CA2394100C - Porous calcium phosphate cement - Google Patents
Porous calcium phosphate cement Download PDFInfo
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- CA2394100C CA2394100C CA002394100A CA2394100A CA2394100C CA 2394100 C CA2394100 C CA 2394100C CA 002394100 A CA002394100 A CA 002394100A CA 2394100 A CA2394100 A CA 2394100A CA 2394100 C CA2394100 C CA 2394100C
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- acid
- carbonate
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- cement
- calcium
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- 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/02—Surgical adhesives or cements; Adhesives for colostomy devices containing inorganic materials
-
- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B28/00—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements
- C04B28/34—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements containing cold phosphate binders
- C04B28/344—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements containing cold phosphate binders the phosphate binder being present in the starting composition solely as one or more phosphates
-
- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B38/00—Porous mortars, concrete, artificial stone or ceramic ware; Preparation thereof
- C04B38/02—Porous mortars, concrete, artificial stone or ceramic ware; Preparation thereof by adding chemical blowing 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
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
-
- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B2111/00—Mortars, concrete or artificial stone or mixtures to prepare them, characterised by specific function, property or use
- C04B2111/00474—Uses not provided for elsewhere in C04B2111/00
- C04B2111/00836—Uses not provided for elsewhere in C04B2111/00 for medical or dental applications
Abstract
A kit and a method for making a porous cement which self sets to hydroxyapatite and has an interconnected porosity is produced by mixing a calcium source and a phosphate source with a carbona te source and mixing this powdered component with a liquid component having an acid component. The liquid component comprises water on an aqueous solution containing an acid. The acid and the carbonate react to form carbon dioxide thereby producing an interconnected porosity in the normally solid self-hardening bone cement. The method requires only a relatively low weight percent of the acid and base to be mixed with the liquid and powder cement components.
Description
POROUS CALCIUM PHOSPHATE CEMENT
FIELD OF THE INVENTION
This invention relates to calcium phosphate cements which set after the mixing of a powdered calcium and phosphate source in an aqueous solution to form hydroxyapatite (HA).
More particularly, it relates to the addition of citric acid and sodium bicarbonate to produce carbon dioxide during the setting of a calcium phosphate cement, thereby introducing macroporosity into the structure.
BACKGROUND OF THE INVENTION
It is sometimes desired that bone cements and bone filler materials which harden or set have an interconnected porosity (macroporosity) throughout their structure after hardening. This interconnected porosity, if of sufficient pore size, allows for vascularization and tissue ingrowth to occur into the structure. Pores greater than 70 microns in diameter have been found to allow tissue ingrowth. This tissue ingrowth can be encouraged by coating or filling the pores with osteoinductive or osteoconductive factors such as bone morphogenic proteins (BMPs). Such factors are well known to those skilled in the art. Other therapeutic agents such as antibiotics or chemo-therapeutic agents may be introduced into the porosity by adding them to the liquid or powder.
In the past, porosity has been generated by including fillers which are soluble in physiological fluids or which are resorbed after implantation. These systems have the disadvantage that the porosity only occurs after implantation and thus the pores cannot be filled with growth factors or other therapeutic agents prior to implantation. In addition, to form the required interconnected porosity, up to 50 volume percent of resorbable filler must be added to the calcium and phosphate source precursor powdered material. This sometimes adversely affects material properties and reduces the amount of hydroxyapatite formed in the reaction of the calcium and phosphate precursors.
Also, foaming agents, such as citrimide BP which reduce the surface tension of the water have been used. However, this produces unwanted ammonium compounds when used in vivo.
U.S. patent 5,820,632 to Constantz et al. relates to a calcium phosphate cement wherein when a porous structure is desired, various additives may be included which may be leached out so 3o as to provide for porosity in the cement. This porosity is in addition to any porosities achieved with a release of gas formed during the reaction to produce the product. Constantz et al. teaches including aggregates of soluble materials generally above 25 volume percent to develop sufficient interconnected porosity to foster bony ingrowth with the volume of aggregate normally being less than 50 volume percent. Specifically, Constantz et al. suggests the addition of calcium chloride and.
sodium or potassium hydroxide which are water soluble and will be leached out to provide the porosity.
U.S. patent 5,525,148 to Chow et al. teaches the use of pore forming agents that are preferably, substantially insoluble in the cement itself and can be removed by either resorbtion into body tissue, dissolution into physiological solutions, dissolution in solvents or heating after the cement has hardened. The pore forining agents taught by Chow et al. include sugar, sodium bicarbonate and phosphate salts.
Thus, there is a need to fmd a simple way of forming an interconnected porosity of io sufficient pore size during cement hardening or setting and which avoids adding large amounts of filler to the cement. It has been found that the production or introduction of sufficient amounts of carbon dioxide gas during the reaction of the calcium and phosphate precursors to form HA
produces the desired porosity.
It has been found that adding sodium bicarbonate and citric acid to the calcium and phosphate precursors to the formation of hydroxyapatite with a ratio of these acid and alkaline components selected such that the final result of their reaction does not change the pH of the aqueous solution, that a final cement having the desired porosity, sufficient hydroxyapatite and sufficient physical properties are produced.
SUNIMARY OF THE INVENTION
It is an object of this invention to provide a method of preparing calcium phosphate cement compositions, which self-harden substantially to hydroxyapatite at ambient temperatures when in contact with an aqueous medium, comprising, combining one or more sparingly soluble calcium phosphates along with an acid and base to produce a set material having an interconnected porosity.
It is another object of the invention to provide an acid and base which react to form carbon dioxide during the setting process of the calcium phosphate cement compositions and which does not alter the final pH of the mixture of the one or more sparingly soluble calcium phosphate powders when combined with the aqueous medium normally added thereto.
These and other objects of the invention are provided by a method for making a porous cement which sets to hydroxyapatite at ambient temperatures comprising mixing a powder comprising a calcium source, a phosphate source and a base with a liquid comprising an aqueous solution containing an acid wherein the calcium source and the phosphate source mix with the liquid component to form hydroxyapatite and the acid and base react to form carbon dioxide producing an interconnected porosity in the material. In the preferred embodiment, the base is a carbonate selected from the group consisting of sodium carbonate, sodium bicarbonate, calcium carbonate and calcium bicarbonate or a combination thereof. The preferred acid is selected from the group consisting of citric acid, malic acid, fiamaric acid, lactic acid, succinic acid and orthophosphoric acid or a combination thereot The preferred calcium and phosphate sources may be selected from the group consisting of tetra-calcium phosphate, dicalcium phosphate, tricalcium phosphate and monocalcium phosphate.
The preferred ratio of acid to carbonate to produce a neutral pH has been found to be about 0.7 grams of acid to about 1.0 grams of carbonate. The preferred ratio of the acid and carbonate to the combined powdered and liquid components forming the calcium phosphate cement is,about 10 to 20% by weight.
These and other objects and advantages of the present invention will become apparent from the following description of the accompanying drawings, which disclose several embodiments of the invention. It is to be understood that the drawings are to be used for the purposes of illustration only and not as a definition of the invention.
BRIEF DESCRIPTION OF THE DRAVJIlNGS
In the drawings wherein similar reference characters denote similar elements throughout the several views, in which:
FIG. I is a cross-sectional micrograph of the porous bone cement of the present invention formed at liquid to powder ratio of .25 and an acid/base weight percent of 10%; and FIG. 2 is a cross-sectional micrograph of the porous bone cement of the present invention made from a liquid to powder ratio of .35 and an weight percent of acid to base of 20%.
DESCRIPTION OF TBF, PREFERRED EMBODIIIONTS
This invention relates to calcium phosphate cements of the type taught in Brown and Chow, U.S. reissued patents RE 33,161 and RE 33,221 and in Chow and Takagi U.S.
patent 5,525,148 and in Constantz U.S. patent 4,880,610.
The method for porosity generation of the present invention is the addition of citric acid monohydrate in an aqueous mixture and sodium bicarbonate in powder form into the calcium phosphate powder mixture taught by the patents refen-ed to above in which tetra-calcium phosphate and dicalcium phosphate powders are mixed with a liquid component which may be dionized water or a sodium phosphate solution. In the preferred embodiment, the ratio of acid to base is I gram of a base such as sodium bicarbonate to 0.7 grams of an acid such as citric acid.
In the preferred embodiment, the sodium bicarbonate powder is mixed with the tetra-calcium phosphate and dicalcium phosphate powders with the resultant mixture then being combined with an aqueous liquid into which the citric acid has been added as a liquid. The preferred liquid to powder ratio is between about .25 to .35. The preferred weight percent of the acid/base to the liquid and powder combination is between about 10 to about 20 weight percent.
Example:
The ratio of acid to base (citric acid to sodium bicarbonate) was determined by reacting various ratios of each component in 10m1 of water. The ratio that left the pH
of the water unchanged after completion of the reaction was chosen to be mixed with the powdered tetra-calcium phosphate and dicalcium phosphate combination. It was determined that the ratio of 0.7 1o grams of citric acid to 1.0 grams of sodium bicarbonate produced a neutral pH.
Sodium bicarbonate was mixed as a powder into the powdered tetra-calcium phosphate and dicalciuin phosphate. Citric acid monohydrate was mixed into the deionized water liquid component. The acid/base ratio (A/B) was 0.7 grams of citric acid to 1.0 grams of sodium bicarbonate. A series of tests were performed in which the citric acid was added to deionized water and also was added to a .25 M sodium phosphate solution. Various liquid/powder (1/p) ratios were evaluated. Although the acid used was in solution, the invention would work equally well if an acid in dry form (free of uncombined water) was used as part of the powdered component.
After twenty-four (24) hours of setting at 37 C in greater than 95% relative humidity, each cement specimen was dried to stop the reaction. X-ray diffraction measurements were made to 2o determine the percent conversion to hydroxyapatite (HA) and the cement was sectioned to reveal the porosity. Figures 1 and 2 show the sections of two samples for illustrative purposes only.
The results of those tests are summarized in Table I. From this table, it can be seen that the specimen number 10 and specimen number 11 produced the most acceptable levels of hydroxyapatite of 67 and 69%, respectively and greater than 35% porosity. The pore sizes were between 440 and 580 microns. Pore sizes of at least 70 microns are desirable.
Specimen 10 include a liquid to powder to ratio of .35 and 20% by weight of the citric acid and sodium bicarbonate added in with the aforementioned ratio of .7 grams of the citric acid to every gram of sodium bicarbonate and had a 35% porosity with 67% HA. Likewise, specimen 11 which utilized a .251iquid to powder ratio and a 10% acid base weight ratio produced a 47%
porosity with 69% HA.
While the Example deals with a calcium phosphate bone material, the method of producing a porous structure in a bone cement or filler could be utilized on any bone cement type such as a glass ionomer cement, poly (propylene fumarate) or a methacrylate cement where liquid and powdered components are mixed. A methacrylate cement is made by reacting a liquid methacrylate monomer with a powdered methacrylate polymer. Again, the powdered sodium bicarbonate is added to the powdered component and an acid source, such as citric acid, is added to the liquid component. Also, any gas producing chemical reaction could be used to form the pores. Rather than having the acid in the liquid component, it is possible to add the acid in a crystalline form as a solid component. An example of such an acid material is phosphoric acid free of uncombined water.
It is also possible to introduce carbon dioxide, nitric oxide or an inert gas such as nitrogen or helium directly into the setting cement mixture to form the porosity. This can be accomplished through a port in the mixing container.
TABLE I
Cements Mixed Using Deionized Water *aps = average pore size specimen wt% A/B % %converted I/P in mix porosity to HA comments 1 .125 20 12 31 2 .188 5 13 -- 109 m aps*
2o 3 .188 20 20 45 4 .25 2 8 37 5 .25 5 36 50 580 m aps*
specimen wt% A/B % %converted 1/p in mix porosily to HA comments 6 .35 10 36 64 7 .25 20 32 55 440 m aps*
FIELD OF THE INVENTION
This invention relates to calcium phosphate cements which set after the mixing of a powdered calcium and phosphate source in an aqueous solution to form hydroxyapatite (HA).
More particularly, it relates to the addition of citric acid and sodium bicarbonate to produce carbon dioxide during the setting of a calcium phosphate cement, thereby introducing macroporosity into the structure.
BACKGROUND OF THE INVENTION
It is sometimes desired that bone cements and bone filler materials which harden or set have an interconnected porosity (macroporosity) throughout their structure after hardening. This interconnected porosity, if of sufficient pore size, allows for vascularization and tissue ingrowth to occur into the structure. Pores greater than 70 microns in diameter have been found to allow tissue ingrowth. This tissue ingrowth can be encouraged by coating or filling the pores with osteoinductive or osteoconductive factors such as bone morphogenic proteins (BMPs). Such factors are well known to those skilled in the art. Other therapeutic agents such as antibiotics or chemo-therapeutic agents may be introduced into the porosity by adding them to the liquid or powder.
In the past, porosity has been generated by including fillers which are soluble in physiological fluids or which are resorbed after implantation. These systems have the disadvantage that the porosity only occurs after implantation and thus the pores cannot be filled with growth factors or other therapeutic agents prior to implantation. In addition, to form the required interconnected porosity, up to 50 volume percent of resorbable filler must be added to the calcium and phosphate source precursor powdered material. This sometimes adversely affects material properties and reduces the amount of hydroxyapatite formed in the reaction of the calcium and phosphate precursors.
Also, foaming agents, such as citrimide BP which reduce the surface tension of the water have been used. However, this produces unwanted ammonium compounds when used in vivo.
U.S. patent 5,820,632 to Constantz et al. relates to a calcium phosphate cement wherein when a porous structure is desired, various additives may be included which may be leached out so 3o as to provide for porosity in the cement. This porosity is in addition to any porosities achieved with a release of gas formed during the reaction to produce the product. Constantz et al. teaches including aggregates of soluble materials generally above 25 volume percent to develop sufficient interconnected porosity to foster bony ingrowth with the volume of aggregate normally being less than 50 volume percent. Specifically, Constantz et al. suggests the addition of calcium chloride and.
sodium or potassium hydroxide which are water soluble and will be leached out to provide the porosity.
U.S. patent 5,525,148 to Chow et al. teaches the use of pore forming agents that are preferably, substantially insoluble in the cement itself and can be removed by either resorbtion into body tissue, dissolution into physiological solutions, dissolution in solvents or heating after the cement has hardened. The pore forining agents taught by Chow et al. include sugar, sodium bicarbonate and phosphate salts.
Thus, there is a need to fmd a simple way of forming an interconnected porosity of io sufficient pore size during cement hardening or setting and which avoids adding large amounts of filler to the cement. It has been found that the production or introduction of sufficient amounts of carbon dioxide gas during the reaction of the calcium and phosphate precursors to form HA
produces the desired porosity.
It has been found that adding sodium bicarbonate and citric acid to the calcium and phosphate precursors to the formation of hydroxyapatite with a ratio of these acid and alkaline components selected such that the final result of their reaction does not change the pH of the aqueous solution, that a final cement having the desired porosity, sufficient hydroxyapatite and sufficient physical properties are produced.
SUNIMARY OF THE INVENTION
It is an object of this invention to provide a method of preparing calcium phosphate cement compositions, which self-harden substantially to hydroxyapatite at ambient temperatures when in contact with an aqueous medium, comprising, combining one or more sparingly soluble calcium phosphates along with an acid and base to produce a set material having an interconnected porosity.
It is another object of the invention to provide an acid and base which react to form carbon dioxide during the setting process of the calcium phosphate cement compositions and which does not alter the final pH of the mixture of the one or more sparingly soluble calcium phosphate powders when combined with the aqueous medium normally added thereto.
These and other objects of the invention are provided by a method for making a porous cement which sets to hydroxyapatite at ambient temperatures comprising mixing a powder comprising a calcium source, a phosphate source and a base with a liquid comprising an aqueous solution containing an acid wherein the calcium source and the phosphate source mix with the liquid component to form hydroxyapatite and the acid and base react to form carbon dioxide producing an interconnected porosity in the material. In the preferred embodiment, the base is a carbonate selected from the group consisting of sodium carbonate, sodium bicarbonate, calcium carbonate and calcium bicarbonate or a combination thereof. The preferred acid is selected from the group consisting of citric acid, malic acid, fiamaric acid, lactic acid, succinic acid and orthophosphoric acid or a combination thereot The preferred calcium and phosphate sources may be selected from the group consisting of tetra-calcium phosphate, dicalcium phosphate, tricalcium phosphate and monocalcium phosphate.
The preferred ratio of acid to carbonate to produce a neutral pH has been found to be about 0.7 grams of acid to about 1.0 grams of carbonate. The preferred ratio of the acid and carbonate to the combined powdered and liquid components forming the calcium phosphate cement is,about 10 to 20% by weight.
These and other objects and advantages of the present invention will become apparent from the following description of the accompanying drawings, which disclose several embodiments of the invention. It is to be understood that the drawings are to be used for the purposes of illustration only and not as a definition of the invention.
BRIEF DESCRIPTION OF THE DRAVJIlNGS
In the drawings wherein similar reference characters denote similar elements throughout the several views, in which:
FIG. I is a cross-sectional micrograph of the porous bone cement of the present invention formed at liquid to powder ratio of .25 and an acid/base weight percent of 10%; and FIG. 2 is a cross-sectional micrograph of the porous bone cement of the present invention made from a liquid to powder ratio of .35 and an weight percent of acid to base of 20%.
DESCRIPTION OF TBF, PREFERRED EMBODIIIONTS
This invention relates to calcium phosphate cements of the type taught in Brown and Chow, U.S. reissued patents RE 33,161 and RE 33,221 and in Chow and Takagi U.S.
patent 5,525,148 and in Constantz U.S. patent 4,880,610.
The method for porosity generation of the present invention is the addition of citric acid monohydrate in an aqueous mixture and sodium bicarbonate in powder form into the calcium phosphate powder mixture taught by the patents refen-ed to above in which tetra-calcium phosphate and dicalcium phosphate powders are mixed with a liquid component which may be dionized water or a sodium phosphate solution. In the preferred embodiment, the ratio of acid to base is I gram of a base such as sodium bicarbonate to 0.7 grams of an acid such as citric acid.
In the preferred embodiment, the sodium bicarbonate powder is mixed with the tetra-calcium phosphate and dicalcium phosphate powders with the resultant mixture then being combined with an aqueous liquid into which the citric acid has been added as a liquid. The preferred liquid to powder ratio is between about .25 to .35. The preferred weight percent of the acid/base to the liquid and powder combination is between about 10 to about 20 weight percent.
Example:
The ratio of acid to base (citric acid to sodium bicarbonate) was determined by reacting various ratios of each component in 10m1 of water. The ratio that left the pH
of the water unchanged after completion of the reaction was chosen to be mixed with the powdered tetra-calcium phosphate and dicalcium phosphate combination. It was determined that the ratio of 0.7 1o grams of citric acid to 1.0 grams of sodium bicarbonate produced a neutral pH.
Sodium bicarbonate was mixed as a powder into the powdered tetra-calcium phosphate and dicalciuin phosphate. Citric acid monohydrate was mixed into the deionized water liquid component. The acid/base ratio (A/B) was 0.7 grams of citric acid to 1.0 grams of sodium bicarbonate. A series of tests were performed in which the citric acid was added to deionized water and also was added to a .25 M sodium phosphate solution. Various liquid/powder (1/p) ratios were evaluated. Although the acid used was in solution, the invention would work equally well if an acid in dry form (free of uncombined water) was used as part of the powdered component.
After twenty-four (24) hours of setting at 37 C in greater than 95% relative humidity, each cement specimen was dried to stop the reaction. X-ray diffraction measurements were made to 2o determine the percent conversion to hydroxyapatite (HA) and the cement was sectioned to reveal the porosity. Figures 1 and 2 show the sections of two samples for illustrative purposes only.
The results of those tests are summarized in Table I. From this table, it can be seen that the specimen number 10 and specimen number 11 produced the most acceptable levels of hydroxyapatite of 67 and 69%, respectively and greater than 35% porosity. The pore sizes were between 440 and 580 microns. Pore sizes of at least 70 microns are desirable.
Specimen 10 include a liquid to powder to ratio of .35 and 20% by weight of the citric acid and sodium bicarbonate added in with the aforementioned ratio of .7 grams of the citric acid to every gram of sodium bicarbonate and had a 35% porosity with 67% HA. Likewise, specimen 11 which utilized a .251iquid to powder ratio and a 10% acid base weight ratio produced a 47%
porosity with 69% HA.
While the Example deals with a calcium phosphate bone material, the method of producing a porous structure in a bone cement or filler could be utilized on any bone cement type such as a glass ionomer cement, poly (propylene fumarate) or a methacrylate cement where liquid and powdered components are mixed. A methacrylate cement is made by reacting a liquid methacrylate monomer with a powdered methacrylate polymer. Again, the powdered sodium bicarbonate is added to the powdered component and an acid source, such as citric acid, is added to the liquid component. Also, any gas producing chemical reaction could be used to form the pores. Rather than having the acid in the liquid component, it is possible to add the acid in a crystalline form as a solid component. An example of such an acid material is phosphoric acid free of uncombined water.
It is also possible to introduce carbon dioxide, nitric oxide or an inert gas such as nitrogen or helium directly into the setting cement mixture to form the porosity. This can be accomplished through a port in the mixing container.
TABLE I
Cements Mixed Using Deionized Water *aps = average pore size specimen wt% A/B % %converted I/P in mix porosity to HA comments 1 .125 20 12 31 2 .188 5 13 -- 109 m aps*
2o 3 .188 20 20 45 4 .25 2 8 37 5 .25 5 36 50 580 m aps*
specimen wt% A/B % %converted 1/p in mix porosily to HA comments 6 .35 10 36 64 7 .25 20 32 55 440 m aps*
8 .25 30 51 66 9 .25 40 51 63 Cements Mixed With Sodium Phosphate Solution specimen wt% A/B % %converted I/P in mix orosi to HA
10 .35 20 35 67 11 .25 10 47 69 1o 12 .30 10 26 58 The calcium phosphate materials mixed without the gas forming citric acid and sodium bicarbonate components had a macroporosity of only 4%.
The pore size can be controlled by using less liquid in the liquid to powder ratio and/or less of the acid-base mixture to obtain smaller pore sizes. Conversely, more liquid or a higher weight percent of acid-base results in more porosity and larger pores. FIGS. 1 and 2 show the porous bone cements of Examples 11 and 10 respectively, showing average pore sizes greater than 70 microns.
While several examples of the present invention have been described, it is obvious that many changes and modifications may be made thereunto, without departing from the spirit and scope of the invention.
The pore size can be controlled by using less liquid in the liquid to powder ratio and/or less of the acid-base mixture to obtain smaller pore sizes. Conversely, more liquid or a higher weight percent of acid-base results in more porosity and larger pores. FIGS. 1 and 2 show the porous bone cements of Examples 11 and 10 respectively, showing average pore sizes greater than 70 microns.
While several examples of the present invention have been described, it is obvious that many changes and modifications may be made thereunto, without departing from the spirit and scope of the invention.
Claims (13)
1. A kit for producing a self-setting bone cement comprising:
water;
an acid source selected from the group consisting of citric acid, malic acid, phosphoric acid, fumaric acid, lactic acid, succinic acid and a combination thereof; and a powdered composition containing at least two powdered components mixed together, at least one component containing a calcium phosphate source and at least one component containing a phosphate source, said at least two powdered components capable of reacting with said water to form said self-setting bone cement and said mixed at least two powdered components containing a carbonate selected from the group consisting of sodium carbonate, sodium bicarbonate, calcium carbonate, calcium bicarbonate and a combination thereof, wherein the ratio of the weights of the acid source to the carbonate are chosen such that the final result of their reaction does not change the final pH of the mixture of the at least two powdered components and water with the ratio of acid to the weight of carbonate being about 0.7.
water;
an acid source selected from the group consisting of citric acid, malic acid, phosphoric acid, fumaric acid, lactic acid, succinic acid and a combination thereof; and a powdered composition containing at least two powdered components mixed together, at least one component containing a calcium phosphate source and at least one component containing a phosphate source, said at least two powdered components capable of reacting with said water to form said self-setting bone cement and said mixed at least two powdered components containing a carbonate selected from the group consisting of sodium carbonate, sodium bicarbonate, calcium carbonate, calcium bicarbonate and a combination thereof, wherein the ratio of the weights of the acid source to the carbonate are chosen such that the final result of their reaction does not change the final pH of the mixture of the at least two powdered components and water with the ratio of acid to the weight of carbonate being about 0.7.
2. The kit as set forth in claim 1, wherein the weight ratio of the acid and the carbonate to the combined water and the at least two powdered components forming the cement is about 10 to 20%.
3. The kit as set forth in claim 1, wherein the acid and water are supplied as a mixture in the kit.
4. A method for making a porous cement which self sets to hydroxyapatite as the predominant product at ambient temperatures comprising:
mixing powdered components at least one being a calcium source and at least one being a phosphate source and at least one powdered component being a carbonate selected from the group consisting of sodium carbonate, sodium bicarbonate, calcium carbonate, calcium bicarbonate and a combination thereof to form a powdered mixture, the calcium source and the phosphate source capable of reacting with water to form the self-setting cement;
mixing a liquid component comprising water and an acid; and mixing said powdered mixture and said liquid component causing said acid and carbonate to react to form a gas and causing said calcium and phosphate sources to react with water to form the self-setting hydroxyapatite cement wherein the ratio of the weights of acid to the carbonate is chosen such that the final result of their reaction does not change the final pH of the mixture of the powder and water with the ratio of the weight of acid to carbonate being about 0.7.
mixing powdered components at least one being a calcium source and at least one being a phosphate source and at least one powdered component being a carbonate selected from the group consisting of sodium carbonate, sodium bicarbonate, calcium carbonate, calcium bicarbonate and a combination thereof to form a powdered mixture, the calcium source and the phosphate source capable of reacting with water to form the self-setting cement;
mixing a liquid component comprising water and an acid; and mixing said powdered mixture and said liquid component causing said acid and carbonate to react to form a gas and causing said calcium and phosphate sources to react with water to form the self-setting hydroxyapatite cement wherein the ratio of the weights of acid to the carbonate is chosen such that the final result of their reaction does not change the final pH of the mixture of the powder and water with the ratio of the weight of acid to carbonate being about 0.7.
5. The method as set forth in claim 4, wherein the acid is selected from the group consisting of citric acid, malic acid, phosphoric acid, fumaric acid, lactic acid, succinic acid and a combination thereof.
6. The method as set forth in claim 5, wherein said acid and carbonate react to form carbon dioxide.
7. The method as set forth in claim 6, wherein the gas produces a cement having an average pore size of at least 70 microns after setting.
8. The method as set forth in claim 7, wherein the gas produces a cement having an average pore size of between 440 microns and 580 microns after setting.
9. The method of claim 4, wherein the weight ratio of the acid and carbonate to the water and powdered mixture forming the cement is 10% to 20%.
10. A bone treatment material comprising:
an acid source selected from the group consisting of citric acid, malic acid, phosphoric acid, fumaric acid, lactic acid, succinic acid and a combination thereof; and a powdered combination containing at least two powdered calcium phosphate mineral components mixed together, said at least two powdered calcium phosphate components capable of reacting with said water to form said self-setting bone cement and said mixed at least two powdered calcium phosphate components containing a carbonate selected from the group consisting of sodium carbonate, sodium bicarbonate, calcium carbonate, calcium bicarbonate and a combination thereof, wherein the ratio of the weights of the acid to the carbonate are chosen such that the final result of their reaction does not change the final pH of the mixture of the at least two powdered components and water with the ratio of the weight of the acid to carbonate being about 0.7.
an acid source selected from the group consisting of citric acid, malic acid, phosphoric acid, fumaric acid, lactic acid, succinic acid and a combination thereof; and a powdered combination containing at least two powdered calcium phosphate mineral components mixed together, said at least two powdered calcium phosphate components capable of reacting with said water to form said self-setting bone cement and said mixed at least two powdered calcium phosphate components containing a carbonate selected from the group consisting of sodium carbonate, sodium bicarbonate, calcium carbonate, calcium bicarbonate and a combination thereof, wherein the ratio of the weights of the acid to the carbonate are chosen such that the final result of their reaction does not change the final pH of the mixture of the at least two powdered components and water with the ratio of the weight of the acid to carbonate being about 0.7.
11. The bone treatment material as set forth in claim 10, wherein said acid and carbonate react to form carbon dioxide gas.
12. The bone treatment material as set forth in claim 11, wherein the gas produces a cement having an average pore size of at least 70 microns after setting.
13. The bone treatment material as set forth in claim 11, wherein the gas produces a cement having an average pore size of between 440 microns and 580 microns after setting.
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US09/699,662 | 2000-10-30 | ||
US09/699,662 US6547866B1 (en) | 2000-10-30 | 2000-10-30 | Porous calcium phosphate cement |
PCT/US2001/031480 WO2002036518A1 (en) | 2000-10-30 | 2001-10-10 | Porous calcium phosphate cement |
Publications (2)
Publication Number | Publication Date |
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CA2394100A1 CA2394100A1 (en) | 2002-05-10 |
CA2394100C true CA2394100C (en) | 2007-12-11 |
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CA002394100A Expired - Fee Related CA2394100C (en) | 2000-10-30 | 2001-10-10 | Porous calcium phosphate cement |
Country Status (7)
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US (2) | US6547866B1 (en) |
EP (1) | EP1335757B1 (en) |
JP (1) | JP2004512880A (en) |
AU (1) | AU777599B2 (en) |
CA (1) | CA2394100C (en) |
DE (1) | DE60115703T2 (en) |
WO (1) | WO2002036518A1 (en) |
Families Citing this family (60)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20040081704A1 (en) * | 1998-02-13 | 2004-04-29 | Centerpulse Biologics Inc. | Implantable putty material |
US6840995B2 (en) * | 1999-07-14 | 2005-01-11 | Calcitec, Inc. | Process for producing fast-setting, bioresorbable calcium phosphate cements |
US7169373B2 (en) * | 1999-07-14 | 2007-01-30 | Calcitec, Inc. | Tetracalcium phosphate (TTCP) having calcium phosphate whisker on surface and process for preparing the same |
US6960249B2 (en) * | 1999-07-14 | 2005-11-01 | Calcitec, Inc. | Tetracalcium phosphate (TTCP) having calcium phosphate whisker on surface |
US7270705B2 (en) * | 1999-07-14 | 2007-09-18 | Jiin-Huey Chern Lin | Method of increasing working time of tetracalcium phosphate cement paste |
US7094282B2 (en) * | 2000-07-13 | 2006-08-22 | Calcitec, Inc. | Calcium phosphate cement, use and preparation thereof |
DK1223990T3 (en) * | 1999-10-15 | 2004-11-29 | Inst Genetics Llc | Formulations of hyaluronic acid for delivery of osteogenic proteins |
DE10032220A1 (en) | 2000-07-03 | 2002-01-24 | Sanatis Gmbh | Magnesium ammonium phosphate cements, their manufacture and use |
US7204876B2 (en) * | 2000-07-13 | 2007-04-17 | Calcitec, Inc. | Calcium phosphate cements made from (TTCP) with surface whiskers and process for preparing same |
US7156915B2 (en) * | 2000-07-13 | 2007-01-02 | Calcitec, Inc. | Tetracalcium phosphate (TTCP) with surface whiskers and method of making same |
US20020114795A1 (en) | 2000-12-22 | 2002-08-22 | Thorne Kevin J. | Composition and process for bone growth and repair |
US20020193883A1 (en) * | 2001-01-25 | 2002-12-19 | Wironen John F. | Injectable porous bone graft materials |
US20030216777A1 (en) * | 2002-05-16 | 2003-11-20 | Yin-Chun Tien | Method of enhancing healing of interfacial gap between bone and tendon or ligament |
US7273523B2 (en) | 2002-06-07 | 2007-09-25 | Kyphon Inc. | Strontium-apatite-cement-preparations, cements formed therefrom, and uses thereof |
FR2841897B1 (en) * | 2002-07-08 | 2004-12-10 | Rousselot Sas | PROCESS FOR THE PREPARATION OF AN APATITIC CEMENT, SAID CEMENT AND ITS USE FOR TRAPPING POLLUTANTS |
US20040254668A1 (en) * | 2003-06-16 | 2004-12-16 | Jang Bor Z. | Macro-porous hydroxyapatite scaffold compositions and freeform fabrication method thereof |
US7118705B2 (en) * | 2003-08-05 | 2006-10-10 | Calcitec, Inc. | Method for making a molded calcium phosphate article |
US7163651B2 (en) * | 2004-02-19 | 2007-01-16 | Calcitec, Inc. | Method for making a porous calcium phosphate article |
TWI275386B (en) * | 2003-08-05 | 2007-03-11 | Cana Lab Corp | Methods for preparing medical implants from calcium phosphate cement and medical implants |
US6994726B2 (en) * | 2004-05-25 | 2006-02-07 | Calcitec, Inc. | Dual function prosthetic bone implant and method for preparing the same |
CA2545185A1 (en) * | 2003-11-07 | 2005-05-26 | Calcitec, Inc. | Spinal fusion procedure using an injectable bone substitute |
US7351280B2 (en) * | 2004-02-10 | 2008-04-01 | New York University | Macroporous, resorbable and injectible calcium phosphate-based cements (MCPC) for bone repair, augmentation, regeneration, and osteoporosis treatment |
MXPA06012420A (en) | 2004-04-27 | 2007-03-28 | Kyphon Inc | Bone substitute compositions and method of use. |
US7175858B2 (en) | 2004-07-26 | 2007-02-13 | Skeletal Kinetics Llc | Calcium phosphate cements and methods for using the same |
US20060110422A1 (en) * | 2004-11-19 | 2006-05-25 | Tas Ahmet C | Conversion of calcite powders into macro- and microporous calcium phosphate scaffolds for medical applications |
US7312989B2 (en) * | 2004-12-06 | 2007-12-25 | Chenbro Micom Co., Ltd. | Cooler |
DE102004062739A1 (en) * | 2004-12-27 | 2006-07-06 | Degussa Ag | Self-cleaning surfaces with protrusions formed by hydrophobic particles, with improved mechanical strength |
US7713542B2 (en) | 2005-01-14 | 2010-05-11 | Ada Foundation | Three dimensional cell protector/pore architecture formation for bone and tissue constructs |
US7651701B2 (en) * | 2005-08-29 | 2010-01-26 | Sanatis Gmbh | Bone cement composition and method of making the same |
US8147860B2 (en) * | 2005-12-06 | 2012-04-03 | Etex Corporation | Porous calcium phosphate bone material |
US7754005B2 (en) * | 2006-05-02 | 2010-07-13 | Kyphon Sarl | Bone cement compositions comprising an indicator agent and related methods thereof |
US7507286B2 (en) * | 2006-06-08 | 2009-03-24 | Sanatis Gmbh | Self-foaming cement for void filling and/or delivery systems |
WO2008039382A2 (en) * | 2006-09-21 | 2008-04-03 | Kyphon Sarl | Diammonium phosphate and other ammonium salts and their use in preventing clotting |
WO2008073190A2 (en) * | 2006-11-03 | 2008-06-19 | Kyphon Sarl | Materials and methods and systems for delivering localized medical treatments |
US8388626B2 (en) * | 2006-11-08 | 2013-03-05 | Warsaw Orthopedic, Inc. | Methods of employing calcium phosphate cement compositions and osteoinductive proteins to effect vertebrae interbody fusion absent an interbody device |
US7718616B2 (en) | 2006-12-21 | 2010-05-18 | Zimmer Orthobiologics, Inc. | Bone growth particles and osteoinductive composition thereof |
US8268010B2 (en) * | 2007-01-12 | 2012-09-18 | Warsaw Orthopedic, Inc. | System and method for forming bone filling materials with microparticles |
WO2008089019A2 (en) * | 2007-01-12 | 2008-07-24 | Warsaw Orthopedic, Inc. | System and method for forming porous bone filling material |
US8926623B2 (en) * | 2007-01-12 | 2015-01-06 | Warsaw Orthopedic, Inc. | System and method for forming porous bone filling material |
US8840618B2 (en) * | 2007-01-12 | 2014-09-23 | Warsaw Orthopedic, Inc. | System and method for pressure mixing bone filling material |
ITRM20070363A1 (en) | 2007-06-27 | 2008-12-28 | Univ Bologna Alma Mater | POROUS SECTOR FROM CEMENTITIOUS MATERIAL OF CALCIUM PHOSPHATE AND ITS USE IN FLUID-SCALE EQUIPMENT |
US20090036564A1 (en) * | 2007-08-03 | 2009-02-05 | Feng-Huei Lin | Bio-Degenerable Bone Cement and Manufacturing Method thereof |
US7968616B2 (en) * | 2008-04-22 | 2011-06-28 | Kyphon Sarl | Bone cement composition and method |
EP2365994B1 (en) | 2008-11-12 | 2017-01-04 | Howmedica Osteonics Corp. | Tetra calcium phosphate based organophosphorus compositions and methods |
CN101891174B (en) * | 2009-03-11 | 2011-11-02 | 北京林业大学 | Hydroxyapatite with hollow sphere structure and preparation method thereof |
JPWO2010119897A1 (en) | 2009-04-17 | 2012-10-22 | Hoya株式会社 | Calcium phosphate cement composition for bone filling material and kit thereof |
WO2010119953A1 (en) | 2009-04-17 | 2010-10-21 | Hoya株式会社 | Calcium phosphate cement composite for bone filling, and kit thereof |
WO2010124110A1 (en) * | 2009-04-22 | 2010-10-28 | American Dental Association Foundation | Dual-phase calcium phosphate cement composition |
EP2512537B1 (en) * | 2009-12-18 | 2015-08-26 | Howmedica Osteonics Corp. | Dual paste direct injectable bone cement precursor systems and methods of making same |
CA2798710C (en) | 2010-05-11 | 2019-08-27 | Venkat R. Garigapati | Organophosphorous, multivalent metal compounds, & polymer adhesive interpenetrating network compositions & methods |
ES2714701T3 (en) | 2010-11-10 | 2019-05-29 | Stryker European Holdings I Llc | Process for the preparation of a polymeric bone foam |
CA2817584C (en) | 2010-11-15 | 2018-01-02 | Zimmer Orthobiologics, Inc. | Bone void fillers |
MY171424A (en) * | 2011-01-27 | 2019-10-12 | Sirim Berhad | Composition containing injectable self-hardened apatite cement |
WO2012158527A2 (en) | 2011-05-13 | 2012-11-22 | Howmedica Osteonics | Organophosphorous & multivalent metal compound compositions & methods |
NL2007850C2 (en) * | 2011-11-24 | 2013-05-27 | Stichting Katholieke Univ | Injectable calcium phosphate cement comprising glucono-delta-lactone. |
CN102552986B (en) * | 2012-02-28 | 2013-12-18 | 河南科技大学 | Method for preparing porous bone cement by using metal porogen |
US9820791B2 (en) | 2014-08-22 | 2017-11-21 | Kyphon SÀRL | Methods of filling bone using bone cement mixing and delivery devices |
US9820792B2 (en) | 2014-08-22 | 2017-11-21 | Kyphon SÀRL | Bone cement mixing and delivery device |
US11020160B2 (en) * | 2016-03-21 | 2021-06-01 | Warsaw Orthopedic, Inc. | Surgical injection system and method |
JP6807099B2 (en) * | 2016-09-07 | 2021-01-06 | 公立大学法人大阪 | Kits for producing bioactive cement pastes and bioactive cements, bioactive cement pastes and methods for producing them |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US33221A (en) * | 1861-09-03 | Improvement in soap | ||
JPS5171896A (en) * | 1974-12-20 | 1976-06-22 | Kinto Kk | TANSANAPATAITOKEIRINKOSEKINO SHORIHO |
USRE33221E (en) | 1982-04-29 | 1990-05-22 | American Dental Association Health Foundation | Dental restorative cement pastes |
USRE33161E (en) | 1982-04-29 | 1990-02-06 | American Dental Association Health Foundation | Combinations of sparingly soluble calcium phosphates in slurries and pastes as mineralizers and cements |
US5180426A (en) | 1987-12-28 | 1993-01-19 | Asahi Kogaku Kogyo K.K. | Composition for forming calcium phosphate type setting material and process for producing setting material |
US5047031A (en) * | 1988-04-20 | 1991-09-10 | Norian Corporation | In situ calcium phosphate minerals method |
US4880610A (en) | 1988-04-20 | 1989-11-14 | Norian Corporation | In situ calcium phosphate minerals--method and composition |
DE4124898A1 (en) * | 1990-07-27 | 1992-01-30 | Osaka Cement | APETITE-CONTAINED TETRACALCIUM PHOSPHATE PARTICLES |
US5149368A (en) * | 1991-01-10 | 1992-09-22 | Liu Sung Tsuen | Resorbable bioactive calcium phosphate cement |
EP0520690B1 (en) | 1991-06-26 | 1995-11-02 | Nitta Gelatin Inc. | Calcium phosphate type hardening material for repairing living hard tissue |
JPH0734817B2 (en) * | 1992-06-01 | 1995-04-19 | 新田ゼラチン株式会社 | Medical and dental curable and porous materials |
US5525148A (en) | 1993-09-24 | 1996-06-11 | American Dental Association Health Foundation | Self-setting calcium phosphate cements and methods for preparing and using them |
JPH1036106A (en) * | 1996-07-26 | 1998-02-10 | Taihei Kagaku Sangyo Kk | Porous bulk apatite carbonate and its production |
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US6670293B2 (en) | 2003-12-30 |
DE60115703T2 (en) | 2006-10-05 |
AU9673001A (en) | 2002-05-15 |
US20030019396A1 (en) | 2003-01-30 |
AU777599B2 (en) | 2004-10-21 |
US6547866B1 (en) | 2003-04-15 |
DE60115703D1 (en) | 2006-01-12 |
EP1335757A1 (en) | 2003-08-20 |
CA2394100A1 (en) | 2002-05-10 |
WO2002036518A1 (en) | 2002-05-10 |
EP1335757A4 (en) | 2003-08-20 |
JP2004512880A (en) | 2004-04-30 |
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