WO2016185509A1

WO2016185509A1 - Ginsenoside composition

Info

Publication number: WO2016185509A1
Application number: PCT/JP2015/063977
Authority: WO
Inventors: 金　昌樹; 慶光金; 昌康長谷川
Original assignee: 金氏高麗人参株式会社
Priority date: 2015-05-15
Filing date: 2015-05-15
Publication date: 2016-11-24

Abstract

[Problem] The purpose is to provide a ginsenoside composition derived from ginseng wherein the "Rg3 family-based composition" is capable of actualizing more reliable and superior efficacy than in the past. [Solution] A composition containing components belonging to the Rg3 family comprising Rg3(S), Rg3(R), Rk1, Rg5, and Rz1 as base components wherein the ginsenoside composition is characterized in that this composition also contains as an essential component ginsenoside F3 (and also contains ginsenoside Rk2).

Description

Ginsenoside composition

The present invention relates to a ginseng-derived ginsenoside composition that has an effect of improving indefinite complaints such as fatigue and stiff shoulders, and more particularly to a composition containing a ginsenoside component belonging to the Rg3 family.

(About Rg3 family)
-1-
Ginsenoside, which is easily soluble in water, undergoes hydrolysis under heating conditions or in an acidic environment, and the number of side chain sugars is reduced to produce ginsenoside (eg, Rg3) that is sparingly soluble in water. Come on.
-2-
One of the degradation pathways of ginsenosides Rb1, Rb2, and Rc, which are diol major ginsenosides, is subjected to Rd, which is a primary degradation product, and further to Rg3 (S and R, ie, Rg3 (S) and Rg3 ( There is a route to convert to R).
Rb1, Rb2, Rc → Rd → Rg3
-3-
The produced Rg3 is further changed into secondary decomposition products such as Rg5, Rz1, and Rk1 by heat treatment.
Rg3 → Rg5, Rk1, Rz1
-4-
In addition, Rz1 and Rg5 are in an isomer relationship with each other, and the former Rz1 is a trans type (when viewed from “C20 = C22”, “C20-C21” and “C22-C23” are in opposite directions. The latter Rg5 is a cis type (when viewed from “C20 = C22”, “C20-C21” and “C22-C23” are on the same direction side).
-5
Rk1 is similar in structure to Rz1, but the position of the double bond in the “side chain” part that binds to the 5-membered ring of a polycyclic compound consisting of three 6-membered rings and one 5-membered ring is Is different. In Rz1, side chains “C20 = C22” and “C24 = C25” are double bonds, and in Rk1, side chains “C20 = C21” and “C24 = C25” are double bonds.
-6-
In the present application, these Rg3 (S), Rg3 (R), Rg5, Rk1, and Rz1 are referred to as “Rg3 family” or “Rg3 family member”.
-7-
As described above, members of the Rg3 family produced by the degradation of major ginsenoside are minor ginsenosides and are easily absorbed when ingested.

(Regarding patent literature on Rg3 family)
-0-
There are many patent documents related to the Rg3 family, and the main ones are listed below.
-1-
(Patent Document 1)
JP 2006-502082 (Patent Document 1) describes a composition having a ratio of (Rg3 + Rg5) / (Rb1 + Rb2 + Rc + Rd) ”of 10 to 45.
-2-
(Patent Document 2)
JP-A-2004-519224 describes a composition in which the product contains Rh1, Rh2, CK, Rg2, Rg3, F2, Rg1, Rd, aglycone, and the like.
-3-
(Patent Document 3)
JP 2008-501791 (Patent Document 3) describes a composition for preventing or treating vascular stenosis and restenosis containing ginsenoside Rg3, Rg5 or Rk1 as an active ingredient.
-4-
(Patent Document 4)
JP-T-2008-502711 (Patent Document 4) discloses that carrot is acid-treated at a temperature of 50 to 80 ° C. and the treated carrot is steam-treated at a temperature of less than 110 ° C. for 0.5 to 15 hours. The processed carrot extract or its freeze-dried product is described. .
-5
(Patent Document 5)
JP 2011-512404 (Patent Document 5) describes a composition in which at least one of a leaf extract and a processed product thereof contains at least one ginsenoside component of Rg3, Rg5 and Rk1 as an active ingredient. .
-6-
(Patent Document 6)
JP-T-11-501322 (Patent Document 6) describes a ginseng or ginseng extract having a ratio of (Rg3 + Rg5) / (Rc + Rd + Rb1 + Rb2) of ginsenoside of 1.0 or more.
-7-
(Patent Document 7)
In JP-T-2007-520418 (Patent Document 7), vinegar having a pH of 2 to 4 is added to ginseng or a carrot extract and heated and extracted for 0.5 to 24 hours, and Rg3 is Rb1, Rb2, Rc, Rd, Re, Rf. , Rg1 and Rg3 are contained in an amount of 5 to 100%, and Rg3 + Rg5 + Rh1 is contained in an amount of 1 to 15%.

Special table 2006-502082 Special table 2004-519224 Special table 2008-501791 Special table 2008-502711 Special table 2011-512404 Special table flat 11-501322 Special table 2007-520418

(Task)
-1-
As mentioned above, the Rg3 family member produced by the degradation of major ginsenoside obtained from medicinal carrots by extraction method etc. is minor ginsenoside, so it is much more than when taking the extract from medicinal ginseng as it is. It is easily absorbed by the human body and contributes to the reduction of symptoms such as indefinite complaints.
-2-
However, there are those who actually feel the effect and those who do not feel the effect so much only by ingesting the composition mainly composed of each component of Rg3 (S), Rg3 (R), Rg5, Rk1, and Rz1. In addition, even for those who feel the effectiveness of the former, it is strongly desired that the medicinal effect be further improved.
In this case, increasing the amount of intake is one of the means for improving the medicinal effect, but increasing the amount of intake is not a “qualitative” medicinal effect improving means. Therefore, the composition based on the conventional Rg3 family While securing goodness, it is strongly desired to find a means to break through the present situation by contriving from another viewpoint.

(Object of invention)
An object of the present invention is to provide an “Rg3 family composition” capable of exhibiting a medicinal effect that is more reliable and more excellent than before in order to meet such demands.

The ginsenoside composition of the present invention comprises:
A composition containing a component belonging to the Rg3 family consisting of Rg3 (S), Rg3 (R), Rk1, Rg5 and Rz1, as a base component,
The composition further contains ginsenoside F3 as an essential component;
It is characterized by.

In this case, it is also preferable to further contain ginsenoside Rk2 as an essential component.

(Function and effect)
The composition of the present invention belongs to the category of “Rg3 family composition”. For example, indefinite complaints such as fatigue, stiff shoulders, loss of appetite, insomnia, headache, cold limbs, and reduced energy On the other hand, compared with the conventional same type of Rg3 family-based composition, it is possible to exert a more reliable action effect.

(Initiative to Invent)
-1-
The Rg3 family composition is typically obtained by concentrating an extract extracted from ginseng by an alcohol extraction method, adjusting the pH with an acid, and then aging under a predetermined temperature condition for a predetermined time. It is obtained by collecting a precipitated portion of the powder and drying it into powder.
Since the powder thus obtained is rich in Rg3 (S), Rg3 (R), Rk1, Rg5 and Rz1, these are referred to as “Rg3 family”. F3 and Rk2 that are target components are not detected.
-2-
In the search of patent documents including the above-mentioned patent documents 1 to 7, there is no hit even when searching using “F3” or “Rk2” as a keyword. This is probably because “Rk2” does not exist, or even if it exists, it is a trace amount that does not reach the detection limit.
-3-
In the present applicant, when ginsenoside components are obtained from ginseng by extraction, they are sampled many times during the production process that takes about 1 to 3 days and are used for analysis. Although it is checked whether or not it is produced, no unusual components appear when obtaining the Rg3 family composition.
-4-
However, because the power was forgotten to be turned off only once in the aging process, and it was a weekend, the time required for the aging process was increased by 2 days.
When comparing the component chart at that time with the chart in the normal case, it was found that an unknown component was generated although it was an amount close to the trace amount, so an attempt was made to identify that component, but the amount was small And because the specimens are not readily available, identification took days.
Later, it was confirmed that the unknown component was “F3”.
-5
As for the thing obtained by the above failure process as well as the one obtained by other normal processes, when it was subjected to a clinical trial just in case, a good result was obtained rather than a normal prototype. I thought.
Therefore, various investigations were made on the production conditions of ginsenoside rich in the Rg3 family, and attempts were made to change the production conditions that did not produce “F3” to the conditions that “F3” generates.
-6-
By the way, although the production | generation of F3 can be confirmed also by said new process, the production amount is few. Therefore, it is certain that F3 itself contributes to the improvement of medicinal effects, but in an environment where F3 is produced (manufacturing process), the quantitative balance between other components of the Rg3 family is also It can be said that it is optimal for the manifestation of the alleviation of symptoms such as indefinite complaints.
-7-
F3 is a “triol-based” ginsenoside, and its official name is as follows.
“3β, 6α, 12β-trihydroxy-5α-dhamara-24-en-20-yl 6-O-α-L-arabinopyranosyl-β-D-glucopyranoside (20S) -20- (6-O -Α-L-arabinopyranosyl-β-D-glucopyranosyloxy) -5α-damala-24-ene-3β, 6α, 12β-triol "

(Manufacturing process)
The manufacturing process in the present invention is not largely different from the conventional process for obtaining the composition of the Rg3 family described in the above-mentioned section “Initiation to Invention”, but the number of factors is extremely large. Since it is normal that F3 is not generated even by a difference of one factor, it is certain that the “manufacturing conditions in which F3 has been confirmed” is faithfully reproduced.

(Analysis method etc.)
(Sample pretreatment method for HPLC analysis (common))
1 g of sample powder is accurately measured, and ginsenoside components are extracted by the methods described in Japanese Pharmacopoeia “Carrot” and “Koujin”.
Further, after roughly purifying the ginsenoside component using a C18 column, it is filtered through a membrane filter to obtain a sample solution.
Next, the target ginsenoside is separated and quantified by injecting the sample solution into high performance liquid chromatography (HPLC) using an octadecylsilylated silica gel packed column (C18 column).

(F3 analysis method)
When quantifying F3, separation is performed by HPLC using 18-30% acetonitrile as a mobile phase to obtain a peak of each ginsenoside.
Then, the content of F3 in the sample is calculated by comparing the peak area of the ginsenoside standard solution with the peak area of the sample solution.

(Analytical method of Rg3 (S), Rg3 (R), Rk1, Rg5, Rk2)
When quantifying Rg3 (S), Rg3 (R), Rk1, Rg5, and Rk2, separation is performed by HPLC using 40 to 90% acetonitrile as a mobile phase to obtain a peak of each ginsenoside.
Then, the content of each ginsenoside in the sample is calculated by comparing the peak area of the ginsenoside standard solution with the peak area of the sample solution.

(Ratio of “Rk2 / F3”)
When Rk2 is contained together with F3, the ratio of “Rk2 / F3” is preferably within a range of 1 to 8, but a suitable result can be obtained with F3 alone, so that it is not necessarily limited to this range. is not.

Example 1
The production methods of the 8 types of tablets shown in Table 1 described below are as follows ("parts" is parts by weight).
First, an extract was extracted from red ginseng, but extracted at various temperatures and times with an extraction solvent having a different water / alcohol ratio to obtain various extract extracts.
Next, the extract was heat-aged at various temperatures and times and pulverized by a spray drying method to obtain fine powders having different ginsenoside contents.

-1-
Seven types of extract powder having the composition shown in Table 1 were selected, and 94 parts of the extract powder and 6 parts of sucrose fatty acid ester were mixed to prepare a tablet. The weight per tablet is 300 mg. (However, tablet 1 is for comparison and consists of 94 parts of dextrin and 6 parts of sucrose fatty acid ester.)

-2-
Next, 80 men and women aged 45 to 75 (40 men and 40 women) with fatigue were randomly divided into 8 groups (with 1 group consisting of 5 men and women). A total of 10 people from 5 people were considered, and a monitor test for fatigue was conducted.

-3-
As shown in Table 1, in each group, all the groups ingested 3 tablets each day, and continuously ingested for 1 month.
Before the start of the test and one month after ingestion, all the subjects checked subjective symptoms for fatigue.
In the subjective symptom chart, the situation for fatigue is divided into seven stages as follows.

-4-
State 1: A feeling of fatigue is strong, and nothing can be done when bedridden.
State 2: A feeling of fatigue is strong and can only be around.
State 3: Although there is a feeling of fatigue, it becomes better to rest for about half a day.
State 4: There is a feeling of fatigue, but it does not last for hours.
State 5: I feel tired, but I almost forget it when I work.
State 6: There is almost no fatigue.
State 7: There is no feeling of fatigue and it is healthy.

-5
All the subjects were asked to fill in the numbers corresponding to the above for the state before the start of the test and one month after ingestion, and the improvement effect on fatigue feeling was evaluated based on whether the number increased or not, and scored as follows.
・ When the number rises by 3 or more levels ... …… It is effective and gives 3 points ・ When the number rises by 2 levels ……………… It is valid and gets 2 points ・ When the number rises by 1 level ... ……… Slightly valid and give 1 point ・ If there is no change in the number or if it falls… Disable and give 0 point

-6-
And the score of 10 people of a group was totaled and the improvement degree of each group (each tablet) was calculated | required. The results are shown in Table 1.
Total score is 26 or more ◎ Very effective 21 to 25 ● Large effect 16 to 20 ○ Medium effect 9 to 15 □ Small effect 6 to 8 △ Slight effect 5 or less × No effect

Example 2
-1-
Tablet No. 1 shown in Example 1 was used. 6 (content in 1 grain is 120 mg for Rg3 family, 0.33 mg for F3, 1.39 mg for Rk2, 4.2 for Rk2 / F3) The effect was confirmed.
-2-
Sixty men and women aged 48 to 70 (30 men and 30 women) with stiff shoulders were randomly divided into 6 groups (1 group consists of 5 men and 5 women). A monitor test was conducted on the feeling of stiff shoulders.

-3-
As shown in Table 2, the 6 groups were distributed from the daily intake group to the 6 intake group. The intake time was arbitrary during the day, and the intake was divided into multiple times. Ingested continuously for 1 month, all subjects checked subjective symptoms of stiff shoulders before and 1 month after ingestion.
All subjects checked subjective symptoms for stiff shoulders before the start of the study and one month after ingestion.
In the subjective symptom table, the situation for stiff shoulders is divided into seven stages as follows.

-4-
State 1: Shoulder and neck are severely stiff, nausea, dizziness, and cannot move.
Condition 2: Shoulders and necks are stiff, and if you massage you get better temporarily, and you can do things around you.
State 3: The shoulders and neck are stiff and painful, but if you do not, you can work.
State 4: The shoulders and neck are stiff and anxious, but often forget if they are focused on things.
State 5: Shoulder and neck are stiff, but not so much, always leave them alone.
State 6: The shoulders and neck are slightly stiff, but heales naturally even if left alone.
Condition 7: The shoulders and neck are not stiff and the body is always light.

-5
All subjects were asked to fill in the numbers that apply to the above conditions before the start of the study and one month after ingestion, and the improvement effect on stiff shoulders was evaluated based on whether the number increased, and was scored as follows: .
・ When the number rises by 3 or more levels ... …… It is effective and gives 3 points ・ When the number rises by 2 levels ……………… It is valid and gets 2 points ・ When the number rises by 1 level ... ……… Slightly valid and give 1 point ・ If there is no change in the number or if it falls… Disable and give 0 point

-6-
And the score of 10 people of a group was totaled and the improvement degree of each group (each tablet) was calculated | required.
Total score is 26 or more ◎ Very effective 21 to 25 ● Large effect 16 to 20 ○ Medium effect 9 to 15 □ Small effect 6 to 8 △ Slight effect 5 or less × No effect

-7-
The results are shown in Table 2 below.

Since the ginsenoside composition of the present invention is improved against indefinite complaints such as fatigue, stiffness of shoulders and neck, loss of appetite, insomnia, headache, cold limbs, and reduced energy, it is an oral composition. It is useful as a dietary supplement or health food. Expected to be used as a medicine. In addition, it is also useful as a body-related parenteral (percutaneous penetration) composition (cosmetics, hair restorer, bath preparation, etc.).

Claims

A composition containing a component belonging to the Rg3 family consisting of Rg3 (S), Rg3 (R), Rk1, Rg5 and Rz1, as a base component,
The composition further contains ginsenoside F3 as an essential component;
A ginsenoside composition characterized by the above.
The ginsenoside composition according to claim 1, further comprising ginsenoside Rk2 as an essential component.
The ginsenoside composition according to claim 1 or 2, which is a composition obtained by heating and aging an extract from ginseng.
The ginsenoside composition according to claim 1, 2 or 3, which is a composition for improving indefinite complaints.