CN1709515A - Stable liquid compound fibrillarin blocking agent, and its preparation and use - Google Patents
Stable liquid compound fibrillarin blocking agent, and its preparation and use Download PDFInfo
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- CN1709515A CN1709515A CNA2005100271894A CN200510027189A CN1709515A CN 1709515 A CN1709515 A CN 1709515A CN A2005100271894 A CNA2005100271894 A CN A2005100271894A CN 200510027189 A CN200510027189 A CN 200510027189A CN 1709515 A CN1709515 A CN 1709515A
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- fibrillarin
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention relates to a stable liquid compound fibre protein blocking agent composition, its preparation method and application. The described stable liquid compound fibre protein blocking agent is formed from portion I and portion II. Said two portions are independently stored, when they are used, both are mixed so as to obtain several functions of blocking, repairing, blocking leakage and promoting healing in clinical surgery field. Said invention mainly utilizes addition of function-intensifying factor, stabilizing agent I and citrate buffer solution or phosphate buffer solution to provide a stable liquid compound fibre protein blocking agent which can be used as bone repairing material and medicine slowly-releasing carrier.
Description
Technical field
The present invention relates to a kind of compositions of stable liquid compound fibrillarin blocking agent, can be used as the carrier of bone renovating material or the slow-released carrier of medicine, be applied to tissue defect sealing, reparation, hemostasis, leak stopping, anti and promote wound healing, the invention still further relates to the preparation method of this stable liquid compound fibrillarin blocking agent, and uses thereof, belong to medical product and technical field.
Technical background
Medical involution product synthesizes and two kinds of biological involution products from developing the history of existing nine more than ten years so far, mainly being divided into.Because synthetic involution product is a high-molecular organic material, exist to absorb and the rejection problem, so unsatisfactory.After definite bioprotein sewn product in 1972 is as binding agent, nineteen eighty-two is the fibrin sealant widespread usage of raw material with the human blood, infectious hepatitis and AIDS's is popular and U.S. FDA is because of the large-scale production meeting of misgivings people blood product causes, therefore, past long-standing ban commercialization always, the approval of product acquisition U.S. FDA was just arranged, but product price is extremely expensive after 98 years.Traditional fibrin sealant is owing to the imperfection at aspects such as technology and dosage forms, caused it on medical effect, to have more or less shortcoming, this mainly shows the following aspects: 1) agent of traditional fibre protein blocking is a freeze-dried formulation, need dissolve preparation during use, dissolution time is long, and formality is loaded down with trivial details; And whole lyophilizing course of dissolution again makes that the main component fibrinogen concentration can not be very high in the product; 2) traditional handicraft adopts " cryoprecipitate technology " to carry out separation and purification, and the content and the purity of gained main component Fibrinogen, the XIII factor, fibronectin are lower; 3) traditional process using Co60 radiation exposure is killed virus and the antibacterial in the product.The method deficiency is: 1. the Co60 intensity of radiation is non-constant, and is inhomogeneous to the effect of product, and it is incomplete to cause bacterial virus to kill easily; 2. bacterial body remains in the product behind the radiation exposure, is potential pyrogen.3. can make fibrinogenic purity decline in the product behind the Co60 radiation exposure, solidifiable albumen rate descends about 10%, and dissolution time significantly prolongs; 4) traditional product so products with adhesive power is not strong, becomes film-strength low because fibrinogen concentration is not high enough, can only be used for general wound surface hemostasis sealing, and what can not be used to organize be effectively bonding, and clinical result of use is not good enough.
Summary of the invention
The object of the present invention is to provide a kind of stable liquid compound fibrillarin blocking agent safe, effective, easy to use, and provide the preparation method of this stable liquid compound fibrillarin blocking agent and the purposes of this stable liquid compound fibrillarin blocking agent.
Stable liquid compound fibrillarin blocking agent of the present invention, constitute by part I and part II, two parts are independently preserved, and both mixing reach the multiple function such as sealing, reparation, leak stopping, promotion healing in Clinical Surgery field during use, and two parts composition separately is respectively:
Part I comprises:
Fibrinogen concentration is 35mg/ml～100mg/ml
Stabilizing agent I 2%～20%
Citrate buffer or phosphate buffer pH value are 6.5-8.0
Part II comprises:
Thrombin 50IU/ml～1000IU/ml
Ca2+ 5mM～50mM
Stabilizing agent II 2%～20%
Citrate buffer or phosphate buffer pH value are 6.5-8.0
Stable liquid compound fibrillarin blocking agent of the present invention also comprises the function intensified factor, the function intensified factor both can be included among the part I separately, also can be included among the part II separately, but also can be included in simultaneously among part I and the part II, the function intensified factor and proportioning thereof are factor XI, plasma thromboplastin antecedent II10～60IU/ml, factor Fn10～120IU/ml, collagen protein 0.5%～15%, elastin laminin 0.5～15%, the combination of one or more of hyaluronic acid 0.5～10% and soluble chitosan 0.5～10%; Stabilizing agent I and stabilizing agent II are one or more combinations in sugar, aminoacid and the protein, and wherein steamed bun stuffed with sugar is drawn together monosaccharide, oligosaccharide and polysaccharide, as Sargassum polysaccharides etc.; Aminoacid such as glycine etc., protein such as albumin, globulin etc.And stabilizing agent I and stabilizing agent II can be the same or different.
Stable liquid compound fibrillarin blocking agent provided by the invention, the Fibrinogen that wherein relates to, thrombin and intensifier XIII and Fn by mammal or people's blood plasma by isoelectric precipitation, saltout or method such as organic solvent deposit prepares.
The preparation method of stable liquid compound fibrillarin blocking agent provided by the invention, because part I and part II are independent the preservations before using, so its preparation also is divided into two parts:
(1) preparation of the part I of stable liquid compound fibrillarin blocking agent:
1. the cold preservation blood plasma that anticoagulant killed the virus utilization salt analysis method obtains Fibrinogen crude product precipitation, and after reuse citrate buffer or the phosphate buffer dissolving, the ultrafiltration desalination obtains desalting soln;
2. desalting soln utilization organic solvent isolation technics obtains precipitation, and precipitation is removed organic solvent with ultrafiltration once more after citrate buffer or phosphate buffer dissolving, obtain Fibrinogen;
3. Fibrinogen, the function intensified factor, stabilizing agent I and citrate buffer or phosphate buffer are carried out proportioning by claim 1, get finished product;
4. with the finished product aseptic filtration, adopt ultraviolet radiation and-40～-120 ℃ of ultralow temperature to handle, and adopt the ultraviolet radiation kill virus and adopt multistage microporous filter membrane and the degerming of pressurization nano-film filtration technology, obtain part I;
(2) stable liquid compound fibrillarin blocking agent part II preparation technology is as follows:
1. use isoelectric precipitation, saltout or organic solvent precipitation method prepares thrombin from mammal or people's blood plasma, again with thrombin, Ca
2+, stabilizing agent II and citrate solution carry out proportioning by claim 1, finished product;
2. with the finished product aseptic filtration, adopt ultraviolet radiation and-40～-120 ℃ of ultralow temperature to handle, and adopt the ultraviolet radiation kill virus and adopt multistage microporous filter membrane and the degerming of pressurization nano-film filtration technology, obtain part II.
The preparation method of stable liquid compound fibrillarin blocking agent of the present invention, the wherein function intensified factor not only can be carried out proportioning when preparation part I, also can when preparation part II, carry out proportioning, perhaps when preparation part I and preparation part II, carry out proportioning simultaneously.In brief, as long as in stable liquid compound fibrillarin blocking agent integral body, contain a certain amount of function intensified factor.
Can need not to prepare Fibrinogen separately when preparation stable liquid compound fibrillarin blocking agent of the present invention, be that raw material directly carries out proportioning and directly get the freeze-dried type Fibrinogen.Simultaneously, also can directly to get the freeze-dried type thrombin be that raw material directly carries out proportioning to the thrombin among the part II.The Fibrinogen or the thrombin that perhaps will be added with the function intensified factor are prepared into freeze-dried formulation.
Stable liquid compound fibrillarin blocking agent of the present invention can be used for the carrier as bone renovating material.Bone renovating material is meant as a certain proportion of chondroitin sulfate, chitosan, animal or human's's (comprising gene expression) fibroblast growth factor and bone morphogenetic protein etc.
Stable liquid compound fibrillarin blocking agent of the present invention can be used for as slow releasing carrier of medication, as the slow-released carrier of antibiotic slow-released carrier, cell growth factor slow-released carrier, analgesic and the slow-released carrier of medicine for treating tumor thing etc.
Compared with the prior art the present invention has remarkable result.Because stable liquid compound fibrillarin blocking agent of the present invention adds the function intensified factor and stabilizing agent, mainly having adopted saltouts adds organic separated from solvent, multistage microporous filter membrane adds technology such as nanometer membrane filtration, make the agent of freezable liquid composite fibre protein blocking in the storage steady in a long-term of-18 ℃ of energy, 37 ℃ of water-baths are melted fast and are liquid, liquid formulation can be stablized storage 1～90 day between+4 ℃ to+20 ℃, clinical extremely easy to use.The present invention is mainly used in Clinical Surgery each section office's operation and field of tissue engineering technology, anthemorrhagic speed to oozing of blood is faster than thrombin, only need oozing of blood was stopped in several seconds, can protect from infection, promote wound healing, reduce cicatrix etc., and need not stitch bundle, eliminated because of seam and pricked damage and the pain of bringing, had the sealing of the defective tissue of promotion and repair advantages such as healing acceleration.The outstanding advantage of the relative traditional product of the present invention is that function is superior, fast convenient and safe and effective.Because this sealer contains multiple intensifiers such as collagen protein, elastin laminin, hyaluronic acid, soluble chitosan, make it to become the strong composite organization engineering stent material by using of a kind of novel plasticity, have multiple functions such as sealing, reparation, leak stopping, promotion healing in the Clinical Surgery field.
Be by adopting ultraviolet radiation and ultralow temperature (40 ℃～-120 ℃) to handle, reducing product immunogenicity (being antigenicity) in the preparation method provided by the invention; And adopt the ultraviolet radiation kill virus and adopt multistage microporous filter membrane and pressurization nano-film filtration degerming technology realizes.Overcome traditional handicraft Co60 radiation exposure and killed the virus in the product and the deficiency of antibacterial method.The present invention adopts thin layer blood plasma ultraviolet radiation kill virus, antibacterial, and uitraviolet intensity is constant, to the product even action, can effectively kill virus and antibacterial in the product; Product adopts the residual body of the thorough filtering antibacterial of nano-film filtration again after irradiation, guarantee aseptic, no thermal source, and product is safe and reliable.And have very strong rheological properties, as viscosity, elasticity etc., and very strong adhesive power is arranged.Bonding force can reach 150～300g/cm
2Setting time was less than 8 seconds; Fine former solidifiable albumen rate reaches 75～95%.
Specific embodiment
What the preparation of stable liquid compound fibrillarin blocking agent of the present invention was adopted is the associated methods of salting out method and organic solvent precipitation method, and specific embodiment is as follows:
Embodiment 1:
The selection of the function intensified factor: selecting factor XI, plasma thromboplastin antecedent II in the present embodiment is the function intensified factor;
Stabilizing agent I selects the mixture of Sargassum polysaccharides and glycine, and stabilizing agent II selects Sargassum polysaccharides;
(1) preparation of part I:
1. the anticoagulant cold preservation blood plasma that kills the virus adds saturated ammonium salt, produces precipitation, the centrifugal crude product precipitation that obtains.
2. after the crude product precipitation was the dissolving of 6.5 citrate buffers with pH value, ultrafiltration desalination again got desalting soln.
3. desalting soln adds low temperature 30% ethanol, and recentrifuge must precipitate.
4. precipitate with after the citrate buffer dissolving, remove organic solvent with ultrafiltration once more.
5. add the function intensified factor, and concentrate, add stabilizing agent I and citrate buffer, carry out proportioning by claim 1, function intensified factor XI, plasma thromboplastin antecedent II10IU/ml, fibrinogen concentration are that 35mg/ml, stabilizing agent I 2%, citrate buffer pH value are 6.5, get finished product.
6. aseptic filtration adopts ultraviolet radiation and-120 ℃ of ultralow temperature to handle, and reduces the product immunogenicity; And adopt the ultraviolet radiation kill virus and adopt multistage microporous filter membrane and the degerming of pressurization nano-film filtration degerming technology.
7. finished product is distinguished fill in syringe, aseptic packaging ,-18 ℃ of refrigerated storages.
(2) preparation of part II:
1. get mammal or people's blood plasma, adopt the organic solvent deposit method to prepare thrombin;
2. add Ca
2+, the function intensified factor, stabilizing agent and citrate buffer solution are by claim 1 proportioning, wherein thrombin 1000IU/ml, Ca
2+50mM, stabilizing agent II 2%, citrate buffer pH value are 6.5
3. aseptic filtration adopts ultraviolet radiation and-120 ℃ of ultralow temperature to handle, and reduces the product immunogenicity; And adopt the ultraviolet radiation kill virus and adopt multistage microporous filter membrane and the degerming of pressurization nano-film filtration degerming technology.
4. finished product is distinguished fill in syringe, aseptic packaging ,-18oC refrigerated storage.
Embodiment 2:
The selection of the function intensified factor: selecting the mixture of collagen protein and elastin laminin in the present embodiment is the function intensified factor; Stabilizing agent I and stabilizing agent II select the mixture of Sargassum polysaccharides, albumin and glycine;
(1) preparation of part I:
1. the anticoagulant cold preservation blood plasma that kills the virus adds saturated ammonium salt, produces precipitation, the centrifugal crude product precipitation that obtains.
2. after the crude product precipitation was the dissolving of 8.0 phosphate buffers with pH value, ultrafiltration desalination again got desalting soln.
3. desalting soln adds low temperature 20% Polyethylene Glycol, and recentrifuge must precipitate.
4. precipitate with after the phosphate buffer dissolving, remove organic solvent with ultrafiltration once more.
5. add the function intensified factor, and concentrate, add stabilizing agent I and phosphate buffer, carry out proportioning by claim 1, the mixture of function intensified factor collagen protein 5% and elastin laminin 3%, fibrinogen concentration is that 100mg/ml, stabilizing agent I 20%, phosphate buffer pH value are 8.0, gets finished product.
6. aseptic filtration adopts ultraviolet radiation and-40 ℃ of ultralow temperature to handle, and reduces the product immunogenicity; And adopt the ultraviolet radiation kill virus and adopt multistage microporous filter membrane and the degerming of pressurization nano-film filtration degerming technology.
7. finished product is distinguished fill in cillin bottle, aseptic packaging, storage at normal temperature.
(2) preparation of part II:
1. get mammal or people's blood plasma, adopt the isoelectric precipitation method to prepare thrombin;
2. add Ca
2+, the function intensified factor, stabilizing agent and phosphate buffered solution, by claim 1 proportioning, the mixture of function intensified factor collagen protein 5% and elastin laminin 3%, wherein thrombin 50IU/ml, Ca
2+50mM, stabilizing agent II 20%, phosphate buffer pH value are 8.0.
3. aseptic filtration adopts ultraviolet radiation and-40 ℃ of ultralow temperature to handle, and reduces the product immunogenicity; And adopt the ultraviolet radiation kill virus and adopt multistage microporous filter membrane and the degerming of pressurization nano-film filtration degerming technology.
4. finished product is distinguished fill in cillin bottle, aseptic packaging, storage at normal temperature.
Embodiment 3:
The selection of the function intensified factor: selecting factor soluble chitosan in the present embodiment is the function intensified factor; Stabilizing agent I selects the mixture of Sargassum polysaccharides and glycine, and stabilizing agent II selects Sargassum polysaccharides, glycine and globulin;
(1) preparation of part I:
1. the anticoagulant cold preservation blood plasma that kills the virus adds saturated ammonium salt, produces precipitation, the centrifugal crude product precipitation that obtains.
2. after the crude product precipitation was the dissolving of 7.0 citrate buffers with pH value, ultrafiltration desalination again got desalting soln.
3. desalting soln adds low temperature 30% ethanol, and recentrifuge must precipitate.
4. precipitate with after the citrate buffer dissolving, remove organic solvent with ultrafiltration once more.
5. add the function intensified factor, and concentrate, add stabilizing agent I and citrate buffer, carry out proportioning by claim 1, function intensified factor soluble chitosan 7%, fibrinogen concentration are that 70mg/ml, stabilizing agent I 13%, citrate buffer pH value are 7.0, get finished product.
6. aseptic filtration adopts ultraviolet radiation and-100 ℃ of ultralow temperature to handle, and reduces the product immunogenicity; And adopt the ultraviolet radiation kill virus and adopt multistage microporous filter membrane and the degerming of pressurization nano-film filtration degerming technology.
7. finished product is distinguished fill in syringe, aseptic packaging ,-18 ℃ of refrigerated storages.
(2) preparation of part II:
1. get mammal or people's blood plasma, adopt the organic solvent deposit method to prepare thrombin;
2. add Ca
2+, the function intensified factor, stabilizing agent and citrate buffer solution are by claim 1 proportioning, wherein thrombin 600IU/ml, Ca
2+40mM, stabilizing agent II 10%, citrate buffer pH value are 7.0
3. aseptic filtration adopts ultraviolet radiation and-100 ℃ of ultralow temperature to handle, and reduces the product immunogenicity; And adopt the ultraviolet radiation kill virus and adopt multistage microporous filter membrane and the degerming of pressurization nano-film filtration degerming technology.
4. finished product is distinguished fill in syringe, aseptic packaging ,-18 ℃ of refrigerated storages.
Embodiment 4:
The function intensified factor can be made up by any in factor XI, plasma thromboplastin antecedent II, factor Fn, collagen protein, elastin laminin, hyaluronic acid and the soluble chitosan or more than one, other steps are with embodiment 1, because basic step is just the same, one list so differ.
In like manner, stabilizing agent I and stabilizing agent II are one or more combinations in sugar, aminoacid and the protein, and wherein steamed bun stuffed with sugar is drawn together as monosaccharide, oligosaccharide and polysaccharide, as Sargassum polysaccharides etc.; Aminoacid such as glycine etc., protein such as albumin, globulin etc.And stabilizing agent I and stabilizing agent II can be the same or different, and other steps are with embodiment 1, because basic step is just the same, one lists so also differ.
Embodiment 5:
After making finished product among the embodiment 1, all can directly carry out lyophilizing after the aseptic filtration, cooperate citrate buffer or phosphate buffer to use, other steps are with embodiment 1.
Embodiment 6:
The stable liquid compound fibrillarin blocking agent that is prepared from by any scheme of embodiment 1～4, add the human bone morphogenesis protein of 12ug/ml, the fibroblast growth factor of 5mg/ml among the part I, the part I and the part II that are added with bone renovating material are distinguished fill in Chinese patent, use in the duplex syringe of patent No. ZL99240314.6, using method is seen the duplex syringe patent specification of Chinese patent ZL99240314.6 in detail.
Embodiment 7:
The stable liquid compound fibrillarin blocking agent that is prepared from by any scheme of embodiment 1～4, add the human bone morphogenesis protein of 12ug/ml, the fibroblast growth factor of 5mg/ml among the part II, part I and the part II that is added with bone renovating material are distinguished fill in Chinese patent, use in the duplex syringe of patent No. ZL99240314.6, using method is seen the duplex syringe patent specification of Chinese patent ZL99240314.6 in detail.
Embodiment 8:
The stable liquid compound fibrillarin blocking agent that is prepared from by any scheme of embodiment 1～4, the tumor necrosis factor (TNF) that adds common dose among the part I, the part I and the part II that are added with antitumor drug are distinguished fill in Chinese patent, use in the duplex syringe of patent ZL99240314.6, using method is seen the duplex syringe patent specification of Chinese patent ZL99240314.6 in detail.
Embodiment 9:
The stable liquid compound fibrillarin blocking agent that is prepared from by any scheme of embodiment 1～4, the epidermal growth factor or the antibiotics that add common dose among the part II, part I and part II are distinguished fill in Chinese patent, use in the duplex syringe of patent No. ZL99240314.6, using method is seen the duplex syringe patent specification of Chinese patent ZL99240314.6 in detail.
Bone renovating material joins the part I or the part II of stable liquid compound fibrillarin blocking agent, perhaps adds part I simultaneously or part II all can.
Medicine joins the part I or the part II of stable liquid compound fibrillarin blocking agent, perhaps adds part I simultaneously or part II all can.
Claims (8)
1, a kind of stable liquid compound fibrillarin blocking agent is made of part I and part II, and two parts are independently preserved, and mixes and uses, and it is characterized in that two-part consisting of:
Part I comprises:
Fibrinogen concentration is 35mg/ml～100mg/ml
Stabilizing agent I 2%～20%
Citrate buffer or phosphate buffer pH value are 6.5-8.0
Part II comprises:
Thrombin 50IU/ml～1000IU/ml
Ca
2+ 5mM～50mM
Stabilizing agent II 2%～20%
Citrate buffer or phosphate buffer pH value are 6.5-8.0
In part I and/or part II, add the function intensified factor, the function intensified factor is factor XI, plasma thromboplastin antecedent II10～60IU/ml, factor Fn10～120IU/ml, collagen protein 0.5%～15%, elastin laminin 0.5～15%, the combination of one or more in hyaluronic acid 0.5～10% and the soluble chitosan 0.5～10%; Stabilizing agent I and stabilizing agent II are one or more combinations in sugar, aminoacid and the protein.
2, stable liquid compound fibrillarin blocking agent as claimed in claim 1 is characterized in that stabilizing agent I is identical with stabilizing agent II or different.
3, stable liquid compound fibrillarin blocking agent as claimed in claim 1 or 2, it is characterized in that Fibrinogen, thrombin and intensifier XIII and Fn by mammal or people's blood plasma by isoelectric precipitation, saltout or the organic solvent deposit method prepares.
4, a kind of preparation method of stable liquid compound fibrillarin blocking agent is characterized in that the preparation process of part I and part II is as follows:
(1) preparation of the part I of stable liquid compound fibrillarin blocking agent:
1. the cold preservation blood plasma that anticoagulant killed the virus utilization salt analysis method obtains Fibrinogen crude product precipitation, and after reuse citrate buffer or the phosphate buffer dissolving, the ultrafiltration desalination obtains desalting soln;
2. desalting soln utilization organic solvent isolation technics obtains precipitation, and precipitation is removed organic solvent with ultrafiltration once more after citrate buffer or phosphate buffer dissolving, obtain Fibrinogen;
3. Fibrinogen, the function intensified factor, stabilizing agent I and citrate buffer or phosphate buffer are carried out proportioning by claim 1, get finished product;
4. with the finished product aseptic filtration, adopt ultraviolet radiation and-40 ℃～-120 ℃ ultralow temperature to handle, and adopt the ultraviolet radiation kill virus and adopt multistage microporous filter membrane and the degerming of pressurization nano-film filtration technology, obtain part I;
(2) preparation of the part II of stable liquid compound fibrillarin blocking agent:
1. use isoelectric precipitation, saltout or organic solvent precipitation method prepares thrombin from mammal or people's blood plasma, again with thrombin, Ca
2+, stabilizing agent II and citrate buffer or phosphate buffer carry out proportioning by claim 1, finished product;
2. with the finished product aseptic filtration, adopt ultraviolet radiation and-40 ℃～-120 ℃ ultralow temperature to handle, and adopt the ultraviolet radiation kill virus and adopt multistage microporous filter membrane and the degerming of pressurization nano-film filtration technology, obtain part II.
5, the preparation method of stable liquid compound fibrillarin blocking agent as claimed in claim 4 is characterized in that the function intensified factor is included among the part II, perhaps all comprises the function intensified factor among part I and the part II.
6, as the preparation method of claim 4 or 5 described stable liquid compound fibrillarin blocking agents, it is characterized in that part I and part II are prepared into freeze-dried formulation.
7, stable liquid compound fibrillarin blocking agent is as the application of the carrier of bone renovating material.
8, stable liquid compound fibrillarin blocking agent is as the application of slow releasing carrier of medication.
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| CNB2005100271894A CN100522248C (en) | 2005-06-28 | 2005-06-28 | Stable liquid compound fibrillarin blocking agent, and its preparation and use |
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| CNB2005100271894A CN100522248C (en) | 2005-06-28 | 2005-06-28 | Stable liquid compound fibrillarin blocking agent, and its preparation and use |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101214391B (en) * | 2007-12-27 | 2010-05-19 | 广州倍绣生物技术有限公司 | High-efficiency biogum sealant and uses thereof |
| CN101849850A (en) * | 2010-04-12 | 2010-10-06 | 苏州博创同康生物工程有限公司 | Bionic in-situ regeneration repair nano sticking patch and preparation method and application thereof |
| CN105007841A (en) * | 2012-12-31 | 2015-10-28 | 乔治·D.·福卢什 | Lyophilized fibrin sealant for high volume hemorrhage |
| CN105435299A (en) * | 2016-01-08 | 2016-03-30 | 广州市众为生物技术有限公司 | Albumin glue containing chitosan and use method of albumin glue |
-
2005
- 2005-06-28 CN CNB2005100271894A patent/CN100522248C/en active Active
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101214391B (en) * | 2007-12-27 | 2010-05-19 | 广州倍绣生物技术有限公司 | High-efficiency biogum sealant and uses thereof |
| CN101849850A (en) * | 2010-04-12 | 2010-10-06 | 苏州博创同康生物工程有限公司 | Bionic in-situ regeneration repair nano sticking patch and preparation method and application thereof |
| CN101849850B (en) * | 2010-04-12 | 2013-03-06 | 苏州博创同康生物工程有限公司 | Bionic in-situ regeneration repair nano sticking patch and preparation method and application thereof |
| CN105007841A (en) * | 2012-12-31 | 2015-10-28 | 乔治·D.·福卢什 | Lyophilized fibrin sealant for high volume hemorrhage |
| CN105435299A (en) * | 2016-01-08 | 2016-03-30 | 广州市众为生物技术有限公司 | Albumin glue containing chitosan and use method of albumin glue |
| WO2017117995A1 (en) * | 2016-01-08 | 2017-07-13 | 广州市众为生物技术有限公司 | Chitosan-containing fibrin glue and use method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100522248C (en) | 2009-08-05 |
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