JPH0114232B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel compound that has a blood pressure lowering effect and is useful as a medicine.

Until now, mulberry root bark has been referred to as mulberry white bark in Chinese medicine, and has been included in Chinese medicine preparations as an anti-inflammatory diuretic, laxative, and antitussive expectorant.

In addition, recently, the blood pressure lowering effect of the methanol extract (Proceedings of the 99th Annual Meeting of the Pharmaceutical Society of Japan, p. 162,
29A2-3), hyperglycemic lowering effect of the extract (Japanese Patent Publication No. 53-44530), interferon-inducing effect of the high molecular weight polysaccharide contained in the extract (Japanese Patent Application Laid-Open No. 53-99313), etc. It has been known.

However, regarding the active substance in the blood pressure lowering effect, two types of 8-substituted cyclohexenylflavone derivatives Quanon G and Quanon H [Chemical and Pharmaceutical Bulletin (Chem.
Pharm.Bull.) Volume 28, No. 8, Page 2548 (1980),
HETEROCYCLES Volume 14,
No. 12, p. 1943 (1980)] have not yet been elucidated.

As a result of intensive research, the present inventor extracted a plant of the genus Morus, family Moraceae, with an organic solvent, and discovered that a compound obtained by isolation from this extracted extract had a blood pressure lowering effect, and completed the present invention. This was named Mulberofuran C.

That is, the present invention is based on the following formula () This relates to the compound (Mulberofuran C) shown in the following.

First, a method for producing Mulberofuran C will be explained.

The mulberry root bark is cut into small pieces, degreased with an organic solvent with relatively low polarity, extracted with lower fatty acid ester, lower alcohol, ether or acetone, and the liquid is dried under reduced pressure to obtain a purple-red powder. This powder is subjected to column chromatography in a conventional manner to separate impurities and obtain crude Mulberofuran C. Next, this crude product is isolated and purified by preparative thin layer chromatography or high performance liquid chromatography to produce Mulberofuran C.

The mulberry used here is commercially available mulberry bark produced in Japan, Morus alba L., Morus alba L.
bombycis Koidz), Morus Lhou
Koidz or Morus multicaulis Perr.), and the root bark thereof is particularly preferred. These should be thoroughly dried into fine powders.

Suitable organic solvents with relatively low polarity for use in the degreasing treatment include n-hexane and benzene.

As the lower fatty acid ester for extraction, methyl acetate, ethyl acetate, butyl acetate, etc. can be used, as the lower alcohol, methanol, ethanol, etc. can be used, and as the ether, methyl ether, ethyl ether, etc. can be used.

In conventional column chromatography, for example, first a column packed with polyamide resin is used to elute and separate a fraction containing Mulberofuran C with methanol, and then a polyamide resin column is used to elute and separate a methanol-dichloromethane mixture or methanol-chloroform. Crude Mulberofuran C can be obtained by elution with the mixed solution.

For the subsequent purification operation, for example, mulberofuran C is developed by preparative thin layer chromatography on silica gel using solvents such as hexane, benzene, chloroform, acetone, ethyl acetate, or methanol alone or in combination, and fractionated.
can be obtained.

Note that during the above extraction/separation operation, the degreasing treatment can also be omitted.

Mulberofuran C obtained by processing as above
The blood pressure lowering effect of was confirmed by the following animal experiment.

First, the sample was dissolved and adjusted to a concentration of 10 mg/ml in propylene glycol, and then intravenously injected into a male rabbit weighing 3.3 kg under anesthesia (pentobarbital 30 mg/Kg, intravenous injection) to measure femoral artery blood pressure. did.

As a result, a decrease in blood pressure of 37 mmHg was observed at a dose of 1 mg/Kg.

In addition, the LD ₅₀ for acute toxicity is for mice (5 weeks old,
ddY strain, male) was 172 mg/Kg when administered intraperitoneally.

As described above, the mulberofuran C compound of the present invention represented by the above formula () can be produced from mulberry root bark through a relatively simple extraction and purification procedure, and also exhibits an excellent blood pressure lowering effect. It is suitable as an antihypertensive agent because of its low toxicity.

The method for producing Mulberofuran C of the present invention will be specifically explained below.

Production example: 2 kg of shredded dried commercially available mulberry bark and 20 kg of n-hexane.
Degrease twice with benzene 20 and then twice with benzene 20 at room temperature for one week, then extract twice with ethyl acetate 20 at room temperature for 4 days each, take the extract, and evaporate the solvent under reduced pressure. 155 g of purple-red powder was obtained.

The entire amount of this purple-red powder was dissolved in the minimum necessary amount of ethyl ether and adsorbed onto 150 g of polyamide resin (Wako Polyamide C-200, manufactured by Wako Pure Chemical Industries).
After evaporating the solvent, the column was packed in layers on a column packed with 600 g of polyamide resin and eluted with methanol. After 5 elution from the start of elution, 5 more
The eluate was collected, concentrated under reduced pressure, and further subjected to column chromatography using 200 g of polyamide resin. First, 6 elutions were performed using 20% methanol-dichloromethane as a developing solvent, and then 35%
Elution was carried out with methanol-dichloromethane for 6 minutes, and the eluate was concentrated under reduced pressure to obtain crude Mulberofuran C.

This crude Mulberofuran C was subjected to preparative thin layer chromatography [Wakogel B-5F (manufactured by Wako Pure Chemical Industries),
Developing solvent: benzene:acetone=1:1] to obtain 0.08 g of Mulberofuran C. Its physical and chemical properties were as follows.

(1) Melting point (decomposition point): 210℃ (white powder) (2) Specific rotation: [α] ¹⁸ _D +161° (C = 0.913, methanol) (3) Elemental analysis value Experimental value (%): C = 67.88, H=5.02 (4) Molecular weight: 580 (from M ⁺ of field desorption mass spectrum) (5) IR spectrum (KB〓) (see Figure 1) ν _nax : 3350, 1625, 1600 (cm ^-1 ) (6) UV spectrum (see Figure 2) λ ^CH3OH _nax (log ε): 222 (shoulder 4.70), 285 (4.49
),
320 (4.69), 334 (4.62) (nm) (7) Color reaction Ferric chloride reaction positive (purple brown)

[Brief explanation of drawings]

FIG. 1 is a diagram showing the infrared absorption spectrum (KB) of the mulberofuran compound of the present invention, and FIG. 2 is a diagram showing the ultraviolet absorption spectrum (methanol) of the mulberofuran compound of the present invention.

Claims (1)

[Claims] 1st-order equation () A compound represented by (Mulberofuran C).