JPS5826820A - Hypotensive substance - Google Patents

Abstract

PURPOSE:To titled substance that is composed of the neutral fraction of the SHIITAKE extract which has been obtained by extracting SHIITAKE mushrooms with an aqueous solvent, treating and purifying the extract, thus being used as a preventive or remedy for hypertension and permitting continuous administration for a long period of time, because of its causing of no habituation and side-effects. CONSTITUTION:SHIITAKE mushrooms are extracted with an aqueous solvent such as water-ethanol, the extract is treated with an ion-exchange resin and the resultant neutral fraction is purified by means of column chromatography or not purified to give the objective hypotensive substance. The substance is a white powder that is positive to the ninhydrin reaction and alpha-naphthol reaction, however, it is not a pure and single substance but seems to be a mixture mainly consisting of oligosaccharides. Side-effects caused by constinuous administraction is low and the safety range is wide, these properties are required for a hyportensor, and further the odor characteirstic in SHIITAKE is removed to cause no inappetence by continuous administration.

Description

[Detailed description of the invention] The present invention relates to the prevention and treatment of hypertension.

More specifically, the present invention relates to a substance having a blood pressure lowering effect, which is composed of the neutral part of a Shiitake extract obtained by extracting, processing, and purifying Shiitake mushrooms.

Hypertension accounts for 115 of the diseases of the high-income class in Japan, and is a disease of direct concern to the people.

The requirements for antihypertensive drugs are low habit-forming, low long-term action, wide safety margin, expected effectiveness for more than half a day with a single administration, heart, eyelid bulge, brain, I # castle, etc. The blood flow of the patient does not decrease. However, the current situation is that there is no drug in sight that satisfies these requirements, and this is an area where the development of new drugs is expected.

The present inventors focused on the blood pressure-lowering effect of shiitake mushrooms, which have various medicinal effects and have been prized as an elixir for longevity since ancient times. It has been found that there are problems such as decreased appetite and vomiting in some cases, and that a large amount is required for one administration, making long-term continuous administration necessary as an antihypertensive agent difficult.

As a result of repeated research to solve these problems, the present inventors found that the neutral part of the extract obtained by treating the aqueous solvent extract of shiitake mushrooms with an ion exchange resin has a strong blood pressure control effect. Moreover, the odor characteristic of shiitake mushrooms has disappeared, and they have found that they are satisfactory as antihypertensive agents, and have incorporated them into the present invention.

An object of the present invention is to obtain a substance suitable for the prevention and treatment of hypertension, which has low habit-forming properties, low side effects, and can be used over a long period of time.

In the present invention, after extracting shiitake mushrooms with an aqueous solvent, the extract is treated with an ion exchanger, and the resulting extract is purified with or without purification by a neutral St column chromadog':)7. Formulations containing rugose substances and vine bodies that are acceptable as drugs or foods, providing substances with a lowering effect, have been passed as antihypertensive prophylactic and therapeutic agents.

In the present invention, shiitake mainly refers to shiitake, naan,
J1!4-ru1 p1 fruiting bodies and thread bodies were used for the four-basidium-dl141 xing group that parasitizes decayed trees of the oak family and birchaceae, such as chestnut, oak, oak, etc., and these were cut as necessary. What is the purpose of milling to increase surface area and increase extraction efficiency?

The desired blood pressure lowering agent can be extracted by shaking extraction with an aqueous solvent, continuous extraction, or heating extraction with stirring. The aqueous solvent used as the extraction solvent is a solvent mainly composed of water. 1. Water alone, or an organic solvent that is miscible with water or dissolved in water, such as methanol, ethanol, impropatol, acetone, Although it is a solvent containing ethyl acetate etc., a mixed solvent of water and ethanol (ethanol 60-80 volumes)
Economically, it is best to extract with water alone and then treat with the above-mentioned mixed solvent.

Next, the extract is treated in a conventional manner using a suitable a-condensed bond and an ion exchange resin to obtain a neutral part of the extract.

The ion exchange resins used are strongly acidic ones with sulfonic acid groups, weakly acidic ones with carboxyl groups,
Strongly basic substances with quaternary ammonium, No. 1~
Although it is possible to use any weakly basic resin with a tertiary aino group, it is preferable to use a combination of strongly acidic and weakly basic ion exchange resins. −
Filled with +1- and weakly basic ion exchange resin [, impurities are adsorbed and removed by ion exchange 4M fat by passing through a nine column or stirring and standing with ion exchange resin in a batch method, and flow out to form nine neutral parts. to obtain the blood pressure lowering active ingredient. Although the neutral part obtained in this way exhibits a sufficient blood pressure lowering effect with 11, it still contains ineffective or ineffective components, so it can be further analyzed by adsorption chromatography. 111! It is possible to separate and collect highly pure blood pressure-lowering components. After the neutral part is appropriately bridged or evaporated to dryness, it is dissolved in water and adsorbed on various adsorbents.
Elute with an aqueous solvent. The adsorbents used here include activated carbon, activated carbon-Celite, Celite, Alina,
Examples include silica gel, starch, cellulose, etc., and they may be used alone or in combination of two or more. Next, the active ingredients adsorbed on the adsorbent are the various aqueous lIIi! In l medium,
By extracting the extract and collecting the eluate, the active ingredient can be separated and collected as a white powder.

The antihypertensive agent of the present invention obtained from shiitake mushrooms obtained in this way is characterized by the following points, but it is not a pure single substance, and from the viewpoint of various properties, the main component is It is considered to be a mixed substance.

l) Engineering R spectrum As shown in FIG.

1) UV spectrum As shown in FIG.

m) Ckb.

As shown in FIG.

IV) TLO This is shown in FIG.

■) Various Qualitative Reactions Ninhydrin Reaction - Rumored α-S7 Tol Reaction - In Shiitake Mushroom Extract Characterized by 41 Products of Elson, Morgan & Hfjh, Juki The genital area is excellent as a blood pressure lowering substance as it is, CJ, - like,
Carriers that can be administered as they are or dissolved in water, but can be packaged as medicines or foods, such as medicines for anti-inflammatory drugs, anti-cholesterol drugs, hypoglycemic agents, or fruit juices, seasoning agents, sweeteners It can be mixed with flavoring agents such as, to enhance the blood pressure lowering effect or palatability. father,
It can be administered in the form of a tablet, capsule, tote, pill, rice grain, powder, syrup, injection, etc.

The formulation containing the neutral part of the shiitake mushroom extract of the present invention exhibits a remarkable blood pressure lowering effect even in a small amount, has low habit-forming and depleting effects, and can be used continuously for a long period of time.

Next, the effects of the present invention will be explained by giving examples.

Commercially available dried shiitake caps were cut into pieces and dried at 70°C for 2 hours, then 10 times the weight of water was added to the dried shiitake mushrooms, left to stand overnight for extraction, and the resulting product was compressed using a rotary evaporator.

Extraction # After adding 5 times the volume of ethanol to the radiation source and removing the precipitate produced, 75% ethanol extraction 1 [tliIIl
Aeon Exchange 13 Exchange (Amber 2 Itoe R-120
), the mixture was sequentially passed through a cassym filled with ion exchange resin C Amberlite R-451 to obtain a neutral part.

For comparison, we extracted R-120@Kibu with 2-chloride ammonia water and 45V of Meshii and 0.5N acetic acid to obtain the extract basicity category and the extract kneadability category, respectively. .

The freshness of each category found from 100 tons of dried shiitake mushrooms was as follows:

Water extraction section 40.1F 751 ethanol precipitation section 14.
4f base+! P category: 5.72 Acidic category: 0.42 Neutral category: 104 tons The neutral category was white and odorless.

Using each category, it can withstand high plate pressure spontaneously under a certain official test)
(8HR1ii historical 1″C dish pressure low F animal experiment was conducted.

BHN was maintained during the entire test period at 26 ± 2°C and humidity 50°C.
Top 10-'9! Using solid food in a prepared animal room (−
I inherited it. For each class, 50 pieces of shiitake mushrooms were dissolved in 1 ton of equivalent mt water, and the mushrooms were given ad libitum instead of water.

Test on SNH during the period of increased blood pressure〉 Inject into the l1J1 test solution of 12 to 15 years of age with water (1 kl + 411f for 8 m) until 12 weeks of age, and then return to water and continue to test with water until 16 weeks of age. We then observed changes in blood pressure and physical condition.

The results are shown in Table 1 below, and a significant effect of preventing blood pressure increase was observed in the Topo, water-extracted and neutral categories, and a slight effect in preventing blood pressure increase in the acidic category.

High blood pressure u) i8 HR test> Next, let's talk about the categories that were effective in the test during the period of increased blood pressure.
The effect of lowering blood pressure in rats was tested. 8) For IB, which developed high blood pressure after being pre-fed with water until the age of 25,
The animals were kept in a test solution from 25 to 27 years of age, and then returned to water until they were 28 years of age, and changes in blood pressure and physical condition were observed.

- The results are shown in Table 2 below, and a significant blood pressure lowering effect was observed only in the neutral category.

From the above ◆, it can be seen that the neutral part in the shiitake mushroom extract has the effect of preventing an increase in blood pressure and lowering blood pressure.

No abnormalities such as Iul's were observed in the straightness of the body, external fit, etc. of the father, 8i1R, and it is thought that there is little effect on the side of continuous use.

Therefore, the formulation containing the neutral part of the shiitake extract of the present invention is suitable as a preparation for preventing and treating hypotension.

[Brief explanation of drawings]

Figure 1 shows the infrared S absorption spectrum (K) of the neutral part of the shiitake extract.
Figure 2 shows the UV S absorption spectrum of the neutral part of the shiitake extract, Figure 5 shows the TMB gas chromatogram of the neutral part of the shiitake extract, and Figure 4 shows the spectrum of the neutral part of the shiitake extract. The results of analysis by thin layer chromatography are shown. Patent Applicant Asahi Denka Kogyo Co., Ltd. Procedural Amendment Form C] February 25, 1980 Haruki Shimada, Commissioner of the Japan Patent Office 1, Indication of the case Patent Application No. 125498/1982 2, Name of the invention Has a blood pressure lowering effect Substance 3, Relationship with the amended person case Patent applicant (01g) Asahi Denka Kogyo Co., Ltd. 4, Agent No. 601 Pacific Nogizaka, 6-29 Akasaka 9-chome, Minato-ku, Tokyo January 46, 1982 (shipped) 6. Target of correction Figure t 7. Details of correction As shown in the attached sheet, the drawing has been corrected to a drawing that was clearly drawn using a drafting method using white tracing paper with no cross-section lines, etc. (no change in existence) 0 or more

Claims (1)

[Claims] After extracting shiitake mushrooms with an aqueous medium, the extract is treated with an ion exchange resin, and the neutral part of the resulting extract is purified using column chromatography to obtain a substance that has a hypotensive effect.