CN102921011B - Thermosensitive polymer microspheres imitating morphology of blood cells and preparation method thereof - Google Patents
Thermosensitive polymer microspheres imitating morphology of blood cells and preparation method thereof Download PDFInfo
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- CN102921011B CN102921011B CN201210448911.1A CN201210448911A CN102921011B CN 102921011 B CN102921011 B CN 102921011B CN 201210448911 A CN201210448911 A CN 201210448911A CN 102921011 B CN102921011 B CN 102921011B
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Abstract
The invention relates to thermosensitive polymer microspheres imitating morphology of blood cells and a preparation method thereof. Components of the microspheres comprise thermosensitive polymer poly N-isopropyl acrylamide and human body compatible material phosphatidyl choline, and the mass ratio of the thermosensitive polymer poly N-isopropyl acrylamide and the human body compatible material phosphatidyl choline is 1-5:10; the preparation method comprises (1) hanging the thermosensitive polymer poly N-isopropyl acrylamide and the human body compatible material phosphatidyl choline in organic solvent and stirring in at room temperature, so that electrospray stock solution is blended; and (2) carrying out electrostatic spray for the electrospray stock solution and carrying out vacuum drying for collected samples, so that the polymer microspheres can be obtained. The preparation method is simple in process, fast and convenient, and safe in operation, the thermosensitive polymer microspheres are evenly distributed and are similar to the blood cells of human body in shape and appearance, and can be used in the fields of drug release and temperature response.
Description
Technical field
The invention belongs to temperature sensitive polymer microsphere and preparation field thereof, be specifically related to a kind of imitative hemocyte pattern temperature sensitive polymer microsphere and preparation method thereof.
Background technology
In recent years, along with emerging in large numbers and the fast development of pharmaceutical preparation industry of many novel high polymer materials, macromolecular material is more and more widely for the research and development of new drug, and brought into play very important effect.In human body environment, medicine not only will discharge, and need at specific temperature, discharge and just can reach better therapeutic effect.
Poly-N-isopropyl acrylamide is a kind of typical temperature sensitivity macromolecule, no matter is in the medicine hierarchy of control, or has tempting application prospect in the field such as artificial muscle, biomaterial.Current research shows that poly-N-isopropyl acrylamide chain has an obvious phase change near 32 DEG C, 32 DEG C of following polymer chains exist with the random coil form stretching, can be curled into the bead of collapsing higher than 32 DEG C of polymer chains, this temperature is called as minimum critical solution temperature (LCST).In recent years, people are devoted to utilize the functional material of this feature development temperature-responsive for experiments such as differential calorimetric, nuclear magnetic resonance, NMR, fluorescence spectruies.
Electrostatic spray obtains people's extensive concern in recent years as a kind of new method of preparing microsphere, utilize the Macromolecule Prodrug microsphere that electrostatic spray method makes aspect medicament slow release, to have good therapeutic effect.The cardinal principle of electrostatic spray be macromolecular solution under the pushing of syringe pump, be split into many tiny droplets thereby enter into high voltage electric field, thereby droplet solvent evaporation in course of injection forms needed microsphere.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of imitative hemocyte pattern temperature sensitive polymer microsphere and preparation method thereof, and this microsphere has human body hemocyte pattern, can temperature-responsive; The method is simple, quick, handling safety is applicable to fairly large generation, has a good application prospect.
One of the present invention is imitated hemocyte pattern temperature sensitive polymer microsphere, and the temperature sensitive polymer that is 1-5:10 by mass ratio and human compatibility material phosphatidylcholine form.
The diameter of described microsphere is at 2-3 μ m.
Described microsphere pattern is similar to human body hemocyte, becomes spheroid or elliposoidal, and has depression.
Described temperature sensitive polymer is poly-N-isopropyl acrylamide.
The preparation method of a kind of imitative hemocyte pattern temperature sensitive polymer microsphere of the present invention, comprising:
(1) temperature sensitive polymer and human compatibility material phosphatidylcholine are suspended from organic solvent, under room temperature, stir, be mixed with EFI stock solution; The mass volume ratio of temperature sensitive polymer and organic solvent is 10g:5-15mL, and the mass ratio of temperature sensitive polymer and human compatibility material phosphatidylcholine is 1-5:10;
(2) the EFI stock solution of above-mentioned gained is carried out to electrostatic spray, the sample of collecting carries out vacuum drying and obtains temperature sensitive polymer microsphere.
Organic solvent in described step (1) is one or more in dichloromethane, dehydrated alcohol; Wherein, in the time that organic solvent is dichloromethane and dehydrated alcohol, the volume ratio of dichloromethane and dehydrated alcohol is 2-3:2.
The process conditions of the electrostatic spray in described step (2) are: flow velocity 0.5-1.2mL/h, and dash receiver is 10-25cm from the distance of EFI mouth, and voltage is 8-18kv, and ambient temperature is 15-27 DEG C, and ambient humidity is 40-70%.
The number of times of the electrostatic spray in described step (2) is 3 ~ 4 times.
beneficial effect
(1) simple, quick, the handling safety of the inventive method is applicable to fairly large generation, has a good application prospect;
(2) the prepared microsphere of the present invention has human body hemocyte pattern, has temperature-responsive simultaneously, for the drug release experiment in later stage provides basis.
Brief description of the drawings
Fig. 1 is electrostatic spray process schematic representation;
Fig. 2 is imitative hemocyte pattern temperature sensitive polymer microsphere stereoscan photograph;
Fig. 3 is stereoscan photograph under imitative hemocyte pattern temperature sensitive polymer microsphere different in flow rate;
Fig. 4 is stereoscan photograph under the different voltage of imitative hemocyte temperature sensitive polymer microsphere.
Detailed description of the invention
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment are only not used in and limit the scope of the invention for the present invention is described.In addition should be understood that those skilled in the art can make various changes or modifications the present invention after having read the content of the present invention's instruction, these equivalent form of values fall within the application's appended claims limited range equally.
Embodiment 1
Take the phosphatidylcholine of 0.1g, be dissolved in 5ml dichloromethane, add 1g poly-N-isopropyl acrylamide, on magnetic stirring apparatus, at room temperature stir, obtain temperature sensitive polymer EFI stock solution.
The EFI stock solution preparing is imported in administrator (5mL syringe), adopt No. 9 injection needles as playpipe, connect the positive pole of high voltage power supply, aluminium foil microsphere receiver sheet connects negative pole.Electrostatic spray process conditions are: voltage 8kv, and flow velocity 0.5mL/h, dash receiver is apart from 10cm, 15 DEG C of temperature, air humidity 40%.Both obtained temperature sensitive polymer microsphere.After vacuum drying, with scanning electron microscopic observation, result as shown in Figure 2.
Embodiment 2
Take the phosphatidylcholine of 0.1g, be dissolved in the ethanol and dichloromethane (ethanol: dichloromethane=1:1) of 5ml, add 0.5g poly-N-isopropyl acrylamide, on magnetic stirring apparatus, at room temperature stir, obtain temperature sensitive polymer EFI stock solution.
The EFI stock solution preparing is imported in administrator (5ml syringe), adopt No. 9 injection needles as playpipe, connect the positive pole of high voltage power supply, aluminium foil microsphere receiver sheet connects negative pole.Electrostatic spray process conditions are: voltage 13kv, and flow velocity 1.2mL/h, dash receiver is apart from 15cm, 24 DEG C of temperature, air humidity 60%.Both obtained temperature sensitive polymer microsphere.After vacuum drying, with scanning electron microscopic observation, result as shown in Figure 3.
Embodiment 3
Take the phosphatidylcholine of 0.2g, be dissolved in 15ml ethanol and dichloromethane (ethanol: dichloromethane=6:4), add 1g poly-N-isopropyl acrylamide, on magnetic stirring apparatus, at room temperature stir, obtain temperature sensitive polymer EFI stock solution.
The EFI stock solution preparing is imported in administrator (5ml syringe), adopt No. 9 injection needles as playpipe, connect the positive pole of high voltage power supply, aluminium foil microsphere receiver sheet connects negative pole.Electrostatic spray process conditions are: voltage 18kv, and flow velocity 0.8mL/h, dash receiver is apart from 25cm, 27 DEG C of temperature, air humidity 70%.Both obtained temperature sensitive polymer microsphere.After vacuum drying, with scanning electron microscopic observation, result as shown in Figure 4.
Claims (5)
1. an imitative hemocyte pattern temperature sensitive polymer microsphere, is characterized in that: the temperature sensitive polymer that is 1-5:10 by mass ratio and human compatibility material phosphatidylcholine form, and wherein temperature sensitive polymer is poly-N-isopropyl acrylamide;
The wherein preparation method of temperature sensitive polymer microsphere, comprising:
(1) temperature sensitive polymer and human compatibility material phosphatidylcholine are suspended from organic solvent, under room temperature, stir, be mixed with EFI stock solution; The mass volume ratio of temperature sensitive polymer and organic solvent is 10g:5-15mL; Wherein organic solvent is one or more in dichloromethane, dehydrated alcohol; Wherein, in the time that organic solvent is dichloromethane and dehydrated alcohol, the volume ratio of dichloromethane and dehydrated alcohol is 2-3:2;
(2) the EFI stock solution of above-mentioned gained is carried out to electrostatic spray, the sample of collecting carries out vacuum drying and obtains temperature sensitive polymer microsphere; Wherein the process conditions of electrostatic spray are: flow velocity 0.5-1.2mL/h, and dash receiver is 10-25cm from the distance of EFI mouth, and voltage is 8-18kv, and ambient temperature is 15-27 DEG C, and ambient humidity is 40-70%.
2. the imitative hemocyte pattern temperature sensitive polymer microsphere of one according to claim 1, is characterized in that: the diameter of described microsphere is at 2-3 μ m.
3. the imitative hemocyte pattern temperature sensitive polymer microsphere of one according to claim 1, is characterized in that: described microsphere pattern is similar to human body hemocyte, becomes spheroid or elliposoidal, and has depression.
4. the preparation method of a kind of imitative hemocyte pattern temperature sensitive polymer microsphere according to claim 1, comprising:
(1) temperature sensitive polymer and human compatibility material phosphatidylcholine are suspended from organic solvent, under room temperature, stir, be mixed with EFI stock solution; The mass volume ratio of temperature sensitive polymer and organic solvent is 10g:5-15mL, and the mass ratio of temperature sensitive polymer and human compatibility material phosphatidylcholine is 1-5:10; Wherein organic solvent is one or more in dichloromethane, dehydrated alcohol; Wherein, in the time that organic solvent is dichloromethane and dehydrated alcohol, the volume ratio of dichloromethane and dehydrated alcohol is 2-3:2;
(2) the EFI stock solution of above-mentioned gained is carried out to electrostatic spray, the sample of collecting carries out vacuum drying and obtains temperature sensitive polymer microsphere; Wherein the process conditions of electrostatic spray are: flow velocity 0.5-1.2mL/h, and dash receiver is 10-25cm from the distance of EFI mouth, and voltage is 8-18kv, and ambient temperature is 15-27 DEG C, and ambient humidity is 40-70%.
5. the preparation method of a kind of imitative hemocyte pattern temperature sensitive polymer microsphere according to claim 4, is characterized in that:
The number of times of the electrostatic spray in described step (2) is 3～4 times.
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Citations (7)
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| CN101173020A (en) * | 2007-10-11 | 2008-05-07 | 同济大学 | Method for producing temperature sensing polymer gel microsphere |
| CN101310852A (en) * | 2008-04-23 | 2008-11-26 | 东华大学 | Preparation method of temperature sensitive type microcapsule coated by hydrophobic core material |
| CN101653714A (en) * | 2009-09-10 | 2010-02-24 | 复旦大学 | Fibroin nanosphere prepared by electrostatic spraying technology as well as preparation method and preparation device thereof |
| CN102020855A (en) * | 2010-11-25 | 2011-04-20 | 北京化工大学 | Electrostatic spraying forming method of amino-acid ester substituted polyphosphazene microspheres |
| CN102198102A (en) * | 2011-05-30 | 2011-09-28 | 东华大学 | Preparation method of drug-carrying microspheres |
| CN102648897A (en) * | 2012-04-28 | 2012-08-29 | 东华大学 | Ketoprofen macromolecular prodrug polymer microsphere and preparation method thereof |
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- 2012-11-09 CN CN201210448911.1A patent/CN102921011B/en not_active Expired - Fee Related
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1438877A (en) * | 2000-05-23 | 2003-08-27 | 迈内实验室 | Prolonged release micro spheres for injection delivery and preparation method |
| CN101173020A (en) * | 2007-10-11 | 2008-05-07 | 同济大学 | Method for producing temperature sensing polymer gel microsphere |
| CN101310852A (en) * | 2008-04-23 | 2008-11-26 | 东华大学 | Preparation method of temperature sensitive type microcapsule coated by hydrophobic core material |
| CN101653714A (en) * | 2009-09-10 | 2010-02-24 | 复旦大学 | Fibroin nanosphere prepared by electrostatic spraying technology as well as preparation method and preparation device thereof |
| CN102020855A (en) * | 2010-11-25 | 2011-04-20 | 北京化工大学 | Electrostatic spraying forming method of amino-acid ester substituted polyphosphazene microspheres |
| CN102198102A (en) * | 2011-05-30 | 2011-09-28 | 东华大学 | Preparation method of drug-carrying microspheres |
| CN102648897A (en) * | 2012-04-28 | 2012-08-29 | 东华大学 | Ketoprofen macromolecular prodrug polymer microsphere and preparation method thereof |
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