TW200930387A - Pharmaceutical composition for treating aristolochic acid nephropathy - Google Patents

Abstract

A pharmaceutical composition comprises a ginseng extract which includes ginsenosides for the active ingredient of treating aristolochic acid nephropathy.

Description

200930387 IX. DESCRIPTION OF THE INVENTION: TECHNICAL FIELD OF THE INVENTION The present invention relates to a pharmaceutical composition for treating kidney disease, and more particularly to a pharmaceutical composition for treating kidney disease caused by aristolochic acid. [Prior Art] In 1991, young women in Belgium took kidney failure after taking a fat-reducing drug containing a Chinese herbal medicine component, and further analysis revealed that these diet pills contained a component of sedative. The damaged part of the kidney is confined to the proximal convoluted tubule, with obvious cell infiltration, tubular atrophy, and interstitial fibrosis. Aristolochic acid (AA) is a common component of the family of the genus Ranunculaceae, and contains a mixture of 10-nitrophenanthrene-l-acid as the basic skeleton. It is Aristolochic acid I (AAI) and Aristolochic acid II (AAII) (Fig. 1). Maple Point of Maplecan Acid I

(Boiling point, BP) is 275-278 ° C, the onset O temPerature 〇f decomposition is 28 l-286 ° c; while the aristolochic acid II has a boiling point of 270-273 ° C, the pyrolysis temperature is 270 -272X: Because the boiling point and cracking temperature are very high, the general method of decoction does not decompose. Aristolochic acid nephropathy (ANN) is a persistently worsening kidney disease. In terms of clinical characterization, it mainly includes early severe anemia, normal aseptic pyuria, mild renal tubular proteinuria, such as low molecular weight proteinuria, and low molecular weight proteins in urine including: microspheres. Protein (cd_microglobulin), 02-microglobulin (02-micr〇gi〇buHn), Krebs 5 200930387 dam cell protein, retin〇l binding protein, etc. will all rise. In terms of pathological features, the kidneys are reduced in size and asymmetry. The renal interstitial fibrosis of the limbs is visible in the kidney slices of the patient, and the tubular atrophy and hollowing are formed. The interstitial cells are infiltrated. The lesion is the most severe in the surface of the skin. The ball and the afferent arterioles are fibrotic and not thickened, and the glomerular damage is mild. About 40% of patients develop urinary malignancies and mainly occur in the upper urinary tract. At present, the pathogenesis of AAN is still unclear. The possible causes are as follows: (1) AA may have direct cytotoxicity, leading to tubular damage and subsequent non-cellular interstitial fibrosis; (2) AA and DNA-added adducts (AA-DNA adducts) may induce mutations leading to AAN-related, malignant tumors and fibrosis processes; (3) elevated intracellular calcium concentration may be one of the causes of AAI-induced cell wilting; (4) μ thickens the renal tubules to cause ischemia of the lumen, and finally leads to tubular atrophy; (5) renal tubular mesenchymal immune cells, activated immunity leading to fibrosis. The treatment of aristolochic acid nephropathy remains inconclusive. Clinically, only retrospective, non-randomized small studies and a small number of cases report that primary alcohol can delay the progression of the kidneys. ^== Long-term use of steroids produces predictable and unavoidable side effects, including fractures, abnormal blood glucose levels, and deep vein thrombosis. ', ulcers, changes in type, etc.' often cause another new problem in treatment. The progression of AAN to end stage renal disease is so rapid that some kidney-protecting drugs such as Cangiotensin-converting enzyme inhibit rss or calcium channel blockers 6 200930387 (calcium-channelblockers) are also used. Can not delay the deterioration of kidney disease. Therefore, finding effective and safe drugs to treat AAN has its value in clinical applications. 'A Summary of the Invention>> It is an object of the present invention to provide a pharmaceutical composition comprising a ginseng concentrate for the treatment of nephrotic kidney disease. It is an object of the present invention to provide a pharmaceutical composition comprising ginsenoside for the treatment of aristolochic acid nephropathy. In order to achieve one or a part or all of the above or other objects, an embodiment of the present invention is a pharmaceutical composition for treating kidney disease for treating kidney disease induced by aristolochic acid, the pharmaceutical composition comprising- The ginseng concentrate obtained by extraction has ginsenoside as an active ingredient. The effective dose of the ginseng concentrate is from USmg/kg to 5〇〇mg/kg, and the preferred effective dose is 250 mg/kg. The ginseng concentrate agent was prepared by placing red ginseng in a round bottom flask, heating and extracting with a 5 〇% aqueous solution of acetol for 6 hours, repeating the operation three times, collecting the filtrate three times after filtration, and performing the steps of concentration under reduced pressure and freeze-drying. Got it. The red ginseng can be made into 39 grams of the ginseng concentrate per gram. In the preferred embodiment, the pharmaceutical composition for treating the above disease comprises a kidney disease caused by at least a ginseng soap insenGside) m silk by aristolochic acid. The ginseng 43⁄41 is selected from the group consisting of ginsenosidei^, 丨咖咖咖丨, and _咖也, and its effective desertility is 5 mg/kg ° 7 200930387 [Embodiment] The invention relates to a "pharmaceutical composition for treating aristolochic acid nephropathy" and exemplifies a preferred embodiment for explaining the pharmacology of the pharmaceutical composition, which is used to enable those skilled in the art to disclose the contents, the illustration and the following. The description 'will make full use of the present invention for industrial use without difficulty. The following examples are based on the evaluation of ginseng concentrate (10, QE) and its constituent ginsenosides (ginsenoside Rh, Rd and Rgl) to improve AAN by administering AA. Effect, © The relationship between cytokines TGF-/3, protease MMP-9, HGF (Hepatocyte Growth Factor) and this nephropathy was investigated by immunofluorescence staining. In the following examples, 'ginseng gi like C.A. Meyer' is a perennial herb of the ginseng genus of the genus Jac/kcefle, and the medicinal part is a dry root. There are many kinds of ginseng. According to their different basic sources, they can be roughly divided into Korean ❾ and C.A. Meyer produced in the northeast of China, and P·guinquefoHus L produced by the United States and Canada. There are other ginsengs of the same kind but different species such as: bamboo ginseng / Japanese ginseng ^ A. Meyer); Sanqi / Tianqi [p (10) kiss sigh (Burkm) FH] •, Vietnamese ginseng ( household We仂ame «Into Ha & Grushv) and so on. According to the growth method of ginseng, it can be divided into cultivated ginseng, wild ginseng and ginseng. The cultivated ginseng, also known as the garden ginseng, is artificially cultivated. The ginseng is a young wild mixed with the frequency, and it will grow into a mountain. According to the addition, the silk distinction can be divided into self-referential (Ginseng 8 200930387) and 'Ginseng Radix Rubra'. The difference between the two is that the red ginseng has been steamed and finally dried. However, embodiments of the invention do not need to limit the ginseng species. • The efficacy of ginseng is related to the type and age of growth. In general, ginseng, which is a six-year-old ginseng, has a large variety of ingredients, a balanced composition, an average distribution, and better efficacy. The main active ingredient of ginseng is ginsen〇side. At present, there are about 30 kinds of human ginseng glycosides. According to different types and parts of ginseng, the types and contents of soaps are different. The composition of ginseng In addition to sugar, nitrogen compounds, amino acids, phytosterols, essential oils, organic acids, vitamins and minerals. Ginsenosides (ginsenoside ribs, Rd and Rgl) account for about 3 6 / 〇 of ginseng belongs to diterpene steroids (pool erpene (7) gde), composed of glycosyl and non-glycosyl (saP〇genin). According to its non-glycosyl structure, ginseng can be divided into three categories: protopanaxadi () ls € PpD 〇,

Pr〇t〇Panaxatri〇ls (PPTs) and 〇leanolic acid (Fig. 2a to Fig. 1 ❹ C). One ginsenoside Rb! protects the nerves, improves learning and melody, oxidizes, protects the liver, and fights cancer. The production of 'anti-inflammatory substances such as: interleukin_^ mterleukin-6 (IL-6) also inhibited the production. In addition, ginseng soap Rg! can improve kidney tissue while ginseng also protects the kidneys. [Example 1] Efficacy evaluation of ginseng concentrate in AAN Experimental animals C3H/He six-week-old male mice were fed with normal mouse feed 9 200930387 (brown brand 'Taiwan) for free food intake and sufficient drinking water In the environment of about 2H at room temperature and about 7〇~8〇% relative humidity, I2 hours of automatic light and illumination are maintained in the animal room. This experimental animal is suitable for use in all of the invention. Incidentally, the examples of the present invention are directed to BALB/C, C3H/He, (5:6, 6 strains of mice, intraperitoneal injection or oral administration of AA, and found that C3H/He has significant renal interstitial fibrosis and cells. Infiltration, the most similar to the clinical symptoms of AAN patients, so choose C3 wake mice as the experimental animals. Preparation of ginseng concentrate (GE) 'red ginseng (Korea) 3 gram in a round bottom flask Add 1:1 water alcohol solution (1:1〇, _〇1), place it in a water bath and heat it for reflux for six hours, anti-hewn three times, (four) three times the furnace liquid is combined and filtered, and concentrated under reduced pressure. , lyophilized, that is, ginseng concentrate

In this example, the average drinking water per sputum per mouse was approximately 3.5 ml before the start of the experiment. Dissolve sodium sulphate s〇dium sak (AAI © 63%, AAII 31%) (Sigma, USA) in distilled water (dW) as drinking water for mice at a dose of 3.0 μg/mL (0.5 mg/kg/day) 'The normal drinking water was returned after 56 days of continuous administration, and 0_1 ml ginseng concentrate (ge) 125, 250, 500 mg/kg was administered orally, and the drug was administered continuously for 14 days. The same amount of distilled water was given, and the N〇rmal group was given steaming water throughout. In order to observe the therapeutic effect of ginseng concentrate on AAN, animals of each group were sacrificed 14 days after the administration of the therapeutic drugs, and 10 animals in each group of the experimental group, the control group and the normal group, a total of 5 animals. The results of urine and blood analysis were as follows: 200930387 Urinary protein content analysis: In the analysis of urine protein, 'therapeutic drug GE was administered for 7 days, 125 mg/kg (2.52±0.20* mg/day), 250 mg/ in the experimental group. Kg (2.12 ± 0.27 * mg / day), 500 mg / kg group (2.34 ± 0.03 * • mg / day) 24 hours urine protein content decreased, compared to the AAN control group (2.88 ± 0.04 mg / day) Statistically significant. After 14 days of treatment, the 125 mg/kg group (2.12±0.15* mg/day), the 250 mg/kg group (1.94±0·2Γ mg/day), and the 500 mg/kg group (2.00±0.2Γ) The urine protein content of mg/day) continued to decrease, which was statistically significant compared with the control group (3.02 ± 0.09 ❹ mg/day) (>< 〇.〇5). (Fig. 3) NAG content analysis: In the analysis of NAG content, after administration of GE for 7 days, the experimental group was 125 mg/kg (2.88±0.22* //M/min/L), 250 mg/kg (2.82±). 0.22* /zM/min/L), the NAG content in the urine of the 500 mg/kg group (2.91±0.09* //M/min/L) was compared with the control group (3.29±0.01 a M/min/L). Reduced trend. After 14 days of treatment,! 25 mg/kg (2.66 ± 0.07* " M/min/L), 250 mg/kg (2.36 ± 0·〇Γ " M/min/L) and 500 mg/kg group (2.46 ± 0.05 material // M/min/T.) can be lowered. The NAG content in low urine is statistically significant compared with the control group (3.39±0.15 /zM/min/L) (*Ρ<〇.〇5,* *ρ<〇.〇ι). (Fig. 4) BUN value in the clearing: Continuous administration of GE天GE 250 mg/kg (20.00 ± 1.22 mg /dL) reduced the BUN value in serum compared with the AAN control group (23.75±2.06 mg/dL). Statistical significance (·><0.05). However, there was no significant improvement in the group administered at 125 mg/kg (21.25 ± 0.96 mg/dL) and 500 mg/kg (23.33 ± 1.15 mg/dL). Analysis in Qiqing: After 14 days of treatment, the 25〇 mg/kg group (〇·33±〇·〇4 mg/dL) can reduce the claratinine value of Jinqing.

II 200930387 The control group (0.40±0.01 mg/dL) was statistically significant (>< 0.05) but administered 125 mg/kg (〇.38±0.〇4 mg/dL), 500 There were no significant changes in the mg/kg, (〇.36±0.05 mg/dL) group. • Blood glucose values • 125 mg/kg (122.00 ± 2.65* mg/dL) was found in the experimental group of 14 days of GE treatment in AAN mice » 250 mg/kg (122.00 ± 6.24* mg/dL) '500 The blood glucose level of the mg/kg group (130.00±4.36* mg/dL) was lower than that of the control group (141.70±5.81 mg/dL), and there was a statistically significant difference (><〇.〇 5). ❹ Under the optical microscope 200 times, the pathological changes of the kidney tissue of the mice treated with the therapeutic drug GE were observed. Normal (Fig. 5A), control group (Fig. 5B) and continuous administration for 14 days GE (125 mg/kg). , 250 mg/kg, 500 mg/kg) of the treatment group (Fig. 5 c, D, E). Compared with the control group, the two groups of treatment groups were found to have a significant slowing of tubular atrophy, interstitial cell infiltration and fibrosis, and less damage to the renal tubules. The tissue stained with PAS was observed under a microscope and scored according to the pathological tissue damage quantitative index (THIS). Quantitative results showed that 组织 125 mg / kg (3.38 ± 0 · 74 *), 250 mg / kg (2.33 ± 〇.87 material), 500 mg / kg (3.29 ± 0.49 ^ treatment group, tissue damage The degree of alleviation was statistically significant compared with the control group (7.14±1.21) (cadax <0.01). (Fig. 6) TGF-β tissue was stained with immunofluorescence using a common focal laser scan Microscopic observation of renal tissue chemical hormone TGF-no deposition. Compared with the control group (95.75±8.62) of kidney tissue, GE 125 (32.00±4.9 (T) antibody ^ 12 200930387 point decreased by 67 %, GE 250 The antibody (29.00±1.55”) decreased by 70%, and the GE 500 (32.20±1.33, antibody decreased by 66%. The red color of the renal tubules and renal interstitial sites decreased in all three groups, indicating that GE was given to GE. 125 '250,500 mg/kg can reduce the accumulation of TGF-/S. (Fig. 7) MMP-9 was observed after deposition of MMP-9 immunofluorescence staining in kidney tissue compared with the control group (1.25±0.50). The highlight of GE 125 (11.50±4.20*) increased by 8.2 times, the highlight of GE250 (20.67±4.99*) increased by 15.5 times, and the highlight of GE500 (13.00±2.94) increased. 9.4 times, between the three groups in the renal tubules and red coloring matter portion of the case are increased, represents a given GE 125, is deposited 250 '500 mg / kg increase of MMP-9. (Figure 7)

The HGF tissues were stained with immunofluorescence, and the deposition of HGF in renal tissues was observed by a conjugated-focus laser scanning microscope. Compared with the kidney tissue of the control group (8.±±.82), the bright spot of GE 125 (21.00±2.83*) increased by 1.6 times, GE250 ❹ (67.00±8.55, the bright spot increased by 7.4 times, GE 500 The highlights of (52.50±7.6 guang) increased by 5.6 times. The red coloration of the renal tubules and renal interstitial sites was found in all three groups, indicating that the administration of GE 125 '250,500 mg/kg increased HGF deposition. ).

[Example 2] Evaluation of the efficacy of Ginsenoside Rbl, Rd, Rgl on chronic AAN In this example, AA was dissolved in dw as drinking water of mice at a dose of 3-0 /zg/mL (0.5 mg/kg/day). ), after 56 days of continuous administration, return to normal 13 200930387 drinking water, and sputum lml ginsen〇side Rbl,hi, such as (GS) 5 mg/kg, for 14 days, the control group was administered. The same amount of distilled water 'Normal group is given to the steaming water. 4 The effect of the therapeutic drug = AAN was observed. The animals in each group were sacrificed 14 days after the administration of the therapeutic drug. The experimental group and the control group and the normal group each had 1 各 each, a total of 5 〇. The results of urine and blood analysis are as follows:

Ο Urine protein content analysis: In the analysis of urinary protein, the therapeutic drug GS 5 mgAg was administered for 7 days, and in the experimental group, Rbl (191±〇〇9* mg/day): rib (2.05±〇.14*mg/day) ), the age of urine protein in the Rgl group (2.03 ± 〇〇 3 * mg / day), the equivalent AAN_i (2 98 ± G G5 are statistically significant. After 14 days of treatment, Called group (umn** mg/day), Rd group (2 〇6±〇〇Γ _ kiss), nausea group (1.83±0.l/*mg/day) urinary protein content continued to decrease, and the control group ( 3.06±0.08 mg/day) is statistically significant (>= 0.05,*>< 〇.〇1). (Fig. 8) NAG inclusion #analysis: analysis of NAG content, investment After Gs 5 mg/kg for 7 days, 'Rbl (10) in the experimental group said (10) ^ purchase flow), such as (2·98±〇·13* "M/min/L), Rgi group (2_7*_ urine t NAG) The content was lower than that of the control group (3.65±〇〇5(10) claw flow), and after 14 days of treatment, the % group (2 85±read, M/min/L) ' Rd group (3.01_8, M/) Min/L) and the secret group (10) bandit.〇4 vM/min/L) group can reduce the NAG content in urine, compared with the control New Zealand (3.85±0.M /zM/min/L) Significant statistically significant on < 〇.〇5). (Fig. 9) BUN value in serum: continuous administration of 14 days GS kiss 5 mg/kg (19 5〇200930387 soil 1.29 mg /dL), Rd 5 mg/kg (17.40±1.52** mg /dL), Rgi 5 Both mg/kg (20.50 ± 0.58 * mg / dL) reduced the BUN value in serum, which was statistically significant compared to the AAN control group (22.55 ± 1,08 mg/dL) (><0.05,&gt ;<〇.〇1). Creatinine analysis in serum: After administration of the therapeutic drug GS 5 mg/kg for 14 days, (OJOiO.ofmg/dL^RgiM (0.30±0.〇rmg /dL) can reduce serum creatinine value, compared with the control group (0.38±0.04 mg) /dL) was statistically significant (>< 0.05), but there was no significant decrease in the group administered with Rd (0.33 ± 0.05 ❺ mg/dL). Blood glucose values. In AAN mice. In the 14-day GS-treated group, the Rbi group (132.00±3.46* mg/dL) was found, and the Rgi group (131.75±2.36* mg/dL) was compared with the control group (142.20±.92 mg/dL). There was a trend of decrease, and there was a statistically significant difference (*P<〇〇5). There was no significant decrease in the tMiRd group (137.75±9.74 mg/dL). Under the optical microscope 200 times, the therapeutic drug Gs was observed. The pathological changes of mouse kidney tissue were observed in the N〇rmal group (Fig. 10A), the control group (Fig. 10B) and the continuous administration of 5 mg/kg GS, Rd, Rgl treatment group for 14 days (Fig. 10C, D, E) pathological tissue map. Compared with the control group, the three groups of treatment groups can be found that renal tubular and interstitial cell infiltration and fibrosis significantly slowed down, renal tubular damage is also lighter The PAS-stained tissue was observed under a light microscope and scored according to the pathological tissue damage quantitative index (TIHS). Quantitative results were found to be GS (2.50±0.55**), Rd (3.84±0.83, Rgl ( 2.33±0.65**) In the treatment group, the degree of tissue damage was alleviated, compared with the control: (7.14±1.21) was statistically significant (*><〇〇1). I) I. 200930387 TGF^ tissue was stained with immunofluorescence, and the renal tissue chemical hormone TGF-β deposition was observed by conjugated-focus laser scanning microscopy. The renal tissue of the control group and the TGF- of the GS Rbi, Rd, and Rgl treatment groups. The degree of deposition of yS was different. Compared with the control group (95.75±8.62), the antibody of GSRbl (32.50±7.18**) decreased by 66%, and the antibody of Rd (29.00±3.79**) decreased. The 70%, Rgl (22.67±6.62**) antibody decreased by 76%. In both groups, the red coloration of the renal tubules and renal interstitial sites was reduced, and ❹ showed a decrease in TGF-Million accumulation. MMP-9 was observed after deposition of MMP-9 immunofluorescence staining in kidney tissue compared with the control group (1.25±0.50) ’ GS (35.67±5.38, the highlights added 27.5 times, Rd (26.86±5.98**) increased by 2〇 5 times, and his (28 5〇 ±3.94) points increased by 21_8 times. The red coloration of the renal tubules and the renal interstitium was increased in the three treatment groups, indicating that gs Rth, Rd, and Rgl were added to increase the deposition of MMP-9. (Fig. 12) _ Immunofluorescence staining' The HGF deposition of renal tissue was observed using a co-focus laser scanning microscope. Compared with the control group (8 〇〇 ± 〇 82), the kidney tissue 'G! is called (22.67±3.36, the bright spot increased by 8 times, such as (Π.00±2·94), the bright spot increased 〇.6 Times, Rgi (23 5 points increased by 1.9 times. In all three groups, the renal tubules and kidneys (4) were found to have an increase in color coloration. This shows that GS Rbi, Rd, % can increase the deposition of the clothes (Figure 12). 16 200930387 ^ The examples of the present invention found that GE can reduce the urine protein content of ααν mice. The pure component part, Rd can reduce the urinary protein caused by cephal〇ridine; the ruler can effectively reduce the urine protein; except for Rd & In addition to Rgi, the examples of the present invention also found that Rbl has the same effect, and it is speculated that the monthly b can increase renal blood flow due to ginseng and its pure components, thereby improving renal function. In the embodiment of the present invention, we find continuous 14 days of ginseng concentrate and ginsenoside Rb! 'Rd'Rgl will reduce the urine NAG content, showing that GE and GS can reduce the damage of AA caused by tubular damage. BUN, serum creatinine, the embodiment of the present invention found ginseng The shrinkage agent 250 mg/kg can be clearly Lowering the serum bun and creatinine values; pure component part 'The examples of the present invention found that Rbi and Rgi significantly reduced BUN and creatinine, while Rd reduced BUN. In terms of blood sugar level, ginseng concentrate 125, 250, 500 mg was given. /kg The three groups all showed a downward trend; the pure component part, the group also observed a decline in blood glucose levels 'presumably because ginseng can reduce the absorption of glucose in the small intestine and promote insulin secretion. Kidney tissue microscopy It was observed that administration of 〇£ and 〇8111)1,11(1,1^1 can reduce tubular damage, interstitial cell infiltration and fibrosis.

In the examples of the present invention, TGF-/31, MMP-9 and HGF were further used as primary antibodies, and the immunopathological changes of the nephritis model were investigated by immunofluorescence staining. In the examples of the present invention, it was found that the case of TGF-stone deposition of 'GE and GS was lowered under the conjugate focal-focus microscope observation, and the deposition of MMP-9 and HGF 17 200930387 was increased, showing that the fibrosis caused by aa was improved. It has also been observed in the examples of the present invention that the deposition of TGF-No is significantly reduced after administration of GE and GS. In addition, the increase in deposition of mmp_9 and HGF after administration of GE and GS is presumed to be related to the anti-inflammatory effect of ginseng. In terms of ginseng concentrates, GE 250 has the best results, and it is estimated that the efficacy of ginseng concentrate may be saturated at 25 〇 mg/kg. Combining the above discussion, the possible mechanism for the therapeutic effect of the pharmaceutical composition of the present invention is that ginseng has anti-inflammatory and anti-oxidative effects, and the ginseng structure similar to steroid may increase the content of corticosterone in the body, and can effectively treat the kidney caused by AA. Injury, inhibiting the progression of kidney damage. Oral administration of ginseng concentrate reduced mouse urine protein, nag, BUN 'SCr' kidney tissue microscopy also showed significant improvement, immunofluorescence staining found that TGF-call performance decreased 'MMP-9 and HGF increased. It was shown that ginseng concentrate can alleviate kidney damage in AAN mice, with ginseng concentrate 250 mg/kg being the best. In the part of ginsenosides, oral administration of ginsenosides reduced urine protein, NAG, BUN and SCr in mice, and renal tissue microscopy also showed significant improvement. Immunofluorescence staining revealed a decrease in TGF-/3 expression and an increase in Mjyjpj and expression. It was shown that ginsenoside can alleviate the kidney damage in AAN mice, and the results of the above various aspects of the measurement are evaluated. The evaluation of the therapeutic effect of the therapeutic drug in the nephritis model of the embodiment of the present invention is Rgi, Rbi, and Rd. The above detailed description of the preferred embodiments of the present invention is intended to be limited to the scope of the invention, which is not intended to limit the scope of the invention. The patent scope of this case. [Simplified illustration] Figure 1. Chemical structure of Aristolochic acid I, II; Figure 2A to Figure 2C, structural classification of ginsenosides; Figure 3. Analysis of urine protein content of ginseng concentrate in this nephritis model; 4. Analysis of NAG content of ginseng concentrate in this nephritis model; Figure 5A to Figure 5E, renal tissue pathological changes of ginseng concentrate in this nephritis model; Figure 6. Quantification of tissue damage in ginseng concentrate in this nephritis model Figure 7. Quantitative analysis of immunofluorescence staining of ginseng in this nephritis model; Figure VIII. Analysis of urine protein content of Ginsenosides in this nephritis model; Figure 9. Analysis of NAG content of Ginsenosides in this nephritis model; Figure 10A to Ten E, Ginsenosides in this nephritis model of renal tissue pathological changes; Figure Η, Ginsenosides in this nephritis model of tissue damage quantitative analysis; and Figure 12, Ginsenosides in this nephritis model immunofluorescence staining quantitative analysis. [Main component symbol description] None

Claims (1)

200930387 X. Patent application scope: Diligent treatment of kidney-like medicinal compounds, including - ginseng concentrate, ^-containing ginseng soap active ingredient, wherein the ginseng concentrate is produced through a stroke procedure, wherein the kidney disease system Induced by aristolochic acid. 2. The pharmaceutical composition according to claim 1, wherein the ginseng concentration #! is effective at 125 mg/kg i 5 () () mg/kg. ❹ 3. If you apply for a patent scope! The pharmaceutical composition according to the invention, wherein the effective dose of the ginseng concentrate is 25 〇 mg/kg. 4. The pharmaceutical composition according to claim 1, wherein the ginseng is concentrated, and the red ginseng is placed in a bottoming flask and heated and extracted with a 5G% aqueous solution of ethanol for 6 hours. It is prepared by collecting three times of filtration and liquid, and concentrating under reduced pressure and freeze-drying. 5. The pharmaceutical composition according to claim 4, wherein the red ginseng is made into 39 grams of the ginseng concentrate per 100 grams. 6. A pharmaceutical composition for treating kidney disease for treating kidney disease caused by aristolochic acid, the pharmaceutical composition comprising at least one ginsenoside wherein the ginseng 4# is selected from the group consisting of ginsenGSide(R), ginsenGSide, and ginsenoside Rd In the group formed. 7. The pharmaceutical composition according to claim 6, wherein the effective concentration of the ginsenoside is 5 mg/kg. 20