CN107115562A - A kind of injection aquagel and its preparation and application for myocardial repair - Google Patents
A kind of injection aquagel and its preparation and application for myocardial repair Download PDFInfo
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Abstract
The invention discloses a kind of injection aquagel available for myocardial repair, main component is bioactivity glass, sodium alginate and glucolactone；The invention further relates to a kind of preparation and application of the injection aquagel for myocardial repair simultaneously.The injection aquagel original state that the present invention is provided is liquid, the position for entering myocardial damage can be injected by syringe, into after damage location, bioactivity glass decomposed under the weak acid environment that glucolactone is built the cross-linking sodium alginate of calcium ion of generation so as in wound site into gel, prevent cardiac chamber dilation, hydrogel solidify simultaneously after is in concrete dynamic modulus state, is easy to growth of the cell in hydrogel to promote myocardial repair；The calcium ion and silicon ion and some other ion that bioactivity glass decomposes generation under the weak acid environment that glucolactone is built can promote revascularization and cardiac muscle cell to repair by promoting cell to secrete key growth factors.
Description
Technical field
The present invention relates to biomedical material, organizational project and medical domain, more particularly to it is a kind of for myocardial repair
Injection aquagel and its preparation and application.
Background technology
Miocardial infarction frequently results in the damage of cardiac muscular tissue and the expansion of ventricular chamber, so that the normal function of heart
Receive damage.Heart failure is still the main cause for causing the death rate high caused by after miocardial infarction.The patient of heart failure
The 1-5 death rate substantially 43%, and the death rate of one term is 33%.Therefore, many treatment means are used in
In the treatment of miocardial infarction, but these treatment means are all drug therapy or coronary artery bypass surgery and heart mostly
Transplanting etc..But these treatment methods are frequently subjected to many restrictions and prognosis is nor very good, so needing to find new
Means go to treat miocardial infarction, solve due to caused by miocardial infarction the problem of myocardial damage
Sodium Alginate Hydrogel Films are a kind of natural polymer hydrogels, and it is under conditions of multivalent ion presence easily into solidifying
Glue.By controlling the rate of release and total volume of multivalent ion, it can effectively control the gelation rate of sodium alginate and obtain
To the hardness of gel.So as to play certain filling effect for myocardial damage position, ventricle is prevented to a certain extent
Chamber is expanded.And multi-pore structure is presented after hydrogel solidification, these spaces can provide effective space for the growth of cell.
Bioactivity glass is a kind of containing calcium (Ca), the ceramic material of silicon (Si), with controllable mechanical performance and drop
Speed, good bioactivity are solved, inflammation can be suppressed in vivo and promote into blood vessel differentiation.Its ion discharged can be stimulated carefully
Intracrine VEGF (VEGF), the growth factor such as basic fibroblast growth factor (bFGF) stimulates endothelium
Cells such as cell etc. are bred and broken up, so as to promote revascularization, are had well for the situation for improving site of myocardial infarction
Effect.
Glucolactone is a kind of coagulator, can be as medicament additive, with nontoxic, and oral administration, solidification effect is good
The features such as, it can be applied in multi-medicament preparation.
The current myocardial damage caused by biomaterial and medical domain, miocardial infarction, which is still one, needs what is solved to ask
Topic, scientific and technical personnel are also constantly searching for new thinking and method.
Therefore, those skilled in the art is directed to developing a kind of injection aquagel and its preparation for myocardial repair
With application.
The content of the invention
In view of the drawbacks described above of prior art, the technical problems to be solved by the invention are to provide one kind and repaiied for cardiac muscle
Multiple injection aquagel and its preparation and application.
To achieve the above object, first aspect present invention provides a kind of injection aquagel for myocardial repair.
In a preferred embodiment, the injection aquagel main component for being used for myocardial repair is sodium alginate,
Bioactivity glass and medicated premix
Further, the medicated premix in the above-mentioned injection aquagel for myocardial repair is glucolactone.
Further, sodium alginate, bioactivity glass and grape in the above-mentioned injection aquagel for myocardial repair
The mass ratio (gram) of saccharic acid lactone includes but is not limited to 1:1:1 to 4:2:1.
Further, sodium alginate, bioactivity glass and addition in the above-mentioned injection aquagel for myocardial repair
Quality volume (grams per milliliter) percentage of agent (glucolactone) in hydrogel each stands alone as 1%~2%.Further
Contain sodium alginate, bioactivity glass, glucolactone, Portugal in ground, the above-mentioned injection aquagel for myocardial repair
Grape saccharic acid lactone can make to form weak acid environment in hydrogel, have so that bioactivity glass continues slowly to discharge
Calcium ion, the silicon ion on concentration are imitated, after injection aquagel is injected in vivo with liquid, any surface of a wound can be filled, simultaneously
Multi-pore structure is presented after gel, cell growth is available for, promotes revascularization, improves miocardial infarction.
Wherein, the time of gel is 30sec to 3min.
Second aspect of the present invention provides the preparation method of above-mentioned injection aquagel, in a preferred embodiment,
The step of preparation method, is as follows：
1) sodium alginate is configured to sodium alginate aqueous solution；
2) glucolactone and the sodium alginate aqueous solution are mixed；
3) bioactivity glass is added into step 2) in acquisition solution in, be well mixed, obtain the injectable water
Gel.
Preferably, in this method：
(1) by sodium alginate soln inhalation syringe；
(2) glucolactone is uniformly mixed in sodium alginate soln using three-way pipe；
(3) bioactivity glass is added in the sodium alginate soln for be mixed with glucolactone in proportion, and by
Bioactivity glass is uniformly dispersed in sodium alginate soln by three-way pipe；
Further, it is liquid after above-mentioned injection aquagel is well mixed, myocardial defect is entered by syringe injection
Position, liquid hydrogel meeting gel-forming solid, prevents from being discharged by heart
Further, in the preparation method of above-mentioned injection aquagel, the quality volume of sodium alginate soln in step (1)
(grams per milliliter) percentage is 1%~2%；
Further, in the preparation method of above-mentioned injection aquagel, sodium alginate in step (2), bioactivity glass,
The mixed solution of additive, wherein sodium alginate, bioactivity glass, quality volume (grams per milliliter) percentage of medicated premix
Than including but is not limited to be 1%~2%；
Further, in the preparation method of above-mentioned injection aquagel, carried out in step (2), step (3) using three-way pipe
Mix.
The third aspect of the invention provides application of the above-mentioned injection aquagel on myocardial damage is repaired.
Above-mentioned injection aquagel, which has, promotes revascularization, improves miocardial infarction, prevents what ventricular chamber from further expanding
Effect.Bioactivity glass in hydrogel can constantly be produced under the weak acid environment of glucolactone calcium, silicon etc. from
Son, promotes the vascularization of endothelial cell, so as to improve the situation of myocardial damage.
The injection aquagel of the present invention can by controlling different proportionings to control the time of gel so that ensure with
The hydrogel that liquid condition injection enters heart can sufficiently fit the surface of a wound, and form support and protect, so that in certain journey
The further expansion of ventricular chamber is avoided on degree.Meanwhile, the multi-pore structure of injection aquagel can carry for the growth of cell
For sufficient space and support.
In actual applications, the ventricular chamber of myocardial damage can protected not enter one using the injection aquagel of the present invention
While step expansion, the calcium of generation, silicon plasma are decomposed in the environment of faintly acid by bioactivity glass to promote VEGF,
The secretion of the growth factors such as bFGF promotes cells such as endothelial cell etc. into blood vessel function, so as to largely improve impaired
The pathophysiological conditions of myocardial sites, while substantial amounts of space provides better growing conditions for cell in hydrogel.
Injection aquagel preparation method in the present invention is simple, and easy to operate, cost is low.Clinically can individually or coordinate
Medicine performs the operation to improve damaged myocardium.Compared to current existing operative treatment and drug therapy, injectable water of the invention
Gel can for filling the position of myocardial defect and playing a part of support, so as to prevent the further expansion of myocardial damage,
The further expansion of ventricular chamber is effectively prevented, while the prices of raw materials are cheap, it is easy to sterilize, by stimulating the cell of human body in itself
To improve the heart after miocardial infarction.Injection aquagel in the present invention is easy to operate, can be used for minimally invasive injection and uses, subtracts
Few sufferer pain over the course for the treatment of and secondary injury is avoided, reduce the working strength of medical personnel, and for sufferer
Without special requirement, it is widely used and practicality is high.
Obviously, according to the above of the present invention, according to the ordinary technical knowledge and customary means of this area, do not departing from
Under the premise of the above-mentioned basic fundamental thought of the present invention, the modification of other diversified forms can also be made, replaces or changes.
All features disclosed in this specification, or disclosed all methods or during the step of, except mutually exclusive
Feature and/or step beyond, can combine in any way.
Any feature disclosed in this specification, unless specifically stated otherwise, can be equivalent by other or with similar purpose
Alternative features are replaced.I.e., unless specifically stated otherwise, each feature is an example in a series of equivalent or similar characteristics
.
Below in conjunction with specific accompanying drawing to injection aquagel of the present invention and its preparation method be described further, to fill
Ground is divided to understand the purpose of the present invention, feature and effect.
Brief description of the drawings
Fig. 1 is that injection aquagel is used for the schematic diagram of myocardial repair；
Fig. 2 is schematic diagram of the injection aquagel by syringe；
Fig. 3 is the internal structure schematic diagram after injection aquagel gel；
Fig. 4 is the schematic diagram of the bioactivity glass Size Distribution in hydrogel；
Fig. 5 is the schematic diagram of Internal biological activity glass degraded ratio after gel；
Fig. 6 is the schematic diagram of human endothelial cells culture experiment cellular control unit vascularization；
Fig. 7 is the schematic diagram of human endothelial cells culture experiment hydrogel test group cellular vascular；
Fig. 8 is the signal of human endothelial cells culture experiment hydrogel test group and the contrast of cellular control unit vascularization index
Figure；
Fig. 9 is to prevent cardiac chamber dilation from testing HE dyeing and the schematic diagram of Manson staining versus；
Figure 10 is the schematic diagram for preventing the relative scar thickness of cardiac chamber dilation experiment and infarct expanding index from contrasting.
Embodiment
It is known product, by buying city if the raw material used in the specific embodiment of the invention, equipment are without specified otherwise
Sell product acquisition.SA as described below is sodium alginate, and BG is bioactivity glass, and GDL is glucolactone.
Embodiment 1
The preparation of injection aquagel：
(1) 2g sodium alginates (SA) powder is dissolved in 100mL deionized waters be stirred continuously prepare 2% in viscosity sea
Solution of sodium alginate；
(2) 2% SA solution is well mixed with grape saccharic acid lactones (GDL) powder mull, wherein, GDL final mass
Volume (grams per milliliter) percentage is 2%；
(3) bioactivity glass (BG) powder is added in step (2) in obtained mixed solution, it is well mixed, wherein,
BG final mass volume (grams per milliliter) percentage is 2%.Finally, sodium alginate, gluconic acid lactone, biology are configured to living
Property glass quality volume (grams per milliliter) percentage is 2% injection aquagel.
In above-mentioned preparation method, it can be mixed by any mode, such as by three-way pipe by glucolactone
It is uniformly mixed in sodium alginate soln, bioactivity glass is uniformly dispersed in by three-way pipe and is mixed with gluconic acid
In the sodium alginate soln of lactone.
Injection aquagel is transferred in syringe, and injection in fluid form enters at myocardial damage, so as to fill full
The whole surface of a wound, then hydrogel can be within 30S to 3min time in surface of a wound solidification.
As shown in figure 1, injection aquagel enters behind heart damage position by injecting, gel is formed, while gel is released
Calcium ion, the silicon ion put can stimulate the release of VEGF, basic fibroblast growth factor, promote blood
Pipe is generated, and then reaches reduction myocardial infarction area, promotes the purpose of heart damage position regeneration.
Embodiment 2
The outward appearance of injection aquagel and Micro-Structure Analysis.
Shown in Fig. 2 is the schematic diagram that the injection aquagel prepared in embodiment 1 passes through syringe.By in embodiment 1
After the injection aquagel freeze-drying of preparation, with observation by light microscope hydrogel and its linkage interface, as shown in figure 3, can
Bioactive glass particle can be evenly distributed with by showing a large amount of spaces in injection hydrogel.
SEM sweep electron microscopic measures its Size Distributions is carried out to the bioactivity glass that is distributed in hydrogel, such as Fig. 4 institutes
Show that a diameter of normal distribution of bioactivity glass grain focuses primarily upon 30 microns.
By the hydrogel containing bioactivity glass by volume 1:4 are immersed in Du Shi improvement Iger (DMEM) nutrient solutions
In, the ion concentration that is discharged in nutrient solution of hydrogel of the measurement containing bioactivity glass, with bioactivity glass from
Sub- ratio calculates its degradation rate, and projectional technique is the concentration of ion in measurement nutrient solution, is converted into the amount of ion, passes through element
Conservation is scaled the amount of bioactivity glass degraded.As shown in figure 5, in hydrogel in the bioactivity glass time of 5 to 15 days
It can slowly degrade and discharge effective ion., and wherein the concentration of silicon ion is stablized in 0.5ug/ml~1.06ug/ml always,
Substantially it is in valid density.
Embodiment 3
Facilitation of the injection aquagel for revascularization.
The injection aquagel prepared in embodiment 1 and the endothelial cell of people are co-cultured, cultural method：The water-setting of use
Its proportioning of glue is sodium alginate soln 1ml, the 0.02g glucolactone of 2% mass volume fraction, 0.02g bioactivity glass
Glass is prepared into hydrogel in the way of in embodiment 1, is immersed in 4ml culture fluid of endothelial cell, will soak 1d, 3d, 5d
Nutrient solution take out, remained after filtering standby.Endothelial cell is seeded in 24 orifice plates with 600000/ml density, set
Control group and experimental group, control group are cultivated with endothelial cell culture medium (ECM) all the time, as a result as shown in Figure 6.Experimental group treats cell
After adherent, nutrient solution is replaced by the hydrogel leaching liquor and normal nutrient solution 1 extracted before:1 to cultivate, injectable water-setting
Glue test group cultivation results are as shown in fig. 7, injection aquagel can greatly facilitate the vascularization of endothelial cell, as schemed
Shown in 8, compared with control group, injection aquagel test group is respectively in annulus area, node area and vessel area tripartite
Face significantly promotes the vascularization of endothelial cell.Annulus area referred to during Human umbilical vein endothelial cells vascularization,
The cell of formation joins end to end to form the area of specific ring-type.Node area then refers to during vascularization, the ring-type of formation
The node area intersected in structure, and vessel area is then to refer to that the face of vessel-like structure is tentatively presented in the ring-type to form closing
Product.
Embodiment 4
Injection aquagel is for preventing the effect of cardiac chamber dilation.
Rat heart infarction model is prepared first.Male using Sprague-Dawley (SD) rat, body weight 200g or so is pressed
Yellow Jackets are injected intraperitoneally in body weight 3%, rat are placed on into operating table center position with the posture lain on the back, using external light
Tracheae is irradiated in source, and glottis inserts homemade conduit when opening, trachea cannula is connected with toy lung ventilator, and naked eyes are visible
The most strong area of heartbeat carry out open chest surgery, the Article 3 rib and Article 4 rib being usually located on the left of breastbone it
Between.It is placed in the gauze of ready modest size around rat otch；Then pericardium is gently lifted with pincet.In the left heart
Anticipation left anterior descending branch and its trend, left anterior descending coronary artery is ligatured with 7-0 surgical threads slip-knot between ear and pulmonary conus.Enter
Pin depth is 1~1.5mm, wide 2~3mm.The injection aquagel that will be prepared in embodiment 1, is injected by syringe and entered
Site of myocardial infarction, the rat of Normal group is injected with not carrying out hydrogel, the rat of sodium alginate soln is only injected respectively,
The rat of only injection bioactivity glass is contrasted.Experiment is sutured to rat after terminating and prevents to infect to penicillin.
Detected as shown in figure 9, being dyed by HE dyeing and Masson, injection aquagel can obviously reduce myocardial damage position ventricular chamber
Further expansion.As shown in Figure 10, following index is measured using image analysis software ImageJ：IVSTd (mm), the heart
Obstruct scar thickness (mm), left ventricular cavity area (mm2), left room area (mm2).Each three calculation average values of index measurement.Then calculate
Once index：Heart infarction scar thickness ratio=heart infarction scar thickness/IVSTd.Heart infarction expansion exponent=left ventricular cavity area/
Left room area.The thickness and infarct expanding index for detecting relative scar by contrast experiment prove subject hydrogel to the heart
The obvious repair of muscle injury site.
Preferred embodiment of the invention described in detail above.It should be appreciated that the ordinary skill of this area is without wound
The property made work just can make many modifications and variations according to the design of the present invention.Therefore, all technical staff in the art
Pass through the available technology of logical analysis, reasoning, or a limited experiment on the basis of existing technology under this invention's idea
Scheme, all should be in the protection domain being defined in the patent claims.
Claims (10)
1. a kind of injection aquagel, it is characterised in that the injection aquagel contain sodium alginate, bioactivity glass and
Medicated premix.
2. injection aquagel as claimed in claim 1, it is characterised in that the medicated premix is glucolactone.
3. injection aquagel as claimed in claim 2, it is characterised in that in the injection aquagel, sodium alginate, life
The quality ratio scope of thing activity glass and glucolactone is 1:1:1 to 4:2:1.
4. injection aquagel as claimed in claim 2, it is characterised in that in the injection aquagel, sodium alginate, life
The quality percent by volume of thing activity glass and glucolactone is 1%~2%.
5. injection aquagel as claimed in claim 2, it is characterised in that the injection aquagel can continue slowly
Discharge calcium, the silicon plasma on valid density.
6. the injection aquagel as described in claim 1-5, it is characterised in that the injection aquagel is injected into liquid
Enter myocardial defect position.
7. a kind of application of injection aquagel as described in claim any one of 1-5 in myocardial repair material is prepared.
8. a kind of preparation method of injection aquagel as described in claim any one of 1-5, step is as follows：
1) sodium alginate is configured to sodium alginate aqueous solution；
2) glucolactone and the sodium alginate aqueous solution are mixed；
3) bioactivity glass is added into step 2) in acquisition solution in, be well mixed, obtain the injection aquagel.
9. preparation method as claimed in claim 8, it is characterised in that 1 the step of wherein described) in sodium alginate soln matter
Measure percent by volume be 1%~2%, described step 2), step 3) in, bioactivity glass, glucolactone are in water-setting
Quality percent by volume is respectively 1%~2% in glue.
10. preparation method as claimed in claim 8, it is characterised in that wherein step 2), step 3) in, entered using three-way pipe
Row is mixed.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108578785A (en) * | 2018-04-26 | 2018-09-28 | 福州大学 | A kind of preparation method of magnetism self-healing property bio-vitric/hydrogel composite material |
| CN110124103A (en) * | 2019-05-08 | 2019-08-16 | 上海交通大学 | A kind of active substance release material system and preparation method thereof for tissue repair |
| CN112043865A (en) * | 2019-06-06 | 2020-12-08 | 天津大学 | Strontium hydroxyapatite and sodium alginate composite injectable hydrogel with adhesion and preparation method and application thereof |
| CN114409932A (en) * | 2022-03-11 | 2022-04-29 | 江苏集萃功能材料研究所有限公司 | Preparation method and application of intraoperative gastric filling hydrogel |
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| CN110124103A (en) * | 2019-05-08 | 2019-08-16 | 上海交通大学 | A kind of active substance release material system and preparation method thereof for tissue repair |
| CN112043865A (en) * | 2019-06-06 | 2020-12-08 | 天津大学 | Strontium hydroxyapatite and sodium alginate composite injectable hydrogel with adhesion and preparation method and application thereof |
| CN114409932A (en) * | 2022-03-11 | 2022-04-29 | 江苏集萃功能材料研究所有限公司 | Preparation method and application of intraoperative gastric filling hydrogel |
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