CN105832653A - Biological absorbable foamed magnesium adhesive-matrix type targeted drug slow-release carrier and preparation method - Google Patents
Biological absorbable foamed magnesium adhesive-matrix type targeted drug slow-release carrier and preparation method Download PDFInfo
- Publication number
- CN105832653A CN105832653A CN201610336630.5A CN201610336630A CN105832653A CN 105832653 A CN105832653 A CN 105832653A CN 201610336630 A CN201610336630 A CN 201610336630A CN 105832653 A CN105832653 A CN 105832653A
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- Prior art keywords
- magnesium
- targeted drug
- cylinder
- preparation
- biological absorbable
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
Abstract
The invention discloses a biological absorbable foamed magnesium adhesive-matrix type targeted drug slow-release carrier and a preparation method. The carrier comprises a barrel body and a barrel cover, wherein one end of the barrel body is opened and the barrel cover is matched with the opened part; the barrel body is in threaded connection with the barrel cover; the barrel body and the barrel cover are prepared of foamed magnesium materials; communication micropores with pore diameters of 100-500 microns are uniformly distributed in the foamed magnesium materials and are used for slowly releasing drugs. After being filled with drugs, the carrier is implanted into pathological bone tissues, so as to realize the fixed-point controlled release and biodegradable absorption of the drugs and facilitate the ingrowth of new bone tissues. The mechanical properties of the foamed magnesium are similar to the mechanical properties of the natural bones, so that the foamed magnesium can be used at the bearing parts of human body. According to the preparation method, the foamed magnesium is prepared from polystyrene microspheres and magnesium powder by adopting a powder metallurgy method, the foamed magnesium is processed into a barrel with the barrel cover by adopting a machining method so as to form a capsule-shaped drug carrier, and MgF2 chemical conversion coatings with thicknesses of 1-2 microns are generated on the inner and outer surfaces of the carrier; the method is simple, convenient, feasible and high in reliability.
Description
Technical field
The invention belongs to embedded type bio-medical pharmaceutical carrier technical field, be specifically related to the foam magnesium storage of biological absorbable
Storehouse type targeted drug controlled release carrier and preparation method.
Background technology
Controlled-release administrating system is that a class can provide steadily continued administration and can effectively control blood concentration, overcome peak valley existing
The new formulation of elephant.For diseases such as human body osteocarcinoma, bone tuberculosis in clinical treatment, need to use truly have curative effect but toxicity is relatively big or
Being easily generated the medicine of the toxic and side effects such as liver and kidney dysfunction after using in a large number, a kind of biological absorbable targeting formula medicine controlled releasing of research carries
Body is the most necessary, and this carrier filling medicine also implants human lesion position, and only direct to patient part sustained release drugs reduces
Side effect to other positions；Meanwhile, this carrier also needs to energy degradation in vivo, the formation improving bone tissue and recovery, thus
Avoid second operation.
The Chinese patent of Application No. 200410060732.6 discloses PLA and apatite depot dosage form pharmaceutical carrier
And preparation method thereof.Utilize the method to prepare absorbable, the porous drug carrier of slow releasing pharmaceutical that aperture is 10 ~ 500 μm.So
And, apatite itself is brittle, and the intensity of porous PLA and elastic modelling quantity are below again nature bone, and apatite and PLA
The interface bond strength of the composite constituted is low, and these factors cause apatite and the mechanical property of polylactic acid porous pharmaceutical carrier
Can be poor, it is difficult to use at human bearing position.It addition, the abnormity shaping of carrier and pore-creating more difficulty, pore-size distribution width and
Wayward.Therefore exploitation has the medicine load of mechanical property and loose structure the biodegradable absorption being similar to nature bone
Body has important using value.
Other biological pottery or polymer depot type porous drug carrier there is also poor mechanical property equally, abnormity carrier becomes
Type and the problem of pore-creating difficulty.
Summary of the invention
For deficiencies of the prior art, it is an object of the invention to provide that a kind of mechanical property is good, be prone to by
Human body degraded absorbs and is avoided that the foam magnesium depot targeted drug controlled release carrier of biological absorbable of second operation, carries simultaneously
For preparation method, when using the method to prepare carrier, shaping is with pore-creating is simple and easy to do, aperture is controlled.
To achieve these goals, the technical solution used in the present invention is as follows:
The foam magnesium depot targeted drug controlled release carrier of biological absorbable, including open at one end cylinder and with this uncovered phase
The cover joined；It is threaded between described cylinder and cover；Described cylinder and cover are made up of foam magnesium material, described
Foam magnesium material in be evenly distributed with the connection micropore that aperture is 100 ~ 500 μm, be suitable for medicine diffusion control type sustained release.
During use, in medicine is loaded cylinder and screw cover, then this carrier is implanted human bone patient part.Medicine meeting
Affected part is the most directly penetrated into by connection micropore.Connection micropore is excessive, then do not reach the effect of sustained release, too small, affects medicine
The expansion of thing is oozed and is caused dosage not reach requirement.
Further, the cumulative volume of described connection micropore accounts for 30 ~ 60% that described foam magnesium all materials is long-pending.Only connect
Suitable scale shared by the cumulative volume of micropore could also ensure what material and bone tissue matched while meeting dosage
Mechanical property.Ratio is excessive, and the mechanical strength of material is likely difficult to match with host bone tissue, if ratio is too small, then can
Cause dosage not enough.
Further, described cylinder and the inner and outer surfaces of cover are all covered with the MgF that thickness is 1 ~ 2 μm2Chemical conversion
Film, in order to delay the degradation rate of foam magnesium material.
Further, the wall thickness of described cylinder is 2 ~ 5mm.The thickness direct relation of cylinder release effect and the power of carrier
Learn intensity.Crossing thin, carrier is yielding even broken and causes medicine to collapse in advance releasing and do not have slow releasing function；Blocked up, can limit
The filling volume of pharmacy thing also too reduces injection speed and affects the treatment.
The preparation method of the foam magnesium depot targeted drug controlled release carrier of above-mentioned biological absorbable, comprises the following steps:
1) base: microballoon pore creating material and magnesium powder that particle diameter is 150 ~ 800 μm are put in ball grinder, mixes on roll-type ball mill
Uniformly, form base raw material, then base raw material loading mould tablet press machine is pressed under 50 ~ 100MPa the base of cylinder
Body.The particle diameter of microballoon pore creating material directly affects the size of the connection micropore of finished product, owing to pore creating material is compressing and follow-up
Having the linear shrinkage ratio of 30% ~ 40% in thermal degradation process, therefore its particle diameter should be greater than the average pore size of foam magnesium connection micropore about
50%~60%。
2) foam magnesium is prepared: base substrate is placed in pressure less than 5 × 10-3In the vacuum atmosphere tube type electric furnace of Pa, with 2 DEG C/min
It is warming up to 200 DEG C and is incubated 2h；It is warming up to 500 DEG C with 5 DEG C/min again and is incubated 2 ~ 5h；Then allow described base substrate with vacuum atmosphere
Electric tube furnace naturally cools to room temperature under vacuum, prepares foamed magnesium cylinders.In heating process, microballoon pore creating material meeting
The thermal degradation when temperature is 300 ~ 450 DEG C and magnesium powder sinters solid matrix in the heating in vacuum environment of described temperature, thus
Make the local micropore that formed originally having microballoon pore creating material in green body cylinders, and then make formation porous knot after green body cylinders heating
Structure.
3) machining shaping: foamed magnesium cylinders is radially cut in two so that it is in the bus length of a section big
In another section, form long section and short section；Long section is processed into the cylinder of open at one end again, and in the open-mouth of this cylinder is processed
Screw thread；Short section is processed the external screw thread mated with internal thread, makes cover；Process is watered pouring absolute ethyl alcohol cool down
To prevent cylinder and cover thermal deformation or thermal oxide；Then with absolute ethyl alcohol ultrasonic cleaning 15min, to remove the broken of processing generation
Bits, thus obtain the foam magnesium depot targeted drug controlled release carrier of described biological absorbable.
Also include the step of the foam magnesium depot targeted drug controlled release carrier overlay film of the following biological absorbable to obtaining:
Described cylinder and cover are placed in 40wt% hydrofluoric acid immersion 48h, to form MgF2Chemical composition coating；Use deionized water again
Ultrasonic cleaning 5min, and put in air dry oven in 105 ~ 110 DEG C of drying 0.5 ~ 1h.
Wherein, microballoon pore creating material described in step 1) is polystyrene microsphere, and it is total that described microballoon pore creating material accounts for base raw material
The 20 ~ 50% of weight, if the too small meeting of weight ratio shared by pore creating material causes porosity and hole link degree low, ratio is too high then
Cause intercommunicating pore size too big and mechanical strength reduces.
Meso-position radius ＜ 200 μm of the magnesium powder described in step 1), purity are more than 99.9%, and particle diameter and the purity of magnesium powder are direct
Affect end properties: magnesium powder crosses sintered density and the mechanical strength thereof that slightly can reduce magnesium-based matter；High-purity can prevent from introducing
The impurity of poor biocompatibility or toxic element.
The ratio of the bus length with short section of the long section described in step 3) is 3:1.The most both it had been easy to machining, had also ensured
Cylinder and cover can fully screw and have enough medicine carrying volumes.
Foam magnesium has the connected porous structure close to nature bone and mechanical property, good biocompatibility, degradable absorption
And magnesium is the element that human body is necessary, foam magnesium depot targeted drug controlled release carrier is capable of control release and the battalion of medicine
Support the transmission of material and contribute to growing into of new bone, thus realizing the sick targeted therapy of orthopaedics and the regeneration of bone tissue.
Compared with prior art, there is advantages that
1, it is implanted to disease after biological absorbable foam magnesium depot targeted drug controlled release carrier provided by the present invention filling medicine
Become bone tissue and be capable of the position control release of medicine, biodegradable absorption the regeneration of beneficially bone tissue.Foam magnesium
The loose structure being similar to nature bone having contributes to carrier controllable sustained-release medicine, carries nutriment and new bone group of growing into
Knit.
2, the mechanical property being similar to nature bone that foam magnesium has so that it is can use at human bearing position.And
MgF2Chemical composition coating can delay the degradation rate of foam magnesium, thus ensures that carrier possesses due mechanics before bone tissue is grown into
Performance.
3, polystyrene can be selected to account for the Different Weight ratio of mixture, the polystyrene microsphere of different-grain diameter controls to carry
The porosity of body and aperture, and the personalized customization of carrier profile, capacity is realized by machining；Preparation process is easy easily
Row, reliability are high.
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention is described in further detail.
Embodiment one
Following steps are used to prepare the foam magnesium depot targeted drug controlled release carrier of biological absorbable:
1) take polystyrene that 10.5g particle diameter is 300 μm as microballoon pore creating material, be 120 μm, pure by itself and 19.5g meso-position radius
The magnesium powder of degree 99.9% is put in polyurethane ball-milling pot together, mixes on roll-type ball mill.Weigh mixture 10g to load
Mould tablet press machine is pressed into the fine and close cylindrical base substrate of diameter phi 15 × 40mm under 50MPa.
2) base substrate is placed in pressure less than 5 × 10-3In the vacuum atmosphere tube type electric furnace of Pa, it is warming up to 200 DEG C with 2 DEG C/min
And it is incubated 2h；It is warming up to 500 DEG C with 5 DEG C/min again and is incubated 4h；Then allow described base substrate with vacuum atmosphere tube type electric furnace very
Naturally cool to room temperature under empty condition, prepare foamed magnesium cylinders；
3) prepared foamed magnesium cylinders is cut into long and short two sections by 3:1.With Miniature machine tool, long section boring is gone out φ 11 × 28mm
Endoporus, be processed into wall thickness be 2mm, one end close cylinder and in open-mouth tapping thread, process correspondence by short section
External screw thread to form cover, process is watered pouring absolute ethyl alcohol cool down, use absolute ethyl alcohol ultrasonic cleaning after processing again
15min, thus obtains the foam magnesium depot targeted drug controlled release carrier of described biological absorbable.
Cylinder and cover can spin together, and form the foam magnesium cylinder of the sealing of capsule shape, are used for loading targeting medicine
Thing.
4) cylinder and cover are soaked in 40wt% hydrofluoric acid and take out after 48h, with deionized water ultrasonic cleaning 5min, and
Put in air dry oven and dry 0.5h in 105 DEG C.
Embodiment two
1) take polystyrene that 6.0g particle diameter is 800 μm as microballoon pore creating material, be 180 μm, purity by it with 24.0g meso-position radius
The magnesium powder of 99.9% is put in polyurethane ball-milling pot together, mixes on roll-type ball mill.Weigh mixture 11g and load mould
Tool is pressed under 50MPa the fine and close green body cylinders of diameter phi 15 × 40mm with tablet press machine.
2) base substrate is placed in pressure less than 5 × 10-3In the vacuum atmosphere tube type electric furnace of Pa, it is warming up to 200 DEG C with 2 DEG C/min
And it is incubated 2h；It is warming up to 500 DEG C with 5 DEG C/min again and is incubated 2h；Then allow described base substrate with vacuum atmosphere tube type electric furnace very
Naturally cool to room temperature under empty condition, prepare foamed magnesium cylinders；
3) prepared foamed magnesium cylinders is cut into long and short two sections by 3:1.With Miniature machine tool, long section boring is gone out φ 5 × 25mm
Endoporus, be processed into wall thickness be 5mm, one end close cylinder and in open-mouth tapping thread, process correspondence by short section
External screw thread to form cover, process is watered pouring absolute ethyl alcohol cool down, use absolute ethyl alcohol ultrasonic cleaning after processing again
15min, thus obtains the foam magnesium depot targeted drug controlled release carrier of described biological absorbable.
Cylinder and cover can spin together, and form the foam magnesium cylinder of the sealing of capsule shape, are used for loading targeting medicine
Thing.
4) cylinder and cover are soaked in 40wt% hydrofluoric acid and take out after 48h, with deionized water ultrasonic cleaning 5min, and
Put in air dry oven and dry 0.5h in 105 DEG C.
Embodiment three
1) take polystyrene that 15.0g particle diameter is 153 μm as microballoon pore creating material, be 110 μm, pure by itself and 15.0g meso-position radius
The magnesium powder of degree 99.9% is put in polyurethane ball-milling pot together, mixes on roll-type ball mill.Weigh mixture 9.3g to load
Mould is pressed under 50MPa the fine and close cylindrical base substrate of diameter phi 15 × 40mm with tablet press machine.
2) base substrate is placed in pressure less than 5 × 10-3In the vacuum atmosphere tube type electric furnace of Pa, it is warming up to 200 DEG C with 2 DEG C/min
And it is incubated 2h；It is warming up to 500 DEG C with 5 DEG C/min again and is incubated 5h；Then allow described base substrate with vacuum atmosphere tube type electric furnace very
Naturally cool to room temperature under empty condition, prepare foamed magnesium cylinders；
3) prepared foamed magnesium cylinders is cut into long and short two sections by 3:1.With Miniature machine tool, long section boring is gone out φ 9 × 27mm
Endoporus, be processed into wall thickness be 3mm, one end close cylinder and in open-mouth tapping thread, process correspondence by short section
External screw thread to form cover, process is watered pouring absolute ethyl alcohol cool down, use absolute ethyl alcohol ultrasonic cleaning after processing again
15min, thus obtains the foam magnesium depot targeted drug controlled release carrier of described biological absorbable.
Cylinder and cover can spin together, and form the foam magnesium cylinder of the sealing of capsule shape, are used for loading targeting medicine
Thing.
4) cylinder and cover are soaked in 40wt% hydrofluoric acid and take out after 48h, with deionized water ultrasonic cleaning 5min, and
Put in air dry oven and dry 1h in 105 ~ 110 DEG C.
The above embodiment of the present invention is only for example of the present invention is described, and is not the enforcement to the present invention
The restriction of mode.For those of ordinary skill in the field, can also be made other not on the basis of the above description
Change with form.Here cannot all of embodiment be given exhaustive.Every technical scheme that belongs to is amplified
Go out obviously change still in protection scope of the present invention within.
Claims (9)
1. the foam magnesium depot targeted drug controlled release carrier of biological absorbable, it is characterised in that include the cylinder of open at one end
And with this uncovered cover matched；It is threaded between described cylinder and cover；Described cylinder and cover are by foam
Magnesium material is made, and is evenly distributed with the connection micropore that aperture is 100 ~ 500 μm, for slow releasing medicinal in described foam magnesium material
Thing.
The foam magnesium depot targeted drug controlled release carrier of biological absorbable the most according to claim 1, it is characterised in that
The cumulative volume of described connection micropore accounts for 30 ~ 60% that described foam magnesium all materials is long-pending.
The foam magnesium depot targeted drug controlled release carrier of biological absorbable the most according to claim 1, it is characterised in that
Described cylinder and the inner and outer surfaces of cover are all covered with the MgF that thickness is 1 ~ 2 μm2Chemical composition coating, in order to delay foam magnesium
The degradation rate of material.
The foam magnesium depot targeted drug controlled release carrier of biological absorbable the most according to claim 1, it is characterised in that
The wall thickness of described cylinder is 2 ~ 5mm.
5. the preparation method of the foam magnesium depot targeted drug controlled release carrier of biological absorbable as claimed in claim 1, its
It is characterised by, comprises the following steps:
1) base: microballoon pore creating material and magnesium powder that particle diameter is 150 ~ 800 μm are put in ball grinder, mixes on roll-type ball mill
Uniformly, base raw material is formed；Base raw material loading mould tablet press machine is pressed under 50 ~ 100MPa the base of cylinder again
Body；
2) foam magnesium is prepared: base substrate is placed in pressure less than 5 × 10-3In the vacuum atmosphere tube type electric furnace of Pa, heat up with 2 DEG C/min
To 200 DEG C and be incubated 2h；It is warming up to 500 DEG C with 5 DEG C/min again and is incubated 2 ~ 5h；Then allow described base substrate with vacuum atmosphere tube type
Electric furnace naturally cools to room temperature under vacuum, prepares foamed magnesium cylinders；
3) machining shaping: foamed magnesium cylinders is radially cut in two so that it is in the bus length of a section more than another
One section, form long section and short section；Long section is processed into the cylinder of open at one end, and spiral shell in the open-mouth of this cylinder is processed again
Line；Short section is processed the external screw thread mated with internal thread, makes cover；Process is watered pouring absolute ethyl alcohol cool down；
Then with absolute ethyl alcohol ultrasonic cleaning 15min, to remove the chip that processing produces, the bubble of described biological absorbable is thus obtained
Foam magnesium depot targeted drug controlled release carrier.
Preparation method the most according to claim 5, it is characterised in that also include the bubble of the following biological absorbable to obtaining
The step of foam magnesium depot targeted drug controlled release carrier overlay film:
Described cylinder and cover are placed in 40wt% hydrofluoric acid immersion 48h, to form MgF2Chemical composition coating；Use deionization again
Water ultrasonic cleaning 5min, and put in air dry oven in 105 ~ 110 DEG C of baking 0.5 ~ 1h.
Preparation method the most according to claim 5, it is characterised in that microballoon pore creating material described in step 1) is polystyrene
Microballoon, described microballoon pore creating material accounts for the 20 ~ 50% of base raw material gross weight.
Preparation method the most according to claim 5, it is characterised in that meso-position radius ＜ 200 μ of the magnesium powder described in step 1)
M, purity are more than 99.9%.
Preparation method the most according to claim 5, it is characterised in that the long section described in step 3) is long with the bus of short section
The ratio of degree is 3:1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610336630.5A CN105832653A (en) | 2016-05-20 | 2016-05-20 | Biological absorbable foamed magnesium adhesive-matrix type targeted drug slow-release carrier and preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610336630.5A CN105832653A (en) | 2016-05-20 | 2016-05-20 | Biological absorbable foamed magnesium adhesive-matrix type targeted drug slow-release carrier and preparation method |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019155321A1 (en) * | 2018-02-12 | 2019-08-15 | 香港科能有限公司 | Implant capable of releasing drug, and manufacturing and usage methods therefor |
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| US20020009493A1 (en) * | 1999-12-15 | 2002-01-24 | Schwendeman Steven P. | Methods for stabilizing biologically active agents encapsulated in biodegradable controlled-release polymers |
| CN1628855A (en) * | 2004-08-17 | 2005-06-22 | 武汉理工大学 | Multifunctional depot type medicine carrier and preparation method thereof |
| CN103862051A (en) * | 2014-04-11 | 2014-06-18 | 重庆大学 | Method for preparing foamed magnesium used as buffering energy absorption material |
-
2016
- 2016-05-20 CN CN201610336630.5A patent/CN105832653A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020009493A1 (en) * | 1999-12-15 | 2002-01-24 | Schwendeman Steven P. | Methods for stabilizing biologically active agents encapsulated in biodegradable controlled-release polymers |
| CN1628855A (en) * | 2004-08-17 | 2005-06-22 | 武汉理工大学 | Multifunctional depot type medicine carrier and preparation method thereof |
| CN103862051A (en) * | 2014-04-11 | 2014-06-18 | 重庆大学 | Method for preparing foamed magnesium used as buffering energy absorption material |
Non-Patent Citations (2)
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| C.E. WEN,ET AL: ""Compressibility of porous magnesium foam: dependency on porosity and pore size"", 《MATERIALS LETTERS》 * |
| C.E.WEN，ET AL: ""processing of biocompatible porous Ti and Mg"", 《SCRIPTA MATERIALIA》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2019155321A1 (en) * | 2018-02-12 | 2019-08-15 | 香港科能有限公司 | Implant capable of releasing drug, and manufacturing and usage methods therefor |
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