CN100372552C - Pharmaceutical composition for treating renal failure and its preparation and application - Google Patents
Pharmaceutical composition for treating renal failure and its preparation and application Download PDFInfo
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Abstract
The present invention discloses a composition for treating renal failure, a preparation method thereof and the application thereof. The composition comprises the following ingredients in weight percentages: 1 to 50% of rhubarb, 1 to 30% of glycyrrhiza, 1 to 20% of danshen root, 1 to 20% of poria cocos wolf, 0.1 to 20% of fructus aurantii immaturus and 0.1 to 20% of calcined concha ostreae. The composition has obvious inhibiting effect on the increase of blood urea nitrogen (BUN) and creatinine (Cr) of rats with adenine renal failure model, and also has obvious effect on the increase of blood total protein (TP), albumin (ALB) and haemoglobin (HB) of rats with renal failure. The composition has the function for stimulating circulation to end stasis. Acute toxicity tests on mice show that no obvious toxic reaction occurs, and long-term toxicity tests on rats show that no obvious toxic reaction occurs.
Description
One, technical field:
The present invention relates to a kind of medicine for the treatment of nephropathy, specifically relate to a kind of pharmaceutical composition for the treatment of renal failure and its production and application.
Two, technical background:
Up to the present, in the world wide chronic kidney hypofunction is also lacked satisfied medicine and method.Main by hemodialysis, saturating, the kidney transplantation treatment of abdomen, and not only there are many also insoluble medical difficult problems at present in these Therapeutic Method, and costly, in a single day renal failure appears in patient just needs to earn a bare living by dialysis, and at present domestic have quite a few unit and individual can not bear its huge costing.Particularly vast rural area, because of limited by armarium and technical conditions on the one hand, be subjected to the restriction of economic situation on the other hand, most patients are still by the non-dialysis therapy for treating, but all lack both at home and abroad at present a kind of effectively, few side effects, economic treatment renal failure medicine.From the whole country, in the treatment of chronic kidney hypofunction, there is serious shortage of medical services and medicines state.
During chronic kidney hypofunction, the excretory medicine of oral acceleration toxin can reduce patient's blood urea nitrogen, creatinine and other toxin, improves ordinary circumstance, and relief of symptoms prolongs life cycle.
According to the literature, with Radix Et Rhizoma Rhei, Rhizoma Smilacis Glabrae, Radix Glycyrrhizae, Radix Salviae Miltiorrhizae, Concha Ostreae, Fructus Aurantii treatment renal failure, falling blood urea nitrogen, serum creatinine, it is better to alleviate uremia's symptom aspect curative effect.But find above-mentioned six kinds of prescriptions are mixed the back with water extraction or Radix Salviae Miltiorrhizae is mixed the curative effect of medication of making after the five kinds of Chinese medicine merging of back with water extraction after with ethanol extraction with other not obvious through clinical practice present inventor for many years.The applicant has done a large amount of experiments for this reason, find that Radix Et Rhizoma Rhei is the monarch drug in the side in the above-mentioned prescription, the main eight big constituents such as anthraquinone class, stilbene glycoside, chromone class, naphthols glycoside that contain, wherein anthraquinone component is its main active ingredient, emodin, chrysophanol are represented composition for the anthraquinone class, Radix Et Rhizoma Rhei anthraquinone has two kinds on conjunction type and free type, wherein combined anthraquinone can dissolve in ethanol preferably, if water decocts, can only propose the part of anthraquinone, and Radix Et Rhizoma Rhei anthraquinone can dissolve preferably in ethanol.
This prescription Radix Et Rhizoma Rhei can Profilin decompose, and quickens urotoxic drainage, and the absorption medium molecular substance suppresses the intestinal bacteria growth, stimulates enterokinesia, and toxin is drained to be increased, and the plain concentration of blood poisoning reduces.Radix Glycyrrhizae, Rhizoma Smilacis Glabrae have Detoxication to the endogenous toxin, and Concha Ostreae, Fructus Aurantii can be alleviated side effect such as Radix Et Rhizoma Rhei diarrhoea, abdominal distention stomachache, and can replenish calcium preparation, improve the alcium and phosphor metabolization obstacle of chronic kidney hypofunction.Radix Salviae Miltiorrhizae can act on multiple thrombin, reduces platelet aggregation, promotes fibrinolytic, alleviates the hypercoagulability of renal failure, changes hemorheological property, and microcirculation improvement increases the kidney blood flow, promotes graft function.
Raw material Radix Et Rhizoma Rhei in this compositions, Poria, Radix Glycyrrhizae, Concha Ostreae, Radix Salviae Miltiorrhizae, Fructus Aurantii are all on the books in herbal ancient books such as Shennong's Herbal, Compendium of Material Medica, and one one of 2005 years version of China's " pharmacopeia " is equal incomes also.Modern Chinese medicine is learned monograph and has been put down in writing the main pharmaceutical component and the mechanism of action that above medicine extracts through the modern study method, particularly carries out the discovery of drug research in conjunction with nephritis, renal failure pathogeny in recent years.As the anti-kidney proliferation of mesangial cells of Radix Et Rhizoma Rhei, suppress the glomerule fibrosis, absorption urotoxin and medium molecular substance; The antiinflammatory action of Radix Glycyrrhizae, the antiplatelet aggregative activity of Radix Salviae Miltiorrhizae etc., " Chinese combination of Chinese and Western medicine magazine ", " Chinese nephropathy magazine " etc. all have series report.
Three, summary of the invention
The objective of the invention is to overcome weak point of the prior art, a kind of pharmaceutical composition for the treatment of renal failure is provided.
Another object of the present invention provides a kind of preparation of drug combination method for the treatment of renal failure.
Another purpose of the present invention is to provide a kind of application for the treatment of the pharmaceutical composition of renal failure.
The pharmaceutical composition of treatment renal failure of the present invention, form by Radix Et Rhizoma Rhei, Radix Glycyrrhizae, Radix Salviae Miltiorrhizae, Poria, Fructus Aurantii and Concha Ostreae (calcined), wherein said described Radix Et Rhizoma Rhei is to use ethanol water to extract separately to form, other component blending water extracts and forms, and the content of Radix Et Rhizoma Rhei is in the amount of active ingredient emodin and chrysophanol in the compositions extract, must not be less than 0.25%, emodin and chrysophanol content must not be less than 0.2% of prescription total amount in the finished product.
Further, composition prescription of the present invention (percentage by weight) is: Radix Et Rhizoma Rhei 1-50%, Radix Glycyrrhizae 1-30%, Radix Salviae Miltiorrhizae 1-20%, Poria 1-20%, Fructus Aurantii 0.1-20% and Concha Ostreae (calcined) 0.1-20%.
Further, composition prescription of the present invention (percentage by weight) is: Radix Et Rhizoma Rhei 20-40%, Radix Glycyrrhizae 10-20%, Radix Salviae Miltiorrhizae 10-20%, Poria 10-20%, Fructus Aurantii 1-20% and Concha Ostreae (calcined) 1-20%.
Preferably, described composition prescription (percentage by weight) is: Radix Et Rhizoma Rhei 20-30%, Radix Glycyrrhizae 15-20%, Radix Salviae Miltiorrhizae 15-20%, Poria 15-20%, Fructus Aurantii 5-10% and Concha Ostreae (calcined) 5-10%.
Most preferred, composition prescription is: Radix Et Rhizoma Rhei 521 grams, Radix Glycyrrhizae 417 grams, Radix Salviae Miltiorrhizae 417 grams, Poria 417 grams, Fructus Aurantii 209 grams and Concha Ostreae (calcined) 209 grams.
Be preferred best extracting technology, the inventor adopts orthogonal experiment to choose the lixiviate number of times, extraction time and each time solubilization dosage.Result of the test is handled by statistics, variance analysis, determines the Radix Et Rhizoma Rhei optimum extraction process.
Adopt the decompression thin film concentration, make extracting solution at a lower temperature (65～70 ℃) concentrate; Use spray drying method, drying time is short, equal like this destruction and the loss that reduces effective ingredient.
1. the test of Radix Et Rhizoma Rhei extraction process
1.1 Radix Et Rhizoma Rhei and all the other five tastes medical material mixing waters decoct
Get Radix Et Rhizoma Rhei 10.42g, mix with all the other five tastes medical materials, add 12 times of water gagings and soak in the prescription ratio, decocted 1.5 hours, and filtered, medicinal residues add 8 times of water gagings and decocted 1 hour, collecting decoction filters, and filtrate is concentrated into 500ml; get this product 15ml; add hydrochloric acid 2ml, chloroform 30ml, reflux, extract, 1 hour; put cold; be transferred in the separatory funnel is divided and is got chloroform solution, continues and extracts with chloroform 20ml jolting; and and chloroform solution; evaporate to dryness, residue add methanol and quantitatively are transferred in the 10ml measuring bottle, add methanol to scale; shake up, as need testing solution I.
Other gets Radix Et Rhizoma Rhei fine powder 0.178g, adds methanol 25ml, and reflux, extract, 30 minutes is put cold, filter, get filtrate 5ml, evaporate to dryness, residue adds water 10ml, hydrochloric acid 1ml, chloroform 20ml, refluxed 1 hour, and divided and get chloroform solution, continue and extract with chloroform 20ml jolting, combined chloroform liquid, evaporate to dryness, residue add ethanol and quantitatively are transferred in the 10ml measuring bottle, add ethanol to scale, shake up, as need testing solution II (being used as medical material content).
According to high performance liquid chromatography (appendix VID of Chinese Pharmacopoeia version in 2000) experiment chromatographic condition and system suitability test
With octadecylsilane chemically bonded silica is filler, and methanol-0.1% phosphoric acid solution (80: 20) is a mobile phase, and the detection wavelength is 254nm.Number of theoretical plate is pressed the emodin peak and is calculated, and should be not less than 3000.
The preparation of reference substance solution:
Precision takes by weighing emodin 11.36mg, chrysophanol 11.46mg, puts in the 100ml measuring bottle, adds dissolve with methanol to scale, shakes up.Precision is measured 5ml, puts in the 50ml measuring bottle, adds dissolve with methanol to scale, shakes up, in contrast product solution.
Algoscopy
Accurate respectively reference substance solution and the need testing solution 10 μ l of drawing inject chromatograph of liquid, measure.The results are shown in Table 1.
The alcohol extraction of table 1 Radix Et Rhizoma Rhei with mix decocting assay comparison sheet
| The reference substance integrated value | Test sample I integrated value | Test sample II integrated value | |||
| Emodin | Chrysophanol | Emodin | Chrysophanol | Emodin | Chrysophanol |
| 426166 | 614742 | 47442 | 89011 | 308113 | 879277 |
| Content (%) | 0.0040 | 0.0053 | 0.231 | 0.460 | |
| The rate of transform (%) | 1.74 | 1.15 | Medical material content | ||
As seen from the above table, mix decoction and make the not fried or loss of most Radix Et Rhizoma Rhei anthraquinones.1.2 the independent decocting process test of Radix Et Rhizoma Rhei
Get Radix Et Rhizoma Rhei fine powder 1.05g, add water 50ml, boiled 20 minutes, put coldly, filter, filtrate is diluted to 200ml, precision is measured 10ml, adds hydrochloric acid 2ml, chloroform 20ml, refluxed 1 hour, and divided and get chloroform solution, evaporate to dryness, residue adds dissolve with ethanol, and is transferred in the 10ml measuring bottle, adds ethanol to scale, shake up, make test liquid.According to high performance liquid chromatography (appendix VID of Chinese Pharmacopoeia version in 2000) experiment, reference substance and test condition are the same, the results are shown in Table 2.
Alcohol extraction of table 2 Radix Et Rhizoma Rhei and water list are fried in shallow oil the assay comparison sheet
| The reference substance integrated value | Singly fry in shallow oil the test sample integrated value | Test sample II integrated value | |||
| Emodin | Chrysophanol | Emodin | Chrysophanol | Emodin | Chrysophanol |
| 426166 | 614742 | 254842 | 284744 | 308113 | 879277 |
| Content (%) | 0.136 | 0.106 | 0.231 | 0.460 | |
| The rate of transform (%) | 58.88 | 21.90 | (medical material content) | ||
Last table as can be known, it is also lower that the Radix Et Rhizoma Rhei list is fried in shallow oil the anthraquinone extraction ratio.
1.3 the Radix Et Rhizoma Rhei alcohol extraction process is investigated
Radix Et Rhizoma Rhei anthraquinone extracts, and adopts alcohol reflux more, and in the reflux, extract, process, concentration of alcohol, ethanol consumption, extraction time, extraction time and the particulate size of medical material etc. all are the principal elements that influence extraction effect.Now the granular size factor is investigated separately.
1.3.1 the Radix Et Rhizoma Rhei granular size is to the influence of extraction effect
Get the Radix Et Rhizoma Rhei pulverize separately and become coarse powder, coarse powder, middle powder is respectively got 40g, measures 70% alcohol reflux 3 times with 7 times, each 1 hour, filter and and filtrate, change in the 500ml measuring bottle, add 70% ethanol, shake up to scale, precision is measured 2.5ml, puts in the 25ml measuring bottle, adds ethanol to scale, shake up, precision is measured 5ml, evaporate to dryness, add water 20ml, hydrochloric acid 2ml, chloroform 20ml, refluxed 1 hour, anti-cold, divide and get chloroform solution, continue and extract combined chloroform liquid, evaporate to dryness with chloroform 20ml jolting, residue adds ethanol and quantitatively is transferred in the 5ml measuring bottle, add ethanol to scale, shake up, as need testing solution.According to high performance liquid chromatography (appendix VID of Chinese Pharmacopoeia version in 2000) experiment, reference substance and test condition are the same, the results are shown in Table 3.
Table 3 Radix Et Rhizoma Rhei granular size is to content influence table as a result
| Reference substance | Coarse powder | Coarse powder | Middle powder | ||||
| Emodin | Chrysophanol | Emodin | Chrysophanol | Emodin | Chrysophanol | Emodin | Chrysophanol |
| 432347 | 627396 | 701566 | 1250309 | 717226 | 1255439 | 746904 | 1315171 |
| Content (%) | 0.230 | 0.286 | 0.236 | 0.287 | 0.245 | 0.300 | |
As seen from the above table, coarse powder and coarse powder content are more or less the same, and middle powder content slightly increases, but middle powder particles is too thin, and industrial operation is difficulty comparatively, finally selects coarse powder.
1.3.2 Radix Et Rhizoma Rhei alcohol reflux orthogonal experiment
Granular size as fixed factor, is respectively got three levels to four factors such as concentration of alcohol, carry out L
9(3
4) orthogonal test, be evaluation index with the summation of emodin, chrysophanol, screen best reflux, extract, condition, see Table 4.
Table 4 Radix Et Rhizoma Rhei backflow orthogonal test factor level table
| Factor | Concentration of ethanol (%) (A) | Consumption of ethanol (doubly) (B) | Return time (hour) (C) | Backflow number of times (D) |
| Level | 55 70 85 | 5 7 9 | 0.5 1.0 1.5 | 1 2 3 |
1.3.2.1 the preparation of sample and mensuration
Get totally 9 parts of Radix Et Rhizoma Rhei coarse powder, every part of 40g presses L
9(3
4) orthogonal test gauge outfit experiment arrangement, add alcohol reflux, filter, filtrate is settled to 500ml, precision is measured 2.5ml, puts in the 25ml measuring bottle, adds ethanol to scale, shakes up, precision is measured 5ml, and evaporate to dryness adds water 20ml, hydrochloric acid 2ml, chloroform 20ml refluxed 1 hour, put coldly, divided and to get chloroform solution, continue and extract with chloroform 20ml jolting, combined chloroform liquid, evaporate to dryness, residue add ethanol and quantitatively are transferred in the 5ml measuring bottle, add ethanol to scale, shake up, as need testing solution.According to high performance liquid chromatography (appendix VID of Chinese Pharmacopoeia version in 2000) experiment, reference substance and test condition are the same, the results are shown in Table 5.
Table 5 Radix Et Rhizoma Rhei reflux, extract, orthogonal test assay is table as a result
1.3.2.2 assay variance analysis as a result (seeing Table 6) to table 8
The variance analysis of table 6 emodin content measurement result
| Soruces of variation work property | Sum of deviation square | Degree of freedom | Variance | The F value | Marginal value shows |
| A B C (error) D * | 0.00062 0.00099 0.00043 0.01040 | 2 2 2 | 0.00031 0.00050 0.00022 2 | 1 2 0.00520 | F 0.05＝19 F 0.01＝99 24 |
As shown in Table 6, the factor that influences emodin backflow effect is D in proper order〉B〉A〉C, secondly the times influence that promptly refluxes maximum is the ethanol consumption, is concentration of alcohol once more, the return time influence is minimum, can be as the error of variance analysis; Through variance analysis, the backflow number of times has significance influence to the emodin reflux, extract,, and all the other three factors are to the stripping of emodin there are no significant influence.Can draw the best reflux technique condition of emodin thus is: A
3B
2C
2D
3, promptly, extracted 1 hour with 7 times of amount alcohol reflux of 85% 3 times at every turn.
The variance analysis as a result of table 7 chrysophanol assay
| The soruces of variation significance | Sum of deviation square | Degree of freedom | Variance | The F value | Marginal value |
| A B (error) C D | 0.02576 0.00283 0.00403 0.03507 | 2 2 2 2 | 0.01288 0.00142 0.00202 0.01754 | 9 / 1 12 | F 0.05＝19 F 0.01＝99 |
Analyzed as can be known by table 7, the factor that influences the chrysophanol reflux, extract, is D in proper order〉A〉C〉B, promptly extraction time has the greatest impact, and is concentration of alcohol secondly, is extraction time once more, and the influence of ethanol consumption is minimum, can be as the error of variance analysis; Through variance analysis, four factors to the chrysophanol reflux, extract, there are no significant the influence.Can draw the best reflux technique condition of emodin thus is: A
3B
2C
2D
2, promptly, extracted 1 hour with 7 times of amount alcohol reflux of 85% 2 times at every turn.
The variance analysis as a result of table 8 paste-forming rate assay
| The soruces of variation significance | Sum of deviation square | Degree of freedom | Variance | The F value | Marginal value |
| A B (error) C D * | 167.60 13.36 15.43 713.81 | 2 2 2 | 83.80 6.68 7.72 2 | 13 / 1 356.90 | F 0.05＝19 F 0.01＝99 53 |
Analyzed as can be known by table 8, the factor that influences emodin backflow effect is D in proper order〉A〉C〉B, secondly the times influence that promptly refluxes maximum is concentration of alcohol, is return time once more, the influence of ethanol consumption is minimum, can be as the error of variance analysis; Through variance analysis, the backflow number of times has significance influence to the emodin reflux, extract,, and all the other three factors are to the stripping of emodin there are no significant influence.Can draw the best reflux technique condition of emodin thus is: A
2B
3C
2D
3, promptly, extracted 1 hour with 9 times of amount alcohol reflux of 70% 3 times at every turn.
Through above-mentioned orthogonal experiment analysis-by-synthesis, the preferred plan of reflux, extract, Radix Et Rhizoma Rhei anthraquinone is: A
3B
2C
2D
3Actual in conjunction with industry, concentration of alcohol selects 70% for use, is: A
2B
2C
2D
31.3.3 Radix Et Rhizoma Rhei reflux, extract, confirmatory experiment
Get totally 2 parts of Radix Et Rhizoma Rhei coarse powder, every part of 100g presses 1. A respectively
3B
2C
2D
32. A
2B
2C
2D
3The scheme reflux, extract, filters, and filtrate concentrates and is settled to 500ml, and precision is measured 1ml, put in the 25ml measuring bottle, add ethanol to scale, shake up, precision is measured 5ml, evaporate to dryness adds water 20ml, hydrochloric acid 2ml, chloroform 20ml, refluxed 1 hour, and put coldly, divide and to get chloroform solution, continue and extract with chloroform 20ml jolting, combined chloroform liquid, evaporate to dryness, residue add ethanol and quantitatively are transferred in the 5ml measuring bottle, add ethanol to scale, shake up, as need testing solution.According to high performance liquid chromatography (appendix VID of Chinese Pharmacopoeia version in 2000) test, reference substance and test condition are the same, the results are shown in Table 9.
Table 9 Radix Et Rhizoma Rhei return schemes confirmatory experiment
| The reference substance integrated value | A 3B 2C 2D 3 | A 2B 2C 2D 3 | |||
| Emodin | Chrysophanol | Emodin | Chrysophanol | Emodin | Chrysophanol |
| 435136 | 632443 | 770849 | 1620657 | 778471 | 1648789 |
| Content (%) | 0.252 | 0.367 | 0.254 | 0.373 | |
As shown in Table 9, two kinds of proof schemes all can obtain satisfied result, and actual in conjunction with producing, choosing No. 2 proof schemes is final Radix Et Rhizoma Rhei reflux, extract, scheme.
1.3.4 conclusion and process certification
According to orthogonal experiments, handle through mathematical statistics, we determine that best alcohol extraction technology is: add 7 times of amount 70% alcohol reflux 3 times, extracted 1 hour at every turn, collecting decoction filters, and concentrates spray and does.By this optimum process condition scale-up, feed intake 3 batches (each 521g) carry out process certification, and total extraction ratio of the every batch of emodin and chrysophanol is respectively: 87.1%, 88.6% and 89.3%.The result shows that this technology extraction is the most complete.
2. selection of spray drying condition and preparation technology's establishment
All the other five tastes recipe quantity decoction pieces add 12 times of water gagings and decocted 1.5 hours, filter, medicinal residues add 8 times of water gagings, decocted 1 hour, and filtered, medicinal liquid merges, the rhababerone extract merges, plate-and-frame filtration, filtrate decompression thin film concentration to relative density is the clear paste of 1.08～1.10 (50～60 ℃), chooses 1.08～1.10 (60 ℃), atomize when dry, granularity is moderate.As concentration rare (as 1.05～1.08), then atomized drop is little, and dry back dry extract granule is too thin, easily runs out of with dry gas stream, and drying loss is big.
Whether the spray drying condition is selected suitable, and product quality (as the reservation of color, mouthfeel, composition, the water content of dry extract etc.) is all had considerable influence.Drying condition comprises exsiccant inlet temperature, leaving air temp, tower internal pressure, charging rate etc.Result of the test shows: the spray drying inlet temperature should be selected 180 ℃, and temperature Gao Zeyi produces coking; Leaving air temp should be selected about 80 ℃, and leaving air temp is low, then the moisture of dry extract defective (moisture of granule should be lower than 5.0%).In sum, preparation of drug combination method of the present invention is: get Radix Et Rhizoma Rhei, be ground into coarse powder, add 7 times of amount alcohol reflux of 70% 3 times, and each 1 hour, put coldly, filter merging filtrate; The five tastes such as all the other Radix Glycyrrhizaes, decocting boils secondary, adding for the first time 12 times of water gagings decocted 1.5 hours, add for the second time 8 times of water gagings and decocted 1 hour, collecting decoction filters, filtrate and above-mentioned alcohol extract merge, it is the medicinal liquid of 1.08～1.10 (50～60 ℃) that concentrating under reduced pressure becomes relative density, and spray drying is made dried cream powder
Pharmacology, drug effect and toxicologic study result
Pharmacodynamic test of active extract, this product 8g/kg, 4g/kg, 2g/kg irritate stomach, observe the therapeutical effect to 2 kinds of renal failure models of rat.The result shows, this product to the serum urea nitrogen (BUN) of rat adenine renal failure model, creatinine (Cr) raises that remarkable inhibitory action is arranged, the decline of renal failure rat blood serum total protein (TP), albumin (ALB), hemoglobin (HB) also is significantly improved.To 5/6 nephrectomy model, the rising of BUN is significantly suppressed, other indexs also have improvement but are not remarkable.To normal rat paw inflammatory swelling, Mice Auricle inflammatory swelling, significant resist inflammation on repercussive function is arranged.Above result shows that this product has therapeutical effect to the kidney of rats failure model.Effective dose is converted to clinical consumption, and take granule 32g every day or 48g is advisable to be grown up
Acute toxicity test in mice gavages also deadly with this product heavy dose.The test of employing maximum dosage-feeding, mouse gavaging this product 100g/kg body weight is equivalent to medical material amount 250g/kg, for 217 times of clinical adult's consumption, observes 7, does not see the overt toxicity reaction.
The rat long term toxicity test adopts 160 of SD rats, 3 dosage group ig this product 40g/kg, 20g/kg, 10g/kg (be equivalent to medical material amount 100g/kg, 50g/kg, 25g/kg, high dose is 85 times of clinical adult's usual amounts), continuous 6 months.Overview during administration, administration mid-term, administration finish and convalescent period opisthosoma resurvey fixed, blood test, serum biochemistry check, organ coefficient is measured and the histopathology check, every index is normal substantially.The result shows that this product is oral for a long time, and the overt toxicity reaction does not appear in laboratory animal.
Embodiment
Embodiment 1: gets Radix Et Rhizoma Rhei 521g, is ground into coarse powder, add 7 times of amount alcohol reflux of 70% 3 times, and each 1 hour, put coldly, filter merging filtrate; All the other five tastes Radix Glycyrrhizae 417g, Radix Salviae Miltiorrhizae 417g, Poria 417g, Fructus Aurantii 209g, Concha Ostreae (calcined) 209g decoction pieces, decocting boils secondary, adds 12 times of water gagings for the first time and decocts 1.5 hours, adding for the second time 8 times of water gagings decocted 1 hour, collecting decoction filters, and filtrate and above-mentioned alcohol extract merge, it is the medicinal liquid of 1.08～1.10 (50～60 ℃) that concentrating under reduced pressure becomes relative density, spray drying is made dried cream powder 878g, adds dextrin and micropowder silica gel is an amount of, mixing, make granule, sieve, drying, make the 1000g granule, be distributed into every bag of 16g.
Embodiment 2: the dried cream powder among the embodiment 1, add an amount of magnesium sulfate, dextrin and micropowder silica gel, and mixing is granulated granulate, tabletting.
Embodiment 3: the dried cream powder among the embodiment 1, add an amount of magnesium sulfate, dextrin and micropowder silica gel, and mixing is granulated, and is encapsulated.
Embodiment 4: the dried cream powder among the embodiment 1, add an amount of magnesium sulfate, dextrin and micropowder silica gel, and granulate granulate, tabletting.
Embodiment 5: the concentrated solution among the embodiment 1 adds an amount of dextrin and micropowder silica gel, mixing, pill.
Embodiment 5: the concentrated solution among the embodiment 1, add an amount of soluble starch and sucrose, and mixing is made oral liquid.
Embodiment 6: preparation method is with embodiment 1, and just formula proportion changes into: Radix Et Rhizoma Rhei 30%, Radix Glycyrrhizae 15%, Radix Salviae Miltiorrhizae 15%, Poria 20%, Fructus Aurantii 10%, Concha Ostreae (calcined) 10%.
Embodiment 7: preparation method is with embodiment 1, and just formula proportion changes into: Radix Et Rhizoma Rhei 50%, Radix Glycyrrhizae 10%, Radix Salviae Miltiorrhizae 10%, Poria 15%, Fructus Aurantii 5%, Concha Ostreae (calcined) 10%.
Embodiment 8: preparation method is with embodiment 1, and just formula proportion changes into: Radix Et Rhizoma Rhei 10%, Radix Glycyrrhizae 20%, Radix Salviae Miltiorrhizae 20%, Poria 20%, Fructus Aurantii 15%, Concha Ostreae (calcined) 15%.
Claims (5)
1. pharmaceutical composition for the treatment of renal failure is characterized in that the active component and/or the pharmaceutically acceptable additives that are made by following raw materials according form:
Radix Et Rhizoma Rhei 20-40 weight % Radix Glycyrrhizae 10-20 weight %
Radix Salviae Miltiorrhizae 10-20 weight % Poria 10-20 weight %
Fructus Aurantii 1-20 weight % Concha Ostreae (calcined) 1-20 weight %
Wherein: described Radix Et Rhizoma Rhei is an ethanol water reflux, extract, 3 times of using separately 7 times of amount 70 weight %, extraction in each 1 hour forms, and other component blending water extracts and forms, and in pharmaceutical composition, the content of Radix Et Rhizoma Rhei must not be less than 0.2% in the amount of active ingredient emodin and chrysophanol.
2. the pharmaceutical composition of treatment renal failure according to claim 1 is characterized in that the active component and/or the pharmaceutically acceptable additives that are made by following raw materials according form:
Radix Et Rhizoma Rhei 20-30 weight % Radix Glycyrrhizae 15-20 weight %
Radix Salviae Miltiorrhizae 15-20 weight % Poria 15-20 weight %
Fructus Aurantii 5-10 weight % Concha Ostreae (calcined) 5-10 weight %
3. the pharmaceutical composition of treatment renal failure according to claim 1 is characterized in that the active component and/or the pharmaceutically acceptable additives that are made by following raw materials according form: Radix Et Rhizoma Rhei 521 grams, Radix Glycyrrhizae 417 grams, Radix Salviae Miltiorrhizae 417 grams, Poria 417 grams, Fructus Aurantii 209 grams and Concha Ostreae (calcined) 209 grams.
4. according to the preparation of drug combination method of the described treatment renal failure of one of claim 1-3, it is characterized in that getting earlier Radix Et Rhizoma Rhei, be ground into coarse powder, add the alcohol reflux 3 times of 7 times of amount 70 weight %, each 1 hour, put coldly, filter merging filtrate; All the other five tastes waters decoct secondary, add 12 times of water gagings for the first time and decoct 1.5 hours, add 8 times of water gagings for the second time and decoct collecting decoction 1 hour, filter, filtrate and above-mentioned alcohol extract merge, and concentrating under reduced pressure becomes medicinal liquid, spray drying is made dried cream powder, adds adjuvant and makes oral agents.
5. the preparation of drug combination method of treatment renal failure according to claim 4 is characterized in that wherein said peroral dosage form is granule, tablet, capsule, oral liquid or pill.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100034944A CN100372552C (en) | 2006-02-10 | 2006-02-10 | Pharmaceutical composition for treating renal failure and its preparation and application |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100034944A CN100372552C (en) | 2006-02-10 | 2006-02-10 | Pharmaceutical composition for treating renal failure and its preparation and application |
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| Publication Number | Publication Date |
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| CN1843429A CN1843429A (en) | 2006-10-11 |
| CN100372552C true CN100372552C (en) | 2008-03-05 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNB2006100034944A Active CN100372552C (en) | 2006-02-10 | 2006-02-10 | Pharmaceutical composition for treating renal failure and its preparation and application |
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| Country | Link |
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| CN (1) | CN100372552C (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1125582A (en) * | 1994-12-27 | 1996-07-03 | 湖南医科大学附属第二医院 | Medicine for treating renal failure |
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2006
- 2006-02-10 CN CNB2006100034944A patent/CN100372552C/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1125582A (en) * | 1994-12-27 | 1996-07-03 | 湖南医科大学附属第二医院 | Medicine for treating renal failure |
Non-Patent Citations (1)
| Title |
|---|
| 中医药诊疗慢性肾衰临床进展. 王常元等.天津中医，第16卷第3期. 1999 * |
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| Publication number | Publication date |
|---|---|
| CN1843429A (en) | 2006-10-11 |
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