JP3059243B2 - Anti-ulcer agent - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a novel anti-ulcer agent containing 7- (4 "-hydroxy-3" -methoxyphenyl) -1-phenyl-4-hepten-3-one as an active ingredient.

[0002]

2. Description of the Related Art Many antiulcer agents have been developed in the past, but new and useful antiulcer agents are always required. Ryokyo (Alp
inia officinarum Rhizoma) is a crude drug that has long been used as a medicinal or spice. It is prescribed also in Kampo prescriptions such as Annaka-san and has a low stomach effect despite its stomachic effect. Therefore, its pharmacological action is almost unknown, and only reports on the prostaglandin biosynthesis inhibitory action of hot water extract of Ryokyo [Ayumi of Medicine, 126 , 867].
(1983)].

[0003]

Means for Solving the Problems The present inventors have carried out screening tests in various disease state models using experimental animals in order to find materials that can be developed as pharmaceuticals among natural products. In this process, 7- (4 "-) contained in Ryokyo for ulcer animal model
Hydroxy-3 "-methoxyphenyl) -1-phenyl-
The present inventors have found that 4-hepten-3-one has a remarkable antiulcer activity, and completed the present invention. That is, the present invention
The present invention relates to an anti-ulcer agent containing-(4 "-hydroxy-3" -methoxyphenyl) -1-phenyl-4-hepten-3-one as an active ingredient.

Next, the present invention will be described in more detail. Isolation of 7- (4 "-hydroxy-3" -methoxyphenyl) -1-phenyl-4-hepten-3-one from Ryokyo was carried out first by lower alkyl ketone, lower alcohol, lower fatty acid ester, lower aliphatic ester. Extraction with an organic solvent such as ether can be performed, and then the concentrate of the extract is subjected to column chromatography using silica gel, alumina or the like as an adsorbent. As the lower alkyl ketone, for example, acetone and methyl ethyl ketone are used, as the lower alcohol, for example, methanol, ethanol, and the like, as the lower fatty acid ester, for example, ethyl acetate, and the like, and as the lower aliphatic ether, for example, ethyl ether, isopropyl ether, and the like are used. An example of extraction and separation from Ryokyo is shown in Reference Example. Basically, the above-described extraction is suitable, but other separation means (such as distillation) may be used, or these separation means may be combined.

[0005] The present invention relates to an anti-ulcer agent containing 7- (4 "-hydroxy-3" -methoxyphenyl) -1-phenyl-4-hepten-3-one as an active ingredient, wherein the ulcer agent is in the form of tablets, capsules, powders. It can be in the form of liquid preparations, such as agents, granules or sterile solutions or suspensions for oral or parenteral administration. Tablets, granules, and powders are suitable for oral administration of the active ingredient of the present invention as needed, and granules and powders can be made into capsules as needed in dosage forms.

[0006] Solid preparations for oral administration include conventional pharmaceutical additives such as excipients (silicic anhydride, synthetic aluminum silicate, lactose, corn starch, microcrystalline cellulose, etc.), binders (gum arabic, gelatin, polyvinylpyrrolidone, Hydroxypropyl cellulose, etc.), a lubricant (eg, magnesium stearate, talc, silicic anhydride), a disintegrant (eg, corn starch, calcium carboxymethyl cellulose) and the like. Tablets may be coated according to conventional methods.

The oral liquid preparation may be in the form of an aqueous or oily suspension, solution, syrup or the like, or may be a dried product which can be redissolved with a suitable solvent before use. Such liquid preparations are commonly used preparation additives such as water, emulsifiers (lecithin, sorbitan monooleate, etc.), dispersion stabilizers (sodium carboxymethyl cellulose, gelatin, etc.), non-aqueous solvents (coconut oil, peanut oil, etc.) , An antioxidant, a coloring agent, a flavor and the like. For use in parenteral administration, 7- (4 "-hydroxy-3" -methoxyphenyl) -1-phenyl-4-hepten-3-one may be dissolved or suspended in a sterile solvent to obtain a liquid preparation. Good. The solution may contain conventional buffers, isotonic agents, solubilizing agents and the like.

According to the present invention, 7- (4 "-hydroxy-3" -methoxyphenyl) -1-phenyl-4-heptene-3-
The pharmaceutical composition containing ON as an active ingredient is effective for treating and preventing ulcers in humans and animals, particularly peptic ulcers. The effective amount or dose of the compound varies depending on factors such as the degree of ulcer and the constitution of the patient, but generally speaking, the dose is suitably in the range of 10 to 500 mg per adult.

[0009]

The present invention will be described in more detail with reference to examples.
The present invention is not limited to these examples. Based on the extraction and separation method of 7- (4 "-hydroxy-3" -methoxyphenyl) -1-phenyl-4-hepten-3-one from Ryokyo, the anti-ulcer effect, acute toxicity test and formulation example were described. Examples will be shown.

Reference Example Extraction and separation from Ryokyo 10 kg of crushed Ryokyo (Osaka market product) is immersed in 5 times the volume of acetone, left for 2 days, and filtered. The same operation was repeated three times on the residue, and the filtrates were combined and concentrated to dryness under reduced pressure to obtain an acetone extract (500 g). The resulting acetone extract was subjected to silica gel chromatography [Silica gel 60, manufactured by Merck, developing solvent hexane / ethyl acetate (the ratio of ethyl acetate was gradually increased)] to fractionate Fr. Fr.6 showing activity was fractionated by silica gel chromatography using chloroform and methanol as developing solvents. The obtained three fractions were further isolated and purified to obtain five compounds including the product of the present invention.

Example 1 Anti-ulcer activity Wistar male rats (body weight 250-280 g) fasted for 24 hours were given 60% ethanol and 150 mM.
1.5 ml of an HCl / ethanol solution consisting of HCl was orally administered to each rat, and one hour later, ether was killed.
The stomach is removed and 10 ml of 2% formalin is placed in the stomach for 15 minutes.
After fixing for a minute, cut open along the greater curvature Length of injury (mm)
Was measured. The sum of the length of injury per animal was defined as the ulcer index. The samples were suspended in 5% gum arabic powder, and each of them was orally administered 1 hour before administration of HCl / ethanol. The difference in the ulcer index between the control group and the sample administration group was divided by the ulcer index of the control group to calculate the inhibition rate. Table 1 shows the results.

[0012]

[Table 1]

Example 2 Acute toxicity An acute toxicity test by single oral administration was performed using 10 dd-Y male mice (body weight 23 to 27 g) per group. Active ingredient is 7 of the present invention (4 "- hydroxy-3" - methoxyphenyl)-1-LD ₅₀ values of the phenyl-4-heptene-3-one is greater than 2000 mg / kg, compared with the effective amount And high security was confirmed.

[0014]Example 3 Drugs suitable for oral administration (tablets) Mix the following ingredients and form the resulting mixture with a tablet machine
To produce tablets. Amount per tablet (mg) 7- (4 "-hydroxy-3" -methoxyphenyl) 25-1-phenyl-4-hepten-3-one corn starch 20 hydroxypropylcellulose 3 magnesium stearate 2 lactoseAppropriate amount  Total 150

[0015]Example 4 Drugs suitable for oral administration (granules) The following components are used to produce granules according to a conventional method. 7- (4 "-hydroxy-3" -methoxyphenyl) 25-1-phenyl-4-hepten-3-one corn starch 20 hydroxypropylcellulose 3 lactoseAppropriate amount  Total 150

[0016]

According to the present invention, 7- (4 "-hydroxy-3" -methoxyphenyl) -1-having no known anti-ulcer effect has been known.
Provided is an anti-ulcer agent containing phenyl-4-hepten-3-one as an active ingredient.

Claims (1)

(57) [Claims] 1. An anti-ulcer agent comprising 7- (4 "-hydroxy-3" -methoxyphenyl) -1-phenyl-4-hepten-3-one as an active ingredient.