JP3166103B2 - Method for producing fructose-extracted saponin extract liquid, method for producing fructose-extracted saponin extract solution, method for producing crystalline saponin mannitol adduct, and method for producing fructose-containing crystalline saponin mannitol adduct - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing a saponin extract solution for extracting a saponin body from ginseng and its related crude drugs which are conventionally regarded as physiologically and pharmacologically effective, and a fructose extraction. How to make saponin extract solution
Law, method for producing a crystalline saponin mannitol adduct, and fructose-containing crystalline saponin mannitol adduct powders manufactured in
Construction method .

[0002]

2. Description of the Related Art Conventionally, substances having an extracting effect include sodium chloride (sodium chloride), sucrose (cyclose),
Alcohol and the like are known. For example, conventionally menstruation,
In order to obtain an extract extract from ginseng and the like, which are considered to be pharmacologically effective, extraction is performed with an aqueous solvent, and then the active ingredient is extracted from an aqueous layer into an alcohol layer using an alcohol such as n-butanol. Was concentrated to obtain an extract. In addition, in homes and the like, there has been a history of extracting ginseng ginseng roots with hot water or extracting them with alcoholic water such as shochu over a long period of time, diluting them and drinking them. Further, a method of taking an extract obtained by concentrating and solidifying the extract is also known.

[0003]

However, there is a problem that the conventional extract requires a long time of several tens of days or more for the extraction. This means that industrially, huge equipment for long-term extraction is required. Furthermore, beverages extracted with, for example, alcohol cannot be provided to children and toddlers, sick persons, and the like, and salt has a narrow range of use due to basic taste problems. In addition, sucrose is a favorite product having almost no physiological or pharmacological effect, and cannot be at least actively provided to diabetic patients and the like.

[0004] Further, in such a conventional method, only the main roots and fine roots which are the underground part of ginseng are used,
Regarding stems, leaves, buds, seeds, etc., despite containing useful saponin bodies, their effective use was not measured, and they had to be discarded. Therefore, the extracted saponin body and the preparation containing it have been extremely expensive.

[0005] Further, when the extract of ginseng obtained by the conventional method is stored for a long period of time, it may not only be deteriorated by the absorption of moisture or oxygen in the air, but also be contaminated by microorganisms (mold).

The present inventor has found that fructose is used as an extraction medium to extract components contained therein from plant nuts or bulbs or mycelia (Japanese Patent Application Laid-Open No. 61-831).
No. 29) and found that mannitol is added to the extracted saponin to crystallize it (Japanese Patent Laid-Open No. Sho 5).
JP-A-7-128632) could not solve the problem of long-term immersion and high-priced raw materials using ginseng root as raw materials.

[0007]

Means for Solving the Problems The present invention has been proposed in view of the above, and a liquid fructose having a concentration DS of 60 ± 10 is added to a ginseng and / or a related crude drug in an amount of 1 to 2.5 times. Production of a fructose-extracted saponin extract liquid, characterized in that the mixture is supplied to the ultrasonic vibrating horn continuously or in batches to perform cavitation operation of the oscillating body and extraction by synergy of osmosis of fructose. It is about the method.

[0008] The present invention also provides a saponin extract solution obtained by treating the above-mentioned fructose-extracted saponin extract solution with a Ca-type cation exchange resin to separate fructose from the system. The present invention also proposes a method for producing a crystalline saponin mannitol adduct characterized by adding a double amount of mannitol and concentrating the mixture to obtain a crystalline form.

[0009]

DESCRIPTION OF THE PREFERRED EMBODIMENTS First, liquid fructose used as an extraction medium in the present invention will be described. The fructose used in the present invention is a monosaccharide having a chemically difficult property, which can be seen from the fact that crystallization has been successfully completed one third century ago. This fructose has properties that other saccharides do not have such as deliquescence, large solubility, large permeability, weak heat resistance, etc., and these properties hindered development, but metabolism in vivo, especially It has been recognized that it is an absolutely necessary monosaccharide because it is the basic substance of the citric acid cycle as a heat energy source, and it is described in the Japanese Pharmacopoeia. It should be noted that the properties of fructose are (i) the degree of sweetness is 1.5 times (20 ° C.) that of sugar, and the sweetness is the highest quality among monosaccharides. (B)
It has high osmotic pressure and is second only to inorganic salt NaCl. A characteristic of fructose as a medicament is that glycolysis of the metabolic pathway can be carried out without the help of insulin hormones and that it can be converted into energy, so that diabetic patients who cannot use glucose can also take it positively. In addition, it has been proved that glycogen production in the liver is highly efficient and has a positive effect on the activities of ordinary people. In addition, fructose helps to activate alcohol detoxifying NAD in the liver. In addition, it does not interfere with gastric juice secretion as compared to sucrose and is used safely. Incidentally, the osmotic pressure of fructose is a phenomenon in which the concentration of fructose moves in the direction of decreasing the concentration difference of fructose.
The value of 0 is based on the finding that DS is favorable for mixer processing and ultrasonic processing.

Next, the ginseng used in the present invention and its related crude drug will be described. Ginseng has a long history of being described in Shinnobu herbs, and its medicinal efficacy is still firmly maintained in modern times. However, for general consumers, ginseng (main root) and conventional preparations using it are so-called "Takamine flowers" because of their high price.
Ginseng and related crude drugs are originally cultivated by cultivation, and some of them are naturally grown, but they are not only rare but also extremely expensive religious crude drugs.
In recent years, a new method for mass production by the bio-bio method has been developed, but requires a cultivation period of at least 6 years or more like the cultivation method. The point is to expect the expansion of the main roots due to the cultivation for many months, and to acquire high-priced products.

The remarkable effect of the physiological action of ginseng is due to the
It is a drug that has a solid position in the east and west with experience. Day
If you refer to the information described in the Pharmacopoeia,
You can see that this is the largest gem. Pharmacology; Choline production by stimulating cerebral cortex in human and rat experiments
Shows kinetic effects, lowers blood pressure, promotes breathing, improves hyperglycemia,
Increased insulin action, increased red blood cell count and hemoglobin level
In addition, it promotes the appearance of early evoked potentials of EEG,
In addition to showing effects such as enhancing adrenal cortex function,
Improvements in learning and memory processes are also recognized. Essence; crude drug, health tonic, stomach medicine History;
Drow, calm the mind, set the soul, stop the palpitations, wake up
Open the heart and gain wisdom. And so on.
You. Ingredients: ginsenoside R as saponin₀ , R_a ~ R_h But
Are separated. That genuine sapogenin R₀ Is oleanolic
 acid, but the others are dammarane _b1,
R_b2, R_c , R_d Such as (20S) -protopanaxadio
l and R_e , R _f , R_g1, R_g2Such as (20 S) -prot
opanaxatriol, the ratio of both is 3: 1 and 3,
A sugar is bound at positions 6 and 20. Some of the descriptions in the Pharmacopoeia have been given above,
Are listed in detail. The above is true of ginseng
Prove that it is a reliable crude drug that tells the essence
are doing. The following ginsenoside R₀ , R_x of
The chemical structure is shown.

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Although the main roots of these ginsengs may be expensive ones marketed, the ginseng or related crude drugs used in the present invention may be other ginsengs other than the roots of the above-mentioned ginseng, such as mustard ginseng. Ginseng, ginseng, ginseng leaves, roots,
It is preferable to use low-priced products such as buds, related crude drugs such as bamboo nodes, and ginseng ginseng, or wastes. These ginseng or related crude drugs contain a steroidal compound saponin as an ingredient, and nine kinds of saponins (R ₀ , R _b1 , R
_{b2, R c, R d,} R e, R f, the structure of R _g1, R _g2) has been found. Then, R _c and R _b groups hemolytic defense activity, but R _g groups are to be hemolytic activity, the type of sugar moiety attached thereto for the expression of both effects, number, or the binding position is more It has also been reported that it is an important factor. In the present invention, it is desirable to select crude drugs so that the hemolytic activity is always greater than the hemolytic activity in view of safety, and the saponins contained in the crude drugs are at least 3.0% by weight or more. Is preferably 0.1 to 0.5% (according to the Pharmacy Law). In addition, saponin is a glycoside in sapogenin glycosides on study,
Consisting of the tetracyclic nucleus shown in the above structure, the kind of saccharide such as glucose, glucose, albinopyranose arabinop
yranose, rhamnose rhamnose etc. Steroids in a broad sense that have different properties depending on the binding position, type, number of sugars, etc.
oide.

[0013] Next, Table 1 shows an example of the locality, kind and saponin-containing example of the crude drug used from the Japanese Pharmacopoeia Magazine.
Furthermore, haemolytic activity factors in these crude drugs such Hemoritiku das _{Hemolyticdose (HD 50; μg / ml} ) and hemolytic defense activator Protective Das in Protective dos
e (P ₅₀ ; μg / ml) is also shown in Table 1.
Although representing a dosage or amount and Das dose referred by medical and drug industry, HD _50, 50 of the animal for example rats and P ₅₀
% Represents the dose at which death occurs. Thus, a higher dosage indicates less toxicity, ie, less activity, and a lower dosage indicates greater toxicity, ie, greater activity.

[0014]

[Table 1]

[0015] As described above, in the present invention than it is desirable to select a galenical such as is always hemolytic defend activating action> hemolytic activity acting safety haemolytic activity factor (HD ₅₀ which is specifically included Μg / ml) is inactive or 1000 μg / ml or more, and the hemolytic protective activator (P ₅₀ ; μg / ml) is inactive or 500 μg / ml or more. By using a crude drug so as to have the activity> hemolytic activity, the hemolytic active factor and the hemolytic protective active factor of the saponin compound are coexistent and mixed in a physiologically completely safe range in which they cancel each other.
Hemolysis is a phenomenon in which hemoglobin elutes through the erythrocyte coating. For example Otane ginseng leaves Table 2 As is clear from sample number 6, 7, Otane ginseng bud is HD ₅₀ indicates 1120,1300, since P ₅₀ is not (active), hemolytic defense activity strong herbal May be used in combination. That is, in this case, the Otane ginseng leaves of Sample No. 6 and 7, Otane ginseng in the bud, thinning of Sample No. 4 which red ginseng and P ₅₀ of Sample No. 3 P ₅₀ indicates 1040 indicates 1350 carrots, or P _What is necessary is just to mix and mix the ginseng with 4-year rawhide of sample number 5 in which ₅₀ is 750.

Next, an ultrasonic generator used in the present invention will be described. As this ultrasonic generator, a commercially available product called a homogenizer Homogenizer is used. Its processing capacity is 15 to 1500 l / H, the frequency is 25 kHz to 19 kHz, and the heat generation is 50 ° C. or less. Vibration of large amplitude, for example, 2000 times / second is transmitted to the dispersion tool horn horn from the ultrasonic oscillating unit, and based on a cavitation phenomenon called cavitation cavitation occurring on the surface of the horn, the ultrasonic impact force generated in the vicinity of the cavitation cavitation causes 2 It is believed that a vacuum is created in one of the phase systems and instantaneously exerts the extractability of the present invention. In the case of batch processing, only the horn (corner) is operated in the container except for the horn chamber.

In the method for producing a saponin extract solution of the present invention, liquid fructose is used as an extraction medium when extracting saponins contained in ginseng and related crude drugs which have not been used at the industrial level. Since the ultrasonic energy for physically moving molecules is used, the saponin body can be extracted in a much shorter time than in the prior art by the synergistic effect of the permeability of liquid fructose and the ultrasonic energy. Specifically, the manufacturing according to the process diagram as shown in FIG. 1 is suitably adopted.

As shown in the dotted line in FIG. 1, it is desirable that the ginseng and the related crude drug to be used are appropriately subjected to a mixer treatment, and this mixer treatment may be performed before or after blending fructose. In the most important ultrasonic extraction process, as described above, the saponin body can be extracted efficiently and in a short time by utilizing the synergistic effect of the permeability of liquid fructose and the ultrasonic energy. In the past, this extraction process was the most rate-determining during the process, and what was extracted over a long time of several tens of days or more can be extracted in a very short time of about tens of seconds to several minutes in the present invention Becomes In addition, conventionally, a huge, closed system equipment was required for performing long-term extraction, but the present invention does not require such equipment at all. Therefore, according to the present invention, regardless of the size of the production lot, the production can be easily carried out with the simple equipment of the open system. Further, since the cells are killed by the ultrasonic energy, there is no need to perform a sterilization treatment by heating or the like. This means that the effect of preventing deterioration of fructose due to heating is also achieved. That is, fructose is 80-100
Above ℃, the function (physiology, pharmacological function) changes from a mono-form to a dimer, but the ultrasonic treatment is usually carried out at 50 ℃ or less, so that such deterioration of fructose is prevented. Therefore, the ultrasonic treatment has an effect of dramatically improving the extraction effect, and also has an excellent effect of removing bacteria while preventing deterioration of fructose, and has an excellent effect of removing bacteria.
Furthermore, the present method has knowledge that it can be widely applied not only to ginseng but also to various other crude drugs. Thereafter, if necessary, impurities and the like are removed by pressure filtration or an ion exchanger to obtain a saponin extract solution containing fructose. When a beverage product such as juice that is to be continuously consumed over a long period of time is to be diluted with water or the like, the concentration DS of fructose contained in the solution is adjusted to 10 ± 5, and the concentration of the saponin body is reduced. It is desirable that the content be 0.1 to 0.5% by weight. According to empirical findings, setting the fructose concentration DS to 10 ± 5 has the best sweetness.

The fructose-extracted saponin extract liquid thus obtained is expected to be used not only for beverage products but also for various processed foods. In other words, the saponin body itself has a unique bitterness, but exerts excellent pharmacology and physiological effects, and fructose has physiological characteristics that can be taken into the body without consuming insulin as a sweetener or nutrient in the living body. Since they are monosaccharides, health drink products or health processed foods can be developed very easily by their coexistence.

Further, a method for obtaining a crystalline saponin mannitol adduct having excellent preservability from the fructose-extracted saponin extract solution will be described. It should be noted that, specifically, the production according to the process chart as shown outside the dotted line in FIG. 1 is suitably adopted.
First, the fructose extraction filtrate in the production process of the fructose extraction saponin extract solution was subjected to Ca-type cation exchange resin (R-SO
₃ ) Ca) treatment to separate the contained fructose out of the system. Fructose selectively R-SO ₃ Ca (R represents a resin backbone) to affinity adsorption. Thus, the fructose separated out of the system can be reused. Incidentally, the cation exchange resin is generally represented by R-SO ₃ Cl or R-SO ₃ H, but calcium hydroxide Ca
(OH) ₂ is used as R—SO ₃ Ca. By performing this defructose, the following addition reaction between a saponin compound and mannitol is smoothly performed. Next, mannitol is added in an amount of 1 to 3 times the amount of the saponin body in the defructose saponin extract solution, and concentrated to obtain a crystal. In addition, the content of the saponin body was measured by performing a preliminary test by a solvent method,
The addition amount of mannitol may be set. The mannitol used in the present invention is obtained by hydrolyzing sucrose (invert sugar) or reducing mannose with hydrogen in the presence of Raney nickel catalyst or the like, and is a sweet, soluble, non-hygroscopic sugar. Which is widely used in the food and pharmaceutical fields.

Since the method for producing the crystalline saponin mannitol adduct of the present invention is carried out in accordance with the above-mentioned method for producing a fructose-containing saponin extract solution, as described above, the extraction step, which has conventionally been the most rate-limiting step in the process, has been described. Can be completed in a remarkably short time, and there are advantages such as a merit of greatly shortening a manufacturing time, a merit of not requiring a huge facility, and a merit that a small lot can be sufficiently handled.

The crystalline saponin mannitol adduct thus obtained is a crystal having no hygroscopicity and thus has excellent storage stability. In addition, a high-purity substance having a small amount of substances other than saponins, such as corrosion substances, vegetable proteins, and coloring substances, can be obtained.

[0023]

【Example】

Example 1 HD ₅₀ is inactive, P ₅₀ is 700 [mu] g / m
1, 500 g of mustard ginseng with saponin content of 14.8%
500 g of rapeseed ginseng leaves having an HD ₅₀ of 1120 μg / ml, an inactive P ₅₀ and a saponin content of 12.6%;
1500 g of a fructose solution having a concentration DS of 70 was mixed and subjected to a mixer treatment to prepare a mud-like mixture. Next, this mixture is
The batch was placed in a container (homogenizer) having an ultrasonic horn and extracted for 30 seconds. The extract was washed with vacuum filtration and water, and then treated with a mixed bed of ion-exchange resin to remove impurities such as collagenous plant proteins and the like, to obtain a fructose extract filtrate. The fructose-extracted saponin extract solution obtained by adjusting the fructose concentration DS to 15 by adding pure water to the obtained fructose-extracted filtrate had a saponin body concentration of 0.5% in a solvent method assay comparison test.

[0024] Example 2 in place of the beard carrot HD ₅₀
There except that inert, P ₅₀ was used thinning carrots 1350μg / ml, saponin content of 3.0%, Example 1
The fructose-extracted saponin extract solution prepared by performing fructose extraction according to the method described above and adjusting the fructose concentration DS to 10 had a saponin body concentration of 0.4%.

Example 3 The fructose extract filtrate in Example 1 was treated with a Ca-type cation exchange resin to separate fructose, and 10 g of the defructose saponin extract solution (saponin body concentration 10%) was added to mannitol. By adding 15 g of (crystal), concentrating and drying, 16.5 g of a crystal (crystalline saponin mannitol adduct) was obtained. A powder was obtained by adding crystalline fructose to this crystalline saponin mannitol adduct.

Although the embodiment of the present invention has been described above, the present invention is not limited to the above-described embodiment, and can be implemented in any manner as long as the configuration described in the claims is not changed. .

[0027]

As described above, the method for producing a fructose-extracted saponin extract according to the present invention is efficient and utilizes the synergistic effect of the liquid fructose permeability and ultrasonic energy in a very short time. The body can be extracted. In addition, since the cells are killed by the ultrasonic energy, the cells are sterilized without performing a known sterilization treatment by heating or the like. This means that the effect of preventing deterioration of fructose due to heating is also achieved. And
Unlike the conventional case, there is no need for a huge facility for industrially performing long-term extraction, and in the present invention, the production can be easily performed regardless of the size of the production lot. Therefore,
Extremely practical value.

In addition, the fructose-extracted saponin extract solution obtained according to the present invention comprises a saponin body which exerts a unique and excellent pharmacological and physiological action, and a sweetener and a nutrient, without consuming insulin in the living body. Since it is made of fructose that can be taken in, it can be actively provided to children and toddlers, sick persons, diabetic patients, etc., and is suitable as a health drink or processed food.

In particular, when a crude drug is used so that the hemolytic activity is greater than that of the saponin body, it is expected that stems, leaves, buds, seeds, etc., which have been discarded conventionally, can be effectively used. Therefore, the price of the extracted saponin body and the preparation containing the same can be reduced.

Further, since the method for producing the crystalline saponin mannitol adduct of the present invention is carried out in accordance with the above-mentioned method for producing a fructose-containing saponin extract solution, as described above, the extraction which was conventionally the most rate-limiting in the process was carried out. The process can be completed in a remarkably short time, resulting in advantages such as a significant reduction in manufacturing time, an advantage of not requiring a huge facility, and an advantage of being able to sufficiently cope with a small lot.

The fructose-containing crystalline saponin mannitol adduct powder obtained as described above is a crystalline substance having no hygroscopicity, and thus has excellent storage stability without fear of deterioration or contamination by microorganisms (mold). For example, it is a high-purity substance having a small amount of corrosion substances, vegetable proteins, coloring substances, and the like.

[Brief description of the drawings]

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a production process diagram of a fructose-extracted saponin extract solution, and the outside of the dotted line is a production process diagram of a fructose-containing crystalline saponin mannitol adduct powder.

Continuation of front page (56) References JP-A-61-83129 (JP, A) JP-A-2-211202 (JP, A) JP-A-60-47699 (JP, A) JP-A-61-242600 (JP, A) , A) JP-A-57-128632 (JP, A) Acta Pharmaceutical a Sinica, vol. 23, no. 2, p137-141, 1988 (58) Fields investigated (Int. Cl. ⁷ , DB name) A61K 35/78 A23L 1/212 B01D 11/02 C07J 63/00 BIOSIS (DIALOG) CA (STN Medline (STN) (54) [Title of the Invention] Method for producing fructose-extracted saponin extract solution, method for producing fructose-extracted saponin extract solution, method for producing crystalline saponin mannitol adduct, and fructose-containing crystalline saponin mannitol Manufacturing method of adduct powder

Claims (5)

(57) [Claims] 1. A mixture obtained by adding liquid fructose having a concentration DS of 60 ± 10 by 1 to 2.5 times the amount of ginseng and / or a related crude drug to the ultrasonic vibration horn continuously or in batches. A method for producing a fructose-extracted saponin extract solution, wherein cavitation operation of the oscillator and extraction by synergy of the permeability of fructose are performed. 2. The use of a crude drug such as ginseng and / or a related crude drug that contains 3.0% or more of saponins and has a greater hemolytic protection activity than a hemolytic activity. 2. The composition according to claim 1, wherein the hemolytic activity factor of the saponin body and the hemolytic protection activity factor coexist and are completely mixed within a physiologically completely safe range.
3. The method for producing a fructose-extracted saponin extract liquid according to item 1. 3. A fructose concentration D of a fructose-extracted saponin extract solution obtained by the production method according to claim 1 or 2.
S is set to 10 ± 5, and the saponin body concentration is set to 0.1 to 0.5.
Fructose-extracted saponin extract solution characterized by adjusting
Manufacturing method . 4. A fructose-extracted saponin extract solution obtained by the production method according to claim 1 or 2, which is treated with a Ca-type cation exchange resin to fractionate the fructose contained therein, and then obtained. A method for producing a crystalline saponin mannitol adduct, characterized in that mannitol is added in an amount of 1 to 3 times the amount of the saponin body in the saponin extract solution and concentrated to obtain a crystal. 5. The crystalline saponin mannitol adduct obtained by the method according to claim 4 as a base material, the fructose-containing crystalline saponin mannitol adduct powder, characterized in that the addition of crystalline fructose as a vehicle agent Manufacturing method .