CN101357213B - Compound cantharis liquid formulation and preparation method thereof - Google Patents
Compound cantharis liquid formulation and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a compound cantharis liquid preparation and a preparation method thereof, and the compound cantharis liquid preparation is prepared by cantharis, ginseng, radix astragali, acanthopanax, sparganium, herba scutellariae barbatae, rhizoma zedoariae, common macrocarpium fruit, glossy privet fruit, bear bile powder, liquorice and appropriate auxiliary materials. The invention adopts the methods of water extraction, ethanol depositing and centrifugation to extract, the extraction yield is high, water extract liquid is uniform, the stability is good, no residual solvent exist,and the production cost is lower; the rest nine drug ingredients except the bear bile powder and the cantharis are extracted by adopting the method of water decoction; meanwhile, the active ingredient of total saponin extracted from the nine drug ingredients is purified by using macroporous resin column, so that the purity quotient reaches over 55%; the extracted amyloses is purified by adopting the method of ethanol depositing for a plurality of times or hollow fiber column ultrafiltration. The preparation method combines the traditional Chinese medicine and advanced preparation technique, applies the modern scientific method and is on the basis of various scientific and clinical experiments and studies, as well as the summary of a great deal of documents and materials; the obtained compound cantharis oral preparation has high bioavailability and more remarkable drug action.
Description
Technical field: the present invention relates to a kind of compound cantharis liquid formulation and preparation method thereof, belong to the technical field of herbal pharmaceutical.
Background technology: compound mylabris preparation is a kind of to have that removing blood stasis is become thin, the medicine of the effect of counteracting toxic substances phagedenoma.Wherein FUFANG BANMAO JIAONANG is recorded kind for " health ministry drug standard " the 17 in Chinese traditional patent formulation preparation.The side by Mylabris, Radix Ginseng, the Radix Astragali, Radix Et Caulis Acanthopanacis Senticosi, rhizoma sparganic, Herba Scutellariae Barbatae, Rhizoma Curcumae, Fructus Corni, Fructus Ligustri Lucidi, Fel Ursi powder, Radix Glycyrrhizae totally ten simply medicine forms, be one of better medicine for the treatment of primary hepatocarcinoma, pulmonary carcinoma, rectal cancer, malignant lymphoma, gynecologic malignant tumor etc.In recent years, the sickness rate of pulmonary carcinoma, primary hepatocarcinoma, colorectal cancer, gynecologic malignant tumor etc. rises year by year, has become the modal malignant tumor of serious harm human health, brings many constant for our society, economy, life.
The method of producing compound mylabris preparation has a lot, and wherein, the extraction of monarch drug Mylabris has that powder directly is used as medicine, chloroform soaks and extracts or the extraction of chloroform percolation in the side; Radix Ginseng, Fructus Corni, Fructus Ligustri Lucidi, Herba Scutellariae Barbatae four Chinese medicine material or be ground into fine powder and be used as medicine, or adopt water carry/pure extracting method obtains the clear paste concentrated solution; The five tastes such as the Radix Astragali decoct with water and are condensed into thick paste; Fel Ursi powder is dissolved in water.But find after deliberation, access medicines such as Mylabris, Radix Ginseng, Fructus Corni, Fructus Ligustri Lucidi, Herba Scutellariae Barbatae can cause the impurity content height in the above-mentioned dosage form technology, be that solvent extracts and can cause that solvent has residual in leaching process with the chloroform, therefore bring inconvenience to formulation preparation, be unfavorable for the quality control of product; Simultaneously, be mixed with different dosage form with the powder medicine, the extraction separation purification imperfection of its effective ingredient behind thick paste after product is and concentrates or the clear paste convection drying.
At present, cantharides series of products on the market and that produce in application have cantharides granule, tablet, capsule, pill, chewable tablet etc., are a kind of classical Chinese patent medicines.Its prescription is formed rationally, compatibility appropriately has the good and clinical curative effect support.Its route of administration is oral, and oral formulations is that the process gastrointestinal absorption enters body circulation and then performance curative effect, has shortcomings such as onset is slow, absorption is incomplete, bioavailability is low; Simultaneously, to the patient of oral inconvenience, the application of oral formulations has limitation.
Summary of the invention:
At above the deficiencies in the prior art, research worker of the present invention is through a large amount of experiments, and compound cantharis liquid formulation of a kind of good stability, absorptions is abundant, rapid-action, curative effect is high confession drug administration by injection and preparation method thereof is provided.Mylabris among the present invention adopts more scientific methods to extract, and makes that the cantharidin content in the preparation obviously improves; Adopt decocting cooking method, infusion process extraction all the other nine flavor medical materials except that Fel Ursi powder, Mylabris, avoided Radix Ginseng, Fructus Corni, Fructus Ligustri Lucidi, Herba Scutellariae Barbatae four Chinese medicine material directly to pulverize the too high shortcoming of impurity content of being used as medicine and causing; Simultaneously the total saponins effective site of extracting in this nine flavors medical material is carried out purification, its purity is reached more than 45%; To the polysaccharide that nine flavors such as Radix Ginseng extract, adopt repeatedly alcohol deposition method or purify the collection component that pharmacological action is good, untoward reaction is little with hollow fiber column ultrafilter.At last Mylabris extract, total saponin extracts and polysaccharide active component are prepared ejection preparation together.
The objective of the invention is to disclose a kind of compound cantharis liquid formulation.Another object of the present invention is the preparation method that discloses this compound cantharis liquid formulation.This liquid preparation comprises transfusion, lyophilized injectable powder and aqueous injection.The compound cantharis liquid formulation effective component content of the inventive method preparation is higher, can reach the effect that improves bioavailability.
Compound cantharis liquid formulation of the present invention is to constitute like this: composition by weight is: Mylabris 0.6-6 part, Radix Ginseng 1.5-15 part, Radix Astragali 7.5-100 part, Radix Et Caulis Acanthopanacis Senticosi 7.5-100 part, rhizoma sparganic 2.4-24 part, Herba Scutellariae Barbatae 9-100 part, Rhizoma Curcumae 2.4-24 part, Fructus Corni 3-30 part, Fructus Ligustri Lucidi 3-30 part, Fel Ursi powder 0.05-1.0 part, Radix Glycyrrhizae 1.5-15 part.
The present invention is achieved through the following technical solutions:
One: the Mylabris extract preparation
The extract of Mylabris is by obtaining Mylabris decocting in water, precipitate with ethanol, centrifugation method.
Concrete preparation method is: powder of cantharide is broken into coarse powder, decocts with water, extracting liquid filtering precipitates with ethanol then, filters, and concentrates, be dissolved in water, and high speed centrifugation, centrifugal liquid concentrates, and drying is pulverized, promptly.
Method is more specifically: get Mylabris, be ground into 40-60 purpose coarse powder, add the water that 15-25 doubly measures, soaked 30-50 minute, water is carried 2-3 time, rises for the second time to add the water that 10-15 doubly measures at every turn, extracts 0.5-1.5 hour, filters, merging filtrate adds ethanol and reaches 60%-80% to containing the alcohol amount, leaves standstill, and filters, filtrate decompression is condensed into thick paste, adds the water that 6-10 doubly measures, and stirs, and leaves standstill, filter, filtrate is with the centrifugal 10-25 of the speed more than 10000 rev/mins minute, the centrifugal liquid concentrating under reduced pressure, drying is pulverized, promptly.
Two: the extraction of nine flavor medical materials such as Radix Ginseng
Get nine flavor medical materials such as all the other Radix Ginsengs except that Fel Ursi powder, the Radix Astragali, the water of doubly measuring with 6-12 extracts 2-3 time by decocting method, infusion process, merge extractive liquid,, filter, filtrate decompression is condensed into relative density and is the medicinal liquid of 1.05-1.20 at 60 ℃, adds ethanol to containing the alcohol amount for 50%-70%, leaves standstill 24 hours, filter, must precipitate and supernatant.
1, total saponin extracts preparation
Total saponin extracts is by the extracting solution with Radix Ginseng etc., goes up later polyamide column with water precipitation, washes with water earlier to colourless, use the 50%-60% ethanol elution again instead, collect ethanol elution, decompression recycling ethanol, macroporous adsorptive resins on the concentrated solution, wash with water earlier to colourless, use the 50%-80% ethanol elution again instead, collect ethanol elution, concentrating under reduced pressure, drying, promptly.
Concrete preparation method is: with the extracting solution of nine flavor medical materials such as Radix Ginseng, the Radix Astragali, concentrating under reduced pressure becomes thick paste, the water that adds 10 times of amounts, stirring is left standstill, filter, the polyamide column of having handled well on the filtrate washes with water earlier to colourless, use the 50%-60% ethanol elution that 5-8 doubly measures again instead, collect ethanol elution, decompression recycling ethanol, the macroporous adsorptive resins of having handled well on the concentrated solution, wash with water earlier to colourless, use the 50%-80% ethanol elution again instead, collect ethanol elution, concentrating under reduced pressure, drying, promptly.
2, polysaccharide active component preparation
The active component of polysaccharide is that drying under reduced pressure is dissolved in water by the precipitation with nine flavor medical materials such as above-mentioned Radix Ginseng, the Radix Astragali, and precipitate with ethanol leaves standstill, and filters, and precipitation is dissolved in water, and crosses hollow fiber column ultrafilter, and it is dried that ultrafiltrate is evaporated to; The gained precipitation is dissolved in water after perhaps getting the secondary precipitate with ethanol, and precipitate with ethanol leaves standstill, and filters, and gets precipitation with an amount of absolute ethanol washing, promptly.
Concrete preparation method is: with the precipitation of nine flavor medical materials such as above-mentioned Radix Ginseng, the Radix Astragali, the decompression cold drying, add an amount of dissolved in distilled water, add ethanol and reach 50-85% to containing the alcohol amount, left standstill 24 hours, and filtered, the precipitation adding distil water is dissolved into the solution of 1-2%, cross hollow fiber column ultrafilter (molecular cut off is greater than 6000), ultrafiltrate is evaporated to dried; Get perhaps that the gained precipitation adds an amount of dissolved in distilled water again behind the secondary precipitate with ethanol, add ethanol and reach 50-85%, left standstill 24 hours, filter, get precipitation with an amount of absolute ethanol washing 1-2 time, promptly to containing the alcohol amount.
Macroporous adsorbent resin in the above-mentioned preparation method is nonpolar or low pole, comprises D101 type, DA-201 type, AB-8 type etc.
So extraction process of the present invention is: Fang Zhongshi simply, except that Fel Ursi powder, powder of cantharide is broken into 40-60 purpose coarse powder, add the water that 15-25 doubly measures, soaked 30-50 minute, water is carried 2-3 time, rise for the second time and add the water that 10-15 doubly measures at every turn, extracted 0.5-1.5 hour, and filtered merging filtrate, add ethanol and reach 60%-80% to containing the alcohol amount, leave standstill, filter, filtrate decompression is condensed into thick paste, add the water that 6-10 doubly measures, stir, leave standstill, filter, filtrate was with the centrifugal 10-25 of the speed more than 10000 rev/mins minute, the centrifugal liquid concentrating under reduced pressure, drying is pulverized standby; 9 flavors such as all the other Radix Ginsengs extract 2-3 time by decocting method, infusion process with the water that 6-12 doubly measures, and merge extractive liquid, filters, filtrate decompression is condensed into relative density and is the medicinal liquid of 1.05-1.20 at 60 ℃, adds ethanol to containing the alcohol amount for 50%-70%, leaves standstill 24 hours, filter, must precipitate and supernatant.The supernatant concentrating under reduced pressure becomes thick paste, adds the water of 10 times of amounts, and stirring is left standstill, filter, the polyamide column of having handled well on the filtrate washes with water earlier to colourless, use the 50%-60% ethanol elution that 5-8 doubly measures again instead, collect ethanol elution, decompression recycling ethanol, the macroporous adsorptive resins of having handled well on the concentrated solution, wash with water earlier to colourless, use the 50%-80% ethanol elution again instead, collect ethanol elution, concentrating under reduced pressure, drying for standby; Get precipitation decompression cold drying, add an amount of dissolved in distilled water, add ethanol and reach 50-85% to containing the alcohol amount, left standstill 24 hours, and filtered, the precipitation adding distil water is dissolved into the solution of 1-2%, cross hollow fiber column ultrafilter (molecular cut off is greater than 6000), ultrafiltrate is evaporated to dried; Get perhaps that the gained precipitation adds an amount of dissolved in distilled water again behind the secondary precipitate with ethanol, add ethanol and reach 50-85%, left standstill 24 hours, filter, get precipitation with an amount of absolute ethanol washing 1-2 time, promptly to containing the alcohol amount.
Liquid preparation of the present invention comprises infusion preparation, freeze-dried powder and hydro-acupuncture preparation.
The preparation method of infusion solution of the present invention is: get above-mentioned Mylabris extract, total saponin extracts, polysaccharide active component and dissolve with water for injection, add Fel Ursi powder again and make dissolving, regulate to wait and oozes, adjust pH 4.0-5.5, filter with 0.22 μ m microporous filter membrane, sterilization is prepared into infusion solution.Isoosmotic adjusting agent in the infusion solution of the present invention can be one or more the compositions in glucose, xylitol, sorbitol, sodium chloride, calcium chloride, magnesium chloride, potassium chloride, sodium lactate and the dextran etc.
The preparation method of lyophilized injectable powder of the present invention is: get above-mentioned Mylabris extract, total saponin extracts, polysaccharide active component and dissolve with water for injection, add Fel Ursi powder again and make dissolving, add freeze-dried excipient, adjust pH 4.0-5.5, filter with 0.22 μ m microporous filter membrane, lyophilization is prepared into lyophilized injectable powder.Wherein freeze-dried excipient can be one or more the compositions in mannitol, fructose, glucosan, dextran, the polyethylene pyrrole Lip river alkane ketone etc.
The preparation method of aqueous injection of the present invention is: get above-mentioned Mylabris extract, total saponin extracts, polysaccharide active component and dissolve with water for injection, add Fel Ursi powder again and make dissolving, adjust pH 4.0-5.5 filters with 0.22 μ m microporous filter membrane, and sterilization is prepared into aqueous injection.
Compared with prior art, the present invention is based on FUFANG BANMAO JIAONANG, the preparation process of traditional Chinese medicine with the advanced person combined, the utilization modern scientific method, new product newly developed on the basis of summing up in conjunction with the experimentation of Chemistry for Chinese Traditional Medicine, analytical chemistry, pharmacology of Chinese materia medica and clinical efficacy thereof and amount of literature data.The present invention with water carry, precipitate with ethanol, centrifugation method extract the Mylabris medical material, the extraction ratio height, water extract homogeneous, good stability, no solvent residue, production cost is lower; Adopt decocting cooking method extraction all the other nine flavor medical materials except that Fel Ursi powder, Mylabris, avoided Radix Ginseng, Fructus Corni, Fructus Ligustri Lucidi, Herba Scutellariae Barbatae four Chinese medicine material directly to pulverize the too high shortcoming of impurity content of being used as medicine and causing; The total saponins effective ingredient that extracts is carried out purification with macroporous resin column, purity is reached more than 55%; Adopt repeatedly the method for precipitate with ethanol or hollow fiber column ultrafilter to purify to the polysaccharide that extracts.The product bioavailability that obtains is higher, and drug effect is more remarkable.
At preparation technology of the present invention, the applicant has carried out great deal of experimental, and is specific as follows:
Experiment 1: Mylabris extract technological experiment research
Main component contained in the Mylabris is a cantharidin etc., and with reference to ministry standard with publication, we have selected for use chloroform, water to extract as solvent simultaneously, or Mylabris directly is ground into fine powder and is used as medicine, content with cantharidin is index, and distinct methods is compared, and the result is as follows:
| Test method | Chloroform extraction | Water extraction | Directly be used as medicine |
| Cantharidin content (mg/g) | 12.11 | 14.46 | 10.78 |
By above assay result as can be seen, adopt water extracting method of the present invention to prepare Mylabris extract, its content is higher than chloroform extraction and directly is used as medicine, and chloroform belongs to toxic organic solvent, having residually in preparation, is rational so select preparation method of the present invention for the extraction of effective ingredient in the Mylabris.
Experiment 2: nine flavor Study on extraction such as Radix Ginseng
According to process conditions of the present invention, prepare three batches of total saponin extracts, be index with the content and the total saponin content of scutellarin, the results are shown in following table.
The extraction process experimental result
| Tested number | Scutellarin content (mg/g) | Total saponin content (%) |
| 1 | 0.9315 | 78.8 |
| 2 | 0.9427 | 81.5 |
| 3 | 0.9588 | 83.2 |
| Meansigma methods | 0.9443 | 81.2 |
| RSD(％) | 1.45 | 2.73 |
By experimental result as seen, the scutellarin average content is 0.9443, and RSD is 1.45%, and total saponin content is 81.2%, and RSD is 1.45%, proves that this process stabilizing is feasible, and is quality controllable.
Experiment 3: preparation of the present invention is to experiment mice transplanted tumor S
180, H
22Inhibitory action
One, material
1, animal: laboratory animal: Kunming mouse, body weight 18-22g, male and female half and half.
2, medicine: medicine of the present invention, commercially available FUFANG BANMAO JIAONANG.
Two, method and result
1, to mice transplanted tumor S
180Influence:
Get the good S of tumor growth
180Mice, aseptic condition extract ascites down, and by dilution in 1: 3, microscopically was counted with physiological saline solution, and transferring the oncocyte number is 1.0 * 10
7Individual/ml (putting in the ice bath).Get the subcutaneous vaccination of 0.2ml mice armpit then, weigh after 24 hours.Get trial drug, dosage is a matched group: normal saline 20ml/kg; Commercially available FUFANG BANMAO JIAONANG group: 2.0g/kg; Medicine group of the present invention: 2.0g crude drug/kg.Be administered once every day, and continuous ten days, after the last administration 24 hours, get mice and put to death the dissection tumor according to a conventional method, weigh.The results are shown in following table.
To mouse entity tumor S
180Influence
| Group | Tumor body weight (g) | Suppression ratio (%) |
| Matched group | 1.87 | - |
| Commercially available | 1.36 | 27.3 |
| Medicine group of the present invention | 1.19 | 36.4 |
2, to mice transplanted tumor H
22Influence:
Get the well-grown H in back that goes down to posterity
22Mice, aseptic condition extract down ascites, add 4 times of amount physiological saline solution mixings, and it is subcutaneous to be inoculated in mice right fore axillary fossa place, every inoculation 0.2ml, random packet after 24 hours, tail vein injection administration and gastric infusion, dosage is the same, and be administered once every day, continuous ten days.Day by day write down the dead mouse situation of respectively organizing after the last administration, calculate and respectively organize mice The average survival time natural law, calculate increase in life span.The results are shown in following table.
To mice H
22The influence of ascites tumor
| Group | The The average survival time natural law | Rate elongation (%) |
| Matched group | 11.6 | - |
| Commercially available | 14.5 | 25.0 |
| Medicine group of the present invention | 15.2 | 31.0 |
According to above experimental result, the cantharides ejection preparation can obviously suppress mice inhibition tumor S
180Growth, it is heavy to reduce tumor; To mouse inoculation H
22Certain prolongation effect is arranged the life cycle behind the ascites tumor.Owing between the treatment group significant difference (P＜0.05) is arranged, so preparation group of the present invention and commercially available FUFANG BANMAO JIAONANG group are relatively, under the identical situation of clinical consumption, preparation group of the present invention contrasts the better efficacy of commercially available FUFANG BANMAO JIAONANG, and bioavailability is higher.
Show through experimental study: preparation technology of the present invention has stronger science, feasibility, and the gained sample quality is stable, meets the prescription of treatment.This product route of administration is a drug administration by injection, need not digest and assimilate through gastrointestinal, has determined curative effect, the fast characteristics of special effect.Expanded the administering mode of this medicine, be convenient to extensive patients and use.
The specific embodiment:
The embodiment of the invention 1: Mylabris 3.97g, Radix Ginseng 9.92g, Radix Astragali 49.58g, Radix Et Caulis Acanthopanacis Senticosi 49.58g, rhizoma sparganic 15.83g, Herba Scutellariae Barbatae 59.5g, Rhizoma Curcumae 15.83g, Fructus Corni 19.83g, Fructus Ligustri Lucidi 19.83g, Fel Ursi powder 0.4g, Radix Glycyrrhizae 9.92g
Preparation method is: Fang Zhongshi simply, except that Fel Ursi powder, powder of cantharide is broken into 60 purpose coarse powder, water is carried 3 times, adds the water of 20 times of amounts for the first time, soaks 40 minutes, extracted 1.5 hours, second and third time adds the water of 15 times of amounts at every turn, extracts 1.0 hours, filter, merging filtrate adds ethanol and reaches 80% to containing the alcohol amount, leave standstill, filter, filtrate decompression is condensed into thick paste, adds the water of 8 times of amounts, stir, leave standstill, filter filtrate centrifugal 20 minutes with 10000 rev/mins speed, the centrifugal liquid concentrating under reduced pressure, drying is pulverized, promptly;
Get 9 flavor medical materials such as all the other Radix Ginsengs, pulverize, with the water of 10 times of amounts by decocting method, infusion process extraction 3 times, merge extractive liquid,, filter, it is 1.10 medicinal liquid at 60 ℃ that filtrate decompression is condensed into relative density, and adding ethanol is 60% to containing the alcohol amount, left standstill 24 hours, and filtered, must precipitate and supernatant.The supernatant concentrating under reduced pressure becomes thick paste, adds the water of 10 times of amounts, and stirring is left standstill, filter, the polyamide column of having handled well on the filtrate washes with water earlier to colourless, use 50%% ethanol elution of 8 times of amounts again instead, collect ethanol elution, decompression recycling ethanol, the macroporous adsorptive resins of having handled well on the concentrated solution washes with water earlier to colourless, uses 60% ethanol elution again instead, collect ethanol elution, concentrating under reduced pressure, drying promptly gets total saponin extracts;
Get precipitation decompression cold drying, add an amount of dissolved in distilled water, add ethanol and reach 80% to containing the alcohol amount, left standstill 24 hours, filter, the precipitation adding distil water is dissolved into 1% solution, crosses hollow fiber column ultrafilter (molecular cut off is greater than 6000), and ultrafiltrate is evaporated to dried; Get perhaps that the gained precipitation adds an amount of dissolved in distilled water again behind the secondary precipitate with ethanol, add ethanol and reach 75%, left standstill 24 hours, filter, get precipitation, promptly get the polysaccharide active component with an amount of absolute ethanol washing 1-2 time to containing the alcohol amount;
Above-mentioned Mylabris extract, total saponin extracts, polysaccharide active component are dissolved with water for injection, add Fel Ursi powder again and make dissolving, ooze with sodium chloride adjusting etc., adjust pH is 5.0, filters with 0.22 μ m microporous filter membrane, and sterilization is prepared into 1000 bottles of infusion solutions.Usage and dosage: intravenous drip, a 2-3 bottle, 1-2 time on the one.
The embodiment of the invention 2: Mylabris 0.6g, Radix Ginseng 1.5g, Radix Astragali 7.5g, Radix Et Caulis Acanthopanacis Senticosi 7.5g, rhizoma sparganic 2.4g, Herba Scutellariae Barbatae 9g, Rhizoma Curcumae 2.4g, Fructus Corni 3g, Fructus Ligustri Lucidi 3g, Fel Ursi powder 0.05g, Radix Glycyrrhizae 1.5g
Preparation method is: Fang Zhongshi simply, except that Fel Ursi powder, powder of cantharide is broken into 40 purpose coarse powder, adds the water of 15 times of amounts, soaked 30 minutes, extracted 1 hour, add the water of 10 times of amounts for the second time, extracted 0.5 hour, filter, merging filtrate adds ethanol and reaches 60% to containing the alcohol amount, leaves standstill, filter, filtrate decompression is condensed into thick paste, adds the water of 6 times of amounts, stirs, leave standstill, filter filtrate centrifugal 10 minutes with the speed more than 10000 rev/mins, the centrifugal liquid concentrating under reduced pressure, drying, pulverize Mylabris extract;
Get 9 flavors such as all the other Radix Ginsengs and extract 2 times by decocting method with the water of 6 times of amounts, merge extractive liquid, filters, and it is 1.05 medicinal liquid at 60 ℃ that filtrate decompression is condensed into relative density, and adding ethanol is 50% to containing the alcohol amount, leaves standstill 24 hours, and filtration must precipitate and supernatant.The supernatant concentrating under reduced pressure becomes thick paste, adds the water of 10 times of amounts, and stirring is left standstill, filter, the polyamide column of having handled well on the filtrate washes with water earlier to colourless, use 50% ethanol elution of 5 times of amounts again instead, collect ethanol elution, decompression recycling ethanol, the macroporous adsorptive resins of having handled well on the concentrated solution, wash with water earlier to colourless, use 50% ethanol elution again instead, collect ethanol elution, concentrating under reduced pressure, the dry total saponin extracts that gets;
Get precipitation decompression cold drying, add an amount of dissolved in distilled water, add ethanol and reach 50% to containing the alcohol amount, left standstill 24 hours, filter, the precipitation adding distil water is dissolved into 1% solution, crosses molecular cut off greater than 6000 hollow fiber column ultrafilter, and ultrafiltrate is evaporated to dried; The gained precipitation adds an amount of dissolved in distilled water again after perhaps getting the secondary precipitate with ethanol, adds ethanol and reaches 50% to containing the alcohol amount, leaves standstill 24 hours, filters, and gets precipitation with an amount of absolute ethanol washing, promptly gets polyoses extract;
Above-mentioned Mylabris extract, total saponin extracts, polysaccharide active component are dissolved with water for injection, add Fel Ursi powder again and make dissolving, ooze with glucose adjusting etc., adjust pH is 4.0, filters with 0.22 μ m microporous filter membrane, and sterilization is prepared into 1000 bottles of infusion solutions.
The embodiment of the invention 3: Mylabris 6g, Radix Ginseng 15g, Radix Astragali 100g, Radix Et Caulis Acanthopanacis Senticosi 100g, rhizoma sparganic 24g, Herba Scutellariae Barbatae 100g, Rhizoma Curcumae 24g, Fructus Corni 30g, Fructus Ligustri Lucidi 30g, Fel Ursi powder 1.0g, Radix Glycyrrhizae 15g
Preparation method is: Fang Zhongshi simply, except that Fel Ursi powder, powder of cantharide is broken into 50 purpose coarse powder, adds the water of 25 times of amounts, soaked 50 minutes, water is carried 3 times, plays the water that at every turn adds 15 times of amounts for the second time, extracts 1.5 hours, filter, merging filtrate adds ethanol and reaches 80% to containing the alcohol amount, leaves standstill, filter, filtrate decompression is condensed into thick paste, adds the water of 10 times of amounts, stirs, leave standstill, filter filtrate centrifugal 25 minutes with the speed more than 10000 rev/mins, the centrifugal liquid concentrating under reduced pressure, drying is pulverized standby;
Get 9 flavors such as all the other Radix Ginsengs and extract 3 times by decocting method, infusion process with the water that 6-12 doubly measures, merge extractive liquid, filters, it is 1.20 medicinal liquid at 60 ℃ that filtrate decompression is condensed into relative density, and adding ethanol is 70% to containing the alcohol amount, leaves standstill 24 hours, filter, must precipitate and supernatant.The supernatant concentrating under reduced pressure becomes thick paste, adds the water of 10 times of amounts, and stirring is left standstill, filter, the polyamide column of having handled well on the filtrate washes with water earlier to colourless, use 60% ethanol elution of 8 times of amounts again instead, collect ethanol elution, decompression recycling ethanol, the macroporous adsorptive resins of having handled well on the concentrated solution, wash with water earlier to colourless, use 80% ethanol elution again instead, collect ethanol elution, concentrating under reduced pressure, drying for standby;
Get precipitation decompression cold drying, add an amount of dissolved in distilled water, add ethanol and reach 85% to containing the alcohol amount, left standstill 24 hours, filter, the precipitation adding distil water is dissolved into 2% solution, crosses molecular cut off greater than 6000 hollow fiber column ultrafilter, and ultrafiltrate is evaporated to dried; Get perhaps that the gained precipitation adds an amount of dissolved in distilled water again behind the secondary precipitate with ethanol, add ethanol and reach 85%, left standstill 24 hours, filter, get precipitation with an amount of absolute ethanol washing 2 times, promptly to containing the alcohol amount;
Get above-mentioned Mylabris extract, total saponin extracts, polysaccharide active component and dissolve, add Fel Ursi powder again and make dissolving, add mannitol and fructose with water for injection, adjust pH 5.5, filter with 0.22 μ m microporous filter membrane, lyophilization is prepared into 1000 of lyophilized injectable powders.Usage and dosage: intramuscular or intravenous injection, instillation, one time 1-2 props up, 2 times on the one.
The embodiment of the invention 4: Mylabris 4.76g, Radix Ginseng 11.9g, Radix Astragali 59.5g, Radix Et Caulis Acanthopanacis Senticosi 59.5g, rhizoma sparganic 19g, Herba Scutellariae Barbatae 71.4g, Rhizoma Curcumae 19g, Fructus Corni 23.8g, Fructus Ligustri Lucidi 23.8g, Fel Ursi powder 0.48g, Radix Glycyrrhizae 11.9g
Preparation method is: Fang Zhongshi simply, except that Fel Ursi powder, powder of cantharide is broken into 50 purpose coarse powder, adds the water of 25 times of amounts, soaked 50 minutes, water is carried 3 times, plays the water that at every turn adds 15 times of amounts for the second time, extracts 1.5 hours, filter, merging filtrate adds ethanol and reaches 80% to containing the alcohol amount, leaves standstill, filter, filtrate decompression is condensed into thick paste, adds the water of 10 times of amounts, stirs, leave standstill, filter filtrate centrifugal 25 minutes with the speed more than 10000 rev/mins, the centrifugal liquid concentrating under reduced pressure, drying is pulverized standby;
Get 9 flavors such as all the other Radix Ginsengs and extract 3 times by decocting method, infusion process with the water that 6-12 doubly measures, merge extractive liquid, filters, it is 1.20 medicinal liquid at 60 ℃ that filtrate decompression is condensed into relative density, and adding ethanol is 70% to containing the alcohol amount, leaves standstill 24 hours, filter, must precipitate and supernatant.The supernatant concentrating under reduced pressure becomes thick paste, adds the water of 10 times of amounts, and stirring is left standstill, filter, the polyamide column of having handled well on the filtrate washes with water earlier to colourless, use 60% ethanol elution of 8 times of amounts again instead, collect ethanol elution, decompression recycling ethanol, the macroporous adsorptive resins of having handled well on the concentrated solution, wash with water earlier to colourless, use 80% ethanol elution again instead, collect ethanol elution, concentrating under reduced pressure, drying for standby;
Get precipitation decompression cold drying, add an amount of dissolved in distilled water, add ethanol and reach 85% to containing the alcohol amount, left standstill 24 hours, filter, the precipitation adding distil water is dissolved into 2% solution, crosses molecular cut off greater than 6000 hollow fiber column ultrafilter, and ultrafiltrate is evaporated to dried; Get perhaps that the gained precipitation adds an amount of dissolved in distilled water again behind the secondary precipitate with ethanol, add ethanol and reach 85%, left standstill 24 hours, filter, get precipitation with an amount of absolute ethanol washing 2 times, promptly to containing the alcohol amount;
Get above-mentioned Mylabris extract, total saponin extracts, polysaccharide active component and dissolve with water for injection, add Fel Ursi powder again and make dissolving, adjust pH 4.8 filters with 0.22 μ m microporous filter membrane, and sterilization is prepared into 1000 of aqueous injection.Usage and dosage: intramuscular or intravenous injection, one time 1-2 props up, 2 times on the one.
The embodiment of the invention 5: Mylabris 3.4g, Radix Ginseng 8.5g, Radix Astragali 42.5g, Radix Et Caulis Acanthopanacis Senticosi 42.5g, rhizoma sparganic 13.57g, Herba Scutellariae Barbatae 51g, Rhizoma Curcumae 8.5g, Fructus Corni 17g, Fructus Ligustri Lucidi 17g, Fel Ursi powder 0.34g, Radix Glycyrrhizae 8.5g
Preparation method is: the method according to embodiment 1 prepares Mylabris extract, total saponin extracts and polysaccharide active component.
Above-mentioned Mylabris extract, total saponin extracts, polysaccharide active component are dissolved with water for injection, add Fel Ursi powder again and make dissolving, adjust pH 5.2 filters with 0.22 μ m microporous filter membrane, and sterilization is prepared into 1000 of aqueous injection.
The embodiment of the invention 6:
Prescription and method according to embodiment 2 prepare Mylabris extract, total saponin extracts and polysaccharide active component.
Above-mentioned Mylabris extract, total saponin extracts, polysaccharide active component are dissolved with water for injection, add Fel Ursi powder again and make dissolving, add dextran, adjust pH 4.5 filters with 0.22 μ m microporous filter membrane, and lyophilization is prepared into 1000 of lyophilized injectable powders.
The embodiment of the invention 7:
Prescription and method according to embodiment 4 prepare Mylabris extract, total saponin extracts and polysaccharide active component.
Above-mentioned Mylabris extract, total saponin extracts, polysaccharide active component are dissolved with water for injection, add Fel Ursi powder again and make dissolving, add glucosan and polyethylene pyrrole Lip river alkane ketone, adjust pH 4.3, filter with 0.22 μ m microporous filter membrane, lyophilization is prepared into 1000 of lyophilized injectable powders.
Claims (6)
1. compound cantharis liquid formulation is characterized in that, preparation method may further comprise the steps:
(1) calculates according to composition by weight: Mylabris 0.6-6 part, Radix Ginseng 1.5-15 part, Radix Astragali 7.5-100 part, Radix Et Caulis Acanthopanacis Senticosi 7.5-100 part, rhizoma sparganic 2.4-24 part, Herba Scutellariae Barbatae 9-100 part, Rhizoma Curcumae 2.4-24 part, Fructus Corni 3-30 part, Fructus Ligustri Lucidi 3-30 part, Fel Ursi powder 0.05-1.0 part, Radix Glycyrrhizae 1.5-15 part;
(2) powder of cantharide is broken into coarse powder, decocts with water, extracting liquid filtering precipitates with ethanol then, filters, and concentrates, be dissolved in water, and high speed centrifugation, centrifugal liquid concentrates, and drying is pulverized, and promptly gets Mylabris extract;
(3) get nine flavor medical materials such as all the other Radix Ginsengs except that Fel Ursi powder, the Radix Astragali, the water of doubly measuring with 6-12 extracts 2-3 time by decocting method, infusion process, merge extractive liquid,, filter, filtrate decompression is condensed into relative density and is the medicinal liquid of 1.05-1.20 at 60 ℃, adds ethanol to containing the alcohol amount for 50%-70%, leaves standstill 24 hours, filter, must precipitate and supernatant;
(4) with the extracting solution of Radix Ginseng etc., go up later polyamide column, wash with water earlier to colourless with water precipitation, use the 50%-60% ethanol elution again instead, collect ethanol elution, decompression recycling ethanol, macroporous adsorptive resins on the concentrated solution, wash with water earlier to colourless, use the 50%-80% ethanol elution again instead, collect ethanol elution, concentrating under reduced pressure, drying promptly gets total saponin extracts;
(5) with the precipitation of nine flavor medical materials such as above-mentioned Radix Ginseng, the Radix Astragali, drying under reduced pressure is dissolved in water, and precipitate with ethanol leaves standstill, and filters, and precipitation is dissolved in water, and crosses hollow fiber column ultrafilter, and it is dried that ultrafiltrate is evaporated to; The gained precipitation is dissolved in water after perhaps getting the secondary precipitate with ethanol, and precipitate with ethanol leaves standstill, and filters, and gets precipitation with an amount of absolute ethanol washing, promptly gets the active component of polysaccharide.
2. preparation method according to claim 1 is characterized in that further comprising the steps of:
(1) gets Mylabris, be ground into 40-60 purpose coarse powder, add the water that 15-25 doubly measures, soaked 30-50 minute, water is carried 2-3 time, rises for the second time to add the water that 10-15 doubly measures at every turn, extracts 0.5-1.5 hour, filters, merging filtrate adds ethanol and reaches 60%-80% to containing the alcohol amount, leaves standstill, and filters, filtrate decompression is condensed into thick paste, adds the water that 6-10 doubly measures, and stirs, and leaves standstill, filter, filtrate is with the centrifugal 10-25 of the speed more than 10000 rev/mins minute, the centrifugal liquid concentrating under reduced pressure, drying is pulverized, and promptly gets Mylabris extract;
(2) with the extracting solution of nine flavor medical materials such as Radix Ginseng, the Radix Astragali, concentrating under reduced pressure becomes thick paste, adds the water of 10 times of amounts, stirring is left standstill, and filters the polyamide column of having handled well on the filtrate, wash with water earlier to colourless, use the 50%-60% ethanol elution that 5-8 doubly measures again instead, collect ethanol elution, decompression recycling ethanol, the macroporous adsorptive resins of having handled well on the concentrated solution washes with water earlier to colourless, use the 50%-80% ethanol elution again instead, collect ethanol elution, concentrating under reduced pressure, drying promptly gets total saponin extracts;
(3) with the precipitation of above-mentioned Radix Ginseng, the Radix Astragali etc. nine flavor medical materials, the decompression cold drying, add an amount of dissolved in distilled water, add ethanol and reach 50-85% to containing the alcohol amount, left standstill 24 hours, and filtered, the precipitation adding distil water is dissolved into the solution of 1-2%, cross molecular cut off greater than 6000 hollow fiber column ultrafilter, ultrafiltrate is evaporated to dried; Get perhaps that the gained precipitation adds an amount of dissolved in distilled water again behind the secondary precipitate with ethanol, add ethanol and reach 50-85%, left standstill 24 hours, filter, get precipitation, promptly get the active component of polysaccharide with an amount of absolute ethanol washing 1-2 time to containing the alcohol amount.
3. preparation method according to claim 1 and 2 is characterized in that further comprising the steps of:
The preparation method of infusion solution is: get above-mentioned Mylabris extract, total saponin extracts, polysaccharide active component and dissolve with water for injection, add Fel Ursi powder again and make dissolving, regulate to wait and oozes, adjust pH 4.0-5.5, filter with 0.22 μ m microporous filter membrane, sterilization is prepared into infusion solution;
The preparation method of lyophilized injectable powder is: get above-mentioned Mylabris extract, total saponin extracts, polysaccharide active component and dissolve with water for injection, add Fel Ursi powder again and make dissolving, add freeze-dried excipient, adjust pH 4.0-5.5, filter with 0.22 μ m microporous filter membrane, lyophilization is prepared into lyophilized injectable powder;
The preparation method of aqueous injection is: get above-mentioned Mylabris extract, total saponin extracts, polysaccharide active component and dissolve with water for injection, add Fel Ursi powder again and make dissolving, adjust pH 4.0-5.5 filters with 0.22 μ m microporous filter membrane, and sterilization is prepared into aqueous injection.
4. the preparation method of liquid preparation according to claim 3, it is characterized in that described isoosmotic adjusting agent, can be one or more the compositions in glucose, xylitol, sorbitol, sodium chloride, calcium chloride, magnesium chloride, potassium chloride, sodium lactate and the dextran etc.
5. the preparation method of liquid preparation according to claim 3 is characterized in that described freeze-dried excipient can be one or more the compositions in mannitol, fructose, glucosan, dextran, the polyethylene pyrrole Lip river alkane ketone etc.
6. liquid preparation according to claim 1 is characterized in that, preparation method is:
Extraction process is: Fang Zhongshi simply, except that Fel Ursi powder, powder of cantharide is broken into 40-60 purpose coarse powder, add the water that 15-25 doubly measures, soaked 30-50 minute, water is carried 2-3 time, rise for the second time and add the water that 10-15 doubly measures at every turn, extracted 0.5-1.5 hour, and filtered merging filtrate, add ethanol and reach 60%-80% to containing the alcohol amount, leave standstill, filter, filtrate decompression is condensed into thick paste, add the water that 6-10 doubly measures, stir, leave standstill, filter, filtrate was with the centrifugal 10-25 of the speed more than 10000 rev/mins minute, the centrifugal liquid concentrating under reduced pressure, drying is pulverized standby; 9 flavors such as all the other Radix Ginsengs extract 2-3 time by decocting method, infusion process with the water that 6-12 doubly measures, and merge extractive liquid, filters, filtrate decompression is condensed into relative density and is the medicinal liquid of 1.05-1.20 at 60 ℃, adds ethanol to containing the alcohol amount for 50%-70%, leaves standstill 24 hours, filter, must precipitate and supernatant.The supernatant concentrating under reduced pressure becomes thick paste, adds the water of 10 times of amounts, and stirring is left standstill, filter, the polyamide column of having handled well on the filtrate washes with water earlier to colourless, use the 50%-60% ethanol elution that 5-8 doubly measures again instead, collect ethanol elution, decompression recycling ethanol, the macroporous adsorptive resins of having handled well on the concentrated solution, wash with water earlier to colourless, use the 50%-80% ethanol elution again instead, collect ethanol elution, concentrating under reduced pressure, drying for standby; Get precipitation decompression cold drying, add an amount of dissolved in distilled water, add ethanol and reach 50-85% to containing the alcohol amount, left standstill 24 hours, and filtered, the precipitation adding distil water is dissolved into the solution of 1-2%, cross molecular cut off greater than 6000 hollow fiber column ultrafilter, ultrafiltrate is evaporated to dried; Get perhaps that the gained precipitation adds an amount of dissolved in distilled water again behind the secondary precipitate with ethanol, add ethanol and reach 50-85%, left standstill 24 hours, filter, get precipitation with an amount of absolute ethanol washing 1-2 time, promptly to containing the alcohol amount;
Preparation process is: the preparation method of infusion solution is: get above-mentioned Mylabris extract, total saponin extracts, polysaccharide active component and dissolve with water for injection, add Fel Ursi powder again and make dissolving, regulate to wait and oozes, adjust pH 4.0-5.5, filter with 0.22 μ m microporous filter membrane, sterilization is prepared into infusion solution;
The preparation method of lyophilized injectable powder is: get above-mentioned Mylabris extract, total saponin extracts, polysaccharide active component and dissolve with water for injection, add Fel Ursi powder again and make dissolving, add freeze-dried excipient, adjust pH 4.0-5.5, filter with 0.22 μ m microporous filter membrane, lyophilization is prepared into lyophilized injectable powder;
The preparation method of aqueous injection is: get above-mentioned Mylabris extract, total saponin extracts, polysaccharide active component and dissolve with water for injection, add Fel Ursi powder again and make dissolving, adjust pH 4.0-5.5 filters with 0.22 μ m microporous filter membrane, and sterilization is prepared into aqueous injection.
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