CN101134784A - Agarose and hyaluronic acid grafts and preparation method and uses thereof - Google Patents
Agarose and hyaluronic acid grafts and preparation method and uses thereof Download PDFInfo
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Abstract
The present invention relates to hyaluronic acid-agarose graft and its preparation process and application. The hyaluronic acid-agarose graft is prepared through the following steps: dissolving degraded agarose powder in hot water, cooling to room temperature, and adding sodium hydroxide solution and epoxy chloropropane to react under magnetic stirring; repeated vacuum concentrating, water dissolving and alcohol precipitating to eliminate epoxy chloropropane and obtain activated agarose precipitate; dissolving activated agarose powder in hot water, cooling to room temperature, adding hyaluronic acid to produce grafting reaction under magnetic stirring; vacuum concentrating the solution, dialyzing in bag filter for 72 hr to eliminate un-reacted hyaluronic acid, and freeze drying to obtain hyaluronic acid-agarose graft. The hyaluronic acid-agarose graft as one new biomedical material has bioactivity and targeting property from hyaluronic acid, gel forming feature, improved biodegradability and certain stability.
Description
Technical field
The present invention relates to biomedical material, particularly a kind of agarose and hyaluronic acid grafts preparation method and application.
Background technology
Biomedical material has been played the part of extremely important role in the raising of modern medical service state of the art, almost relate to clinical every field with its various drug delivery systems of making, tissue engineering bracket, artificial organs, medical dressing etc.Be accompanied by the raising of medical technique level, the single biomedical material of those structure propertiess can not satisfy the needs of medical development, and the biomedical material of development of new is current pressing for.Wherein targeted drug controlled release carrier material and functional activity tissue engineering bracket material are the important directions of following biomedical material research.
1976, Langer and Folkman successfully realized the macromolecular drug controlled release of polymkeric substance as carrier.After this year people attempt with various macromolecular materials as pharmaceutical carrier, to improve release kinetics, biocompatibility and the biological degradability of corresponding controlled drug delivery system always surplus in the of 30.Polymer drug sustained release material is to prepare medicine sustained release preparation with macromolecular material, makes medicine produce the treatment effect at specific position with minimum doses, optimizes drug release rate to improve curative effect, reduces toxic side effect.The targeted drug controlled release is to utilize the characteristics of targeted drug to come accurate control drug release, medicine is slowly discharged and the prolongation drug effect at focal zone, the targeted drug preparation can be with the medicine orientation be transported to target organ or target cell, and normal tissue site is subjected to the influence of medicine hardly, targeting drug delivery system is primarily aimed at treatment for cancer in early days, but along with going deep into of research, targeting drug delivery system is amplified the multiple medicine of delivery.
Drug carrier material as the sustained release system is macromolecule polymer material mostly at present.Biological degradation polyalcohol can be hydrolyzed within a certain period of time or enzymolysis becomes small molecules, can excrete by the physiological pathway metabolism, and is therefore safer, more reliable than bio-inert material, and better biocompatibility is arranged, and becomes the preferred material of pharmaceutical carrier.The degradable high polymer controlled-release material mainly contains natural and the synthetic degradable macromolecule.
The eighties in 20th century, the Robert Langer of the U.S. and P.Vacanti propose the notion of " organizational project ".1987, National Science Foundation's biotechnology can be gone up formal proposition " organizational project " speech.In the time in 20 years, the organizational project development has obtained plentiful and substantial achievement rapidly.Can tissue engineering bracket affects the biological behaviour of cell, more determined engineered tissue to adapt with body and combine, and reaches the effect of reparation.The ideal stent material will have excellent biological compatibility, biological degradability, suitable biomechanical property and material cell interface etc.
At present mainly contain natural materials, synthetic organic polymer material, biological ceramics and matrix material as tissue engineering bracket material.Sum up through years of researches, it is found that natural materials, the incomparable advantage of synthetic material is being arranged aspect biocompatibility, biological activity and the biological degradability as tissue engineering bracket material.
Hyaluronic acid and agarose are two kinds of natural macromolecular materials that are widely used in medicine controlled release carrier and tissue engineering bracket, and relative merits are respectively arranged.
Hyaluronic acid has reduced immunogenicity, excellent biological compatibility, the differentiation of the infiltration of may command cell and molecule and some cell in vivo.Hyaluronic acid can be used for tissue engineering bracket, can the chondrocyte be sticked thereon as hyaluronan molecule, and promotes chondrocyte's amplification.Hyaluronic acid also extensively is studied the carrier that is used for the target slow-release medicine.Studies show that, tumour cell or be subjected to the tumour cell stimulated cells to produce a large amount of hyaluronic acids, hyaluronic acid is subjected to the mediation of the hyaluronic acid acceptor (as CD44 etc.) on the tumour cell, to the adhering to, breed and move the generation effect of tumour cell, tumour cell depends on hyaluronic existence from lymphatic vessel equally to nodus lymphoideus transferring rate.Hyaluronic acid activates the scavenger cell in the lymphoglandula, shifts thereby suppress tumor lympha.Hyaluronic acid targeted drug and metastasis inhibition element can suppress tumor growth and transfer.But hyaluronic some character, as very easily water-soluble, poor stability to strong acid, highly basic, heat, free radical and Unidasa sensitivity, is degraded easily, and retention time is short in human body, has limited the application of hyaluronic acid on biomedicine greatly.Therefore, it is water-soluble to reduce to carry out chemical modification to hyaluronic acid, slows down the absorption rate in human body.That method commonly used has is crosslinked, esterification, grafting etc.Hyaluronic acid can be grafted on natural or the synthetic polymer, is formed with the type material of special biological property and physicochemical property.
Agarose is an inert support commonly used in the biochemical analysis, and sepharose has certain intensity and bigger water ratio, usually is used as cell culture medium and tissue engineering bracket material.Low temperature of solidification is the distinguishing feature of agarose with becoming gelling properties, utilize this character, can be before the tissue engineering bracket moulding just cell and biomacromolecule and agarose solution be mixed, and cell and biomacromolecule non-inactivation, after waiting to solidify, cell and biomacromolecule will be evenly distributed on the whole agarose aquogel.Agarose also is widely used in the targeted drug controlled release carrier, but agarose itself is not had a target effect, also need add magnetic or grafting antibody etc. and reach the target effect.
Summary of the invention
The material that the objective of the invention is to exist at prior art is selected problem, a kind of hyaluronic acid and agarose grafts preparation methods are provided, with hyaluronic acid and agarose graft copolymerization, obtain a kind of new biomedical material, be expected both to keep hyaluronic biological activity and target, had the one-tenth gel property of agarose simultaneously, improved biodegradability, had certain stability simultaneously.
The present invention also aims to provide the agarose and the hyaluronic acid grafts of described method preparation.
The present invention also aims to provide described agarose and the application of hyaluronic acid grafts in preparation targeted drug controlled release carrier or tissue engineering bracket material.Select for use the agarose of different molecular weight to carry out grafting, the one-tenth gel degree difference of product can be applicable to targeted drug controlled release carrier material and tissue engineering bracket material respectively.
The present invention obtains powder by agarose (after the degraded, the different molecular weight agarose) and hyaluronic acid grafting postlyophilization.
The preparation method of hyaluronic acid of the present invention and agarose grafts comprises the steps:
(1) degraded agarose powder is dissolved in 90-95 ℃ of hot water, is cooled to room temperature, adds sodium hydroxide solution and epoxy chloropropane, magnetic agitation reaction 2-4 hour;
(2) adopt the concentrating under reduced pressure method to remove unnecessary epoxy chloropropane, solution decompression is concentrated, add and be equivalent to liquor capacity 4-5 ethanol doubly, the centrifugal precipitation that obtains will precipitate and use water dissolution, repeat to use ethanol sedimentation, to remove residual epoxy chloropropane, obtain the activated agarose precipitation;
(3) the activated agarose precipitation is dissolved in 90-95 ℃ of hot water, is cooled to room temperature, add hyaluronic acid in the activated agarose solution, the normal temperature lower magnetic force stirs, graft reaction 48-60 hour; Agarose and hyaluronic acid grafted grafting proportioning are 1: 1-1: 5 mass ratioes;
(4) solution decompression is concentrated,, obtain hyaluronic acid and agarose grafts powder after the lyophilize with dialysis tubing dialysis 72 hours.
In the step (1), each concentration of component is preferred: agarose 1.0-2.0% quality, sodium hydroxide 0.5-1% quality, epoxy chloropropane 3-5% quality.
The described degraded agarose of step (1) powder can prepare by following method:
(1) agarose is dissolved in the 90-95 ℃ of hot water, and concentration is the 1-5% quality, is cooled to 50-60 ℃, and adding concentration is the hydrogen peroxide of 30% quality, makes its ultimate density reach the 1-3% volume, at 50 ℃ of-60 ℃ of following isothermal reaction 6-15 hours;
(2) after the solution decompression that step (1) is obtained concentrates, add and be equivalent to liquor capacity 4-5 ethanol doubly, the centrifugal precipitation that obtains, to precipitate and use water dissolution, repeat to use ethanol sedimentation, to remove residual hydrogen dioxide, the agarose that obtains degrading precipitation, to precipitate and use water dissolution, put into the freeze drier freeze-drying agarose powder of must degrading;
In the step (2), described lyophilize be-40 ℃ freezing 2 hours, the vacuum lower pumping is the freeze-drying agarose powder of must degrading more than 17 hours.
When described hyaluronic acid and agarose grafts are used to prepare pharmaceutical carrier, select for use degradation time more than 15 hours, molecular weight is that agarose and the hyaluronic acid of 13-15kDa is 1 by grafting quality proportioning: 1-1: 2 hyaluronic acids that prepare and agarose grafts.
Described hyaluronic acid and agarose grafts are when preparation is used for the porous support materials of dressing for skin, selected for use degradation time 8-10 hour, molecular weight is about the agarose of 30kDa-40kDa and hyaluronic acid by 1: 1-1: hyaluronic acid and agarose grafts that 3 grafting quality proportioning prepares.
Described hyaluronic acid and agarose grafts are when preparation soft tissue engineering scaffold material, selected for use degradation time 8-10 hour, molecular weight is about the agarose of 30kDa-40kDa and hyaluronic acid by 1: 1-1: hyaluronic acid and agarose grafts that 3 grafting quality proportioning prepares.
When described hyaluronic acid and agarose grafts are repaired dressing at preparation film like skin wound, adopt agarose and hyaluronic acid by 1: 2-1: 5. hyaluronic acid and agarose grafts that grafting quality proportioning prepares.
Can select the agarose of different palliating degradation degrees according to service requirements.Under the condition of certain temperature and hydrogen peroxide concentration, control the palliating degradation degree of agarose by the time of control degradation.
The molecular weight of agarose is chosen, and agarose and hyaluronic graft ratio and state (microparticle, support or film) are determined according to purposes, and the microparticle that obtains, film and support oxirane disinfection obtain the finished product envelope and preserve.
The present invention compared with prior art has following advantage:
(1) the hyaluronic acid particle that contains that the inventive method obtains has target, and good stability can retain in vivo for a long time, and biodegradable, is suitable for as the targeted drug controlled release carrier;
(2) support that obtains maybe can spray dressing, can make the nutrition supply of healing district tissue unaffected, keep the normal healing mechanism of tissue, and the propagation of degraded product pair cell and matrix group harness have promoter action, accelerate the generation of tissue, can be used as burn, the reparation of the big big area skin wound of ulcer, and be used for soft tissue engineering scaffold materials such as cartilage, cornea, fat.
(3) can prepare the aquagel tissue engineering rack, (≤37 ℃) mix seed cell and sample solution when lesser temps, and solution becomes hydrogel under the room temperature, and cell can be evenly distributed in the aquagel tissue engineering rack.
(4) value added of the inventive method raising agarose and derivative thereof helps to promote the plantation (agar extracts) of kelp from kelp, helps the rich restoration of the ecosystem of supporting in offshore sea waters.
Embodiment
Embodiment 1, preparation of preparation porous compound support frame and dressing for skin
Preparation hyaluronic acid and agarose grafts comprise the steps:
(1) agarose is dissolved in 90 ℃ of hot water, and concentration is 5% quality, is cooled to 60 ℃, and adding concentration is the hydrogen peroxide of 30% quality, makes its ultimate density reach 1% volume, 50 ℃ of following isothermal reactions 15 hours;
(2) after the solution decompression that step (1) is obtained concentrates, add the ethanol that is equivalent to 4 times of liquor capacities, the centrifugal precipitation that obtains, to precipitate and use water dissolution, repeat to use ethanol sedimentation, to remove residual hydrogen dioxide, to precipitate and use water dissolution, put into the freeze drier freeze-drying agarose powder of must degrading;
(3) degraded agarose powder is dissolved in 95 ℃ of hot water, is cooled to room temperature, adds sodium hydroxide solution and epoxy chloropropane, each concentration of component is respectively: agarose 1.0% quality, sodium hydroxide 0.5% quality, epoxy chloropropane 4% quality, under the room temperature, magnetic agitation reaction 4 hours;
(4) adopt the concentrating under reduced pressure method to remove unnecessary epoxy chloropropane.Solution decompression is concentrated, add the ethanol that is equivalent to 4 times of liquor capacities, the centrifugal precipitation that obtains will precipitate and use water dissolution, repeat to use ethanol sedimentation, to remove residual epoxy chloropropane, obtain the activated agarose precipitation;
(5) the activated agarose precipitation is dissolved in 95 ℃ of hot water, is cooled to room temperature, add hyaluronic acid in the activated agarose solution, the normal temperature lower magnetic force stirs, graft reaction 48-60 hour; Agarose and hyaluronic acid grafted grafting quality proportioning are 1: 1;
(6) solution decompression is concentrated,, obtain hyaluronic acid and agarose grafts powder after the lyophilize with dialysis tubing dialysis 72 hours.
With hyaluronic acid and agarose grafts powder heating for dissolving, pour die for molding (making mixed solution is 5-6mm at the mould camber) into; (3) put into freeze drier, descended freezing 3 hours, bleed more than 17 hours at 0 ℃ then, be lyophilized into porous support at-35 ℃, thick about 3-4mm, oxirane disinfection is standby
Embodiment 2, preparation adipose tissue engineering support
Preparation hyaluronic acid and agarose grafts comprise the steps:
(1) agarose is dissolved in 95 ℃ of hot water, and concentration is 1% quality, is cooled to 60 ℃, and adding concentration is the hydrogen peroxide of 30% quality, makes its ultimate density reach 1% volume, 60 ℃ of following isothermal reactions 6 hours;
(2) after the solution decompression that step (1) is obtained concentrates, add the ethanol that is equivalent to 5 times of liquor capacities, the centrifugal precipitation that obtains, to precipitate and use water dissolution, repeat to use ethanol sedimentation, to remove residual hydrogen dioxide, to precipitate and use water dissolution, put into the freeze drier freeze-drying agarose powder of must degrading;
(3) degraded agarose powder is dissolved in 90 ℃ of hot water, is cooled to room temperature, adds sodium hydroxide solution and epoxy chloropropane, each concentration of component is respectively: agarose 2.0% quality, sodium hydroxide 0.5% quality, epoxy chloropropane 4% quality, under the room temperature, magnetic agitation reaction 2 hours;
(4) adopt the concentrating under reduced pressure method to remove unnecessary epoxy chloropropane.Solution decompression is concentrated, add the ethanol that is equivalent to 5 times of liquor capacities, the centrifugal precipitation that obtains will precipitate and use water dissolution, repeat to use ethanol sedimentation, to remove residual epoxy chloropropane, obtain the activated agarose precipitation;
(5) the activated agarose precipitation is dissolved in 90 ℃ of hot water, is cooled to room temperature, add hyaluronic acid in the activated agarose solution, the normal temperature lower magnetic force stirs, graft reaction 48-60 hour; Agarose and hyaluronic acid grafted grafting quality proportioning are 1: 3;
(6) solution decompression is concentrated,, obtain hyaluronic acid and agarose grafts powder after the lyophilize with dialysis tubing dialysis 72 hours.
With hyaluronic acid and agarose grafts powder heating for dissolving, treat that temperature reduces to 37 ℃, add adult fat stem cell suspension, mix, pour die for molding (making mixed solution is 5-6mm at the mould camber) into; Treat that solution reduces to room temperature, become the aquagel tissue engineering rack; 0.8 centimetre of diameter, thick 3-4 millimeter.Add conventional nutrient solution (replenishing 10ng/ml bFGF), become the fat-like soft tissue, scaffold degradation after three weeks.
Embodiment 3, preparation target controlling and releasing pharmaceutical carrier
Preparation hyaluronic acid and agarose grafts comprise the steps:
(1) agarose is dissolved in 93 ℃ of hot water, and concentration is 3% quality, is cooled to 55 ℃, and adding concentration is the hydrogen peroxide of 30% quality, makes its ultimate density reach 2% volume, 55 ℃ of following isothermal reactions 10 hours;
(2) after the solution decompression that step (1) is obtained concentrates, add the ethanol that is equivalent to 4.5 times of liquor capacities, the centrifugal precipitation that obtains, to precipitate and use water dissolution, repeat to use ethanol sedimentation, to remove residual hydrogen dioxide, to precipitate and use water dissolution, put into the freeze drier freeze-drying agarose powder of must degrading;
(3) degraded agarose powder is dissolved in 93 ℃ of hot water, is cooled to room temperature, adds sodium hydroxide solution and epoxy chloropropane, each concentration of component is respectively: agarose 1.5% quality, sodium hydroxide 0.5% quality, epoxy chloropropane 4% quality, under the room temperature, magnetic agitation reaction 3 hours;
(4) adopt the concentrating under reduced pressure method to remove unnecessary epoxy chloropropane.Solution decompression is concentrated, add the ethanol that is equivalent to 4.5 times of liquor capacities, the centrifugal precipitation that obtains will precipitate and use water dissolution, repeat to use ethanol sedimentation, to remove residual epoxy chloropropane, obtain the activated agarose precipitation;
(5) the activated agarose precipitation is dissolved in 92 ℃ of hot water, is cooled to room temperature, add hyaluronic acid in the activated agarose solution, the normal temperature lower magnetic force stirs, graft reaction 55 hours; Agarose and hyaluronic acid grafted grafting quality proportioning are 1: 1-1: 2;
(6) solution decompression is concentrated,, obtain hyaluronic acid and agarose grafts powder after the lyophilize with dialysis tubing dialysis 72 hours.
With hyaluronic acid and agarose grafts heating for dissolving, treat that temperature reduces to 37 ℃, add Regular Insulin (Regular Insulin and hyaluronic acid mass ratio 5: 1), mix stirring; Treat that solution reduces to room temperature, form the drug particle of particle diameter 300-600nm.By being injected into mouse blood or oral administration, glucose level obviously reduces.
Embodiment 4, and preparation can spray skin wound and repair dressing
Preparation hyaluronic acid and agarose grafts comprise the steps:
(1) agarose is dissolved in 92 ℃ of hot water, and concentration is 2% quality, is cooled to 54 ℃, and adding concentration is the hydrogen peroxide of 30% quality, makes its ultimate density reach 2% volume, 54 ℃ of following isothermal reactions 10 hours;
(2) after the solution decompression that step (1) is obtained concentrates, add the ethanol that is equivalent to 4.5 times of liquor capacities, the centrifugal precipitation that obtains, to precipitate and use water dissolution, repeat to use ethanol sedimentation, to remove residual hydrogen dioxide, to precipitate and use water dissolution, put into the freeze drier freeze-drying agarose powder of must degrading;
(3) degraded agarose powder is dissolved in 93 ℃ of hot water, is cooled to room temperature, adds sodium hydroxide solution and epoxy chloropropane, each concentration of component is respectively: agarose 1.5% quality, sodium hydroxide 0.5% quality, epoxy chloropropane 4% quality, under the room temperature, magnetic agitation reaction 3 hours;
(4) adopt the concentrating under reduced pressure method to remove unnecessary epoxy chloropropane.Solution decompression is concentrated, add the ethanol that is equivalent to 4.5 times of liquor capacities, the centrifugal precipitation that obtains will precipitate and use water dissolution, repeat to use ethanol sedimentation, to remove residual epoxy chloropropane, obtain the activated agarose precipitation;
(5) the activated agarose precipitation is dissolved in 92 ℃ of hot water, is cooled to room temperature, add hyaluronic acid in the activated agarose solution, the normal temperature lower magnetic force stirs, graft reaction 55 hours; Agarose and hyaluronic acid grafted grafting quality proportioning are 1: 2-1: 5;
(6) solution decompression is concentrated,, obtain hyaluronic acid and agarose grafts powder after the lyophilize with dialysis tubing dialysis 72 hours.
With hyaluronic acid and agarose grafts powder heating for dissolving, cross 0.22 micron microfiltration membrane degerming, behind the cool to room temperature, directly solution spraying is spread on skin wound, the external application gauze is simply fungi-proofing, trauma repair behind the fortnight, tissue slice shows the recovery skin texture.
Claims (9)
1. the preparation method of hyaluronic acid and agarose grafts is characterized in that comprising the steps:
(1) degraded agarose powder is dissolved in 90-95 ℃ of hot water, is cooled to room temperature, adds sodium hydroxide solution and epoxy chloropropane, magnetic agitation reaction 2-4 hour;
(2) adopt the concentrating under reduced pressure method to remove unnecessary epoxy chloropropane, solution decompression is concentrated, add and be equivalent to liquor capacity 4-5 ethanol doubly, the centrifugal precipitation that obtains will precipitate and use water dissolution, repeat to use ethanol sedimentation, to remove residual epoxy chloropropane, obtain the activated agarose precipitation;
(3) the activated agarose precipitation is dissolved in 90-95 ℃ of hot water, is cooled to room temperature, add hyaluronic acid in the activated agarose solution, the normal temperature lower magnetic force stirs, graft reaction 48-60 hour; Agarose and hyaluronic acid grafted grafting proportioning are 1: 1-1: 5 mass ratioes;
(4) solution decompression is concentrated,, obtain hyaluronic acid and agarose grafts powder after the lyophilize with dialysis tubing dialysis 72 hours.
2. method according to claim 1 is characterized in that each concentration of component is respectively in the step (1): agarose 1.0-2.0% quality, sodium hydroxide 0.5-1% quality, epoxy chloropropane 3-5% quality.
3. method according to claim 1 and 2 is characterized in that the described degraded agarose of step (1) powder prepares by following method:
(1) agarose is dissolved in the 90-95 ℃ of hot water, and concentration is the 1-5% quality, is cooled to 50-60 ℃, and adding concentration is the hydrogen peroxide of 30% quality, makes its ultimate density reach the 1-3% volume, at 50 ℃ of-60 ℃ of following isothermal reaction 6-15 hours;
(2) after the solution decompression that step (1) is obtained concentrates, add and be equivalent to liquor capacity 4-5 ethanol doubly, the centrifugal precipitation that obtains, to precipitate and use water dissolution, repeat to use ethanol sedimentation, to remove residual hydrogen dioxide, the agarose that obtains degrading precipitation, to precipitate and use water dissolution, put into the freeze drier freeze-drying agarose powder of must degrading;
4. method according to claim 3 is characterized in that in the step (2), described lyophilize be-40 ℃ freezing 2 hours, the vacuum lower pumping is the freeze-drying agarose powder of must degrading more than 17 hours.
5. the hyaluronic acid and the agarose grafts of the preparation of the described method of one of claim 1-4.
6. described hyaluronic acid of claim 5 and the agarose grafts application in the preparation pharmaceutical carrier, it is characterized in that selecting for use degradation time more than 15 hours, molecular weight is that agarose and the hyaluronic acid of 13-15kDa is 1 by grafting quality proportioning: 1-1: 2 hyaluronic acids that prepare and agarose grafts.
7. described hyaluronic acid of claim 4 and agarose grafts are used for the application of the porous support materials of dressing for skin in preparation, it is characterized in that selecting for use degradation time 8-10 hour, molecular weight is about the agarose of 30kDa-40kDa and hyaluronic acid by 1: 1-1: hyaluronic acid and agarose grafts that 3 grafting quality proportioning prepares.
8. described hyaluronic acid of claim 4 and the agarose grafts application in preparation soft tissue engineering scaffold material, it is characterized in that selecting for use degradation time 8-10 hour, molecular weight is about the agarose of 30kDa-40kDa and hyaluronic acid by 1: 1-1: hyaluronic acid and agarose grafts that 3 grafting quality proportioning prepares.
9. described hyaluronic acid of claim 4 and agarose grafts is characterized in that adopting agarose and hyaluronic acid by 1: 2-1: 5. hyaluronic acid and agarose grafts that grafting quality proportioning prepares preparing the application that can spray in the skin wound reparation dressing.
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Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| CN1644221A (en) * | 2005-01-26 | 2005-07-27 | 徐小良 | Composite material for porous material and gel use thereof |
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2007
- 2007-08-16 CN CN2007100297408A patent/CN101134784B/en not_active Expired - Fee Related
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