CN1682928A - Novel process for preparing Mailuoing freeze-dried powder injection - Google Patents
Novel process for preparing Mailuoing freeze-dried powder injection Download PDFInfo
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Abstract
The present invention belongs to the field of Chinese medicine preparing technology, and novel preparation process of freeze dried Mailuoning powder for injection. The present invention has officinal dendrobium stem with rich resource to replace lacking wild dendrobium stem, and has obviously raised effective Chinese medicinal component extracting rate, resulting in reduced dendrobium resource consumption. Pharmacodynamic experiment shows that the present invention has excellent effects of clearing away heat, nourishing yin and promoting blood circulation to disperse blood clots.
Description
Technical field
The invention belongs to technical field of traditional Chinese medicine pharmacy, be specifically related to a kind of novel preparation method of freeze dried Mailuoning powder injection.
Background technology
MAILUONING ZHUSHEYE is made by Herba Dendrobii, Flos Lonicerae, Radix Achyranthis Bidentatae, Radix Scrophulariae, be on the basis of famous hospital " SIMIAOYONGAN TANG ", with the theory of Chinese medical science is guidance, and the Chinese medicine compound injection that the method for the employing combination of Chinese and Western medicine is studied has the effect of replenishing YIN and removing heat, liver and kidney tonifying, activating blood circulation to dissipate blood stasis.The syndrome of blood stasis and the thrombus angiopathy that are used for the treatment of each section clinically, the especially various hearts, cerebrovascular disease.So far gone through 20 years from dropping into clinical verification, determined curative effect, onset is rapid, and untoward reaction is few, is chosen as " the indispensable Chinese patent medicine of hospital of traditional Chinese hospital's emergency treatment section office " by State Administration of Traditional Chinese Medicine, is extensive use of in nationwide hospital.
Meanwhile, the crisis of resource exhaustion is also come up in big strides, especially the Herba Dendrobii medical material.According to list of references [Zhang Zunjian, etc.The research of MAILUONING ZHUSHEYE HPLC/UV/MS finger printing.Chinese patent medicine, 2004,26 (3): 175], what the Herba Dendrobii of one of MAILUONING ZHUSHEYE primary raw material medicine was used is dendrobium or Herba Dendrobii oculati, but the Herba Dendrobii of these hyoscines is because excessively gathering of medicinal herb grower adds the destruction of forest, present domestic most original producton locations have not had available wild resource, and the Herba Dendrobii fecund of use is from the virgin forest of states such as Burma, Laos, Vietnam, Bangladesh.Because the Dendrobium plant is put into " endangered species of wild fauna and flora international trade pact " appendix II class, country gathers, manages, imports and exports it and carries out strictness restriction and management, and these Herba Dendrobiis more and more can't be met the need of market at present.The consequence that supply falls short of demand directly causes is that price raises up, and this is undoubtedly a very big burden for the patient.The effect of Herba Dendrobii in prescription is extremely important, if remove, can directly influence the curative effect of medicine.
In recent years, though the Herba Dendrobii industrial base occur in succession throughout the country, especially Herba Dendrobii in Shanghai first multitudinous transplant succeed, artificial growth also under study for action, resource remains that supply falls short of demand.In present research, also do not find a kind of aboundresources, the eutherapeutic Chinese medicine that can substitute Herba Dendrobii, make medicine under the prerequisite of determined curative effect, still can keep lower price.More feasible method is exactly under the prerequisite that guarantees curative effect, reduces the consumption of medical material, reduces the cost and price of medicine with this.
Application number is 92107848 patent documentation, discloses the process of MAILUONING ZHUSHEYE: adopt water extract-alcohol precipitation, the method for ethyl acetate extraction obtains effective site.Though it is said method is classical, very big for loss of active ingredients.Water can only extract the bigger composition of polarity, for very poor of the less extracts active ingredients effect of polarity; In the ethanol precipitation process, be deposited in formation, the sedimentary process and can adsorb, wrap up effective ingredient; The Herba Dendrobii medical material goes into that compound recipe should be decocted first, single [" Chinese pharmacopoeia version in 2000,70], as seen said method is to the extraction of Herba Dendrobii medical material effective ingredient very science not, and is very unreasonable with frying in shallow oil for a long time.So, cause in the MAILUONING ZHUSHEYE in each crude drug the extraction efficiency of effective ingredient very low, especially the extraction ratio of the effective ingredient escoparone in the Herba Dendrobii medical material is very low.This Herba Dendrobii medical material for scarcity of resources is a kind of very big waste.
MAILUONING ZHUSHEYE a drug dosage is big, in clinical practice, show a lot of untoward reaction [Chen Aiqun, etc.70 routine MAILUONING ZHUSHEYE untoward reaction document analysis.The adverse effect magazine, 2003,2:162].
It is active weak composition or invalid components that the poor stability of injection, wherein contained effective ingredient are easy to rotten, and injection is very inconvenient in storage, transportation.
Summary of the invention
In view of this, the patient exists very big expectation to good effect, cheap MAILUONING new product; And pharmacy corporation is also craved for a kind of good effect, the appearance of MAILUONING new product cheaply.Research worker of the present invention finds a kind of preparation method of MAILUONING through exploring repeatedly.Preparation method of the present invention all has higher extraction ratio for the crude drug Herba Dendrobii in the MAILUONING, Flos Lonicerae, Radix Achyranthis Bidentatae, Radix Scrophulariae, can reduce the use amount of crude drug.Research worker of the present invention replaces other Herba Dendrobii medical material that is endangered, wild, expensive, import with abundant, the cheap relatively Herba Dendrobii of resource, with preparation method of the present invention the Herba Dendrobii medical material is extracted separately, can obviously improve extraction ratio of effective constituents in the Herba Dendrobii, thereby make the use amount of Herba Dendrobii reduce.This has not only reduced the use amount of Herba Dendrobii medical material, has protected the resource of Herba Dendrobii medical material, and has reduced the price of crude drug, makes the medicine cost of finally making reduce.The reduction of crude drug also makes the adverse reaction rate of lyophilized injectable powder of the present invention reduce greatly simultaneously.Make lyophilized injectable powder, make its stability better, use more convenient.Patent of the present invention is to be the result of the further research and development carried out of the deficiency in 200410002309 the relevant patent documentation to application number.
An object of the present invention is to disclose a kind of novel preparation method of freeze dried Mailuoning powder injection.
The present invention realizes by following scheme.
One, preparation method
Freeze dried Mailuoning powder injection of the present invention prepares by the following method:
(1) raw material medicines in portions by weight consists of: Herba Dendrobii 2-3 part, Flos Lonicerae 3-6 part, Radix Achyranthis Bidentatae 3-6 part, Radix Scrophulariae 3-6 part.
(2) get above-mentioned weight portion Radix Achyranthis Bidentatae, Radix Scrophulariae medical material, pulverize, add 10%-40% alcoholic solution reflux, extract, 1-3 time that 6-15 doubly measures, each 1-2 hour, merge extractive liquid, filtered, filtrate decompression concentrated extractum A;
(3) get above-mentioned weight portion Herba Dendrobii medical material, pulverize, add the 30%-60% alcoholic solution that 5-10 doubly measures and soaked 1-2 hour at 50 ℃-70 ℃, reflux, extract, is 2-3 time then, and each 2 hours, merge extractive liquid, filtered, filtrate decompression concentrated extractum B;
(4) above-mentioned extractum A and extractum B are merged, obtain extractum C;
(5) with low pole or the nonpolar macroporous adsorption resin handled well on the above-mentioned extractum C, with the water elution of 3-5 times of column volume, reuse 60%-80% alcoholic solution eluting is collected ethanol elution earlier, solution adds entry and makes that concentration of alcohol is 20%-30%, leave standstill, centrifugal with 14000-20000 rev/min speed, the centrifugal liquid molecular cut off is 5000 ultrafilter membrane ultrafiltration, filtrate decompression concentrates, drying is pulverized, and obtains extract X;
(6) get above-mentioned weight portion Chinese medicine honeysuckle, pulverize, according to following 1) or 2) in method extract:
1) Chinese medicine honeysuckle is added the water that 8-14 doubly measures, soak half an hour, put into the supersound extraction jar, carry out supersound extract, time is 30-60 minute, and frequency of oscillation is 20-80kHz, and the control temperature is a room temperature, extract 3-4 time, merge extractive liquid,, extracting solution leaves standstill, and filters, decompression filtrate recycling ethanol, last D101 macroporous adsorbent resin with the water elution of 4-6 times of column volume, is collected water lotion, speed with 14000-20000 rev/min is centrifugal, the centrifugal liquid molecular cut off is 3000 ultrafilter membrane ultrafiltration, and filtrate decompression concentrates, drying, pulverize, obtain extract Y;
2) Chinese medicine honeysuckle is added the water that 8-14 doubly measures, soak half an hour, put into the supersound extraction jar, carry out supersound extract, the time is 30-60 minute, frequency of oscillation is 20-80kHz, the control temperature is a room temperature, extracts merge extractive liquid, 3-4 time, filter, filtrate decompression is concentrated into solution: medical material is 1: 1, last NKA-II type macroporous adsorbent resin, first water elution with 3-5 times of column volume, reuse 60%-80% alcoholic solution eluting, collect ethanol elution, concentrating under reduced pressure, drying, pulverize, obtain extract Y;
(7) said extracted thing X and extract Y are merged, with the water for injection dissolving, add the water solublity freeze-dried excipient, regulating pH value with meglumine is 4.0-7.0, and with 0.22 μ m filtering with microporous membrane, lyophilization is packaged to be freeze-dried powder.
In the above-mentioned preparation method: the crude drug Herba Dendrobii comprises dendrobium, Herba Dendrobii oculati and Herba Dendrobii; Meglumine regulator solution pH value is preferably 5.0-6.0.
The extraction efficiency height of preparation method of the present invention, if but content of effective has surpassed its safe handling dosage, will damage human body, untoward reaction takes place.Research worker of the present invention is found crude drug composition of the present invention in above-mentioned weight portion scope through a large amount of explorations, and the freeze dried Mailuoning powder injection that utilizes the inventive method preparation also has very high safety when having good therapeutic effect.
The invention described above raw material medicines in portions by weight consist of Herba Dendrobii 2-3 part, Flos Lonicerae 3-6 part, Radix Achyranthis Bidentatae 3-6 part, Radix Scrophulariae 3-6 part the time, application number is that the weight portion of the recipe quantity of each crude drug of patent documentation median nexus injection for curing of 92107848 is 10 parts.
Two, the comparison of two kinds of preparation methoies
For science, reasonability that preparation method of the present invention is described, research worker of the present invention has been carried out following comparative experiments.
Medical material amount: Herba Dendrobii 1000g, Flos Lonicerae 1000g, Radix Achyranthis Bidentatae 1000g, Radix Scrophulariae 1000g.
The 'Mailuoning ' injection liquid and preparation method thereof: application number is that the method in 92107848 the patent documentation is prepared;
Freeze dried Mailuoning powder injection of the present invention: make by the invention described above preparation method.
Provide by Tianzhijiao Medication Development Co., Ltd., Guangdong.The results are shown in Table 1.
The comparison of two kinds of preparation methoies of table 1
| Lot number | Output (propping up) | |
| MAILUONING ZHUSHEYE | Freeze dried Mailuoning powder injection of the present invention | |
| ??1 ??2 ??3 ??4 ??5 | ??40 ??40 ??40 ??40 ??40 | ??100 ??105 ??102 ??110 ??106 |
As can be seen from Table 1, when the raw medicinal material of same amount, the quantity of the freeze dried Mailuoning powder injection that preparation method of the present invention is made be application number be the product quantity that obtains of the preparation method in 92107848 the patent documentation 2-3 doubly.This proves absolutely the inventive method conservation medicine greatly, reduces the medicine cost.
Three, content analysis
The reduction of every contained raw medicinal material content of freeze dried Mailuoning powder injection of the present invention does not make that content of effective descends in the freeze dried Mailuoning powder injection of the present invention; On the contrary, utilize preparation method of the present invention can improve content of effective in the medicine greatly, lay the first stone for medicine has good clinical therapeutic efficacy.For science, the reasonability of investigating preparation method of the present invention, research worker is measured the main effective ingredient of the medical material of respectively distinguishing the flavor of in the freeze dried Mailuoning powder injection of the present invention.Freeze dried Mailuoning powder injection of the present invention is provided by Tianzhijiao Medication Development Co., Ltd., Guangdong; Commercially available MAILUONING ZHUSHEYE is produced by Nanjing, Nanjing pharmaceutical Co. Ltd.
1, escoparone assay
Content assaying method is with reference to MAILUONING ZHUSHEYE standard (WS
3-thin layer chromatography in B-3462-98) is carried out.Assay the results are shown in Table 2.
Table 2 escoparone assay result
| Lot number | Content (μ g/ props up) | |
| MAILUONING ZHUSHEYE | Freeze dried Mailuoning powder injection of the present invention | |
| ??1 ??2 ??3 ??4 ??5 | ??61.7 ??56.8 ??53.2 ??60.4 ??58.8 | ??84.2 ??80.7 ??77.6 ??79.4 ??81.5 |
Annotate: MAILUONING ZHUSHEYE standard (WS
3-B-3462-98) in the following regulation of assay item: MAILUONING ZHUSHEYE contains escoparone and must not be less than 50 μ g/ and prop up.
By table 2 assay result as can be seen, the content of escoparone illustrates the preparation method science of freeze dried Mailuoning powder injection of the present invention, rationally apparently higher than the content of MAILUONING ZHUSHEYE in the freeze dried Mailuoning powder injection of the present invention.
2, determination of chlorogenic acid
Content assaying method with reference to list of references [Li Wenli, etc.Chlorogenic acid contents in the high effective liquid chromatography for measuring MAILUONING ZHUSHEYE.Chinese Pharmaceutical Journal, 2003,38 (3): 210] method in is carried out.Assay the results are shown in Table 3.
Table 3 determination of chlorogenic acid result
| Lot number | Content (mg/ props up) | |
| MAILUONING ZHUSHEYE | Freeze dried Mailuoning powder injection of the present invention | |
| ??1 ??2 ??3 ??4 ??5 | ??1.37 ??1.40 ??1.34 ??1.30 ??1.42 | ??3.82 ??3.46 ??2.25 ??3.50 ??3.44 |
By table 3 assay result as can be seen, chlorogenic acid contents illustrates the preparation method science of freeze dried Mailuoning powder injection of the present invention, rationally apparently higher than the content of MAILUONING ZHUSHEYE in the freeze dried Mailuoning powder injection of the present invention.
3, ecdysterone assay
Content assaying method with reference to list of references [Li Wenli, etc.RP-HPLC measures the content of ecdysterone in the MAILUONING ZHUSHEYE.The West China pharmaceutical journal, 2001,16 (4): 382] method in is carried out.Assay the results are shown in Table 4.
Table 4 ecdysterone assay result
| Lot number | Content (mg/ props up) | |
| MAILUONING ZHUSHEYE | Freeze dried Mailuoning powder injection of the present invention | |
| ??1 ??2 ??3 ??4 ??5 | ??0.323 ??0.376 ??0.285 ??0.410 ??0.358 | ??0.772 ??0.845 ??0.826 ??0.810 ??0.804 |
By table 4 assay result as can be seen, the content of ecdysterone illustrates the preparation method science of freeze dried Mailuoning powder injection of the present invention, rationally apparently higher than the content of MAILUONING ZHUSHEYE in the freeze dried Mailuoning powder injection of the present invention.
4, cinnamic acid assay
Content assaying method with reference to list of references [surplus bright and beautiful, etc.The content of cinnamic acid in the rp-hplc determination MAILUONING ZHUSHEYE.China's Chinese medicine magazine, 2000,25 (7): 415] method in is carried out.Assay the results are shown in Table 5.
Table 5 cinnamic acid assay result
| Lot number | Content (mg/ props up) | |
| MAILUONING ZHUSHEYE | Freeze dried Mailuoning powder injection of the present invention | |
| ??1 ??2 ??3 ??4 ??5 | ??6.23 ??5.64 ??6.52 ??5.88 ??5.94 | ??12.7 ??11.4 ??13.5 ??13.8 ??12.0 |
By table 5 assay result as can be seen, the content of cinnamic acid illustrates the preparation method science of freeze dried Mailuoning powder injection of the present invention, rationally apparently higher than the content of MAILUONING ZHUSHEYE in the freeze dried Mailuoning powder injection of the present invention.
Sum up: as can be seen by above assay result, active constituent content in the medical material respectively distinguish the flavor of in the freeze dried Mailuoning powder injection of the present invention all apparently higher than MAILUONING ZHUSHEYE, and the recipe quantity of the medical material of respectively distinguishing the flavor of in the freeze dried Mailuoning powder injection prescription of the present invention has only the 20%-60% of MAILUONING ZHUSHEYE prescription Chinese crude drug recipe quantity, illustrate and improve manyly in the preparation method of freeze dried Mailuoning powder injection of the present invention for extraction ratio of effective constituents in each flavor medical material than MAILUONING ZHUSHEYE that the preparation method that further specifies freeze dried Mailuoning powder injection of the present invention is a science, reasonably.The preparation method of freeze dried Mailuoning powder injection of the present invention is easy to realize under existing technical merit, and can realize automatization fully, production method compared with MAILUONING ZHUSHEYE, the present invention is with short production cycle, method step is few, and consumption of raw materials is few, illustrates that freeze dried Mailuoning powder injection of the present invention is successful for the insufficient improvement on the preparation method in the MAILUONING ZHUSHEYE, reasonably, science.
Four, pharmacology embodiment
In order to confirm the therapeutic effect of freeze dried Mailuoning powder injection of the present invention, research worker of the present invention has been carried out pharmacodynamics test to freeze dried Mailuoning powder injection of the present invention.
Freeze dried Mailuoning powder injection of the present invention is provided by Tianzhijiao Medication Development Co., Ltd., Guangdong; Commercially available MAILUONING ZHUSHEYE is produced by Nanjing, Nanjing pharmaceutical Co. Ltd.
1, the influence of anoxia in mice endurance is tested
Experimental technique: get 40 of healthy Kunming mouses, body weight 18-22g.Be divided into matched group at random, MAILUONING ZHUSHEYE group, freeze dried Mailuoning powder injection low dose group of the present invention and high dose group.Every group 10, male and female half and half, sub-cage rearing.Intraperitoneal injection, MAILUONING ZHUSHEYE group 10.0g/kg, freeze dried Mailuoning powder injection group 5g/kg of the present invention and 2.5g/kg, matched group gives isopyknic normal saline.1 time/day, continuous 5d.1h after the last administration, it is the 150ml port grinding bottle that mice is placed volume respectively, in put the 15g sodica calx, its time-to-live of airtight observation.The results are shown in Table 6.
The influence of table 6 pair mice normobaric hypoxia (X ± SD)
| Group | Mus number (only) | Mean survival time (min) |
| Matched group MAILUONING ZHUSHEYE group freeze dried Mailuoning powder injection of the present invention low dose group freeze dried Mailuoning powder injection of the present invention high dose group | ??10 ??10 ??10 ??10 | ??16.25±5.24 ??30.68±4.08 **??31.02±4.37 **??33.15±4.46 ** |
Annotate: compare with matched group:
*P＜0.05,
*P＜0.01.
Found out that by table 6 experimental result freeze dried Mailuoning powder injection of the present invention can significantly improve mice normobaric hypoxia endurance, mean survival time is than matched group significant prolongation.
2, to the anoxybiotic protective effect experiment of mouse cardiac muscle
Experimental technique: get 40 of healthy Kunming mouses, body weight 18-22g is divided into matched group at random, MAILUONING ZHUSHEYE group, freeze dried Mailuoning powder injection low dose group of the present invention and high dose group.Every group of male and female half and half, sub-cage rearing.Administering mode and dosage are the same.Matched group gives isopyknic normal saline.1 time/day, continuous 5 days.Back fixation was separated trachea with urethane 1.2g/kg intraperitoneal injection of anesthesia in 1 hour after the last administration, with the bulldog clamp folder pipe of holding one's breath, observed electrocardio with electrocardiogram equipment, and write down the little mousetrap with stopwatch and hold one's breath time of Guan Houzhi electrocardio disappearance.The results are shown in Table 7.
The anoxybiotic influence of table 7 pair mouse cardiac muscle (X ± SD)
| Group | Mus number (only) | Mean survival time (min) |
| Matched group MAILUONING ZHUSHEYE group freeze dried Mailuoning powder injection of the present invention low dose group freeze dried Mailuoning powder injection of the present invention high dose group | ??10 ??10 ??10 ??10 | ??5.83±0.84 ??13.10±0.72 **??12.94±0.62 **??15.58±0.68 ** |
Annotate: compare with matched group:
*P＜0.05;
*P＜0.01.
Found out that by table 7 experimental result freeze dried Mailuoning powder injection of the present invention plays significant protective effect to the mouse cardiac muscle anoxia, the mice mean survival time is than matched group significant prolongation.
3, the influence that the rat thrombus in vivo is formed
Rat is divided into 4 groups at random, 10 every group, is divided into matched group at random, MAILUONING ZHUSHEYE group, freeze dried Mailuoning powder injection low dose group of the present invention and high dose group.Administering mode and dosage are the same.Matched group gives isopyknic normal saline.Every day 1 time, successive administration 5 days, after the last administration 1 hour, rat is used 10% chloral hydrate, it is fixing to press 0.3g/kg body weight anesthesia back, separates left common carotid artery, on the thrombosis instrument with 2mA galvanism blood vessel 7min after, the record thrombus formation time.The results are shown in Table 8.
The influence that table 8 pair rat thrombus in vivo forms (X ± SD)
| Group | Mus number (only) | Thrombus formation time (min) |
| Matched group MAILUONING ZHUSHEYE group freeze dried Mailuoning powder injection of the present invention low dose group freeze dried Mailuoning powder injection of the present invention high dose group | ??10 ??10 ??10 ??10 | ??557.2±66.3 ??826.6±50.4 **??844.3±54.7 **??963.2±45.3 ** |
Annotate: compare with matched group:
*P＜0.05;
*P＜0.01.
Find out by table 8 experimental result, the formation of freeze dried Mailuoning powder injection energy significant prolongation rat thrombus in vivo of the present invention, thrombus formation time is than matched group significant prolongation.
By above pharmacodynamic experiment as can be seen, under Isodose, freeze dried Mailuoning powder injection of the present invention has better pharmacological action.Explanation is under the prerequisite of the minimizing of prescription Chinese crude drug amount, and the active constituent content of freeze dried Mailuoning powder injection Chinese crude drug of the present invention does not reduce on the contrary and improves, and illustrates that the preparation method that the present invention adopts is a science, reasonably, has more practicality.
Research worker of the present invention is also found in pharmacodynamic experiment, and the adverse reaction rate of freeze dried Mailuoning powder injection of the present invention is than the obvious reduction of MAILUONING ZHUSHEYE.Can find out that thus the freeze dried Mailuoning powder injection that preparation method of the present invention is made has not only improved the clinical efficacy of medicine, and has reduced the generation of adverse effect, is to kill two birds with one stone.
Five, preparation embodiment
Embodiment 1
(1) crude drug is: Herba Dendrobii 7500g, Flos Lonicerae 15000g, Radix Achyranthis Bidentatae 15000g, Radix Scrophulariae 15000g.
(2) get above-mentioned Radix Achyranthis Bidentatae, Radix Scrophulariae medical material, pulverize, add the 10% alcoholic solution reflux, extract, 3 times of 15 times of amounts, each 2 hours, merge extractive liquid, filtered, filtrate decompression concentrate extractum A;
(3) get above-mentioned Herba Dendrobii medical material, pulverize, 60% alcoholic solution that adds 10 times of amounts soaked 2 hours at 70 ℃, and reflux, extract, is 3 times then, and each 2 hours, merge extractive liquid, filtered, filtrate decompression concentrate extractum B;
(4) above-mentioned extractum A and extractum B are merged, obtain extractum C;
(5) with the D101 macroporous adsorbent resin of having handled well on the above-mentioned extractum C, with the water elution of 5 times of column volumes, reuse 60% alcoholic solution eluting is collected ethanol elution earlier, solution adds entry and makes that concentration of alcohol is 20%, leave standstill, centrifugal with 20000 rev/mins speed, the centrifugal liquid molecular cut off is 5000 ultrafilter membrane ultrafiltration, filtrate decompression concentrates, drying is pulverized, and obtains extract X;
(6) above-mentioned Chinese medicine honeysuckle is added the water of 14 times of amounts, soak half an hour, put into the supersound extraction jar, carry out supersound extract, time is 30 minutes, and frequency of oscillation is 20kHz, and the control temperature is a room temperature, extract 3 times, merge extractive liquid,, extracting solution leaves standstill, and filters, decompression filtrate recycling ethanol, last D101 macroporous adsorbent resin with the water elution of 6 times of column volumes, is collected water lotion, speed with 14000 rev/mins is centrifugal, the centrifugal liquid molecular cut off is 3000 ultrafilter membrane ultrafiltration, and filtrate decompression concentrates, drying, pulverize, obtain extract Y;
(7) said extracted thing X and extract Y are merged, with the water for injection dissolving, add polyvinylpyrrolidone, regulating pH value with meglumine is 4.0, and with 0.22 μ m filtering with microporous membrane, lyophilization is packaged to be 1000 of freeze-dried powders.
Embodiment 2
(1) crude drug is: dendrobium 5000g, Flos Lonicerae 7500g, Radix Achyranthis Bidentatae 7500g, Radix Scrophulariae 7500g.
(2) get above-mentioned Radix Achyranthis Bidentatae, Radix Scrophulariae medical material, pulverize, add the 40% alcoholic solution reflux, extract, 1 time of 6 times of amounts, each 1 hour, merge extractive liquid, filtered, filtrate decompression concentrate extractum A;
(3) get above-mentioned Herba Dendrobii medical material, pulverize, 30% alcoholic solution that adds 5 times of amounts soaked 1 hour at 50 ℃, and reflux, extract, is 2 times then, and each 2 hours, merge extractive liquid, filtered, filtrate decompression concentrate extractum B;
(4) above-mentioned extractum A and extractum B are merged, obtain extractum C;
(5) with the NKA macroporous adsorbent resin of having handled well on the above-mentioned extractum C, with the water elution of 3 times of column volumes, reuse 80% alcoholic solution eluting is collected ethanol elution earlier, solution adds entry and makes that concentration of alcohol is 30%, leave standstill, centrifugal with 14000 rev/mins speed, the centrifugal liquid molecular cut off is 5000 ultrafilter membrane ultrafiltration, filtrate decompression concentrates, drying is pulverized, and obtains extract X;
(6) Chinese medicine honeysuckle is added the water of 8 times of amounts, soak half an hour, put into the supersound extraction jar, carry out supersound extract, time is 60 minutes, and frequency of oscillation is 80kHz, and the control temperature is a room temperature, extract 4 times, merge extractive liquid, filters, filtrate decompression is concentrated into solution: medical material is 1: 1, last NKA-II type macroporous adsorbent resin, first water elution with 5 times of column volumes, reuse 80% alcoholic solution eluting is collected ethanol elution, concentrating under reduced pressure, drying is pulverized, and obtains extract Y;
(7) said extracted thing X and extract Y are merged, with the water for injection dissolving, add glucosan, regulating pH value with meglumine is 7.0, and with 0.22 μ m filtering with microporous membrane, lyophilization is packaged to be 1000 of freeze-dried powders.
Embodiment 3
(1) crude drug is: Herba Dendrobii 6250g, Flos Lonicerae 12500g, Radix Achyranthis Bidentatae 12500g, Radix Scrophulariae 12500g.
(2) get above-mentioned Radix Achyranthis Bidentatae, Radix Scrophulariae medical material, pulverize, add the 30% alcoholic solution reflux, extract, 2 times of 10 times of amounts, each 2 hours, merge extractive liquid, filtered, filtrate decompression concentrate extractum A;
(3) get above-mentioned Herba Dendrobii medical material, pulverize, 50% alcoholic solution that adds 8 times of amounts soaked 2 hours at 60 ℃, and reflux, extract, is 2 times then, and each 3 hours, merge extractive liquid, filtered, filtrate decompression concentrate extractum B;
(4) above-mentioned extractum A and extractum B are merged, obtain extractum C;
(5) with the AB-8 macroporous adsorbent resin of having handled well on the above-mentioned extractum C, with the water elution of 4 times of column volumes, reuse 70% alcoholic solution eluting is collected ethanol elution earlier, solution adds entry and makes that concentration of alcohol is 25%, leave standstill, centrifugal with 18000 rev/mins speed, the centrifugal liquid molecular cut off is 5000 ultrafilter membrane ultrafiltration, filtrate decompression concentrates, drying is pulverized, and obtains extract X;
(6) above-mentioned Chinese medicine honeysuckle is added the water of 10 times of amounts, soak half an hour, put into the supersound extraction jar, carry out supersound extract, time is 40 minutes, and frequency of oscillation is 60kHz, and the control temperature is a room temperature, extract 4 times, merge extractive liquid,, extracting solution leaves standstill, and filters, decompression filtrate recycling ethanol, last D101 macroporous adsorbent resin with the water elution of 5 times of column volumes, is collected water lotion, speed with 18000 rev/mins is centrifugal, the centrifugal liquid molecular cut off is 3000 ultrafilter membrane ultrafiltration, and filtrate decompression concentrates, drying, pulverize, obtain extract Y;
(7) said extracted thing X and extract Y are merged, with the water for injection dissolving, add the manna alcohol and glucose, regulating pH value with meglumine is 6.0, and with 0.22 μ m filtering with microporous membrane, lyophilization is packaged to be 1000 of freeze-dried powders.
Embodiment 4
(1) crude drug is: Herba Dendrobii oculati 6250g, Flos Lonicerae 10000g, Radix Achyranthis Bidentatae 10000g, Radix Scrophulariae 10000g.
(2) get above-mentioned Radix Achyranthis Bidentatae, Radix Scrophulariae medical material, pulverize, add the 20% alcoholic solution reflux, extract, 3 times of 8 times of amounts, each 2 hours, merge extractive liquid, filtered, filtrate decompression concentrate extractum A;
(3) get above-mentioned Herba Dendrobii medical material, pulverize, 40% alcoholic solution that adds 7 times of amounts soaked 1 hour at 55 ℃, and reflux, extract, is 1 time then, and each 2 hours, merge extractive liquid, filtered, filtrate decompression concentrate extractum B;
(4) above-mentioned extractum A and extractum B are merged, obtain extractum C;
(5) with the D101 macroporous adsorbent resin of having handled well on the above-mentioned extractum C, with the water elution of 5 times of column volumes, reuse 65% alcoholic solution eluting is collected ethanol elution earlier, solution adds entry and makes that concentration of alcohol is 22%, leave standstill, centrifugal with 17000 rev/mins speed, the centrifugal liquid molecular cut off is 5000 ultrafilter membrane ultrafiltration, filtrate decompression concentrates, drying is pulverized, and obtains extract X;
(6) Chinese medicine honeysuckle is added the water of 12 times of amounts, soak half an hour, put into the supersound extraction jar, carry out supersound extract, time is 50 minutes, and frequency of oscillation is 50kHz, and the control temperature is a room temperature, extract 3 times, merge extractive liquid, filters, filtrate decompression is concentrated into solution: medical material is 1: 1, last NKA-II type macroporous adsorbent resin, first water elution with 3 times of column volumes, reuse 60% alcoholic solution eluting is collected ethanol elution, concentrating under reduced pressure, drying is pulverized, and obtains extract Y;
(7) said extracted thing X and extract Y are merged, with the water for injection dissolving, add dextran, regulating pH value with meglumine is 5.0, and with 0.22 μ m filtering with microporous membrane, lyophilization is packaged to be 1000 of freeze-dried powders.
Embodiment 5
(1) crude drug is: Herba Dendrobii 7000g, Flos Lonicerae 13750g, Radix Achyranthis Bidentatae 13750g, Radix Scrophulariae 13750g.
(2) get above-mentioned Radix Achyranthis Bidentatae, Radix Scrophulariae medical material, pulverize, add the 15% alcoholic solution reflux, extract, 2 times of 12 times of amounts, each 1 hour, merge extractive liquid, filtered, filtrate decompression concentrate extractum A;
(3) get above-mentioned Herba Dendrobii medical material, pulverize, 45% alcoholic solution that adds 9 times of amounts soaked 2 hours at 65 ℃, and reflux, extract, is 2 times then, and each 2 hours, merge extractive liquid, filtered, filtrate decompression concentrate extractum B;
(4) above-mentioned extractum A and extractum B are merged, obtain extractum C;
(5) with the AB-8 macroporous adsorbent resin of having handled well on the above-mentioned extractum C, with the water elution of 4 times of column volumes, reuse 75% alcoholic solution eluting is collected ethanol elution earlier, solution adds entry and makes that concentration of alcohol is 27%, leave standstill, centrifugal with 19000 rev/mins speed, the centrifugal liquid molecular cut off is 5000 ultrafilter membrane ultrafiltration, filtrate decompression concentrates, drying is pulverized, and obtains extract X;
(6) above-mentioned Chinese medicine honeysuckle is added the water of 9 times of amounts, soak half an hour, put into the supersound extraction jar, carry out supersound extract, time is 45 minutes, and frequency of oscillation is 30kHz, and the control temperature is a room temperature, extract 3 times, merge extractive liquid,, extracting solution leaves standstill, and filters, decompression filtrate recycling ethanol, last D101 macroporous adsorbent resin with the water elution of 4 times of column volumes, is collected water lotion, speed with 15000 rev/mins is centrifugal, the centrifugal liquid molecular cut off is 3000 ultrafilter membrane ultrafiltration, and filtrate decompression concentrates, drying, pulverize, obtain extract Y;
(7) said extracted thing X and extract Y are merged, with the water for injection dissolving, add polyvinylpyrrolidone and fructose, regulating pH value with meglumine is 5.5, and with 0.22 μ m filtering with microporous membrane, lyophilization is packaged to be 1000 of freeze-dried powders.
Embodiment 6
(1) crude drug is: Herba Dendrobii 6000g, Flos Lonicerae 8750g, Radix Achyranthis Bidentatae 8750g, Radix Scrophulariae 8750g.
(2) get above-mentioned Radix Achyranthis Bidentatae, Radix Scrophulariae medical material, pulverize, add the 35% alcoholic solution reflux, extract, 1 time of 9 times of amounts, each 2 hours, merge extractive liquid, filtered, filtrate decompression concentrate extractum A;
(3) get above-mentioned Herba Dendrobii medical material, pulverize, 35% alcoholic solution that adds 6 times of amounts soaked 1 hour at 68 ℃, and reflux, extract, is 1 time then, and each 3 hours, merge extractive liquid, filtered, filtrate decompression concentrate extractum B;
(4) above-mentioned extractum A and extractum B are merged, obtain extractum C;
(5) with the NKA macroporous adsorbent resin of having handled well on the above-mentioned extractum C, with the water elution of 3 times of column volumes, reuse 62% alcoholic solution eluting is collected ethanol elution earlier, solution adds entry and makes that concentration of alcohol is 24%, leave standstill, centrifugal with 16000 rev/mins speed, the centrifugal liquid molecular cut off is 5000 ultrafilter membrane ultrafiltration, filtrate decompression concentrates, drying is pulverized, and obtains extract X;
(6) Chinese medicine honeysuckle is added the water of 11 times of amounts, soak half an hour, put into the supersound extraction jar, carry out supersound extract, time is 35 minutes, and frequency of oscillation is 40kHz, and the control temperature is a room temperature, extract 4 times, merge extractive liquid, filters, filtrate decompression is concentrated into solution: medical material is 1: 1, last NKA-II type macroporous adsorbent resin, first water elution with 4 times of column volumes, reuse 70% alcoholic solution eluting is collected ethanol elution, concentrating under reduced pressure, drying is pulverized, and obtains extract Y;
(7) said extracted thing X and extract Y are merged, with the water for injection dissolving, add fructose, regulating pH value with meglumine is 5.2, and with 0.22 μ m filtering with microporous membrane, lyophilization is packaged to be 1000 of freeze-dried powders.
Embodiment 7
(1) crude drug is: Herba Dendrobii 5750g, Flos Lonicerae 10000g, Radix Achyranthis Bidentatae 10000g, Radix Scrophulariae 10000g.
(2) get above-mentioned Radix Achyranthis Bidentatae, Radix Scrophulariae medical material, pulverize, add the 25% alcoholic solution reflux, extract, 3 times of 11 times of amounts, each 1 hour, merge extractive liquid, filtered, filtrate decompression concentrate extractum A;
(3) get above-mentioned Herba Dendrobii medical material, pulverize, 55% alcoholic solution that adds 8 times of amounts soaked 2 hours at 54 ℃, and reflux, extract, is 2 times then, and each 3 hours, merge extractive liquid, filtered, filtrate decompression concentrate extractum B;
(4) above-mentioned extractum A and extractum B are merged, obtain extractum C;
(5) with the D101 macroporous adsorbent resin of having handled well on the above-mentioned extractum C, with the water elution of 4 times of column volumes, reuse 78% alcoholic solution eluting is collected ethanol elution earlier, solution adds entry and makes that concentration of alcohol is 25%, leave standstill, centrifugal with 15000 rev/mins speed, the centrifugal liquid molecular cut off is 5000 ultrafilter membrane ultrafiltration, filtrate decompression concentrates, drying is pulverized, and obtains extract X;
(6) above-mentioned Chinese medicine honeysuckle is added the water of 13 times of amounts, soak half an hour, put into the supersound extraction jar, carry out supersound extract, time is 55 minutes, and frequency of oscillation is 70kHz, and the control temperature is a room temperature, extract 3 times, merge extractive liquid,, extracting solution leaves standstill, and filters, decompression filtrate recycling ethanol, last D101 macroporous adsorbent resin with the water elution of 6 times of column volumes, is collected water lotion, speed with 19000 rev/mins is centrifugal, the centrifugal liquid molecular cut off is 3000 ultrafilter membrane ultrafiltration, and filtrate decompression concentrates, drying, pulverize, obtain extract Y;
(7) said extracted thing X and extract Y are merged, with the water for injection dissolving, add polyvinylpyrrolidone, regulating pH value with meglumine is 2.7, and with 0.22 μ m filtering with microporous membrane, lyophilization is packaged to be 1000 of freeze-dried powders.
The present invention is used for intravenous drip, and one time 2-4 props up, and 1 time on the one, uses with sodium chloride injection dissolving back; If insoluble matter is arranged, can add solubilizing agent.
Claims (5)
1, a kind of preparation method of freeze dried Mailuoning powder injection is characterized in that, it may further comprise the steps:
(1) raw material medicines in portions by weight consists of: Herba Dendrobii 2-3 part, Flos Lonicerae 3-6 part, Radix Achyranthis Bidentatae 3-6 part, Radix Scrophulariae 3-6 part.
(2) get above-mentioned weight portion Radix Achyranthis Bidentatae, Radix Scrophulariae medical material, pulverize, add polar solvent M reflux, extract, 1-3 time that 6-15 doubly measures, each 1-2 hour, merge extractive liquid, filtered, filtrate decompression concentrated extractum A;
(3) get above-mentioned weight portion Herba Dendrobii medical material, pulverize, add the polar solvent N that 5-10 doubly measures and soaked 1-2 hour at 50 ℃-70 ℃, reflux, extract, is 2-3 time then, and each 2 hours, merge extractive liquid, filtered, filtrate decompression concentrated extractum B;
(4) above-mentioned extractum A and extractum B are merged, obtain extractum C;
(5) with low pole or the nonpolar macroporous adsorption resin handled well on the above-mentioned extractum C, with the water elution of 3-5 times of column volume, reuse 60%-80% alcoholic solution eluting is collected ethanol elution earlier, solution adds entry and makes that concentration of alcohol is 20%-30%, leave standstill, centrifugal with 14000-20000 rev/min speed, the centrifugal liquid molecular cut off is 5000 ultrafilter membrane ultrafiltration, filtrate decompression concentrates, drying is pulverized, and obtains extract X;
(6) get above-mentioned weight portion Chinese medicine honeysuckle, pulverize, according to following method 1) or 2) extract:
1) Chinese medicine honeysuckle is added the water that 8-14 doubly measures, soak half an hour, put into the supersound extraction jar, carry out supersound extract, time is 30-60 minute, and frequency of oscillation is 20-80kHz, and the control temperature is a room temperature, extract 3-4 time, merge extractive liquid,, extracting solution leaves standstill, and filters, decompression filtrate recycling ethanol, last D101 macroporous adsorbent resin with the water elution of 4-6 times of column volume, is collected water lotion, speed with 14000-20000 rev/min is centrifugal, the centrifugal liquid molecular cut off is 3000 ultrafilter membrane ultrafiltration, and filtrate decompression concentrates, drying, pulverize, obtain extract Y;
2) Chinese medicine honeysuckle is added the water that 8-14 doubly measures, soak half an hour, put into the supersound extraction jar, carry out supersound extract, the time is 30-60 minute, frequency of oscillation is 20-80kHz, the control temperature is a room temperature, extracts merge extractive liquid, 3-4 time, filter, filtrate decompression is concentrated into solution: medical material is 1: 1, last NKA-II type macroporous adsorbent resin, first water elution with 3-5 times of column volume, reuse 60%-80% alcoholic solution eluting, collect ethanol elution, concentrating under reduced pressure, drying, pulverize, obtain extract Y;
(7) said extracted thing X and extract Y being merged, with the water for injection dissolving, add the water solublity freeze-dried excipient, is 4.0-7.0 with meglumine regulator solution pH value, and with 0.22 μ m filtering with microporous membrane, lyophilization is packaged to be freeze-dried powder.
2, preparation method according to claim 1 is characterized in that, described Herba Dendrobii medical material comprises dendrobium, Herba Dendrobii oculati and Herba Dendrobii.
3, preparation method according to claim 1 is characterized in that, polar solvent M is the 10%-40% alcoholic solution.
4, preparation method according to claim 1 is characterized in that, polar solvent N is the 30%-60% alcoholic solution.
5, preparation method according to claim 1 is characterized in that, meglumine regulator solution pH value is 5.0-6.0.
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| CN 200510051522 CN1286511C (en) | 2005-03-04 | 2005-03-04 | Novel process for preparing Mailuoing freeze-dried powder injection |
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| CN 200510051522 CN1286511C (en) | 2005-03-04 | 2005-03-04 | Novel process for preparing Mailuoing freeze-dried powder injection |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101085224B (en) * | 2006-06-08 | 2011-11-30 | 天津天士力之骄药业有限公司 | Detection method of 'Mailuoning' injection preparation |
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| CN101085224B (en) * | 2006-06-08 | 2011-11-30 | 天津天士力之骄药业有限公司 | Detection method of 'Mailuoning' injection preparation |
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