CN101012306B - Collagen modified poly(3-hydroxybutyrate-3-hydroxyvalerate) and its preparing method and application - Google Patents
Collagen modified poly(3-hydroxybutyrate-3-hydroxyvalerate) and its preparing method and application Download PDFInfo
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- CN101012306B CN101012306B CN2007100264283A CN200710026428A CN101012306B CN 101012306 B CN101012306 B CN 101012306B CN 2007100264283 A CN2007100264283 A CN 2007100264283A CN 200710026428 A CN200710026428 A CN 200710026428A CN 101012306 B CN101012306 B CN 101012306B
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- butyric ester
- hydroxyl valerate
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Abstract
The invention discloses a modified collagen with 5-30% collagen, 50-90% poly-3-hydrobutanoate-3-hydrovalerate and 5-20% partial amidifying polyacrylamide and making method and application, which comprises the following steps: adopting PHBV as basic material to make PHBV film; irradiating through ultraviolet; grafting polyacrylamide; making amidified PHBV to do Hofmann decomposing reaction; producing amidifying PHBV; bonding PHBV and collagen with excellent compatibility and dynamics.
Description
Technical field
The present invention relates to a kind of modified biological material and technology of preparing thereof, particularly a kind of collagen modified poly (3-butyric ester-3-hydroxyl valerate) that has good biocompatibility and mechanical property concurrently and preparation method thereof.
Background technology
Poly-(3-butyric ester-3-hydroxyl valerate) is by microorganism synthetic natural polyester family macromolecule (PHBV).Because it has excellent biological compatibility, degradable and piezoelectricity, and it is had broad application prospects in medicine controlled releasing, suture, artificial skin, cartilage and bone tissue engineer field.But the PHBV wetting ability is poor, cell its surface adhesion a little less than.For this reason, introduce functional groups on the surface of PHBV, thereby improve the wetting ability and the biological activity on PHBV surface, and then the interaction that improves cell and storeroom is the focus of bio-medical material functionalization research always.
Though traditional collagem membrane has better biocompatibility, its instability, mechanical property is relatively poor, is absorbed too fastly in vivo, has limited its application in biomedical materials field.Make up mould material with degradable high polymer material, aspects such as its chemical ingredients, form, microtexture, mechanical property and degradation speed all have Modulatory character, and processing characteristics is good, have become the focus of bio-medical material circle research.But degradable high polymer material does not contain bioinformation, lacks the cell recognition signal, is unfavorable for that cell-specific sticks and the activation of specific gene.Therefore, the ideal mould material should not only have suitable mechanical strength and excellent biological compatibility, suitable water-intake rate and wetting ability and better cell adhesion more will be arranged, and degradation rate is adjustable, and degraded product is nontoxic to human body, nonirritant.Preparation meets the mould material of above-mentioned requirements, makes it realize that aspect 26S Proteasome Structure and Function imitation biochemistry is the difficult problem that bio-medical material faces.
Summary of the invention
The objective of the invention is to overcome the shortcoming of prior art, a kind of collagen modified poly (3-butyric ester-3-hydroxyl valerate) that has good biocompatibility and mechanical property concurrently is provided.
Another object of the present invention is to provide the preparation method of above-mentioned collagen modified poly (3-butyric ester-3-hydroxyl valerate).
The present invention also has a purpose to be to provide collagen modified poly (3-butyric ester-3-hydroxyl valerate) preparation Application of Biomaterial.
Purpose of the present invention is achieved through the following technical solutions:
A kind of collagen modified poly (3-butyric ester-3-hydroxyl valerate) has following structural formula:
Wherein, x is 2～143; Y is 62～183; Col is a collagen.
Described collagen modified poly (3-butyric ester-3-hydroxyl valerate) is at 1653cm
-1And 1551cm
-1The feature acid amides I band and the II band of secondary acid amides appearred respectively in the place.Each composition weight percent is as follows in the described collagen modified poly (3-butyric ester-3-hydroxyl valerate):
Poly-(3-butyric ester-3-hydroxyl valerate) 50～90%
Collagen 5～30%
The polyacrylamide 5～20% that part is aminated.
The preparation method of collagen modified poly (3-butyric ester-3-hydroxyl valerate) comprises the steps:
(1) will gathering (3-butyric ester-3-hydroxyl valerate), to be dissolved in purity be in chloroform, methylene dichloride or the propylene carbonate solvent more than 99%, and poly-(3-butyric ester-3-hydroxyl valerate) film of cast preparation; Poly-(3-butyric ester-3-hydroxyl valerate) weight is 60～180mg: 1ml with the solvent volume ratio;
(2) poly-(3-butyric ester-3-hydroxyl valerate) film of step (1) preparation being soaked in concentration is initiator acetone soln 4～24hr of 0.5～5%; Described initiator is benzophenone, michaelis ketone or thioxanthone; The amount ratio 5 * 10 of initiator and PHBV
-4～5 * 10
-3: 1;
(3) to immerse concentration be in the aqueous solution of 5～30% acrylamides to poly-(3-butyric ester-3-hydroxyl valerate) film that will soak initiator, UV-irradiation 0.5～4hr;
(4) solvent extraction, distilled water embathe and dry;
(5) add 20～60 minutes after washings of aqueous slkali soaking; Described alkaline solution is that 5～20% aqueous sodium hydroxide solution and 53.8g concentration are 6～24% the clorox or the mixing solutions of sodium hypobromite for 90ml concentration.The volume of alkaline solution and initiator weight ratio are 100～340ml: 1mg;
(6) distilled water embathes behind adding coupling agent 5～30ml.The weight ratio of coupling agent volume and initiator is 100～170ml: 1mg;
(7) adding concentration is that 3～6mg/ml collagen solution room temperature is placed 6～24h after washing, and the weight ratio of collagen and initiator is 600～1000: 1;
(8), promptly get collagen modified poly of the present invention (3-butyric ester-3-hydroxyl valerate) material at-50～-20 ℃ of following lyophilize 12～24hr.
Described poly-(3-butyric ester-3-hydroxyl valerate) is 0～70% for the content of 3-hydroxyl valerate.Solvent is an acetone in the described step (4).Coupling agent in the described step (6) is for being formaldehyde or glutaraldehyde solution.
The biomaterial of collagen modified poly (3-butyric ester-3-hydroxyl valerate) preparation, its inside can be laminate structure or inierpeneirating network structure; The tensile strength of material can reach 4MPa, and cell increases by 100% in its surperficial adherence rate, and cell stretches out uropodium and joins together and cover material surface.
Principle of the present invention: poly-(3-butyric ester-3-hydroxyl valerate) contained polar group is an ester group only, is the inert polymer, and shortage can be carried out the site of chemical bonding with collagen.For this reason, introducing active group is the material modified key of preparation.Under action of ultraviolet light, initiator benzophenone etc. can be extracted the hydrogen atom of tertiary carbon on the PHBV main chain, thereby makes PHBV form macromolecular radical, and then acrylamide triggered graft polymerization.Amidated PHBV also need pass through the Hofmann DeR, makes amide group be converted into amido; The amido of PHBV modify and graft is to be connected by coupling agent formaldehyde etc. with the amido of collagen, has formed firm chemical bonding between PHBV and the collagen thereby make.The structure of collagen modification PHBV material can be laminate structure or inierpeneirating network structure, by the structures shape of amidation PHBV material.
The present invention compared with prior art has following advantage:
(1) the present invention is material modified has laminate structure or an inierpeneirating network structure, and grafted collagen macromolecular chain makes it have good biological activity and biocompatibility.
(2) the material modified middle collagen macromole of introducing of the present invention is hydrophilic, has improved the hydrophobicity of PHBV, and material modified water-intake rate is improved; Effective distribution of hydrophilic and hydrophobic group has simultaneously further improved the cell adhesion rate.
(3) the present invention can regulate PHBV and the ratio of collagen and material modified structure by changing the processing parameter (time, intensity etc.) and the monomer content of ultraviolet lighting.
(4) technology of the present invention's employing is simple, helps large-scale production.
Description of drawings
Fig. 1 is material modified surperficial total reflection figure (ATR).
Fig. 2 is material modified surface light electronic energy spectrum (XPS).
Fig. 3 is material modified chemical structural formula.
Fig. 4 is the collagen modification PHBV layer structure material surface SEM figure of embodiment 1 preparation.
Fig. 5 is the collagen modification PHBV layer structure material profile scanning Electronic Speculum figure of embodiment 1 preparation.
Fig. 6 is the surface scan Electronic Speculum figure of the collagen modification PHBV network structure material of embodiment 2 preparations.
Fig. 7 is the profile scanning Electronic Speculum figure of the collagen modification PHBV network structure material of embodiment 2 preparations.
Embodiment
For better understanding the present invention, below in conjunction with embodiment the present invention is described further, but the scope of protection of present invention is not limited to the scope that embodiment represents.
Embodiment 1
The process of preparation protocollagen modification PHBV material comprises the steps: that (1) is dissolved in 0.06gPHBV in the 1ml chloroformic solution, and solution casting prepares the PHBV film; (2) the PHBV film of step (1) preparation being soaked in concentration is 0.5% initiator benzophenone acetone soln 4hr; (3) to immerse concentration be in the aqueous solution of 5% acrylamide to the PHBV film that will soak initiator, UV-irradiation 0.5hr; (4) acetone extracting 48hr, distilled water embathe and in 60 ℃ of oven dry; (5) adding 10ml concentration is that 5% sodium hydroxide and concentration are the mixed ammonium/alkali solutions of 6% clorox, soaks 20 minutes after washings; (6) add 5ml formaldehyde soaking at room temperature after washing; (7) adding concentration is that water logging was washed after 3mg/ml I type bovine collagen solution 10ml room temperature was placed 6hr; (8)-50 ℃ lyophilize 12hr promptly gets of the present invention material modified.
As shown in Figure 1, ATR analyzes and confirms that the distinctive carbonylic stretching vibration of PHBV peak has not only appearred in collagen modification PHBV material, makes the acid amides I band of collagen and II band move on to 1653cm respectively simultaneously
-1And 1551cm
-1Locate, the characteristic peak of secondary acid amides occurred, illustrate that chemical bonding has taken place for macromolecular amido of collagen and modification PHBV.As shown in Figure 2, XPS then further illustrates the content of collagen modification PHBV material surface chemical element, and wherein the content of nitrogen element is 15%, with the ratio of carbon element content be 0.2: 1.According to above analysis, the chemical structural formula that has proposed collagen modification PHBV as shown in Figure 3.Fig. 4 and Fig. 5 are respectively the surface and the profile scanning Electronic Speculum figure of the collagen modification PHBV material of embodiment 1 preparation.Collagen modification PHBV material is after lyophilize is handled, and the surface has formed irregular pore space structure, makes original slick PHBV become coarse.As seen, collagen and PHBV are tangible layered distribution from the SEM figure of section, but bonding is good between the two.Imporosity is PHBV, and short texture is a grafted collagen macromole.This laminate structure is material modified to comprise following component:
PHBV 90％
Collagen 5%
The polyacrylamide 5% that part is aminated
Each component all is weight percentage.
Embodiment 2
The process of preparation protocollagen modification PHBV material comprises the steps: that (1) is dissolved in 0.06gPHBV in the 0.3ml dichloromethane solution, and solution casting prepares the PHBV film; (2) the PHBV film of step (1) preparation being soaked in concentration is 5% initiator michaelis ketone acetone soln 24hr; (3) to immerse concentration be in the aqueous solution of 30% acrylamide to the PHBV film that will soak initiator, UV-irradiation 4hr; (4) acetone extracting 48hr, distilled water embathe and in 60 ℃ of oven dry; (5) adding 30ml concentration is that 20% sodium hydroxide and concentration are the mixed ammonium/alkali solutions of 24% clorox, soaks 60 minutes after washings; (6) add 30ml formaldehyde soaking at room temperature after washing; (7) adding concentration is that water logging was washed after 6mg/ml I type bovine collagen solution 30ml room temperature was placed 24hr; (8)-20 ℃ lyophilize 24hr promptly gets of the present invention material modified.
Fig. 6 and Fig. 7 are respectively the surface and the profile scanning Electronic Speculum figure of the collagen modification PHBV material of embodiment 2 preparations.Collagen modification PHBV material surface is a hole not of uniform size, the pore space structure of its section forms through the lyophilize processing for the collagen of introducing, the PHBV material of previous compact structure no longer exists, and the substitute is the inierpeneirating network structure of collagen in the PHBV base material.This inierpeneirating network structure is material modified to comprise following component:
PHBV 50％
Collagen 30%
The polyacrylamide 20% that part is aminated
Each component all is weight percentage.
Embodiment 3
The process of preparation protocollagen modification PHBV material comprises the steps: that (1) is dissolved in 0.06gPHBV in the 0.6ml propylene carbonate solution, and solution casting prepares the PHBV film; (2) the PHBV film of step (1) preparation being soaked in concentration is 1% initiator thioxanthone acetone soln 8hr; (3) to immerse concentration be in the aqueous solution of 10% acrylamide to the PHBV film that will soak initiator, UV-irradiation 1hr; (4) acetone extracting 48hr, distilled water embathe and in 60 ℃ of oven dry; (5) adding 15ml concentration is that 10% sodium hydroxide and concentration are the mixed ammonium/alkali solutions of 12% sodium hypobromite, soaks 30 minutes after washings; (6) add 10ml glutaraldehyde soaking at room temperature after washing; (7) adding concentration is that water logging was washed after 3mg/ml I type bovine collagen solution 20ml room temperature was placed 12hr; (8)-50 ℃ lyophilize 24hr promptly gets of the present invention material modified.
Comprise following component through the laminate structure of this method preparation is material modified:
PHBV 85％
Collagen 10%
The polyacrylamide 5% that part is aminated
Each component all is weight percentage.
Claims (6)
1. a collagen modified poly (3-butyric ester-3-hydroxyl valerate), it is characterized in that: this collagen modified poly (3-butyric ester-3-hydroxyl valerate) has following structural formula:
Wherein, x is 2～143; Y is 62～183; Col is a collagen;
Described collagen modified poly (3-butyric ester-3-hydroxyl valerate) is at 1653cm
-1And 1551cm
-1The feature acid amides I band and the II band of secondary acid amides appearred respectively in the place.
2. a kind of collagen modified poly according to claim 1 (3-butyric ester-3-hydroxyl valerate) is characterized in that, each composition weight percent is as follows in the described collagen modified poly (3-butyric ester-3-hydroxyl valerate):
Poly-(3-butyric ester-3-hydroxyl valerate) 50～90%
Collagen 5～30%
The polyacrylamide 5～20% that part is aminated.
3. the preparation method of collagen modified poly (3-butyric ester-3-hydroxyl valerate) is characterized in that comprising the steps:
(1) will gathering (3-butyric ester-3-hydroxyl valerate), to be dissolved in purity be in chloroform, methylene dichloride or the propylene carbonate solvent more than 99%, and poly-(3-butyric ester-3-hydroxyl valerate) film of cast preparation; Poly-(3-butyric ester-3-hydroxyl valerate) weight is 60～180mg: 1ml with the solvent volume ratio;
(2) poly-(3-butyric ester-3-hydroxyl valerate) film of step (1) preparation being soaked in concentration is initiator acetone soln 4～24hr of 0.5～5%; Described initiator is benzophenone, michaelis ketone or thioxanthone; Initiator and the amount ratio 5 * 10 that gathers (3-butyric ester-3-hydroxyl valerate)
-4～5 * 10
-3: 1;
(3) to immerse concentration be in the aqueous solution of 5～30% acrylamides to poly-(3-butyric ester-3-hydroxyl valerate) film that will soak initiator, UV-irradiation 0.5～4hr;
(4) solvent extraction, distilled water embathe and dry;
(5) add 20～60 minutes after washings of aqueous slkali soaking; Described alkaline solution is that 5～20% aqueous sodium hydroxide solution and 53.8g concentration are 6～24% the clorox or the mixing solutions of sodium hypobromite for 90ml concentration; The volume of alkaline solution and initiator weight ratio are 100～340ml: 1mg;
(6) distilled water embathes behind adding coupling agent 5～30ml, and the weight ratio of coupling agent volume and initiator is 100～170ml: 1mg;
(7) adding concentration is that 3～6mg/ml collagen solution room temperature is placed 6～24h after washing, and the weight ratio of collagen and initiator is 600～1000: 1;
(8), promptly get collagen modified poly (3-butyric ester-3-hydroxyl valerate) material at-50～-20 ℃ of following lyophilize 12～24hr.
4. method according to claim 3 is characterized in that solvent is an acetone in the described step (4).
5. method according to claim 3 is characterized in that the coupling agent in the described step (6) is formaldehyde or glutaraldehyde solution.
6. the biomaterial of the described collagen modified poly of claim 1 (3-butyric ester-3-hydroxyl valerate) preparation is characterized in that collagen modified poly (3-butyric ester-3-hydroxyl valerate) material internal is laminate structure or inierpeneirating network structure; The tensile strength of material can reach 4MPa, and cell increases by 100% in its surperficial adherence rate, and cell stretches out uropodium and joins together and cover material surface.
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|---|---|---|---|
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| CN108743566B (en) * | 2018-05-23 | 2021-02-02 | 中南大学湘雅二医院 | Preparation method and application of PHBV/rosiglitazone sustained-release membrane |
| CN114618015B (en) * | 2022-04-13 | 2022-11-25 | 珠海麦得发生物科技股份有限公司 | PHA microsphere containing collagen and preparation method and application thereof |
| CN114752566B (en) * | 2022-04-21 | 2023-08-25 | 中国科学院苏州纳米技术与纳米仿生研究所 | Tumor stem cell screening and tumor organoid construction method based on tumor stem cells |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1435438A (en) * | 2002-09-24 | 2003-08-13 | 重庆大学 | Diamine modified poly-latic acid, method for preparing same and use thereof |
| WO2005117810A1 (en) * | 2004-06-04 | 2005-12-15 | Shiseido Co., Ltd. | External preparation for the skin |
| US20060147412A1 (en) * | 2004-12-30 | 2006-07-06 | Hossainy Syed F | Polymers containing poly(hydroxyalkanoates) and agents for use with medical articles and methods of fabricating the same |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1435438A (en) * | 2002-09-24 | 2003-08-13 | 重庆大学 | Diamine modified poly-latic acid, method for preparing same and use thereof |
| WO2005117810A1 (en) * | 2004-06-04 | 2005-12-15 | Shiseido Co., Ltd. | External preparation for the skin |
| US20060147412A1 (en) * | 2004-12-30 | 2006-07-06 | Hossainy Syed F | Polymers containing poly(hydroxyalkanoates) and agents for use with medical articles and methods of fabricating the same |
Non-Patent Citations (2)
| Title |
|---|
| 卢玲 等.聚羟基烷酸酯薄膜的亲水性改性.应用化学23 1.2006,23(1),22-23. |
| 卢玲等.聚羟基烷酸酯薄膜的亲水性改性.应用化学23 1.2006,23(1),22-23. * |
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