CN1903238A - Extractive of traditional Chinese medicine, its prepns., preparing method and application thereof - Google Patents
Extractive of traditional Chinese medicine, its prepns., preparing method and application thereof Download PDFInfo
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Abstract
A Chinese-medicinal extract is prepared from Chinese angelica root, Chuan-xiong rhizome and optional safflower through extracting by supercritical CO2 fluid. A Chinese medicine in the form of capsule, tablet, dripping pill, or particle for treating cardiovascular and cerebrovascular diseases contains said extract and optional borneol.
Description
Technical field
The present invention relates to technical field of Chinese medicines, specifically, be the extract that extracts by Radix Angelicae Sinensis, Rhizoma Chuanxiong or Radix Angelicae Sinensis, Rhizoma Chuanxiong, Flos Carthami proportioning, contain preparation of this extract and preparation method thereof.
Background technology
According to China's Epidemiological study, though over nearly 50 years in the rural area or the city, the M ﹠ M of cardiovascular and cerebrovascular disease is all in rising trend.50-60 age China population cause of death central vessel disease and cerebrovascular occupy the five or six respectively, then rise to the two or three respectively later in 1970, and cardiovascular and cerebrovascular disease death person has accounted for first of whole disease cause of the death.China accounts for the percentage ratio of total dead population because of cardiovascular and cerebrovascular disease death person, rise to 42.6% of calendar year 2001 by 12.07% of nineteen fifty-seven, the person reaches 2,000,000 to die from the cardiovascular and cerebrovascular disease every year, though other has the part patient to survive through rescue, but majority stays deformity, can't take care of oneself, cause serious burden to relatives and society.Cardiovascular and cerebrovascular disease also is western countries crowd main causes of death.Infer that according to present existing epidemiologic data advancing of disease trend is: to the year two thousand twenty, the human diseases cause of the death puts in order will have great change, but coronary heart disease and apoplexy will be first and second of the human cause of the death.Till that time, estimate that global coronary heart disease death number will increase to 1,100 ten thousand from 6,300,000 of nineteen ninety; Apoplexy increases to 7,700,000 from 4,400,000.Blood circulation cause of the death formation will increase 59.6% in 30 years, and coronary heart disease and apoplexy increase 74.6% and 75% respectively.These data prove absolutely that cardiovascular and cerebrovascular disease is not only the principal disease of harm humans health, especially human " the No.1 killer " who causes death, disables at present and in following 20 years.
In the medicine of cardiovascular and cerebrovascular disease, 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.For example: the benefiting QI for activating blood circulation side [Zhu Weifeng, Shandong College of Traditional Chinese Medicine's journal, 1994,18 (5)] that forms by the Radix Astragali, Radix Codonopsis, Radix Angelicae Sinensis, Radix Salviae Miltiorrhizae, Flos Carthami; Add the red stilbene SHENGMAI YIN that Radix Salviae Miltiorrhizae, the Radix Astragali, Radix Notoginseng, Flos Carthami, Rhizoma Corydalis, Fructus Crataegi are formed, [Chen Yuchun, the bright traditional Chinese medical science, 1999,14 (5)] by SHENGMAI YIN; The coronary heart disease of being made up of the Radix Astragali, Radix Codonopsis, Radix Ophiopogonis, Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, Lignum Dalbergiae Odoriferae is square [Wang Jinrong etc., Liaoning Journal of Traditional Chinese Medicine, 2001,28 (8)] substantially; By Radix Salviae Miltiorrhizae, Rhizoma Corydalis, the Radix Astragali, Radix Paeoniae Rubra, Rhizoma Chuanxiong, when the Shuxintongmai sheet that is grouped into [Wang Xiue etc., Shandong journal of Chinese medicine, 1997,16 (8)]; Or the like.But above clinical prescription and Chinese patent medicine all have certain weak point, or are partial to QI invigorating, or relatively activate yang, or relatively invigorate blood circulation, or dosage form is relatively poor, do not obtain clinically popularizing in an all-round way.
And in the prior art, how Radix Angelicae Sinensis, Rhizoma Chuanxiong and Flos Carthami extract its effective ingredient with steam distillation and organic solvent circumfluence method, because of extract the temperature height, the time is long, step is many, cause the loss of effective ingredient, as the main component ligustilide isomerization in the volatile oil, thereby cause the reduction of active constituent content.
Therefore it is concise, original to develop a kind of prescription, the active constituent content height, and the Chinese medicine preparation of treatment cardiovascular and cerebrovascular disease evident in efficacy is the direction that people make great efforts.
Summary of the invention
One of purpose of the present invention provides a kind of refining formula, original, the Chinese medicine extract of the treatment cardiovascular and cerebrovascular disease that active constituent content is high.
Another object of the present invention provides the compound Chinese medicinal preparation that comprises this extract.
Another purpose of the present invention provides the preparation method of this Chinese medicine extract and preparation thereof.
The present invention realizes by following technical scheme.
Medicine of the present invention is at the classics of " general Ji ability side " the hemostasis prescription of invigorating blood circulation---the improvement of carrying out on the basis of foshousan.Radix Angelicae Sinensis, hot, sweet, warm, return liver, the heart, spleen channel; Rhizoma Chuanxiong, hot, warm, return liver, gallbladder, pericardium channel; Two flavor medicine blood circulation promoting and blood stasis dispelling, removing obstruction in the collateral to relieve pain.In order to reach better therapeutic, the present invention also selects Flos Carthami and Borneolum Syntheticum to be used as medicine, and Flos Carthami is hot, warm, GUIXIN, spleen, lung meridian; Borneolum Syntheticum, hot, bitter, be slightly cold, GUIXIN, spleen, lung meridian, hot and suffocating clearly, pain relieves the pain.More than all medicines, on the theoretical basis of science of TCM formulas, ingenious compatibility, exquisite combination, tight prescription according to rational modern extraction process effective component extracting and be prepared into pharmaceutical preparation, thereby reaches blood circulation promoting and blood stasis dispelling, the purpose of regulating QI to relieve pain.
The raw material of preparation Chinese medicine extract of the present invention is mainly Radix Angelicae Sinensis, Rhizoma Chuanxiong, and its weight portion proportioning is:
20～65 parts of 30～75 parts of Rhizoma Chuanxiongs of Radix Angelicae Sinensis
The raw material of preparation Chinese medicine extract of the present invention also can add Flos Carthami, and its each amounts of components is:
5～10 parts on 20～65 parts of Flos Carthamis of 30～75 parts of Rhizoma Chuanxiongs of Radix Angelicae Sinensis
Be preferably: 8～10 parts on 40～50 parts of Flos Carthamis of 40～50 parts of Rhizoma Chuanxiongs of Radix Angelicae Sinensis
" Chinese medicine extract " of the present invention is meant the mixture of crude drug low-polarity component and hydrophilic composition in the above-mentioned prescription.In the present invention, during all uses " Chinese medicine extract " term, promptly show the general name of the mixture of above-mentioned two kinds of extracts.
Described Chinese medicine extract is extracted by supercritical fluid extraction, preferred CO
2Supercritical fluid extraction extracts.Preferred extraction conditions is: extraction temperature is 30 ℃～50 ℃, and pressure is 25MPa～45Mpa, and extraction time is 1～3h, CO
2Flow is 10～30kg/L, and entrainer is 0.5%～5% acetone; More preferably extraction conditions is: extraction temperature is 40 ℃, and pressure is 35Mpa, and extraction time is 2.5h, CO
2Flow is 25kg/L, and entrainer is 2% acetone.
As active component, add excipient with above-mentioned Chinese medicine extract, can make various pharmaceutical dosage forms, as tablet, capsule, granule, pill, drop pill, oral liquid, injection etc.
As active component, can also add Borneolum Syntheticum and excipient with above-mentioned Chinese medicine extract again, make various pharmaceutical dosage forms, as tablet, capsule, granule, pill, drop pill, oral liquid, injection etc.
Chinese medicine preparation of the present invention is meant the regular dosage form in the medicament, can be: tablet, sugar coated tablet, film coated tablet, enteric coated tablet, capsule (hard capsule and soft capsule), oral liquid, suck agent, granule, electuary, pill, powder, unguentum, sublimed preparation, suspensoid, powder, solution, injection, suppository, ointment, plaster, drop pill etc.; Preferably granule, capsule (hard capsule and soft capsule), tablet, pill; The best is a soft capsule.The adjuvant that adds can be: starch, sucrose, lactose, mannitol, silicon derivative, cellulose and derivant thereof, gelatin, glycerol, agar, calcium carbonate, surfactant, Polyethylene Glycol, dextrin etc.
With Chinese medicine extract of the present invention is active component when preparing soft capsule, and each composition weight proportioning is:
Chinese medicine extract 2.5%～10% vegetable oil 85%～96% suspending agent 1.5%～5%
Optimum ratio is: 5%～8% vegetable oil, 87%～92% suspending agent is 2%～4%
Wherein, described vegetable oil is selected from soybean oil, Oleum Sesami, Semen Maydis oil, Oleum Brassicae campestris, Oleum Arachidis hypogaeae semen, Oleum sesami, Oleum Helianthi, walnut oil; Preferred soybean oil, Oleum Sesami; Described suspending agent is selected from Cera Flava, Cera Flava, cera alba, insect wax; Preferred Cera Flava, Cera Flava.
Concrete preparation method may further comprise the steps: the Chinese medicine extract, suspending agent and an amount of vegetable oil that take by weighing formula ratio; Heating makes the suspending agent dissolving; Be trimmed to suitable dispersion with shearing dispersing emulsification machine; Add the surplus vegetable oil to formula ratio, be trimmed to and be uniformly dispersed; Medicinal liquid and capsule material liquid are prepared into soft capsule with rotating rolling capsule machine automatically.Wherein, described heating-up temperature is preferred 70 ℃～85 ℃.
When preparing soft capsule with Chinese medicine extract adding Borneolum Syntheticum of the present invention, each composition weight proportioning is:
Chinese medicine extract 2.5%～10% vegetable oil 80%～95.8% suspending agent 1.5%～5% Borneolum Syntheticum 0.2%～5%
Optimum ratio is:
Chinese medicine extract 5%～8% vegetable oil 86%～91.5% suspending agent is 2%～4% Borneolum Syntheticum 0.5%～2%
Wherein, described vegetable oil is selected from soybean oil, Oleum Sesami, Semen Maydis oil, Oleum Brassicae campestris, Oleum Arachidis hypogaeae semen, Oleum sesami, Oleum Helianthi, walnut oil; Preferred soybean oil, Oleum Sesami; Described suspending agent is selected from Cera Flava, Cera Flava, cera alba, insect wax; Preferred Cera Flava, Cera Flava.
The preparation method of above-mentioned soft capsule may further comprise the steps: the Chinese medicine extract, suspending agent, Borneolum Syntheticum and an amount of vegetable oil that take by weighing formula ratio; Heating makes the suspending agent dissolving; Be trimmed to suitable dispersion with shearing dispersing emulsification machine; Add the surplus vegetable oil to formula ratio, be trimmed to and be uniformly dispersed; Medicinal liquid and capsule material liquid are prepared into soft capsule with rotating rolling capsule machine automatically.Wherein, described heating-up temperature is preferred 70 ℃～85 ℃.
The capsule material of above-mentioned soft capsule is a sizing material, water, plasticizer and antiseptic.Wherein, sizing material is selected from gelatin or arabic gum, preferred gelatin; Plasticizer is the mixture of glycerol or sorbitol or glycerol and sorbitol; Dried sizing material is 1: 0.3～1 with the ratio of dried plasticizer; Sizing material is 1: 0.4～1.4 with the ratio of water.
Medicine of the present invention can improve the blood circulation of the small tremulous pulse of brain, help improving the blood supply of cerebral cortex cerebrovascular bed, the sphincteral opening of the small tremulous pulse of brain, can be used for the prevention and the treatment heart, cerebrovascular disease, especially transient apoplexy, nonsystemic vertigo, cerebral infarction sequela, coronary heart disease, angina pectoris etc. are had significant curative effect.
The extraction process of medicine of the present invention is the result through a large amount of tests, below by concrete test explanation.
Experiment material and detection method
1. test medical material, reagent
1.1 medical material: Rhizoma Chuanxiong, Radix Angelicae Sinensis and Flos Carthami are purchased in base, medicine source, Shanglou, Shaanxi, are certified products by check of China's version pharmacopeia in 2005.Wherein, the ferulaic acid content of Radix Angelicae Sinensis and Rhizoma Chuanxiong is respectively 0.053% and 0.025%; The content of Hydroxy Carthamus yellow is 1.05% in the Flos Carthami.
1.2 reagent: methanol, acetonitrile are import reagent, chromatographic grade; Reagent such as phosphoric acid (Tianjin reagent two factories) are AG; Water is double distilled water for self-control.
2. check is prepared with reference substance and reference substance solution
2.1 ferulic acid and S-A Hydroxysafflor yellow A reference substance and Rhizoma Chuanxiong control medicinal material (purchasing) in Nat'l Pharmaceutical ﹠ Biological Products Control Institute.
2.2 it is an amount of that the ferulic acid reference substance solution takes by weighing the ferulic acid reference substance, is diluted to 13.2 μ g/ml with precision behind 70% dissolve with methanol, brown bottle is put refrigerator cold-storage and preserved, and is standby.
2.3 it is an amount of that the S-A Hydroxysafflor yellow A reference substance solution takes by weighing the S-A Hydroxysafflor yellow A reference substance, adds 25% dissolve with methanol and be diluted to 0.13mg/ml.
2.4 Rhizoma Chuanxiong and Radix Angelicae Sinensis control medicinal material solution are got Rhizoma Chuanxiong and Radix Angelicae Sinensis control medicinal material powder 1g and Radix Angelicae Sinensis control medicinal material respectively, ether 20ml refluxed 1 hour, filtered, and filtrate evaporate to dryness, residue add the 2ml acetic acid ethyl dissolution, in contrast product solution.
3. sample solution preparation
3.1 the sample solution precision that ferulic acid is measured takes by weighing the 0.1g supercritical extract, puts in the volumetric flask, and with an amount of ultrasonic dissolving that makes of 70% methanol, and accurate dilution, every 1ml solution contains the Radix Angelicae Sinensis medical material of 20mg, and microporous filter membrane filters, and gets subsequent filtrate and uses for measuring.
3.2 the sample solution precision that S-A Hydroxysafflor yellow A is measured takes by weighing the 0.1g supercritical extract, puts in the volumetric flask, and with an amount of ultrasonic dissolving that makes of 70% methanol, and accurate dilution, every 1ml solution contains the flos carthami of 12mg, filters, and gets subsequent filtrate and uses for measuring.
3.3 supercritical extract sample solution precision takes by weighing the 0.1g supercritical extract, it is an amount of to add ethyl acetate, makes the solution that every 1ml contains Radix Angelicae Sinensis medical material 1g.
4. instrument, equipment
4.1 supercritical extraction equipment HA121-50-05 type (Huaan, Nantong supercritical extraction company limited)
4.2 high performance liquid chromatograph Waters Alliance HPLC (waters company)
4.3 ultrasonic cleaner KQ-100DB type numerical control supersonic washer
5. detection method detects by Chinese Pharmacopoeia version in 2005 " discrimination method of Rhizoma Chuanxiong ", " the ferulaic acid content assay method of Radix Angelicae Sinensis " and " the Hydroxy Carthamus yellow content assaying method of Flos Carthami ".
Study on extraction
1. add the supercritical extraction parallel laboratory test research of pressing from both sides agent
1.1 supercritical extraction method is got Radix Angelicae Sinensis, Rhizoma Chuanxiong and the Flos Carthami mixed powder end 400g of mixing respectively in the prescription ratio, puts in the supercritical extraction reactor, acetone is entrainer, adds CO by 0%, 2% and 4% respectively
2Flow is that 25kg/h carries out supercritical extraction by parameter in the table 1, and the extract that obtains is measured by given TLC and HPLC condition determination, the results are shown in Table 1.
1.2 experimental result shows the adding of entrainer acetone, and is less to the extraction influence of volatile oil (ligustilide class), ferulic acid, and bigger to the influence of Hydroxy Carthamus yellow.Therefore, it is necessary adding entrainer.But entrainer concentration increases, and influence diminishes to the amplitude of the extraction increase of S-A Hydroxysafflor yellow A, considers other factors, and entrainer concentration adopts the acetone of adding 2%.
2. CO in the supercritical extraction
2Flow is to the influence of extraction results
2.1 supercritical extraction method is got Radix Angelicae Sinensis, Rhizoma Chuanxiong and the Flos Carthami mixed powder end 400g of mixing respectively in the prescription ratio, puts in the supercritical extraction reactor CO
2Flow is 25kg/h, carries out supercritical extraction by parameter in the table 2.
2.2 extract is measured by given detection TLC and HPLC condition determination, the results are shown in Table 2.
Table 1. entrainer is to supercritical extraction result's influence
| Parameter | TLC differentiates | HPLC measures (mg/g medical material) | The extract yield | ||
| Volatile oil | Ferulic acid | S-A Hydroxysafflor yellow A | |||
| 40℃ 35Mpa 2h | Acetone 0% | + | 0.337 | 5.114 | 2.95％ |
| Acetone 2% | + | 0.351 | 7.699 | 3.21％ | |
| Acetone 4% | + | 0.360 | 7.856 | 3.51％ | |
| Annotate | Separate 1:10Mpa, 45 ℃; Separate 2:5Mpa, 40 ℃; | ||||
Table 2. supercritical extraction CO
2Flow is to the influence of extraction results
| Parameter | TLC differentiates | HPLC measures (mg/g medical material) | Extraction yield | ||
| Volatile oil | Ferulic acid | S-A Hydroxysafflor yellow A | |||
| 40 ℃, 35Mpa, 2h, 2% acetone | 20kg/h | + | 0.345 | 7.335 | 3.15％ |
| 25kg/h | + | 0.355 | 7.473 | 3.29％ | |
| 30kg/h | + | 0.349 | 7.440 | 3.31％ | |
| Annotate | Separate 1:10Mpa, 45 ℃; Separate 2:5Mpa, 40 ℃; | ||||
By the result as can be known, under the condition of fixedly entrainer, extracting pressure, time and temperature, CO
2Flow is very little to the influence of extraction results, when the flow velocity of supercritical fluid reaches one regularly, supercritical extraction CO
2Flow is accessory to the influence of extraction results.Therefore, fixation of C O during supercritical extraction
2Flow is 25kg/h, and orthogonal experiment is no longer investigated this factor.
3. the orthogonal experiment of extraction process research
At entrainer, CO
2Flow is to the parallel laboratory test of supercritical extraction influence as a result on the base of optimum selection, according to the pharmacological action of each flavor medicine and the character of effective ingredient thereof, and in conjunction with the requirement of production technology and dosage form, intend investigating temperature, time and three factors of pressure flow, every factor has been selected three horizontal design experiments, with the extraction total amount and the supercritical CO of ferulic acid and S-A Hydroxysafflor yellow A
2The extraction yield is an index, tests preferred.
Table 3. water extraction orthogonal test factor-level design table
| Level | Factor | ||
| A (temperature t ℃) | B (extraction time min) | C (extracting pressure Mpa) | |
| 1 | 30 | 90 | 25 |
| 2 | 40 | 120 | 35 |
| 3 | 50 | 150 | 45 |
| Note | CO 2Flow: 25kg/h; Entrainer: 2% acetone | ||
3.1CO
2The supercritical fluid extraction method
In the ratio of each medical material in the prescription, accurately take by weighing each medicinal powder and add up to 400 grams, totally 9 parts, under the operation repetitive condition, press L
9(3
4) orthogonal table test 9 times.Extraction finishes, from separating still 1,2 receive extract, weigh, calculate the extract yield.Measure the ferulic acid in the extract and the content of S-A Hydroxysafflor yellow A respectively, be converted to extraction total amount in every gram medical material respectively according to extraction yield.
3.2 extraction yield is calculated
3.3 supercritical extraction Orthogonal experiment results and analysis
The results are shown in Table 4.
3.4 variance analysis
The results of analysis of variance shows: in the investigation factor, extraction does not have significance influence (P＞0.05) to ferulic acid for A (temperature), B (extracting pressure) (time), C (extracting pressure), but extraction has considerable influence (P＜0.10) to ferulic acid.Extraction has significance influence (P＜0.05) to factor A (temperature) to S-A Hydroxysafflor yellow A, and extraction all has certain influence (P＜0.10) to S-A Hydroxysafflor yellow A for B (time), C (extracting pressure); Each factor is then to the influence of the yield of extract there are no significant difference.
Design of table 4. supercritical extraction orthogonal experiment and experiment table
Each factor of table 5 influences the significance The results of analysis of variance to ferulic acid and S-A Hydroxysafflor yellow A extraction
| Soruces of variation | Sum of deviation square | Degree of freedom | Mean square deviation | The F value | Significance (P value) | |
| Extraction rate of ferulaic acid form | A | 0.06283 | 2 | 0.03185 | 9.40 | 0.05＜P＜0.10 |
| B | 0.08034 | 2 | 0.04017 | 12.08 | 0.05＜P＜0.10 | |
| C | 0.06061 | 2 | 0.003031 | 9.11 | 0.05＜P＜0.10 | |
| D (error) | 0.006650 | 2 | 0.003325 | |||
| The S-A Hydroxysafflor yellow A extraction ratio | A | 2.1748 | 2 | 1.0874 | 20.43 | ＜0.05 |
| B | 1.8303 | 2 | 0.9157 | 17.20 | 0.05＜P＜0.10 | |
| C | 1.2028 | 2 | 0.6014 | 11.31 | 0.05＜P＜0.10 | |
| D (error) | 0.1064 | 2 | 0.0532 | |||
| Extract yield % | A | 0.3018 | 2 | 0.1509 | 1.25 | ＞0.10 |
| B | 0.4384 | 2 | 0.2192 | 2.62 | ＞0.10 | |
| C | 0.2085 | 2 | 0.1043 | 1.25 | ＞0.10 | |
| D (error) | 0.1674 | 2 | 0.0837 | |||
F
0.90(2，2)＝9.0，F
0.95(2，2)＝19.0
3.5 result of the test analysis-by-synthesis
According to the result of and variance analysis directly perceived to test data, the primary condition that can draw extraction process is fixedly being carried agent concentration (acetone of adding 2%) and CO secretly promptly for we
2Under the condition of flow (25kg/h), the optimal processing parameter of ferulic acid extraction is combined as A
3B
3C
2, promptly temperature is 50 ℃, and the time is 2.5 hours, and extracting pressure is 35Mpa; And concerning S-A Hydroxysafflor yellow A, the optimum extraction process parameter combinations is A
2B
3C
3, promptly temperature is 40 ℃, and the time is 2.5 hours, and extracting pressure is 45Mpa; Each factor of extract yield is not all made significant difference.Although for ferulic acid and Hydroxy Carthamus yellow extraction, best extraction temperature separately is respectively 50 ℃ and 40 ℃, extracting pressure is respectively 35Mpa and 45Mpa, but it is all not very big that extraction efficiency differs, the safety of consider producing and cutting down the consumption of energy, and under the condition of 40 ℃ and 35Mpa, ferulic acid and Hydroxy Carthamus yellow extract the rate of transform and have all surpassed 65%, take all factors into consideration, determine that optimal processing parameter is combined as: extraction CO
2Flow is 25kg/h, and the entrainer addition is 2% acetone, and extraction temperature is 40 ℃, and extracting pressure is that 35Mpa and extraction time are 2.5 hours.
3.6 process certification
3.6.1, accurately take by weighing each medicinal powder that mixes and add up to 4000 grams to put in the extraction kettle in the ratio of preferred technological parameter condition in each medical material in the prescription, press the technological parameter condition of integrated optimization, under the operation repetitive condition, extract; Extraction finish the back from separating still 1,2 receive extract and weighing, measure by given TLC and HPLC condition determination and method, calculate extract yield and active constituent content, measure the ferulic acid in the extract and the content of S-A Hydroxysafflor yellow A respectively, be converted to extraction total amount in every gram medical material, triplicate respectively according to extraction yield.Concrete outcome sees Table 6.
Table 6. process certification result
| Numbering | TLC differentiates | Assay (mg/g medical material) | Extract yield (%) | |
| Volatile oil | Ferulic acid | S-A Hydroxysafflor yellow A | ||
| 1 | + | 0371 | 7.531 | 3.41 |
| 2 | + | 0.365 | 7.631 | 3.40 |
| 3 | + | 0.372 | 7.562 | 3.36 |
| X±SD | 0.369±0.00379 | 7.575±0.0512 | 3.397±0.0265 | |
Process certification is the result show, the supercritical extraction process that optimizes is feasible, not only the extract yield is stable, every quality index is all stable, the extraction rate of transform of ferulic acid and S-A Hydroxysafflor yellow A has also reached more than 70%, simultaneously, the yield of extract is more moderate, is fit to very much soft capsule preparation.Illustrate that the technology of selecting is feasible, can satisfy the needs of preparation process fully.
3.6.2 Study on extraction explanation
Getting mixed powder in the prescription ratio adopts vapor distillation to obtain volatile oil; In identical medical material ratio, adopt the TLC detection method, at the 365nm place, the contrast vapor distillation obtains the speckle and the fluorescence intensity of volatile oil and supercritical extract, the fluorescence intensity of finding the speckle of supercritical extract obviously surpasses the speckle of the volatile oil that vapor distillation obtains, illustrate among the present invention, extract volatile oil and adopt supercritical extraction obviously to be better than steam distillation.
Medicine of the present invention is on the basis of seeking the card ancient prescription, fully analytic demonstration, and ingenious compatibility, exquisite combination, tight prescription, treating both the principal and secondary aspects of a disease, evident in efficacy, have following outstanding advantage:
1. the present invention selects Flos Carthami to be used as medicine on the basis of foshousan, has significantly improved drug effect.
2. increase Borneolum Syntheticum and be used as medicine, improved bioavailability.
3. the physicochemical property with the main effective ingredient of each single medicinal material is a theoretical foundation, adopts CO
2Supercritical liquid extraction technique extracts lipotropy and hydrophilic composition, has avoided the isomerization of ligustilide, thereby has established material base for the raising of curative effect.
With the pharmacodynamics test of medicine of the present invention (hereinafter referred to as returning the rhizome of chuanxiong soft capsule), toxicology test and specific embodiment are further set forth beneficial effect of the present invention, but are not construed as limiting the invention below.
Pharmacodynamics test
1. materials and methods
1.1 material:
Healthy Wistar rat, male and female are not limit, body weight 230-270g, provide by Institute of Experimental Animals, Chinese Academy of Medical Sciences, (the animal quality certification number: the moving word of doctor 01-3008 number): healthy Kunming mouse, male and female half and half, body weight 19-25g provides the (quality certification number: the moving word of doctor 01-3001 number) by Institute of Experimental Animals, Chinese Academy of Medical Sciences.Experiment prospective adaptation raising 3 days, 24 ± 1 ℃ of Animal House temperature.
Return rhizome of chuanxiong soft capsule (GXRJN:Gui Xiong Ruan Jiao Nang) to provide by full Europe Chinese medicine expert group of the Chinese medicine chamber of commerce, lot number 028170, adult's (is that 60kg calculates by body weight) oral dose is 2000mg/d, be equivalent to crude drug amount 0.625g/ (kgd), by equivalent conversion rat is 3.5g/ (kgd), mice 6g/ (kgd); Tongxinluo, Yiling Pharmaceutical Co., Ltd, Shijiazhuang, lot number 050613; Aspirin, first pharmaceutical factory of Shijiazhuang medicine Group Co.,Ltd, lot number 050103LC; Propranolol, Suzhou medicine Group Co.,Ltd, lot number 041101; Nimodipine, the healthy pharmaceutcal corporation, Ltd in Shandong, lot number 0501068.
Instrument: BS-634 platelet aggregation instrument, Beijing biochemical instrument factory.WXG-1 type microcomputer animal cardio function meter, Nanjing Railway College of Medicine.
1.2 method
1.2.1 rat suppository forms experiment 1: get 40 of wistar rats, be divided at random and return 5 groups of the large, medium and small dosage group of rhizome of chuanxiong soft capsule, positive controls and negative control group, whenever knit 8.5 groups before experiment 24h and 1h irritate stomach respectively and give low dose and return rhizome of chuanxiong soft capsule 3.0g/kg (being equivalent to people's equivalent), middle dosage to return rhizome of chuanxiong soft capsule 6.0g/kg, heavy dose to return rhizome of chuanxiong soft capsule 12.0g/kg, aspirin 0.3g/kg and water.The administration volume is 5ml/kg.Intraperitoneal injection of ketamine 50mg/kg anesthetized rat, separate left external jugular vein and left neck artery, the quality of No. 4 silk threads of 1 long 5cm of precision weighing in advance, place stage casing (the long 8cm of 3 sections polyethylene tubes, internal diameter 1.8mm), two ends respectively connect a segment length 10cm, the polyethylene tube of internal diameter 1mm, and in pipe, be full of heparin-saline (containing the heparin amount is 50U/ml), after an end of pipe inserts left external jugular vein, inject above-mentioned heparin-saline 1ml/kg from polyethylene tube, clamp tube wall and the other end of pipe inserted left neck artery, decontrol blood flow then, during 15min in Herba Clinopodii, and take out the silk thread weighing rapidly, deduct former line weight with this line weight and be wet weight of thrombus.Calculate the thrombosis suppression ratio: suppression ratio=(matched group wet weight of thrombus one administration group wet weight of thrombus) ÷ matched group wet weight of thrombus * 100%.
1.2.2 rat suppository forms experiment 2: get 50 of Wistar rats, be divided into 5 groups at random, 10 every group.4 groups before experiment 24h and 1h irritate respectively stomach give in, low dose of rhizome of chuanxiong soft capsule 6.0 and 3.0g/kg and etc. the dosage Tongxinluo, the 5th group is that matched group gives water, filling stomach volume, assay method and data processing method are all the same.
1.2.3 clotting time of mice is measured: get 50 of mices, be divided at random and return 5 groups of the large, medium and small dosage group of rhizome of chuanxiong soft capsule, positive controls and negative control group, 10 every group.Irritate stomach respectively for 5 groups and return rhizome of chuanxiong soft capsule 24.0,12.0 and 6.0g/kg, aspirin 0.3g/kg and water are irritated the stomach volume and are 10ml/kg, and 1h observes clotting time of mice with slide method after irritating stomach.
1.2.4 timing is exhausted in mice swimming: get 90 of healthy mices, be divided into 6 groups at random, 15 every group.Irritate stomach respectively for 5 groups and give large and small dosage and return rhizome of chuanxiong soft capsule 6.0,24.0g/kg and same dose Tongxinluo and amfetamine 0.2g/kg, the 6th group is that matched group gives water.Irritate the stomach volume and be 10ml/kg, 1 time/d, continuous irrigation stomach 5 days, 1h measures the mice swimming exhaustion time after administration in the 5th day.Method:, after Mus tail heel bears a heavy burden mice is dropped in the water by mice body constitution amount 6%, observed mice and haul oneself willingly in the entry to head and sink to the time that can not lift more than the 7s, this time is the swimming exhaustion time.Calculate and respectively organize the mice meansigma methods of swimming exhaustion time.
1.2.5 to the thrombotic influence of rat artery-vein bypass: 60 of male rats, body weight 2804 ± 20g, be divided into 6 groups at random, received 7 days (aspirin administration 4 days) continuously, after the last administration 1 hour, rat pentobarbital sodium intraperitoneal injection of anesthesia (0.05g/kg), tracheal intubation, separate right common carotid artery and left external jugular vein, put into 4 long trumpeter's art silk threads of 5cm in the polyethylene tube stage casing, be full of heparin-saline 50u/ml in the pipe, will manage two ends and insert right common carotid artery and left external jugular vein respectively, form the bypass of artery-vein blood flow, the rat femoral vein injects heparin-saline 50u/kg, promptly open blood flow, blocking blood flow after 15 minutes, removal of thromboses is weighed rapidly, and gross weight deducts silk thread and heavily is wet weight of thrombus.
1.2.6 influence: 60 of Mus great and mighty or powerful to the rat platelet aggregation function, body weight 200 ± 20g, divide equally 6 groups, administration is with experiment 2.2, after 1 hour, rat pentobarbital sodium intraperitoneal injection of anesthesia is taken a blood sample from the rat ventral aorta with the silication syringe in the last administration, put in the silication centrifuge tube, with the anticoagulant in 9: 1 of 3.8% citric acid solution, with 1000 rev/mins centrifugal 5 minutes, make platelet rich plasma (PRP), with 2000 rev/mins, centrifugal 10 minutes, make platelet poor plasma (PPP), by turbidimetry, add 60umol ADP solution 20ul, measure with RS-634 type platelet aggregation instrument and respectively organize the rat platelet maximum agglutination rate.
1.2.7 influence to mouse brain circulatory disturbance: 70 of mices, male and female half and half, body weight 21 ± 2g divides equally 7 groups.Successive administration 7 days, nimodipine are in experiment oral administration on the same day once.After the last administration 30 minutes, urethane 1.2g/kg intraperitoneal injection of anesthesia separates bilateral carotid, with No. 0 surgical thread while ligation bilateral carotid and vagus nerve, and the death time of immediate record mice after because of cerebral hypoxia ischemia.
1.2.8 the injected in mice air is caused the anoxybiotic influence of heart and brain: 90 of mices, male and female half and half, body weight 20 ± 2g divides equally 6 groups, and administration is with experiment 2.4, and gains in depth of comprehension are satisfied with to test and were administered once the same day.After 30 minutes, mouse tail vein injection air 0.1ml/ only injected the air-breathing dwell time of immediate record mice in 0.1 second in the last administration.
1.2.9 the influence to people Mus ischemic cerebral edema: body weight 230g ± 18g, 60 of female people Mus are divided into 6 groups at random, 10 every group.Each organizes rat ig administration, continuous 5 days.Pseudo-ligation group and model control group give with the volume normal saline.After the last administration, rat is with the dosage ip anesthesia of chloral hydrate 350mg/kg.Each treated animal ligation bilateral common carotid arteries, pseudo-ligation group only exposes, separates bilateral common carotid arteries, not ligation.The postoperative animal is observed 48h in temperature is 28-30 ℃ observation ward.If any animal dead, broken end is got brain and is claimed weight in wet base immediately.Animal is the whole sacrificed by decapitation of 48h after surgery, get brain, and analytical balance claims weight in wet base.Afterwards, brain is put into 110 ℃ baking oven baking 48h to constant weight, analytical balance claims dry weight.
2 results
2.1 the influence of returning the rhizome of chuanxiong soft capsule that rat suppository is formed: return the formation of the rat platelet thrombosis of 3 dosage groups of rhizome of chuanxiong soft capsule and aspirin group to be subjected to remarkable inhibition, significance meaning (P＜0.01) is more all arranged, the results are shown in Table 1 with matched group.
Table 1. is returned the influence that the rhizome of chuanxiong soft capsule forms rat suppository (n=8, X ± S)
| Group | Dosage (g/kg) | Wet weight of thrombus (mg) | Suppression ratio (%) |
| Control returns rhizome of chuanxiong soft capsule I group to return rhizome of chuanxiong soft capsule II group to return rhizome of chuanxiong soft capsule III group aspirin | - 3.0 6.0 12.0 0.3 | 38.5±7.1 23.8±3.5 * 20.8±4.1 * 16.2±5.8 * 16.9±3.1 * | - 38 46 59 56 |
Annotate: compare with matched group,
*P＜0.01
2.2 return rhizome of chuanxiong soft capsule and Tongxinluo anti thrombotic action relatively: return the rhizome of chuanxiong soft capsule that the thrombotic inhibitory action of rat artery significantly is better than the Tongxinluo of same dose, the results are shown in Table 2.
Table 2. is returned rhizome of chuanxiong soft capsule and Tongxinluo anti thrombotic action relatively (n=10, X ± S)
| Group | Dosage (g/kg) | Wet weight of thrombus (m/mg) | Suppression ratio (%) |
| Control returns rhizome of chuanxiong soft capsule I group to return rhizome of chuanxiong soft capsule II group Tongxinluo I group Tongxinluo II group | - 3.0 6.0 3.0 6.0 | 42.4±2.0 30.5±2.2 *Δ 23.7±2.5 *ΔΔ 33.2±1.5 * 29.8±4.2 * | - 28 44 22 29 |
Annotate: compare with matched group
*Compare with the Tongxinluo group P＜0.01
ΔP＜0.05
The Δ ΔP＜0.01
2.3 return of the influence of rhizome of chuanxiong soft capsule: return the equal significant prolongation of clotting time of mice of big or middle dosage group of rhizome of chuanxiong soft capsule and aspirin group, the significance statistical significance is more all arranged, the results are shown in Table 3 with matched group to clotting time of mice.
Table 3. returns the rhizome of chuanxiong soft capsule to the influence of clotting time of mice (n=10, X ± S)
| Group | Dosage (g/kg) | Clotting time (s) |
| Control returns rhizome of chuanxiong soft capsule I group to return rhizome of chuanxiong soft capsule II group to return rhizome of chuanxiong soft capsule III group aspirin | - 3.0 6.0 12.0 0.3 | 117±27 137±51 191±50 * 232±65 * 197±63 * |
Annotate: compare with matched group
*P＜0.01
2.4 return the influence of rhizome of chuanxiong soft capsule to the mice swimming exhaustion time: equal significant prolongation of time is exhausted in the swimming of each administration group mice, with matched group the significance meaning is arranged more all, and return the heavy dose of group of rhizome of chuanxiong soft capsule that highly significant difference is arranged, illustrate that but Rhizoma Chuanxiong soft capsule dose dependent ground prolongs the mice swimming exhaustion time, has resisting fatigue, strengthen the effect of animal muscle power and endurance, the results are shown in Table 4.
Table 4. returns the rhizome of chuanxiong soft capsule to the influence of mice swimming exhaustion time (n=15, X ± S)
| Group | Dosage (g/kg) | The swimming exhaustion time (s) |
| Control returns rhizome of chuanxiong soft capsule I group to return rhizome of chuanxiong soft capsule II to organize stupid propylamine Tongxinluo I group Tongxinluo II group | - 6.0 24.0 0.2 6.0 24.0 | 502±100 899±403 * 2512±1244 ** 1577±1099 ** 1206±645 ** 1805±100 ** |
Annotate: compare with matched group
*P＜0.05,
*P＜0.01
2.5 return the rhizome of chuanxiong soft capsule to the thrombotic influence of rat artery-vein bypass: to return three dosage groups of rhizome of chuanxiong soft capsule all can obviously suppress rat artery-vein bypass thrombosis, the high and low dose group presents tangible effect difference, return rhizome of chuanxiong soft capsule and Tongxinluo relatively with the dosage group, its thrombosis suppression ratio does not have marked difference, the results are shown in Table 5.
Table 5. returns the rhizome of chuanxiong soft capsule to the thrombotic influence of rat artery-vein bypass (n=10, X ± S)
| Group | Dosage (the g crude drug/kgd) | Wet weight of thrombus (mg) | Suppression ratio (%) |
| Control aspirin Tongxinluo returns rhizome of chuanxiong soft capsule I group to return rhizome of chuanxiong soft capsule II group to return rhizome of chuanxiong soft capsule III group | NS 0.1×4 6.0×7 3.0×7 6.0×7 9.0×7 | 41.9±6.40 23.5±3.29 ** 27.9±2.80 * 31.7±3.31 ** 29.5±3.57 ** 28.9±2.95 **Δ | - 43.93 33.41 27.10 33.12 35.28 |
Annotate: compare with matched group
*P＜0.05,
*Compare with returning rhizome of chuanxiong soft capsule I group P＜0.01
ΔP＜0.05
2.6 return of the influence of rhizome of chuanxiong soft capsule: return three dosage groups of rhizome of chuanxiong soft capsule that platelet aggregation in the inductive rat body of ADP is all had the obvious suppression effect to the rat platelet aggregation function, return rhizome of chuanxiong soft capsule and Tongxinluo relatively with the dosage group, its platelet aggregation inhibition rate does not have marked difference, sees Table 6.
Table 6. returns the rhizome of chuanxiong soft capsule to the influence of rat platelet aggregation function (n=10, X ± S)
| Group | Dosage (the g crude drug/kgd) | Maximum agglutination rate (mg) | Assemble suppression ratio (%) |
| Control aspirin Tongxinluo returns rhizome of chuanxiong soft capsule I group to return rhizome of chuanxiong soft capsule II group to return rhizome of chuanxiong soft capsule III group | NS 0.2×4 6.0×7 3.0×7 6.0×7 9.0×7 | 57.7±7.89 25.1±11.02 ** 38.9±10.98 ** 38.9±9.47 ** 37.8±9.59 ** 31.7±9.79 **Δ | - 57.8 31.7 33.3 34.1 47.8 |
Annotate: compare with matched group
*Compare with returning rhizome of chuanxiong soft capsule I group P＜0.01
ΔP＜0.05
2.7 return of the influence of rhizome of chuanxiong soft capsule: return three dosage groups of rhizome of chuanxiong soft capsule all can obviously prolong the time-to-live of disturbance of cerebral circulation mice to mouse brain circulatory disturbance, present certain dose-effect relationship between each group, return rhizome of chuanxiong soft capsule and Tongxinluo with the dosage group relatively, its time-to-live indifference sees Table 7.
Table 7 returns the rhizome of chuanxiong soft capsule to the influence of mouse brain circulatory disturbance (n=10, X ± S)
| Group | Dosage (the g crude drug/kgd) | The mice time-to-live (min) | Survival rate elongation (%) |
| Pseudo-operation group Control Nimodipine Tongxinluo returns rhizome of chuanxiong soft capsule I group to return rhizome of chuanxiong soft capsule II group to return rhizome of chuanxiong soft capsule III group | NS NS 0.04×7 6.0×7 3.0×7 6.0×7 12.0×7 | ＞120.00 7.21±1.89 26.29±8.90 ** 22.98±9.31 * 17.28±5.89 ** 23.72±7.97 **ΔΔ 29.21±10.21 ** # | - - 263.5 228.8 109.2 223.2 332.4 |
Annotate: compare with matched group
*P＜0.05,
*Compare with returning rhizome of chuanxiong soft capsule I group P＜0.01
The Δ ΔCompare with returning rhizome of chuanxiong soft capsule II group P＜0.01
#P＜0.05
2.8 return the rhizome of chuanxiong soft capsule that the injected in mice air is caused the anoxybiotic influence of heart and brain: return three dosage groups of rhizome of chuanxiong soft capsule all can obviously prolong the mice inspiratory duration, the effect of middle and high dosage group is close, return rhizome of chuanxiong soft capsule and Tongxinluo relatively with the dosage group, the former has prolongation slightly than the latter at air-breathing dwell time, sees Table 8.
Table 8 returns the rhizome of chuanxiong soft capsule that the injected in mice air is caused the anoxybiotic influence of heart and brain (n=15, X ± S)
| Group | Dosage (the g crude drug/kgd) | The air-breathing dwell time of mice (s) | Survival rate elongation (%) |
| Control | NS | 37.18±5.72 | - |
| The propranolol Tongxinluo returns rhizome of chuanxiong soft capsule I group to return rhizome of chuanxiong soft capsule II group to return rhizome of chuanxiong soft capsule III group | 0.03×1 6.0×7 3.0×7 6.0×7 9.0×7 | 63.92±9.21 ** 49.81±12.31 ** 49.92±9.21 ** 53.23±9.27 **ΔΔ 57.51±8.41 **ΔΔ | 73.50 34.48 18.06 47.68 51.43 |
Annotate: compare with matched group
*P＜0.05,
*Compare with returning rhizome of chuanxiong soft capsule I group P＜0.01
The Δ ΔP＜0.01
2.9 return the influence of rhizome of chuanxiong soft capsule to the rat ischemia cerebral edema: return the middle and high dosage group of rhizome of chuanxiong soft capsule all can obviously alleviate the water content of cerebral tissue, relatively there were significant differences with matched group, the results are shown in Table 9.
Table 9 returns the rhizome of chuanxiong soft capsule to the influence of rat ischemia cerebral edema (n=10, X ± S)
| Group | Dosage (mg/kg) | Cutaneous horn heavy (g) | Brain stem heavy (g) | Brain water content (%) |
| Pseudo-operation group Control Tongxinluo returns rhizome of chuanxiong soft capsule I group to return rhizome of chuanxiong soft capsule II group to return rhizome of chuanxiong soft capsule III group | NS NS 1.0 0.2 0.4 0.8 | 1.298±0.089 1.407±0.085 1.371±0.060 1.339±0.100 1.321±0.080 1.379±0.098 | 0.295±0.019 0.281±0.015 0.286±0.012 0.272±0.013 0.289±0.018 0.292±0.016 | 77.88±0.41 *** 80.33±1.29 79.11±1.14 * 79.66±1.27 78.89±1.15 * 78.77±0.79 ** |
Annotate: compare with matched group
*P＜0.05,
*P＜0.01,
* *P＜0.001
Acute toxicity test
After returning the rhizome of chuanxiong soft capsule by the administration of 225g/kg crude drug in whole body weight mouse stomach, once a day, raise routinely after the administration, observe the situation of mice drinking-water, feed, defecation, activity and hair color aspect every day, continuous 7 days, every observation index of requirement was all normal, and any toxic reaction does not appear in mice.Can not obtain its LD
50, the maximum tolerance of mice multiple is 363.63 times of clinical adult's consumption.
The specific embodiment
Embodiment 1 active component prepares embodiment
Take by weighing Radix Angelicae Sinensis 600g, Rhizoma Chuanxiong 400g is in extraction kettle, and regulating extraction temperature is 35 ℃, and pressure is 30Mpa, CO
2Flow is 30kg/h, and entrainer is 3% acetone, separating still 1: 45 ° of temperature, and pressure 10Mpa, separating still 2: 40 ℃ of temperature, pressure 5Mpa receives to such an extent that extract amounts to 56g from separating still 1,2 behind the extraction 3h.
Embodiment 2 active component prepare embodiment
Take by weighing Radix Angelicae Sinensis 460g, Rhizoma Chuanxiong 540g is in extraction kettle, and regulating extraction temperature is 30 ℃, and pressure is 40Mpa, CO
2Flow is 20kg/h, and entrainer is 4% acetone, separating still 1: 45 ° of temperature, and pressure 10Mpa, separating still 2: 40 ℃ of temperature, pressure 5Mpa receives to such an extent that extract amounts to 52g from separating still 1,2 behind the extraction 1.5h.
Embodiment 3 active component prepare embodiment
Take by weighing Radix Angelicae Sinensis 480g, Rhizoma Chuanxiong 520g is in extraction kettle, and regulating extraction temperature is 40 ℃, and pressure is 35Mpa, CO
2Flow is 25kg/h, and entrainer is 2% acetone, separating still 1: 45 ° of temperature, and pressure 10Mpa, separating still 2: 40 ℃ of temperature, pressure 5Mpa receives to such an extent that extract amounts to 52g from separating still 1,2 behind the extraction 2.5h.
Embodiment 4 active component prepare embodiment
Take by weighing Radix Angelicae Sinensis 500g, Rhizoma Chuanxiong 500g is in extraction kettle, and regulating extraction temperature is 45 ℃, and pressure is 40Mpa, CO
2Flow is 25kg/h, and entrainer is 1% acetone, separating still 1: 45 ° of temperature, and pressure 10Mpa, separating still 2: 40 ℃ of temperature, pressure 5Mpa receives to such an extent that extract amounts to 50g from separating still 1,2 behind the extraction 2.5h.
Embodiment 5 active component prepare embodiment
Take by weighing Radix Angelicae Sinensis 400g, Rhizoma Chuanxiong 600g is in extraction kettle, and regulating extraction temperature is 45 ℃, and pressure is 35Mpa, CO
2Flow is 25kg/h, and entrainer is 2% acetone, separating still 1: 45 ° of temperature, pressure 10Mpa, separating still 2; 40 ℃ of temperature, pressure 5Mpa receives to such an extent that extract amounts to 52g from separating still 1,2 behind the extraction 3h.
Embodiment 6 active component prepare embodiment
Take by weighing Radix Angelicae Sinensis 500g, Rhizoma Chuanxiong 420g, Flos Carthami 80g are in extraction kettle, and regulating extraction temperature is 50 ℃, and pressure is 40Mpa, CO
2Flow is 25kg/h, and entrainer is 0.5% acetone, separating still 1: 45 ° of temperature, and pressure 10Mpa, separating still 2: 40 ℃ of temperature, pressure 5Mpa receives to such an extent that extract amounts to 55g from separating still 1,2 behind the extraction 2.5h.
Embodiment 7 active component prepare embodiment
Take by weighing Radix Angelicae Sinensis 750g, Rhizoma Chuanxiong 200g, Flos Carthami 50g are in extraction kettle, and regulating extraction temperature is 40 ℃, and pressure is 45Mpa, CO
2Flow is 25kg/h, and entrainer is 2% acetone, separating still 1: 45 ° of temperature, and pressure 10Mpa, separating still 2: 40 ℃ of temperature, pressure 5Mpa receives to such an extent that extract amounts to 53g from separating still 1,2 behind the extraction 3h.
Embodiment 8 active component prepare embodiment
Take by weighing Radix Angelicae Sinensis 300g, Rhizoma Chuanxiong 600g, Flos Carthami 100g are in extraction kettle, and regulating extraction temperature is 38 ℃, and pressure is 43Mpa, CO
2Flow is 25kg/h, and entrainer is 2% acetone, separating still 1: 45 ° of temperature, and pressure 10Mpa, separating still 2: 40 ℃ of temperature, pressure 5Mpa receives to such an extent that extract amounts to 50g from separating still 1,2 behind the extraction 2h.
Embodiment 9 active component prepare embodiment
Take by weighing Radix Angelicae Sinensis 400g, Rhizoma Chuanxiong 500g, Flos Carthami 100g are in extraction kettle, and regulating extraction temperature is 45 ℃, and pressure is 35Mpa, CO
2Flow is 25kg/h, and entrainer is 2% acetone, separating still 1: 45 ° of temperature, and pressure 10Mpa, separating still 2: 40 ℃ of temperature, pressure 5Mpa receives to such an extent that extract amounts to 54g from separating still 1,2 behind the extraction 1.5h.
Embodiment 10 active component prepare embodiment
Take by weighing Radix Angelicae Sinensis 350g, Rhizoma Chuanxiong 650g, Flos Carthami 50g are in extraction kettle, and regulating extraction temperature is 38 ℃, and pressure is 45Mpa, CO
2Flow is 25kg/h, and entrainer is 3% acetone, separating still 1: 45 ° of temperature, and pressure 10Mpa, separating still 2: 40 ℃ of temperature, pressure 5Mpa receives to such an extent that extract amounts to 56g from separating still 1,2 behind the extraction 2.5h.
Embodiment 11 active component prepare embodiment
Take by weighing Radix Angelicae Sinensis 485g, Rhizoma Chuanxiong 427g, Flos Carthami 88g are in extraction kettle, and regulating extraction temperature is 40 ℃, and pressure is 35Mpa, CO
2Flow is 25kg/h, and entrainer is 2% acetone, separating still 1: 45 ° of temperature, and pressure 10Mpa, separating still 2: 40 ℃ of temperature, pressure 5Mpa receives to such an extent that extract amounts to 53g from separating still 1,2 behind the extraction 2.5h.
Embodiment 12 active component prepare embodiment
Take by weighing Radix Angelicae Sinensis 515g, Rhizoma Chuanxiong 400g, Flos Carthami 85g are in extraction kettle, and regulating extraction temperature is 45 ℃, and pressure is 35Mpa, CO
2Flow is 25kg/h, and entrainer is 2% acetone, separating still 1: 45 ° of temperature, and pressure 10Mpa, separating still 2: 40 ℃ of temperature, pressure 5Mpa receives to such an extent that extract amounts to 51g from separating still 1,2 behind the extraction 2h.
Embodiment 13 soft capsule preparation embodiment
Get in 120 parts of water of 100 parts of addings of gelatin and make its imbibition, in addition 30 parts of glycerol are heated to 60 ℃～80 ℃, expansible gelatin is added, stir fusion, heat preservation for standby use;
Get the active component 56g of embodiment 1 preparation, soybean oil 400g, Cera Flava 25g, 80 ℃ are heated to the Cera Flava dissolving, are trimmed to suitable dispersion with shearing dispersing emulsification machine, add the soybean oil 300g of surplus, are trimmed to be uniformly dispersed;
With gelatin solution and the medicinal liquid rotation rolling capsule machine automatically of packing into, be pressed into the soft capsule that specification is the 0.4g/ grain.
Embodiment 14 soft capsule preparation embodiment
Get in 140 parts of water of 100 parts of addings of gelatin and make its imbibition, in addition 30 parts of glycerol are heated to 60 ℃～80 ℃, expansible gelatin is added, stir fusion, heat preservation for standby use;
Get the active component 52g of embodiment 3 preparations, soybean oil 400g, Cera Flava 25g, 80 ℃ are heated to the Cera Flava dissolving, are trimmed to suitable dispersion with shearing dispersing emulsification machine, add the soybean oil 300g of surplus, are trimmed to be uniformly dispersed;
With gelatin solution and the medicinal liquid rotation rolling capsule machine automatically of packing into, be pressed into the soft capsule that specification is the 0.4g/ grain.
Embodiment 15 soft capsule preparation embodiment
Get in 130 parts of water of 100 parts of addings of gelatin and make its imbibition, in addition 30 parts of glycerol are heated to 60 ℃～80 ℃, expansible gelatin is added, stir fusion, heat preservation for standby use;
Get the active component 53g of embodiment 11 preparations, Semen Maydis oil 400g, Cera Flava 30g, 85 ℃ are heated to the Cera Flava dissolving, are trimmed to suitable dispersion with shearing dispersing emulsification machine, add the Semen Maydis oil 200g of surplus, are trimmed to be uniformly dispersed;
With gelatin solution and the medicinal liquid rotation rolling capsule machine automatically of packing into, be pressed into the soft capsule that specification is the 0.4g/ grain.
Embodiment 16 soft capsule preparation embodiment
Get in 140 parts of water of 100 parts of addings of gelatin and make its imbibition, in addition 35 parts of glycerol are heated to 60 ℃～80 ℃, expansible gelatin is added, stir fusion, heat preservation for standby use;
Get the active component 53g of embodiment 11 preparations, Oleum Sesami 500g, Cera Flava 35g, Borneolum Syntheticum 5.5g, 75 ℃ are heated to the Cera Flava dissolving, are trimmed to suitable dispersion with shearing dispersing emulsification machine, add the Oleum Sesami 350g of surplus, are trimmed to be uniformly dispersed;
With gelatin solution and the medicinal liquid rotation rolling capsule machine automatically of packing into, be pressed into the soft capsule that specification is the 0.4g/ grain.
Embodiment 17 soft capsule preparation embodiment
Get in 120 parts of water of 100 parts of addings of gelatin and make its imbibition, in addition 40 parts of glycerol are heated to 60 ℃～80 ℃, expansible gelatin is added, stir fusion, heat preservation for standby use;
Get the active component 56g of embodiment 10 preparations, Semen Maydis oil 500g, insect wax 20g, 80 ℃ are heated to the insect wax dissolving, are trimmed to suitable dispersion with shearing dispersing emulsification machine, add the Semen Maydis oil 300g of surplus, are trimmed to be uniformly dispersed;
With gelatin solution and the medicinal liquid rotation rolling capsule machine automatically of packing into, be pressed into the soft capsule that specification is the 0.4g/ grain.
Embodiment 18 soft capsule preparation embodiment
Get in 120 parts of water of 100 parts of addings of gelatin and make its imbibition, in addition 30 parts of glycerol are heated to 60 ℃～80 ℃, expansible gelatin is added, stir fusion, heat preservation for standby use;
Get the active component 52g of embodiment 3 preparations, Oleum Sesami 500g, Cera Flava 20g, Borneolum Syntheticum 5g, 85 ℃ are heated to the Cera Flava dissolving, are trimmed to suitable dispersion with shearing dispersing emulsification machine, add the Oleum Sesami 300g of surplus, are trimmed to be uniformly dispersed;
With gelatin solution and the medicinal liquid rotation rolling capsule machine automatically of packing into, be pressed into the soft capsule that specification is the 0.4g/ grain.
Embodiment 19 soft capsule preparation embodiment
Get in 120 parts of water of 100 parts of addings of gelatin and make its imbibition, in addition 30 parts of sorbitol are heated to 60 ℃～80 ℃, expansible gelatin is added, stir fusion, heat preservation for standby use;
Get the active component 55g of embodiment 6 preparations, Oleum Brassicae campestris 400g, Cera Flava 30g, 70 ℃ are heated to the Cera Flava dissolving, are trimmed to suitable dispersion with shearing dispersing emulsification machine, add the Oleum Brassicae campestris 400g of surplus, are trimmed to be uniformly dispersed;
With gelatin solution and the medicinal liquid rotation rolling capsule machine automatically of packing into, be pressed into the soft capsule that specification is the 0.4g/ grain.
Embodiment 20 soft capsule preparation embodiment
Get in 140 parts of water of 100 parts of addings of gelatin and make its imbibition, in addition 30 parts of sorbitol are heated to 60 ℃～80 ℃, expansible gelatin is added, stir fusion, heat preservation for standby use;
Get the active component 52g of embodiment 3 preparations, Oleum Arachidis hypogaeae semen 400g, Cera Flava 30g, Borneolum Syntheticum 2g, 85 ℃ are heated to the Cera Flava dissolving, are trimmed to suitable dispersion with shearing dispersing emulsification machine, add the Oleum Arachidis hypogaeae semen 300g of surplus, are trimmed to be uniformly dispersed;
With gelatin solution and the medicinal liquid rotation rolling capsule machine automatically of packing into, be pressed into the soft capsule that specification is the 0.4g/ grain.
Embodiment 21 soft capsule preparation embodiment
Get in 140 parts of water of 100 parts of addings of gelatin and make its imbibition, in addition 30 parts of glycerol are heated to 60 ℃～80 ℃, expansible gelatin is added, stir fusion, heat preservation for standby use;
Get the active component 53g of embodiment 11 preparations, Oleum Sesami 450g, insect wax 20g, Borneolum Syntheticum 5g, 85 ℃ are heated to the insect wax dissolving, are trimmed to suitable dispersion with shearing dispersing emulsification machine, add the Oleum Sesami 300g of surplus, are trimmed to be uniformly dispersed;
With gelatin solution and the medicinal liquid rotation rolling capsule machine automatically of packing into, be pressed into the soft capsule that specification is the 0.4g/ grain.
Embodiment 22 soft capsule preparation embodiment
Get in 120 parts of water of 100 parts of addings of gelatin and make its imbibition, in addition 30 parts of glycerol are heated to 60 ℃～80 ℃, expansible gelatin is added, stir fusion, heat preservation for standby use;
Get the active component 50g of embodiment 8 preparations, Oleum Sesami 350g, Cera Flava 20g, Borneolum Syntheticum 4.5g, 80 ℃ are heated to the Cera Flava dissolving, are trimmed to suitable dispersion with shearing dispersing emulsification machine, add the Oleum Sesami 300g of surplus, are trimmed to be uniformly dispersed;
With gelatin solution and the medicinal liquid rotation rolling capsule machine automatically of packing into, be pressed into the soft capsule that specification is the 0.4g/ grain.
Embodiment 23 soft capsule preparation embodiment
Get in 130 parts of water of 100 parts of addings of arabic gum and make its imbibition, in addition 30 parts of glycerol are heated to 60 ℃～80 ℃, expansible gelatin is added, stir fusion, heat preservation for standby use;
Get the active component 55g of embodiment 11 preparations, Oleum Sesami 450g, Cera Flava 25g, Borneolum Syntheticum 4.5g, 80 ℃ are heated to the Cera Flava dissolving, are trimmed to suitable dispersion with shearing dispersing emulsification machine, add the Oleum Sesami 300g of surplus, are trimmed to be uniformly dispersed;
With gelatin solution and the medicinal liquid rotation rolling capsule machine automatically of packing into, be pressed into the soft capsule that specification is the 0.4g/ grain.
Embodiment 24 preparation tablets embodiment
With the active component 56g among the embodiment 1 and 1: 1 mixed of starch, with 25g sodium carboxymethyl cellulose and said mixture mix homogeneously, the alcoholic solution of adding 75% is as adhesive, cross 22 mesh sieves, 40 degree oven dryings add an amount of magnesium stearate, tabletting is made the tablet of 300mg/ sheet.
Embodiment 25 coated tablets prepare embodiment
Active component 53g among the embodiment 11 is mixed with the 17g light magnesium oxide, add 17g starch, lactose 17g, 0.5% HPMC aqueous solution is made adhesive, makes the plain sheet of 300mg/ sheet, with the strange RL30D coating of 30% You Te, makes the coated preparation of 300mg/ sheet.
Embodiment 26 capsules prepare embodiment
With the active component 52g among the embodiment 3 and 1: 1 mixed of starch, with 25g sodium carboxymethyl cellulose and said mixture mix homogeneously, the alcoholic solution of adding 75% is as adhesive, cross 22 mesh sieves, 40 degree oven dryings, granulate, adorn hard capsule, make the capsule of 270mg/ grain.
Embodiment 27 concentrated pills prepare embodiment
Active component 53g among the embodiment 11 is mixed with microcrystalline Cellulose, and wherein the consumption of microcrystalline Cellulose is 40% of an extract powder, adds entry and makes plain ball as binding agent.
The Opadry (stomach dissolution type) of selecting above-mentioned plain ball for use Shanghai Ka Lekang (COLORCON) packaging technique company limited is for the coating material of this product carries out coating, the concentrated pill preparation.
Coating conditions is as follows: selecting water for use is lytic agent; Coating solution concentration is 20%; Coating weightening finish 5%; 80 ℃ of inlet temperature; 45 ℃ of sheet bed tempertaures; Atomizing pressure 2.0bar; Coating pan rotating speed 17rmp; Charging flow velocity 3g/min.
Embodiment 28 granules prepare embodiment
Get the active component 53g among the embodiment 11, methylcellulose 9g, Icing Sugar 820g behind the mix homogeneously, adds an amount of 70% ethanol, makes soft material, granulates, and flings to ethanol, and 80 ℃ of spray dryinges are made granule.
Embodiment 29 drop pills prepare embodiment
Get 300g Polyethylene Glycol-6000 and be heated to 80 ℃, add the active component 53g among the embodiment 11 after the fusion, stir, move in the drop pill machine, keep 70 ℃ of fused solution temperature, from top to bottom, drip moderate the splashing in 10 ℃ of methyl-silicone oils of speed, make 1000 of drop pills.
Claims (13)
1, a kind of Chinese medicine extract is characterized in that, it is mainly made by following raw materials in weight portion medicine:
Radix Angelicae Sinensis 30～75 Rhizoma Chuanxiongs 20～65.
2, Chinese medicine extract according to claim 1 is characterized in that, crude drug also has Flos Carthami 5～10.
3, Chinese medicine extract according to claim 2 is characterized in that, the raw material medicines in portions by weight proportioning is:
Radix Angelicae Sinensis 40～50 Rhizoma Chuanxiongs 40～50 Flos Carthamis 8～10.
4, the extracting method of the described Chinese medicine extract of the arbitrary claim of claim 1～3 is characterized in that, adopts supercritical fluid extraction, and condition is: extraction temperature is 30 ℃～50 ℃, and pressure is 25MPa～45Mpa, and extraction time is 1～3h, CO
2Flow is 10～30kg/L, and entrainer is 0.5%～5% acetone.
5, the extracting method of Chinese medicine extract according to claim 4 is characterized in that, adopts CO
2Supercritical fluid extraction, condition is: extraction temperature is 40 ℃, and pressure is 35Mpa, and extraction time is 2.5h, CO
2Flow is 25kg/L, and entrainer is 2% acetone.
6, contain the preparation of the described Chinese medicine extract of the arbitrary claim of claim 1～3, it is characterized in that, it comprises acceptable carrier in this Chinese medicine extract and the medicament.
7, Chinese medicine preparation according to claim 6 is characterized in that, is soft capsule, comprises following components in weight percentage:
Chinese medicine extract 2.5%～10% vegetable oil 85%～96% suspending agent 1.5%～5%.
8, Chinese medicine preparation according to claim 6 is characterized in that, is soft capsule, and it comprises following components in weight percentage:
Chinese medicine extract 2.5%～10% vegetable oil 80%～95.8% suspending agent 1.5%～5% Borneolum Syntheticum 0.2%～5%.
9, according to claim 7 or 8 described Chinese medicine preparation, it is characterized in that described vegetable oil is selected from soybean oil, Oleum Sesami, Semen Maydis oil, Oleum Brassicae campestris, Oleum Arachidis hypogaeae semen, Oleum sesami, Oleum Helianthi, walnut oil.
10, according to claim 7 or 8 described Chinese medicine preparation, it is characterized in that suspending agent is selected from Cera Flava, Cera Flava, cera alba, insect wax.
11, the preparation method of claim 7 or 8 described Chinese medicine preparation is characterized in that, may further comprise the steps: all the other each components that take by weighing an amount of vegetable oil and formula ratio; Heating makes the suspending agent dissolving; Be trimmed to suitable dispersion with shearing dispersing emulsification machine; Add the surplus vegetable oil to formula ratio, be trimmed to and be uniformly dispersed; Medicinal liquid and capsule material liquid are prepared into soft capsule with rotating rolling capsule machine automatically.
12, the preparation method of Chinese medicine preparation according to claim 11 is characterized in that, heating-up temperature is 70 ℃～85 ℃.
13, the described Chinese medicine extract of the arbitrary claim of claim 1～3 improves the small arterial blood circulation of brain in preparation, improve the blood supply of cerebral cortex cerebrovascular bed, promote the application in the cardiovascular and cerebrovascular diseases medicaments such as small tremulous pulse sphincter opening of brain and prevention and treatment transient apoplexy, nonsystemic vertigo, cerebral infarction sequela, cerebrovascular blood supply insufficiency, coronary heart disease, angina pectoris.
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| CNA200610066051XA CN1903238A (en) | 2005-07-28 | 2006-03-28 | Extractive of traditional Chinese medicine, its prepns., preparing method and application thereof |
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| CN200510014651 | 2005-07-28 | ||
| CN200510014651.7 | 2005-07-28 | ||
| CN200510015006.7 | 2005-09-07 | ||
| CNA200610066051XA CN1903238A (en) | 2005-07-28 | 2006-03-28 | Extractive of traditional Chinese medicine, its prepns., preparing method and application thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101380344B (en) * | 2007-09-06 | 2011-06-08 | 上海医药工业研究院 | Method for extracting total effective parts in mixture of angelica and ligusticum wallichii rhizome by supercritical carbon dioxide gradient |
| CN102488724A (en) * | 2011-12-21 | 2012-06-13 | 天津中新药业集团股份有限公司第六中药厂 | Brain-soothing dripping pills for treating cardiovascular and cerebrovascular diseases and preparation method thereof |
| CN102614234A (en) * | 2012-04-25 | 2012-08-01 | 湖南天济草堂制药有限公司 | Anti-stroke medicinal composition, tablet and preparation methods thereof |
| CN113304187A (en) * | 2021-05-31 | 2021-08-27 | 勾大卉 | Composition for preventing and treating cardiovascular and cerebrovascular diseases and preparation method thereof |
-
2006
- 2006-03-28 CN CNA200610066051XA patent/CN1903238A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101380344B (en) * | 2007-09-06 | 2011-06-08 | 上海医药工业研究院 | Method for extracting total effective parts in mixture of angelica and ligusticum wallichii rhizome by supercritical carbon dioxide gradient |
| CN102488724A (en) * | 2011-12-21 | 2012-06-13 | 天津中新药业集团股份有限公司第六中药厂 | Brain-soothing dripping pills for treating cardiovascular and cerebrovascular diseases and preparation method thereof |
| CN102614234A (en) * | 2012-04-25 | 2012-08-01 | 湖南天济草堂制药有限公司 | Anti-stroke medicinal composition, tablet and preparation methods thereof |
| CN113304187A (en) * | 2021-05-31 | 2021-08-27 | 勾大卉 | Composition for preventing and treating cardiovascular and cerebrovascular diseases and preparation method thereof |
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