CN106176938A - A kind of Chinese medicine composition of antipyretic analgesic and preparation method thereof - Google Patents
A kind of Chinese medicine composition of antipyretic analgesic and preparation method thereof Download PDFInfo
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Abstract
The invention discloses Chinese medicine composition of a kind of antipyretic analgesic and preparation method thereof.Crude drug including following weight portion: Radix Bupleuri 200～300 parts, Rhizoma Et Radix Notopterygii 130～200 parts, Ramulus Cinnamomi 65～90 parts and Herba Artemisiae Scopariae 300～450 parts.The cheaper starting materials of the Chinese medicine composition of the antipyretic analgesic of the present invention is easy to get, have no side effect, and there is significant antipyretic analgesic drug effect, it can be clinical efficacy offer pharmacology's foundation of the Chinese medicine composition of antipyretic analgesic, for the Research Thinking that the secondary development offer of Chinese medicine compound is new, the most also the new drug development for the Chinese medicine composition of this antipyretic analgesic lays the first stone.
Description
Technical field:
The invention belongs to field of traditional Chinese, be specifically related to Chinese medicine composition of a kind of antipyretic analgesic and preparation method thereof.
Background technology:
Flu, is commonly called as cold, is respiratory tract common disease, and clinic mainly shows as respiratory symptom, is often accompanied by headache, sends out
The symptoms such as heat.General clinic is common with wind and cold, anemopyretic cold.Anemofrigid cold Symptoms is aversion to cold weight, generate heat light, lossless, head
Dilute white expectorant, the most thirsty or thirsty desire for hot drinks of mouth, white and thin fur are told in general pain, stuffy nose with watery discharge, cough bitterly.Though flu is considered as little by most people
Disease, but the commonly encountered diseases of clinic and frequently-occurring disease, greatly affect the normal study and work of patient, can cause Other diseases,
The most serious goes back life-threatening.At present, it is clinical practice with the nonsteroidal antiinflammatory drug (NSAID) the antipyretic analgesic medicine as representative
At most, a widest class medicine.But, there is a lot of untoward reaction in life-time service, such as gastrointestinal tract, cardiovascular, liver, kidney
Dirty, central nervous system etc. damage.Thus, seek the research side that the antipyretic analgesic medicine of good effect and few side effects has become new
To.
Summary of the invention:
First purpose of the present invention is to provide the Chinese medicine composition of a kind of antipyretic analgesic.
The Chinese medicine composition of a kind of antipyretic analgesic, it is characterised in that include the crude drug of following weight portion: Radix Bupleuri 200
～300 parts, Rhizoma Et Radix Notopterygii 130～200 parts, Ramulus Cinnamomi 65～90 parts and Herba Artemisiae Scopariae 300～450 parts.
Preferably, including the crude drug of following weight portion: Radix Bupleuri 250 parts, Rhizoma Et Radix Notopterygii 166.7 parts, Ramulus Cinnamomi 83.3 parts and Herba Artemisiae Scopariae
333.3 part.
A kind of soft capsule of the Chinese medicine composition containing above-mentioned antipyretic analgesic.Preferably, in described soft capsule includes capsule
Thing and softgel shell, in described capsule, thing includes the Chinese medicine composition of above-mentioned antipyretic analgesic.
The preparation method of a kind of above-mentioned soft capsule, it is characterised in that comprise the following steps: claim respectively by required weight portion
Take Radix Bupleuri, Rhizoma Et Radix Notopterygii, Ramulus Cinnamomi and Herba Artemisiae Scopariae, after clean system, pulverizing, use supercritical CO2Fluid extraction is extracted thing, will extraction
Thing beta-schardinger dextrin-carries out embedding and obtains clathrate, and extract is 1:8 with the mass ratio of beta-schardinger dextrin-, by clathrate and soybean oil
1:1.5 in mass ratio mixes, and adds soybean phospholipid, and its addition accounts in capsule the 1% of thing gross mass, and mixing grinds well and obtains
Thing in capsule, powder charge capsule, prepare soft capsule.
Preferably, described extract first passes through after molecular distillation obtains steaming thing, then will steam thing beta-schardinger dextrin-and carry out
Embedding obtains clathrate, and the mass ratio steaming thing and beta-schardinger dextrin-is 1:8.
Preferably, described through clean system, pulverize after, use supercritical CO2It is by warp system, powder only that fluid extraction is extracted thing
Crude drug after broken, in extracting pressure 25Mpa, extraction temperature 45 DEG C, resolves pressure 6.7Mpa, resolution temperature 50 DEG C, CO2Flow velocity
Under the conditions of 300kg/h, constant temperature and pressure extraction 3.5h, it is extracted thing.
Described extract first pass through molecular distillation obtain steaming thing be water-soluble for extract heating is dissolved after, in temperature
100 DEG C, vacuum 100Pa, scrape Membrane Materials rotating speed 260～280r min-1, sample introduction speed 1.5mL min-1Under the conditions of, carry out
Molecular distillation, obtains steaming thing.
The cheaper starting materials of the Chinese medicine composition of the antipyretic analgesic of the present invention is easy to get, and has no side effect, and has significantly solution
Hot pain relieving drug effect, can be that the clinical efficacy of the Chinese medicine composition of antipyretic analgesic provides pharmacology's foundation, for the secondary of Chinese medicine compound
Exploitation provides new Research Thinking, and the most also the new drug development for the Chinese medicine composition of this antipyretic analgesic lays the first stone.
Accompanying drawing illustrates:
Fig. 1 is the impact on the rat temperature that generates heat caused by LPS of the Chinese medicine composition of antipyretic analgesic.
Detailed description of the invention:
Following example are to further illustrate the present invention rather than limitation of the present invention.
Embodiment 1:
The Chinese medicine composition of the antipyretic analgesic of the present embodiment, including following crude drug: Radix Bupleuri 2500g, Rhizoma Et Radix Notopterygii 1667g,
Ramulus Cinnamomi 833g and Herba Artemisiae Scopariae 3333g.
The preparation method of the soft capsule of the Chinese medicine composition of the antipyretic analgesic of the present embodiment, comprises the following steps:
A, weigh above-mentioned 4 taste crude drug, through clean system, pulverize after, cross 30 mesh sieves, the crude drug after sieving puts into supercritical
In extraction kettle, in extracting pressure 25MPa, extraction temperature 45 DEG C, resolve pressure 6.7MPa, resolution temperature 50 DEG C, CO2Flow velocity is
Under the conditions of 300kg/h, constant temperature and pressure extraction 3.5h discharging, it is extracted thing, puts and add a cover in wide mouthed bottle, 4 DEG C of Refrigerator stores are standby；
B, take extract 470g, after water-soluble heating is dissolved, according to temperature 100 DEG C, vacuum 100Pa, scrape Membrane Materials rotating speed
260～280r min-1Under conditions of, with 1.5mL min-1Constant sample introduction speed sample introduction, carries out molecular distillation, is steamed
Go out thing a about 200mL, distillation b about l200mL；Again distillation b is added from charging aperture, open thermostatic heater and be heated to 70
DEG C, it is allowed to be melt into liquid, according to temperature 200 DEG C, vacuum 100Pa, scrapes Membrane Materials rotating speed 300r min-1, flow velocity is 1mL
min-1Under the conditions of fully distill, thing a1 about 50mL, distillation b1 about 800mL must be steamed, distillation b1 is given up, obtains steaming thing
A is 210g, and yield is 1.4%；Steaming thing a1 is 48g, and yield is 0.32%；
The preparation of thing in c, capsule: the ethanol solution of thing a (or steaming thing a and the mixture steaming thing a1) will be steamed
(steaming thing a with the mass volume ratio of dehydrated alcohol is 1g:2mL) is slowly dropped in the saturated aqueous solution of beta-schardinger dextrin-(saturated
Aqua-solution method), on magnetic force heating stirrer 40 DEG C, stirring 2h embeds, and cooling is placed in cold preservation 24h in refrigerator, and decompression is taken out
Filter, precipitate washs to odorlessness with a small amount of distilled water and acetic acid ethyl fluid successively, 40 DEG C of vacuum drying 24h, grinds, is wrapped
Compound (mass ratio steaming thing a and beta-schardinger dextrin-is 1:8)；Clathrate is mixed for 1:1.5 in mass ratio with soybean oil,
Adding soybean phospholipid, its addition accounts in capsule the 1% of thing gross mass, and mixing grinds well, and obtains thing in capsule；
D, the preparation of glue: by glycerol, water, methyl butex (its addition accounts for the 0.2% of glue gross mass), dioxy
Change titanium (its addition accounts for the 0.03% of glue gross mass) and put in glue pot, stir and make dissolving, be heated to 80 DEG C, add bright
Glue stirring mixing 30min (mass ratio of glycerol, gelatin and water is 0.4:1:1), ultrasonic degassing 30min, 60 DEG C of insulations, standby；
E, the preparation of soft capsule: thing in above-mentioned prepared capsule and glue are placed in encapsulating machine, by running parameter (glue box
Temperature 50 C, sprinkler body temperature 40 DEG C, rotating speed 1r/min, rubber thickness 0.6～0.02mm) powder charge capsule, temperature 20 DEG C, relatively
Humidity 20%～30% rotating cage is dried 48h, and by 95% ethanol purge post-drying, prepared specification is 0.5g soft capsule 1000
Grain.
Embodiment 2:
The Chinese medicine composition of the antipyretic analgesic of the present embodiment, including following crude drug: Radix Bupleuri 2000g, Rhizoma Et Radix Notopterygii 2000g,
Ramulus Cinnamomi 900g and Herba Artemisiae Scopariae 3000g.
The preparation method of the soft capsule of the Chinese medicine composition of the antipyretic analgesic of the present embodiment, comprises the following steps:
A, weigh above-mentioned 4 taste crude drug, through clean system, pulverize after, cross 30 mesh sieves, the crude drug after sieving puts into supercritical
In extraction kettle, in extracting pressure 20MPa, extraction temperature 40 DEG C, resolve pressure 7.1MPa, resolution temperature 30 DEG C, CO2Flow velocity is
Under the conditions of 300kg/h, constant temperature and pressure extraction 3.5h discharging, it is extracted thing, puts and add a cover in wide mouthed bottle, 4 DEG C of Refrigerator stores are standby；
B, take extract, after water-soluble heating is dissolved, according to temperature 100 DEG C, vacuum 100Pa, scrape Membrane Materials rotating speed 260～
280r·min-1Under conditions of, with 1.5mL min-1Constant sample introduction speed sample introduction, carries out molecular distillation, obtains steaming thing；
The preparation of thing in c, capsule: (mass volume ratio steaming thing and dehydrated alcohol is by the ethanol solution that steams thing
1g:2mL) it is slowly dropped in the saturated aqueous solution of beta-schardinger dextrin-(saturated water solution method), on magnetic force heating stirrer 40 DEG C,
Stirring 2h embeds, and cooling is placed in cold preservation 24h in refrigerator, and reduce pressure sucking filtration, and precipitate is successively by a small amount of distilled water and acetic acid second
Ester liquid washs to odorlessness, 40 DEG C of vacuum drying 24h, grinds, obtain clathrate (mass ratio steaming thing and beta-schardinger dextrin-is 1:
8)；Being mixed for 1:1.5 in mass ratio with soybean oil by clathrate, add soybean phospholipid, in its addition accounts for capsule, thing is total
The 1% of quality, mixing grinds well, and obtains thing in capsule；
D, the preparation of glue: by glycerol, water, methyl butex (its addition accounts for the 0.2% of glue gross mass), dioxy
Change titanium (its addition accounts for the 0.03% of glue gross mass) and put in glue pot, stir and make dissolving, be heated to 80 DEG C, add bright
Glue stirring mixing 30min (mass ratio of glycerol, gelatin and water is 0.4:1:1), ultrasonic degassing 30min, 60 DEG C of insulations, standby；
E, the preparation of soft capsule: thing in above-mentioned prepared capsule and glue are placed in encapsulating machine, by running parameter (glue box
Temperature 50 C, sprinkler body temperature 40 DEG C, rotating speed 1r/min, rubber thickness 0.6～0.02mm) powder charge capsule, temperature 20 DEG C, relatively
Humidity 20%～30% rotating cage is dried 48h, and by 95% ethanol purge post-drying, prepared specification is 0.5g soft capsule.
Through analgesic experiment (glacial acetic acid writhing method) and antipyretic it is demonstrated experimentally that the Chinese medicine composition of antipyretic analgesic of the present embodiment
The mice threshold of pain can be significantly improved and reduce rat temperature, there is significant antipyretic effect.
Embodiment 3:
The Chinese medicine composition of the antipyretic analgesic of the present embodiment, including following crude drug: Radix Bupleuri 3000g, Rhizoma Et Radix Notopterygii 1300g,
Ramulus Cinnamomi 650g and Herba Artemisiae Scopariae 3000g.
The preparation method of the soft capsule of the Chinese medicine composition of the antipyretic analgesic of the present embodiment, comprises the following steps:
A, weigh above-mentioned 4 taste crude drug, through clean system, pulverize after, cross 30 mesh sieves, the crude drug after sieving puts into supercritical
In extraction kettle, in extracting pressure 30MPa, extraction temperature 35 DEG C, resolve pressure 6.3MPa, resolution temperature 40 DEG C, CO2Flow velocity is
Under the conditions of 300kg/h, constant temperature and pressure extraction 3.5h discharging, it is extracted thing, puts and add a cover in wide mouthed bottle, 4 DEG C of Refrigerator stores are standby；
B, take extract, after water-soluble heating is dissolved, according to temperature 100 DEG C, vacuum 100Pa, scrape Membrane Materials rotating speed 260～
280r·min-1Under conditions of, with 1.5mL min-1Constant sample introduction speed sample introduction, carries out molecular distillation, obtains steaming thing；
The preparation of thing in c, capsule: (mass volume ratio steaming thing and dehydrated alcohol is by the ethanol solution that steams thing
1g:2mL) it is slowly dropped in the saturated aqueous solution of beta-schardinger dextrin-(saturated water solution method), on magnetic force heating stirrer 40 DEG C,
Stirring 2h embeds, and cooling is placed in cold preservation 24h in refrigerator, and reduce pressure sucking filtration, and precipitate is successively by a small amount of distilled water and acetic acid second
Ester liquid washs to odorlessness, 40 DEG C of vacuum drying 24h, grinds, obtain clathrate (mass ratio steaming thing and beta-schardinger dextrin-is 1:
8)；Being mixed for 1:1.5 in mass ratio with soybean oil by clathrate, add soybean phospholipid, in its addition accounts for capsule, thing is total
The 1% of quality, mixing grinds well, and obtains thing in capsule；
D, the preparation of glue: by glycerol, water, methyl butex (its addition accounts for the 0.2% of glue gross mass), dioxy
Change titanium (its addition accounts for the 0.03% of glue gross mass) and put in glue pot, stir and make dissolving, be heated to 80 DEG C, add bright
Glue stirring mixing 30min (mass ratio of glycerol, gelatin and water is 0.4:1:1), ultrasonic degassing 30min, 60 DEG C of insulations, standby；
E, the preparation of soft capsule: thing in capsule and glue are placed in encapsulating machine, by running parameter (glue box temperature 50 C,
Sprinkler body temperature 40 DEG C, rotating speed 1r/min, rubber thickness 0.6～0.02mm) powder charge capsule, at temperature 20 DEG C, relative humidity 20%
～30% be dried 48h in rotating cage, and by 95% ethanol purge post-drying, prepared specification is 0.5g soft capsule.
Through analgesic experiment (glacial acetic acid writhing method) and antipyretic it is demonstrated experimentally that the Chinese medicine composition of antipyretic analgesic of the present embodiment
The mice threshold of pain can be significantly improved and reduce rat temperature, there is significant antipyretic effect.
Embodiment 4:
The Chinese medicine composition of the antipyretic analgesic of the present embodiment, including following crude drug: Radix Bupleuri 2800g, Rhizoma Et Radix Notopterygii 1850g,
Ramulus Cinnamomi 850g and Herba Artemisiae Scopariae 4000g.
The preparation method of the soft capsule of the Chinese medicine composition of the antipyretic analgesic of the present embodiment, comprises the following steps:
A, weigh above-mentioned 4 taste crude drug, through clean system, pulverize after, cross 30 mesh sieves, the crude drug after sieving puts into supercritical
In extraction kettle, in extracting pressure 20MPa, extraction temperature 35 DEG C, resolve pressure 6.3MPa, resolution temperature 40 DEG C, CO2Flow velocity is
Under the conditions of 300kg/h, constant temperature and pressure extraction 3.5h discharging, it is extracted thing, puts and add a cover in wide mouthed bottle, 4 DEG C of Refrigerator stores are standby；
B, take extract, after water-soluble heating is dissolved, according to temperature 100 DEG C, vacuum 100Pa, scrape Membrane Materials rotating speed 260～
280r·min-1Under conditions of, with 1.5mL min-1Constant sample introduction speed sample introduction, carries out molecular distillation, obtains steaming thing；
The preparation of thing in c, capsule: (mass volume ratio steaming thing and dehydrated alcohol is by the ethanol solution that steams thing
1g:2mL) it is slowly dropped in the saturated aqueous solution of beta-schardinger dextrin-(saturated water solution method), on magnetic force heating stirrer 40 DEG C,
Stirring 2h embeds, and cooling is placed in cold preservation 24h in refrigerator, and reduce pressure sucking filtration, and precipitate is successively by a small amount of distilled water and acetic acid second
Ester liquid washs to odorlessness, 40 DEG C of vacuum drying 24h, grinds, obtain clathrate (mass ratio steaming thing and beta-schardinger dextrin-is 1:
8)；By clathrate and soybean oil, carrying out for 1:1.5 in mass ratio mixes, and adds soybean phospholipid, and its addition accounts for thing in capsule
The 1% of gross mass, mixing grinds well, and obtains thing in capsule；
D, the preparation of glue: by glycerol, water, methyl butex (its addition accounts for the 0.2% of glue gross mass), dioxy
Change titanium (its addition accounts for the 0.03% of glue gross mass) and put in glue pot, stir and make dissolving, be heated to 80 DEG C, add bright
Glue stirring mixing 30min (mass ratio of glycerol, gelatin and water is 0.4:1:1), ultrasonic degassing 30min, 60 DEG C of insulations, standby；
E, the preparation of soft capsule: thing in capsule and glue are placed in encapsulating machine, by running parameter (glue box temperature 50 C,
Sprinkler body temperature 40 DEG C, rotating speed 1r/min, rubber thickness 0.6～0.02mm) powder charge capsule, at temperature 20 DEG C, relative humidity 20%
～30% be dried 48h in rotating cage, and by 95% ethanol purge post-drying, prepared specification is 0.5g soft capsule.
Through analgesic experiment (glacial acetic acid writhing method) and antipyretic it is demonstrated experimentally that the Chinese medicine composition of antipyretic analgesic of the present embodiment
The mice threshold of pain can be significantly improved and reduce rat temperature, there is significant antipyretic effect.
Embodiment 5:
The Chinese medicine composition of the antipyretic analgesic of the present embodiment, including following crude drug: Radix Bupleuri 2800g, Rhizoma Et Radix Notopterygii 1667g,
Ramulus Cinnamomi 700g and Herba Artemisiae Scopariae 4500g.
The preparation method of the soft capsule of the Chinese medicine composition of the antipyretic analgesic of the present embodiment, comprises the following steps:
A, weigh above-mentioned 4 taste crude drug, through clean system, pulverize after, cross 30 mesh sieves, the crude drug after sieving puts into supercritical
In extraction kettle, in extracting pressure 20MPa, extraction temperature 35 DEG C, resolve pressure 6.3MPa, resolution temperature 30 DEG C, CO2Flow velocity is
Under the conditions of 300kg/h, constant temperature and pressure extraction 3.5h discharging, it is extracted thing, puts and add a cover in wide mouthed bottle, 4 DEG C of Refrigerator stores are standby；
B, take extract, after water-soluble heating is dissolved, temperature 100 DEG C, vacuum 100Pa, scrape Membrane Materials rotating speed 260～
280r·min-1Under the conditions of, with 1.5mL min-1Constant sample introduction speed sample introduction, carries out molecular distillation, obtains steaming thing；
The preparation of thing in c, capsule: (mass volume ratio steaming thing and dehydrated alcohol is by the ethanol solution that steams thing
1g:2mL) it is slowly dropped in the saturated aqueous solution of beta-schardinger dextrin-(saturated water solution method), on magnetic force heating stirrer 40 DEG C,
Stirring 2h embeds, and cooling is placed in cold preservation 24h in refrigerator, and reduce pressure sucking filtration, and precipitate is successively by a small amount of distilled water and acetic acid second
Ester liquid washs to odorlessness, 40 DEG C of vacuum drying 24h, grinds, obtain clathrate (mass ratio steaming thing and beta-schardinger dextrin-is 1:
8)；By clathrate and soybean oil, ratio for 1:1.5 in mass ratio mixes, and adds soybean phospholipid, and its addition accounts for capsule
The 1% of interior thing gross mass, mixing grinds well, and obtains thing in capsule；
D, the preparation of glue: by glycerol, water, methyl butex (its addition accounts for the 0.2% of glue gross mass), dioxy
Change titanium (its addition accounts for the 0.03% of glue gross mass) and put in glue pot, stir and make dissolving, be heated to 80 DEG C, add bright
Glue stirring mixing 30min (mass ratio of glycerol, gelatin and water is 0.4:1:1), ultrasonic degassing 30min, 60 DEG C of insulations, standby；
E, the preparation of soft capsule: thing in capsule and glue are placed in encapsulating machine, by running parameter (glue box temperature 50 C,
Sprinkler body temperature 40 DEG C, rotating speed 1r/min, rubber thickness 0.6～0.02mm) powder charge capsule, at temperature 20 DEG C, relative humidity 20%
～30% be dried 48h in rotating cage, and by 95% ethanol purge post-drying, prepared specification is 0.5g soft capsule.
Through analgesic experiment (glacial acetic acid writhing method) and antipyretic it is demonstrated experimentally that the Chinese medicine composition of antipyretic analgesic of the present embodiment
The mice threshold of pain can be significantly improved and reduce rat temperature, there is significant antipyretic effect.
Embodiment 6: the antipyretic-antalgic drug effect test of the Chinese medicine composition of antipyretic analgesic
1 material
1.1 instrument
M D-S80 type M D device (the Guangzhou Chinese dimension cold air electromechanics company limited)；YLS-6A type intelligence hot-plate instrument (Shandong Province
Supply of equipment station, the Academy of Medical Sciences).
1.2 reagent
What embodiment 1 prepared steams thing a and steams thing a1；Tween-60 (chemical reagent glass apparatus wholesale department, Guangzhou)；
1% rotundine (Boluo County, Guangdong Province with INAA pioneer Pharmaceutical Group Co., Ltd, lot number: 021001)；Remaining reagent is analytical pure.
1.3 animal
NIH mice 120, ♀ ♂ has concurrently, body weight 18～22g, Nanfang Medical Univ's animal experimental center provide (animal
Produce the quality certification number: 2005A067).
2 methods and result
2.1 analgesia effect experiments
2.1.1 the preparation of Experimental agents: take above-mentioned steaming thing a and steam thing a1, add Tween-60 appropriate, with the 2 of mice
Individual bioequivalence is low dosage, and 4 bioequivalences are high dose, i.e. steam thing a high and low dose group be respectively 46.67,
23.33mg·kg-1.Steam thing a1 high and low dose group be respectively 10.67,5.33mg kg-1.Rotundine (the 6mg kg of 1%-1) it is positive controls, the normal saline containing Tween-60 is blank group.
2.1.2 hot-plate analgesia experiment: take ♀ NIH mice 60, before measuring mice administration with YLS-6A type intelligence hot-plate instrument
Pain threshold, rejects pain threshold and is less than the mice of 5s more than 60s and pain threshold.Be divided into 6 groups by said medicine, i.e. blank group,
Rotundine group, steam thing a high and low dose group and steam thing a1 high and low dose group.Mice is with the continuous gavage of 0.2mL/10g body weight
(ig) 2d, to adapt to laboratory condition, within the 3rd day, regulation hot-plate instrument temperature is 55 DEG C, gives by 0.2mL/10g body weight gavage (ig)
Medicine, respectively at be administered before and administration after 30,60,90min measure mice pain threshold.Hot plate method measures and steams the thing analgesia to mice
Effect is shown in Table 1.
Table 1 hot plate method measures and steams the thing analgesic activity (χ ± S, n=10) to mice
Note: compare with blank group:*P < 0.05,**P<0.01
2.1.3 writhing assay: NIH mice 60, ♀ ♂ half and half, is grouped, is administered same 2.1.2 item, 1h after last is administered,
Mouse peritoneal injection (ip) 0.6% glacial acetic acid solution (0.1mL/10g body weight), then observes 20min mouse writhing number of times.Calculate
Analgesia percentage rate: analgesia percentage rate=(blank group average writhing number of times experimental group average writhing number of times)/blank
Organize average writhing number of times.Writhing method mensuration steams thing and the analgesic activity of mice is shown in Table 2.
Table 2 writhing method measures and steams the thing analgesic activity to mice
Note: compare with blank group:*P < 0.05,**P<0.01
From table 1, table 2 analgesic experiment data, the analgesic effect steaming thing a is better than steaming thing a1, and this steams thing a has
Well antipyretic-antalgic effect, thus show that the clinical efficacy of the Chinese medicine composition of the antipyretic analgesic of the present invention has clear and definite medicine
Effect basis, the most also the new drug development for Chinese medicine composition based on this antipyretic analgesic lays the foundation.
Embodiment 7:
What Example 1 obtained steam thing a carries out further antipyretic-antalgic drug effect evaluation
1 material and instrument
1.1 medicines and reagent: what embodiment 1 prepared steam thing a about 250mL, and Hyndarin (sulphuric acid Hyndarin injection, extensively
East saves Boluo pioneer Pharmaceutical Group Co., Ltd, lot number 070802)；Purification LPS lipopolysaccharide (Sigma subpackage)；Aspirin is (military
The Chinese long-range pharmacy Group Co., Ltd, every contains aspirin 220mg, phenacetin 150mg, caffeine 35mg, produces batch
Number: 070304)；Tween 80 (Sigma company subpackage, numbering P1754)；Glacial acetic acid, domestic analytical pure.
1.2 experimental apparatus: YLS-6B intelligence hot-plate instrument (factory number 004060042, Shandong Academy of Medical Sciences)；BL-
2000S electronic balance (Setra company)；KD-204 digital electronic clinical thermometer (Pola Kanggong department of Germany).
1.3 laboratory animals: SPF level NIH mice, weight 18～22g, SPF level SD rat, weight 180～220g, all
It is purchased from Nanfang Medical Univ's Experimental Animal Center, the quality certification number: SCXK (Guangdong) 2006-0015.The equal sub-cage rearing of laboratory animal, mark
Quasi-pellet, drinking-water of freely ingesting, room temperature 20 DEG C ± 2 DEG C, relative humidity 55%～60%.
2 methods
2.1 medicine preparation and packets: analgesic experiment, select people: mice=1:12 multiple proportions relation is prepared, and this is only brought down a fever
The Chinese medicine composition quantity of pain is adult 50g/d, selects the 1 of clinical dosage, 2,4 multiple proportions relations, will steam thing a and be configured to
Basic, normal, high 3 bioequivalence dosage, add appropriate tween 80 and do solubilizing agent, i.e. 140mg/kg (is equivalent to crude drug 10.27g/
Kg), 280mg/kg (being equivalent to crude drug 20.54g/kg), 560mg/kg (being equivalent to crude drug 41.08g/kg).Positive controls is
2% Hyndarin (12mg/kg), blank group is normal saline.Antipyretic experiment, selection people: rat=1:6 compounding pharmaceutical, side
Method ibid, i.e. 14mg/kg (being equivalent to crude drug 1.027g/kg), 28mg/kg (being equivalent to crude drug 2.054g/kg), 56mg/kg (phase
When in crude drug 4.108g/kg), positive controls is aspirin 200mg/kg, and blank group is normal saline.LPS dilutes
Being configured to the solution of 20 μ g/mL in physiological saline solution ,-20 DEG C of Refrigerator stores are standby.
2.2 analgesic experiments (hot plate method): take female NIH mice, the threshold of pain screening before testing, mice is placed in 55 DEG C
On the hot-plate instrument of ± 0.5 DEG C, contact hot plate in record mice vola is to the response time (incubation period) licking metapedes occur as the threshold of pain
Index.The screening threshold of pain 5～30s person formally test for qualified mice, are randomly divided into 5 groups, and packet situation, with 2.1, is administered
2 times, the front mensuration threshold of pain, is spaced the threshold of pain based on 10min averages.After gastric infusion 30,60,90,120min respectively repeats to survey
Surely lick sufficient incubation period, record pain threshold, calculate by 60s more than 60s.
2.3 analgesic experiments (glacial acetic acid writhing method): take NIH mice, male and female half and half, are randomly divided into 5 groups, and packet situation is same
On, the equal gastric infusion of each group, 1 times/day, continuous 3d.1h after last is administered, each group mouse peritoneal injects 0.6% glacial acetic acid
0.1mL/10g, mouse writhing reaction in record 20min (abdominal part contraction indent, stretching, extension hind leg, buttocks are raised) number of times, calculate and turn round
Precursor reactant suppression ratio.
Response inhabitation rate/%=(blank group average writhing number of times experimental group average writhing number of times)/blank
Organize average writhing number of times × 100%.
2.4 antipyretic experiments: rat is placed in simulation experiment operation in experimental situation in first 3 days and (includes arresting, admittedly by formal experiment
Fixed, gavage, lay thermometer) to adapt to laboratory condition, measure body temperature (anus temperature) every day 2 times, single body temperature is more than 38 DEG C or 2
The rejecting more than 0.5 DEG C of the secondary body temperature difference need not, filter out qualified rat 48, body temperature is 37.5 DEG C ± 0.5 DEG C, is randomly divided into 5
Group, packet situation is with 2.1.Started formal experiment in the 4th day, before experiment, water is can't help in 6h animal fasting, makes emptying defecate, modeling
Pre-test body temperature 2 times, is spaced 10min, body temperature based on averaging.Gavage LPS (20 μ g/kg) replicates rat fever mould
Type, measures body temperature and raises, it was demonstrated that fever model is successfully established after 30min.Then, respectively organizing gastric infusion, every 30min measures 1 time
Body temperature, measures 3h continuously, records Temperature changing △ T.
2.5 statistical procedures: experimental data all withRepresent, use SPSS13.0 statistical software to be analyzed.
3 results
Before the impact that mouse hot-plate is tested by the Chinese medicine composition of 3.1 antipyretic analgesics: result is as shown in table 3, with medication and
Matched group compares, and each Experimental agents group all can be obviously prolonged mouse hot-plate and lick sufficient incubation period.High dose group all exists with positive group
30min i.e. starts effective (P < 0.05), and when 90min and 120min, each dosage group is significantly increased the mice threshold of pain, extends and licks foot
Incubation period (P < 0.01 or P < 0.05).
Table 3 is respectively organized the hot plate method in mice threshold of pain and is compared incubation period
Note: compare with matched group:*P < 0.05,**P<0.01
The impact that glacial acetic acid mouse writhing is reacted by the Chinese medicine composition of 3.2 antipyretic analgesics
Result is as shown in table 4, and lumbar injection glacial acetic acid can induce mouse writhing reaction, compares with matched group, antipyretic analgesic
Dissipating each dosage group and all can substantially reduce mouse writhing reaction (P < 0.01), the suppression ratio of basic, normal, high dosage group is respectively
48.81%, 61.80%, 63.91%, present a certain amount of effect relationship.
Table 4 is respectively organized mice glacial acetic acid writhing response number of times and is compared
Note: compare with matched group,**P<0.01
The impact on the rat temperature that generates heat caused by LPS of the Chinese medicine composition of 3.3 antipyretic analgesics
Result as it is shown in figure 1, after matched group gavage LPS 30min rat temperature start raise, peak at 120min.
Rat temperature averagely raises 1～1.5 DEG C.Each modeling rat all body temperature risings after gavage LPS 30min, it was demonstrated that modeling success.
Each experimental group be administered after compared with matched group body temperature substantially reduce, slightly above positive controls, 120min be down to minimum (P <
0.01), 3 the dosage groups steaming thing a all have obvious refrigeration function, but without obvious dose-effect relationship between 3 dosage groups.
Above result of study shows, the Chinese medicine composition of this antipyretic analgesic has good antipyretic-antalgic drug effect, but it has
The body mechanism of action needs further to study.This experiment is by the steaming of the Chinese medicine composition of the antipyretic analgesic to embodiment 1
Go out thing a and carry out pharmacodynamic evaluation, can be that the clinical efficacy of the Chinese medicine composition of antipyretic analgesic provides pharmacology's foundation, for middle recurrence due to taking drug
The secondary development of side provides new Research Thinking, and the most also the new drug development of the Chinese medicine composition of this antipyretic analgesic lays the first stone.
Claims (8)
1. the Chinese medicine composition of an antipyretic analgesic, it is characterised in that include the crude drug of following weight portion: Radix Bupleuri 200～
300 parts, Rhizoma Et Radix Notopterygii 130～200 parts, Ramulus Cinnamomi 65～90 parts and Herba Artemisiae Scopariae 300～450 parts.
The Chinese medicine composition of antipyretic analgesic the most according to claim 1, it is characterised in that include the raw material of following weight portion
Medicine: Radix Bupleuri 250 parts, Rhizoma Et Radix Notopterygii 166.7 parts, Ramulus Cinnamomi 83.3 parts and Herba Artemisiae Scopariae 333.3 parts.
3. the soft capsule of the Chinese medicine composition containing the antipyretic analgesic described in claim 1 or 2.
Soft capsule the most according to claim 3, it is characterised in that described soft capsule includes thing and softgel shell in capsule, described
Capsule in thing include the Chinese medicine composition of the antipyretic analgesic described in claim 1 or 2.
5. the preparation method of the soft capsule described in a claim 3, it is characterised in that comprise the following steps: by required weight
Part weighs Radix Bupleuri, Rhizoma Et Radix Notopterygii, Ramulus Cinnamomi and Herba Artemisiae Scopariae respectively, after clean system, pulverizing, uses supercritical CO2Fluid extraction is extracted
Thing, carries out extract beta-schardinger dextrin-embedding and obtains clathrate, and extract is 1:8 with the mass ratio of beta-schardinger dextrin-, by inclusion
Thing mixes with soybean oil 1:1.5 in mass ratio, adds soybean phospholipid, and its addition accounts in capsule the 1% of thing gross mass, mixed
Conjunction grinds well and obtains thing in capsule, powder charge capsule, prepares soft capsule.
The preparation method of soft capsule the most according to claim 5, it is characterised in that described extract first passes through molecule and steams
Evaporate after obtaining steaming thing, then thing beta-schardinger dextrin-will be steamed carry out embedding and obtain clathrate, steam the quality of thing and beta-schardinger dextrin-
Ratio is 1:8.
The preparation method of soft capsule the most according to claim 5, it is characterised in that described through clean system, pulverize after, use
Supercritical CO2It is by the crude drug after clean system, pulverizing that fluid extraction is extracted thing, in extracting pressure 25Mpa, extraction temperature
45 DEG C, parsing pressure 6.7Mpa, resolution temperature 50 DEG C, CO2Under the conditions of flow velocity is 300kg/h, constant temperature and pressure extraction 3.5h, obtain
Extract.
The preparation method of soft capsule the most according to claim 6, it is characterised in that described extract first passes through molecule and steams
Evaporate obtain steaming thing be water-soluble for extract heating is dissolved after, in temperature 100 DEG C, vacuum 100Pa, scrape Membrane Materials rotating speed 260
～280r min-1, sample introduction speed 1.5mL min-1Under the conditions of, carry out molecular distillation, obtain steaming thing.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN112190597A (en) * | 2019-07-08 | 2021-01-08 | 上海凯宝药业股份有限公司 | Application of biotransformation bear gall powder in preparation of antipyretic medicine |
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