CN105944106A - Method for local intervention treatment of osteosarcoma by degradable multiple drug-loading controlled-release internal implant - Google Patents
Method for local intervention treatment of osteosarcoma by degradable multiple drug-loading controlled-release internal implant Download PDFInfo
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- CN105944106A CN105944106A CN201610291629.5A CN201610291629A CN105944106A CN 105944106 A CN105944106 A CN 105944106A CN 201610291629 A CN201610291629 A CN 201610291629A CN 105944106 A CN105944106 A CN 105944106A
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- 239000007943 implant Substances 0.000 title claims abstract description 44
- 238000000034 method Methods 0.000 title claims abstract description 24
- 238000013270 controlled release Methods 0.000 title claims abstract description 19
- 201000008968 osteosarcoma Diseases 0.000 title abstract description 8
- 238000011282 treatment Methods 0.000 title abstract description 6
- 239000003814 drug Substances 0.000 claims abstract description 73
- 238000013461 design Methods 0.000 claims abstract description 22
- 238000004519 manufacturing process Methods 0.000 claims abstract description 17
- 239000000463 material Substances 0.000 claims abstract description 13
- 229940079593 drug Drugs 0.000 claims abstract description 12
- 238000011160 research Methods 0.000 claims abstract description 10
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 claims description 27
- 229920001432 poly(L-lactide) Polymers 0.000 claims description 27
- 238000002360 preparation method Methods 0.000 claims description 18
- 239000000203 mixture Substances 0.000 claims description 13
- 238000005507 spraying Methods 0.000 claims description 13
- 239000008187 granular material Substances 0.000 claims description 12
- 239000011230 binding agent Substances 0.000 claims description 11
- 238000007493 shaping process Methods 0.000 claims description 9
- 238000002560 therapeutic procedure Methods 0.000 claims description 9
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 6
- 210000003484 anatomy Anatomy 0.000 claims description 6
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 6
- 229960004316 cisplatin Drugs 0.000 claims description 6
- 238000001514 detection method Methods 0.000 claims description 6
- 239000004744 fabric Substances 0.000 claims description 6
- 238000009472 formulation Methods 0.000 claims description 6
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 claims description 6
- 229960001101 ifosfamide Drugs 0.000 claims description 6
- 229960000485 methotrexate Drugs 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 6
- 238000012545 processing Methods 0.000 claims description 5
- 239000007921 spray Substances 0.000 claims description 5
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims description 4
- 230000000052 comparative effect Effects 0.000 claims description 2
- 229960004679 doxorubicin Drugs 0.000 claims description 2
- 238000012216 screening Methods 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 5
- 230000008901 benefit Effects 0.000 abstract description 4
- 238000005516 engineering process Methods 0.000 abstract description 4
- 206010013654 Drug abuse Diseases 0.000 abstract description 3
- 206010059866 Drug resistance Diseases 0.000 abstract description 3
- 230000000399 orthopedic effect Effects 0.000 abstract description 3
- 208000011117 substance-related disease Diseases 0.000 abstract description 3
- 230000004888 barrier function Effects 0.000 abstract description 2
- 239000006227 byproduct Substances 0.000 abstract description 2
- 238000009509 drug development Methods 0.000 abstract description 2
- 239000002699 waste material Substances 0.000 abstract description 2
- 206010061623 Adverse drug reaction Diseases 0.000 abstract 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 abstract 1
- 239000002994 raw material Substances 0.000 abstract 1
- 238000001356 surgical procedure Methods 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 description 5
- 210000000988 bone and bone Anatomy 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 238000002512 chemotherapy Methods 0.000 description 3
- 230000007547 defect Effects 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000000560 biocompatible material Substances 0.000 description 2
- 239000012620 biological material Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 229940044683 chemotherapy drug Drugs 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000035876 healing Effects 0.000 description 2
- 238000011337 individualized treatment Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 238000005457 optimization Methods 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000002980 postoperative effect Effects 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 210000004872 soft tissue Anatomy 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 206010005949 Bone cancer Diseases 0.000 description 1
- 206010065553 Bone marrow failure Diseases 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000009429 distress Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000002758 humerus Anatomy 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000000505 pernicious effect Effects 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 230000009291 secondary effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 210000002303 tibia Anatomy 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
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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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
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- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Health & Medical Sciences (AREA)
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- Biomedical Technology (AREA)
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Abstract
The invention belongs to the technical field of clinical treatment of orthopedic surgery, novel drug development and special drug research and discloses a method for local interventional treatment of osteosarcoma by degradable multi-drug-loading controlled-release internal implants, which comprises the following steps: the method comprises the following steps: preparing individual degradable multiple drug-loading controlled-release inner plants; step two: preparing the components of the rapid prototyping raw materials and setting the process parameters. The invention has the advantages of individual customization, no need of secondary operation, multiple drug loading, controllable release, precise entity manufacture, diversified materials, no need of assembly, short manufacture time, small manufacture required space, high portability, little amount of waste byproducts, no design space limitation, no manufacturing technology barrier, no direct association between manufacture cost and design complexity, no direct association between manufacture cost and manufacture diversification, optimized treatment effect, minimized drug side effect and avoidance of drug resistance and drug abuse.
Description
Technical field
Present invention relates particularly to the degradable multiple medicine carrying controlled release osteosarcomatous method of implants partial interventional therapy, belong to bone
Surgical clinical treatment, newtype drug development, special medicaments studying technological domain.
Background technology
Osteosarcoma is the tumor that primary marrow inner height is pernicious, is modal malignant bone tumor, accounts for whole body constitutional and dislikes
The 40% of property bone tumor, poor prognosis, there are high fatality rate and disability rate.Osteosarcoma is apt to occur in the teenager in 10-20 year, good
Sending out position is distal femur, proximal tibia, proximal humerus, especially metaphysis (91%) and key (9%).Osteosarcoma is sent out in recent years
Sick rate constantly rises violently, and up to (4-5)/106, newly make a definite diagnosis Patients with Osteosarcoma and be up to more than 5000 people, to countless patients and family
Bring considerable distress.Classical clinical treatment of osteosarcoma mode by preoperative high-dose chemotherapy, radical-ability osteosarcoma excision, postoperative big dose
Quantify to treat three part compositions, disease free survival rate can be improved to 60%-80% by preoperative and postoperative high-dose chemotherapy.But it is
Reach focus local drug concentration and the side effect of whole body high-dose chemotherapy is obvious, bone marrow depression, hepatic and renal function injure, maincenter god
Be probably fatal through system damage, convenient administration mode not only could not effectively extend the survival of patients time limit, makes patient raw on the contrary
Bioplasm amount drastically declines.
Medicine carrying implants is to be combined with biocompatible materials by medicine, inserts internal rear slow Slow release, whereby
Reach the effect that local is treated.Suitably making material is also the key building good inner matter, is clinical conventional biological material
One of material.In Orthopedic Clinical is treated, PLLA, as Biodegradable material, both can make pediatric Orthopaedics inside-fixture, it is possible to
Make tissue-engineered scaffolds, have that good biocompatibility, plasticity is strong, degradation speed can be relatively uniform with bone defect healing etc.
Advantage.Tradition medicine carrying inner matter can only carry a kind of medicine, and drug release rate, concentration are uncontrollable, need secondary hands
Art, can not individualized treatment.
Summary of the invention
The technical problem to be solved in the present invention overcomes existing defect, it is provided that degradable multiple medicine carrying controlled release implants local
The osteosarcomatous method of interventional therapy, individuation customization, without second operation, multiple medicine carrying, discharge controlled, accurate physical make,
Material diversification, without assembling, Production Time is short, make that requisite space is little, portability is high, waste by-product amount is few, without setting
Meter space limit, various with making without direct correlation, cost of manufacture with design complexity without manufacturing technology barrier, cost of manufacture
Change without direct correlation, can effectively solve the problem in background technology.
In order to solve above-mentioned technical problem, the invention provides following technical scheme:
The present invention provides the degradable multiple medicine carrying controlled release osteosarcomatous method of implants partial interventional therapy, comprises the following steps:
Step one: the preparation of individuation degradable multiple medicine carrying controlled release implants；Step 2: the preparation of rapid shaping material composition and technique
Parameter sets.
As a preferred technical solution of the present invention, described step one includes that the CAD of medicine carrying implants stereochemical structure sets
Meter.
As a preferred technical solution of the present invention, described CAD design includes: mimics, autoCAD are soft for (1), utilization
Part, according to human anatomy feature and solid geometry principle design spheroid or cylinder or fan arc or the different geometric shape of lamellar
Implants, and carry out computer contrast and detection；(2), design methotrexate, cisplatin, doxorubicin, ifosfamide etc. are single carries
The medicine of medicine and many medicine carryings various combination implants joins mode for cloth and manufacturing process.
As a preferred technical solution of the present invention, described step 2 includes: prepared by (1), PLLA: grind preparation PLLA
Granule, studies different-diameter PLLA granule internal inside plants compact structure and the impact of porosity after screening；(2), bonding
Prepared by agent: comparative study different formulations organic solution is as the performance of PLLA binding agent；(3), technological parameter research: research difference
Shower nozzle moves speed, nozzle diameter, hydrojet rheological parameter, hydrojet liquid-drop diameter, overlay thickness, spraying number of times, spray angle, spraying position
Put, drip spacing, distance between centers of tracks, the saturation coefficient impact on Rapid Prototyping technique.
The present invention is reached to provide the benefit that: degradable multiple medicine carrying controlled release implants partial interventional therapy is osteosarcomatous
Method, can make strong chemotherapeutic drug combination targetedly according to Patient drug's sensitivity tests and tumor pathological characteristics,
And various dose or the medicine carrying implants of variable dose can be made according to patient's own situation, thus realize single medicine carrying, double
Medicine carrying, the four the most multiple medicine carryings of medicine carrying discharge simultaneously, alternately release, gradient release, make the release concentration of medicine and speed all
Precisely controlled, and rapid shaping technique simultaneously can be according to concrete condition or surgical outcome systems such as cancer position, forms
Make the implants of different shape and size to adapt to the demand of different patient, can make according to the concrete condition of therapeutic scheme
Bone marrow is interior, the selectivity individuation medicine carrying implants of perilesional soft tissue, metastasis site, makes therapeutic effect optimization, medicine
Side effect minimizes, and avoids the generation of drug resistance and Drug Abuse simultaneously.
Detailed description of the invention
Hereinafter the preferred embodiments of the present invention are illustrated, it will be appreciated that preferred embodiment described herein is only used
In the description and interpretation present invention, it is not intended to limit the present invention.
Medicine carrying implants is to be combined with biocompatible materials by medicine, inserts internal rear slow Slow release, whereby
Reach the effect that local is treated.Suitably making material is also the key building good inner matter, the poly-left side selected by this experiment
Rotation lactic acid (PLLA) has been used safely as suture nearly 30 years, and its good biocompatibility and biodegradability are by extensively
Accept, be one of clinical conventional biomaterial.In Orthopedic Clinical is treated, PLLA, as Biodegradable material, both can make
Make pediatric Orthopaedics inside-fixture, it is possible to make tissue-engineered scaffolds, have that good biocompatibility, plasticity is strong, degradation speed
Can be relatively uniform with bone defect healing etc. advantage.Tradition medicine carrying inner matter can only carry a kind of medicine, and drug release rate,
Concentration is uncontrollable, need second operation, can not individualized treatment.
Embodiment 1:
Step one: the preparation of individuation degradable multiple medicine carrying controlled release implants；By the CAD to medicine carrying implants stereochemical structure
Design, uses mimics, autoCAD software, according to human anatomy feature and solid geometry principle design spheroid or cylinder
Or fan arc or lamellar difference geometric shape implants, and carry out computer contrast and detection, design methotrexate, cisplatin, many
The medicine of soft medicine carrying more single than star, ifosfamide etc. and many medicine carryings various combination implants joins mode for cloth and manufacturing process；
Step 2: the preparation of rapid shaping material composition and processing parameter setting；(1) prepared by PLLA: grind preparation PLLA granule, sieve
Different-diameter PLLA granule internal inside plants compact structure and the impact of porosity is studied after choosing；(2) prepared by binding agent: right
Than studying the different formulations organic solution performance as PLLA binding agent；(3) technological parameter research: study different shower nozzles with phase
Same speed moves, and keeps nozzle diameter, hydrojet rheological parameter, hydrojet liquid-drop diameter, overlay thickness, spraying number of times, angle of spray
Degree, spraying position, a spacing, distance between centers of tracks are identical with saturation coefficient, the impact on Rapid Prototyping technique.
Embodiment 2:
Step one: the preparation of individuation degradable multiple medicine carrying controlled release implants；By the CAD to medicine carrying implants stereochemical structure
Design, uses mimics, autoCAD software, according to human anatomy feature and solid geometry principle design spheroid or cylinder
Or fan arc or lamellar difference geometric shape implants, and carry out computer contrast and detection, design methotrexate, cisplatin, many
The medicine of soft medicine carrying more single than star, ifosfamide etc. and many medicine carryings various combination implants joins mode for cloth and manufacturing process；
Step 2: the preparation of rapid shaping material composition and processing parameter setting；(1) prepared by PLLA: grind preparation PLLA granule, sieve
Different-diameter PLLA granule internal inside plants compact structure and the impact of porosity is studied after choosing；(2) prepared by binding agent: right
Than studying the different formulations organic solution performance as PLLA binding agent；(3) technological parameter research: study different shower nozzles with not
Same speed moves, and keeps nozzle diameter, hydrojet rheological parameter, hydrojet liquid-drop diameter, overlay thickness, spraying number of times, angle of spray
Degree, spraying position, a spacing, distance between centers of tracks are identical with saturation coefficient, the impact on Rapid Prototyping technique.
Embodiment 3:
Step one: the preparation of individuation degradable multiple medicine carrying controlled release implants；By the CAD to medicine carrying implants stereochemical structure
Design, uses mimics, autoCAD software, according to human anatomy feature and solid geometry principle design spheroid or cylinder
Or fan arc or lamellar difference geometric shape implants, and carry out computer contrast and detection, design methotrexate, cisplatin, many
The medicine of soft medicine carrying more single than star, ifosfamide etc. and many medicine carryings various combination implants joins mode for cloth and manufacturing process；
Step 2: the preparation of rapid shaping material composition and processing parameter setting；(1) prepared by PLLA: grind preparation PLLA granule, sieve
Different-diameter PLLA granule internal inside plants compact structure and the impact of porosity is studied after choosing；(2) prepared by binding agent: right
Than studying the different formulations organic solution performance as PLLA binding agent；(3) technological parameter research: study identical shower nozzle with phase
Same speed moves, and keeps nozzle diameter, hydrojet rheological parameter, hydrojet liquid-drop diameter, overlay thickness, spraying number of times, angle of spray
Degree, spraying position, a spacing, distance between centers of tracks are identical with saturation coefficient, the impact on Rapid Prototyping technique.
Embodiment 4:
Step one: the preparation of individuation degradable multiple medicine carrying controlled release implants；By the CAD to medicine carrying implants stereochemical structure
Design, uses mimics, autoCAD software, according to human anatomy feature and solid geometry principle design spheroid or cylinder
Or fan arc or lamellar difference geometric shape implants, and carry out computer contrast and detection, design methotrexate, cisplatin, many
The medicine of soft medicine carrying more single than star, ifosfamide etc. and many medicine carryings various combination implants joins mode for cloth and manufacturing process；
Step 2: the preparation of rapid shaping material composition and processing parameter setting；(1) prepared by PLLA: grind preparation PLLA granule, sieve
Different-diameter PLLA granule internal inside plants compact structure and the impact of porosity is studied after choosing；(2) prepared by binding agent: right
Than studying the different formulations organic solution performance as PLLA binding agent；(3) technological parameter research: the shower nozzle that differs of research with
Different speed moves, and keeps nozzle diameter, hydrojet rheological parameter, hydrojet liquid-drop diameter, overlay thickness, spraying number of times, spraying
Angle, spraying position, a spacing, distance between centers of tracks are identical with saturation coefficient, the impact on Rapid Prototyping technique.
Conclusion: rapid shaping technique is prepared the sharpest edges of individuation degradable multiple medicine carrying controlled release implants and is individuality
Change, strong chemotherapeutic drug combination targetedly can be made according to Patient drug's sensitivity tests and tumor pathological characteristics, and
And various dose or the medicine carrying implants of variable dose can be made according to patient's own situation, thus realize single medicine carrying, double load
Medicine, the four the most multiple medicine carryings of medicine carrying discharge simultaneously, replace release, gradient release, make the release concentration of medicine and speed all obtain
To accurately controlling, and rapid shaping technique can make according to the concrete conditions such as cancer position, form or surgical outcome simultaneously
Go out the implants of different shape and size to adapt to the demand of different patient, bone can be made according to the concrete condition of therapeutic scheme
Marrow is interior, the selectivity individuation medicine carrying implants of perilesional soft tissue, metastasis site, makes therapeutic effect optimization, medicine secondary
Effect minimizes, and avoids the generation of drug resistance and Drug Abuse simultaneously.
Finally it is noted that the foregoing is only the preferred embodiments of the present invention, it is not limited to the present invention,
Although being described in detail the present invention with reference to previous embodiment, for a person skilled in the art, it still may be used
So that the technical scheme described in foregoing embodiments to be modified, or wherein portion of techniques feature is carried out equivalent.
All within the spirit and principles in the present invention, any modification, equivalent substitution and improvement etc. made, should be included in the present invention's
Within protection domain.
Claims (4)
1. the degradable multiple medicine carrying controlled release osteosarcomatous method of implants partial interventional therapy, it is characterised in that: include following step
Rapid:
Step one: the preparation of individuation degradable multiple medicine carrying controlled release implants；
Step 2: the preparation of rapid shaping material composition and processing parameter setting.
The degradable the most according to claim 1 multiple medicine carrying controlled release osteosarcomatous method of implants partial interventional therapy, its
It is characterised by: described step one includes the CAD design of medicine carrying implants stereochemical structure.
The degradable the most according to claim 2 multiple medicine carrying controlled release osteosarcomatous method of implants partial interventional therapy, its
It is characterised by: described CAD design includes:
(1), mimics, autoCAD software is used, according to human anatomy feature and solid geometry principle design spheroid or cylinder
Body or fan arc or lamellar difference geometric shape implants, and carry out computer contrast and detection；
(2), single medicine carrying such as design methotrexate, cisplatin, doxorubicin, ifosfamide etc. and many medicine carryings various combination implants
Medicine joins mode for cloth and manufacturing process.
The degradable the most according to claim 1 multiple medicine carrying controlled release osteosarcomatous method of implants partial interventional therapy, its
It is characterised by: described step 2 includes:
(1), prepared by PLLA: grinds preparation PLLA granule, studies different-diameter PLLA granule internal inside plants structure after screening
Compactness and the impact of porosity；
(2), prepared by binding agent: comparative study different formulations organic solution is as the performance of PLLA binding agent；
(3), technological parameter research: the different shower nozzle of research moves speed, nozzle diameter, hydrojet rheological parameter, hydrojet liquid-drop diameter, laying
Thickness, spraying number of times, spray angle, spraying position, droplet spacing, distance between centers of tracks, the saturation coefficient impact on Rapid Prototyping technique.
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| CN201610291629.5A CN105944106A (en) | 2016-05-05 | 2016-05-05 | Method for local intervention treatment of osteosarcoma by degradable multiple drug-loading controlled-release internal implant |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610291629.5A CN105944106A (en) | 2016-05-05 | 2016-05-05 | Method for local intervention treatment of osteosarcoma by degradable multiple drug-loading controlled-release internal implant |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2652547C1 (en) * | 2018-01-09 | 2018-04-26 | Алексей Валерьевич Юмашев | Method of complex treatment of patients with lower jaw osteosarcoma |
Citations (1)
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| CN101862230A (en) * | 2009-04-17 | 2010-10-20 | 华中科技大学同济医学院附属协和医院 | Controlled-release multilayer drug-loaded artificial bone and preparation method thereof |
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- 2016-05-05 CN CN201610291629.5A patent/CN105944106A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101862230A (en) * | 2009-04-17 | 2010-10-20 | 华中科技大学同济医学院附属协和医院 | Controlled-release multilayer drug-loaded artificial bone and preparation method thereof |
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| 吴贵: ""快速成形技术制备聚乳酸/异烟肼缓释体及其体外释放特征的实验研究"", 《中国优秀硕士学位论文全文数据库》 * |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| RU2652547C1 (en) * | 2018-01-09 | 2018-04-26 | Алексей Валерьевич Юмашев | Method of complex treatment of patients with lower jaw osteosarcoma |
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