CN103656701A - Low-temperature sterilizing method suitable for biodegradable scaffold - Google Patents

Low-temperature sterilizing method suitable for biodegradable scaffold Download PDF

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Publication number
CN103656701A
CN103656701A CN201210337139.6A CN201210337139A CN103656701A CN 103656701 A CN103656701 A CN 103656701A CN 201210337139 A CN201210337139 A CN 201210337139A CN 103656701 A CN103656701 A CN 103656701A
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CN
China
Prior art keywords
support
sterilizing
temperature
carrier
method described
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Pending
Application number
CN201210337139.6A
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Chinese (zh)
Inventor
王一涵
黄楚波
孟娟
罗七一
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Shanghai Microport Medical Group Co Ltd
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Shanghai Microport Medical Group Co Ltd
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Publication date
Application filed by Shanghai Microport Medical Group Co Ltd filed Critical Shanghai Microport Medical Group Co Ltd
Priority to CN201210337139.6A priority Critical patent/CN103656701A/en
Priority to PCT/CN2013/083357 priority patent/WO2014040542A1/en
Publication of CN103656701A publication Critical patent/CN103656701A/en
Pending legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/16—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
    • A61L2/20—Gaseous substances, e.g. vapours
    • A61L2/206—Ethylene oxide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2202/00—Aspects relating to methods or apparatus for disinfecting or sterilising materials or objects
    • A61L2202/20—Targets to be treated
    • A61L2202/24—Medical instruments, e.g. endoscopes, catheters, sharps

Abstract

The invention relates to field of medical appliances. The invention specifically relates to a sterilizing technology of medical appliances and particularly relates to a low-temperature sterilizing method suitable for a biodegradable scaffold. The biodegradable scaffold is sterilized by adopting a low-temperature and low-moisture ethylene oxide (EO) sterilizing method. According to the method disclosed by the invention, the molecular chain structures of macromolecules are not influenced in a sterilizing process, the molecular weight of the sterilized scaffold material is hardly reduced compared with that of the non-sterilized scaffold, and the properties such as crystallinity, toughness and strength of the sterilized biodegradable scaffold do not change remarkably, thereby eliminating the adverse effects of the existing EO sterilization on a degradable high polymer material.

Description

A kind of low temperature sterilization method that is applicable to Biodegradable scaffold
Technical field
The present invention relates to medical instruments field.Particularly, the present invention relates to the sterilization technology of medical apparatus and instruments, particularly a kind of low temperature sterilization method that is applicable to Biodegradable scaffold.
Background technology
Support is one of apparatus in current the most frequently used angioplasty, is used for the treatment of the luminal stenosis that various diseases causes.In existing metal rack prolonged stay human body, can cause thrombus in stents and form and blood vessel restenosis in late period, therefore biodegradable polymeric stent becomes the study hotspot of intravascular stent of new generation.Sterilizing is support manufacture link together with requisite in producing, and existing metal rack (particularly drug stent) sterilizing is mainly in the mode of oxirane (EO), to carry out under higher temperatures.The Bactericidal Mechanism of oxirane is to utilize the ethylene oxide gas molecule that diffusivity is strong, penetration capacity is fast to combine with amino, hydroxyl, carboxyl or sulfydryl in bacterioprotein molecule, enzyme, nucleic acid, the metabolism of somatic cells is produced to irreversible destruction, thus kill bacteria.In the process of oxirane effect, must there is the auxiliary of temperature and two factors of water, temperature strengthens the deactivation ability of EO, and hydrone promotes protein denaturation, so the temperature range of current ethylene oxide sterilizing is generally 40-55 ℃.
EO sterilizing relates to four key elements: temperature, humidity, concentration and time.Temperature reaches more than 60 ℃, and polymerization will occur EO, so the optimum temperature of sterilizing is 55 ℃ of left and right.Below 40 ℃, 10 ℃ of the every risings of temperature, double the killing rate of spore; 40 ~ 55 ℃, bactericidal effect does not increase with temperature.Water extraction has supplied the medium of sterilizing, can promote EO open loop, can impel microprotein degeneration again.When relative humidity is 30% ~ 60%, bactericidal effect is best, and humidity is less than 20% or be greater than 80%, and bactericidal effect weakens.The relation of EO concentration and bactericidal effect, determines according to different temperature, and below 40 ℃, EO concentration is higher, and germicidal efficiency is higher; 40 ℃ of above this relations are not obvious.Concentration height also can cause other negative effects, such as EO residual quantity is large, product is resolved and is caused difficulty etc.Sterilization time is longer, and inactivating efficacy is better.
Degradable macromolecule support is different from traditional metal rack, has non-refractory, the weakness such as poor, unstable properties of humidity, radiation resistance not, so the sterilizing methods of metal rack or sterilizing parameter are not suitable for degradable macromolecule support.Ethylene oxide sterilizing requires support to be placed in for a long time higher temperatures, wet environment, can cause the character of degradable macromolecule to change, such as hydrolysis, crystallization etc.
Due to these problems of EO sterilizing, also have the method for some research and utilization electron beams or gamma ray to carry out radiation sterilization to biodegradable stent at present, but radiation sterilization is very large to high molecular molecular weight damage, also exists larger problem.
U.S. Patent No. 20110209442 discloses a kind of electron beam that utilizes and biodegradable stent has been carried out to the method for sterilizing, requires irradiation dose must not surpass 15kGy.Another piece of U.S. Patent No. 7964136 discloses a kind of gamma ray that utilizes and biodegradable stent carried out to the method for sterilizing, and requiring radiation dose is that 2.5Mrad(conversion equals 25kGy), but before sterilizing, must make sample be sealed in atmosphere of inert gases.
Above-mentioned these patents adopt and reduce the methods such as dosage, gas shield, are intended to reduce the damage of radiation sterilization process to degradable macromolecule as far as possible.But high molecular molecular weight still has the decline of 20%-30%.Be accompanied by molecular weight and molecular weight, high molecular intensity, degradation cycle all can reduce, thereby affect the performance of biodegradable stent.
Yet there are no the report that ethylene oxide sterilizing method is applied to biodegradable stent sterilizing.
Summary of the invention
In order to solve the sterilization technology problem of Biodegradable scaffold, overcome deficiency of the prior art and defect, patent application of the present invention provides a kind of sterilizing methods, has adopted the method for the ethylene oxide sterilizing of low temperature, low humidity to carry out sterilizing to biodegradable stent.The method can not exert an influence to high molecular molecular chain structure at sterilization process, the molecular weight of sterilizing after-poppet material declines with not comparing before sterilizing almost, after sterilizing there is not significant change in the performance such as the degree of crystallinity of biodegradable stent, toughness, intensity yet, thereby solved the harmful effect of existing EO sterilizing to degradable high polymer material.
Particularly, the invention provides a kind of ethylene oxide sterilizing method that is applicable to degradable polymer support, comprise the following steps:
Degradable polymer support is provided;
Support pressure is held on carrier, and by support together with carrier, adopt bag filter to pack;
Send into sterile chamber, then EO sterilizing parameter: temperature 20-40 ℃ is set, the interval 30-35 ℃ of Optimal Temperature; Relative humidity 20-60%, 35-50% between optimum humidity province; EO concentration 500-800mg/L, optimum interval 600-700mg/L; Sterilization time 4-8 hour; And
After sterilizing, support and carrier are resolved, resolution temperature 20-45 ℃, optimum interval 25-30 ℃, the time is greater than 24 hours, and resolving environment is vacuum.
According to the present invention, this support can be that bare bracket can be also the support with medication coat.The macromolecule polymer material that support adopts includes but not limited to copolymer, polycaprolactone, polydioxanone, poly-anhydride, the tyrosine Merlon of polylactic acid, polyglycolic acid, polylactic acid and polyglycolic acid, and their blend or copolymer etc.According to the difference of material and component thereof, the degradation cycle of support in human body can be selected arbitrarily from two months by 3 years.Support adopts the method for cut polymer pipe or polymer fiber braiding to obtain, and forms columniform network structure, can reach the object of compression and expansion.
According to the present invention, bracket conveyer comprises the ingredients such as sacculus, conduit, seal wire, development point, connector, conduit and seal wire play the effect that support is imported to human lesion position, and sacculus plays the effect of expandable stent, and the point that develops plays the effect of following the tracks of in vivo backing positions.
According to the present invention, the temperature and humidity in sterile chamber, before reaching balance, can be carried out the step of preheating or pre-dehumidifying.Discharge EO gas and can adopt the mode of evacuation, blowing air repeatedly to take a breath, until the EO gas residue on support and carrier reaches the requirement of standard.
Support molecular weight after sterilizing is compared with before sterilizing, and the amplitude of decline is no more than 10%, and mechanical property maintains in former level and has no decline.The aseptic test result of support and carrier shows, exists the probability of survival microorganism can reach standard YY/T 0615-1:2007 desired 1 * 10 on apparatus -6below.EO residual quantity is also at the desired 10 μ g/cm of standard ISO 10993 2in scope.
The specific embodiment
In order further to understand the present invention, below in conjunction with embodiment, preferred version of the present invention is described.These descriptions just illustrate the feature and advantage of the inventive method, but not limit the scope of the invention.
Embodiment mono-:
In the present embodiment, by the method melt extruding, gathered (D-lactic acid-glycolic) copolymer (PLGA, wherein the copolymerization ratio of two monomers is 85:15) tubing, wall thickness 1.5mm, external diameter 3mm.Aforementioned tubes is cut into the support of length 15mm with femtosecond laser machine.Utilize to press on the machine of holding folds support pressure sacculus at carrier front end, the length of sacculus flat segments is larger than stent length.To be with standoff carrier to put into coil pipe, and pack with bag filter.
Packaged support is put into sterile chamber, and temperature setting is set to 35 ℃, and relative humidity is set to 45%, and after the pre-heating humidification stage, sterilized environment is basicly stable.Adding the concentration of EO is 600mg/L, and making support open-assembly time in EO environment is 4 hours.Then evacuation venting repeatedly, emptying EO gas, resolves EO residual on product, room temperature after 72 hours residual quantity can meet the requirement of sterilizing standard.
Aseptic test and cell toxicant test (testing establishing criteria GB 18281.1-2000 and GB/T 16886.5-2003 respectively carries out) is carried out in sample censorship after sterilizing, test result shows, support and carrier all reach desirable sterilization effect, and cell toxicant test result is 1 grade.Before the radial support power of support and sterilizing, in same level, have no obvious decline; The molecular weight and molecular weight 6% of support, can not affect its degradation behavior.
Embodiment bis-:
It is 12mm that the present embodiment has gone out length with Poly-L-lactic acid (PLLA) fibrage of diameter 1mm, the biodegradable stent of external diameter 3.5mm.Support pressure is held and with bag filter packing, put into sterile chamber.Sterilising temp is set to 33 ℃, and relative humidity is that 40%, EO concentration is 700mg/L, and sterilizing open-assembly time is 6 hours.After sterilizing, under 30 ℃ of vacuum conditions, resolve 72 hours.
The EO residual quantity of support and carrier meets 10 μ g/cm of standard-required 2below, product surface and inside are all aseptic, and cytotoxicity test result shows 0 grade.The radial support power fall of support is no more than 4%, and molecular weight and molecular weight degree is no more than 6%, degradation cycle with before sterilizing, compare unchanged.
Embodiment tri-:
In the present embodiment, by the method that melt extrudes, obtain Poly-L-lactic acid (PLLA) tubing, wall thickness 1.2mm, external diameter 3.5mm, cuts into the support of 18mm with femtosecond laser machine.Ratio blend by drug rapamycin and poly-dl-lactide (PDLLA) with 1:1, and be dissolved in oxolane, adopt the technique of spraying, at rack surface, form medication coat.This drug stent is pressed and held and pack with bag filter.
Support is put into behind sterile chamber, 32 ℃ of set temperatures, humidity 35%, EO concentration 600mg/L, 4 hours open-assembly times.Normal-temperature vacuum is resolved 72 hours.
After sterilizing, with the surface of microscopic examination support, medication coat is complete, does not find the phenomenon of coating shedding or cracking.The HPLC test result of medicine shows, significant change does not all occur for the area of characteristic peak and position, and medicines structure and function are not subject to the impact of sterilization process.Testing drug release profiles in vitro, in 3 days, release amount of medicine reaches release amount of medicine in 60%, 30 day and reaches 80%.After 30 days, with the surface of microscopic examination support, drug-carried coat and rack surface laminating are good, do not occur tympanites and obscission.
Beneficial effect of the present invention
Patent application of the present invention has adopted a kind of existing sterilizing methods that is different from, and oxirane (EO) carries out sterilizing to Biodegradable scaffold.Sterilizing parameter feature is low temperature and low humidity, is different from traditional metal rack.
Support molecular weight after sterilizing is compared with before sterilizing, and the amplitude of decline is no more than 10%, and mechanical property maintains in former level and has no decline.The aseptic test result demonstration of support and carrier, microorganism killing rate can reach standard-required, and EO residual quantity is also in the scope of standard-required.
The explanation of above embodiment is just for helping to understand core concept of the present invention.It should be pointed out that for the ordinary skill in the art, under the premise without departing from the principles of the invention, can also carry out some improvement and modification to the inventive method, but these improvement and modify also fall in the scope that the claims in the present invention ask for protection.

Claims (7)

1. an ethylene oxide sterilizing method that is applicable to degradable polymer support, comprises the following steps:
Degradable polymer support is provided;
Support pressure is held on carrier, and by support together with carrier, adopt bag filter to pack;
Send into sterile chamber, then EO sterilizing parameter: temperature 20-40 ℃ is set, the interval 30-35 ℃ of Optimal Temperature; Relative humidity 20-60%, 35-50% between optimum humidity province; EO concentration 500-800mg/L, optimum interval 600-700mg/L; Sterilization time 4-8 hour; And
After sterilizing, support and carrier are resolved, resolution temperature 20-45 ℃, optimum interval 25-30 ℃, the time is greater than 24 hours, and resolving environment is vacuum.
2. method claimed in claim 1, its medium-height trestle is bare bracket, or with the support of medication coat.
3. the method described in claim 1 or 2, the macromolecule polymer material that its medium-height trestle adopts includes but not limited to, the copolymer of polylactic acid, polyglycolic acid, polylactic acid and polyglycolic acid, polycaprolactone, polydioxanone, poly-anhydride, tyrosine Merlon, and their blend or copolymer.
4. the method described in aforementioned claim any one, wherein according to the difference of material and component thereof, the degradation cycle of support in human body selected arbitrarily from two months to 3 years.
5. the method described in aforementioned claim any one, its medium-height trestle adopts the method for cut polymer pipe or polymer fiber braiding to obtain, and forms columniform network structure, can compress and expand.
6. the method described in aforementioned claim any one, wherein bracket conveyer comprises sacculus, conduit, seal wire, development point and connector ingredient.
7. the method described in aforementioned claim any one, wherein the temperature and humidity in sterile chamber is before reaching balance, can carry out the step of preheating or pre-dehumidifying, discharge EO gas and can adopt the mode of evacuation, blowing air repeatedly to take a breath, until the EO gas residue on support and carrier reaches standard-required.
CN201210337139.6A 2012-09-12 2012-09-12 Low-temperature sterilizing method suitable for biodegradable scaffold Pending CN103656701A (en)

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CN201210337139.6A CN103656701A (en) 2012-09-12 2012-09-12 Low-temperature sterilizing method suitable for biodegradable scaffold
PCT/CN2013/083357 WO2014040542A1 (en) 2012-09-12 2013-09-12 Low temperature sterilization method suitable for biodegradable stent

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107158483A (en) * 2017-07-12 2017-09-15 上海微特生物技术有限公司 A kind of sterile working method for improving biodegradable stent systematic function
CN111068086A (en) * 2019-12-11 2020-04-28 吉林华碳科技发展有限公司 Method for disinfecting environment-friendly medical material
CN112999388A (en) * 2021-02-08 2021-06-22 大博医疗科技股份有限公司 Method for sterilizing absorbable implant and matched instrument combination product

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002026271A1 (en) * 2000-09-29 2002-04-04 Cordis Corporation Coated medical devices and sterilization thereof
US20020051730A1 (en) * 2000-09-29 2002-05-02 Stanko Bodnar Coated medical devices and sterilization thereof
CN101703789A (en) * 2009-10-29 2010-05-12 无锡中科光远生物材料有限公司 Method for sterilizing polylactic acid type superfine fibrous membrane materials
CN102166141A (en) * 2010-07-30 2011-08-31 深圳市信立泰生物医疗工程有限公司 Process for preparing drug eluting stent
CN102438692A (en) * 2009-01-20 2012-05-02 阿玛安斯医药私人公司 Sterilization methods and apparatus

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050089442A1 (en) * 2003-10-28 2005-04-28 Young William T. Method for sterilization using ethylene oxide
US7993578B2 (en) * 2004-10-29 2011-08-09 Depuy Spine, Inc. Methods and kits for aseptic filling of products

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002026271A1 (en) * 2000-09-29 2002-04-04 Cordis Corporation Coated medical devices and sterilization thereof
US20020051730A1 (en) * 2000-09-29 2002-05-02 Stanko Bodnar Coated medical devices and sterilization thereof
CN102438692A (en) * 2009-01-20 2012-05-02 阿玛安斯医药私人公司 Sterilization methods and apparatus
CN101703789A (en) * 2009-10-29 2010-05-12 无锡中科光远生物材料有限公司 Method for sterilizing polylactic acid type superfine fibrous membrane materials
CN102166141A (en) * 2010-07-30 2011-08-31 深圳市信立泰生物医疗工程有限公司 Process for preparing drug eluting stent

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
秦廷武，杨志明，张姝江: "不同灭菌法对组织工程支架降解性和力学特性的影响", 《中华物理医学与康复》 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107158483A (en) * 2017-07-12 2017-09-15 上海微特生物技术有限公司 A kind of sterile working method for improving biodegradable stent systematic function
CN111068086A (en) * 2019-12-11 2020-04-28 吉林华碳科技发展有限公司 Method for disinfecting environment-friendly medical material
CN112999388A (en) * 2021-02-08 2021-06-22 大博医疗科技股份有限公司 Method for sterilizing absorbable implant and matched instrument combination product
CN112999388B (en) * 2021-02-08 2023-02-10 厦门博创中安医疗技术有限公司 Method for sterilizing absorbable implant and matched instrument combination product

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Application publication date: 20140326