EP0124596A4 - Sterilisation chimique de tissu biologique implantable. - Google Patents

Sterilisation chimique de tissu biologique implantable.

Info

Publication number
EP0124596A4
EP0124596A4 EP19830903751 EP83903751A EP0124596A4 EP 0124596 A4 EP0124596 A4 EP 0124596A4 EP 19830903751 EP19830903751 EP 19830903751 EP 83903751 A EP83903751 A EP 83903751A EP 0124596 A4 EP0124596 A4 EP 0124596A4
Authority
EP
European Patent Office
Prior art keywords
percent
surfactant
tissue
formaldehyde
aliphatic
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.)
Withdrawn
Application number
EP19830903751
Other languages
German (de)
English (en)
Other versions
EP0124596A1 (fr
Inventor
Aws S Nashef
Guy Lowery
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Baxter International Inc
Original Assignee
American Hospital Supply Corp
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by American Hospital Supply Corp filed Critical American Hospital Supply Corp
Publication of EP0124596A1 publication Critical patent/EP0124596A1/fr
Publication of EP0124596A4 publication Critical patent/EP0124596A4/fr
Withdrawn legal-status Critical Current

Links

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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3683—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment
    • A61L27/3687—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix subjected to a specific treatment prior to implantation, e.g. decellularising, demineralising, grinding, cellular disruption/non-collagenous protein removal, anti-calcification, crosslinking, supercritical fluid extraction, enzyme treatment characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents
    • 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
    • A61L2/0005—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
    • A61L2/0082—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using chemical substances
    • A61L2/0088—Liquid substances
    • 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
    • A61L2/18—Liquid substances or solutions comprising solids or dissolved gases
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/507—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor

Definitions

  • the chemical processing of biological tissue such as that used in the preparation of heart valves , ligaments, tendons, tympanic membranes, and the like prior to implantation into humans involves a series of procedures to insure both the compatibility and the structural and functional integrity of the implanted tissue in its new host.
  • these conventionally employed procedures are glutaraldehyde-fixation (tanning) and formaldehyde-sterilization.
  • glutaraldehyde-fixation of tissue prior to implantation renders it relatively biologically inert and has been widely accepted as a necessary step in the processing of the tissue.
  • Microascus cinereus is a fungus from the Ascomycete family which exhibits resistance to various concentrations of both glutaraldehyde and formaldehyde which are conventionally used in the processing of biological tissue prior to implantation.
  • Microascus cinereus is a common environmental organism having worldwide geographic distribution, and has been clinically identified as being associated with minor dermal lesions.
  • This process advantageously improves the efficacy of the tissue sterilization process while maintaining the biochemical, structural, and functional integrity of implantable tissue such as xenograft heart valves prosthesis. Moreover, we have unexpectedly found that many microorganisms already susceptible to formaldehyde or glutaraldehyde sterilization are destroyed considerably faster using the process and related compositions of the present invention.
  • an improved process for treating biological tissue prior to implantation in order to effect sterilization thereof comprises contacting biological tissue under sterilizing conditions with a sterilization effective amount of a solution comprising formaldehyde or glutaraldehyde, alcohol, and a surfactant.
  • OMPI tissue can be derived from various sources including but not limited to bovine , porcine , horse, sheep , kangaroo, or rabbit; and can include tendons , ligaments, heart valves, or tissue used to construct heart valves such as dura mater and pericardium . It is further contemplated that tissue used for augmentation such as skin patches , pericardial patches , aortic patches , and tympanic membranes is suitable in the present invention. Moreover, it is contemplated that the surfaces of non-biological items such as surgical instruments, medical devices , valve conduits and the like made of plastic, cloth, or metal, can be effectively treated according to the present invention.
  • porcine tissue valves and bovine pericardial tissue used in the preparation of bioprosthetic heart valves was fixed in glutaraldehyde and treated with the improved sterilant solution of the present invention and was implanted subcutaneously in rabbits.
  • the treated valve tissue which lost its resistance to conventional sterilants such as glutaraldehyde and formaldehyde showed no significant difference in the integrity of the valve tissue compared to the tissue treated in the conventional manner.
  • formaldehyde-resistant organisms such as Microascus cinereus associated with implantable biological tissue have been made susceptible to sterilization, i.e. , destruction of the organism. It is contemplated from the results of our studies, however, that the present compositions are useful in destroying formaldehyde- resistant organisms on the surfaces of non-biological articles as well. We have unexpectedly found that the sterilant compositions in accordance with the present invention are more effective against these formaldehyde-resistant microorganisms on surfaces such as tissue than in solution.
  • the improved sterilant compositions of the present invention are effective against a large variety of organisms including but not limited to the following organisms: Aspergillus niger, Bacillus licheniformis , Bacillus pumilus, Bacillus subtilis var niger, Brucella suis, Candida albicans, Chaetomium globosum , Clostridium sporogenes , Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Microascus cinereus, Mycobacterium chelonei-like organism , Mycobacterium fortuitum, Pseudomonas aeruginosa, Salmonella typhimurium , Serratia marcescens , Shi
  • the improved sterilant components may be used in admixture with the conventional sterilizing solutions containing glutaraldehyde or formaldehyde, or may be formulated into compositions as described hereinafter. Normally, from about a 0.2 to about 1% glutaraldehyde solution or from about 3 to about 5% formaldehyde solution is used to sterilize biological tissue prior to implantation. Preferable sterilant concentrations are 0.625% glutaraldehyde or from about 4 to about 5% formaldehyde.
  • tissue-stabilizing pH range that is, within a pH range that is not deleterious to the tissue components.
  • the effectiveness of the present invention has been verified in a pH range from about 4.5 to about 7.5 , the preferred pH range is chosen for compatibility with the tissue.
  • OMPI pH range is from about 7.0 to about 7.6 , and a more preferred pH range is from about 7.1 to about 7.4.
  • the most preferred pH in accordance with the present invention is 7.3.
  • sterilant compositions used in accordance with one embodiment of the present invention are preferably stable, non-interacting with the sterilization process, and have a buffering capacity sufficient to maintain a tissue-acceptable pH.
  • the choice of the appropriate buffer, and its concentration will depend upon specific tissue preparation conditions; variations of which have been introduced by several manufacturers.
  • the buffers can be either conventional 0.01-0.02 M phosphate-buffered saline (PBS) or phosphate- deficient solutions such as those containing less phosphate than these 0.01 to 0.02 M PBS solutions, and preferably less than about 0.001 to about 0.002 M phosphate.
  • Preferred buffers in accordance with the present invention include borate, carbonate, bicarbonate, cacodylate (found to be non-toxic in animals) , and other synthetic, artificial, or organic buffers such as HEPES N-2-hydroxyethylpiperazine-N , -2-ethanesulphonic acid; MOPS , 2-(N-morpholino) propanesulphonic acid; and PIPES ,
  • the buffered or unbuffered solutions used in accordance with the present invention should not interfere with the tissue sterilization process afforded by agents such as glutaraldehyde or formaldehyde. That is , they should not react with the agent or prevent the agent from achieving proper sterilization of the tissue.
  • agents such as glutaraldehyde or formaldehyde.
  • buffers containing primary and secondary amines such as tris(hydroxymethyl)aminomethane (Tris) , which are known to react with the aldehyde groups of glutaraldehyde or formaldehyde and thus interfere with the normal tissue sterilization process.
  • the tissue may be stored and processed in conventional well-known conditions , and may be fixed (tanned) conventionally in 0.625% glutaraldehyde in either phosphate-buffered solutions , or phosphate-free buffers as described above. Tissue handling conditions outside of the sterilization process as conventionally known are not considered part of our present invention.
  • alcohols used to render the resistant microorganisms more susceptible to sterilization include aliphatic as well as aromatic alcohols and are preferably lower aliphatic alcohols containing from 1 to about 5 carbon atoms.
  • Aliphatic alcohols include but are not limited to methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, sec-butanol, t-butanol, cyclohexanol, n-octanol, allyl alcohol, and the like.
  • Aromatic alcohols include benzyl alcohol, cresol, carbinol, and the like.
  • Lower aliphatic alcohols in accordance with the present invention include but are not limited to methanol, ethanol, propanol, butanol, isopropanol, and pentanol. More preferably, alcohols in accordance with the present invention are ethanol and isopropanol.
  • the concentration of alcohol to be used in the present invention falls in a range which will be limited at its lower end by the effectiveness in destroying resistant micro ⁇ organisms, and at its upper end by the impact or effect on the integrity of the tissue; and may depend somewhat on the type of alcohol used. We have found that ethanol concentrations falling within a range of from about 10% to about 30% are effective against these microorganisms , and thus describe a preferred range. A more preferred alcohol concentration is from about 20 to about 25% ethanol. The most preferred alcohol concentration is 22.5% ethanol.
  • Organic surfactants within the scope of the present invention include anionic, cationic, and nonionic surfactants and their salts.
  • Preferred salts of the surfactants in the present invention include sodium and potassium.
  • Anionic surfactants of the present invention are those having a relatively large hydrophobic region of hydrocarbon residues including both aliphatic groups , aromatic groups and combinations thereof bonded to a negatively charged ionic group.
  • the aliphatic residues may be branched chains, straight chains , cyclic , heterocyclic , saturated or unsaturated.
  • hydrophobic residues may either be connected directly to an anionic group such as carboxylate, sulfate, or sulfonate; or connected thereto through an intermediate linkage such as an ester, amide, sulfonamide , ether, or aryl group .
  • Anionic surfactants in one embodiment of the present invention are those having carboxylates bonded to the alkyl side chain of a steroid or through amino acids in the side chain; such as in the bile acids.
  • Illustrative bile acids in accordance with the present invention include but are not limited to deoxycholic acid, cholic acid, lithocholic acid, taurocholic acid, and glycocholic acid, and their salts.
  • Anionic surfactants in accordance with the present invention further include those having a carboxylate group bonded to a straight-chained aliphatic group preferably having from about 8 to about 20 carbon atoms; such as the sodium salts of fatty acids.
  • Anionic surfactants containing carboxylate groups in accordance with the present invention further include those having the carboxylate group coupled to a hydrophobic portion through an amide, sulfonamide, or ester linkage such as in the N-alkanoyl amino acids and N-acylated amino acids.
  • N-alkanoyl amino acids are those including but not limited to surfactants having the formula R., CONR 2 CHR 3 CO 2 - where R- is an aliphatic residue preferably having from about 8 to about 18 carbon atoms, Rute is hydrogen or methyl, and RRON is a conventional amino acid side chain.
  • Illustrative side chains include the non-polar aliphatic side chains of alanine, leucine, isoleucine, valine, and proline; the aromatic rings of phenylalanine and tryptophan; the polar side chains of glycine, serine, threonine, cystine, and the like; and the charged polar groups of aspartic acid, glutamic acid, lysine, and the like.
  • Preferred carboxlate containing surfactants in accordance with this embodiment of the present invention are those containing an amide linkage such as N-lauroylsarcosine.
  • Anionic surfactants in accordance with an alternate embodiment of the present invention include sulphates of aliphatic alcohols such as alkyl sulfates having from about 6 to 18 carbon atoms , ethylene oxide modified sulfates of aliphatic alcohols , sulfated ethanol amides, or alkyl phenols such as the sulfonated alkylphenyl ethers.
  • Further anionic surfactants include alkane sulfonic acids and alkylaryl sulfonic acids.
  • Illustrative of the sulphates of aliphatic alcohols is sodium dodecyl sulfate.
  • Alkane sulfonic acids in accordance with the present invention include those having the sulfur directly attached to the hydrophobic residue, such as 1-decane sulfonic acid; or coupled through an ester, amide, or ether; such as N-methyltaurine.
  • Alkylaryl sulfonates are those having the sulfur directly attached to an aromatic ring such as phenyl or napthyl which is, in turn, coupled to the hydrophobic residue preferably having from about 8 to about 18 carbon atoms.
  • Illustrative of this latter type of surfactant is dodecylbenzene sulfonic acid.
  • Cationic surfactants in accordance with the present invention include alkyl quaternary amines and their halide salts.
  • Preferable surfactants in the present invention include the chlorine and bromine salts of tertiary amines connected directly to a hydrophobic residue or connected thereto through an amide linkage.
  • the amines are directly connected to a relatively large hydrophobic portion having an aromatic residue such as benzene, pyridine or napthylene; aliphatic chain which is branched, unb ⁇ anched, cyclic, saturated, or unsaturated; or a combination of both aromatic and aliphatic residues.
  • Illustrative alkyl quaternary ammonium surfactants include but are not limited to cetylpyridinium chloride, cetyltrimethyl ammonium bromide, trimethylphenyl ammonium chloride, decyltrimethyl ammonium bromide, hexdecyltrimethyl ammonium bromide, and the like.
  • Nonionic surfactants in accordacne with the present invention include polyoxyalkylene ethers, polyoxyalkylene alkylaryl ethers , aliphatic esters, polyethers, polyoxyalkylene ester derivatives ,
  • Nonionic polyoxyalkylene , and preferably polyoxyethylene , ethers are those having a relatively long hydrophobic residue and a hydroxyl end connected by one or more alkylene oxide residues.
  • Examples of polyoxyalkylene ethers are polyoxyethylene lauryl ether (Brij) , polyoxyethylene oleyl ether, polyoxyethylene cetyl ether, and the like.
  • Nonionic polyoxyalkylene, and preferably polyoxyethylene, alkylaryl ethers are those having a relatively large hydrophobic residue and a hydroxyl end connected thereto by an aryl, such as benzene or napthaline and one or more alkylene oxide residues.
  • polyoxyalkylene alkylaryl ethers examples include polyethylene Glycol p-Isooctyl phenyl ethers such as Triton X-100 and the like.
  • Nonionic polyethers are those having the formula CH 3 (CH 2 )-O-(C 2 H 4 O M where N is about 11 , and M is about 23.
  • Nonionic aliphatic esters include aliphatic fatty acid esters , polypropyleneglycol fatty acid esters such as propyleneglycol monostearate , and glycerol fatty acid esters such as glycerol monostearate.
  • Aliphatic fatty acid esters are those having the formula R.COORg where R. is an alkyl preferably having from about 8 to about 20 carbon atoms, and R_ is an aliphatic residue having from about 1 to about 5 carbon atoms.
  • Saccharide and polyoxyalkylene ester derivatives are those having either a 5 or 6 carbon sugar in the former or a polyoxyalkylene chain in the latter coupled to a relatively long hydrophobic residue through an ester bond.
  • Illustrative saccharide derivatives include sorbitol coupled to fatty acids to form surfactants such as sorbitan trioleate, sorbitan strearate, sorbitan monooleate, and the like.
  • Polyoxyalkylene ester derivatives include polyoxyethylene monooleate, polyoxyethylene monostearate, and the like.
  • Combinations of polyoxyalkylene ether derivatives and sorbitol ester derivatives found to be useful in the present invention include polyoxyethylene sorbitan fatty acid derivatives such as polyoxyethylene (20) sorbitan monooleate ( Poly sorb ate-80 , Tween-80 manufactured by DIFCO) .
  • the concentration of surfactant is from about 0.1 to about 10 percent (w/v) and more preferably from about 0.5 to about 5 percent. Most preferably, the surfactant concentration is from about 0.5 to about 1.5 percent.
  • the tissue, surgical instruments, and medical devices are treated with the improved sterilant composition at temperatures ranging from about 20°C to about 100°C. More preferably the temperature is maintained from about 20°C to about 40°C.
  • sterilization is enhanced at temperatures above room temperature (20°C) to a range of from about 30 to about 40°C. A most preferred range is from about 32°C to about 38° C. Temperatures above this physiological temperature range might be harmful to the biological tissue, but would not be harmful to other surgical instruments or medical devices in accordance with the present invention.
  • the biological tissue is exposed to the improved sterilant composition for a period of time related to the quantity of microorganism present and the level of sterility assurance desired; and consequently the time can be varied according to needs.
  • tissue requiring a decrease in microorganisms tissue requiring a decrease in microorganisms
  • 0 — 6 cinereus from about 10 to 10 requires an exposure time of at least 7 hours at 35+3° C.
  • the interplay between time and temperature would dictate that if the temperature is increased, the time of exposure would necessarily decrease. Accordingly, if the temperature is decreased, then the exposure time would have to be increased dramatically.
  • a sterilant composition is considered potentially effective if it shows about a
  • sterilant compositions are considered particularly effective if the organism destroyed is on a surface or on tissue (substrate) .
  • tissue biological tissue (bioprosthetic heart valves) exposed to surfactant , rinsed free of surfactant, and then exposed to sterilants such as glutaraldehyde and alcohol are less effective against Microascus cinereus.
  • tissue must be exposed to the glutaralde ⁇ hyde or formaldehyde, alcohol, and surfactant simultaneously for optimal effect.
  • the tissue may be exposed to these three components in separate steps or in a single step .
  • a single-step exposure of tissue to the improved sterilant compositions of the present invention is preferred. c .
  • Example I Extracted porcine aortic heart valve tissue was thoroughly rinsed and shipped in an isotonic (285+15 milliosmols) solution of 0.02M phosphate-buffered saline (0.885 weight percent sodium chloride) at pH 7.3 and at about 4°C , fixed in 0.625 weight percent glutaraldehyde in an isotonic solution at pH 7.4 and at room temperature.
  • Example II A suspension of Microascus cinereus in a phosphate-buffered solution having a spore count of 10 5 " to 106 spores /ml was injected into various portions of a bioprosthetic heart valve prepared from the extracted tissue of Example I to give a final inoculum level of 7.1x10 spores per valve. The valve tissue was further exposed to 100ml of a 0.02M phosphate-buffered
  • OivIPI solution containing 4+0.4 percent formaldehyde, 20 percent ethanol (100% anhydrous ethanol) , pH 7.4 at 20-22°C for 48 hours .
  • the effect of the sterilant solution on the growth of Microascus cinereus was assessed at regular intervals by removing the valves from the solution, placing them in a fluid fungal support nutrient medium and visibly determining the viable spores remaining on the valve after treatment for 48 hours. At the end of 48 hours, no reduction in spore count was evident in any of 5 samples of the valve tissue tested.
  • a suspension of Microascus cinereus in a phosphate-buffered solution having a spore count of 10 to 10 spores /ml was injected into various portions of a bioprosthetic heart valve prepared from the extracted tissue of Example I to q give a final inoculum level of 5.6x10 spores per valve.
  • the valve tissue was further exposed to 100ml of a 0.02M phosphate-buffered solution containing 4+0.4 percent formaldehyde, 20 percent ethanol, 1 percent Tween-80 (sorbitan monooleate polyoxyethylene) , pH 7.4 at 20-22 °C for 48 hours.
  • Example IV A _ suspension of — M—i—c—r—o—a—s—c—u—s———— c—i—n—e—r—e—u—s— having a spore count of 10 to 10 spores /ml was injected into various portions of a bioprosthetic heart valve prepared from the extracted tissue of Example I to give a final inoculum level of 1.6x10 spores per valve was further treated as in Example III. At the end of 24 hours, no logarithmic reduction in spore count was evident in any of 5 samples of the valve tissue tested.
  • Example I tissue of Example I to give a final inoculum level of 7.7x10 spores per valve, after which the valve tissue was further treated as in
  • Example III with the exception that the tissue was treated at 32°C for 24 hours. At the end of 4 hours only 2 of 5 samples tested
  • Example VI A suspension of Bacillus pu _milas in a phosphate- buffered solution having a spore count of 10 to 10 spores per ml was injected into various portions of a bioprosthetic heart valve prepared from the extracted tissue of Example I to give a final
  • Example VII A suspension of Chaetomium globosum in a e a phosphate-buffered solution having a spore count of 10 to 10 spores per ml was injected into various portions of a bioprosthetic heart valve prepared from the extracted tissue of Example I to
  • Example 4 give a final inoculum level of 2.2x10 spores /valve, after which the valve tissue was further treated as in Example III with the exception that the tissue was treated at 32°C. At the end of 30 minutes, there was no growth of Chaetomium globosum detected in any of 5 samples of the valve tissue tested.
  • Example VIII The extracted tissue of Example I was exposed to 100ml of a 0.02M phosphate-buffered saline solution containing
  • Subcutaneous implantation of tissue in growing and mature rabbits was performed, and the degree of collagen fiber degeneration, host cellular infiltration, and tissue calcification (a significant concern for tissue valves) were determined for the tissue exposed to the current sterilant and tissue exposed to the improved sterilant. Host cell infiltration was comparable for both groups, while collagen fiber degeneration was less for the improved process. Tissue calcification was also less for the tissue exposed to the improved sterilant.
  • Example IX A suspension of Microascus cinereus in a phosphate-buffered solution having a spore count of 10 to 10 spores per ml was inoculated into 100 ml of 0.02M phosphate-buffered sterilant solution containing 4+0.4 percent formaldehyde, 20 percent ethanol, and 1 percent Tween-80 , pH 7.51 at 20-22°C to give a final inoculum level of 3.3xl0 3 spores /ml.
  • Example X The experiment of Example IX was repeated in all essential details with the exception that the spore-inoculate sterilant solution was treated at 33°C rather than 20-22°C . After 4 hours of exposure to the sterilant solution, no more spores were detected, and the average time required to reduce the spore count by a . factor of 10 is about 61 minutes.

Abstract

Procédé de traitement de tissu biologique avant son implantation afin d'en effectuer la stérilisation. Le procédé comprend en particulier l'utilisation de solutions améliorées d'agents de stérilisation contenant des agents de stérilisation de tissus conventionnels comme le glutaraldéhyde ou le formaldéhyde, de l'alcool, et des agents tensioactifs pour détruire les micro-organismes résistants.
EP19830903751 1982-11-12 1983-11-03 Sterilisation chimique de tissu biologique implantable. Withdrawn EP0124596A4 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US44102482A 1982-11-12 1982-11-12
US441024 1982-11-12

Publications (2)

Publication Number Publication Date
EP0124596A1 EP0124596A1 (fr) 1984-11-14
EP0124596A4 true EP0124596A4 (fr) 1985-06-26

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
EP19830903751 Withdrawn EP0124596A4 (fr) 1982-11-12 1983-11-03 Sterilisation chimique de tissu biologique implantable.

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Country Link
EP (1) EP0124596A4 (fr)
JP (1) JPS60500014A (fr)
CA (1) CA1211716A (fr)
WO (1) WO1984001894A1 (fr)

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EP0124596A1 (fr) 1984-11-14
CA1211716A (fr) 1986-09-23
JPS60500014A (ja) 1985-01-10
WO1984001894A1 (fr) 1984-05-24

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