CN102861192B

CN102861192B - Medicine composition for chronic renal failure and peritoneal fibrosis

Info

Publication number: CN102861192B
Application number: CN201210393838.2A
Authority: CN
Inventors: 杨洪涛
Original assignee: Individual
Current assignee: Individual
Priority date: 2012-04-26
Filing date: 2012-10-17
Publication date: 2014-04-23
Anticipated expiration: 2032-10-17
Also published as: CN102861192A

Abstract

The invention relates to a medicine composition for chronic renal failure and peritoneal fibrosis. The medicine composition is prepared by the following traditional Chinese materials: Chinese angelica, dried tangerine or orange peel, prepared rhubarb, astragalus mongholicus, pinellia ternate, herba epimedii, salvia miltiorrhiza and ramulus euonymi. The invention further provides a preparation method and application of the medicine composition. The medicine composition can be effectively used for treating chronic renal failure and can prevent or treat peritoneal fibrosis. Particularly, the medicine composition is suitable for chronic renal failure, can slow down kidney function decrease according to clinical effects, and can correct water, electrolyte and acid-base disturbance. Additionally, the medicine composition is suitable for end-stage renal disease peritoneal dialysis patients, improves survival quality of the peritoneal dialysis patients according to clinical effects and delays occurrence and development of peritoneal fibrosis.

Description

Pharmaceutical composition for chronic renal failure and peritoneal fibrosis

Technical field

The invention belongs to technical field of Chinese medicines, relate to the pharmaceutical composition for the treatment of nephropathy, particularly can be used for the pharmaceutical composition for chronic renal failure and peritoneal fibrosis.The invention still further relates to the preparation method of described pharmaceutical composition, and the purposes of this pharmaceutical composition.

Background technology

Chronic renal failure is clinical common refractory disease, Therapeutic Method is to control protopathy at present, protecting remaining nephron function is main target, extremely latter stage at end, western medical treatment adopted kidney dialysis and renal transplantation more, though can make the state of an illness of some patients were temporarily alleviate with small number of patients alleviates completely, but due to somewhat expensive, side effect is many, survival of transplanted kidney time and only have the reasons such as minority symptomatic drugs for kidney derived limited and Western medicine, cause there is no so far the way of fundamentally improving and recovering renal function injury, therefore look primary disease for " the irreversible pathological changes of chronic progressive external ".In recent years, the chronic renal failure of application Chinese medicine has obtained sure curative effect, use tcm therapy, the various symptoms, the sign that for chronic renal failure, exist, the integrally-regulated advantage of performance differentiation of tcm is corrected in time, can make the renal function of some patients were obtain improvement and recovery to a certain extent.

Peritoneal dialysis (PD), as a kind of effective kidney replacement therapy means, is obviously better than conventional hemodialysis with it to the protection of residual renal function, in kidney replacement therapy, has consequence.Can peritoneal dialysis be carried out for a long time and effectively, depends on that to a great extent can peritoneum continue to keep normal physiology and biological function.Along with patients undergoing peritoneal dialysis life-time dilatation, peritoneal membrane function exhaustion and/or peritoneal fibrosis have become and have caused the saturating technical failed most important reason of abdomen, and become " bottleneck " of restriction peritoneal dialysis development.

In recent years, existing a large amount of Chinese medicine preparation were for preventing and treating the research of peritoneal fibrosis, and wherein ligustrazine may be by protection Peritoneal Mesothelial Cells, and antiinflammatory, anticoagulant, fibrosis and improve peritoneum structure increase ultrafiltration, improve dialysisadequacy.The medication of Chinese medicine intraperitoneal is domestic a small amount of bibliographical information, mainly concentrates on QI invigorating and medicine for promoting blood circulation and dispelling blood stasis, as the Radix Astragali, Radix Salviae Miltiorrhizae, Radix Angelicae Sinensis, Rhizoma Chuanxiong etc.In the peritoneal dialysis of animals and humans, observing them can improve efficiency of peritoneal dialysis, promote peritoneum to remove, increase ultrafiltration volume and improve peritoneal membrane function small-molecule substance, but its pharmacological Mechanism it be not immediately clear, less on the impact report of Peritoneal Mesothelial Cells.Prevented and treated the clinical experimental research of peritoneal fibrosis, sclerosis, be the composition that adds certain medicine or change peritoneal dialysis liquid in peritoneal dialysis liquid in the past mostly.But the medicine adding may stimulate former and then cause the generation of new peritoneal fibrosis as a kind of new bio-incompatibility.Oral administration route, with it, after absorption of human body metabolism, make medicine there is certain biocompatibility, and the through sick therapeutical effect of bringing into play, not only avoid the direct stimulation of medicine to Peritoneal Mesothelial Cells, and can bring into play the advantage of the exclusive fibrosis of Chinese medicine, sclerosis.

Therefore, this area still needs to have new treatment nephropathy especially for treatment chronic renal failure, and the method for prevention or treatment peritoneal fibrosis.

Summary of the invention

The object of the invention is to for the clinical treatment nephropathy that provides is especially for treatment chronic renal failure, and the method for prevention or treatment peritoneal fibrosis.The inventor finds to take that the pharmaceutical composition that the Radix Astragali etc. is made as Chinese prescription can be used for the treatment of chronic renal failure effectively, and prevention or treat peritoneal fibrosis.The present invention is based on this discovery and be accomplished.

For this reason, first aspect present invention provides a kind of pharmaceutical composition, and it is by comprising that following Chinese crude drug prepares: Radix Angelicae Sinensis, Pericarpium Citri Reticulatae, Radix Et Rhizoma Rhei, the Radix Astragali, the Rhizoma Pinelliae, Herba Epimedii, Radix Salviae Miltiorrhizae, Ramulus Euonymi.In the present invention, Herba Epimedii also claims Herba Epimedii.

According to the pharmaceutical composition of first aspect present invention, it is to be prepared by the Chinese crude drug that comprises following proportioning:

In an embodiment of the above-mentioned pharmaceutical composition preparing in 10 weight portion Radix Angelicae Sinensis, wherein the amount of Pericarpium Citri Reticulatae is 2-75 weight portion, 3-50 weight portion, 4-40 weight portion, 5-30 weight portion, 5-20 weight portion, 5-15 weight portion, 8-12 weight portion or approximately 10 weight portions.

In an embodiment of the above-mentioned pharmaceutical composition preparing in 10 weight portion Radix Angelicae Sinensis, wherein the amount of Radix Et Rhizoma Rhei is 2-75 weight portion, 3-50 weight portion, 4-40 weight portion, 5-30 weight portion, 5-20 weight portion, 5-15 weight portion, 8-12 weight portion or approximately 10 weight portions.

In an embodiment of the above-mentioned pharmaceutical composition preparing in 10 weight portion Radix Angelicae Sinensis, wherein the amount of the Radix Astragali is 2-150 weight portion, 3-125 weight portion, 4-100 weight portion, 5-75 weight portion, 6-50 weight portion, 7-40 weight portion, 8-30 weight portion, 10-20 weight portion, 12-18 weight portion or approximately 15 weight portions.

In an embodiment of the above-mentioned pharmaceutical composition preparing in 10 weight portion Radix Angelicae Sinensis, wherein the amount of the Rhizoma Pinelliae is 2-150 weight portion, 3-125 weight portion, 4-100 weight portion, 5-75 weight portion, 6-50 weight portion, 7-40 weight portion, 8-30 weight portion, 10-20 weight portion, 12-18 weight portion or approximately 15 weight portions.

In an embodiment of the above-mentioned pharmaceutical composition preparing in 10 weight portion Radix Angelicae Sinensis, wherein the amount of Herba Epimedii is 2-150 weight portion, 3-125 weight portion, 4-100 weight portion, 5-75 weight portion, 6-50 weight portion, 7-40 weight portion, 8-30 weight portion, 10-20 weight portion, 12-18 weight portion or approximately 15 weight portions.

In an embodiment of the above-mentioned pharmaceutical composition preparing in 10 weight portion Radix Angelicae Sinensis, wherein the amount of Radix Salviae Miltiorrhizae is 2-250 weight portion, 3-200 weight portion, 4-175 weight portion, 5-150 weight portion, 10-100 weight portion, 15-75 weight portion, 20-50 weight portion, 25-40 weight portion or approximately 30 weight portions.

In an embodiment of the above-mentioned pharmaceutical composition preparing in 10 weight portion Radix Angelicae Sinensis, wherein the amount of Ramulus Euonymi is 2-250 weight portion, 3-200 weight portion, 4-175 weight portion, 5-150 weight portion, 10-100 weight portion, 15-75 weight portion, 20-50 weight portion, 25-40 weight portion or approximately 30 weight portions.

According to the pharmaceutical composition of first aspect present invention, it is to be prepared by the Chinese crude drug that comprises following proportioning: Radix Angelicae Sinensis 10 weight portions, Pericarpium Citri Reticulatae 10 weight portions, Radix Et Rhizoma Rhei 10 weight portions, the Radix Astragali 15 weight portions, the Rhizoma Pinelliae 15 weight portions, Herba Epimedii 15 weight portions, Radix Salviae Miltiorrhizae 30 weight portions, Ramulus Euonymi 30 weight portions.

According to the pharmaceutical composition of first aspect present invention, it is to be prepared by the Chinese crude drug that comprises following proportioning: Radix Angelicae Sinensis 10 weight portions, Pericarpium Citri Reticulatae 8 weight portions, Radix Et Rhizoma Rhei 12 weight portions, the Radix Astragali 18 weight portions, the Rhizoma Pinelliae 12 weight portions, Herba Epimedii 15 weight portions, Radix Salviae Miltiorrhizae 25 weight portions, Ramulus Euonymi 35 weight portions.

According to the pharmaceutical composition of first aspect present invention, it is to be prepared by the Chinese crude drug that comprises following proportioning: Radix Angelicae Sinensis 10 weight portions, Pericarpium Citri Reticulatae 12 weight portions, Radix Et Rhizoma Rhei 8 weight portions, the Radix Astragali 15 weight portions, the Rhizoma Pinelliae 18 weight portions, Herba Epimedii 12 weight portions, Radix Salviae Miltiorrhizae 35 weight portions, Ramulus Euonymi 25 weight portions.

According to the pharmaceutical composition of first aspect present invention, wherein each medical material is directly used as medicine with medical material or joins in described pharmaceutical composition after extracting.

According to the pharmaceutical composition of first aspect present invention, wherein each medical material joins in described pharmaceutical composition after extracting.In one embodiment, described each medical material through joining in described pharmaceutical composition independently of one another or together after extracting.In one embodiment, described each medical material is after extracting, to join in described pharmaceutical composition together.In one embodiment, described each medical material is after decocting mode is extracted, to join in described pharmaceutical composition together.

According to the pharmaceutical composition of first aspect present invention, wherein can also comprise pharmaceutically acceptable carrier.

According to the pharmaceutical composition of first aspect present invention, it is prepared substantially as follows: each medical material is directly ground into powder, and mix homogeneously, optionally adds pharmaceutically acceptable carrier, obtains.

According to the pharmaceutical composition of first aspect present invention, comprising the extract of each medical material, and optional pharmaceutically acceptable carrier.

According to the pharmaceutical composition of first aspect present invention, it is prepared substantially as follows: by each medical material, with extracting solvent extraction, extract obtained direct packing, obtains.

According to the pharmaceutical composition of first aspect present invention, it is prepared substantially as follows:

(a) by extraction solvent extraction for each medical material;

(b) extracting solution is concentrated, make thick paste, or be further dried to solids;

(c) step (b) gained thick paste or solids are directly packed, obtained; Or optionally add pharmaceutically acceptable carrier, obtain.

In the present invention; each medical material separately or together through extraction process obtain being directly used in prepare preparation (no longer extracting operation) any type of product (such as being extracting solution, thick paste, dried particles or powder etc.; they not yet add pharmaceutic adjuvant); can be referred to as extract, routine thick paste described above or solids all can be described as extract.

According to the pharmaceutical composition of first aspect present invention, wherein said extraction solvent is water, ethanol or ethanol water.

According to the pharmaceutical composition of first aspect present invention, wherein said extract is the extract of preparing according to the method comprising the steps: get each medical material, pulverize, add 5 ~ 20 times (for example 5 ~ 15 times, for example 8 ~ 12 times) water, ethanol or ethanol water decoct and/or reflux, extract, 1 ~ 5 time (for example 2 ~ 3 times), each 0.5 ~ 5 hour (for example 0.5 ~ 3 hour, for example 1 ~ 3 hour), collecting decoction, filter, filtrate decompression is concentrated into the thick paste that relative density is 1.1 ~ 1.5 (25 ° of C) (for example 1.2 ~ 1.4), dry, obtains.

According to the pharmaceutical composition of first aspect present invention, wherein said extract is the extract of preparing according to the method comprising the steps: get each medical material, pulverize, add 5 ~ 20 times (for example 5 ~ 15 times, for example 8 ~ 12 times) water, 80 ~ 100 ° of C left and right, decoct and extract 0.5 ~ 5 hour (for example 0.5 ~ 3 hour, for example 1 ~ 3 hour); Filter, filtrate decompression is concentrated, dry, obtains.

According to the pharmaceutical composition of first aspect present invention, wherein said extract is the extract of preparing according to the method comprising the steps: get each medical material, pulverize, add 5 ~ 20 times (for example 5 ~ 15 times, for example 8 ~ 12 times) water, 80 ~ 100 ° of C left and right, decoct and extract 0.5 ~ 5 hour (for example 0.5 ~ 3 hour, for example 1 ~ 3 hour); Filter, filtrate decompression is condensed into paste; With 2-5, doubly measure 50 ~ 90% alcohol reflux 2-3 time, by ethanol extract in 70-90 ° of C except ethanol, vacuum drying, obtains.

According to the pharmaceutical composition of first aspect present invention, wherein said extract is the extract of preparing according to the method comprising the steps: get each medical material, pulverize, add 5 ~ 20 times (for example 5 ~ 15 times, for example 8 ~ 12 times) water, 80 ~ 100 ° of C left and right, decoct and extract 0.5 ~ 5 hour (for example 0.5 ~ 3 hour, for example 1 ~ 3 hour); It is 1.1 ~ 1.5 (25 ° of C) (for example 1.2 ~ 1.4) that decocting liquid is concentrated into relative density, adds 95% ethanol to concentration of alcohol and reaches 70%, and placement is spent the night, filter, and concentrated filtrate, dry, obtain.

Second aspect present invention also provides following medicinal materials to be combined in for the preparation of the purposes in the medicine of prevention, improvement or treatment kidney disease or disease: Radix Angelicae Sinensis, Pericarpium Citri Reticulatae, Radix Et Rhizoma Rhei, the Radix Astragali, the Rhizoma Pinelliae, Herba Epimedii, Radix Salviae Miltiorrhizae, Ramulus Euonymi.

Second aspect present invention also provides following medicinal materials to be combined in for the preparation of the purposes in the medicine of prevention, improvement or treatment nephropathy and complication or symptom: Radix Angelicae Sinensis, Pericarpium Citri Reticulatae, Radix Et Rhizoma Rhei, the Radix Astragali, the Rhizoma Pinelliae, Herba Epimedii, Radix Salviae Miltiorrhizae, Ramulus Euonymi.Described nephropathy and complication thereof or symptom are such as but not limited to chronic renal failure, peritoneal fibrosis, for example, because of peritoneal fibrosis due to extrinsic factor (peritoneal dialysis), renal hypofunction, because of water, electrolyte and acid base imbalance due to nephropathy.

Second aspect present invention also provides following medicinal materials to be combined in for the preparation of the purposes in the medicine for the treatment of chronic renal failure and/or prevention or treatment peritoneal fibrosis: Radix Angelicae Sinensis, Pericarpium Citri Reticulatae, Radix Et Rhizoma Rhei, the Radix Astragali, the Rhizoma Pinelliae, Herba Epimedii, Radix Salviae Miltiorrhizae, Ramulus Euonymi.

Second aspect present invention also provides following medicinal materials to be combined in for the preparation of improving patients undergoing peritoneal dialysis life quality and/or delaying the purposes in the medicine of generation development of peritoneal fibrosis:

According to the purposes of second aspect present invention, wherein said medicine is to be prepared by the Chinese crude drug that comprises following proportioning:

In an embodiment of the above-mentioned medicine preparing in 10 weight portion Radix Angelicae Sinensis, wherein the amount of Pericarpium Citri Reticulatae is 2-75 weight portion, 3-50 weight portion, 4-40 weight portion, 5-30 weight portion, 5-20 weight portion, 5-15 weight portion, 8-12 weight portion or approximately 10 weight portions.

In an embodiment of the above-mentioned medicine preparing in 10 weight portion Radix Angelicae Sinensis, wherein the amount of Radix Et Rhizoma Rhei is 2-75 weight portion, 3-50 weight portion, 4-40 weight portion, 5-30 weight portion, 5-20 weight portion, 5-15 weight portion, 8-12 weight portion or approximately 10 weight portions.

In an embodiment of the above-mentioned medicine preparing in 10 weight portion Radix Angelicae Sinensis, wherein the amount of the Radix Astragali is 2-150 weight portion, 3-125 weight portion, 4-100 weight portion, 5-75 weight portion, 6-50 weight portion, 7-40 weight portion, 8-30 weight portion, 10-20 weight portion, 12-18 weight portion or approximately 15 weight portions.

In an embodiment of the above-mentioned medicine preparing in 10 weight portion Radix Angelicae Sinensis, wherein the amount of the Rhizoma Pinelliae is 2-150 weight portion, 3-125 weight portion, 4-100 weight portion, 5-75 weight portion, 6-50 weight portion, 7-40 weight portion, 8-30 weight portion, 10-20 weight portion, 12-18 weight portion or approximately 15 weight portions.

In an embodiment of the above-mentioned medicine preparing in 10 weight portion Radix Angelicae Sinensis, wherein the amount of Herba Epimedii is 2-150 weight portion, 3-125 weight portion, 4-100 weight portion, 5-75 weight portion, 6-50 weight portion, 7-40 weight portion, 8-30 weight portion, 10-20 weight portion, 12-18 weight portion or approximately 15 weight portions.

In an embodiment of the above-mentioned medicine preparing in 10 weight portion Radix Angelicae Sinensis, wherein the amount of Radix Salviae Miltiorrhizae is 2-250 weight portion, 3-200 weight portion, 4-175 weight portion, 5-150 weight portion, 10-100 weight portion, 15-75 weight portion, 20-50 weight portion, 25-40 weight portion or approximately 30 weight portions.

In an embodiment of the above-mentioned medicine preparing in 10 weight portion Radix Angelicae Sinensis, wherein the amount of Ramulus Euonymi is 2-250 weight portion, 3-200 weight portion, 4-175 weight portion, 5-150 weight portion, 10-100 weight portion, 15-75 weight portion, 20-50 weight portion, 25-40 weight portion or approximately 30 weight portions.

According to the purposes of second aspect present invention, wherein said medicine is to be prepared by the Chinese crude drug that comprises following proportioning: Radix Angelicae Sinensis 10 weight portions, Pericarpium Citri Reticulatae 10 weight portions, Radix Et Rhizoma Rhei 10 weight portions, the Radix Astragali 15 weight portions, the Rhizoma Pinelliae 15 weight portions, Herba Epimedii 15 weight portions, Radix Salviae Miltiorrhizae 30 weight portions, Ramulus Euonymi 30 weight portions.

According to the purposes of second aspect present invention, wherein said medicine is to be prepared by the Chinese crude drug that comprises following proportioning: Radix Angelicae Sinensis 10 weight portions, Pericarpium Citri Reticulatae 8 weight portions, Radix Et Rhizoma Rhei 12 weight portions, the Radix Astragali 18 weight portions, the Rhizoma Pinelliae 12 weight portions, Herba Epimedii 15 weight portions, Radix Salviae Miltiorrhizae 25 weight portions, Ramulus Euonymi 35 weight portions.

According to the purposes of second aspect present invention, wherein said medicine is to be prepared by the Chinese crude drug that comprises following proportioning: Radix Angelicae Sinensis 10 weight portions, Pericarpium Citri Reticulatae 12 weight portions, Radix Et Rhizoma Rhei 8 weight portions, the Radix Astragali 15 weight portions, the Rhizoma Pinelliae 18 weight portions, Herba Epimedii 12 weight portions, Radix Salviae Miltiorrhizae 35 weight portions, Ramulus Euonymi 25 weight portions.

According to the purposes of second aspect present invention, wherein each medical material is directly used as medicine with medical material or joins in described medicine after extracting.

According to the purposes of second aspect present invention, wherein each medical material joins in described medicine after extracting.In one embodiment, described each medical material through joining in described medicine independently of one another or together after extracting.In one embodiment, described each medical material is after extracting, to join in described medicine together.In one embodiment, described each medical material is after decocting mode is extracted, to join in described medicine together.

According to the purposes of second aspect present invention, in wherein said medicine, can also comprise pharmaceutically acceptable carrier.

According to the purposes of second aspect present invention, wherein said medicine is prepared substantially as follows: each medical material is directly ground into powder, and mix homogeneously, optionally adds pharmaceutically acceptable carrier, obtains.

According to the purposes of second aspect present invention, wherein said medicine comprises the extract of each medical material, and optional pharmaceutically acceptable carrier.

According to the purposes of second aspect present invention, wherein said medicine is prepared substantially as follows: by each medical material, with extracting solvent extraction, extract obtained direct packing, obtains.

According to the purposes of second aspect present invention, wherein said medicine is prepared substantially as follows:

(a) by extraction solvent extraction for each medical material;

According to the purposes of second aspect present invention, wherein said extraction solvent is water, ethanol or ethanol water.

According to the purposes of second aspect present invention, wherein said extract is the extract of preparing according to the method comprising the steps: get each medical material, pulverize, add 5 ~ 20 times (for example 5 ~ 15 times, for example 8 ~ 12 times) water, ethanol or ethanol water decoct and/or reflux, extract, 1 ~ 5 time (for example 2 ~ 3 times), each 0.5 ~ 5 hour (for example 0.5 ~ 3 hour, for example 1 ~ 3 hour), collecting decoction, filter, filtrate decompression is concentrated into the thick paste that relative density is 1.1 ~ 1.5 (25 ° of C) (for example 1.2 ~ 1.4), dry, obtains.

According to the purposes of second aspect present invention, wherein said extract is the extract of preparing according to the method comprising the steps: get each medical material, pulverize, add 5 ~ 20 times (for example 5 ~ 15 times, for example 8 ~ 12 times) water, 80 ~ 100 ° of C left and right, decoct and extract 0.5 ~ 5 hour (for example 0.5 ~ 3 hour, for example 1 ~ 3 hour); Filter, filtrate decompression is concentrated, dry, obtains.

According to the purposes of second aspect present invention, wherein said extract is the extract of preparing according to the method comprising the steps: get each medical material, pulverize, add 5 ~ 20 times (for example 5 ~ 15 times, for example 8 ~ 12 times) water, 80 ~ 100 ° of C left and right, decoct and extract 0.5 ~ 5 hour (for example 0.5 ~ 3 hour, for example 1 ~ 3 hour); Filter, filtrate decompression is condensed into paste; With 2-5, doubly measure 50 ~ 90% alcohol reflux 2-3 time, by ethanol extract in 70-90 ° of C except ethanol, vacuum drying, obtains.

According to the purposes of second aspect present invention, wherein said extract is the extract of preparing according to the method comprising the steps: get each medical material, pulverize, add 5 ~ 20 times (for example 5 ~ 15 times, for example 8 ~ 12 times) water, 80 ~ 100 ° of C left and right, decoct and extract 0.5 ~ 5 hour (for example 0.5 ~ 3 hour, for example 1 ~ 3 hour); It is 1.1 ~ 1.5 (25 ° of C) (for example 1.2 ~ 1.4) that decocting liquid is concentrated into relative density, adds 95% ethanol to concentration of alcohol and reaches 70%, and placement is spent the night, filter, and concentrated filtrate, dry, obtain.

Third aspect present invention provides the method for preparing pharmaceutical composition described in first aspect present invention, it comprises the steps: each pulverizing medicinal materials, and gained powder directly forms pharmaceutical composition as pharmaceutical composition or after optionally mixing with pharmaceutically acceptable carrier; Or by each pulverizing medicinal materials, gained powder obtains extract through extracting, this extract directly forms pharmaceutical composition as pharmaceutical composition or after optionally mixing with pharmaceutically acceptable carrier.

According to the method for third aspect present invention, wherein each medical material joins in described pharmaceutical composition after extracting.In one embodiment, described each medical material through joining in described pharmaceutical composition independently of one another or together after extracting.In one embodiment, described each medical material is after extracting, to join in described pharmaceutical composition together.In one embodiment, described each medical material is after decocting mode is extracted, to join in described pharmaceutical composition together.

According to the method for third aspect present invention, wherein said pharmaceutical composition is prepared substantially as follows: each medical material is directly ground into powder, and mix homogeneously, optionally adds pharmaceutically acceptable carrier, obtains.

According to the method for third aspect present invention, wherein said pharmaceutical composition comprises the extract of each medical material, and optional pharmaceutically acceptable carrier.

According to the method for third aspect present invention, wherein said pharmaceutical composition is prepared substantially as follows: by each medical material, with extracting solvent extraction, extract obtained direct packing, obtains.

According to the method for third aspect present invention, wherein said pharmaceutical composition is prepared substantially as follows:

(a) by extraction solvent extraction for each medical material;

According to the method for third aspect present invention, wherein said extraction solvent is water, ethanol or ethanol water.

According to the method for third aspect present invention, wherein said extract is the extract of preparing according to the method comprising the steps: get each medical material, pulverize, add 5 ~ 20 times (for example 5 ~ 15 times, for example 8 ~ 12 times) water, ethanol or ethanol water decoct and/or reflux, extract, 1 ~ 5 time (for example 2 ~ 3 times), each 0.5 ~ 5 hour (for example 0.5 ~ 3 hour, for example 1 ~ 3 hour), collecting decoction, filter, filtrate decompression is concentrated into the thick paste that relative density is 1.1 ~ 1.5 (25 ° of C) (for example 1.2 ~ 1.4), dry, obtains.

According to the method for third aspect present invention, wherein said extract is the extract of preparing according to the method comprising the steps: get each medical material, pulverize, add 5 ~ 20 times (for example 5 ~ 15 times, for example 8 ~ 12 times) water, 80 ~ 100 ° of C left and right, decoct and extract 0.5 ~ 5 hour (for example 0.5 ~ 3 hour, for example 1 ~ 3 hour); Filter, filtrate decompression is concentrated, dry, obtains.

According to the method for third aspect present invention, wherein said extract is the extract of preparing according to the method comprising the steps: get each medical material, pulverize, add 5 ~ 20 times (for example 5 ~ 15 times, for example 8 ~ 12 times) water, 80 ~ 100 ° of C left and right, decoct and extract 0.5 ~ 5 hour (for example 0.5 ~ 3 hour, for example 1 ~ 3 hour); Filter, filtrate decompression is condensed into paste; With 2-5, doubly measure 50 ~ 90% alcohol reflux 2-3 time, by ethanol extract in 70-90 ° of C except ethanol, vacuum drying, obtains.

According to the method for third aspect present invention, wherein said extract is the extract of preparing according to the method comprising the steps: get each medical material, pulverize, add 5 ~ 20 times (for example 5 ~ 15 times, for example 8 ~ 12 times) water, 80 ~ 100 ° of C left and right, decoct and extract 0.5 ~ 5 hour (for example 0.5 ~ 3 hour, for example 1 ~ 3 hour); It is 1.1 ~ 1.5 (25 ° of C) (for example 1.2 ~ 1.4) that decocting liquid is concentrated into relative density, adds 95% ethanol to concentration of alcohol and reaches 70%, and placement is spent the night, filter, and concentrated filtrate, dry, obtain.

Fourth aspect present invention provides treatment chronic renal failure, and/or the method for prevention or treatment peritoneal fibrosis, and the method comprises to the pharmaceutical composition of first aspect present invention that has the administration effective dose of needs.

Arbitrary embodiment of applicable equally other the arbitrary embodiment of arbitrary technical characterictic that arbitrary embodiment of either side of the present invention or this either side has or other either side, as long as they can be not conflicting, certainly, at where applicable each other, necessary words can be done suitably to modify to individual features.Be further described with feature to various aspects of the present invention below.

All documents that the present invention quotes from, their full content is incorporated to herein by reference, and if when the expressed implication of these documents and the present invention are inconsistent, be as the criterion with statement of the present invention.In addition, various terms and phrase that the present invention uses have the general sense of well known to a person skilled in the art, nonetheless, the present invention still wishes at this, these terms and phrase to be described in more detail and to be explained, the term of mentioning and phrase, if any inconsistent with known implication, are as the criterion with the implication that the present invention was explained.

In the present invention, term " pharmaceutical composition (it also can be described as " compositions " in the present invention) " or " medicine ", it is the dosage form of oral or drug administration by injection.In one embodiment, described pharmaceutical composition is the form of tablet, capsule, granule, pill, oral solutions, injection (liquid drugs injection and/or powder pin) etc.

In the present invention, term " extraction " can be the dipping under room temperature, or extraction at elevated temperatures (for example decoct and/or reflux), or the combination of these modes of operation.Can further include extract is further processed, for example, further carry out purification, such as desolventizing, to remove impurity by means of precipitation matter, solvent extraction, resin absorption separation etc.

As described herein, term " extract " will comprise the extract of any purity that can be used in the present invention object, and according to the present invention, spirit is appreciated that the DNA purity of extract of the present invention can change in the larger context to those skilled in the art.The extract that for example each medicinal material extract of the present invention obtains, according to the difference of different process conditions, the total medical material of 1kg for example, through extracting the arbitrary amount between 10g to 500g that can obtain (10g to 200g, 20g to 200g for example, 50g to 200g for example) that is the extract of different purity, those skilled in the art can, according to different needs, allocate the compositions that is applicable to needs with the extract of different purity.In some embodiments of the present invention, described extract can be called extract powder.

In the present invention, can use the present composition of effective dose to be applied to the tested individuality that has needs.As described herein, term " effective dose " refers to and can in experimenter, realize the object dosage that prevents and/or treats situation of the present invention, obstacle, disease or disease.Those skilled in the art, according to the context of the invention, can easily determine the using dosage of the present composition.Especially, this is according to the present invention, term " effective dose " can be understood as the present composition with reasonable effect/risk of being applicable to any therapeutic treatment and/or prevention than the q.s that treats and/or prevents described situation, obstacle, disease or disease.But the total consumption per day that it should be understood that the present composition can maked decision within the scope of medical judgment reliably by those skilled in the art.For any concrete experimenter, concrete prevention effective dose level must be determined according to many factors, and described factor comprises experimenter's age, body weight, general health situation, sex and diet; The concrete compositions adopting; Other therapeutic active substance that is used in combination with the present composition or uses simultaneously; And the known similar factor of medical field.

The invention provides and comprise the compositions formulated together with one or more nontoxic physiology's acceptable carriers.Described compositions can be mixed with solid or liquid form especially specially for Orally administered or for rectal administration, or is mixed with for injection and uses.

For Orally administered solid dosage forms, include but not limited to capsule, tablet, pill, powder and granule.In this type of solid dosage forms, reactive compound can be accepted excipient or carrier with the physiology of at least one inertia and mix as sodium citrate or dicalcium phosphate and/or following material: a) filler or extender are as starch, lactose, sucrose, glucose, mannitol and silicic acid; B) binding agent is as carboxymethyl cellulose, alginate, gelatin, polyvinylpyrrolidone, sucrose and Radix Acaciae senegalis; C) wetting agent is as glycerol; D) disintegrating agent is as agar, calcium carbonate, Rhizoma Solani tuber osi or tapioca, alginic acid, some silicate and sodium carbonate; E) solution blocker is as paraffin; F) absorb accelerator as quaternary ammonium compound; G) wetting agent is as spermol and glyceryl monostearate; H) adsorbent is as Kaolin and bentonite and i) lubricant is as Pulvis Talci, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium lauryl sulphate and their mixture.The in the situation that of capsule, tablet and pill, in described dosage form, also can comprise buffer agent.

For Orally administered liquid dosage form, comprise the acceptable Emulsion of physiology, solution, suspensoid, syrup and elixir.Liquid dosage form also can contain the conventional inert diluent in this area except containing active component, for example water or other solvents, solubilizing agent and emulsifying agent be ethanol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzylalcohol, benzyl benzoate, propylene glycol, 1,3 butylene glycol, dimethyl formamide, oils (particularly Oleum Gossypii semen, Oleum Arachidis hypogaeae semen, Semen Maydis oil, germ oil, olive oil, Oleum Ricini and Oleum sesami), glycerol, oxolane alcohol, Polyethylene Glycol and the fatty acid ester of sorbitan and their mixture for example.

In one embodiment of the invention, the pharmaceutical composition of each single dose is that medical material by following deal prepares through decocting, concentrated process: Radix Angelicae Sinensis 10g, Pericarpium Citri Reticulatae 10g, Radix Et Rhizoma Rhei 10g, Radix Astragali 15g, Rhizoma Pinelliae 15g, Herba Epimedii 15g, Radix Salviae Miltiorrhizae 30g, Ramulus Euonymi 30g.

Pharmaceutical composition described in first aspect present invention can be prepared into granule, wherein can optionally add the acceptable adjuvant of pharmacy.In the present invention, this granule can be called and hold up kidney granule.

The inventor finds by clinical research, takes Chinese medicine and holds up the patients undergoing peritoneal dialysis of kidney granule to occur that the incidence rate of ultrafiltration decline, malnutrition and peritonitis is far smaller than the patient who does not take Chinese medicine.The generation basis of peritoneal dialysis dependency peritoneal fibrosis is uremia, and its pathogenic characteristic is deficiency in origin and excess in superficiality, on the basis of deficiency of spleen and stomach, insufficiency of vital energy and blood, has the pathological factors such as wet, poison, the stasis of blood, heat simultaneously.In addition, because of life-time service glucose dialysis, for the impact of peritoneum, approach diabetes, the deficiency of YIN is with wet, poison, the stasis of blood, heat and see.Therefore, according to the two total pathological factor, study, select a kind of effective Chinese medicine preparation, for the generation of intervening the relevant peritoneal fibrosis of peritoneal dialysis, must have special income.

Therefore, for peritoneal fibrosis, this causes the basic factor of the saturating patient's ultrafiltration of long-range abdomen exhaustion for we, performance TCM Features, application Chinese medicine is furtherd investigate, the mechanism of intervening the relevant cell factor effect of peritoneal fibrosis to explore Chinese medicine, develops the non-intraperitoneal administration control abdomen compound Chinese medicinal preparation of relevant peritoneal fibrosis thoroughly.

Patients undergoing peritoneal dialysis is many by due to chronic kidney hypofunction, its course of disease delay, and to many positive QI-insufficiency of peritoneal dialysis stage, the domination of pathogen is reluctant to leave, thus must be prudent during using drugs to form a prescription, because the product of QI invigorating, belong to sweet temperature, help the suspicion of heat; The product of yin nourishing have more to be grown greasyly, has the fraud of raw wet love heresy, and sweet temperature, grows the greasy mechanism of qi that easily checks again.And that purging FU-organs is let out is turbid, the product of blood circulation promoting and blood stasis dispelling have the pungent logical property of bitter cold more, with it improper yin-damaging and Qi consuming that is easy to.So must follow eliminating evil during combination drug, just do not hinder righting and do not stay the evil principles of formulating prescriptions.

In the present invention, take the ingredients of holding up kidney granule to be typical pharmaceutical composition, side separates and pharmacological action can be described as follows:

(1) hold up kidney granule mainly Chinese medicines such as the Radix Astragali, Radix Angelicae Sinensis, Pericarpium Citri Reticulatae, the Rhizoma Pinelliae, Radix Et Rhizoma Rhei, Radix Salviae Miltiorrhizaes, to consist of, it is monarch drug that invigorating spleen and kidney, benefiting QI and nourishing blood group medicine be take in the side of sending; Blood circulation promoting and blood stasis dispelling, eliminating evil removing toxic substances group medicine are ministerial drug; Separately take and as helping, make altogether with middle the turbid descending group medicine, mainly share the merit of playing altogether benefiting QI and nourishing blood, dissolving blood stasis and detoxication and middle sending down the abnormal ascending QI.There is benefiting QI and nourishing blood and middle the turbid descending, promoting blood circulation and detoxication function.This prescription confirms to improve renal function and the caused clinical symptoms of many renal failures, sign through clinical and experimentation, simultaneously, for improving patients undergoing peritoneal dialysis life quality, delay patients undergoing peritoneal dialysis peritoneal fibrosis and occur all there is clear and definite curative effect, and safety is good.

(2) in side, the Radix Astragali be take tonify deficiency as main, and by < < Sheng Nong's herbal classic, > > classifies as top grade.Be usually used in asthenia with the passing of time, low, the thready pulse without strength person of speech.< < book on Chinese herbal medicine meets former > > to carry that " all void of Radix Astragali energy tonifying five ZANG-organs, controls stringy pulse spontaneous perspiration, rushes down YIN-fire, removes lung-heat, losslessly sends out, and has antiperspirant to stop." Radix Astragali tool and mending and oiliness feature.Radix Angelicae Sinensis is warm in nature, sweet in the mouth, pungent.Having enriches blood invigorates blood circulation, menstruction regulating and pain relieving, the effect of loosening bowel to relieve constipation.The positive > > of < < book on Chinese herbal medicine: " Radix Angelicae Sinensis, its sweet in the mouth and weigh, therefore specially can enrich blood; its gas is light and pungent, thus again can promoting the circulation of blood, invigorating middle warmer has; in row, have benefit, the gas medicine in sincere blood, also the panacea in blood is also.About mending to mend of assistant, thus can support nutrition blood, QI invigorating spermatogenesis, settling five organs, body by force, beneficial mind, all tangible deficient diseases, nothing is unsuitable.Assistant logical to attack, therefore the pain relieving constipation of dispelling, relieving rigidity of muscles and joints, controls contracture, paralysis, the card such as dry, puckery." share altogether for monarch drug, with the deficiency of qi and blood of tonifying five ZANG-organs, to help kidney qi.

(3) how simultaneously double again chronic renal failure be take void as this, but see that middle burnt taste become estranged, and accumulates, therefore send again Pericarpium Citri Reticulatae, the Rhizoma Pinelliae 2 product in turbid pathogen.Pericarpium Citri Reticulatae acrid in the mouth, hardship, warm in nature, enter spleen, lung meridian, there is the effect of " regulating qi-flowing for strengthening spleen, drying dampness to eliminate phlegm ".< < Compendium of Materia Medica > > cloud: " mend with tonic, rush down with cathartic, rise with Hydrargyri Oxydum Rubrum, fall with falling medicine.Spleen is the mother of Primordial Qi, and lung is the label of taking the photograph gas, therefore Pericarpium Citri tangerinae is two medicines through edema caused by disorder of QI, but with join and reinforcing and reducing lifting also." Rhizoma Pinelliae head is loaded in < < Sheng Nong's herbal classic > >, is listed in low-grades.It is warm in nature, and acrid in the mouth is poisonous, returns spleen, stomach, lung meridian.The effect with drying dampness to eliminate phlegm, stopping nausea and vomiting by lowering the adverse flow of QI, dissolving lump and resolving mass.Share altogether as ministerial drug, with middle the turbid descending, auxiliary monarch drug is cured the disease and is become this.

(4) primary disease course of disease delay, belongs to pathogen usually intruding into collateral in protracted disease, its essence is the pertinacious disease that refers to that some prolonged illness difficulties heal, and treatment needs application dredging collateral method, the method for dredging network road.Select the Radix Salviae Miltiorrhizae of eliminating blood stasis to promote regeneration of blood, this medicine is bitter, is slightly cold, and enters conscience kidney three warps, has stasis-dispelling and pain-killing, promoting blood circulation to restore menstrual flow, the merit of the relieving restlessness that clears away heart-fire.Radix Salviae Miltiorrhizae begins to be loaded in < < Sheng Nong's herbal classic > >, classifies as top grade.< < herbal classic > > cloud: Radix Salviae Miltiorrhizae " main trusted subordinate's pathogen, borborygmus are faint, and as leaked water, cold and heat gather, and broken disease, except abdominal mass, is stopped stuffy sensation with restlessness, QI invigorating." Radix Et Rhizoma Rhei, property is bitter, cold.Return spleen, stomach, large intestine, liver, pericardium channel.There is purging heat and dredging bowels, removing pathogenic heat from blood and toxic substance from the body, the effect of eliminating blood stasis and inducing menstruation.< < do not record > > " expectorant is real for flat stomach, the therapeutic method to keep the adverse QI flowing downwards, stagnation of pathogenic heat between intestinal, trusted subordinate's distension, the cold blood of woman closes swollen, lower abdominal pain, all old blood stays knot." < < Japan hanako materia medica > > " logical all gas of a surname, blood circulation regulating, sharp joint, let out and mould stagnant, aqueous vapor, extremity unbalanced cold and heat, warm miasma heat-phlegm, profit defecation, and apply all furuncle carbuncle poison." Radix Et Rhizoma Rhei rushes down and exert oneself to delay, and lays particular stress on eliminating fire and detoxication.Two medicines use, play altogether assistant and make it merit, for the dead blood of pathogen usually intruding into collateral in protracted disease pertinacious phlegm, stays and the pathogenesis that do not become, and with promoting tissue regeneration by removing blood stasis, purging FU-organs is let out turbid.

(5) all medicines share, can supplement spleen kidney etc. dirty be not enough to righting, can remove again the pathogenic factor such as turbid damp in body, blood stasis with eliminating evil, thereby reach strengthening vital QI to eliminate pathogenic factors, the object for the treatment of both the principal and secondary aspects of a disease.

In the present invention, take and hold up the modern pharmacology analysis that kidney granule is typical pharmaceutical composition to be described as follows:

(a) Astragalus strengthening the body resistance, invigorating the spleen and replenishing QI class Chinese medicine, the Radix Astragali is many-sided to the therapeutical effect of chronic kidney hypofunction, comprehensive.The Radix Astragali is containing coumarin, flavone compound, Saponin and micro-folic acid and several vitamin.Modern medicine study shows, the Radix Astragali includes and multiple antibiotic effective ingredient, and immunologic function that can enhancing body, therefore can also be for preventing the generation of some infectious disease.The prevent and treat aspect of astragalus extraction composition for glomerular sclerosis explained in much research, and think that it for the possible mechanism of the damage of renal tubular interstitium is: (1) lowers renal tubules and interstitial monocyte chemoattractant protein-1 (MCP-1) is expressed, thereby directly alleviate the inflammatory cells such as mononuclear phagocyte in gathering, the activation of renal tubules, interstitial, alleviate RIF-3; (2) make renal tubular interstitium TGF-β 1 and β ig-h3 (downstream molecules of TGF-β 1 and activation index, be now confirmed that it is a kind of ECM composition) albumen and mrna expression obviously lower 24; (3) induction increases people's kidney Stromal fibroblasts expression C-MET HGFr C-met, thus the effect of performance protection renal tubules, anti-RIF.

(b) Radix Angelicae Sinensis, containing basic lactone, n-butene acyl lactone, ferulic acid, nicotinic acid, sucrose and several amino acids, and sesquiterpenoids etc.The shared correlational study of two medicines is being passed through to the fibrosis therapeutical effect of animal experimental observation herbal mixture astragalus angelica mixture, think the Main Function link of the onset time of this medicine in lysis and different phase be from pathological changes in early days, can be by reducing inflammatory cell reaction and TGF-β 1 expression-secretion, reduce the intrinsic cell transformation of kidney, differentiation and extracellular matrix components deposition, alleviate kidney region fibrosis and improve renal function.

(c) Pericarpium Citri Reticulatae, the Rhizoma Pinelliae are clinical herbal pair.Pericarpium Citri Reticulatae is the dry mature skin of rutaceae orange and congener thereof, and acrid in the mouth warm in nature is bitter, has the effect of regulating qi-flowing for strengthening spleen, drying dampness to eliminate phlegm, and main component has Nobiletin, Hesperidin, contains limonene etc. in Pericarpium Citri Reticulatae volatile oil.The Rhizoma Pinelliae is the tuber of the aroid Rhizoma Pinelliae, acrid in the mouth warm in nature, poisonous, there is the effects such as drying dampness to eliminate phlegm, stopping nausea and vomiting by lowering the adverse flow of QI, dissolving lump and resolving mass, main component has choline, cupreol-D-Glucose glycoside, after hydrolysis the compositions such as ephedrine, polysaccharide, pinellin, tannin, also separablely from the Rhizoma Pinelliae go out glucosan.Pericarpium Citri Reticulatae has some similar or close pharmacological action with the Rhizoma Pinelliae, and can mutually supplement again.The two all has the effects such as eliminating phlegm and relieving cough is relievingd asthma, antiinflammatory, antiulcer, enhancing immunologic function, function of gallbladder promoting, and cardiovascular function is had to certain influence.Pericarpium Citri Reticulatae extract also can gastrointestinal peristalsis inhibition, eliminate oxygen-derived free radicals, prevent sperm deformity; The various preparations that the Rhizoma Pinelliae is concocted have certain town to tell effect, the Rhizoma Pinelliae anticancer, short cell division, antileukemie effect in addition in addition, and Rhizoma Pinelliae Preparata total alkali extract has inhibitory action to the growth of chronic myelogenous leukemia cell.

(d) water-soluble components of Radix Salviae Miltiorrhizae has significant inhibitory action to the important substance-methylguanidine of uremic toxins.Pharmacological evaluation shows, this composition has Renal Glomeruli In Rats, the renal tubular function of good raising ARF, improve nephridial tissue SOO, CAT active, suppress the generation of lipid peroxide, infer accordingly this composition the mechanism of action may with resistant activity oxygen, improve active oxygen elimination enzymatic activity relevant, also improved the probability for the treatment of this method of ARF by the method for Scavenger of ROS simultaneously.In addition, Radix Salviae Miltiorrhizae can improve hemodynamic by permeable pressure head inside and outside improving blood capillary, reduces blood pressure, thereby improve renin angiotensin aldosterone system etc., improves renal function.The Renal Glomeruli In Rats filtration rate that Radix Salviae Miltiorrhizae can improve ciclosporin A induction declines, and increases the excretion of N-acetyl-β-D-glucosaminidase (NAG) in urine, lowers the expression of TGF-β 1 in kidney, thereby alleviates kidney region fibrosis and small artery pathological changes.

(e) Radix Rehmanniae Preparata contains catalpol, rehmanin, mannitol, retinoid material, saccharide and aminoacid etc.Research in nearly 2 years further deeply, has confirmed that Radix Et Rhizoma Rhei can effectively prevent and treat chronic renal failure (CRF), closely related with its main active chrysophanic acid, emodin.Emodin can suppress kidney Stromal fibroblasts (RIFS) propagation, induces its apoptosis, and can suppress various kinds of cell somatomedin and ECM composition; Chrysophanic acid can reverse renal cells (RTEC) hypertrophy of TGF-β 1 induction, and the ECM that suppresses its stimulation is synthetic, and can be active by lowering NF-KB (can induce various inflammatory reactions to start factor expression), Caspase-3, alleviates RTEC apoptosis; Also can stop the RIFS propagation of TGF-β 1 induction simultaneously, and can suppress TGF-β 1 and activate the expression of RIFS and its fibronectin causing (FN) of antagonism and synthesize.

In the present invention, take and hold up kidney granule through clinical research confirmation, to there is the peritoneal fibrosis that peritoneal dialysis is relevant as typical pharmaceutical composition, it may mechanism of action be: 1. moving glucose dialysis can induce peritoneal tissues TGF-β 1 obviously to raise, peritoneum TGF-β 1 high expressed and peritoneal dialysis peritoneal fibrosis are closely related, hold up kidney granule by directly reducing Serum of Peritoneal Dialysis Patients TGF-β 1 level, delay peritoneal fibrosis process.2. CTGF is an important downstream factor of mediation TGF-β 1 short fibrosis effect, and TGF-β 1 can make HPMC express CTGF to increase, and the effect of CTGF is confined to Fibrotic generation more.Hold up kidney granule by suppressing TGF-β 1 level, indirectly suppress generation and the expression of CTGF, delay peritoneal fibrosis.3. by the improvement to inflammatory conditions, lower the serum levels of inflammatory factor IL-6, suppress the inflammatory cells such as macrophage and assemble at peritoneum, suppress progression of fibrosis.4. raise serum HGF level, thereby suppress the level of TGF-β 1, reduce the activity of the synthetic of extracellular matrix and inhibition PAI-1 simultaneously, prevented gathering of extracellular matrix, control peritoneal fibrosis.5. raise serum BMP-7 level, anti-TGF-beta 1 short of money is expressed, control peritoneal fibrosis.

In the present invention, take and hold up the therapeutic domain that kidney granule is typical pharmaceutical composition to be applicable to chronic renal failure, clinical efficacy shows as and slows down renal hypofunction, corrects water, electrolyte and acid base imbalance.Be applicable to end stagerenaldisease patients undergoing peritoneal dialysis, clinical efficacy shows as and improves patients undergoing peritoneal dialysis life quality, delays developing of peritoneal fibrosis.

Some English initialisms that the present invention uses gather as follows:

Accompanying drawing explanation

Fig. 1 has described rat peritoneum Pathomorphologic observation result.

The specific embodiment

Below by specific embodiment/experimental example, further illustrate the present invention, still, should be understood to, these embodiment and experimental example are only used for the use specifically describing more in detail, and should not be construed as for limiting in any form the present invention.The present invention carries out generality and/or concrete description to the material and the test method that use in test.Although be well known in the art for realizing many materials and the operational approach that the object of the invention used, the present invention still does to describe in detail as far as possible at this.It will be apparent to those skilled in the art that hereinafter, if not specified, material therefor of the present invention and operational approach are well known in the art.

a, Preparation Example part

embodiment 1: prepare pharmaceutical composition of the present invention

Formula: Radix Angelicae Sinensis 10g, Pericarpium Citri Reticulatae 75g, Radix Et Rhizoma Rhei 2g, Radix Astragali 150g, Rhizoma Pinelliae 2g, Herba Epimedii 150g, Radix Salviae Miltiorrhizae 2g, Ramulus Euonymi 250g.

Method for making: get each medical material of above-mentioned prescription, be ground into powder, encapsulated, every heavy 0.3g, obtains.

embodiment 2: prepare pharmaceutical composition of the present invention

Formula: Radix Angelicae Sinensis 10g, Pericarpium Citri Reticulatae 2g, Radix Et Rhizoma Rhei 75g, Radix Astragali 2g, Rhizoma Pinelliae 150g, Herba Epimedii 2g, Radix Salviae Miltiorrhizae 250g, Ramulus Euonymi 2g.

Method for making: get each medical material of above-mentioned prescription, be ground into the powder of 80 mesh sieves, add the Mel of 1/5 weight portion, make piller, the about 0.1g of every ball, obtains.

embodiment 3: prepare pharmaceutical composition of the present invention

Formula: Radix Angelicae Sinensis 10g, Pericarpium Citri Reticulatae 3g, Radix Et Rhizoma Rhei 50g, Radix Astragali 5g, Rhizoma Pinelliae 75g, Herba Epimedii 5g, Radix Salviae Miltiorrhizae 150g, Ramulus Euonymi 5g.

embodiment 4: prepare pharmaceutical composition of the present invention

Formula: Radix Angelicae Sinensis 10g, Pericarpium Citri Reticulatae 50g, Radix Et Rhizoma Rhei 3g, Radix Astragali 75g, Rhizoma Pinelliae 5g, Herba Epimedii 75g, Radix Salviae Miltiorrhizae 5g, Ramulus Euonymi 150g.

embodiment 5: prepare pharmaceutical composition of the present invention

Formula: Radix Angelicae Sinensis 10g, Pericarpium Citri Reticulatae 5g, Radix Et Rhizoma Rhei 20g, Radix Astragali 8g, Rhizoma Pinelliae 30g, Herba Epimedii 8g, Radix Salviae Miltiorrhizae 50g, Ramulus Euonymi 6g.

Method for making: get each medical material of above-mentioned prescription, add the decocting 1 hour of 8 times of amounts, filter; Filtering residue adds the decocting 1 hour of 5 times of amounts again, filters; Collecting decoction, being concentrated into relative density is 1.15 ~ 1.25 (25 ° of C), adds saccharin sodium 0.1%, fill, to vial, obtains.

embodiment 6: prepare pharmaceutical composition of the present invention

Formula: Radix Angelicae Sinensis 10g, Pericarpium Citri Reticulatae 20g, Radix Et Rhizoma Rhei 5g, Radix Astragali 30g, Rhizoma Pinelliae 8g, Herba Epimedii 30g, Radix Salviae Miltiorrhizae 6g, Ramulus Euonymi 50g.

Method for making: get each medical material of above-mentioned prescription, add the decocting 1 hour of 8 times of amounts, filter; Filtering residue adds the decocting 1 hour of 5 times of amounts again, filters; Collecting decoction, being concentrated into relative density is 1.15 ~ 1.25 (25 ° of C), and spraying is dry, obtains extract powder, adds the starch with the weight such as this extract powder, and mix homogeneously is encapsulated, is pharmaceutical composition of the present invention.

embodiment 7: prepare pharmaceutical composition of the present invention

Formula: Radix Angelicae Sinensis 10g, Pericarpium Citri Reticulatae 5g, Radix Et Rhizoma Rhei 5g, Radix Astragali 10g, Rhizoma Pinelliae 10g, Herba Epimedii 10g, Radix Salviae Miltiorrhizae 25g, Ramulus Euonymi 25g.

Method for making: get each medical material of above-mentioned prescription, add the decocting 1 hour of 8 times of amounts, filter; Filtering residue adds the decocting 1 hour of 5 times of amounts again, filters; Collecting decoction, being concentrated into relative density is 1.15 ~ 1.25 (25 ° of C), adds 95% ethanol to determining alcohol and reaches 70%, standing over night, filter, filtrate spraying is dry, obtains extract powder, adds the sucrose of 2 times of weight of this extract powder, mix homogeneously, granulate, obtain granule, be pharmaceutical composition of the present invention.

embodiment 8: prepare pharmaceutical composition of the present invention

Formula: Radix Angelicae Sinensis 10g, Pericarpium Citri Reticulatae 15g, Radix Et Rhizoma Rhei 15g, Radix Astragali 20g, Rhizoma Pinelliae 20g, Herba Epimedii 20g, Radix Salviae Miltiorrhizae 40g, Ramulus Euonymi 40g.

Method for making: get each medical material of above-mentioned prescription, add the decocting 1 hour of 6 times of amounts, filter; Filtering residue adds the decocting 1 hour of 6 times of amounts again, filters; Collecting decoction, being concentrated into relative density is 1.15 ~ 1.25 (25 ° of C), spraying is dry, obtains extract powder; Get 1 part of above extract powder, add 2 parts of starch, 2 parts of microcrystalline Cellulose, mix homogeneously, encapsulated, be pharmaceutical composition of the present invention.

embodiment 9: prepare pharmaceutical composition of the present invention

Formula: Radix Angelicae Sinensis 10g, Pericarpium Citri Reticulatae 10g, Radix Et Rhizoma Rhei 10g, Radix Astragali 15g, Rhizoma Pinelliae 15g, Herba Epimedii 15g, Radix Salviae Miltiorrhizae 30g, Ramulus Euonymi 30g.

Method for making: get each medical material of above-mentioned prescription, add the water soaking 8 hours of 8 times of amounts, then decoct 2 hours, filter; Filtering residue adds the decocting 1 hour of 6 times of amounts again, filters; Collecting decoction, being concentrated into relative density is 1.15 ~ 1.25 (25 ° of C), and spraying is dry, obtains extract powder, adds the sucrose with the weight such as this extract powder, and mix homogeneously, granulates, and obtains granule, is pharmaceutical composition of the present invention.

embodiment 10: prepare pharmaceutical composition of the present invention

Formula: Radix Angelicae Sinensis 10g, Pericarpium Citri Reticulatae 8g, Radix Et Rhizoma Rhei 12g, Radix Astragali 18g, Rhizoma Pinelliae 12g, Herba Epimedii 15g, Radix Salviae Miltiorrhizae 25g, Ramulus Euonymi 35g.

Method for making: the method according to embodiment 9 prepares granule, is pharmaceutical composition of the present invention.

embodiment 11: prepare pharmaceutical composition of the present invention

Formula: Radix Angelicae Sinensis 10g, Pericarpium Citri Reticulatae 12g, Radix Et Rhizoma Rhei 8g, Radix Astragali 15g, Rhizoma Pinelliae 18g, Herba Epimedii 12g, Radix Salviae Miltiorrhizae 35g, Ramulus Euonymi 25g.

b, biological test example part

In some experiments, the inventor be take pharmaceutical composition provided by the invention as reagent, for having the volunteer of corresponding disease or disease.Result shows, pharmaceutical composition of the present invention can be used for the treatment of chronic renal failure effectively, and prevention or treatment peritoneal fibrosis.Result demonstration, pharmaceutical composition of the present invention goes for chronic renal failure, and clinical efficacy shows as and slows down renal hypofunction, corrects water, electrolyte and acid base imbalance.Result also shows, pharmaceutical composition of the present invention goes for end stagerenaldisease patients undergoing peritoneal dialysis, and clinical efficacy shows as and improves patients undergoing peritoneal dialysis life quality, delays developing of peritoneal fibrosis.

In test example, if not otherwise indicated, the reagent of use is embodiment 9 gained extract powders (also can be described as in the present invention and hold up kidney granule) below, face the used time to form every 1ml medicinal liquid containing the reagent that is 2g of crude drug amount with water dissolution/suspendible, for.

test example 1: hold up the experimentation of kidney granule on peritoneal dialysis rat dialysisadequacy and peritoneal fibrosis impact

One, materials and methods

1. material and instrument

1.1 laboratory animals: 75 of healthy male SD rats, body weight 180-200g; Rat feeding is in zoopery section clean level Animal House; Raising condition: 12h illumination, 24 ℃ of room temperatures, 45% relative humidity, the diet of whole experimentation rat and drink water unrestricted; Poultry raiser has laboratory animal practitioner post certificate.

1.2 experiment reagents: 1.5% peritoneal dialysis solution, 4.25% peritoneal dialysis solution (LPDS), Baxter medical treatment company limited produces; TGF-β 1ELISA test kit, HGF ELISA test kit, CTGF ELISA test kit, BMP-7ELISA test kit, IL-6ELISA test kit, VEGF ELISA test kit: Hao Yang bio tech ltd, Tianjin produces.

2, experimental technique

2.1 experiment groupings: adaptability was raised after 1 week, according to rat body weight grouping, are divided at random:

A group: Normal group (n=15 is only),

B group: renal failure 5/6 excision+1.5%PD group (n=15 is only),

C group: renal failure 5/6 excision+1.5%PD+ holds up kidney groups of grains (n=15 is only),

D group: renal failure 5/6 excision+4.25%PD group (n=15 is only),

E group: renal failure 5/6 excision+4.25%PD+ holds up kidney groups of grains (n=15 only).

2.2 animal model preparations

A group: Normal group: without any processing.Intraperitoneal injection of saline, 100ml/kg/d, continuous 4 weeks;

B group: renal failure 5/6 excision+1.5%PD group: row rat 5/6 nephrectomy method.Experiment is always divided into two steps, the first step: left kidney 2/3 excision: 1. intraperitoneal anesthesia: the capable lumbar injection of chloral hydrate 0.3ml/l00g rat body weight by 10%.2. after anaesthetizing successfully, ventricumbent position is fixed, by 1cm under the rib of rats with left back and the other 0.5cm intersection point of spinal column place, successively cut skin, muscle, free left kidney, divests kidney peplos, after upper and lower each the 1/3 place's suture ligature of level of left kidney, excise successively, the nephridial tissue cutting is weighed and record.Gelfoam hemostasis, confirms without after obviously hemorrhage myometrial suture.3 days prevention infection of postoperative continuous application Cefazolin sodium.Second step: right kidney is cut entirely: carry out for one week after left kidney 2/3 excision.Select right-hand cutout, with same anesthesia method, same position, in right hilus renalis place's ligation kidney base of a fruit, excise right kidney.3 days prevention infection of postoperative continuous application Cefazolin sodium.Within postoperative six weeks, adopt rat eye socket rear vein beard blood collection method blood sampling 1-2ml, censorship renal function, confirms modelling success.Lumbar injection 1.5%LPDS, 100ml/kg/d, continuous 4 weeks;

C group: renal failure 5/6 excision+1.5%PD+ holds up kidney groups of grains: first make renal failure 5/6 excision model (the same).Lumbar injection 1.5%LPDS, 100ml/kg/d, gives gavaging simultaneously and holds up kidney granule (5ml/kg/d), continuous 4 weeks;

D group: renal failure 5/6 excision+4.25%PD group: first make renal failure 5/6 excision model (the same).Lumbar injection 4.25%LPDS, 100ml/kg/d, continuous 4 weeks;

E group: renal failure 5/6 excision+4.25%PD+ holds up kidney groups of grains: first make renal failure 5/6 excision model (the same).Lumbar injection 4.25%LPDS, 100ml/kg/d, gives gavaging simultaneously and holds up kidney granule (5ml/kg/d is equivalent to 10g crude drug/kg/d), continuous 4 weeks;

Lumbar injection method: the Right Lower Abdomen of take is point of puncture near groin mid point, pin H/A plane is 30-45 ° of angle abdomen back inserting needle to the right, and equal conventional povidone iodine skin degerming 2 times wipe away dryly before per injection, prevents that disinfectant solution from entering abdominal cavity with syringe needle.Low level, and slightly tilting to the right, make internal organs to the right upper abdomen concentrate, to reduce the chance of wearing out internal organs.In injection process, be careful having or not and be expelled to stomach wall and have or not anus and urethra leakage.Operating period, note changing injection site, avoid long-time same position injection, cause local subcutaneous scleroma.For the processing of each group institute injecting fluid, all take intraperitoneal to retain, do not extract out.

2.3 hold up preparation and the intervention of kidney granule

2.3.1 hold up kidney granulometric composition and preparation: see embodiment 9.

Hold up gavaging of kidney granule: certainly dialysis starts, to C group and E group, give gavaging and hold up kidney granule, with every 200g body weight SD rat calculating, gavage dosage 1ml/d.All the other each groups are given and are gavaged 1ml normal saline, gavage altogether 4 weeks.

2.4 data acquisitions and sample reception

2.4.1 recording the initial and modeling of modeling respectively organizes rat body weight change for the 4th weekend.Each organizes rat in modeling footline peritoneal membrane function test in the 4th week, and before test, 48h stops peritoneal dialysis.10% chloral hydrate anesthesia rat, lumbar injection 4.25% dialysis solution 25ml, 4h accurately measures the peritoneal fluid scale of construction.Leave and take respectively blood and the about 0.5ml of peritoneal dialysis liquid specimen simultaneously.By blood, peritoneal dialysis liquid specimen centrifuge (1500r/min, 5min), with automatic clinical chemistry analyzer, measure concentration of glucose, calculate ultrafiltration volume (UF) and the glucose transport amount (MGT) of every rat.Specific formula for calculation is as follows:

Ultrafiltration volume=(quality of the quality-gauze after gauze water suction) * 1L/g+ drainage flow-lumbar injection amount

Glucose transport amount (Mass transfer of glucose, MTG)=(dialysis solution initial glucose concentration * injection dialysate volumes)-(the last dialysis solution output at last concentration of glucose * end of dialysing) mmol/kg.

2.4.2 fibrosis correlation factor is measured

A) sample process: room temperature blood natural coagulation 10-20min, the centrifugal 20min of 2000-3000r/min, collects supernatant specimen.

B) dilution of standard substance and application of sample: on the coated plate of enzyme mark, establish gauge orifice 10 holes, in the 1st, the 2nd hole, add respectively standard substance 100 μ l, then in the 1st, the 2nd hole, add standard substance diluent 50 μ l, mix; Then from the 1st, the 2nd hole, respectively get 100 μ l and be added to respectively the 3rd, the 4th hole, then add respectively standard substance diluent 50 μ l in the 3rd, the 4th hole, mix; Then in the 3rd, the 4th hole, first respectively get 50 μ l, mix; After mixing, from the 5th, the 6th hole, respectively get 50 μ l, be added to respectively in the 7th, the 8th hole, then add respectively standard substance diluent 50 μ l from the 7th, the 8th hole, mix; From the 7th, the 8th hole, get respectively 50 μ l again, be added to the 9th, the 10th hole, from the 9th, the 10th hole, add respectively standard substance diluent 50 μ l again, after mixing, from the 9th, the 10th hole, respectively get 50 μ l discard (dilution after each hole application of sample amount be 50 μ l, concentration is respectively 120ng/L, 80ng/L, 40ng/L, 20ng/L, 10ng/L).

C) application of sample: blank well (blank hole does not add sample and enzyme marking reagent, and all the other each step operations are identical), testing sample hole are set respectively.On the coated plate of enzyme mark, in testing sample hole, first add sample diluting liquid 40 μ l, and then add testing sample 10 μ l (the final dilution factor of sample is 5 times).Application of sample is added on bottom, ELISA Plate hole by sample, does not touch hole wall as far as possible, and light rolling mixes.

D) incubation: with the rearmounted 37 ℃ of incubation 30min of shrouding film shrouding.

E) dosing: by 30 times of diluted for use of distilled water for 30 times of concentrated cleaning solutions.

F) washing: throw off shrouding film, discard liquid, dry, cleaning mixture is filled it up with in every hole, discards after standing 30s, so repeats 5 times, pats dry.

G) incubation: biconditional operation 4.

H) washing: biconditional operation 5.

I) colour developing: every hole first adds developer A50 μ l, except blank well.

J) stop: every hole adds stop buffer 50 μ l, cessation reaction (now blueness transfers yellow to).

K) measure: with blank well zeroing, 450nm wavelength is sequentially measured the absorbance (OD value) in each hole.Mensuration should be carried out in 15min after stop buffer.

2.5 observation index: observe cardinal principle state, body weight change, Morphology of Peritoneum Following change, the change of peritoneum filtering function and the Serum Fibrosis regulatory factor of respectively organizing laboratory animal and express variation.

3, statistical analysis: use SPSS11.5 statistics software, mean ± standard deviation for measurement data (x ± s) represents, data are carried out to statistical analysis.The relatively employing t check of two sample averages.Between group, relatively adopt one factor analysis of variance.P<0.05 difference has significance.

Two, result

1. after treatment, respectively organize rat ordinary circumstance: the A group rat mental status good, flexibly movable, sight becomes clear god, and fur light is moist, and diet growth is as usual, and defecation is normal.All the other are respectively organized rat and all occur growth retardation in various degree, lethargy, asthenia drowsiness, sight is dark and gloomy dull, bradykinesia, and fur is withered even to come off without pool, the minimizing of ingesting, oliguria, rare performance that waits of defecating, but within about 2 weeks after dialysis treatment, respectively organize all to go out present condition and go up gradually, movable increasing, hydrouria, the phenomenons such as diet increase, B, C, D, E group rat state have no notable difference.

2. the body weight change of rat see the following form (means standard deviation, gram) before and after treatment:

Note: A organizes relatively with the same period: ^*p<0.05, ^*p<0.01; B organizes relatively with the same period: ^Δp<0.05, ^{Δ Δ}p<0.01; C organizes relatively with the same period: ^◇p<0.05.

3. change in renal function comparative result.

Before treatment, respectively organize Renal Function in Rats testing result

see the following form

Note: compare with A group: ^*p<0.01.Prompting modeling success.

After treatment, respectively organize Renal Function in Rats testing result

see the following form

Note: compare with A group: ^*p<0.01; Compare with B group: ^Δp<0.05; D organizes relatively with the same period: ^◇p<0.05.

4. ultrafiltration volume and the comparison of glucose transport amount: peritoneal effluent is situation substantially: each group model rat is unrealized positive ultrafiltration all, but all has drainage flow in various degree.It is faint yellow that draining fluids is roughly, and minority has pale red to be even courageous and upright.Relatively each treated animal filtering function index, ultrafiltration volume and glucose transport amount comparable situation

see the following form.

Note: compare with A group: ^*p<0.05, ^*p<0.01; Compare with C group: ^●p ﹤ 0.05; Compare with E group: ^Δp<0.05, ^{Δ Δ}p<0.01.

5. peritoneum pathology morphological change

5.1 rat peritoneum Pathomorphologic observations: see Fig. 1.As shown in the figure, through HE dyeing, the demonstration of row PATHOMORPHOLOGICAL OBSERVATION OF PULLORUM, the densification of A group parietal peritoneum is smooth, and peritoneum thickness is without remarkable change; Each concentration model group and intervention group peritoneum thickness thicken in various degree, and peritoneum thickened degree C group and E group are light, but B group and D group are serious, and each group exists cell infiltration in various degree.

5.2 rat peritoneum thickness measures: experiment is respectively organized to specimen slice row Masson dyeing, choose at random upper and lower, left and right, in each 2 high power fields, measure its peritoneum thickness, get its meansigma methods as parietal peritoneum thickness.Experiments of measuring is respectively organized rat peritoneum thickness, and result shows that B group, D group and C group, E group peritoneum average thickness all increase compared with A group.Wherein, each model group and E group peritoneum thickness and A group have significant difference (P ﹤ 0.01).Except between B group and E group, compare there was no significant difference (P>0.05), between variable concentrations model and intervention group, compare tool significant difference (P ﹤ 0.01).Each organizes the comparison of rat peritoneum varied in thickness

the results are shown in following table.

Note: ^●compare P ﹤ 0.05 with A group, ^{● ●}compare P ﹤ 0.01 with A group; ^zerocompare P ﹤ 0.05 with B group, ⁰⁰compare P ﹤ 0.01 with B group; ^◆compare P ﹤ 0.05 with D group, ^{◆ ◆}compare P ﹤ 0.01 with D group; ^★compare P ﹤ 0.05 with C group, ^{★ ★}compare P ﹤ 0.01 with C group;

compare P ﹤ 0.05 with E group,

compare P ﹤ 0.01 with E group.

6. the change of the short peritoneal fibrosis relevant cell factor of each group

the results are shown in following table.

Note: compare with A group: ^*p<0.05, ^*p<0.01; Compare with B group: Δ P<0.05, Δ Δ P<0.01; Compare with D group: ☆ P<0.05, ☆ ☆ P<0.01.

Each group suppresses the change of peritoneal fibrosis relevant cell factor

the results are shown in following table.

Note: A organizes relatively: ^*p<0.05, ^*p<0.01; Compare with B group: ^Δp<0.05, ^{Δ Δ}p<0.01; Compare with D group: ^☆p<0.05, ^{☆ ☆}p<0.01.

Three, brief summary

1. ordinary circumstance and body weight change: in experimentation, while being expert at left kidney 2/3 excision, due to 1 of overdose of anesthesia rat cadavers, be B group, because the hemostasis of excision position is not thorough, 1 of hemorrhagic shock rat cadavers, is E group.Because lumbar injection stings dead 3 of trunk by mistake, wherein B group is 1,1 of C group, 1 of E group; Gavage is strayed into respiratory tract, and dead 1 is E group.6 of unknown causes dead (the whole body organ failure that the cause of the death may cause with serious renal failure is relevant, through obduction, does not occur significantly infecting sign), wherein B group is 1,1 of C group, 2 of D groups, 2 of E groups.In dialysis treatment and Chinese medicine intervention, between each group, rat integrality aspect has no notable difference.Body weight change aspect, each is organized rat body weight and all occurs increasing, but that A group and D group, E group rat body weight increase is obviously faster compared with other groups, consider D group, E group rat body weight increase obvious comparatively fast may be relevant with the application of high concentration peritoneal dialysis.

2. change in renal function: this topic experiment result shows: Scr aspect, after treatment, each model group Scr level is also apparently higher than Normal group (A group) P<0.01.In concentration dialysis treatment group, application holds up its Scr level of kidney granule intervention group to reduce obvious P<0.05, and C group, E group Scr level are obviously organized low compared with B group, D.When also explanation is dialysed, application holds up kidney granule can reduce dialysis rat Scr level, strengthens dialysisadequacy, protection residual renal function.BUN aspect, after treatment, each model group BUN level is still apparently higher than Normal group (A group) P<0.01, but E group BUN level is apparently higher than D group P<0.05.When dialysis is described, application holds up kidney granule can reduce dialysis rat BUN level, strengthens dialysisadequacy, protection residual renal function.

3. hold up the change of kidney granule to efficiency of peritoneal dialysis: ultrafiltration volume and glucose transport amount are to evaluate the important indicator of patients undergoing peritoneal dialysis efficiency of peritoneal dialysis, and itself and peritoneal fibrosis degree have direct relation.This result of study shows, after treatment 4 weeks, except Normal group (A group), all the other each groups are all presented as negative ultrafiltration, but in concentration dialysis treatment group, application is held up its ultrafiltration conditions of kidney granule intervention group to be obviously better than not applying and is held up kidney groups of grains P<0.05, its effect significantly, meanwhile, glucose transport amount aspect is also presented as analog result, and prompting holds up kidney granule for improving efficiency of peritoneal dialysis, improve dialysis ultrafiltration, delay peritoneal fibrosis and there is clearly effect.

4. hold up the impact of kidney granule on peritoneal fibrosis

After 4.1 treatments, respectively organize PATHOMORPHOLOGICAL OBSERVATION OF PULLORUM and show, the densification of A group parietal peritoneum is smooth, and peritoneum thickness is without remarkable change; All the other peritoneum thickness thicken in various degree, and peritoneum thickened degree is heavily respectively C group, E group, B group and D group by gently causing, and each group exists cell infiltration in various degree.Measure and respectively organize rat peritoneum average thickness, each model of result and intervention group all obviously increase compared with A group peritoneum average thickness.Wherein, each model group and E group peritoneum thickness and A group have significant difference.Except between B group and E group, compare there was no significant difference, between variable concentrations model and intervention group, compare tool significant difference.Pathomorphism and the prompting of peritoneum thickness results, the application of variable concentrations peritoneal dialysis liquid all can cause that peritoneal fibrosis in various degree occurs, and peritoneal fibrosis degree and the proportional relation of peritoneal dialysis liquid concentration.Through holding up kidney granule to intervene posterior peritoneum progression of fibrosis, there is notable difference, hold up kidney granule can delay to a certain extent the generation process of peritoneal fibrosis.

4.2 hold up the impact of kidney granule on peritoneal fibrosis relevant cell factor: peritoneum is natural semipermeable membrane, by principles such as disperse, infiltration, ultrafiltration, remove moisture and toxin.Ultrafiltration, i.e. the process that during peritoneal dialysis, moisture is shifted by blood side direction dialysis fluid side, is the main mechanism of moisture in peritoneal dialysis removing body.This afunction is called ultrafiltration exhaustion.The standardized test of international peritoneal dialysis association's committee's suggestion employing in 2000 defines this concept, applies 4.25% glucose dialysis and stays abdomen after 4 hours, if net ultrafiltration amount is less than 400ml, thinks ultrafiltration exhaustion has occurred.Ultrafiltration exhaustion is one of saturating common and serious complication of long-term abdomen, is also the main cause that the saturating patient of abdomen is forced to exit peritoneal dialysis.Along with the prolongation of peritoneal dialysis treatment time, abdomen saturating patient's peritoneum ultrafiltration ability is faded, and about 36% above patient there will be this problem in dialysis after 6 years.The peritoneal dialysis ultrafiltration exhaustion that peritoneal fibrosis causes becomes study hotspot in recent years.Peritoneum structure function keeps for a long time complete and is normally precondition and the essential condition that peritoneal dialysis is long-term, efficient, high-quality carries out.

4.1 short peritoneal fibrosis correlation factors

This result of study shows: compare with A group, the relevant short fibrosis factor expression level of all the other each model group P<0.01 that all obviously raises, thereby the carrying out along with dialysis treatment is described, low concentration and high concentration dialysis solution all can raise the expression of the short fibrosis factor, accelerate the generation of peritoneal fibrosis.TGF-β 1 aspect, the expression of D group is obviously respectively organized rising P<0.05 compared with other, the impact that the high sugar of prompting is expressed TGF-β 1, meanwhile, the change of E group TGF-β 1 level confirms that the inhibitory action of holding up kidney granule to express TGF-β 1 is obvious.CTGF and IL-6 aspect, result is similar to TGF-β 1, and wherein C group, compared with the variation of B group, further confirms to hold up kidney granule clear and definite to the inhibitory action of CTGF and IL-6 expression.VEGF aspect, E group obviously reduces P<0.05 compared with D group, illustrates that to hold up kidney granule obvious to the inhibitory action of vegf expression.

4.2 anti-peritoneal fibrosis correlation factors

This result of study shows: along with carrying out and the Fibrotic generation of dialysis treatment, rise all appears in HGF and BMP-7 expression, the equal compared with normal matched group of the two level of each model group P<0.01 that obviously raises.Wherein, HGF aspect, C group is organized obvious rising P<0.01 compared with B, and prompting holds up kidney granule can obviously raise the expression of HGF, thereby suppresses the generation of peritoneal fibrosis.BMP-7 aspect, E group is organized obvious rising P<0.05 compared with D, and prompting holds up kidney granule can obviously raise the expression of BMP-7, thereby suppresses the generation of peritoneal fibrosis.Visible, hold up kidney granule can suppress the expression such as short fibrosis factor TGF-β 1, CTGF, IL-6, CTGF, meanwhile, can raise again the expression of fibrosis factor HGF, BMP-7, and then play the generation that suppresses the relevant peritoneal fibrosis of peritoneal dialysis.

The inventor is in other test, repeat the method for above test example 1, but use respectively embodiment 1 to 8 and 10 kinds of samples of embodiment 10-11 gained to test, result shows that these 10 kinds of samples of use acquired results in method described in above test example 1 is identical with use embodiment 9 sample acquired results.

test example 2: hold up the clinical research of kidney granule on efficiency of peritoneal dialysis and peritoneal fibrosis impact

The object of this test is to apply holds up kidney granule to carry out dialectical intervention to patients undergoing peritoneal dialysis, the impact of kidney granule on patients undergoing peritoneal dialysis dialysisadequacy, life quality, Efficacy of Traditional Chinese Medicine and peritoneal fibrosis held up in observation, simultaneously, by clinical experimental research, observe the change of peritoneal fibrosis relevant cell factor, the possible mechanism of action of kidney granule control peritoneal fibrosis is held up in discussion, for Chinese medicine prevention peritoneal dialysis peritoneal fibrosis provides theoretical foundation and method.Specifically by December in 2009 1 day to this research of voluntary participation between 31 days Mays in 2010, and patients undergoing peritoneal dialysis 240 examples of signing Informed Consent Form are carried out differentiation of symptoms and signs for classification of syndrome, and give and hold up kidney granule therapy, observe the variation of the indexs such as the saturating life in patients of abdomen, serum creatinine (Scr), blood urea nitrogen (BUN), hemoglobin (HGB), albumin (ALB), electrolyte, serum calcium (Ca), serum paraoxonase (P), peritoneum balance test (PET) and peritoneal fibrosis relevant cell factor, evaluate and hold up the impact of kidney granule on efficiency of peritoneal dialysis and peritoneal fibrosis.

1, case selection

Selected object: December in 2009 1 day is to this research of voluntary participation between 31 days Mays in 2010, and patients undergoing peritoneal dialysis 240 examples of signing Informed Consent Form.

Diagnostic criteria: according to the diagnostic criteria of the chronic kidney disease of the detection of AKF < < chronic renal disease progress in 2002 and guideline of prevention and treatment/Patients With Kidney Diseases life quality guidance (K/DOQI) > > formulation.

Case is selected, case is got rid of, reject case standard: according to chronic kidney disease patients undergoing peritoneal dialysis general standard, formulate.

2, Therapeutic Method:

All cases is first through the primary election phase of one month, and this phase, when continuing to carry out former peritoneal dialysis scheme, gives Primary Care, comprises the treatment of diet, complication etc., and the person that meets inclusive criteria after month enters group and receives treatment.

(1) treatment group: give Primary Care+treatment by Chinese herbs, scheme is as follows:

Primary Care: a. be take peritoneal dialysis as basis, for existing the patient of the complication such as anemia, hypertension according to K/DOQI guide recommend method and dosage medication.Mainly comprise the processing of complication such as controlling blood pressure, anemia; B. dietetic nutrition: carry out with reference to China < < chronic kidney disease proteinaceous nutrient treatment Consensus of experts > >.Treatment by Chinese herbs: using embodiment 9 gained granules (also can be described as in the present invention and hold up kidney granule) be reagent (dosage be the every 60kg body weight of patient take every day to hold up kidney granule to be equivalent to 30 grams of crude drugs).

(2) matched group: give Primary Care+placebo, Primary Care is the same, placebo is and the consistent placebo of Chinese medicine granules outward appearance.

Take 3 months as a course for the treatment of, treat continuously 2 courses for the treatment of.

3, observation index and detection method

(1) Evaluation on quality of life: adopt nineteen ninety-five to be developed by Rand Corporation (RAND), and by Aingen, common < < kidney disease dialysis patient investigation of life quality table > > (seeing appendix 2) the Kidney Disease and Quality of Life completing that subsidizes of Baxter Healthcare CorPoration and Arizona State University (University of Arizona) ^tMshort Form (KDQOL-SF ^tM) 1.3 scales, in this research, KDQOL-SFTM1.3 scale is with reference to classification and the methods of marking of the formulations such as Hays RD, by actual score, be converted to conversion score, compare, the meansigma methods that each field scoring is each the project scoring of this field, scoring higher this field life quality of reflection surveyee in field is higher, and best result is 100 minutes, is minimumly divided into 0 minute.Some term abbreviations that occur in the context of the invention can be referring to above-mentioned < < application form > >.

(2) efficiency of peritoneal dialysis index of correlation: serum creatinine (Scr), blood urea nitrogen (BUN), hemoglobin (HGB), albumin (ALB), electrolyte, serum calcium (Ca), serum paraoxonase (P).Peritoneal dialysis index of correlation: peritoneum balance test (PET), before treatment and when each course for the treatment of finishes, each detects once.Each record patient twenty-four-hour urine amount and ultrafiltration volume before treatment and when each course for the treatment of finishes.

(3) tcm syndrome integration and therapeutic evaluation: before treatment and when each course for the treatment of finishes, three time point application tcm syndrome integration application forms carry out the investigation of tcm syndrome integration, judge curative effect.Tcm syndrome curative effect determinate standard:

A. clinical remission: tcm clinical practice symptom, sign disappear or substantially disappear, 95% of syndrome integration minimizing.

B. effective: tcm clinical practice symptom, sign are obviously improved, syndrome integration reduces >=70%.

C. effective: tcm clinical practice symptom, sign all take a favorable turn, syndrome integration reduces >=30%.

D. invalid: tcm clinical practice symptom, sign are all not improved, even increase the weight of, syndrome integration reduces less than 30%.

(4) peritoneal fibrosis cytokines measurement: before treatment and while treating June, extracting vein blood 3ml left and right, inject blood taking tube, under normal temperature condition, 3000 turn under condition centrifugal 10 minutes, with BT syringe, get the about 1-1.5ml of supernatant (serum), inject 2ml cold storage pipe, sealed membrane sealing, inserts in the preservation environment of-70 ℃ of following conditions.By problem responsible department, please special messenger be collected by serum, adopt ELISA method detection fibers relevant cell factor transforming growth factor-beta 1 (TGF-β 1), Connective Tissue Growth Factor (CTGF), interleukin-6 (IL-6), hepatocyte growth factor (HGF), bone morphogenesis protein-7 (BMP-7) level.

(5) statistical method: data are carried out statistical analysis with SPSS11.5 statistics software, measurement data with mean scholar standard deviation (

) represent, after normality, homogeneity test of variance (usining 0.05 as inspection level), when variance is neat, ask that sample relatively adopts t check, asks for many groups and relatively uses variance analysis for two groups; During heterogeneity of variance, two samples relatively adopt rank test; Enumeration data adopts X 2 test, during nonnormal distribution, adopts rank test.The P<0.05 of take has statistical significance as difference.

4, result:

(1) hold up the impact of kidney granule on life quality

In group, relatively show: in treatment group, after KDTA overall score treatment June, before treatment and after treatment March, all obviously raise (P<0.01); In branch field, (symptom is with uncomfortable at SPL for treatment group, Symptom/problem list) after June is treated in aspect, integration is obviously better than treating front integration (P<0.01), and other field has no notable difference (P>0.05).Aspect SF-36 (general health related quality of life) overall score, before treatment is obviously better than after June treating (P<0.01), in branch field, aspect PF, find to be obviously better than after treatment June (P<0.01) before treatment, remaining field has no notable difference (P>0.05).In matched group, KDTA overall score and SF-36 overall score two aspects obviously reduce (P<0.01) before treatment after all seeing treatment March, and treatment after June, treat March after overall score see obvious rising (P<0.01).In Ge branch field, before and after treatment, be showed no notable difference (P>0.05).Between two groups, relatively, after treatment March and after treatment June, between two groups, aspect KDTA overall score and SF-36 overall score, be showed no notable difference (P>0.05).In branch field, each field also has no notable difference (P>0.05).

(2) hold up the impact of kidney granule on efficiency of peritoneal dialysis index of correlation.Renal function aspect, relatively shows in group: after treatment June, BUN level is treated front remarkable decline (P<0.05), between group, relatively treat June after BUN horizontal stretcher group compared with matched group, significantly reduce (P<0.01); In Scr organizes and between group, be relatively showed no significant difference (P>0.05).Aspect Peritoneal Transport, before and after two groups of internal therapies and between group, be relatively showed no significant difference (P>0.05).Aspect 24h ultrafiltration volume and 24h urine amount, before and after treatment group treatment, have no significant change, treatment of control group after June two all see obvious reduction (P<0.05), and with time point, significantly reduce (P<0.05) with treatment group.

(3) hold up the impact of kidney granule on peritoneal fibrosis relevant cell factor: two groups of horizontal statistical analysis of peritoneal fibrosis relevant cell factor before and after treatment, in group, compare: in treatment group, after treatment, IL-6 level is treated front obvious reduction (P<0.05), HGF, BMP-7 level significantly raise (P<0.01), and other indexs have no significant change (P>0.05).In matched group, after treatment, TGF-β 1 level is treated front remarkable rising (P<0.05), after IL-6 horizontal stretcher, before treatment, obviously reduce (P<0.05), other indexs have no significant change (P>0.05).After treatment, between two groups, compare, treatment group is obviously better than matched group (P<0.05) aspect horizontal controlling TGF-β 1, CTGF, simultaneously, treatment group is at the effect being increased significantly compared with matched group aspect HGF, BMP-7 (P<0.01), and improve IL-6 horizontal aspect, between two groups, curative effect has no significant difference (P>0.05).

(4) hold up kidney granule TCM Therapeutic: treatment group holds up kidney granule can obviously reduce syndrome integration after patient treatment, and along with the prolongation for the treatment of time, syndrome integration obviously reduces, total effective rate obviously raises.More visible by between two groups, after treatment March and after treatment June, treatment group patient's integration changes and total effective rate is all obviously better than matched group.

From above result, the present invention holds up kidney granule can improve clinical symptoms and the sign of patients undergoing peritoneal dialysis, improves life in patients, improves patient's dialysisadequacy; To increase patients undergoing peritoneal dialysis urotoxin and water, remove, delay the loss of patient's residual renal function, improve patient's dialysisadequacy; Suppress to a certain extent the rise of short fibrosis cytokine serum TG F-β 1, CTGF, IL-6 and VEGF level, can raise to a certain extent the anti-fibrosis cytokine HGF short of money, BMP-7 level again, finally suppress or delay the generation of the relevant peritoneal fibrosis of peritoneal dialysis; Film dialysis rat model peritoneal fibrosis degree and the proportional relation of peritoneal dialysis solution concentration; hold up kidney granule can obviously delay the fibrosis progression of peritoneal dialysis rat model peritoneal tissues form; protect the normal of peritoneal tissues morphosis, thus the generation of antagonism peritoneal fibrosis.

Claims

1. a pharmaceutical composition, its medicine activity component is that the Chinese crude drug by following proportioning prepares: Radix Angelicae Sinensis 10 weight portions, Pericarpium Citri Reticulatae 2-75 weight portion, Radix Et Rhizoma Rhei 2-75 weight portion, Radix Astragali 2-150 weight portion, Rhizoma Pinelliae 2-150 weight portion, Herba Epimedii 2-150 weight portion, Radix Salviae Miltiorrhizae 2-250 weight portion, Ramulus Euonymi 2-250 weight portion.

2. according to the pharmaceutical composition of claim 1, its medicine activity component is that the Chinese crude drug by following proportioning prepares: Radix Angelicae Sinensis 10 weight portions, Pericarpium Citri Reticulatae 3-50 weight portion, Radix Et Rhizoma Rhei 3-50 weight portion, Radix Astragali 5-75 weight portion, Rhizoma Pinelliae 5-75 weight portion, Herba Epimedii 5-75 weight portion, Radix Salviae Miltiorrhizae 5-150 weight portion, Ramulus Euonymi 5-150 weight portion.

3. according to the pharmaceutical composition of claim 1, its medicine activity component is that the Chinese crude drug by following proportioning prepares: Radix Angelicae Sinensis 10 weight portions, Pericarpium Citri Reticulatae 5-20 weight portion, Radix Et Rhizoma Rhei 5-20 weight portion, Radix Astragali 8-30 weight portion, Rhizoma Pinelliae 8-30 weight portion, Herba Epimedii 8-30 weight portion, Radix Salviae Miltiorrhizae 6-50 weight portion, Ramulus Euonymi 6-50 weight portion.

4. according to the pharmaceutical composition of claim 1, its medicine activity component is that the Chinese crude drug by following proportioning prepares: Radix Angelicae Sinensis 10 weight portions, Pericarpium Citri Reticulatae 5-15 weight portion, Radix Et Rhizoma Rhei 5-15 weight portion, Radix Astragali 10-20 weight portion, Rhizoma Pinelliae 10-20 weight portion, Herba Epimedii 10-20 weight portion, Radix Salviae Miltiorrhizae 25-40 weight portion, Ramulus Euonymi 25-40 weight portion.

5. according to the pharmaceutical composition of claim 1, its medicine activity component is that the Chinese crude drug by following proportioning prepares: Radix Angelicae Sinensis 10 weight portions, Pericarpium Citri Reticulatae 10 weight portions, Radix Et Rhizoma Rhei 10 weight portions, the Radix Astragali 15 weight portions, the Rhizoma Pinelliae 15 weight portions, Herba Epimedii 15 weight portions, Radix Salviae Miltiorrhizae 30 weight portions, Ramulus Euonymi 30 weight portions.

6. according to the pharmaceutical composition of claim 1, its medicine activity component is that the Chinese crude drug by following proportioning prepares: Radix Angelicae Sinensis 10 weight portions, Pericarpium Citri Reticulatae 8 weight portions, Radix Et Rhizoma Rhei 12 weight portions, the Radix Astragali 18 weight portions, the Rhizoma Pinelliae 12 weight portions, Herba Epimedii 15 weight portions, Radix Salviae Miltiorrhizae 25 weight portions, Ramulus Euonymi 35 weight portions.

7. according to the pharmaceutical composition of claim 1, its medicine activity component is that the Chinese crude drug by following proportioning prepares: Radix Angelicae Sinensis 10 weight portions, Pericarpium Citri Reticulatae 12 weight portions, Radix Et Rhizoma Rhei 8 weight portions, the Radix Astragali 15 weight portions, the Rhizoma Pinelliae 18 weight portions, Herba Epimedii 12 weight portions, Radix Salviae Miltiorrhizae 35 weight portions, Ramulus Euonymi 25 weight portions.

8. according to the pharmaceutical composition of claim 1 to 7 any one, wherein each medical material is that the mode of being directly used as medicine with medical material joins in described pharmaceutical composition.

9. according to the pharmaceutical composition of claim 1 to 7 any one, wherein each medical material joins in described pharmaceutical composition after extracting.

10. according to the pharmaceutical composition of claim 9, wherein each medical material is after extracting, to join in described pharmaceutical composition independently of one another.

11. according to the pharmaceutical composition of claim 9, and wherein each medical material is after extracting, to join in described pharmaceutical composition together.

12. according to the pharmaceutical composition of claim 9, and wherein each medical material is after decocting mode is extracted, to join in described pharmaceutical composition together.

13. according to the pharmaceutical composition of claim 1 to 7 any one, and it prepares as follows: each medical material is directly ground into powder, and mix homogeneously, optionally adds pharmaceutically acceptable carrier, obtains.

14. according to the pharmaceutical composition of claim 1 to 7 any one, and its extract and pharmaceutically acceptable carrier being prepared by described eight kinds of medical materials forms.

15. according to the pharmaceutical composition of claim 1 to 7 any one, and it prepares as follows: by each medical material, with extracting solvent extraction, extract obtained direct packing, obtains.

16. according to the pharmaceutical composition of claim 1 to 7 any one, and it prepares as follows:

(a) by extraction solvent extraction for each medical material;

(c) step (b) gained thick paste or solids are directly packed, obtained; Or optionally to step (b) gained thick paste or solids, add pharmaceutically acceptable carrier, obtain.

17. according to the pharmaceutical composition of claim 16, wherein said extraction solvent is water, ethanol or ethanol water.

18. according to the pharmaceutical composition of claim 1 to 7 any one, wherein each medical material joins in this pharmaceutical composition with form of extract, described extract is to prepare according to the method comprising the steps: get each medical material, pulverize, add that water, ethanol or the ethanol water of 5 ~ 20 times decocts and/or reflux, extract, 1 ~ 5 time, each 0.5 ~ 5 hour, collecting decoction, filters the thick paste that relative density when filtrate decompression is concentrated into 25 ℃ is 1.1 ~ 1.5, dry, obtain.

19. according to the pharmaceutical composition of claim 1 to 7 any one, wherein each medical material joins in this pharmaceutical composition with form of extract, described extract is to prepare according to the method comprising the steps: get each medical material, pulverize, add the water of 5 ~ 20 times, at 80 ~ 100 ℃, decoct and extract 0.5 ~ 5 hour; Filter, filtrate decompression is concentrated, dry, obtains.

20. according to the pharmaceutical composition of claim 1 to 7 any one, wherein each medical material joins in this pharmaceutical composition with form of extract, described extract is to prepare according to the method comprising the steps: get each medical material, pulverize, add the water of 5 ~ 20 times, at 80 ~ 100 ℃, decoct and extract 0.5 ~ 5 hour, filter, filtrate decompression is condensed into paste; With 2-5, doubly measure 50 ~ 90% alcohol reflux 2-3 time, by ethanol extract in 70-90 ℃ except ethanol, vacuum drying, obtains.

21. according to the pharmaceutical composition of claim 1 to 7 any one, wherein each medical material joins in this pharmaceutical composition with form of extract, described extract is to prepare according to the method comprising the steps: get each medical material, pulverize, add the water of 5 ~ 20 times, at 80 ~ 100 ℃, decoct and extract 0.5 ~ 5 hour; Relative density when decocting liquid is concentrated into 25 ℃ is 1.1 ~ 1.5, adds 95% ethanol to concentration of alcohol and reaches 70%, and placement is spent the night, filter, and concentrated filtrate, dry, obtain.

22. following medicinal materials are combined in for the preparation of the purposes in the medicine of prevention, improvement or treatment kidney disease or disease: Radix Angelicae Sinensis 10 weight portions, Pericarpium Citri Reticulatae 2-75 weight portion, Radix Et Rhizoma Rhei 2-75 weight portion, Radix Astragali 2-150 weight portion, Rhizoma Pinelliae 2-150 weight portion, Herba Epimedii 2-150 weight portion, Radix Salviae Miltiorrhizae 2-250 weight portion, Ramulus Euonymi 2-250 weight portion.

23. according to the purposes of claim 22, and wherein said kidney disease or disease are selected from: chronic renal failure, peritoneal fibrosis, because of water, electrolyte and acid base imbalance due to nephropathy.

24. according to the purposes of claim 23, and wherein said peritoneal fibrosis is because of the peritoneal fibrosis due to extrinsic factor.

25. according to the purposes of claim 24, and wherein said extrinsic factor is peritoneal dialysis.

26. according to the purposes of claim 22, and wherein said kidney disease or disease are renal hypofunctions.