CN103768494B - One treats migrainous pharmaceutical composition and its preparation method and application - Google Patents
One treats migrainous pharmaceutical composition and its preparation method and application Download PDFInfo
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- CN103768494B CN103768494B CN201210397369.1A CN201210397369A CN103768494B CN 103768494 B CN103768494 B CN 103768494B CN 201210397369 A CN201210397369 A CN 201210397369A CN 103768494 B CN103768494 B CN 103768494B
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- Medicinal Preparation (AREA)
Abstract
The present invention provides one to treat migrainous pharmaceutical composition and its preparation method and application, described pharmaceutical composition is mainly made up of each raw material of following parts by weight: Rhizoma Chuanxiong 1 ~ 15 part, the Radix Angelicae Dahuricae 1 ~ 11 part, Flos Chrysanthemi 2 ~ 18 parts, Radix Curcumae 1 ~ 15 part, Ramulus Uncariae Cum Uncis 1 ~ 15 part, Herba Asari 0.2 ~ 1.8 part, Rhizoma Ligustici 1 ~ 11 part and Scorpio 0.8 ~ 8 part, described pharmaceutical composition can be used for treating migraine；Described method is undertaken by the method comprised the following steps: weigh above-mentioned medical material water or alcoholic solution extracts, then by after extracting solution concentration, dry, pulverize, to obtain final product.Medicine composite for curing migraine of the present invention, its reasonable recipe, drug effect is clear and definite, and is beneficial to and prepares into modernization preparation and be easy to quality control；Toxic and side effects is little, safely and effectively；And its raw material sources are easy to get, and technical process is prone to industrialization, various common oral can be made as required, for clinic provide convenient, more efficient, quality is more controllable, brings more interests for patient, thus producing huge social benefit.
Description
Technical field
The present invention relates to the field of Chinese medicines.Present invention relates particularly to a kind of pharmaceutical composition and its preparation method and application, particularly relate to one and treat migrainous pharmaceutical composition and its preparation method and application.
Background technology
Migraine is the headache that the nerve-dysfunction of blood vessel of a kind of periodical attack causes, and with the migraine of recurrent exerbation or bilatenal headache for feature, often has family history.
Migraine belongs to most common neurological disorder, is modal symptom in general family medicine, and migrainous prevalence and sickness rate are all very high, and, sharp ache, intermittent recurrent exerbation, touching difficulty longer with the course of disease heal as feature.Bring medicine burden painful and heavy greatly to patient and family thereof, cause psychology in various degree, society and economic problems simultaneously.
Investigation display, it is 13% that domestic 10 city Neurology Departments add up migrainous annual prevalence；Prevalence in Children and teenager is 7.7%；The general population of 3% suffers from chronic headache (namely monthly having a headache >=15 days), and women migraine and the migrainous sex ratio of male are about 2-3:1.Hebetic women is easier to suffer from headaches, and compared with male children and teenager, the risk that women suffers from headaches to exceed 1.5 times, suffers from migrainous risk and exceeds 1.7 times.Chinese Medical Association's pain credit can be announced " China's headache Epidemiological study " result and be shown, in inland of China 18-65 year crowd, migraine attack rate is 23.8%, nearly 1/4 Chinese (by the All population capacities of the 5th national census statistics more than 1,300,000,000 calculating, nearly more than 300,000,000 people) suffer headache puzzlement.Every City patient spends 1098.08 yuan for the treatment of headaches every year on average.
Over nearly 5 years, migrainous sickness rate is in rising trend.Headache number increase mainly has two big reasons.One is that pressure strengthens, and occurs that the people of the emotional problem such as anxiety, depression gets more and more, and the patient being wrapped with by tension headache also increases therewith；Stay up late, bend over one's desk working for a long time, sleep and irregular etc. also can cause headache；Two is that along with the enhancing gradually that health care is realized by people, patient is more willing to hospital and finds the cause of disease with than before.The market of migraine treatment medicine will potentiality unlimited.
At present, serious migraine has been decided to be one of chronic disease of disabling most by World Health Organization, because it has the feature of recurrent exerbation, can increase complication risk, and cerebral infarction risk can be made to increase by 2.16 times, makes alba abnormal risk increase by 3.9 times.Investigation displays that, therefore the people of 85% cannot concentrate one's energy work.
Chemical medicine is mainly used in migrainous acute treatment and prophylactic treatment, and commercially available main species has beta-adrenergic blocking agent: most widely used general, such as Propranolol；Antidepressant: such as amitriptyline, nortriptyline；Calcium-channel antagonists: such as verapamil, nimodipine；5-HT antagonist: such as methysergide；Anticonvulsant: valproic acid；Vitamins: riboflavin (vitamin B2).
Along with the lasting dilatation in migraine remedy market, Chinese patent medicine occupies more and more important position wherein, has the huge market demand.For migraine, the traditional Chinese medical science emphasizes " taking stopgap measures when sending out, effect a permanent cure at ordinary times ", the etiology and pathogenesis complicated for migraine and pathological characteristic, and Chinese patent medicine carries out multipath, Mutiple Targets and multi-level Comprehensive Treatment, has obvious advantage, makes up the deficiency of chemical medicine.
But, the migrainous Chinese medicine of current treatment can not effectively treat migraine, and therefore, exploitation one can effectively treat migrainous Chinese medicine and necessitate.
Summary of the invention
Therefore, it is an object of the invention to for currently without the deficiency that can effectively treat migrainous Chinese medicine, it is provided that one treats migrainous pharmaceutical composition and its preparation method and application such that it is able to effectively treat migraine, and the toxic and side effects of this pharmaceutical composition is little, safely and effectively；And its raw material sources are easy to get, and technical process is prone to industrialization.
Unless specifically stated otherwise, " compound extract " herein refers both to " the migrainous pharmaceutical composition for the treatment of without carrier and/or adjuvant ".
For above-mentioned purpose, technical scheme provided by the invention is as follows:
On the one hand, the present invention provides one to treat migrainous pharmaceutical composition, and described pharmaceutical composition is mainly made up of each raw material of following parts by weight: Rhizoma Chuanxiong 1 ~ 15 part, the Radix Angelicae Dahuricae 1 ~ 11 part, Flos Chrysanthemi 2 ~ 18 parts, Radix Curcumae 1 ~ 15 part, Ramulus Uncariae Cum Uncis 1 ~ 15 part, Herba Asari 0.2 ~ 1.8 part, Rhizoma Ligustici 1 ~ 11 part and Scorpio 0.8 ~ 8 part.
Preferably, described Rhizoma Chuanxiong be 4 ~ 12 parts, the Radix Angelicae Dahuricae be 3 ~ 9 parts, Flos Chrysanthemi be 6 ~ 14 parts, Radix Curcumae be 4 ~ 12 parts, Ramulus Uncariae Cum Uncis be 4 ~ 12 parts, Herba Asari be 0.6 ~ 1.4 part, Rhizoma Ligustici is 3 ~ 9 parts and Scorpio is 2 ~ 6 parts.
Preferably, described Rhizoma Chuanxiong be 8 parts, the Radix Angelicae Dahuricae be 6 parts, Flos Chrysanthemi be 10 parts, Radix Curcumae be 8 parts, Ramulus Uncariae Cum Uncis be 8 parts, Herba Asari be 1 part, Rhizoma Ligustici is 6 parts and Scorpio is 4 parts.
Preferably, described pharmaceutical composition also comprises pharmaceutically acceptable carrier and/or adjuvant.
It is highly preferred that the dosage form of described pharmaceutical composition is capsule, tablet, granule or drop pill.
On the other hand, the present invention provides the preparation method treating migrainous pharmaceutical composition described in the invention described above, described method is undertaken by the method comprised the following steps: weigh Ligusticum chuanxiong, the Radix Angelicae Dahuricae, Flos Chrysanthemi, Radix Curcumae, Ramulus Uncariae Cum Uncis, Herba Asari, Rhizoma Ligustici and Scorpio, with water or alcoholic solution for solvent, extracted by one or more the method being selected from decoction, reflux, extract, vapor distillation extraction, supersound extraction, merceration, microwave extraction and high pressure extract, after again extracting solution being concentrated, dry, pulverize, to obtain final product.
Preferably, concentrated by rotary evaporation, decocting and concentrating or thin film concentration under normal pressure or reduced pressure.
Preferably, it is dried by vacuum drying, spray drying, lyophilization or drying under reduced pressure.
Preferably, said method comprising the steps of:
1) Ligusticum chuanxiong, the Radix Angelicae Dahuricae, Flos Chrysanthemi, Radix Curcumae, Ramulus Uncariae Cum Uncis, Herba Asari, Rhizoma Ligustici and Scorpio are weighed, extraction by steam distillation is passed through with water or alcoholic solution, collect volatile oil, filtrate is standby, it is also preferred that ground, extracts with the water of 10-12 times of volume of the quality of medicinal material weighed or alcoholic solution, more preferably, extract 5-6 hour, it is most preferred that, described alcoholic solution is alcoholic solution；
2) again by medicinal residues water or alcoholic solution reflux, extract, filter, merge with the filtrate in step 1), preferably, extract with the water of 10-12 times of volume of the medical material weight weighed or alcoholic solution, it is also preferred that ground, extract 5-6 hour, it is most preferred that, described alcoholic solution is alcoholic solution；
3) the filtrate concentration that will merge, dry, obtains extract I；
4) after the volatile oil inclusion that obtains in step 1), extract I will be added, to obtain final product.
Preferably, the concentration of described alcoholic solution is 60-80 volume %.
Preferably, said method comprising the steps of:
1) weighing Ligusticum chuanxiong, the Radix Angelicae Dahuricae, Flos Chrysanthemi, Radix Curcumae and Rhizoma Ligustici, after pulverizing and sieving, extracted by supercritical extraction, collect volatile oil, medicinal residues are standby, it is more preferred to, cross 40 mesh sieves；
2) weighing Ramulus Uncariae Cum Uncis, Herba Asari and scorpion powder and be broken into coarse powder, mix with the medicinal residues in step 1), add alcoholic solution and soak, seepage pressure effects, until percolate color is light, it is more preferred to, add the soak with ethanol 24 hours that percent by volume is 60-80%；
3) again by step 2) concentration of the percolate that obtains, dry, spray into volatile oil, mixing, to obtain final product.
Preferably, said method comprising the steps of:
1) weighing Ligusticum chuanxiong, the Radix Angelicae Dahuricae, Flos Chrysanthemi, Radix Curcumae and Rhizoma Ligustici, by water or alcoholic solution reflux, extract, collect volatile oil, filtrate is standby, it is more preferred to, extract with the water of 10-12 times of volume of the quality of medicinal material weighed or alcoholic solution, it is also preferred that ground, extract 5-6 hour；
2) filtrate is concentrated, dry, obtain extract II；
3) weigh Ramulus Uncariae Cum Uncis, Herba Asari and Scorpio, by water or alcoholic solution reflux, extract, filter, filtrate is condensed into thick paste, obtains extract III, it is more preferred to, it is the alcohol reflux of 60-80% by volume ratio, it is also preferred that ground, extracts 2 times, each 1.0 hours；
4) extract II is added in extract III, mixing, after dry, pulverize, spray into the volatile oil that step 1) prepares, mixing, to obtain final product.
Preferably, in step 1), before extracting with water or alcoholic solution, also include the step adding the water soaking of 10-12 times of volume of the medical material weight weighed, it is preferable that soak 2 hours.
Preferably, described method is undertaken by the method comprised the following steps: described method is undertaken by the method comprised the following steps: weigh Ligusticum chuanxiong, the Radix Angelicae Dahuricae, Flos Chrysanthemi, Radix Curcumae, Ramulus Uncariae Cum Uncis, Herba Asari, Rhizoma Ligustici and Scorpio, carries out reflux, extract, by water or alcoholic solution, decocts and extract or seepage pressure effects.
It is highly preferred that when seepage pressure effects, after weighing medical material, after being pulverized, after adding alcohol solution dipping, seepage pressure effects, collect percolation for just filtering 5 times of volumes of liquid, be concentrated into thick paste I；It is further continued for percolation, until percolate color is light, collects percolate, then be concentrated into thick paste II；Then thick paste I and thick paste II are mixed, to obtain final product；It is further preferred that add the alcohol solution dipping 24 hours that percent by volume is 60-85%.
Preferably, when by reflux, extract, after weighing medical material, after water or alcoholic solution reflux, extract, merging filtrate, dry, to obtain final product；It is highly preferred that with take quality of medicinal material 10-12 times of volume or alcoholic solution 2-3 time, each 1-2 hour, it is also preferred that ground, extract three times, each 1.5 hours.
Preferably, when decocting extraction, after weighing medical material, decoct after extracting after soaking, merging filtrate, dry, to obtain final product；It is highly preferred that by water boiling and extraction 2-3 time of the 10-12 times of volume taking quality of medicinal material, each 1-2 hour, it is also preferred that ground, extract three times, each 1.5 hours.
It is further preferred that described alcoholic solution alcoholic solution, more preferably, the concentration of described alcoholic solution is 60-80 volume %.
Preferably, also include adding appropriate pharmaceutically acceptable carrier and/or adjuvant, make the step of capsule, tablet, granule or drop pill.
Preferably, described capsule is soft capsule.
Another further aspect, the present invention provides the migrainous compositions for the treatment of described in a kind of the invention described above preparing for treating the application in migrainous medicine.
Pharmaceutical composition of the present invention, can be used for treating migraine, its reasonable recipe, and drug effect is clear and definite, and is beneficial to and prepares into modernization preparation and be easy to quality control；Toxic and side effects is little, safely and effectively；And its raw material sources are easy to get, technical process is prone to industrialization, can make various common oral as required, the modern Chinese medicine convenient, more efficient for clinic offer, quality is more controllable, more interests are brought, thus producing huge social benefit for patient.
Detailed description of the invention
Below in conjunction with detailed description of the invention, the present invention is described in further detail, and the embodiment provided is in order to illustrate the present invention, rather than in order to limit the scope of the present invention.
Unless specifically stated otherwise, Rhizoma Chuanxiong used in following example, the Radix Angelicae Dahuricae, Flos Chrysanthemi, Radix Curcumae, Ramulus Uncariae Cum Uncis, Herba Asari, Rhizoma Ligustici and Scorpio are all purchased from Chang'an, Anguo City Chinese crude drug company limited.
Unless specifically stated otherwise, ferulic acid used in following example, ligustilide and luteoloside are all purchased from Nat'l Pharmaceutical & Biological Products Control Institute.
Unless specifically stated otherwise, reagent used in following example is analytical pure level reagent, and can from regular distributor available from.
Embodiment 1
Prescription: Rhizoma Chuanxiong 4.6Kg, Radix Angelicae Dahuricae 4.6Kg, Flos Chrysanthemi 9.3Kg, Radix Curcumae 4.6Kg, Ramulus Uncariae Cum Uncis 4.6Kg, Herba Asari 0.9Kg, Rhizoma Ligustici 4.6Kg and Scorpio 3.7Kg.
Take above-mentioned medical material, add 12 times of volume (volume/weight, L/Kg) water soaking 2 hours, extraction by steam distillation 6 hours, collects volatile oil, and filtrate is standby, medicinal residues add 10 times of volume (volume/weight, L/Kg) water reflux, extract, 1h, filters, and all filtrates merge, being evaporated to relative density when 50 DEG C is 1.15 ~ 1.20, add ethanol to concentration of alcohol 80 volume %, place overnight precipitation, filter, decompression filtrate recycling ethanol is to without alcohol taste, it is concentrated into 50 DEG C of relative densities about 1.10, drying under reduced pressure, obtains extract I；
The inclusion of volatile oil: weigh appropriate beta-schardinger dextrin-, add (the volume/weight of 5 times of volumes, L/Kg) water makes beta-schardinger dextrin-saturated solution, keep constant temperature 50 DEG C, mixing speed 700r/min, in volatile oil: beta-schardinger dextrin-=1: 8(volume/mass) ratio be slowly added dropwise volatile oil, with magnetic stirring apparatus inclusion 2h, take out and put cold preservation 24h in refrigerator.Sucking filtration, uses a small amount of water washing.Collecting filtering residue, 40 DEG C dry, obtain volatile oil beta-CD inclusion complex.
Being added by above-mentioned volatile oil inclusion complex in extract I, equal increments mixes, and prepares the compound extract for preparing pharmaceutical composition of the present invention, for the following embodiment of the preparation of pharmaceutical composition of the present invention.
The pharmaceutical formulation of pharmaceutical composition of the present invention is made up of following component:
Adopt 90% ethanol wet granulation, concrete preparation method is as follows: by above-mentioned prepared compound extract, starch+lactose+microcrystalline Cellulose by weighing in right amount, 80 mesh sieves are crossed after mix homogeneously, add 90 volume % alcoholic solution to granulate in right amount, 40 DEG C of forced air dryings crossed 20 mesh sieve granulate after 3 hours, obtained the granule of pharmaceutical composition of the present invention.
Embodiment 2
Prescription: Rhizoma Chuanxiong 2.4Kg, Radix Angelicae Dahuricae 1.8Kg, Flos Chrysanthemi 2.9Kg, Radix Curcumae 2.4Kg, Ramulus Uncariae Cum Uncis 2.4Kg, Herba Asari 0.3Kg, Rhizoma Ligustici 1.8Kg and Scorpio 1.3Kg.
Take Rhizoma Chuanxiong, the Radix Angelicae Dahuricae, Flos Chrysanthemi, Radix Curcumae, Rhizoma Ligustici, pulverized 40 orders, carry out CO2Supercritical extraction, is placed in extraction kettle, sets extracting pressure 25MPa, extraction temperature 50 DEG C, extracts 4 hours, collects volatile oil, and medicinal residues are standby；
All the other flavour of a drug are ground into coarse powder, mix with above-mentioned medicinal residues, add 80 volume % soak with ethanol after 24 hours, slowly percolation, to percolate color light, evaporation and concentration is rotated to 50 DEG C of relative densities about 1.10 under condition of normal pressure, spray drying, sprays into volatile oil, mixing, prepare the compound extract for preparing pharmaceutical composition of the present invention, for the following embodiment of the preparation of pharmaceutical composition of the present invention.
The pharmaceutical formulation of pharmaceutical composition of the present invention is made up of following component:
After adopting wet granulation prepared by tablet forming technique, concrete preparation method is as follows: compound extract, lactose+starch+microcrystalline Cellulose are weighed according to quantity, 80 mesh sieves are crossed after mix homogeneously, the alcoholic solution (1%) adding polyvinylpyrrolidone is granulated in right amount, cross 20 mesh sieve granulate after dry 2 hours for 50 DEG C, it is subsequently adding magnesium stearate lubricant+micropowder silica gel, tabletting, obtains the tablet of pharmaceutical composition of the present invention.
Embodiment 3
Compound extract embodiment 2 prepared, for the following embodiment of the preparation of pharmaceutical composition of the present invention.
The pharmaceutical formulation of pharmaceutical composition of the present invention is made up of following component:
Compound extract, starch+microcrystalline Cellulose+mannitol, citric acid are weighed according to quantity, 80 mesh sieves are crossed after mix homogeneously, the alcoholic solution (2%) adding polyvinylpyrrolidone is granulated in right amount, cross 20 mesh sieve granulate after dry 2 hours for 50 DEG C, it is subsequently adding lubricant micropowder silica gel, encapsulated, obtain the capsule of pharmaceutical composition of the present invention.
Embodiment 4
Prescription: Rhizoma Chuanxiong 5.8Kg, Radix Angelicae Dahuricae 4.4Kg, Flos Chrysanthemi 8.7Kg, Radix Curcumae 5.8Kg, Ramulus Uncariae Cum Uncis 5.8Kg, Herba Asari 0.9Kg, Rhizoma Ligustici 4.4Kg and Scorpio 2.9Kg.
Take Rhizoma Chuanxiong, the Radix Angelicae Dahuricae, Flos Chrysanthemi, Radix Curcumae, Rhizoma Ligustici, add the water soaking 2 hours of 10 times of volumes (volume/weight, L/Kg), extraction by steam distillation 5 hours, collecting volatile oil, when water liquid thin film concentration is to 40 DEG C, relative density is 1.10 ~ 1.15, adds ethanol to concentration of alcohol 70 volume %, place overnight precipitation, filtering, decompression filtrate recycling ethanol is to without alcohol taste, being concentrated into thick paste, drying under reduced pressure or spray drying, obtain extract II；
All the other flavour of a drug 60 volume % alcohol reflux 2 times of 8 times of volumes (volume/weight, L/Kg), each 1.0 hours, concentrating under reduced pressure becomes thick paste, obtain extract III, add extract II, mixing, drying under reduced pressure, pulverize, spray into volatile oil, mixing, prepare the compound extract for preparing pharmaceutical composition of the present invention, for the following embodiment of invention formulation.
The pharmaceutical formulation of pharmaceutical composition of the present invention is made up of following component:
Prepared by employing dry granulation process, concrete preparation method is as described below: compound extract, pregelatinized Starch, lactose, microcrystalline Cellulose, magnesium stearate are weighed according to quantity, crosses 100 mesh sieves after mix homogeneously, dry-pressing is granulated, cross 20 mesh sieve granulate, pack, obtain compound granule of the present invention.
Embodiment 5
Compound extract embodiment 4 prepared, for the following embodiment of the preparation of pharmaceutical composition of the present invention.
The compound preparation formula of pharmaceutical composition of the present invention is made up of following component:
By Macrogol 4000,6000 heating in water-bath to 80 DEG C, after all melted, add compound extract, stirring, to dissolving, is uniformly dispersed；Dripping after 75 DEG C of sealed thermal insulating 30min, instills in the liquid paraffin of 5 ~ 15 DEG C；Drop pill drop to the greatest extent also erasing liquor paraffin body, the drying that will be formed, obtains compound dripping pill of the present invention.
Embodiment 6
Prescription: Rhizoma Chuanxiong 11.6Kg, Radix Angelicae Dahuricae 8.7Kg, Flos Chrysanthemi 13.5Kg, Radix Curcumae 11.6Kg, Ramulus Uncariae Cum Uncis 11.6Kg, Herba Asari 1.4Kg, Rhizoma Ligustici 8.7Kg and Scorpio 5.8Kg.
By above-mentioned medical material by 10 times of volume (volume/weight, L/Kg) 80 volume % alcohol reflux three times, each 1.5h, filter, merge three extracting solution, recycling design, decocting and concentrating is to 50 DEG C of relative densities about 1.10, spray drying, prepares the compound extract for preparing pharmaceutical composition of the present invention, for the following embodiment of the preparation of pharmaceutical composition of the present invention.
The pharmaceutical formulation of pharmaceutical composition of the present invention is made up of following component:
After adopting wet granulation prepared by encapsulated technique, concrete preparation method is as follows: compound extract, lactose+starch, citric acid are weighed according to quantity, 80 mesh sieves are crossed after mix homogeneously, the alcoholic solution (2%) adding polyvinylpyrrolidone is granulated in right amount, cross 20 mesh sieve granulate after dry 2 hours for 50 DEG C, it is subsequently adding lubricant, encapsulated, obtain compound capsule of the present invention.
Embodiment 7
Compound extract embodiment 6 prepared, for the following embodiment of the preparation of pharmaceutical composition of the present invention.
The pharmaceutical formulation of pharmaceutical composition of the present invention is made up of following component:
Compound extract, lactose+starch+microcrystalline Cellulose being weighed according to quantity, cross 80 mesh sieves after mix homogeneously, the alcoholic solution (5%) adding ethyl cellulose is granulated in right amount, cross 20 mesh sieve granulate after dry 1.5 hours for 60 DEG C, it is subsequently adding lubricant, tabletting, obtains compound tablet of the present invention.
Embodiment 8
Embodiment 6 is shown in compound extract of the present invention preparation, for the following embodiment of the preparation of pharmaceutical composition of the present invention.
The pharmaceutical formulation of pharmaceutical composition of the present invention is made up of following component:
Above-mentioned compound extract was pulverized 80 mesh sieves, adds glycerol+vegetable oil+methyl parahydroxybenzoate mixing, make capsule casing material with gelatin, be pressed into soft capsule.
Embodiment 9
Prescription: Rhizoma Chuanxiong 8Kg, Radix Angelicae Dahuricae 6Kg, Flos Chrysanthemi 10Kg, Radix Curcumae 8Kg, Ramulus Uncariae Cum Uncis 8Kg, Herba Asari 1Kg, Rhizoma Ligustici 6Kg and Scorpio 4Kg.
Above-mentioned pulverizing medicinal materials is become coarse powder, add 85 volume % soak with ethanol after 24 hours, slowly percolation, collects the percolate of 5 times of volumes of liquid of just filtering, is individually evaporated to thick paste I, continue percolation, to percolate color light, under reduced pressure rotate evaporation and concentration to thick paste and thick paste II, thick paste I and thick paste II are mixed, prepare the compound extract for preparing pharmaceutical composition of the present invention, for the following embodiment of the preparation of pharmaceutical composition of the present invention.
The pharmaceutical formulation of pharmaceutical composition of the present invention is made up of following component:
By Macrogol 4000,6000 heating in water-bath to 85 DEG C, after all melted, add compound extract, stirring, to dissolving, is uniformly dispersed；Dripping after 70 DEG C of sealed thermal insulating 40min, instills in the dimethicone of 0 ~ 10 DEG C；Dimethicone, drying are use up and wiped to the drop pill drop of formation, makes drop pill.
Embodiment 10
Prescription: Rhizoma Chuanxiong 4Kg, Radix Angelicae Dahuricae 8Kg, Flos Chrysanthemi 14Kg, Radix Curcumae 4Kg, Ramulus Uncariae Cum Uncis 8Kg, Herba Asari 0.6Kg, Rhizoma Ligustici 3Kg and Scorpio 2Kg.
Above-mentioned medical material is added 12 times of volume (volume/weight, L/Kg) water soaking 1 hour, soak by water three times, each 1.5 hours, filtering, filtrate reduced in volume is to thick paste, vacuum drying, prepare the compound extract for preparing pharmaceutical composition of the present invention, for the following embodiment of the preparation of pharmaceutical composition of the present invention.
The pharmaceutical formulation of pharmaceutical composition of the present invention is made up of following component:
Adopt 85% ethanol wet granulation, concrete preparation method is as follows: by above-mentioned prepared compound extract, dextrin+cane sugar powder+citric acid+carboxymethyl cellulose by weighing in right amount, 80 mesh sieves are crossed after mix homogeneously, add 85% alcoholic solution to granulate in right amount, 40 DEG C of forced air dryings crossed 20 mesh sieve granulate after 3 hours, obtained the granule of pharmaceutical composition of the present invention.
Embodiment 11
Prescription: Rhizoma Chuanxiong 8Kg, Radix Angelicae Dahuricae 6Kg, Flos Chrysanthemi 10Kg, Radix Curcumae 8Kg, Ramulus Uncariae Cum Uncis 12Kg, Herba Asari 1Kg, Rhizoma Ligustici 6Kg and Scorpio 4Kg.
Above-mentioned pulverizing medicinal materials is crossed 40 mesh sieves, add 8 times of volume (volume/weight, L/Kg) 80 volume % ethanol are in 50 DEG C of supersound extraction 2 times, each 2 hours, sucking filtration, filtrate merges, decompression and solvent recovery, is concentrated into 50 DEG C of relative densities about 1.05, spray drying, prepare the compound extract for preparing pharmaceutical composition of the present invention, for the following embodiment of the preparation of pharmaceutical composition of the present invention.
The pharmaceutical formulation of pharmaceutical composition of the present invention is made up of following component:
After adopting wet granulation prepared by tablet forming technique, concrete preparation method is as follows: compound extract, modified starch+Icing Sugar+sodium carboxymethyl cellulose+citric acid are weighed according to quantity, 100 mesh sieves are crossed after mix homogeneously, add 85 volume % alcoholic solution to granulate in right amount, cross 20 mesh sieve granulate after dry 2 hours for 50 DEG C, it is subsequently adding magnesium stearate lubricant+Pulvis Talci, tabletting, obtains the tablet of pharmaceutical composition of the present invention.
Embodiment 12
Prescription: Rhizoma Chuanxiong 12Kg, Radix Angelicae Dahuricae 3Kg, Flos Chrysanthemi 6Kg, Radix Curcumae 12Kg, Ramulus Uncariae Cum Uncis 4Kg, Herba Asari 1.4Kg, Rhizoma Ligustici 9Kg and Scorpio 6Kg.
Above-mentioned pulverizing medicinal materials is crossed 40 mesh sieves, carries out the supercritical extraction of carbon dioxide, extracting pressure 25MPa, extraction temperature 50 DEG C, extraction time 4 hours, entrainer 80 volume % ethanol, collect extract.Extract decompression and solvent recovery is to without alcohol taste, being diluted with water to relative density about 1.05, lyophilization, prepare the compound extract for preparing pharmaceutical composition of the present invention, for the following embodiment of the preparation of pharmaceutical composition of the present invention.
The pharmaceutical formulation of pharmaceutical composition of the present invention is made up of following component:
By PEG20000,6000 heating in water-bath to 85 DEG C, after all melted, add compound extract, stirring, to dissolving, is uniformly dispersed；Dripping after 80 DEG C of sealed thermal insulating 50min, instills in the liquid paraffin of 10 ~ 25 DEG C；Drop pill drop to the greatest extent also erasing liquor paraffin body, the drying that will be formed, obtains compound dripping pill of the present invention.
The mensuration of the compound recipe compound extract principle active component content that test example 1 present invention prepares
The contrast of the compound extract that the compound extract of embodiment 9 prepares with traditional method
The compound extract that traditional handicraft method prepares: weigh medical material by prescription, add water to and do not have medical material 5 centimetres, soak 30 minutes, decoct 2 times, each 30 minutes, filters, and filtrate merges, and is concentrated into thick paste, to obtain final product.
The assay of ferulic acid, ligustilide and luteoloside in compound extract described in embodiment 9 and traditional handicraft
1. chromatographic condition and system suitability
Chromatographic column: DikmaDiamonsil-C18Post (250 × 4.6mm, 5 μm), mobile phase is acetonitrile (A)-0.1% phosphate aqueous solution (B), gradient elution program: 0～15minA-B (18:82), 15～30minA-B (18:82 → 20:80), 30～35minA-B (20:80 → 30:70), flow velocity: 1.0ml/min, detection wavelength: 320nm, column temperature: 35 DEG C.
2. mix the preparation of reference substance solution
Weigh ferulic acid, ligustilide and luteoloside reference substance respectively appropriate, accurately weighed, make every 1ml mixing reference substance solution containing ferulic acid 3.22 μ g, ligustilide 1.32 μ g and luteoloside 2.34 μ g.
3. the preparation of need testing solution
Compound extract prepared in Example 9 and traditional handicraft, precision weighs in right amount (about amounting to Flos Chrysanthemi crude drug 0.2g), puts in tool plug triangular flask, accurate addition 25ml methanol, close plug, weighed quality, supersound extraction 30min, put to room temperature, supply the quality of less loss with methanol, shake up, stand, take 0.45 μm of microporous filter membrane of supernatant to filter, take subsequent filtrate and get final product.
4. the mensuration of sample
Being prepared by the preparation method of above-mentioned need testing solution, analyze by above-mentioned chromatographic condition sample introduction, measure the content (taking three parallel sample to be measured, i.e. n=3) of ferulic acid, ligustilide and luteoloside in sample in accordance with the law, result sees below shown in table 1.
Table 1 Different Extraction Method main active compares
Test result indicate that, the technique of the present invention, compared with traditional handicraft, has significant advantage in the rate of transform of main active ferulic acid, ligustilide, luteoloside etc..
The analgesic effect of the pharmaceutical composition of test example 2 present invention
Adopt rat nitroglycerin type migraine test model, observe the analgesic effect of pharmaceutical composition of the present invention.
Reagent: the granule of embodiment 4 invention, embodiment 9 invention drop pill；Ergotamine and caffeine tablet, every containing gynergen 1mg, by Xinyi, Shanghai medicine (group) company limited produce, lot number: 100821；Nitroglycerin injection, every milliliter, containing nitroglycerin 5mg, is produced by Mingxing Pharmaceutical Factory, Guangzhou, lot number: 20100514；Calcitonin-gene-related peptide radioimmunoassay kits Gou Bai PLA General Hospital Science and Technology Development Center puts and exempts from institute.
Animal: SD rat, Beijing experimental animal Technology Co., Ltd. of dimension tonneau China, animal quality certification SCXK (capital) 2006-0009,2007-0001.
Take body weight 180-220gSD rat, successive administration 7 days, after administration in the 7th day except matched group except lumbar injection nitroglycerin 10mg/kg, for three days on end, 1-4h observation Animal Behavior Science index after last modeling, result is as described in Table 2.
The table 2 rat ears red appearing and subsiding time compares (X ± S, n=10)
Result shows, after last modeling, 1-4h rat occurs that ears are rubescent, forelimb is frequently scratched one's head, climb the phenomenons such as cage increased frequency, after giving pharmaceutical composition of the present invention, can significantly improving the behavior symptom of rat: do not occur the red symptom of ear all the time, in the unit interval, number of times difficult to tackle significantly reduces (P < 0.01).
After modeling 6 hours, put to death rat, collect blood, after placing 1h, centrifugal, take serum, adopt the change of its jugular vein Plasma Calcitonin Gene-related Peptide (CGRP) content of measured by radioimmunoassay, result is as described in Table 3.
The relevant phthalein content (X ± S, n=9) of calcitonin gene in table 3 rat carotid artery blood plasma
Result shows, compares with model group, and in medicine jugular vein blood plasma, CGRP content significantly reduces, and has significant difference (P < 0.01).Show that the Migraine Rats behavior symptom that nitroglycerin is induced by pharmaceutical composition of the present invention significantly improves and control action, alleviate migraine.Its mechanism of action may be by regulating the level of CGRP in Migraine Rats blood plasma, thus improving cerebrovascular shrink function obstacle.
Embodiment of the present invention are described in detail now, it is believed that adopt content disclosed above, clearly can do a lot of improvement and change for a person skilled in the art, the present invention can be applied to greatest extent, without departing from the essence spirit of the present invention.All these changes and improvements are regarded as within the scope of the present invention, therefore, before preferred embodiment be merely illustrative of, but not the scope being intended to limit the present invention in any manner.
Claims (39)
1. treating a migrainous pharmaceutical composition, described pharmaceutical composition is made up of each raw material of following parts by weight: Rhizoma Chuanxiong 1～15 part, the Radix Angelicae Dahuricae 1～11 part, Flos Chrysanthemi 2～18 parts, Radix Curcumae 1～15 part, Ramulus Uncariae Cum Uncis 1～15 part, Herba Asari 0.2～1.8 part, Rhizoma Ligustici 1～11 part and Scorpio 0.8～8 part.
2. the migrainous pharmaceutical composition for the treatment of according to claim 1, it is characterized in that, described Rhizoma Chuanxiong is 4～12 parts, the Radix Angelicae Dahuricae is 3～9 parts, Flos Chrysanthemi is 6～14 parts, Radix Curcumae is 4～12 parts, Ramulus Uncariae Cum Uncis is 4～12 parts, Herba Asari is 0.6～1.4 part, Rhizoma Ligustici is 3～9 parts and Scorpio is 2～6 parts.
3. the migrainous pharmaceutical composition for the treatment of according to claim 1, it is characterised in that described Rhizoma Chuanxiong is 8 parts, the Radix Angelicae Dahuricae is 6 parts, Flos Chrysanthemi is 10 parts, Radix Curcumae is 8 parts, Ramulus Uncariae Cum Uncis is 8 parts, Herba Asari is 1 part, Rhizoma Ligustici is 6 parts and Scorpio is 4 parts.
4. treating a migrainous pharmaceutical composition, described pharmaceutical composition is made up of each raw material of following parts by weight: Rhizoma Chuanxiong 1～15 part, the Radix Angelicae Dahuricae 1～11 part, Flos Chrysanthemi 2～18 parts, Radix Curcumae 1～15 part, Ramulus Uncariae Cum Uncis 1～15 part, Herba Asari 0.2～1.8 part, Rhizoma Ligustici 1～11 part and Scorpio 0.8～8 part, pharmaceutically acceptable carrier and/or adjuvant.
5. the migrainous pharmaceutical composition for the treatment of according to any one of claim 1-4, it is characterised in that the dosage form of described pharmaceutical composition is capsule, tablet, granule or drop pill.
6. the preparation method of the migrainous pharmaceutical composition for the treatment of according to any one of claim 1 to 5, described method is undertaken by the method comprised the following steps: weigh Ligusticum chuanxiong, the Radix Angelicae Dahuricae, Flos Chrysanthemi, Radix Curcumae, Ramulus Uncariae Cum Uncis, Herba Asari, Rhizoma Ligustici and Scorpio, with water or alcoholic solution for solvent, extracted by one or more the method being selected from decoction, reflux, extract, vapor distillation extraction, supersound extraction, merceration, microwave extraction and high pressure extract, after again extracting solution being concentrated, dry, pulverize, to obtain final product.
7. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 6, it is characterised in that described in be concentrated by under normal pressure or reduced pressure rotary evaporation, decocting and concentrating or thin film concentration and carry out.
8. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 6, it is characterised in that described drying is undertaken by spray drying, lyophilization or drying under reduced pressure.
9. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 6, it is characterised in that said method comprising the steps of:
1) weighing Ligusticum chuanxiong, the Radix Angelicae Dahuricae, Flos Chrysanthemi, Radix Curcumae, Ramulus Uncariae Cum Uncis, Herba Asari, Rhizoma Ligustici and Scorpio, with extraction by steam distillation, collect volatile oil, filtrate is standby；
2) again by medicinal residues water or alcoholic solution reflux, extract, filter, with step 1) in filtrate merge；
3) the filtrate concentration that will merge, dry, obtains extract I；
4) by step 1) in after the volatile oil inclusion that obtains, add extract I, to obtain final product.
10. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 9, it is characterised in that described step 1) in, described in be extracted as the water extraction of 10-12 times of volume of quality of medicinal material counted in order to L/kg, weigh.
11. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 9, it is characterised in that described step 1) in, described in be extracted as 5-6 hour.
12. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 9, it is characterised in that described step 2) in, described in be extracted as count in order to L/kg, the water of 10-12 times of volume of medicinal residues quality or alcoholic solution extract.
13. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 9, it is characterised in that described step 2) in, described in be extracted as 1 hour.
14. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 9, it is characterised in that described step 2) in, described alcoholic solution is alcoholic solution.
15. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 14, it is characterised in that the concentration of described alcoholic solution is 60-80 volume %.
16. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 6, it is characterised in that said method comprising the steps of:
1) weighing Ligusticum chuanxiong, the Radix Angelicae Dahuricae, Flos Chrysanthemi, Radix Curcumae and Rhizoma Ligustici, after pulverizing and sieving, extracted by supercritical extraction, collect volatile oil, medicinal residues are standby；
2) weigh Ramulus Uncariae Cum Uncis, Herba Asari and scorpion powder and be broken into coarse powder, with step 1) in medicinal residues mixing, add alcoholic solution soak, seepage pressure effects, until percolate color is light；
3) again by step 2) concentration of the percolate that obtains, dry, spray into volatile oil, mixing, to obtain final product.
17. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 16, it is characterised in that described step 1) in, described in sieve into cross 40 mesh sieves.
18. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 16, it is characterised in that described step 2) in, add the alcohol solution dipping 24 hours that percent by volume is 60-85%.
19. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 6, comprise the following steps:
1) weighing Ligusticum chuanxiong, the Radix Angelicae Dahuricae, Flos Chrysanthemi, Radix Curcumae and Rhizoma Ligustici, pass through reflux, extract, with water or alcoholic solution, collect volatile oil, filtrate is standby；
2) filtrate is concentrated, dry, obtain extract II；
3) weigh Ramulus Uncariae Cum Uncis, Herba Asari and Scorpio, pass through reflux, extract, with water or alcoholic solution, filter, filtrate is condensed into thick paste, obtains extract III；
4) extract II is added in extract III, mixing, after dry, pulverize, spray into step 1) prepare volatile oil, mixing, to obtain final product.
20. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 19, it is characterised in that described step 1) in, described in be extracted as count in order to L/kg, the water of 10-12 times of volume of medical material weight that weighs or alcoholic solution extract.
21. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 19, it is characterised in that described step 1) in, described in be extracted as 5-6 hour.
22. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 19, it is characterised in that described step 3) in, described in be extracted as by volume ratio be the alcohol reflux of 60-80%.
23. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 19, it is characterised in that described step 3) in, described in be extracted as extraction 2 times, each 1.0 hours.
24. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 19, it is characterized in that, in step 1) in, before extracting with water or alcoholic solution, also include adding in L/kg, the step of the water soaking of 10-12 times of volume of medical material weight that weighs.
25.RootAccording to the preparation method treating migrainous pharmaceutical composition described in claim 24, it is characterised in that described immersion is for soaking 2 hours.
26. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 6, it is characterized in that, described method is undertaken by the method comprised the following steps: weigh Ligusticum chuanxiong, the Radix Angelicae Dahuricae, Flos Chrysanthemi, Radix Curcumae, Ramulus Uncariae Cum Uncis, Herba Asari, Rhizoma Ligustici and Scorpio, by reflux, extract, decocts and extracts or seepage pressure effects.
27. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 26, it is characterised in that when seepage pressure effects, after weighing medical material, after being pulverized, after adding alcohol solution dipping, seepage pressure effects, collects percolation for 5 times of volumes of liquid of just filtering, is concentrated into thick paste I；It is further continued for percolation, until percolate color is light, collects percolate, then be concentrated into thick paste II；Then thick paste I and thick paste II are mixed, to obtain final product.
28. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 27, it is characterised in that add the alcohol solution dipping 24 hours that percent by volume is 60-85%.
29. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 26, it is characterised in that when by reflux, extract, after weighing medical material, after reflux, extract, merging filtrate, dry, to obtain final product.
30. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 29, it is characterised in that count in order to L/kg, the water of 10-12 times of volume of quality of medicinal material or alcoholic solution extract 2-3 time, each 1-2 hour.
31. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 29, it is characterised in that described in be extracted as extraction three times, each 1.5 hours.
32. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 26, it is characterised in that when decocting extraction, after weighing medical material, decoct after extracting after soaking, merging filtrate, dry, to obtain final product.
33. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 32, it is characterised in that count in order to L/kg, the water boiling and extraction of 10-12 times of volume of quality of medicinal material 2-3 time, each 1-2 hour.
34. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 32, it is characterised in that described in be extracted as extraction three times, each 1.5 hours.
35. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 30, it is characterised in that described alcoholic solution alcoholic solution.
36. the preparation method of the migrainous pharmaceutical composition for the treatment of according to claim 35, it is characterised in that the concentration of described alcoholic solution is 60-80%.
37. the preparation method treating migrainous pharmaceutical composition according to any one of claim 6 to 36, it is characterized in that, also include adding appropriate pharmaceutically acceptable carrier and/or adjuvant, make the step of capsule, tablet, granule or drop pill.
38. the preparation method treating migrainous pharmaceutical composition according to claim 37, it is characterised in that described capsule is soft capsule.
39. the migrainous pharmaceutical composition for the treatment of according to any one of claim 1 to 5 is used for the application treating in migrainous medicine in preparation.
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