CN101721510B - Medicine composition for treating headache or migraine and preparation method thereof - Google Patents

Medicine composition for treating headache or migraine and preparation method thereof Download PDF

Info

Publication number
CN101721510B
CN101721510B CN200910252554XA CN200910252554A CN101721510B CN 101721510 B CN101721510 B CN 101721510B CN 200910252554X A CN200910252554X A CN 200910252554XA CN 200910252554 A CN200910252554 A CN 200910252554A CN 101721510 B CN101721510 B CN 101721510B
Authority
CN
China
Prior art keywords
powder
medicine
micropowders
extracting solution
artificial moschus
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN200910252554XA
Other languages
Chinese (zh)
Other versions
CN101721510A (en
Inventor
朱建英
白玛卓玛
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Gansu Qizheng Tibetan Medicine Co Ltd
Original Assignee
Gansu Qizheng Tibetan Medicine Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Gansu Qizheng Tibetan Medicine Co Ltd filed Critical Gansu Qizheng Tibetan Medicine Co Ltd
Priority to CN200910252554XA priority Critical patent/CN101721510B/en
Publication of CN101721510A publication Critical patent/CN101721510A/en
Application granted granted Critical
Publication of CN101721510B publication Critical patent/CN101721510B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Abstract

The invention relates to a medicine composition for treating headache or migraine and a preparation method thereof. The medicine composition mainly comprises the crude drugs of strawberry, violet, rosarian, pearl and artificial musk. The preparation method of the medicine composition comprises the following steps: mixing the cleaned, selected and dried strawberry, the violet, the rosarian and the concocted pearl, pulverizing into medicinal powder with the particle diameter of 150-200mum, then mixing or directly mixing with the artificial musk after comminuting the artificial musk, putting into superfine pulverization equipment, pulverizing into superfine powder with the particle diameter of 0.1-50mum, taking the superfine powder as an active component and preparing a clinically or pharmaceutically acceptable medicament form according to a conventional process; the composition has very good curative effect in the aspect of treating the headache and the migraine.

Description

Treatment headache or migrainous pharmaceutical composition and preparation method thereof
Technical field
The present invention relates to a kind of pharmaceutical composition and preparation method thereof, particularly a kind of treatment headache or migrainous pharmaceutical composition and preparation method thereof.
Background technology
Headache is meant with head pain to be a kind of pain disease of cardinal symptom.Headache is symptom that ten minutes is common clinically, accounts for 60%~70% of Neurology Department patient sum.When the meninges in the skull, blood vessel and cranial nerve etc. outside the intracranial are upset, pain just can take place, and brain itself does not have pain.The reason that headache produces is very complicated, have intracranial, cranium is outer; There is head partial, general is also arranged; Many headaches that still can not find the cause of disease are so far also arranged.Be primary symptom person with the headache at present, be more common in all visible symptom in the diseases such as infective fever property disease, hypertension, rhinitis, trigeminal neuralgia, intracranial illness, neurosis, cerebral concussion and migraine to headache.It is many because of being invaded by exogenous pathogen, quiet will discord to trace it to its cause, weakness due to chronic disease and eating and drinking without temperance, influence head channels or brains lose foster due to.Migraine: just a kind of vascular headache.Migraine is one group of common headache type, is ictal neural blood vessel dysfunction, is characteristic with migraine or the bilatenal headache that takes place repeatedly.About 60% patient has family's medical history, plays the patient after growing up, and positive family history is less.Prevalence accounts for population more than 10%, and the women is more than the male.Seizure frequency is indefinite, and annual one to arriving every month one for several times to not waiting for several times.Migraine is removed foreign genetic element, and is still relevant with cerebral blood flow, platelet and biochemical factor, diet, endocrine factors etc., and nervous, hungry, lack sleep, noise, high light and climate change etc., all can induce outbreak.Mainly can be divided into three kinds of classical migraine, common migraine and specific types according to its performance.Classical migraine is modal type, also with other symptoms, as feel sick, vomiting etc.; The specific type migraine comprises ophthalmoplegia type, hemiplegia type, basilar artery type etc. again.
Headache or migraine are a kind of commonly encountered diseases, frequently-occurring disease, still lack specific medicament at present.
Nasal-cavity administration is the route of administration of comparatively ideal replacement drug administration by injection performance general action, and drug absorption is rapid, circulates without liver sausage; Avoided the infringement of medicine, but while patient's self-administration does not need professional equipment and nursing staff to liver; Easy to use, compliance is preferably arranged, be applicable to no injecting condition; Especially inconvenient oral or the injection medicine, the risk of single over administration is less.Nasal-cavity administration possibly be a kind of new way to brain transportation medicine.Simultaneously, can reduce nasal mucosa immunity cost, avoid many untoward reaction of present injecting immune.Some drugs absorbs rapidly through nasal mucosa, can be used as the route of administration of first aid medicine.Nasal-cavity administration is traditional administering mode, uses very extensive in department of otorhinolaryngology.As far back as the Ancient Times in China traditional Chinese medical science just with the smoked suction therapy of via intranasal application administrations such as steam agent, fumigant and suction powder.Ancient Chinese sucks the record of nasal cavity antiemetic for Tibet with regard to handlebar sandalwood and Aloe extract; The Flat head treats headache through the powder that nasal cavity is sucked a kind of leaves, and nasal cavity therapy also is already by a kind of treatment approach of people's understanding in the Hindu medicine system.Over nearly 20 years; Development along with new route of administration and novel form; Nasal-cavity administration receives people's attention gradually; Become one of focus of formulation art research, with Tibetan medicine with its pharmacy codes and standards according to strictness be developed to efficiently, the novel formulation of high-quality, safety, stable, taking convenience, will have vast market prospect and far-reaching social meaning.
Fructus Fragariae Ananssae is rosaceous plant Fructus Fragariae Ananssae Fragaria orientalis Lozinsk and the dry herb that belongs to various plants together.Florescence gathers, and removes impurity and root hair, dries.Draw and tell lung expectorant, holder is drawn heat in blood property pyesis, lung stomach congestion, grasserie pus infections.See " Chinese ministry standard Tibetan medicine volume ", standard numbering: WS3-BC-0067-95.
Herba corydalis edulis is the aerial parts of bloodroot Corydalisimpatiens(Pall.)Fisch Carydalis impatiens (Pall.) Fisch. and Corydalis thyrsiflora Prain. Carydalis tsayulensis C.Y.Wu et H.Chuang.Originate in ground such as Tibet, Qinghai, Sichuan, Gansu, the Inner Mongol, Heilungkiang; Corydalis thyrsiflora Prain. is distributed in ground such as Chayu, Tibet, Mangkang, Baxiu County, Jiangda County.Bitter in the mouth, digestion back bitter in the mouth, cool in nature.The heat extraction detumescence, promoting blood circulation to remove blood stasis.
The Flos rosae multiflorae is the dry petal of rosaceous plant mount emei Flos Rosae Multiflorae Rosa omeiensis Rolfe, thin,tough silk hair Flos Rosae Multiflorae Rosa sericea Lindl.Xia Qiu gathers, and dries in the shade.The sending down the abnormal ascending QI clearing gallbladder, promoting blood flow to regulate menstruation.Be used for " dragon " disease, " red crust " disease, the cough due to lung-heat spits blood, menoxenia, vascular becomes silted up bitterly, leucorrhea with red and white discharge, acute mastitis etc.See " Chinese ministry standard Tibetan medicine volume ", standard numbering: WS3-BC-0119-95.
Margarita is the Margarita that the animal Pteria martensii Dunker Pteria martensii of shellfish section (Dunker), Unionidae animal hydriopsis cumingii Hyriopsis cumingii (Lea) or cristaria plicata Cristaria plicata bivalve irriates such as (Leach) form.Sweet in the mouth, salty, cold.GUIXIN, Liver Channel.The arresting convulsion of calming the nerves, the removing nebula that makes eye bright, removing toxic substances and promoting granulation.Be used for the palpitation with fear insomnia, the infantile convulsion epilepsy, order is given birth to nebula, and skin infection is not held back.
Herba Saussureae Involueratae be bent Herba Saussureae Involueratae Saussurea gnaphaloides (Royle) Sch.-Bip. of feverfew Saussurea laniceps Saussurea.laniceps Hand.-Mazz., Mus,, Saussurea medusa Maxim. Saussurea medusa Maxim., three refers to the whole herb with root of Herba Saussureae Involueratae Saussurea tridactyla Sch.-Bip.ex Hook.f., dry measure used in former times leaf Herba Saussureae Involueratae Saussureaquercifolia W.W.Smith.Sweet in the mouth, little hardship, warm in nature.Return liver, kidney channel.Warming the kidney to invigorate YANG, regulating menstruation, hemostasis.Cure mainly sexual impotence, soreness of the waist and knees, woman's leukorrhagia, menoxenia, rheumatic Bi syndrome, traumatic hemorrhage.Herba Saussureae Involueratae has the physiologically active effective ingredient.Wherein umbelliferone have significantly antibiotic, blood pressure lowering is calm, spasmolysis; Scopoletin has and dispels the wind, antiinflammatory, pain relieving, eliminates the phlegm and antitumor action.
Summary of the invention
One object of the present invention is to disclose a kind of treatment headache or migrainous pharmaceutical composition.
Another object of the present invention is to disclose a kind of treatment headache or migrainous preparation of drug combination method.
The present invention seeks to realize through following technical scheme:
Option A:
The crude drug of pharmaceutical composition of the present invention consists of:
Fructus Fragariae Ananssae 10-80 weight portion Herba corydalis edulis 10-80 weight portion Flos rosae multiflorae 10-80 weight portion
Margarita 10-50 weight portion artificial Moschus 0.5-5 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably:
Fructus Fragariae Ananssae 20-70 weight portion Herba corydalis edulis 20-70 weight portion Flos rosae multiflorae 20-70 weight portion
Margarita 20-45 weight portion artificial Moschus 0.5-5 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably:
Fructus Fragariae Ananssae 21-40 weight portion Herba corydalis edulis 45-69 weight portion Flos rosae multiflorae 20-36 weight portion
Margarita 20-45 weight portion artificial Moschus 0.5-5 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably:
Fructus Fragariae Ananssae 55-69 weight portion Herba corydalis edulis 21-40 weight portion Flos rosae multiflorae 51-69 weight portion
Margarita 20-45 weight portion artificial Moschus 0.5-5 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably:
Fructus Fragariae Ananssae 21-40 weight portion Herba corydalis edulis 54-69 weight portion Flos rosae multiflorae 40-69 weight portion Margarita 20-45 is heavy
Amount part artificial Moschus 0.5-5 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably:
The Fructus Fragariae Ananssae 50 weight portion Herba corydalis eduliss 50 weight portion Flos rosae multifloraies 45 weight portions
Margarita 40 weight portion artificial Moschuss 1.8 weight portions.
The crude drug composition of pharmaceutical composition of the present invention is preferably:
The Fructus Fragariae Ananssae 30 weight portion Herba corydalis eduliss 60 weight portion Flos rosae multifloraies 35 weight portions
Margarita 40 weight portion artificial Moschuss 0.8 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably:
The Fructus Fragariae Ananssae 60 weight portion Herba corydalis eduliss 30 weight portion Flos rosae multifloraies 65 weight portions
Margarita 30 weight portion artificial Moschuss 3.8 weight portions.
Option b:
The crude drug of pharmaceutical composition of the present invention consists of:
Fructus Fragariae Ananssae 10-80 weight portion Herba corydalis edulis 10-80 weight portion Flos rosae multiflorae 10-80 weight portion
Margarita 10-50 weight portion artificial Moschus 0.5-5 weight portion Herba Saussureae Involueratae 10-50 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably:
Fructus Fragariae Ananssae 20-70 weight portion Herba corydalis edulis 20-70 weight portion Flos rosae multiflorae 20-70 weight portion
Margarita 20-45 weight portion artificial Moschus 0.5-5 weight portion Herba Saussureae Involueratae 25-50 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably:
Fructus Fragariae Ananssae 21-40 weight portion Herba corydalis edulis 45-69 weight portion Flos rosae multiflorae 20-36 weight portion
Margarita 20-45 weight portion artificial Moschus 0.5-5 weight portion Herba Saussureae Involueratae 36-50 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably:
Fructus Fragariae Ananssae 55-69 weight portion Herba corydalis edulis 21-40 weight portion Flos rosae multiflorae 51-69 weight portion
Margarita 20-45 weight portion artificial Moschus 0.5-5 weight portion Herba Saussureae Involueratae 25-50 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably:
Fructus Fragariae Ananssae 21-40 weight portion Herba corydalis edulis 54-69 weight portion Flos rosae multiflorae 40-69 weight
Part Margarita 20-45 weight portion artificial Moschus 0.5-5 weight portion Herba Saussureae Involueratae 25-35 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably:
The Fructus Fragariae Ananssae 50 weight portion Herba corydalis eduliss 50 weight portion Flos rosae multifloraies 45 weight portions
Margarita 40 weight portion artificial Moschuss 1.8 weight portion Herba Saussureae Involuerataes 40 weight portions.
The crude drug composition of pharmaceutical composition of the present invention is preferably:
The Fructus Fragariae Ananssae 30 weight portion Herba corydalis eduliss 60 weight portion Flos rosae multifloraies 35 weight portions
Margarita 40 weight portion artificial Moschuss 0.8 weight portion Herba Saussureae Involueratae 45 weight portions.
The crude drug composition of pharmaceutical composition of the present invention is preferably:
The Fructus Fragariae Ananssae 60 weight portion Herba corydalis eduliss 30 weight portion Flos rosae multifloraies 65 weight portions
Margarita 25 weight portion artificial Moschuss 3.8 weight portion Herba Saussureae Involuerataes 30 weight portions.
Above-mentioned each crude drug all can the proximate medicine replacement of selection function from " Chinese ministry standard Tibetan medicine volume ", " pharmacopeia " or " Chinese medicine dictionary " etc.
The method for preparing of such scheme A or B is: get option A or B composition material medicine; Be ground into fine powder; Add conventional adjuvant; According to common process, process clinical or pharmaceutics on acceptable forms, include but not limited to tablet, capsule, powder, soft capsule, drop pill, honeyed pill, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, oral liquid, ejection preparation or external preparation.
The method for preparing preferred for preparation of such scheme A or B becomes nasal cavity administrated prepn; Get option A or B composition material medicine; Be ground into fine powder; Add conventional adjuvant,, can be made into nasal drop, aerosol, spray, powder spray, gel, microsphere, microgranule and nanoparticle, cyclodextrin clathrate, liposome, liposome precursor, microcapsule, nanoparticle and other nasal cavity medicines according to common process.
In the preferred following method 1,2 of the method for preparing of the present invention program A pharmaceutical composition active component or 3 any one:
Method 1: will clean, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine Margarita after pulverizing mixes; Being ground into particle diameter is 150-200 μ m medicated powder; Being placed on mixing behind artificial Moschus's porphyrize or directly mixing with the artificial Moschus that to be ground into particle diameter in the micronizing equipment be 0.1-50 μ m micropowders again, is the active component of medicine of the present invention with this micropowders;
Method 1 further is preferably: will clean, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine Margarita after pulverizing mixes; Being ground into particle diameter is 160 μ m medicated powder; Being placed on mixing behind artificial Moschus's porphyrize or directly mixing with the artificial Moschus that to be ground into particle diameter in the micronizing equipment be 0.1-1 μ m micropowders again, is the active component of medicine of the present invention with this micropowders;
Method 1 further is preferably: will clean, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine Margarita after pulverizing mixes; Being ground into particle diameter is 160 μ m medicated powder; Being placed on mixing behind artificial Moschus's porphyrize or directly mixing with the artificial Moschus that to be ground into particle diameter in the micronizing equipment be 1-10 μ m micropowders again, is the active component of medicine of the present invention with this micropowders;
Method 1 further is preferably: will clean, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine Margarita after pulverizing mixes; Being ground into particle diameter is 190 μ m medicated powder; Being placed on mixing behind artificial Moschus's porphyrize or directly mixing with the artificial Moschus that to be ground into particle diameter in the micronizing equipment be 10-40 μ m micropowders again, is the active component of medicine of the present invention with this micropowders;
Method 1 further is preferably: will clean, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine Margarita after pulverizing mixes; Being ground into particle diameter is 180 μ m medicated powder; Being placed on mixing behind artificial Moschus's porphyrize or directly mixing with the artificial Moschus that to be ground into particle diameter in the micronizing equipment be 0.1-40 μ m micropowders again, is the active component of medicine of the present invention with this micropowders.
Method 2: the artificial Moschus is ground to fine powder or superfine powder be broken into micropowders earlier; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine Margarita after pulverizing mixes; The water boiling and extraction of doubly measuring with medical material weight 5-20 1-3 time; And relative density is the extractum of 1.01-1.30 when extracting solution is concentrated into 30 ℃-80 ℃; The water dilution of doubly measuring with extractum volume 1-10, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with the 10%-30% washing with alcohol, resolve with 40%-75% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine of the present invention;
Method 2 further is preferably: the artificial Moschus is ground to fine powder or superfine powder be broken into micropowders earlier; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine Margarita after pulverizing mixes; With the water boiling and extraction of 12 times of amounts of medical material weight 2 times; And relative density is 1.15 extractum when extracting solution is concentrated into 50 ℃, with the water dilution of 5 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 30% washing with alcohol, resolve with 75% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine of the present invention;
Method 2 further is preferably: the artificial Moschus is ground to fine powder or superfine powder be broken into micropowders earlier; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine Margarita after pulverizing mixes; With the water boiling and extraction of 15 times of amounts of medical material weight 2 times; And relative density is 1.20 extractum when extracting solution is concentrated into 60 ℃, with the water dilution of 8 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 30% washing with alcohol, resolve with 75% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine of the present invention;
Method 2 further is preferably: the artificial Moschus is ground to fine powder or superfine powder be broken into micropowders earlier; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine Margarita after pulverizing mixes; With the water boiling and extraction of 15 times of amounts of medical material weight 3 times; And relative density is 1.20 extractum when extracting solution is concentrated into 70 ℃, with the water dilution of 7 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 7 times of bed volumes/hour macroporous adsorptive resins, use water washing earlier, again with 30% washing with alcohol, resolve with 70% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine of the present invention;
Method 2 further is preferably: the artificial Moschus is ground to fine powder or superfine powder be broken into micropowders earlier; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine Margarita after pulverizing mixes; With the water boiling and extraction of 8 times of amounts of medical material weight 3 times; And relative density is 1.05 extractum when extracting solution is concentrated into 40 ℃, with the water dilution of 2 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 3 times of bed volumes/hour macroporous adsorptive resins, use water washing earlier, again with 15% washing with alcohol, resolve with 45% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine of the present invention;
Method 3: the artificial Moschus is ground to fine powder or superfine powder be broken into micropowders earlier; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine Margarita after pulverizing mixes; 75% ethanol of doubly measuring with medical material weight 6-12 decocts extraction 1-3 time; And relative density is the extractum of 1.01-1.30 when extracting solution is concentrated into 30 ℃-70 ℃; The water dilution of doubly measuring with extractum volume 1-10, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with the 10%-30% washing with alcohol, resolve with 40%-75% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine of the present invention;
Method 3 further is preferably: the artificial Moschus is ground to fine powder or superfine powder be broken into micropowders earlier; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine Margarita after pulverizing mixes; With 50% alcohol reflux of 8 times of amounts of medical material weight 1 time; And relative density is 1.10 extractum when extracting solution is concentrated into 60 ℃, with the water dilution of 8 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 20% washing with alcohol, resolve with 45% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine of the present invention;
Method 3 further is preferably: the artificial Moschus is ground to fine powder or superfine powder be broken into micropowders earlier; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine Margarita after pulverizing mixes; With 65% alcohol reflux of 10 times of amounts of medical material weight 3 times; And relative density is 1.05 extractum when extracting solution is concentrated into 40 ℃; With the dilution of the water of 10 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 30% washing with alcohol, resolve with 70% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine of the present invention;
Method 3 further is preferably: the artificial Moschus is ground to fine powder or superfine powder be broken into micropowders earlier; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine Margarita after pulverizing mixes; With 80% alcohol reflux of 12 times of amounts of medical material weight 2 times; And relative density is 1.25 extractum when extracting solution is concentrated into 70 ℃; With the dilution of the water of 9 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 15% washing with alcohol, resolve with 60% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine of the present invention.
The method for preparing of the present invention program B pharmaceutical composition active component is any one in following method 1,2 or 3:
Method 1: will clean earlier, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; Being ground into particle diameter is 150-200 μ m medicated powder; Being placed on mixing behind artificial Moschus's porphyrize or directly mixing with the artificial Moschus that to be ground into particle diameter in the micronizing equipment be 0.1-50 μ m micropowders again, is the active component of medicine of the present invention with this micropowders;
Method 1 further is preferably: will clean earlier, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; Being ground into particle diameter is 160 μ m medicated powder; Being placed on mixing behind artificial Moschus's porphyrize or directly mixing with the artificial Moschus that to be ground into particle diameter in the micronizing equipment be 0.1-1 μ m micropowders again, is the active component of medicine of the present invention with this micropowders;
Method 1 further is preferably: will clean earlier, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; Being ground into particle diameter is 160 μ m medicated powder; Being placed on mixing behind artificial Moschus's porphyrize or directly mixing with the artificial Moschus that to be ground into particle diameter in the micronizing equipment be 1-10 μ m micropowders again, is the active component of medicine of the present invention with this micropowders;
Method 1 further is preferably: will clean earlier, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; Being ground into particle diameter is 190 μ m medicated powder; Being placed on mixing behind artificial Moschus's porphyrize or directly mixing with the artificial Moschus that to be ground into particle diameter in the micronizing equipment be 10-40 μ m micropowders again, is the active component of medicine of the present invention with this micropowders;
Method 1 further is preferably: will clean earlier, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; Being ground into particle diameter is 180 μ m medicated powder; Being placed on mixing behind artificial Moschus's porphyrize or directly mixing with the artificial Moschus that to be ground into particle diameter in the micronizing equipment be 0.1-40 μ m micropowders again, is the active component of medicine of the present invention with this micropowders.
Method 2: the artificial Moschus is ground to fine powder or superfine powder be broken into micropowders earlier; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; The water boiling and extraction of doubly measuring with medical material weight 5-20 1-3 time; And relative density is the extractum of 1.01-1.30 when extracting solution is concentrated into 30 ℃-80 ℃; The water dilution of doubly measuring with extractum volume 1-10, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with the 10%-30% washing with alcohol, resolve with 40%-75% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine of the present invention;
Method 2 further is preferably: the artificial Moschus is ground to fine powder or superfine powder be broken into micropowders earlier; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; With the water boiling and extraction of 20 times of amounts of medical material weight 1 time; And relative density is 1.10 extractum when extracting solution is concentrated into 70 ℃; With the dilution of the water of 8 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 30% washing with alcohol, resolve with 70% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine of the present invention;
Method 2 further is preferably: the artificial Moschus is ground to fine powder or superfine powder be broken into micropowders earlier; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; With the water boiling and extraction of 6 times of amounts of medical material weight 3 times; And relative density is 1.20 extractum when extracting solution is concentrated into 50 ℃; With the dilution of the water of 4 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 20% washing with alcohol, resolve with 50% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine of the present invention;
Method 2 further is preferably: the artificial Moschus is ground to fine powder or superfine powder be broken into micropowders earlier; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; With the water boiling and extraction of 12 times of amounts of medical material weight 2 times; And relative density is 1.25 extractum when extracting solution is concentrated into 65 ℃; With the dilution of the water of 10 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 15% washing with alcohol, resolve with 60% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine of the present invention.
Method 3: the artificial Moschus is ground to fine powder or superfine powder be broken into micropowders earlier; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; 75% ethanol of doubly measuring with medical material weight 6-12 decocts extraction 1-3 time; And relative density is the extractum of 1.01-1.30 when extracting solution is concentrated into 30 ℃-70 ℃; The water dilution of doubly measuring with extractum volume 1-10, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with the 10%-30% washing with alcohol, resolve with 40%-75% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine of the present invention;
Method 3 further is preferably: the artificial Moschus is ground to fine powder or superfine powder be broken into micropowders earlier; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; With 55% alcohol reflux of 10 times of amounts of medical material weight 2 times; And relative density is 1.05 extractum when extracting solution is concentrated into 65 ℃; With the dilution of the water of 8 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 25% washing with alcohol, resolve with 70% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine of the present invention;
Method 3 further is preferably: the artificial Moschus is ground to fine powder or superfine powder be broken into micropowders earlier; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; With 80% alcohol reflux of 6 times of amounts of medical material weight 1 time; And relative density is 1.10 extractum when extracting solution is concentrated into 45 ℃; With the dilution of the water of 9 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 20% washing with alcohol, resolve with 50% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine of the present invention;
Method 3 further is preferably: the artificial Moschus is ground to fine powder or superfine powder be broken into micropowders earlier; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; With 70% alcohol reflux of 12 times of amounts of medical material weight 3 times; And relative density is 1.20 extractum when extracting solution is concentrated into 70 ℃; With the dilution of the water of 10 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 15% washing with alcohol, resolve with 65% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine of the present invention;
The invention described above pharmaceutical composition option A and B crude drug are after getting the pharmaceutical composition active component after the preparation; According to common process, process clinical or pharmaceutics on acceptable tablet, capsule, powder, soft capsule, drop pill, honeyed pill, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, oral liquid, ejection preparation or external preparation and nasal drop, aerosol, spray, powder spray, gel, microsphere, microgranule and nanoparticle, cyclodextrin clathrate, liposome, liposome precursor, microcapsule, nanoparticle and other nasal cavity medicines.
Pharmaceutical composition active component preferred for preparation of the present invention becomes nasal cavity administrated prepn, is nasal drop, aerosol, spray, powder spray, gel, microsphere, microgranule and nanoparticle, cyclodextrin clathrate, liposome, liposome precursor, microcapsule, nanoparticle and other nasal cavity medicines.
Said nasal mist is to become to add behind the medicine activity component PH regulator, buffer agent, cosolvent, isoosmotic adjusting agent, antibacterial, stabilizing agent by preparation of pharmaceutical compositions of the present invention to process nasal mist.
Said nasal drop is to become to add behind the medicine activity component PH regulator, buffer agent, isoosmotic adjusting agent, antibacterial, stabilizing agent by preparation of pharmaceutical compositions of the present invention to process nasal drop.
Said nasal cavity powder spray is to add diluent (carrier material) after becoming medicine activity component by preparation of pharmaceutical compositions of the present invention, processes the nasal cavity powder spray; Diluent (carrier material) is any one in lactose, anhydrous glucose, the mannitol.
Said nasal gel is to be become to add gel-type vehicle, PH regulator, wetting agent, solubilizing agent, antioxidant, antibacterial etc. behind the medicine activity component and process nasal gel by preparation of pharmaceutical compositions of the present invention; Gel-type vehicle is any one in carbomer, hypromellose, methylcellulose, sodium carboxymethyl cellulose, chitosan, polyethylene pyrrole network alkane ketone, polyvinyl alcohol and the hyaluronic acid sodium; The PH regulator is any one in triethanolamine, sodium hydroxide, ethylenediamine, lauryl amine and the sodium bicarbonate; Wetting agent is any one in glycerol, the propylene glycol; Solvent is any one in water, glycerol, propylene glycol and the ethanol; Solubilizing agent is any one in tween 80, polyethylene castor oil hydrogenated and the paregal O; Antioxidant is any one in various sulphite, cysteine, di-tert-butyl hydroxy toluene (BHT), the potassium sorbate; Antiseptic is any one in parabens, thimerosal, chlorocresol, chlorobutanol, benzoic acid and sodium benzoate, the potassium sorbate.
Above-mentioned PH regulator is that PH regulator acids is any one in hydrochloric acid, sulphuric acid, phosphoric acid, acetic acid, boric acid, citric acid, malic acid, tartaric acid, maleic acid, acidic amino acid class, the sodium dihydrogen phosphate; PH regulator bases is any one of sodium hydroxide, sodium bicarbonate, ammonia, sodium hydrogen phosphate, sodium citrate, Borax, organic amine and basic amino acid apoplexy due to endogenous wind;
Buffer is any one in gifford's buffer solutions (Borax sodium carbonate buffer), Sang Shi buffer (phosphate buffer), Pasteur's buffer (borate buffer solution) and the acetate buffer;
Isoosmotic adjusting agent be in sodium chloride, Chile saltpeter, boric acid, Borax, glucose, fructose, glycerol, mannitol, sorbitol and the xylitol any one;
Antibacterial is any one in benzalkonium chloride, phenylmercuric nitrate and phenylmercuric acetate, chlorobutanol, thimerosal, mercuric oxycyanide, parabens, phenethanol and the sorbic acid;
Stabilizing agent is that antioxidant and/or other have chelating agen: antioxidant be in sodium pyrosulfite, sodium sulfite, sodium sulfite, sodium thiosulfate, ascorbic acid, thiourea, cysteine, tocopherol and the lecithin any one; It is in disodiumedetate (EPTA-2Na), ethylenediaminetetraacetic acid, citric acid and the tartaric acid any one that described other have chelating agen.
Cosolvent is any one in glycerol, propylene glycol and the ethanol;
Wetting agent is any one in sorbitol, glycerol, propylene glycol, mineral oil and the vegetable oil;
Solvent is any one in water, glycerol, propylene glycol and the ethanol;
Solubilizing agent is any one in tween 80, polyethylene castor oil hydrogenated and the paregal O.
The active constituents of medicine Margarita that the invention described above adopts is that its concocting method adopts any one in the following method through the Margarita of concocting:
1, water flies: get Margarita, add proper amount of clear water, wear into paste, add water gaging and mix and stir, coarse powder sinks, and inclining immediately suspension, and sinking coarse grain row again grinds, and repeatable operation like this is till whole porphyrizes.Before and after incline the for several times suspension that merge and leave standstill, top clear water is removed in hypsokinesis to be precipitated, and dry sediment is ground into impalpable powder, dries.
2, get clean Margarita, smash to pieces, be ground into impalpable powder.
3, get clean Margarita, cloth bag or the gauze parcel of packing into boiled 2-3 hour together with bean curd or bean milk, took out, and cleaned, and smashed to pieces, and water flies into impalpable powder.Every Margarita 1kg is with bean curd 2kg or bean milk 5kg.
4, get Margarita and wrap, hold under the arm in the thumbnail, steamed about 3 hours, take out, clean, dry, be ground into impalpable powder with cloth.
5, calcine: get clean Margarita, size is separately put in the iron pan, and button is one bowl above, with moderate heat forge to explosive sound to the greatest extent, take out, the cold of drying in the air, water flies or is ground into impalpable powder, drying.
6, milk system: get clean Margarita, put in sheep milk or the milk, slow fire boiling 2~4 hours is taken out, and clear water is cleaned, and porphyrize takes out drying.Per 1 kilogram of medical material is with 8 kilograms of milk.
7, salt is fried: Margarita is put into pot internal heating to bursting apart, and constantly stir, spray saline, fry and do.
Active component according to the invention or active component are meant the drug activity position.
The present invention is with Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, Margarita, Herba Saussureae Involueratae and artificial Moschus's combination, aspect Synergistic treatment headache or the migraine curative effect is preferably being arranged.Be processed into micropowders or solvent extraction, be prepared into different dosage forms, having reduced medicine stimulates gastrointestinal; Be more conducive to the dissolving and the absorption of medicine, improved bioavailability, especially nasal cavity medicine; Adopt the capable drug-supplying system of non-intruding; Make patient's taking convenience, can reach three and absorb, aspect nose suction Drug therapy headache or migraine, wide prospect is being arranged.
Medicine of the present invention has analgesia, anti-hypoxia and improves the effect of blood stasis model rat blood rheological characteristic.
Following experimental example, embodiment all are used to further specify but not as the restriction of the scope of the invention.
Experimental example 1 treatment migraine drug effect test
1. material
1.1 experiment medicine
Medicine first of the present invention (according to the present invention in the description embodiment 11 preparation and get), medicine second of the present invention (embodiment 38 prepares and gets in the description according to the present invention); Cysteine, OPA etc. (Chinese Medicine Shanghai chemical reagents corporation product); Reserpine (Guangdong Bangmin Pharmaceutical Co., Ltd.); 5-hydroxy tryptamine (5-HT, sigma company, lot number: 107F-0791); ZHENGTIAN WAN (Sanjiu Pharmaceutical Co., Ltd, the accurate word Z44020711 of traditional Chinese medicines, specification: every packed 6g).
1.2 animal
The healthy adult Kunming mouse, male and female half and half, (Lanzhou Institute of Biological Products's Experimental Animal Center provides body weight (20 ± 2) g, the quality certification number: the moving word 14-001 of doctor).
2 methods
2.1 the preparation of Nerve in Migraine Model
Meet 90 of the qualified mices (pain threshold 5s-30s) of experiment with hot plate method screening, be divided into 9 groups at random, 10 every group; 1 group is the normal control group, the subcutaneous normal saline that gives, the reserpine of all the other subcutaneous 0.5mg/kg of giving of group (preparing with normal saline); Every day 1 time, 20d altogether.Clotting time of mice shortens after the modeling, and the interior 5-HT content of brain is reduced to model and prepares successfully.
2.2 divide into groups and administration
21d stops to give reserpine in experiment, gives respectively organizing in the mice of reserpine, gets 1 group arbitrarily as model control group, and all the other groups are respectively: ZHENGTIAN WAN group (3.6gkg -1D -1); Medicine first low dose group (0.09gkg of the present invention -1D -1), dose groups (0.18gkg in the medicine first of the present invention -1D -1), medicine first high dose group (0.36gkg of the present invention -1D -1); Medicine second low dose group (0.09gkg of the present invention -1D -1), dose groups (0.18gkg in the medicine second of the present invention -1D -1), medicine second high dose group (0.36gkg of the present invention -1D -1); Model control group gives the normal saline of equivalent.Do following experiment behind the administration 5d.
2.3 the mensuration of pain threshold
The temperature constant of constant temperature electric heating case is 55 ℃, and mice is put on the hot plate, picks up counting simultaneously, begins to lick the pain threshold of the response time of hind paw as mice to mice from timing.
2.4 the mensuration of clotting time
Get blood with glass capillary at angular vein, drip 1 and drop on the clean microscope slide, when blood begins to flow out, pick up counting; Behind the 30s, gently choose blood, see to have or not the blood streak to occur with syringe needle; Later on whenever, choose 1 time with pin at a distance from 15s, from timing begin to time that the blood streak occurs as clotting time.
2.5 the mensuration of 5-HT in the cerebral tissue
Broken end takes out cerebral tissue on the ice pan; After weighing; Add the acid n-butyl alcohol homogenate of pre-cooling in 1: 30 ratio, get supernatant after centrifugal and add hydrochloric acid and normal heptane, vibration, centrifugal back water intaking phase; Add OPA hydrochloric acid boiling water bath postcooling, on the RF510 spectrofluorophotometer of Tianjin, island, measure the fluorescence intensity of 5-HT with 365nm/480nm.
2.6 statistical analysis
(x ± s) expression adopts the SPSS11.5 statistical software to carry out date processing to all data with mean ± standard deviation.Relatively carry out one factor analysis of variance between group, check with LSD when variance has homogeneous, heterogeneity of variance uses Dunnett ' s T3 check to carry out comparing between each group.P<0.05 expression has significant difference.
3 results
This experimentation is found; Compare with model control group, medicine first of the present invention and second all can obviously prolong the clotting time of migraine mice, improve the pain threshold of migraine mice; Improve the content of 5-HT in the brain, this prompting medicine first of the present invention and second all can be improved migrainous symptom.
3.1 medicine first of the present invention and second are to the influence of clotting time
The model control group clotting time significantly reduces than normal control group; After giving medicine first of the present invention and second, clotting time obviously prolongs, and along with the increase of medicine first of the present invention and second dosage; Clotting time is also more and more longer; Show that medicine first of the present invention and second all have blood coagulation resisting function, and difference has significance (P<0.05 or P<0.01), the result sees table 1.
3.2 medicine first of the present invention and second are to the influence of pain threshold
Medicine first of the present invention and second can obviously improve the pain threshold of mice after the modeling; And along with the increase of medicine first of the present invention and second dosage; Pain threshold is also increasing; Show the be improved effect of the migraine mice threshold of pain of medicine first of the present invention and second, and difference has significance (P<0.05 or P<0.01), the result sees table 1.
3.3 medicine first of the present invention and second are to the influence of cerebral tissue 5-HT content
Model control group cerebral tissue 5-HT content obviously reduces than normal control group; Medicine first of the present invention and second have the trend that increases cerebral tissue 5-HT content; Along with the increase of medicine first of the present invention and second dosage, the migraine mouse brain organizes 5-HT content to increase successively, shows the be improved effect of peripheral blood 5-HT content of medicine first of the present invention and second; And difference has statistical significance (P<0.05 or P<0.01), and the result sees table 1.
Table 1 medicine first of the present invention and second are to the influence of clotting time, pain threshold and the cerebral tissue 5-HT content (n=10 of x ± s)
Figure G200910252554XD00131
Annotate: compare with model control group, *P<0.05, *P<0.01
The experimental example 2 treatment headache tests of pesticide effectiveness
1 material
1.1 laboratory animal
The healthy adult Kunming mouse, body weight (20 ± 2) g, the Wistar rat, body weight 160 ~ 250g, Lanzhou Institute of Biological Products's Experimental Animal Center provides.
1.2 medicine, reagent and instrument
Medicine first of the present invention (according to the present invention in the description embodiment 11 preparation and get), medicine second of the present invention (embodiment 38 prepares and gets in the description according to the present invention); ZHENGTIAN WAN (Sanjiu Pharmaceutical Co., Ltd, the accurate word Z44020711 of traditional Chinese medicines, specification: every packed 6g); Sodium nitrite (Hubei University chemical plant, lot number: 061201); Epinephrine inj (Wuhan Pharmaceutical Factory); Glacial acetic acid (the special chemicals company limited in Rui Jin, Tianjin, lot number: 2007-05-22, analytical pure); Stopwatch (SW8-2008, Shenzhen epoch Powerise digital technology Co., Ltd); Syringe (specification: 1ml); Injection needle; Irritate the stomach syringe needle; Psychrometer; The portable balance of electronics (model: YB1201, Haikang, Shanghai Electronic Instruments Plant, precision 0.01g); The full-automatic blood flow of FASCO-3000 accelerates and surveys appearance (Weiduo Bioengineering Institute of Chongqing University); GJ-8402 type hot plate dolorimeter (the white stone electronics medicine in Ninghai, Zhejiang instrument plant).
2 methods
2.1 analgesic experiment---acetic acid twisting method
80 of male mices are divided into 8 groups at random, are respectively: medicine first low dose group (0.09gkg of the present invention -1D -1), dose groups (0.18gkg in the medicine first of the present invention -1D -1), medicine first high dose group (0.36gkg of the present invention -1D -1); Medicine second low dose group (0.09gkg of the present invention -1D -1), dose groups (0.18gkg in the medicine second of the present invention -1D -1), medicine second high dose group (0.36gkg of the present invention -1D -1); ZHENGTIAN WAN group (3.6gkg -1D -1); Model control group; Each organizes administration, and model control group is given equivalent normal saline, successive administration 3 days.Last administration 1h pneumoretroperitoneum is only injected 0.6% acetum 0.2ml/; Turn round body (abdominal part indent, stretching, extension hind leg, buttocks are raised) number of times behind the record injection acetic acid in the 15min, calculate medicine the suppression ratio of writhing response is passed judgment on medicine analgesic effect: suppression ratio %=(model control group is turned round body average-reagent group and turned round the body average)/model control group is turned round body average * 100%.Each is organized under mice the same terms and to feed, freely ingests, and drinking-water, room temperature is controlled at (20 ± 1) ℃, humidity about 60%, the result sees table 2.
2.2 the anti-hypoxia experiment---medicine first of the present invention and second cause the effect of anoxia in mice to sodium nitrite
Get 70 of mices, be divided into 7 groups at random: blank group (irritating stomach equivalent normal saline), medicine first low dose group of the present invention (0.09g/kg), dose groups (0.18g/kg) in the medicine first of the present invention, medicine first high dose group of the present invention (0.36g/kg); Medicine second low dose group of the present invention (0.09g/kg), dose groups (0.18g/kg) in the medicine second of the present invention, medicine second high dose group of the present invention (0.36g/kg); Each group administration respectively, every day 3 times, continuous 7 days, 1h after the last administration, each Mus ip (lumbar injection) sodium nitrite 220mg/kg is an index with the respiratory arrest, the record death time.
2.3 medicine first of the present invention and second are to the influence of stasis syndrome rat model hemorheological property
Rat is divided into 9 groups at random:
The blank group: only irritate stomach normal saline 5ml/ every day, continuous 7 days, fasting after the last administration was got blood examination the 8th day morning and is surveyed.
Blood stasis model group: only irritate stomach normal saline 5ml/ every day, continuous 7d, the 7th day sc (subcutaneous injection) epinephrine 8 μ g/kg; Totally 2 times, 2 minor tick 4h, (each interval 2h of front and back) immerses 5min in the frozen water with rat between 2 injection epinephrines; Dispose the back fasting, get blood examination the 8th day morning and survey.
ZHENGTIAN WAN group: gastric infusion (1.5g/kg), continuous 7 days, the 7th day sc (subcutaneous injection) epinephrine 8 μ g/kg, totally 2 times, 2 minor tick 4h.(each interval 2h of front and back) immerses 5min in the frozen water with rat between 2 injection epinephrines, disposes the back fasting, gets blood examination the 8th day morning and surveys.
Medicine first low dose group of the present invention (0.09g/kg), dose groups (0.18g/kg) in the medicine first of the present invention, medicine first high dose group of the present invention (0.36g/kg); Medicine second low dose group of the present invention (0.09g/kg), dose groups (0.18g/kg) in the medicine second of the present invention, medicine second high dose group of the present invention (0.36g/kg); Each group administration respectively, continuous 7 days, the 7th day sc (subcutaneous injection) epinephrine 8 μ g/kg, totally 2 times, 2 minor tick 4h.(each interval 2h of front and back) immerses 5min in the frozen water with rat between 2 injection epinephrines, disposes the back fasting, gets blood examination the 8th day morning and surveys.
2.4 statistical analysis
(x ± s) expression adopts the SPSS11.5 statistical software to carry out date processing to all data with mean ± standard deviation.Relatively carry out one factor analysis of variance between group, check with LSD when variance has homogeneous, heterogeneity of variance uses Dunnett ' s T3 check to carry out comparing between each group.P<0.05 expression has significant difference.
3 results
3.1 analgesic test---acetic acid twisting method threshold of pain result
The result finds; Medicine first of the present invention and second all show tangible analgesic effect; Can suppress the mouse writhing reaction times significantly, with the model control group comparing difference significance (P<0.05 or P<0.01) arranged, medicine first of the present invention and second are along with the increase of dosage; Analgesic effect strengthens thereupon, and the result sees table 2.
Table 2 acetic acid twisting method threshold of pain experimental result (x ± s, n=10)
Figure G200910252554XD00151
Annotate: compare with model control group, *P<0.05, *P<0.01
3.2 the anti-hypoxia test---medicine first of the present invention and second cause the effect of anoxia in mice to sodium nitrite
In experiment, the process of mice from the injection sodium nitrite to death has symptoms such as tic, rapid breathing and cyanosis successively, is the standard determination dead mouse with heart beating respiratory arrest behind the mice opisthotonus.Through statistical analysis, compare with the blank group, medicine first of the present invention and second all can obviously prolong the time-to-live (belonging to the extracellular fluid anoxia, P<0.05 or P<0.01) that the mice sodium nitrite poisons, and improve the mice hypoxia-bearing capability, and the result sees table 3.
Table 3 medicine first of the present invention and second cause the effect (x ± s) of anoxia in mice to sodium nitrite
Figure G200910252554XD00161
Annotate: compare with the blank group, *P<0.05, *P<0.01
3.3 medicine first of the present invention and second are to the influence of stasis syndrome rat model hemorheological property
Experimental result shows, all groups viscosity when low shear rate raises, and viscosity reduces during high shear rate, under different shear rates, with the normal control group relatively, the blood viscosity value of model control group raises, and has statistical significance (P<0.05 or P<0.01); The WBV value of the basic, normal, high dose groups of ZHENGTIAN WAN group and medicine first of the present invention and second all is lower than model control group; Each group of medicine first of the present invention and second is along with the increase of dosage; The WBV value is on a declining curve, has statistical significance (P<0.05 or P<0.01), and the result sees table 4.
Packed cell volume is the key factor that influences blood viscosity, and blood viscosity increases rapidly with the increase of packed cell volume, otherwise then reduces.The mensuration of packed cell volume helps to understand erythrocytic increasing and minimizing, and when the erythrocyte absolute value due to a variety of causes increased, packed cell volume also had corresponding increase.Table 4 result shows, compares with the normal control group, and the packed cell volume of model control group significantly increases.The packed cell volume of each group of ZHENGTIAN WAN group and medicine first of the present invention and second all is lower than model control group; Each group of medicine first of the present invention and second is along with the increase of dosage; The blood rbc hematocrit presents downward trend; Have statistical significance (P<0.05 or P<0.01), show that medicine first of the present invention and second all have the hemorheological effect of improvement.
Table 4 medicine first of the present invention and second are to the influence of stasis syndrome rat model hemorheological property (x ± s)
Figure G200910252554XD00171
Compare with model control group, *P<0.05, *P<0.01,
Compare with the normal control group, #P<0.05, ##P<0.01
Experimental example 3 nasal mucosa cilium toxicity research
1, material
1.1 instrument and material
Optical microscope (Olympus, Japan produces); Chromatography cylinder; Mosquito forceps.
1.2 medicine and reagent
Normal saline: Beijing Double-Crane Pharmaceutical Co., Ltd; Sodium deoxycholate: lot number 061107, Haidian District, Beijing City microbiological culture media products factory; Medicine first of the present invention (according to the present invention in the description embodiment 11 preparation and get), medicine second of the present invention (embodiment 38 prepares and gets in the description according to the present invention).
1.3 laboratory animal
Bufo siccus, body weight 70-90g, male and female are not limit, and are provided by Lanzhou University's Experimental Animal Center.
2, method
2.1 experimental technique
In this experiment, selected for use the toxic sodium deoxycholate of serious cilium (1% aqueous solution) as positive control, the cilium persistent movement time (LTCM) is measured in the negative contrast of normal saline, estimates the nasal mucosa cilium toxicity of medicine first of the present invention and second.
Get Bufo siccus, 8 every group.Bufo siccus lain on the back be fixed on the frog board, use the mosquito forceps tractive, the oral cavity is opened, every group drips test liquid 0.5mL respectively in palate mucosa place; Make complete submergence palate, behind the contact 30mi n, separate the palate mucosa, wash most clot, foreign material and medicine with normal saline; Mucosa towards on be tiled on the microscope slide, covered gently, the motion conditions in 50 times of biological microscopies are observed the mucosa cilium down is held in the chromatography cylinder that fills a small amount of normal saline subsequently; Airtight, make steam reach nearly saturation, ambient temperature 20-25 ℃; After this every at a distance from appropriate time taking-up BIAO and BEN, microscopic examination continues motion like cilium; Then BIAO and BEN is put back in the chromatography cylinder, after ciliary movement stopped, record began to stop the time to be continued to ciliary movement from administration.Carefully clean mucosa with normal saline, continue to observe ciliary movement and whether recover the persistent movement time that record recovers.In the test with time cilium persistent movement time of administration group divided by the normal saline matched group, the relative percentage of cilium persistent movement time, percentage rate is high more, the expression medicine is more little to effect on ciliary movement.
The medicine first of the present invention of investigating variable concentrations and second are to effect on ciliary movement: investigation 15,25,45mgmL -1The solution of medicine first of the present invention and second is to the toxicity of nasal mucosa cilium.
2.2 statistical analysis
(x ± s) expression adopts the SPSS11.5 statistical software to carry out date processing to all data with mean ± standard deviation.Carry out one factor analysis of variance, check with LSD when variance has homogeneous, heterogeneity of variance uses Dunnett ' s T3 check to carry out comparing between each group.P<0.05 or P<0.01 expression has significant difference.
3, result
The evaluation methodology of nasal mucosa toxic action has: the influence of medicine to the cilium scavenging action estimated in (1).Method commonly used has: and employing transillumination power technology, reflected light power technology, shooting or video technique mensuration CBF (ciliary Beatfrequency, CBF); Adopt toad spider palate cilium body method or vitro method measure the cilium persistent movement time (Lastingtime of ciliary movement, LTCM); Adopt the experiment of human body glucide or measure graphite or dyestuff with stereoscopic microscope and move the method for certain distance required time, measure mucosa cilium turn-over capacity at mucous membrane surface.(2) the mucosa form is investigated: be the most direct evaluation methodology of nasal mucosa toxicity, with the variation of mucous membrane tissue structure and surperficial cilia morphology after optics or ultramicroscope or confocal laser scanning microscope, CLSM (confocal laser scanning microscope) the observation administration.(3) hemolytic experiment: investigate medicine to biomembranous effect.(4) estimate through the biochemical indicators such as burst size of measuring some specific proteins and enzyme.These four kinds of methods comparatively speaking, it is simpler relatively to the method for cilium scavenging action influence to estimate medicine, is applicable to the prescription screening stage.The cilium toxicity of medicine or adjuvant and its influence to nasal mucosa organizational structure and form have good dependency, the nasal mucosa toxicity of ability better prediction medicine and adjuvant.
3.1 feminine gender and positive control experiment
Negative control normal saline group: LTCM is (690 ± 30) min (n=8), and microscopic examination is visible: mucous membrane surface and cilium complete display, ciliary movement is active, is the swing of flowing water shape.Positive control sodium deoxycholate group: after giving sodium deoxycholate, do not observe fibre swing, mucous membrane surface is mixed and disorderly; Cilium comes off fully; Occur a lot of exfoliative cyte on every side, have obviously differently, explain that sodium deoxycholate has a strong impact on nasal mucosa tissue and nose ciliary movement with the normal saline group.
3.2 the medicine first of the present invention of variable concentrations and second are to effect on ciliary movement
Experimental result shows that the medicine first of the present invention of variable concentrations and second solution are along with the increase of drug level, and the percentage rate of cilium relative motion decreases, and osmotic pressure also increases thereupon.Visible from table 5, medicine first of the present invention and second are very little to the inhibitory action of nasal mucosa ciliary movement, relatively do not have significant difference with the normal saline group, P>0.05.Sodium deoxycholate is as positive controls, and relatively there were significant differences with the normal saline group, and P<0.01 explain that sodium deoxycholate has serious nasal mucosa cilium toxicity, and medicine first of the present invention and second does not all have tangible nasal mucosa cilium toxicity, and the result sees table 5.
Table 5 medicine first of the present invention and second body method nasal mucosa cilium toxicity test result (x ± s, n=8)
Figure G200910252554XD00181
Figure G200910252554XD00191
Annotate: each test liquid group compares with the normal saline group respectively: *P>0.05
Following embodiment all can realize the effect of above-mentioned experimental example.
The specific embodiment
Embodiment 1:
With Fructus Fragariae Ananssae 100g, Herba corydalis edulis 100g, Flos rosae multiflorae 100g, Margarita 100g, artificial Moschus 5g is raw material, earlier with the artificial Moschus grind into fine powder subsequent use; Again Fructus Fragariae Ananssae, Herba corydalis edulis, Flos rosae multiflorae medical material are carried out remove impurity, cleaning, drying respectively, mixed powder is broken into the medicated powder that particle diameter is 150-200 μ m, gets mixed powder; Then water behind the Margarita calcine is flown into impalpable powder, incapsulate again with behind Moschus fine powder and the mixed powder mix homogeneously, get final product.
Embodiment 2:
With Fructus Fragariae Ananssae 700g, Herba corydalis edulis 700g, Flos rosae multiflorae 700g, Margarita 450g, artificial Moschus 50g is raw material, the artificial Moschus is ground to be fine powder earlier, subsequent use; Be ground into fine powder behind the Margarita calcine; The two is mixed placing micronizing equipment to be ground into micropowders with other drug, particle diameter is 0.1-1 μ m; With this micropowders is the active component of medicine of the present invention, uses soybean phospholipid, adopts film dispersion method, processes liposome turbid liquor, adopts spray drying method that it is prepared into liposome precursor then, gets final product.
Embodiment 3:
With Fructus Fragariae Ananssae 450g, Herba corydalis edulis 450g, Flos rosae multiflorae 450g, Margarita 300g, artificial Moschus 25g is raw material, the artificial Moschus is ground to be fine powder earlier, subsequent use; Be ground into fine powder after the Margarita milk system; The two is mixed placing micronizing equipment to be ground into micropowders with other drug, particle diameter is 1-10 μ m; With this micropowders is the active component of medicine of the present invention, adds conventional adjuvant and processes oil preparation, gets final product.
Embodiment 4:
With Fructus Fragariae Ananssae 400g, Herba corydalis edulis 200g, Flos rosae multiflorae 400g, Margarita 200g, artificial Moschus 20g is raw material, the artificial Moschus is ground to be fine powder earlier, subsequent use; Margarita salt is ground into fine powder after frying; The two is mixed placing micronizing equipment to be ground into micropowders with other drug, particle diameter is 10-40 μ m; With this micropowders is the active component of medicine of the present invention, adds the 100g magnesium stearate, and tabletting behind the mix homogeneously gets final product.
Embodiment 5:
With Fructus Fragariae Ananssae 650g, Herba corydalis edulis 150g, Flos rosae multiflorae 150g, Margarita 150g, artificial Moschus 30g is raw material, the artificial Moschus is ground to be fine powder earlier, subsequent use; Margarita water flies into impalpable powder; The two is mixed placing micronizing equipment to be ground into micropowders with other drug, particle diameter is 0.1-40 μ m, and the gained micropowders is added 70% ethanol, processes the granule that particle diameter is 1500-2000 μ m, drying, and granulate is processed granule.
Embodiment 6:
With Fructus Fragariae Ananssae 500g, Herba corydalis edulis 500g, Flos rosae multiflorae 400g, Margarita 400g, artificial Moschus 18g is raw material, with artificial Moschus's porphyrize, subsequent use; Grind after the Margarita milk system and be fine powder, and mix with other crude drugs that carried out remove impurity, cleaning, drying, with the water boiling and extraction of 5 times of amounts of medical material weight 3 hours, and extracting solution is concentrated into 65 ℃ of relative densities was 1.20 extractum; With the dilution of the water of 10 times of amounts of extractum volume, filter the clarification extracting solution; Gained is clarified extracting solution feed macroporous adsorptive resins, use water washing earlier,, resolve with 75% ethanol at last again with 30% washing with alcohol; The gained desorbed solution reclaims ethanol, concentrates, must mix with the artificial Moschus behind the extract dry powder after the spray drying, and be oil phase with sad tricaprin, pure water is a water, processes Emulsion, gets final product.
Embodiment 7:
With Fructus Fragariae Ananssae 500g, Herba corydalis edulis 800g, Flos rosae multiflorae 500g, Margarita 500g, artificial Moschus 50g is raw material, and artificial Moschus's superfine powder is broken into the micropowders of 25-50 μ m, and is subsequent use; Grind behind the Margarita calcine and be fine powder, and mix, use the water boiling and extraction 2 times of medical material weight 20 and 15 times of amounts respectively with other crude drugs that carried out remove impurity, cleaning, drying, each 1 hour, and extracting solution is concentrated into 60 ℃ of relative densities is 1.10 extractum; With extractum with the dilution of the water of volume, filter the clarification extracting solution; Gained is clarified extracting solution feed macroporous adsorptive resins, use water washing earlier,, resolve with 75% ethanol at last again with 10% washing with alcohol; The gained desorbed solution reclaims ethanol, concentrate, after the spray drying extract dry powder mixes with the artificial Moschus, it is the fine powder of 15-20 μ m that micronizing becomes particle diameter, with dimethyl-beta cyclodextrin bag and after make cyclodextrin bag and thing, get final product.
Embodiment 8:
With Fructus Fragariae Ananssae 350g, Herba corydalis edulis 550g, Flos rosae multiflorae 150g, Margarita 350g, artificial Moschus 8.0g is raw material, and artificial Moschus's superfine powder is broken into the micropowders of 25-50 μ m, and is subsequent use; Grind after Soup of Tofu Shaped as Pearls is concocted and be fine powder, and mix, use the water boiling and extraction 3 times of 10,8 and 6 times of amounts of medical material weight respectively with other crude drugs that carried out remove impurity, cleaning, drying, each 0.5 hour, and extracting solution is concentrated into relative density is 1.18 extractum; With the dilution of the water of 6 times of amounts of extractum, filter the clarification extracting solution; Gained is clarified extracting solution feed macroporous adsorptive resins, use water washing earlier,, resolve with 75% ethanol at last again with 20% washing with alcohol; The gained desorbed solution reclaims ethanol; Concentrating, get extract dry powder after the spray drying and mix with the artificial Moschus, is gel-type vehicle with the carbomer; Add ethyl hydroxybenzoate, disodiumedetate, ethanol, propylene glycol, tween 80 etc.; Regulating pH value through sodium bicarbonate is about 6.5, processes gel, gets final product.
Embodiment 9:
With Fructus Fragariae Ananssae 400g, Herba corydalis edulis 200g, Flos rosae multiflorae 400g, Margarita 200g, artificial Moschus 20g is raw material, and artificial Moschus's superfine powder is broken into the micropowders of 0.1-1 μ m, and is subsequent use; Grind after the Margarita bean milk is concocted and be fine powder, and mix, use the water boiling and extraction 3 times of 10,8 and 6 times of amounts of medical material weight respectively with other crude drugs that carried out remove impurity, cleaning, drying, each 0.5 hour, and extracting solution is concentrated into relative density is 1.15 extractum; With the dilution of the water of 6 times of amounts of extractum, filter the clarification extracting solution; Gained is clarified extracting solution feed macroporous adsorptive resins, use water washing earlier,, resolve with 75% ethanol at last again with 20% washing with alcohol; The gained desorbed solution reclaims ethanol, concentrate, after the spray drying extract dry powder mixes with the artificial Moschus, the gained medicinal powder adds liquid paraffin and Span-60 and petroleum ether and processes microcapsule after a little, volatilize petroleum ether behind 200 mesh sieves, get the microcapsule finished product, get final product.
Embodiment 10:
With Fructus Fragariae Ananssae 500g, Herba corydalis edulis 500g, Flos rosae multiflorae 500g, Margarita 350g, artificial Moschus 25g is raw material, and artificial Moschus's superfine powder is broken into the micropowders of 1-10 μ m, and is subsequent use; Margarita is ground and is impalpable powder, and mixes with other crude drugs that carried out remove impurity, cleaning, drying; With the water boiling and extraction of 10 times of amounts of medical material weight 2 times; And relative density is 1.10 extractum when extracting solution is concentrated into 50 ℃, with the water dilution of 6 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 20% washing with alcohol, resolve with 50% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, get extract dry powder after the spray drying and mix, get the active component of medicine of the present invention with the artificial Moschus; Medicine activity component is combined with the pharmaceutics acceptable auxiliary, and process ointment, get final product through the routine techniques of galenic pharmacy.
Embodiment 11:
With Fructus Fragariae Ananssae 500g, Herba corydalis edulis 500g, Flos rosae multiflorae 450g, Margarita 400g, artificial Moschus 18g is raw material, and artificial Moschus's superfine powder is broken into the micropowders of 10-40 μ m, and is subsequent use; Margarita water flies to be impalpable powder, and mixes with other crude drugs that carried out remove impurity, cleaning, drying; With the water boiling and extraction of 15 times of amounts of medical material weight 3 times; And relative density is 1.20 extractum when extracting solution is concentrated into 70 ℃, with the water dilution of 8 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 7 times of bed volumes/hour macroporous adsorptive resins, use water washing earlier, again with 30% washing with alcohol, resolve with 75% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with the artificial Moschus dry back, gets the active component of medicine of the present invention; Adding a little acetic acid adjusting pH value is about 6.5, and adding sodium chloride adjusting etc. is oozed, and adds ethyl hydroxybenzoate, disodiumedetate, glycerol, ethanol, propylene glycol etc. to process nasal mist, gets final product.
Embodiment 12:
With Fructus Fragariae Ananssae 750g, Herba corydalis edulis 750g, Flos rosae multiflorae 750g, Margarita 750g, artificial Moschus 40g is raw material, and the artificial Moschus grinds and is fine powder, and is subsequent use; Grind after Soup of Tofu Shaped as Pearls is concocted and be fine powder; And carried out remove impurity, cleaned with other; Exsiccant crude drug mixes, and with the water boiling and extraction of 15 times of amounts of medical material weight 3 times, and relative density is 1.20 extractum when extracting solution is concentrated into 70 ℃; With the dilution of the water of 8 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 7 times of bed volumes/hour macroporous adsorptive resins, use water washing earlier, again with 30% washing with alcohol, resolve with 75% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with the artificial Moschus dry back, gets the active component of medicine of the present invention; Medicine activity component is combined with the pharmaceutics acceptable auxiliary, and process drop pill, get final product through the routine techniques of galenic pharmacy.
Embodiment 13:
With Fructus Fragariae Ananssae 650g, Herba corydalis edulis 650g, Flos rosae multiflorae 650g, Margarita 300g, artificial Moschus 25g is raw material, the artificial Moschus is ground to be fine powder earlier, subsequent use; Again with being ground into fine powder behind the Margarita calcine; And mix with other crude drugs that carried out remove impurity, cleaning, drying, with the water boiling and extraction of 10 times of amounts of medical material weight 2 times; And relative density is 1.10 extractum when extracting solution is concentrated into 50 ℃; With the dilution of the water of 6 times of amounts of extractum volume, filter clarification extract will clarify that extracting solution feeds absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, elder generation uses water washing; With 20% washing with alcohol, resolve with 50% ethanol at last again; Desorbed solution is reclaimed ethanol, concentrate, add the active component that the artificial Moschus gets medicine of the present invention again; Medicine activity component is combined with pharmaceutics acceptable solvent and propellant, and process nasal aerosol, get final product through the routine techniques of galenic pharmacy.
Embodiment 14:
With Fructus Fragariae Ananssae 800g, Herba corydalis edulis 800g, Flos rosae multiflorae 800g, Margarita 500g, artificial Moschus 50g is raw material, the artificial Moschus is ground to be fine powder earlier, subsequent use; Be ground into fine powder after again Margarita salt being fried; And carried out remove impurity, cleaned with other; Exsiccant crude drug mixes, and with the water boiling and extraction of 12 times of amounts of medical material weight 2 times, and relative density is 1.15 extractum when extracting solution is concentrated into 50 ℃; With the dilution of the water of 5 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 30% washing with alcohol, resolve with 75% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix the back again with the artificial Moschus and add gifford's buffer solutions, sodium chloride adjusting etc. is oozed, and adds ethyl hydroxybenzoate, lecithin, ethanol, propylene glycol etc., and regulating pH value through sodium bicarbonate is about 6.5, processes nasal drop, gets final product.
Embodiment 15:
With Fructus Fragariae Ananssae 100g, Herba corydalis edulis 100g, Flos rosae multiflorae 100g, Margarita 100g, artificial Moschus 5g is raw material, earlier artificial Moschus's superfine powder is broken into the micropowders of 0.1-5 μ m, subsequent use; Again with being ground into fine powder after the Margarita milk system; And carried out remove impurity, cleaned with other; Exsiccant crude drug mixes, and with the water boiling and extraction of 15 times of amounts of medical material weight 2 times, and relative density is 1.20 extractum when extracting solution is concentrated into 60 ℃; With the dilution of the water of 8 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 30% washing with alcohol, resolve with 75% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, add the active component that the artificial Moschus gets medicine of the present invention again; With medicine activity component and pharmaceutics acceptable solvent, propellant combines, and processes nasal aerosol through the routine techniques of galenic pharmacy, gets final product.
Embodiment 16:
With Fructus Fragariae Ananssae 400g, Herba corydalis edulis 200g, Flos rosae multiflorae 400g, Margarita 200g, artificial Moschus 20g is raw material, the artificial Moschus is ground to be fine powder earlier, subsequent use; Again with being ground into fine powder behind the Margarita calcine; And carried out remove impurity, cleaned with other; Exsiccant crude drug mixes, and with the water boiling and extraction of 15 times of amounts of medical material weight 3 times, and relative density is 1.20 extractum when extracting solution is concentrated into 70 ℃; With the dilution of the water of 7 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 7 times of bed volumes/hour macroporous adsorptive resins, use water washing earlier, again with 30% washing with alcohol, resolve with 70% ethanol at last; Desorbed solution being reclaimed ethanol, concentrate, get extract dry powder after the spray drying and mix with the artificial Moschus, is oil phase with sad tricaprin, and pure water is a water, processes Emulsion, gets final product.
Embodiment 17:
With Fructus Fragariae Ananssae 650g, Herba corydalis edulis 650g, Flos rosae multiflorae 650g, Margarita 300g, artificial Moschus 25g is raw material, the artificial Moschus is ground to be fine powder earlier, subsequent use; Be ground into fine powder after again the Margarita bean milk being concocted; And carried out remove impurity, cleaned with other; Exsiccant crude drug mixes, and with the water boiling and extraction of 8 times of amounts of medical material weight 3 times, and relative density is 1.05 extractum when extracting solution is concentrated into 40 ℃; With the dilution of the water of 2 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 3 times of bed volumes/hour macroporous adsorptive resins, use water washing earlier, again with 15% washing with alcohol, resolve with 45% ethanol at last; The gained desorbed solution reclaims ethanol, concentrates, and mixes with the artificial Moschus after the spray drying, with machine-processed microgranule and the nanoparticle of getting of fine gtinding, gets final product.
Embodiment 18:
With Fructus Fragariae Ananssae 800g, Herba corydalis edulis 800g, Flos rosae multiflorae 800g, Margarita 500g, artificial Moschus 50g is raw material, earlier artificial Moschus's superfine powder is broken into the micropowders of 25-50 μ m, subsequent use; Grind after Soup of Tofu Shaped as Pearls is concocted and be fine powder; And mix with other crude drugs that carried out remove impurity, cleaning, drying, use 75% ethanol extraction 2 times of medical material weight 12 and 6 times of amounts respectively; Each 1 hour; And extracting solution is concentrated into relative density is 1.10 extractum, and reuse extractum is with the water dilution of volume, filter the clarification extracting solution; To clarify extracting solution and feed macroporous adsorptive resins, use water washing earlier,, resolve with 40% ethanol at last again with 10% washing with alcohol; Desorbed solution reclaims ethanol, concentrates, and gets extract dry powder after the spray drying, mixes with the artificial Moschus again, processes microsphere, gets final product.
Embodiment 19:
With Fructus Fragariae Ananssae 500g, Herba corydalis edulis 500g, Flos rosae multiflorae 400g, Margarita 400g, artificial Moschus 18g is raw material, and artificial Moschus's superfine powder is broken into the micropowders of 0.1-10 μ m, subsequent use; Grind after Margarita salt is fried and be fine powder; And carried out remove impurity, cleaned with other; Exsiccant crude drug mixes, and with 50% alcohol reflux of 8 times of amounts of medical material weight 1 time, and relative density is 1.10 extractum when extracting solution is concentrated into 60 ℃; With the dilution of the water of 8 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 20% washing with alcohol, resolve with 45% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix the back with the artificial Moschus and add sodium chloride adjusting etc. and ooze; Add ethyl hydroxybenzoate, disodiumedetate, glycerol, ethanol, propylene glycol; Adding a little sodium bicarbonate adjusting pH value is about 6.5, processes nasal mist, gets final product.
Embodiment 20:
With Fructus Fragariae Ananssae 200g, Herba corydalis edulis 200g, Flos rosae multiflorae 200g, Margarita 200g, artificial Moschus 5g is raw material, and artificial Moschus's superfine powder is broken into the micropowders of 1-5 μ m, subsequent use; Grind behind the Margarita calcine and be fine powder; And carried out remove impurity, cleaned with other; Exsiccant crude drug mixes, and with 65% alcohol reflux of 10 times of amounts of medical material weight 3 times, and relative density is 1.05 extractum when extracting solution is concentrated into 40 ℃; With the dilution of the water of 10 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 30% washing with alcohol, resolve with 70% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix the back with the artificial Moschus and combine, and process drop pill, get final product through the routine techniques of galenic pharmacy with the pharmaceutics acceptable auxiliary.
Embodiment 21:
With Fructus Fragariae Ananssae 800g, Herba corydalis edulis 800g, Flos rosae multiflorae 800g, Margarita 500g, artificial Moschus 50g is raw material, and artificial Moschus's superfine powder is broken into the micropowders of 10-40 μ m, subsequent use; Grind behind the Margarita calcine and be fine powder; And carried out remove impurity, cleaned with other; Exsiccant crude drug mixes, and with 80% alcohol reflux of 12 times of amounts of medical material weight 2 times, and relative density is 1.25 extractum when extracting solution is concentrated into 70 ℃; With the dilution of the water of 9 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 15% washing with alcohol, resolve with 60% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix the back with the artificial Moschus and add ethyl hydroxybenzoate, disodiumedetate, glycerol, ethanol, propylene glycol etc., adding a little sodium bicarbonate adjusting pH value is about 6.5, processes nasal mist, gets final product.
Embodiment 22:
With Fructus Fragariae Ananssae 500g, Herba corydalis edulis 500g, Flos rosae multiflorae 400g, Margarita 400g, artificial Moschus 18g, Herba Saussureae Involueratae 100g is raw material, with the artificial Moschus grind into fine powder subsequent use; Grind after Margarita uses bean curd to concoct and be fine powder; Other raw medicinal materials are carried out remove impurity, cleaning, drying respectively, and mixed powder is broken into the medicated powder that particle diameter is 150-200 μ m then, mixes the back again with above-mentioned two kinds of fine powders and adds the 100g magnesium stearate, and tabletting behind the mix homogeneously gets final product.
Embodiment 23:
With Fructus Fragariae Ananssae 500g, Herba corydalis edulis 500g, Flos rosae multiflorae 450g, Margarita 300g, artificial Moschus 15g, Herba Saussureae Involueratae 200g is raw material, with the artificial Moschus grind into fine powder subsequent use; Margarita salt is fried back water fly into impalpable powder, subsequent use; Other crude drugs carry out remove impurity, cleaning, drying respectively, and mixed powder is broken into the medicated powder that particle diameter is 150-200 μ m then, mix the back again with artificial Moschus's fine powder and Margarita impalpable powder and use water pill, process the 0.2g pill.
Embodiment 24:
With Fructus Fragariae Ananssae 500g, Herba corydalis edulis 500g, Flos rosae multiflorae 450g, Margarita 400g, artificial Moschus 18g, Herba Saussureae Involueratae 400g is raw material, the artificial Moschus is ground be fine powder, subsequent use; Be fine powder with grinding after the Soup of Tofu Shaped as Pearls system; Carry out remove impurity, clean with other; Exsiccant crude drug mixed powder is broken into the medicated powder that particle diameter is 160 μ m, is placed on artificial Moschus's mix homogeneously and is ground into the micropowders that particle diameter is 0.1-1 μ m in the super micron mill, processes powder and gets final product.
Embodiment 25:
With Fructus Fragariae Ananssae 200g, Herba corydalis edulis 200g, Flos rosae multiflorae 200g, Margarita 200g, artificial Moschus 5g, Herba Saussureae Involueratae 250g is raw material, the artificial Moschus is ground be fine powder, subsequent use; Margarita is concocted back water with bean milk fly into impalpable powder; And carry out remove impurity, clean with other; Exsiccant crude drug mixed powder is broken into the medicated powder that particle diameter is 190 μ m; Be placed on artificial Moschus's mix homogeneously again and be ground into the micropowders that particle diameter is 10-40 μ m in the super micron mill, process soft capsule and get final product.
Embodiment 26:
With Fructus Fragariae Ananssae 700g, Herba corydalis edulis 700g, Flos rosae multiflorae 700g, Margarita 450g, artificial Moschus 50g, Herba Saussureae Involueratae 500g is raw material, the artificial Moschus is ground be fine powder, subsequent use; Be fine powder with grinding behind the Margarita calcine, and be broken into the medicated powder that particle diameter is 180 μ m with other crude drug mixed powders that carry out remove impurity, cleaning, drying; Be placed on artificial Moschus's mixing again and be ground into the micropowders that particle diameter is 0.1-40 μ m in the super micron mill; Add 70% ethanol, process the granule that particle diameter is 1500~2000 μ m, drying; Granulate is processed granule.
Embodiment 27:
With Fructus Fragariae Ananssae 400g, Herba corydalis edulis 300g, Flos rosae multiflorae 300g, Margarita 400g, artificial Moschus 15g, Herba Saussureae Involueratae 280g is raw material; Other crude drugs are ground into the medicated powder that particle diameter is 180 μ m except that the artificial Moschus; Be placed in the micronizing equipment with artificial Moschus's mixing and be ground into micropowders, particle diameter is 0.1-5 μ m, adds the anhydrous glucose after the micronizing; Process powder spray behind the mix homogeneously, get final product.
Embodiment 28:
With Fructus Fragariae Ananssae 650g, Herba corydalis edulis 550g, Flos rosae multiflorae 550g, Margarita 350g, artificial Moschus 25g, Herba Saussureae Involueratae 350g is raw material, the artificial Moschus is ground to be fine powder earlier, subsequent use; Margarita water is flown to impalpable powder, subsequent use; Again other crude drugs are ground into the medicated powder that particle diameter is 190 μ m, are placed on artificial Moschus, Margarita mixing and are ground into the micropowders that particle diameter is 10-40 μ m in the super micron mill, add the lactose that is crushed to micropowder, process powder spray behind the mix homogeneously, get final product.
Embodiment 29:
With Fructus Fragariae Ananssae 400g, Herba corydalis edulis 400g, Flos rosae multiflorae 400g, Margarita 350g, artificial Moschus 25g, Herba Saussureae Involueratae 350g is raw material, the artificial Moschus is ground to be fine powder earlier, subsequent use; Be fine powder with grinding after the Margarita milk system again; And carried out remove impurity, cleaned with other; Exsiccant crude drug mixes, and with the water boiling and extraction of 10 times of amounts of medical material weight 2 times, and relative density is 1.10 extractum when extracting solution is concentrated into 50 ℃; With the dilution of the water of 6 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 20% washing with alcohol, resolve with 50% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate,, combine with pharmaceutics acceptable solvent, propellant again, and process nasal aerosol, get final product through the routine techniques of galenic pharmacy with artificial Moschus's fine powder mix homogeneously.
Embodiment 30:
With Fructus Fragariae Ananssae 500g, Herba corydalis edulis 600g, Flos rosae multiflorae 500g, Margarita 350g, artificial Moschus 20g, Herba Saussureae Involueratae 300g is raw material, earlier artificial Moschus's superfine powder is broken into micropowders, subsequent use; Carried out remove impurity, cleaned with other after the crushing pearl; Exsiccant crude drug mixes, and with the water boiling and extraction of 15 times of amounts of medical material weight 3 times, and relative density is 1.20 extractum when extracting solution is concentrated into 70 ℃; With the dilution of the water of 8 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 7 times of bed volumes/hour macroporous adsorptive resins, use water washing earlier, again with 30% washing with alcohol, resolve with 70% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, with artificial Moschus's fine powder mix homogeneously; Add gifford's buffer solutions, sodium chloride adjusting etc. is oozed, and adds ethyl hydroxybenzoate, lecithin, ethanol, propylene glycol etc.; Regulating pH value through sodium bicarbonate is about 6.5, processes nasal drop, gets final product.
Embodiment 31:
With Fructus Fragariae Ananssae 650g, Herba corydalis edulis 500g, Flos rosae multiflorae 300g, Margarita 300g, artificial Moschus 20g, Herba Saussureae Involueratae 250g is raw material, the artificial Moschus is ground to be fine powder earlier, subsequent use; Other crude drugs that carried out remove impurity, cleaning, drying mix, and with the water boiling and extraction of 10 times of amounts of medical material weight 2 times, and relative density is 1.10 extractum when extracting solution is concentrated into 50 ℃, dilute with the water of 6 times of amounts of extractum volume, filter to such an extent that clarify extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 20% washing with alcohol, resolve with 50% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, with artificial Moschus's fine powder mix homogeneously; Adding sodium chloride adjusting etc. is oozed, and adds ethyl hydroxybenzoate, disodiumedetate, glycerol, ethanol, propylene glycol etc., and adding a little sodium bicarbonate adjusting pH value is about 6.5, processes nasal mist, gets final product.
Embodiment 32:
With Fructus Fragariae Ananssae 500g, Herba corydalis edulis 500g, Flos rosae multiflorae 400g, Margarita 400g, artificial Moschus 18g, Herba Saussureae Involueratae 100g is raw material, the artificial Moschus is ground to be fine powder earlier, subsequent use; Again Margarita milk system back was carried out remove impurity, cleaned with other; Exsiccant crude drug mixes, and with the water boiling and extraction of 12 times of amounts of medical material weight 2 times, and relative density is 1.25 extractum when extracting solution is concentrated into 65 ℃; With the dilution of the water of 10 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 15% washing with alcohol, resolve with 60% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, it is prepared into liposome precursor, get final product with adopting spray drying method behind artificial Moschus's fine powder mix homogeneously.
Embodiment 33:
With Fructus Fragariae Ananssae 650g, Herba corydalis edulis 500g, Flos rosae multiflorae 300g, Margarita 300g, artificial Moschus 20g, Herba Saussureae Involueratae 250g is raw material, earlier the artificial Moschus is ground into micropowders, subsequent use; Again with carrying out remove impurity, clean with other behind the Margarita calcine; Exsiccant crude drug mixes, and with the water boiling and extraction of 20 times of amounts of medical material weight 1 time, and relative density is 1.10 extractum when extracting solution is concentrated into 70 ℃; With the dilution of the water of 8 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 30% washing with alcohol, resolve with 70% ethanol at last; Desorbed solution being reclaimed ethanol, concentrate, get extract dry powder after the spray drying, with artificial Moschus's fine powder mix homogeneously, is oil phase with sad tricaprin again, and pure water is a water, processes Emulsion, gets final product.
Embodiment 34:
With Fructus Fragariae Ananssae 500g, Herba corydalis edulis 500g, Flos rosae multiflorae 450g, Margarita 400g, artificial Moschus 18g, Herba Saussureae Involueratae 400g is raw material, the artificial Moschus is ground to be fine powder earlier, subsequent use; Again Margarita salt being fried the back carried out remove impurity, cleaned with other; Exsiccant crude drug mixes, and with the water boiling and extraction of 6 times of amounts of medical material weight 3 times, and relative density is 1.20 extractum when extracting solution is concentrated into 50 ℃; With the dilution of the water of 4 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 20% washing with alcohol, resolve with 50% ethanol at last; The gained desorbed solution reclaims ethanol, concentrate, after the spray drying extract dry powder, mixes with the artificial Moschus again, it is the micropowders of 0.1-10 μ m that micronizing becomes particle diameter, with dimethyl-beta cyclodextrin bag and after make cyclodextrin bag and thing, get final product.
Embodiment 35:
With Fructus Fragariae Ananssae 450g, Herba corydalis edulis 450g, Flos rosae multiflorae 450g, Margarita 300g, artificial Moschus 20g, Herba Saussureae Involueratae 350g is raw material, and artificial Moschus's superfine powder is broken into the micropowders of 25-50 μ m, subsequent use; Grind behind the Margarita calcine to fine powder and carried out remove impurity, clean with other; Exsiccant crude drug mixes, and with 75% ethanol extraction of 8 times of amounts of medical material weight 2 hours, and extracting solution is concentrated into relative density was 1.15 extractum; The dilution of the water of 10 times of amounts of reuse extractum volume, filter the clarification extracting solution; Gained is clarified extracting solution feed macroporous adsorptive resins, use water washing earlier,, resolve with 75% ethanol at last again with 30% washing with alcohol; Desorbed solution is reclaimed ethanol, concentrate, get extract dry powder after the spray drying and mix with the artificial Moschus; With the carbomer is gel-type vehicle, adds ethyl hydroxybenzoate, disodiumedetate, ethanol, propylene glycol, tween 80 etc., and regulating pH value through sodium bicarbonate is about 6.5, processes gel, gets final product.
Embodiment 36:
With Fructus Fragariae Ananssae 100g, Herba corydalis edulis 100g, Flos rosae multiflorae 100g, Margarita 100g, artificial Moschus 5g, Herba Saussureae Involueratae 100g is raw material, and artificial Moschus's superfine powder is broken into the micropowders of 0.1.-1 μ m, subsequent use; Soup of Tofu Shaped as Pearls is concocted the back to be carried out remove impurity, cleaned with other; Exsiccant crude drug mixes; Use 75% ethanol extraction 3 times of 9,6 and 3 times of amounts of medical material weight respectively, each 2 hours, and extracting solution is concentrated into relative density is 1.15 extractum; The dilution of the water of 6 times of amounts of reuse extractum volume, filter the clarification extracting solution; Gained clarification extracting solution feeds macroporous adsorptive resins, uses water washing earlier, again with 20% washing with alcohol, resolves with 60% ethanol at last; The gained desorbed solution reclaims ethanol, concentrates, and gets extract dry powder after the spray drying and mixes with the artificial Moschus, with machine-processed microgranule and the nanoparticle of getting of fine gtinding, gets final product.
Embodiment 37:
With Fructus Fragariae Ananssae 800g, Herba corydalis edulis 800g, Flos rosae multiflorae 800g, Margarita 500g, artificial Moschus 50g, Herba Saussureae Involueratae 500g is raw material, and artificial Moschus's superfine powder is broken into the micropowders of 1-10 μ m, and is subsequent use; Grind after the Margarita bean milk system and be fine powder; And mix with other crude drugs that carried out remove impurity, cleaning, drying, use 60% ethanol extraction 3 times of 10,8 and 6 times of amounts of medical material weight respectively; Each 1 hour; And extracting solution is concentrated into relative density is 1.20 extractum, the water dilution of 4 times of amounts of reuse extractum volume, filter the clarification extracting solution; Gained is clarified extracting solution feed macroporous adsorptive resins, use water washing earlier,, resolve with 75% ethanol at last again with 25% washing with alcohol; The gained desorbed solution reclaims ethanol, concentrates, and gets extract dry powder after the spray drying and mixes with the artificial Moschus, adds solvent and propellant, processes nasal aerosol, gets final product.
Embodiment 38:
With Fructus Fragariae Ananssae 450g, Herba corydalis edulis 450g, Flos rosae multiflorae 450g, Margarita 300g, artificial Moschus 25g, Herba Saussureae Involueratae 300g is raw material, and artificial Moschus's superfine powder is broken into the micropowders of 10-40 μ m, and is subsequent use; Grind behind the Margarita calcine and be fine powder; And mix with other crude drugs that carried out remove impurity, cleaning, drying, use 45% ethanol extraction 2 times of medical material weight 10 and 5 times of amounts respectively; Each 1.5 hours; And extracting solution is concentrated into relative density is 1.12 extractum, the water dilution of 8 times of amounts of reuse extractum volume, filter the clarification extracting solution; Gained is clarified extracting solution feed macroporous adsorptive resins, use water washing earlier,, resolve with 50% ethanol at last again with 25% washing with alcohol; The gained desorbed solution reclaims ethanol, concentrates, and gets extract dry powder after the spray drying and mixes with the artificial Moschus; Add gifford's buffer solutions, sodium chloride adjusting etc. is oozed, and adds ethyl hydroxybenzoate, sodium sulfite, ethanol, propylene glycol etc.; Regulating pH value through sodium bicarbonate is about 6.5, processes nasal drop, gets final product.
Embodiment 39:
With Fructus Fragariae Ananssae 450g, Herba corydalis edulis 450g, Flos rosae multiflorae 450g, Margarita 300g, artificial Moschus 20g, Herba Saussureae Involueratae 350g is raw material, and artificial Moschus's superfine powder is broken into the micropowders of 0.1-40 μ m, subsequent use; Grind after the Margarita milk system to fine powder and carried out remove impurity, clean with other medical materials; Exsiccant crude drug mixes; With 55% alcohol reflux of 10 times of amounts of medical material weight 2 times; And relative density is 1.05 extractum when extracting solution is concentrated into 65 ℃, with the water dilution of 8 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 25% washing with alcohol, resolve with 70% ethanol at last; The gained desorbed solution reclaims ethanol, concentrates gained concentrated solution and artificial Moschus's mixing; Adding a little sodium bicarbonate adjusting pH value is about 6.5; Adding sodium chloride adjusting etc. is oozed, and adds ethyl hydroxybenzoate, disodiumedetate, glycerol, ethanol, propylene glycol etc. to process nasal mist, gets final product.
Embodiment 40:
With Fructus Fragariae Ananssae 450g, Herba corydalis edulis 450g, Flos rosae multiflorae 450g, Margarita 300g, artificial Moschus 20g, Herba Saussureae Involueratae 350g is raw material, and artificial Moschus's superfine powder is broken into the micropowders of 1-10 μ m, subsequent use; Grind after Margarita salt is fried to fine powder and carried out remove impurity, clean with other medical materials; Exsiccant crude drug mixes; With 80% alcohol reflux of 6 times of amounts of medical material weight 1 time; And relative density is 1.10 extractum when extracting solution is concentrated into 45 ℃, with the water dilution of 9 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 20% washing with alcohol, resolve with 50% ethanol at last; The gained desorbed solution reclaims ethanol, concentrates gained concentrated solution and artificial Moschus's mixing; Add gifford's buffer solutions, sodium chloride adjusting etc. is oozed, and adds ethyl hydroxybenzoate, lecithin, ethanol, propylene glycol etc.; Regulating pH value through sodium bicarbonate is about 6.5, processes nasal drop, gets final product.
Embodiment 41:
With Fructus Fragariae Ananssae 450g, Herba corydalis edulis 450g, Flos rosae multiflorae 450g, Margarita 300g, artificial Moschus 20g, Herba Saussureae Involueratae 350g is raw material, and artificial Moschus's superfine powder is broken into the micropowders of 0.1~10 μ m, subsequent use; Grind behind the Margarita calcine to fine powder and carried out remove impurity, clean with other medical materials; Exsiccant crude drug mixes; With 70% alcohol reflux of 12 times of amounts of medical material weight 3 times; And relative density is 1.20 extractum when extracting solution is concentrated into 70 ℃, with the water dilution of 10 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 15% washing with alcohol, resolve with 65% ethanol at last; The gained desorbed solution reclaims ethanol, concentrates gained concentrated solution and artificial Moschus's mixing; Adding a little sodium bicarbonate adjusting pH value is about 6.5; Adding sodium chloride adjusting etc. is oozed, and adds ethyl hydroxybenzoate, disodiumedetate, glycerol, ethanol, propylene glycol etc. to process nasal mist, gets final product.

Claims (41)

1. pharmaceutical composition of treating headache is characterized in that the crude drug of said composition consists of:
Fructus Fragariae Ananssae 20-70 weight portion Herba corydalis edulis 20-70 weight portion
Flos rosae multiflorae 20-70 weight portion Margarita 20-45 weight portion
Artificial Moschus 0.01-5 weight portion.
2. pharmaceutical composition as claimed in claim 1 is characterized in that the crude drug of said composition consists of:
Fructus Fragariae Ananssae 50 weight portion Herba corydalis eduliss 50 weight portions
The Flos rosae multiflorae 45 weight portion Margaritas 40 weight portions
Artificial Moschus's 1.8 weight portions;
Crude drug is formed or is:
The Fructus Fragariae Ananssae 30 weight portion Herba corydalis eduliss 60 weight portion Flos rosae multifloraies 35 weight portions
Margarita 40 weight portion artificial Moschuss 0.8 weight portion;
Crude drug is formed or is:
The Fructus Fragariae Ananssae 60 weight portion Herba corydalis eduliss 30 weight portion Flos rosae multifloraies 65 weight portions
Margarita 25 weight portion artificial Moschuss 3.8 weight portions.
3. pharmaceutical composition of treating headache is characterized in that the crude drug of said composition consists of:
Fructus Fragariae Ananssae 20-70 weight portion Herba corydalis edulis 20-70 weight portion
Flos rosae multiflorae 20-70 weight portion Margarita 20-45 weight portion
Artificial Moschus 0.01-5 weight portion Herba Saussureae Involueratae 25-50 weight portion.
4. pharmaceutical composition as claimed in claim 3 is characterized in that the crude drug of said composition consists of:
Fructus Fragariae Ananssae 50 weight portion Herba corydalis eduliss 50 weight portions
The Flos rosae multiflorae 45 weight portion Margaritas 40 weight portions
Artificial Moschus's 1.8 weight portion Herba Saussureae Involuerataes 40 weight portions;
Crude drug is formed or is:
The Fructus Fragariae Ananssae 30 weight portion Herba corydalis eduliss 60 weight portion Flos rosae multifloraies 35 weight portions
Margarita 40 weight portion artificial Moschuss 0.8 weight portion Herba Saussureae Involueratae 45 weight portions;
Crude drug is formed or is:
The Fructus Fragariae Ananssae 60 weight portion Herba corydalis eduliss 30 weight portion Flos rosae multifloraies 65 weight portions
Margarita 25 weight portion artificial Moschuss 3.8 weight portion Herba Saussureae Involuerataes 30 weight portions.
5. like any described preparation of drug combination method of claim 1-4; It is characterized in that this method is: composition material medicated powder is broken; Add conventional adjuvant; According to common process, process tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines accepted on clinical or the pharmaceutics.
6. according to claim 1 or claim 2 preparation of drug combination method is characterized in that this method is:
With clean, Margarita behind the exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine mixes; Being ground into particle diameter is 150-200 μ m medicated powder; Be placed on mixing behind artificial Moschus's porphyrize or directly mixing that to be ground into particle diameter in the micronizing equipment be 0.1-50 μ m micropowders again with the artificial Moschus; With this micropowders is active component; According to common process, process tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines accepted on clinical or the pharmaceutics.
7. preparation of drug combination method as claimed in claim 6 is characterized in that this method is:
To clean, Margarita mixes behind the exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine; Being ground into particle diameter is 160 μ m medicated powder; Be placed on mixing behind artificial Moschus's porphyrize or directly mixing that to be ground into particle diameter in the micronizing equipment be 0.1-1 μ m micropowders again with the artificial Moschus; With this micropowders is the active component of medicine; The adjuvant that medicine activity component and pharmaceutics are accepted combines; According to common process, process tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines accepted on clinical or the pharmaceutics.
8. preparation of drug combination method as claimed in claim 6 is characterized in that this method is:
To clean earlier, the Margarita behind the exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine mixes; Being ground into particle diameter is 160 μ m medicated powder; Be placed on mixing behind artificial Moschus's porphyrize or directly mixing that to be ground into particle diameter in the micronizing equipment be 1-10 μ m micropowders again with the artificial Moschus; With this micropowders is the active component of medicine; The adjuvant that medicine activity component and pharmaceutics are accepted combines; According to common process, tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines accepted on the clinical or pharmaceutics.
9. preparation of drug combination method as claimed in claim 6 is characterized in that this method is:
With clean, Margarita behind the exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine mixes; Being ground into particle diameter is 190 μ m medicated powder; Be placed on mixing behind artificial Moschus's porphyrize or directly mixing that to be ground into particle diameter in the micronizing equipment be 10-40 μ m micropowders again with the artificial Moschus; With this micropowders is the active component of medicine; The adjuvant that medicine activity component and pharmaceutics are accepted combines; According to common process, process tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines accepted on clinical or the pharmaceutics.
10. preparation of drug combination method as claimed in claim 6 is characterized in that this method is:
With clean, Margarita behind the exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine mixes; Being ground into particle diameter is 180 μ m medicated powder; Be placed on mixing behind artificial Moschus's porphyrize or directly mixing that to be ground into particle diameter in the micronizing equipment be 0.1-40 μ m micropowders again with the artificial Moschus; With this micropowders is the active component of medicine; The adjuvant that medicine activity component and pharmaceutics are accepted combines; According to common process, process tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines accepted on clinical or the pharmaceutics.
11. preparation of drug combination method according to claim 1 or claim 2 is characterized in that this method is:
Earlier the artificial Moschus is ground to fine powder or superfine powder and be broken into micropowders; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine Margarita after pulverizing mixes; The water boiling and extraction of doubly measuring with medical material weight 5-20 1-3 time; And extracting solution is concentrated into 30 ℃ of-80 ℃ of relative densities is the extractum of 1.01-1.30; The water dilution of doubly measuring with extractum volume 1-10, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with the 10%-30% washing with alcohol, resolve with 40%-75% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine; The adjuvant that medicine activity component and pharmaceutics are accepted combines; According to common process, process tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines accepted on clinical or the pharmaceutics.
12. preparation of drug combination method as claimed in claim 11 is characterized in that this method is:
Earlier the artificial Moschus is ground to fine powder or superfine powder and be broken into micropowders; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine Margarita after pulverizing mixes; With the water boiling and extraction of 12 times of amounts of medical material weight 2 times; And relative density is 1.15 extractum when extracting solution is concentrated into 50 ℃, with the water dilution of 5 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 30% washing with alcohol, resolve with 75% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine; The adjuvant that medicine activity component and pharmaceutics are accepted combines, and processes tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines of accepting on clinical or the pharmaceutics according to common process.
13. preparation of drug combination method as claimed in claim 11 is characterized in that this method is:
Earlier the artificial Moschus is ground to fine powder or superfine powder and be broken into micropowders; To clean again, the Margarita behind the exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine mixes; With the water boiling and extraction of 15 times of amounts of medical material weight 2 times; And relative density is 1.20 extractum when extracting solution is concentrated into 60 ℃, with the water dilution of 8 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 30% washing with alcohol, resolve with 75% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine; The adjuvant that medicine activity component and pharmaceutics are accepted combines, and processes tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines of accepting on clinical or the pharmaceutics according to common process.
14. preparation of drug combination method as claimed in claim 11 is characterized in that this method is:
Earlier the artificial Moschus is ground to fine powder or superfine powder and be broken into micropowders; To clean again, the Margarita behind the exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine mixes; With the water boiling and extraction of 15 times of amounts of medical material weight 3 times; And relative density is 1.20 extractum when extracting solution is concentrated into 70 ℃, with the water dilution of 7 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 7 times of bed volumes/hour macroporous adsorptive resins, use water washing earlier, again with 30% washing with alcohol, resolve with 70% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine; The adjuvant that medicine activity component and pharmaceutics are accepted combines, and processes tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines of accepting on clinical or the pharmaceutics according to common process.
15. preparation of drug combination method as claimed in claim 11 is characterized in that this method is:
Earlier the artificial Moschus is ground to fine powder or superfine powder and be broken into micropowders; To clean again, the Margarita behind the exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine mixes; With the water boiling and extraction of 8 times of amounts of medical material weight 3 times; And relative density is 1.05 extractum when extracting solution is concentrated into 40 ℃, with the water dilution of 2 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 3 times of bed volumes/hour macroporous adsorptive resins, use water washing earlier, again with 15% washing with alcohol, resolve with 45% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine; The adjuvant that medicine activity component and pharmaceutics are accepted combines, and processes tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines of accepting on clinical or the pharmaceutics according to common process.
16. preparation of drug combination method according to claim 1 or claim 2 is characterized in that this method is:
Earlier the artificial Moschus is ground to fine powder or superfine powder and be broken into micropowders; To clean again, the Margarita behind the exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine mixes; The 40-85% alcohol reflux of doubly measuring with medical material weight 6-12 1-3 time; And relative density is the extractum of 1.01-1.30 when extracting solution is concentrated into 30 ℃-70 ℃; The water dilution of doubly measuring with extractum volume 8-10, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with the 10%-30% washing with alcohol, resolve with 40%-75% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine; The adjuvant that medicine activity component and pharmaceutics are accepted combines, and processes tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines of accepting on clinical or the pharmaceutics according to common process.
17. preparation of drug combination method as claimed in claim 16 is characterized in that this method is:
Earlier the artificial Moschus is ground to fine powder or superfine powder and be broken into micropowders; To clean again, the Margarita behind the exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine mixes; With 50% alcohol reflux of 8 times of amounts of medical material weight 1 time; And relative density is 1.10 extractum when extracting solution is concentrated into 60 ℃, with the water dilution of 8 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 20% washing with alcohol, resolve with 45% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine; The adjuvant that medicine activity component and pharmaceutics are accepted combines, and processes tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines of accepting on clinical or the pharmaceutics according to common process.
18. preparation of drug combination method as claimed in claim 16 is characterized in that this method is:
Earlier the artificial Moschus is ground to fine powder or superfine powder and be broken into micropowders; To clean again, the Margarita behind the exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine mixes; With 65% alcohol reflux of 10 times of amounts of medical material weight 3 times; And relative density is 1.05 extractum when extracting solution is concentrated into 40 ℃, with the water dilution of 10 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 30% washing with alcohol, resolve with 70% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine; The adjuvant that medicine activity component and pharmaceutics are accepted combines, and processes tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines of accepting on clinical or the pharmaceutics according to common process.
19. preparation of drug combination method as claimed in claim 16 is characterized in that this method is:
Earlier the artificial Moschus is ground to fine powder or superfine powder and be broken into micropowders; To clean again, the Margarita behind the exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, the process of preparing Chinese medicine mixes; With 80% alcohol reflux of 12 times of amounts of medical material weight 2 times; And relative density is 1.25 extractum when extracting solution is concentrated into 70 ℃, with the water dilution of 9 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 15% washing with alcohol, resolve with 60% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine; The adjuvant that medicine activity component and pharmaceutics are accepted combines, and processes tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines of accepting on clinical or the pharmaceutics according to common process.
20., it is characterized in that this method is like claim 3 or 4 described preparation of drug combination methods:
To clean earlier, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; Being ground into particle diameter is 150-200 μ m medicated powder; Again with mixing behind artificial Moschus's porphyrize or being 0.1-50 μ m micropowders with placing micronizing equipment to be ground into particle diameter again after the artificial Moschus directly mixes; With this micropowders is the active component of medicine; Add conventional adjuvant according to common process, process tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines accepted on clinical or the pharmaceutics.
21. preparation of drug combination method as claimed in claim 20 is characterized in that this method is:
To clean earlier, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; Being ground into particle diameter is 160 μ m medicated powder; Again with mixing behind artificial Moschus's porphyrize or being 0.1-10 μ m micropowders with placing micronizing equipment to be ground into particle diameter again after the artificial Moschus directly mixes; With this micropowders is the active component of medicine; Add conventional adjuvant according to common process, process tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines accepted on clinical or the pharmaceutics.
22. preparation of drug combination method as claimed in claim 20 is characterized in that this method is:
To clean earlier, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; Being ground into particle diameter is 160 μ m medicated powder; Again with mixing behind artificial Moschus's porphyrize or being 1-10 μ m micropowders with placing micronizing equipment to be ground into particle diameter again after the artificial Moschus directly mixes; With this micropowders is the active component of medicine; Add conventional adjuvant according to common process, process tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines accepted on clinical or the pharmaceutics.
23. preparation of drug combination method as claimed in claim 20 is characterized in that this method is:
To clean earlier, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; Being ground into particle diameter is 190 μ m medicated powder; Again with mixing behind artificial Moschus's porphyrize or being 10-40 μ m micropowders with placing micronizing equipment to be ground into particle diameter again after the artificial Moschus directly mixes; With this micropowders is the active component of medicine; Add conventional adjuvant according to common process, process tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines accepted on clinical or the pharmaceutics.
24. preparation of drug combination method as claimed in claim 20 is characterized in that this method is:
To clean earlier, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; Being ground into particle diameter is 180 μ m medicated powder; Again with mixing behind artificial Moschus's porphyrize or being 0.1-40 μ m micropowders with placing micronizing equipment to be ground into particle diameter again after the artificial Moschus directly mixes; With this micropowders is the active component of medicine; Add conventional adjuvant according to common process, process tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines accepted on clinical or the pharmaceutics.
25., it is characterized in that this method is like claim 3 or 4 described preparation of drug combination methods:
Earlier the artificial Moschus is ground to fine powder or superfine powder and be broken into micropowders; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; The water boiling and extraction of doubly measuring with medical material weight 5-20 1-3 time; And relative density is the extractum of 1.01-1.30 when extracting solution is concentrated into 30 ℃-80 ℃; The water dilution of doubly measuring with extractum volume 1-10, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with the 10%-30% washing with alcohol, resolve with 40%-75% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine; The adjuvant that medicine activity component and pharmaceutics are accepted combines; According to common process, process tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines accepted on clinical or the pharmaceutics.
26. preparation of drug combination method as claimed in claim 25 is characterized in that this method is:
Earlier the artificial Moschus is ground to fine powder or superfine powder and be broken into micropowders; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; With the water boiling and extraction of 20 times of amounts of medical material weight 1 time; And relative density is 1.10 extractum when extracting solution is concentrated into 70 ℃; With the dilution of the water of 8 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 30% washing with alcohol, resolve with 70% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine; The adjuvant that medicine activity component and pharmaceutics are accepted combines; According to common process, process tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines accepted on clinical or the pharmaceutics.
27. preparation of drug combination method as claimed in claim 25 is characterized in that this method is:
Earlier the artificial Moschus is ground to fine powder or superfine powder and be broken into micropowders; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; With the water boiling and extraction of 6 times of amounts of medical material weight 3 times; And relative density is 1.20 extractum when extracting solution is concentrated into 50 ℃; With the dilution of the water of 4 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 20% washing with alcohol, resolve with 50% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine; The adjuvant that medicine activity component and pharmaceutics are accepted combines; According to common process, process tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines accepted on clinical or the pharmaceutics.
28. preparation of drug combination method as claimed in claim 25 is characterized in that this method is:
Earlier the artificial Moschus is ground to fine powder or superfine powder and be broken into micropowders; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; With the water boiling and extraction of 12 times of amounts of medical material weight 2 times; And relative density is 1.25 extractum when extracting solution is concentrated into 65 ℃; With the dilution of the water of 10 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 15% washing with alcohol, resolve with 60% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine; The adjuvant that medicine activity component and pharmaceutics are accepted combines; According to common process, process tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines accepted on clinical or the pharmaceutics.
29., it is characterized in that this method is like claim 3 or 4 described preparation of drug combination methods:
Earlier the artificial Moschus is ground to fine powder or superfine powder and be broken into micropowders; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; 75% alcohol reflux of doubly measuring with medical material weight 6-12 1-3 time; And relative density is the extractum of 1.01-1.30 when extracting solution is concentrated into 30 ℃-70 ℃; The water dilution of doubly measuring with extractum volume 1-10, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with the 10%-30% washing with alcohol, resolve with 40%-75% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine; The adjuvant that medicine activity component and pharmaceutics are accepted combines; According to common process, process tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines accepted on clinical or the pharmaceutics.
30. preparation of drug combination method as claimed in claim 29 is characterized in that this method is:
Earlier the artificial Moschus is ground to fine powder or superfine powder and be broken into micropowders; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; With 55% alcohol reflux of 10 times of amounts of medical material weight 2 times; And relative density is 1.05 extractum when extracting solution is concentrated into 65 ℃; With the dilution of the water of 8 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 25% washing with alcohol, resolve with 70% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine; The adjuvant that medicine activity component and pharmaceutics are accepted combines; According to common process, process tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines accepted on clinical or the pharmaceutics.
31. preparation of drug combination method as claimed in claim 29 is characterized in that this method is:
Earlier the artificial Moschus is ground to fine powder or superfine powder and be broken into micropowders; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; With 80% alcohol reflux of 6 times of amounts of medical material weight 1 time; And relative density is 1.10 extractum when extracting solution is concentrated into 45 ℃; With the dilution of the water of 9 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 20% washing with alcohol, resolve with 50% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine; The adjuvant that medicine activity component and pharmaceutics are accepted combines; According to common process, process tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines accepted on clinical or the pharmaceutics.
32. preparation of drug combination method as claimed in claim 29 is characterized in that this method is:
Earlier the artificial Moschus is ground to fine powder or superfine powder and be broken into micropowders; To clean again, exsiccant Fructus Fragariae Ananssae, Herba corydalis edulis, the Flos rosae multiflorae, process of preparing Chinese medicine Margarita, the Herba Saussureae Involueratae after pulverizing mix; With 70% alcohol reflux of 12 times of amounts of medical material weight 3 times; And relative density is 1.20 extractum when extracting solution is concentrated into 70 ℃; With the dilution of the water of 10 times of amounts of extractum volume, filter the clarification extracting solution; With the clarification extracting solution feed absorption, washing, the flow velocity of resolving is 0.1-10 times of bed volume/hour macroporous adsorptive resins, use water washing earlier, again with 15% washing with alcohol, resolve with 65% ethanol at last; Desorbed solution is reclaimed ethanol, concentrate, mix with artificial Moschus's fine powder or micropowders dry back, gets the active component of medicine; The adjuvant that medicine activity component and pharmaceutics are accepted combines; According to common process, process tablet, capsule, powder, pill, granule, soft extract with bee honey agent, oral liquid, ejection preparation or nasal drop, aerosol, spray, powder spray, gel, microgranule, cyclodextrin clathrate, liposome, liposome precursor and other nasal cavity medicines accepted on clinical or the pharmaceutics.
33. like any described preparation of drug combination method of claim 5-32, wherein the method for preparing of nasal drop is:
Nasal drop is processed in adding PH regulator, buffer agent, isoosmotic adjusting agent, antibacterial, stabilizing agent, cosolvent, wetting agent, solubilizing agent in the medicine activity component of preparation;
Described PH regulator is that PH regulator acids is any one in hydrochloric acid, sulphuric acid, phosphoric acid, acetic acid, boric acid, citric acid, malic acid, tartaric acid, maleic acid, acidic amino acid class, the sodium dihydrogen phosphate; PH regulator bases is any one of sodium hydroxide, sodium bicarbonate, ammonia, sodium hydrogen phosphate, sodium citrate, Borax, organic amine and basic amino acid apoplexy due to endogenous wind;
Described buffer agent is any one in gifford's buffer solutions, Sang Shi buffer, Pasteur's buffer and the acetate buffer;
Isoosmotic adjusting agent be in sodium chloride, Chile saltpeter, boric acid, Borax, glucose, fructose, glycerol, mannitol, sorbitol and the xylitol any one;
Described antibacterial is any one in benzalkonium chloride, phenylmercuric nitrate and phenylmercuric acetate, chlorobutanol, thimerosal, mercuric oxycyanide, parabens, phenethanol and the sorbic acid;
Described stabilizing agent is that antioxidant and/or other have chelating agen: antioxidant be in sodium pyrosulfite, sodium sulfite, sodium sulfite, sodium thiosulfate, ascorbic acid, thiourea, cysteine, tocopherol and the lecithin any one; It is in disodiumedetate, ethylenediaminetetraacetic acid, citric acid and the tartaric acid any one that described other have chelating agen;
Described cosolvent is any one in glycerol, propylene glycol and the ethanol;
Described wetting agent is any one in sorbitol, glycerol, propylene glycol, mineral oil and the vegetable oil;
Described solubilizing agent is any one in tween 80, polyethylene castor oil hydrogenated and the peregal 0.
34. like any described preparation of drug combination method of claim 5-32, wherein the method for nasal mist is:
Adding PH regulator, buffer agent, cosolvent, isoosmotic adjusting agent, antibacterial, antioxidant in the medicine activity component of preparation are processed nasal mist;
Described PH regulator is that PH regulator acids is any one in hydrochloric acid, sulphuric acid, phosphoric acid, acetic acid, boric acid, citric acid, malic acid, tartaric acid, maleic acid, acidic amino acid class, the sodium dihydrogen phosphate; PH regulator bases is any one of sodium hydroxide, sodium bicarbonate, ammonia, sodium hydrogen phosphate, sodium citrate, Borax, organic amine and basic amino acid apoplexy due to endogenous wind;
Described buffer agent is any one in gifford's buffer solutions, Sang Shi buffer, Pasteur's buffer and the acetate buffer;
Described isoosmotic adjusting agent be in sodium chloride, Chile saltpeter, boric acid, Borax, glucose, fructose, glycerol, mannitol, sorbitol and the xylitol any one;
Described antibacterial is any one in benzalkonium chloride, phenylmercuric nitrate and phenylmercuric acetate, chlorobutanol, thimerosal, mercuric oxycyanide, parabens, phenethanol and the sorbic acid;
Described antioxidant be in sodium pyrosulfite, sodium sulfite, sodium sulfite, sodium thiosulfate, ascorbic acid, thiourea, cysteine, tocopherol and the lecithin any one;
Described cosolvent is any one in glycerol, propylene glycol and the ethanol.
35. like any described preparation of drug combination method of claim 5-32, wherein the method for preparing of nasal cavity powder spray is:
Add diluent in the medicine activity component with preparation, process the nasal cavity powder spray; Wherein diluent is any one in lactose, anhydrous glucose and the mannitol.
36. like any described preparation of drug combination method of claim 5-32, wherein the method for preparing of nasal gel is:
Add gel-type vehicle, PH regulator, wetting agent, solubilizing agent, antioxidant, antibacterial in the medicine activity component with preparation and process nasal gel;
Described gel-type vehicle is any one in carbomer, hypromellose, methylcellulose, sodium carboxymethyl cellulose, chitosan, polyethylene pyrrole network alkane ketone, polyvinyl alcohol and the hyaluronic acid sodium;
Described PH regulator is any one in triethanolamine, sodium hydroxide, ethylenediamine, lauryl amine and the sodium bicarbonate;
Described wetting agent is any one in glycerol, the propylene glycol;
Described solubilizing agent is any one in tween 80, polyethylene castor oil hydrogenated and the peregal 0;
Described antioxidant is any one in various sulphite, cysteine, di-tert-butyl hydroxy toluene, the potassium sorbate;
Described antibacterial is any one in parabens, thimerosal, benzoic acid and sodium benzoate, the potassium sorbate.
37. like any described preparation of drug combination method of claim 5-32, it is characterized in that said capsule is a soft capsule, said pill is drop pill or honeyed pill, said microgranule is microsphere, nanoparticle, microcapsule or nanoparticle.
38. like the application of any described pharmaceutical composition of claim 1-4 in the medicine of preparation treatment headache.
39. like the application of any described pharmaceutical composition of claim 1-4 in the migrainous medicine of preparation treatment.
40. application as claimed in claim 38 is characterized in that said treatment headache is meant anticoagulation or improves 5-HT content or anti-hypoxia in the brain.
41. application as claimed in claim 39 is characterized in that said treatment migraine is meant anticoagulation or improves 5-HT content or anti-hypoxia in the brain.
CN200910252554XA 2009-01-21 2009-12-25 Medicine composition for treating headache or migraine and preparation method thereof Active CN101721510B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN200910252554XA CN101721510B (en) 2009-01-21 2009-12-25 Medicine composition for treating headache or migraine and preparation method thereof

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN200910077264 2009-01-21
CN200910077264.6 2009-01-21
CN200910252554XA CN101721510B (en) 2009-01-21 2009-12-25 Medicine composition for treating headache or migraine and preparation method thereof

Publications (2)

Publication Number Publication Date
CN101721510A CN101721510A (en) 2010-06-09
CN101721510B true CN101721510B (en) 2012-05-23

Family

ID=42443461

Family Applications (1)

Application Number Title Priority Date Filing Date
CN200910252554XA Active CN101721510B (en) 2009-01-21 2009-12-25 Medicine composition for treating headache or migraine and preparation method thereof

Country Status (1)

Country Link
CN (1) CN101721510B (en)

Also Published As

Publication number Publication date
CN101721510A (en) 2010-06-09

Similar Documents

Publication Publication Date Title
CN104474462A (en) Traditional Chinese medicine preparation for treating prosopalgia and preparation method of traditional Chinese medicine preparation
CN1840166A (en) Modern Chinese medicinal oral liquid of 'Wen Dan Tang' and preparation method thereof
CN103127232A (en) Total extract for mulberry leaf prescription as well as preparation and usage thereof
CN102028700A (en) Medicinal composition and preparation method thereof
CN102068535A (en) Immature bitter orange or bitter orange total flavonoids extract prepared by ethanol reflux and extraction and application thereof
CN104857435B (en) A kind of Traditional Chinese medicine compound composition with antitumor activity and its preparation method and application
CN102512431B (en) Application of centella asiatica triterpenoid component to preparing anti-craniocerebral injury product
CN1471845A (en) Healthy food with glossy and rhizoma as main material and preparing method thereof
CN101822729B (en) Medicine for treating slow arrhythmia sick sinus syndromes
CN103211869A (en) Traditional Chinese medicine eye drops used for treating acute conjunctivitis and preparation method thereof
CN1679697A (en) Chinese medicine preparation for treating cardio vascular disease and containing notoginseng, pericarpium trichosanthis and leech, for treating cardio-cerebral blood vessel diseases and its preparing
CN101721510B (en) Medicine composition for treating headache or migraine and preparation method thereof
CN108567914A (en) It is a kind of that there is the Chinese medicine preparation and its preparation method and application for improving sleep effect
CN102028834B (en) Compound Longxueji preparation and preparation method thereof
CN101721511B (en) Medicine combination for treating headache or migraine and preparation method thereof
CN103463244A (en) Method for extracting blood sugar lowering substance from China roses and application of blood sugar lowering substance
CN1704113A (en) Chinese traditional medicinal preparation containing red sange root and safflower for treating cardiovascular and cerebrovascular diseases and preparing process thereof
CN104491318A (en) Traditional Chinese preparation used for treating asthma and preparation method of traditional Chinese preparation
CN105380985B (en) Pharmaceutical composition for treating cerebral arterial thrombosis
CN104840747B (en) Chinese medicine composition with antithyroid cancer activity and its preparation method and application
CN111643606B (en) Gel plaster for treating insomnia and preparation method thereof
CN103417906A (en) Applications of compound mylabris traditional Chinese medicine composition and preparations thereof in preparing drugs for curing depression
CN100589800C (en) Chinese medicine preparation of total coumarins extract from peu cedanum praeruptorum dunn, and its preparing method and use
CN106074719A (en) Plumula Nelumbinis extract is in the application of preparation treatment pulmonary fibrosis medicine
CN104840727B (en) Chinese medicine composition with anti-cancer of the esophagus activity and its preparation method and application

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant