CN1215060A - Powderly transparent acid making method and crystallization tank thereof - Google Patents
Powderly transparent acid making method and crystallization tank thereof Download PDFInfo
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- CN1215060A CN1215060A CN 98110455 CN98110455A CN1215060A CN 1215060 A CN1215060 A CN 1215060A CN 98110455 CN98110455 CN 98110455 CN 98110455 A CN98110455 A CN 98110455A CN 1215060 A CN1215060 A CN 1215060A
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Abstract
The present invention provides a production method of powdery hyaluronic acid and its crystallizer technical scheme. Said invented method includes the following steps: using fermentation method to obtain wet hyaluronic acid crude product; dissolving by using ionized water; then filtering by using filter plate with diatomite filter-aid and resin column treatment; regulating pH value and converting the hyaluronic acid crude product into hyaluronic sodium; filtering by using microporous sintered polyethylene filter; placing the above-mentioned material into crystallizer and spraying ethyl alcohol; crystallizing,settling, dewatering and drying so as to obtain finished product. Said crystallizer possesses a tank body, its top possesses a motor connected with stirrer shaft and stirring blade, its interior is equipped with ethyl alcohol spreader tube whose undersurface possesses jet orifices and its tank wall is equipped with inlet, and its bottom is equipped with outlet.
Description
What the present invention relates to is the crystallization equipment that is adopted in a kind of hyaluronic manufacture method and this method, especially a kind of Powdered hyaluronic acid manufacture method and crystallizer thereof.
Hyaluronic acid be a kind of transparent, can be dissolved in water and not have the oily acidic mucopolysaccharide, extensively be present in the reticular tissue such as joint, umbilical cord, vitreum, cartilaginous tissue, skin, Aorta, interior adventitia of animal and human's body, be the material that constitutes dermal layer of the skin, flexibility, structure maintenance, the cell metabolism of organizing played an important role.Its major function is to keep intercellular moisture content, or forms jelly at iuntercellular, keeping and to suppress intercellular material and move, and the alienation of cell function, and have the function that prevents cell infection, therefore, be widely used in medicine and the cosmetic industry.In the prior art, the technology comparatively approaching with the present invention is Japanese Patent, the special permission communique is according to 63-12293 number, this patent is the hyaluronic acid crude product mother liquor that utilizes known employing fermentation method to obtain, big netted anionite-exchange resin by this patented invention filters, and obtains refining hyaluronic method.Its concrete grammar is, the matter acid mother liquor water that fermentation is obtained towards rare to the matter acid content be 0.5-2g/l, add the activated carbon of 1-10%, filter through stirring with the paper pulp filter plate, again through this invention exclusive big netted anion exchange process, the gained treatment solution is adjusted to neutrality to pH value with salt acids material, add sodium-chlor again, then, add the water-miscible organic solvent that 1-4 doubly measures, be settled out thick matter acid sodium, through separate thick matter acid sodium, the water-miscible organic solvent that thick matter acid sodium concentration is 50-100% is cleaned, promptly obtained the acid of purified matter through vacuum-drying again.Can obtain to have the matter acid of viscosity higher and larger molecular weight with this method, but have finished product foreign matter content height, mostly be fibrous matter acid, and this fibrous matter sour water dissolubility be poor, need the long time to dissolve and wait problem fully.
Purpose of the present invention, be exactly at the existing in prior technology deficiency, and provide the technical scheme of a kind of Powdered hyaluronic acid manufacture method and crystallizer thereof, adopt method of the present invention to use crystallizer of the present invention simultaneously, can obtain the Powdered Refined Hyaluronic Acid that finished product impurity is few, soluble in water, molecular weight is higher and viscosity is bigger at low cost.
This programme is realized by following technical measures.
The method of this programme comprises the step of following order:
A. get the matter acid mother liquor that obtains by fermentation method, through the centrifugal matter acid crude that must wet of alcohol precipitation;
B. the matter acid crude that will wet places and adds the ionized water stirring and dissolving in the dissolving vessel;
C. will go up the step gained and dissolve lysate completely, the filter plate of making flocculating aids by diatomite filters most of impurity of removal and thalline;
D. gained filtrate is filtered through resin column, obtains smart filtrate;
E. smart filtrate is placed stirred pot, regulating pH value with hydrochloric acid is 7.0, adds sodium-chlor then and makes matter acid convert the matter acid sodium solution to;
F. obtain the matter acid sodium solution and filter through micropore sintered polyethylene filter again, get matter acid sodium seminal fluid;
G. matter acid sodium seminal fluid is inserted crystallizer, and spray ethanol stirs simultaneously and makes matter acid sodium crystalline deposit;
H. get sedimentary Powdered matter acid sodium, through dehydration, vacuum-drying, be packaged into finished product.
Wherein, in step B, when wetting the matter acid crude, adopt the wet matter acid crude of 100L ionized water dissolving 1-1.2Kg with the ionized water dissolving.In step C, described diatomite is made the filter plate of auxiliary agent, is to combine with the sheet frame that installs back up pad with 1-4Kg, 80-200 purpose diatomite.In step D, described resin column is formed by the vinylbenzene macroporous type or the multi-hole type anionite-exchange resin of high Vinylstyrene content, and its filtering velocity per hour is controlled within 1 times the resin volume.In step F, described micropore sintered polyethylene filter is that the micropore sintered polyethylene filter of 0.5-8 μ is filtered.In step G, to drench into amount be the matter acid sodium seminal fluid of 2.5-3 times of volume to alcoholic acid in the crystallizer.
The scheme of employed crystallizer is in the method for the present invention, it is that cylindrical bottom portion is conical tank body that this crystallizer includes a top, above outside the tank body top agitator motor is arranged, the shaft of motor is connected with and extend into a jar intravital stir shaft, the fixedly connected paddle in the following top of stir shaft; At the intravital upper top of jar the ethanol distribution pipe of one closure is arranged, and be connected with outside the ethanol input tube pass-out tank body, equally distributed a plurality of ethanol spray orifice is arranged in the bottom surface of ethanol distribution pipe; In addition on the tank body upper portion side wall, there is feed-pipe the below of ethanol distribution pipe, in the conical lower section of tank body discharge nozzle is arranged.The concrete characteristics of this crystallizer also have, the equally distributed ethanol spray orifice in bottom surface that is described ethanol distribution pipe is two rounds of cross arrangement, the axis in one its hole of round of close tank wall and the angle between the cylinder side wall bus are the 35-50 degree, are preferably 45 degree; Away from the axis in its hole of round of sidewall and the angle between the sidewall bus is the 57-77 degree, is preferably 67 degree.And described paddle is dull and stereotyped paddle.
Further step of the present invention is described below by embodiment and reference examples:
Embodiment 1:
Take matter acid mother liquor that fermentation method obtains and be added in the alcohol of 3 times of volumes and precipitate, slough alcohol by whizzer and get cotton-shaped wet matter acid crude; Get the wet matter acid crude of 1Kg and add the 100L ionized water, stirring is dissolved it fully; Filter plate through make flocculating aids with 2Kg 100 order diatomite filters again, most of impurity of filtering and thalline; Gained filtrate is handled with the filtering velocity of 0.5 resin volume per hour through resin column again, smart filtrate; Place stirred pot to adjust pH value the smart filtrate of 100L gained and be 7.0, add 6KG sodium-chlor, stirred 30 minutes, make it convert the matter acid sodium solution to hydrochloric acid; The matter acid sodium solution is filtered through the micropore sintered polyethylene filter of MFE-2 type 1-5 μ, get matter acid sodium seminal fluid; Matter acid sodium seminal fluid is placed in the crystallizer, under the stirring of the stirring velocity that per minute 100 changes, slowly with the ethanol of 250L, by the ethanol distribution pipe in the crystallizer drench into, make the powdered crystalline deposit of matter acid sodium; Collect Powdered precipitation with filter cloth,, make sorbent material with calcium chloride through centrifuge dehydration, carry out vacuum-drying after, Powdered matter acid 115g.Its leading indicator is:
Viscosity-average molecular weight 2,350,000 dalton;
Glucuronic acid content 36%;
Protein content 0.08%.
Reference examples 1:
Obtain thick matter acid solution with embodiment 1 identical method, but make flocculating aids without diatomite, but filter with conventional paper pulp filter plate strainer, gained filtrate is 80L, and following steps are identical with embodiment 1, at last the sour 98g of Powdered matter.Its leading indicator is:
Viscosity-average molecular weight 1,500,000 dalton;
Glucuronic acid content 34%;
Protein content 0.85%.
Embodiment 2:
Take matter acid mother liquor that fermentation method obtains and be added in the alcohol of 3 times of volumes and precipitate, slough alcohol by whizzer and get cotton-shaped wet matter acid crude; Get the wet matter acid crude of 1Kg and add the 100L ionized water, stirring is dissolved it fully; Filter plate through make flocculating aids with diatomite filters again, most of impurity of filtering and thalline; Gained filtrate is handled with the filtering velocity of 0.8 resin volume per hour through resin column again, smart filtrate; Place stirred pot to adjust pH value the smart filtrate of gained and be 7.0, add 6KG sodium-chlor, stirred 30 minutes, make it convert the matter acid sodium solution to hydrochloric acid; The matter acid sodium solution is filtered through the micropore sintered polyethylene filter of MFE-2 type 1-5 μ, get matter acid sodium seminal fluid; Matter acid sodium seminal fluid is placed in the crystallizer, under the stirring of the stirring velocity that per minute 100 changes, slowly with 3 times of matter acid sodium seminal fluid volume of ethanol, by the ethanol distribution pipe in the crystallizer drench into, make the powdered crystalline deposit of matter acid sodium; Collect Powdered precipitation with filter cloth,, make sorbent material with calcium chloride through centrifuge dehydration, carry out vacuum-drying after, Powdered matter acid 115g.Its leading indicator is:
Viscosity-average molecular weight 2,450,000 dalton;
Glucuronic acid content 40%;
Protein content 0.05%.
Reference examples 2:
The methods identical with embodiment 2 obtain the matter acid sodium solution, but filter without micropore sintered polyethylene filter, and directly identical with embodiment 2 method precipitates, after dehydrating, the sour 126g of Powdered matter.Its leading indicator is:
Viscosity-average molecular weight 2,050,000 dalton:
Glucuronic acid content 34%;
Protein content 0.17%.
For clearly demonstrating the technical characterstic of this programme crystallizer,, and, this programme is set forth in conjunction with its accompanying drawing below by a specific embodiment.
Description of drawings:
Fig. 1 is the part sectional structure synoptic diagram of crystallizer embodiment among the present invention;
Fig. 2 is that the A-A of Fig. 1 is to the sectional structure synoptic diagram.
Can find out used crystallization in the Powdered hyaluronic acid manufacture method of the present invention by accompanying drawing It is that cylindrical bottom portion is conical tank body 1 that tank, this crystallizing tank include a top, on tank body 1 top There is stirring motor 7 top outside the section, and the shaft of motor 7 is connected with the shaft 6 that extend in the tank body 1, The lower top of shaft 6 is fixedly connected with a paddle 2; Upper top in tank body 1 has a closure Ethanol distributor pipe 5, and be connected with outside the ethanol input pipe 8 pass-out tank bodies 1, at the end of ethanol distributor pipe 5 Face has equally distributed a plurality of ethanol spray orifice 4; In addition on tank body 1 upper portion side wall, ethanol distributor pipe 5 There is a feed pipe 3 below, in the conical lower section of tank body 1 discharge nozzle 9 is arranged. And described ethanol distributor pipe 5 The equally distributed ethanol spray orifice 4 in bottom surface are two rounds of cross arrangement, near tank body 1 sidewall one row Angle between the axis of Kong Qikong and cylinder side wall bus is the 35-50 degree, is preferably 45 degree; Away from side The axis in one its hole of round of wall and the angle between the sidewall bus are the 57-77 degree, are preferably 67 degree. In addition Outward, described paddle 2 is dull and stereotyped paddle.
According to the narration of such scheme as can be known, make filter aid owing in this scheme, adopted by diatomite Filter plate and micropore sintered polyethylene filter, the crystallizing tank that adopts when adding again the Sodium Hyaluronate crystallization makes The production cost decrease of matter acid, Powdered matter acid yield height becomes the impurity of quality acid to greatly reduce, And the molecular weight height is soluble in water. This shows that the present invention compared with prior art has outstanding reality Matter characteristics and significant progressive, its implementation result also is apparent.
Claims (9)
1. Powdered hyaluronic acid manufacture method, this method comprises the step of following order:
A. get the matter acid mother liquor that obtains by fermentation method, through the centrifugal matter acid crude that must wet of alcohol precipitation;
B. the matter acid crude that will wet places and adds the ionized water stirring and dissolving in the dissolving vessel;
C. will go up the step gained and dissolve lysate completely, and make flocculating aids by diatomite and filter most of impurity of removal and thalline;
D. gained filtrate is filtered through resin column, obtains smart filtrate;
E. smart filtrate is placed stirred pot, regulating pH value with hydrochloric acid is 7.0, adds sodium-chlor then and makes matter acid convert matter acid sodium to;
F. obtain the matter acid sodium solution and filter through micropore sintered polyethylene filter again, get matter acid sodium seminal fluid;
G. matter acid sodium seminal fluid is inserted crystallizer, and spray ethanol stirs simultaneously and makes matter acid sodium crystalline deposit;
H. get sedimentary matter acid sodium, through dehydration, vacuum-drying, be packaged into finished product.
2. Powdered hyaluronic acid manufacture method according to claim 1 when wherein dissolving the acid of thick matter with ionized water, adopts the wet matter acid crude of 100L ionized water dissolving 1-1.2Kg.
3. Powdered hyaluronic acid manufacture method according to claim 1, wherein said diatomite is made the filter plate of auxiliary agent, is to combine with the sheet frame that installs back up pad with 1-4Kg, 80-200 purpose diatomite.
4. Powdered hyaluronic acid manufacture method according to claim 1, wherein said resin column is formed by the vinylbenzene macroporous type or the multi-hole type anionite-exchange resin of high Vinylstyrene content, and its filtering velocity per hour is controlled within 1 times the resin volume.
5. Powdered hyaluronic acid manufacture method according to claim 1, wherein said micropore sintered polyethylene filter are that the micropore sintered polyethylene filter of 0.5-8 μ is filtered.
6. Powdered hyaluronic acid manufacture method according to claim 1, wherein in crystallizer alcoholic acid to drench into amount be the matter acid sodium seminal fluid of 2.5-3 times of volume.
7. used crystallizer in the Powdered hyaluronic acid manufacture method, it is that cylindrical bottom portion is conical tank body 1 that this crystallizer includes a top, above outside tank body 1 top agitator motor 7 is arranged, the shaft of motor 7 is connected with the stir shaft 6 that extend in the tank body 1, the fixedly connected paddle 2 in the following top of stir shaft 6; Upper top in tank body 1 has the ethanol distribution pipe 5 of a closure, and is connected with outside the ethanol input tube 8 pass-out tank bodies 1, and equally distributed a plurality of ethanol spray orifice 4 is arranged in the bottom surface of ethanol distribution pipe 5; In addition on tank body 1 upper portion side wall, there is feed-pipe 3 below of ethanol distribution pipe 5, in the conical lower section of tank body 1 discharge nozzle 9 is arranged.
8. crystallizer according to claim 7, the equally distributed ethanol spray orifice 4 in bottom surface that it is characterized in that described ethanol distribution pipe 5 is two rounds of cross arrangement, the axis in one its hole of round of close tank body 1 sidewall and the angle between the cylinder side wall bus are the 35-50 degree, are preferably 45 degree; Away from the axis in its hole of round of sidewall and the angle between the sidewall bus is the 57-77 degree, is preferably 67 degree.
9. crystallizer according to claim 7 is characterized in that described paddle 2 is dull and stereotyped paddle.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 98110455 CN1215060A (en) | 1998-09-16 | 1998-09-16 | Powderly transparent acid making method and crystallization tank thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 98110455 CN1215060A (en) | 1998-09-16 | 1998-09-16 | Powderly transparent acid making method and crystallization tank thereof |
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| CN1215060A true CN1215060A (en) | 1999-04-28 |
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| CN 98110455 Pending CN1215060A (en) | 1998-09-16 | 1998-09-16 | Powderly transparent acid making method and crystallization tank thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110922505A (en) * | 2019-12-27 | 2020-03-27 | 华熙生物科技股份有限公司 | Preparation method of hyaluronic acid for eye drops |
| CN110981992A (en) * | 2019-12-27 | 2020-04-10 | 华熙生物科技股份有限公司 | Preparation method of hyaluronic acid for injection |
| CN111978432A (en) * | 2019-05-23 | 2020-11-24 | 北京中源合聚生物科技有限公司 | Hyaluronic acid protein nucleic acid removing device and method |
-
1998
- 1998-09-16 CN CN 98110455 patent/CN1215060A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111978432A (en) * | 2019-05-23 | 2020-11-24 | 北京中源合聚生物科技有限公司 | Hyaluronic acid protein nucleic acid removing device and method |
| CN110922505A (en) * | 2019-12-27 | 2020-03-27 | 华熙生物科技股份有限公司 | Preparation method of hyaluronic acid for eye drops |
| CN110981992A (en) * | 2019-12-27 | 2020-04-10 | 华熙生物科技股份有限公司 | Preparation method of hyaluronic acid for injection |
| CN110981992B (en) * | 2019-12-27 | 2021-08-13 | 华熙生物科技股份有限公司 | Preparation method of hyaluronic acid for injection |
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