CN105199115A - Preparation and application of porous injectable hydrogel adopting three-dimensional network structure - Google Patents
Preparation and application of porous injectable hydrogel adopting three-dimensional network structure Download PDFInfo
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- CN105199115A CN105199115A CN201510724511.2A CN201510724511A CN105199115A CN 105199115 A CN105199115 A CN 105199115A CN 201510724511 A CN201510724511 A CN 201510724511A CN 105199115 A CN105199115 A CN 105199115A
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- tridimensional network
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Abstract
The invention discloses preparation and an application of porous injectable hydrogel adopting a three-dimensional network structure and belongs to the field of biological materials. Abietic acid, hydroxyl propyl cellulose and bovine serum albumin are taken as raw materials for the hydrogel, and the gel formation time is controlled through adjustment of the temperature, the pH value and the proportion of two aqueous solutions. Meanwhile, the hydrogel has good moisture retention, drug release performance, biocompatibility and degradation property, and introduction of exogenous toxic materials before and after gel formation is avoided.
Description
Technical field
The invention belongs to biomedicine technical field, be specifically related to a kind of preparation of injection aquagel of tridimensional network of porous and the application in makeup, medicine carrying etc. thereof.
Background technology
Hydrogel is that a kind of main chain or side chain contain a large amount of hydrophilic radical and be adsorbed with the cross-linked polymer with tridimensional network of large quantity of moisture.According to the characteristic of stimuli responsive to external world, hydrogel can be divided into Common hydrogels and intelligent aqueous gel capable.In recent years, along with the development of intelligent aqueous gel capable, injection aquagel becomes one of focus in hydrogel research as a kind of novel hydrogels.So-called injection aquagel is flowing fluid before pointed injection, after injecting subcutis or muscle tissue, at injection site gelatinizing-in-situ, forms the hydrogel with certain space structure and intensity by syringe.Because its Forming Mechanism is the response utilizing macromolecular material to stimulate (such as pH value, temperature, ionic concn etc.) to external world, makes the change of polymkeric substance generation state or conformation under physiological environment, complete the conversion process of solution to gel.Therefore, the practicality that this kind of hydrogel is stronger in physiological conditions receives the extensive concern of investigator.At cosmetic industry, owing to containing a large amount of moisture in hydrogel, and there is good performance of keeping humidity, so hydrogel can be used for facial mask, foundation cream etc.In field of tissue engineering technology, injection aquagel class material has also adapted to the requirement doing Micro trauma technical development, there is Micro trauma repair tissue defect or deformity, tissue injury is little, do not destroy and repair district's blood for, the advantage such as easy to operation, have a good application prospect.Especially it should be noted that, the application of injection aquagel in carrying medicament, injection aquagel is widely studied owing to avoiding surgical risk, injection aquagel carrying medicament can slow releasing medicine, thus reach minimizing administration number of times, reduce toxic side effect and alleviate ailing object, by regulating the structure of hydrogel, the speed of all right regulating medicine release, reaches best result for the treatment of.Therefore hydrogel drug carrier is very suitable for the diseases such as local injection treatment tumour
A desirable injection aquagel, often need possess following condition: can keep low viscosity sols shape before (1) injection, be easy to injection; (2) after injection, gelation occurs immediately, and completes at short notice; (3) gel is biodegradable or can dissolve gradually, and degraded product can bio-absorbable; (4) gel self and degraded product thereof all have good biocompatibility; (5) contained medicine need be met for drug controlled release system and present certain slowly-releasing rule etc.
Hydroxypropylcellulose is a kind of natural macromolecular material, in white or slightly the particle of the yellow or grey of band or fibering Powdered, there is the features such as hypotoxicity, good biocompatibility and biological degradability.In addition, hydroxypropylcellulose also can be used as the excipient of medicine.Compared with traditional starch excipient, its good moldability, anti-mildew sex change can improve.Due to tablet disintegrates rate can be made to improve, easily absorbed by the body, therefore improve the curative effect of medicine.Thermoplasticity, film-forming properties are all good, in makeup available it make emulsifying agent, fruit glaze agent, clouding agent, thickening material, dispersion agent, stablizer, membrane-forming agent etc., as being applied to shampoo, body lotion and the goods such as emulsion and consolidating hair.Bovine serum albumin, also known as BSA, be a kind of sphaeroprotein in bovine serum, comprise 583 amino-acid residues, molecular weight is 66.430kDa, and iso-electric point is 4.7.Bovine serum albumin is widely used in biochemical test: (1) is for Biochemical Research, genetic engineering and medical research; (2) as medicines and health protection food, seasonings; (3) osmotic pressure, pH buffering, carrier function is maintained; (4) in PCR system, contribute to stability and the activity of Taq enzyme, the efficiency etc. of PCR can be improved.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of injection aquagel of tridimensional network of porous, preparation and application thereof.This hydrogel has pH sensitivity characteristic, can complete the transition process of solution-gel under Human Physiology condition.Simply and environmental protection, prepared gel has good performance of keeping humidity, biocompatibility and biological degradability to the technique of gel preparation and medicine carrying, can slow releasing pharmaceutical in a long time.
The injection aquagel of the tridimensional network of porous provided by the invention, its component is: bovine serum albumin, rosinyl hydroxypropylcellulose and water.
In the present invention, in hydrogel, the massfraction of bovine serum albumin is 1%-20%, is wherein preferably 2%-19%, most preferably is 3%-18%; The massfraction of rosin acidic group hydroxypropylcellulose is 0.1%-15%, is wherein preferably 0.2%-14%, most preferably is 0.3%-13%; Bovine serum albumin and rosinyl hydroxypropyl mass ratio are 1-10, are wherein preferably 2-9, most preferably are 3-7.
In the present invention, in medicine carrying hydrogel, the concentration of contained medicine is: doxorubicin hydrochloride strengths is 20-3200 μ g/ml, is preferably 200-3000 μ g/ml, most preferably is 250-2800 μ g/ml.
The preparation method of the injection aquagel of the tridimensional network of porous of the present invention, concrete steps are as follows:
The synthesis of rosinyl hydroxypropylcellulose:
(1) about 5.0g (0.015mol) hydroxypropylcellulose is dissolved in 125ml N,N-DIMETHYLACETAMIDE, heats while stirring, to obtaining consoluet transparent hydroxypropyl cellulose solution.
(2) add in hydroxypropyl cellulose solution by 2.84g (0.015mol) p-methyl benzene sulfonic chloride, 4.50g (0.015mol) sylvic acid, this reaction reacts 24h under nitrogen protection, and temperature is 70 DEG C.In order to react fully, completely, heat while stirring.
(3) product of reaction gained is precipitated in 500ml ether, and clean 3 times with 250ml ether.
(4) by dry for being deposited in vacuum drying oven of gained, set temperature is 60 DEG C.
The formation of injection aquagel:
(1) dissolved in deionized water by bovine serum albumin, obtained massfraction is the transparent bovine serum albumen solution of 10%.
(2) dissolved in deionized water by obtained rosinyl hydroxypropylcellulose, obtained massfraction is the rosinyl hydroxypropyl cellulose solution of 10%.
(3) by bovine serum albumen solution and rosinyl hydroxypropyl cellulose solution at 40 DEG C with the mixing of different ratios, and with the pH of hydrochloric acid regulation system, the hydrogel of the tridimensional network of porous can be obtained.
The formation of medicine carrying hydrogel:
(1) doxorubicin hydrochloride is water-soluble, be made into the doxorubicin hydrochloride solution that concentration is 100-8000 μ g/ml.
(2) solution of step (1) and step (2) gained is mixed, and add doxorubicin hydrochloride solution.Mixed solution is in 40 DEG C of constant temperature, and 10-60min forms medicine carrying hydrogel.In medicine carrying hydrogel, doxorubicin hydrochloride strengths is 20-3200 μ g/ml, is preferably 200-3000 μ g/ml, most preferably is 250-2800 μ g/ml.
The present invention has the following advantages:
(1) raw material of hydrogel of the present invention is wide material sources ground hydroxypropylcellulose and bovine serum albumin, and with low cost, the hydrogel obtained has good biocompatibility and biological degradability.
(2) method preparing hydrogel of the present invention only need be heated by certain temperature, and simple process, preparation process is convenient and swift, environmental protection, and biological safety is kept, and is expected to for scale operation.
(3) preparation of hydrogel of the present invention, controls the speed forming gel by regulating the ratio, pH value etc. of bovine serum albumen solution and rosinyl hydroxypropyl cellulose solution.
(4) hydrogel of the present invention, water content is high, and performance of keeping humidity is good, can be used for cosmetic industry.
(5) hydrogel that prepared by the present invention has thixotropy, can be used for local injection (including, but not limited to intratumor injection) and treats the diseases such as malignant tumour.
(6) preparation of medicine carrying hydrogel of the present invention, medicine-carrying method is simple, and drug loading is high.
(7) the medicine carrying hydrogel prepared by the present invention, can control the rate of release of medicine by the pH value regulating and controlling solid content and damping fluid.
Accompanying drawing explanation
Fig. 1 is the SEM figure of the injection aquagel of the tridimensional network of porous.
Fig. 2 is the performance of keeping humidity figure of the injection aquagel of the tridimensional network of porous.
Fig. 3 is the vitro drug release figure of medicine carrying hydrogel.
Embodiment
Below in conjunction with drawings and Examples, the invention will be further described:
Embodiment 1
(1) dissolved in deionized water by bovine serum albumin, obtained massfraction is the transparent bovine serum albumen solution of 10%.
(2) dissolved in deionized water by obtained rosinyl hydroxypropylcellulose, obtained massfraction is the rosinyl hydroxypropyl cellulose solution of 10%.
(3) by bovine serum albumen solution and rosinyl hydroxypropyl cellulose solution at 40 DEG C in the ratio mixing of 3: 7, and with the pH of hydrochloric acid regulation system, make system pH=1, the hydrogel of the tridimensional network of porous after half an hour, can be obtained.
Embodiment 2
(1) dissolved in deionized water by bovine serum albumin, obtained massfraction is the transparent bovine serum albumen solution of 10%.
(2) dissolved in deionized water by obtained rosinyl hydroxypropylcellulose, obtained massfraction is the rosinyl hydroxypropyl cellulose solution of 10%.
(3) by bovine serum albumen solution and rosinyl hydroxypropyl cellulose solution at 40 DEG C in the ratio mixing of 5: 5, and with the pH of hydrochloric acid regulation system, make system pH=1, the hydrogel of the tridimensional network of porous after 20 minutes, can be obtained.
Embodiment 3
(1) dissolved in deionized water by bovine serum albumin, obtained massfraction is the transparent bovine serum albumen solution of 10%.
(2) dissolved in deionized water by obtained rosinyl hydroxypropylcellulose, obtained massfraction is the rosinyl hydroxypropyl cellulose solution of 10%.
(3) by bovine serum albumen solution and rosinyl hydroxypropyl cellulose solution at 40 DEG C in the ratio mixing of 3: 7, and with the pH of hydrochloric acid regulation system, make system pH=4, the hydrogel of the tridimensional network of porous after thirties minutes, can be obtained.
Embodiment 4
(1) dissolved in deionized water by bovine serum albumin, obtained massfraction is the transparent bovine serum albumen solution of 10%.
(2) dissolved in deionized water by obtained rosinyl hydroxypropylcellulose, obtained massfraction is the rosinyl hydroxypropyl cellulose solution of 10%.
(3) by bovine serum albumen solution and rosinyl hydroxypropyl cellulose solution at 40 DEG C in the ratio mixing of 5: 5, and with the pH of hydrochloric acid regulation system, make system pH=4, the hydrogel of the tridimensional network of porous after twenties minutes, can be obtained.
Embodiment 5
(1) dissolved in deionized water by bovine serum albumin, obtained massfraction is the transparent bovine serum albumen solution of 10%.
(2) dissolved in deionized water by obtained rosinyl hydroxypropylcellulose, obtained massfraction is the rosinyl hydroxypropyl cellulose solution of 10%.
(3) by bovine serum albumen solution and rosinyl hydroxypropyl cellulose solution at 40 DEG C in the ratio mixing of 7: 3, and with the pH of hydrochloric acid regulation system, make system pH=4, the hydrogel of the tridimensional network of porous after tens minutes, can be obtained.
Embodiment 6
(1) dissolved in deionized water by bovine serum albumin, obtained massfraction is the transparent bovine serum albumen solution of 10%.
(2) dissolved in deionized water by obtained rosinyl hydroxypropylcellulose, obtained massfraction is the rosinyl hydroxypropyl cellulose solution of 10%.
(3) by bovine serum albumen solution and rosinyl hydroxypropyl cellulose solution at 40 DEG C in the ratio mixing of 7: 3, and with the pH of hydrochloric acid regulation system, make system pH=1, the hydrogel of the tridimensional network of porous after ten minutes, can be obtained.
Embodiment 7
(1) dissolved in deionized water by bovine serum albumin, obtained massfraction is the transparent bovine serum albumen solution of 10%.
(2) dissolved in deionized water by obtained rosinyl hydroxypropylcellulose, obtained massfraction is the rosinyl hydroxypropyl cellulose solution of 10%.
(3) by bovine serum albumen solution and rosinyl hydroxypropyl cellulose solution at 40 DEG C in the ratio mixing of 7: 3, and with the pH of hydrochloric acid regulation system, make system pH=1, the hydrogel of the tridimensional network of porous after ten minutes, can be obtained.
(4) hydrogel of gained is lyophilized into powder, claps SEM figure.
Embodiment 8
(1) dissolved in deionized water by bovine serum albumin, obtained massfraction is the transparent bovine serum albumen solution of 10%.
(2) dissolved in deionized water by obtained rosinyl hydroxypropylcellulose, obtained massfraction is the rosinyl hydroxypropyl cellulose solution of 10%.
(3) by bovine serum albumen solution and rosinyl hydroxypropyl cellulose solution at 40 DEG C in the ratio mixing of 7: 3, and with the pH of hydrochloric acid regulation system, make system pH=1, the hydrogel of the tridimensional network of porous after ten minutes, can be obtained.
(4) obtained hydrogel is placed in 37 DEG C of thermostat water baths, gets a sample at regular intervals, until constant weight.
Embodiment 9
(1) dissolved in deionized water by bovine serum albumin, obtained massfraction is the transparent bovine serum albumen solution of 10%.
(2) dissolved in deionized water by obtained rosinyl hydroxypropylcellulose, obtained massfraction is the rosinyl hydroxypropyl cellulose solution of 10%.
(3) bovine serum albumen solution and rosinyl hydroxypropyl cellulose solution are mixed according to a certain percentage at 40 DEG C, and add doxorubicin hydrochloride solution, after for some time, form medicine carrying hydrogel.
Claims (10)
1. an injection aquagel for the tridimensional network of porous, is characterized in that: the component of hydrogel is bovine serum albumin, rosinyl hydroxypropylcellulose and water.
2. the injection aquagel of the tridimensional network of porous according to claim 1, is characterized in that: synthesize the rosinyl hydroxypropylcellulose obtained and dissolve completely in water.
3. the injection aquagel of the tridimensional network of porous according to claim 1, is characterized in that: the substitution value of rosinyl hydroxypropylcellulose controls by sylvic acid/hydroxypropylcellulose feed ratio.
4. the injection aquagel of the tridimensional network of porous according to claim 1, it is characterized in that: the massfraction of bovine serum albumin is 1%-20%, the massfraction of rosin acidic group hydroxypropylcellulose is 0.1%-15%, and bovine serum albumin and rosinyl hydroxypropyl mass ratio are 1-10.
5. the injection aquagel of the tridimensional network of porous according to claim 1, is characterized in that: described acidic conditions is regulation system pH is 1-4.
6. the injection aquagel of the tridimensional network of porous according to claim 1, it is characterized in that: the injection aquagel of the tridimensional network of described porous under human physiological environment to introduce a part of hydrophobic grouping and hydrophilic residue in the water-soluble polymer with cross-linked network, hydrophilic residue and water molecules, water molecules is connected to netted inside, and hydrophobic residue water-swellable, finally form gel.
7. an injection aquagel for the tridimensional network of porous, is characterized in that: step is as follows:
(1) respectively bovine serum albumin and rosinyl hydroxypropylcellulose are made into the aqueous solution, make its massfraction be respectively 1%-20%, 0.1%-15%;
(2) two kinds of aqueous solution are mixed in different ratios, regulate the pH of mixing solutions with the HCl solution of 0.1mol/L.
8. the preparation method of the injection aquagel of the tridimensional network of porous according to claim 6, is characterized in that: the temperature of reaction of described step (2) is 37-45 DEG C.
9. the injection aquagel of the tridimensional network of porous according to claim 1 is in the application of cosmetic industry.
10. the application of the injection aquagel of the tridimensional network of porous according to claim 1 in medicine carrying.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110358115A (en) * | 2019-07-25 | 2019-10-22 | 中国林业科学研究院林产化学工业研究所 | A kind of method that 3D printing prepares biomass-based conductive hydrogel |
| CN112225937A (en) * | 2020-10-14 | 2021-01-15 | 中山大学 | Temperature-sensitive macroporous biological hydrogel and preparation method and application thereof |
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| GB706772A (en) * | 1949-12-19 | 1954-04-07 | Bataafsche Petroleum | Improvements in and relating to the manufacture of lubricating greases |
| CN101410096A (en) * | 2006-03-27 | 2009-04-15 | 万能药生物有限公司 | Sustained release pharmaceutical composition on the basis of a release system comprising an acid-soluble polymer and a pH-dependent polymer |
| CN101701051A (en) * | 2009-10-28 | 2010-05-05 | 东北师范大学 | Hydrogel with pH sensibility and temperature sensibility and preparation method thereof |
| CN104069120A (en) * | 2014-06-10 | 2014-10-01 | 复旦大学 | Double-drug loaded thixotropic hydrogel for tumor local treatment and preparation method thereof |
| CN104845382A (en) * | 2015-05-08 | 2015-08-19 | 复旦大学 | Silk protein/cellulose derivative blending hydrogel and preparation method thereof |
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2015
- 2015-10-27 CN CN201510724511.2A patent/CN105199115B/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB706772A (en) * | 1949-12-19 | 1954-04-07 | Bataafsche Petroleum | Improvements in and relating to the manufacture of lubricating greases |
| CN101410096A (en) * | 2006-03-27 | 2009-04-15 | 万能药生物有限公司 | Sustained release pharmaceutical composition on the basis of a release system comprising an acid-soluble polymer and a pH-dependent polymer |
| CN101701051A (en) * | 2009-10-28 | 2010-05-05 | 东北师范大学 | Hydrogel with pH sensibility and temperature sensibility and preparation method thereof |
| CN104069120A (en) * | 2014-06-10 | 2014-10-01 | 复旦大学 | Double-drug loaded thixotropic hydrogel for tumor local treatment and preparation method thereof |
| CN104845382A (en) * | 2015-05-08 | 2015-08-19 | 复旦大学 | Silk protein/cellulose derivative blending hydrogel and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| MUHAMMAD A. HUSSAIN: "Unconventional synthesis and characterization of novel abietic acid esters of hydroxypropylcellulose as potential macromolecular prodrugs", 《JOURNALOF POLYMER SCIENCE:PART A: POLYMER CHEMISTRY》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110358115A (en) * | 2019-07-25 | 2019-10-22 | 中国林业科学研究院林产化学工业研究所 | A kind of method that 3D printing prepares biomass-based conductive hydrogel |
| CN110358115B (en) * | 2019-07-25 | 2022-06-14 | 中国林业科学研究院林产化学工业研究所 | Method for preparing biomass-based conductive hydrogel through 3D printing |
| CN112225937A (en) * | 2020-10-14 | 2021-01-15 | 中山大学 | Temperature-sensitive macroporous biological hydrogel and preparation method and application thereof |
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