JPH069421A - Oily preparation and method for producing the same - Google Patents

Abstract

(57) [Summary] [Object] To provide an oil-based preparation having a high activity of an active oxygen-inhibiting substance as an active ingredient and a high penetration into cells at a disease site, and a method for producing the same. [Structure] A grain raw material composed of rice or wheat germ and soybeans is roasted at a temperature not exceeding 100 ° C., then koji is added and fermented, and then finely pulverized, which is roasted by the above method. It is added to a mixed oil consisting of oil collected from sesame and oil collected from raw sesame, and the ratio of the mixed oil to the total amount of the fine powder and the mixed oil is 60 to 95% by weight.
It is an oil-based formulation. This oily preparation is applied to the prevention and treatment of various inflammations and incurable diseases caused by destruction of cell tissues by active oxygen and lipid peroxides produced in the human body.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an oily preparation and a method for producing the same, and in particular, a substance that suppresses the production of active oxygen and lipid peroxide in human body (hereinafter referred to as active oxygen inhibitor) as an active ingredient. The present invention relates to an oily preparation to be contained.

[0002]

2. Description of the Related Art In recent years, various inflammations and incurable diseases (rheumatoid arthritis, thrombophlebitis, progressive systemic skin) caused by destruction of cell tissues by active oxygen and lipid peroxides produced in the human body. Attention has been focused on active oxygen-suppressing substances that exert excellent effects when used for the prevention and treatment of sclerosis, Burger's disease, Raynaud's disease, and intractable skin ulcers.

The above-mentioned active oxygen suppressing substances are low molecular substances such as flavonoids, polyphenols, tannins, tocopherols and vitamin B ₁ contained in plants.
It has been clarified by the study of the present inventors that the oral production of this as a medicine or a health food suppresses the above-mentioned production of active oxygen and lipid peroxide in the body (published on December 1, 1987). , Japan Association of Pharmacists No. 3
Vol. 9 No. 12 Separate Volume "SOD (Superoxide dismutase) and Bioavailability of Crude Drugs" P1097 to P
1119).

Conventionally, as a preparation containing an active oxygen suppressing substance of this kind, a plant-based nutrient as disclosed in Japanese Patent No. 1366268 and JP-A-63-798 developed by the present inventors.
The active oxygen suppressing composition described in JP-A No. 34-34 is known.

The former plant nutrient is a mixture of brown rice powder and soybean powder that have been roasted and crushed with green tea powder, and this is then mixed with koji.
The powder was prepared by adding a small amount of bacteria and soaked in a vegetable oil mixture consisting of sesame oil and soybean oil for about 4 days to extract the active ingredient, and then the precipitate was removed by centrifugation to remove the remaining oily substance from gelatin. It is enclosed in a capsule such as.

The latter active oxygen-inhibiting composition is obtained by roasting plant seeds or their germs, then adding microorganisms and fermenting them, and adding vegetable oil obtained from the roasted plants to them. Vitamin C, a vitamin C derivative, or a plant body containing them is further added, if necessary.

Examples of the plant seeds include rice, wheat, barley, soybeans, red beans, corn, corn, pea and pea, which are rich in active oxygen suppressing substances such as flavonoids, polyphenols, tannins, tocopherols and vitamin B _1. Seeds such as are used as vegetable oil,
Sesame oil, soybean oil, cottonseed oil, corn oil, safflower oil, evening primrose oil, bran oil, rapeseed oil, olive oil and the like are used.

[0008]

However, the above-mentioned plant-based nutrient has a problem that the active oxygen-suppressing substance, which is an active ingredient, has a low activity because it has a problem in a method of processing a plant body as a raw material. It was

The active oxygen-suppressing composition developed by the present inventors has been made for the purpose of improving such drawbacks, and a raw material plant is slowly roasted by far infrared rays to suppress active oxygen. Prevents deactivation due to high temperature of the substance,
By reducing the free molecular weight of the active ingredient and further fermenting the raw material after roasting to promote the free low molecular weight of the active ingredient, the activity of the active oxygen inhibitor has been remarkably improved.

However, according to the subsequent research conducted by the present inventors, the above active oxygen-suppressing composition remarkably suppressed the production of active oxygen and lipid peroxide in a test tube.
It was revealed that this inhibitory effect is not always effectively exerted in the human body.

The present inventors consider the cause as follows. That is, in order for an active oxygen inhibitor to reach a cell in which a disease such as an inflammatory reaction is caused by active oxygen or lipid peroxide, it must pass through the cell membrane covering the surface of the cell. However, since human cell membranes are rich in fats and oils, and therefore have the property of allowing only oily substances to pass, the above active oxygen-suppressing composition having a low oily substance content has the ability to penetrate cells through cell membranes. Low.

[0012] Therefore, the inventors of the present invention have conducted repeated studies to improve the ability of the above active oxygen-suppressing composition to cross cell membranes,
As a result of further improvements in the selection of plant species used as raw materials and their processing methods, the active oxygen inhibitor, which is the active ingredient, has a high activity, and the ability to penetrate into cells with disease is high. The invention has been reached by finding a formulation.

That is, an object of the present invention is to provide an oily preparation having a high activity of an active oxygen suppressing substance which is an active ingredient and a high penetrating power into cells at a disease site, and a method for producing the same.

[0014]

The oil-based preparation of the present invention comprises 100 grains of raw material of rice germ or wheat germ and soybean.
Roasted at a temperature not exceeding ℃, then fermented by adding malt and then pulverized into oil, which consists of oil extracted from sesame roasted in the same manner as above and oil extracted from raw sesame It is added to the mixed oil, and the ratio of the mixed oil to the total amount of the fine powder and the mixed oil is 60 to 95.
% By weight.

As a raw material rich in active oxygen suppressing substances, in addition to the above-mentioned rice germ, wheat germ and soybean, the plant species (barley, red bean, corn, corn) described in the above-mentioned JP-A-63-79834. However, rice germ, wheat germ and soybean are the most suitable raw materials according to the studies by the present inventors.

Next to the rice germ, wheat germ and soybean, the preferred grain raw materials are bran, hatomugi and wheat. Therefore, rice germ or wheat germ (both may be used in combination)
Also, a grain raw material containing at least one of these bran, potato and wheat together with soybean may be used. In any case, the proportion of the germ (rice germ or wheat germ) in the grain raw material is preferably at least 1% by weight or more.

The active oxygen suppressing substance in the grain raw material forms a complicated high molecular weight polymer together with other substances and is not active as it is. Therefore, the polymer bond is cut by means such as roasting, It is necessary to lower the molecular weight. However, if the roasting temperature is too high, the low molecular weight active oxygen suppressing substance will be inactivated, and thus the roasting conditions must be selected in consideration of this point as well.

In order to satisfy such conditions, the grain raw material must be roasted slowly at a temperature not exceeding 100 ° C. for a long time. Specifically, the grain raw material is put into a ceramic container such as a pottery that emits far infrared rays (especially, far infrared rays having a wavelength of 4 to 14 μm is preferable), and the temperature is slowly maintained at about 90 to 96 ° C. And roast while stirring.

The roasting time varies depending on the grain type and cannot be specified unconditionally, but is preferably about 30 minutes to 3 hours. The roasting method is not limited to the above method as long as the active oxygen suppressing substance in the grain raw material has a sufficiently low molecular weight and its deactivation can be prevented.

Next, koji (Asp
ergillus orizae) and ferment. Fermentation conditions are 2
About 2 to 6 days at 0 to 36 ° C is preferable. When fermenting using a fermentor, it takes about 2 to 3 hours. This fermentation is carried out in order to further promote the free and low molecular weight reduction of the active oxygen suppressing substance in the grain raw material, and by going through this process, the active oxygen content is higher than that of the simply roasted grain raw material. The activity of the inhibitor is significantly enhanced.

Next, the fermented grain raw material is pulverized into a fine powder. The crushing may be performed using a commercially available crusher, but depending on the type of the crusher, high heat is generated during use, and the active oxygen suppressing substance is deactivated.
Therefore, it is preferable to use a stone mill that does not generate high heat.

Next, an oil prepared by mixing an oil collected from roasted sesame (hereinafter referred to as sesame paste oil) and an oil collected from raw sesame at an appropriate ratio is prepared, and the above-mentioned fine powder is added to the mixed oil. Added. Sesame paste oil uses 100 sesame seeds
It is an oil obtained by roasting slowly at a temperature not exceeding ℃ and slowly crushing it, then squeezing it, but since the fine solid matter made by crushing sesame remains as it is, the appearance is It is pasty. This sesame paste oil contains abundant low molecular weight active oxygen suppressing substances, and by using this, an oily preparation having a high activity of active oxygen suppressing substances can be obtained.

However, this sesame paste oil has a high viscosity,
Moreover, since the size of the oil droplets is also large, the sesame paste oil obtained by simply adding the fine powder described above has a poor penetrating power into cells, which is a disease site. However, when sesame oil collected from raw sesame is added to this sesame paste oil, the size of oil droplets is reduced, and the osmotic force into cells, which is a disease site, is improved.

The oil collected from raw sesame is an oil obtained by crushing raw sesame as it is, squeezing the sesame and removing the solid matter, and commercially available ordinary sesame oil corresponds to this. The mixing ratio of sesame paste oil and normal sesame oil varies depending on the amount of fine powder to be added, and therefore cannot be specified unconditionally, but 1 to 3 parts by weight of normal sesame oil is used per 1 part by weight of sesame paste oil. Is preferred.

The ratio of the mixed oil to the fine powder added thereto is such that the mixed oil accounts for 60 to 95% by weight of the total amount of both. If the mixed oil is less than 60% by weight, the ability to pass through the cell membrane is low. On the other hand, when the mixed oil exceeds 95% by weight, the concentration of the active oxygen inhibitor which is an active ingredient is low, and therefore the effect of inhibiting the production of active oxygen and lipid peroxide also decreases.

The oily preparation of the present invention obtained by adding fine powder to the above mixed oil may be orally taken by rapidly encapsulating the oily preparation in a gelatin capsule or the like, but preferably 20 to
At 35 ° C. for about 3 to 30 days, more preferably 28 to 30
It is recommended to ripen at ℃ for about 1 week.

By performing this aging treatment, the active oxygen-suppressing substance is further reduced to a low molecular weight due to the koji remaining in the fine powder, and the active oxygen-suppressing substance and the mixed oil are well compatible with each other. The activity and penetration into cells are further improved.

The oil-based preparation of the present invention is used as it is without roasting and fermenting a grain raw material comprising rice germ or wheat germ and soybean (or a grain raw material in which at least one of bran, hatomugi or wheat is added). It can also be prepared by adding it to the above mixed oil together with the above-mentioned roasted and fermented fine powder.

In the finely pulverized grain raw material without roasting and fermenting, the active oxygen-inhibiting substance which is the active ingredient does not have a free low molecular weight, but this is mixed with fine powder that has been roasted and fermented. When added to oil, the koji remaining in the latter fine powder gradually reduces the free molecular weight of the active oxygen suppressor (even after encapsulation), thus producing active oxygen and lipid peroxides. There is an advantage that the suppressing effect is maintained for a long period of time.

On the other hand, in the oily preparation using only fine powder that has been roasted and fermented, the active oxygen-inhibiting substance as the active ingredient is gradually decomposed due to the enzymatic reaction which continues to proceed even after encapsulation. Therefore, the shelf life is shorter than that of the one added with fine powder that is not roasted or fermented.

However, if the addition amount of the fine powder that is not roasted or fermented is too large, the activity of the active ingredient will be reduced, so the ratio of both is 1 fine powder that has been roasted and fermented. Fine powder without these treatments for parts by weight.
It is preferable that the amount is about 5 to 1 part by weight. In this case, too,
The ratio of the mixed oil to the above-mentioned two kinds of fine powders is such that the mixed oil is 60 to 95% by weight of the total amount.

The oily preparation of the present invention obtained as described above has a high activity of the active oxygen inhibitor and a high penetrating power into cells, and as is clear from the results of the clinical tests described below, the existing It exerts a remarkable effect against various inflammations and intractable diseases for which the therapeutic effect was insufficient with anti-inflammatory agents.

The oily preparation of the present invention is enclosed in a gelatin capsule or the like and orally taken as a medicine. In addition, in the case of pigmentation abnormalities such as dermatitis, spots, and freckles, and wrinkles, it may be directly applied to the affected area. Indications include, in addition to the above dermatitis, chronic diseases such as rheumatoid arthritis, thrombophlebitis, progressive systemic skin sclerosis, Burger's disease, Raynaud's disease, and intractable diseases such as intractable skin ulcers. However, it is also effective in treating and preventing various pollution diseases, burns, injuries, fatigue, sickness, constipation, etc.

The oil-based preparation of the present invention has no side effects because it is made of only cereals, koji and sesame, so that it can be taken orally as a health food to help maintain and improve health. Needless to say, when formulating, auxiliary drugs such as various vitamins and minerals or components useful for health, flavors, flavors, coloring agents and the like may be added, if necessary.

[0035]

[Examples] Rice germ, soybean, bran, adlay, and wheat (1 part by weight each) were placed in a pot made of earthenware that emits far infrared rays of 4 to 14 μm, and roasted at 90 to 96 ° C. for 3 hours with slow stirring. . Next, 3% of the total amount of seed koji was added and fermented at 36 to 40 ° C. for 72 hours, and then finely powdered using a stone mill. Further, the above-mentioned five kinds of grain raw materials which were neither roasted nor fermented were ground with a stone mill to obtain the same amount of fine powder. On the other hand, sesame was roasted by the same method as described above, ground with a stone mill, and then pressed to obtain sesame paste oil.

Next, 28.1 parts by weight of sesame paste oil and 48.9 parts by weight of commercially available sesame oil were mixed, and 11.5 parts by weight of the fine powder roasted and fermented and neither roasted nor fermented 11.5 parts by weight of the fine powder was added to each and stirred uniformly. This was aged at 28 ° C. for 1 week and then encapsulated in a gelatin capsule to obtain an oily preparation.

[0037]

【The invention's effect】

[I] Test tube test An oily unsaturated fatty acid (docosahexaenoic acid) is used as a method for measuring the ability of a test tube to reach and penetrate oily sites.
When the oily preparation of the present invention (Example) is added to a reaction system (TBA (thiobarbituric acid) reaction) in which is reacted with an active enzyme generated by ultraviolet rays to produce lipid peroxide, the production of this lipid peroxide is suppressed. The degree was measured.

That is, 1 stock solution of docosahexaenoic acid
Using 0.1 cc diluted to 00 times, 1.8 mg / ml of the sample of the oily preparation of the present invention was added to produce the lipid peroxide produced in TB.
It was measured by A reaction. TBA reaction is 7% sodium dodecy
l sulfate 0.2ml, 0.1N HCl2ml, phosphotungstic aci
d 0.3 ml was mixed, and 1.8 mg / ml sample was added thereto, and 0.6
Add 1 ml of a 1: 1 mixture of 7% TBA and acetic acid and use a fluorescence spectrophotometer to excite at 515 nm, emiss.
The measurement was performed at ion 553 nm.

As comparative examples, the plant nutritional supplement of Japanese Patent No. 1366268 (Comparative Example 1) and JP-A-63-7983.
The same measurement was carried out using the active oxygen suppressing composition (Comparative Example 2) described in JP-A No. 4 as a sample. The results are shown in Table 1.

[0040]

[Table 1]

-Test Results- All samples were oily unsaturated fatty acids (docosahexaenoic a
(Cid) is irradiated with ultraviolet rays ( ¹ O ₂ ) and lipid peroxide (TBA r
The production of eactive substances was significantly suppressed, but the oily preparation of the present invention markedly suppressed this (P <0.
0001) I did. This result indicates that the oil-based preparation of the present invention has a higher activity of the active oxygen suppressor than the conventional similar products (Comparative Example 1 and Comparative Example 2) and has a high penetrating power into diseased cells. I support it.

The isotope ⁽³ H) labeled to a low molecular weight active oxygen inhibitors which are included in the present invention the oily formulation ^[3,4-3 H
₂ ] -The active oxygen inhibitor was prepared, added to human histiocytes in a test tube, and the count (cpm) of [ ³ H ₂ ] bound to the cell membrane was measured by a scintillation counter to obtain a cell membrane. The ability to reach was tested (2 Ci / mM labeled tritiated thymidine).

Similar tests were conducted on Comparative Examples 1 and 2. The results are shown in Table 2. As is clear from Table 2, the oily preparation of the present invention had the highest affinity for the cell membrane as compared with Comparative Examples 1 and 2.

[0044]

[Table 2]

The oily preparation of the present invention is subjected to ultrasonic waves and added to an active oxygen generating system (neutrophil and xanthine-xanthine oxidase) which is an active oxygen measuring solution so that the bio-converted concentration thereof becomes 1.6 mg / ml. Three types of active oxygen (O ₂ ⁻ , H ₂ O ₂ , OH.) Were measured and compared with the active oxygen value in the case of no addition (control). The bio-concentration is the amount assumed to exist in the blood when one daily oral dose (9 g in the case of the oil-based preparation of the present invention) is absorbed by the living body.

The three types of active oxygen measuring methods are as follows. O ₂ ⁻ is the amount of O ₂ ⁻ that reduces ferricytochrome C determined by Beckman's spectrophotometer at a wavelength of 550 nm.
H ₂ O ₂ is converted into O ₂ ⁻ using the method
Since the fluorescence emitted by scopoletin is reduced in the presence of peroxidase, scopoletin and peroxidase were used.
Fluorescence reduction of scopoletin with Hitachi spectrophotometer
It was measured at excitation 370 nm and emission 460 nm. OH
Is a method of quantifying ethylene gas by gas chromatography made by Hitachi and converting it into OH. By utilizing the principle that α-keto-methiol-butylic acid (KMB) reacts with OH. To produce ethylene gas. Was used. Similar tests were performed for Comparative Example 1 and Comparative Example 2. The results are shown in Table 3.
Shown in.

[0047]

[Table 3]

-Test Results- Although the active oxygen suppressing effect of the oil-based preparation of the present invention is slightly inferior to that of Comparative Example 2, a stronger active oxygen suppressing effect was exhibited as compared with Comparative Example 1 having the same oiliness. However, as is clear from Tables 1 and 2 above, Comparative Example 2 has a low ability to reach cells in which a disease has occurred because the content of the oily substance is small.

Therefore, when comprehensively judged, the oily preparation of the present invention has a high effect of suppressing active oxygen and has a high penetrating power into the cells at the disease site, and is the most excellent active oxygen suppressing preparation.

[II] Clinical test Up to now, mainly autoimmune diseases and rheumatoid arthritis, which have been resistant to or exacerbated by any of non-steroidal anti-inflammatory agents, steroids and Comparative Example 2 (active oxygen suppressing composition), have been investigated. The therapeutic effect was examined in 96 patients with collagen disease, blood circulation disorder, nephritis, cirrhosis, and spots / freckles. The results are shown in Table 4.

[0051]

[Table 4]

Continuation of the front page (51) Int.Cl. ⁵ Identification number Office reference number FI technical display location A61K 9/107 W 7329-4C

Claims (7)

[Claims] 1. A grain raw material comprising rice germ or wheat germ and soybean is roasted at a temperature not exceeding 100 ° C., then malted by adding koji and then pulverized, and then roasted by the above method. It is added to a mixed oil consisting of oil collected from roasted sesame and oil collected from raw sesame, and the ratio of the mixed oil to the total amount of the fine powder and the mixed oil is 60 to 95.
An oil-based preparation characterized by being made into a weight%. 2. A grain raw material composed of rice germ or wheat germ and soybean is pulverized into fine powder without roasting and fermentation,
The oily preparation according to claim 1, which is obtained by adding this to the mixed oil together with the fine powder according to claim 1. 3. In addition to rice germ or wheat germ and soybean,
The oil-based preparation according to claim 1 or 2, wherein a grain raw material containing at least one of bran, hatomugi or wheat is used. 4. The oily preparation according to claim 1, which is encapsulated and orally administered as a medicine or health food. 5. A method for producing an oily preparation, which comprises using far infrared rays having a wavelength of 4 to 14 μm when roasting the grain raw material according to claim 1, 2 or 3. 6. A method for producing an oily preparation, which comprises roasting the grain raw material according to claim 1, 2 or 3 and then fermenting the grain raw material at 20 to 36 ° C. for 2 to 6 days. 7. A method for producing an oily preparation, which comprises adding the fine powder according to claim 1, 2 or 3 to a mixed oil and aging it at 20 to 35 ° C. for 3 to 30 days.