CN105169469B - A kind of tissue seal and its preparation method and application - Google Patents
A kind of tissue seal and its preparation method and application Download PDFInfo
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- CN105169469B CN105169469B CN201510544144.8A CN201510544144A CN105169469B CN 105169469 B CN105169469 B CN 105169469B CN 201510544144 A CN201510544144 A CN 201510544144A CN 105169469 B CN105169469 B CN 105169469B
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Abstract
The present invention relates to a kind of tissue seal and its preparation method and application, the sealant mainly includes four kinds of components, the first component is hydrophilic material, is primarily referred to as the derivative of polyethylene glycol；Second of component is nucleophilic raw material, is primarily referred to as polyamino acid；The third component is label；4th kind of component is physiological diluent, and four kinds of components covalent cross-linking after blend tool physical mixed forms hydrogel；The sealant has preferable tissue cohesive force and film forming, good biocompatibility, is mainly used for the sealing of small wound after ophthalmologic operation, promote epithelialization agglutination, sepage is prevented to leak, Product Process preparation method is simple, it can quantify, form steady production line, there is preferable clinical value.
Description
Technical field
The invention belongs to biodegradable polymer fields, and molding medical group is cross-linked in situ more particularly to one kind
Knit sealer or hydrogel and preparation method and application.
Background technology
Cataract is the disease that a kind of crystalline lens increasingly obscures, be typically aging as a result, it is possible that it is other because
Element.Data show that the U.S. to receive cataract operation there are about 3,300,000 people every year, and cataract operation is to remove the crystalline lens of itself, so
Manually crystalline lens substitutes to recover a process of vision afterwards.During cataract operation, oculist can do on cornea
One small notch removes the crystalline lens of patient itself by this notch, due to implantable artificial crystalline lens in most cases,
Notch is smaller (within usual 3mm), therefore incision tissue's meeting self-heal after artificial lens is put into, however, many factors are to leading
The time for causing notch self-heal is unstable, if there is liquid from notch leakage (has been reported that display leakage mostly occurs after surgery 1
My god, occasional continues 7 days or more), hypotony can cause the compensatory sexual dysfunction of cornea, and endothelialization is inversely grown, it is also possible to
It is present with intraocular lens's dislocation (refractive problem) and intraocular inflammation.Surgeon may just need to be sealed notch.Mesh
Before be essentially all by the way of suture, it is necessary to relatively suture operative skill, but the wound that cornea can be caused new, and have postoperative by force
The risk of infection is removed and increased, also increases the feeling of pain and sense of discomfort of patient, therefore the doctor of external coat is being expected always except seam
There can also be one kind easy to use outside closing, to patient comfort, and the notch of postoperative removal not required to seal scheme.
Hydrogel as a kind of biocompatible materials, be medically mainly used for tissue encapsulation, prevent tissue fluid leakage,
Hand post-operation adhesion preventing, hemostat fill up defective tissue, slow releasing carrier of medication etc..Gel variations are various, and the mode of action is different.
Hydrogel has been widely used as the sealant of clinical operation wound tissue at present, especially in ophthalmologic operation,
Existing common ophthalmology tissue seal is most to glue egg for natural material, such as absorbable gelatin, fibrin sealant and mussel
White adhesive etc., but such substance belongs to animal derived, and there are the risks that animal virus is propagated；Followed by fully synthetic biological high score
Sub- material, such as a-cyanoacrylate class such as isobutyl ester, n-octyl and its derivative etc., but since the adhesive is non-drop
Solution, setting time are short, and irritation is big, and the inferior positions such as hardness height, effect is unsatisfactory in clinical practice, it is necessary to be improved.
It summarizes both at home and abroad using the experience obtained by adhesive of medical, good ophthalmology tissue seal needs to have following spy
Property：1. there is the sufficient time to be operated for patient before solidification；2. enough bonding forces can be generated after solidification, make wound closed；3. glue
Body is transparent, reduces the influence to eyesight；4. inflammatory reaction is lighter；5. liquid and metabolin is allowed to permeate, tissue necrosis is avoided；⑥
Finally disappear in bonding mouth in favor of healing.Based on the requirement of above 6 product developments, the present invention, which designs a kind of biology, to drop
Solution is cross-linked in situ molding hydrogel, as medical tissue sealant.
The content of the invention
The object of the present invention is to provide it is a kind of it is fully synthetic, without it is potential it is animal derived be cross-linked in situ shaping immediately, can be biological
Degrade and physical property and the adjustable medical tissue sealant of degradation property.
For this purpose, the present invention provides a kind of medical tissue sealant, which is characterized in that it is prepared by following four component,
The first component is hydrophilic material；Contain branch, straight chain, star or the tree-like knot of succinoamino selected from end
Structure hydrophilic compounds,
Second of component is nucleophilic raw material；Selected from oligopeptide, the amino acid contained residue number of oligopeptide for 2-6 or
The salt that oligopeptide and acid are formed,
The third component is label；Selected from water-soluble non-azo-based colorant,
4th kind of component is physiological diluent, selected from water or buffer solution,
The proportioning of each component is as follows：
Hydrophilic material constituent content is 10~1000mg/mL；
Nucleophilic Feedstock Component content is 0.5~50mg/mL；
The content of label is 0.05~0.2mg/mL；
Remaining is physiological diluent.
Preferably,
Wherein described first component is selected from polyethylene glycol (PEG), polyvinyl alcohol (PVA), polyoxyethylene (PEO), molecule
It measures as 500-20000 or the polyethyleneglycol derivative selected from following compound：Four arm N- hydroxysuccinimide propionic acid ester groups gather
Ethylene glycol (4-arm-PEG-SPA, molecular weight 10000), four arm N- hydroxysuccinimide succinic acid ester group polyethylene glycol (4-
Arm-PEG-SS, molecular weight 10000), two arm N- hydroxysuccinimide succinic acid ester groups polyethylene glycol (2-arm-PEG-SS,
Molecular weight 10000), two arm N- hydroxysuccinimides esters (2-arm-PEG-NHS, molecular weight 5000)；
Second component is selected from oligopeptide, and amino acid contained residue number is 3-4；Amino acid therein is selected from：
The salt that lysine, cysteine, leucine, histidine or oligopeptide and acid are formed,
The third component is selected from the edible light blue that molecular weight is 792.86；
The 4th component buffer solution is selected from the buffering that phosphate, carbonate, borate, phosphoric acid, acetic acid, hydrochloric acid are prepared
Liquid, the osmotic pressure of buffer solution should be identical with the colloidal osmotic pressure of organism.
It is furthermore preferred that
Wherein described first component is selected from polyethylene glycol (PEG), polyvinyl alcohol (PVA), polyoxyethylene (PEO), molecule
It measures as 2000-10000
Second component is selected from the salt that lysine, the oligopeptide of cysteine or oligopeptide and acid are formed,
The 4th component buffer solution is selected from phosphate, borate buffer solution.
It is particularly preferred,
Wherein described first component is selected from the polyethylene glycol of molecular weight 5000
Second component is selected from two lysines, three lysines, four lysines, five lysines or they and acid and is formed
Salt,
The 4th component buffer solution is selected from phosphate buffer.
It is particularly preferred,
Wherein described first component is selected from the polyethyleneglycol derivative of following compound：Four arm N- hydroxysuccinimides third
Perester radical polyethylene glycol (4-arm-PEG-SPA, molecular weight 10000), the four poly- second of arm N- hydroxysuccinimide succinic acid ester groups
Glycol (4-arm-PEG-SS, molecular weight 10000), two arm N- hydroxysuccinimide succinic acid ester group polyethylene glycol (2-arm-
PEG-SS, molecular weight 10000), two arm N- hydroxysuccinimides esters (2-arm-PEG-NHS, molecular weight 5000)；
Second component is selected from the salt that three lysines or they and acid are formed,
The 4th component buffer solution is selected from the sodium tetraborate aqueous solution that PH is 9.58 or the sodium phosphate that PH is 5.8-7.0 delays
Fliud flushing.
Most have preferably,
Wherein described first component is selected from two arm N- hydroxysuccinimides esters (2-arm-PEG-NHS, molecular weight 5000)；
Second component is selected from three lysines or three lysine acetates.
The third component is the edible light blue that molecular weight is 792.86；
The 4th component buffer solution ph is the sodium phosphate buffer of 5.8-7.0.
Wherein the nonstoichiometric molar ratio of hydrophilic functional groups and nucleophilic functional group is 1:1.
The preparation method of the sealant of the present invention, the method step are as follows：Second component and third component are dissolved in
In 4th component, just solution is obtained, then the solution and the first component and color developing agent are mixed, reaction is crosslinked and forms water-setting
Glue.
The present invention further provides a kind of kits, which is characterized in that including four kinds of components of the present invention.
Preferably, kit of the invention, including：
First component is two arm N- hydroxysuccinimide esters of molecular weight 5000；124 parts
Second component, three lysine；5 parts
Third component is the edible light blue that molecular weight is 792.86；0.01 part
4th component buffer solution is 1000 parts of the PBS buffer solutions of pH=7.4.
The medical tissue sealant of the present invention, wherein, the ratio of the weight between each component is as follows：
Hydrophilic component PEG derivatives：Nucleophilic component oligopeptide：The weight ratio of label light blue is 100:10:1~
1000000:10000:1
Preferably, the ratio of the weight between each component is as follows：
Hydrophilic component PEG derivatives：Nucleophilic component oligopeptide：The weight ratio of label light blue is 1000:100:1~
100000:1000:1
Most preferably, the ratio of each component is as follows：
Hydrophilic component PEG derivatives：Nucleophilic component oligopeptide：The weight ratio of label light blue is 10000:500:1
The ratio that the total solid content of wherein the first component, the second component and third component accounts for hydrogel total volume is less than
10%.
Wherein, the ratio of the first component and the second component can also be calculated with active function groups mole, and molar ratio is
1:1。
It is exemplified as：PEG-NHS:Three lysine acetates, the active function groups of PEG-NHS are：- NHS, three lysine acetic acid
The active function groups of salt are：-NH2, the molar ratio of the two is 1:1, weight ratio is converted into as 30:1.
The present invention also provides the preparation method of medical tissue sealant of the present invention, the method step is as follows：
Second component and third component are dissolved in the 4th component, just solution is obtained, then by the solution and first group
Divide mixing, crosslink reaction and form hydrogel.
The present invention also provides the clinical practice of medical tissue sealant, the application is mainly used for small wound after operated eye
The closing of discharge surface prevents sepage from leaking, and the problems such as avoiding causing intraocular inflammation or dioptric, the replacement as suture way is treated
Method.
Hydrogel prepared by the present invention, the polyethylene glycol of hydrophilic component selection n-hydroxysuccinimide sealing end,
Contain ester bond in structure, after being reacted with nucleophilic component, ester bond is still in final cross-linking products, can be degraded in human body, and
And hydrophilic compounds main body polyethylene glycol can also resolve into small molecule in human body.It can make degradation time by adjusting component ratio
Control was at 3-7 days.
The hydrogel can be cross-linked in situ shaping, in use, can be with Extemporaneous, therefore, the present invention also provides one
Kind of kit, including four kinds of components of the present invention, using the 4th the second component of component buffer solution during use, so
It is mixed in immediately in the first component afterwards and forms hydrogel, hydrogel coating is covered in by wound tissue surface by spreader, is had
Beneficial to adherency, which, which should have, is sufficient to resist by the generations such as existing hydrostatic in patient motion, tissue displacement, tissue
Tension mechanical property.
The kit of the present invention can be packaged into the dosage of 1 people's first use, can also be packaged into the use of 10 people once
Dosage, it is changeable, preparation to be suitble to be advisable.It can also include specification in kit, using instrument, with container etc., with
It is easy to use.
For the ease of the service condition of tissues observed sealant, third component is color developing agent in the present invention, and color developing agent can be with
It is added in the first component or the second component powders, color developing agent includes but not limited to FD＆C bluenesss #1, FD＆C blueness #2, FD＆C indigo plant
Color #3.
The medical tissue sealant of the present invention is mainly used for closing the postoperative cornea wound of intraocular lens, prevents sepage
Leak and cause the complication such as infection, pain, it may also be used in the surgical procedures such as heart, abdominal cavity, thoracic cavity prevent blood oozing from the wound surface and
Veinlet bleeding promotes wound healing, prevents tissue adhesion, closing defective tissue etc..The main original of hydrogel of the present invention
Material is using material that is fully synthetic, having biocompatibility, and active hydrophilic and nucleophilic group are linked by chemical modification, during use
By physical mixed hydrogel formed in situ.By adjusting the ratio of the second component of the first component of hydrophily and nucleophilicity, system
Standby a series of physical performance is different, the different hydrogel of degradation time.The hydrogel prepared using Biodegradable material, in life
Natural degradation excludes that in vitro, second operation can be avoided into small molecule after a certain period of time for holding in object, reduces patient's pain, reduction
Medical expense, while can also avoid causing the risk of transmission due to the use of natural material.
Description of the drawings：
The swelling ratio of the formula hydrogel of Fig. 1 different hydrophilics component and nucleophilic component
The gelation time of the hydrogel of Fig. 2 different hydrophilics component and nucleophilic component formula
3 days animal experimental observation results after Fig. 3 hydrogel implantations
7 days animal experimental observation results after Fig. 4 hydrogel implantations
Specific embodiment
It further illustrates the present invention by the following examples.Embodiment provides detailed embodiment and concrete operations, uses
It is of the invention in understanding.
The preparation of the medical tissue sealant of the present invention, wherein mainly by the first component and the second component through mixing work
Tool mixing occurs covalent cross-linking and forms hydrogel.Reaction mechanism is：The NHS of hydrophilic component (the first component) and nucleophilic component (the
Two components) NH2Polymerisation occurs for Covalent bonding together, generates hydrogel, a small amount of by-product biocompatibility is preferable, nontoxic
It is nonirritant, it is excluded in vitro with the degradation of gel, reaction is schematically as follows：
Any one wherein in R1, R3 H, CH3, CH2CH3, CH2CH2CH3 is identical structure etc. including R1, R3；
R2 is OCCH2CO, OCCH2CH2CO, OCCH2CH2CH2CO etc.；R4 is NH or S；R5 is OC (CH2)nCO, polyethylene glycol etc..
Medical tissue sealant provided by the present invention, meets following characteristics index：
1) gel time is less than 20s；
2) swelling ratio is preferably 0-300%
3) rupture strength is not less than 50mmHg；
4) degradation time is 3-7 days.
Medical tissue sealant kit
The kit of the present invention, including foregoing the first component containing hydrophilic functional groups, second group of nucleophilic functional group
Point, the 4th component of color developing agent third component and physiological buffer, wherein：
Hydrophilic functional groups (the first component)：It is preferred that two arm N- hydroxysuccinimides macrogol esters (2-arm-PEG-NHS,
Molecular weight 5000), structural formula is seen below：
Nucleophilic functional group (the second component)：Three lysines (structural formula is seen below), purchased from Mike woods Reagent Company.
Color developing agent (third component)：FD＆C bluenesss #1 (structural formula is seen below), purchased from Mike's woods reagent.
Physiological buffer (the 4th component) has PBS buffer solutions, the carbonate buffer of 0.2M pH=6.5 of pH=7.4
The carbonate buffer solution of liquid and 0.2M pH=9.78.
The preparation method of hydrogel：Hydrophilic functional groups and the nonstoichiometric molar ratio of electrophilic functional group are 1:1.
One hydrophilic component of embodiment is the derivative of PEG
Nucleophilic component is three lysines, and hydrophilic component is the derivative of PEG, and solvent is the PBS buffer solution of pH=7.4, is pressed
The experiment of gel is carried out according to following process.
First three lysines containing nucleophilic functional group are dissolved in the PBS buffer solutions of pH=7.4 of 5 μ L, it is molten to obtain A
Liquid；PEG derivatives containing hydrophilic functional groups and color developing agent are dissolved in solution A, stirring, about 15s is sufficiently mixed, sees respectively
Examine the situation to form gel.
The formula of the PBS buffer solution of the pH=7.4 of 0.1M：The sodium chloride for weighing 4.005g is reagent A；Weigh the chlorine of 0.1g
Change potassium is reagent B；It is reagent C to weigh disodium hydrogen phosphate dodecahydrate 1.7907g；The potassium dihydrogen phosphate of 0.135g is referred to as reagent D；
By tetra- kinds of reagent A, B, C and D substances, it is successively placed in the volumetric flask of 500mL, is then dissolved, that obtain is pH=7.4
PBS buffer solution.
By the observation of more than experimental phenomena, the PEG derivatives of different hydrophilic component form water-setting with identical nucleophilic component
The gelation time of glue, swelling ratio and degradation cycle are different, and detection method is as follows：
1) gelation time：The gelation time of hydrogel directly affects the surgical procedure before and after clinical gel use, specific to examine
Survey method is that the second component and third component are first dissolved in physiological diluent, then with the first component miscibility, stir about 5s
Start timing, until gel is formed, criterion is to provoke gel solution using toothpick or the like, is in wire drawing state
Can, it is recorded as gel time.
2) swelling ratio：Detection method is weighed for the hydrogel of certain mass, is recorded original quality, is then placed in hydrogel
37 ± 1 DEG C of pH is pre-heated in 7.4 phosphate buffers, to take out sample every a few houres and sucking surface moisture with filter paper, claim
Amount until weight is not further added by, terminates to weigh.Gel swelling rate is calculated as follows.
3) the external degradation cycle：The gel of certain mass is placed in 37 ± 1 DEG C with the isotonic pH of blood for 7.4 phosphate to delay
In fliud flushing, daily observation is denoted as gel degradation time in vitro until invisible.
The results are shown in table below with nucleophilic component composition hydrogel for the PEG derivatives of different hydrophilic component：
As can be seen that using three lysines as nucleophilic component, the PEG derivatives of different molecular weight are hydrophilic component, with PEG
The molecular weight of derivative increases, and the gelation time of hydrogel is faster, and swelling ratio becomes larger, and degradation cycle can partly extend, therefore can
It is flexibly selected according to practical situations.
Two nucleophilic component of embodiment is three lysine derivatives
Nucleophilic component is three lysine derivatives, and hydrophilic component 2-arm-PEG-NHS, solvent is that the PBS of pH=7.4 delays
Fliud flushing, the preparation that gel is carried out according to following process are tested.
First three lysine derivatives containing nucleophilic functional group are dissolved in the PBS buffer solutions of pH=7.4 of 70 μ L, obtained
To solution；Immediately by the 2-arm-PEG-NHS dissolvings containing hydrophilic functional groups in the solution, stirring, about 5s are sufficiently mixed, is observed
Form the situation of gel.
Different three lysine derivatives form the situation of hydrogel such as with hydrophilic component PEG derivatives 2-arm-PEG-NHS
Shown in following table：
Embodiment three is using different physiological diluent buffer solutions as solvent
Nucleophilic component is three lysines, and hydrophilic component 2-arm-PEG-NHS, solvent is that different physiological diluents delays
Fliud flushing carries out the experiment of gel according to following process.
First three lysine derivatives containing nucleophilic functional group are dissolved in the different physiological diluent solvents of 70 μ L, are obtained
Solution；By the 2-arm-PEG-NHS dissolvings containing hydrophilic functional groups in the solution, stirring, about 5s are sufficiently mixed, observation forms solidifying
The situation of glue.
The formula of the phosphate buffer of 0.2M pH=6.5：Claim 4.9g sodium dihydrogen phosphates, it is fixed molten to 68.5mL, obtain solution A；
Claim 2.4g disodium hydrogen phosphate dodecahydrates, constant volume to 31.5mL obtains solution B；Two kinds of solution of A, B are mixed, obtain 100mL,
The phosphate buffer solution of the pH=6.5 of 0.2M.
The formula of the carbonate buffer solution of 0.2M pH=9.78：Claim sodium carbonate 1.1448g, be dissolved in surely in 40mL water, stir
Dissolve to obtain solution A；Claim sodium acid carbonate 0.504g, be dissolved in surely in 60mL water, stirring and dissolving obtains solution B；A, B solution is sufficiently mixed
Uniformly, 100mL, the carbonate buffer solution of the pH=9.78 of 0.2M are obtained.
The situation that different physiological diluent buffer solutions prepares hydrogel is as shown in the table：
Pass through above-described embodiment two and embodiment three, it can be seen that with 2-arm-PEG-NHS molecular weight 5000 for hydrophilic group
Point, three lysines, three lysine acetates or hydrochloride are nucleophilic component, using the physiological diluent solution of different PH to be molten
Agent, the hydrogel of preparation in gelation time, swelling ratio and degradation cycle without significant difference, simply in two kinds of component reaction processes
In, the acid-base value of reaction dissolvent system is different, main to influence plastic speed and the final use environment requirement of hydrogel, such as water
Gel application can consider the finished product using slant acidity when gynaecologic vaginal wound seals；If during applied to ophthalmology site tissue, meeting
Consider using neutral finished product, therefore can flexibly be selected according to clinical practice applicable cases.
In summary embodiment, the different component formula of hydrogel can influence its preparation process, while in hydrogel
Also variant in terms of gelation time, swelling ratio and degradation cycle, using three lysines as nucleophilic component, the PEG of different molecular weight spreads out
Biology is hydrophilic component, is increased with the molecular weight of PEG derivatives, and the gelation time of hydrogel is faster, and swelling ratio becomes larger, drop
Solve the cycle can part extend, specific statistical result as depicted in figs. 1 and 2, can be according to different requirements therefore in practical application
The ratio of each substance and the buffer solution system of reaction are adjusted, prepares the medical aquogel sealant to meet clinical needs.
Example IV animal is subcutaneously implanted medical sealant sample
Healthy adult New Zealand White Rabbit is selected, is subcutaneously implanted at it with the 1 composition of raw materials group of experiment sequence number in embodiment one
Into the hydrogel sample of preparation, the implantation cycle is 3 days and 7 days, and sample method for implantation is with reference to GBT16886.6-1997 Medical treatment devices
The 6th part of tool biological assessment：Operative process specified in local reaction experiment carries out after implantation, and postoperative daily observation is dynamic
Object, without any abnormal phenomenon, no part, whole body and abnormal behavior.
In the observation point of 3 days cycles and 7 days, animal is put to death respectively, and implant site is taken to carry out histopathology using HE dyeing
Evaluation, as shown in Fig. 3 (after hydrogel implantation 3 days) and Fig. 4 (after hydrogel implantation 7 days), show within postoperative 3 days it is acute with
Chronic inflammatory cell has fibroblast proliferation around residual sample；Display acute inflammatory cells disappear within postoperative 7 days, have a small amount of slow
Property inflammatory cell, but hydrogel sample film has been degraded, noresidue.Therefore medical sealant hydrogel according to the present invention is respectively provided with
Similar preferable biological safety.Embodiment five
A kind of kit
Including
First component is two arm N- hydroxysuccinimide esters of molecular weight 5000；124 parts
Second component, three lysine；5 parts
Third component is the edible light blue that molecular weight is 792.86；0.01 part
4th component buffer solution is 1000 parts of the PBS buffer solutions of pH=7.4
Described part is parts by weight.
Application method is as follows：In the PBS buffer solutions for the pH=7.4 that first three lysines are dissolved in, solution A is obtained；It will divide
Two arm N- hydroxysuccinimide esters of son amount 5000 are dissolved in solution A, and it is abundant to add in the edible light blue that molecular weight is 792.86
It is mixed evenly, workable gel can be formed within about 15 seconds.
Embodiment described above is the preferred embodiment of the present invention, but the embodiment of the present invention 5 is tested 1 raw material of sequence number and matched somebody with somebody
The hydrogel sample just prepared is compared with other formulas unexpectedly has stronger analgesic effect in use, pretends as this
The most preferred formula of invention.
For persons skilled in the art, or else away from the principle of the invention and spirit on the premise of to made by it
Any obvious change should be all contemplated as falling within the claims of the present invention.
Claims (1)
1. a kind of application method of kit, the kit includes following components
First component is two arm N- hydroxysuccinimide esters of molecular weight 5000；124 parts
Second component, three lysine；5 parts
Third component is the edible light blue that molecular weight is 792.86；0.01 part
4th component buffer solution is 1000 parts of the PBS buffer solutions of pH=7.4
Application method is as follows：In the PBS buffer solutions for the pH=7.4 that first three lysines are dissolved in, solution A is obtained；By molecular weight
5000 two arm N- hydroxysuccinimide esters are dissolved in solution A, are added in the edible light blue that molecular weight is 792.86 and are sufficiently mixed
It stirs evenly, workable gel can be formed within 15 seconds.
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| CN115869456A (en) * | 2021-08-09 | 2023-03-31 | 上海其胜生物制剂有限公司 | Preparation of in-situ gelation anti-swelling enhanced tissue adhesive material |
| CN114099784B (en) * | 2021-10-26 | 2022-09-16 | 四川兴科蓉药业有限责任公司 | Injection type skin filling composition and preparation method and application thereof |
| CN115837093B (en) * | 2021-12-13 | 2023-08-04 | 北京博辉瑞进生物科技有限公司 | Medical tissue glue and preparation method and application thereof |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1496241A (en) * | 2001-02-14 | 2004-05-12 | �������ɭ | Radiation cross-linked hydrogels |
| CN102911493A (en) * | 2012-09-28 | 2013-02-06 | 山东赛克赛斯药业科技有限公司 | Biodegradable medical hydrogel and preparation method and application thereof |
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Application publication date: 20151223 Assignee: Beijing Connaught Pharmaceutical Co., Ltd. Assignor: BEIJING NUOKANGDA PHARMACEUTICAL CO., LTD. Contract record no.: 2016990000511 Denomination of invention: Tissue sealant and preparation method and application thereof License type: Common License Record date: 20161220 |
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Address after: 100176 Beijing Beijing economic and Technological Development Zone, Chuang Chuang thirteen Street 31 hospital two District 7 Building 101 room. Patentee after: Beijing nukangda medicine Polytron Technologies Inc Address before: 100176 Beijing Fengtai District Beijing economic and Technological Development Zone Yongchang road 3 No. 8 Yongchang science and Technology Plaza 505 room Patentee before: BEIJING NUOKANGDA PHARMACEUTICAL CO., LTD. |