CN101703781A - Magnetic medicament loading method for immunosuppressant - Google Patents
Magnetic medicament loading method for immunosuppressant Download PDFInfo
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- CN101703781A CN101703781A CN200910218613A CN200910218613A CN101703781A CN 101703781 A CN101703781 A CN 101703781A CN 200910218613 A CN200910218613 A CN 200910218613A CN 200910218613 A CN200910218613 A CN 200910218613A CN 101703781 A CN101703781 A CN 101703781A
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Abstract
The invention belongs to the technical fields of macromolecular materials and biological medicine, and relates to a medicament loading method for a magnetic macromolecular immunosuppressant with magnetic response performance. The method comprises the steps of adding magnetic particles into immunosuppressant solution to obtain magnetic medicament loading particles of the immunosuppressant by fully and evenly mixing, vibration treatment and the like. The method improves the dispersing state of the immunosuppressant, improves the bioavailability, reduces the dosage, enables the immunosuppressant to have targeting property, reduces the toxic and side effects of the medicament, and can be applied in the targeted treatment. The magnetic medicament loading particles of the immunosuppressant have the advantages of large medicament loading amount, high packing rate, simple method and low cost, and is favorable for popularization.
Description
Technical field
The invention belongs to macromolecular material and biological medicine technology field, relate to a kind of immunosuppressant magnetic drug-carrying method with magnetic response performance.
Background technology
Along with the progress of surgical technic and the continuous release of new immunosuppressant, organ transplantation patient's short-term survival rate obviously improves, 1 year people/kidney survival rate as renal transplantation surpasses 90%, but the long-term surviving rate of graft still is subjected to many factor restrictions and goes no further.Except chronic rejection, malignant tumor and the death of transplant organ band function have become two big principal elements of restriction graft long-term surviving.Because immunosuppressant, is accepted the organ transplant patient to human immune system's The Long-term Effect along with the growth of transplanting the time limit, the sickness rate of its malignant tumor is more and more higher.Seek a kind of existing immunosuppressive action, have the medicine of antitumor action very necessary again.The mammal rapamycin target protein inhibitor that with the sirolimus is representative has the targeted therapy effect again to malignant tumor in the powerful immunosuppressive action of performance, shown great attention to.But this medicine is a kind of fat-soluble medicine, therefore improves the dispersity of fat-soluble medicine, improves its bioavailability, reduces the drug use amount, protects national resource and has played significant meaning.
The magnetic high-molecular microgranule is a kind of multifunctional material that is widely used in biomedical sector.Magnetic macromolecular microsphere is that organic polymer combines the microsphere with magnetic and special construction that forms with the inorganic magnetic material, because the magnetic high-molecular microgranule has biocompatibility and distinctive magnetic responsiveness, the not only surperficial various function group that have can also be separated it rapidly by externally-applied magnetic field from various media.Above-mentioned characteristic makes the magnetic high-molecular microgranule have a wide range of applications at aspects such as clinical diagnosis, target administration, cell separation, immunoassays.Most immunosuppressant all is a fat-soluble medicine, i.e. insoluble drug, because the absorption of medicine is closely related with the dispersity of medicine, general medicine dispersity is poor more, and bioavailability is low more.Therefore improve the dispersity of these medicines, to reach the purpose that improves drug bioavailability.Yet the preparation of the package carrier of some fat-soluble medicines of having reported does not have magnetic, does not also have the magnetic targeting, and complicated process of preparation, time-consuming, as Chinese patent publication number CN1736488A, reports among the CN1457886A.And the medicine-carrying method of the fat-soluble medicine that patent CN1813682A is reported, though have magnetic, this method complexity, and envelop rate low excessively (only being 30%) do not reach officinal requirement, have limited its follow-up application.
Summary of the invention
The objective of the invention is:
In order to solve the above-mentioned technical problem that exists in the background technology, the invention provides a kind of easy and simple to handle, the magnetic drug-carrying method of the immunosuppressant that production cost is low, this method has been improved the dispersity of medicine, improved bioavailability, reduced use amount, also made it have targeting, reduced the toxic and side effects of medicine, it can be applied in the targeted therapy.Simultaneously, this medicine carrying microgranule of proof has slow-releasing, the medicine realeasing rate advantages of higher in external release experiment.
Technical scheme of the present invention:
A kind of magnetic drug-carrying method of immunosuppressant, its special character is: this method may further comprise the steps:
1) lytic immunity inhibitor
Immunosuppressant is dissolved in the solvent, is mixed with the solution of 0.1mg/ml-10mg/ml; Described solvent is the mixed liquor of methanol, ethanol, chloroform, acetone, cyclohexane extraction, Ketohexamethylene, tetrahydrofuran solution or above-mentioned two or more solution, or the mixed liquor of above-mentioned solution and ultra-pure water;
2) magnetic drug-carrying particle of preparation immunosuppressant
Magnetic particle is joined in the pyriform bottle, mass ratio according to magnetic particle and immunosuppressant agent solution is 5: 1-2: 1 dissolves good immunosuppressant with step 1) adds in the bottle, mixing, place shaking table fully to vibrate after, solvent evaporation is fallen, promptly got the magnetic drug-carrying particle of immunosuppressant.
The above-mentioned magnetic particle magnetic composite particle that to be magnetic nanoparticle form with biopolymer or inorganic material.Wherein biopolymer is that gelatin, albumin, starch and derivant thereof, chitosan, glucosan, cyclodextrin, liposome, polylactic acid, polyamino acid, poly butyric ester or second hand over third to hand over copolymer; Inorganic material is silicon dioxide, gold or silver-colored.
Above-mentioned immunosuppressant is adrenocortical hormone, microbial metabolic products, alkylating agent, antimetabolite, biological preparation, penicillamine, ethyliminum or tripterygium glycosides.Wherein adrenocortical hormone is prednisone, andrographolide or medrat; Microbial metabolic products is a cyclosporin; Alkylating agent is cyclophosphamide or chlorambucil; Antimetabolite is azathioprine or methotrexate; Biological preparation is antilymphocyte albumen or antithymocyte globulin.
Advantage of the present invention:
1, the magnetic drug-carrying particle prepared of this method owing to used the magnetic high-molecular microgranule, so have high magnetic responsiveness, can be fixed to specific position under the effect in magnetic field, carry out targeted therapy.
2, the magnetic drug-carrying particle of this immunosuppressant, realized the bag of the immunosuppressant of indissoluble is carried, and can be used as magnetic nano drug and be applied in the targeted therapy of tumor and immunity, simultaneously, this medicine carrying microgranule of proof has slow-releasing, the medicine realeasing rate advantages of higher in external release experiment.
3, the drug loading of the magnetic drug-carrying particle of this immunosuppressant is big, the envelop rate height, and technology is simple, and is with low cost, helps promoting.
Description of drawings
The drug loading and the medicine carrying time relation figure of the magnetic composite particle that carries rapamycin that Fig. 1 obtains for embodiment 2.
The specific embodiment
Embodiment 1
The adding volume ratio is 3: 1 Ketohexamethylene and a cyclohexane extraction mixed liquor in tacrolimus, is mixed with the immunosuppressant agent solution of 1mg/ml.Getting the 5mg magnetic particle joins in the 10ml pyriform bottle, add the tacrolimus solution 1mg for preparing again, under 25 ℃, rotating speed is the 48h that vibrates on the shaking table of 200rpm, reach the medicine carrying balance, the reuse Rotary Evaporators falls organic solvent evaporation, preserves under 4 ℃ of conditions, promptly gets the magnetic composite particle that carries tacrolimus.Record remaining tacrolimus in the solution by high performance liquid chromatography, utilizing following two formula to calculate drug loading again is 20%, and envelop rate is 90%.
Embodiment 2
Be mixed with the rapamycin solution of 3mg/ml with methanol.Getting the 8mg magnetic particle joins in the 10ml pyriform bottle, add 2.4mg rapamycin solution, under 25 ℃, at rotating speed the 54h that vibrates on the shaking table of 180rpm, reach the medicine carrying balance, use Rotary Evaporators that organic solvent evaporation is fallen, under 4 ℃ of conditions, preserve, promptly get the magnetic composite particle that carries rapamycin.Record remaining rapamycin in the solution by high performance liquid chromatography, utilize following two formula to calculate drug loading again, envelop rate, the gained drug loading is 25%, referring to Fig. 1, envelop rate is 95%.
Embodiment 3
With volume ratio is the mycophenolate solution that 2: 3 oxolane and cyclohexane extraction are mixed with 5mg/ml.Getting the 10mg magnetic particle joins in the 10ml pyriform bottle, add 4mg mycophenolate solution, under 25 ℃ of conditions, rotating speed is the 63h that vibrates on the shaking table of 190rpm, reach the medicine carrying balance, use Rotary Evaporators that organic solvent evaporation is fallen, under 4 ℃ of conditions, preserve, promptly get the magnetic composite particle that carries mycophenolate.Record remaining mycophenolate in the solution by high performance liquid chromatography, utilize following two formula to calculate drug loading again, envelop rate, gained drug loading are 30%, and envelop rate is 92%.
Claims (5)
1. the magnetic drug-carrying method of an immunosuppressant, it is characterized in that: this method may further comprise the steps:
1) lytic immunity inhibitor
Immunosuppressant is dissolved in the solvent, is mixed with the solution of 0.1mg/ml-10mg/ml; Described solvent is the mixed liquor of methanol, ethanol, chloroform, acetone, cyclohexane extraction, Ketohexamethylene, tetrahydrofuran solution or above-mentioned two or more solution, or the mixed liquor of above-mentioned solution and ultra-pure water;
2) magnetic drug-carrying particle of preparation immunosuppressant
Magnetic particle is joined in the pyriform bottle, mass ratio according to magnetic particle and immunosuppressant agent solution is 5: 1-2: 1 dissolves good immunosuppressant with step 1) adds in the bottle, mixing, place shaking table fully to vibrate after, solvent evaporation is fallen, promptly got the magnetic drug-carrying particle of immunosuppressant.
2. the magnetic drug-carrying method of immunosuppressant according to claim 1 is characterized in that: the described magnetic particle magnetic composite particle that to be magnetic nanoparticle form with biopolymer or inorganic material.
3. the magnetic drug-carrying method of immunosuppressant according to claim 2 is characterized in that: biopolymer is that gelatin, albumin, starch and derivant thereof, chitosan, glucosan, cyclodextrin, liposome, polylactic acid, polyamino acid, poly butyric ester or second hand over third to hand over copolymer; Inorganic material is silicon dioxide, gold or silver-colored.
4. the magnetic drug-carrying method of immunosuppressant according to claim 1, it is characterized in that: described immunosuppressant is adrenocortical hormone, microbial metabolic products, alkylating agent, antimetabolite, biological preparation, penicillamine, ethyliminum or tripterygium glycosides.
5. the magnetic drug-carrying method of immunosuppressant according to claim 4, it is characterized in that: described adrenocortical hormone is prednisone, andrographolide, medrat; Microbial metabolic products is a cyclosporin; Alkylating agent is cyclophosphamide, chlorambucil; Antimetabolite is azathioprine, methotrexate; Biological preparation is antilymphocyte albumen, antithymocyte globulin.
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| CN200910218613A CN101703781A (en) | 2009-10-28 | 2009-10-28 | Magnetic medicament loading method for immunosuppressant |
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| CN200910218613A CN101703781A (en) | 2009-10-28 | 2009-10-28 | Magnetic medicament loading method for immunosuppressant |
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Cited By (5)
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| CN105339012A (en) * | 2013-05-03 | 2016-02-17 | 西莱克塔生物科技公司 | Local, concomitant administration of tolerogenic synthetic nanocarriers to reduce type i and type iv hypersensitivity |
| CN107890465A (en) * | 2017-08-11 | 2018-04-10 | 深圳市第二人民医院 | A kind of preparation method for the magnetic Nano carried medicine sustained-release microsphere for wrapping up 5 fluorouracils |
| US9987354B2 (en) | 2011-04-29 | 2018-06-05 | Selecta Biosciences, Inc. | Tolerogenic synthetic nanocarriers for antigen-specific deletion of T effector cells |
| US10046064B2 (en) | 2014-09-07 | 2018-08-14 | Selecta Biosciences, Inc. | Methods and compositions for attenuating exon skipping anti-viral transfer vector immune responses |
| US11426451B2 (en) | 2017-03-11 | 2022-08-30 | Selecta Biosciences, Inc. | Methods and compositions related to combined treatment with antiinflammatories and synthetic nanocarriers comprising an immunosuppressant |
-
2009
- 2009-10-28 CN CN200910218613A patent/CN101703781A/en active Pending
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| US11235057B2 (en) | 2011-04-29 | 2022-02-01 | Selecta Biosciences, Inc. | Methods for providing polymeric synthetic nanocarriers for generating antigen-specific tolerance immune responses |
| US9987354B2 (en) | 2011-04-29 | 2018-06-05 | Selecta Biosciences, Inc. | Tolerogenic synthetic nanocarriers for antigen-specific deletion of T effector cells |
| US11779641B2 (en) | 2011-04-29 | 2023-10-10 | Selecta Biosciences, Inc. | Tolerogenic synthetic nanocarriers for allergy therapy |
| US11717569B2 (en) | 2011-04-29 | 2023-08-08 | Selecta Biosciences, Inc. | Tolerogenic synthetic nanocarriers |
| US10420835B2 (en) | 2011-04-29 | 2019-09-24 | Selecta Biosciences, Inc. | Tolerogenic synthetic nanocarriers for antigen-specific deletion of T effector cells |
| US10039822B2 (en) | 2011-04-29 | 2018-08-07 | Selecta Biosciences, Inc. | Method for providing polymeric synthetic nanocarriers for generating antigen-specific tolerance immune responses |
| US10441651B2 (en) | 2011-04-29 | 2019-10-15 | Selecta Biosciences, Inc. | Tolerogenic synthetic nanocarriers for generating CD8+ regulatory T cells |
| US9993548B2 (en) | 2011-04-29 | 2018-06-12 | Selecta Biosciences, Inc. | Tolerogenic synthetic nanocarriers for inducing regulatory B cells |
| US10004802B2 (en) | 2011-04-29 | 2018-06-26 | Selecta Biosciences, Inc. | Tolerogenic synthetic nanocarriers for generating CD8+ regulatory T cells |
| US11298342B2 (en) | 2013-05-03 | 2022-04-12 | Selecta Biosciences, Inc. | Methods providing a therapeutic macromolecule and synthetic nanocarriers comprising immunosuppressant locally and concomitantly to reduce both type I and type IV hypersensitivity |
| US10357482B2 (en) | 2013-05-03 | 2019-07-23 | Selecta Biosciences, Inc. | Methods providing a therapeutic macromolecule and synthetic nanocarriers comprising immunosuppressant locally and concomitantly to reduce both type I and type IV hypersensitivity |
| US10335395B2 (en) | 2013-05-03 | 2019-07-02 | Selecta Biosciences, Inc. | Methods of administering immunosuppressants having a specified pharmacodynamic effective life and therapeutic macromolecules for the induction of immune tolerance |
| US10668053B2 (en) | 2013-05-03 | 2020-06-02 | Selecta Biosciences, Inc. | Tolerogenic synthetic nanocarriers to reduce or prevent anaphylaxis in response to a non-allergenic antigen |
| CN105339012A (en) * | 2013-05-03 | 2016-02-17 | 西莱克塔生物科技公司 | Local, concomitant administration of tolerogenic synthetic nanocarriers to reduce type i and type iv hypersensitivity |
| US10434088B2 (en) | 2013-05-03 | 2019-10-08 | Selecta Biosciences, Inc. | Methods related to administering immunosuppressants and therapeutic macromolecules at a reduced pharmacodynamically effective dose |
| US10357483B2 (en) | 2013-05-03 | 2019-07-23 | Selecta Biosciences, Inc. | Methods comprising dosing combinations for reducing undesired humoral immune responses |
| US10071114B2 (en) | 2014-09-07 | 2018-09-11 | Selecta Biosciences, Inc. | Methods and compositions for attenuating gene expression modulating anti-viral transfer vector immune responses |
| US10046064B2 (en) | 2014-09-07 | 2018-08-14 | Selecta Biosciences, Inc. | Methods and compositions for attenuating exon skipping anti-viral transfer vector immune responses |
| US11633422B2 (en) | 2014-09-07 | 2023-04-25 | Selecta Biosciences, Inc. | Methods and compositions for attenuating anti-viral transfer vector immune responses |
| US11426451B2 (en) | 2017-03-11 | 2022-08-30 | Selecta Biosciences, Inc. | Methods and compositions related to combined treatment with antiinflammatories and synthetic nanocarriers comprising an immunosuppressant |
| CN107890465A (en) * | 2017-08-11 | 2018-04-10 | 深圳市第二人民医院 | A kind of preparation method for the magnetic Nano carried medicine sustained-release microsphere for wrapping up 5 fluorouracils |
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Application publication date: 20100512 |