JP2001163791A - Prophylactic and improver for ulcer of digestive tract - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an economically advantageous prophylactic or an improver for ulcer of digestive tract having excellent safety by using sweet potato as a raw material. SOLUTION: This prophylactic or improver for ulcer of digestive tract comprises an essence derived from sweet potato as an active ingredient. The food, the beverage and the health food comprise the essence.

Description

[Detailed description of the invention]

[0001]

TECHNICAL FIELD The present invention relates to an agent for preventing or improving gastrointestinal ulcers containing a cane-derived extract as an active ingredient. The present invention also relates to foods, beverages and health foods for preventing or improving gastrointestinal ulcers containing an effective amount of the cane-derived extract.

[0002]

2. Description of the Prior Art Ulcers arise from a variety of causes. In the case of peptic ulcers, the cause is an imbalance between factors that act destructively on the gastrointestinal mucosa, such as gastric acid, pepsin, bile, and food, and factors that act defensively, such as mucosal blood flow, mucus secretion, and bicarbonate ion secretion. believed to be caused by bankruptcy. Anti-ulcer agents are classified according to their action and broadly classified into inhibitors of aggressive factors and enhancers of protective factors. H2 blockers such as cimetidine and ranitidine and _acid secretion inhibitors such as proton pump inhibitors such as omeprazole are well known as aggressive factor inhibitors. On the other hand, sodium bicarbonate, cetraxate hydrochloride, sucralfate and the like are well known as protective factor enhancers.

[0003] Conventional drug treatments are known to cause side effects, and ulcers that have been healed by drugs often recur after drug withdrawal. A problem remains. Therefore, it is desired to develop an edible composition having an effect of preventing or improving gastrointestinal ulcers in daily diet.

[0004]

DISCLOSURE OF THE INVENTION Accordingly, the present invention provides a substance comprising a plant-derived extract fraction whose safety has been guaranteed over a long period of food experience, and which extract is used as an edible composition or food. It is an object of the present invention to provide a substance that exhibits preventive or ameliorative action on gastrointestinal ulcers by adding it to and ingesting it in daily diet.

[0005]

SUMMARY OF THE INVENTION The inventors of the present invention have prepared sugar cane juice,
Either a solvent extract of cane or molasses derived from cane is passed through a column filled with a synthetic adsorbent, and then eluted from the column with a solvent selected from water, methanol, ethanol, and mixtures thereof. It has been found that a cane-derived extract, which is used for the prevention of gastrointestinal ulcers, is effective in preventing gastrointestinal ulcers. They have also found that adding this sugar cane-derived extract to foods that are ingested on a daily basis makes it possible to prevent gastrointestinal ulcers in daily eating habits, and is also expected to improve them.

[0006] That is, the present invention is a gastrointestinal ulcer preventive or ameliorating agent containing a cane-derived extract as an active ingredient.
In particular, the present invention relates to a gastrointestinal tract containing, as an active ingredient, a cane-derived extract obtained by subjecting a raw material selected from cane juice, a solvent extract of cane, and cane-derived molasses to column chromatography using a fixed carrier. It is an ulcer preventive or ameliorating agent.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION As used herein, the term "effective amount" refers to the agent for preventing or improving gastrointestinal ulcers of the present invention, or the food or drink or health food for preventing or improving gastrointestinal ulcers. , means the amount of cane-derived extract that produces the effect.

[0008] As used herein, the term "cane juice" refers to the pressed juice obtained by squeezing sugarcane, the juice obtained by leaching sugarcane with water, or the purified juice obtained by liming in raw sugar manufacturing plants. Includes juices and concentrated juices.

[0009] In the present specification, "cane solvent extract"
Concentrate the extract obtained by extracting sugar cane with a general-purpose organic solvent,
It means an extract redissolved in water after drying. Examples of such extraction solvents include alcohols such as methanol and ethanol.

[0010] As used herein, the term "cane-derived molasses" means the shaken molasses obtained by centrifuging a mixture of sugar crystals and mother liquor obtained in the crystallization step to separate the sugar crystals. 1st nectar, 2nd nectar, raw molasses at a raw sugar manufacturing plant, and washed molasses, 1st to 7th nectars, and refined sugar molasses at a refined sugar manufacturing plant. In addition, molasses obtained by desugaring can be similarly used, such as the separated liquid obtained by subjecting molasses to alcoholic fermentation.

[0011] In particular, the present invention uses, as an active ingredient, a cane-derived extract obtained by subjecting raw materials selected from cane juice, a solvent extract of cane, and cane-derived molasses to column chromatography using a fixed carrier. It is a gastrointestinal ulcer preventive or improving agent.

[0012] The cane-derived extract used in the present invention is more preferably prepared by adding a raw material selected from cane juice, a solvent extract of cane and molasses derived from cane to a column filled with a synthetic adsorbent as a fixed carrier. It is obtained by passing liquid through and eluting the component adsorbed by the synthetic adsorbent with a solvent selected from water, methanol, ethanol and mixtures thereof.

[0013] More specifically, such a cane-derived extract can be obtained by, for example, the following treatment.

[0014] Cane juice, cane solvent extract or cane-derived molasses is passed through a column using a fixed carrier. The above-mentioned cane juice, cane solvent extract, or cane-derived molasses can be passed through a column filled with a solid carrier as is or after being adjusted to an arbitrary concentration with water. In order to remove foreign matter, it is desirable to filter the cane juice, the solvent extract of the cane, or the molasses derived from the cane prior to the column treatment.
The method of filtration is not particularly limited, and means such as screen filtration, diatomaceous earth filtration, microfiltration, and ultrafiltration, which are widely used in the food industry, can be preferably used.

Synthetic adsorbents are preferred as fixed carriers. As the synthetic adsorbent, an organic resin can be preferably used, for example, an aromatic resin, an acrylic acid-based methacrylic resin, an acrylonitrile aliphatic resin, or the like can be used. Aromatic resins are more preferable, and unsubstituted aromatic resins can be particularly used. Examples of synthetic adsorbents include aromatic resins such as styrene-divinylbenzene resins. Examples of aromatic resins include aromatic resins having hydrophobic substituents and unsubstituted aromatic resins. A porous resin such as an aromatic resin obtained by applying a special treatment to an unsubstituted type can be used. More preferably, a non-substituted aromatic resin that has undergone a special treatment can be used. Such synthetic adsorbents are commercially available, e.g. HP-10, HP-20, HP-2 in the Diaion™ series.
1, HP-30, HP-40, HP-50 (these are unsubstituted aromatic resins, trade names, manufactured by Mitsubishi Chemical Corporation); SP-825, SP-800, SP-85
0, SP-875, SP-70, SP-700 (above,
Aromatic resins that are unsubstituted and have been specially treated, both trade names, manufactured by Mitsubishi Chemical Corporation); SP-900 (aromatic resin, trade name, manufactured by Mitsubishi Chemical Corporation); Amberlite (trademark) ), XAD-2, XAD-4, XAD-
16, XAD-2000 (above, aromatic resins, all trade names, manufactured by Organo Co., Ltd.);
07 (Aromatic resins having hydrophobic substituents, all trade names, manufactured by Mitsubishi Chemical Corporation); HP-2MG, E
X-0021 (above, aromatic resins having hydrophobic substituents, both trade names, manufactured by Mitsubishi Chemical Corporation); Ester resin, both trade names, manufactured by Organo Co., Ltd.);
P1MG, HP2MG (above, acrylic acid-based methacrylic resin, both trade names, manufactured by Mitsubishi Chemical Corporation); LH20, LH60 (above,
Derivatives of crosslinked dextran, all of which are trade names, manufactured by Pharmacia Biotech Co., Ltd.) and the like. Among them, SP-850 is particularly preferred.

[0016] The amount of the immobilized carrier varies depending on the size of the column, the type of solvent, the type of the immobilized carrier, and the like. The wet volume is preferably 0.01 to 5 times the solid content of the raw material (selected from cane juice, cane solvent extract, and cane-derived molasses).

By passing raw materials (selected from sugar cane juice, solvent extracts of sugar cane and molasses derived from sugar cane) through the above-mentioned column, the components in the raw materials having preventive and ameliorating effects on gastrointestinal ulcers are adsorbed onto the fixed carrier. sucrose, glucose, fructose and most of the inorganic salts flow out intact.

Components adsorbed to the immobilizing carrier are eluted with a solvent. Here, in order to efficiently elute the components having the effect, it is preferable to sufficiently wash off the remaining sucrose, glucose, fructose and inorganic salts prior to this. As a result, the adsorbed fraction having the desired effect of preventing and improving gastrointestinal ulcers can be recovered more efficiently. Elution solvents are water, methanol,
selected from ethanol and mixtures thereof; The elution solvent is preferably a mixed solvent of water and alcohol, particularly an ethanol-water mixed solvent. A 40 (v/v) ethanol-water mixed solvent is preferred. Furthermore, by raising the column temperature, the ethanol mixing ratio of the ethanol-water mixed solvent can be reduced, and the desired fraction can be eluted. In this case, the inside of the column is under normal pressure or pressurized. In this way, the component having the effect of preventing and improving gastrointestinal ulcers is present in the fraction eluted with the solvent. The elution rate is not particularly limited because it varies depending on the size of the column, the type of solvent, the type of immobilizing carrier, etc., but SV=0.1 to 10 hr ^-1 is preferred. In addition, SV
(Space Velocity) is a unit indicating how many times the resin volume of liquid is passed per hour.

[0019] The fraction having an effect of preventing and improving gastrointestinal ulcers is preferably obtained as follows, although it is not limited thereto. That is, a column filled with unsubstituted aromatic resin in a wet volume of 0.01 to 5 times as much as the solid content of the raw material was charged at a column temperature of 60 to 9.
After passing the raw material at 7°C, the inside of the column is washed with water, and then the components adsorbed in the column are removed at a column temperature of 20-40.
Elute with a 50/50 to 60/40 (volume/volume) ethanol-water mixture at °C, and the amount of eluate collected from the start of elution with the ethanol-water mixture is 4 times the wet volume of the resin. Collect the fractions that elute within

The fraction obtained by the above column chromatography treatment can be further concentrated by conventional means (solvent removal under reduced pressure, freeze-drying, etc.) to obtain a cane-derived extract. The extract thus obtained can be stored in a liquid or powder form concentrated to a solids content of 60% or more. Refrigerated storage is preferable for storage, especially when it is liquid.

[0021] The cane-derived extract thus obtained exhibits an excellent prophylactic effect against a peptic ulcer model, as shown in Test Examples 1 to 3 of the present specification.

[0022] The effective amount of the cane-derived extract is not particularly limited because it varies depending on the degree of refinement, form, health condition, etc. of the cane-derived extract. is 1-1000 mg per day, preferably 50-1000 mg per day.

[0023] The form of administration of the cane-derived extract according to the present invention is not particularly limited. It can also be mixed with food regardless of whether it is formulated or not.

[0024] When preparing an oral solid preparation, excipients, binders, binders, disintegrants, lubricants, colorants,
After adding a flavoring agent, an antioxidant, a solubilizing agent, etc., tablets, coated tablets, granules, powders, capsules, etc. are formed by conventional methods.

The above excipients, binders, binders, disintegrants,
Lubricants, coloring agents, flavoring agents, antioxidants, solubilizers and the like may be those permitted to be added to pharmaceuticals and foods.

The present invention also provides foods, drinks and health foods for preventing or improving gastrointestinal ulcers containing an effective amount of the above-mentioned cane-derived extract. They may be solid or liquid and include, for example, confectionery, soft drinks, condiments and the like. Health foods include functional foods and foods for specified health uses. When used as a health food, the sugar cane-derived extract can be used as it is, or it can be used in combination with other foods or other food ingredients. Health foods are in solid form (powder,
granules, etc.), jelly, liquid, or suspension, and a health drink form that further contains sweeteners, acidulants, vitamins, and various other ingredients used in the production of health drinks is preferred.

[0027]

EXAMPLES The present invention will now be described in detail with reference to manufacturing examples and test examples, but the present invention is not limited to these examples.

[Manufacturing example] Preparation of extract extracted from cane juice About 1000 liters of compressed cane juice (solid content: 18.5%) obtained in the manufacturing process at a raw sugar manufacturing plant was heated to 80°C with a juice heater. It is heated and filtered by tubular ultrafiltration (MH-25 type, effective membrane area: 2 m ² × 3, molecular weight cut off: 100,000, manufactured by Daicel Chemical Industries, Ltd.), and about 750 liters of the treated liquid is filtered. Obtained.

15 liters of synthetic adsorbent SP-850 (trade name, Mitsubishi Chemical Corporation) was added to a column with a water jacket (column size: inner diameter 17.0 cm, height 1
00 cm), and the above-mentioned compressed juice filtrate was passed through it at a flow rate of 75 liters/hour (SV=5 hr ⁻¹ ). Water at 65° C. was constantly circulated in the water jacket during the passage of the filtered squeezed juice. Next, 45 liters of ion-exchanged water was passed through the column at a flow rate of 30 liters/hour (SV=2 hr ⁻¹ ) to wash the column. After washing with ion-exchanged water, sugars were detected in the fraction eluted from the column using a hand-reflex Brix (Bx) meter (N-1E type, manufactured by Atago Co., Ltd.).
, Bx was confirmed to be about 0. After that, 30 liters of 55% ethanol aqueous solution (ethanol/water = 55/45 (volume/volume)) as an elution solvent was passed through the column at a flow rate of 30 liters/hour (SV = 2 hr ^-1 ) to synthesize Components adsorbed on the adsorbent were eluted. After that, ion-exchanged water is added at 30 liters/hour (SV=
2 hr ⁻¹ ). Water at 25° C. was constantly circulated in the water jacket during the passage of the elution solvent and the ion-exchanged water thereafter. The eluate eluted from the column with a 55% ethanol aqueous solution and the eluate obtained by running ion-exchanged water for 20 minutes were mixed, concentrated under reduced pressure by a concentrator to about 20 times, and freeze-dried overnight. Thus, 435 g of brown powder (extract derived from sugar cane) was obtained.

[Test Example 1] Alcoholic Ulcer Prophylaxis 6-week-old male SD rats (weighing 190-210 g) were used. The dry powder (test substance) administration group of the extract obtained in Production Example 1 (100 mg/10 ml/kg, 500 m
g/10ml/kg, 1000mg/10ml/k
g, ), a sucralfate-administered group as a positive control group (5
00 mg/10 ml/kg), and a distilled water administration group (10 ml/kg) as a negative control group (6 animals per group) were set (Fig. 1).

After fasting for 24 hours, test substances dissolved or suspended in distilled water, sucralfate, or distilled water were orally administered. 30 minutes later, 5 ml/kg of 99.5% ethanol
Administered orally. Sixty minutes after ethanol administration, the mice were dissected under ether anesthesia and the stomach was removed. The excised stomach was fixed in 2% formalin solution. After that, an incision was made along the gulf, and the length of the damage occurring in the glandular stomach was measured, and the total value of all damage values was taken as the total ulcer value. The results are shown in FIG.

From the figure, when the dosage is 500 mg/kg (P<
0.01) and 1000 mg/kg (P<0.001) showed a significant ulcer-inhibiting effect. No animals in the 1000 mg/kg administration group developed gastric injury. That is, it is clear that the extract powder has an extremely excellent ulcer-preventing effect.

[Test Example 2] Preventive effect of the extract powder against ammoniacal ulcer In the same manner as in Test Example 1, 6-week-old SD strain male rats (body weight: 190-210 g) were used to prevent ulcer from ammoniacal ulcer. investigated the effect. 5 ml/kg of 1% ammonia solution was administered instead of alcohol.
The results are shown in FIG.

From the figure, when the dosage is 500 mg/kg (P<
0.001) and 1000 mg/kg (P<0.001), a significant inhibitory effect was observed, demonstrating that this ulcer model also exhibited an extremely excellent effect.

[Test Example 3] Hydrochloric acid ulcer-preventing effect The ulcer-preventing effect of the extract powder on hydrochloric acid ulcers was evaluated in the same manner as in Test Example 1 using 6-week-old male SD rats (body weight: 190-210 g). Examined. 5 ml/kg of 0.6M hydrochloric acid was administered instead of alcohol. The results are shown in FIG.

From the figure, when the dosage is 250 mg/kg (P<
0.01), at 500 mg/kg (P<0.01) and 10
A significant inhibitory effect was observed at 00 mg/kg (P<0.001). In particular, it was found that administration of 1000 mg/kg exhibited excellent effects.

[Test Example 4] Toxicity Test A single-dose toxicity test in rats of the cane-derived extract of the present invention obtained in Production Example was conducted by the following method. 1. Dissolve the test article extract powder in water to reach the suspension limit of 1
The one adjusted to 500 mg/ml was used. 2. Test animals SD-IGS rats (male) were purchased from Charles River Laboratories Japan at 6 weeks of age (weighing 200-230 g). Six rats were housed in one cage and used after 24 hours of fasting.
In addition, water was taken ad libitum. 3. The administration method and dosage route were forced oral administration using a metal probe. The dosage was 20000 mg/13.3 ml/kg. After administration of the test substance, the animals were fed with CRF-1 solid feed (manufactured by Oriental Yeast Co., Ltd.). 4. Inspection items 1) General condition Observation was continued until 5 hours after administration of the test substance, and then for 1 week. 2) Body weight was measured once every 2 days for 7 days. 3) Pathological Anatomical Examination After observation of general conditions, all animals were dissected and various organs were macroscopically observed. 5. Results No deaths were observed after administration of 20000 mg/kg of the test substance. No particular abnormalities were observed in general condition after administration of the test substance. Body weight increased steadily, and there was no suppression of body weight gain during this period. In pathological anatomical examination, there were no abnormalities in macroscopic observation of various organs. From the above results, it was found that the extract of the present invention had no toxicity at a single oral dose of 20000 mg/kg.

[0038]

INDUSTRIAL APPLICABILITY The extract of the present invention can prevent gastrointestinal ulcers in daily diets by adding them to foods to be ingested on a daily basis, and can be expected to improve them.

[0039]

[Brief description of the drawing]

FIG. 1 is a diagram showing the results of an alcoholic ulcer preventive effect test conducted in Test Example 1. FIG. ^** : P<0.0
1, ^*** : P<0.001.

FIG. 2 is a diagram showing the results of a test on an ammoniacal ulcer preventive effect conducted in Test Example 2; ^＊＊＊ : P<
0.001.

3 is a diagram showing the results of a test on the preventive effect of hydrochloric acid for ulcers conducted in Test Example 3. FIG. ^** : P<0.01, ^*** : P<0.001.

──────────────────────────────────────────────────── ──── continuation of the front page (72) Inventor Yasuko Sawai 540 Narita, Odawara City, Kanagawa Prefecture Meiji Dairies Inside Health Science Laboratory Co., Ltd. (72) Inventor Hajime Tsunoo 540 Narita, Odawara City, Kanagawa Prefecture Meiji Dairies Inside Health Science Laboratory Co., Ltd. (72) Inventor Takeo Mizutani 1194-33 Hazawacho, Kanagawa Ward, Yokohama City, Kanagawa Prefecture (72) Inventor Kenji Furuya 4-12-9-201 Dai, Kamakura City, Kanagawa Prefecture F term (reference) 4B018 LE05 MD53 ME14 4C088 AB12 AC13 BA08 BA09 BA10 CA03 CA05 CA06 CA14 NA14 ZA68

Claims (9)

[Claims] 1. A gastrointestinal ulcer preventive or ameliorating agent containing a cane-derived extract as an active ingredient. 2. The cane-derived extract is a fraction obtained by subjecting a raw material selected from cane juice, a solvent extract of cane and cane-derived molasses to column chromatography using a solid carrier. Item 1. The agent for preventing or improving gastrointestinal ulcers according to item 1. 3. A raw material for the cane-derived extract, which is selected from cane juice, a solvent extract of cane, and cane-derived molasses, is passed through a column filled with a synthetic adsorbent as a fixed carrier,
The agent for preventing or improving gastrointestinal ulcer according to claim 2, which is a fraction obtained by eluting the component adsorbed by said synthetic adsorbent with a solvent selected from water, methanol, ethanol and mixtures thereof. 4. A food or drink for preventing or improving gastrointestinal ulcers containing an effective amount of a cane-derived extract. 5. The cane-derived extract is a fraction obtained by subjecting a raw material selected from cane juice, a solvent extract of cane and cane-derived molasses to column chromatography using a solid carrier. Item 5. The food or drink for preventing or improving gastrointestinal ulcers according to item 4. 6. A raw material for the cane-derived extract, which is selected from cane juice, a solvent extract of cane, and cane-derived molasses, is passed through a column filled with a synthetic adsorbent as a fixed carrier,
6. The method for preventing or improving gastrointestinal ulcer according to claim 5, which is a fraction obtained by eluting the component adsorbed by said synthetic adsorbent with a solvent selected from water, methanol, ethanol and mixtures thereof. food and drink. 7. A health food for preventing or improving gastrointestinal ulcers, containing an effective amount of a cane-derived extract. 8. The cane-derived extract is a fraction obtained by subjecting a raw material selected from cane juice, a solvent extract of cane and cane-derived molasses to column chromatography using a solid carrier. Item 8. A health food for preventing or improving gastrointestinal ulcers according to Item 7. 9. A raw material for the cane-derived extract, which is selected from cane juice, a solvent extract of cane, and cane-derived molasses, is passed through a column filled with a synthetic adsorbent as a fixed carrier,
9. Health for preventing or improving gastrointestinal ulcer according to claim 8, which is a fraction obtained by eluting the component adsorbed by said synthetic adsorbent with a solvent selected from water, methanol, ethanol and mixtures thereof. food.