CN106176579B - A kind of preparation with pH response characteristic injectable Nanometer composite hydrogel system - Google Patents
A kind of preparation with pH response characteristic injectable Nanometer composite hydrogel system Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/40—Cyclodextrins; Derivatives thereof
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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Abstract
The invention discloses a kind of preparation methods with pH response characteristic injectable Nanometer composite hydrogel, include the following steps: the preparation of 1, material, have cyclodextrin, the double bond gelatin of pH sensitivity characteristic according to prior art preparation；2: the preparation of the hydrogel precursor solution of the particle containing cyclodextrin nano, pH sensitivity cyclodextrine derivatives are dissolved and form cyclodextrin/dichloromethane solution in methylene chloride, it seals ice-bath ultrasonic to crush, double bond gelatin/PBS solution of the pH=7.5 of a certain concentration and volume is added；Sealing supersonic cell crushes to form colostric fluid, and double bond gelatin/PBS solution that the pH=7.5 of a certain concentration and volume is added obtains mixed emulsion, magnetic agitation, and the gelatin of double bond is added in organic solvent after sufficiently evaporating；3, a certain amount of photoinitiator is added in the solution, forms Nanometer composite hydrogel after a certain period of time with illumination in ultraviolet lamp reactor.PH response injectable Nanometer composite hydrogel prepared by the present invention has a wide range of applications in biomedicine field.
Description
Technical field
The invention belongs to new material technology fields, and in particular to a kind of preparation of multi-functional syringeability composite hydrogel.
Background technique
In bio-medical field, it is using rate of release, time and the place of carrier material control drug in human body
Improve the curative effect of drug, the toxic side effect of reduction and reduction drug and a kind of effective means for reducing administration number of times.Ideal medicine
Object carrier should have good biocompatibility, biodegradability, physics and chemistry and biological stability and extremely low toxicity, and have compared with
High load pharmacological property.And carrier material is utilized to realize the transmitting and one of transfection and this area research hot spot of cell, the mankind are good for
Health plays a crucial role.It is many currently used as the material of carrier, including hydrogel, microballoon, film, functionalized particles.Its
In, injectable type biomaterial is implanted by the method injected, and has the characteristics that minimal invasive, has in bio-medical field
Broad application prospect.
Hydrogel predecessor is solution state, is easily injected, in vivo can rapid shaping, be a kind of most common injectable
Type biomaterial.Injectable type biomaterial is implanted by the method injected, and has the characteristics that minimal invasive, in organizational project
It has a wide range of applications in terms of surgical plastic.The structure of hydrogel has the property of solid and liquid double grading concurrently, this
Loading of the drug in hole may be implemented in kind structure, and realizes that the control of drug is released by modes such as diffusion, infiltration, degradations
It puts, while the characteristic of hydrogel solid can guarantee drug in the release at the position of lesion.In addition, the environment of water-setting glue solution
To tissue and its similar, soft, wetting surface and material is greatly reduced to surrounding tissue with the affinity of tissue
Stimulation so that hydrogel have good biocompatibility.But most of anticancer drug such as adriamycin, taxol etc. is thin
The water solubility of aqueous pharmaceutical, hydrophobic drug is poor, and loading of these drugs in hydrogel receives certain limitation.This
Outside, as syringeability material, hydrogel also have that mechanical strength is lower, degradation speed is very fast, hydrogel occurs to be crushed quickly or
Collapse the disadvantages of cannot continuing to the space of cell growth.
Particle from micron-scale to nano-scale is another form of injectable type bracket.This micro- load of injectable type
Body mainly has the microballoons such as PLA, PLGA, gelatin, sodium alginate.It is cured in addition, stimulating responsive is also nanoparticle one in biology
The significant advantage applied with field.Especially low pH responsive materials, have a wide range of applications in terms of anti-tumor drug transmitting.
But the carrier material of nanometer is while realizing its flexible responsiveness, also there is that the stability of material is poor, can not fill spy
The shortcomings that setting shape.Therefore, by the two it is compound can in conjunction with both the advantages of, while the shortcomings that both overcome again.
Existing syringeability hydrogel carrier material composition is relatively simple, is difficult to realize the multifunctionality of carrier material
The characteristics of response.Nano particle composite hydrogel of the invention just improves the shortcomings that this respect.
Have independently to fill by supermolecule in the prior art and be prepared for syringeability graphene/PVA hydrogel drug carrier,
But drug release is mainly realized by the surface corrosion of hydrogel in the hydrogel carrier of such syringeability, there is no special
The characteristic of fixed stimuli responsive, and PVA is a kind of non-degradable material, when molecular weight is more than certain value, the generation of material in vivo
It thanks and has certain problem.Nanometer composite hydrogel material of the invention is a kind of material that can be degraded into small molecule completely,
And the characteristic with stimuli responsive.
Summary of the invention
The purpose of the present invention is to provide a kind of composite hydrogel for simply preparing injectable with low pH response characteristic and
Its method prepared.
The present invention prepares the nanoparticle of low pH response characteristic by acetalation cyclodextrin, passes through the gelatin conduct of double bond
The presoma of emulsifier and hydrogel realizes the preparation of compound syringeability hydrogel by light-initiated free radical polymerization.
Step includes: step 1: the preparation of material, has cyclodextrin, the double bond gelatin of pH sensitivity characteristic according to prior art preparation,
Wherein double bond gelatin is solid；Step 2: the preparation of the hydrogel precursor solution of the particle containing cyclodextrin nano, by certain mass
PH sensitivity cyclodextrine derivatives, which dissolve, forms cyclodextrin/dichloromethane solution in methylene chloride, sealing ice-bath ultrasonic crushes, then plus
Enter double bond gelatin/PBS solution of the pH=7.5 of a certain concentration and volume；It seals supersonic cell and crushes 3min formation colostrum
Liquid, the double bond gelatin/PBS solution for being subsequently added into the pH=7.5 of a certain concentration and volume obtains mixed emulsion, in magnetic agitation
Device stirring, is added the gelatin of certain double bond after allowing organic solvent sufficiently to evaporate；Step 3: light-initiated free radical polymerization, molten
A certain amount of photoinitiator is added in liquid, is placed in thin layer sealing container one timing of illumination in the ultraviolet lamp reactor of 365nm
Between after formed Nanometer composite hydrogel.
The specific steps of the present invention are as follows:
Step 1: the preparation of material: (1) with pH sensitivity characteristic cyclodextrin preparation (see number of patent application:
2010101817859,2015103967228), (2) double bond gelatin preparation (Macromol.Biosci.2009,9,1194-
1201): 1g gelatin being added in small beaker and 50ml deionized water is added, beaker is put into baking oven and is dissolved, set temperature is
50 degrees Celsius.800 microlitres of acrylic acid are pipetted with liquid-transfering gun and 50 ml deionized waters are added, and 1 mole every liter of hydrogen is then added
Sodium oxide molybdena adjusts its pH value (dosage is about 8 milliliters) between 4 to 5.0.5geEDC (chemical reagent 1- (3- bis- is added wherein
Methyl aminopropyl) -3- ethyl carbimide) and 0.15 to 0.16gNHS (N-N- HOSu NHS) react 20 minutes,
Using heat collecting type constant temperature blender with magnetic force 35 degrees Celsius lower stirring in water bath 12 hours.Double bond gelatin solution must be contained.Use bag filter
Obtained solution dialysis (is finally used into distilled water) more than ten times several times, time interval two hours or more.It has just obtained pure
Double bond gelatin solution.Gelatin double bond solid is obtained after freeze-drying.
Step 2: the preparation of the hydrogel precursor solution of the particle containing cyclodextrin nano
Certain mass pH sensitivity cyclodextrine derivatives are dissolved and form cyclodextrin/dichloromethane solution in methylene chloride,
Preferred concentration is 1%-20% (w/v), and further concentration is 5%-15% (w/v), and optimal concentration is 9%-11% (w/
v)；It seals ice-bath ultrasonic and crushes 2min, add double bond gelatin/PBS (pH=7.5) solution of a certain concentration and volume；Its
Preferred concentration is 0.1%-10% (w/v), and further concentration is 0.5%-3% (w/v), and optimal concentration is 0.8%-
1.2% (w/v)；Preferred water-oil factor is 2:1-20:1, is further 5:1-15:1, optimal for 9:1-10:1；Sealing ultrasound
Wave cell pulverization 3min forms colostric fluid, is subsequently added into double bond gelatin/PBS (pH=7.5) solution of a certain concentration and volume
Mixed emulsion is obtained, preferred concentration is 0.03%-5% (w/v), and further concentration is 0.1%-1% (w/v), optimal
Concentration is 0.3%-0.5% (w/v)；Preferred colostric fluid and mixed emulsion ratio are 2:1-1:10, are further 1:1-1:5, most
Excellent is 1:2-1:3；10h is stirred at magnetic stirring apparatus 1300r/min, certain double bond is added after allowing organic solvent sufficiently to evaporate
The gelatin of change, be final gelatin concentration at 3%-20% (w/v), be further 5%-15% (w/v), it is optimal to be
10%-15% (w/v).
Step 3: light-initiated free radical polymerization
A certain amount of photoinitiator is added in the solution, is placed in the ultraviolet lamp reactor in thin layer sealing container in 365nm
Nanometer composite hydrogel is formed after one section of middle illumination.Preferred photoinitiator is I2959, I1173, I651, I184, optimal to be
I2959, preferred initiator concentration are 0.01-0.5% (w/v), are further 0.05-0.1% (w/v).Preferred illumination
Time 10min-1h is further 10-30min, optimal for 20-30min.
Beneficial effects of the present invention:
A kind of syringeability gelatin hydrogel and its processing method with pH responsiveness provided by the invention, products obtained therefrom
Performance meet the basic demand of bio-medical carrier material.With biggish Social benefit and economic benefit.
Specific embodiment
The present invention will be further described with reference to embodiments, but following embodiments have no protection scope of the present invention
Clearly limit.
The measurement of gel time:
The variation of hydrogel monomer mobility, the timing definition hydrogel to lose flowability from solution are observed by observation
Gel time.
Swelling behavior performance test:
Weighing is denoted as W after hydrogel freeze-dryingdry, dry glue immerses in 37 DEG C of water that weighing is denoted as W after a period of time1, swelling ratio
It is defined as W1/Wdry.Weighing is denoted as W afterwards for 24 hours in the water of 37 DEG C of dry glue immersion2.Equilibrium swelling ratio is defined as W2/Wdry。
The measurement of Dynamic Rheological Properties:
It is 50mm, the highly shape for 1mm size that hydrogel, which is prepared into diameter, with flat on Anton Paar MCR rheometer
Andante mode measures its modulus, viscosity with the variation of frequency, setting strain is 1% under 37 degree.
Hydrogel pH responsiveness:
Hydrogel is placed in the medium of different pH, is taken out at regular intervals, hydrogel is detected by ultraviolet spectra and is existed
Transmitance at 400nm.
The present invention, min indicate minute, and h indicates hour, and w/v indicates to use mass volume ratio concentration.
Embodiment 1
PH sensitivity cyclodextrine derivatives are dissolved and form cyclodextrin/dichloromethane solution, concentration 10% in methylene chloride
(w/v), sealing ice-bath ultrasonic crushes 2min；Double bond gelatin/PBS (pH=7.5) solution of a certain concentration and volume is added,
Concentration is 1% (w/v)；Double bond gelatin/PBS (pH=7.5) solution and cyclodextrin/dichloromethane solution volume ratio are 6:1；It is close
It seals supersonic cell and crushes 3min formation colostric fluid, be subsequently added into double bond gelatin/PBS (pH=of a certain concentration and volume
7.5) solution obtains mixed emulsion, and concentration is 0.3% (w/v)；Colostric fluid and mixed emulsion volume ratio are 1:2, in magnetic agitation
10h is stirred under device 1300r/min, organic solvent is allowed sufficiently to evaporate the lotion for forming the cyclodextrin nano particle of pH sensitivity characteristic.
The gelatin of certain double bond is added, makes the concentration of final gelatin 15%.0.05% (w/v) I2959 is added in above-mentioned emulsion
It is placed in thin layer sealing container and forms Nanometer composite hydrogel after one section of illumination in the ultraviolet lamp reactor of 365nm.
The correlated performance measurement of the present embodiment product is as follows:
The gel time 22min of this hydrogel, equilibrium swelling ratio are 11.6, and storage modulus is between 3000-4000, loss
Modulus is between 50-100.Nanoparticle is more stable in the medium of pH=7.5, does not occur significantly dissolving in 48 hours existing
As；It in the medium of pH=6.5, is slowly dissolved in 24 hours, until 36 hours, nearly all nanoparticle all dissolved；In pH
In=5.5 medium, quickly dissolved in 8 hours.
Embodiment 2
PH sensitivity cyclodextrine derivatives are dissolved and form cyclodextrin/dichloromethane solution, concentration 15% in methylene chloride
(w/v), sealing ice-bath ultrasonic crushes 2min；Double bond gelatin/PBS (pH=7.5) solution of a certain concentration and volume is added,
Concentration is 1% (w/v)；Water-oil factor is 6:1；It seals supersonic cell and crushes 3min formation colostric fluid, be subsequently added into a certain concentration
Mixed emulsion is obtained with double bond gelatin/PBS (pH=7.5) solution of volume, concentration is 0.3% (w/v)；Colostric fluid with mix
Lotion ratio is 1:2, stirs 10h at magnetic stirring apparatus 1300r/min, allows organic solvent sufficiently to evaporate and form pH sensitivity characteristic
The lotion of cyclodextrin nano particle.The gelatin of certain double bond is added, makes the concentration of final gelatin 20%.In above-mentioned emulsion
0.05% (w/v) I2959 of addition, which is placed in be formed after one section of illumination in the ultraviolet lamp reactor of 365nm in thin layer sealing container, to be received
Rice composite hydrogel.
The correlated performance measurement of the present embodiment product is as follows:
The gel time 15min of this hydrogel, equilibrium swelling ratio are 10.3, and storage modulus is between 12000-20000, damage
Modulus is consumed between 300-500.Nanoparticle is more stable in the medium of pH=7.5, does not occur in 48 hours apparent molten
Solve phenomenon；It in the medium of pH=6.5, is slowly dissolved in 24 hours, until 36 hours, nearly all nanoparticle all dissolved；
In the medium of pH=5.5, quickly dissolved in 8 hours.
Embodiment 3
PH sensitivity cyclodextrine derivatives are dissolved and form cyclodextrin/dichloromethane solution, concentration 5% in methylene chloride
(w/v), sealing ice-bath ultrasonic crushes 2min；Double bond gelatin/PBS (pH=7.5) solution of a certain concentration and volume is added,
Concentration is 1% (w/v)；Water-oil factor is 6:1；It seals supersonic cell and crushes 3min formation colostric fluid, be subsequently added into a certain concentration
Mixed emulsion is obtained with double bond gelatin/PBS (pH=7.5) solution of volume, concentration is 0.3% (w/v)；Colostric fluid with mix
Lotion ratio is 1:2, stirs 10h at magnetic stirring apparatus 1300r/min, allows organic solvent sufficiently to evaporate and form pH sensitivity characteristic
The lotion of cyclodextrin nano particle.The gelatin of certain double bond is added, makes the concentration of final gelatin 15%.In above-mentioned emulsion
0.05% (w/v) I2959 of addition, which is placed in be formed after one section of illumination in the ultraviolet lamp reactor of 365nm in thin layer sealing container, to be received
Rice composite hydrogel.
The correlated performance measurement of the present embodiment product is as follows:
The gel time 21min of this hydrogel, equilibrium swelling ratio are 12.3, and storage modulus is between 1900-2500, loss
Modulus is between 30-100.Nanoparticle is more stable in the medium of pH=7.5, does not occur significantly dissolving in 48 hours existing
As；It in the medium of pH=6.5, is slowly dissolved in 24 hours, until 36 hours, nearly all nanoparticle all dissolved；In pH
In=5.5 medium, quickly dissolved in 8 hours.
Embodiment 4
PH sensitivity cyclodextrine derivatives are dissolved and form cyclodextrin/dichloromethane solution, concentration 10% in methylene chloride
(w/v), sealing ice-bath ultrasonic crushes 2min；Double bond gelatin/PBS (pH=7.5) solution of a certain concentration and volume is added,
Concentration is 1% (w/v)；Water-oil factor is 6:1；It seals supersonic cell and crushes 3min formation colostric fluid, be subsequently added into a certain concentration
Mixed emulsion is obtained with double bond gelatin/PBS (pH=7.5) solution of volume, concentration is 0.3% (w/v)；Colostric fluid with mix
Lotion ratio is 1:2, stirs 10h at magnetic stirring apparatus 1300r/min, allows organic solvent sufficiently to evaporate and form pH sensitivity characteristic
The lotion of cyclodextrin nano particle.The gelatin of certain double bond is added, makes the concentration of final gelatin 10%.In above-mentioned emulsion
0.05% (w/v) I2959 of addition, which is placed in be formed after one section of illumination in the ultraviolet lamp reactor of 365nm in thin layer sealing container, to be received
Rice composite hydrogel.
The correlated performance measurement of the present embodiment product is as follows:
The gel time 28min of this hydrogel, equilibrium swelling ratio are 26.9, and storage modulus is between 1000-1500, loss
Modulus is between 20-100.Nanoparticle is more stable in the medium of pH=7.5, does not occur significantly dissolving in 48 hours existing
As；It in the medium of pH=6.5, is slowly dissolved in 24 hours, until 36 hours, nearly all nanoparticle all dissolved；In pH
In=5.5 medium, quickly dissolved in 8 hours.
Comparative example 1
By the Gelatin Yu Shuizhong of double bond, make the concentration of final gelatin 10%.It is added in above-mentioned emulsion
It is multiple that 0.05% (w/v) I2959 is placed in thin layer sealing container in the ultraviolet lamp reactor of 365nm formation nanometer after one section of illumination
Heshui gel.
The correlated performance measurement of this comparative example product is as follows:
The gel time 31min of this hydrogel, equilibrium swelling ratio are 27.5, and storage modulus is between 800-1000, loss
Modulus is between 20-80.Without pH sensitivity phenomenon.
Comparative example 2
By the Gelatin Yu Shuizhong of double bond, make the concentration of final gelatin 15%.It is added in above-mentioned emulsion
It is multiple that 0.05% (w/v) I2959 is placed in thin layer sealing container in the ultraviolet lamp reactor of 365nm formation nanometer after one section of illumination
Heshui gel.
The correlated performance measurement of this comparative example product is as follows:
The gel time 22min of this hydrogel, equilibrium swelling ratio are 12.5, and storage modulus is between 1000-2000, loss
Modulus is between 20-100.Without pH sensitivity phenomenon.
Comparative example 3
By the Gelatin Yu Shuizhong of double bond, make the concentration of final gelatin 20%.It is added in above-mentioned emulsion
It is multiple that 0.05% (w/v) I2959 is placed in thin layer sealing container in the ultraviolet lamp reactor of 365nm formation nanometer after one section of illumination
Heshui gel.
The correlated performance measurement of this comparative example product is as follows:
The gel time 16min of this hydrogel, equilibrium swelling ratio are 12.1, and storage modulus is between 8000-10000, damage
Modulus is consumed between 200-300.Without pH sensitivity phenomenon.
Comparing embodiment and comparative example product, obtain as drawn a conclusion:
It is approached in the gel time and comparative example of syringeability hydrogel in embodiment, illustrates the addition of nanoparticle simultaneously
The gelling performance of syringeability gel is not influenced, this hydrogel has operability.Balance after water-setting gum forming, in embodiment
Swelling ratio is slightly less than comparative example, the mainly addition due to the nanoparticle of low swellability, but not to the swelling behavior of hydrogel
The influence for generating essence will not influence it and transport to moisture and nutriment.
Storage modulus and loss modulus are above the hydrogel in comparative example in hydrogel in embodiment, illustrate to have preferable
Mechanical property.Hydrogel in embodiment has the characteristic of low pH response, and does not have this response in comparative example.
Embodiment realizes the purpose of the present invention.But protection scope of the present invention is not limited to embodiment.
Claims (6)
1. a kind of preparation method with pH response characteristic injectable Nanometer composite hydrogel, includes the following steps:
Step 1: the preparation of material specifically includes:
Cyclodextrin, the double bond gelatin with pH sensitivity characteristic are prepared, wherein double bond gelatin is solid；
Step 2: the preparation of the hydrogel precursor solution of the particle containing cyclodextrin nano specifically includes:
Certain mass pH sensitivity cyclodextrine derivatives are dissolved and form cyclodextrin/dichloromethane solution in methylene chloride, seal ice
Ultrasonic Pulverization is bathed, double bond gelatin/PBS solution of the pH=7.5 of a certain concentration and volume is added；Seal supersonic cell powder
Broken 3min forms colostric fluid, and the double bond gelatin/PBS solution for being subsequently added into the pH=7.5 of a certain concentration and volume is mixed
The gelatin of certain mass double bond is added in magnetic stirrer in lotion after allowing organic solvent sufficiently to evaporate；
Step 3: light-initiated free radical polymerization specifically includes:
A certain amount of photoinitiator is added in the solution, is placed in thin layer sealing container the light in the ultraviolet lamp reactor of 365nm
According to forming Nanometer composite hydrogel after a certain period of time；
The gelatin of the double bond the preparation method comprises the following steps:
1g gelatin is added in small beaker and 50ml deionized water is added, beaker is put into baking oven and is dissolved, set temperature 50
Degree Celsius；800 microlitres of acrylic acid are pipetted with liquid-transfering gun and 50 ml deionized waters are added, and 1 mole every liter of hydrogen-oxygen is then added
Change sodium and adjusts its pH value between 4 to 5；0.5g EDC and 0.15 to 0.16gNHS is added wherein to react 20 minutes, is using
Heat collecting type constant temperature blender with magnetic force 35 degrees Celsius lower stirring in water bath 12 hours, obtain gelatin solution containing double bond；With bag filter by institute
Solution dialysis obtained more than ten times, time interval two hours or more, has just obtained pure double bond gelatin solution, after freeze-drying
To gelatin double bond solid.
2. a kind of preparation method with pH response characteristic injectable Nanometer composite hydrogel according to claim 1,
Be characterized in that: in the step 3, the photoinitiator is I2959, I1173, I651 or I184.
3. a kind of preparation method with pH response characteristic injectable Nanometer composite hydrogel according to claim 2,
Be characterized in that: in step 2, certain mass pH sensitivity cyclodextrine derivatives, which dissolve, forms cyclodextrin/methylene chloride in methylene chloride
The concentration of solution is 1%-20%w/v；It seals ice-bath ultrasonic and crushes 2min；Add the pH=7.5's of a certain concentration and volume
Double bond gelatin/PBS solution, concentration 0.1%-10%w/v；Double bond gelatin/PBS solution and cyclodextrin/methylene chloride are molten
The volume ratio of liquid is 2:1-20:1；It seals supersonic cell and crushes 3min formation colostric fluid；It is subsequently added into a certain concentration and volume
Double bond gelatin/PBS solution of pH=7.5 obtain mixed emulsion, concentration 0.03%-5%w/v；Colostric fluid with mix cream
The volume ratio of liquid is 2:1-1:10；10h is stirred at magnetic stirring apparatus 1300r/min, is added after allowing organic solvent sufficiently to evaporate
The gelatin of certain mass double bond, the concentration of final gelatin is in 3%-20%w/v；
In the step 3, photoinitiator concentration 0.01-0.5%w/v；Light application time 10min-1h.
4. a kind of preparation method with pH response characteristic injectable Nanometer composite hydrogel according to claim 3,
Be characterized in that: in step 2, certain mass pH sensitivity cyclodextrine derivatives, which dissolve, forms cyclodextrin/methylene chloride in methylene chloride
The concentration of solution is 5%-15%w/v；It seals ice-bath ultrasonic and crushes 2min；Add the pH=7.5's of a certain concentration and volume
Double bond gelatin/PBS solution, concentration 0.5%-3%w/v；Double bond gelatin/PBS solution and cyclodextrin/dichloromethane solution
Volume ratio be 5:1-15:1；It seals supersonic cell and crushes 3min formation colostric fluid；It is subsequently added into a certain concentration and volume
Double bond gelatin/PBS solution of pH=7.5, obtains mixed emulsion, concentration 0.1%-1%w/v；Colostric fluid and mixed emulsion
Volume ratio be 1:1-1:5；10h is stirred at magnetic stirring apparatus 1300r/min, is added after allowing organic solvent sufficiently to evaporate certain
The gelatin of quality double bond, the concentration of final gelatin is in 5%-15%w/v；
In the step 3, photoinitiator concentration 0.05-0.1%w/v；Light application time 10-30min.
5. a kind of preparation method with pH response characteristic injectable Nanometer composite hydrogel according to claim 4,
Be characterized in that: in step 2, certain mass pH sensitivity cyclodextrine derivatives, which dissolve, forms cyclodextrin/methylene chloride in methylene chloride
The concentration of solution is 9%-11%w/v；It seals ice-bath ultrasonic and crushes 2min；Add the pH=7.5's of a certain concentration and volume
Double bond gelatin/PBS solution, concentration 0.8%-1.2%w/v；Double bond gelatin/PBS solution and cyclodextrin/methylene chloride are molten
The volume ratio of liquid is 9:1-10:1；It seals supersonic cell and crushes 3min formation colostric fluid；It is subsequently added into a certain concentration and volume
Double bond gelatin/PBS solution of pH=7.5 obtain mixed emulsion, concentration 0.3%-0.5%w/v；Colostric fluid with mix cream
The volume ratio of liquid is 1:2-1:3；10h is stirred at magnetic stirring apparatus 1300r/min, is added one after allowing organic solvent sufficiently to evaporate
Determine the gelatin of quality double bond, the concentration of final gelatin is in 10%-15%w/v；
In the step 3, photoinitiator concentration 0.05-0.1%w/v；Light application time is 20-30min.
6. there is pH response characteristic injectable Nanometer composite hydrogel body according to one kind prepared by claim 1-5 either method
System.
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| CN107652452B (en) * | 2017-09-19 | 2019-07-16 | 华南理工大学 | A kind of Subjective and Objective supramolecular hydrogel and the preparation method and application thereof |
| CN118121761B (en) * | 2024-05-08 | 2024-07-09 | 天津市天津医院 | Preparation method and application of three-dimensional through-hole gelatin stent |
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| CN104958767A (en) * | 2015-07-08 | 2015-10-07 | 金陵科技学院 | Preparation method of pH-sensitive cyclodextrin nanoparticles having biocompatibility |
| CN105125478A (en) * | 2015-08-26 | 2015-12-09 | 金陵科技学院 | Injectable nano-composite hydrogel having pH sensitive property |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104958767A (en) * | 2015-07-08 | 2015-10-07 | 金陵科技学院 | Preparation method of pH-sensitive cyclodextrin nanoparticles having biocompatibility |
| CN105125478A (en) * | 2015-08-26 | 2015-12-09 | 金陵科技学院 | Injectable nano-composite hydrogel having pH sensitive property |
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| "Gelatin Hydrogel Prepared by Photo-initiated Polymerization and Loaded with TGF-β1 for Cartilage Tissue Engineering";Xiaohong Hu et al.;《Macromolecular Bioscience》;20091201;第9卷(第12期);第1194-1201页 |
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