CN109529096A - A kind of uniform grading gelatin embolism agent and preparation method thereof - Google Patents
A kind of uniform grading gelatin embolism agent and preparation method thereof Download PDFInfo
- Publication number
- CN109529096A CN109529096A CN201811389703.2A CN201811389703A CN109529096A CN 109529096 A CN109529096 A CN 109529096A CN 201811389703 A CN201811389703 A CN 201811389703A CN 109529096 A CN109529096 A CN 109529096A
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- Prior art keywords
- gelatin
- microsphere
- photoinitiator
- solution
- microchannel
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/10—Polypeptides; Proteins
- A61L24/104—Gelatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/12—Nanosized materials, e.g. nanofibres, nanoparticles, nanowires, nanotubes; Nanostructured surfaces
Abstract
The invention discloses a kind of uniform grading gelatin microsphere embolization agents and preparation method thereof, the method steps are as follows: the mixture of gelatin or gelatin and drug is dissolved in water at 40~70 DEG C, 0.1~1% photoinitiator is added, stirs evenly and filters, obtain 15~50% gelatin solution mixture.Gelatin solution mixture is formed into gelatine microsphere by shearing in microchannel with containing the oil phase liquid paraffin that mass ratio is 1~20%span80, wherein water/oil volume ratio is 1/1~1/10, it shears the gelatine microsphere formed and is wound on radiation source device in microchannel with certain rate, radiation source is 3~30cm with a distance from gelatine microsphere, it is 1~30min by the time, it is collected in container after overshoot, then washed dehydration obtains microsphere embolization agent.The method of the present invention preparation gelatine microsphere roundness is good, uniform particle sizes and there is certain elasticity and dilatancy, microspherulite diameter to be distributed in any relatively narrow range of 50~1000um.
Description
Technical field
The present invention relates to interventional medicine field of material technology, and it is micro- to particularly relate to a kind of gelatin for embolotherapy
The application of ball bolt suppository and preparation method thereof.
Background technique
Minimally-invasive vascular intervenien therapy technology is gradually promoted at home in recent years as emerging medicine,
Therapeutic effect gains universal acceptance.Its general procedure be under the guiding of medical imaging device, it is selective to intervene Medical treatment device
Tool is sent to many vitals of human body and position through naturally occurring blood vessel access, such as: heart, liver, brain, kidney, digestive system
And reproductive system, it is the important technology and method for carrying out diagnosing and treating, has without operation, wound is small, medical expense is opposite
Cheap advantage.
Progress of the treatment and effect of interventional medicine highly dependent upon related equipment and material, Endovascular Embolization material, especially
It is that gelatin particle embolism materials play essential effect in the treatment of minimally invasive interventional medicine.Excellent embolism materials are in the blood vessels
In interventional procedure, with its good biocompatibility, controllable internal degradation rate, antigenic extremely faint, embolism materials
Grain size can select the characteristics of, in vascular malformation occlusion, body vessel rupture urgent quick-acting haemostatic powder, inhibit tumour production,
It blocks internal abnormal blood flow channel, tissue blood flow to redistribute again, carry curative drug or bioactive molecule (such as gene material
Material, stem cell, immune vaccine, anticancer drugs, tracer material etc.) etc. diagnosing and treating during play irreplaceable work
With.Novel embolism materials will further widen use scope and medical effect, make to intervene intravascular diagnosing and treating field
Application prospect is more wide.
Gelatin is a kind of natural high-molecular compound, has good biocompatibility, the spies such as cheap, water imbibition is strong
Point, is widely used in embolotherapy.It is domestic at present clinical mainly using absorbable gelatin sponge particle suppository or the gelatin shredded sea
Silk floss, there are no gelatin microsphere embolization agent listings.According to the literature, microballoon class suppository can more embolism to distal vessels,
Better than granular pattern suppository, it is therefore necessary to optimize microspheric gelatin embolism agent.
Summary of the invention
Gelatine microsphere of the present invention is a kind of microballoon to be processed from strand by gelatin, which can be directly used for blood vessel
Embolism can also be used for embolism after attached medicine.
Technical scheme is as follows: the suppository includes following components by mass parts:
Aqueous gelatin solution: 10~30%；
Photoinitiator: 0.1~1%；
Continuous phase solution: 1~20%；
Other is water.
Further, the photoinitiator include one of Irgacure2959 photoinitiator, 819 photoinitiators or
The solution of Irgacure2959 photoinitiator, 819 photoinitiators being mixed to form.
Further, the continuous phase solution is added in oily phase by surfactant and is formulated.
Further, the surfactant includes span80 activating agent, span60 activating agent, tween20 activating agent
A kind of or any two combination is formed.
Further, the oil mutually includes the mixture of one of vegetable oil, mineral oil or vegetable oil, mineral oil.
A kind of preparation method of the uniform grading gelatin microsphere embolization agent, method includes the following steps:
The preparation of step 1, dispersed phase and continuous phase solution:
Dispersed phase: the pharmagel aqueous solution that mass concentration is 10~30% is prepared, and 0.1~1% is added in aqueous gelatin solution
Photoinitiator is as dispersed phase；
Continuous phase: surfactant is added in oily phase, and preparing containing surfactant qualities percent concentration is 1~20%
Continuous phase solution；
Step 2, the formation of gelatine microsphere:
Dispersed phase described in step 1 is respectively charged into syringe with continuous phase and microchannel is connected by micro-injection pump, is led to
The flow velocity for crossing control micro pump, flows through dispersed phase in micro passage reaction and is sheared by continuous phase, be continuously generated of uniform size, outer
See the w/o type gelatin drop of rounding；
Step 3, the collection of gelatine microsphere:
The gelatin drop that step 2 shearing is generated is in microchannel by being collected in container after being wrapped in radiation source certain distance；
The radiation source is gamma-rays, and radiation source intensity is 10~80kGy, and radiation source is 5~30cm apart from gelatin drop；
Step 4, gelatine microsphere separation, drying:
Cured gelatine microsphere is sunken to container bottom, removes upper oil phase, uses isopropanol mode of washing will be bright after supplementing pure water
Glue microballoon and residual separation of oil and the gelatine microsphere after being dried.
Further, in step 1, the gelatin mass concentration in aqueous gelatin solution mixture is 10~30%, photoinitiator
Concentration be 0.1~1%, the photoinitiator include one of Irgacure2959 photoinitiator, 819 photoinitiators or
The solution of Irgacure2959 photoinitiator, 819 photoinitiators being mixed to form.
Further, in step 1, concentration containing surfactant qualities is 1~20% in continuous phase, the surfactant
It is formed including one of span80 activating agent, span60 activating agent, tween20 activating agent or the combination of any two, it is described
Oily mutually includes the mixture of one of vegetable oil, mineral oil or vegetable oil, mineral oil.
Further, in step 2, the microchannel is the micro-pipe of T-shape structure, the diameter of the microchannel 0.2~
2mm；Gelatin drop forming process is completed in the T-shape structure of microchannel；The dispersed phase and the flow rate of continuous phase point
It Wei not 0.2~2mL/h, 4~15 mL/h.
Further, in step 3, through microchannel, the required time into container is 1~20min to the gelatin solution drip.
The beneficial effects of the present invention are: the method for the present invention preparation gelatine microsphere roundness is good, uniform particle sizes and has one
Fixed elasticity and dilatancy, microspherulite diameter are distributed in any relatively narrow range of 50~1000um, compensate for the domestic prior art at present
Deficiency.
Detailed description of the invention
Fig. 1 is the preparation method schematic diagram of uniform grading gelatin microsphere embolization agent of the present invention.
Specific embodiment
The present invention will be further described for son with reference to the accompanying drawings and examples.
Attached drawing 1 is please referred to, a kind of uniform grading gelatin microsphere embolization agent, which includes following components by mass parts:
Aqueous gelatin solution: 10~30%；
Photoinitiator: 0.1~1%；
Continuous phase solution: 1~20%；
Other is water.
Further, the photoinitiator include one of Irgacure2959 photoinitiator, 819 photoinitiators or
The solution of Irgacure2959 photoinitiator, 819 photoinitiators being mixed to form.
Further, the continuous phase solution is added in oily phase by surfactant and is formulated.
Further, the surfactant includes span80 activating agent, span60 activating agent, tween20 activating agent
A kind of or any two combination is formed.
Further, the oil mutually includes the mixture of one of vegetable oil, mineral oil or vegetable oil, mineral oil.
A kind of preparation method of the uniform grading gelatin microsphere embolization agent, method includes the following steps:
The preparation of step 1, dispersed phase and continuous phase solution:
Dispersed phase: the aqueous gelatin solution that mass percent concentration is 20% is prepared, and the Irgacure2959 of addition 0.2% is light-initiated
Mixed liquor is made as in dispersed phase solution injection dispersed phase syringe 1 in agent；
Continuous phase: preparing the atoleine solution for the Span80 for being 3% containing mass percent, continuous as continuous phase solution injection
In phase syringe 7；
Step 2, the formation of gelatine microsphere:
By dispersed phase syringe 1 described in step 1 and continuous phase syringe 7, pass through the T-shape microchannel of micro passage reaction 3
Connection, is 1mL/h by the flow that dispersed phase syringe pump 2 adjusts dispersed phase solution, adjusts continuous phase by continuous phase syringe pump 6
The flow of solution is 10mL/h, flows through dispersed phase in micro passage reaction and is sheared by continuous phase, is continuously generated of uniform size, outer
See the w/o type gelatin drop of rounding；
Step 3, the collection of gelatine microsphere:
The gelatin drop that step 2 shearing generates is collected in appearance after microchannel passes through and is wrapped in radiation 4 certain distance of source device
In device 5, the radiation source is gamma-rays, and radiation intensity 30kGy, adjusting radiation source apart from gelatin drop is 20cm；
Step 4, gelatine microsphere separation, drying:
Microballoon is 2min by the microtubular time, obtains the microsphere particle that partial size is 150 μm, and cured gelatine microsphere is sunken to container
5 bottoms remove upper oil phase, supplement and separation of oil and are freezed gelatine microsphere with remaining using isopropanol mode of washing after pure water
It is dry, solidification.
Further, in step 1, the gelatin mass concentration in aqueous gelatin solution mixture is 10~30%, photoinitiator
Concentration be 0.1~1%, the photoinitiator include one of Irgacure2959 photoinitiator, 819 photoinitiators or
The solution of Irgacure2959 photoinitiator, 819 photoinitiators being mixed to form.
Further, in step 1, concentration containing surfactant qualities is 1~20% in continuous phase, the surfactant
It is formed including one of span80 activating agent, span60 activating agent, tween20 activating agent or the combination of any two, it is described
Oily mutually includes the mixture of one of vegetable oil, mineral oil or vegetable oil, mineral oil.
Further, in step 2, the microchannel is the micro-pipe of T-shape structure, the diameter of the microchannel 0.2~
2mm；Gelatin drop forming process is completed in the T-shape structure of microchannel；The dispersed phase and the flow rate of continuous phase point
It Wei not 0.2~2mL/h, 4~15 mL/h.
Further, in step 3, through microchannel, the required time into container is 1~20min to the gelatin solution drip.
The foregoing is merely one of specific embodiment of the invention, but the scope of protection of the present invention is not limited thereto, any
Those skilled in the art without departing from the spirit and scope of the invention, can details to technical solution of the present invention and form into
Row modifications or substitutions, but these modifications and replacement are encompassed by within protection scope of the present invention.
Claims (10)
1. a kind of uniform grading gelatin microsphere embolization agent, which is characterized in that the suppository includes following components by mass parts:
Aqueous gelatin solution: 10~30%；
Photoinitiator: 0.1~1%；
Continuous phase solution: 1~20%；
Other is water.
2. a kind of uniform grading gelatin microsphere embolization agent according to claim 1, which is characterized in that the photoinitiator packet
Include one of Irgacure2959 photoinitiator, 819 photoinitiators or Irgacure2959 photoinitiator, 819 photoinitiators
The solution being mixed to form.
3. a kind of uniform grading gelatin microsphere embolization agent according to claim 1, which is characterized in that the continuous phase solution
It is added in oily phase and is formulated by surfactant.
4. a kind of uniform grading gelatin microsphere embolization agent according to claim 3, which is characterized in that the surfactant
It is formed including one of span80 activating agent, span60 activating agent, tween20 activating agent or the combination of any two.
5. a kind of uniform grading gelatin microsphere embolization agent according to claim 3, which is characterized in that the oil mutually includes planting
The mixture of one of object oil, mineral oil or vegetable oil, mineral oil.
6. a kind of preparation method with uniform grading gelatin microsphere embolization agent described in Claims 1 to 5 any one, feature
Be method includes the following steps:
The preparation of step 1, dispersed phase and continuous phase solution:
Dispersed phase: the pharmagel aqueous solution that mass concentration is 10~30% is prepared, and 0.1~1% is added in aqueous gelatin solution
Photoinitiator is as dispersed phase；
Continuous phase: surfactant is added in oily phase, and preparing containing surfactant qualities percent concentration is 1~20%
Continuous phase solution；
Step 2, the formation of gelatine microsphere:
Dispersed phase described in step 1 is respectively charged into syringe with continuous phase and microchannel is connected by micro-injection pump, is led to
The flow velocity for crossing control micro pump, flows through dispersed phase in micro passage reaction and is sheared by continuous phase, be continuously generated of uniform size, outer
See the w/o type gelatin drop of rounding；
Step 3, the collection of gelatine microsphere:
The gelatin drop that step 2 shearing is generated is in microchannel by being collected in container after being wrapped in radiation source certain distance；
The radiation source is gamma-rays, and radiation source intensity is 10~80kGy, and radiation source is 5~30cm apart from gelatin drop；
Step 4, separation, the drying of gelatine microsphere:
Cured gelatine microsphere is sunken to container bottom, removes upper oil phase, uses isopropanol mode of washing will be bright after supplementing pure water
Glue microballoon and residual separation of oil and the gelatine microsphere after being dried.
7. the preparation method of monodisperse gelatine microsphere as claimed in claim 6, it is characterised in that in step 1, aqueous gelatin solution
Gelatin mass concentration in mixture is 10~30%, and the concentration of photoinitiator is 0.1~1%, and the photoinitiator includes
One of Irgacure2959 photoinitiator, 819 photoinitiators or Irgacure2959 photoinitiator, 819 photoinitiators
The solution being mixed to form.
8. the preparation method of monodisperse gelatine microsphere as claimed in claim 6, it is characterised in that in step 1, contain in continuous phase
Surfactant qualities concentration be 1~20%, the surfactant include span80 activating agent, span60 activating agent,
One of tween20 activating agent or the combination of any two are formed, it is described oil mutually include one of vegetable oil, mineral oil or
The mixture of vegetable oil, mineral oil.
9. the preparation method of monodisperse gelatine microsphere as claimed in claim 6, it is characterised in that in step 2, the microchannel
It is the micro-pipe of T-shape structure, the diameter of the microchannel is in 0.2~2mm；T-shape of the gelatin drop forming process in microchannel
It is completed in structure；The dispersed phase and the flow rate of continuous phase are respectively 0.2~2mL/h, 4~15 mL/h.
10. the preparation method of monodisperse gelatine microsphere as claimed in claim 6, it is characterised in that in step 3, the gelatin
Drop is 1~20min the time required to flowing through microchannel into container.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811389703.2A CN109529096A (en) | 2018-11-21 | 2018-11-21 | A kind of uniform grading gelatin embolism agent and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811389703.2A CN109529096A (en) | 2018-11-21 | 2018-11-21 | A kind of uniform grading gelatin embolism agent and preparation method thereof |
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| CN109529096A true CN109529096A (en) | 2019-03-29 |
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| CN201811389703.2A Pending CN109529096A (en) | 2018-11-21 | 2018-11-21 | A kind of uniform grading gelatin embolism agent and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113198041A (en) * | 2021-04-27 | 2021-08-03 | 四川大学 | Visible monodisperse embolism microsphere with internal radiation therapeutic performance and preparation method thereof |
| CN114392384A (en) * | 2021-12-24 | 2022-04-26 | 河南驼人医疗器械研究院有限公司 | Method for preparing high drug-loading rate embolism microsphere and collecting device |
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| CN114392384A (en) * | 2021-12-24 | 2022-04-26 | 河南驼人医疗器械研究院有限公司 | Method for preparing high drug-loading rate embolism microsphere and collecting device |
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