CN100566739C - Composition containing Panax notoginseng, Eucommia ulmoides and American ginseng - Google Patents

Abstract

A kind of compositions that contains Radix Notoginseng, the Cortex Eucommiae and Radix Panacis Quinquefolii.

Description

Composition containing Panax notoginseng, Eucommia ulmoides and American ginseng

Background of the invention

(1) Field of invention

The present invention relates to a composition containing "Denhichi" (Notoginseng), "Tochu" (Eucommia bark) and "SeiyoNinjin" (American ginseng), which may further contain "Osei" (Polygonatum rhizome or similar ) and/or herbal extracts containing gallic acid and/or "Kanzo" (licorice root). The invention also provides its manufacturing method.

The composition of the present invention can be used as conventional medicine or alternative medicine and food supplement, and it is not only useful for maintaining human health and promoting health and improving nutritional status and immune system, but also effective for treating or preventing hepatitis and infectious diseases .

In addition, the composition of the present invention can also be used as a food supplement not only to prevent hypertension and diabetes in animals such as dogs, cats, pigs, cows, horses and other animals, but also to maintain the (including birds and fish) and improve their nutritional status and immune system.

(2) Description of related fields

The results of a nationwide study showed that the number of overweight, hypertensive, and diabetic individuals increased significantly due to environmental conditions, physical inactivity, and a high-calorie diet. In addition, the ability to resist hepatitis, infectious diseases and immune diseases is also significantly reduced.

These observations have also been observed in animal settings. Indeed, pets kept in small enclosures, eg, indoors, suffer from maladies in terms of nutritional status, hypertension, psychological stress and excess weight associated with fatty substances.

On the other hand, the increase in the number of patients suffering from HBV and HCV is also a serious problem to be solved.

Typically, patients with HBV and HCV are treated with interferon, although interferon is known to have serious adverse side effects.

Summary of the invention

An object of the present invention is to provide food supplements and alternative medicines which can significantly improve the symptoms of high cholesterol, high blood pressure, diabetes and certain cancers and maintain a healthy state.

Another object of the present invention is to provide an alternative drug that can significantly improve the symptoms of HBV and HCV compared to interferon therapy.

The first object of the present invention has been achieved by providing herbal extracts containing "Pseudo-ginseng", "Eurocommia" and "American ginseng", if desired, "Polygonatum rhizome" and/or containing gallic acid and/or "Glycyrrhiza root (Glycyrrhiza glabra)" food supplements and related products as well as alternative medicines are realized.

Another object of the present invention is to provide products containing "Sanqi", "Eucommia" and "American ginseng", if desired, "Polygonatum rhizome" and/or herbal extracts containing gallic acid and/or "Glycyrrhiza root" Alternative to medicines, it is effective in treating symptoms of various liver diseases.

Compositions containing "Notoginseng", "Eurocommia", "American ginseng", herbal extracts containing gallic acid and, if desired, licorice root (Glycyrrhiza glabra)" are also offered here as healthy food supplements It can be effectively used as a food supplement for the maintenance of health, a replacement drug for the treatment of liver diseases, supplements, beverages, animal feed and compound food for animals, birds and fish.

At the same time, there is also provided a composition containing "Sanqi", "Eucommia", "American Ginseng", "Rhizome of Rhizoma Polygonatum", and if necessary, "Glycyrrhiza Root".

The present invention provides a method for manufacturing the above composition, which method comprises hot water (60-100°C) or ethanol (room temperature-100°C) of concentrated chopped dried "Notoginseng", "Eucommia" and "American Ginseng" extracts to obtain concentrated extracts of "Notoginseng", "Eurocommia" and "American Ginseng", which can be dried by heating to obtain their pulverized products if necessary; hot water (60-100°C) or ethanol (room temperature-100°C) extract to obtain a concentrated herb extract containing gallic acid, and if necessary, dry it by heating to obtain its pulverized product; mix them, and then dry "three Seven", extracts of pulverized products of "Eurocommia" and "American ginseng", extracts of pulverized products of herbal extracts containing gallic acid, and optionally extracts or pulverized products of "licorice root".

The present invention provides a method for manufacturing the above composition, which method comprises hot water (60-100°C) or ethanol (room temperature-100°C) of concentrated chopped dried "Notoginseng", "Eucommia" and "American Ginseng" extracts to obtain concentrated extracts of "Notoginseng", "Eurocommia" and "American Ginseng", and if necessary, can be heated and dried to obtain their pulverized products; hot water (60 -100°C) or ethanol (room temperature -100°C) extract to obtain concentrated extracts of "Polygonatum Rhizome", if necessary, can be dried by heating to obtain its pulverized product; mix them, and then dry "Sanqi", Extracts or pulverized products of "Eucommia" and "American ginseng", extracts or pulverized products of "Polygonatum rhizome", and optionally extracts or pulverized products of "Glycyrrhiza root".

Human and animal replacement medicines, food supplements, beverage products, and health maintenance foods containing the above composition can effectively lower blood sugar and cholesterol and strengthen the immune system.

In addition, the compositions of the present invention were shown to reduce elevated levels of GOT and GTP. In particular, oral administration of a composition containing "Polygonatum rhizome" and/or a herbal extract containing gallic acid can reduce elevated alpha-fetoprotein and albumin in humans, which shows that the composition of the present invention can effectively prevent or alleviate symptoms associated with Symptoms associated with high blood cholesterol, high blood pressure and diabetes, and effective in preventing chronic hepatitis. Although it is known that "Polygonatum rhizome" and/or herbal extracts containing gallic acid are difficult to be absorbed by human or animal bodies, the composition of the present invention containing "Polygonatum rhizome" and/or herbal extracts containing gallic acid can be easily absorbed absorbed by the human or animal body.

The composition of the present invention is effective in improving liver diseases such as various types of hepatitis, but surprisingly, it does not raise blood pressure.

Brief description of the drawings

Figure 1 shows the effect of the composition Youjo-Hensikoh according to the present invention in patients with acute hepatitis.

Figure 2 shows the effect of Youjo-Hensikoh in HCV patients.

Figure 3 shows the effect of Youjo-Hensikoh in HAV and HBV patients.

Figure 4 shows the effect of Youjo-Hensikoh in patients with alcoholic hepatitis.

Figure 5 shows the effect of Youjo-Hensikoh in patients with toxic hepatitis.

Figure 6 shows the effect of Youjo-Hensikoh in patients with hepatic steatosis.

Figure 7 shows the effect of Youjo-Hensikoh in galactosamine-treated rats.

Figure 8 shows the effect of composition K-17.22 according to the invention on body weight and liver wet weight in rats.

Figure 9 shows the effect of K-17.22 on the liver content of rat Y-protein.

Figure 10 shows the effect of K-17.22 on GSH content in rat liver.

Figure 11 shows the effect of K-17.22 on the GSH S-transferase activity of the Y-part measured with selective substrates.

Figure 12 shows the effect of K-17.22 on plasma levels of transaminases.

Figure 13 shows the effect of K-17.22 on plasma levels of cholestatic parameters.

Figure 14 shows the effect of K-17.22 on liver histological score (necrosis + inflammatory infiltration).

Figure 15 shows changes in GPT in HCV patients.

Figure 16 shows changes in GPT in 20 HCV patients.

Description of the preferred embodiment

The present invention uses the root of Panax pseudoginseng (Wall), which is called "Denhichi", a traditional Chinese medicine known to improve fat metabolism failure and control high blood pressure and relieve pain.

Eucommia bark is usually the dried bark of Eucommiae ulmoides, which is called "Tochu". This traditional Chinese medicine is known to reduce high blood pressure and high blood fat levels.

However, Eucommia or "Tochu" in the present invention refers not only to "bark of Eucommia", but also includes leaves and fruits of Eucommia.

"Denhichi-Tochu-Sei" is a new Chinese medicine composition containing Panax notoginseng and Eucommia bark, which was invented by the present inventor. "Denhichi-Tochu-Sei" is made by extracting the root of Sanchi and Eucommia with hot water. The composition "Denhichi-Tochu-Sei" may contain honey and ginseng (Chinese ginseng) as additives.

The term "Denhichi-Tochu-Sei" in the present invention refers to a composition containing dried extracts of traditional Chinese medicines (mainly like Sanqi and Eucommia).

In the "Denhichi-Tochu-Sei" of the present invention, the composition of the Chinese medicine is 10-90% by weight of Panax notoginseng (Denhichi), preferably 30-90% by weight, and 10-90% by weight of Eucommia ( Tochu), preferably 10-70% by weight or 40-90% by weight, 0-20% by weight of ginseng (Chinese ginseng), preferably 5-20% by weight, and 0-30% by weight of honey. The preferred "Denhichi-Tochu-Sei" composition of the present invention contains 30% by weight of Panax notoginseng, 40% by weight of Eucommia ulmoides, 20% by weight of ginseng (Chinese ginseng) and 10% by weight of honey, or 30% by weight of three Seven, 40% by weight of Eucommia, 10% by weight of Ginseng (Chinese ginseng), 10% by weight of honey and 10% by weight of other substances.

In the present invention, although the most preferred ratio of Panax notoginseng and Eucommia ulmoides in the composition is 3:4, even with a ratio of 1:0.1-1:9, it still has biological effects such as lowering blood pressure and blood cholesterol and enhancing immunity. effect.

American ginseng is the dried root, leaf or stem of American ginseng (Panax quinguefolium L.) belonging to the family Araliaceae, and it is also called "Seiyo Ninjin". Originally grown in North America, this herb has been cultivated in China. This herb is effective in patients with marked dry mouth and physical exhaustion from diabetes; weak cardiopulmonary function; and immunocompromised patients due to side effects of anticancer drugs or radiation therapy. American ginseng is used in amounts of 4-50% by weight. It is known in the art that American ginseng can be used as a tonic. However, it is not known in the art that American ginseng lowers blood pressure in patients.

Gallic acid is 3,4,5-trihydroxybenzoic acid, which is contained in "Gallae halepensis", "Gallaerhois", "Gallae chinensis" and other herbs used in traditional Chinese medicine. Herbal extracts containing gallic acid include these traditional Chinese medicines. It is optionally used in an amount of 0-20% by weight, preferably 4-20% by weight, most preferably 6-12% by weight.

Polygonatum rhizome, Siberian Solomonseal rhizome, etc. are called "Osei", which are obtained from the rhizome of Polygonatum falcatum A. Gray, other plants belonging to this genus, or similar plants. The original plants of "Osei" include Polygonatum falcatum, Polygonatum multiflorum, Polygonatum odoratum, Polygonatum polyflorum, Polygonatum sibiricum Redoute, Polygonatum sibiricum, Polygonatum sibiricum, Polygonatum sibiricum, Polygonatum two-sacred, Polygonatum Jehol, Curly Polygonatum Polygonatum, Polygonatum Polygonatum, Polygonatum Dianhua, Polygonatum from Hubei, Polygonatum vulgaris, Polygonatum lasianthum Maxim. In this specification, the term "Polygonatum rhizome" refers to all "Osei" used as traditional Chinese medicine. "Osei" is known and used as a traditional Chinese medicine, and it is effective for improving nutritional status and promoting health. "Osei" is optionally used in an amount of 0-20% by weight, preferably 4-20% by weight, most preferably 6-12% by weight.

Licorice root is obtained from the roots or kernels of Glycyrrhiza glabra Linn etc., also known as "glycyrrhiza", "licorice", "liquorice", "Glycyrrhiza radix" or "Kanzo". Licorice root is used in an amount of 0-15% by weight, preferably 4-15% by weight, most preferably 6-11% by weight.

Through double-blind experiments, it is known that Glycyrricine, the main component of licorice root, can improve some symptoms related to liver damage and improve serum transaminases. Furthermore, glycyrricine was shown to prevent CCl ₄ -induced liver damage (Y. Ishii, Japan J. Pharmaco, 120, 71, 1971).

Denhichi-Tochu-Sei and compositions containing Denhichi-Tochu-Sei, Polygonatum rhizome extract and/or Gallae rhois and licorice root in the present invention can be dissolved in water and can be easily absorbed by the living body, while discovering their The effect can be provided continuously.

Particularly, the granules or tablets obtained by drying and heating the composition containing Polygonatum rhizome and/or Gallae rhois, licorice root, "Denhichi-Tochu-Sei" and American ginseng and an emulsifier not only show Polygonatum rhizome and/or Gallae rhois and The effect of licorice, also showed the synergistic effect of "Denhichi-Tochu-Sei" and American ginseng to improve blood cholesterol and blood sugar levels and liver function.

The composition of the present invention preferably contains the traditional Chinese medicine called "Osei" of "Polygonatum rhizome" (or Siberian Solomonseal rhizome, etc.).

The present inventors have invented another traditional Chinese medicine which contains hot water or ethanol extracts of Denhichi (Sanqi), Tochu (Eucommia), Osei (such as Polygonatum falcatum, Polygonatum rhizome, Siberian Solomonseal rhizome), Kanzo (Glycyrrhiza root) and Honey. This traditional Chinese medicine may contain ginseng root (ginseng) to prepare "Youjyo-Hensikoh" as described in Examples XUI-XIX below. However ginseng root often raises blood pressure in patients receiving medication. In this case, American ginseng can be further used together with ginseng root (ginseng) or instead of ginseng root. American ginseng and the above-mentioned traditional Chinese medicines, especially "Youjyo Hensikoh" can be used together so that the latter does not increase the patient's blood pressure.

An exemplary method of preparing the compositions of the present invention is described below.

First, the dried eucommia (leaves, fruits, bark) and dried notoginseng were chopped, and the chopped mixture was extracted with hot water at 60-100°C for 0.5-2 hours, or with ethanol at room temperature-100°C or A mixed solution of ethanol and water is extracted (extraction step). Then, after filtering and concentrating steps, the extract thus obtained is mixed with Chinese ginseng (ginseng) and honey in extract form or other suitable form (mixing step). Powdered "Denhichi-Tochu-Sei" can be obtained by further treating under hot air.

Similarly, if necessary, dried American ginseng is chopped and extracted with hot water at 60-100°C for 0.5-2 hours, or with ethanol or a mixed solution of ethanol and water at room temperature-100°C (extraction step). After filtration and concentration steps, the extract can be obtained and then processed under hot air. Thus, powdered American ginseng can be obtained.

In a similar manner, Polygonatum Rhizome Extract and/or Gallic Acid-Containing Herb Extract can be obtained by extracting chopped dry rhizome of Polygonatum Rhizome and/or Chinese herbal medicine containing gallic acid with hot water or ethanol, and then extracting liquid concentration. The powder of Polygonatum rhizome and/or gallic acid-containing medicinal herb extract can be obtained by heating and drying the extract.

In the present invention, hot water at 60-100° C., or ethanol at room temperature-100° C. or a mixed solution of ethanol and water at a ratio of 100:0-0:100 can be used for extraction. Extracts obtained with ethanol or a mixed solution of ethanol and water are referred to as alcoholic extracts in this specification.

An emulsifier is added to the above mixture to manufacture tablets by drying with heat.

The above-mentioned "Denhichi-Tochu-Sei" and/or American ginseng may contain Polygonatum rhizome (extract) and/or herbs containing gallic acid (herb extract) and licorice extract.

Emulsifiers are added to the tablet making mixture. Powders, tablets, liquids and food supplements are prepared by processing the above composition. Honey, vegetable oil, xylitol, etc. can be used as an emulsifier. The weight percentage of emulsifier is preferably 0-20%.

"Denhichi-Tochu-Sei", American ginseng, Polygonatum rhizome (extract) (and/or herbs containing gallic acid (herb extract)) and licorice root are mixed at a ratio of 10-80% by weight, 4-50% by weight, respectively , 0-20% by weight and 0-15% by weight. For Polygonatum rhizome (extract) and/or herbal medicine (herb extract) containing gallic acid, a more specific mixing ratio is 0-20% by weight, preferably 4-20% by weight, more preferably 6 -12% weight. For licorice, a more specific mixing ratio is 0-15% by weight, preferably 4-15% by weight, more preferably 6-11% by weight, depending on the condition of each patient.

Specifically, 60% by weight of Panax notoginseng, 20% by weight of "Denhichi-Tochu-Sei", 4-50% by weight of American ginseng, 8% by weight of Polygonatum rhizome (and/or medicinal herbs containing gallic acid extract), 8% by weight of licorice and 4% by weight of emulsion, the composition prepared by mixing is suitable for making food supplements in various forms.

The compositions of the present invention can be formulated as powders, granules, tablets and dry syrups suitable as alternative medicines, food supplements and the like. The content of the composition of the present invention is 0.1-0.5g per tablet, or 0.1-30% by weight of the replacement medicine or food supplement, preferably 1-5% by weight.

For tablets obtained by heat-drying a mixture of "Denhichi powder", "Denhichi-Tochu-Sei", American ginseng, Polygonatum rhizome and/or herb extract containing gallic acid and licorice, the content of the composition of the present invention should be 0.25g/tablet or less.

A suitable daily intake of the above "Denhichi-Tochu-Sei" is 0.1-2 g/kg, preferably 0.1-0.25 g/kg.

In the present invention, pets include animals, birds and fish (dogs, cats, monkeys, rabbits, chickens, ducks, goldfish) that can be kept by humans.

In addition, pigs, cows and horses (including racehorses) are also covered.

In addition, the composition of the present invention can be added to cakes, candies, bread, wine, liquor, curry and any food for maintaining health.

Detailed explanations and examples of the present invention are written below.

Example 1: Analysis of "Denhichi-Tochu-Sei" (granules):

Table (i) presents the analytical data of "Denhichi-Tochu-Sei" (granules) containing 30% by weight of Panax notoginseng, 40% by weight of bark of Eucommia ulmoides, 20% by weight of ginseng and 10% by weight of honey.

In the following examples, the composition of Example 1 was used as "Denhichi-Tochu-Sei" (granules).

Table (i): Analysis table of "Denhichi-Tochu-Sei" (granule)

protein content 8.28% (w/w) sugar content 25.30% (w/w) Elemental analysis value C: 40.95% H: 6.68% N: 0.29% Free amino acids: mg/100g granules Asp: 2.18Ser: 2.74Gly: 0.34Ala: 0.28Gln: 6.41Ile: 0.65Lys: 1.79

Table (ii) shows the contents of trace elements of the above-mentioned "Denhichi-Tochu-Sei" (granules) measured by atomic absorption spectrometry.

Table (ii): Results of trace element tests on the above "Denhichi-Tochu-Sei" (granules)

elements µg/g elements µg/g Na 25.0 Fe 7.63 K 51.0 Ca 304 Si 0.181 water 8.88% Sn ＜0.413 Ash 0.42% Mg 526 Zn 4.39

Example II: Effect of "Denhichi-Tochu-Sei" (granule) on serum cholesterol in rats suffering from hyperlipidemia

Rats (180-200 g weight) and mice (18-20 g weight) were divided into four groups (10 rats and mice per group). The four groups are A) normal group, B) hyperlipidemic group (obtained by feeding with high-fat feed), C) hyperlipidemic group (using high-dose "Denhichi-Tochu-Sei" (granules)) and D) ) hyperlipidemia group (with a low dose of "Denhichi-Tochu-Sei" (granules)). In groups C and D, "Denhichi-Tochu-Sei" and a high-fat feed were continuously administered into the stomach through a gastric cannula for 30 days. One hour after the last administration, blood samples were taken from the ophthalmic veins of the rats, from which serum was separated. Serum cholesterol, triglyceride, low molecular weight lipoprotein, LDL and high molecular weight lipoprotein levels were detected with Beckman's serum biochemical analyzer CX5. The results are shown in Table (iii).

Table (iii) clearly shows that the addition of "Denhichi-Tochu-Sei" (granules) to the high-fat feed prevents the occurrence of hyperlipidemia. That is, reductions in serum cholesterol and low-molecular-weight lipoproteins, and slight increases in high-molecular-weight lipoproteins, as well as reductions in triglycerides were observed in groups C and D. In fact, there was a statistically significant difference between the values obtained from the normal group (A) or the group (B) using only the high-fat diet, and the value obtained from the group using the high-dose "Denhichi-Tochu-Sei" (ref. Table (iii)).

Example III: Effect of "Denhichi-Tochu-Sei" (particles) on immune compromised mice

The mice were divided into three groups, ie, a normal group for comparison, an immunocompromised group, and a "Denhichi-Tochu-Sei" (granule)-administered immunocompromised group. The immune systems of the three groups were compared. As can be seen from Table (iv), the immune system of each mouse seemed to be improved after the administration of "Denhichi-Tochu-Sei" (particles).

Table (iv): Effects of "Denhichi-Tochu-Sei" (granules) on the immune system

Group number of animals Dose (g/kg) K value normal group (control) 10 0.079±0.098 Model group with compromised immune system 10 0.034±0.015 Model group with compromised immune system and administration of "Denhichi-Tochu-Sei" (granules) 10 2 0.060±0.024

*Compared with the model group with impaired immune system, P<0.01

Embodiment IV: anti-fatigue test:

Mice (weighing 18-20 g) were divided into two groups. One group was a normal group, and the other was a group administered with "Denhichi-Tochu-Sei" (granule) for 20 days. Table (v) shows the results of the anti-fatigue test, which was carried out 1 hour after the last application. In the experiment, an iron block equivalent to 10% of its body weight was attached to the tail of the mouse, and the mouse was allowed to swim in a constant temperature pool of 40 cm long x 28 cm wide x 30 cm deep and the water temperature was 20°C. The time (in seconds) of swimming is recorded. The results are shown in Table (v).

Table (v): Swimming time of weight-bearing mice administered "Denhichi-Tochu-Sei" (granules)

Group number of animals Dose (g/kg) Swimming time (seconds) normal group 10 60.42±18.81 Group administered with "Denhichi-Tochu-Sei" (granule) 10 2 100.72±31.91

P<0.01

Table (v) clearly shows that the swimming time of the group administered with "Denhichi-Tochu-Sei" (granules) was significantly longer than that of the normal group. This result shows that "Denhichi-Tochu-Sei" (granules) can promote the ability to resist fatigue.

Example V: Effects on mice with hyperglycemia

Mice with blood glucose levels above 180 mg/dl were used in this test. Mice (21-23 g in weight) were divided into three groups, a group of normal mice, a group with high blood sugar level, and a group with high blood sugar level and "Denhichi-Tochu-Sei" (granule) administered. Check their blood sugar levels. The results are shown in Table (vi). After hyperglycemic mice received "Denhichi-Tochu-Sei" (granules), the high blood sugar levels of the mice were reduced to normal levels. The results showed that "Denhichi-Tochu-Sei" (granules) possessed the ability to effectively control the blood sugar level in diabetic mice.

Example VI: Effects of "Denhichi-Tochu-Sei", "Gallae rhois" and "Licorice root" (mixed extracts) on blood cholesterol in rats suffering from hyperlipidemia

Rats and mice were divided into the following four groups (10 rats and 10 mice per group). They are A) normal group, B) hyperlipidemic group (obtained by feeding with high-fat diet), C) hyperlipidemic group (using high doses of "Denhichi-Tochu-Sei", "Gallae rhois" and "licorice root" (hereinafter also referred to as mixed extract)), D) hyperlipidemia group (using a small amount of mixed extract of "Denhichi-Tochu-Sei", "Gallae rhois" and "licorice root").

The ingredients of the mixed extract composition in this example and the following examples are 20% by weight of "Denhichi-Tochu-Sei", 8% by weight of "Gallaerhois" and 8% by weight of "Glycyrrhiza root". In groups C and D, the mixed extract and high-fat feed were continuously administered through gastric intubation for 30 days. One hour after the last administration, blood samples were taken from the ophthalmic veins of the rats, from which serum was separated. Serum cholesterol, triglyceride, low molecular weight lipoprotein, LDL and high molecular weight lipoprotein levels were detected with Beckman's serum biochemical analyzer CX5. The results are shown in Table (vii).

From the results in Table (vii), it can be seen that adding the mixed extracts of "Denhichi-Tochu-Sei", "Gallae rhois" and "Glycyrrhiza root" in the high-fat feed can prevent the occurrence of hyperlipidemia. That is, in groups C and D, reductions in serum cholesterol and low-molecular-weight lipoproteins, slight increases in high-molecular-weight lipoproteins, and reductions in triglycerides were observed. There was a statistically significant difference between the values obtained from the normal group (A) or the group given only the high-fat feed (B), and the values obtained from the groups C) and D) given the mixed extract.

Example VII: Effects of Mixed Extracts of "Denhichi-Tochu-Sei", "Gallae rhois" and "Licorice Root" on Liver Diseases

Table (Viii) shows the effect of mixed extracts of "Denhichi-Tochu-Sei", "Gallae rhois" and "Glycyrrhiza root" on rats (n= 8) The role of.

Table (viii): Effects of mixed extracts of "Denhichi-Tochu-Sei", "Gallae rhois" and "Licorice root" (2000mg/kg) on liver disease induced by D-glucosamine (800mg/kg) Effect of mice (n=8)

normal group The group administered a certain dose of mixed extract GPT(μ%±S.D) 1012±220 730±17 GOT(μ%±S.D) 1696±130 1252±35

Example VIII: Effect of mixed extracts of "Denhichi-Tochu-Sei", "Gallae rhois" and "Glycyrrhizae root" on lipid peroxidation induced by carbon tetrachloride, binding of lipids to ¹⁴ CCl ₄ , CO Effects on Production, NADPH Oxidation, and Oxygen Consumption

Table (ix) shows the effects on lipid peroxidation _{induced by carbon tetrachloride, lipid binding to 14CCl4} ^, CO production, NADPH oxidation and oxygen consumption

Example X: Effects on mice with high blood glucose levels

When streptozotocin solution (90 mg/kg) was administered intravenously to mice (body weight 21-23 g) every day, the mice had hyperglycemia, lost body weight and had increased water intake and urine output.

This example used mice with blood glucose levels of 180 mg/dl or higher. Mice (body weight 21-23 g) were divided into three groups, a group of normal mice, a group with high blood sugar level, and a group with high blood sugar level and administered the mixed extract (granule). Check their blood sugar levels. The results are shown in Table (x). After hyperglycemic mice received the mixed extract (granules), the mice's higher blood sugar levels became closer to normal. The mixed extract (granule) of the present invention can effectively control the increase of blood sugar level in mice with diabetes.

The following conclusions can be clearly drawn from the above animal experiments.

1) Administration of "Denhichi-Tochu-Sei" and "Denhichi-Tochu-Sei", herbal extracts containing gallic acid and mixed extracts of "licorice root" has the effect of reducing hyperlipidemia in rats, and at the same time can reduce the Serum cholesterol and low molecular weight lipoproteins, slightly increased high molecular weight lipoproteins, and decreased triglycerides.

2) Administration of "Denhichi-Tochu-Sei" can activate monocyte-macrophages in mice with impaired immune system.

3) Long-term administration of "Denhichi-Tochu-Sei" is effective in improving the anti-fatigue ability of mice.

4) Administration of "Denhichi-Tochu-Sei", a herbal extract containing gallic acid and a mixed extract of "Glycyrrhiza root" reduced elevated serum GTP, GOT level is effective.

5) Application of "Denhichi-Tochu-Sei", a herbal extract containing gallic acid and a mixed extract of "Glycyrrhiza root" on MDA production in rats induced by carbon tetrachloride, binding of lipids to ¹⁴ CCl ₄ , CO production, NADPH oxidation and oxygen consumption are inhibited.

6) Administration of "Denhichi-Tochu-Sei", and administration of "Denhichi-Tochu-Sei", an extract of herbs containing gallic acid and a mixed extract of "licorice root" reduced the risk of hypertrophy induced by streptozotocin The role of blood glucose levels in rats.

The above results show that "Denhichi-Tochu-Sei" has a preventive effect on hyperlipidemia, and "Denhichi-Tochu-Sei" and the mixed extracts of "Denhichi-Tochu-Sei", "Gallae rhois" and "Licorice Root" , or adding them to the food and feeding them with feed can significantly reduce blood sugar levels. At the same time, the mixed extract has the effect of improving liver function. These results demonstrate that the present invention is effective in promoting the health of humans and animals.

Moreover, it is worth mentioning that no side effects, including acute toxic side effects, were observed in any animal tests.

Example 11: Therapeutic effect of mixed extracts of "Denhichi-Tochu-Sei", "Gallae rhois" and "Glycyrrhiza root" on symptoms of patients with chronic viral hepatitis C

A HCV patient (male, 50 years old) was treated with interferon (IFN) for about 3.5 months and no improvement in his GOP and GTP was observed. On the other hand, the GOP level decreased from 159 to 89 and the GTP decreased from 204 to 48 after the patient was treated for 10 days by administering a mixed extract of "Denhichi-Tochu-Sei", "Gallae rhois" and "Glycyrrhiza root". The results are shown in Table (xi).

Example XII: The therapeutic effect of the mixed extract of "Denhichi-Tochu-Sei", "Gallae rhois" and "Glycyrrhiza root" on patients with non-viral hepatitis:

After treating a female patient with non-viral hepatitis with a certain dose of mixed extracts of "Denhichi-Tochu-Sei", "Gallae rhois" and "Licorice Root" for 10 days, the GOP level decreased from 53 to 39, and the GTP decreased from 58 to 35 . The results are shown in Table (xii).

Example XIII: The effect of the mixed extract of "Denhichi-Tochu-Sei", "Gallae rhois" and "Glycyrrhiza root" on patients with hepatitis B:

A HBs antibody-positive patient (male, 70 years old) was treated with a certain dose of mixed extracts of "Denhichi-Tochu-Sei", "Gallae rhois" and "Glycyrrhiza root" for 10 days. On the fourth day after receiving the dose, his GOP level dropped from 28 to 23 and his GTP dropped from 60 to 28. The results are shown in Table (xiii).

Table (xiii)

99/199/2 Visiting doctor Administer mixed extract (fourth day) (eighth day) (first day) AST(GOT)ALT(GTP)γ-GTP 55-115 82 23 2756-123 60 28 1533-51 35 27 24

Example XIV: The effect of the mixed extract of "Denhichi-Tochu-Sei", "Gallae rhois" and "Glycyrrhiza root" on patients with drug-induced hepatitis:

A drug-induced hepatitis patient (male, 30 years old) was treated with a certain dose of mixed extracts of "Denhichi-Tochu-Sei", "Gallae rhois" and "Glycyrrhiza root" for 10 days. On the fifth day after stopping the drug, the GOP level dropped from 43 to 32, and the GTP level dropped from 121 to 27. The results are shown in Table (xiv).

Table (xiv)

’98/11 ’99/1 Leave the hospital Start administering the mixture Day 17 of the 5th day after cessation of the extract after cessation of administration AST(GOT)ALT(GTP) 66 43 32 38200 121 27 88

Example XV: Effect of mixed extracts of "Denhichi-Tochu-Sei", "Gallae rhois" and "Glycyrrhiza root" on symptoms of patients with chronic active hepatitis C:

A patient with abnormal liver function (GOT 80, GTP 102, γ-GTP 68) was treated with a dose of interferon three times a week for two weeks. Side effects occurred on day 11 of treatment. Therefore, "Denhichi-Tochu-Sei" at a dose of 6 g per day was used instead of interferon for 6 days of treatment. Side effects disappeared and liver function improved (GOT60, GTP 47, γ-GTP 17). However, the amount of virus remained unchanged. After leaving the hospital, the patient received interferon three times a week, and after about two weeks, was treated with a daily dose of 3g of a mixed extract of "Denhichi-Tochu-Sei", "Gallae rhois" and "licorice root" for a week. The amount of virus is reduced to 0.5 Meq/ml or less. Liver function returned to normal levels (GOT 31, GPT 8, γ-GTP 14). Normal liver function (GOT 25, GTP 9, γ-GTP 12) was observed after administration of a mixed extract of "Denhichi-Tochu-Sei", "Gallaerhois" and "Licorice root" for two months. The results are shown in Table (xv).

Table (xv)

7/29 8/18 8/19*1 8/25 9/11*2 9/18 11/24 AST(GOT)ALT(GTP)γ-GTP 8010268 505883 604717 31814 25912

*1 Started administration of interferon and "Denhichi-Tochu-Sei"

*2 Mixed extract of "Denhichi-Tochu-Sei", "Gallae rhois" and "Licorice root"

As described above, "Denhichi-Tochu-Sei" and "Denhichi-Tochu-Sei" of the present invention, extracts of herbs containing gallic acid, and mixed extracts of "licorice root" can be used as food supplements for maintaining health (feed supplement). The composition of the present invention has been shown to be effective in preventing hypertension and liver disease. They have also been shown to be effective in maintaining health and improving nutritional status and the immune system. In particular, if it is an extract of medicinal herbs containing gallic acid and a mixed preparation of "Licorice Root" and "Denhichi-Tochu-Sei", these two ingredients can be easily absorbed by humans and animals. Furthermore, it was observed that the above-mentioned formulations produced a rapid effect.

Example XVI: Effect of Youjyo-Hensikoh on Patients with Various Liver Diseases

From Panax notoginseng ("Denhichi") (55% by weight), Eucommia ("Tochu") (25% by weight), Polygonatum falcatum ("Osei") (10% by weight), Glycyrrhiza licorice (" Kanzo") (5% by weight), Ginseng root (ginseng) (3% by weight) and honey (2% by weight) made a Chinese herbal medicine prescription called "Youjyo-Hensikoh".

Under the guidance of physicians, patients (n=20) suffering from various liver diseases including HCV were allowed to take 1 gram of the above prescription orally after meals, three times a day. Serum levels of ALT, AST and γ-GTP were detected.

These serum levels were significantly reduced after 10 days of treatment with "Youjyo-Hensikoh" (average 18% reduction in ALT and 59% reduction in AST). For normal people, serum ALT and AST levels hardly changed. No side effects were observed during the treatment.

The results are shown in Figures 1-6.

Example XVII: Effect of Youjyo-Hensikoh on D-glucosamine-treated rats

Rats in group 3 (n=9) were orally administered 2 ml of Youjyo-Hensikoh (50 mg/ml), and rats in groups 2 (n=9) and 3 were subcutaneously injected with 1 ml of D-glucosamine solution (800mg/kg). Group 1 (n=8) served as a control. After 24 hours, stop eating. Blood was collected 48 hours after the administration of Youjyo-Hensikoh, and then ALT and AST were measured. The results are shown in Figure 7, where the results are expressed in the form of mean ± SD, * indicates p<0.01 when compared with group 1 (control), ** indicates p when compared with group 2 (D-glucosamine) <0.01.

Example XVIII: Effect of Youjyo-Hensikoh on Glutathione Metabolism in _CCl4- Induced Cirrhosis

From Panax notoginseng ("Denhichi") (55% by weight), Eucommia ("Tochu") (25% by weight), Polygonatum falcatum or Siberian Solomonseal rhizome ("Osei") (10% by weight), Licorice root (Glycyrrhizalicorice or Glycyrrhiza glabra Linn) (“Kanzo”) (5% by weight), Ginseng root (ginseng) (3% by weight) and honey (2% by weight) in hot water extracts known as “Youjyo-Hensikoh” ( k-17.22) Chinese herbal composition.

Female albino Wistar rats (3 weeks old, weighing 60-75 g) housed in isolated cages in a controlled environment ecoviary with free access to standard chow and deionized water were divided into three groups:

A) Subcutaneous injection of 0.1ml/100g body weight of CCl ₄ (1:1v/v) dissolved in olive oil, twice a week for 5 weeks;

B) As in A, 50 mg/kg of K-17.22 dissolved in 5% glucose was orally administered simultaneously with _CCl injection;

C) Like A, 50 mg/kg of K-17.22 dissolved in 5% glucose was orally administered one week after the first injection of CCl ₄ .

Subcutaneous injection of olive oil alone served as the control group.

At the end of the study period (3 days after the last injection) the rats were sacrificed and blood and liver samples were obtained. Preparation of liver supernatant fraction

A 50% tissue homogenate was prepared by the method of Iga et al. (Biochem Pharmacol, 1977). A portion of the tissue homogenate was used for the GSH assay. The remainder was centrifuged at 150,000g for 120 minutes at 4°C in a Hitachi 65p-7 ultracentrifuge. The supernatant fraction was gel filtered immediately after volume measurement.

Elution of the supernatant

3 ml of the supernatant was applied to a Sephadex G-75 column (2.5 x 100 cm). At 4°C, use a pump to drive downward flow (2ml/40min/test tube), and perform elution with 0.01M phosphate buffer (pH7.4). 200 [mu]l aliquots from all tubes corresponding to the Y-section were assayed for GST activity using 1-chloro-2,4-dinitrobenzene (CDNB) as substrate. All tubes showing GST activity were pooled, lyophilized at -80°C and stored at -40°C until measurement.

Analysis

The dried Y-protein was dissolved in phosphate buffer (pH 7.4) and treated with CDNB and 1,2-dichloro-4-nitrobenzene (DCNB) using the method described by Habig et al. (J.Biol.Chem., 1951). ) was used as a substrate to measure the activity of GST, and the concentrations of Y-protein and GSH in liver tissue homogenate were determined by Lowry-Folin and Ellman methods, respectively. Plasma ALT and AST were determined by pyruvate oxidase-p-chlorophenol method.

Liver histology for necrosis and inflammatory infiltration was assessed blinded to the examiner on 3 separate sections (1+: one lesion per field of view, 2+: two or more lesions per field of view ).

Statistical analysis

Standard errors (mean ± SE) are listed along with the means. A t-test was used to determine the significance of differences between control and _CCl4- or _CCl4 +K-17.22 treated groups.

The results are shown in Figures 8-14.

These figures show the effect of composition K-17.22 according to the invention on the body weight and liver wet weight of rats (Fig. 8), the effect of K-17.22 on rat Y-protein liver content (Fig. 9), K - Effect of 17.22 on rat liver GSH content (Fig. 10), determined using selected substrates, effect of K-17.22 on GSH S-transaminase activity in the Y-fraction (Fig. 11), effect of K-17.22 on transferase The effect of plasma levels of K-17.22 on plasma levels of cholestatic parameters ( FIG. 13 ), the effect of K-17.22 on liver histological scores (necrosis + inflammatory infiltration) ( FIG. 14 ). These data illustrate:

1) K-17.22 has a significant inhibitory effect on the reduction of GSH and Y-protein in _CCl4- induced liver injury, and can significantly improve blood parameters related to liver necrosis and cholestasis;

2) This change was paralleled by a marked decrease in necrotic-inflammatory and fibrotic changes in the liver;

3) Interestingly, this abnormality improved even after the onset of _CCl4 intoxication;

4) Antioxidative effects may occur due to the intrinsic beneficial mechanism of K-17.22.

Example XIX: Effect of Youjyo-Hensikoh on GPT Changes in Hepatitis C Patients

From Panax notoginseng (55% by weight), Eucommia ulmoides (25% by weight), Polygonatum falcatum (10% by weight), Glycyrrhiza licorice (5% by weight), Ginseng root (Ginseng) (3% by weight) Youjyo-Hensikoh was prepared from aqueous extracts of honey and honey (2% by weight). Tablets containing 250mg Youjyo-Hensikoh each were manufactured.

Let 20 hepatitis C patients take two tablets three times a day after each meal. Table (xvi) and Figures 15 and 16 show the changes in patient GPT.

Example 1

This example is to show that when "Youjyo-Hensikoh" is used together with American ginseng to formulate the composition of the present invention, the increase in blood pressure of the patient is suppressed.

The leaves and stems of American ginseng are rinsed with water, dried and cut into slices. A part of these pieces was soaked in 8 times the amount of water and heated to 40° C. or higher for 30 minutes, and filtered after 2.5 hours. Then, soak another part of the above-mentioned slices with 6 times the amount of water, and filter after 1.5 hours. The two filtrate fractions were combined and concentrated to original volume by heating. 40 parts by weight of the concentrate and 60 parts by weight of "Youjyo-Hensikoh" prepared in Example XVI were mixed, then dried and granulated. The obtained granules were enclosed in capsules so that the capsules contained 150 mg of each ingredient.

Two patients with different liver diseases, one a 56-year-old male (patient A) and the other a 61-year-old male (patient B), used the thus prepared capsules containing the composition of the present invention. Each patient was given two capsules orally, three times a day, after each meal. The patient's blood pressure was measured every day before breakfast.

Table 1 shows changes in blood pressure of patients before and after administration of the composition of the present invention. Patient A's blood pressure was 152-168/93-107 (maximum/minimum) in the month before the drug, but his blood pressure was lower, 144-158/ 82-96 (Maximum/Minimum). Patient B's blood pressure was 157-170/99-110 (maximum/minimum) in the month before the drug, but his blood pressure was lower during the month he was continuously receiving the composition of the invention, 140-175/ 89-102 (Maximum/Minimum).

Example 2

Flavonoids (hereinafter referred to as American ginseng flavonoids) were extracted from the leaves of American ginseng by conventional methods commonly used in this field, and were used to study the effects on the circulatory system of cats and rats. If this study is confirmed, whether there is a new effect on the circulatory system, whether American ginseng flavonoids can be used in food, food supplements, drugs, etc.

Cats (weighing 1.2-1.7 kg, equal number of males and females) and Wister rats (weighing 220-270 g, equal number of males and females) were used in this study.

The 24 cats were divided into four groups. They were anesthetized intraperitoneally with pentobarbital (concentration 30 g/l, 3.0 mg/kg). American ginseng flavonoids were administered via the jugular vein at a dose of 0.1 g/kg (group 2), 0.3 g/kg (group 3), or 1.0 g/kg (group 4). Group 1 received no dose and served as a control. HR, MAP, LVP, LVEDP and "±dp/dtmax" were determined before and after administration. The resulting data were statistically processed and summarized in Table 2 below.

Meanwhile, 18 rats were divided into two groups. They were anesthetized intraperitoneally with urethane (concentration 200 g/l, 2 g/kg). American ginseng flavonoids were administered via inguinal vein at a dose of 1.0 g/kg. The control group received normal saline. Changes in the number and frequency of breathing, blood pressure and heart rate were observed before and after administration. The resulting data were statistically processed and summarized in Table 3 below.

It can be seen from Table 2 that administration of American ginseng flavonoids reduced the MAP of cats. LVP and "+dp/dtmax" were dose dependent in the range of 0.1 g/kg, 0.3 g/kg and 1.0 g/kg. "-dp/dtmax" tends to decrease. Medication did not affect LVEDP or HR.

It can be seen from Table 3 that compared with the control group receiving normal saline, the administration of American ginseng flavonoids lowered the blood pressure of the rats, and at the same time reduced the heart rate and the number of respirations, but had no substantial effect on the respiration rate.

As mentioned above, American ginseng flavonoids can significantly reduce MAP, LVP and "+dp/dtmax" in cats, and at the same time have a hypotensive effect that lowers blood pressure and heart rate. This suggests that the mechanism of blood pressure reduction is due to dilation of peripheral blood vessels.

Claims (14)

1. A composition, which contains Panax notoginseng; Eucommia ulmoides; Polygonatum falcatum, Rhizome Polygonatum, or Siberian Solomonseal rhizome; hot water or ethanol extract of licorice root, and honey; it is characterized in that the composition also contains American ginseng. 2. The composition of claim 1, wherein the composition contains ginseng. 3. compositions as claimed in claim 1, wherein said composition contains the Denhichi-Tochu-Sei of 10-80% by weight; The American ginseng of 4-50% by weight; Gallic acid herb, 4-15% by weight of licorice root, wherein said Denhichi-Tochu-Sei consists of 10-90% by weight of Panax notoginseng, 10-90% by weight of Eucommia ulmoides, 5-20% by weight of ginseng, and 0 - 30% by weight honey composition. 4. A medicament containing the composition of claim 1, 2 or 3. 5. The application of the composition according to claim 1, 2 or 3 in the preparation of medicines for maintaining health and improving nutritional status. 6. The use of the composition according to claim 1, 2 or 3 in the preparation of medicines for improving liver diseases without raising blood pressure. 7. The use as claimed in claim 6, wherein said liver disease is hepatitis. 8. The use according to claim 7, wherein said hepatitis is selected from hepatitis C, chronic hepatitis and hepatitis B. 9. The use of the composition according to claim 1, 2 or 3 in the preparation of a medicament for preventing or treating pancreatitis. 10. A food supplement comprising a composition as claimed in claim 1 , 2 or 3. 11. Food supplement as claimed in claim 10, said composition contains 10-80% by weight of Panax notoginseng and Eucommia ulmoides, 4-50% by weight of American ginseng, 4-20% by weight of Osei members and 4-15% by weight licorice root. 12. A food for maintaining health, which contains 0.1-20% by weight of the food supplement as claimed in claim 10. 13. The food for maintaining health as claimed in claim 12, which is in the form of powder, powder granule, tablet, drink and emulsion. 14. A feed comprising the composition of claim 1, 2 or 3.

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