CA1124931A - Method for fixation of prostheses to bone - Google Patents
Method for fixation of prostheses to boneInfo
- Publication number
- CA1124931A CA1124931A CA313,564A CA313564A CA1124931A CA 1124931 A CA1124931 A CA 1124931A CA 313564 A CA313564 A CA 313564A CA 1124931 A CA1124931 A CA 1124931A
- Authority
- CA
- Canada
- Prior art keywords
- polymer
- bone
- polycaprolactone
- prostheses
- polymers
- 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
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
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
-
- 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
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
Abstract
ABSTRACT OF THE DISCLOSURE
Method for fixation Or prostheses to bone with sterile non-toxic polymers such as polycoproloctone which ore formable viscous liquids or putty-like solids at temperatures within the range of 45°-75°C and hard, rigid solids at tempera ares below about 42°C, and to 8 sterile package containing such polymers.
Method for fixation Or prostheses to bone with sterile non-toxic polymers such as polycoproloctone which ore formable viscous liquids or putty-like solids at temperatures within the range of 45°-75°C and hard, rigid solids at tempera ares below about 42°C, and to 8 sterile package containing such polymers.
Description
112493~.
CoD-4 0 BACKGROUND OF THE INVENTION
FIELD OF THE INVENTION
This invention relates to the surgical fixation of prostheses in fractured, diseased and necrotic bones.
More specifically, it concerns the use of sterile, biocom-patible, non-biodegradable, high molecular weight, atoxic, inelastic, thermoplastic polymers which melt at ranges of from about 45C to about 75C and are rigid solids below about 42C for fixation of prostheses to bone in surgical procedures of the hip joint, in osteoarthritis, rheumatoid arthritis, traumatic arthritis, avascular necrosis, non-union of fractures of neck and femur, sickle cell anemia, revision of previous arthroplasty procedures, fractures of the neck of the femur in the elderly suitable for prosthetic replacement, and unstable fractures in indi-viduals with metastatic malignancies.
~ DESCRIPTION OF THE PRIOR ART
The fixation of endoprostheses in calcified tissue plays an important role in orthopedic surgery. Ideally, products used for this purpose should have handling charac-teristics and physical and chemical properties which are peculiarly suitable for this purpose. For example, the material should not adhere to the surgeon's glove when it is ready to be used and it should be easy to apply in the presence of moisture and set soon after without dimensional changes or the generation of excess heat.
Most importantly, a material for use in fixing prostheses into bone should be biocompatible, non-absorbable, rigid at body temperatures, sterilizable, have a low level of histotoxicity and lack carcinogenicity.
A number of polymeric compositions have been used by surgeons in recent years for fixing prostheses into bone, the most widely used being polymethyl meth-acrylate. However, many difficulties are associated with this material, both with respect to the surgeon and the patient. Since the monomer is highly volatile and flammable, the operating room must be provided with adequate air circulation. In practice, the monomer must be admixed with methyl methacrylate-styrene copolymer to give it the desired cementitious characteristics. During the mixing, caution must be exercised to prevent excessive exposure to the vapors of the monomer which may produce irritation of the respiratory tract, eyes and possibly liver.
Another disadvantage of methyl methacrylate is its property as a powerful lipid solvent. It should not be allowed to come into direct contact with sensitive tissues or be absorbed by the body since the monomer is suspected of being toxic. Furthermore, the uncontrolled heat rise resulting from the polymerization reaction may cause necrosis of the bone.
Other materials recommended for use in bone fixation include various derivatives of alpha-cyanoacrylate such as methyl alpha-cyanoacrylate, monomeric alkoxyalkyl
CoD-4 0 BACKGROUND OF THE INVENTION
FIELD OF THE INVENTION
This invention relates to the surgical fixation of prostheses in fractured, diseased and necrotic bones.
More specifically, it concerns the use of sterile, biocom-patible, non-biodegradable, high molecular weight, atoxic, inelastic, thermoplastic polymers which melt at ranges of from about 45C to about 75C and are rigid solids below about 42C for fixation of prostheses to bone in surgical procedures of the hip joint, in osteoarthritis, rheumatoid arthritis, traumatic arthritis, avascular necrosis, non-union of fractures of neck and femur, sickle cell anemia, revision of previous arthroplasty procedures, fractures of the neck of the femur in the elderly suitable for prosthetic replacement, and unstable fractures in indi-viduals with metastatic malignancies.
~ DESCRIPTION OF THE PRIOR ART
The fixation of endoprostheses in calcified tissue plays an important role in orthopedic surgery. Ideally, products used for this purpose should have handling charac-teristics and physical and chemical properties which are peculiarly suitable for this purpose. For example, the material should not adhere to the surgeon's glove when it is ready to be used and it should be easy to apply in the presence of moisture and set soon after without dimensional changes or the generation of excess heat.
Most importantly, a material for use in fixing prostheses into bone should be biocompatible, non-absorbable, rigid at body temperatures, sterilizable, have a low level of histotoxicity and lack carcinogenicity.
A number of polymeric compositions have been used by surgeons in recent years for fixing prostheses into bone, the most widely used being polymethyl meth-acrylate. However, many difficulties are associated with this material, both with respect to the surgeon and the patient. Since the monomer is highly volatile and flammable, the operating room must be provided with adequate air circulation. In practice, the monomer must be admixed with methyl methacrylate-styrene copolymer to give it the desired cementitious characteristics. During the mixing, caution must be exercised to prevent excessive exposure to the vapors of the monomer which may produce irritation of the respiratory tract, eyes and possibly liver.
Another disadvantage of methyl methacrylate is its property as a powerful lipid solvent. It should not be allowed to come into direct contact with sensitive tissues or be absorbed by the body since the monomer is suspected of being toxic. Furthermore, the uncontrolled heat rise resulting from the polymerization reaction may cause necrosis of the bone.
Other materials recommended for use in bone fixation include various derivatives of alpha-cyanoacrylate such as methyl alpha-cyanoacrylate, monomeric alkoxyalkyl
2-cyanoacrylate, alpha-cyanoacrylate esters and composi-tions containing these substances together with other additives including polymers. Like the polymethyl meth-acrylates, the use of these materials requires the introduction of monomers into the bone area, and the monomers polymerize in situ to form a permanent, poly-meric composition.
This invention provides a method for fixing prosthetic devices into bone tissue which is simple, convenient, atoxic to surgeon and patient, and reversi-ble. It eliminates the present need for conducting polymerization reactions in situ, avoids the preparation of the compositions requiring volatile monomers or solvents, and affords the opportunity to remove the prosthesis at I5 any time by the simple application of heat within a temperature range which is not dangerous to the patient.
SUMMARY
In accordance with the method of the present inven-tion, a biocompatible, preformed, thermoplastic polymer having a melting point within the range of from about 45C
to 75C, and which is a rigid solid at body temperatures is employed to secure an artificial prosthesis in a bone member. The bone member is prepared to receive the pros-thesis in a conventional manner as, for example, when using a polymethyl methacrylate cement. The thermoplastic polymer of the present invention is warmed until it becomes soft ~12493~ COD-40 and moldable, and is packed into the prosthesis receiving opening in the bone member. The prosthesis is then inserted into the bone while the polymer is still soft, and excess polymer which extrudes from the opening is removed The prosthesis is held immobile until the polymer cools and hardens after which the operation is concluded in a conventional manner.
Should it become necessary to remove the prosthesis, heat is applied gently to the prosthesis until the surrounding polymer softens after which the prosthesis may be easily withdrawn.
DESCRIPTION OF PREFERRED EMBODIMENTS
In a specific embodiment of my invention, a biocompatible, non-absorbable, preformed polymer whose melting point is from about 45C to about 75C and which is a rigid solid at body temperatures below about 42C is placed in a standard Toomeytype disposable syringe with a wide aperture and appropriate capacity of about 50-100 milliliters. The filled syringe is placed in a peel-apart package for sterile delivery and sterilized with cobalt radiation or heat, the former being preferred. Alternatively, the polymer can be placed in a squeeze bottle of suitable capacity and having a slit orifice In actual use, the surgeon's aid simply peels apart the sterile package, and using sterile techniques 1~2~931 COD-40 heats the syringe in an autoclave to melt the polymer and prepare the material for application. While in the molten state, the polymer is expressed into the prepared cavity of the intermedullary canal of the open bone and the prosthesis is inserted. Alternatively, it may be ejected from the syringe in molten form into cool sterile water to create a workable mass suitable for digital application into, for example, the acetabulum or femur. Whether the surgery involves the joint of the hip, knee, or elbow, a similar procedure is conducted on the end of the adjoining bone. Within a short period of time, about five minutes, the cooled polymer becomes a tough, rigid mass and the surgeon concludes the operation.
Although the preferred method of the present inven-tion is directed to the use of a single homopolymer or a copolymer, it is conceivable that a mixture of polymers chosen specifically to obtain a low melting point eutectic composition may also be employed.
A wide range of polymers which fulfill the physical and chemical characteristics required for the method of this invention may be employed, the preferred polymer being polycaprolactone, a known substance available commercially from the Union Carbide Corporation and described in its new product information bulletin F44221, Polycaprolactone Polymer PCL-700.
1~24~1 The polymers useful in the method of the present invention preferably have minimum strength characteris-tics at least as great as those of present acrylic bone cements. Ihe proposed ASTM specification for esters of methacrylic acid to be used as bone cements as reported in J. Biomed. Mater. Res. Symp. 6, 105-117 (1975) include the following mechanical properties determined at 25C
in accordance with the procedure set forth in that article:
Compressive strength, MPa ...... 80 min.
Indentation, mm .............. 0.11 max.
Recovery, ~ .................... 60 min.
The preferred polymer of the present invention, polycaprolactone, has the following corresponding proper-ties at 25C
Compressive strength, MPa .... .... 19,30 Indentation, mm .................. o.o89 Recovery, ~ ...................... . 84.4 Polycaprolactone is a linear polyester formed through the ring opening of the monomer epsilon-caprolactone.
Polycaprolactone is a crystalline thermoplastic resin which can be readily molded at moderate temperatures to yield tough transluscent products. Its crystalline melting point is about 60C, which represents a theoretical upper tempera-ture limit of use for the present invention. Above its melting point the material is characterized by a high 1~2A93~. COD-40 degree of conformability and workability. Additional polymers which are suitable ~or use in the method of this invention are the following:
, Rigid Thermoplastic Materials with Melt Ranges From 45C - 75C
Class of Polymer Polymer Structure Supplier and No.
Polyurethane MDI + OH terminated K. J. Quinn PA 93 polycaprolactone ester MDI + OH terminated K. J. Quinn PA 01 polycaprolactone +
adipate esters MDI + adipate ester Hooker Chemical P-250 MDI + adipate ester Mobay Chemical + OH chain extender Desmocoll E4 39T
(small chain glycol) Polyurethane TDI + OH terminated Mobay Chemical adipate ester Desmocoll 400T
MDI + OH terminated B. F. Goodrich Chemical adipate ester Estane 5711 Polyamide C36 Dimer (saturated) Emery Industries acid + ethylene diamine EM 1553 + caprolactam TDI = Toluene-2,4-Di isocyanate MDI = Methylene bis (4 phenyl isocyanate) Other polymers such as poly(dodecene-l) and transpolyisoprene are also useful in this invention. All ~124931 of these polymers are characterized by being crystalline at room temperature, non-crystalline at about 70C and having a relatively rapid rate of crystallization when cooled to body temperature. These polymers do not crystal-lize like simple compounds so that there is a reasonable time lag after the polymer reaches body temperature before crystallization is complete. This permits sufficient time for the prosthesis to be positioned in the bone member while the polymer is still pliable.
If desired, substances such as antibiotics, anti-bacterial agents, ard antifungal agents may also be admixed with the polymer. Examples of antimicrobial agents which may be employed include tetracycline, oxytetracycline, chlorotetracycline, neomycin, erithromycin, and its deriva-tive, bacitracin, streptomycin, rifampicin and its derivatives such as N-dimethylrifampicin, kanamycin and chloromycetin.
Useful antifungal agents include griseofulvin, mycostatin, miconazole and its derivatives as described in U.S. Patent No. 3,717,655; bisdiguanides such as chlorhexidine; and more particularly quaternary ammonium compounds such as domiphen bromide, domiphen chloride, domiphen fluoride, benzalkonium chloride, cetyl pyridinium chloride, dequali-nium chloride, the cis isomer of 1-(3-chlorallyl)-3,5,7-triaza-l-azoniaadamantane chloride (available commercially ~rom the Dow Chemical Company under the trademark Dowicil 200) and its analogues as described in U.S. Patent No. 3,228,828 cetyl trimethyl ammonium bromide as well as benzethonium _g_ 1~2~3~ COD-40 chloride and methylbenzethonium chloride such as described in U.S. Patent Nos. 2,170,111, 2,115,250 and 2,229,024; the carbanilides and sal~cylanilides such 3,4,4'-trichlorocarbanilide, and 3,4'5-tribromosalicy-lanilide; the hydroxydiphenyls such as dichlorophene, tetrachlorophene, hexachlorophene, and 2,4,4'-trichloro-2'-hydroxydiphenylether; and organometallic and halogen antiseptics such as zinc pyrithione, silver sulfadiazone, silver uracil, iodine, and the iodophores derived from non-ionic surface active agents such as are described in U.S, Patent Nos. 2,710,277 and 2,977,315 and from poly-vinylpyrrolidone such as described in U.S. Patent Nos, 2,706,701, 2,826,532 and 2,900,305.
TOXICITY STUDIES
Male, Swiss Webster mice, weighing 22 - 28 grams, were used in this study. The animals were acclimated for one week prior to use, and were housed in groups of 5 mice per cage. They were allowed free access to food and water at all times.
To reduce the pellets of PCL-700 polycaprolactone to a fine powder, the m~terial was ground with dry ice in a high speed micro mill (Janke & Kunkel) and then passed through a #80 sieve. A 15% (w/v) suspension of polycapro-lactone was prepared in 2~ pectin solution (0.9~ saline).
. 112493 1 The maximum dose tested by both the intraperi-toneal (IP) and subcutaneous (SC) routes was 10 g/kg;
therefore, the control mice in the IP group received 67 ml/kg of 2~ pectin. Animals were examined frequently the day o~ dosing and daily thereafter for 14 days. At this time the survivors were killed and examined for gross pathologic changes.
The LD50 f PCL-700 when given IP or SC was greater than lOg/kg. The doses tested and results are summarized:
Route Dose Mortality IP 5 g/kg 0/10 10 g/kg 0/10 IP None 0/10 (2~ Pectin) ~67 ml/kg) SC 10 g/kg 0/10 At necropsy, inspection of peritoneal cavities of mice given polycaprolactone revealed numerous deposits of powder. Some were off white with thin walled capsules, ot~ rs tan with thicker walled capsules. These were variously adherent to liver, pancreas, stomach, spleen, intestine and mesentery. The anterior surfaces of the livers had patchy cloudy areas, and portions of the liver were tenaciously adherent to the diaphragm.
1124931 COD-4 o There were no apparent toxic effects following subcutaneous injection of lOg/kg of polycaprolactone, At necropsy, the powder in the subcutis was contained in a moderately thick walled capsule, and the adjacent tissues appeared normal.
The only overt symptoms noted following intra-peritoneal injection of polycaprolactone were occasional episodes of varying degrees of abdominal twisting and stretching. The treated mice had a 3 to 9~ body weight loss the first 2 days after injection, whereas the control mice (2~ pectin) gained weight. Thereafter, the weight gains of experimental animals were similar to those of the controls.
HYDROLYSIS STUDIES
The hydrolysis of polycaprolactone in sodium phosphate buffer, pH 7.25, was investigated up to 100 days at 37.5C. Approximately 0,2 g of the polymer is placed in a 250 ml Erlenmeyer flask containing 200 ml of sterile buffer solution. It was then capped and placed in the incubator maintained at 37.5C. Similarly, three more samples were prepared for various time periods and placed in the incubator. At the end of each time period, the flask was taken out and the polymer was isolated by filtra-tion, washed several times with distilled water) and it was then dried overnight under vacuum. The final weight f the dry polymer was measured and the percent weis~ht ~Z493~
loss calculated. To follow the extent of hydrolysis of the polymer, the inherent viscosities were measured at the end of each period in chloroform (0.lg/dl) at 25C, The results are summarized below.
Sample Time, Weight No. Days Loss I.V.
1 0 - 0.94 2 21 0% o.88
This invention provides a method for fixing prosthetic devices into bone tissue which is simple, convenient, atoxic to surgeon and patient, and reversi-ble. It eliminates the present need for conducting polymerization reactions in situ, avoids the preparation of the compositions requiring volatile monomers or solvents, and affords the opportunity to remove the prosthesis at I5 any time by the simple application of heat within a temperature range which is not dangerous to the patient.
SUMMARY
In accordance with the method of the present inven-tion, a biocompatible, preformed, thermoplastic polymer having a melting point within the range of from about 45C
to 75C, and which is a rigid solid at body temperatures is employed to secure an artificial prosthesis in a bone member. The bone member is prepared to receive the pros-thesis in a conventional manner as, for example, when using a polymethyl methacrylate cement. The thermoplastic polymer of the present invention is warmed until it becomes soft ~12493~ COD-40 and moldable, and is packed into the prosthesis receiving opening in the bone member. The prosthesis is then inserted into the bone while the polymer is still soft, and excess polymer which extrudes from the opening is removed The prosthesis is held immobile until the polymer cools and hardens after which the operation is concluded in a conventional manner.
Should it become necessary to remove the prosthesis, heat is applied gently to the prosthesis until the surrounding polymer softens after which the prosthesis may be easily withdrawn.
DESCRIPTION OF PREFERRED EMBODIMENTS
In a specific embodiment of my invention, a biocompatible, non-absorbable, preformed polymer whose melting point is from about 45C to about 75C and which is a rigid solid at body temperatures below about 42C is placed in a standard Toomeytype disposable syringe with a wide aperture and appropriate capacity of about 50-100 milliliters. The filled syringe is placed in a peel-apart package for sterile delivery and sterilized with cobalt radiation or heat, the former being preferred. Alternatively, the polymer can be placed in a squeeze bottle of suitable capacity and having a slit orifice In actual use, the surgeon's aid simply peels apart the sterile package, and using sterile techniques 1~2~931 COD-40 heats the syringe in an autoclave to melt the polymer and prepare the material for application. While in the molten state, the polymer is expressed into the prepared cavity of the intermedullary canal of the open bone and the prosthesis is inserted. Alternatively, it may be ejected from the syringe in molten form into cool sterile water to create a workable mass suitable for digital application into, for example, the acetabulum or femur. Whether the surgery involves the joint of the hip, knee, or elbow, a similar procedure is conducted on the end of the adjoining bone. Within a short period of time, about five minutes, the cooled polymer becomes a tough, rigid mass and the surgeon concludes the operation.
Although the preferred method of the present inven-tion is directed to the use of a single homopolymer or a copolymer, it is conceivable that a mixture of polymers chosen specifically to obtain a low melting point eutectic composition may also be employed.
A wide range of polymers which fulfill the physical and chemical characteristics required for the method of this invention may be employed, the preferred polymer being polycaprolactone, a known substance available commercially from the Union Carbide Corporation and described in its new product information bulletin F44221, Polycaprolactone Polymer PCL-700.
1~24~1 The polymers useful in the method of the present invention preferably have minimum strength characteris-tics at least as great as those of present acrylic bone cements. Ihe proposed ASTM specification for esters of methacrylic acid to be used as bone cements as reported in J. Biomed. Mater. Res. Symp. 6, 105-117 (1975) include the following mechanical properties determined at 25C
in accordance with the procedure set forth in that article:
Compressive strength, MPa ...... 80 min.
Indentation, mm .............. 0.11 max.
Recovery, ~ .................... 60 min.
The preferred polymer of the present invention, polycaprolactone, has the following corresponding proper-ties at 25C
Compressive strength, MPa .... .... 19,30 Indentation, mm .................. o.o89 Recovery, ~ ...................... . 84.4 Polycaprolactone is a linear polyester formed through the ring opening of the monomer epsilon-caprolactone.
Polycaprolactone is a crystalline thermoplastic resin which can be readily molded at moderate temperatures to yield tough transluscent products. Its crystalline melting point is about 60C, which represents a theoretical upper tempera-ture limit of use for the present invention. Above its melting point the material is characterized by a high 1~2A93~. COD-40 degree of conformability and workability. Additional polymers which are suitable ~or use in the method of this invention are the following:
, Rigid Thermoplastic Materials with Melt Ranges From 45C - 75C
Class of Polymer Polymer Structure Supplier and No.
Polyurethane MDI + OH terminated K. J. Quinn PA 93 polycaprolactone ester MDI + OH terminated K. J. Quinn PA 01 polycaprolactone +
adipate esters MDI + adipate ester Hooker Chemical P-250 MDI + adipate ester Mobay Chemical + OH chain extender Desmocoll E4 39T
(small chain glycol) Polyurethane TDI + OH terminated Mobay Chemical adipate ester Desmocoll 400T
MDI + OH terminated B. F. Goodrich Chemical adipate ester Estane 5711 Polyamide C36 Dimer (saturated) Emery Industries acid + ethylene diamine EM 1553 + caprolactam TDI = Toluene-2,4-Di isocyanate MDI = Methylene bis (4 phenyl isocyanate) Other polymers such as poly(dodecene-l) and transpolyisoprene are also useful in this invention. All ~124931 of these polymers are characterized by being crystalline at room temperature, non-crystalline at about 70C and having a relatively rapid rate of crystallization when cooled to body temperature. These polymers do not crystal-lize like simple compounds so that there is a reasonable time lag after the polymer reaches body temperature before crystallization is complete. This permits sufficient time for the prosthesis to be positioned in the bone member while the polymer is still pliable.
If desired, substances such as antibiotics, anti-bacterial agents, ard antifungal agents may also be admixed with the polymer. Examples of antimicrobial agents which may be employed include tetracycline, oxytetracycline, chlorotetracycline, neomycin, erithromycin, and its deriva-tive, bacitracin, streptomycin, rifampicin and its derivatives such as N-dimethylrifampicin, kanamycin and chloromycetin.
Useful antifungal agents include griseofulvin, mycostatin, miconazole and its derivatives as described in U.S. Patent No. 3,717,655; bisdiguanides such as chlorhexidine; and more particularly quaternary ammonium compounds such as domiphen bromide, domiphen chloride, domiphen fluoride, benzalkonium chloride, cetyl pyridinium chloride, dequali-nium chloride, the cis isomer of 1-(3-chlorallyl)-3,5,7-triaza-l-azoniaadamantane chloride (available commercially ~rom the Dow Chemical Company under the trademark Dowicil 200) and its analogues as described in U.S. Patent No. 3,228,828 cetyl trimethyl ammonium bromide as well as benzethonium _g_ 1~2~3~ COD-40 chloride and methylbenzethonium chloride such as described in U.S. Patent Nos. 2,170,111, 2,115,250 and 2,229,024; the carbanilides and sal~cylanilides such 3,4,4'-trichlorocarbanilide, and 3,4'5-tribromosalicy-lanilide; the hydroxydiphenyls such as dichlorophene, tetrachlorophene, hexachlorophene, and 2,4,4'-trichloro-2'-hydroxydiphenylether; and organometallic and halogen antiseptics such as zinc pyrithione, silver sulfadiazone, silver uracil, iodine, and the iodophores derived from non-ionic surface active agents such as are described in U.S, Patent Nos. 2,710,277 and 2,977,315 and from poly-vinylpyrrolidone such as described in U.S. Patent Nos, 2,706,701, 2,826,532 and 2,900,305.
TOXICITY STUDIES
Male, Swiss Webster mice, weighing 22 - 28 grams, were used in this study. The animals were acclimated for one week prior to use, and were housed in groups of 5 mice per cage. They were allowed free access to food and water at all times.
To reduce the pellets of PCL-700 polycaprolactone to a fine powder, the m~terial was ground with dry ice in a high speed micro mill (Janke & Kunkel) and then passed through a #80 sieve. A 15% (w/v) suspension of polycapro-lactone was prepared in 2~ pectin solution (0.9~ saline).
. 112493 1 The maximum dose tested by both the intraperi-toneal (IP) and subcutaneous (SC) routes was 10 g/kg;
therefore, the control mice in the IP group received 67 ml/kg of 2~ pectin. Animals were examined frequently the day o~ dosing and daily thereafter for 14 days. At this time the survivors were killed and examined for gross pathologic changes.
The LD50 f PCL-700 when given IP or SC was greater than lOg/kg. The doses tested and results are summarized:
Route Dose Mortality IP 5 g/kg 0/10 10 g/kg 0/10 IP None 0/10 (2~ Pectin) ~67 ml/kg) SC 10 g/kg 0/10 At necropsy, inspection of peritoneal cavities of mice given polycaprolactone revealed numerous deposits of powder. Some were off white with thin walled capsules, ot~ rs tan with thicker walled capsules. These were variously adherent to liver, pancreas, stomach, spleen, intestine and mesentery. The anterior surfaces of the livers had patchy cloudy areas, and portions of the liver were tenaciously adherent to the diaphragm.
1124931 COD-4 o There were no apparent toxic effects following subcutaneous injection of lOg/kg of polycaprolactone, At necropsy, the powder in the subcutis was contained in a moderately thick walled capsule, and the adjacent tissues appeared normal.
The only overt symptoms noted following intra-peritoneal injection of polycaprolactone were occasional episodes of varying degrees of abdominal twisting and stretching. The treated mice had a 3 to 9~ body weight loss the first 2 days after injection, whereas the control mice (2~ pectin) gained weight. Thereafter, the weight gains of experimental animals were similar to those of the controls.
HYDROLYSIS STUDIES
The hydrolysis of polycaprolactone in sodium phosphate buffer, pH 7.25, was investigated up to 100 days at 37.5C. Approximately 0,2 g of the polymer is placed in a 250 ml Erlenmeyer flask containing 200 ml of sterile buffer solution. It was then capped and placed in the incubator maintained at 37.5C. Similarly, three more samples were prepared for various time periods and placed in the incubator. At the end of each time period, the flask was taken out and the polymer was isolated by filtra-tion, washed several times with distilled water) and it was then dried overnight under vacuum. The final weight f the dry polymer was measured and the percent weis~ht ~Z493~
loss calculated. To follow the extent of hydrolysis of the polymer, the inherent viscosities were measured at the end of each period in chloroform (0.lg/dl) at 25C, The results are summarized below.
Sample Time, Weight No. Days Loss I.V.
1 0 - 0.94 2 21 0% o.88
3 62 0.17~ -
4 100 0.95% 0.80 204 1.7~ o.68 About 1% weight loss is observed at the end of 100 days. m ere is a 15% decrease in I.V. during this period, indicating some degradation of the polymer chain.
Even after 204 days, only a small percent of weight loss was observed and no significant change in the physical state of the polymer was observed visually, i.e., the polymer pellets were intact.
Even after 204 days, only a small percent of weight loss was observed and no significant change in the physical state of the polymer was observed visually, i.e., the polymer pellets were intact.
Claims (4)
1. A sterile package containing a non-toxic, biocompatible, non-absorbable polymer having a melt temperature of from about 45°C to about 75°C, being solid at a temperature below about 42°C and being suitable for use in fixing prostheses into bone tissue.
2. A package as in Claim 1 wherein the polymer is further characterized by the following mechanical properties at 25°C:
Compressive Strength, MPa... 80 min.
Indentation, mm ............. 0.11 max.
Recovery, % ................... 60 min.
Compressive Strength, MPa... 80 min.
Indentation, mm ............. 0.11 max.
Recovery, % ................... 60 min.
3. A package as in Claim 1 wherein the polymer is polycaprolactone.
4. A package as in Claim 1 wherein the polymer is poly(dodecene-l).
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US843,754 | 1977-10-19 | ||
| US05/843,754 US4200939A (en) | 1977-10-19 | 1977-10-19 | Method for fixation of prostheses to bone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1124931A true CA1124931A (en) | 1982-06-01 |
Family
ID=25290921
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA313,564A Expired CA1124931A (en) | 1977-10-19 | 1978-10-17 | Method for fixation of prostheses to bone |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US4200939A (en) |
| JP (1) | JPS5464897A (en) |
| CA (1) | CA1124931A (en) |
| DE (1) | DE2844960A1 (en) |
| GB (1) | GB2009200B (en) |
Families Citing this family (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3220932A1 (en) * | 1982-06-03 | 1983-12-08 | Vsesojuznyj naučno-issledovatel'skij i ispytatel'nyj institut medicinskoj techniki, Moskva | Composition for temporary bone tissue replacement |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB433278A (en) * | 1933-11-04 | 1935-08-12 | Emanuel Raab | Improvements in or relating to artificial dentures |
| US2155658A (en) * | 1936-01-08 | 1939-04-25 | Chemische Forschungs Gmbh | Surgical and medical preparations |
| MC139A7 (en) * | 1957-11-07 | 1966-11-02 | Planel Claude | Hair curler and its heating device |
| US3030951A (en) * | 1959-04-10 | 1962-04-24 | Michael P Mandarino | Methods and materials for orthopedic surgery |
| US3524537A (en) * | 1968-09-25 | 1970-08-18 | American Cyanamid Co | Package containing 2-cyanoacrylic ester adhesives |
| CA912202A (en) * | 1969-03-13 | 1972-10-17 | V. Chambers Harold | Artificial hip joint |
| US3692023A (en) * | 1970-07-20 | 1972-09-19 | Union Carbide Corp | Formable orthopedic cast materials, resultant casts and method |
| US3968791A (en) * | 1975-01-29 | 1976-07-13 | The Lubrizol Corporation | Orthopedic bandage comprising diacetone acrylamide, and cast prepared therefrom |
-
1977
- 1977-10-19 US US05/843,754 patent/US4200939A/en not_active Expired - Lifetime
-
1978
- 1978-10-16 DE DE19782844960 patent/DE2844960A1/en active Granted
- 1978-10-17 CA CA313,564A patent/CA1124931A/en not_active Expired
- 1978-10-17 JP JP12690878A patent/JPS5464897A/en active Granted
- 1978-10-18 GB GB7840931A patent/GB2009200B/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| DE2844960A1 (en) | 1979-05-10 |
| JPS6236695B2 (en) | 1987-08-08 |
| DE2844960C2 (en) | 1988-11-10 |
| GB2009200A (en) | 1979-06-13 |
| US4200939A (en) | 1980-05-06 |
| JPS5464897A (en) | 1979-05-25 |
| GB2009200B (en) | 1982-05-12 |
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