JP3161882B2 - Ginseng-derived polysaccharide, its production method and use - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention is intended for patients diagnosed with nephrotic syndrome, which is an early stage leading to chronic renal failure, especially kidney disease, which is increasing in young people as well as elderly people, or for viral and drug use. The present invention relates to an invention that provides a safe and therapeutic agent for oral and intramuscular administration that can be visited in a patient with symptoms of liver disorder such as hereditary hepatitis.

[0002]

BACKGROUND OF THE INVENTION Dansin is a herb that has been traditionally used in China for improving blood circulation and blood circulation arrest, and has recently been shown to have a vasodilator effect (Hikichi Ohura: Journal of the Wakan Pharmaceutical Society., 5:
227-237. 1988. ), Antihypertensive effect (Nakayama Medical School theory: Medical and Dental Publishing, Tokyo., 257-258., 198)
0. ), Anticoagulant effect (Ra Thao Ul et al .: Acta Pharm)
aceutica Sinica. , 23 (11): 8
30-834. 1988. ), Inhibition of intracellular cholesterol synthesis (Sun Xi-ming; herbal medicine.,
22 (1): 20-23. 1991. ), Protection of hepatocytes (Rinshin Hiroshi: Nakanishi Medical Combined Magazine., 11 (2): 102-)
104. 1991. ) And radical scavenging action (Tianki Hu: Shanghai China Pharmaceutical Magazine, 9: 28-30, 1988.)
And various other physiologically active activities, and improvement of renal function (Oura Hikichi: 2nd Japan-China Symposium on Medical and Pharmaceutical Research on Wakan Yakuhin pp. 148-157, 198)
8. ), Effective for patients with chronic kidney disease and uremic disease (Zhang Jingjin: Shanghai China Pharmaceutical Magazine, 1.17-18., 198)
1. ) Is reported internally and externally, but the substance is not mentioned at all, or even if it is mentioned, it is a low molecular substance completely different from the substance of the present invention.

[0003] Steroid drugs as synthetic drugs or dipyridamole as antiplatelet drugs have been used as medical treatments for minimal change nephrosis, but they must be used for a long time and are administered to young people. In some cases, especially full moon-like face, irregular menstruation, dizziness, headache, nausea, vomiting, and in severe cases, such as infection, gastrointestinal bleeding, metabolic abnormalities, osteoporosis, thrombosis, adrenal insufficiency, mental disorders, etc. Side effects are a concern.

[0004] Although active research has been conducted on remedies for renal diseases from the same raw materials as in the present invention, tanshinone analogs, which are low-molecular phenanthrenequinones, and magnesium lithospermine, which is a tetramer of caffeic acid Acid B and the like have been isolated (T. Yozawa, HY.
g, H .; Oura, G .; Nonaka, and I .; N
isioka, Chem. Pharm. Bull. ,
36, 316 (1988)), all of which are only fat-soluble substances extracted in the presence of an organic solvent, and have not yet reached clinical application.

[0005] Hepatitis includes viral and drug-related hepatitis, but most of them are viral. Therapeutic agents include biologic response such as interferon and interleukin-2.
Modifier (BRM), neominophagen C, which is an intravenous injection of glycyrrhizin, and the like are used. However, there is a problem with long-term administration of BRM due to side effects such as fever. Glycyrrhizin is basically an anti-inflammatory agent, and when used for a long period of time, it is necessary to control blood pressure and electrolyte concentration. In addition, saikosaponin, saponin, gomisin and the like, which are crude drug components, are known, but none of them has been applied to clinical applications.

[0006]

[0006] Kidney diseases are roughly classified into primary glomerular-derived diseases and secondary diseases derived from other diseases, with the former accounting for about 80% or more, and are more common in lower age groups ( About 90%) ¹⁵⁾ . From the histopathological findings, a group of small changes,
Monoglomerular sclerosis, membranous nephropathy, mesangial proliferative nephropathy (IgA nephropathy, non-IgA nephropathy), membranous proliferative glomerulonephritis,
It is classified as crescent-forming glomerulonephritis. Proteinuria is a common clinical feature of all histological types, and is diagnosed as nephrotic syndrome in severe cases16 ⁾ . In recent years, renal diseases, especially those induced by the organic deterioration of the kidney, are increasing not only in the elderly but also in younger people. There is a need for the development of a drug that can be administered orally or intramuscularly.

[0007] Hepatitis can be roughly classified into two types: viral ones and drugs such as alcohol.
Mostly due to hepatitis virus. In recent years, interferon has been reported to be particularly effective as a therapeutic agent against hepatitis C, and its use has been increasing (Shiro Iino et al .: Basic and Clinical. 26: 339, 199).
2: Hiroshi Suzuki et al .: Liver, gall, and pancreas. 23: 1065, 199
1). However, short-term administration showed flu-like symptoms such as fever, and long-term administration resulted in weight loss, diarrhea, vomiting,
Side effects such as arrhythmia, hair loss, and autoimmune abnormalities are observed. In addition, since all of these drugs are injections, they can be used as a new therapeutic agent that can be used more easily or as a supplementary drug combined with interferon, etc. There is a need for the development of therapeutic drugs.

[0008]

DISCLOSURE OF THE INVENTION The present inventors have developed a nephrotic syndrome in rats induced by puromycin, which is prominent in the widely used proteinuria excretion and is also well known to show renal organic changes. As a result of intensive studies using a model and a liver injury model, a polysaccharide effective for the above model was found from a water extract of Danshen.

The present invention is based on this finding, and (I) a polysaccharide having the following properties, which can be extracted from water ginseng with water or an aqueous solvent. Sugar content: 60-100% (1) Sugar composition: uronic acid 40-80% Neutral sugar 10-30% (2) Neutral sugar composition: rhamnose 0-15% glucose 0-15% galactose 25-55% arabinose 30-60% Mannose 0-15% B. Molecular weight 150,000-300,000 (II) Dansin is extracted with water or an aqueous solvent, and the liquid obtained by removing the residue from the extract is passed through a non-polar porous polymer resin, concentrated by ultrafiltration, and then concentrated by ultrafiltration. A method for producing the above polysaccharide, which is characterized by subjecting the polysaccharide to filtration chromatography, and (III) an agent for ameliorating nephrotic syndrome comprising the above polysaccharide.

The ginseng is a plant ginseng (Salvia milt)
iorrhiza Bunge's roots and root-like stems, but a congener plant, S. bowleyana.
Dunn), Gansu Dansin (S.przewalskii)
Maxim), Yunnan Dansin (S. yunnanensis)
C. H. The roots such as Wright are also used. In the present invention, these are collectively referred to as Dansin.

The place of production of ginseng used in the present invention is not particularly limited, but preferably ginseng from Sichuan, China can efficiently extract and purify the polysaccharide of the present invention.

It is desirable that the ginseng be extracted as small pieces as possible. As the extraction solvent, water or an aqueous solvent is used, and as the aqueous solvent, a buffer such as a phosphate buffer or an acetate buffer or an aqueous salt solution such as a salt is preferably used.

[0013] Preferably, the pH of the extraction solvent is adjusted to about 4 to about 9. The extraction is preferably performed at about 50 to about 100C, more preferably at 70 to 90C. For example, ginseng is pre-heated to 50 to 100 ° C, preferably 70 to 90 ° C.
It is added to warm water or a buffer solution or a salt solution having a pH in the range of 4 to 9, or after it is added, it is heated to a predetermined temperature in a warm bath or the like and extracted.

Thus, 1 to 8 hours, preferably 3 to 5 hours
A crude extract can be obtained by extraction over time. Dansin residues mixed in the extract can be filtered off with a coarse filter cloth or Nutsche.

The extract from which the residue has been removed is further purified by column chromatography using a nonpolar porous polymer resin equilibrated with water as a filler. Examples of the polymer resin include HP-20 and MCI-gel (manufactured by Mitsubishi Kasei Co., Ltd.) and Amberlite XAO-2 (manufactured by Organo Corporation).

It has been reported that magnesium lithospermic acid B, which is a low molecular weight substance eluted with a 50% methanol solution in the MCI-gel adsorption fraction of the active ingredient of Dansin, was reported by the present inventors. Was confirmed to have an activity to suppress proteinuria excretion. However, as a result of a detailed test of the effect of suppressing proteinuria excretion of all the eluted fractions including the non-adsorbed part, contrary to the initial expectation, there is a component that has the above effect even in the pass-through fraction. It turned out to be the starting point of the discovery of the substance of the present invention. At this point, the flow-through fraction from this treatment was expected to be highly polar and would not be a protein-specific UV absorption spectrum, indicating a non-protein component.

A portion of the flow-through fraction was then separated by two ultrafiltration membranes (cut-off, molecular weight 300,000 and 50,000
A review of the concentration and purification steps was performed throughout the system. In practice, the molecular weight is more than 300,000, 50,
Each substance group was divided into 000 to 300,000 and 50,000 or less, and the activity of suppressing proteinuria excretion was tested for each component using a purominsin-induced rat model. As a result, a strong activity has a molecular weight of 50,000-30.
It was found in fractions in the range of 0000, with weak activity below 50,000.

Accordingly, the concentration of the molecular weight of 3
A 000 cut-off, ultrafiltration membrane was used. Any type of ultrafiltration membrane in this step can be used for concentrating the substance of the present invention, as long as it has the same cutoff size.

Next, in order to limit the active ingredient in the concentrated solution to a narrower molecular weight range, purification was performed by gel filtration column chromatography. Generally, in the case of proteins and the like, as carriers for gel filtration chromatography, Sephadex and Sepharose (manufactured by Pharmacia),
Cellulofine (manufactured by Seikagaku Corporation), biogel (manufactured by Bio-Rad) and the like can be used, and the above-mentioned substances can also be used for the chromatography of the substance of the present invention. Chromatographic materials such as biogels are suitable for the purification of the substances according to the invention. There are various types of chromatographic materials depending on the stitch size, that is, the exclusion limit.
Any one of 0000 is acceptable. The inventors prefer biogels P-30, -60, -100,
Among them, Biogel P-60 was used. Therefore, the concentrate was passed through a column filled with Biogel P-60 equilibrated with water. The monitor was tentatively performed at 280 nm absorption, and the fraction with absorption and the fraction without absorption were measured at the column capacity of 2 columns.
The fraction was divided into several fractions up to twice the amount, and the inhibitory effect on proteinuria excretion in a puromycin-induced rat model was examined. As a result, it was found that a polysaccharide having activity in the high molecular weight region was eluted.

This polysaccharide loses its activity when subjected to periodate oxidation or reduction treatment. In addition, this substance has an inhibitory effect on platelet aggregation and a protective effect on erythrocyte membrane in vitro.
It became clear from the experimental result. Further, it is known that radicals are involved in puromycin-induced nephrotic model rats or carbon tetrachloride-induced liver injury model rats. However, it has been confirmed by experiments using ESR that this substance has no action of directly scavenging radicals. Indicated.

In Test Examples and Examples, the properties of polysaccharide obtained by purifying (purified fraction) the extract of Dansin using a nonpolar porous polymer resin and gel filtration chromatography were tested as follows.

(1) Total sugar content: phenol-sulfuric acid method (Ho
dge, J.M. E. FIG. and Hoofreiter, B.A.
T. (1962) Methods in Carboh
ydrate Chemistry (Academic
Press). Vol. 1, p. 338) Take 0.5 ml of the test solution into a test tube, add 0.5 ml of 5% (w / v) phenol solution, immediately add 2.5 ml of concentrated sulfuric acid directly to the liquid surface, mix well, and keep at room temperature for 20 minutes. ,
The absorbance at 480 nm is measured. An aqueous solution of glucose (10 to 90 μg / ml) was used as a standard solution.

(2) Uronic acid content: metahydroxydiphenyl method (Blumenkrantz, N. and A.
sboe Hansen, G .; (1973) Anal.
Biochem. 54, 484-489. ) Add 0.2 ml of a 0.0125 M sodium borate concentrated sulfuric acid solution to 0.2 ml of the sample solution, and stir after cooling on ice.
After treatment at 100 ° C. for 5 minutes, the mixture was cooled on ice, and 0.5% sodium hydroxide solution of 0.15% metahydroxydiphenyl 2
Add 0 μl and measure the absorbance at 520 nm. A galacturonic acid solution was used as a standard solution.

(3) Neutral sugar content (Alditol acetate-GC-MS method) (Borchardt, LGa)
nd Piper, C.I. V. (1970) Tappi.
53, 257-260. )

The purified fraction of Dansin 50 mg was added to 72% (v / v
v) After dissolving in 3 ml of sulfuric acid and treating at 30 ° C. for 1 hour, add 84 ml of distilled water and autoclave at 120 ° C. for 1 hour. Inositol 4mg was added as an internal standard,
30 ml thereof is adjusted to pH 5.5 by adding barium hydroxide, and then centrifuged to obtain a supernatant. 80 mg of sodium borohydride is added to 25 ml of the mixture, and the mixture is treated at room temperature for 2 hours, and the reaction is stopped with acetic acid. After concentration and drying, the residue is dissolved in distilled water and passed through a DEAE Sephadex column to collect a flow-through fraction. After concentration and drying, the mixture is acetylated with acetic anhydride and pyridine, and then extracted with a mixture of dichloromethane and 1N hydrochloric acid. The organic layer was washed with distilled water, concentrated, dissolved in acetone, and quantified by gas chromatography mass spectrometry (GC-MS) (column: Supelco).
Use a capillary column for sugar analysis). The sample was processed by the above-mentioned reduction operation and analyzed in the same manner.

(4) Measurement of molecular weight Asahi Pack GS-520 (Asahi Kasei) column (7.6 mmI) was applied to a Tosoh HPLC system (Tosoh).
Dx500 mm), and using Milli-Q water, add 10 μl of the sample solution of the substance of the present invention to the column and measure the molecular weight (temperature: room temperature, flow rate: 0.5 ml / min, detection: RID)
did. Amylose kit (manufactured by Nakano Vinegar Co., Ltd.): molecular weight 10200, 30100, 75200,
Using 111400 and 364200, the molecular weight of the substance of the present invention was calculated from a calibration curve obtained from these elution patterns.

(5) Evaluation using a puromycin-induced nephrotic syndrome model rat 1) Preparation of a nephrotic syndrome model rat: Puromycin aminonucleoside (hereinafter referred to as puromycin, sigma) was administered to a Wistar female rat (about 9 weeks old, weighing about 150 g). A nephrotic syndrome model rat was prepared by injecting 60 mg / kg once into the jugular vein (Shizuo Tojo et al .: Nephrotic Syndrome Hikaru Kyogoku, Soft Science Publishing, 479-488, 1984).

2) Administration of sample solutions: Each sample solution was orally or intramuscularly administered for 21 days through a gastric cannula once a day from the start of puromycin administration. Water for injection was used for the negative control group, and dipyridamole solution was used for the positive control group.

3) Measurement of urine protein content: From the 5th day after the end of puromycin administration, urine was collected for 24 hours every 2 to 3 days using a rat metabolic cage, and the amount of urine protein was measured. . Then centrifugation (3000 rpm x 10 minutes)
3 ml of sulfosalicylic acid was added to 1 ml of the resulting supernatant,
After standing at room temperature for 10 minutes, the absorption at a wavelength of 660 nm was measured, the protein concentration in the urine was determined from a calibration curve, and the total protein excretion in the urine was calculated by multiplying the urine volume. In preparing a calibration curve, bovine serum albumin (Sigma) was used as a standard protein.

4) Measurement of serum cholesterol, serum albumin, total protein content in serum and serum lipid peroxide: Rats of each group were anesthetized with ether on days 7, 14 and 21 after completion of puromycin administration. After the administration, blood was collected from a vein, and cholesterol 1 albumin, total protein and lipid peroxide in serum were measured (all manufactured by Wako Pure Chemical Industries, Ltd.).

(6) Evaluation using a carbon tetrachloride-induced liver injury model 1) Preparation of a liver injury model: Female Wistar rats (9-11 weeks old, weighing around 160 g) were mixed with olive oil in an equal amount. It was prepared by injecting 1.5 ml / kg of carbon tetrachloride (manufactured by Wako Pure Chemical Industries) solution intraperitoneally once. (Inflammation book: Inflammation inflammation animal experiment method, experimental liver fibrosis. Medical Shoin Publishing, 253-277)

2) Administration of the sample solution: The sample was administered intramuscularly once a day from 3 days before the administration of carbon tetrachloride to the day before the administration, or orally from 7 days before the administration to the day before the administration. Water for injection was administered to the negative control group.

3) Serum biochemical test: administration of carbon tetrachloride 2
Four hours later, the chest was opened under ether anesthesia, 2 ml of blood was collected from the heart, left at room temperature for 1 hour, and centrifuged to obtain serum. Serum transaminase (GOT: glutam)
ic oxaloacetic transamino
se, GPT: glutamic pyruvictr
An activity of the enzyme was measured using a kit manufactured by Wako Pure Chemical Industries.

7) Statistical analysis: All measured data are mean ± SEM This was indicated by E and statistically analyzed by Student's t-test.

As shown in the following examples, the polysaccharides of the present invention are effective in ameliorating nephrotic syndrome and ameliorating hepatic impairment symptoms in animal experiments. Usually, a daily dose per adult is about 10 to 100 mg orally, and about 0.5 to 10 mg can be administered as an intramuscular injection.

[0036]

The present invention will be further described below with reference to examples and test examples. Example 1 Water was added to 10 kg of small pieces of ginseng root from Sichuan, China.
L, add a throwing heater and bring to 80 ° C.
Extracted with time stirring. The root residue in the extract was removed by filtration with Nutsche, and the collected root residue was further treated with 80 L of water and treated in the same manner as the first time to obtain a re-extract. The first and second extractions (130 L) were combined, and concentrated under reduced pressure at 40 ° C. using an evaporator to obtain a concentrated liquid (10 L).

Next, the concentrate was added to a column (11 × 45 cm) packed with HP-20 (4 L, manufactured by Mitsubishi Kasei). Chromatography was performed at room temperature using water as the equilibrating solution and the developing solution, and a flow-through fraction and a water-washed fraction (non-adsorbed) solution were collected. The column was washed with 50% methanol and acetonitrile, and finally was completely replaced with water and reused. The non-adsorbed fraction was repeatedly treated in the same manner about three times to obtain a completely non-adsorbed fraction (55 L). The total non-adsorbed liquid was subjected to ultrafiltration and concentration using an ultrafiltration apparatus SEP-1013 (Asahi Kasei) equipped with an ultrafiltration membrane having a molecular weight cutoff of 3000, and the passed liquid (molecular weight of about 3000 or less, S
EP-OUT) and non-passing liquid (molecular weight about 3000 or more,
(SEP-IN) was obtained. Concentrated non-passage liquid (SEP-I
N) was added to a column (1.5 × 100 cm) packed with Biogel P-60 equilibrated with water, and chromatography was performed using water as a developing solution. The monitor tentatively measures the absorption at a wavelength of 280 nm, and displays the fraction number on the horizontal axis,
A graph in which the vertical axis represents the absorption of each fraction was prepared, the total sugar was measured mainly on the fractions showing no absorption, and the measurement results were described in the same graph (FIG. 1).

The objective polysaccharide components are fractions 11 to 22
And then freeze-dried to obtain a powder (30 g, lot A). The properties of the purified polysaccharide obtained here were tested by the test method described above, and as a result, the following durability was obtained.

1) Sugar content (phenol-sulfuric acid method): 79% (1) Sugar composition: uronic acid content (62%, metahydroxydiphenyl method) Neutral sugar content (17%, alditol acetate-GC-)
MS method) (2) Neutral sugar composition (Alditol acetate-GC-M)
Method S) Glucose content (5.5%) Galactose content (39.7%) Arabinose content (44.6%) Mannose content (5.5%) Rhamnose content (4.7%) (3) Other sugars: Amino sugar, aldohexose, 2-
Does not contain deoxy sugar.

2) Molecular weight: 259000 (standard polysaccharide: amylase kit, molecular weight 100-360K)

3) Evaluation by Nephrotic Syndrome Model Rat Orally administered purified samples 10 mg / kg and 40 mg / kg,
When 0.5 mg / kg and 2.5 mg / kg were intramuscularly administered, urine protein excretion was significantly suppressed in each case as shown in FIGS. In addition, as shown in Tables 1 and 2, serum cholesterol (Cholesterol)
Value, serum albumin (Albumin) value and A / G
A significant improvement was also observed in the ratio and serum lipid peroxide (MDA) value.

[0042]

[Table 1] (In the table, PA is puromycin aminonucleoside,
AF represents a polysaccharide of the invention. The same applies to the table below)

[0043]

[Table 2]

4) Evaluation by carbon tetrachloride-induced liver injury model Purified samples (AF) were orally administered at 7 mg / kg and 35 mg / kg and intramuscularly administered at 0.3 mg / kg and 1.5 mg / kg. As shown in FIG.
In the pre-administration group, increases in serum GOT and GPT levels were suppressed in a dose-dependent manner.

Example 2 According to the method described in Example 1, purification was carried out from raw materials of different lots of Dansan, and purified lots of 3 lots (lots B, C, D) were obtained in addition to those described in 1 above. Was evaluated.

1) Sugar content (phenol sulfate): Lot B
(65%), Lot C (80%), Lot D (93%) (1) Sugar composition

[0047]

[Table 4]

(2) Neutral sugar composition (alditol acetate-GC-MS method)

[0049]

[Table 5]

(3) Other sugars: None of lots B, C and D contain amino sugars, aldohexoses and 2-deoxy sugars.

2) Molecular weight: (Standard polysaccharide: amylose cat, molecular weight 100-360K) Lot B (150,000), Lot C (280,00)
0), Lot D (250,000)

3) Evaluation by Nephrotic Syndrome Model Rat In the evaluation of drug efficacy, all purified products obtained almost the same effects as those obtained in Example 1.

Example 3 The purified product was oxidized and reduced by the following operation to examine the fact that the main ingredient of the activity was sugar and the contribution of uronic acid to the medicinal effect, and the effects thereof were examined. The dose was 40 mg / k for nephrotic syndrome rats.
g was orally administered to the liver-impaired rats.
/ Kg was administered intramuscularly.

(1) Oxidation (Noble, DW and
Sturgeon, R .; J. (1970) Carbo
hyd, Res. 12,448) purified sample 600
mg is dissolved in 150 ml of distilled water, 150 ml of a 0.2 M sodium periodate solution is added, and the mixture is reacted at 37 ° C. for 240 hours. After stopping the reaction by adding 150 ml of ethylene glycol, 500 mg of sodium borohydride is added and the mixture is treated at room temperature for 24 hours. The reaction is stopped with acetic acid, dialyzed against water, and lyophilized.

(2) Reduction (Taylor, RL ann)
d Conrad, H .; E. FIG. (1972) Bioche
mistry. Dissolve 50 mg of purified sample (according to 11,1383-1388) in distilled water and add EDC (1-ethyl
l-3- (dimethyl-aminopropy)
After adding 249 mg of l) -carbodiimide), the mixture is reacted for 19 hours while maintaining pH 4.75 with 0.1N hydrochloric acid. Thereafter, 10 ml of a 2M sodium borohydride solution are added dropwise over 1 hour, during which the pH is kept at 7.
After stirring for an additional hour, the mixture is dialyzed against water and freeze-dried.

The results are shown in FIG. 4 and Tables 3, 4 and 5.
No effect was observed for the oxidized and reduced samples. This indicates that the active substance in the purified sample is indeed a polysaccharide, and that uronic acid in particular greatly contributes to the drug efficacy. Comparison of the neutral sugar content before and after the reduction indicated that most of the uronic acid contained in this sample was galacturonic acid.

[0057]

[Table 3]

[0058]

[Table 4]

[0059]

[Table 5]

[0060]

According to the present invention, there is provided a novel polysaccharide extracted from ginseng, which can be used for remission of nephrotic syndrome and improvement of liver disorder symptoms.

[0061]

[Brief description of the drawings]

FIG. 1 shows the absorbance at ₂₈₀ nm (A ₂₈₀ ) and 480 nm (A ₄₈₀ ) of the fraction developed by gel filtration chromatography in Example 1, and FIGS. 2 and 3 show the present invention in a nephrotic syndrome model rat in Example 1. FIG. 4 is a graph showing the amount of urinary protein excreted when the polysaccharide (AF) is orally administered at various doses, and FIG. 4 is a graph showing the amount of urinary protein excreted when the same is administered by oxidizing or reducing AF.

────────────────────────────────────────────────── ─── Continuation of front page (72) Inventor Hiroko Abe 4-10-8 Kouri Nishimachi, Sakai City, Osaka Sunrise Garden Mikunigaoka 406 (58) Field surveyed (Int. Cl. ⁷ , DB name) C08B 37/00 A61K 35/78 CA (STN)

Claims (8)

(57) [Claims] 1. A polysaccharide having the following properties, which can be extracted from ginseng with water or an aqueous solvent. Sugar content: 60-100% (1) Sugar composition: uronic acid 40-80% Neutral sugar 10-30% (2) Neutral sugar composition: rhamnose 0-15% glucose 0-15% galactose 25-55% arabinose 30-60% Mannose 0-15% B. Molecular weight 150,000-300,000 2. Ginseng is extracted with water or an aqueous solvent, and the liquid obtained by removing the residue from the extract is passed through a non-polar porous polymer resin, concentrated by ultrafiltration, and then subjected to ultrafiltration chromatography. The method for producing a polysaccharide according to claim 1, wherein 3. The method according to claim 2, wherein the ginseng is extracted at a pH of about 4 to about 8. 4. The method according to claim 2, wherein the aqueous solvent is a buffer or an aqueous salt solution. 5. The method according to claim 2, wherein the ginseng is extracted at about 40 to about 100 ° C. 6. An agent for ameliorating nephrotic syndrome comprising the polysaccharide according to claim 1. 7. An agent for ameliorating hepatic disorder comprising the polysaccharide according to claim 1. 8. The ameliorating agent according to claim 5, which is administered intramuscularly or orally.