Summary of the invention
Goal of the invention of the present invention provides a kind of medicine for the treatment of chronic nephritis.
Another object of the present invention provides the preparation method of this medicine.
Medicine of the present invention is made up of effective ingredient and/or acceptable accessories, wherein prepares raw materials of effective components to be: Radix Ginseng, the Rhizoma Atractylodis Macrocephalae, Fructus Corni, Carapax et Plastrum Testudinis, Carapax Trionycis, Radix Scutellariae, Poria, Rhizoma Alismatis, Radix Bupleuri, Periostracum Cicadae, Polyporus, Ramulus Cinnamomi, Semen Plantaginis, Rhizoma Dioscoreae, Ootheca Mantidis.
Radix Ginseng, the strong Pi QI invigorating of the Rhizoma Atractylodis Macrocephalae; Fructus Corni, Carapax et Plastrum Testudinis, Rhizoma Dioscoreae, Ootheca Mantidis, Carapax Trionycis nourishing kidney replenishing essence; Radix Scutellariae, Poria, Semen Plantaginis, Rhizoma Alismatis clearing away heat-damp and promoting diuresis; Radix Bupleuri, Periostracum Cicadae, Ramulus Cinnamomi dispel the wind and remove heresy; Modern medicine study shows that Radix Ginseng, the Rhizoma Atractylodis Macrocephalae, Poria, Polyporus have the adjustment immunologic function, and renal function protecting reduces effects such as urine protein; Fructus Corni, Carapax et Plastrum Testudinis, Rhizoma Dioscoreae, Ootheca Mantidis, Carapax Trionycis also have renal function protecting, suppress the immunologic injury effect, and Carapax et Plastrum Testudinis, Carapax Trionycis be rich in aminoacid, protein, phospholipid, and liver detoxification is arranged, and the strengthening by means of tonics effect can promote plasma albumin synthetic.Heat-clearing and diuresis-promoting drugs such as Radix Scutellariae, Semen Plantaginis, Rhizoma Alismatis can be removed immune complex in the blood, suppress antigen antibody reaction, renal function protecting; The medical instruments that dispel the wind such as Radix Bupleuri, Periostracum Cicadae, Ramulus Cinnamomi have tangible antiallergic, antiallergic action effect.All medicines share has spleen invigorating taste stomach, clearing away heat-damp and promoting diuresis, the evil effect of loosing of dispeling the wind, and is used for the treatment of chronic nephritis, can improve clinical symptoms, can reduce urine protein significantly again, and raising albumin improves and renal function protecting.
In order to obtain better therapeutic, the consumption of raw material is:
Radix Ginseng 5-10 weight portion, Rhizoma Atractylodis Macrocephalae 5-10 weight portion, Fructus Corni 10-15 weight portion, Carapax et Plastrum Testudinis 10-15 weight portion, Carapax Trionycis 10-15 weight portion, Radix Scutellariae 3-9 weight portion, Poria 10-15 weight portion, Rhizoma Alismatis 25-30 weight portion, Radix Bupleuri 5-10 weight portion, Periostracum Cicadae 10-15 weight portion, Polyporus 10-15 weight portion, Ramulus Cinnamomi 1-5 weight portion, Semen Plantaginis 10-15 weight portion, Rhizoma Dioscoreae 15-20 weight portion and Ootheca Mantidis 25-30 weight portion.
In order to obtain best curative effect, the consumption of raw material is:
Radix Ginseng 9 weight portions, the Rhizoma Atractylodis Macrocephalae 9 weight portions, Fructus Corni 15 weight portions, Carapax et Plastrum Testudinis 15 weight portions, Carapax Trionycis 15 weight portions, Radix Scutellariae 6 weight portions, Poria 15 weight portions, Rhizoma Alismatis 30 weight portions, Radix Bupleuri 10 weight portions, Periostracum Cicadae 15 weight portions, Polyporus 15 weight portions, Ramulus Cinnamomi 3 weight portions, Semen Plantaginis 15 weight portions, Rhizoma Dioscoreae 20 weight portions and Ootheca Mantidis 30 weight portions.
The preparation method of effective ingredient can adopt the routine fashion of pharmaceutical field, as decoction and alcohol sedimentation technique or ethanol extract from water precipitation, and perhaps convection drying, pulverize.
The preferred for preparation method is: Carapax Trionycis and Carapax et Plastrum Testudinis are decocted with water 2-3 time, and each 20-24 hour, collecting decoction filtered, and filtrate is left standstill; Radix Ginseng is decocted with water 2-3 time, and each 0.5-1.5 hour, collecting decoction filtered, and filtrate is left standstill; All the other medicines decoct with water 2-3 time, wherein Semen Plantaginis decocted a drug wrapped, and each 0.5-1.5 hour, merge decoction, filter, filtrate is left standstill; Merge above-mentioned three kinds of filtrates, filter, it is 90-95 ℃ of survey 1.08 that filtrate is concentrated into relative density, room temperature to be chilled to adds equivalent ethanol and makes precipitation, gets supernatant concentration to relative density 60-65 ℃ of survey 1.20, add water, stir, leave standstill, get supernatant concentration to the relative density 60-65 ℃ of thick paste of surveying 1.38-1.40.
More preferably preparation method is: take by weighing raw material, Carapax Trionycis and Carapax et Plastrum Testudinis are decocted with water 3 times, each 24 hours, collecting decoction filtered, and filtrate is left standstill; Radix Ginseng is decocted with water twice, and each 1.5 hours, collecting decoction filtered, and filtrate is left standstill; All the other medicines decoct with water twice, wherein Semen Plantaginis are decocted a drug wrapped, and each 1.5 hours, merge decoction, filter, filtrate is left standstill; Merge above-mentioned three kinds of filtrates, filter, it is 90-95 ℃ of survey 1.08 that filtrate is concentrated into relative density, room temperature to be chilled to adds equivalent ethanol and makes precipitation, gets supernatant concentration to relative density 60-65 ℃ of survey 1.20, add 1 times of amount of water, stir, left standstill 8 hours, get supernatant concentration to the relative density 60-65 ℃ of thick paste of surveying 1.38-1.40.
Medicine of the present invention can be with above-mentioned effective ingredient convection drying, and pulverize is made powder; Perhaps above-mentioned effective ingredient and pharmaceutically acceptable conventional adjuvant are made various dosage forms, preferred electuary, granule, oral liquid, tablet or capsule.Preparation is during granule, preferably gets 1 part of the thick paste of effective ingredient, and with 3 parts of sucrose, 1.25 parts in dextrin and ethanol are made granule, drying, granulate, packing.
Medicine of the present invention has spleen invigorating taste stomach, clearing away heat-damp and promoting diuresis, the evil effect of loosing of dispeling the wind, and can be used for treating chronic nephritis, can improve clinical symptoms, can reduce urine protein significantly again, and raising albumin improves and renal function protecting, and without any side effects.
Embodiment 1:
1) takes by weighing following raw materials according: Radix Ginseng 9g, Rhizoma Atractylodis Macrocephalae 9g, Fructus Corni 15g, Carapax et Plastrum Testudinis 15g, Carapax Trionycis 15g, Radix Scutellariae 6g, Poria 15g, Rhizoma Alismatis 30g, Radix Bupleuri 10g, Periostracum Cicadae 15g, Polyporus 15g, Ramulus Cinnamomi 3g, Semen Plantaginis 15g, Rhizoma Dioscoreae 20g, Ootheca Mantidis 30g;
2) Carapax Trionycis and Carapax et Plastrum Testudinis are decocted with water 3 times, each 24 hours, collecting decoction filtered, and filtrate is left standstill;
3) Radix Ginseng is decocted with water twice, each 1.5 hours, collecting decoction filtered, and filtrate is left standstill;
4) all the other medicines decoct with water twice, wherein Semen Plantaginis are decocted a drug wrapped, and each 1.5 hours, merge decoction, filter, filtrate is left standstill; Merge above-mentioned three kinds of filtrates, filter, it is 90-95 ℃ of survey 1.08 that filtrate is concentrated into relative density, room temperature to be chilled to adds equivalent ethanol and makes precipitation, gets supernatant concentration to relative density 60-65 ℃ of survey 1.20, add 1 times of amount of water, stir, left standstill 8 hours, get supernatant concentration to the relative density 60-65 ℃ of thick paste of surveying 1.38-1.40;
5) get 1 part of thick paste, with 3 parts of sucrose, 1.25 parts in dextrin and ethanol are made granule, drying, granulate, packing.
Embodiment 2:
Take by weighing following raw materials according: Radix Ginseng 5g, Rhizoma Atractylodis Macrocephalae 5g, Fructus Corni 10g, Carapax et Plastrum Testudinis 10g, Carapax Trionycis 10g, Radix Scutellariae 3g, Poria 10g, Rhizoma Alismatis 25g, Radix Bupleuri 5g, Periostracum Cicadae 10g, Polyporus 10g, Ramulus Cinnamomi 1g, Semen Plantaginis 10g, Rhizoma Dioscoreae 15g, Ootheca Mantidis 25g; All the other are with embodiment 1.
Embodiment 3:
Take by weighing following raw materials according: Radix Ginseng 10g, Rhizoma Atractylodis Macrocephalae 10g, Fructus Corni 15g, Carapax et Plastrum Testudinis 15g, Carapax Trionycis 15g, Radix Scutellariae 9g, Poria 15g, Rhizoma Alismatis 30g, Radix Bupleuri 10g, Periostracum Cicadae 15g, Polyporus 15g, Ramulus Cinnamomi 5g, Semen Plantaginis 15g, Rhizoma Dioscoreae 20g, Ootheca Mantidis 30g; All the other are with embodiment 1.
Test example 1: medicine of the present invention is to the effect viewing test of mice basement membrane nephritis
One, material and method:
1. material:
Animal: large ear rabbit, male, 2-2.5Kg, the Beijing Medical University animal center provides; BALB/C mice, female, 18-22g, institute of biological products, Beijing animal center provides.
The medicine of medicine: embodiment 1 preparation.Rabbit igg: U.S. Miles company product.
2. method: the method that adopts rabbit igg accelerating type mice anti-basement membrane nephritis
2.1. nephrolytic sera preparation
With the Emulsion immunize rabbit that contains mice glomerular basement membrane and Freund's complete adjuvant, 1 time weekly, totally 6 times, getting rabbit anteserum is nephrolytic sera.
2.2. glomerulonephritis is made film and administration
Mice elder generation lumbar injection rabbit igg, the intravenous injection nephrolytic sera is made film again, evenly is divided into 5 groups according to the mouse retention protein level after 5 days.Model group: medicine 1.87g/Kg of the present invention, 3.75g/Kg (dose,equivalent); Cyclophosphamide (CY) 10mg/Kg lumbar injection, positive matched group.Other establishes the blank group.Every group 13-14,3 weeks of continuous oral administration.Survey urine protein, plasma albumin, blood urea nitrogen and cholesterol weekly.
Two, result:
See Table 1-4.
Made film (notes nephrolytic sera) back 5 days, mouse retention albumen plant all reach 300mg/dl or more than, model is set up.After the administration 7 days, mouse retention protein content, plasma albumin, cholesterol level all have clear improvement in basic, normal, high dosage group (except that low agent group cholesterol P value near 0.05, equal P<0.05), similar to the CY group.After the administration 14 days, the urine protein of each dosage group still is better than model group, and other indexs also have in various degree to be improved, wherein high dose group plasma albumin, blood urea nitrogen, cholesterol] the low dose group cholesterol obviously is better than model group (P<0.05).After 21 days, the urine protein of each dosage group and plasma urea nitrogen, high dose group cholesterol still obviously are better than model group, has certain dose-effect relationship, though each test group plasma albumin is a little more than model group, but all there has not been marked difference, this moment, the model group measured value gradually rose, and estimated that pathological changes has begun to recover.
Three, brief summary
1. medicine 1.87g/Kg of the present invention, 3.75g/Kg, oral urine protein, plasma urea nitrogen and the cholesterol of reducing of 7.5g/Kg, the rising plasma albumin has the obvious treatment effect to the mice anti-basement membrane nephritis.
2. medicine of the present invention has a certain amount of effect relationship to the therapeutical effect of chronic nephritis, and effect of high dosage is good, and is similar to cyclophosphamide 10mg/Kg lumbar injection action intensity, and 1.87g/Kg group (1/2 dose,equivalent) is slightly poor.
3. begun onset in the time of 7 days from administration, its curative effect can keep for 3 weeks at least.
The variation of protein content in table 1 urine (X ± SD)
Group | Dosage (g/Kg) | Urine protein (mg/dl) |
Before the medicine | Administration 7 days | Administration 14 days | Administration 21 days |
Blank | | 23±8(13) | 25.8±8(13) | 24±8(13) | 25±8(13) |
Model | | 343±85(14) | 392±104(12) | 318±60(11) | 254±52(11) |
Cyclophosphamide | 0.01 | 346±88(13) | *308±67(12)
| *265±47(10)
| *180±63(10)
|
Medicine of the present invention | 1.87 | 346±88(13) | *292±73(12)
| Δ275±40(12) | *212±38(12)
|
3.75 | 343±85(14) | *307±62(14)
| *261±63(14)
| *200±58(13)
|
7.5 | 343±85(14) * | *277±101 (13)
| *241±77(11)
| **177±61(11)
|
Annotate: the t test:
*P<0.05,
*P<0.01, Δ P is near 0.05.
The variation of table 2 plasma albumin (X ± SD)
Group | Dosage (g/Kg) | Albumin (g/L) |
Administration 7 days | Administration 14 days | Administration 21 days |
Blank | | 33.9±0.9 | 33.7±1.5 | 32.9±2.1 |
Model | | 20.5±2.0 | 23.5±3.3 | 25.1±2.2 |
Cyclophosphamide | 0.01 | *24.2±4.0
| Δ26.3±2.6 | 27.0±1.9 |
Medicine of the present invention | 1.87 | **24.8±3.4
| 24.7±3.1 | 25.6±2.2 |
3.75 | *23.6±3.4
| 25.5±3.5 | 25.5±2.4 |
7.5 | *24.8±5.2
| *28.1±4.4
| 26.9±2.8 |
Annotate: the t test:
*P<0.05,
*P<0.01, Δ P is near 0.05.
The variation of table 3 plasma urea nitrogen (X ± SD)
Group | Dosage (g/Kg) | Albumin (g/L) |
Administration 7 days | Administration 14 days | Administration 21 days |
Blank | | 7.2±0.5 | 5.4±0.8 | 6.8±0.5 |
Model | | 10.2±4.4 | 8.1±2.7 | 8.3±2.3 |
Cyclophosphamide | 0.01 | 9.9±5.6 | *5.4±2.0
| **5.4±0.6
|
Medicine of the present invention | 1.87 | 8.1±3.5 | Δ6.2±1.7 | Δ6.5±1.7 |
3.75 | 7.4±2.3 | 6.9±1.3 | *6.7±0.6
|
7.5 | 8.5±4.0 | *6.2±1.0
| *6.6±1.0
|
Annotate: the t test:
*P<0.05,
*P<0.01, Δ P is near 0.05.
The variation of table 4 total plasma cholesterol (X ± SD)
Group | Dosage (g/Kg) | Albumin (g/L) |
Administration 7 days | Administration 14 days | Administration 21 days |
Blank | | 2.2±0.4 | 2.3±0.2 | 2.7±0.2 |
Model | | 11.1±3.0 | 7.8±2.4 | 8.1±2.3 |
Cyclophosphamide | 0.01 | 9.1±2.2 | *5.8±1.0
| **4.6±1.0
|
Medicine of the present invention | 1.87 | Δ8.8±2.6 | *5.6±1.8
| 7.3±1.9 |
3.75 | *8.2±2.4
| 6.1±1.8 | 6.5±1.6 |
7.5 | **7.6±2.8
| *5.6±1.9
| *5.8±2.2
|
Annotate: the t test:
*P<0.05,
*P<0.01, Δ P is near 0.05.
Experimental example 2: the clinical observation of treatment chronic nephritis
One, general clinical data
Diagnose and the typing standard according to the primary glomerulonephritis that Nanjing gastropathy meeting in 1985 is formulated, select Urology Department outpatient service of qualified Hebei Prov. Traditional Chinese Medicine Hospital and inpatient 30 examples as the object of observation, wherein male 17 examples, woman's 13 examples, age 7-62 year, 29.9 years old mean age, the shortest person of the course of disease 1 month, elder 3 years; The Chinese medical discrimination typing, spleen kidney qi deficiency of YIN person 20 examples, deficiency of spleen-YANG and kidneyYANG person 4 examples, hepatic and renal YIN deficiency person's 6 examples.
Two, Therapeutic Method
All case all adopts the Drug therapy of the embodiment of the invention 1 preparation, and each 1 bag, every day 3 times, 1 month is a course of treatment, forbidding other treatment medicine during the medication.
Three, observation index and statistical procedures
Observe the improvement situation of clinical symptoms and laboratory checking index before and after the treatment, laboratory checking index comprises 24 hours protein quantifications of urine, blood total protein, albumin, serum creatinine, blood urea nitrogen, routine blood test, immunoglobulin etc.T checked before and after statistical procedures adopted treatment.
Four, therapeutic outcome analysis
1. clinical curative effect analysis: the criterion of therapeutical effect in " the clinical research guideline of treatment by Chinese herbs chronic nephritis " formulated in 1987 according to State Administration of Traditional Chinese Medicine is judged curative effect.Alleviation person's 14 examples fully behind the 30 routine patient treatments, alleviation person's 8 examples substantially, 6 examples that take a turn for the better, 2 examples are invalid, and total effective rate is 93.3%.
2. the relation of clinical efficacy and traditional Chinese medical science typing sees Table 5.Medicine of the present invention is best to spleen kidney qi Yin bivacuity type curative effect, and is relatively poor to deficiency of spleen-YANG and kidneyYANG and liver-kidney yin deficiency effect.
Table 5
Curative effect | Spleen kidney qi Yin bivacuity (20 example) | Deficiency of spleen-YANG and kidneyYANG (4 example) | The hepatic and renal YIN deficiency (6 example) |
Alleviate fully | 13 | 1 | 0 |
The basic alleviation | 5 | 1 | 2 |
Take a turn for the better | 2 | 1 | 3 |
Invalid | 0 | 1 | 1 |
3. to the improvement situation of laboratory checking index, see Table 6.By table 6 as seen, treatment back urine 24 hours albumen, serum creatinine, blood urea nitrogen obviously reduce, and have compared notable difference before the treatment, and blood albumin treatment back obviously raises, and compare before the treatment that there were significant differences.
Table 6
| Twenty-four-hour urine protein quantification (g/L) n=30 | Blood albumin (g/L) n=30 | Blood urea nitrogen (mmol/L) n=13 | Serum creatinine (μ mol/L) n=13 |
Before the treatment | 3.36±1.44 | 3.68±9.35 | 12.8±8.6 | 167.3±38.1 |
After the treatment | 1.21±1.11 | 44.6±8.61 | 7.4±3.9 | 128.6±45.2 |
The P value | <0.01 | <0.05 | <0.01 | <0.01 |