CN103656651A - Drug-loaded composite microsphere and preparation method thereof - Google Patents
Drug-loaded composite microsphere and preparation method thereof Download PDFInfo
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Abstract
The invention relates to a drug-loaded composite microsphere and a preparation method thereof. The drug-loaded composite microsphere comprises a drug-loaded core microsphere and a polyester coating, wherein the drug-loaded core microsphere mainly comprises a polyester high molecular polymer matrix, an inorganic raw material ingredient and a loaded drug. The mass fraction of the drug-loaded core microsphere accounts for 2-80%, and the drug loading rate is 0.0002-15%. The preparation method of the composite microsphere comprises the steps of preparing the drug-loaded core microsphere and preparing the polyester coating. The drug-loaded composite microsphere is used for treating osteoporosis, administrated locally, can achieve a long-term stable slow release effect, effectively prolongs a medication cycle and avoids drug complementation injection for many times.
Description
Technical field
The invention belongs to biomedical materials field.Or rather, the present invention relates to a kind of medicine carrying complex microsphere and preparation method thereof.
Background technology
Osteoporosis is modal metabolic osteopathy, and its incidence of fracture causing is high.Nearly 200,000,000 people in the whole world suffer from osteoporosis at present, and its sickness rate has leapt to the 7th of the various commonly encountered diseases in the world.Wherein, 50-69 year women's sickness rate is higher than 50%, and male of the same age is 27.51%.According to statistics, will there is osteoporotic fracture in U.S. postmenopausal women 25%, and after 60 years old, every increase of women's age 5 years old, fracture incidence rate increases by 1 times.Bone amount due to osteoporosis obviously reduces, and this has greatly increased bone and has repaired difficulty.In China, within 2006, statistics shows, in the above crowd of China 50 years old, approximately 6,944 ten thousand people suffer from primary osteoporosis, and the men and women about 1:8 of ratio that falls ill more than newly-increased nearly 7,000,000 people of patient of annual China, cannot heal after the patient who surpasses half fractures completely.Osteoporosis is known as serious social public health problem by the whole world.
At present, the Therapeutic Method of osteoporosis mainly comprises: outside operation is fixing, bone material is filled and three kinds of methods of osteosporosis resistant medicament, but because local bone amount declines and further bone resorption, first two method is difficult to reach lastingly, effectively knitting, and clinical efficacy is not good.
For example, in osteosporosis resistant medicament, insulin-like growth factor-i (IGF-1) is a kind of important cytokine that regulates bone metabolism and bone remodeling process, with promote osteanagenesis and maintain bone density closely related.Supplement IGF-1 content in old people's serum and osseous tissue and become the new way of preventing and treating osteoporosis.Yet the IGF-1 metabolism cycle is in vivo short, needs regularly hormone, and be difficult for the local valid density that remains stable.Scholar's research confirms to have chronicity with IGF-1 treatment osteoporosis, at least need within the treatment phase more than 1 year, keep its valid density, and long-term hormone, not only causes suffering to patient, to treatment, causes very big inconvenience; And cannot keep for a long time the local valid density of IGF-1, therapeutic effect is also restricted.
Summary of the invention
The technical problem that the present invention solves is to provide a kind of medicine carrying complex microsphere, solves the prior art Chinese medicine action period short, cannot the stable valid density of long term maintenance, treat the problems such as not convenient and therapeutic effect is not good.
Another technical problem that the present invention solves is to provide the preparation method of described medicine carrying complex microsphere.
For solving the problems of the technologies described above, the technical scheme that the present invention takes: a kind of medicine carrying complex microsphere is provided, comprise medicine carrying core microsphere and and the polyester coatings of coated described medicine carrying core microsphere surface; Described medicine carrying core microsphere is mainly to consist of matter polyesters high molecular polymer matrix, inorganic raw material composition and contained medicine.
Preferably, in described medicine carrying core microsphere, polyesters high molecular polymer substrate quality percent is 30-99%, and the mass percent of inorganic raw material composition is 0.001-65%, and contained ingredient accounts for 0.0002 ~ 15% of core microspheres quality.
Preferably, described polyester coatings mass percent 20 ~ 98%; Described polyesters high molecular polymer matrix is selected from least one in polylactic acid, polyglycolic acid, poly lactic coglycolic acid, polyhydroxyalkanoate, polycaprolactone; Described inorganic matter raw material composition is selected from least one in hydroxyapatite, tricalcium phosphate, bio-vitric; Contained medicine is selected from least one in hydrophilic insulin-like growth factor-i, bone morphogenetic protein, VEGF, epidermal growth factor, antibacterial.
Preferably, described polyester coatings material is selected from least one in polyacrylate, polycaprolactone, polyhydroxyalkanoate.
For solving the problems of the technologies described above, the another technical scheme that the present invention takes: prepare the method for medicine carrying complex microsphere, comprising:
Step 1: adopt emulsifying soln legal system for medicine carrying core microsphere; And
Step 2: adopt emulsifying soln legal system for polyester coatings;
Further, described step 1 specifically comprises:
1) provide drug solution, solute is contained medicine;
2) described inorganic raw material is scattered in and in drug solution, forms suspension;
3) provide the organic solution of described polyesters high molecular polymer matrix, and described suspension is added to and in this organic solution, carries out emulsifying and form interior emulsion;
4) aqueous solution of preparation table surface-active agent obtains outer water; And
5) described interior emulsion is added outer water carry out emulsifying and obtain double emulsion, isolate described medicine carrying core microsphere.
Further, described in step 1, providing drug solution is to prepare drug solution by treating that medicine carrying thing is dissolved in pure water or phosphate buffer or acid solution; The organic solution organic solvent used that forms described polyesters high molecular polymer matrix is to be selected from least one in dichloromethane, chloroform and ethyl acetate; Described surfactant is tween series, span is serial or polyvinyl alcohol at least one.
Preferably, described in step 1, drug solution mass percent concentration is 0.000001 ~ 15%; The described inorganic matter raw material of 0.1 ~ 35mg is dispersed in this drug solution and forms suspension; Suspension is joined to emulsifying in the organic solution of the described polyesters high molecular polymer matrix that 5 ~ 10mL, concentration are 1 ~ 100mg/mL and form interior emulsion; Described interior emulsion is joined and in the outer water of aqueous surfactant solution of concentration expressed in percentage by volume 0.5 ~ 5% of 200mL, carry out emulsifying and obtain double emulsion.
Further, described step 2 specifically comprises:
A) described medicine carrying core microsphere is joined in the organic solution of polyester and form mixed liquor;
B) described mixed liquor is joined in the liquid paraffin that is mixed with surfactant and carries out stirring reaction, after separation, obtain the medicine carrying complex microsphere with polyester coatings.
Further, the organic solution of polyester described in step 2 organic solvent used is selected from least one in methanol, acetonitrile; Described surfactant is selected from least one in tween series, polyvinyl alcohol (PVA), span series.
The organic solution of polyester described in step 2 organic solvent used is selected from least one in methanol, acetonitrile; Described surfactant is selected from least one in tween series, polyvinyl alcohol (PVA), span series; In a) step of described step 2, be by the medicine carrying core microsphere of every 40 ~ 800mg join 10 ~ 20mL, concentration is in the organic solution of 2 ~ 15% polyester, mix homogeneously forms mixed liquor, the b of step 2) be that mixed liquor is joined in the liquid paraffin that is mixed with the surfactant that 200 ~ 600mL, mass percent concentration are 0.1 ~ 8% in step.
Technique scheme at least has following beneficial effect:
In the present invention, mainly pass through: the one, utilize the absorption property of inorganic particulate matter in core microsphere matrix itself and prepare the complex microsphere of high carrying drug ratio with the absorption property at organic polymer interface, the 2nd, by preparing coated and iris action that polyester coatings forms, reach and delay the object that internal drug discharges; Make contained medicine reach the target of long-term slow release, obtain the high carrying drug ratio carrier material of long-term slow release IGF-1 or other medicines, effectively prolong drug treatment cycle, avoids multiple injection tonic.
The specific embodiment
The embodiment of the present invention relates to a kind of medicine carrying complex microsphere and preparation method thereof, for loading IGF-1 or other medicines, to increase the action period of medicine, is specially adapted to treat osteoporosis, or other bone is repaired or treatment.
Medicine carrying complex microsphere of the present invention comprises medicine carrying core microsphere and polyester coatings, and it is outer that this polyester coatings is coated on described medicine carrying core microsphere; Described medicine carrying core microsphere is mainly to consist of matter polyesters high molecular polymer matrix, inorganic raw material composition and contained medicine.
In preferred embodiment, medicine carrying core microspheres quality mark accounts for 2 ~ 80%, and polyester coatings mass fraction accounts for 20-98%.Further, contained ingredient accounts for 0.0002 ~ 15% of core microspheres quality.
In a preferred embodiment, described medicine carrying core microsphere is mainly that the contained medicine of 30-99% polyesters high molecular polymer matrix, 0.001-65% inorganic raw material composition and microsphere forms.Wherein: described polyesters high molecular polymer matrix is selected from least one in the polyesters high molecular polymers such as polylactic acid (PLA), polyglycolic acid (PGA), poly lactic coglycolic acid (PLGA), polyhydroxyalkanoate (PHA), polycaprolactone (PCL); Inorganic matter raw material composition is selected from least one in hydroxyapatite (HA), tricalcium phosphate (TCP), bio-vitric (SiO2); The contained medicine of microsphere includes but not limited to hydrophilic insulin-like growth factor-i (IGF-1), bone morphogenetic protein (BMPs), VEGF (VEGF), epidermal growth factor (EGF), antibacterial (as gentamycin, vancomycin etc.).Wherein bone morphogenic protein BMP-2 s includes but not limited to BMP-1, BMP-2, BMP-3, BMP-7, BMP-14 etc.
Described coating material is preferably polyesters macromolecule, as one or more in polyacrylate (Eudrugit etc.), polycaprolactone (PCL), polyhydroxyalkanoate (PHA).
Medicine carrying complex microsphere preparation method of the present invention comprises:
Step 1: prepare medicine carrying core microsphere
0.001 ~ 20mg treats that medicine carrying thing is dissolved in pure water or phosphate buffer (PBS) or acid solution and prepares drug solution, or directly takes drug solution, and mass percentage concentration is 0.000001 ~ 15%; Again the above-mentioned inorganic matter raw material of 0.1 ~ 35mg is dispersed in this drug solution and forms suspension; Suspension is joined in the organic solution of the core microsphere polyesters high molecular polymer matrix that 5 ~ 10mL, concentration are 1 ~ 100mg/mL, and emulsifying 0.5 ~ 1min, make interior emulsion (w/o); Providing or preparing 200mL concentration expressed in percentage by volume is 0.5 ~ 5% aqueous surfactant solution, and for example 200mL, 0.5 ~ 5% polyvinyl alcohol water solution or 2% Tween solution, as outer water; Interior emulsion is added to outer water, and emulsifying 2 ~ 3min, make double emulsion (w/o/w); Double emulsion is stirred to 3h and treat organic solvent volatilization, standing over night; Centrifugal and washing, in triplicate, then after lyophilization, obtain dry medicine carrying microballoons.
The high molecular polymer of polyesters described in step 1 matrix organic solution organic solvent used is selected from least one in dichloromethane, chloroform and ethyl acetate.
When step 1 is prepared core, adopt emulsifying soln method, the surfactant of selection can be tween series (as Tween-20, Tween-60, Tween-80), polyvinyl alcohol (PVA), span series (Span-20, Span-60, Span-80) etc.
Step 2: prepare polyester coatings
The core microsphere of 40 ~ 800mg joins 10 ~ 20mL, mass percentage concentration is in the organic solution of 2 ~ 15% polyester, and mix homogeneously forms mixed liquor; Mixed liquor is joined again and be mixed with surfactant that 200 ~ 600mL, mass percentage concentration are 0.1 ~ 8% as in the liquid paraffin of span series, certain speed stirs 4 ~ 8h volatilization organic solvent; After solvent evaporates, with two kinds of isopropyl alcohols, petroleum ether, combine washing or wash with hexane; The medicine carrying complex microsphere with polyester coatings that obtains after lyophilization being dried.
The organic solvent of the material of coated substrate described in step 2 polyester can be selected one of methanol, acetonitrile etc. or its binary mixture; The surfactant that adopts emulsifying soln method to select during preparation coating can be tween series (Tween-20, Tween-60, Tween-80), polyvinyl alcohol (PVA), span series (as Span-20, Span-60, Span-80) etc.
With instantiation, be exemplary of the invention below, but not as the restriction of protection domain of the present invention.Those skilled in the art can realize the whole technical schemes of the present invention and obtain technique effect of the present invention according to following instance.
example 1
(1) prepare medicine carrying core microsphere
1mg IGF-1 is dissolved in and in 0.5mLPBS solution, forms mass percent concentration is 0.20% solution, and 30mgHA is dispersed in and in drug solution, forms suspension; Suspension is joined in the dichloromethane of PLA of 100mg/mL of 10mL, with refiner, with 3000rpm rotating speed emulsifying 30s, make interior emulsion (w/o).In 200mL water, add the Tween-80 of 2% (v/v), be stirred to and be uniformly dispersed, make outer water; Interior emulsion is added to outer water, with refiner, with 5000rpm rotating speed emulsifying 120s, make double emulsion (w/o/w); Double emulsion is stirred to 3h and treat organic solvent volatilization, standing over night.Centrifugal and washing, in triplicate, then after lyophilization, obtain dry medicine carrying core microsphere.
(2) prepare polyester coatings
The core microsphere of 800mg joins in the acetonitrile solution of 10mL, 2% PHA, mix homogeneously; Mixed liquor is joined to 200mL and be mixed with in the liquid paraffin that mass percent concentration is 2%Span-80, stir 4h, mixing speed is 1000rpm, with the organic solvent that volatilizees; After solvent evaporates with isopropyl alcohol, petroleum ether cyclic washing; The medicine carrying complex microsphere with polyester coatings that obtains after lyophilization being dried.
In this example, medicine carrying complex microsphere comprises medicine carrying core microsphere and polyester coatings, and polyester layer mass percent is 19.61%, and surplus is medicine carrying core microsphere.Further, medicine carrying core microsphere, carrying drug ratio is that 0.0870%, HA and PLA mass percent are respectively 2.8612% and 97.05%.The prepared external slow release IGF-1 of medicine carrying microballoons of this example reaches 76 days.
example 2
(1) prepare medicine carrying core microsphere
0.005 μ gVEGF is dissolved in and in 0.5mL pure water, forms mass percent concentration is 0.000001% solution, then 15mgTCP is dispersed in this drug solution and forms suspension; Suspension is joined in the chloroform of PGA of 1mg/mL of 8mL, with refiner, with 3000rpm rotating speed emulsifying 30s, make interior emulsion (w/o).In 200mL water, add the Tween-20 of 2% (v/v), be stirred to and be uniformly dispersed, make outer water; Interior emulsion is added to outer water, with refiner, with 5000rpm rotating speed emulsifying 120s, make double emulsion (w/o/w); Double emulsion is stirred to 3h and treat organic solvent volatilization, standing over night.Centrifugal and washing, in triplicate, then after lyophilization, obtain dry medicine carrying core microsphere.
(2) prepare polyester coatings
The core microsphere of 400mg joins in the methanol solution of 20mL, 2% PCL, mix homogeneously; Mixed liquor is joined to 400mL again and be mixed with in the liquid paraffin that mass percent concentration is 0.1%Span-60, stir 6h, mixing speed is 800rpm, with the organic solvent that volatilizees; After solvent evaporates with hexane cyclic washing; The medicine carrying complex microsphere with polyester coatings that obtains after lyophilization being dried.
In this example, medicine carrying complex microsphere comprises medicine carrying core microsphere and polyester coatings, and polyester coatings mass percent is 48.13%, and surplus is medicine carrying core microsphere.In medicine carrying core microsphere, carrying drug ratio is that 3.8667%, TCP and PGA mass percent are respectively 59.20% and 36.93%.The prepared external slow release VEGF of medicine carrying microballoons of this example reaches 66 days.
example 3
(1) prepare medicine carrying core microsphere
1 μ g BMP-2 is dissolved in and in 0.5mL2% acetum, forms mass percent concentration is 0.0002% solution, then by 25mg SiO
2be dispersed in to form in drug solution and form suspension; Suspension is joined in the dichloromethane of PLGA of 50mg/mL of 9mL, with refiner, with 3000rpm rotating speed emulsifying 60s, make interior emulsion (w/o).At 70 ℃, PVA is dissolved to the aqueous solution that forms 200mL 1%, as outer water; Interior emulsion is added to outer water, with refiner, with 4000rpm rotating speed emulsifying 120s, make double emulsion (w/o/w); Double emulsion is stirred to 3h and treat organic solvent volatilization, standing over night.Centrifugal and washing, in triplicate, then after lyophilization, obtain dry medicine carrying core microsphere.
(2) prepare polyester coatings
The core microsphere of 300mg joins in the methanol solution of 20mL, 5% Eudrugit, mix homogeneously; Mixed liquor is joined to 600mL again and be mixed with in the liquid paraffin that mass percent concentration is 8%Span-60, stir 8h, mixing speed is 800rpm, with the organic solvent that volatilizees; After solvent evaporates with hexane cyclic washing; The medicine carrying complex microsphere with polyester coatings that obtains after lyophilization being dried.
In this example, medicine carrying complex microsphere comprises core and polyester coatings, and polyester layer mass percent is 73.20%, and surplus is medicine carrying core microsphere.In medicine carrying core microsphere, core carrying drug ratio is 0.0002%, SiO
2be respectively 4.601% and 95.40% with PLGA mass percent.The prepared external slow release BMP-2 of medicine carrying microballoons of this example reaches 85 days.
example 4
(1) prepare medicine carrying core microsphere
15mg BMP-7 is dissolved in and in 0.5mL2% acetum, forms mass percent concentration 2.91% drug solution, then 35mg TCP is dispersed in and wherein forms suspension; Suspension is joined in the ethyl acetate of PHA of 5mg/mL of 10mL, with refiner, with 3000rpm rotating speed emulsifying 60s, make interior emulsion (w/o).At 70 ℃, PVA is dissolved to the aqueous solution that forms 200mL 0.5%, as outer water; Interior emulsion is added to outer water, with refiner, with 5000rpm rotating speed emulsifying 180s, make double emulsion (w/o/w); Double emulsion is stirred to 3h and treat organic solvent volatilization, standing over night.Centrifugal and washing, in triplicate, then after lyophilization, obtain dry medicine carrying core microsphere.
(2) prepare polyester coatings
The core microsphere of 300mg joins in the acetonitrile solution of 20mL, 5% PHA, mix homogeneously; Mixed liquor is joined to 600mL again and be mixed with in the liquid paraffin that mass percent concentration is 3%Span-60, stir 4h, mixing speed is 800rpm, with the organic solvent that volatilizees; After solvent evaporates with isopropyl alcohol, petroleum ether cyclic washing; The medicine carrying complex microsphere with polyester coatings that obtains after lyophilization being dried.
In this example, medicine carrying complex microsphere comprises core and polyester coatings, and polyester layer mass percent is 73.26%, and surplus is medicine carrying core microsphere.In medicine carrying core microsphere, core carrying drug ratio is that 14.95%, TCP and PHA mass percent are respectively 37.11% and 47.94%; .The prepared external slow release BMP-7 of medicine carrying microballoons of this example reaches 97 days.
example 5
(1) prepare medicine carrying core microsphere
88.23mg EGF is dissolved in and in 0.5mLPBS, forms mass percent concentration is 15% solution, then 5mgHA is dispersed in and wherein forms suspension; Suspension is joined in the chloroform of PCL of 80mg/mL of 10mL, with refiner, with 3000rpm rotating speed emulsifying 60s, make interior emulsion (w/o).In 200mL water, add the Tween-20 of 2% (v/v), be stirred to and be uniformly dispersed, make outer water; Interior emulsion is added to outer water, with refiner, with 5000rpm rotating speed emulsifying 120s, make double emulsion (w/o/w); Double emulsion is stirred to 3h and treat organic solvent volatilization, standing over night.Centrifugal and washing, in triplicate, then after lyophilization, obtain dry medicine carrying core microsphere.
(2) prepare polyester coatings
The core microsphere of 300mg joins in the acetonitrile and methanol mixed solution of 15mL, 15% PCL, mix homogeneously; Mixed liquor is joined to 600mL again and be mixed with in the liquid paraffin that mass percent concentration is 5%Span-20, stir 5h, mixing speed is 1250rpm, with the organic solvent that volatilizees; After solvent evaporates with isopropyl alcohol, petroleum ether cyclic washing; The medicine carrying complex microsphere with polyester coatings that obtains after lyophilization being dried.
In this example, medicine carrying complex microsphere comprises core and polyester coatings, and polyester layer mass percent is 86.59%, and surplus is medicine carrying core microsphere.In medicine carrying core microsphere, core carrying drug ratio is that 0.0002063%, HA and PCL mass percent are respectively 0.5824% and 41.75%; .The prepared external slow release EGF of medicine carrying microballoons of this example reaches 91 days.
example 6
(1) prepare medicine carrying core microsphere
Get the vancomycin solution of 0.1mL, 100mg/mL as drug solution, the TCP of 100 μ g is dispersed in to drug solution and forms suspension; Suspension is joined in the dichloromethane solution of PLA that the total concentration of 10mL is 80mg/mL and PCL, with refiner, with 3000rpm rotating speed emulsifying 60s, make interior emulsion (w/o).In 200mL water, add the Tween-80 of 2% (v/v), be stirred to and be uniformly dispersed, make outer water; Interior emulsion is added to outer water, with refiner, with 5000rpm rotating speed emulsifying 120s, make double emulsion (w/o/w); Double emulsion is stirred to 3h and treat organic solvent volatilization, standing over night.Centrifugal and washing, in triplicate, then after lyophilization, obtain dry medicine carrying core microsphere.
(2) prepare polyester coatings
The core microsphere of 46mg joins in the acetonitrile and methanol mixed solution of 15mL, 15% Eudrugit, mix homogeneously; Mixed liquor is joined to 400mL again and be mixed with in the liquid paraffin that mass percent concentration is 0.5%Span-80, stir 4h, mixing speed is 1250rpm, with the organic solvent that volatilizees; After solvent evaporates with isopropyl alcohol, petroleum ether cyclic washing; The medicine carrying complex microsphere with polyester coatings that obtains after lyophilization being dried.
In this example, medicine carrying complex microsphere comprises core and polyester coatings, and polyester layer mass percent is 97.65%, and surplus is medicine carrying core microsphere.In described medicine carrying core microsphere, core carrying drug ratio is that 1.087%, HA and PLA mass percent are respectively 0.001164% and 98.91%.The prepared external slow release EGF of medicine carrying microballoons of this example reaches 106 days.
The above is the specific embodiment of the present invention; it should be pointed out that for those skilled in the art, under the premise without departing from the principles of the invention; can also make some improvements and modifications, these improvements and modifications are also considered as protection scope of the present invention.
Claims (10)
1. a medicine carrying complex microsphere, comprise medicine carrying core microsphere and and the polyester coatings of coated described medicine carrying core microsphere surface; Described medicine carrying core microsphere is mainly to consist of matter polyesters high molecular polymer matrix, inorganic raw material composition and contained medicine.
2. medicine carrying complex microsphere as claimed in claim 1, it is characterized in that: in described medicine carrying core microsphere, polyesters high molecular polymer substrate quality percent is 30-99%, the mass percent of inorganic raw material composition is 0.001-65%, and contained ingredient accounts for 0.0002 ~ 15% of core microspheres quality.
3. medicine carrying complex microsphere as claimed in claim 1, is characterized in that: described polyester coatings mass percent 20 ~ 98%; Described polyester coatings material is selected from least one in polyacrylate, polycaprolactone, polyhydroxyalkanoate.
4. medicine carrying complex microsphere as claimed in claim 1, is characterized in that: described polyesters high molecular polymer matrix is selected from least one in polylactic acid, polyglycolic acid, poly lactic coglycolic acid, polyhydroxyalkanoate, polycaprolactone; Described inorganic matter raw material composition is selected from least one in hydroxyapatite, tricalcium phosphate, bio-vitric; Contained medicine is selected from least one in hydrophilic insulin-like growth factor-i, bone morphogenetic protein, VEGF, epidermal growth factor, antibacterial.
5. prepare the method for the medicine carrying complex microsphere as described in any one in claim 1 ~ 4, comprising:
Step 1: adopt emulsifying soln legal system for medicine carrying core microsphere; And
Step 2: adopt emulsifying soln legal system for polyester coatings.
6. prepare as claimed in claim 5 the method for medicine carrying complex microsphere, it is characterized in that: described step 1 further comprises:
Drug solution is provided, and solute is contained medicine;
Described inorganic raw material is scattered in and in drug solution, forms suspension;
The organic solution of described polyesters high molecular polymer matrix is provided, and described suspension is added to and in this organic solution, carries out emulsifying and form interior emulsion;
The aqueous solution of preparation table surface-active agent obtains outer water; And
5) described interior emulsion is added outer water carry out emulsifying and obtain double emulsion, isolate described medicine carrying core microsphere.
7. prepare as claimed in claim 6 the method for medicine carrying complex microsphere, it is characterized in that: it is to prepare drug solution by treating that medicine carrying thing is dissolved in pure water or phosphate buffer or acid solution that drug solution is provided described in step 1; The organic solution organic solvent used that forms described polyesters high molecular polymer matrix is to be selected from least one in dichloromethane, chloroform and ethyl acetate; Described surfactant is tween series, span is serial or polyvinyl alcohol at least one.
8. prepare as claimed in claim 7 the method for medicine carrying complex microsphere, it is characterized in that: in step 1, described drug solution mass percent concentration is 0.000001 ~ 15%; The described inorganic matter raw material of 0.1 ~ 35mg is dispersed in this drug solution and forms suspension; Suspension is joined to emulsifying in the organic solution of the described polyesters high molecular polymer matrix that 5 ~ 10mL, concentration are 1 ~ 100mg/mL and form interior emulsion; Described interior emulsion is joined and in the outer water of aqueous surfactant solution of concentration expressed in percentage by volume 0.5 ~ 5% of 200mL, carry out emulsifying and obtain double emulsion.
9. prepare as claimed in claim 5 the method for medicine carrying complex microsphere, it is characterized in that: described step 2 further comprises:
A) described medicine carrying core microsphere is joined in the organic solution of polyester and form mixed liquor;
B) described mixed liquor is joined in the liquid paraffin that is mixed with surfactant and carries out stirring reaction, after separation, obtain the medicine carrying complex microsphere with polyester coatings.
10. prepare as claimed in claim 9 the method for medicine carrying complex microsphere, it is characterized in that: the organic solution of polyester described in step 2 organic solvent used is selected from least one in methanol, acetonitrile; Described surfactant is selected from least one in tween series, polyvinyl alcohol, span series; In a) step of described step 2, that the mass percentage concentration that joins 10 ~ 20mL by the medicine carrying core microsphere of every 40 ~ 800mg is in the organic solution of 2 ~ 15% polyester, mix homogeneously forms mixed liquor, the b of step 2) be that mixed liquor is joined in the liquid paraffin that is mixed with the surfactant that 200 ~ 600mL, mass percent concentration are 0.1 ~ 8% and carries out stirring reaction in step.
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| CN115252913A (en) * | 2022-08-02 | 2022-11-01 | 赛诺神畅医疗科技有限公司 | Vascular drug delivery coating and preparation method and application thereof |
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Cited By (8)
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| CN103894122A (en) * | 2014-04-14 | 2014-07-02 | 浙江大学 | Preparation method of soluble medicine loaded microcapsule |
| CN103894122B (en) * | 2014-04-14 | 2015-09-16 | 浙江大学 | The preparation method of soluble type drug loading microcapsules |
| CN108744035A (en) * | 2018-06-20 | 2018-11-06 | 信阳师范学院 | The method that VEGF loads microballoon and prepares injectable complex microsphere hydrogel solution using it |
| CN109793920A (en) * | 2019-03-22 | 2019-05-24 | 华南农业大学 | A kind of collagen dressing of the microballoon containing PCL and preparation method thereof and 3D printing application |
| WO2021008215A1 (en) * | 2019-07-18 | 2021-01-21 | 广东省医疗器械研究所 | Polymer composite microsphere, preparation method therefor and use thereof |
| CN111388739A (en) * | 2020-01-06 | 2020-07-10 | 太原理工大学 | Nano silicon dioxide/decomposition enzyme/polycaprolactone composite microsphere and preparation method and application thereof |
| CN114053245A (en) * | 2020-08-04 | 2022-02-18 | 华东理工大学 | Polymer micro-nano composite microsphere and controllable preparation method thereof |
| CN115252913A (en) * | 2022-08-02 | 2022-11-01 | 赛诺神畅医疗科技有限公司 | Vascular drug delivery coating and preparation method and application thereof |
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