JP2000072685A - Food and medicament compositions for inhibiting ulcer of digestive organ - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a food composition and a medicament composition for inhibiting ulcer of digestive organs by including an antiulcer substance having high safety and no side effect as an active principle. SOLUTION: The food composition and the medicament composition include rosemary extract or rosemarinic acid as an active principle. The rosemary extract is prepared by extracting rosemary with a proper solvent. The rosemary is used in a state of the entire plant, its leaf, root bark, stem, root, branch, fruit, seed, flower, or a mixture of two kinds of them. The plant raw material is used in a raw or dried state, and is pref. crushed and then subjected to extraction.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a food composition and a pharmaceutical composition containing a rosemary extract or rosmarinic acid as an active ingredient for inhibiting gastrointestinal ulcer.

[0002]

2. Description of the Related Art Rosemary, which is a Labiatae plant, is also known as "mannen wax" and is widely used as a herb for medicinal use, flavoring, and cooking. Various effects of rosemary as a medicinal agent have been variously described since ancient times. For example, British Herbal Pharmacopoei [British Herbal Pharmacopoei]
a] in 1983, including carminative, analgesic, disinfecting, preservative,
Effects such as sedation, diuresis, and antibacterial are described. Also,
According to a patent application published in recent years, deodorization (Japanese Unexamined Patent Publication No.
73070), anti-corrosion (JP-A-4-13630), anti-oxidation
(JP-A-3-197595), antivirus and antitumor
(Japanese Unexamined Patent Publication No. Hei 4-247504),
Effects such as 6) are disclosed. In addition, many other effects have been reported in the past as the effect of the essential oil component of rosemary [“Effect of rosemary in aromatherapy”, aromatopia, No. 4, p47]. However, after examining these numerous reports, it was not previously known that rosemary had an antiulcer effect.

[0003] In recent years, excellent anti-ulcer drugs such as H2 blockers and proton pump inhibitors have been developed as anti-ulcer drugs, and the treatment of ulcers by conventional surgery has been drastically reduced.
However, these anti-ulcer agents repeatedly repeat remission and recurrence, and are often required to be taken for a long period of time. Therefore, side effects such as anti-androgen action, hypersensitivity, and liver damage have been reported.

[0004]

SUMMARY OF THE INVENTION An object of the present invention is to provide a highly safe anti-ulcer substance having no side effects as described above, and to provide a gastrointestinal ulcer containing such an anti-ulcer substance as an active ingredient. It is intended to provide a food composition and a pharmaceutical composition for suppressing the occurrence of lipase.

[0005]

Means for Solving the Problems In order to solve the above problems, the present inventors have focused on plant herbs which have been used in daily life, and have searched for many herbs.
It has been found that rosemary extract and rosmarinic acid contained in the extract have an anti-ulcer effect, and that this effect can be used for prevention and / or treatment of gastrointestinal ulcer. Reached. That is, the present invention provides a food composition and a pharmaceutical composition for preventing and / or treating gastrointestinal ulcer, which comprises a rosemary extract or rosmarinic acid as an active ingredient. .

[0006]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail. The rosemary extract used in the present invention is obtained by extracting rosemary with a suitable solvent. Rosemary whole plant or its leaves, root bark, stem,
Any of roots, branches, fruits, seeds or flowers, or a mixture of two or more of these plant parts can be used for extraction. These plant raw materials may be raw or dried. Preferably, these plant raw materials are pulverized and then used for extraction.

[0007] The extraction may be performed in a conventional manner. That is, it is common to extract the above-mentioned plant material with a solvent at normal temperature or under heating. However, a special extraction method such as a critical extraction method can be used.

As the solvent used for the extraction, water or one or more kinds of organic solvents such as lower alcohols (eg, methyl alcohol, ethyl alcohol or butanol), acetone and ethyl acetate are appropriately mixed and used. it can. Preferred extraction solvents are water or lower alcohols alone or a mixture of water and lower alcohols.

[0009] The extraction temperature is usually in the range of 5 to 120 ° C, preferably 40 to 100 ° C. Although the extraction time varies depending on the extraction temperature, it is generally 1 to 10 days for extraction near room temperature, and 1 for extraction at 50 ° C. or higher.
~ 48 hours.

The extract thus obtained can be used as it is in the present invention, but the extract can also be used after being concentrated or diluted with an appropriate solvent (eg, water or lower alcohol). Further, the extract can be evaporated to dryness, and the solid content can be used in the present invention. Furthermore, these extracts can be fractionated using a suitable resin carrier, and the fraction containing a large amount of the active ingredient thus obtained can be used in the present invention.

As a resin carrier which can be used for fractionation of the extract, for example, a synthetic adsorbent composed of a copolymer of styrene and divinylbenzene, or a sulfonyl group or a quaternary ammonium group is introduced into this polymer. Ion exchange copolymers and the like. The fractionation of the extract can be performed, for example, by adsorbing the extract on such a resin carrier, packing the extract in a column, and eluting with a suitable solvent. The solvent for elution of the extract may be the same as the above-mentioned solvent for extraction, or may be a commonly used organic solvent such as ethyl acetate or hexane, or an aqueous solution having a changed hydrogen ion concentration and / or ionic strength. It may be.

The present inventors, as shown in the examples below,
Diaion SP207 (manufactured by Mitsubishi Kasei; styrene-divinylbenzene copolymer) was used as a resin carrier, and 10 to 50% ethanol water and 100%
By fractionating the rosemary extract using ethanol, a fraction rich in the active ingredient and a fraction high in rosmarinic acid were obtained. In addition, it has been found that all of these fractions have a strong anti-ulcer effect. That is, such a fraction is preferably used in the present invention. Accordingly, the rosemary extract used in the present invention is a primary extract obtained by solvent extraction of plant materials, a diluent and a concentrate thereof, a dried product thereof, and
It means the active ingredient or its fraction enriched in rosmarinic acid. In addition, the rosmarinic acid-rich fraction can be further purified according to a conventional method. Rosmarinic acid thus highly purified can also be used in the present invention.

The food (health food or food for specified health use) composition and the pharmaceutical composition of the present invention contain the above-mentioned rosemary extract or rosmarinic acid. Examples of the food composition include granules, tablet confectionery, jelly, candy, and beverages, and these can be taken as needed. Pharmaceutical compositions include tablets, pills, powders, capsules, solutions, emulsions, suspensions, syrups and the like, and these can be orally administered as needed.

The ingredients used in preparing the food composition may be those commonly used in the art, for example,
Lactose, dextrose, sucrose, sorbitol, mannitol, apple fiber, soy fiber, meat extract, black vinegar extract, gelatin, corn starch, honey, animal and vegetable fats and oils, polysaccharides and the like can be mentioned.

[0015] Carriers used in preparing a pharmaceutical composition include, for example, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, alginate, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose. Derivatives, tragacanth, gelatin, syrup, methyl hydroxybenzoate, talc, magnesium stearate, water, mineral oil and the like can be mentioned.

The food and pharmaceutical composition of the present invention may further contain a lubricant, an emulsifier, a suspending agent, an antioxidant, a preservative, a sweetener and / or a flavor, and the like.
It may contain other active ingredients (including water-soluble vitamins and oil-soluble vitamins, etc.). The food and pharmaceutical compositions of the present invention comprising such components may be manufactured according to methods well known in the art.

Rosemary extract and rosmarinic acid are effective over a wide dosage range. Therefore, the daily dose is usually about 0.01 per kg of body weight.
It can range from about 1000 mg, preferably about 0.1 to 500 mg, more preferably about 1 to 300 mg.
This amount is taken or administered in one or several divided doses. However, the actual dose is determined in consideration of the subject's age, body weight, severity of symptoms, and the like.

[0018]

EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

Example 1 Preparation of rosemary extract 20 kg of water was added to 15 kg of rosemary (whole plant, crudely cut) and digested at 95 ° C. or higher for 2 hours. After cooling to 65 ° C., the mixture was centrifuged to obtain an extract. Eight volumes of water was again added to the residue, followed by digestion in the same manner, and the obtained extract was combined with the previous extract. This extract was concentrated under reduced pressure at 60 ° C. to obtain 13 L of a concentrated extract. The concentrated extract was spray-dried to obtain 3 kg of a rosemary extract.

Example 2 Preparation of Rosemary Extract Fraction 100 g of the rosemary extract obtained in Example 1 was purified water 2
And stirred at 80 ° C. to dissolve. After allowing to cool to room temperature, 1 kg of Diaion SP207 (manufactured by Mitsubishi Kasei) was added, and the mixture was stirred at room temperature for 3 hours. The Diaion SP207, to which the rosemary component was sufficiently adsorbed, was filtered and packed in a column.
The eluted fractions were collected using 30% ethanol water, 30% ethanol water, 40% ethanol water, 50% ethanol water and 100% ethanol. 10% ethanol water, 20%
The fractions eluted with ethanol water and 30% ethanol water were combined, and this fraction (15 L) was spray-dried to obtain 50 g of a rosemary extract fraction (1). The fractions eluted with 40% aqueous ethanol and 50% aqueous ethanol were combined, and the solvent of this fraction (10 L) was distilled off at 50 ° C. under reduced pressure. Next, 300 ml of purified water was added to the residue to suspend it, adjusted to pH 4 with 1N hydrochloric acid, and extracted three times with 300 ml of ether. The extracted ether layers were combined, the ether was distilled off under reduced pressure, and the residue was dissolved in 20 ml of 25% methanol. This was purified on Sephadex LH-20 (5 × 75 cm) equilibrated with 25% methanol,
A fraction containing rosmarinic acid was obtained. The solvent of this fraction was distilled off under reduced pressure at 50 ° C., and the residue was crystallized from hot purified water.
A rosmarinic acid-rich fraction (1.2 g) was obtained. About the fraction (5 L) eluted with 100% ethanol, ethanol was distilled off under reduced pressure at 45 ° C., 300 ml of purified water was added to the residue, and the residue was suspended and freeze-dried to obtain a rosemary extract fraction (2).
20 g were obtained.

Example 3 Effect on ethanol ulcer Weight of 180-200 g fasted for 24 hours before the start of the test
Wistar male rats (5 per group) were given the rosemary extract obtained in Example 1 at a dose of 250 mg / kg.
Further, the rosemary extract fraction obtained in Example 2 was 100 m
g / kg was orally administered, and 30 minutes later, ethanol (99.5%) was administered at a dose of 1 ml / rat. One hour later, the laparotomy was performed, and the lengths of all ulcers generated in the stomach were measured and the total was determined. (A group to which ethanol was administered). As shown in FIGS. 1 and 2, the rosemary extract obtained in Example 1 and the rosemary extract fraction obtained in Example 2 exhibited a strong antiulcer effect. Particularly, the rosemary extract fraction (2) and the rosmarinic acid-rich fraction showed extremely strong antiulcer activity.

Example 4 Effect on stress ulcer Weight of 180-200 g fasted for 24 hours before the start of the test
The Wistar male rats (5 per group) were orally administered with the rosemary extract obtained in Example 1 at a dose of 250 mg / kg, and after 30 minutes, fixed with a stress gauge to 23-
The breast was immersed in a water bath at 24 ° C. 7 hours later,
The lengths of all ulcers generated in the stomach were measured and their total was calculated, and this total length was compared with the control group as an ulcer index.
As shown in FIG. 3, the rosemary extract obtained in Example 1 had a strong anti-ulcer effect.

Example 5 Evaluation of safety The rosemary extract obtained in Example 1 was 4000 mg / k.
A 5-week-old Crj: CD (SD) (SPF) male rat [Charles River Japan Co., Ltd.] was forcibly and orally administered at a dose of g / day for 28 days using a disposable oral sonde. As test items, 1) observation of general condition, 2) body weight measurement, 3) food consumption, 4) urine test (pH, occult blood, protein, ketone, urobilinogen, bilirubin, etc.), 5) hematological test (red blood cell count) , Hemoglobin level, average red blood cell volume, average red blood cell pigment amount, white blood cell count, platelet count, etc.), 6) blood chemistry test, 7) histopathological test, 8) histopathological test, As a result, no abnormality was recognized. This revealed an extremely high safety of the rosemary extract.

Example 6 Food A Using the rosemary extract obtained in Example 1, a food having the following composition was prepared.

[Table 1] After mixing each component in a fluidized-granulation apparatus, water was sprayed to perform granulation, and the mixture was dried at an air inlet temperature of 80 ° C.

Example 7 Food B Using the rosemary extract obtained in Example 1, a food having the following composition was prepared.

[Table 2] After sufficiently mixing the above components with 10 kg of water, the mixture was heated to 60 ° C. to form a paste. This was put into 50 kg of soybean oil which had been heated to 70 ° C. in advance, and thoroughly mixed with a stirrer equipped with squid-type stirring blades (two pieces). After confirming that the paste was dispersed in the soybean oil, the mixture was cooled to 5 ° C.
And filtered to separate the resulting particles. The obtained particles were washed with n-hexane and then dried to obtain microcapsules containing the above components.

Example 8 Hard gelatin capsule A hard gelatin capsule was prepared using the rosmarinic acid-rich fraction obtained in Example 2.

[Table 3] Ingredient (mg / capsule) Rosmarinic acid-rich fraction 250 Starch 100 Cellulose 100 Magnesium stearate 10 Total 460 mg

Example 9 Tablet A tablet was prepared using the rosemary extract fraction (2) obtained in Example 2.

[Table 4] Component amount (mg / tablet) Rosemary extract fraction (2) 250 Cellulose 400 Silicon dioxide 10 Stearic acid 5 Total 665mg

Example 10 Suspension Using the rosemary extract fraction (2) obtained in Example 2, a suspension was prepared.

[Table 5] Ingredients Amount used Rosemary extract fraction (2) 50mg Sodium carboxymethylcellulose 50mg Syrup 1.25ml Benzoic acid solution 0.10ml Flavoring agent qs colorant qs pure water up to 5ml

[0029]

The food and the pharmaceutical composition containing the rosemary extract or rosmarinic acid as an active ingredient of the present invention are highly safe and have a strong anti-ulcer effect. Accordingly, these compositions can be used for the prevention and / or treatment of gastrointestinal ulcers.

[Brief description of the drawings]

FIG. 1 is a graph showing the effect of rosemary extract on ethanol ulcer.

FIG. 2 is a graph showing the effect of a rosemary extract fraction on ethanol ulcer.

FIG. 3 is a graph showing the effect of rosemary extract on stress ulcer.

 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor Kunio Kosaka 2-3-2 Muroya, Nishi-ku, Kobe-shi, Hyogo F-term in the R & D Center of Nagase & Co., Ltd. (Reference) 4B018 LB10 LE03 LE05 MS04 MS11 4C088 AB38 AC01 AC03 AC04 AC05 AC06 AC11 BA08 BA09 BA10 BA11 MA01 MA52 NA14 ZA68 4C206 AA01 AA02 DA01 DA11 KA18 MA01 MA04 MA72 NA14 ZA68

Claims (4)

[Claims] 1. A food composition for suppressing gastrointestinal ulcer, comprising a rosemary extract as an active ingredient. 2. A food composition for suppressing gastrointestinal ulcer, which comprises rosmarinic acid as an active ingredient. 3. A pharmaceutical composition for suppressing gastrointestinal ulcer, comprising a rosemary extract as an active ingredient. 4. A pharmaceutical composition for suppressing gastrointestinal ulcer, which comprises rosmarinic acid as an active ingredient.