CN2920163Y - Nanometer hemostatic plaster - Google Patents
Nanometer hemostatic plaster Download PDFInfo
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- CN2920163Y CN2920163Y CN 200620057985 CN200620057985U CN2920163Y CN 2920163 Y CN2920163 Y CN 2920163Y CN 200620057985 CN200620057985 CN 200620057985 CN 200620057985 U CN200620057985 U CN 200620057985U CN 2920163 Y CN2920163 Y CN 2920163Y
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- hemostasis
- nanometer
- hemostasia
- chitosan
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Abstract
The utility model relates to a nanometer hemostasia patch, and consists of a supporting layer and a hemostasia layer. The hemostasia layer is adhered onto the face side of the supporting layer, wherein, the hemostasia layer consists of a hemostasia mixture of a thrombin and a linking object, the linking object appears to be of the nanometer class size. A drug-loading layer is arranged on the reverse side of the supporting layer, the drug-loading layer consists of a medical mixture of the linking object of the nanometer class size and therapeutic drug. The utility model has the advantages of that the compatibility of the hemostasia material and the organism is good, without toxic and side effect, and can be degraded thoroughly in the body; and the operation is convenient and quick; the physic and chemical stability are greatly increased, the storage and the transport can be performed under the normal temperature, the price is low, and the utility model can be widely applied to a plurality of occasions where the hemostasia is needed.
Description
[technical field]
This utility model relates to field of medicaments, relates in particular to a kind of novel nano hemostasis and pastes.
[background technology]
At present, one or more steps that local hemostatic mostly is imitation or amplifies coagulation process, clinical commonly used have gelfoam, oxidized cellulose and oxidized regenerated cellulose, Fibrin Glue and chitosan etc.Gelfoam destroys the rack that platelet forms blood coagulation, sealing blood vessels breach or wound surface by absorption wound surface blood; Owing to need the thrombin of body to participate in to obtain last hemostasis result, so not good enough to disturbances of blood coagulation person effect.Oxidized cellulose and oxidized regenerated cellulose then by with hemoglobin generation chemical reaction, condense into the material of blood clot sample, be covered in hemorrhage wound surface and reach the hemostasis purpose; But the acidity of these two kinds of fibers can be destroyed the anastalsis of thrombin.Fibrin Glue is widely used clinically because of its good histocompatibility and haemostatic effect.But Fibrin Glue cost height, storage and use are complicated, and anthemorrhagic speed is slow, and be low to the hemorrhage hemostasis success rate of trunk, also may bring human body or animal blood borne disease to infect.
At the shortcoming of current local hemostatic, the applicant once attempted having developed the fibrin card, though overcome the above-mentioned shortcoming of hemorrhages such as Fibrin Glue, to adapt to operation and first aid hemostatic needs.But find in zoopery and the clinical practice that current fibrin card has following deficiency:
1. relatively poor, the easy degraded of mechanical property in the clinical practice, thereby influence the safety of haemostatic effect and use;
2. during fibrin pastes protein stability a little less than, can not store under the room temperature;
3. can not be used as pharmaceutical carrier, as can not be as the carrier of local chemotherapy in tumorectomy etc.
Because of above-mentioned former thereby limited its promoting the use of clinically.
Chitosan is a natural biologic material, can degradation in vivo be the glucosamine of safety non-toxic, and no antigen has good biocompatibility; Chitosan is the unique positively charged glucosamine of occurring in nature, because of its unique physics and chemistry structure, make chitosan can by and erythrocyte membrane between charge effect coagulation erythrocyte stop blooding, and hemostatic mechanism does not rely on thrombin and platelet, can mediate solidifying of heparinization patient blood, not good patient is also effective to platelet function.Aspect the enzyme immobilization of thrombin, chitosan is because of there being the alpha-amido of N-terminal, and available cross-linking agent forms schiff bases with it and thrombin, thereby demonstrates special immobilization effect.
Along with the developmental research of nanotechnology, nano-scale chitosan etc. have the alpha-amino material of N-terminal now to be considered to the medicine controlled release carrier that a class has application prospect, are specially adapted to the embedding and the release of biologically active macromolecular drug; Simultaneously, chitosan nanoparticles has the characteristic attached to the organism mucomembranous surface; After chitosan is made nanoparticle, but the immobilization thrombin also can be used as the carrier of medicines such as chemotherapeutics, antibacterials, somatomedin, plays the preservation condition that reduces biological product, reduces antigenicity and medicament slow release effect.
How nanotechnology and modern biotechnology are combined, the utilization enzyme immobilization technology, prepare novel nano-scale multifunctional hemostasis subsides just becomes current this field and demands the important topic studying and explore urgently.
[utility model content]
Main purpose of the present utility model be to provide a kind of easy to operate, need not loaded down with trivial details preparation, safe and reliable, can play quick-acting haemostatic powder, quicken wound healing and can be used as the multifunctional hemostatic preparation methods of pharmaceutical carrier.
For achieving the above object, this utility model adopts following technical scheme:
The hemostasis of this utility model nanometer is pasted, and comprises supporting layer and hemostatic layer, and hemostatic layer is attached to the one side of supporting layer, and wherein, described hemostatic layer comprises thrombin and connect the hemostasis mixture of thing that described connection thing is nanoscale size.
The another side of described supporting layer also is provided with drug-loaded layer, and this drug-loaded layer includes the described connection thing of nanoscale size and the treatment mixture of medicine of being.
Described connection thing be in chitosan, chitin, gelatin particle or the little collagen protein any one.
Described supporting layer is collagen sponge, chitosan sponge or oxidized cellulose.
The thickness of described supporting layer is 0.4～1cm.
The density of described hemostatic layer and supporting layer roughly is 1/2 of drug-loaded layer density.
Every square centimeter of hemostasis mixture that has 10～15mg at least of described hemostatic layer.
Compared with prior art, the utlity model has following advantage:
By this utility model and body good biocompatibility, have no side effect, can thoroughly degrade in vivo; Tearing packing can use, easy to use, quick; Thrombin is that nanoscale connects especially chitosan institute immobilization of thing, and physics and chemical stability greatly improve, and can store transportation down in room temperature, and is cheap;
2. internal layer (hemostatic layer) and middle level (supporting layer) loosen, and (as density is 0.004-0.008g/cm
2), skin is fine and close relatively, and (as density is 0.008-0.0015g/cm
2), form special interior close outer structure of dredging, can strengthen the siphonage that hemostasis is pasted, fast Absorption is organized sepage; And adhesion is preferably arranged, can be used for surgical wound surface moistening relatively and the wriggling organ;
Below in conjunction with accompanying drawing, the specific embodiment of the present utility model is further described.
[description of drawings]
Fig. 1 is the structural representation of the product using this utility model method and produced, and wherein stain is represented the density of this layer, and bright its density of multilist is big more more for stain, otherwise then more little.
[specific embodiment]
See also Fig. 1, the hemostasis of this utility model nanometer is pasted, and comprises supporting layer and hemostatic layer 1, and hemostatic layer is attached to the front of supporting layer 2, and hemostatic layer 1 comprises thrombin and connect the hemostasis mixture of thing that described connection thing is nanoscale size.The reverse side of supporting layer 2 then is provided with drug-loaded layer 3, and this drug-loaded layer 3 includes the described connection thing of nanoscale size and the treatment mixture of medicine of being.
Described connection thing be in chitosan, chitin, gelatin particle or the little collagen protein any one.
Described supporting layer 2 is collagen sponge, chitosan sponge or oxidized cellulose.
The thickness of described supporting layer 2 is 0.4～1cm.Hemostatic layer 1 roughly is 1/2 of drug-loaded layer 3 density with the density of supporting layer 2.
The following describes manufacture method of the present utility model:
1. make nano-scale chitosan immobilization thrombin with the ionic gel reaction of polyelectrolyte: chitosan is as connecting thing, and it has the alpha-amido of N-terminal.With thrombin and chitosan blend, dissolving, add sodium tripolyphosphate as cross-linking agent and stir, strict control temperature is in below 10 ℃, and pH value is between 4-7.3, perhaps be controlled between the 4.2-4.8 preparation nano-scale chitosan immobilization thrombin more accurately;
2. the collagen solution that will extract from the animal tendon (amount of collagen be solution weight 4%) is poured in the flat pallet, the high 0.4-1cm of liquid, vacuum lyophilization, thickness is collagen sponge about 0.4-1cm as supporting layer 2, biocompatibility such as the also available gelfoam of described supporting layer 2, chitosan sponge, oxidized cellulose and the good material of haemostatic effect replace;
3. 1 make the chitosan drug-loading nanoparticle set by step, seal antibacterials, cancer therapy drug, somatomedin etc. respectively, add cross-linking agent such as calcium gluconate or calcium chloride, preparation medicine-nanoparticle medicine carrying suspension;
4. medicine-nanoparticle medicine carrying solution is poured in the flat chassis, making supporting layer 2 is that one of collagen sponge is looked like reverse side and contacted with suspension, and to its vacuum drying under low temperature rapidly, sterilization just forms adheres to or macerate is gone into the drug-loaded layer 3 of collagen sponge;
5. Fibrinogen, chitosan-immobilized thrombin dry powder are dissolved in absolute ethyl alcohol and stirring and become uniform suspension, add 10～15mg mixed powder in per 1 milliliter of dehydrated alcohol, concussion makes the particle uniform distribution;
6. equally distributed suspension is poured in the flat chassis, the one side of collagen sponge is contacted with suspension, granule in the suspension is attached on the collagen sponge, stick on every square centimeter the collagen sponge 10～15mg mixed powder granule is arranged, to being stained with the particulate collagen sponge evacuation of mixed powder drying can be the front formation hemostatic layer 1 of collagen sponge at supporting layer 2, thereby forms concrete product.
In the practical application, also can only hemostatic layer 1 be created on the supporting layer 2, needn't set up drug-loaded layer 3, the product that generates like this just only has hemostasia effect, and does not possess therapeutic efficiency.
Above-mentioned making chitosan nano is the chitosan quaternary ammonium salt nanometer system, this system processing technology maturation, and the product good biocompatibility has certain adhesion, and can be used as the carrier of multiple medicine.Simultaneously, along with the research and development of the remodeling and the new material of old material, chitosan nano also can be materials such as chitin, gelatin particle, little collagen protein and substitutes.
Above-mentioned thrombin, Fibrinogen, collagen protein are from pig, and preparation method is as follows:
(1) with the Sanguis sus domestica be raw material, through high speed centrifugation, filtration, the freezing solid destination protein that obtains through the purified water dissolving, add auxiliary substance again, and virus removal, aseptic filtration obtain fibrinogen solution.
(2) with the Sanguis sus domestica be raw material, through high speed centrifugation, barium sulfate precipitate, saline solution eluting, desalination, calcium chloride activate and concentrate, and with protective agent, virus removal, aseptic filtration, obtain thrombin solution.
(3) be raw material with the pig tendon, clean the degrease fragmentation, obtain collagen, acidic aqueous solution dissolves centrifugal acquisition collagen solution.
Since the outside of collagen sponge and inner face respectively with medicine-crosslinked suspension of nanoparticle medicine carrying and Fibrinogen, the lyophilization of chitosan-immobilized thrombin dehydrated alcohol suspension, formed special hierarchy: internal layer is more loose, constitute by Fibrinogen, chitosan-immobilized thrombin and collagen protein, play the hemostasis effect; Skin is medicine-nanoparticle medicine carrying cross-linked layer, can be used as pharmaceutical carrier and carries medicine.
Be that example is introduced several processes of utilizing method manufacturing of the present utility model to form corresponding product below with the chitosan:
Process one:
(1) with chitosan quaternary ammonium salt 0.1g, the ofloxacin and the normal saline 10ml that add 0.1g make solution, concentration with 4ml is that 0.5mg/ml tripolyphosphate sodium water solution joins in the solution then, and strict control reaction condition stirs and generates nanoparticle (particle diameter 50～200nm) suspensions.Add 1% calcium chloride solution 1ml behind the purification, in the flat chassis of packing into;
(2) one side of collagen sponge is contacted with suspension, to its vacuum drying under low temperature rapidly, sterilization;
(3) with chitosan quaternary ammonium salt 0.5g, add in the 50ml normal saline, again thrombin 500UI is dissolved in chitosan season by in the saline solution, concentration with 20ml is that 0.5mg/ml tripolyphosphate sodium water solution joins in the chitosan quaternary ammonium saline solution then, temperature is controlled at below 10 ℃, and pH value is controlled between the 4.2-4.8, and stirring condition generates nanoparticle down, particle diameter 50～200nm, purification and vacuum drying become dry powder;
(4) Fibrinogen 1000mg and chitosan-immobilized thrombin 250UI add abundant porphyrize in the mortar; Add dehydrated alcohol and stir into uniform suspension for 100 milliliters, concussion makes the particle uniform distribution;
(6) equally distributed suspension is poured in 10 * 20 square centimeters the flat pallet, the another side of collagen sponge is contacted with suspension, the granule in the suspension is attached on the collagen sponge; To being stained with the particulate collagen sponge evacuation of mixed powder drying.
Process two:
(1) with chitosan quaternary ammonium salt 0.1g, the cry of certain animals of first ammonia butterfly and the normal saline 10ml that add 0.1g make solution, concentration with 4ml is that 0.5mg/ml tripolyphosphate sodium water solution joins in the solution then, and strict control reaction condition stirs and generates nanoparticle (particle diameter 50～200nm) suspensions.Add 1% calcium chloride solution 1ml behind the purification, in the flat chassis of packing into;
(2) one side of collagen sponge is contacted with suspension, to its vacuum drying under low temperature rapidly, sterilization;
(3) with chitosan quaternary ammonium salt 0.5g, add in the 50ml normal saline, again thrombin 500UI is dissolved in chitosan season by in the saline solution, concentration with 20ml is that 0.5mg/ml tripolyphosphate sodium water solution joins in the chitosan quaternary ammonium saline solution then, temperature is controlled at below 10 ℃, and pH value is controlled between the 4.2-4.8, and stirring condition generates nanoparticle down, particle diameter 50～200nm, purification and vacuum drying become dry powder;
(4) Fibrinogen 1000mg and chitosan-immobilized thrombin 250UI add abundant porphyrize in the mortar; Add dehydrated alcohol and stir into uniform suspension for 100 milliliters, concussion makes the particle uniform distribution;
(5) equally distributed suspension is poured in 10 * 20 square centimeters the flat pallet, the another side of collagen sponge is contacted with suspension, the granule in the suspension is attached on the collagen sponge; To being stained with the particulate collagen sponge evacuation of mixed powder drying.
Process three:
(1) with chitosan quaternary ammonium salt 0.1g, the 500000U/ml basic fibroblast growth factor that adds 10ml is made solution, concentration with 4ml is that 0.5mg/ml tripolyphosphate sodium water solution joins in the solution then, strict control reaction condition stirs and generates nanoparticle (particle diameter 50～200nm) suspensions.Add 1% calcium chloride solution 1ml behind the purification, in the flat chassis of packing into;
(2) one side of collagen sponge is contacted with suspension, to its vacuum drying under low temperature rapidly, sterilization;
(3) with chitosan quaternary ammonium salt 0.5g, add in the 50ml normal saline, again thrombin 500UI is dissolved in chitosan season by in the saline solution, concentration with 20ml is that 0.5mg/ml tripolyphosphate sodium water solution joins in the chitosan quaternary ammonium saline solution then, temperature is controlled at below 10 ℃, and pH value is controlled between the 4.2-4.8, and stirring condition generates nanoparticle down, particle diameter 50～200nm, purification and vacuum drying become dry powder;
(4) Fibrinogen 1000mg and chitosan-immobilized thrombin 250UI add abundant porphyrize in the mortar; Add dehydrated alcohol and stir into uniform suspension for 100 milliliters, concussion makes the particle uniform distribution;
(5) equally distributed suspension is poured in 10 * 20 square centimeters the flat pallet, the another side of collagen sponge is contacted with suspension, the granule in the suspension is attached on the collagen sponge; To being stained with the particulate collagen sponge evacuation of mixed powder drying.
In sum, the relative prior art of this utility model has bigger improvement, the product of should method of the present utility model producing can be widely used in general surgery, neurosurgery, cardiothoracic surgery, Urology Surgery, department of obstetrics and gynecology, the department of stomatology, minimally invasive surgery (as peritoneoscope, thoracoscope, pelvioscope) etc. to be needed in the operation of hemostasis, leak stopping (fistula), shorten operating time, reduce operation risk, accelerated wound healing shortens the hospital stays.Also can be used for the first aid hemostasis in war wound, the accident.
Claims (7)
1, a kind of nanometer hemostasis is pasted, and comprises supporting layer and hemostatic layer, and hemostatic layer is characterized in that attached to the one side of supporting layer: described hemostatic layer comprises thrombin and connects the hemostasis mixture of thing that this connection thing is nanoscale size.
2, nanometer hemostasis according to claim 1 is pasted, and it is characterized in that: the another side of described supporting layer also is provided with drug-loaded layer, and this drug-loaded layer includes the described connection thing of nanoscale size and the treatment mixture of medicine of being.
3, nanometer according to claim 2 hemostasis is pasted, and it is characterized in that: described connection thing be in chitosan, chitin, gelatin particle or the little collagen protein any one.
4, paste according to any described nanometer hemostasis in the claim 1 to 3, it is characterized in that: described supporting layer is collagen sponge, chitosan sponge or oxidized cellulose.
5, nanometer hemostasis according to claim 4 is pasted, and it is characterized in that: the thickness of described supporting layer is 0.4～1cm.
6, nanometer hemostasis according to claim 5 is pasted, and it is characterized in that: the density of described hemostatic layer and supporting layer roughly is 1/2 of drug-loaded layer density.
7, nanometer hemostasis according to claim 6 is pasted, and it is characterized in that: every square centimeter of hemostasis mixture that has 10～15mg at least of described hemostatic layer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200620057985 CN2920163Y (en) | 2006-04-20 | 2006-04-20 | Nanometer hemostatic plaster |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200620057985 CN2920163Y (en) | 2006-04-20 | 2006-04-20 | Nanometer hemostatic plaster |
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| Publication Number | Publication Date |
|---|---|
| CN2920163Y true CN2920163Y (en) | 2007-07-11 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200620057985 Expired - Fee Related CN2920163Y (en) | 2006-04-20 | 2006-04-20 | Nanometer hemostatic plaster |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103027788A (en) * | 2013-01-05 | 2013-04-10 | 吴斌 | Absorbable medical dressing and preparation method thereof |
| CN103169957A (en) * | 2011-12-22 | 2013-06-26 | 国家纳米科学中心 | Nano thrombin and preparation method thereof |
| CN115595317A (en) * | 2022-12-14 | 2023-01-13 | 保龄宝生物股份有限公司（Cn） | Immobilized beta-fructofuranosidase and method for preparing lactosucrose by using immobilized beta-fructofuranosidase |
-
2006
- 2006-04-20 CN CN 200620057985 patent/CN2920163Y/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103169957A (en) * | 2011-12-22 | 2013-06-26 | 国家纳米科学中心 | Nano thrombin and preparation method thereof |
| CN103027788A (en) * | 2013-01-05 | 2013-04-10 | 吴斌 | Absorbable medical dressing and preparation method thereof |
| CN115595317A (en) * | 2022-12-14 | 2023-01-13 | 保龄宝生物股份有限公司（Cn） | Immobilized beta-fructofuranosidase and method for preparing lactosucrose by using immobilized beta-fructofuranosidase |
| CN115595317B (en) * | 2022-12-14 | 2023-03-10 | 保龄宝生物股份有限公司 | Immobilized beta-fructofuranosidase and method for preparing lactosucrose by using immobilized beta-fructofuranosidase |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20070711 Termination date: 20100420 |