CN101375954B - Medicament composition, preparation method thereof and use - Google Patents
Medicament composition, preparation method thereof and use Download PDFInfo
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- CN101375954B CN101375954B CN2007100593204A CN200710059320A CN101375954B CN 101375954 B CN101375954 B CN 101375954B CN 2007100593204 A CN2007100593204 A CN 2007100593204A CN 200710059320 A CN200710059320 A CN 200710059320A CN 101375954 B CN101375954 B CN 101375954B
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- aconitum sinomontanum
- sinomontanum nakai
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Abstract
The invention provides a medicament combination and a preparation method for the medicinal composition. Meanwhile, the invention further relates to the application of an aconitum sinomontanum extractive and a radix paeoniae alba extractive on preparing an anti-inflammatory analgesic medicament. The medicament combination takes the aconitum sinomontanum extractive and the radix paeoniae alba extractive as active ingredients, and has obvious synergistic functions on the anti-inflammatory analgesic aspect; the invention has a curative effect obviously prior to single use of aconitum sinomontanum total alkaloids or total glucosides of paeony, and provides a compound combination and/or a preparation thereof with better curative effect and more convenient use for clinic.
Description
Technical field
The present invention relates to field of traditional Chinese.Specifically, the present invention relates to a kind of pharmaceutical composition, two kinds of active component Aconitum sinomontanum Nakai extracts and Radix Paeoniae Alba extract in the said composition have synergistic function aspect anti-inflammatory and antalgic.The invention still further relates to described preparation of drug combination method.The present invention relates to a kind of Aconitum sinomontanum Nakai extract and Radix Paeoniae Alba extract simultaneously and is used for purposes on the anti-inflammation analgesis medicament in preparation.
Background technology
Painful diseases such as rheumatoid arthritis, cancer pain, chronic pain are the diseases of serious threat human health.Wherein rheumatoid arthritis is more common in person between twenty and fifty, accounts for about 80% in 20～45 years old, and the women sees that than the male men and women's ratio is 1:3 more.RA is a kind of common multiple disease, external sickness rate about 1%, and domestic nothing is accurately added up, and according to investigation in 1984, sickness rate was about 0.24%-0.5%.Cancer pain is as a The main concomitant symptoms of cancer, and its shared whole cancer patient's ratio is about 30% 50%, and patient with advanced cancer is about 60% 90%.Chronic pain, its essence are exactly a kind of serious disease, and this has become the common recognition of international pain medical circle.According to nearest statistics is the second largest commonly encountered diseases that is only second to upper respiratory tract infection at the north America region chronic pain.Chronic pain has caused global great attention as a kind of disease, and world's pain conference is confirmed as " human the 5th big vital signs " after breathing, pulse, body temperature and blood pressure with pain.Show according to World Health Organization's statistics: about 400,000,000 people of global rheumatisant, in China, rheumatic arthritis, patient with rheumatoid arthritis have more than 8,000 ten thousand approximately, and the sickness rate in some high-risk group is unexpectedly up to 70%.According to another IMS statistics, arthritic's number of China surpasses 100,000,000, and wherein the osteoarthritis patient is about 6,500,000, and annual medical expense expenditure is more than 13,500,000,000 yuan.China's rheumatoid arthritis prevalence is 0.34%～0.36%, in prediction on such basis, 400～500 all creation rheumatic arthritis patients is arranged approximately.Thereby the treatment antalgesic is more and more paid attention to by people and is paid close attention to.Though it is more to treat the pain medication kind at present, the pain medication of research and development highly effective and safe is still the task of top priority.
In the treatment of pain medicine, the application of Chinese medicine and western medicine emphasizes particularly on different fields, and Chinese medicine also occupies the bigger market share with the little advantage of its side effect.In the Chinese patent medicine of present numerous antalgesics, be that Chinese patent medicines such as main active such as Aconitum sinomontanum Nakai total alkaloids, Radix Paeoniae Alba total glucosides, triptolide, tetrahydropalmatine, sinomenine more and more are subject to people's attention with effective site.The effect of the various effective ingredient in Chinese of treatment antalgesic is had nothing in common with each other and is stressed, and therefore, has the great demand of drug combination clinically.And the medicine of treatment antalgesic needs long-term prescription mostly, can cause side effect such as serious nephrotoxicity, genotoxicity behind chemical drugs and the indivedual Chinese medicine monomer composition long-term prescriptions.Therefore, provide convenient effective ingredient in Chinese compound preparation effective, that have synergistic function, minimizing dosage to have important clinical meaning and important social value.
The Aconitum sinomontanum Nakai total alkaloids is the effective ingredient in the Chinese medicine Aconitum sinomontanum Nakai, and wherein contained lappaconitine is one of its effective ingredient, and the test of pesticide effectiveness shows that it simultaneously by periphery and maincenter performance analgesic activity, has substantial connection with monoamine neurotransmitter level in the brain.Maincenter Ca2+ level variation simultaneously has substantial connection with the generation of lappaconitine (LA) analgesic activity.Exogenous Ca2+ injects and changes the inside and outside Ca2+ concentration of cell under the physiological condition and antagonism LA analgesic activity.Lappaconitine is non-addicted analgesics clinically, has stronger analgesic activity.This product also has the effect of local anesthesia, cooling, analgesic and anti-inflammation detumescence.This product and Pethidine be warp mutually, and suppression pain effect is suitable, and onset time is slow slightly, and it is longer to hold time; Analgesic activity is 7 times of antipyretic analgesic aminophenazone.Can be used for cancer pain, headache, toothache, shoulder brachialgia, cervical vertebra pain, lumbago, calculus pain, the outer pain of injury of fracture, rheumatalgia, postoperative pain, neuropathic pain, sciatica etc.Yet the Aconitum sinomontanum Nakai total alkaloids has higher toxic and side effects, and its use clinically is subjected to certain limitation.
Radix Paeoniae Alba total glucosides has effects such as antiinflammatory, immunomodulating, analgesia, calmness preferably, is the common drug of treatment of arthritis clinically always.
Can produce synergistic function when the inventor's Aconitum sinomontanum Nakai total alkaloids and Radix Paeoniae Alba total glucosides drug combination, and reduce the toxic and side effects of Aconitum sinomontanum Nakai total alkaloids, thereby finish the present invention.
Summary of the invention
The object of the present invention is to provide a kind of pharmaceutical composition that comprises Aconitum sinomontanum Nakai extract and two kinds of active components of Radix Paeoniae Alba extract, these two kinds of active components can produce synergism aspect anti-inflammatory and antalgic, raising evident in efficacy, can significantly reduce the consumption and the toxic and side effects of Aconitum sinomontanum Nakai total alkaloids again, thereby reduce the probability that untoward reaction clinically takes place, overcome simultaneously the deficiency that single middle pharmaceutically active ingredient is difficult to satisfy the demand for the treatment of antalgesic drug combinations such as rheumatoid arthritis clinically again, avoid medicine simply to mix the side reaction that use may cause, a kind of better efficacy clinically is provided, convenient effective ingredient in Chinese compound and preparation thereof.The present invention also aims to provide a kind of described preparation of drug combination method.Another purpose of the present invention is to provide being combined in of a kind of ingredient to prepare the application that is used on the anti-inflammation analgesis medicament.
At the foregoing invention purpose, the invention provides following technical scheme:
On the one hand, the invention provides a kind of pharmaceutical composition, described compositions comprises Aconitum sinomontanum Nakai extract and Radix Paeoniae Alba extract as active component, and pharmaceutically acceptable carrier.
Preferably, in the described pharmaceutical composition, the weight proportion of two kinds of extracts is, Aconitum sinomontanum Nakai extract: Radix Paeoniae Alba extract=1:2-1:40 is preferably 1:4.5-1:30, and more preferably 1:4.5-1:20 most preferably is 1:5-1:10.
Preferably, the Aconitum sinomontanum Nakai total alkaloid contents of described Aconitum sinomontanum Nakai extract is more than 50%, and wherein the content of lappaconitine is about 40%; And/or content of paeoniflorin is preferably more than 80% more than 50% in the described Radix Paeoniae Alba extract.
Further preferred, the Aconitum sinomontanum Nakai total alkaloid contents of described Aconitum sinomontanum Nakai extract is more than 80%, and wherein the content of lappaconitine is about 60%.
Preferably, described compositions is the form of oral, injection and/or exterior-applied formulation.
Further preferred, described peroral dosage form is selected from: tablet, capsule, soft capsule, granule, drop pill, dispersible tablet, slow releasing tablet, controlled release tablet and/or oral cavity quick disintegrating slice; Described injection type is selected from: infusion solution and/or injectable powder; Described exterior-applied formulation is selected from: ointment, rubber-emplastrum and/or cataplasma.
Further preferred, described carrier comprises: excipient, filler, diluent, lubricant, wetting agent, disintegrating agent, surfactant, antiseptic, sweeting agent, and/or aromatic.
On the other hand, the invention provides a kind of described preparation of drug combination method, this method comprises, after described Aconitum sinomontanum Nakai extract and Radix Paeoniae Alba extract mixing, adds pharmaceutically acceptable carrier.
Preferably, described Aconitum sinomontanum Nakai extract adopts the alcohol extraction method, and described Radix Paeoniae Alba total glucosides adopts water extracting method.
Further preferred, the alcohol extraction method that described Aconitum sinomontanum Nakai extract adopts comprises: after the Aconitum sinomontanum Nakai pulverizing medicinal materials, with extracting solvent soaking, percolation, the percolate of collection certain volume, last resin column, left standstill 24 hours, and washed decontamination earlier with water, the certain density ethanol elution of reuse, reclaim ethanol to doing, promptly.
Further preferred, the extraction solvent of described extraction Aconitum sinomontanum Nakai is the salt sour water of pH2.0,5% acidic alcohol and/or 5% hydrochloric acid methanol; And/or used ion exchange resin is cation exchange resin, nonpolar or low pole macroporous adsorbent resin.
Further preferred, the water extracting method that described Radix Paeoniae Alba total glucosides adopts comprises: with the white Peony Root water extraction, extracting solution is concentrated into proper volume; Add ethanol to finite concentration, the precipitate with ethanol certain hour is concentrated into proper volume; The concentrated solution macroporous resin adsorption washes with water to effluent colourlessly earlier, and ethanol elution is collected in reuse finite concentration ethanolysis absorption, reclaims ethanol, drying, promptly.
On the other hand, the invention provides being combined in of a kind of ingredient and prepare the application that is used on the anti-inflammation analgesis medicament, described ingredient combination is selected from one or more in the following combination: Aconitum sinomontanum Nakai extract and Radix Paeoniae Alba extract, Aconitum sinomontanum Nakai total alkaloids and Radix Paeoniae Alba total glucosides, and lappaconitine and peoniflorin.
Preferably, the invention provides being combined in of a kind of ingredient and prepare the application that is used for the treatment of on the antalgesic medicine, described ingredient combination is selected from one or more in the following combination: Aconitum sinomontanum Nakai extract and Radix Paeoniae Alba extract, Aconitum sinomontanum Nakai total alkaloids and Radix Paeoniae Alba total glucosides, and lappaconitine and peoniflorin.
Further preferred, described antalgesic is selected from one or more in the following disease: rheumatoid arthritis, cancer pain, chronic pain and postoperative pain.
One of extract in said composition Radix Paeoniae Alba extract prepares with conventional method.For example, can adopt following method preparation:
Described Radix Paeoniae Alba total glucosides also can be according to the preparation of following method: get white Peony Root 10Kg, and with 10 times of water gaging reflux, extract, three times, each 2h, filtration, merge three times aqueous extract, reclaim solvent, be concentrated into about 10L, add ethanol to the alcohol amount of containing and reach about 70%, leave standstill 12h, centrifugal; Supernatant reclaims ethanol to there not being the alcohol flavor, and with the wet HPD-300 macroporous resin adsorption of 15L, with the 90L washing, reuse 30% concentration ethanol 75L desorption is collected 30% ethanol elution, reclaims ethanol earlier, and drying under reduced pressure promptly gets Radix Paeoniae Alba total glucosides.
Content of paeoniflorin assay method (high performance liquid chromatography) in the above-mentioned Radix Paeoniae Alba extract
Chromatographic condition and system suitability test: closing silica gel with the octadecylsilane chain is filler; Acetonitrile-0.1% phosphoric acid (14:86) is mobile phase; The detection wavelength is 230nm.Number of theoretical plate is pressed the peoniflorin peak and is calculated, and should be not less than 5000.
The preparation of reference substance solution: it is an amount of that precision takes by weighing the peoniflorin reference substance, makes the solution that every ml contains 0.06mg with 30% ethanol.
The preparation of need testing solution: precision takes by weighing the about 10mg of this product, puts in the 100ml measuring bottle, adds 30% dissolve with ethanol and is diluted to scale, shakes up promptly.
Algoscopy: accurate respectively reference substance and each 10ul of need testing solution of drawing, inject chromatograph of liquid and measure, collection of illustrative plates is seen Fig. 1.
Another extract Aconitum sinomontanum Nakai extract in the present composition can adopt following method to extract from Aconitum sinomontanum Nakai: after Aconitum sinomontanum Nakai medical material 10Kg is pulverized, extract solvent soaking with 12 times of amounts, spend the night percolation on the secondth, the percolate of collection certain volume, last resin column, left standstill 24 hours, and washed decontamination earlier with water, the certain density ethanol elution of reuse, reclaim ethanol to doing, promptly.
(1) assay (high performance liquid chromatography) of lappaconitine in the above-mentioned Aconitum sinomontanum Nakai extract
Chromatographic condition and system suitability test: with octadecylsilane chemically bonded silica is filler; Flow velocity: 1.0ml/min; The detection wavelength is 252nm; Column temperature: 35 ℃; Mobile phase: 0.2mol/L sodium dihydrogen phosphate-methanol (55:45)
The preparation of reference substance solution: it is an amount of that precision takes by weighing the lappaconitine reference substance, adds methanol and make the solution that every ml contains the 0.15mg lappaconitine respectively.
The preparation of need testing solution: precision takes by weighing the about 10mg of this product, puts in the 25ml measuring bottle, adds the mobile phase dissolving and is diluted to scale, shakes up, promptly.
Algoscopy: accurate respectively reference substance solution and each 10ul of need testing solution of drawing, inject chromatograph of liquid, measure, that is, see Fig. 2.
(2) assay method (ultraviolet visible spectrophotometry) of above-mentioned Aconitum sinomontanum Nakai extract total alkaloids
The preparation of reference substance solution: it is an amount of that precision takes by weighing the lappaconitine reference substance, makes the solution that every ml contains 0.3mg with methanol, promptly.
The preparation of need testing solution: precision takes by weighing the about 10mg of this product, puts in the 25ml measuring bottle, with dissolve with methanol and be diluted to scale, shakes up, promptly.
Algoscopy: getting reference substance and need testing solution respectively, is blank with methanol, according to ultraviolet visible spectrophotometry (appendix VA of Chinese Pharmacopoeia version in 2005)), measure trap at 252nm wavelength place, calculate, promptly.
Preparation of drug combination of the present invention can adopt the conventional method of pharmaceutical field, uses conventional pharmaceutical carrier to carry out.After for example adopting conventional method with Aconitum sinomontanum Nakai extract and Radix Paeoniae Alba extract uniform mixing, mix, make various required dosage forms then with carrier or the adjuvant used always on any or more than one pharmaceuticss.Described carrier is excipient, filler, diluent, lubricant, wetting agent, disintegrating agent, surfactant, antiseptic, sweeting agent, aromatic etc. for example.Concrete, described carrier is starch, dextrin, lactose, microcrystalline Cellulose, hydroxypropyl methylcellulose, Polyethylene Glycol, magnesium stearate, micropowder silica gel, glucose, mannitol, xylitol, glycine etc. for example.
As required, pharmaceutical composition of the present invention can be made into the preparation that is suitable for various approach medications, particularly is suitable for the dosage form of oral, external and injection.Described to be suitable for oral dosage form can be to be selected from following arbitrary dosage form: tablet, capsule, soft capsule, granule, drop pill, dispersible tablet, slow releasing tablet, controlled release tablet or oral cavity quick disintegrating slice.The described dosage form that is suitable for external can be ointment, rubber-emplastrum or cataplasma.The described dosage form that is suitable for injecting can be injection, transfusion or powder injection formulation.
When pharmaceutical composition of the present invention was made into the dosage form that is suitable for injecting such as injection or injectable powder, wherein total alkaloid content was more than 80% in the Aconitum sinomontanum Nakai extract, and paeoniflorin content is more than 80% in the Radix Paeoniae Alba extract.
Beneficial effect of the present invention is:
This pharmaceutical composition contains Aconitum sinomontanum Nakai extract and Radix Paeoniae Alba extract, can anti-inflammatory and antalgic, the uniting use and can produce synergism of two kinds of active components, than singly using with dosage Aconitum sinomontanum Nakai extract or singly using with the dosage Radix Paeoniae Alba extract or singly use with dosage lappaconitine effect and all improve greatly, prove that through pharmacodynamics test it is evident in efficacy.Can significantly reduce the consumption of Aconitum sinomontanum Nakai extract again, thereby reduce the probability that untoward reaction clinically takes place.
In addition, Chinese medicine composition raw material sources of the present invention are easy to get, and are easy to industrialization, can make various dosage forms as required, for clinical provide convenient, more effectively, the more controlled modern Chinese medicine of quality, for the patient brings more benefits, thereby produce the huge social benefit.
Description of drawings
Fig. 1 is the HPLC assay collection of illustrative plates of Radix Paeoniae Alba total glucosides;
Fig. 2 is the HPLC assay collection of illustrative plates of Aconitum sinomontanum Nakai total alkaloids.
The specific embodiment
The present invention is described in further detail below in conjunction with the specific embodiment, and the embodiment that provides is only in order to illustrate the present invention, rather than in order to limit the scope of the invention.
Embodiment 1, raw material are prepared:
(1) Radix Paeoniae Alba extract
Get white Peony Root 10Kg, with 10 times of water gaging reflux, extract, three times, each 2h filters, and merges three times aqueous extract, reclaims solvent, is concentrated into about 10L, adds ethanol and purely measures approximately 70% to containing, and leaves standstill 12h, and is centrifugal; Supernatant reclaims ethanol to there not being the alcohol flavor, and with the wet HPD-100 macroporous resin adsorption of 15L, first water 90L eluting, reuse 30% concentration ethanol 75L desorption is collected 30% ethanol elution, reclaims ethanol, and drying under reduced pressure promptly gets Radix Paeoniae Alba total glucosides.Wherein paeoniflorin content is 83.02%.
(2) Aconitum sinomontanum Nakai extract
With Aconitum sinomontanum Nakai medical material 1000g, be ground into coarse powder, with the hydrochloric acid water logging bubble of 12 times of pH2.0, spend the night, percolation on the secondth is collected the percolate of 15 times of amounts, last cation exchange resin column treats that the percolation liquid level drops to when equal with post surface, stops, left standstill 24 hours, and took out ion exchange resin, transfer pH to 9.0 10.0 with ammonia, oven dry, with 95% alcohol reflux 2 hours, reclaim ethanol to doing, promptly.The total alkaloid contents of gained is 85%, and wherein the content of lappaconitine is about 60%.
Get lappaconitine medical material 1000g, be ground into coarse powder, add 85% ethanol (containing 5% hydrochloric acid) and soak 3 times, each 4 hours, collect filtrate, decompression and solvent recovery is to there not being the alcohol flavor, thin up is to 0.2g crude drug/ml, use the HPD-300 macroporous resin adsorption, use the water elution of 3 times of amount resin volumes earlier, discard collection liquid, the volume of 5 times of amounts of reuse 70% alcoholic solution eluting, collect 70% ethanol elution, decompression recycling ethanol is also dry, promptly.The total alkaloid contents of gained is 73.1%, and the content of lappaconitine is 49.7%.
The injectable powder type of embodiment 2, pharmaceutical composition of the present invention
Prescription:
Aconitum sinomontanum Nakai extract 1g, Radix Paeoniae Alba extract 4.5g, mannitol 5g and 500ml water for injection.
Preparation:
The embodiment 1 described Aconitum sinomontanum Nakai extract 1g that makes, Radix Paeoniae Alba extract 4.5g that embodiment 1 makes and mannitol 5g are mixed and be dissolved in the 500ml water for injection, filter, sterilization, spray drying, aseptic subpackaged, make the pharmaceutical composition of the injectable powder type that contains 1 part of Aconitum sinomontanum Nakai extract and 4.5 parts of Radix Paeoniae Alba extracts.
The injectable powder type of embodiment 3, pharmaceutical composition of the present invention
Prescription:
Aconitum sinomontanum Nakai extract 1g, Radix Paeoniae Alba extract 20g, mannitol 5g and 1500ml water for injection.
Preparation:
The embodiment 1 described Aconitum sinomontanum Nakai extract 1g that makes, Radix Paeoniae Alba extract 20g that embodiment 1 makes and mannitol 5g are mixed and be dissolved in the 1500ml water for injection, filter, sterilization, aseptic subpackaged, lyophilization makes the pharmaceutical composition of the injectable powder type that contains 1 part of Aconitum sinomontanum Nakai extract and 20 parts of Radix Paeoniae Alba extracts.
The injectable powder type of embodiment 4, pharmaceutical composition of the present invention
Prescription:
Aconitum sinomontanum Nakai extract 2g, Radix Paeoniae Alba extract 26g, mannitol 10g and 2000ml water for injection.
Preparation:
Adopt the method identical, make the pharmaceutical composition of the injectable powder type that contains 1 part of Aconitum sinomontanum Nakai extract and 13 parts of Radix Paeoniae Alba extracts according to above-mentioned prescription with embodiment 3.
The injection of embodiment 5, pharmaceutical composition of the present invention or contain the transfusion dosage form
Prescription:
Aconitum sinomontanum Nakai extract 1g, Radix Paeoniae Alba extract 2g, 0.05g EDTA-Na and 200ml50% propylene glycol.
Preparation:
Adopt conventional process for preparation of injection, the raw material with embodiment 1 is provided makes the injection that contains 1 part of Aconitum sinomontanum Nakai extract and 2 parts of Radix Paeoniae Alba extracts or contains the transfusion forms of pharmaceutical compositions according to above-mentioned prescription.
The injection of embodiment 6, pharmaceutical composition of the present invention or contain the transfusion dosage form
Prescription:
Aconitum sinomontanum Nakai total alkaloids 0.1g, Radix Paeoniae Alba total glucosides 4g, 0.05g EDTA-Na and 100ml50% propylene glycol.
Preparation:
Adopt conventional process for preparation of injection, the raw material with embodiment 1 is provided makes the injection that contains 1 part of Aconitum sinomontanum Nakai extract and 40 parts of Radix Paeoniae Alba extracts or contains the transfusion forms of pharmaceutical compositions according to above-mentioned prescription.
The drops of embodiment 7, pharmaceutical composition of the present invention
Prescription:
Aconitum sinomontanum Nakai extract 1g and Radix Paeoniae Alba extract 30g.
Preparation:
Adopt the technology of conventional preparation drop pill, the raw material with embodiment 1 is provided makes the drop pill that contains 1 part of Aconitum sinomontanum Nakai extract and 20 parts of Radix Paeoniae Alba extracts according to above-mentioned prescription.
The soft capsule dosage form of embodiment 8, pharmaceutical composition of the present invention
Prescription:
Aconitum sinomontanum Nakai extract 1g, Radix Paeoniae Alba extract 35g and vegetable oil 25g.
Preparation:
Adopt the technology of conventional preparation soft capsule,, get Aconitum sinomontanum Nakai extract 1g with the raw material that embodiment 1 is provided, Radix Paeoniae Alba extract 35g, vegetable oil 25g, mixing, make capsule casing material with gelatin, be pressed into soft capsule, make the soft capsule that contains 1 part of Aconitum sinomontanum Nakai extract and 35 parts of Radix Paeoniae Alba extracts.
The capsule formulation of embodiment 9, pharmaceutical composition of the present invention
Prescription:
Aconitum carmichjaelii Debx. extract 1g, Radix Paeoniae Alba extract 5g and starch 100g.
Preparation:
Adopt the technology of conventional preparation capsule, with the raw material that embodiment 1 is provided, get Aconitum sinomontanum Nakai extract 1g, Radix Paeoniae Alba extract 5g and starch 100g mixing incapsulate shell, make capsule.Make the capsule that contains 1 part of Aconitum sinomontanum Nakai extract and 5 parts of Radix Paeoniae Alba extracts.
The granule of embodiment 10, pharmaceutical composition of the present invention or Tabules
Prescription:
Aconitum sinomontanum Nakai extract 1g, Radix Paeoniae Alba extract 30g and sucrose 80g.
Preparation:
Adopt the technology of conventional preparation granule,, get Aconitum sinomontanum Nakai extract 1g with the raw material that embodiment 1 is provided, Radix Paeoniae Alba extract 30g and sucrose 80g mixing are granulated, sieve, drying promptly makes the granule forms of pharmaceutical compositions of closing 1 part of Aconitum sinomontanum Nakai extract and 30 parts of Radix Paeoniae Alba extracts.
Through further tabletting, drying promptly makes the pharmaceutical composition of the Tabules that closes 1 part of Aconitum sinomontanum Nakai extract and 1 part of Radix Paeoniae Alba extract with the granule that makes.
The slow releasing tablet dosage form of embodiment 11, pharmaceutical composition of the present invention
Prescription:
Aconitum sinomontanum Nakai extract 2g, Radix Paeoniae Alba extract 20g, and polyvinylpyrrolidone (K30) 70g
Preparation:
Adopt the technology of conventional preparation tablet,, get Aconitum sinomontanum Nakai extract 2g, Radix Paeoniae Alba extract 20g with the raw material that embodiment 1 is provided, with polyethylene 70g mixing, granulate, sieve, tabletting, drying promptly makes the pharmaceutical composition of the slow releasing tablet dosage form that contains 1 part of Aconitum sinomontanum Nakai extract and 10 parts of Radix Paeoniae Alba extracts.
The dispersible tablet dosage form of embodiment 12, pharmaceutical composition of the present invention
Prescription:
Aconitum sinomontanum Nakai extract 2g, Radix Paeoniae Alba extract 15g, microcrystalline Cellulose 22g, hyprolose 8g and micropowder silica gel 0.1g.
Preparation:
Adopt the technology of conventional preparation tablet, the raw material that is provided with embodiment 1, get Aconitum sinomontanum Nakai extract 2g, Radix Paeoniae Alba extract 15g, microcrystalline Cellulose 22g, hyprolose 8g and micropowder silica gel 0.1g mix homogeneously, tabletting promptly makes the pharmaceutical composition of the tablet formulation that contains 7.5 parts of Radix Paeoniae Alba extracts and 1 part of Aconitum sinomontanum Nakai extract.
Prescription:
Aconitum sinomontanum Nakai extract 2g, Radix Paeoniae Alba extract 16g, dodecyl sodium sulfate 1g, octadecanol 25g, white vaseline 30g, ethylparaben 0.04g, propylene glycol 12g adds purified water to 100g
Preparation:
Get octadecanol, white vaseline melts in water-bath, is heated to 75 ℃ (oil phase).Getting ethyl hydroxybenzoate, propylene glycol, sodium lauryl sulphate adds an amount of purified water dissolving and is heated to 75 ℃ (waters).Oil phase is added aqueous phase, stir and add and use dissolved Aconitum sinomontanum Nakai extract of purified water and Radix Paeoniae Alba extract, be stirred to and solidify, promptly get the emulsifiable paste forms of pharmaceutical compositions that contains 8 parts of Radix Paeoniae Alba extracts and 1 part of Aconitum sinomontanum Nakai extract.
Prescription:
Aconitum sinomontanum Nakai extract 1g, Radix Paeoniae Alba extract 7g, Acritamer 940 2g, propylene glycol 15ml, sodium sulfite 0.4g, dehydrated alcohol 30ml, triethanolamine 3g, purified water adds to 100g
Preparation:
Carbomer evenly is spread in an amount of purified water, leaves standstill, make abundant swelling.Aconitum sinomontanum Nakai extract, Radix Paeoniae Alba extract, sodium sulfite are dissolved with an amount of purified water, be added in the carbomer substrate, add propylene glycol and dehydrated alcohol mixing again, stir, add triethanolamine, transfer pH6.0～6.5, add purified water to capacity, packing promptly gets and promptly gets the gel forms of pharmaceutical compositions that contains 7 parts of Radix Paeoniae Alba extracts and 1 part of Aconitum sinomontanum Nakai extract.
The test of pesticide effectiveness of embodiment 13, pharmaceutical composition of the present invention
The curative effect of medicine of the present invention is proved by following pharmacodynamics test: designed Aconitum sinomontanum Nakai extract, Radix Paeoniae Alba extract and both different proportioning samples, adopt the lumbar injection glacial acetic acid to cause mouse writhing test, hot plate test and auricle swelling model, observe the action effect of Aconitum sinomontanum Nakai extract and the different proportionings of Radix Paeoniae Alba extract, determine best proportioning.
(1) experiment material
1, medicine and reagent
(1) Aconitum sinomontanum Nakai extract: chocolate brown powder, lot number 060301 is according to the method preparation of embodiment 1;
(2) Radix Paeoniae Alba extract: buff powder, lot number 060811, available from Yunnan Plant Pharmaceutical Industry Co., Ltd., total saponin content 82.7%;
(3) tramadol: Shijiazhuang Pharmaceutical Group Co Ltd produces, product batch number 061003, and specification 50mg/ sheet * 10 slice are made into 2% medicinal liquid with distilled water during test, and are standby.
(4) dexamethasone acetate: pharmaceutical Co. Ltd produces by the celestial jade pendant in Zhejiang, product batch number 060924, and specification 0.75mg/ sheet * 100 slice are made into 0.015% medicinal liquid with distilled water during test, and are standby.
(5) glacial acetic acid: analytical pure, Tianjin chemical reagent three factories, lot number 20060518 is made into 0.6% solution with distilled water during test, and is standby.
(6) dimethylbenzene: analytical pure, Tianjin chemical reagent three factories, lot number 20060315
2, instrument
RB-200 type intelligence hot plate analgesia instrument is produced by Chengdu TME Technology Co., Ltd.
3, animal KM mice: male and female have concurrently, and body weight 20 ± 2g or 27 ± 2g are provided by animal housing of Tianjin medicine institute.
(2) experimental technique and result
1, the Aconitum sinomontanum Nakai extract of different proportionings and Radix Paeoniae Alba extract cause the influence of pain mice to glacial acetic acid
Get 130 mices (male and female half and half) be divided at random model control group (N=10), positive controls (N=10), Aconitum sinomontanum Nakai extract group (N=10), 1:5 compatibility group (ratio of Aconitum sinomontanum Nakai extract and Radix Paeoniae Alba extract) (N=10), 1:10 compatibility group (N=10), 1:25 compatibility group (N=10), 1:35 compatibility group (N=10), Radix Paeoniae Alba extract group (N=10).By group irritate stomach distilled water, 2% tramadol medicinal liquid, 1% Aconitum sinomontanum Nakai extract medicinal liquid respectively, contain Aconitum sinomontanum Nakai extract 1% 1:5 compatibility liquid, contain Aconitum sinomontanum Nakai extract 1% 1:10 compatibility liquid, contain Aconitum sinomontanum Nakai extract 1% 1:25 compatibility liquid, contain the 1:35 compatibility liquid of Aconitum sinomontanum Nakai extract 1%, 1% Radix Paeoniae Alba extract medicinal liquid 10ml/kg.1h after the administration, each Mus lumbar injection 0.6% glacial acetic acid 10ml/kg observes interior each Mus of 15min and the incubation period of writhing response occurs and turn round the body number of times.The experimental data data is carried out statistical procedures with the SPSS statistical package.The results are shown in Table 1.
Table 1 Aconitum sinomontanum Nakai extract Radix Paeoniae Alba extract compatibility causes the influence (X ± SD) of pain mice to glacial acetic acid
| Group | Animal (only) | Dosage (g/kg) | Incubation period (second) | Turn round the body number of times (inferior/15min) |
| |
10 | Distilled water | 245.90±125.41 | 26.70±11.55 |
| |
10 | 0.2 | 847.20±166.97** | 1.00±3.16** |
| Aconitum sinomontanum |
10 | 0.6 | 420.00±86.59 | 9.10±6.45** |
| Radix Linderae 1:5 |
10 | 0.6 | 509.60±218.84 | 4.20±6.27** |
| Radix Linderae 1:10 |
10 | 0.6 | 520.80±229.93 | 4.80±6.78** |
| Radix Linderae 1:25 |
10 | 0.6 | 529.90±145.48 | 5.20±9.64** |
| Radix Linderae 1:35 |
10 | 0.6 | 404.40±56.63 | 11.20±4.08** |
| The Radix Paeoniae |
10 | 0.6 | 465.40±108.25 | 10.10±5.45** |
Annotate: compare * P≤0.05, * * P≤0.01 with model group
The result of table 1 shows with model control group and compares that each administration group mice pain threshold all increases, and shows as prolongation of latency and turns round the minimizing of body number of times.Wherein, proportioning is that (the Aconitum sinomontanum Nakai extract: Radix Paeoniae Alba extract) effect is the strongest, and proportioning is that (the Aconitum sinomontanum Nakai extract: Radix Paeoniae Alba extract) action intensity is close with it for 1:10 for 1:5.
2, different proportioning Aconitum sinomontanum Nakai extracts and Radix Paeoniae Alba extract cause the influence of pain mice to hot plate
With RB-200 type intelligence hot plate analgesia instrument screening basis pain value of closing (time of licking metapedes with mice cuts off from as pain) 130 of the female mices of 5-30 second, in the basis bitterly the height of news value be divided into model control group (N=10), positive controls (N=10), Aconitum sinomontanum Nakai extract (N=10), (ratio of Aconitum sinomontanum Nakai extract and Radix Paeoniae Alba extract) 1:5 compatibility group (N=10), 1:10 compatibility group (N=10), 1:25 compatibility group (N=10), 1:35 compatibility group (N=10), the Radix Paeoniae Alba at random and organize (N=10).By group irritate stomach distilled water, 2% tramadol medicinal liquid, 1% Aconitum sinomontanum Nakai extract medicinal liquid respectively, contain Aconitum sinomontanum Nakai extract 1% 1:5 compatibility liquid, contain Aconitum sinomontanum Nakai extract 1% 1:10 compatibility liquid, contain Aconitum sinomontanum Nakai extract 1% 1:25 compatibility liquid, contain the 1:35 compatibility liquid of Aconitum sinomontanum Nakai extract 1%, 1% Radix Paeoniae Alba medicinal liquid 10ml/kg.d-1,4d continuously.4d, 0.5h after the administration of mensuration last, 1h, the pain threshold of 1.5h and 2h.The experimental data data is carried out statistical procedures with the SPSS statistical package.
Table 2 Aconitum sinomontanum Nakai extract and Radix Paeoniae Alba extract compatibility cause the influence (X ± SD) of pain mice to hot plate
| Group | Animal (only) | Dosage (g/kg) | The threshold of pain (s), basis | 30min(s) | 60min(s) |
| |
10 | Distilled water | 21.71±1.99 | 15.88±4.91 | 10.03±2.02 |
| |
10 | 0.2 | 21.49±4.42 | 35.29±12.98** | 31.97± 11.55** |
| Aconitum sinomontanum |
10 | 0.6 | 21.07±5.46 | 21.93±5.67 | 21.24±7.08 |
| Radix Linderae 1:5 |
10 | 0.6 | 21.37±2.88 | 29.22±6.06 | 20.37±4.35 |
| Radix Linderae 1:10 |
10 | 0.6 | 21.31±1.75 | 31.93±5.24* | 30.35±2.60** |
| Radix Linderae 1:25 |
10 | 0.6 | 21.58±4.61 | 23.86±3.66* | 27.02±4.07** |
| Radix Linderae 1:35 |
10 | 0.6 | 20.71±4.23 | 16.61±2.32 | 15.62±3.01 |
| The Radix Paeoniae |
10 | 0.6 | 21.25±5.69 | 19.71±7.27 | 25.69±7.30** |
Annotate: compare * P≤0.05, * * P≤0.01 with model group
Table 2 result shows and respectively organizes mice basis pain threshold there are no significant difference, behind the administration 30min, positive group pain threshold and model group significantly raise, be that 1:5 and 1:10 group pain threshold raises the most remarkable with Aconitum sinomontanum Nakai extract and Radix Paeoniae Alba extract ratio in the compatibility group, with positive group there was no significant difference, other each groups also all have rising.Behind the administration 60min, positive group, 1:5 compatibility group, 1:10 compatibility group, 1:25 compatibility group and Radix Paeoniae Alba extract group pain threshold raise apparent in view, and notable difference is arranged; Behind the administration 120min, Radix Paeoniae Alba extract group and 1:10,1:20 compatibility group pain threshold still keeps higher level.
3, different proportioning Aconitum sinomontanum Nakai extracts and Radix Paeoniae Alba extract xylol cause the influence of scorching mice auricle swelling
Get 130 of male mices, be divided into model control group (N=10), positive controls (N=10), Aconitum sinomontanum Nakai extract (N=10), (ratio of Aconitum sinomontanum Nakai extract and Radix Paeoniae Alba extract) 1:5 compatibility group (N=10), 1:10 compatibility group (N=10), 1:25 compatibility group (N=10), 1:35 compatibility group (N=10), Radix Paeoniae Alba extract group (N=10) at random.By group irritate stomach distilled water, 0.015% dexamethasone medicinal liquid, 1% Aconitum sinomontanum Nakai extract medicinal liquid respectively, contain Aconitum sinomontanum Nakai extract 1% 1:5 compatibility liquid, contain Aconitum sinomontanum Nakai extract 1% 1:10 compatibility liquid, contain Aconitum sinomontanum Nakai extract 1% 1:25 compatibility liquid, contain the 1:35 compatibility liquid of Aconitum sinomontanum Nakai extract 6%, 6% Radix Paeoniae Alba extract medicinal liquid 10ml/kg.d-1,4d continuously.Behind the last administration 0.5h, every the wide instillation 0.04ml of mouse right ear dimethylbenzene, 1.5h takes off cervical vertebra execution after the modeling, wins mice ears sheet respectively at same position with the 6mm card punch, weighs, and asks the difference of two auricles, is the ear swelling degree.Experimental data is handled with the SPSS statistical software.
Table 3 Aconitum sinomontanum Nakai extract and Radix Paeoniae Alba extract compatibility xylol cause the influence (X ± SD) of scorching mice auricle swelling
| Group | Animal (only) | Dosage (g/kg) | Swelling degree (mg) |
| |
10 | Distilled water | 12.80±2.94 |
| |
10 | 0.0015 | 5.60±3.95** |
| Aconitum sinomontanum |
10 | 0.6 | 9.10±2.95** |
| Radix Linderae 1:5 |
10 | 0.6 | 6.40±2.72** |
| Radix Linderae 1:10 |
10 | 0.6 | 7.10±1.43** |
| Radix Linderae 1:25 |
10 | 0.6 | 8.60±2.64 |
| Radix Linderae 1:35 |
10 | 0.6 | 9.90±3.00* |
| The Radix Paeoniae |
10 | 0.6 | 8.60±3.02** |
Annotate: compare * P≤0.05, * * P≤0.01 with model group
The result of table 3 shows that each administration Mice Auricle weight all alleviates to some extent than model group, and wherein positive group, Aconitum sinomontanum Nakai extract and Radix Paeoniae Alba extract 1:5 compatibility group, 1:10 compatibility group auricle weight and model group relatively alleviate significantly, and significant differences is arranged.
(3) experiment conclusion
Above experimental result shows that Aconitum sinomontanum Nakai extract, the Radix Paeoniae Alba extract of different proportionings all have obvious anti-inflammatory and analgesic effect, and its effect is near the curative effect that contrasts medicine.Wherein, (the Aconitum sinomontanum Nakai extract: Radix Paeoniae Alba extract) 1:5 or 1:10 compatibility group best results, effect is better than isodose Aconitum sinomontanum Nakai extract or Radix Paeoniae Alba extract, and showing has certain synergism.
Described embodiment of the present invention now in detail, clearly can do a lot of improvement and variation for a person skilled in the art and can not deviate from essence spirit of the present invention.All these changes and improvements think all within the scope of the present invention that its feature is determined by above-mentioned description.
Claims (13)
- One kind be used for anti-inflammatory and antalgic or the treatment antalgesic pharmaceutical composition, it is characterized in that, described compositions by Aconitum sinomontanum Nakai extract and Radix Paeoniae Alba extract as active component, and pharmaceutically acceptable carrier is formed, the Aconitum sinomontanum Nakai total alkaloid contents of wherein said Aconitum sinomontanum Nakai extract is more than 50%, and wherein the content of lappaconitine is 40%; Content of paeoniflorin is more than 50% in the described Radix Paeoniae Alba extract, andThe weight proportion of described two kinds of extracts is 1: 5-1: 10.
- 2. pharmaceutical composition according to claim 1 is characterized in that content of paeoniflorin is more than 80% in the described Radix Paeoniae Alba extract.
- 3. pharmaceutical composition according to claim 2 is characterized in that, the Aconitum sinomontanum Nakai total alkaloid contents of described Aconitum sinomontanum Nakai extract is more than 80%, and wherein the content of lappaconitine is 60%.
- 4. according to each described pharmaceutical composition of claim 1-3, it is characterized in that said composition is the form of oral, injection or exterior-applied formulation.
- 5. pharmaceutical composition according to claim 4, wherein said peroral dosage form is selected from: tablet, capsule, granule or drop pill; Described injection type is selected from: infusion solution or injectable powder; Described exterior-applied formulation is selected from: ointment, rubber-emplastrum or cataplasma.
- 6. pharmaceutical composition according to claim 5, wherein said capsule is selected from: soft capsule; Described tablet is selected from: dispersible tablet, slow releasing tablet, controlled release tablet or oral cavity quick disintegrating slice.
- 7. pharmaceutical composition according to claim 1 is characterized in that, described carrier is selected from: excipient, filler, diluent, lubricant, wetting agent, disintegrating agent, surfactant, antiseptic, sweeting agent, and/or aromatic.
- 8. each described preparation of drug combination method of claim 1-7 is characterized in that, after described Aconitum sinomontanum Nakai extract and Radix Paeoniae Alba extract mixing, adds pharmaceutically acceptable carrier.
- 9. the described preparation of drug combination method of claim 8 is characterized in that, described Aconitum sinomontanum Nakai extract adopts the alcohol extraction method, and described Radix Paeoniae Alba extract adopts water extracting method.
- 10. preparation of drug combination method according to claim 9, it is characterized in that the alcohol extraction method that wherein said Aconitum sinomontanum Nakai extract adopts comprises: after the Aconitum sinomontanum Nakai pulverizing medicinal materials, with extracting solvent soaking, percolation, collect the percolate of certain volume, last resin column left standstill 24 hours, wash decontamination earlier with water, the certain density ethanol elution of reuse reclaims ethanol to doing, promptly.
- 11. preparation of drug combination method according to claim 10 is characterized in that, the extraction solvent of described extraction Aconitum sinomontanum Nakai is the salt sour water of pH2.0,5% acidic alcohol and/or 5% hydrochloric acid methanol; And/or used ion exchange resin is cation exchange resin, nonpolar or low pole macroporous adsorbent resin.
- 12. preparation of drug combination method according to claim 9 is characterized in that, the water extracting method that wherein said Radix Paeoniae Alba extract adopts comprises: with the white Peony Root water extraction, extracting solution is concentrated into proper volume; Add ethanol to finite concentration, the precipitate with ethanol certain hour is concentrated into proper volume; The concentrated solution macroporous resin adsorption washes with water to effluent colourlessly earlier, and ethanol elution is collected in reuse finite concentration ethanolysis absorption, reclaims ethanol, drying, promptly.
- 13. one kind is used for application on anti-inflammation analgesis medicament or the treatment antalgesic medicine according to each described pharmaceutical composition of claim 1-7 in preparation.
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| CN1416888A (en) * | 2002-12-19 | 2003-05-14 | 中国医药研究开发中心 | White peony and licorice extract and its prepn process |
| CN1817865A (en) * | 2006-03-03 | 2006-08-16 | 甘肃奇正藏药有限公司 | Preparation of sinomontanine and its hydrobromide |
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| CN1416888A (en) * | 2002-12-19 | 2003-05-14 | 中国医药研究开发中心 | White peony and licorice extract and its prepn process |
| CN1817865A (en) * | 2006-03-03 | 2006-08-16 | 甘肃奇正藏药有限公司 | Preparation of sinomontanine and its hydrobromide |
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| Title |
|---|
| 张茂清等.白芍总苷的临床应用进展.《儿科药学杂志》.2006,第12卷(第1期), * |
| 无.甘肃一些地产药材具有新的开发价值.《医学信息》.1997,第10卷(第10期), * |
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