CN101919914A - Medicinal composition with anti-inflammatory and analgesic effect and preparation method and application thereof - Google Patents
Medicinal composition with anti-inflammatory and analgesic effect and preparation method and application thereof Download PDFInfo
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Abstract
The invention provides a medicinal composition with anti-inflammatory and analgesic effect, which is prepared from raw material medicaments of aconitum excelsum reichb and lamiophlomis rotata flavonoids. Through pharmacological research on interaction of the aconitum excelsum reichb and the lamiophlomis rotata flavonoids and the compatability of the medicaments, results show that the medicinal composition can obviously improve the pain threshold value of mice compared with the single aconitum excelsum reichb and single lamiophlomis rotata flavonoids; the medicinal composition is subjected to experiments of acetic acid twisting-body reaction of mice, water bah tail flick reaction of rats, croton oil induced ear edema of mice and carrageenin induced paw edema of rats, so the optimal formula of the medicinal composition is obtained. The medicinal composition has obvious anti-inflammatory and analgesic effect and wide application prospect.
Description
Invention field
The present invention relates to a kind of pharmaceutical composition and its production and use, particularly a kind of have anti-inflammatory and analgesic effect with the effective site Radix Lamiophlomidis Rotatae flavone of the effective site Aconitum sinomontanum Nakai total alkaloids of Aconitum sinomontanum Nakai and Radix Lamiophlomidis Rotatae as pharmaceutical composition of crude drug and its production and use.
Background technology
Aconitum sinomontanum Nakai is the dry root of ranunculaceae plant Aconitum sinomontanum Nakai Aconitum Sinomontanum Nakai, and excavate autumn, removes fibrous root and aerial parts, and flush away earth dries.Be distributed in provinces such as each county to the east of Wei County, Hebei Xiaowutai Shan Mountain, Shanxi, the Qinghai Sun-Moon Mountain, Shaanxi, Gansu, Hubei, Sichuan and Guizhou.Its root is poisonous, is used as medicine, can reducing swelling and alleviating pain, promoting blood circulation to remove blood stasis, dispel the wind, have powerful pain-stopping effect and analgesic, anti-inflammatory effect, and cure mainly diseases such as fracture, rheumatic lumbago and scelalgia, furuncle, syphilis, cardiopalmus, stomachache, traumatic injury.Aconitum sinomontanum Nakai contains multiple alkaloid, and its mesaconitine (Aconitine) is to have very that Johnson ﹠ Johnson manages active di esters alkaloid, and modern pharmacology studies have shown that aconitine has effects such as analgesia, anesthesia, antiinflammatory, blood pressure lowering; Aconitum sinomontanum Nakai total alkaloids is the effective ingredient that extracts in the Chinese medicine Aconitum sinomontanum Nakai root, clinically as non-addicted analgesics, has very strong analgesic activity, also has resist inflammation on repercussive function.
Radix Lamiophlomidis Rotatae is the dry herb of dicotyledon Labiatae Radix Lamiophlomidis Rotatae Lamiophlomis rotata (Benth.) Kudo..Its property is sweet, bitter, and is flat.Its main chemical compositions is flavone, saponins, iridoids, has hemostasis, dispels the wind, effect such as alleviating pain and detumescence, blood circulation promoting and blood stasis dispelling, anti-inflammation, enhancing immunity, is used for the treatment of traumatic injury, traumatic hemorrhage, rheumatic arthralgia, grasserie etc.Just on the books in the Tibetanmedicine masterpiece Four-Volume Medical Code of China before more than 1,000 year and " brilliant pearl book on Chinese herbal medicine ".Radix Lamiophlomidis Rotatae is born in the rubble beach of high mountain intensity air slaking or alpine meadow, main product in Tibet, provinces and regions such as Qinghai, Yunnan, Sichuan, Gansu, the Tibetan medicine uses it for osteomyelitis, joint, grasserie, fractures, gets injured by a fall, gunshot wound etc.Discover that the contained flavones ingredient of Radix Lamiophlomidis Rotatae has the effect of tangible pain easing and hemostasis.
Pain is modal multiple common symptoms in the medicine clinical research disease, the medicine of nowadays treating pain is many based on Western medicine, mainly be divided into non_steroidal anti_inflammatory drug and narcosis analgesic two classes, in this two classes medicine, though anaesthetic analgesic effect is strong, but the side effect of self big (addiction), though and the non-steroidal anti-inflammatory analgesic does not have the so big side effect of narcotic analgesic medicine, the untoward reaction of aspects such as many gastrointestinal tract is also arranged.Medical domain is also constantly being sought the minimum anti-inflammation analgesia medicine of the good and side effect (as addiction) of analgesic effect.
Application number is that the patent of 200810180489.x discloses the pharmaceutical composition of being made up of Aconitum sinomontanum Nakai and Radix Lamiophlomidis Rotatae crude drug that is used for anti-inflammatory and antalgic; Another application number is that 200810152101.5 patent discloses the pharmaceutical composition of being made up of Aconitum sinomontanum Nakai total alkaloids and Radix Lamiophlomidis Rotatae total glycosides site of action that is used for the treatment of rheumatoid arthritis.At present be not used for antiinflammatory and analgesic medicine as yet by the pharmaceutical composition that Aconitum sinomontanum Nakai total alkaloids and Radix Lamiophlomidis Rotatae flavone site of action are formed.
Summary of the invention
The object of the invention is to disclose a kind of pharmaceutical composition with anti-inflammatory and analgesic effect, the present invention also aims to disclose this preparation of drug combination method, the present invention also aims to disclose the purposes of this pharmaceutical composition.
The present invention seeks to be achieved by the following scheme.
The crude drug of pharmaceutical composition of the present invention consists of:
Aconitum sinomontanum Nakai total alkaloids 10-100 weight portion Radix Lamiophlomidis Rotatae flavone 10-100 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably:
Aconitum sinomontanum Nakai total alkaloids 10-40 weight portion Radix Lamiophlomidis Rotatae flavone 60-100 weight portion;
Or: Aconitum sinomontanum Nakai total alkaloids 60-100 weight portion Radix Lamiophlomidis Rotatae flavone 10-40 weight portion;
Or: Aconitum sinomontanum Nakai total alkaloids 40-60 weight portion Radix Lamiophlomidis Rotatae flavone 40-60 weight portion.
The crude drug composition of pharmaceutical composition of the present invention is preferably:
Aconitum sinomontanum Nakai total alkaloids 15 weight portion Radix Lamiophlomidis Rotatae flavone 95 weight portions;
Or: Aconitum sinomontanum Nakai total alkaloids 95 weight portion Radix Lamiophlomidis Rotatae flavone 15 weight portions;
Or: Aconitum sinomontanum Nakai total alkaloids 50 weight portion Radix Lamiophlomidis Rotatae flavone 50 weight portions;
Or: Aconitum sinomontanum Nakai total alkaloids 20 weight portion Radix Lamiophlomidis Rotatae flavone 80 weight portions;
Or: Aconitum sinomontanum Nakai total alkaloids 80 weight portion Radix Lamiophlomidis Rotatae flavone 20 weight portions;
Or: Aconitum sinomontanum Nakai total alkaloids 30 weight portion Radix Lamiophlomidis Rotatae flavone 70 weight portions;
Or: Aconitum sinomontanum Nakai total alkaloids 70 weight portion Radix Lamiophlomidis Rotatae flavone 30 weight portions.
Get pharmaceutical composition crude drug of the present invention, add conventional adjuvant, according to common process, make dosage form clinical or that pharmaceutically accept, 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, controlled release preparation, oral liquid, ejection preparation or external preparation.
Preparation of drug combination method of the present invention comprises the steps:
A. the preparation method of Aconitum sinomontanum Nakai total alkaloids is:
Get dry Aconitum sinomontanum Nakai medical material, pulverize, the 60%-95% ethanol extraction of usefulness 4-25 times of weight 1-3 time, the each extraction 0.5-5 hour, collection, merge extractive liquid,, and reclaim ethanol, get ethanol extraction, with hydrochloric acid, sulphuric acid or acetate dissolution ethanol extraction, behind the adjusting PH to 1-3, after hydro-oxidation sodium solution, sodium bicarbonate solution or ammonia are regulated PH to 9-12, use chloroform extraction, merge chloroform soln, reclaim chloroform, drying gets Aconitum sinomontanum Nakai total alkaloids;
B. the preparation method of Radix Lamiophlomidis Rotatae flavone is:
The Radix Lamiophlomidis Rotatae medical material is extracted 1-5 time with the aqua calcis of the 20%-95% of 4-25 times of weight or the alcoholic solution of sodium carbonate liquor preparation, the each extraction 0.5-5 hour, collect, merge extractive liquid,, filter, filtrate is under 55 ℃ of-85 ℃ of temperature, after being condensed into the concentrated solution that relative density is 1.0-1.5, with 40-80% alcoholic solution heating for dissolving, cooling removes by filter alcohol insoluble matter impurity, and filtrate adds the water heating for dissolving after removing ethanol, put cold, with 2-4 weeding of grease soluble components of petroleum ether extraction, the water intaking layer leaves standstill 8-16h by cation exchange resin or HPD-300 or HPD-100 or HPD-450 or HPD-600 macroporous adsorbent resin, colourless with the 5%-45% ethanol elution to eluent, reuse 30%-75% ethanol is resolved, absorption, washing and the flow velocity of resolving be 0.1-10 times of bed volume/hour, collect alcoholic solution, reclaim ethanol to there not being the alcohol flavor, drying is pulverized, and gets the Radix Lamiophlomidis Rotatae flavone;
C. above Radix Lamiophlomidis Rotatae flavone is mixed with Aconitum sinomontanum Nakai total alkaloids, add conventional adjuvant, according to common process, make clinical or pharmaceutically acceptable tablet, capsule, powder, soft capsule, drop pill, honeyed pill, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation, oral liquid, ejection preparation or external preparation.
Preparation of drug combination method of the present invention preferably includes following steps:
A. the preparation method of Aconitum sinomontanum Nakai total alkaloids is preferably:
Get dry Aconitum sinomontanum Nakai medical material, pulverize, with 75% ethanol extraction of 10 times of weight 2 times, the each extraction 2 hours, collection, merge extractive liquid,, and reclaim ethanol, with hydrochloric acid, sulphuric acid or acetate dissolution ethanol extraction, after regulating PH to 2, hydro-oxidation sodium solution, sodium bicarbonate solution or ammonia are used chloroform extraction after regulating PH to 10, merge chloroform soln, reclaim chloroform, drying gets Aconitum sinomontanum Nakai total alkaloids;
B. the preparation method of Radix Lamiophlomidis Rotatae flavone is preferably:
The Radix Lamiophlomidis Rotatae medical material is extracted 2 times with 70% the aqua calcis of 10 times of weight or the alcoholic solution of sodium carbonate liquor preparation, the each extraction 2 hours, collect, merge extractive liquid,, filter, filtrate under 70 ℃ of temperature, be condensed into the concentrated solution that relative density is 1.15-1.25 after, with 60% alcoholic solution heating for dissolving, cooling removes by filter alcohol insoluble matter impurity, and filtrate adds the water heating for dissolving after removing ethanol, put cold, with 3 weeding of grease soluble components of petroleum ether extraction, the water intaking layer leaves standstill 12h by cation exchange resin or HPD-300 or HPD-100 or HPD-450 or HPD-600 macroporous adsorbent resin, colourless with 15% ethanol elution to eluent, reuse 60% ethanol is resolved, absorption, washing, the flow velocity of resolving be 5 times of bed volumes/hour, collect alcoholic solution, reclaim ethanol to there not being the alcohol flavor, drying is pulverized, and gets the Radix Lamiophlomidis Rotatae flavone;
C. above Radix Lamiophlomidis Rotatae flavone is mixed with Aconitum sinomontanum Nakai total alkaloids, add conventional adjuvant, according to common process, make clinical or pharmaceutically acceptable tablet, capsule, powder, soft capsule, drop pill, honeyed pill, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation, oral liquid, ejection preparation or external preparation.
Preparation of drug combination method of the present invention preferably includes following steps:
A. the preparation method of Aconitum sinomontanum Nakai total alkaloids is preferably:
Get dry Aconitum sinomontanum Nakai medical material, pulverize, with 65% ethanol extraction of 20 times of weight 1 time, the each extraction 4.5 hours, collection, merge extractive liquid,, and reclaim ethanol, with hydrochloric acid, sulphuric acid or acetate dissolution ethanol extraction, after regulating PH to 1, hydro-oxidation sodium solution, sodium bicarbonate solution or ammonia are used chloroform extraction after regulating PH to 11, merge chloroform soln, reclaim chloroform, drying gets Aconitum sinomontanum Nakai total alkaloids;
B. the preparation method of Radix Lamiophlomidis Rotatae flavone is preferably:
The Radix Lamiophlomidis Rotatae medical material is extracted 3 times with 50% the aqua calcis of 20 times of weight or the alcoholic solution of sodium carbonate liquor preparation, the each extraction 1 hour, collect, merge extractive liquid,, filter, filtrate under 80 ℃ of temperature, be condensed into the concentrated solution that relative density is 1.05-1.15 after, with 75% alcoholic solution heating for dissolving, cooling removes by filter alcohol insoluble matter impurity, and filtrate adds the water heating for dissolving after removing ethanol, put cold, with 2 weeding of grease soluble components of petroleum ether extraction, the water intaking layer leaves standstill 10h by cation exchange resin or HPD-300 or HPD-100 or HPD-450 or HPD-600 macroporous adsorbent resin, colourless with 30% ethanol elution to eluent, reuse 70% ethanol is resolved, absorption, washing, the flow velocity of resolving be 3 times of bed volumes/hour, collect alcoholic solution, reclaim ethanol to there not being the alcohol flavor, drying is pulverized, and gets the Radix Lamiophlomidis Rotatae flavone;
C. above Radix Lamiophlomidis Rotatae flavone is mixed with Aconitum sinomontanum Nakai total alkaloids, add conventional adjuvant, according to common process, make clinical or pharmaceutically acceptable tablet, capsule, powder, soft capsule, drop pill, honeyed pill, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation, oral liquid, ejection preparation or external preparation.
Preparation of drug combination method of the present invention preferably includes following steps:
A. the preparation method of Aconitum sinomontanum Nakai total alkaloids is preferably:
Get dry Aconitum sinomontanum Nakai medical material, pulverize, with 95% ethanol extraction of 5 times of weight 3 times, the each extraction 1 hour, collection, merge extractive liquid,, and reclaim ethanol, with hydrochloric acid, sulphuric acid or acetate dissolution ethanol extraction, after regulating PH to 3, hydro-oxidation sodium solution, sodium bicarbonate solution or ammonia are used chloroform extraction after regulating PH to 8, merge chloroform soln, reclaim chloroform, drying gets Aconitum sinomontanum Nakai total alkaloids;
B. the preparation method of Radix Lamiophlomidis Rotatae flavone is preferably:
The Radix Lamiophlomidis Rotatae medical material is extracted 4 times with 90% the aqua calcis of 5 times of weight or the alcoholic solution of sodium carbonate liquor preparation, the each extraction 1 hour, collect, merge extractive liquid,, filter, filtrate under 60 ℃ of temperature, be condensed into the concentrated solution that relative density is 1.25-1.35 after, with 50% alcoholic solution heating for dissolving, cooling removes by filter alcohol insoluble matter impurity, and filtrate adds the water heating for dissolving after removing ethanol, put cold, with 4 weeding of grease soluble components of petroleum ether extraction, the water intaking layer leaves standstill 14h by cation exchange resin or HPD-300 or HPD-100 or HPD-450 or HPD-600 macroporous adsorbent resin, colourless with 20% ethanol elution to eluent, reuse 45% ethanol is resolved, absorption, washing, the flow velocity of resolving be 9 times of bed volumes/hour, collect alcoholic solution, reclaim ethanol to there not being the alcohol flavor, drying is pulverized, and gets the Radix Lamiophlomidis Rotatae flavone;
C. above Radix Lamiophlomidis Rotatae flavone is mixed with Aconitum sinomontanum Nakai total alkaloids, add conventional adjuvant, according to common process, make clinical or pharmaceutically acceptable tablet, capsule, powder, soft capsule, drop pill, honeyed pill, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation, oral liquid, ejection preparation or external preparation.
The invention provides a kind of effective site Aconitum sinomontanum Nakai total alkaloids and pharmaceutical composition that is used for anti-inflammatory and antalgic of forming of the effective site Radix Lamiophlomidis Rotatae flavone of Radix Lamiophlomidis Rotatae by Aconitum sinomontanum Nakai, this pharmaceutical composition and the pharmaceutical composition of being made up of Aconitum sinomontanum Nakai and Radix Lamiophlomidis Rotatae crude drug, the pharmaceutical composition of being made up of Aconitum sinomontanum Nakai total alkaloids and Radix Lamiophlomidis Rotatae total glycosides site of action are compared, have advantages such as effect is lasting, Transdermal absorption is good, and anti-inflammatory and analgesic effect is strong.The applicant shows by a large amount of experiments and clinical research, and the Aconitum sinomontanum Nakai medical material obtains Aconitum sinomontanum Nakai total alkaloids through extracting, and it is compared with the Aconitum sinomontanum Nakai crude drug, and its antiinflammatory, analgesic effect are best, and action time is also longer, and Transdermal absorption is also better; The Radix Lamiophlomidis Rotatae medical material obtains the Radix Lamiophlomidis Rotatae total glycosides through extracting, continue purification, the refining Radix Lamiophlomidis Rotatae flavone that obtains, its antiinflammatory, analgesic effect also obviously are better than Radix Lamiophlomidis Rotatae crude drug, Radix Lamiophlomidis Rotatae total glycosides, and action time and Transdermal absorption also are better than Radix Lamiophlomidis Rotatae crude drug, Radix Lamiophlomidis Rotatae total glycosides.In addition, Aconitum sinomontanum Nakai total alkaloids and Radix Lamiophlomidis Rotatae flavone are united use, can reduce the dosage of Aconitum sinomontanum Nakai total alkaloids, and analgesic effect does not reduce, in the antiinflammatory test, Radix Lamiophlomidis Rotatae flavone and Aconitum sinomontanum Nakai total alkaloids logotype can strengthen independent medication effect, potentiation is also arranged, and the Radix Lamiophlomidis Rotatae flavone does not increase the toxicity of Aconitum sinomontanum Nakai total alkaloids simultaneously.Pharmaceutical composition of the present invention compared with prior art has following advantage:
1, the invention provides a kind of new Chinese medicine compound that is used for anti-inflammatory and antalgic, satisfied clinical needs; 2, the present invention has carried out pharmaceutical research to the interaction and the composition of prescription of Aconitum sinomontanum Nakai total alkaloids and Radix Lamiophlomidis Rotatae flavone, and the result shows pharmaceutical composition of the present invention and singly compares with Aconitum sinomontanum Nakai total alkaloids or Radix Lamiophlomidis Rotatae flavone, can significantly improve the pain threshold of mice; 3, pharmaceutical composition of the present invention is carried out the experiment of mice acetic acid twisting, the experiment of rat water-bath whipping, the experiment of mouse knoting oil ear swelling, rat carrageenan foot swelling experiment, thereby drawn the optimum formula of pharmaceutical composition of the present invention; 4, the Aconitum sinomontanum Nakai effective site Aconitum sinomontanum Nakai total alkaloids that is made by preparation method of the present invention is compared with the Aconitum sinomontanum Nakai crude drug, and its anti-inflammatory pain-stopping effect is better than the Aconitum sinomontanum Nakai crude drug; By the Radix Lamiophlomidis Rotatae effective site Radix Lamiophlomidis Rotatae flavone that preparation method of the present invention makes, to compare with Radix Lamiophlomidis Rotatae crude drug, Radix Lamiophlomidis Rotatae total glycosides, its anti-inflammatory pain-stopping effect is better than Radix Lamiophlomidis Rotatae crude drug, Radix Lamiophlomidis Rotatae total glycosides, is with a wide range of applications; 5, pharmaceutical composition of the present invention is processed into any preparation by Aconitum sinomontanum Nakai total alkaloids and Radix Lamiophlomidis Rotatae flavone, meets the needs of large-scale production; 6, the various dosage forms of pharmaceutical composition of the present invention can be by those skilled in the art, according to the conventional production method preparation of pharmaceutical field.
Following experimental example and embodiment are used to further specify but are not limited to the present invention.
Experimental example 1: pharmaceutical composition of the present invention and prior art (application number 200810180489.x and application number are 200810152101.5 two patented technology schemes) contrast experiment's data action time
1, laboratory sample:
Pharmaceutical composition of the present invention: embodiment 11 is prepared from the description according to the present invention;
Pharmaceutical composition a: be prepared from according to embodiment 11 in application number 200810152101.5 description;
Pharmaceutical composition b: be prepared from according to embodiment 10 in the application number 200810180489.x description.
2, experimental technique:
The present invention adopts the transdermal test method that exsomatizes, get white mice, etherization, carefully cut off the back fur with shears, put to death, peel off skin of back, remove subcutaneous fat and mucous tissue, after cleaning with physiological saline solution, place the joint portion of the vertical diffusion cell of Franz, dermis of skin is towards receiving liquid, accurately take by weighing the invention described above pharmaceutical composition, pharmaceutical composition 1 and pharmaceutical composition 2, evenly be applied to skin surface, reception tank adds 30ml receiver media (constant temperature (32 ± 1) ℃, mixing speed 100r/min).Respectively at 0,1,3,6,9,12,24,36h sampling 2ml (replenishing receiver media 2ml simultaneously) puts in the 25ml measuring bottle, is diluted to scale with methanol solution, as need testing solution, operate with method with blank sample, make blank solution, with high effective liquid chromatography for measuring luteolin accumulative total transit dose, experimental result is seen accompanying drawing 1.
By accompanying drawing 1 as can be seen, pharmaceutical composition of the present invention luteolin behind 36h sees through in addition, and pharmaceutical composition 2 and pharmaceutical composition 3 luteolin behind 24h just tends to be steady, and no longer increase, so the action time of pharmaceutical composition of the present invention is than pharmaceutical composition 2 and pharmaceutical composition 3 long action times.
Experimental example 2: pharmaceutical composition of the present invention and prior art (application number 200810180489.x and application number are 200810152101.5 two patented technology schemes) medicine transmitance contrast test
1, laboratory sample:
Pharmaceutical composition of the present invention: embodiment 11 is prepared from the description according to the present invention;
Pharmaceutical composition a: be prepared from according to embodiment 11 in application number 200810152101.5 description;
Pharmaceutical composition b: be prepared from according to embodiment 10 in the application number 200810180489.x description.
2, the preparation of isolated skin
The disconnected neck of nude mice is put to death, and strips skin of back and measures whole bark thickness, wraps standby then with preservative film.
3, transdermal experiment
Whole bark is placed the joint portion of the vertical diffusion cell of Franz, and (volume is 10ml, and effective area is 3.2cm
2), add pharmaceutical composition solution (5ml) in skin surface.Receive liquid and adopt 20% ethanol water.Respectively setting-up time (1,3,6,9,12,24h) sampling, the 400 μ l that at every turn take a sample replenish the release medium with volume.The accumulative total transit dose is calculated by following formula:
Q＝(C
n×V+∑C
n-1×0.15)/A
Q: the unit are accumulation sees through dose; V: it is long-pending to receive liquid; A: diffusion cell open area; The concentration of Cn n sub-sampling.Test triplicate at least at every turn.
4, the preparation of need testing solution
Get the about 2g of pharmaceutical composition of the present invention, the accurate title, decide, the accurate methanol hydrochloride solution 25ml that adds 2.5mol/L, claim to decide weight, reflux 60 minutes is put cold, claim again to decide weight, supply the weight that it subtracts mistake, shake up with methanol hydrochloride solution, filter, precision is measured subsequent filtrate 2ml, puts in the measuring bottle, be diluted to scale with methanol, shake up, the microporous filter membrane filtration with 0.45 μ m promptly gets need testing solution 1;
The about 2g of compositions a that gets it filled, accurate claim fixed, the accurate methanol hydrochloride solution 25ml that adds 2.5mol/L, claim to decide weight, reflux 60 minutes is put cold, claim again to decide weight, supply the weight that it subtracts mistake, shake up with methanol hydrochloride solution, filter, precision is measured subsequent filtrate 2ml, puts in the measuring bottle, be diluted to scale with methanol, shake up, the microporous filter membrane filtration with 0.45 μ m promptly gets need testing solution 2;
The about 2g of compositions b that gets it filled, accurate claim fixed, the accurate methanol hydrochloride solution 25ml that adds 2.5mol/L, claim to decide weight, reflux 60 minutes is put cold, claim again to decide weight, supply the weight that it subtracts mistake, shake up with methanol hydrochloride solution, filter, precision is measured subsequent filtrate 2ml, puts in the measuring bottle, be diluted to scale with methanol, shake up, the microporous filter membrane filtration with 0.45 μ m promptly gets need testing solution 3.
5, the preparation of reference substance solution
Precision takes by weighing through the exsiccant luteolin reference substance of phosphorus pentoxide 1.5mg, puts in the measuring bottle, adds methanol and makes the solution that every 1ml contains 0.15mg, promptly.
6, the chromatographic condition of marker ingredients luteolin and system suitability:
High performance liquid chromatography (HPLC) analytical method
With the octadecylsilane chemically bonded silica is filler (250mm * 4.6mm, 5 μ m);
With acetonitrile-oxolane-0.5% phosphoric acid (20: 6.4: 73.6) is mobile phase;
The detection wavelength is 350nm;
Column temperature: 40 ℃;
Flow velocity: 1ml/min;
Number of theoretical plate is pressed luteolin (C
15H
10O
6) peak calculates and should be not less than 3000.
7, experimental result, see accompanying drawing 2:
Show by Fig. 2, in 24 hours, luteolin is compared with luteolin in the pharmaceutical composition 3 with pharmaceutical composition 2 in the pharmaceutical composition of the present invention, the skin transit dose of pharmaceutical composition of the present invention is greater than the skin transit dose of pharmaceutical composition 2 and pharmaceutical composition 3, from the curve as can be seen, the skin transit dose of pharmaceutical composition of the present invention has improved more than 1 times than the skin transit dose of pharmaceutical composition 2 and pharmaceutical composition 3, and As time goes on, transit dose is still increasing.Experimental example 3: pharmaceutical composition of the present invention is to the influence of mice acetic acid twisting experiment
1 reagent, animal and instrument
(1) reagent
Aconitum sinomontanum Nakai total alkaloids (embodiment 4 is prepared from the description according to the present invention); Radix Lamiophlomidis Rotatae flavone (embodiment 4 is prepared from the description according to the present invention); Pharmaceutical composition 1 (being prepared from) according to embodiment 1 in the application number 200810180489.x description; Pharmaceutical composition 2 (being prepared from) according to embodiment 1 in application number 200810152101.5 description; Pharmaceutical composition of the present invention (embodiment 4 is prepared from the description according to the present invention); Diclofenac potassium tablet, Novartis Pharma AG, lot number: X0035; Acetic acid, analytical pure, Beijing Chemical Plant, lot number: 20070522.
(2) animal
KM kind mice, male, body weight (18-22) g, cleaning level provides production licence number by Lanzhou University medical college zoopery center: No. 20050007, SCXK (sweet), the quality certification number: No. 0000285.Laboratory temperature: (18-25) ℃, humidity: (40-60) %.
(3) instrument
The portable balance of YB1201 type electronics, Haikang, Shanghai Electronic Instruments Plant; SW8-2008 type stopwatch; Enumerator; 1ml syringe etc.
2 methods and result
(1) method
Get 80 of KM mices, male, be divided into 8 groups at random by body weight, every group 10, be respectively: the blank group, diclofenac potassium tablet group (10mg/kg), the Aconitum sinomontanum Nakai total alkaloids group (the 2g crude drug/kg), Radix Lamiophlomidis Rotatae flavone group (the 2g crude drug/kg), 1 group of pharmaceutical composition (Aconitum sinomontanum Nakai 1.2g+ Radix Lamiophlomidis Rotatae 0.8g/kg), 2 groups of pharmaceutical compositions (Aconitum sinomontanum Nakai total alkaloids 1.2g+ Radix Lamiophlomidis Rotatae total glycosides 0.8g crude drug/kg), pharmaceutical composition high dose group of the present invention (Aconitum sinomontanum Nakai total alkaloids 1.2g crude drug+Radix Lamiophlomidis Rotatae flavone 0.8g crude drug/kg), pharmaceutical composition low dose group of the present invention (Aconitum sinomontanum Nakai total alkaloids 0.3g crude drug+Radix Lamiophlomidis Rotatae flavone 0.2g crude drug/kg).Every day, gastric infusion was 1 time, and for three days on end, behind the last administration 1h, lumbar injection 0.6% acetum 0.2ml/ only respectively organizes mouse writhing number of times and matched group relatively in the 15min behind the record injection acetic acid, carry out statistical test.
(2) date processing
Adopt the SPSS13.0 statistical software to carry out date processing, organize an one factor analysis of variance.
(3) result
The result shows: compare with the blank group, diclofenac potassium tablet group, Aconitum sinomontanum Nakai total alkaloids group, Radix Lamiophlomidis Rotatae flavone group, 1 group of pharmaceutical composition, 2 groups of pharmaceutical compositions, pharmaceutical composition high and low dose group of the present invention all have analgesic activity (P＜0.05 or P＜0.01), and the big more analgesic effect trend of dosage is good more.Compare with the Aconitum sinomontanum Nakai total alkaloids group, pharmaceutical composition high and low dose group of the present invention has significantly or utmost point significant difference (P＜0.05 or P＜0.01).Compare with Radix Lamiophlomidis Rotatae flavone group, pharmaceutical composition high and low dose group of the present invention has utmost point significant difference (P＜0.01).Compare for 1 group with pharmaceutical composition, pharmaceutical composition high and low dose group of the present invention has utmost point significant difference (P＜0.01).Compare for 2 groups with pharmaceutical composition, pharmaceutical composition high and low dose group of the present invention has utmost point significant difference (P＜0.01).Prompting: pharmaceutical composition Dichlorodiphenyl Acetate of the present invention causes the pain mice stronger analgesic activity, and analgesic activity is better than Aconitum sinomontanum Nakai total alkaloids group, Radix Lamiophlomidis Rotatae flavone group, 1 group of pharmaceutical composition, 2 groups of pharmaceutical compositions.The results are shown in Table 1.
The influence of table 1 pair mice acetic acid twisting experiment
Annotate: compare with the blank group: * p＜0.05, * * p＜0.01; Compare with the Aconitum sinomontanum Nakai total alkaloids group:
▲P＜0.05,
▲ ▲P＜0.01; Compare with Radix Lamiophlomidis Rotatae flavone group:
△P＜0.05,
△ △P＜0.01; Compare for 1 group with pharmaceutical composition,
P＜0.05,
P＜0.01; Compare for 2 groups with pharmaceutical composition,
##P＜0.01.
Experimental example 4: pharmaceutical composition of the present invention is to the influence of rat water-bath whipping experiment
1 reagent, animal and instrument
(1) reagent
Aconitum sinomontanum Nakai total alkaloids (embodiment 9 is prepared from the description according to the present invention); Radix Lamiophlomidis Rotatae flavone (embodiment 9 is prepared from the description according to the present invention); Pharmaceutical composition 1 (being prepared from) according to embodiment 3 in the application number 200810180489.x description; Pharmaceutical composition 2 (being prepared from) according to embodiment 9 in application number 200810152101.5 description; Pharmaceutical composition of the present invention (embodiment 9 is prepared from the description according to the present invention); Indometacin, Linfen, Shanxi Yun Peng pharmaceutcal corporation, Ltd produces, lot number: 20080101.
(2) animal
The Wistar rat, male and female half and half, body weight (180-220) g, cleaning level provides production licence number by Lanzhou University medical college zoopery center: No. 20050007, SCXK (sweet), the quality certification number: No. 0000285.Laboratory temperature: (18-25) ℃, humidity: (40-60) %.
(3) instrument
The super water-bath of HH-501, Changzhou Guohua Electric Appliance Co., Ltd.; SW8-2008 type stopwatch.
2 methods and result
(1) method
Get 80 of Wistar rats, be divided into 8 groups at random by body weight, be respectively: the blank group, indometacin group (20mg/kg), the Aconitum sinomontanum Nakai total alkaloids group (the 1g crude drug/kg), Radix Lamiophlomidis Rotatae flavone group (the 1g crude drug/kg), 1 group of pharmaceutical composition (Aconitum sinomontanum Nakai 0.6g+ Radix Lamiophlomidis Rotatae 0.4g/kg), 2 groups of pharmaceutical compositions (Aconitum sinomontanum Nakai total alkaloids 0.6g+ Radix Lamiophlomidis Rotatae total glycosides 0.4g crude drug/kg), pharmaceutical composition high dose group of the present invention (Aconitum sinomontanum Nakai total alkaloids 0.6g crude drug+Radix Lamiophlomidis Rotatae flavone 0.4g crude drug/kg), pharmaceutical composition low dose group of the present invention (Aconitum sinomontanum Nakai total alkaloids 0.15g crude drug+Radix Lamiophlomidis Rotatae flavone 0.1g crude drug/kg).1 gastric infusion, 0.5h, 1h, 2h, 3h survey the incubation period of rat whipping reaction respectively in (55 ± 0.5) ℃ water bath with thermostatic control before the administration and after the administration, as threshold of pain index.
(2) date processing
Adopt the SPSS13.0 statistical software to carry out date processing, organize an one factor analysis of variance.
(3) result
The result shows: with the blank group relatively, each group there are no significant difference (p＞0.05) before the administration.0.5h after the administration compares with the blank group, and pharmaceutical composition high dose group of the present invention has significant difference (p＜0.05).Compare with the Aconitum sinomontanum Nakai total alkaloids group, pharmaceutical composition high dose group of the present invention has utmost point significant difference (p＜0.01).Compare with Radix Lamiophlomidis Rotatae flavone group, pharmaceutical composition high dose group of the present invention has significant difference (p＜0.05).Compare for 1 group with pharmaceutical composition, pharmaceutical composition high dose group of the present invention has utmost point significant difference (p＜0.01).Compare for 2 groups with pharmaceutical composition, pharmaceutical composition high dose group of the present invention has utmost point significant difference (p＜0.01).1h after the administration, compare with the blank group, indometacin group, pharmaceutical composition high and low dose group of the present invention have utmost point significant difference (p＜0.01), and Aconitum sinomontanum Nakai total alkaloids group, Radix Lamiophlomidis Rotatae flavone group, 1 group of pharmaceutical composition, pharmaceutical composition have significant difference (p＜0.05) for 2 groups.2h after the administration, compare with the blank group, 1 group of pharmaceutical composition, pharmaceutical composition low dose group of the present invention have utmost point significant difference (p＜0.01), and Radix Lamiophlomidis Rotatae flavone group, 2 groups of pharmaceutical compositions, pharmaceutical composition high dose group of the present invention have significant difference (p＜0.05).3h after the administration compares with the blank group, and pharmaceutical composition high and low dose group of the present invention has utmost point significant difference (p＜0.01).Compare with the Aconitum sinomontanum Nakai total alkaloids group, pharmaceutical composition high dose group of the present invention has significant difference (p＜0.05).Compare for 1 group with pharmaceutical composition, pharmaceutical composition high and low dose group of the present invention has significant difference (p＜0.05).Compare for 2 groups with pharmaceutical composition, pharmaceutical composition high and low dose group of the present invention has significant difference (p＜0.05).Prompting: pharmaceutical composition analgesic activity of the present invention is remarkable, can prolong the threshold of pain, and onset time is fast, the longer duration characteristics, is better than Aconitum sinomontanum Nakai total alkaloids group, Radix Lamiophlomidis Rotatae flavone group, 1 group of pharmaceutical composition, 2 groups of pharmaceutical compositions.The results are shown in Table 2.
The influence of table 2 pair rat water-bath whipping experiment (
N=10)
Annotate: compare with the blank group: * p＜0.05, * * p＜0.01; Compare with the Aconitum sinomontanum Nakai total alkaloids group:
▲P＜0.05,
▲ ▲P＜0.01; Compare with Radix Lamiophlomidis Rotatae flavone group:
△P＜0.05; Compare for 1 group with pharmaceutical composition,
P＜0.05,
P＜0.01; Compare for 2 groups with pharmaceutical composition,
#P＜0.05,
##P＜0.01.
Experimental example 5: pharmaceutical composition of the present invention is to the influence of mouse knoting oil ear swelling experiment
1 reagent, animal and instrument
(1) reagent
Aconitum sinomontanum Nakai total alkaloids (embodiment 11 is prepared from the description according to the present invention); Radix Lamiophlomidis Rotatae flavone (embodiment 11 is prepared from the description according to the present invention); Pharmaceutical composition 1 (being prepared from) according to embodiment 10 in the application number 200810180489.x description; Pharmaceutical composition 2 (being prepared from) according to embodiment 11 in application number 200810152101.5 description; Pharmaceutical composition of the present invention (embodiment 11 is prepared from the description according to the present invention); Indometacin, Linfen, Shanxi Yun Peng pharmaceutcal corporation, Ltd produces, lot number: 20080101; Oleum Tiglii, this research department provides, lot number: 090821.
(2) animal
The KM mice, male, body weight (18-22) g, cleaning level provides production licence number by Lanzhou University medical college zoopery center: No. 20050007, SCXK (sweet), the quality certification number: No. 0000285.Laboratory temperature: (18-25) ℃, humidity: (40-60) %.
(3) instrument
Card punch; Tweezers; Analytical balance, Sai Duolisi scientific instrument (Beijing) company limited.
2 methods and result
(1) method
Get 80 of male mices, be divided into 8 groups at random by body weight, every group 10, be respectively: the blank group, indometacin group (5mg/kg), the Aconitum sinomontanum Nakai total alkaloids group (the 2g crude drug/kg), Radix Lamiophlomidis Rotatae flavone group (the 2g crude drug/kg), 1 group of pharmaceutical composition (Aconitum sinomontanum Nakai 1.2g+ Radix Lamiophlomidis Rotatae 0.8g/kg), 2 groups of pharmaceutical compositions (Aconitum sinomontanum Nakai total alkaloids 1.2g+ Radix Lamiophlomidis Rotatae total glycosides 0.8g crude drug/kg), pharmaceutical composition high dose group of the present invention (Aconitum sinomontanum Nakai total alkaloids 1.2g crude drug+Radix Lamiophlomidis Rotatae flavone 0.8g crude drug/kg), pharmaceutical composition low dose group of the present invention (Aconitum sinomontanum Nakai total alkaloids 0.3g crude drug+Radix Lamiophlomidis Rotatae flavone 0.2g crude drug/kg).Every day, gastric infusion was 1 time, and continuous 5 days, the last administration was after 30 minutes, with warm water with the auris dextra wiped clean, drip Oleum Tiglii 0.05ml and cause inflammation, behind the 2h, animal is put to death in the cervical vertebra dislocation, cut left and right sides auricle, sweep away auricle with the card punch of diameter 9mm, weigh with analytical balance at the ears corresponding position.With two auricle weight differences is swelling degree index, and obtains inhibitory rate of intumesce.
(2) date processing
Adopt the SPSS13.0 statistical software to carry out date processing, organize an one factor analysis of variance.
(3) result
The result shows: indometacin group, Aconitum sinomontanum Nakai total alkaloids group, Radix Lamiophlomidis Rotatae flavone group, 1 group of pharmaceutical composition, 2 groups of pharmaceutical compositions, pharmaceutical composition high and low dose group of the present invention all can suppress Oleum Tiglii and cause mice ear.Compare with the blank group, indometacin group, pharmaceutical composition high and low dose group of the present invention have utmost point significant difference (P＜0.01), and Aconitum sinomontanum Nakai total alkaloids group, Radix Lamiophlomidis Rotatae flavone group, 1 group of pharmaceutical composition, pharmaceutical composition have significant difference (p＜0.05) for 2 groups.Compare with the Aconitum sinomontanum Nakai total alkaloids group, pharmaceutical composition high dose group of the present invention has significant difference (p＜0.05).Compare with Radix Lamiophlomidis Rotatae flavone group, pharmaceutical composition high dose group of the present invention has significant difference (p＜0.05).Compare for 1 group with pharmaceutical composition, pharmaceutical composition high dose group of the present invention has utmost point significant difference (p＜0.01), and pharmaceutical composition low dose group of the present invention has significant difference (p＜0.05).Compare for 2 groups with pharmaceutical composition, pharmaceutical composition high dose group of the present invention has utmost point significant difference (p＜0.01), and pharmaceutical composition low dose group of the present invention has significant difference (p＜0.05).Pharmaceutical composition high and low dose suppression ratio of the present invention is respectively 45.9% and 37.8%.Prompting: pharmaceutical composition of the present invention causes inflammation to Oleum Tiglii all stronger inhibitory action, and antiinflammatory action is better than Aconitum sinomontanum Nakai total alkaloids group, Radix Lamiophlomidis Rotatae flavone group, 1 group of pharmaceutical composition, 2 groups of pharmaceutical compositions.The results are shown in Table 3.
The influence of table 3 pair mouse knoting oil ear swelling experiment
Annotate: compare * p＜0.05, * * p＜0.01 with the blank group; Compare with the Aconitum sinomontanum Nakai total alkaloids group,
▲P＜0.05; Compare with Radix Lamiophlomidis Rotatae flavone group,
△P＜0.05; Compare for 1 group with pharmaceutical composition,
P＜0.05,
P＜0.01; Compare with pharmaceutical composition 2,
#P＜0.05,
##P＜0.01.
Experimental example 6: pharmaceutical composition of the present invention is to the influence of rat carrageenan foot swelling experiment
1 reagent, animal and instrument
(1) reagent
Aconitum sinomontanum Nakai total alkaloids (embodiment 12 is prepared from the description according to the present invention); Radix Lamiophlomidis Rotatae flavone (embodiment 12 is prepared from the description according to the present invention); Pharmaceutical composition 1 (being prepared from) according to embodiment 11 in the application number 200810180489.x description; Pharmaceutical composition 2 (being prepared from) according to embodiment 5 in application number 200810152101.5 description; Pharmaceutical composition of the present invention (embodiment 12 is prepared from the description according to the present invention); Indometacin, Linfen, Shanxi Yun Peng pharmaceutcal corporation, Ltd produces, lot number: 20080101; Carrageenin, SIGMA company product, lot number G1023-25G.
(2) animal
The Wistar rat, male and female half and half, body weight (180-220) g provides production licence number by Lanzhou University medical college zoopery center: No. 20050007, SCXK (sweet), the quality certification number: No. 0000285.Laboratory temperature: (18-25) ℃, humidity: (40-60) %.
(3) instrument
The BS110S electronic balance, Beijing Sai Duolisi company; The dynamic projector of rainbow, Shenzhen Australian telecommunications satellite audio-visual equipment company limited; 5ml syringe and filling stomach syringe needle etc.
2 methods and result
(1) method
Get 80 of Wistar rats, be divided into 8 groups at random by body weight, be respectively: the blank group, indometacin group (20mg/kg), the Aconitum sinomontanum Nakai total alkaloids group (the 1g crude drug/kg), Radix Lamiophlomidis Rotatae flavone group (the 1g crude drug/kg), 1 group of pharmaceutical composition (Aconitum sinomontanum Nakai 0.6g+ Radix Lamiophlomidis Rotatae 0.4g/kg), 2 groups of pharmaceutical compositions (Aconitum sinomontanum Nakai total alkaloids 0.6g+ Radix Lamiophlomidis Rotatae total glycosides 0.4g crude drug/kg), pharmaceutical composition high dose group of the present invention (Aconitum sinomontanum Nakai total alkaloids 0.6g crude drug+Radix Lamiophlomidis Rotatae flavone 0.4g crude drug/kg), pharmaceutical composition low dose group of the present invention (Aconitum sinomontanum Nakai total alkaloids 0.15g crude drug+Radix Lamiophlomidis Rotatae flavone 0.1g crude drug/kg).Measure 0.5cm place diameter under every hot-tempered joint of rat right hind leg with projector (amplifying 6 times) earlier, make normal value.30min behind the gastric infusion, cause inflammation at every the right back sufficient pad sc of portion 1% lrish moss mucilage 0.05ml of rat, survey rat and cause diameter under the hot-tempered joint of scorching limb causing scorching back 0.5,1,2,3 and 4h reuse projector respectively, so that the difference before and after scorching is made the bullate degree of rat foot.
(2) date processing
Adopt the SPSS13.0 statistical software to carry out date processing, organize an one factor analysis of variance.
(3) result
The result shows: prednisolone acetate group, Aconitum sinomontanum Nakai total alkaloids group, Radix Lamiophlomidis Rotatae flavone group, 1 group of pharmaceutical composition, 2 groups of pharmaceutical compositions, pharmaceutical composition high and low dose group of the present invention all have remarkable inhibition carrageenin to cause rat paw edema.Compare with the blank group, each organizes normal value there was no significant difference (p＞0.05).0.5h after the administration compares with the blank group, and each group all has significantly or utmost point significant difference (p＜0.05 or p＜0.01).Compare with the Aconitum sinomontanum Nakai total alkaloids group, pharmaceutical composition high and low dose group of the present invention has utmost point significant difference (p＜0.01).Compare with Radix Lamiophlomidis Rotatae flavone group, pharmaceutical composition high and low dose group of the present invention has utmost point significant difference (p＜0.01), and the indometacin group has significant difference (p＜0.05).Compare for 1 group with pharmaceutical composition, pharmaceutical composition high and low dose group of the present invention has significantly or utmost point significant difference (p＜0.05 or p＜0.01).Compare for 2 groups with pharmaceutical composition, pharmaceutical composition high and low dose group of the present invention has utmost point significant difference (p＜0.01).1h after the administration compares with the blank group, and each group all has utmost point significant difference (p＜0.01).Compare with the Aconitum sinomontanum Nakai total alkaloids group, pharmaceutical composition high and low dose group of the present invention has utmost point significant difference (p＜0.01).Compare with Radix Lamiophlomidis Rotatae flavone group, pharmaceutical composition high and low dose group of the present invention has significant difference (p＜0.05).Compare for 1 group with pharmaceutical composition, pharmaceutical composition high and low dose group of the present invention has significant difference (p＜0.05).Compare for 2 groups with pharmaceutical composition, pharmaceutical composition high and low dose group of the present invention has significant difference (p＜0.05).2h after the administration compares with the blank group, and each group all has significantly or utmost point significant difference (p＜0.05 or p＜0.01).Compare with Radix Lamiophlomidis Rotatae flavone group, pharmaceutical composition high and low dose group of the present invention has utmost point significant difference (p＜0.01).Compare for 1 group with pharmaceutical composition, pharmaceutical composition high and low dose group of the present invention has significant difference (p＜0.05).Compare for 2 groups with pharmaceutical composition, pharmaceutical composition high and low dose group of the present invention has utmost point significant difference (p＜0.01).3h after the administration compares with the blank group, and 1 group of pharmaceutical composition, pharmaceutical composition high dose group of the present invention have significantly or utmost point significant difference (p＜0.05 or p＜0.01).Compare with Radix Lamiophlomidis Rotatae flavone group, pharmaceutical composition high and low dose group of the present invention has significant difference (p＜0.05).4h after the administration compares with the blank group, and pharmaceutical composition high dose group of the present invention has significant difference (p＜0.05).Compare with the Aconitum sinomontanum Nakai total alkaloids group, pharmaceutical composition high dose group of the present invention has significant difference (p＜0.05).Prompting: pharmaceutical composition antiinflammatory action of the present invention is strong, and onset time is fast, and longer duration is better than Aconitum sinomontanum Nakai total alkaloids group, Radix Lamiophlomidis Rotatae flavone group, 1 group of pharmaceutical composition, 2 groups of pharmaceutical compositions.The results are shown in Table 4.
The influence of table 4 pair rat carrageenan foot swelling experiment (
N=10)
Annotate: compare with the blank group: * p＜0.05, * * p＜0.01; Compare with the Aconitum sinomontanum Nakai total alkaloids group:
▲P＜0.05,
▲ ▲P＜0.01; Compare with Radix Lamiophlomidis Rotatae flavone group:
△P＜0.05,
△ △P＜0.01; Compare for 1 group with pharmaceutical composition,
P＜0.05,
P＜0.01; Compare for 2 groups with pharmaceutical composition,
#P＜0.05,
##P＜0.01.
Description of drawings
Fig. 1: pharmaceutical composition of the present invention and prior art comparison diagram action time;
Fig. 2: pharmaceutical composition of the present invention and the contrast of prior art medicine transmitance.
Following embodiment all can realize the described effect of above-mentioned experimental example.
The specific embodiment
Embodiment 1: pharmaceutical composition tablet of the present invention
Aconitum sinomontanum Nakai total alkaloids 15g Radix Lamiophlomidis Rotatae flavone 95g;
A. the preparation method of Aconitum sinomontanum Nakai total alkaloids:
Get dry Aconitum sinomontanum Nakai medical material, pulverize, with 75% ethanol extraction of 10 times of weight 2 times, the each extraction 2 hours, collection, merge extractive liquid,, and reclaim ethanol, use the dissolving with hydrochloric acid ethanol extraction, after regulating PH to 2, the hydro-oxidation sodium solution is used chloroform extraction after regulating PH to 10, merge chloroform soln, reclaim chloroform, drying gets Aconitum sinomontanum Nakai total alkaloids;
B. the preparation method of Radix Lamiophlomidis Rotatae flavone:
The alcoholic solution of Radix Lamiophlomidis Rotatae medical material with 70% the aqua calcis preparation of 10 times of weight extracted 2 times, the each extraction 2 hours, collect, merge extractive liquid,, filter, filtrate under 70 ℃ of temperature, be condensed into the concentrated solution that relative density is 1.15-1.25 after, with 60% alcoholic solution heating for dissolving, cooling removes by filter alcohol insoluble matter impurity, and filtrate adds the water heating for dissolving after removing ethanol, put cold, with 3 weeding of grease soluble components of petroleum ether extraction, the water intaking layer leaves standstill 12h by cation exchange resin, colourless with 15% ethanol elution to eluent, reuse 60% ethanol is resolved, absorption, washing, the flow velocity of resolving be 5 times of bed volumes/hour, collect alcoholic solution, reclaim ethanol to there not being the alcohol flavor, drying is pulverized, and gets the Radix Lamiophlomidis Rotatae flavone;
C. above Radix Lamiophlomidis Rotatae flavone is mixed with Aconitum sinomontanum Nakai total alkaloids, add conventional adjuvant,, make clinical or pharmaceutically acceptable tablet according to common process.
Embodiment 2: medicament composition capsule agent of the present invention
Aconitum sinomontanum Nakai total alkaloids 95g Radix Lamiophlomidis Rotatae flavone 15g;
A. the preparation method of Aconitum sinomontanum Nakai total alkaloids:
Get dry Aconitum sinomontanum Nakai medical material, pulverize, with 65% ethanol extraction of 20 times of weight 1 time, the each extraction 4.5 hours, collection, merge extractive liquid,, and reclaim ethanol, use the dissolving with hydrochloric acid ethanol extraction, after regulating PH to 1, after adding sodium bicarbonate solution and regulating PH to 11, use chloroform extraction, merge chloroform soln, reclaim chloroform, drying gets Aconitum sinomontanum Nakai total alkaloids;
B. the preparation method of Radix Lamiophlomidis Rotatae flavone:
The alcoholic solution of Radix Lamiophlomidis Rotatae medical material with 50% the sodium carbonate liquor preparation of 20 times of weight extracted 3 times, the each extraction 1 hour, collect, merge extractive liquid,, filter, filtrate under 80 ℃ of temperature, be condensed into the concentrated solution that relative density is 1.05-1.15 after, with 75% alcoholic solution heating for dissolving, cooling removes by filter alcohol insoluble matter impurity, and filtrate adds the water heating for dissolving after removing ethanol, put cold, with 2 weeding of grease soluble components of petroleum ether extraction, the water intaking layer leaves standstill 10h by the HPD-300 macroporous adsorbent resin, colourless with 30% ethanol elution to eluent, reuse 70% ethanol is resolved, absorption, washing, the flow velocity of resolving be 3 times of bed volumes/hour, collect alcoholic solution, reclaim ethanol to there not being the alcohol flavor, drying is pulverized, and gets the Radix Lamiophlomidis Rotatae flavone;
C. above Radix Lamiophlomidis Rotatae flavone is mixed with Aconitum sinomontanum Nakai total alkaloids, add conventional adjuvant,, make clinical or pharmaceutically acceptable capsule according to common process.
Embodiment 3: medicinal composition powders of the present invention
Aconitum sinomontanum Nakai total alkaloids 50g Radix Lamiophlomidis Rotatae flavone 50g;
A. the preparation method of Aconitum sinomontanum Nakai total alkaloids:
Get dry Aconitum sinomontanum Nakai medical material, pulverize, with 95% ethanol extraction of 5 times of weight 3 times, the each extraction 1 hour, collection, merge extractive liquid,, and reclaim ethanol, use the dissolving with hydrochloric acid ethanol extraction, after regulating PH to 3, after adding ammonia and regulating PH to 8, use chloroform extraction, merge chloroform soln, reclaim chloroform, drying gets Aconitum sinomontanum Nakai total alkaloids;
B. the preparation method of Radix Lamiophlomidis Rotatae flavone:
The alcoholic solution of Radix Lamiophlomidis Rotatae medical material with 90% the aqua calcis preparation of 5 times of weight extracted 4 times, the each extraction 1 hour, collect, merge extractive liquid,, filter, filtrate under 60 ℃ of temperature, be condensed into the concentrated solution that relative density is 1.25-1.35 after, with 50% alcoholic solution heating for dissolving, cooling removes by filter alcohol insoluble matter impurity, and filtrate adds the water heating for dissolving after removing ethanol, put cold, with 4 weeding of grease soluble components of petroleum ether extraction, the water intaking layer leaves standstill 14h by the HPD-100 macroporous adsorbent resin, colourless with 20% ethanol elution to eluent, reuse 45% ethanol is resolved, absorption, washing, the flow velocity of resolving be 9 times of bed volumes/hour, collect alcoholic solution, reclaim ethanol to there not being the alcohol flavor, drying is pulverized, and gets the Radix Lamiophlomidis Rotatae flavone;
C. above Radix Lamiophlomidis Rotatae flavone is mixed with Aconitum sinomontanum Nakai total alkaloids, add conventional adjuvant,, make clinical or pharmaceutically acceptable powder according to common process.
Embodiment 4: medicinal composition soft capsule agent of the present invention
Aconitum sinomontanum Nakai total alkaloids 20g Radix Lamiophlomidis Rotatae flavone 80g;
A. the preparation method of Aconitum sinomontanum Nakai total alkaloids:
Get dry Aconitum sinomontanum Nakai medical material, pulverize, with 75% ethanol extraction of 10 times of weight 2 times, the each extraction 2 hours, collection, merge extractive liquid,, and reclaim ethanol, use the sulfuric acid dissolution ethanol extraction, after regulating PH to 2, the hydro-oxidation sodium solution is used chloroform extraction after regulating PH to 10, merge chloroform soln, reclaim chloroform, drying gets Aconitum sinomontanum Nakai total alkaloids;
B. the preparation method of Radix Lamiophlomidis Rotatae flavone:
The alcoholic solution of Radix Lamiophlomidis Rotatae medical material with 70% the sodium carbonate liquor preparation of 10 times of weight extracted 2 times, the each extraction 2 hours, collect, merge extractive liquid,, filter, filtrate under 70 ℃ of temperature, be condensed into the concentrated solution that relative density is 1.15-1.25 after, with 60% alcoholic solution heating for dissolving, cooling removes by filter alcohol insoluble matter impurity, and filtrate adds the water heating for dissolving after removing ethanol, put cold, with 3 weeding of grease soluble components of petroleum ether extraction, the water intaking layer leaves standstill 12h by the HPD-600 macroporous adsorbent resin, colourless with 15% ethanol elution to eluent, reuse 60% ethanol is resolved, absorption, washing, the flow velocity of resolving be 5 times of bed volumes/hour, collect alcoholic solution, reclaim ethanol to there not being the alcohol flavor, drying is pulverized, and gets the Radix Lamiophlomidis Rotatae flavone;
C. above Radix Lamiophlomidis Rotatae flavone is mixed with Aconitum sinomontanum Nakai total alkaloids, add conventional adjuvant,, make clinical or pharmaceutically acceptable soft capsule according to common process.
Embodiment 5: medicament composition dropping pills of the present invention
Aconitum sinomontanum Nakai total alkaloids 80g Radix Lamiophlomidis Rotatae flavone 20g;
A. the preparation method of Aconitum sinomontanum Nakai total alkaloids:
Get dry Aconitum sinomontanum Nakai medical material, pulverize, with 65% ethanol extraction of 20 times of weight 1 time, the each extraction 4.5 hours, collection, merge extractive liquid,, and reclaim ethanol, use the sulfuric acid dissolution ethanol extraction, after regulating PH to 1, after adding sodium bicarbonate solution and regulating PH to 11, use chloroform extraction, merge chloroform soln, reclaim chloroform, drying gets Aconitum sinomontanum Nakai total alkaloids;
B. the preparation method of Radix Lamiophlomidis Rotatae flavone:
The alcoholic solution of Radix Lamiophlomidis Rotatae medical material with 50% the aqua calcis preparation of 20 times of weight extracted 3 times, the each extraction 1 hour, collect, merge extractive liquid,, filter, filtrate under 80 ℃ of temperature, be condensed into the concentrated solution that relative density is 1.05-1.15 after, with 75% alcoholic solution heating for dissolving, cooling removes by filter alcohol insoluble matter impurity, and filtrate adds the water heating for dissolving after removing ethanol, put cold, with 2 weeding of grease soluble components of petroleum ether extraction, the water intaking layer leaves standstill 10h by cation exchange resin, colourless with 30% ethanol elution to eluent, reuse 70% ethanol is resolved, absorption, washing, the flow velocity of resolving be 3 times of bed volumes/hour, collect alcoholic solution, reclaim ethanol to there not being the alcohol flavor, drying is pulverized, and gets the Radix Lamiophlomidis Rotatae flavone;
C. above Radix Lamiophlomidis Rotatae flavone is mixed with Aconitum sinomontanum Nakai total alkaloids, add conventional adjuvant,, make clinical or pharmaceutically acceptable drop pill according to common process.
Embodiment 6: pharmaceutical composition honeyed pill of the present invention
Aconitum sinomontanum Nakai total alkaloids 30g Radix Lamiophlomidis Rotatae flavone 70g;
A. the preparation method of Aconitum sinomontanum Nakai total alkaloids:
Get dry Aconitum sinomontanum Nakai medical material, pulverize, with 95% ethanol extraction of 5 times of weight 3 times, the each extraction 1 hour, collection, merge extractive liquid,, and reclaim ethanol, use the sulfuric acid dissolution ethanol extraction, after regulating PH to 3, after adding ammonia and regulating PH to 8, use chloroform extraction, merge chloroform soln, reclaim chloroform, drying gets Aconitum sinomontanum Nakai total alkaloids;
B. the preparation method of Radix Lamiophlomidis Rotatae flavone:
The alcoholic solution of Radix Lamiophlomidis Rotatae medical material with 90% the sodium carbonate liquor preparation of 5 times of weight extracted 4 times, the each extraction 1 hour, collect, merge extractive liquid,, filter, filtrate under 60 ℃ of temperature, be condensed into the concentrated solution that relative density is 1.25-1.35 after, with 50% alcoholic solution heating for dissolving, cooling removes by filter alcohol insoluble matter impurity, and filtrate adds the water heating for dissolving after removing ethanol, put cold, with 4 weeding of grease soluble components of petroleum ether extraction, the water intaking layer leaves standstill 14h by cation exchange resin, colourless with 20% ethanol elution to eluent, reuse 45% ethanol is resolved, absorption, washing, the flow velocity of resolving be 9 times of bed volumes/hour, collect alcoholic solution, reclaim ethanol to there not being the alcohol flavor, drying is pulverized, and gets the Radix Lamiophlomidis Rotatae flavone;
C. above Radix Lamiophlomidis Rotatae flavone is mixed with Aconitum sinomontanum Nakai total alkaloids, add conventional adjuvant,, make clinical or pharmaceutically acceptable honeyed pill according to common process.
Embodiment 7: pharmaceutical composition pill of the present invention
Aconitum sinomontanum Nakai total alkaloids 70g Radix Lamiophlomidis Rotatae flavone 30g.
A. the preparation method of Aconitum sinomontanum Nakai total alkaloids:
Get dry Aconitum sinomontanum Nakai medical material, pulverize, with 75% ethanol extraction of 10 times of weight 2 times, the each extraction 2 hours, collection, merge extractive liquid,, and reclaim ethanol, use the acetate dissolution ethanol extraction, after regulating PH to 2, the hydro-oxidation sodium solution is used chloroform extraction after regulating PH to 10, merge chloroform soln, reclaim chloroform, drying gets Aconitum sinomontanum Nakai total alkaloids;
B. the preparation method of Radix Lamiophlomidis Rotatae flavone:
The alcoholic solution of Radix Lamiophlomidis Rotatae medical material with 70% the aqua calcis preparation of 10 times of weight extracted 2 times, the each extraction 2 hours, collect, merge extractive liquid,, filter, filtrate under 70 ℃ of temperature, be condensed into the concentrated solution that relative density is 1.15-1.25 after, with 60% alcoholic solution heating for dissolving, cooling removes by filter alcohol insoluble matter impurity, and filtrate adds the water heating for dissolving after removing ethanol, put cold, with 3 weeding of grease soluble components of petroleum ether extraction, the water intaking layer leaves standstill 12h by the HPD-300 macroporous adsorbent resin, colourless with 15% ethanol elution to eluent, reuse 60% ethanol is resolved, absorption, washing, the flow velocity of resolving be 5 times of bed volumes/hour, collect alcoholic solution, reclaim ethanol to there not being the alcohol flavor, drying is pulverized, and gets the Radix Lamiophlomidis Rotatae flavone;
C. above Radix Lamiophlomidis Rotatae flavone is mixed with Aconitum sinomontanum Nakai total alkaloids, add conventional adjuvant,, make clinical or pharmaceutically acceptable pill according to common process.
Embodiment 8: medicament composition granule agent of the present invention
Aconitum sinomontanum Nakai total alkaloids 60g Radix Lamiophlomidis Rotatae flavone 40g;
A. the preparation method of Aconitum sinomontanum Nakai total alkaloids:
Get dry Aconitum sinomontanum Nakai medical material, pulverize, with 65% ethanol extraction of 20 times of weight 1 time, the each extraction 4.5 hours, collection, merge extractive liquid,, and reclaim ethanol, use the acetate dissolution ethanol extraction, after regulating PH to 1, after adding sodium bicarbonate solution and regulating PH to 11, use chloroform extraction, merge chloroform soln, reclaim chloroform, drying gets Aconitum sinomontanum Nakai total alkaloids;
B. the preparation method of Radix Lamiophlomidis Rotatae flavone:
The alcoholic solution of Radix Lamiophlomidis Rotatae medical material with 50% the sodium carbonate liquor preparation of 20 times of weight extracted 3 times, the each extraction 1 hour, collect, merge extractive liquid,, filter, filtrate under 80 ℃ of temperature, be condensed into the concentrated solution that relative density is 1.05-1.15 after, with 75% alcoholic solution heating for dissolving, cooling removes by filter alcohol insoluble matter impurity, and filtrate adds the water heating for dissolving after removing ethanol, put cold, with 2 weeding of grease soluble components of petroleum ether extraction, the water intaking layer leaves standstill 10h by the HPD-100 macroporous adsorbent resin, colourless with 30% ethanol elution to eluent, reuse 70% ethanol is resolved, absorption, washing, the flow velocity of resolving be 3 times of bed volumes/hour, collect alcoholic solution, reclaim ethanol to there not being the alcohol flavor, drying is pulverized, and gets the Radix Lamiophlomidis Rotatae flavone;
C. above Radix Lamiophlomidis Rotatae flavone is mixed with Aconitum sinomontanum Nakai total alkaloids, add conventional adjuvant,, make clinical or pharmaceutically acceptable granule according to common process.
Embodiment 9: pharmaceutical composition soft extract with bee honey of the present invention agent
Aconitum sinomontanum Nakai total alkaloids 40g Radix Lamiophlomidis Rotatae flavone 60g;
Preparation of drug combination method of the present invention preferably includes following steps:
A. the preparation method of Aconitum sinomontanum Nakai total alkaloids:
Get dry Aconitum sinomontanum Nakai medical material, pulverize, with 95% ethanol extraction of 5 times of weight 3 times, the each extraction 1 hour, collection, merge extractive liquid,, and reclaim ethanol, use the acetate dissolution ethanol extraction, after regulating PH to 3, after adding ammonia and regulating PH to 8, use chloroform extraction, merge chloroform soln, reclaim chloroform, drying gets Aconitum sinomontanum Nakai total alkaloids;
B. the preparation method of Radix Lamiophlomidis Rotatae flavone:
The alcoholic solution of Radix Lamiophlomidis Rotatae medical material with 90% the aqua calcis preparation of 5 times of weight extracted 4 times, the each extraction 1 hour, collect, merge extractive liquid,, filter, filtrate under 60 ℃ of temperature, be condensed into the concentrated solution that relative density is 1.25-1.35 after, with 50% alcoholic solution heating for dissolving, cooling removes by filter alcohol insoluble matter impurity, and filtrate adds the water heating for dissolving after removing ethanol, put cold, with 4 weeding of grease soluble components of petroleum ether extraction, the water intaking layer leaves standstill 14h by the HPD-450 macroporous adsorbent resin, colourless with 20% ethanol elution to eluent, reuse 45% ethanol is resolved, absorption, washing, the flow velocity of resolving be 9 times of bed volumes/hour, collect alcoholic solution, reclaim ethanol to there not being the alcohol flavor, drying is pulverized, and gets the Radix Lamiophlomidis Rotatae flavone;
C. above Radix Lamiophlomidis Rotatae flavone is mixed with Aconitum sinomontanum Nakai total alkaloids, add conventional adjuvant,, make clinical or pharmaceutically acceptable soft extract with bee honey agent according to common process.
Embodiment 10: pharmaceutical composition slow releasing preparation of the present invention
Aconitum sinomontanum Nakai total alkaloids 10g Radix Lamiophlomidis Rotatae flavone 10g;
A. the preparation method of Aconitum sinomontanum Nakai total alkaloids:
Get dry Aconitum sinomontanum Nakai medical material, pulverize, with 75% ethanol extraction of 10 times of weight 2 times, the each extraction 2 hours, collection, merge extractive liquid,, and reclaim ethanol, use the dissolving with hydrochloric acid ethanol extraction, after regulating PH to 2, the hydro-oxidation sodium solution is used chloroform extraction after regulating PH to 10, merge chloroform soln, reclaim chloroform, drying gets Aconitum sinomontanum Nakai total alkaloids;
B. the preparation method of Radix Lamiophlomidis Rotatae flavone:
The alcoholic solution of Radix Lamiophlomidis Rotatae medical material with 70% the sodium carbonate liquor preparation of 10 times of weight extracted 2 times, the each extraction 2 hours, collect, merge extractive liquid,, filter, filtrate under 70 ℃ of temperature, be condensed into the concentrated solution that relative density is 1.15-1.25 after, with 60% alcoholic solution heating for dissolving, cooling removes by filter alcohol insoluble matter impurity, and filtrate adds the water heating for dissolving after removing ethanol, put cold, with 3 weeding of grease soluble components of petroleum ether extraction, the water intaking layer leaves standstill 12h by the HPD-600 macroporous adsorbent resin, colourless with 15% ethanol elution to eluent, reuse 60% ethanol is resolved, absorption, washing, the flow velocity of resolving be 5 times of bed volumes/hour, collect alcoholic solution, reclaim ethanol to there not being the alcohol flavor, drying is pulverized, and gets the Radix Lamiophlomidis Rotatae flavone;
C. above Radix Lamiophlomidis Rotatae flavone is mixed with Aconitum sinomontanum Nakai total alkaloids, add conventional adjuvant,, make clinical or pharmaceutically acceptable slow releasing preparation according to common process.
Embodiment 11: pharmaceutical composition quick releasing formulation of the present invention
Aconitum sinomontanum Nakai total alkaloids 100g Radix Lamiophlomidis Rotatae flavone 10g;
A. the preparation method of Aconitum sinomontanum Nakai total alkaloids:
Get dry Aconitum sinomontanum Nakai medical material, pulverize, with 65% ethanol extraction of 20 times of weight 1 time, the each extraction 4.5 hours, collection, merge extractive liquid,, and reclaim ethanol, use the sulfuric acid dissolution ethanol extraction, after regulating PH to 1, after adding sodium bicarbonate solution and regulating PH to 11, use chloroform extraction, merge chloroform soln, reclaim chloroform, drying gets Aconitum sinomontanum Nakai total alkaloids;
B. the preparation method of Radix Lamiophlomidis Rotatae flavone:
The alcoholic solution of Radix Lamiophlomidis Rotatae medical material with 50% the aqua calcis preparation of 20 times of weight extracted 3 times, the each extraction 1 hour, collect, merge extractive liquid,, filter, filtrate under 80 ℃ of temperature, be condensed into the concentrated solution that relative density is 1.05-1.15 after, with 75% alcoholic solution heating for dissolving, cooling removes by filter alcohol insoluble matter impurity, and filtrate adds the water heating for dissolving after removing ethanol, put cold, with 2 weeding of grease soluble components of petroleum ether extraction, the water intaking layer leaves standstill 10h by cation exchange resin, colourless with 30% ethanol elution to eluent, reuse 70% ethanol is resolved, absorption, washing, the flow velocity of resolving be 3 times of bed volumes/hour, collect alcoholic solution, reclaim ethanol to there not being the alcohol flavor, drying is pulverized, and gets the Radix Lamiophlomidis Rotatae flavone;
C. above Radix Lamiophlomidis Rotatae flavone is mixed with Aconitum sinomontanum Nakai total alkaloids, add conventional adjuvant,, make clinical or pharmaceutically acceptable quick releasing formulation according to common process.
Embodiment 12: pharmaceutical composition controlled release preparation of the present invention
Aconitum sinomontanum Nakai total alkaloids 10g Radix Lamiophlomidis Rotatae flavone 100g;
A. the preparation method of Aconitum sinomontanum Nakai total alkaloids:
Get dry Aconitum sinomontanum Nakai medical material, pulverize, with 95% ethanol extraction of 5 times of weight 3 times, the each extraction 1 hour, collection, merge extractive liquid,, and reclaim ethanol, use the acetate dissolution ethanol extraction, after regulating PH to 3, after adding ammonia and regulating PH to 8, use chloroform extraction, merge chloroform soln, reclaim chloroform, drying gets Aconitum sinomontanum Nakai total alkaloids;
B. the preparation method of Radix Lamiophlomidis Rotatae flavone:
The alcoholic solution of Radix Lamiophlomidis Rotatae medical material with 90% the sodium carbonate liquor preparation of 5 times of weight extracted 4 times, the each extraction 1 hour, collect, merge extractive liquid,, filter, filtrate under 60 ℃ of temperature, be condensed into the concentrated solution that relative density is 1.25-1.35 after, with 50% alcoholic solution heating for dissolving, cooling removes by filter alcohol insoluble matter impurity, and filtrate adds the water heating for dissolving after removing ethanol, put cold, with 4 weeding of grease soluble components of petroleum ether extraction, the water intaking layer leaves standstill 14h by cation exchange resin, colourless with 20% ethanol elution to eluent, reuse 45% ethanol is resolved, absorption, washing, the flow velocity of resolving be 9 times of bed volumes/hour, collect alcoholic solution, reclaim ethanol to there not being the alcohol flavor, drying is pulverized, and gets the Radix Lamiophlomidis Rotatae flavone;
C. above Radix Lamiophlomidis Rotatae flavone is mixed with Aconitum sinomontanum Nakai total alkaloids, add conventional adjuvant,, make clinical or pharmaceutically acceptable controlled release preparation according to common process.
Embodiment 13: drug composition oral liquid of the present invention
Aconitum sinomontanum Nakai total alkaloids 50g Radix Lamiophlomidis Rotatae flavone 50g;
A. the preparation method of Aconitum sinomontanum Nakai total alkaloids:
Get dry Aconitum sinomontanum Nakai medical material, pulverize, with 75% ethanol extraction of 10 times of weight 2 times, the each extraction 2 hours, collection, merge extractive liquid,, and reclaim ethanol, use the acetate dissolution ethanol extraction, after regulating PH to 2, after adding ammonia and regulating PH to 10, use chloroform extraction, merge chloroform soln, reclaim chloroform, drying gets Aconitum sinomontanum Nakai total alkaloids;
B. the preparation method of Radix Lamiophlomidis Rotatae flavone:
The alcoholic solution of Radix Lamiophlomidis Rotatae medical material with 70% the aqua calcis preparation of 10 times of weight extracted 2 times, the each extraction 2 hours, collect, merge extractive liquid,, filter, filtrate under 70 ℃ of temperature, be condensed into the concentrated solution that relative density is 1.15-1.25 after, with 60% alcoholic solution heating for dissolving, cooling removes by filter alcohol insoluble matter impurity, and filtrate adds the water heating for dissolving after removing ethanol, put cold, with 3 weeding of grease soluble components of petroleum ether extraction, the water intaking layer leaves standstill 12h by cation exchange resin, colourless with 15% ethanol elution to eluent, reuse 60% ethanol is resolved, absorption, washing, the flow velocity of resolving be 5 times of bed volumes/hour, collect alcoholic solution, reclaim ethanol to there not being the alcohol flavor, drying is pulverized, and gets the Radix Lamiophlomidis Rotatae flavone;
C. above Radix Lamiophlomidis Rotatae flavone is mixed with Aconitum sinomontanum Nakai total alkaloids, add conventional adjuvant,, make clinical or pharmaceutically acceptable oral liquid according to common process.
Embodiment 14: pharmaceutical composition ejection preparation of the present invention
Aconitum sinomontanum Nakai total alkaloids 20g Radix Lamiophlomidis Rotatae flavone 80g.
A. the preparation method of Aconitum sinomontanum Nakai total alkaloids:
Get dry Aconitum sinomontanum Nakai medical material, pulverize, with 65% ethanol extraction of 20 times of weight 1 time, the each extraction 4.5 hours, collection, merge extractive liquid,, and reclaim ethanol, use the dissolving with hydrochloric acid ethanol extraction, after regulating PH to 1, after adding sodium bicarbonate solution and regulating PH to 11, use chloroform extraction, merge chloroform soln, reclaim chloroform, drying gets Aconitum sinomontanum Nakai total alkaloids;
B. the preparation method of Radix Lamiophlomidis Rotatae flavone:
The alcoholic solution of Radix Lamiophlomidis Rotatae medical material with 50% the sodium carbonate liquor preparation of 20 times of weight extracted 3 times, the each extraction 1 hour, collect, merge extractive liquid,, filter, filtrate under 80 ℃ of temperature, be condensed into the concentrated solution that relative density is 1.05-1.15 after, with 75% alcoholic solution heating for dissolving, cooling removes by filter alcohol insoluble matter impurity, and filtrate adds the water heating for dissolving after removing ethanol, put cold, with 2 weeding of grease soluble components of petroleum ether extraction, the water intaking layer leaves standstill 10h by cation exchange resin, colourless with 30% ethanol elution to eluent, reuse 70% ethanol is resolved, absorption, washing, the flow velocity of resolving be 3 times of bed volumes/hour, collect alcoholic solution, reclaim ethanol to there not being the alcohol flavor, drying is pulverized, and gets the Radix Lamiophlomidis Rotatae flavone;
C. above Radix Lamiophlomidis Rotatae flavone is mixed with Aconitum sinomontanum Nakai total alkaloids, add conventional adjuvant,, make clinical or pharmaceutically acceptable ejection preparation according to common process.
Claims (10)
1. pharmaceutical composition with anti-inflammatory and analgesic effect is characterized in that the crude drug of this pharmaceutical composition consists of:
Aconitum sinomontanum Nakai total alkaloids 10-100 weight portion Radix Lamiophlomidis Rotatae flavone 10-100 weight portion.
2. pharmaceutical composition as claimed in claim 1 is characterized in that the crude drug of this pharmaceutical composition consists of:
Aconitum sinomontanum Nakai total alkaloids 10-40 weight portion Radix Lamiophlomidis Rotatae flavone 60-100 weight portion;
Or: Aconitum sinomontanum Nakai total alkaloids 60-100 weight portion Radix Lamiophlomidis Rotatae flavone 10-40 weight portion;
Or: Aconitum sinomontanum Nakai total alkaloids 40-60 weight portion Radix Lamiophlomidis Rotatae flavone 40-60 weight portion.
3. pharmaceutical composition as claimed in claim 1 is characterized in that the crude drug of this pharmaceutical composition consists of:
Aconitum sinomontanum Nakai total alkaloids 15 weight portion Radix Lamiophlomidis Rotatae flavone 95 weight portions;
Or: Aconitum sinomontanum Nakai total alkaloids 95 weight portion Radix Lamiophlomidis Rotatae flavone 15 weight portions;
Or: Aconitum sinomontanum Nakai total alkaloids 50 weight portion Radix Lamiophlomidis Rotatae flavone 50 weight portions;
Or: Aconitum sinomontanum Nakai total alkaloids 20 weight portion Radix Lamiophlomidis Rotatae flavone 80 weight portions;
Or: Aconitum sinomontanum Nakai total alkaloids 80 weight portion Radix Lamiophlomidis Rotatae flavone 20 weight portions;
Or: Aconitum sinomontanum Nakai total alkaloids 30 weight portion Radix Lamiophlomidis Rotatae flavone 70 weight portions;
Or: Aconitum sinomontanum Nakai total alkaloids 70 weight portion Radix Lamiophlomidis Rotatae flavone 30 weight portions.
4. as the arbitrary described pharmaceutical composition of claim 1-3, the compositions crude drug is characterized in that getting it filled, add conventional adjuvant, according to common process, make dosage form clinical or that pharmaceutically accept, 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, controlled release preparation, oral liquid, ejection preparation or external preparation.
5. as the arbitrary described preparation of drug combination method of claim 1-3, it is characterized in that this method comprises the steps:
A. the preparation method of Aconitum sinomontanum Nakai total alkaloids is:
Get dry Aconitum sinomontanum Nakai medical material, pulverize, the 60%-95% ethanol extraction of usefulness 4-25 times of weight 1-3 time, the each extraction 0.5-5 hour, collection, merge extractive liquid,, and reclaim ethanol, get ethanol extraction, with hydrochloric acid, sulphuric acid or acetate dissolution ethanol extraction, behind the adjusting PH to 1-3, after hydro-oxidation sodium solution, sodium bicarbonate solution or ammonia are regulated PH to 9-12, use chloroform extraction, merge chloroform soln, reclaim chloroform, drying gets Aconitum sinomontanum Nakai total alkaloids;
B. the preparation method of Radix Lamiophlomidis Rotatae flavone is:
The Radix Lamiophlomidis Rotatae medical material is extracted 1-5 time with the aqua calcis of the 20%-95% of 4-25 times of weight or the alcoholic solution of sodium carbonate liquor preparation, the each extraction 0.5-5 hour, collect, merge extractive liquid,, filter, filtrate is under 55 ℃ of-85 ℃ of temperature, after being condensed into the concentrated solution that relative density is 1.0-1.5, with 40-80% alcoholic solution heating for dissolving, cooling removes by filter alcohol insoluble matter impurity, and filtrate adds the water heating for dissolving after removing ethanol, put cold, with 2-4 weeding of grease soluble components of petroleum ether extraction, the water intaking layer leaves standstill 8-16h by cation exchange resin or HPD-300 or HPD-100 or HPD-450 or HPD-600 macroporous adsorbent resin, colourless with the 5%-45% ethanol elution to eluent, reuse 30%-75% ethanol is resolved, absorption, washing and the flow velocity of resolving be 0.1-10 times of bed volume/hour, collect alcoholic solution, reclaim ethanol to there not being the alcohol flavor, drying is pulverized, and gets the Radix Lamiophlomidis Rotatae flavone;
C. above Radix Lamiophlomidis Rotatae flavone is mixed with Aconitum sinomontanum Nakai total alkaloids, add conventional adjuvant, according to common process, make clinical or pharmaceutically acceptable tablet, capsule, powder, soft capsule, drop pill, honeyed pill, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation, oral liquid, ejection preparation or external preparation.
6. preparation of drug combination method as claimed in claim 5 is characterized in that this method comprises the steps:
A. the preparation method of Aconitum sinomontanum Nakai total alkaloids is:
Get dry Aconitum sinomontanum Nakai medical material, pulverize, with 75% ethanol extraction of 10 times of weight 2 times, the each extraction 2 hours, collection, merge extractive liquid,, and reclaim ethanol, with hydrochloric acid, sulphuric acid or acetate dissolution ethanol extraction, after regulating PH to 2, hydro-oxidation sodium solution, sodium bicarbonate solution or ammonia are used chloroform extraction after regulating PH to 10, merge chloroform soln, reclaim chloroform, drying gets Aconitum sinomontanum Nakai total alkaloids;
B. the preparation method of Radix Lamiophlomidis Rotatae flavone is:
The Radix Lamiophlomidis Rotatae medical material is extracted 2 times with 70% the aqua calcis of 10 times of weight or the alcoholic solution of sodium carbonate liquor preparation, the each extraction 2 hours, collect, merge extractive liquid,, filter, filtrate under 70 ℃ of temperature, be condensed into the concentrated solution that relative density is 1.15-1.25 after, with 60% alcoholic solution heating for dissolving, cooling removes by filter alcohol insoluble matter impurity, and filtrate adds the water heating for dissolving after removing ethanol, put cold, with 3 weeding of grease soluble components of petroleum ether extraction, the water intaking layer leaves standstill 12h by cation exchange resin or HPD-300 or HPD-100 or HPD-450 or HPD-600 macroporous adsorbent resin, colourless with 15% ethanol elution to eluent, reuse 60% ethanol is resolved, absorption, washing, the flow velocity of resolving be 5 times of bed volumes/hour, collect alcoholic solution, reclaim ethanol to there not being the alcohol flavor, drying is pulverized, and gets the Radix Lamiophlomidis Rotatae flavone;
C. above Radix Lamiophlomidis Rotatae flavone is mixed with Aconitum sinomontanum Nakai total alkaloids, add conventional adjuvant, according to common process, make clinical or pharmaceutically acceptable tablet, capsule, powder, soft capsule, drop pill, honeyed pill, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation, oral liquid, ejection preparation or external preparation.
7. preparation of drug combination method as claimed in claim 5 is characterized in that this method comprises the steps:
A. the preparation method of Aconitum sinomontanum Nakai total alkaloids is:
Get dry Aconitum sinomontanum Nakai medical material, pulverize, with 65% ethanol extraction of 20 times of weight 1 time, the each extraction 4.5 hours, collection, merge extractive liquid,, and reclaim ethanol, with hydrochloric acid, sulphuric acid or acetate dissolution ethanol extraction, after regulating PH to 1, hydro-oxidation sodium solution, sodium bicarbonate solution or ammonia are used chloroform extraction after regulating PH to 11, merge chloroform soln, reclaim chloroform, drying gets Aconitum sinomontanum Nakai total alkaloids;
B. the preparation method of Radix Lamiophlomidis Rotatae flavone is:
The Radix Lamiophlomidis Rotatae medical material is extracted 3 times with 50% the aqua calcis of 20 times of weight or the alcoholic solution of sodium carbonate liquor preparation, the each extraction 1 hour, collect, merge extractive liquid,, filter, filtrate under 80 ℃ of temperature, be condensed into the concentrated solution that relative density is 1.05-1.15 after, with 75% alcoholic solution heating for dissolving, cooling removes by filter alcohol insoluble matter impurity, and filtrate adds the water heating for dissolving after removing ethanol, put cold, with 2 weeding of grease soluble components of petroleum ether extraction, the water intaking layer leaves standstill 10h by cation exchange resin or HPD-300 or HPD-100 or HPD-450 or HPD-600 macroporous adsorbent resin, colourless with 30% ethanol elution to eluent, reuse 70% ethanol is resolved, absorption, washing, the flow velocity of resolving be 3 times of bed volumes/hour, collect alcoholic solution, reclaim ethanol to there not being the alcohol flavor, drying is pulverized, and gets the Radix Lamiophlomidis Rotatae flavone;
C. above Radix Lamiophlomidis Rotatae flavone is mixed with Aconitum sinomontanum Nakai total alkaloids, add conventional adjuvant, according to common process, make clinical or pharmaceutically acceptable tablet, capsule, powder, soft capsule, drop pill, honeyed pill, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation, oral liquid, ejection preparation or external preparation.
8. preparation of drug combination method as claimed in claim 5 is characterized in that this method comprises the steps:
A. the preparation method of Aconitum sinomontanum Nakai total alkaloids is:
Get dry Aconitum sinomontanum Nakai medical material, pulverize, with 95% ethanol extraction of 5 times of weight 3 times, the each extraction 1 hour, collection, merge extractive liquid,, and reclaim ethanol, with hydrochloric acid, sulphuric acid or acetate dissolution ethanol extraction, after regulating PH to 3, hydro-oxidation sodium solution, sodium bicarbonate solution or ammonia are used chloroform extraction after regulating PH to 8, merge chloroform soln, reclaim chloroform, drying gets Aconitum sinomontanum Nakai total alkaloids;
B. the preparation method of Radix Lamiophlomidis Rotatae flavone is:
The Radix Lamiophlomidis Rotatae medical material is extracted 4 times with 90% the aqua calcis of 5 times of weight or the alcoholic solution of sodium carbonate liquor preparation, the each extraction 1 hour, collect, merge extractive liquid,, filter, filtrate under 60 ℃ of temperature, be condensed into the concentrated solution that relative density is 1.25-1.35 after, with 50% alcoholic solution heating for dissolving, cooling removes by filter alcohol insoluble matter impurity, and filtrate adds the water heating for dissolving after removing ethanol, put cold, with 4 weeding of grease soluble components of petroleum ether extraction, the water intaking layer leaves standstill 14h by cation exchange resin or HPD-300 or HPD-100 or HPD-450 or HPD-600 macroporous adsorbent resin, colourless with 20% ethanol elution to eluent, reuse 45% ethanol is resolved, absorption, washing, the flow velocity of resolving be 9 times of bed volumes/hour, collect alcoholic solution, reclaim ethanol to there not being the alcohol flavor, drying is pulverized, and gets the Radix Lamiophlomidis Rotatae flavone;
C. above Radix Lamiophlomidis Rotatae flavone is mixed with Aconitum sinomontanum Nakai total alkaloids, add conventional adjuvant, according to common process, make clinical or pharmaceutically acceptable tablet, capsule, powder, soft capsule, drop pill, honeyed pill, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation, oral liquid, ejection preparation or external preparation.
9. has application in the medicine of anti-inflammatory and analgesic effect as the arbitrary described pharmaceutical composition of claim 1-3 in preparation.
10. pharmaceutical composition as claimed in claim 4 has application in the medicine of anti-inflammatory and analgesic effect in preparation.
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