CN100404020C - Chuanxiong rhizome volatile oil soft capsule and its preparation method - Google Patents
Chuanxiong rhizome volatile oil soft capsule and its preparation method Download PDFInfo
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Abstract
The present invention provides a Chuanxiong rhizome volatile oil soft capsule and its preparation method and use. The Chuanxiong rhizome volatile oil described in the invention is prepared by a carbon dioxide supercritical extraction method, the contend of the effective component Chuanxiong rhizome phthalide in the Chuanxiong rhizome volatile oil reaches the medicinal standard, and the quality is stable and can be controlled. The invention also provides the use of the Chuanxiong rhizome volatile oil soft capsule for preparing the medicine for curing cerebral apoplexy during recovery period.
Description
Technical field
The present invention relates to a kind of soft capsule and its production and use, relate to Rhizoma Chuanxiong oil soft capsule and its production and use particularly.
Background technology
Rhizoma Chuanxiong records in " 2 years versions of Pharmacopoeia of People's Republic of China " (one one).Rhizoma Chuanxiong is a kind of Chinese medicine, has activating blood circulation to dissipate blood stasis, a medicinal efficacy of the analgesic therapy of regulating the flow of vital energy.Theory of Chinese medical science is paid attention to the normal operation of gas, blood, body fluid, and thinking that the stagnation of QI is not all right then has a blood stasis.Cerebral ischemia is exactly that blood vessels are obstructed, thereby cause nervous system dysfunction owing to qi stagnation blood stasis.Rhizoma Chuanxiong is " a gas medicine in the blood ", the thin gas hero of flavor, and property circulates most, and suffering is loose, and to walk to scurry effect very strong, and can rise and can loose, the rising head, the side reaches extremity, and the descending sea of blood has the effect of activating blood circulation to dissipate blood stasis, circulation of qi promoting analgesic therapy, cures mainly apoplexy and goes into brain and have a headache diseases such as hemiplegia.Domestic Rhizoma Chuanxiong function of promoting blood circulation to disperse blood clots and mechanism have been carried out big quantity research; confirm that Rhizoma Chuanxiong can improve brain and periphery microcirculation, obviously the cerebral blood flow increasing amount can suppress platelet activation; reduce erythrocyte and platelet aggregation, experimental cerebral ischemia tectology and brain function are had protective effect.
Effective site is volatile oil (to call Rhizoma Chuanxiong oil in the following text) in the Rhizoma Chuanxiong, Rhizoma Chuanxiong oil can make the blood capillary spasmolytic, increase the open number of blood capillary, accelerate blood flow rate, make accumulative erythrocyte depolymerization, wherein the erythrocyte depolymerisation is particularly remarkable, see that [ligustilide decomposes the comparison of front and back Rhizoma Chuanxiong oil to the influence of rabbit bulbar Conjunctiva Microcirculation, stone coolie, Zheng Xiaomei etc., Chinese J Pharmacol Toxicol, 1995,9 (2) 157-158].Main component in the Rhizoma Chuanxiong oil is phthalide analog compound (to call the Rhizoma Chuanxiong Phthalide in the following text), sees
[Li HX,
Ding MY,
Yu JYJ Separation and identification of the phthalic anhydridederivatives of Liqusticum Chuanxiong Hort by GC-MS, TLC, HPLC-DAD, and HPLC-MSChromatogr Sci 2002 Mar 40:156-61], the main component in the phthalide analog compound is the Z-ligustilide.After ligustilide in the Rhizoma Chuanxiong oil decomposed, except that the erythrocyte depolymerization, pharmacological action obviously descended even disappears, and sees [stone coolie, Zheng Xiaomei etc., Chinese J Pharmacol Toxicol, 1995,9 (2) 157-158].Although this shows that the catabolite of ligustilide or some other composition in the Rhizoma Chuanxiong oil may still have certain pharmacologically active, its effect can not show a candle to ligustilide.The Rhizoma Chuanxiong injection that has gone on the market at present adopts traditional extraction process-steam distillation, and its extract yield is low, and ligustilide easy isomery inactivation under hot conditions, sees [Li Guisheng etc.The stability study of ligustilide and the GC-MS of isomerization product analyze.Chinese herbal medicine, 2000,31 (6): 405].Therefore traditional handicraft has caused very big destruction to phthalide analog compound, will influence the curative effect of medicine.Given this develop a kind of quality controllable, determined curative effect and suitable industrial oral formulations has far-reaching clinical meaning.
Summary of the invention
The invention provides a kind of Rhizoma Chuanxiong oil soft capsule.
The invention provides a kind of Rhizoma Chuanxiong oil preparation of soft capsule method.
The present invention also provides the purposes of Rhizoma Chuanxiong oil soft capsule in the convalescent medicine of preparation treatment apoplexy (cerebral infarction).
Soft capsule provided by the invention is become with the medicinal liquid line of oils by softgel shell, and its herb liquid oil is made up of with 1: 0～10 weight ratios Rhizoma Chuanxiong oil and vegetable oil, and its preferred proportion is 1: 0～5.
Rhizoma Chuanxiong oil in the soft capsule provided by the invention is by CO
2Supercritical fluid extraction prepares and gets, and its extracting pressure is: 10MPa 〉=extracting pressure 〉=8MPa.The concrete preparation method of Rhizoma Chuanxiong oil is: get the Rhizoma Chuanxiong decoction pieces, place supercritical extraction equipment, carry out CO
2Supercritical fluid extraction, extracting pressure are that 8-10MPa, temperature are that 30-60 ℃, time are 2-12 hour, CO
2Circular flow is 10-30Kg CO
2/ Kg Rhizoma Chuanxiong h; Introduce pressure in turn from the effusive carbon dioxide of extractor and be 4-10MPa, the I and II separator that temperature is between 20-40 ℃ carries out decompression separation, and the extract in the separator of the second level is filtered, and leaves standstill, and gets oil reservoir, promptly.Adopt this method to prepare volatile oil, do not destroy effective ingredient, the content of its main component Rhizoma Chuanxiong Phthalide greater than 50% (in the Z-ligustilide) less than 100%; the content of Z-ligustilide greater than 30% less than 100%; and favorable reproducibility has been protected effective ingredient effectively, and is stable and controllable for quality.
Vegetable oil in the soft capsule provided by the invention is selected from one or more in Oleum Sesami, Oleum Arachidis hypogaeae semen, Semen Maydis oil, Oleum Glycines, almond oil, peach kernel oil, Oleum Gossypii semen, Oleum Helianthi, Oleum Ricini or the olive oil.The capsule material contains sizing material, plasticizer and water, and wherein the weight ratio of sizing material and plasticizer is 1: 0.4～0.6, and the weight ratio of water and sizing material is 1: 0.7～1.4.Sizing material can be a kind of or its combination in gelatin, the arabic gum, plasticizer can be a kind of or its combination in glycerol, the sorbitol, can also add opacifier in the capsule material, it is selected from iron sesquioxide, titanium dioxide, the pigment one or more, when opacifier was iron sesquioxide, its using dosage was the 0.0075-0.075mg/kg gelatin.
Soft capsule provided by the invention can adopt conventional soft capsule preparation prepared to form, and as manual die pressing, rotating mould platen press or dropping preparation method etc., generally selects the rotating mould platen press for use, uses rotation rolling capsule machine automatically, and temperature is controlled between 40-50 ℃.
The dosage unit of Rhizoma Chuanxiong oil soft capsule is 20-300mg.
The present invention has not only advantageously protected the effective ingredient of Rhizoma Chuanxiong oil on preparation of soft capsule technology, and has protected the effective ingredient of Rhizoma Chuanxiong oil from the extracting method of volatile oil.The present invention preferably uses the rotating mould platen press when the preparation soft capsule, control its temperature between 40-50 ℃, and Rhizoma Chuanxiong main body of oil Rhizoma Chuanxiong Phthalide (as ligustilide) just is difficult for isomerization takes place like this, thereby has protected effective ingredient.Rhizoma Chuanxiong oil provided by the invention adopts low-temp low-pressure carbon dioxide supercritical fluid extraction method, thereby has prevented the isomerization of Rhizoma Chuanxiong Phthalide (as ligustilide), and active constituent content is higher, has advantageously protected effective ingredient.
The Rhizoma Chuanxiong oil soft capsule that the present invention prepares can obviously improve the behavior disorder of rats with cerebral ischemia through gastrointestinal administration, dwindles the ischemic region necrosis area, and ischemic brain injury is had significant protective effect; Increase anesthetized dog ICAF amount, reduce cerebral vascular resistance; Reduce rat whole blood viscosity, plasma viscosity and rat packed cell volume.Therefore, be the active drug of treatment apoplexy (cerebral infarction at restoration stage).
The specific embodiment
Preparation example 1: preparation Rhizoma Chuanxiong oil soft capsule
A Rhizoma Chuanxiong oil preparation: exsiccant Rhizoma Chuanxiong raw material 120 kg is crossed sieve after crushed No. two, place 600L supercritical extraction equipment, extract, extracting pressure is that 10MPa, extraction temperature are that 40 ℃, extraction time are 4 hours, CO
2Flow is 20Kg/Kg Rhizoma Chuanxiong h, first order separating still pressure 8MPa, and 35 ℃ of temperature, extract filter, and filtrate is left standstill, and gets oil reservoir, promptly.
The preparation of B gelatin solution: gelatin 100g, glycerol 60g and water 100g.Get an amount of water of gelatin adding and make its imbibition.In addition the water of glycerol and remainder is put and be heated to 70～80 ℃ in the glue pot, mix homogeneously adds expansible gelatin and stirs, and fusion is incubated 1～2 hour, leaves standstill, and makes the foam come-up, scrapes off the foam of come-up, filters with clean calico, adds 0.0075mgFe
2O
3Powder, mixing, heat preservation for standby use; The viscosity that is configured to glue is generally 2.8～3.2 degree.
The preparation of C medicinal liquid oil: take by weighing Rhizoma Chuanxiong oil 100g and clarifying soybean oil 200g fully stirs evenly promptly.
D suppresses soft capsule: gelatin glycerol that will make and Rhizoma Chuanxiong oil are packed into and are rotated in the rolling capsule machine automatically, and temperature is controlled at 40 ~ 50 ℃, and each capsule contains the Rhizoma Chuanxiong oil of 100mg.
Preparation example 2: preparation soft capsule
The preparation of A Rhizoma Chuanxiong oil; Exsiccant Rhizoma Chuanxiong raw material 120 kg is crossed sieve after crushed No. two, place 600L supercritical extraction equipment, extract, extracting pressure is that 8MPa, extraction temperature are that 30 ℃, extraction time are 2 hours, CO
2Flow is 10Kg/Kg Rhizoma Chuanxiong h, first order separating still pressure 4MPa, and 20 ℃ of temperature, extract filter, and filtrate is left standstill, and gets oil reservoir, promptly.
The preparation of B gelatin solution: gelatin 100g, glycerol 40g and water 70g.Get an amount of water of gelatin adding and make its imbibition.In addition the water of glycerol and remainder is put and be heated to 70～80 ℃ in the glue pot, mix homogeneously adds expansible gelatin and stirs, and fusion is incubated 1～2 hour, leaves standstill, and makes the foam come-up, scrapes off the foam of come-up, filters with clean calico, adds 0.0075mgFe
2O
3Powder, mixing, heat preservation for standby use; The viscosity that is configured to glue is generally 2.8～3.2 degree.
The preparation of C medicinal liquid oil: Rhizoma Chuanxiong oil 300g.
D suppresses soft capsule: gelatin glycerol that will make and Rhizoma Chuanxiong oil are packed into and are rotated in the rolling capsule machine automatically, and temperature is controlled at 40 ~ 50 ℃, and each capsule contains the Rhizoma Chuanxiong oil of 300mg.
Preparation example 3
A Rhizoma Chuanxiong oil preparation: exsiccant Rhizoma Chuanxiong raw material 120 kg is crossed sieve after crushed No. two, place 600L supercritical extraction equipment, extract, extracting pressure is that 10MPa, extraction temperature are that 60 ℃, extraction time are 12 hours, CO
2Flow is 30Kg/Kg Rhizoma Chuanxiong h, first order separating still pressure 10MPa, and 40 ℃ of temperature, extract filter, and filtrate is left standstill, and gets oil reservoir, promptly.
The preparation of B gelatin solution: gelatin 100g, glycerol 60g and water 140g.Get an amount of water of gelatin adding and make its imbibition.In addition the water of glycerol and remainder is put and be heated to 70～80 ℃ in the glue pot, mix homogeneously adds expansible gelatin and stirs, and fusion is incubated 1～2 hour, leaves standstill, and makes the foam come-up, scrapes off the foam of come-up, filters with clean calico, adds 0.0075mgFe
2O
3Powder, mixing, heat preservation for standby use; The viscosity that is configured to glue is generally 2.8～3.2 degree.
The preparation of C medicinal liquid oil: Rhizoma Chuanxiong oil 50g.
D suppresses soft capsule: gelatin glycerol that will make and Rhizoma Chuanxiong oil are packed into and are rotated in the rolling capsule machine automatically, and temperature is controlled at 40 ~ 50 ℃, and each capsule contains the Rhizoma Chuanxiong oil of 50mg.
Preparation example 4
All the other steps are identical with example 1, just take by weighing Rhizoma Chuanxiong oil 50g in the preparation of medicinal liquid oil and clarifying soybean oil 250g fully stirs evenly promptly, at last Ya Zhi soft capsule each comprise the Rhizoma Chuanxiong oil of 50mg.
Preparation example 5
All the other steps are identical with example 1, just take by weighing Rhizoma Chuanxiong oil 20g in the preparation of medicinal liquid oil and clarifying Oleum Arachidis hypogaeae semen 160g fully stirs evenly promptly, at last Ya Zhi soft capsule each comprise the Rhizoma Chuanxiong oil of 20mg.
Preparation example 6
All the other steps are identical with example 1, just take by weighing Rhizoma Chuanxiong oil 20g in the preparation of medicinal liquid oil and clarifying Semen Maydis oil 200g fully stirs evenly promptly, at last Ya Zhi soft capsule each comprise the Rhizoma Chuanxiong oil of 20mg.
Preparation example 7
All the other steps are identical with example 1, just in the preparation of gelatin solution, add 0.075mgFe
2O
3Powder is as opacifier.Test example 1 extracting pressure is to the influence of Rhizoma Chuanxiong Phthalide in the Rhizoma Chuanxiong oil and ligustilide content
The inventor finds that according to repeatedly prerun extracting pressure is for Z-ligustilide in the Rhizoma Chuanxiong oil and Rhizoma Chuanxiong Phthalide content influence maximum.Therefore we are a certain value with other parameter setting, and have selected for use different extracting pressure to investigate.
1.1 instrument and reagent
Equipment: 5 liters of CO
2Supercritical extraction equipment (prototype version) is by force (forcing) pump, extraction kettle, separation reactor I, separation reactor I I, CO
2Compositions such as storage tank are manufactured and designed by Huaan, Jiangsu supercritical extraction company limited.Day island proper Tianjin UV-2401 type ultraviolet spectrophotometer; Gas chromatograph (Tianjin, island GC-14B); Diethyl phthalate (Shanghai reagent one factory); (Rhizoma Chuanxiong oil 2g is got in company's self-control to Z-ligustilide reference substance, is dissolved in the 5ml ether and adds the 2g column chromatography stirring with silica gel (100 ~ 120 order), and nitrogen dries up standby.Get thin layer chromatography silica gel H 100g, the decompression dry column-packing, with sample on the sample of above-mentioned preparation, the chloroform eluting, fraction collection, gas chromatographic detection gets the about 100mg of the pure product of Z-ligustilide.Purity＞98.0%)
1.2. experimental technique
CO
2Circular flow: 20Kg CO
2/ Kg Rhizoma Chuanxiong h; Extraction kettle temperature: 40 ℃; The extraction time: 3～5h; The pressure 8Mpa of first order separating still, 35 ℃ of temperature, second level separating still pressure-regulating valve standard-sized sheet, promptly second level separating still pressure and storage tank pressure balance are generally about 5Mpa, and temperature is 25 ℃.Select that extracting pressure is respectively 10,15,20Mpa for use.
1.3 detection index:
Determined by ultraviolet spectrophotometry Rhizoma Chuanxiong Phthalide content, GC detects (Z)-ligustilide content.
1.3.1 Rhizoma Chuanxiong Phthalide assay
The preparation reference substance solution: draw the about 9mg of (Z)-ligustilide reference substance and put in the 50ml measuring bottle, the accurate title, decide, and adds chloroform to scale, shakes up, and the accurate 5ml that draws puts in the 50ml measuring bottle, adds chloroform to scale, shakes up, promptly.
The preparation need testing solution: by preparation example 1 preparation Rhizoma Chuanxiong oil, draw about 35mg and put in the 50ml measuring bottle, accurate title is fixed, adds chloroform to scale and shakes up, and accurate the absorption in 1ml to the 25ml measuring bottle adds chloroform to scale, shakes up, promptly.
Algoscopy is blank with the chloroform, measures trap at 285nm wavelength place, calculates, promptly.
1.3.2 (Z)-ligustilide shines gas chromatography (VI E) to be measured.
Chromatographic condition and system suitability test: polymethyl-benzene base vinylsiloxane (SE-54) fixative capillary column, detector FID, 240 ℃ of column temperatures, number of theoretical plate should be not less than 100000 in (Z)-ligustilide peak.
The mensuration of correction factor: get the about 15 μ l of (Z)-ligustilide reference substance, put in the 1ml measuring bottle, the accurate title, decide, add internal standard substance diethyl phthalate 16 μ l, the accurate title, decide, and adds chloroform and be diluted to scale, shake up, get solution 1 μ l inject gas chromatograph, the calculation correction factor.
Algoscopy: by preparation example 1 preparation Rhizoma Chuanxiong oil, get about 50 μ l, put in the 1ml measuring bottle, accurate title is decided, and adds the about 16 μ l of internal standard substance diethyl phthalate, and accurate the title decides, and adds chloroform and is diluted to scale, shakes up, and gets need testing solution.Get need testing solution 1 μ l, inject gas chromatograph calculates, promptly.
1.4 experimental result sees Table 1.
Table 1 supercritical extraction Rhizoma Chuanxiong oil orthogonal experiments
The result: extracting pressure reduces, and Rhizoma Chuanxiong Phthalide and Z-ligustilide content raise, when pressure is 10MP, Rhizoma Chuanxiong Phthalide content＞50%, the content of Ligustilide＞30% meets medicinal standard, consider industrial pressure adaptation, 10MPa 〉=extracting pressure 〉=8MPa.
Test example 2: the Rhizoma Chuanxiong oil soft capsule is to the influence of rat local cerebral ischemia damage
2.1 material
The Rhizoma Chuanxiong oil soft capsule: by preparation example 1 preparation, the time spent dilutes with soybean oil.
Nimodipine tablet (Jinan Min Kang pharmaceutical factory, 30mg/ sheet, lot number: 010101), be made into suspension with preceding normal saline.
NAODESHENG chewable tablet (Shandong Green Leaf Pharmaceutical Co., Ltd, 1.1g/ sheet, 20010426 batches) is made into suspension with preceding normal saline.
Soybean oil: north Asia, Tieling medicinal oil company, lot number: 010718.Digital camera: Olympus company
Red tetrazolium: U.S. Sigma company product, face with preceding and be made into 4.0% solution with normal saline.
Laboratory animal: regular grade SD rat, male, body weight 300g-350g, Shandong Green Leaf Pharmaceutical Co., Ltd's Experimental Animal Center provides, the quality certification number: No. 200106005, Shandong kinoplaszm word.
2.2 method and result
Animal is divided into sham operated rats (soybean oil) at random, model control group (soybean oil), nimodipine group (Nim, 12mg/kg), the NAODESHENG group (NAODESHENG, 1g/kg), soft capsule small dose group (Rhizoma Chuanxiong Phthalide, 15mg/kg), dosage group in the soft capsule (the Rhizoma Chuanxiong Phthalide, 30mg/kg), the heavy dose of group of soft capsule (Rhizoma Chuanxiong Phthalide, 60mg/kg), 10 every group.After the animal fasting 12 hours, each treated animal is irritated the corresponding medicine of stomach respectively.After 2 hours, and chloral hydrate (360mg/kg, i.p.) anesthesia separates right carotid, and folder closes in the neck, common carotid artery, external carotid artery proximal part and distal end ligation, cut off the centre.The external carotid artery free-end is pulled to internal carotid artery in alignment, bolt line (selecting diameter 0.24mm nylon wire for use, length 5.0cm) is inserted into intracranial by external carotid artery, stop when meeting slight resistance, insertion depth is about 2cm.Ligation external carotid artery opening, and open the common carotid artery bulldog clamp, the disinfection and stitching wound causes left side middle cerebral artery ischemia model; Sham operated rats is only carried out the separation (above experiment is all carried out at 23 ℃～25 ℃) of right carotid, internal carotid artery, external carotid artery.Observe and write down the behavior disorder of rat by document [1] method and standard after 24 hours: (1) is carried the Mus tail and is observed forelimb flexing situation, stretch to ground as two forelimb symmetries, count 0 fen, as the offside forelimb of performing the operation the wrist flexing occurs and counts 1 fen, the elbow flexing is counted 2 fens, and the shoulder inward turning is counted 3 fens, existing wrist flexing and/or elbow flexing, shoulder inward turning person is arranged again, count 4 fens.(2) animal is placed on the plane earth, push away both shoulders respectively, check resistance to side shifting.As bilateral resistance equity and strong, count 0 fen, as resistance descender when the operation offside promotes, according to decline degree difference be divided into gently, in, weigh three degree, count 1,2 and 3 fen respectively.(3) the two forelimbs of animal are put on the wire netting, observed the muscular tension of two forelimbs.Two muscle of anterior limb tension force equities and strong person count 0 fen.Count 1,2 and 3 fen according to operation offside muscular tension decline degree difference equally.(4) animal has ceaselessly to a side person of turn-taking, and counts 1 fen.According to the standard scoring, full marks are 11 minutes, and mark is high more, and expression animal behavior obstacle is serious more.Data are represented with x ± s, carry out statistical test with the reference differential technique.
Put to death rat behind the behavior scoring, get brain, remove olfactory bulb, cerebellum and low brain stem, crownly be cut into 5, the brain sheet takes on a red color after normal structure is dyed with red tetrazolium (TTC) dyeing, and blocking tissue is white in color, taking a picture in dyeing back, asks the infarct size ratio with Chinese Aero-Space university pathological image analysis software.Data are represented with x ± s, carry out the F check between group.
The result shows that ischemia is after 24 hours, and rat model shows tangible behavior disorder, and tangible kitchen range shape ischemic region also appears in rat cerebral tissue, and necrosis area reaches about 25% of full brain; Give the soft capsule of various dose, the animal behavior obstacle has alleviating in various degree, and rat cerebral ischemia district necrosis area also has obvious reduction, and is dose dependent (table 2).
The influence that table 2 Rhizoma Chuanxiong oil soft capsule damages the rat local cerebral ischemia (n=10, x ± s)
Compare with model control group
*P＜0.05,
*P＜0.01.
Conclusion: the Rhizoma Chuanxiong oil soft capsule can obviously improve the behavior disorder of rats with cerebral ischemia, dwindles the ischemic region necrosis area, and ischemic brain injury is had significant protective effect.
Test example 3: the Rhizoma Chuanxiong oil soft capsule is to the cerebrovascular influence of anesthetized dog
3.1 material: the Rhizoma Chuanxiong oil soft capsule, by the preparation of preparation example 2 methods, the time spent dilutes with soybean oil.
The cinnarizine sheet, Nanjing second pharmaceutical factory; Lot number: 2000502; Be made into suspension solution with preceding with normal saline.Powerlab/8sp: Australian ADInstrments company; The effusion meter probe: No. 4, No. 4.5, Japanese photoelectricity company.ELECTROMAGNETIC BLOOD FLOWMETER:MF-27 type, Japanese photoelectricity company.
The single track electrocardiograph, FX-2111 type, Feitian, Beijing electronic medical instruments company limited.
Laboratory animal: the Beagle dog, male and female half and half, body weight 8～12kg, Shandong Province's natural drug Engineering Technical Research Centre Experimental Animal Center provides, the animal quality certification number: Shandong kinoplaszm word B20021136 number.
3.2 method and result: animal is divided into blank group (soybean oil) at random, cinnarizine group (cinnarizine, 4mg/kg), the soft capsule small dose group (the Rhizoma Chuanxiong Phthalide, 5mg/kg), dosage group (Rhizoma Chuanxiong Phthalide in the soft capsule, 10mg/kg), (the Rhizoma Chuanxiong Phthalide, 20mg/kg), animal is weighed the back dog with 3.5% pentobarbital sodium 1.0ml/kg hind leg outside saphena injecting anesthetic to the heavy dose of group of soft capsule.Separate right carotid, the ligation external carotid artery hangs on the common carotid artery with probe, and loads onto movable bolt, in case the tremulous pulse slippage is measured the common carotid artery flow and represented the internal carotid artery flow.Separate femoral artery, intubate is connected into the tremulous pulse mean pressure of Powerlab/8sp Records Unit.Open the abdominal cavity, find out and fixing duodenum (selecting the mesentery in one section no trunk district), the pocket suture, an osculum is opened in the centre, imports ureter, and thoroughly hemostasis is sewed up, and fixedly draws and clamps free-end so that administration (1ml/kg) with alligator clamp.By down-off key (Flow) and output mean blood flow key (Mean flow), the subcutaneous insertion needle electrode of femoral artery extremity is traced electrocardiogram.After stablizing 20min, write down every index and contrast before as administration; Every index when 5min, 15min, 30min, 60min, 90min, 120min, 180min, 240min after the record administration.
Get brain after mensuration finishes and weigh, and calculate the blood flow ml/ (100gmin) of every 100g cerebral tissue; Cerebral vascular resistance (mmHgmin100g)/ml=blood pressure/ICAF amount.Data are represented with x ± s, and are compared the t-test check with the blank group.
The result shows that soft capsule 10mg/kg, 20mg/kg dosage group 30min～90min dog ICAF amount after administration obviously increases, and cerebral vascular resistance obviously descends, and with the blank group significant difference is arranged relatively; Blood pressure does not have significant change (table 2,3).
Table 2 Rhizoma Chuanxiong oil soft capsule to the influence of anesthetized dog ICAF amount (x ± s, n=6)
With comparison before the administration
*P＜0.05,
*P＜0.01
Table 3 soft capsule to the influence of anesthetized dog cerebral vascular resistance (x ± s, n=6)
With comparison before the administration
*P＜0.05,
*P＜0.01
Conclusion: duodenum gives Rhizoma Chuanxiong soft capsule (Rhizoma Chuanxiong Phthalide 10mg/kg, 20mg/kg), can increase anesthetized dog ICAF amount after the administration between 30min～90min, reduce cerebral vascular resistance.
Test example 4: the Rhizoma Chuanxiong oil soft capsule is to the influence of rat blood rheological characteristic
4.1 material
The Rhizoma Chuanxiong oil soft capsule, by preparation example 1 preparation, the time spent dilutes with soybean oil.
NAODESHENG chewable tablet (Shandong Green Leaf Pharmaceutical Co., Ltd, 1.1g/ sheet, 20010426) is made into suspension with preceding with normal saline.
Regular grade SD rat, male, body weight 350～430g, Shandong Green Leaf Pharmaceutical Co., Ltd's Experimental Animal Center provides,
The quality certification number: No. 200106005, Shandong kinoplaszm word.
LBY-N6A hemorheology tester: Beijing Puli gives birth to company.
4.2 method and result
Animal is divided into blank group (soybean oil) at random, NAODESHENG group (NAODESHENG 1g/kg), soft capsule small dose group (Rhizoma Chuanxiong Phthalide 15mg/kg), dosage group in the soft capsule (Rhizoma Chuanxiong Phthalide 30mg/kg), the heavy dose of group of soft capsule (Rhizoma Chuanxiong Phthalide 60mg/kg), 10 every group.After the fasting 12 hours, each treated animal is irritated the stomach relative medicine respectively, and after 2 hours, (360mg/kg, i.p.) heart blood sampling 5ml/ only with the 50U anticoagulant heparin, measures indexs such as whole blood viscosity, plasma viscosity to chloral hydrate anesthesia with the hemorheology tester.Data are represented with x ± s, and are compared the t-test check with the blank group.The result shows that the big or middle dosage of soft capsule all can reduce rat whole blood viscosity, plasma viscosity and packed cell volume (table 4).
Table 4 Rhizoma Chuanxiong oil soft capsule to the influence of rat blood rheological characteristic (x ± s, n=10)
Compare with the blank group
*P＜0.05,
*P＜0.01.
Conclusion: soft capsule can reduce rat whole blood viscosity, plasma viscosity, and 60mg/kg can reduce the rat packed cell volume.
Claims (9)
1. a Chuanxiong rhizome volatile oil soft capsule is become with the medicinal liquid line of oils by softgel shell, and its herb liquid oil is made up of with 1: 0～10 weight ratio Rhizoma Chuanxiong volatile oil and vegetable oil, and the preparation method of Rhizoma Chuanxiong volatile oil is: get the Rhizoma Chuanxiong decoction pieces, carry out CO
2Supercritical fluid extraction, extracting pressure are that 8-10MPa, temperature are that 30-60 ℃, time are 2-12 hour, CO
2Circular flow is 10-30Kg CO
2/ Kg Rhizoma Chuanxiong h; Introduce pressure in turn from the effusive carbon dioxide of extractor and be 4-10MPa, the I and II separator that temperature is between 20-40 ℃ carries out decompression separation, and the extract in the separator of the second level is filtered, and leaves standstill, and gets oil reservoir promptly.
2. soft capsule according to claim 1, the weight ratio of Rhizoma Chuanxiong volatile oil and vegetable oil are 1: 0～5.
3. soft capsule according to claim 1 and 2, vegetable oil is selected from one or more in Oleum Sesami, Oleum Arachidis hypogaeae semen, Semen Maydis oil, Oleum Glycines, almond oil, peach kernel oil, Oleum Gossypii semen, Oleum Helianthi, Oleum Ricini or the olive oil.
4. soft capsule according to claim 1 and 2, the capsule material contains sizing material, plasticizer and water, the weight ratio of sizing material and plasticizer is 1: 0.4～0.6, the weight ratio of water and sizing material is 1: 0.7～1.4, sizing material is a kind of or its combination in gelatin, the arabic gum, and plasticizer is a kind of or its combination in glycerol, the sorbitol.
5. soft capsule according to claim 4, the capsule material contains opacifier, is in iron sesquioxide, titanium dioxide, the pigment one or more.
6. soft capsule according to claim 5, when opacifier was iron sesquioxide, its using dosage was the 0.0075-0.075mg/kg gelatin.
7. soft capsule according to claim 1 and 2, its dosage unit are 20mg-300mg.
8. the arbitrary described soft capsule of claim 1-7 is preparing the purposes for the treatment of in the convalescent medicine of apoplexy.
9. the purposes of the arbitrary described soft capsule of claim 1-7 in the medicine of preparation treatment cerebral infarction at restoration stage.
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| CN101677989B (en) * | 2008-02-14 | 2012-10-10 | 清华大学 | A drug composition for treatment and prevention of ischemic stroke and its preparation methods |
| CN102293800A (en) * | 2010-06-23 | 2011-12-28 | 中国人民解放军第二军医大学 | Hemlock parsley volatile oil soft capsule |
| CN102293801A (en) * | 2010-06-23 | 2011-12-28 | 中国人民解放军第二军医大学 | Ligusticum wallichii volatile oil pills |
| CN103484254A (en) * | 2013-09-18 | 2014-01-01 | 上海中医药大学 | Method for extraction of ligusticum chuanxiong hort. volatile oil by utilizing supercritical carbon dioxide |
| CN106138135B (en) * | 2016-08-18 | 2020-09-22 | 四川省中医药科学院 | Medicine for preventing and treating vascular cognitive disorder and preparation method thereof |
| CN109078046B (en) * | 2018-10-12 | 2021-06-25 | 广州医科大学 | Supercritical CO2Method for extracting volatile oil from anti-dizziness decoction |
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| CN1256143A (en) * | 1999-11-26 | 2000-06-14 | 化学工业部西南化工研究设计院 | Supercritical CO2 extraction process of effective medicine component in Rhizoma Lihustici chuanxiong |
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