CN1023630C - Method of chemical modification for iso-species of biological valve - Google Patents
Method of chemical modification for iso-species of biological valve Download PDFInfo
- Publication number
- CN1023630C CN1023630C CN 92100096 CN92100096A CN1023630C CN 1023630 C CN1023630 C CN 1023630C CN 92100096 CN92100096 CN 92100096 CN 92100096 A CN92100096 A CN 92100096A CN 1023630 C CN1023630 C CN 1023630C
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- China
- Prior art keywords
- species
- iso
- biological
- valves
- modification
- 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.)
- Expired - Fee Related
Links
- 238000000034 method Methods 0.000 title claims abstract description 16
- 238000007385 chemical modification Methods 0.000 title claims abstract description 7
- XRSBTDBLFNPGOE-UHFFFAOYSA-M O[Cr] Chemical compound O[Cr] XRSBTDBLFNPGOE-UHFFFAOYSA-M 0.000 claims abstract description 9
- 210000003516 pericardium Anatomy 0.000 claims abstract description 8
- 230000002308 calcification Effects 0.000 claims abstract description 7
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims abstract description 6
- 210000001765 aortic valve Anatomy 0.000 claims abstract 2
- 239000011651 chromium Substances 0.000 claims description 10
- 238000012986 modification Methods 0.000 claims description 10
- 230000004048 modification Effects 0.000 claims description 10
- 239000000463 material Substances 0.000 claims description 9
- 241000283690 Bos taurus Species 0.000 claims description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 238000012545 processing Methods 0.000 claims description 3
- 241000282894 Sus scrofa domesticus Species 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 230000020477 pH reduction Effects 0.000 claims 1
- 239000007788 liquid Substances 0.000 abstract description 7
- 239000012620 biological material Substances 0.000 abstract description 3
- 210000003709 heart valve Anatomy 0.000 abstract description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 238000012360 testing method Methods 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 102000008186 Collagen Human genes 0.000 description 3
- 108010035532 Collagen Proteins 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 229920001436 collagen Polymers 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 241001269238 Data Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000013098 chemical test method Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000013031 physical testing Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- XMWGSPLTTNCSMB-UHFFFAOYSA-M sodium;2-hydroxypropane-1,2,3-tricarboxylic acid;chloride Chemical compound [Na+].[Cl-].OC(=O)CC(O)(C(O)=O)CC(O)=O XMWGSPLTTNCSMB-UHFFFAOYSA-M 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
Landscapes
- Materials For Medical Uses (AREA)
- Prostheses (AREA)
Abstract
The present invention relates to a method of chemical modification for iso-species of biological valves, which is used for preparing artificial cardiac valves. The original method adopts the treatment of glutaraldehyde, etc. An artificial resistance program obtained by the stability of a biological material modified by the original method already achieves limit to result in use restriction. In order to prolong the service life of a biological valve, the present invention adopts hydroxyl chromium (HC) for treatment. After being rinsed conventionally, the iso-species of biological valves (including ox pericardium, pig pericardium and pig aortic valves, etc.) are treated through GA, acidized and treated by hydroxyl chromium application liquid. A pH value is kept from 2.0 to 5.0 at the environment temperature of 30 to 50 DEG C to prepare the modified iso-species of biological valves. The treated iso-species of biological valves have obviously strong stability, good biocompatibility and strong calcification resisting capability. The shrinkproof temperatures of the iso-species of biological valves can be up to more than 100 DEG C.
Description
The present invention is a kind of method of chemical modification for iso-species of biological valve, makes Cardiac valve prosthesis.
At present, the core problem the most that bioprosthetic valve faced is exactly the lobe leaf texture poor durability due to regression and the calcification prematurely.A large amount of research and clinical datas show that its stable durable degree that can reach of biomaterial that always is leveraged to modern glutaraldehyde (GA) modification has arrived the limit, causes using limited.For this reason, before not finding better biomaterial and other synthetic material as yet, make existing heterogenous biological valve material, particularly bovine pericardial material fundamentally improves the stability and the durability of tissue, then must find the new method of the chemical modification of the crosslinking degree that can further improve effectively between the mechanics of biological tissue molecule and crosslinked quality, along with the research of new chemical modification method with explore obviously prolonged the service life of bioprosthetic valve.
It at first is because along with the lobe leaf opens and closes, the effect of secular alternate stress makes collagen fiber mechanical damage and regression in the tissue that bioprosthetic valve is damaged topmost factor.741 pieces of bovine pericardium valve that Fu Wai Hospital, Chinese Academy of Medical Sciences was implanted from year April in May, 1976 to 1991, only there are 10 pieces to lose merit in 71 pieces of bioprosthetic valve that secondary changing valve takes out in calcification.All the other are organizing regression and tear due to the alternate stress effect.Find also that simultaneously calcification all occurs in the position that lobe leaf stress ratio is concentrated to a great extent.Therefore, we think must manage the crosslinked of enhanced tissue effectively, improving the stability in the large of lobe leaf texture, and anti-on this basis calcification, the side might prolong the working life of bioprosthetic valve effectively.In view of this, the present invention tries hard to start with from strengthening the common molecule of the skeleton-collagen cross-linking of biological tissue, adopt hydroxyl chromium (Hydroxyl-Chromum, HC) handle bovine pericardium (Bovine Pericardium BP) tissue, by structure stability to test piece after the modification, mechanical characteristic, the test and the Ultrastructural observation of anti-calcification performance etc. are tentatively inquired into the modifying function of hydroxyl chromium.
Get analytical pure CrCl
3, Cr
2(SO
4)
3, Cr(NO
3)
3Or other chromic salts is mixed with certain density solution, presses OH/Cr
3+Certain ratio (1: 1-1: between 5) adds isocyatic NaOH solution, makes Cr
3+Working concentration be that the HC that forms of 0.1-0.2% uses liquid.
The conventional rinsing of heterogenous biological valve material (comprising bovine pericardium, Cor Sus domestica bag, pig master pulse lobe and other) is after the GA preliminary treatment, the material acidify, use HC to use liquid and handle and keep between the pH2.0-5.0, ambient temperature 30-50 ℃, make the heterogenous biological valve after the modification.
A large amount of physical and chemical testings show, obviously improved in the heterogenous biological valve tissue after the HC modification in the collagen molecules with intermolecular, between collagen protein and PG substrate and crosslinking degree between PG substrate and crosslinked quality, obviously strengthen the stability of material monolithic, improved the physicochemical property and the mechanical performance of material significantly.The test of animal subcutaneous transplantation shows that the material after the HC modification has biocompatibility and stronger calcification ability preferably, and its crease-resistant temperature that contracts can reach more than 100 ℃.
Embodiment:
1. reagent preparation
1) citric acid solution of .10%NaCl (pH2.0)
Take by weighing NaCl(A.R) 200g, get citric acid 51.84g and add water-soluble back to graduation mark in the 2000ml volumetric flask after the adding distil water 800ml dissolving.
2) .NaHCO
3Solution 5%
Take by weighing 16.2gAR level NaHCO
3Adding distil water 324ml dissolving.
3) .HC uses liquid
Get analytically pure Cr(NO
3)
3In acid medium, be prepared into the Cr that contains 0.58mmol/L with titrimetry
3+, basicity is 33.3% HC application liquid.
2. the preparation of test piece
Get the fresh bovine pericardium, select the uniform position of printing opacity, right front district, intercepting BP test piece.
3. processing procedure:
The 0.6%GA processing is 24 hours after the conventional rinsing of BP test piece, takes out test piece, and normal saline vibration 3 minutes added citric acid NaCl liquid by 1: 5, and 32 ℃ of water-baths were vibrated 30 minutes.Discard citric acid solution, add HC use liquid at 1: 5.32 ℃ of water-baths were vibrated 1.5 hours, surveyed pH2.6 and added 5%NaHCO
3Improve pH0.4, pH2.8 is surveyed in water-bath vibration 20 minutes, adds NaHCO
3Transfer pH3.2,36 ℃ of water-baths were vibrated 20 minutes, surveyed pH3.0, added NaHCO
3Transfer pH3.4,40 ℃ of water-baths were vibrated 40 minutes, added NaHCO
3Survey pH4.2, pH4.0 is surveyed in water-bath in 40 minutes vibration, adds isopyknic distilled water, and material is 72 hours after the modification of room temperature preservation bioprosthetic valve, and 4% formaldehyde etc. oozes Na
2SO
4Preserve standby in the solution.
Claims (6)
1, a kind of chemical modification method that strengthens heterogenous biological valve physiological stability and calcification ability, this method is included in after the rinsing of heterogenous biological valve organizational routine, glutaraldehyde preliminary treatment and the acidification, carry out modification and handle, it is characterized in that said modification treatment step is to use the hydroxyl chromium solution to finish.
2, method according to claim 1, when it is characterized in that with hydroxyl chromium modification processing, pH value remains between 2.0～5.0, and ambient temperature is between 30～50 ℃.
3, method according to claim 1 is characterized in that Cr in the employed hydroxyl chromium solution
3+Concentration be 0.1～0.2%, add NaOH and Cr
3+The molar concentration ratio be 1: 1～1: 5.
4, method according to claim 1 is characterized in that used hydroxyl chromium is selected from CrCl
3Or Cr
2(SO
4)
3Or Cr(NO
3)
3In any chromic salts.
5, method according to claim 1 is characterized in that handled heterogenous biological valve material structure is selected from bovine pericardium, Cor Sus domestica bag and porcine aortic valve.
6, method according to claim 1 is characterized in that the time that the modification of hydroxyl chromium solution is handled is about 75 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 92100096 CN1023630C (en) | 1992-01-17 | 1992-01-17 | Method of chemical modification for iso-species of biological valve |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 92100096 CN1023630C (en) | 1992-01-17 | 1992-01-17 | Method of chemical modification for iso-species of biological valve |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1063047A CN1063047A (en) | 1992-07-29 |
| CN1023630C true CN1023630C (en) | 1994-02-02 |
Family
ID=4938364
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 92100096 Expired - Fee Related CN1023630C (en) | 1992-01-17 | 1992-01-17 | Method of chemical modification for iso-species of biological valve |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1023630C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1701770B (en) * | 2005-07-08 | 2011-04-27 | 北京佰仁医疗科技有限公司 | Elastic artificial biological heart valve |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102350008A (en) * | 2011-10-25 | 2012-02-15 | 微创医疗器械(上海)有限公司 | Method for treating animal-derived collagen fiber material |
| CN115998955A (en) * | 2022-12-09 | 2023-04-25 | 首都医科大学附属北京安贞医院 | Aldehyde-chromium composite crosslinking method of venous bridge |
-
1992
- 1992-01-17 CN CN 92100096 patent/CN1023630C/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1701770B (en) * | 2005-07-08 | 2011-04-27 | 北京佰仁医疗科技有限公司 | Elastic artificial biological heart valve |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1063047A (en) | 1992-07-29 |
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| C06 | Publication | ||
| PB01 | Publication | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
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| CF01 | Termination of patent right due to non-payment of annual fee |