JPS59116226A - Hypotensive agent made from juice of gramineous plant - Google Patents

Abstract

PURPOSE:To provide the titled agent free from side effect, and containing the hypotensive component of the juice of raw leaves of gramineous plant as an active component. CONSTITUTION:An aqueous solution of a water-soluble component of the juice obtained from the raw leaves of a gramineous plant is mixed with 60-80vol%, based on the aqueous solution, of a polar solvent (e.g. methanol) and/or the solution is heated at 70-100 deg.C. The produced insoluble solid component is removed from the juice, and if necessary, the obtained liquid is subjected to gel-filtration treatment, and the product is used as the active component. The juice contains complex natural components, and the nature and the composition of the hypotensive components in the complex system are still unknown. However, the component can be used as a drug effective to various hypotensions without causing side effects e.g. by oral administration, intravenous injection, subcutaneous injection, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides a green juice source antihypertensive agent from the grass family, which is characterized by containing, as an active ingredient, a component exhibiting a blood pressure lowering effect, which is contained in the green juice component of the green leaves of a grass family plant. Regarding.

More specifically, the present invention provides an insoluble solid that is formed by adding 60 to 80% by volume of a polar solvent based on the volume of the aqueous solution from an aqueous solution of a water-soluble portion obtained from a green juice component of green leaves of a grass family plant. minutes and/or the aqueous solution at 70° to 100°C.
A gramineous plant characterized by containing as an active ingredient a component obtained by removing an insoluble solid content formed by heating to , or a component obtained by further gel filtration of a liquid phase after removing the insoluble solid content. Regarding green juice source blood pressure lowering agent.

The green juice component of the green leaves of gramineous plants, such as barley, contains a wide variety of useful ingredients that are useful for a wide range of food and pharmaceutical applications, including foods, beverages, luxury goods, health drugs, cosmetics, and pharmaceuticals. Moreover, in order to produce the dry powder of eel green juice ingredients, barley Seiso I (stage 1ii) is used.
From the mechanical crushing of j to Jll-', to: solid It? Blue that can be separated and removed and 4jY! A known method is to spray-dry or freeze/dry a mixture that has been neutralized to 1 + I- (G ~ 9) as a sign of 1.
6th l! , ', No. 478; Special Publication Show 4G-985
No. 48; Me 1J International Special Edition 3' [No. 48; 787 + 5
No. 91). The inventor named the powder of the extract of young leaves of the gramineous plant, ie, the powder of green juice, as barley green (=1 digit), and conducted research on the action of the green juice component for food use, as a health drug, or as a medicine. I proceeded.

The present inventor found that green juice, especially green juice of grass family plants and its dry powder, is extremely effective in regulating blood pressure abnormalities in humans and preventing hypertension. This is considered to be one of the benefits of taking green juice from grasses, and the inventor's book ``Amazing Healthy Barley Green'' suggests that there is something in the green juice of grasses that has the effect of preventing hypertension. , published by Shodensha on April 5, 1976. Green Blood, The Benefits of Green Juice, Old Book of Green Juice - Published by Azusa Okikai. ] and various other publications.

The name of the invention was further researched and it was discovered that green juice had a blood-depressing effect, and research was carried out to develop a method for producing this effect by an industrially advantageous method. I finished 1j. As a result, we found that even when the green juice of green leaves (stem and leaves are collectively called) of grasses and its extract powder, that is, barley green itself, was orally administered to test animals, it clearly showed a blood pressure lowering effect. We have now confirmed that the extract powder itself is useful as a hypotensive agent.

Furthermore, it contains more concentrated blood pressure lowering active ingredients than green juice and its extract powder. We have discovered a way to obtain this product in a more highly pure state, which is advantageous for both businesses. That is, from the green juice component obtained by separating and removing coarse solids from the mechanically crushed green leaves (generally referred to as stems and leaves) of grass plants, green juice is extracted by means such as centrifugation, filtration, and coagulation sedimentation. water-soluble part, such as that obtained by removing fine suspended solids in juice;
The green juice component from which the solid content has been removed is pulverized by spray drying, freeze drying, etc., and the green juice extract powder is redissolved in an aqueous medium to remove the fine suspended solid content. It has been found that the resulting water-soluble portion has a blood pressure lowering effect, that is, Ir, which exhibits a blood pressure lowering effect, is present in the water-soluble portion.

Furthermore, about 60% to about 80% by volume, preferably about 70% to about 80% by volume, is added to the aqueous solution of the water rif-soluble portion, based on the volume of the aqueous solution.
The solid content and/or the aqueous solution formed by adding % by volume of a polar solvent such as a lower alcohol is approximately 70% by volume.
The industrially easy-to-operate means of removing the solid content formed when heated to about 100°C can eliminate the disadvantage that the blood pressure-lowering components in the green juice component may coexist in the water-soluble portion. It was discovered that it can be selectively separated from other complex components.

Furthermore, for example, the green juice obtained by removing the solid content from the squeezed juice described in Section 2, or the redissolved product of the green juice component powder as described above, may be heated to a temperature of about 60° C. or higher to form it. By removing the solid content, it is possible to use the water-soluble part that has been subjected to a heat history of about 6 (1"C or more), or alternatively, If a polar solvent is added to the part under conditions that deviate from the above concentration conditions and/or the solid content is removed by heating under conditions deviating from the above heating conditions, the resulting product It was found that the blood pressure-lowering effect of green juice or
It has been found that it is not preferable to heat the water redissolved liquid of the f-juice component powder to a temperature of about 60° or higher for a substantial period of time and to subject it to a substantial thermal history of about 60° or higher.

Although the reason for 1M1 is not clear, the green juice component of the green leaves of the grass family, which is the raw material, is a complex compound of natural sources, such as amino acids, proteins, camouflages, polysaccharides, and saccharides. A very wide variety of types, properties, and states of ingredients, such as pigments such as macrophytes, chlorophyll, and carotene, minerals, and saponins, interact with each other to maintain a chemical and physical balance. It is a system in which +q*, a, bonding, and detachment (1) coexist in a colloidal state.

Furthermore, the actual state of the component system that exhibits the blood pressure lowering effect that exists in this complex system and the state of υ77 are completely unknown. Therefore, if the polar solvent concentration conditions and heating conditions are deviated from 1-thermal history article 1'1, the effect (the part of the component system that exhibits a blood pressure lowering effect depending on the order), and how it is lost is unknown. Although it is completely unclear, changes in the timing when the above conditions are applied will result in many changes that influence each other among the various components present in the above complex coexistence system, such as:
Phenomena such as adsorption or inclusion of useful components in coagulating solids, unfavorable denaturation, decomposition, or association of useful components, undesirable release of inhibitor components or non-useful components, or binding phenomena with useful components, etc. It is speculated that this is caused by mutual influence and innovation. For example, in Comparative Example A, which will be shown later for comparison, a green juice obtained by removing coarse solids from the squeezed juice of young barley leaves using a heating concentration method conventionally used to collect aqueous extracts of plants. A component obtained by processing in the same manner as in Production Example 1, except that the water-soluble part was heated as it was at about 90 ° C for 20 minutes without collecting the water-soluble part, and the solid content formed was removed and the water-soluble part was used. t'l+ was found to be significantly inferior in blood pressure lowering effect.

Therefore, the object of the present invention is to provide a naturally sourced hypotensive agent containing as an active ingredient a component that exhibits a hypotensive effect contained in the natural green juice component of the green leaves of a grass family plant. It is in.

The advantages of the above objects and other objects of the present invention will become more apparent from the following description.

The active ingredient used in the present invention is obtained from a green juice component of green leaves of a grass family plant, preferably from an aqueous solution of the water-soluble portion of the green juice component that has not undergone a thermal history of about 6+1' or more. Solids formed by about 60% to about 80% by volume of polar solvent and/or about 70° to about 70% of the aqueous solution
By removing the solid content formed by heating at about 100''C, it can be collected as a blood pressure lowering component in the green juice.

Examples of the above-mentioned grasses include rice, wheat, barley, rye, oats, adlay, Italian dicrase, corn, sugarcane, solium, and grains. Among these, it is preferable to use wheat.

In order to obtain the active ingredient used in the present invention, the water-soluble portion in the green juice component of the green leaves (a term that includes leaves and stems) of grass plants such as those illustrated in Section 2 is utilized. When using wheat as the green leaves, it is preferable to use green leaves at or around the maximum ripening stage. At this time, it is preferable not to subject the green juice component to a thermal history of about 60° C. or higher before collecting the water-soluble portion. However, here, the term "not imparting a thermal history of about 60° C. or higher" means that the material is not exposed to such a temperature for a period of time during which a substantial thermal history occurs. Therefore, it is not excluded that the green juice component is added to fabrications that do not give the green juice component a substantial thermal history of about 60° C. or higher, such as instant heat sterilization or heat spray drying. For example, it is meant to exclude imparting a substantial thermal history, such as boiling and heat concentration of green juice components.

For example, by mechanically squeezing green leaves of grasses, for example, solids including coarse solids and fine solids are removed from shredded green leaves of grasses using a crushing stone, a juicer, etc. The squeezed aqueous phase can be used as the water-soluble portion in the green juice component described in -.

The solid content may be removed in one stage or in multiple stages. For example, after first removing coarse solids by furnace,
Furthermore, it is possible to use an aqueous phase from which fine solids have been removed by chewing with suitable paper, oven cloth, or other materials, or by centrifugation. Alternatively, for example, the above-mentioned squeezed juice from which coarse solids have been removed, that is, green juice, or the squeezed juice from which coarse and fine solids have been removed, may be spray-dried or freeze-dried to the water-soluble portion, preferably at about 60°C. The dried green juice component obtained by drying under conditions that do not substantially give the above thermal history or the dried product of its water-soluble portion is redissolved in water, and if necessary, the solid content is removed. By using the obtained aqueous phase,
Wear. The aqueous phase used in the present invention as exemplified above is usually a light yellowish brown to yellowish brown aqueous phase.

To collect the active ingredients used in the present invention, the following example is used.
- obtained from the green juice component of the green leaves of Poaceae 411′i which can be obtained as described above, preferably about 6+1
From an aqueous solution of the water-soluble portion of the green juice component that has not undergone a thermal history of 'C or higher, approximately 60 to approximately 8 (
) volume %, preferably from about 7 ( ) to about 80 volume % polarity 1
The solid content and the water solution formed when adding 8 poro 5 are approximately Ma()°-4,! 31 (l O'C1 Preferably, either or both of the solids formed when heated to about 80° to about 100'C, preferably both, are removed. When both are removed, Which solid content can be removed first? After removing the heated solid content,
It is operationally advantageous to remove solids using polar solvents.

Examples of the polar solvent include alcohols such as methanol, ethanol, propyl, and acetone. Further, the removal of the solid content using the polar solvent and/or the removal of the solid content by heating may be performed multiple times. Removal of the solid content can be carried out using any liquid separation means, such as 2-filtration and centrifugation.

In addition, the solid content formation operation using the polar solvent may be carried out at room temperature, or if desired, a temperature condition below the boiling point of the polar solvent aqueous solution may be adopted. The liquid phase is obtained by removing the liquid component in 12 steps such as vacuum drying, uni'Is drying, and freeze drying, and converting it into a brown to yellowish brown powder. I can do it.

In order to collect the active ingredient used in the present invention, the liquid phase obtained as described above or the powder obtained by removing the liquid from the liquid phase is added to the polar solvent-water mixed system as described above. The liquid phase re-dissolved in can be further purified by the del 7ρ filtration method. Preferably, the del filtration process reduces the molecular weight to about 5.
(It is possible to remove the fraction 1 (11 (month), 2) and collect the blood pressure-lowering components in the green juice in a more purified state as the lower fractions. IT- or molecular weight Approximately 1
It is possible to collect the fraction below o Oo, and the fraction below the molecule is about 10 + i o,
It is also possible to collect fractions.

Del? Examples of materials used in the filtration method include dextrandel, which is a synthetic gel, Sepl+adcx C
; -25+S (Kou 11adex G-15, 5ep
hadex Ll-120 (PI+ar1nacia
Fine Cbe mouth + 1 cals), F3'+o-
C: clP-6,Blo-Ge1 P-4,8io-
Polyacrylamide gels such as GetP-2 or gels such as various agarose gels can be opened. Dell 1
The filtration operation itself can be carried out by a known method, for example, by adding enal alcohol to an aqueous solution of the water-soluble portion of the green juice component as already removed, and reducing the concentration of ethyl alcohol to about G (lv/v). %.The insoluble aggregates that can be precipitated are precipitated by centrifugal sedimentation, and the supernatant liquid is collected.

This is concentrated under reduced pressure to approximately 115 volumes. Water is added to this to dilute the solution to a concentration of about 1% solids. Cefatex G-2 that can be dried
Add approximately 30% of the column volume to the column and dissolve with water. Discard the eluate until it reaches 35% of the elution volume or column bed volume, and then
Collect the effluent until it reaches 0%. This liquid has a molecular weight of about 500 in the water-soluble component of the green juice of green leaves of grasses.
Components with a value of 0 or less and around 1000 are removed by 9u. In addition, the elution volume from the above-mentioned column bed was collected fractionally and the molecular weight was 1oo.
It is possible to selectively collect those before and after o. It is also possible to use a low del of separation range, such as -15, for Sephadex for this purpose. Furthermore, it can be further purified using conventional means to produce injections and the like.

The grass-based green juice-based blood-lowering agent of the present invention can be used as an excellent drug without side effects for various types of hypertension. Examples of the administration means include oral administration, intravenous administration, subcutaneous injection, and the like.

The antihypertensive agent of the present invention can be used in various dosage forms.
Wear. Examples of such dosage forms include powders, granules, tablets, liquids, and the like.

Furthermore, examples of adjuvants used for use in various dosage forms include diluents or carriers, whether liquid or solid, such as starch, sugar, lactose, dextrin, water, and alcohol. can be exemplified. The dosage of the antihypertensive agent of the present invention is appropriately selected depending on the type of hypertension, symptoms, etc., and is, for example, about 10 to about 51) Omg/kg.
A dosage such as body weight/day may be exemplified. In addition, I-D5o is 12(')OOm8/kg or more, and almost no toxicity is observed.

Hereinafter, some examples of the pharmacological effects of the agent of the present invention will be explained in more detail using Examples as well as production examples of the active ingredients.

Production example 1 Young barley leaves (both leaves and stems) plant height 20-25cm later 100k
After thoroughly washing with water and draining, the juice is pressed and ground using a squeezer, and then compressed and crushed using a compression extractor to remove coarse solids (mainly fibers), resulting in a green colored green juice 801. This was spray-dried to obtain about 4 fil kg of green barley juice extract powder. Hontsuri 401 was added to this to prepare a homogeneous green juice emulsion due to IL conversion. The fine insoluble components were separated and removed using a basket-type centrifugal centrifugal machine and a furnace cloth to obtain a water-soluble part of the green juice component that turned brown. After heating to JO°C to coagulate and precipitate the heat-coagulable insolubilized components, this was separated into a furnace and was heated to about 30°C.
I got just under 1. This material is vacuum frozen* and dried to form a powder.
, 0 kg was obtained.

This is designated as sample B.

Production Example 2 An aqueous solution of about 301 water-soluble green juice components was obtained in the same manner as in Production Example 1. While stirring this solution, gradually add ethyl alcohol (12()1). Approximately 3 (lv) that can be coagulated and precipitated
/v% Ethyl alcohol-insoluble components were separated by centrifugation to obtain a supernatant of approximately 110%. 80% ethyl alcohol 301 was added to the separated coagulated precipitate fraction, washed with stirring, and centrifuged to obtain a clear liquid.

This was combined with the previous ``2 (σ liquid), distilled under reduced pressure to remove most of the ethyl alcohol, and then dried under reduced pressure at low temperature to obtain a powder of 1㎜g. Soluble part: 80
V/V% ethyl alcohol-soluble component extract powder, designated as Formula 3 Feeding C.

Production Example 3 4 kg of extract powder of the water-soluble part of the green juice component obtained in the same manner as Production Example 1 was dissolved in water 201 and filtered.

Obtain 201 points. This diameter is 40c + n height is about 10f
-, Sephadex G-25 in a l cm glass tube.
, Coarse mold packed (gelpera)/volume 661)
(flow rate 41/ml). Excluding the first outflow contract 301, subsequent outflow contracts 531 are collected. This substance contains low molecular weight substances with a molecular weight of approximately 50 (10 or less).This was freeze-dried to obtain 850 g of powder. It is called fraction extract powder (sample D).

Comparative Production Example 1 Barley grass green juice 80 obtained in the same manner as Production Example 1
1 was heated and concentrated at a temperature of 90° C. for 20 minutes, and then the same liquid separation operation was performed using a basket-type centrifugal rock to obtain the water-soluble portion of the green juice component.

The water-soluble portion was vacuum freeze-dried in the same manner as in Production Example 1 to obtain 1.8 kg of powder (Sample A).

Example 1 Drug efficacy test [Effect on blood pressure of spontaneously hypertensive rats (SHR)] Specimen was forcibly administered orally to 10- to 12-week-old male SI-iRs 2... [3 times at time intervals] Immediately after administration and 1.
2.4 hours later (24 hours after the third administration), foot artery pressure (systolic pressure) was measured non-invasively using a mercury manometer. The dose is that of Sample A, which is a comparative example.
1500 + nε/1 (g) for the sample group B of Production Example 1, 1000 Ing/kg for the sample C group of Production Example 2, and 11000 Io for the sample group of Production Example 3. (Y And so.

The number of animals used was 6 per group, and the body weight at the start of the study was 2 +1 (1-3 (+ +, IE), blood pressure was 150-2 f, l Omu Hg. During the test period These animals are housed in stainless steel cages (1 medium).
(Nl, Depth G Cm, Height 20 cm) The animals were housed in groups of two and given free access to solid feed (Oriental Ij￥t!NMDO) and tap water.

The changes in blood pressure after administering the test results are shown in Table 1 below. In the Moonshine group, almost no change was observed at 1 day, whereas a decrease in blood pressure was observed at 5 days in each administration group.

Comparative Example Sample A] 50 (+ +ngl axis administration group; 1 to 2 hours after each administration, a decline was observed, and then it gradually increased, and by the 24th hour, the level had returned to its original level.

Sample 81.5 (1 (l mg/k8 administration group: showing the price immediately after each administration, decreasing 11) is greater than the comparative sample, showing a lower value with a significant level]. Restoration over time. Although there is a tendency, as the number of times is repeated, it shows a lower νF offshore than the first time, and the effect on the ratio is clearly recognized in the comparative example △.

Sample (: ] (+1 for month) + n3/kg, sample 1)
The 100 mountain n3/kHz throwing group showed a significant decrease in several jts. Samples 3 and 1) also show a significantly greater blood pressure lowering effect.

\ ゛＼

[Brief explanation of the drawing]

The accompanying drawing is Figure 7 showing the relationship between blood pressure and hour as an example of the effect of the antihypertensive agent of the present invention on the blood pressure of spontaneously hypertensive rats shown in Table 1.

Claims (1)

[Scope of Claims] 1. From an aqueous solution of the water-soluble portion of the juice component obtained from the green juice component of green leaves of a grass family plant, based on the volume of the aqueous solution, 6.
Contains as an active ingredient an insoluble solid content formed by 0 to 80% by volume of a polar solvent / or a component from which insoluble solid content formed by heating the aqueous solution at 70° to 100'C is removed. Characteristic antihypertensive agent. 2. From an aqueous solution of the water-soluble portion of the green juice component obtained from the green juice component of green leaves of grasses, based on the volume of the aqueous solution, 6.
The insoluble solids formed by 0 to 80% by volume of polar solvent and/or the liquid phase from which the insoluble solids formed by heating the aqueous solution at 7()° to 111 (1"C) are removed,
A hypotensive agent further comprising a gel-filtrated component as an active ingredient.