CN101401976B - Process for producing anti- bone tumor composite bone reconstruction bracket - Google Patents
Process for producing anti- bone tumor composite bone reconstruction bracket Download PDFInfo
- Publication number
- CN101401976B CN101401976B CN2008100423462A CN200810042346A CN101401976B CN 101401976 B CN101401976 B CN 101401976B CN 2008100423462 A CN2008100423462 A CN 2008100423462A CN 200810042346 A CN200810042346 A CN 200810042346A CN 101401976 B CN101401976 B CN 101401976B
- Authority
- CN
- China
- Prior art keywords
- nanocapsule
- bone
- solution
- tumor
- calcium phosphate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a preparation method for a scaffold for regenerating a bone tumor resisting composite bone, which comprises the following steps: step a, preparing a nanometer zirconium oxide/ calcium phosphate artificial skeleton according to the prior art; step b, preparing nanocapsule composite microspheres; and step c, compounding the prepared nanocapsule composite microspheres and the zirconium oxide/ calcium phosphate artificial skeleton, and then obtaining the scaffold for regenerating the composite bone. The preparation method has the following advantages: if the zirconium oxide/ calcium phosphate controlled-release bone scaffold made from nanocapsule composite microspheres for chemotherapeutic medicament is implanted in a tumor bed excised from an osteosarcoma model in vivo of a nude mouse, the tumor does not relapse within 4 weeks, while a pure nanometer zirconium oxide/ calcium phosphate bone scaffold is implanted, the local tumor relapses visually within 9 days, the local tumor relapses and grows after 14 days, and then the tumor is transferred to the visceral organ of the animal after 3 to 4 weeks. The experiment shows that the preparation method has favorable bone tumor resisting effect.
Description
Technical field
The present invention relates to a kind of method for preparing of anti-bone tumor composite bone reconstruction bracket.
Background technology
Bone tumour therapy is the Comprehensive Treatment that collection operation, chemotherapy and radiation combine; Because the treatment of guarantor's limb of extremity malignant bone tumor, spinal column malignant bone tumor adjacent structure is complicated, and focus is difficult to thorough excision; Postoperative prevents that recurrence from just becoming more and more important problem; And the shortage that bone is rebuild required a large amount of bone-grafting materials behind this problem and the tumor resection is still the difficult problem of puzzlement surgeon, is the bottleneck that influence bone tumour therapy effect and the development of treatment idea, also is focus and the difficult point of studying at present.
Mainly concentrate at present two aspects of research of reconstruction biomaterials and postoperative chemotherapy dosage regimen and approach behind the tumor resection, mainly containing at present from body bone, allograph bone, bone cement and various artificial prosthesis etc. aspect the bone reconstruction substitution material for the research of the Therapeutic Method of bone tumor.Postoperative chemotherapy scheme and route of administration aspect mainly concentrate on the medicine or the dosage form of exploitation high-efficiency low-toxicity, and develop different route of administration aspects.
Chinese patent ZL200310122687.8 discloses a kind of " nano zircite Strengthening and Toughening high porosity calcium phosphate artificial bone support and method for making thereof ", behind the artificial bone scaffold implant into body by this method preparation, because its voidage increases considerably; Osseous tissue is easy to grow into; Fusion speed is fast, and it forms similar " armored concrete " structure with after host bone combines; With the host bone strong bonded, be difficult for producing obvious foreign body reaction.
Summary of the invention
The technical problem that the present invention will solve provides method for preparing a kind of and nano zircite/anti-bone tumor composite bone reconstruction bracket that the calcium phosphate artificial bone frame combines mutually.
In order to address the above problem, the method for preparing that the invention provides a kind of anti-bone tumor composite bone reconstruction bracket comprises the steps:
Step a: according to prior art for preparing nano zircite/calcium phosphate artificial bone frame;
Step b: preparation nanocapsule complex microsphere
Step b1: get the 100mg methotrexate and join among the 0.25M NaOH solution 2ml, make the methotrexate alkaline solution of 50mg/ml; 100～200mgPLGA (polylactic acid-glycolic guanidine-acetic acid copolymer) is dissolved in the 5ml dichloromethane, stirs the abundant dissolving in back and process the PLGA that concentration is 20～40mg/ml (polylactic acid-glycolic guanidine-acetic acid copolymer)-CH
2Cl
2Solution;
Step b2: the methotrexate alkaline solution of getting 20～100 μ l injects the PLGA-CH of 0.5～4ml
2Cl
2Solution obtains W/O (water/oil phase) colostrum after the ultrasonic emulsification;
Step b3: above-mentioned colostrum is joined in 1～4at% sodium cholate of 0.5～4ml, obtain W/O/W (water/oil phase/water) emulsion after the ultrasonic emulsification;
Step b4: the sodium cholate that the gained emulsion is placed 10～100ml0.5at% is reduction vaporization at room temperature, removes CH
2Cl
2, promptly get nanocapsule grain suspension;
Step b5: prepared nanocapsule grain suspension is centrifugal under 2～10 ℃, deposition; The free MTX that flush away does not wrap up (methotrexate); After nanocapsule grain deposition was disperseed with the piping and druming of 1～10ml distilled water, adding mannitol to mannitol final concentration was 3～10at%, and lyophilization promptly gets the nanocapsule grain;
Step b6: the Polyethylene Glycol that the nanocapsule grain is joined 10at% is bluffed in bat sour vitamin e (VitaminETPGS) solution, fully stirring and evenly mixing;
Step b7: 100～250mgPLGA (polylactic acid-glycolic guanidine-acetic acid copolymer) is dissolved in the 5ml dichloromethane; Stir the back and fully dissolve the solution of processing 20～50mg/ml, get this solution of 2ml and then add 5～15mg MTX (methotrexate), be uniformly dispersed with dispersing emulsification machine; Pour into rapidly in 100ml2～5at% poly-vinyl alcohol solution; Stir fast at normal temperatures, again that step 6 is prepared nanocapsule Polyethylene Glycol succinic acid vitamin e solution 2ml pours into fast and powerful the stirring after 1～3 second used the microporous filter membrane sucking filtration, washes with deionized water; Final drying promptly makes the nanocapsule complex microsphere;
Step c: adopt ultrasonic concussion method that prepared nanocapsule complex microsphere is packed in the space of nano zircite/calcium phosphate artificial bone frame, promptly make compound bone reconstruction bracket.
Preferably, in said step b2 and step b3, adopt ultrasonic cell disruptor to carry out ultrasonic emulsification.
Preferably, in said step b4, adopt Rotary Evaporators to carry out reduction vaporization.
Prepared composite bone reconstruction bracket of the present invention has following advantage:
1, in nude mouse, implants chemotherapy medicament nano capsule complex microsphere zirconium oxide/calcium phosphate controlled release bone support tumor on the tumor bed of osteosarcoma model excision and in 4 weeks, do not have recurrence; Implant simple nano zircite/calcium phosphate bone groups of holders visible local tumor recurrence in 9 days; Tumor local recur grows up after 14 days, and the internal organs transfer appears in animal after 3～4 weeks.Show that chemotherapeutics nanocapsule complex microsphere zirconium oxide/calcium phosphate controlled release bone support has good resisting bone tumor effect;
2, implant 8 weeks back execution animal, draw materials and find bone support of the present invention and merge from the body bone parts, the bone of display material is rebuild repairing performance.
The specific embodiment
Embodiment 1
The preparation technology of the anti-bone tumor composite bone reconstruction bracket of present embodiment is specific as follows:
Step a: according to prior art for preparing nano zircite/calcium phosphate artificial bone frame;
Step b: preparation nanocapsule complex microsphere
Step b1: get the 100mg methotrexate and join among the 0.25M NaOH solution 2ml, make the methotrexate alkaline solution of 50mg/ml; 100mgPLGA (polylactic acid-glycolic guanidine-acetic acid copolymer) is dissolved in the 5ml dichloromethane, stirs the abundant dissolving in back and process (polylactic acid-glycolic guanidine-acetic acid copolymer)-CH that concentration is 20mg/ml
2Cl
2Solution;
Step b2: the MTX alkaline solution of getting 20 μ l injects the PLGA-CH of 0.5ml
2Cl
2Solution after ultrasonic cell disruptor 120w continuous ultrasound 15s emulsifying, obtains the W/O colostrum;
Step b3: above-mentioned colostrum is joined in the 1at% sodium cholate of 0.5ml,, after each 1s emulsifying at interval, obtain the W/O/W emulsion with ultrasonic cell disruptor 120w impulse ultrasound 15s;
Step b4: place 10ml to contain the 0.5at% sodium cholate gained emulsion, the room temperature reduction vaporization is removed CH in Rotary Evaporators
2Cl
2, promptly get nanocapsule grain suspension;
Step b5: with prepared nanocapsule grain suspension centrifugal 45min of 11000 * g under 2 ℃; Abandoning supernatant, deposition is with distillation washing 2 times; Remove the not free MTX of parcel; After nanocapsule grain deposition was disperseed with the piping and druming of 1ml distilled water, adding mannitol to mannitol final concentration was 3at%, and lyophilization promptly gets the nanocapsule grain;
Step b6: prepared nanocapsule grain is joined 10% Polyethylene Glycol bluff and clap in sour vitamin e (VitaminETPGS) solution, fully stirring and evenly mixing;
Step b7: earlier 100mgPLGA (polylactic acid-glycolic guanidine-acetic acid copolymer) is dissolved in the 5ml dichloromethane, stirs the back and fully dissolve the solution of processing 20mg/ml, get the PLGA that 2ml concentration is 20mg/ml (polylactic acid-glycolic guanidine-acetic acid copolymer)-CH
2Cl
2Solution, and then add 5mg MTX (methotrexate), be uniformly dispersed with dispersing emulsification machine; Pour into rapidly in the 100ml2at% poly-vinyl alcohol solution; Stir fast at normal temperatures, again the Polyethylene Glycol succinic acid vitamin e solution 2ml of nanocapsule prepared in the step 6 is poured into fast and powerful the stirring after 1 second, wash with deionized water with the quick sucking filtration of microporous filter membrane; Final drying promptly makes the nanocapsule complex microsphere;
Step c: adopt conventional ultrasonic concussion method that prepared nanocapsule complex microsphere is packed in the space of nano zircite/calcium phosphate artificial bone frame, promptly make compound bone reconstruction bracket.
The particle diameter of the nanocapsule microsphere of the above-mentioned prepared of process is 48.40 ± 2.16 μ m.The drug loading of microsphere is 6.8 ± 0.42%, and envelop rate is 61.4 ± 5.5%, and drug release has the characteristics of peak value release and steady release, has two release peaks, and the effective antitumor active medicine reaches 31 days release time.
In nude mouse, implant chemotherapy medicament nano capsule complex microsphere zirconium oxide/calcium phosphate controlled release bone support tumor on the tumor bed of osteosarcoma model excision and in 4 weeks, do not have recurrence; Implant simple nano zircite/calcium phosphate bone groups of holders visible local tumor recurrence in 9 days; Tumor local recur grows up after 14 days, and the internal organs transfer appears in animal after 3～4 weeks.Show that chemotherapeutics nanocapsule complex microsphere zirconium oxide/calcium phosphate controlled release bone support has good resisting bone tumor effect.
In addition, implanted for 8 weeks and put to death animal, draw materials and find bone support of the present invention and merge from the body bone parts, the bone of display material is rebuild repairing performance.
Embodiment 2
The preparation technology of the anti-bone tumor composite bone reconstruction bracket of present embodiment is specific as follows:
Step a: according to prior art for preparing nano zircite/calcium phosphate artificial bone frame;
Step b: preparation nanocapsule complex microsphere
Step b1: get the 100mg methotrexate and join among the 0.25M NaOH solution 2ml, make the methotrexate alkaline solution of 50mg/ml; 150mgPLGA (polylactic acid-glycolic guanidine-acetic acid copolymer) is dissolved in the 5ml dichloromethane, stirs the abundant dissolving in back and process (polylactic acid-glycolic guanidine-acetic acid copolymer)-CH that concentration is 30mg/ml
2Cl
2Solution;
Step b2: the MTX alkaline solution of getting 50 μ l injects the PLGA-CH of 0.5ml
2Cl
2Solution after ultrasonic cell disruptor 120w continuous ultrasound 15s emulsifying, obtains the W/O colostrum;
Step b3: above-mentioned colostrum is joined in the 1at% sodium cholate of 2ml,, after each 1s emulsifying at interval, obtain the W/O/W emulsion with ultrasonic cell disruptor 120w impulse ultrasound 15s;
Step b4: place 40ml to contain the 0.5at% sodium cholate gained emulsion, the room temperature reduction vaporization is removed CH in Rotary Evaporators
2Cl
2, promptly get nanocapsule grain suspension;
Step b5: with prepared nanocapsule grain suspension centrifugal 45min of 11000 * g under 4 ℃; Abandoning supernatant, deposition is with distillation washing 2 times; Remove the not free MTX of parcel; After nanocapsule grain deposition was disperseed with the piping and druming of 5ml distilled water, adding mannitol to mannitol final concentration was 5at%, and lyophilization promptly gets the nanocapsule grain;
Step b6: prepared nanocapsule grain is joined 10% Polyethylene Glycol bluff and clap in sour vitamin e (VitaminETPGS) solution, fully stirring and evenly mixing;
Step b7: earlier 150mgPLGA (polylactic acid-glycolic guanidine-acetic acid copolymer) is dissolved in the 5ml dichloromethane, stirs the back and fully dissolve the solution of processing 30mg/ml, get the PLGA that 2ml concentration is 30mg/ml (polylactic acid-glycolic guanidine-acetic acid copolymer)-CH
2Cl
2Solution, and then add 10mg MTX (methotrexate), be uniformly dispersed with dispersing emulsification machine; Pour into rapidly in the 100ml3at% poly-vinyl alcohol solution; Stir fast at normal temperatures, the Polyethylene Glycol succinic acid vitamin e solution 2ml of again that step b6 is prepared nanocapsule pours into and powerful the stirring after 1 second with the quick sucking filtration of microporous filter membrane fast, washes with deionized water; Final drying promptly makes the nanocapsule complex microsphere;
Step c: adopt conventional ultrasonic concussion method that prepared nanocapsule complex microsphere is packed in the space of nano zircite/calcium phosphate artificial bone frame, promptly make compound bone reconstruction bracket.
Particle diameter through the present embodiment microspheres prepared is 48.40 ± 2.16 μ m.It is 6.8 ± 0.42% that microsphere gets drug loading, and envelop rate is 61.4 ± 5.5%, and drug release has the characteristics of peak value release and steady release, has two release peaks, and the effective antitumor active medicine reaches 31 days release time.
In nude mouse, implant chemotherapy medicament nano capsule complex microsphere zirconium oxide/calcium phosphate controlled release bone support tumor on the tumor bed of osteosarcoma model excision and in 4 weeks, do not have recurrence; Implant simple nano zircite/calcium phosphate bone groups of holders visible local tumor recurrence in 9 days; Tumor local recur grows up after 14 days, and the internal organs transfer appears in animal after 3～4 weeks.Show that chemotherapeutics nanocapsule complex microsphere zirconium oxide/calcium phosphate controlled release bone support has good resisting bone tumor effect.
In addition, implanted for 8 weeks and put to death animal, draw materials and find bone support of the present invention and merge from the body bone parts, the bone of display material is rebuild repairing performance.
Embodiment 3
The preparation technology of the anti-bone tumor composite bone reconstruction bracket of present embodiment is specific as follows:
Step a: according to prior art for preparing nano zircite/calcium phosphate artificial bone frame;
Step b: preparation nanocapsule complex microsphere
Step b1: get the 100mg methotrexate and join among the 0.25M NaOH solution 2ml, make the methotrexate alkaline solution of 50mg/ml; 200mgPLGA (polylactic acid-glycolic guanidine-acetic acid copolymer) is dissolved in the 5ml dichloromethane, stirs the abundant dissolving in back and process (polylactic acid-glycolic guanidine-acetic acid copolymer)-CH that concentration is 40mg/ml
2Cl
2Solution;
Step b2: the concentration of getting the MTX alkaline solution injection 0.5ml of 100 μ l is 40mg/mlPLGA (polylactic acid-glycolic guanidine-acetic acid copolymer)-CH
2Cl
2Solution after ultrasonic cell disruptor 120w continuous ultrasound 15s emulsifying, obtains the W/O colostrum;
Step b3: above-mentioned colostrum is joined in the 1at% sodium cholate of 4ml,, after each 1s emulsifying at interval, obtain the W/O/W emulsion with ultrasonic cell disruptor 120w impulse ultrasound 15s;
Step b4: place 100ml to contain the 0.5at% sodium cholate gained emulsion, the room temperature reduction vaporization is removed CH in Rotary Evaporators
2Cl
2, promptly get nanocapsule grain suspension;
Step b5: with prepared nanocapsule grain suspension centrifugal 45min of 11000 * g under 10 ℃; Abandoning supernatant, deposition is with distillation washing 2 times; Remove the not free MTX of parcel; After nanocapsule grain deposition was disperseed with the piping and druming of 10ml distilled water, adding mannitol to mannitol final concentration was 10at%, and lyophilization promptly gets the nanocapsule grain;
Step b6: prepared nanocapsule grain is joined 10% Polyethylene Glycol bluff and clap in sour vitamin e (VitaminETPGS) solution, fully stirring and evenly mixing;
Step b7: earlier 250mgPLGA (polylactic acid-glycolic guanidine-acetic acid copolymer) is dissolved in the 5ml dichloromethane, stirs the back and fully dissolve the solution of processing 50mg/ml, get the PLGA that 2ml concentration is 30mg/ml (polylactic acid-glycolic guanidine-acetic acid copolymer)-CH
2Cl
2Solution, and then add 15mg MTX, be uniformly dispersed with dispersing emulsification machine; Pour into rapidly in the 100ml5at% poly-vinyl alcohol solution; Stir fast at normal temperatures, the Polyethylene Glycol succinic acid vitamin e solution 2ml of again that step a is prepared nanocapsule pours into and powerful the stirring after 1 second with the quick sucking filtration of microporous filter membrane fast, washes with deionized water; Final drying promptly makes the nanocapsule complex microsphere;
Step c: adopt conventional ultrasonic concussion method that prepared nanocapsule complex microsphere is packed in the space of nano zircite/calcium phosphate artificial bone frame, promptly make compound bone reconstruction bracket.
Particle diameter through the prepared nanocapsule microsphere of present embodiment is 42.60 ± 3.22 μ m.It is 7.4 ± 0.53% that microsphere gets drug loading, and envelop rate is 58.4 ± 4.9%, and drug release has the characteristics of peak value release and steady release, has two release peaks, and the effective antitumor active medicine reaches 30 days release time.
In nude mouse, implant chemotherapy medicament nano capsule complex microsphere zirconium oxide/calcium phosphate controlled release bone support tumor on the tumor bed of osteosarcoma model excision and in 4 weeks, do not have recurrence; Implant simple nano zircite/calcium phosphate bone groups of holders visible local tumor recurrence in 9 days; Tumor local recur grows up after 14 days, and the internal organs transfer appears in animal after 3～4 weeks.Show that chemotherapeutics nanocapsule complex microsphere zirconium oxide/calcium phosphate controlled release bone support has good resisting bone tumor effect.
In addition, implanted for 8 weeks and put to death animal, draw materials and find bone support of the present invention and merge from the body bone parts, the bone of display material is rebuild repairing performance.
In addition, the anti-tumor activity experiment in the face of the nanocapsule complex microsphere under remarks additionally.Specifically:
Step 1: make 18 on the subcutaneous osteosarcoma model of nude mice, tumor bearing nude mice is divided into three groups of A, B, C at random, 6 every group, when tumor length to 1.0 * 1.0cm size, most of tumor resection of performing the operation;
Step 2: that adopts that the method for embodiment 2 makes carries MTX nanocapsule complex microsphere and adopts embodiment 2 methods but do not add the blank nanocapsule complex microsphere of MTX.With the tumor bed position of carrying after MTX nanocapsule complex microsphere is implanted to A group tumor resection, with blank not the nanocapsule complex microsphere of drug be implanted to the tumor bed position behind the tumor resection of two groups of B, C.
The situation that step 3:A group is observed tumor recurrence, B group are calculated according to the 0.1mg/Kg body weight and are given continuous 10 days of every nude mice medication continuously, and the C group is matched group, need not any intervening measure.
Observe and put to death three groups of nude mice tumor recurrence situation after 30 days, 6 nude mices of A group all become alive, and tumor does not have recurrence, dissects each internal organs behind the execution animal and does not find neoplasm metastasis; B group medication 1 nude mice death in the 8th day, 14,18 days each dead 1 examples, all the other 3 examples become to live, and 1 routine tumor local recur is arranged, and dissect each internal organs behind the execution animal and do not find neoplasm metastasis; C organizes the 27th day dead 1 example, the equal original position recurrence of all the other 5 routine tumors, and dissecting each internal organs 4 example behind the execution animal has lung transfer, 3 routine hepatic metastasess.Prompting is carried MTX nanocapsule complex microsphere and is had good antineoplastic activity.
In sum; More than being merely preferred embodiment of the present invention, is not to be used to limit protection scope of the present invention, therefore; All any modifications of within spirit of the present invention and principle, being done, be equal to replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (3)
1. the method for preparing of anti-bone tumor composite bone reconstruction bracket is characterized in that, comprises the steps:
Step a: according to prior art for preparing nano zircite/calcium phosphate artificial bone frame;
Step b: preparation nanocapsule complex microsphere
Step b1: get the 100mg methotrexate and join among the 0.25M NaOH solution 2ml, make the methotrexate alkaline solution of 50mg/ml; 100～200mg polylactic acid-glycolic guanidine-acetic acid copolymer is dissolved in the 5ml dichloromethane, stirs the abundant dissolving in back and process polylactic acid-glycolic guanidine-acetic acid copolymer-CH that concentration is 20～40mg/ml
2Cl
2Solution;
Step b2: the methotrexate alkaline solution of getting 20～100 μ l injects polylactic acid-glycolic guanidine-acetic acid copolymer-dichloromethane solution of 0.5～4ml, obtains water/oil phase colostrum after the ultrasonic emulsification;
Step b3: above-mentioned colostrum is joined in 1～4at% sodium cholate of 0.5～4ml, obtain water/oil phase/water emulsion after the ultrasonic emulsification;
Step b4: the sodium cholate that the gained emulsion is placed 10～100ml 0.5at% is reduction vaporization at room temperature, removes CH
2Cl
2, promptly get nanocapsule grain suspension;
Step b5: prepared nanocapsule grain suspension is centrifugal under 2～10 ℃, deposition; The free methotrexate that flush away does not wrap up; After nanocapsule grain deposition was disperseed with the piping and druming of 1～10ml distilled water, adding mannitol to mannitol final concentration was 3～10at%, and lyophilization promptly gets the nanocapsule grain;
Step b6: the nanocapsule grain is joined in the Polyethylene Glycol succinic acid vitamin e solution of 10at%, fully stirring and evenly mixing;
Step b7: 100～250mg polylactic acid-glycolic guanidine-acetic acid copolymer is dissolved in the 5ml dichloromethane; Stir the back and fully dissolve the solution of processing 20～50mg/ml, get this solution of 2ml and then add 5～15mg methotrexate, be uniformly dispersed with dispersing emulsification machine; Pour into rapidly in 100ml 2～5at% poly-vinyl alcohol solution; Stir fast at normal temperatures, again that step b6 is prepared nanocapsule Polyethylene Glycol succinic acid vitamin e solution 2ml pours into fast and powerful the stirring after 1～3 second used the microporous filter membrane sucking filtration, washes with deionized water; Final drying promptly makes the nanocapsule complex microsphere;
Step c: adopt ultrasonic concussion method that prepared nanocapsule complex microsphere is packed in the space of nano zircite/calcium phosphate artificial bone frame, promptly make compound bone reconstruction bracket.
2. the method for claim 1 is characterized in that, in said step b2 and step b3, adopts ultrasonic cell disruptor to carry out ultrasonic emulsification.
3. the method for claim 1 is characterized in that, in said step b3, adopts Rotary Evaporators to carry out reduction vaporization.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008100423462A CN101401976B (en) | 2008-09-01 | 2008-09-01 | Process for producing anti- bone tumor composite bone reconstruction bracket |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008100423462A CN101401976B (en) | 2008-09-01 | 2008-09-01 | Process for producing anti- bone tumor composite bone reconstruction bracket |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101401976A CN101401976A (en) | 2009-04-08 |
| CN101401976B true CN101401976B (en) | 2012-11-14 |
Family
ID=40536224
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2008100423462A Expired - Fee Related CN101401976B (en) | 2008-09-01 | 2008-09-01 | Process for producing anti- bone tumor composite bone reconstruction bracket |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101401976B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1554449A (en) * | 2003-12-24 | 2004-12-15 | 中国人民解放军第二军医大学 | Nano zirconium oxide tough-ened high porosity calcium phosphate artificial bone rack and its preparing method |
| CN101219241A (en) * | 2007-11-27 | 2008-07-16 | 清华大学 | Biological activity bone renovation material with bone-inducing factor control-release function and production method thereof |
-
2008
- 2008-09-01 CN CN2008100423462A patent/CN101401976B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1554449A (en) * | 2003-12-24 | 2004-12-15 | 中国人民解放军第二军医大学 | Nano zirconium oxide tough-ened high porosity calcium phosphate artificial bone rack and its preparing method |
| CN101219241A (en) * | 2007-11-27 | 2008-07-16 | 清华大学 | Biological activity bone renovation material with bone-inducing factor control-release function and production method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 史国栋等.脑源性神经营养因子缓释注射纳米粒的制备及其释药特性评价.《第二军医大学学报》.2008,第29卷(第5期),538-542. * |
| 陈华江等.抗肿瘤药物复合磷酸钙骨水泥的理化性质研究.《第二军医大学学报》.2007,第28卷(第3期),250-253. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101401976A (en) | 2009-04-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Mei et al. | Self-assembling Collagen/Alginate hybrid hydrogels for combinatorial photothermal and immuno tumor therapy | |
| Chen et al. | Bone-targeted nanoparticle drug delivery system: an emerging strategy for bone-related disease | |
| US20180105430A1 (en) | Generation of mesoporous materials using multiphase surfactant systems | |
| CN105030795B (en) | A kind of nano medicament carrying system and its preparation method and application | |
| US20180110831A1 (en) | Cd 47 containing porous nanoparticle supported lipid bilayers (protocells) field of the invention | |
| CN103330680A (en) | Nano drug transdermal preparation and preparation method thereof | |
| Li et al. | CaCO3/tetraethylenepentamine–graphene hollow microspheres as biocompatible bone drug carriers for controlled release | |
| CN107233577A (en) | A kind of pH responses and the double medicine-carried nano particles and preparation method of cancer target and application | |
| Montejo et al. | Effective antiproliferative effect of meloxicam on prostate cancer cells: development of a new controlled release system | |
| Qiu et al. | Lipid-coated hollow mesoporous silica nanospheres for co-delivery of doxorubicin and paclitaxel: preparation, sustained release, cellular uptake and pharmacokinetics | |
| CN109328249A (en) | Nanofiber mat containing the ceramic particle with releasable dopant therein | |
| Duan et al. | A novel electrospun nanofiber system with PEGylated paclitaxel nanocrystals enhancing the transmucus permeability and in situ retention for an efficient cervicovaginal cancer therapy | |
| CN107308457A (en) | A kind of deep layer degraded with tumor microenvironment response penetrates nanoscale medicine delivery system | |
| CN100344277C (en) | Nano-magnetic medicinal microglobule, its preparation method and application | |
| Sun et al. | A combined electrohydrodynamic atomization method for preparing nanofiber/microparticle hybrid medicines | |
| CN101401792B (en) | Method for preparing nanocapsule and nanocapsule composite microsphere | |
| CN113663079A (en) | Carrier-free self-assembly nano particle and preparation method and application thereof | |
| Yu et al. | Research progress of natural silk fibroin and the application for drug delivery in chemotherapies | |
| CN101156854A (en) | Method for preparing camptothecin medicine slow releasing microcapsule | |
| Haidar et al. | Electrospun nanofibers for dual and local delivery of neuroprotective drugs | |
| CN112294751A (en) | Preparation method and application of calcium peroxide-loaded metal organic framework pharmaceutical composition | |
| CN104689374A (en) | Organic/inorganic biphase hybridization target magnetic traditional Chinese medicine carrying composite microsphere | |
| CN104288093A (en) | Application of nano-drug transdermal preparation in tumors | |
| KR20180014042A (en) | Cross-linked hyaluronic acid for delivering drugs and pharmaceutical preparations using the same | |
| CN101401976B (en) | Process for producing anti- bone tumor composite bone reconstruction bracket |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20121114 Termination date: 20130901 |