Bio-fermentation technique for composite vegetable drug and vegetable fermented drug for treating nephritis
Technical Field The invention relates to a composite plant medicine biological fermentation process and vegetable fermented drug for the treatment of nephritis. Background Art In our people 4000 years ago will be using the microbial fermentation technology to microbrewery, future production sauce, vinegar, bean drum , soy sauce, foods such as strong. In the field of the processing of traditional Chinese medicine, not see a mixed with the adjuvant compound medicine, controlled in a certain temperature, humidity for fermentation, to be made into pharmaceutical technology. By using composite plant medicine biological fermentation production process for preparing pharmaceutical is a branch of modernization of traditional Chinese medicine, to its in-depth study will contribute to modernization and International standards. Content of the invention The purpose of this invention is to provide a composite plant medicine biological fermentation process, the process can improve the potency of the drug, changing the drug resistance, expansion of clinical indications, reduce toxic side effects. Another purpose of this invention is to prepare a vegetable fermented drug for the treatment of nephritis, the drug selection composite plant as the culture medium, at a specific time, humidity, the temperature, produced in the fermentation process of fungal microorganism, and improve the curative effect. 1st to realize a purpose of this invention, the technical scheme is composite plant medicine biological fermentation process steps are as follows: (1) pre-treatment: selecting plant medicine according to the formulation, to remove the woman, ovum, such as debris, cleaning, dewatering, the 65 ± 5 the drying [...] ; (2) pulverizing: the plant after completely dried crushed to 40 mesh; (3) sterilizing: conventional ultraviolet sterilizing; (4) according to the raw material formulation, with aseptic water in a stainless steel material by the step (2), (3) in plant powder, mix thoroughly; (5) fermentation culture: step (4) the resulting mixture, to the fermentation tank under aseptic conditions, to 80r/min stirring while adding, the temperature is 36.5 the the ± 0.5 [...] , relative humidity 75%-85%, ventilation 1m3/m3, carried out under the condition of the fermentation, the fermentation time 34-36 hours; (6) drying: the fermentation medicine in the 60 ± 5 the drying [...] ; (7) crushing: fermentation after drying crushed to 100 mesh; (8) is made according to the conventional method of any one of said formulation on pharmacy. To achieve another object of the present invention, the technical scheme is the vegetable fermented drug for treating nephritis is composed of the following weight proportion of the raw material: Radix et Rhizoma rhei palm leaf 8-12 licorice 3-7 gardenias 2-6 Bile 4-6 sterile water 8-12. The process for preparing the drug: (1) pre-treatment: according to the above-mentioned raw materials the weight ratio of plant medicine selected, removing the adherent ages, ovum, such as debris, cleaning, dewatering, the 65 ± 5 the drying [...] ; (2) pulverizing: the plant after completely dried crushed to 40 mesh; (3) sterilizing: conventional ultraviolet sterilizing; (4) under aseptic conditions, withdrawing bile, with aseptic water in a stainless steel mixing adjuvants barrel, then adding step (2), (3) the treated plant powder, mix thoroughly; (5) fermentation culture: step (4) the resulting mixture, to the fermentation tank under aseptic conditions, to 80r/min stirring while adding, the temperature is 36.5 the the ± 0.5 [...] , relative humidity 75%-85%, ventilation 1m3/m3, carried out under the condition of the fermentation, the fermentation time 34-36 hours; (6) drying: the fermentation medicine in the 60 ± 5 the drying [...] ; (7) crushing: fermentation after drying crushed to 100 mesh; (8) is made according to the conventional method of any one of said formulation on pharmacy. The weight ratio of the raw materials is: Radix et Rhizoma rhei palm leaf 9-11 licorice 4-6 gardenias 3-5 Bile 3-5 sterile water 9-11. The weight ratio of the raw materials is Radix et Rhizoma rhei palm leaf 10 licorice 5 gardenias 4 bile 4 sterilized water 10. The bile is bovine bile, porcine bile or chicken bile. Said medicine is on any kind of pharmacy that the dosage form. Said medicine is capsule. Composite vegetable drug of the present invention the biological fermentation process, the mixed compound with a sterilized water, controlled in a certain temperature, the humidity of the fermentation treatment. Therefore can improve the potency, change drug resistance, expansion of clinical indications, reduce toxic side effects. Its production process is simple, advanced technology, the operation is simple. Composite vegetable drug in the biological fermentation process, the microbial growth will produce various active substances, such as various enzyme, such as antibiotics, the chemical reaction of vegetable medicine, decomposing the original component, the effective ingredient a new; the microorganism in the fermentation process decomposition conversion capacity there is a strong, can produce abundant secondary metabolite, this metabolic product is also good drug, and in certain plant medicine synergistic effect of the active ingredient occurs, in order to increase the effect; of the microbes in the composite plant medicine in the special environment of the biological fermentation, generate a new metabolic reaction, the composite plant medicine a growth or the microorganism of this ingredient for promoting or inhibiting role is, to change the metabolism of the microorganisms, to form a new effective component or changing the proportion of each component; the decomposition of the microbe in a fermentation process for the decomposition of the toxic substances in and reduce toxicity. Because the growth of the microbe in a fermentation process need to be dynamic, vegetable protein, sugar, and the like and other nutritional substances play the role of the concentrated vegetable medicine. Microbial biodiversity as we have found that different kinds of plant medicine combined, produce different pharmacological, pharmacodynamic effects, generated in the human body and of different kind of physiologically active substances play an anti-viral, anti-tumor, anti-oxidation, reducing blood lipid, increase immunity and the like. The treatment of SD RAT animal model of nephritis experiment result 1, the experiment adopts passive Heymann nephritis RAT model, rapid onset, the practicability is strong. The invention is mainly characterized in that: the epithelial side of glomerular basement membrane immune complex deposition, urinary protein-based, the human membranous nephropathy similar pathological changes, both at home and abroad recognized nephritis model. 2, the medicine of the present invention used for SD RAT passive Heymann nephritis model therapeutic effect Passive Heymann nephritis model (using SD RAT the kidney brushesshape reason glycoprotein immune rabbit blood serum 1.5 ml/only) group, 48 only SD RAT is divided into 6 groups, the negative control (normal SD RAT), positive control (dexameth 3 × 10-4 g.kg-1), the drug of the present invention is high, middle, low (0.1, 0.2, 0.4g.kg-1) dose, model set. Each group of rats above except the negative control and model contrast, all intragastrically to the medicine, two times a day. Continuous administration 28 days. Weighing body weight per week, metabolic cage is, collection of 24-hour urine. After the end of the experiment, according to 30 mg. kg-1 intraperitoneal 2% sodium fifth heavenly stem compared to proper narcotic, exposed anocelia, heart blood sampling, separation of serum; heating the left kidney with 3% glutaraldehyde fixed, 4 the preservation [...] ; Observing the indicators and statistical method Weight, urine volume: once a week; serum: detecting serum creatinine (Cr), urea nitrogen (BUN), (TG) triglycerides, total cholesterol (T-CHO) content. Urine: detecting protein content, the volume of the urine. Kidney: scanning electron microscope observation kidney perspective electron microscope inspection. Statistical method: the SPSS11.0 for analysis of variance. Experimental results (1), the drug of the present invention the passive Heymann nephritis RAT urine protein content of Heymann nephritis RAT subjected to a test drug and positive control group intragastrically 14d, compared with the model control group, the urinary protein content is reduced, there is significant difference, with highly significant difference of high dosage. Negative contrast comparison with the model, after manufacturing, to medicine 7, 14d is highly significant difference, 21d, 28d there is significant difference. High, in, the low-dose group 21d, 28d is compared with the negative control group no obvious differences. Results are shown in table 1. Table 1 the drug to the passive Heymann nephritis RAT urine protein content of (n=9, x±s) The dose groups after being 7d 14d 21d 28d (g.Kg-1) mg. 24h-1 mg. 24h-1 mg. 24h-1 mg. 24h-1 mg. 24h-1 Negative contrast 3.853±1 . 749 3.656±1 . 292 3.557±1 . 991 * 3.595±2 . 327 * 5.454±2 . 926* Model comparison 15.392±3 . 535 ## 17.805±1 . 882 ## 14.402±4 . 369 ## 9.618±4 . 941 # 9.554±2 . 133# High dose 0.40 15.111±2 . 473 18.394±3 . 836 6.414±2 . 635 ** 4.758±1 . 668 4.560±1 . 820 Dosage in 0.20 13.367±4 . 020 17.104±2 . 979 7.468±2 . 818 * 5.742±3 . 026 5.234±0 . 954 Low doses of 0.10 13.757±1 . 100 16.069±5 . 230 8.908±1 . 986 * 3.933±2 . 247 * 5.085±2 . 209 Positive contrast 3 × 10-3 14.683±3 . 432 15.628±3 . 395 12.722±2 . 709 * 9.323±3 . 863 7.768±2 . 536 Notes: comparison with the model, *P <0.05, **P <0.01 Compared with the negative control, #P <0.05, ##P <0.01 (2), the drug of the present invention the passive Heymann nephritis the effects of RAT urine Heymann nephritis RAT subjected to dry reagent, in, low-dose and positive control drug delivery 14d, compared with the negative control, high, middle, low-dose group 24h reducing urine, there is significant difference, the dosage in comparison with the model there is significant difference. Negative contrast with model comparisons, 14d there is significant difference, high dosage 21d, 28d is compared with the negative control group no obvious difference, note a diuretic effects of high dosage, results shown in table 2. Table 2. Compound Ganong yellow Heymann nephritis RAT passive capsule in the impact of urine (n=9, x±s) The dose groups after being 7d 14d 21d 28d (g.Kg-1) ml ml ml ml ml Negative contrast 25.111±7 . 785 31.113±9 . 252 36.778±9 . 361 * 19.713±4 . 619 30.367±8 . 097 Model comparison 15.910±3 . 764 25.300±1 . 889 15.400±3 . 380 # 25.540±8 . 598 12.20±4 . 461# High dose 0.40 14.375±4 . 749 25.083±3 . 541 17.083±5 . 766 # 22.167±3 . 532 30.017±9 . 673 Dosage in 0.20 14.313±6 . 524 17.125±3 . 613 30.083±9 . 140 * 20.333±5 . 716 11.083±4 . 737# Low doses of 0.10 13.563±3 . 977 12.625±2 . 200 * 18.333±3 . 077 # 12.500±6 . 052 * 13.700±1 . 342 ## Positive contrast 3 × 10-3 11.125±4 . 650 26.938±7 . 048 15.967±3 . 262 # 15.341±5 . 432 # 14.912±6 . 135# Notes: comparison with the model, *P <0.05 **P <0.01 ; #P with negative comparisons <0.05 ##P <0.01 (3), the drug of the present invention the passive Heymann nephritis RAT influence of the weight of the Heymann nephritis RAT the low-dose group 7d and positive control group compared with the negative control, reduce the weight, there is significant difference, the other group have no significant difference. Results are shown in table 3. Table 3. The passive Heymann nephritis the impact of body weight of the RAT (n=9 ±s) The dose groups after being 7d 14d 21d 28d (g.Kg-1) g g g g g Negative control - 248.44±12 . 69 311.13±20 . 57 334.22±26 . 75 326.44±33 . 34 342.33±34 . 35 Model comparison - 231.40±9 . 73 314.20±16 . 75 336.80±24 . 47 351.80±34 . 11 345.83±20 . 92 High dose 0.40 235.00±15 . 33 272.00±30 . 98 309.00±18 . 94 274.33±119 . 92 343.67±29 . 12 Dosage in 0.20 226.38±7 . 64 285.85±38 . 26 314.67±33 . 88 321.17±27 . 30 351.67±27 . 43 Low doses of 0.10 227.69±4 . 70 267.71±28 . 03 # 284.83±29 . 61 294.80±13 . 37 300.00±20 . 92 Positive contrast 3 × 10-3 232.56±11 . 67 232.50±11 . 81 # 207.83±27 . 97 # 190.91±31 . 21 # 185.94±47 . 14# Notes #P <0.05 (compared with the negative control) (4), the drug of the present invention the passive Heymann nephritis RAT serum creatinine, urea nitrogen, triglyceride, the impact of total cholesterol Heymann nephritis RAT serum creatitine: high, medium, low dose comparison with the model, is obviously reduced, there is significant difference, with the model comparisons of the low dose, a highly significant difference; serum urea nitrogen: the model comparisons of the low dose, is obviously reduced, there is significant difference; serum triglyceride: high, in comparison with the model dosage, there is significant difference, with the model comparisons of the low dose, a highly significant difference; results are shown in table 4. Table 4. The RAT serum to the passive Heymann nephritis creatnine, urea nitrogen, triglyceride, The impact of the total cholesterol content (n=9, x±s) Constituency dose creatnine urea nitrogen total cholesterol, triglycerides (g.Kg-1) μmol/L mmol/L mmol/L mmol/L Negative contrast 42.903±7 . 894 * 3.654±0 . 796 * 1.939±0 . 951 0.303±0 . 109 Model comparison 57.528±6 . 826 7.935±1 . 064 4.552±0 . 442 0.650±0 . 281 High dose 0.40 39.353±6 . 146 * 6.458±1 . 437 1.714±0 . 487 0.418±0 . 164* Dosage in 0.20 40.635±4 . 578 * 5.761±1 . 489 1.913±0 . 467 0.341±0 . 095* Low doses of 0.10 35.229±9 . 357 ** 4.950±1 . 064 * 2.786±0 . 390 0.496±0 . 279 ** Notes: comparison with the model, *P <0.05, **P <0.01; compared with the negative control, #P <0.05 Mode of execution Embodiment 1: vegetable fermented drug for the treatment of nephritis the process: According to the weight ratio of the raw material formulation: palm leaf Chinese rhubarb 10, licorice 5, gardenias 4, bile 4, the sterilized water 10; (1) pre-treatment: plant medicine formulation selected according to the raw material, to remove the plant by woman, ovum, such as debris, cleaning, dewatering, the 65 ± 5 the drying [...] ; (2) pulverizing: the plant of all dry crushed to 40 mesh; (3) sterilizing: conventional ultraviolet sterilizing; (4) under aseptic conditions, takes the cow bile, with aseptic water in a stainless steel mixing adjuvants barrel, then adding step (2), (3) in plant powder, mix thoroughly; (5) fermentation culture: step (4) the resulting mixture, to the fermentation tank under aseptic conditions, to 80r/min stirring while adding, the temperature is 36.5 the the ± 0.5 [...] , relative humidity 75%-85%, ventilation 1m3/m3, carried out under the condition of the fermentation, the fermentation time 34-36 hours; (6) drying: the fermentation medicine in the 60 ± 5 the drying [...] ; (7) crushing: fermentation after drying crushed to 100 mesh; (8) dispensing capsule machine: 1, capsule, each bottle 60 granulata, label, packaging, each box 10 bottle. Usage consumption; according to the usage and the dosage of different determining the condition of a patient, daily oral 2--3 times, each 4--6 granulata. This medicine curative effect is prominent, convenient, safe and effective, which is suitable for long-term use. Embodiment 2: used for the treatment of lobar pneumonia, pulmonary infection. The Staphylococcus aureus, white Staphylococcus, Streptococcus pneumoniae negational. The drug of the present invention is made is composed of the following components : (by the consumption amount is) Honeysuckle 10 arundinella Chrysanthemum 10 sterilized water 10 Herba Taraxaci (taraxacum, dandelion) 5 Chinese violet 4 1, preprocessing: the above-mentioned various plant medicine removing the adherent ages, ovum, such as debris, cleaning, dewatering, the 65 ± 5 the drying [...] ; 2, crushing: the plant after completely dried crushed to 40 mesh; 3, sterilization: conventional ultraviolet sterilizing; 4, according to the raw material formulation, the stainless steel ingredients added to the above powder in the barrel, mixed with sterile water; 5, fermentation culture: the step 4 in the absence of the resulting mixture of the fermentation tank to move down to, stirring while adding (80r/min), the temperature is 36.5 the the ± 0.5 [...] , relative humidity 75%-85%, ventilation 1m3/m3, carried out under the condition of the fermentation, the fermentation time 34-36 hours; 6, drying: the fermentation medicine in the 60 ± 5 the drying [...] ; 7, crushing: fermentation after drying crushed to 100 mesh; 8, packing: fermentation powder in the capsule. Embodiment 3: used for the treatment of coronary heart disease, arrhythmia, heart failure. The drug of the present invention is made is composed of the following components : (the amount of parts by weight) Orange rind 6 Poria (Indian bread) 4.5 rehmanniae 3 schizandrae 1.5 licorice 1.5 sterile water 6 1, preprocessing: the above-mentioned various plant medicine removing the adherent ages, ovum, such as debris, cleaning, dewatering, the 65 ± 5 the drying [...] ; 2, crushing: the plant after completely dried crushed to 40 mesh; 3, sterilization: conventional ultraviolet sterilizing; 4, according to the raw material formulation, the stainless steel ingredients added to the above powder in the barrel, mixed with sterile water; 5, fermentation culture: the step 4 in the absence of the resulting mixture of the fermentation tank to move down to, stirring while adding (80r/min), the temperature is 36.5 the the ± 0.5 [...] , relative humidity 75%-85%, ventilation 1m3/m3, carried out under the condition of the fermentation, the fermentation time 34-36 hours; 6, drying: the fermentation medicine in the 60 ± 5 the drying [...] ; 7, crushing: fermentation after drying crushed to 100 mesh; 8, packing: fermentation powder in the capsule. The invention relates to a bio-fermentation technique for composite vegetable drug and vegetable fermented drug for treating nephritis, wherein the bio-fermentation technique consists of compound recipe medicament and sterilized water, which is prepared by using composite plants as the culture medium, and carrying out fermentation treatment under predetermined time, temperature and degree of humidity. 1, a composite plant medicine biological fermentation process, the process steps are as follows: (1) pre-treatment: selecting plant medicine according to the formulation, to remove the woman, ovum, such as debris, cleaning, dewatering, the 65 ± 5 the drying [...] ; (2) pulverizing: the plant after completely dried crushed to 40 mesh; (3) sterilizing: conventional ultraviolet sterilizing; (4) the formulation according to the raw material, the stainless steel with the sterilized water to add adjuvants barrel by the step (2), (3) in plant powder, mix thoroughly; (5) fermentation culture: step (4) the resulting mixture, to the fermentation tank under aseptic conditions, to 80r/min stirring while adding, the temperature is 36.5 the the ± 0.5 [...] , relative humidity 75%-85%, ventilation 1m3/m3, carried out under the condition of the fermentation, the fermentation time 34-36 hours; (6) drying: the fermentation medicine in the 60 ± 5 the drying [...] ; (7) crushing: fermentation after drying crushed to 100 mesh; (8) is made according to the conventional method of any one of said formulation on pharmacy. 2, a vegetable fermented drug for the treatment of nephritis, characterized in that it is comprised of the following weight proportion of the raw material: Radix et Rhizoma rhei palm leaf 8-12 licorice 3-7 gardenias 2-6 Bile 4-6 sterile water 8-12; The process for preparing the drug: (1) pre-treatment: according to the above-mentioned raw materials the weight ratio of plant medicine selected, removing the adherent ages, ovum, such as debris, cleaning, dewatering, the 65 ± 5 the drying [...] ; (2) pulverizing: the plant after completely dried crushed to 40 mesh; (3) sterilizing: conventional ultraviolet sterilizing; (4) bile is taken out under aseptic conditions, the times with sterile water mixed in a stainless steel adjuvants barrel, then adding step (2), (3) the treated plant powder, mix thoroughly; (5) fermentation culture: step (4) the resulting mixture, to the fermentation tank under aseptic conditions, to 80r/min stirring while adding, the temperature is 36.5 the the ± 0.5 [...] , relative humidity 75%-85%, ventilation 1m3/m3, carried out under the condition of the fermentation, the fermentation time 34-36 hours; (6) drying: the fermentation medicine in the 60 ± 5 the drying [...] ; (7) crushing: fermentation after drying crushed to 100 mesh; (8) is made according to the conventional method of any one of said formulation on pharmacy. 3, vegetable fermented drug for the treatment of nephritis according to Claim 2, characterized in that the weight ratio of the raw materials is: Radix et Rhizoma rhei palm leaf 9-11 licorice 4-6 gardenias 3-5 Bile 3-5 sterile water 9-11. 4, vegetable fermented drug for the treatment of nephritis according to Claim 2, characterized in that the weight ratio of the raw materials is Radix et Rhizoma rhei palm leaf 10 licorice 5 gardenias 4 bile 4 sterilized water 10. 5, according to claim 2, 3 or 4 wherein the vegetable fermented drug for treating nephritis, characterized in that the bile is bovine bile, porcine bile or chicken bile. 6, according to claim 2, 3 or 4 wherein the vegetable fermented drug for treating nephritis, characterized in that the medicine is any said formulation on pharmacy. 7, vegetable fermented drug for the treatment of nephritis according to Claim 6, characterized in that the medicine is capsule.