CN1954883B - Method for stabilizing hemoglobin oxygen carrier sample - Google Patents
Method for stabilizing hemoglobin oxygen carrier sample Download PDFInfo
- Publication number
- CN1954883B CN1954883B CN2005100962568A CN200510096256A CN1954883B CN 1954883 B CN1954883 B CN 1954883B CN 2005100962568 A CN2005100962568 A CN 2005100962568A CN 200510096256 A CN200510096256 A CN 200510096256A CN 1954883 B CN1954883 B CN 1954883B
- Authority
- CN
- China
- Prior art keywords
- hemoglobin
- hematoglobin
- antioxidant
- ascorbate
- ascorbic acid
- 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
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 title claims abstract description 14
- 238000000034 method Methods 0.000 title claims abstract description 14
- 229910052760 oxygen Inorganic materials 0.000 title claims abstract description 14
- 239000001301 oxygen Substances 0.000 title claims abstract description 14
- 230000000087 stabilizing effect Effects 0.000 title claims abstract description 10
- 108010054147 Hemoglobins Proteins 0.000 title claims description 74
- 102000001554 Hemoglobins Human genes 0.000 title claims description 74
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims abstract description 149
- 235000010323 ascorbic acid Nutrition 0.000 claims abstract description 75
- 239000011668 ascorbic acid Substances 0.000 claims abstract description 75
- 229960005070 ascorbic acid Drugs 0.000 claims abstract description 38
- 229940072107 ascorbate Drugs 0.000 claims abstract description 37
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 claims abstract description 37
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 36
- 235000006708 antioxidants Nutrition 0.000 claims abstract description 36
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 34
- 235000003969 glutathione Nutrition 0.000 claims abstract description 34
- 229960003180 glutathione Drugs 0.000 claims abstract description 34
- 239000013078 crystal Substances 0.000 claims abstract description 5
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 5
- 241001465754 Metazoa Species 0.000 claims description 5
- INGWEZCOABYORO-UHFFFAOYSA-N 2-(furan-2-yl)-7-methyl-1h-1,8-naphthyridin-4-one Chemical compound N=1C2=NC(C)=CC=C2C(O)=CC=1C1=CC=CO1 INGWEZCOABYORO-UHFFFAOYSA-N 0.000 claims description 3
- 238000007385 chemical modification Methods 0.000 claims description 3
- 108010002255 deoxyhemoglobin Proteins 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 2
- 238000007254 oxidation reaction Methods 0.000 abstract description 10
- 238000004321 preservation Methods 0.000 abstract description 5
- 102000004169 proteins and genes Human genes 0.000 abstract description 2
- 238000000338 in vitro Methods 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 231100000956 nontoxicity Toxicity 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 38
- 230000003647 oxidation Effects 0.000 description 7
- 238000006701 autoxidation reaction Methods 0.000 description 6
- 230000003064 anti-oxidating effect Effects 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 108010024636 Glutathione Proteins 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 150000000996 L-ascorbic acids Chemical class 0.000 description 2
- 108010061951 Methemoglobin Proteins 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000000680 avirulence Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 235000013601 eggs Nutrition 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 108010076770 hemoglobin polymer Proteins 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 238000007348 radical reaction Methods 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 1
- JQRLYSGCPHSLJI-UHFFFAOYSA-N [Fe].N1C(C=C2N=C(C=C3NC(=C4)C=C3)C=C2)=CC=C1C=C1C=CC4=N1 Chemical compound [Fe].N1C(C=C2N=C(C=C3NC(=C4)C=C3)C=C2)=CC=C1C=C1C=CC4=N1 JQRLYSGCPHSLJI-UHFFFAOYSA-N 0.000 description 1
- 230000003026 anti-oxygenic effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000002144 chemical decomposition reaction Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- -1 iron ion Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Abstract
A method for stabilizing the hematoglobin oxygen carrier specimen features in that the crystal or solution of the antioxidant chosen from ascorbic acid or ascorbate, glutathion, or mixer of glutathion and ascorbic acid or ascorbate is added to the solution of hematoglobin product to make the hematoglobin in a deoxy-hematoglobin state, wherein the final concentration of the hematoglobin oxygen is at least 0.5%, and the final concentration of the antioxidant is at least 10 [mu]g/ml, and the content of the deoxy-hematoglobin is over 80%. The invention solves the technical problem of short in vitro preservation of hematoglobin oxygen carrier, decribed in the background art. The invention is a method for stablizing hematoglobin molecular in hematoglobin product, which has no toxicity and excellent biocompatibility, optimum antioxidant can be chosed based on the preservation of hematoglobin product solution and use temperature, thus effectively inhibiting self-oxidation of hematoglobin product and stablizing the protein structure thereof.
Description
Technical field
The present invention relates to the method for haemoglobin molecule in a kind of avirulence, the biocompatibility good stable hemoglobin based article, be specifically related to a kind of method of stabilizing hemoglobin oxygen carrier sample.
Background technology
The hemoglobin based article is easy to take place autoxidation, and the result of autoxidation has two: one, and the intra-annular iron ion of iron porphyrin is oxidized to trivalent by bivalence in the hemoglobin, forms metahemoglobin, makes hemoglobin lose the oxygen carrier performance.The 2nd, but the radical reaction coup injury haemoglobin molecule that autoxidation produced causes the degraded of haemoglobin molecule.Therefore, the external storage life of the hemoglobin carrier of oxygen is very short.
The application of antioxidant might solve this class problem, but not relevant as yet at present report.
Ascorbic acid or Ascorbate are antioxidants commonly used in the food, can be used for the preservation of food in low temperature or the room temperature usually.But the use of antioxidant at present, research mainly are to pay close attention to its inhibited oxidation reaction, i.e. the characteristic of inhibited oxidation thing generation still finds no and closes the report of temperature to the antiopxidant effect influence of antioxidant.
Summary of the invention
The object of the present invention is to provide a kind of method of stabilizing hemoglobin oxygen carrier sample, it has solved the very short technical problem of external storage life of the hemoglobin carrier of oxygen in the background technology.
Technical solution of the present invention is:
A kind of method of stabilizing hemoglobin oxygen carrier sample, its special character is: the performing step of this method is as follows
1) gets the crystal or the solution of antioxidant, add in the hemoglobin based article solution;
2) make the final concentration of hemoglobin in the hemoglobin based article solution be at least 0.5%;
3) make the final concentration of antioxidant in the hemoglobin based article solution be at least 10 μ g/ml;
4) described antioxidant is ascorbic acid or Ascorbate, or described antioxidant is glutathion, or described antioxidant is the mixture of ascorbic acid or Ascorbate and glutathion;
5) hemoglobin in the described hemoglobin based article solution is to exist with the deoxidation state, and deoxyhemoglobin content accounts for more than 80%.
The final concentration of hemoglobin is advisable with 0.5%～18% in the above-mentioned hemoglobin based article solution.
Above-mentioned ascorbic acid or Ascorbate or and the preparation of glutathione solution, be with ascorbic acid or Ascorbate or and glutathion add in aqueous solution or the Laemmli buffer system Laemmli, be dissolved as suitable with mechanical agitation.
Above-mentioned hemoglobin can be an animal or with the hemoglobin of the unmodified of gene engineering expression or hemoglobin of chemical modification etc.; Described hemoglobin can be polyethyleneglycol modified hemoglobin or hemoglobin polymer etc.
When above-mentioned antioxidant was ascorbic acid or Ascorbate, this ascorbic acid or the Ascorbate final concentration in hemoglobin solutions was advisable to be at least 10 μ g/ml.
Above-mentioned ascorbic acid or the Ascorbate final concentration in hemoglobin solutions with 10-120 μ g/ml is
When above-mentioned antioxidant was glutathion, the final concentration of this glutathion in hemoglobin solutions was advisable to be at least 50 μ g/ml.
The final concentration of above-mentioned glutathion in hemoglobin solutions is good with 50-750 μ g/ml.
When above-mentioned antioxidant was ascorbic acid or Ascorbate and glutathion, described ascorbic acid or the Ascorbate final concentration in hemoglobin solutions was advisable to be at least 30 μ g/ml; The final concentration of described glutathion in hemoglobin solutions is advisable to be at least 100 μ g/ml.
When above-mentioned antioxidant was ascorbic acid or Ascorbate and glutathion, ascorbic acid or the Ascorbate final concentration in the white solution of red eggs was good with 30-100 μ g/ml; The final concentration of described glutathion in hemoglobin solutions is good with 100-950 μ g/ml.
The present invention has the following advantages:
1 the present invention utilizes antioxidation mechanism, the hemoglobin in the stabilizing solution, make the hemoglobin based article can be under low temperature or room temperature condition long preservation.Storage life can reach more than 3 years at least.
2 ascorbic acid or Ascorbate, glutathion all are antioxidants of using always, are in animal or human's body or the natural anti-oxidation material that can use in animal or human's body, have good water-solubility, to the body free of toxic effects.Therefore, the present invention is the method for haemoglobin molecule in a kind of avirulence, the biocompatibility good stable hemoglobin based article.
3 ascorbic acid of the present invention or Ascorbate and glutathion can make already oxidised material reduction, that is: oxidation reaction is reversed.
4 can choose the antioxidant of optimum efficiency according to preservation, the serviceability temperature of hemoglobin based article solution, thereby can effectively suppress the autoxidation of hemoglobin based article, stablize its protein structure.
The specific embodiment
The present invention be with ascorbic acid or Ascorbate or and glutathion add by a certain percentage in the hemoglobin based article, make it under 4～8 ℃ or room temperature condition, produce special antioxygenic property, suppress the autoxidation and the consequent radical reaction of hemoglobin, reach the result who safeguards the hemoglobin long-term stability.
Realize key step of the present invention:
1. get the crystal of antioxidant or the solution of higher concentration.
Antioxidant can use ascorbic acid or Ascorbate separately, use glutathion or use ascorbic acid simultaneously or Ascorbate and glutathion crystal separately, or uses ascorbic acid or Ascorbate separately, uses glutathion or use ascorbic acid simultaneously or Ascorbate and glutathione solution separately.
Ascorbic acid or Ascorbate and glutathion all should be in the above purity grades of chemical pure.The preparation of ascorbic acid or Ascorbate and glutathione solution, can with ascorbic acid or Ascorbate or and glutathion be dissolved in aqueous solution or any Laemmli buffer system Laemmli, and be dissolved as suitable with mechanical agitation.
2. add in the hemoglobin based article solution, make in the solution ascorbic acid or Ascorbate or and glutathion and hemoglobin reach certain final concentration.
Hemoglobin can be that unmodified hemoglobin, various chemical modification hemoglobin comprise polyethyleneglycol modified hemoglobin and various hemoglobin polymer from various animals or with the product of gene engineering expression.
The final concentration of hemoglobin can be more than 0.5%, generally 0.5%～18% or higher in the solution.
Experimental result of the present invention shows: the degree of ascorbic acid or Ascorbate, glutathion antioxidation can change with the different of temperature with character.
The influence of ascorbic acid or ascorbic acid salt pair hemoglobin goods self oxidation is duality:
1) in the time of 4～8 ℃ Celsius, ascorbic acid or Ascorbate can in several days, suppress the formation of metahemoglobin in the solution in a short time preferably, even can make the hemoglobin reduction of oxidation.But along with the prolongation of time, the metahemoglobin in the solution can increase gradually, and promptly the antioxidation of ascorbic acid or Ascorbate can weaken gradually.
2) when temperature was higher than 10 ℃ Celsius, ascorbic acid or Ascorbate can promote the formation of metahemoglobin, i.e. the effect of ascorbic acid or Ascorbate accelerating oxidation.
Experimental result of the present invention also shows:
1) in the time of 4～8 ℃ Celsius, glutathion as the effect of antioxidant a little less than.
2) in the time of 10～25 ℃ Celsius, glutathion is as the best results of antioxidant.
During storage, hemoglobin must mainly be to exist with the deoxidation state in the solution, and deoxyhemoglobin content should account for more than 80%.And final preparation should be preserved under the lucifuge condition.
The embodiment of the invention 1:
In the time of 4～10 ℃ Celsius, use ascorbic acid or Ascorbate to make antioxidant separately, add in the hemoglobin solutions; Make ascorbic acid or the Ascorbate final concentration in hemoglobin solutions more than 10 μ g/ml, be advisable with 10～120 μ g/ml, also can be to more than the 120 μ g/ml.
The embodiment of the invention 2:
In the time of 10～25 ℃ Celsius, use glutathion to make antioxidant separately, add in the hemoglobin solutions; Make the final concentration of glutathion in hemoglobin solutions more than 50 μ g/ml, be advisable with 50～750 μ g/ml, also can be to more than the 750 μ g/ml.
The embodiment of the invention 3:
In the time of 4 ℃～25 ℃ Celsius, use ascorbic acid or Ascorbate and glutathion to make antioxidant simultaneously, add in the hemoglobin solutions; Make ascorbic acid or the Ascorbate final concentration in the white solution of red eggs more than 30 μ g/ml, be advisable with 30-100 μ g/ml, also can be to 100 μ g/ml; Make the final concentration of glutathion in hemoglobin solutions more than 100 μ g/ml, be advisable with 100-950 μ g/ml, also can be to 950 μ g/ml.
Purposes of the present invention:
1. be used for the reduction of oxide: add antioxidant, make the oxide reduction that has generated in the solution, increase reduction-state and reduce oxidation state. For example: make established ferrihemoglobin content minimizing in the hemoglobin solution after adding antioxidant.
2. be used for preventing the oxidation of object: add antioxidant, to suppress the oxidation of object molecule. Keep object to exist with reduction-state as far as possible. For example: add and make that the reduced hemoglobin molecule is not easy autoxidation in the hemoglobin solution, be not easy to form ferrihemoglobin behind the above-mentioned antioxidant.
3. be used for preventing the degraded of object: add antioxidant, suppress the chemical degradation of object molecule. For example: make the degraded that suppresses hemoglobin in the hemoglobin solution after adding above-mentioned antioxidant.
Claims (3)
1. the method for a stabilizing hemoglobin oxygen carrier sample, it is characterized in that: the performing step of this method comprises
1) gets the crystal or the solution of antioxidant, add in the hemoglobin based article solution;
2) make the final concentration of hemoglobin in the hemoglobin based article solution be at least 0.5%;
3) make the final concentration of antioxidant in the hemoglobin based article solution be: when antioxidant was ascorbic acid or Ascorbate, final concentration was 10-120 μ g/ml; When antioxidant was glutathion, final concentration was 50-750 μ g/ml; When antioxidant was the mixture of ascorbic acid or Ascorbate and glutathion, the final concentration of ascorbic acid or Ascorbate was 30-100 μ g/ml, and the final concentration of glutathion is 100-950 μ g/ml;
4) hemoglobin in the described hemoglobin based article solution is to exist with the deoxidation state, and deoxyhemoglobin content accounts for more than 80%.
2. the method for stabilizing hemoglobin oxygen carrier sample according to claim 1, it is characterized in that: the final concentration of hemoglobin is 0.5%～18% in the described hemoglobin based article solution.
3. the method for stabilizing hemoglobin oxygen carrier sample according to claim 1 is characterized in that: described hemoglobin is an animal or with the hemoglobin of the unmodified of gene engineering expression or the hemoglobin of chemical modification.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2005100962568A CN1954883B (en) | 2005-10-28 | 2005-10-28 | Method for stabilizing hemoglobin oxygen carrier sample |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2005100962568A CN1954883B (en) | 2005-10-28 | 2005-10-28 | Method for stabilizing hemoglobin oxygen carrier sample |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1954883A CN1954883A (en) | 2007-05-02 |
| CN1954883B true CN1954883B (en) | 2011-06-15 |
Family
ID=38062554
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2005100962568A Active CN1954883B (en) | 2005-10-28 | 2005-10-28 | Method for stabilizing hemoglobin oxygen carrier sample |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1954883B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110522904A (en) * | 2019-09-09 | 2019-12-03 | 润方（北京）生物医药研究院有限公司 | A kind of raised polymeric hemoglobin of inhibition blood pressure |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4704352A (en) * | 1985-06-25 | 1987-11-03 | Baxter Travenol Laboratories, Inc. | L-ascorbate-2-phosphate salts in blood cell storage |
| WO1999060849A1 (en) * | 1998-05-26 | 1999-12-02 | Lifecell Corporation | Cryopreservation of human red blood cells |
| US6242417B1 (en) * | 1994-03-08 | 2001-06-05 | Somatogen, Inc. | Stabilized compositions containing hemoglobin |
| CN1499978A (en) * | 2001-02-28 | 2004-05-26 | ض� | Manufacture of hemoglobin-based oxygen carrier |
| CN1516550A (en) * | 2001-04-18 | 2004-07-28 | ������ʵ���ҹ�˾ | Flexible container system for storage of stabilized hemoglobin solutions |
-
2005
- 2005-10-28 CN CN2005100962568A patent/CN1954883B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4704352A (en) * | 1985-06-25 | 1987-11-03 | Baxter Travenol Laboratories, Inc. | L-ascorbate-2-phosphate salts in blood cell storage |
| US6242417B1 (en) * | 1994-03-08 | 2001-06-05 | Somatogen, Inc. | Stabilized compositions containing hemoglobin |
| WO1999060849A1 (en) * | 1998-05-26 | 1999-12-02 | Lifecell Corporation | Cryopreservation of human red blood cells |
| CN1499978A (en) * | 2001-02-28 | 2004-05-26 | ض� | Manufacture of hemoglobin-based oxygen carrier |
| CN1516550A (en) * | 2001-04-18 | 2004-07-28 | ������ʵ���ҹ�˾ | Flexible container system for storage of stabilized hemoglobin solutions |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1954883A (en) | 2007-05-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Mahaseth et al. | Potentiation of hydrogen peroxide toxicity: From catalase inhibition to stable DNA-iron complexes | |
| Fridovich | Oxygen is toxic! | |
| Drath et al. | Bactericidal activity of metal-mediated peroxide-ascorbate systems | |
| Maiti | Cross‐talk between (Hydrogen) Sulfite and metalloproteins: impact on human health | |
| AU2010201151B2 (en) | Forming Iron Nitrosyl Hemoglobin | |
| CN1954883B (en) | Method for stabilizing hemoglobin oxygen carrier sample | |
| Inoue et al. | Cross-talk of NO, superoxide and molecular oxygen, a majesty of aerobic life | |
| CN105776490A (en) | Preparation method of vitamin C hydrogen-enriched water and vitamin C hydrogen-enriched water prepared according to method | |
| Osawa et al. | Accelerated redox reaction of hydrogen peroxide by employing locally concentrated state of copper catalysts on polymer chain | |
| Heck et al. | An epigrammatic (abridged) recounting of the myriad tales of astonishing deeds and dire consequences pertaining to nitric oxide and reactive oxygen species in mitochondria with an ancillary missive concerning the origins of apoptosis | |
| Hassan | Superoxide dismutases | |
| Koppenol et al. | Hydrogen peroxide, a molecule with a Janus face: its history, chemistry, and biology | |
| CN115317515A (en) | Multi-effect synergetic biomimetic mineralized nano preparation of lonidamine/bovine serum albumin/iron phosphate and preparation method and application thereof | |
| Geisser | Iron therapy and oxidative stress | |
| CN101112385A (en) | Application of sodium thiosulfate in the preparation of clinical selenium-complementing and cancer-treating medicine and fast- preparing method for the same | |
| CN107183010A (en) | A kind of in vitro tissue preserves liquid | |
| JPS61502933A (en) | Electrolyte solutions and their in vitro use | |
| Awasthi et al. | Modulation of oxidative stability of haemoglobin inside liposome-encapsulated haemoglobin | |
| Lindh | Metal biology: aspects of beneficial effects | |
| JP2005021875A (en) | Method for maintaining oxidation-reduction potential of water | |
| JP7036324B2 (en) | Anti-blood coagulation agent, blood coagulation improving device, blood coagulation improving method, vascular endothelial cell function improving method and metabolism improving method | |
| Benjamin et al. | Implications for Nitrate Intake | |
| Hartman et al. | The competitive effects of metallic ions on citrate oxidation. II | |
| Rojas-Espinosa | Macrophages, myeloperoxidase, and Mycobacterium lepraemurium | |
| Face | 1 Hydrogen Peroxide |
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 | ||
| ASS | Succession or assignment of patent right |
Owner name: XI'AN BEIMEI BIO-PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: SHAANXI BAIMEI GENE CO., LTD. Effective date: 20140307 |
|
| C56 | Change in the name or address of the patentee |
Owner name: SHAANXI BAIMEI GENE CO., LTD. Free format text: FORMER NAME: SHAANXI LIFEGEN CO., LTD. |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 710069 XI'AN, SHAANXI PROVINCE TO: 710077 XI'AN, SHAANXI PROVINCE |
|
| CP01 | Change in the name or title of a patent holder | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 386 box 710069, Northwestern University, 229 Taibai North Road, Shaanxi, Xi'an Patentee after: SHAANXI LIFEGEN Co.,Ltd. Address before: 386 box 710069, Northwestern University, 229 Taibai North Road, Shaanxi, Xi'an Patentee before: Shaanxi North American Gene Co.,Ltd. |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20140307 Address after: 710077 No. five, No. 2, hi tech Zone, Xi'an hi tech Zone, Shaanxi Patentee after: Xi'an North America Biological Pharmaceutical Co.,Ltd. Address before: 386 box 710069, Northwestern University, 229 Taibai North Road, Shaanxi, Xi'an Patentee before: SHAANXI LIFEGEN Co.,Ltd. |
|
| TR01 | Transfer of patent right |