CN108403663A - GO-PEG gel micro-balls with nucleocapsid and its preparation method and application - Google Patents
GO-PEG gel micro-balls with nucleocapsid and its preparation method and application Download PDFInfo
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- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
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Abstract
The present invention proposes a kind of GO PEG gel micro-balls with nucleocapsid, the chitosan polyvinyl alcohol sodium alginate plural gel shell that medicine kernel is carried by GO PEG and is wrapped in outside the kernel forms, it further include preparation method, using physical blending, emulsification and etc., in addition, the application the present invention also provides the GO PEG gel micro-balls with nucleocapsid as water-soluble or water-insoluble tumor therapeutic agent carrier.Solve the problems, such as that the slow release effect of complex environment in vivo after GO PEG carrying medicaments is bad, not only internal had good sustained release effect, but also drugloading rate and microballoon homogeneity are good.
Description
Technical field
The invention belongs to technical field of biological material, are related to gel micro-ball and its preparation method and application, and in particular to a kind of tool
There are the GO-PEG gel micro-balls and its preparation method and application of nucleocapsid.
Background technology
Graphene oxide has low-solubility in physiological solution, and verified its has certain poison to cell
Property, this is so that it can not be directly used in inside of human body, and the graphene oxide graphene oxide after PEG modifications can pass through kidney
Urination is rapidly from internal discharge, to cause the apparent toxicity (reference of histoorgan (such as liver, spleen)《Graphite alkenes are received
Progress and its potential risk of the rice material as pharmaceutical carrier》).But it is multiple in vivo after GO-PEG load water soluble drugs
The slow release effect in heterocycle border is bad, it is therefore desirable to prepare the GO-PEG pharmaceutical carrier materials with good sustained release performance in human body
Material.
Invention content
In order to solve the above technical problems, the present invention provide a kind of GO-PEG gel micro-balls with nucleocapsid and its
Preparation method, the GO-PEG gel micro-balls with nucleocapsid obtained using preparation method of the present invention are not only slow in vivo
It is good to release effect, and drugloading rate and microballoon homogeneity are good.
The present invention provides a kind of preparation method of the GO-PEG gel micro-balls with nucleocapsid, includes the following steps:
(1) it prepares GO-PEG and carries medicine kernel:Using physical blending process by drug loading to GO-PEG, wherein the GO-
PEG carries out amide with graphene oxide using existing known amino polyethylene glycol and is obtained by the reaction;
(2) chitosan-polyvinyl alcohol-sodium alginate plural gel liquid is prepared:Polyvinyl alcohol is added simultaneously into deionized water
Dissolving is complete, continuously adds acetic acid solution and Chitosan powder, and stirring is completely dissolved to chitosan, continuously adds sodium alginate powder
End, stirring are completely dissolved to sodium alginate, obtain chitosan-polyvinyl alcohol-sodium alginate plural gel liquid, wherein chitosan,
Polyvinyl alcohol, sodium alginate mass ratio be (2-5):(4-9):1;
(3) chitosan-polyvinyl alcohol-made from step (2) is added in step (1) GO-PEG obtained for having loaded drug
In sodium alginate plural gel liquid, ultrasonic disperse is uniform, forms mixing water phase coagulant liquid, which is added drop-wise to dropwise
In 80 oil phases of paraffin oil-Span, emulsification is stirred at room temperature uniformly, crosslinking agent is added and is crosslinked, is formed with nucleocapsid
GO-PEG gel micro-ball suspension;
(4) isopropanol is added into above-mentioned suspension, is stood, is centrifuged and is dry with organic solvent washing, filtering, vacuum
It is dry to constant weight, obtain the GO-PEG gel micro-balls with nucleocapsid.
Preferably, the crosslinking agent in the step (3) is glutaraldehyde or Geniposide.
Preferably, carrying out can be heated to 50-70 DEG C when the crosslinking of step (3), constant temperature stirs 2-4h.
Preferably, carrying out can be heated to 50 DEG C when the crosslinking of step (3), constant temperature stirs 3h.
Preferably, the organic solvent of the step (4) is the combination of one or more of ether, acetone, ethyl acetate.
Preferably, the organic solvent of the step (4) is ether.
The invention also includes a kind of GO-PEG with nucleocapsid being prepared according to above-described preparation method
Gel micro-ball.
Preferably, the drug of the load is water-soluble or water-insoluble drug.
Preferably, the drug of the load is tumor therapeutic agent.
The invention also includes the GO-PEG gel micro-balls with nucleocapsid as water-soluble or water-insoluble swollen
The application of tumor medicine carrier.
It has the advantages that:
1, the chitosan-polyvinyl alcohol-alginic acid for being carried medicine kernel by GO-PEG and be wrapped in outside the kernel of the invention
The GO-PEG gel micro-balls of sodium plural gel shell composition, on the one hand using the GO-PEG almost without cytotoxicity as load medicine
Matrix, remaining GO-PEG can quickly be fallen by body metabolism after being absorbed into human body medicine, will not be long-term stagnant in human body
It stays, damages;On the other hand, it has been wrapped up outside outside chitosan-polyvinyl alcohol (PVA)-sodium alginate (SA) plural gel
Shell has had both the pH sensibility of chitosan, the blood compatibility of the hydrophily of PVA and SA, while the PVA added can overcome the disadvantages that shell
The defect of easy disintegrating after the brittleness and SA gel water absorption and swellings of polysaccharide gel so that the GO-PEG gel micro-balls of preparation have good
Good pH sensibility and swellability, this can adapt to physiological environment complicated in human body, especially be different pH environment (such as stomaches
Portion and enteron aisle), realize the sustained release and controlled release of carrying medicament.
2, the preparation method of the GO-PEG gel micro-balls of the present invention with nucleocapsid uses GO-PEG conducts first
Carrier loaded drug prepares GO-PEG and carries medicine kernel, due to GO-PEG have to water-soluble and water-insoluble drug it is stronger
Affinity, so obtained GO-PEG is carried, medicine kernel drugloading rate is higher, and the raising of drugloading rate helps to reduce the medication time of patient
Number mildly, slowly discharges active ingredient, plays dauer effect, the disease for needing the long period to treat in this way particularly with tumour
Disease has good market prospects;
3, the present invention is mixed by the chitosan, polyvinyl alcohol, sodium alginate of certain mass, obtains shell that is uniform, stablizing
Glycan-polyvinyl alcohol-sodium alginate plural gel liquid, plural gel liquid are uniformly dispersed, do not assemble, and GO-PEG is contributed to carry in medicine
The crosslinking of core therewith;The preparation of GO-PEG gel micro-balls with nucleocapsid, is utilized the difference of water phase and oil phase solubility
The method emulsified, obtained gel micro-ball homogeneity are good.
Description of the drawings
Fig. 1 is the scanning electron microscope of the GO-PEG gel micro-balls with nucleocapsid prepared by the embodiment of the present invention 1
Figure;
Fig. 2 is the scanning electron microscope of the GO-PEG gel micro-balls with nucleocapsid prepared by the embodiment of the present invention 2
Figure;
Fig. 3 is the scanning electron microscope of the GO-PEG gel micro-balls with nucleocapsid prepared by the embodiment of the present invention 3
Figure;
The GO-PEG gel micro-balls with nucleocapsid that Fig. 4 is the embodiment of the present invention 1-3, prepared by comparative example 1-2
Drug release patterns figure.
Attached drawing identifies:1 is the drug release patterns of embodiment 1, and 2 be the drug release patterns of embodiment 2, and 3 be embodiment 3
Drug release patterns, 4 be comparative example 1 drug release patterns, 5 be comparative example 2 drug release patterns.
Specific implementation mode
In order to make the purpose of the present invention, technical solution and advantageous effect be more clearly understood, below in conjunction with specific embodiment,
The present invention will be described in further detail.It should be appreciated that described herein, specific examples are only used to explain the present invention, and
It is not construed as limiting the invention.
Embodiment 1
A kind of GO-PEG gel micro-balls with nucleocapsid are carried medicine kernel by GO-PEG and are wrapped in outside the kernel
The drug of chitosan-polyvinyl alcohol-sodium alginate plural gel shell composition, load is water soluble drug fluorouracil.
The preparation method of the GO-PEG gel micro-balls with nucleocapsid, includes the following steps described in the present embodiment:
(1) it prepares GO-PEG and carries medicine kernel:4g fluorouracils powder and 10g GO-PEG are weighed, is uniformly mixed, wherein institute
GO-PEG is stated to be obtained by the reaction using existing known amino polyethylene glycol and graphene oxide progress amide;
(2) chitosan-polyvinyl alcohol-sodium alginate plural gel liquid is prepared:The poly- second of 4g is added into 100ml deionized waters
Enol simultaneously dissolves completely, continuously adds 20ml acetic acid solutions and 2g Chitosan powders, and stirring is completely dissolved to chitosan, continues to add
Enter 1g sodium alginate powders, stirring is completely dissolved to sodium alginate, obtains chitosan-polyvinyl alcohol-sodium alginate plural gel
Liquid;
(3) chitosan-polyvinyl alcohol-made from step (2) is added in step (1) GO-PEG obtained for having loaded drug
In sodium alginate plural gel liquid, ultrasonic disperse is uniform, forms mixing water phase coagulant liquid, which is added drop-wise to dropwise
In 80 oil phase of paraffin oil-Span of 200ml, emulsification is stirred at room temperature uniformly, crosslinking agent glutaraldehyde 10g is added, is heated to 50 DEG C,
Constant temperature stirs 3h, is crosslinked, and the GO-PEG gel micro-ball suspension with nucleocapsid is formed;
(4) 50ml isopropanols are added into above-mentioned suspension, stand 40min, centrifugation and are washed with 10ml ether, mistake
It filters, be dried under vacuum to constant weight, obtain the GO-PEG gel micro-balls with nucleocapsid, the form of observed under electron microscope microballoon
And measure microspherulite diameter.Refering to fig. 1, outer layer grain size is 90 microns, 60 microns of internal layer grain size, and Microsphere Size deviation is 3%, microballoon
Homogeneity is good.
By the GO-PEG gel micro-balls with nucleocapsid that the present embodiment obtains carry out drugloading rate test, vitro Drug is released
To one's heart's content experiments, specific method and the result such as slow release effect are shown in experimental example 1 in condition and animal body.
Embodiment 2
A kind of GO-PEG gel micro-balls with nucleocapsid are carried medicine kernel by GO-PEG and are wrapped in outside the kernel
The drug of chitosan-polyvinyl alcohol-sodium alginate plural gel shell composition, load is water-insoluble medicine Tegafur.
The preparation method of the GO-PEG gel micro-balls with nucleocapsid, includes the following steps described in the present embodiment:
(1) it prepares GO-PEG and carries medicine kernel:4g fluorouracils powder and 10g GO-PEG are weighed, is uniformly mixed, wherein institute
GO-PEG is stated to be obtained by the reaction using existing known amino polyethylene glycol and graphene oxide progress amide;
(2) chitosan-polyvinyl alcohol-sodium alginate plural gel liquid is prepared:The poly- second of 9g is added into 100ml deionized waters
Enol simultaneously dissolves completely, continuously adds 20ml acetic acid solutions and 5g Chitosan powders, and stirring is completely dissolved to chitosan, continues to add
Enter 1g sodium alginate powders, stirring is completely dissolved to sodium alginate, obtains chitosan-polyvinyl alcohol-sodium alginate plural gel
Liquid;
(3) chitosan-polyvinyl alcohol-made from step (2) is added in step (1) GO-PEG obtained for having loaded drug
In sodium alginate plural gel liquid, ultrasonic disperse is uniform, forms mixing water phase coagulant liquid, which is added drop-wise to dropwise
In 80 oil phase of paraffin oil-Span of 200ml, emulsification is stirred at room temperature uniformly, crosslinking agent Geniposide 10g is added, is heated to 70 DEG C,
Constant temperature stirs 4h, is crosslinked, and the GO-PEG gel micro-ball suspension with nucleocapsid is formed;
(4) 50ml isopropanols are added into above-mentioned suspension, stand 40min, centrifugation and are washed with 10ml acetone, mistake
It filters, be dried under vacuum to constant weight, obtain the GO-PEG gel micro-balls with nucleocapsid, the form of observed under electron microscope microballoon
And measure microspherulite diameter.Referring to Fig.2, outer layer grain size is 85 microns, 60 microns of internal layer grain size, Microsphere Size deviation is 4%, microballoon
Homogeneity is good.
By the GO-PEG gel micro-balls with nucleocapsid that the present embodiment obtains carry out drugloading rate test, vitro Drug is released
To one's heart's content experiments, specific method and the result such as slow release effect are shown in experimental example 1 in condition and animal body.
Embodiment 3
A kind of GO-PEG gel micro-balls with nucleocapsid are carried medicine kernel by GO-PEG and are wrapped in outside the kernel
The drug of chitosan-polyvinyl alcohol-sodium alginate plural gel shell composition, load is water-insoluble medicine Tegafur.
The preparation method of the GO-PEG gel micro-balls with nucleocapsid, includes the following steps described in the present embodiment:
(1) it prepares GO-PEG and carries medicine kernel:5g fluorouracils powder and 12g GO-PEG are weighed, is uniformly mixed, wherein institute
GO-PEG is stated to be obtained by the reaction using existing known amino polyethylene glycol and graphene oxide progress amide;
(2) chitosan-polyvinyl alcohol-sodium alginate plural gel liquid is prepared:The poly- second of 4g is added into 100ml deionized waters
Enol simultaneously dissolves completely, continuously adds 20ml acetic acid solutions and 2g Chitosan powders, and stirring is completely dissolved to chitosan, continues to add
Enter 1g sodium alginate powders, stirring is completely dissolved to sodium alginate, obtains chitosan-polyvinyl alcohol-sodium alginate plural gel
Liquid;
(3) chitosan-polyvinyl alcohol-made from step (2) is added in step (1) GO-PEG obtained for having loaded drug
In sodium alginate plural gel liquid, ultrasonic disperse is uniform, forms mixing water phase coagulant liquid, which is added drop-wise to dropwise
In 80 oil phase of paraffin oil-Span of 200ml, emulsification is stirred at room temperature uniformly, crosslinking agent glutaraldehyde 10g is added, is heated to 50 DEG C,
Constant temperature stirs 2h, is crosslinked, and the GO-PEG gel micro-ball suspension with nucleocapsid is formed;
(4) 50ml isopropanols are added into above-mentioned suspension, are stood 45min, are centrifuged and washed with 10ml ethyl acetate
It washs, filter, be dried under vacuum to constant weight, obtain the GO-PEG gel micro-balls with nucleocapsid, observed under electron microscope microballoon
Form and measure microspherulite diameter.Refering to Fig. 3, outer layer grain size is 75 microns, 50 microns of internal layer grain size, and Microsphere Size deviation is
4%, microballoon homogeneity is good.
By the GO-PEG gel micro-balls with nucleocapsid that the present embodiment obtains carry out drugloading rate test, vitro Drug is released
To one's heart's content experiments, specific method and the result such as slow release effect are shown in experimental example 1 in condition and animal body.
Comparative example 1
(1) take the full skin of ICR mouse that the round acellular dermal matrix holder of certain diameter is made;
(2) carboxylated graphene oxide is made in ultrasound to graphene oxide under alkaline condition, under EDC catalysis, by poly- second
Glycol, which is grafted to, is made polyethyleneglycol modified graphene oxide in carboxylated graphene oxide;
(3) Tegafur is adsorbed onto on polyethyleneglycol modified graphene oxide by magnetic agitation again;
(4) manufactured polyethyleneglycol modified graphene oxide is carried into Tegafur crosslinking complexes to acellular dermal matrix
Rack surface is made and carries the 3D composite supports that Tegafur is crosslinked acellular dermal matrix based on polyethyleneglycol modified graphene oxide
Frame;
(5) chitosan-made from the present embodiment 1 is added in step (4) the 3D compound rests obtained for having loaded drug to gather
In vinyl alcohol-sodium alginate plural gel liquid, ultrasonic disperse is uniform, formed mixing water phase coagulant liquid, by the gel aqueous phase liquid by
It is added drop-wise in 80 oil phases of paraffin oil-Span of 200ml, emulsification is stirred at room temperature uniformly, crosslinking agent glutaraldehyde 10g, heating is added
To 50 DEG C, constant temperature stirs 2h, is crosslinked, and forms the GO-PEG gel micro-ball suspension with nucleocapsid;
(6) 50ml isopropanols are added into above-mentioned suspension, are stood 45min, are centrifuged and washed with 10ml ethyl acetate
It washs, filter, be dried under vacuum to constant weight, obtain the GO-PEG gel micro-balls with nucleocapsid, observed under electron microscope microballoon
Form and measure microspherulite diameter.
By the GO-PEG gel micro-balls with nucleocapsid that the present embodiment obtains carry out drugloading rate test, vitro Drug is released
To one's heart's content experiments, specific method and the result such as slow release effect are shown in experimental example 1 in condition and animal body.
Comparative example 2
(1) preparation of discrete phase fluid and continuous phase fluid
Discrete phase fluid and continuous phase fluid are prepared respectively;The discrete phase fluid by internal phase fluid, intermediate phase fluid and
Catalyst or aqueous solution of curing agent collectively constitute:The internal phase fluid is the GO-PEG of load Tegafur prepared by the present embodiment 2
Kernel;The intermediate phase fluid is chitosan-polyvinyl alcohol-sodium alginate plural gel liquid prepared by the present embodiment 2;Crosslinking agent
For glutaraldehyde;
(2) the double-deck emulsion droplet is formed
By internal phase fluid and intermediate phase fluid each lead into prior art has disclosed a kind of double-deck emulsion droplet preparation
The internal phase fluid channel of the first order microchannel of device and interphase fluid channel are logical in internal phase fluid channel and intermediate phase fluid
The intersection in road forms single layer emulsion droplet, and single layer emulsion droplet is collected by the collection channel of first order microchannel;
In the microchannel of the second level, single layer emulsion droplet is passed through single layer emulsion droplet channel, by catalyst or curing agent
Solution is passed through catalyst or curing agent channel, and continuous phase fluid is passed through continuous phase fluid channel, single layer emulsion droplet, catalyst
Or curing agent, continuous phase fluid form the double-deck emulsion droplet in intersection, are collected by the collection channel of second level microchannel
To the double-deck emulsion droplet;
(3) synchronous solidification
While forming the double-deck emulsion droplet, catalyst or curing agent in the microchannel of the second level in intermediate phase fluid
High molecular polymer be sufficiently mixed, the double-deck emulsion droplet, which is synchronized, is formed by curing microballoon, then stands 24 at a temperature of 80 DEG C
Hour, ensure the fully crosslinked solidification of microballoon, obtains drug bearing microsphere;
(4) microballoon detaches
By the reaction solution filtering after step (3) crosslinking curing, solid particle is collected, ether, water washing are used successively, after dry
Obtain drug bearing microsphere product.
By the GO-PEG gel micro-balls with nucleocapsid that the present embodiment obtains carry out drugloading rate test, vitro Drug is released
To one's heart's content experiments, specific method and the result such as slow release effect are shown in experimental example 1 in condition and animal body.
Experimental example 1
1, drugloading rate is tested:
High performance liquid chromatography measures the GO- with nucleocapsid that Examples 1 to 3 and comparative example 1~2 obtain respectively
The drugloading rate of PEG gel micro-ball drugs, the results are shown in Table 1.
1 drugloading rate test experiments result of table
Group | Carry medicine content (%) |
Embodiment 1 | 3.14% |
Embodiment 2 | 3.04% |
Embodiment 3 | 3.12% |
Comparative example 1 | 2.1% |
Comparative example 2 | 1.8% |
As seen from Table 1, the drugloading rate of Examples 1 to 3 is apparently higher than comparative example 1~2, so gel prepared by the present invention is micro-
Ball drug carrying ability is good.
2, drug release in vitro situation:
Release in vitro measures the GO- with nucleocapsid that Examples 1 to 3 and comparative example 1~2 obtain with Rotating shaker respectively
PEG gel micro-ball drug-eluting curves.Concrete operations:A certain amount of drug bearing microsphere is weighed in turning in basket, 37 ± 0.5 DEG C of water-bath turns
Fast 50rmin-1.Dissolution medium is simulated intestinal fluid.In the separately sampled 1mL of different time sections, Syrups by HPLC sample contains
Amount, and calculate drug and add up release rate, stripping curve is refering to Fig. 4.
From fig. 4, it can be seen that comparing comparative example 1~2 (4,5 in Fig. 4), the drug of Examples 1 to 3 (1,2,3 in Fig. 4) is tired
It is 90% or more to count release rate, and persistent, slow release effect are good.
3, slow release effect is tested in animal body:
Dog is tested:It will implement gel micro-ball prepared by 1~3, comparative example 1~2 before experiment respectively and respectively take 0.2g, given birth to 18mL
Reason brine is mixed into 20mL syringes, and every part uses for 4 animals.By 5 groups of 20 beasle dogs point, corresponding configuration is given in grouping
Good gel micro-ball injection.Dog general anesthesia, guides through fibrescope respectively, and it is slow to carry medicinal gel microsphere suspensions by 5 kinds respectively
Inject dog stomach, every dog 4mL.Every 12 hours later, use fiber sem observation beasle dog stomach medicine-feeding part microballoon quantity.
Experimental result is shown in Table 2.
Slow release effect experimental result in 2 animal body of table
As known from Table 2, the slow-release time of 3 groups of 1~embodiment of embodiment is obviously longer than 1~2 group of comparative example, illustrates this hair
The gel micro-ball slow release effect of bright preparation is good, has significant advantageous effect.
Certainly, above description is not limitation of the present invention, and the present invention is also not limited to the example above, the art
Those of ordinary skill, any variation, addition or the replacement made in the essential scope of the present invention should also belong to the present invention's
Protection domain.
Claims (10)
1. a kind of preparation method of the GO-PEG gel micro-balls with nucleocapsid, which is characterized in that include the following steps:
(1) it prepares GO-PEG and carries medicine kernel:Using physical blending process by drug loading to GO-PEG, wherein the GO-PEG is adopted
Amide is carried out with existing known amino polyethylene glycol with graphene oxide to be obtained by the reaction;
(2) chitosan-polyvinyl alcohol-sodium alginate plural gel liquid is prepared:Polyvinyl alcohol is added into deionized water and dissolves
Completely, acetic acid solution and Chitosan powder are continuously added, stirring is completely dissolved to chitosan, continuously adds sodium alginate powder,
Stirring is completely dissolved to sodium alginate, obtains chitosan-polyvinyl alcohol-sodium alginate plural gel liquid, wherein chitosan, poly- second
Enol, sodium alginate mass ratio be (2-5):(4-9):1;
(3) chitosan-polyvinyl alcohol-seaweed made from step (2) is added in step (1) GO-PEG obtained for having loaded drug
In sour sodium plural gel liquid, ultrasonic disperse is uniform, forms mixing water phase coagulant liquid, which is added drop-wise to paraffin dropwise
In 80 oil phases of oil-Span, emulsification is stirred at room temperature uniformly, crosslinking agent is added and is crosslinked, the GO-PEG with nucleocapsid is formed
Gel micro-ball suspension;
(4) add isopropanol into above-mentioned suspension, stand, centrifuge and with organic solvent washing, filter, be dried under vacuum to
Constant weight obtains the GO-PEG gel micro-balls with nucleocapsid.
2. the preparation method of the GO-PEG gel micro-balls according to claim 1 with nucleocapsid, which is characterized in that institute
It is glutaraldehyde or Geniposide to state the crosslinking agent in step (3).
3. the preparation method of the GO-PEG gel micro-balls according to claim 1 with nucleocapsid, which is characterized in that into
It can be heated to 50-70 DEG C when the crosslinking of row step (3), constant temperature stirs 2-4h.
4. the preparation method of the GO-PEG gel micro-balls according to claim 3 with nucleocapsid, which is characterized in that into
It can be heated to 50 DEG C when the crosslinking of row step (3), constant temperature stirs 3h.
5. the preparation method of the GO-PEG gel micro-balls according to claim 1 with nucleocapsid, which is characterized in that institute
The organic solvent for stating step (4) is the combination of one or more of ether, acetone, ethyl acetate.
6. the preparation method of the GO-PEG gel micro-balls according to claim 5 with nucleocapsid, which is characterized in that institute
The organic solvent for stating step (4) is ether.
7. a kind of GO-PEG gel micro-balls with nucleocapsid, which is characterized in that according to claims 1 to 6 has
The preparation method of the GO-PEG gel micro-balls of nucleocapsid is prepared.
8. the GO-PEG gel micro-balls according to claim 7 with nucleocapsid, which is characterized in that the medicine of the load
Object is water-soluble or water-insoluble drug.
9. the GO-PEG gel micro-balls according to claim 8 with nucleocapsid, which is characterized in that the medicine of the load
Object is tumor therapeutic agent.
10. the GO-PEG gel micro-balls with nucleocapsid described in claim 7 are controlled as water-soluble or water-insoluble tumour
Treat the application of pharmaceutical carrier.
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CN111317861A (en) * | 2020-03-20 | 2020-06-23 | 西安理工大学 | Expansion acrylic acid bone cement capable of controlling release of antibiotics and preparation method thereof |
CN111317861B (en) * | 2020-03-20 | 2022-02-18 | 西安理工大学 | Expansion acrylic acid bone cement capable of controlling release of antibiotics and preparation method thereof |
CN111333749A (en) * | 2020-03-27 | 2020-06-26 | 广州古泉生物科技有限公司 | Preparation and application of polypropylene oxide-sodium alginate hydrogel |
CN113679660A (en) * | 2020-05-19 | 2021-11-23 | 北京智慧客科技创新有限公司 | Slow-release drug carrier and preparation method and application thereof |
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