only has a histological improvement effect on ulcerative colitis, but also has an inhibitory effect on inflammation and an effect on improving serum transglutaminase level which can be a diagnostic marker for ulcerative colitis. It became clear to have. On the other hand, BDF, which is a dietary fiber, had no improving effect, and no significant improving effect was observed on the inflammatory marker and serum transglutaminase level.

Test example 2

Two types of biscuits having the compositions shown in Table 3 and having almost the same indigestible components obtained by the total dietary fiber determination method were prepared according to a conventional method. A sensory test was performed on the obtained biscuit for 20 panelists. The test items were three items of color, taste, and texture, and a preferable one was selected for each item. Thereafter, the test was performed based on the test table of the two-point preference test method.
The dietary fiber content was calculated from the Japanese dietary fiber component table (edited by the Science and Technology Agency Resource Research Committee).
Also, Hi-Maize ^™ was used as the HAS.

　得られた試験結果を表４に示した。

Table 4 shows the obtained test results.

As shown in Table 4, biscuits containing HAS (Hi-maize) were better in color, taste, and texture, and the texture was particularly favored for the biscuits in the test plot (containing Hi-maize) compared to the control plot. Results were obtained.
The indigestible component in the wheat bran was quantified based on the method of Prosky et al.

以下、実施例をあげて本発明を具体的に説明する。

Hereinafter, the present invention will be described specifically with reference to examples.

 An equivalent amount of a 5% by weight aqueous solution of corn starch is added to HAS powder, kneaded with a kneader, granulated into granules of about 300 μm, dried with warm air to obtain a product in the form of granules useful for the prevention and treatment of ulcerative colitis. Obtained.

An equivalent amount of corn starch is added to HAS powder, and a small amount of lactose is further added as an excipient, and the mixture is molded using a tableting machine by a conventional method to form a tablet-form product useful for the prevention and treatment of ulcerative colitis. Obtained.

To a mixture of 160 parts by weight of flour, 4 parts by weight of salt, and 10 parts by weight of HAS powder, 32 parts by weight of water is added and kneaded. The obtained noodle dough is rolled by a noodle band machine, cut into noodle strings by a cutting machine and dried, and then dried. Noodles with noodles were obtained.

80 parts by weight of flour and 80 parts by weight of HAS powder are mixed with 40 parts by weight of butter and 75 parts by weight of sugar, 50 parts by weight of egg and 10 parts by weight of milk are added, kneaded well, molded, and baked at 170 ° C. for 12 to 15 minutes. To obtain a biscuit containing HAS powder.

Mix 24 parts by weight of vegetable margarine and 18.5 parts by weight of sugar, add eggs, add 22 parts by weight of HAS powder, 16 parts by weight of flour, 12 parts by weight of protein component, and a small amount of vitamin mix, knead and add vanilla extract. It was molded and baked at 150 ° C. for about 20 minutes to obtain a block confection containing the HAS powder.

100 parts by weight of tuna meat and 3 parts by weight of salt are added and kneaded, and 30 parts by weight of HAS powder, 1 part by weight of sugar and a small amount of sodium glutamate, starch, spice, preservative, wood vinegar, vitamin A, etc. are added. Shortening oil was added, the casing was filled and sealed, immersed in hot water at 85 to 88 ° C. for 50 minutes for heat sterilization, and cooled to obtain a fish sausage containing HAS.

45 parts by weight of unsalted butter and 45 parts by weight of salted butter are mixed with 70 parts by weight of sugar, eggs are added, 110 parts by weight of HAS powder and 25 parts by weight of gluten are cut and mixed, matured, and baked at 180 ° C. for 15 to 20 minutes. To obtain a cookie with HAS.

１２ 12 parts by weight of rice was absorbed by a conventional method, boiled, allowed to cool, and then sprinkled with seed koji for miso to make koji. 30 parts by weight of soybeans were steamed, 20 parts by weight of HAS powder and seed water were mixed, and the mixture was choppered. This was put in a fermentation tank and brewed warm at 26-28 ° C. for about 75 days, followed by miso straining to obtain HAS-containing miso.

10 parts by weight of HAS powder was added to 100 parts by weight of durum flour, a small amount of egg, and 3 to 4 parts by weight of salt, and the mixture was stirred and kneaded to prepare a dough, which was appropriately shaped into flakes to obtain a raw pasta having a water content of about 30%. . This raw pasta was stuffed with meat, cheese, vegetables and the like as a stuffing, or was packaged by heating at about 100 ° C. for 2 minutes without using the stuffing to obtain a pasta with preservability.

(3) 3 parts by weight of HAS powder and 97 parts by weight of flour are mixed, and 6 parts by weight of sugar, 2 parts by weight of sodium chloride, and 5 parts by weight of shortening are added, and kneaded while further adding 68 parts by weight of water. Dissolve 2 parts by weight of yeast in 6 parts by weight of water, add well, knead well, ferment the obtained dough at about 27 ° C for 2 hours, degas, and continue fermentation to obtain an appropriate size. Divided. This was proofed, put in a mold, and roasted at 200 to 280 ° C to obtain a bread containing HAS.

１００ Softly knead 100 parts by weight of butter, 75 parts by weight of sugar, and add egg yolk. Egg whites were mixed with meringue to which 25 parts by weight of sugar was added, and 50 parts by weight of flour and 50 parts by weight of HAS powder were added and kneaded. It was placed in a mold and baked at 170 ° C. for 15 to 18 minutes to obtain a Madeleine containing HAS.

(4) When 100 parts by weight of cream cheese was smoothed by boiling in water, 16 parts by weight of milk, 15 parts by weight of sugar, 10 parts by weight of corn starch, 10 parts by weight of HAS powder, egg yolk and lemon juice were added. Egg whites were whipped and kneaded with meringue to which 15 parts by weight of sugar was added, and the mixture was baked at 180 ° C. for about 30 minutes to obtain a cheese cake containing HAS.

HAS clearly has an ulcerative colitis inhibitory action as described above, and by eating a composition obtained by blending it with other food materials as various forms of food, ulcerative colitis can be obtained. It can treat or prevent inflammation, especially chronic ulcerative colitis. Further, HAS has a better texture, taste, and color than dietary fiber, so that a food containing the same can be ingested in the same manner as ordinary food, and can be ingested in large quantities or for a long time.

1 shows macroscopic findings of the large intestine of Test Example 1 (macro score; 0 to 5). 3 shows changes in body weight of rats during administration of each test feed of Test Example 1. 3 shows the myeloperoxidase activity after administration of each test feed of Test Example 1. 3 shows serum transglutaminase activity after administration of each test feed of Test Example 1.

Claims (1)

A composition for suppressing chronic ulcerative colitis, comprising high amylose starch as an active ingredient.

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