CN101322693B - Carthamus tinctorius yellow colour injection and preparation technique thereof - Google Patents
Carthamus tinctorius yellow colour injection and preparation technique thereof Download PDFInfo
- Publication number
- CN101322693B CN101322693B CN2008101348191A CN200810134819A CN101322693B CN 101322693 B CN101322693 B CN 101322693B CN 2008101348191 A CN2008101348191 A CN 2008101348191A CN 200810134819 A CN200810134819 A CN 200810134819A CN 101322693 B CN101322693 B CN 101322693B
- Authority
- CN
- China
- Prior art keywords
- carthamus yellow
- lyophilized injectable
- injectable powder
- carthamus
- production method
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a carithamine injection and a preparation technique thereof, and which more particularly provides a new technique for producing a carithamine freeze-dried powder-injection. The production technique of the invention can remarkably improve the extraction yield and product purity of carithamine and lower cost; more particularly, the stability of the carithamine freeze-dried powder-injection produced by the technique is greatly enhanced and the shelf life of the product is significantly prolonged.
Description
Technical field
The present invention relates to a kind of carthamus tinctorius yellow colour injection and production technology thereof, particularly relate to a kind of production new technique of Carthamus yellow lyophilized injectable powder.Belong to field of medicine preparations.
Background technology
Flos Carthami belongs to the dried floral of feverfew Flos Carthami Carthamus tinctorius L., the effect of have activating blood circulation to dissipate blood stasis, stimulating the menstrual flow.Flos Carthami is world today's research and uses one of " focus " plant, to its The Chemical Constituents, existing lot of documents report, its water soluble ingredient is mainly Carthamus yellow (saffloryellow), proves the main pharmacodynamics position of Flos Carthami through pharmacological research.
The bibliographical information of existing a large amount of Carthamus yellows of prior art and preparation thereof.For example CN 1600817A discloses a kind of Carthamus yellow and preparation technology and application, and it has disclosed by macroporous adsorbent resin and gel filtration chromatography method and has prepared the purification Carthamus yellow, obtains the injection Carthamus yellow.
Summary of the invention
The present invention by Carthamus yellow freeze-dried powder agent producing process is studied, is surprised to find that a kind of production new technique that is more suitable for improving Carthamus yellow lyophilized injectable powder quality and stability, thereby realizes the present invention on the prior art basis.
The invention provides a kind of Carthamus yellow freeze-dried powder agent and process for producing same, it comprises following steps:
(1) gets the Flos Carthami water extraction, make the Flos Carthami water extract;
(2) the Flos Carthami water extract that obtains of step (1) separates with macroporous adsorbent resin column chromatography, makes the Carthamus yellow crude product;
(3) the Carthamus yellow crude product that obtains of step (2) separates with gel filtration chromatography, makes the Carthamus yellow elaboration;
(4) take by weighing the Carthamus yellow elaboration that step (3) obtains by recipe quantity, be dissolved in water for injection, behind filtering with microporous membrane, be sub-packed in the bottle, after the lyophilization, obtain the Carthamus yellow lyophilized injectable powder;
It is characterized in that: the described macroporous adsorbent resin of step (2) is macroporous adsorbent resin HZ801, and after the middle lyophilization of step (4), charges into nitrogen, tamponade again, sealing.
Macroporous adsorbent resin HZ801 is in the macroporous adsorbent resin one type, domestic existing commodity, for example the macroporous adsorbent resin HZ801 of East China University of Science's development and production.
Wherein, the production method of above-mentioned described Carthamus yellow lyophilized injectable powder, in the wherein said step (2), the ratio of the column internal diameter of macroporous adsorptive resins and the post height of bed is 1: (8~15), eluant are deionized water, elution flow rate is (10~30) ml/min; Preferably: the ratio of the column internal diameter of macroporous adsorptive resins and the post height of bed is 1: (10~12), elution flow rate are 20ml/min.
Wherein, the production method of above-mentioned described Carthamus yellow lyophilized injectable powder, wherein said step (1) are that the Flos Carthami crude drug directly extracts without pulverizing water, and wherein the temperature of preferred water extraction is 80~100 ℃, extraction time 1~3 time, each 15~30 minutes time.
Wherein, gel in the production method of above-mentioned described Carthamus yellow lyophilized injectable powder, wherein said step (3) is preferably polydextran gel Sephadex G-25 or Sephadex LH-20.The separation condition of gel filtration chromatography, can be 1 for the blade diameter length ratio value of post for example: (5~10), applied sample amount be 5%~15% of bed volume, and eluant can be water for injection, and elution flow rate is (5~10) ml/min, collect to contain the Carthamus yellow part.
If desired, can also carry out gel filtration chromatography repeatedly, improve the purity of Carthamus yellow.The Carthamus yellow eluent of collecting behind 80-90 ℃ of concentrating under reduced pressure, through lyophilization, promptly makes the Carthamus yellow elaboration powder of reddish yellow.
Wherein, the production method of above-mentioned described Carthamus yellow lyophilized injectable powder can adopt the filtering with microporous membrane of 0.22 μ m in the wherein said step (4).
As preferred version of the present invention, the production method of above-mentioned described Carthamus yellow lyophilized injectable powder, wherein said Carthamus yellow elaboration purity is 75-95%, calculates with wherein contained effective ingredient S-A Hydroxysafflor yellow A amount.
The production method of the above-mentioned described Carthamus yellow lyophilized injectable powder of the present invention, the specification of wherein said Carthamus yellow lyophilized injectable powder is not particularly limited, and for example can contain Carthamus yellow 50mg, 100mg, 150mg or 200mg for every bottle.
Compare with existing Carthamus yellow production technology, the present invention finds, by selecting HZ801 purification with macroreticular resin explained hereafter Carthamus yellow for use, has that adsorbance is big, an outstanding advantage of eluting yield height, good product quality, obtains unexpected effect.Simultaneously, the present invention also finds unexpectedly, in Carthamus yellow lyophilized injectable powder production process, charges into nitrogen and seal after lyophilization, can significantly improve the stability of Carthamus yellow lyophilized injectable powder.Compare with existing Carthamus yellow lyophilized injectable powder, Carthamus yellow lyophilized injectable powder effect duration that the inventive method is produced can prolong 1 year, can reach 3 year effect duration.
In addition, the present invention finds that also flos carthami not only can not produce the influence of loss property to the Carthamus yellow extraction rate, but also be beneficial to the technology purification without pulverizing direct water extraction, has improved extraction efficiency, simplifies production technology, saves technique process and cost.
The specific embodiment
Come by the following examples further to explain and purport of the present invention is described, but should not be understood that restriction claim scope of the present invention.
Embodiment 1
Take by weighing Flos Carthami, add the deionized water of 10-13 times of medical material weight, in 100 ℃ of extractions 20-25 minute, filter, the deionized water that filtering residue adds 10 times of medical material weight repeats to extract once by above-mentioned condition again, filters.Merge secondary raffinate, be cooled to room temperature, after the usefulness centrifuge was centrifugal, extracting centrifugal liquid was standby.
Above-mentioned centrifugal liquid slowly is added to handled in the good HZ801 of balance (macroporous adsorbent resin HZ801 is available from the East China University of Science) macroporous adsorptive resins, the post blade diameter length ratio is 1: 12, and last sample flow velocity is per minute 10ml.Behind the end of the sample, use the flow velocity eluting of the deionized water of room temperature with per minute 20ml.The eluent of Carthamus yellow is rich in collection, and eluent gets Carthamus yellow crude product concentrated solution in 80~90 ℃ of concentrating under reduced pressure, and in Flos Carthami, the per kilogram Flos Carthami gets Carthamus yellow crude product concentrated solution 100ml.
Gel LH-20 post on the Carthamus yellow crude product concentrated solution, the blade diameter length ratio of post is 1: 5, and applied sample amount is 10% of a bed volume, and water for injection is the eluant eluting, and elution flow rate is per minute 5ml, collects to contain the Carthamus yellow part.Collect liquid behind 80~90 ℃ of concentrating under reduced pressure, get Carthamus yellow elaboration concentrated solution, in Flos Carthami, the per kilogram Flos Carthami gets Carthamus yellow elaboration concentrated solution 80~100ml, through lyophilization, promptly get the Carthamus yellow elaboration powder of reddish yellow, hydroxyl carthamin yellow A-containing content is 94.6% after testing.
Press the preparation specification requirement, make the Carthamus yellow lyophilized injectable powder.For example make the lyophilized injectable powder of 100mg specification, take by weighing the above-mentioned Carthamus yellow elaboration powder of 100 grams, be dissolved in the water for injection, stir evenly, add water to 2000 milliliters, through the filtering with microporous membrane of 0.22 μ m, aseptic filtration also is sub-packed in the antibiotic bottle, every bottle of 2ml, false add plug; About frozen drying 30 hours, inflated with nitrogen, covers aluminium-plastic cap again at tamponade, rolls mouthful promptly.
Embodiment 2 (contrast test)
2a) according to embodiment 1 same procedure, prepare Carthamus yellow elaboration powder, wherein adopt D
4020The macroporous adsorbent resin detached dowel;
2b) according to embodiment 1 same procedure, prepare Carthamus yellow elaboration powder, wherein adopt B201 macroporous adsorbent resin detached dowel;
2c) according to embodiment 1 same procedure, prepare Carthamus yellow elaboration powder, wherein adopt AB-8 macroporous adsorbent resin detached dowel;
2d) according to embodiment 1 same procedure, prepare Carthamus yellow elaboration powder, wherein adopt X-5 macroporous adsorbent resin detached dowel;
Technic index: A-adsorbance (mg/g), B-desorption efficiency (%), C-Carthamus yellow elaboration powder purity (%, hydroxyl carthamin yellow A-containing content), D-Carthamus yellow elaboration powder yield (%) (in Flos Carthami).The results are shown in following table 1.
Table 1: different macroporous adsorbent resin process results
A | B | C | D | |
Embodiment 1 | 120 | 92.5 | 94.6 | 3.38 |
Embodiment 2a | 110 | 88.6 | 89.4 | 3.21 |
Embodiment 2b | 105 | 85.6 | 77.2 | 3.12 |
Embodiment 2c | 96 | 83.3 | 71.3 | 3.14 |
Embodiment 2d | 84 | 92.8 | 78.5 | 3.02 |
Result of the test shows that the present invention adopts the HZ801 macroporous adsorbent resin can significantly improve process efficiency.
Embodiment 3 (stability test)
According to embodiment 1 technology, the preparation specification reaches not each three batches of Carthamus yellow lyophilized injectable powder of inflated with nitrogen for the 100mg inflated with nitrogen, carries out stability test relatively.Wherein lot number is: 040601,040602,040603 for inflated with nitrogen three lot samples not this, 040604,040605,040606 be inflated with nitrogen three lot samples.The results are shown in following table .2-3.
Result of the test shows, not inflated with nitrogen three lot samples this, during to 36 months, obviously descending appears in content, and that acidity raises is very fast.And inflated with nitrogen three lot samples originally, and during to 42 months, every index is all very stable, does not have significant change substantially.Therefore inflated with nitrogen can increase the stability of product, and effect duration was increased to more than 3 years by original 2 years.
Table 2 is inflated with nitrogen Carthamus yellow lyophilized injectable powder (100mg) stability data not
Table 3 inflated with nitrogen injection Carthamus yellow (100mg) stability data gathers
The present invention is described according to preferred embodiment.Should be understood that the description of front and embodiment are just to illustrating the present invention.Under prerequisite without departing from the spirit and scope of the present invention, those skilled in the art can design multiple alternative of the present invention and improvement project, and it all should be understood to be within protection scope of the present invention.
Claims (7)
1. the production method of a Carthamus yellow lyophilized injectable powder, it comprises following steps:
(1) gets the Flos Carthami water extraction, make the Flos Carthami water extract;
(2) the Flos Carthami water extract that obtains of step (1) separates with macroporous adsorbent resin column chromatography, is eluant with the deionized water, makes the Carthamus yellow crude product;
(3) the Carthamus yellow crude product that obtains of step (2) separates with gel filtration chromatography, is eluant with water for injection, makes the Carthamus yellow elaboration, and described gel is polydextran gel Sephadex G-25 or SephadexLH-20;
(4) take by weighing the Carthamus yellow elaboration that step (3) obtains by recipe quantity, be dissolved in water for injection, microporous filter membrane through adopting 0.22 μ m or hold back the ultrafiltration membrance filter of 8000-10000 molecular weight after be sub-packed in the bottle, after the lyophilization, obtain the Carthamus yellow lyophilized injectable powder;
It is characterized in that: the described macroporous adsorbent resin of step (2) is macroporous adsorbent resin HZ801, and after the middle lyophilization of step (4), charges into nitrogen, tamponade again, sealing.
2. the production method of Carthamus yellow lyophilized injectable powder according to claim 1, in the wherein said step (2), the ratio of the column internal diameter of macroporous adsorptive resins and the post height of bed is 1: 8~15.
3. the production method of Carthamus yellow lyophilized injectable powder according to claim 2, in the wherein said step (2), the ratio of the column internal diameter of macroporous adsorptive resins and the post height of bed is 1: 10~12.
4. according to the production method of each described Carthamus yellow lyophilized injectable powder of claim 1-3, wherein said step (1) is that the Flos Carthami crude drug directly extracts without pulverizing water.
5. the production method of Carthamus yellow lyophilized injectable powder according to claim 4,80~100 ℃ of the temperature of wherein said step (1) water extraction, extraction time 1~3 time, each 15~30 minutes time.
6. according to the production method of each described Carthamus yellow lyophilized injectable powder of claim 1-3, wherein said Carthamus yellow elaboration hydroxyl carthamin yellow A-containing is 75-95%.
7. according to the production method of each described Carthamus yellow lyophilized injectable powder of claim 1-3, the specification of wherein said Carthamus yellow lyophilized injectable powder is every bottle and contains Carthamus yellow 50mg, 100mg, 150mg or 200mg.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2008101348191A CN101322693B (en) | 2008-07-31 | 2008-07-31 | Carthamus tinctorius yellow colour injection and preparation technique thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN2008101348191A CN101322693B (en) | 2008-07-31 | 2008-07-31 | Carthamus tinctorius yellow colour injection and preparation technique thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101322693A CN101322693A (en) | 2008-12-17 |
CN101322693B true CN101322693B (en) | 2010-06-23 |
Family
ID=40186497
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN2008101348191A Active CN101322693B (en) | 2008-07-31 | 2008-07-31 | Carthamus tinctorius yellow colour injection and preparation technique thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN101322693B (en) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102657691A (en) * | 2012-06-02 | 2012-09-12 | 悦康药业集团安徽天然制药有限公司 | Extraction process of carthamin yellow |
CN102702150B (en) * | 2012-06-19 | 2014-09-17 | 浙江永宁药业股份有限公司 | Preparation method and application of hydroxysafflor yellow A |
CN103127197B (en) * | 2013-03-21 | 2015-02-18 | 悦康药业集团有限公司 | Preparation method of freeze-drying preparation for safflower yellow injection |
CN104721179B (en) * | 2015-01-20 | 2017-09-05 | 哈尔滨医科大学 | Purposes of the hydroxyl radical carthamin yellow carthamus A in the health medicine or functional food for the treatment of hypoxic pulmonary hypertension is prepared |
CN104721152B (en) * | 2015-01-20 | 2017-10-17 | 哈尔滨医科大学 | A kind of preparation method of hydroxyl radical carthamin yellow carthamus A freeze drying powder injection and products thereof |
-
2008
- 2008-07-31 CN CN2008101348191A patent/CN101322693B/en active Active
Also Published As
Publication number | Publication date |
---|---|
CN101322693A (en) | 2008-12-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN102702150B (en) | Preparation method and application of hydroxysafflor yellow A | |
CN102351819B (en) | Extraction, purification and preparation method of high-purity salvianolic acid B | |
CN101322693B (en) | Carthamus tinctorius yellow colour injection and preparation technique thereof | |
CN107998212B (en) | Preparation method of rehmannia iridoid glycoside extract | |
CN111228317A (en) | Preparation method and application of inonotus obliquus extract | |
CN105859803B (en) | A kind of preparation method of galloyl glucose | |
CN111039914A (en) | Extraction and separation method of cannabinol | |
CN110818585B (en) | Separation method for simultaneously preparing five dopamine compounds from aspongopus | |
JP2022543794A (en) | Method for producing tetragalloyl glucose | |
CN105998103B (en) | Chestnut flower activity extract and its preparation method and application | |
CN110878010A (en) | Extraction and separation method of cannabigerol | |
CN113264974A (en) | Preparation of type B cardiac glycoside and anti-angiogenesis application thereof | |
CN113440547B (en) | Method for separating and purifying Japanese thistle herb total glycosides by adopting macroporous resin series dynamic axial compression column | |
CN107213180B (en) | Separation and extraction method of notoginseng flavone | |
CN109776515A (en) | The method of mangiferin is extracted from myrica rubra leaf | |
CN113429442B (en) | Method for separating tectoridin and tectorigenin from water extraction residues of rhizoma et radix Sichuan blackberry lily | |
CN110776541B (en) | Preparation method and application of quercetin-3-gentiobioside | |
CN110240585B (en) | Preparation method of agilawood tetraol | |
CN109517017B (en) | Flavone contrast extract and preparation method and application thereof | |
CN109678981B (en) | Preparation method, product and application of safflower polysaccharide | |
CN108997457B (en) | Method for extracting luteolin and quercetin-3-o-beta-glucopyranoside from populus tomentosa leaves | |
CN109627153B (en) | Method for extracting and separating p-hydroxybenzaldehyde from nostoc commune | |
CN111675741A (en) | Separation method for simultaneously obtaining four kinds of epimedium rare flavone by using preparative liquid phase method | |
CN114456138B (en) | Method for separating three coumarin compounds from fingered citron extract | |
CN110623995A (en) | Method for extracting total flavonoids from aerial parts of liquorice and preparing liposome of total flavonoids |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant |