CA2176334A1 - Resorbable bioactive phosphate containing cements - Google Patents
Resorbable bioactive phosphate containing cementsInfo
- Publication number
- CA2176334A1 CA2176334A1 CA002176334A CA2176334A CA2176334A1 CA 2176334 A1 CA2176334 A1 CA 2176334A1 CA 002176334 A CA002176334 A CA 002176334A CA 2176334 A CA2176334 A CA 2176334A CA 2176334 A1 CA2176334 A1 CA 2176334A1
- Authority
- CA
- Canada
- Prior art keywords
- calcium
- setting
- cement
- citrate
- surgical cement
- 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.)
- Abandoned
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K6/00—Preparations for dentistry
- A61K6/80—Preparations for artificial teeth, for filling teeth or for capping teeth
- A61K6/849—Preparations for artificial teeth, for filling teeth or for capping teeth comprising inorganic cements
- A61K6/864—Phosphate cements
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K6/00—Preparations for dentistry
- A61K6/80—Preparations for artificial teeth, for filling teeth or for capping teeth
- A61K6/831—Preparations for artificial teeth, for filling teeth or for capping teeth comprising non-metallic elements or compounds thereof, e.g. carbon
- A61K6/838—Phosphorus compounds, e.g. apatite
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K6/00—Preparations for dentistry
- A61K6/80—Preparations for artificial teeth, for filling teeth or for capping teeth
- A61K6/849—Preparations for artificial teeth, for filling teeth or for capping teeth comprising inorganic cements
-
- 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
-
- 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
-
- 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
- C04B22/00—Use of inorganic materials as active ingredients for mortars, concrete or artificial stone, e.g. accelerators, shrinkage compensating agents
- C04B22/06—Oxides, Hydroxides
- C04B22/062—Oxides, Hydroxides of the alkali or alkaline-earth metals
- C04B22/064—Oxides, Hydroxides of the alkali or alkaline-earth metals of the alkaline-earth metals
-
- 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
- C04B22/00—Use of inorganic materials as active ingredients for mortars, concrete or artificial stone, e.g. accelerators, shrinkage compensating agents
- C04B22/08—Acids or salts thereof
- C04B22/12—Acids or salts thereof containing halogen in the anion
- C04B22/124—Chlorides of ammonium or of the alkali or alkaline earth metals, e.g. calcium chloride
-
- 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
- C04B24/00—Use of organic materials as active ingredients for mortars, concrete or artificial stone, e.g. plasticisers
- C04B24/04—Carboxylic acids; Salts, anhydrides or esters thereof
- C04B24/06—Carboxylic acids; Salts, anhydrides or esters thereof containing hydroxy groups
-
- 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
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Ceramic Engineering (AREA)
- Engineering & Computer Science (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Inorganic Chemistry (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Materials Engineering (AREA)
- Structural Engineering (AREA)
- Organic Chemistry (AREA)
- Plastic & Reconstructive Surgery (AREA)
- Transplantation (AREA)
- Medicinal Chemistry (AREA)
- Dermatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Surgery (AREA)
- Materials For Medical Uses (AREA)
Abstract
A surgical cement of high biocompatibility, useful in orthopedic, maxillofacial and dental applications, comprising a calcium alkali phosphate cement with relatively high surface pH of about 7 or higher, and having a wide variety of chemical compositions, permitting flexibility in controlling the bioresorption rate by changing the chemical composition of the cementing powder.
Description
2 ~ 76334 wo 95/13835 Pcr/uss3/l10 RESOBBABLE BIOACTIVE PHOSPHATE CONTAINING CEMENTS
BACKGROUND OF THE INVENTION
1. Field of the Invention This invention relates to a surgical cement, also known as bone 5 cement or bi~ sol LaLlr~ i" ")la"lalion material, and its process of formation.
The cements of this invention are formed from calcium alkali pl~,uhaLe ceramics and acidic citrate setting reagents, which when combined with an aqueous solution form a moldable paste having high biOcOlll~Jai :' Ly. The paste is easy to Illdll', ~"tQ and reaches neutral pH or higher shortly after 10 lla~ . The resulting cements are useful in o,Ll,opedic and Illa~ oral~ial sur~eries and in dental .~r r : S.
2. Desc,iuLion of the Prior Art In the last two decades, many artificial hard tissue implant materials have been made. since the Major inorganic c~l"pone"l of human hard tissue l5 le.g. bone, teeth) is a calcium phOslJha~a compound, which is biological apatite, hydroxy-apatite and other calcium phO:~JllaL~ ceramics were logically selected for hard tissue implant materials.
Most of the previous calcium phospllal~ cements developed used hydroxyapatite or tricalcium pl-O~ lalt: as the c~"~"Li"~ ceramic and 20 phosphoric acid, bifunctional organic acids or other polyfunctional organic acids as setting reagents. These cements are normally very acidic in nature and take a very long time to reach neutral pH. After illl~lallLdLion, these cements may cause irritation and illrlallllllalury reactions.
Bioc~" lua i ' " :y has been the limiting factor in successful .~ ions 25 of implant materials. The most successful artificial implant materials to WO 95/13835 2 ~ 7 6 3 3 4 PCT/US93111071 achieve the excellent b;oco~ Jai ' "~y have been hydroxyapatite, bioglass', and other calcium phOs~haL~ ceramics. Hydroxyapatite and B-tricalcium pho:~lla~e cerarrics and calcium pho~,halt: co"l..;., ,9 g~ass have been extensively studied. Clinical studies co,lri""~d that most of the calcium pllo~,ullale cerarics such as hydroxyapatite, tricalcium phOspha~, ~ d~ ;um p~lu:~hale and dicalcium phG .~Jhdl~ have excellent bioco"~, ' ."b~ and are well accepted by both hard tissue and soft tissue.
The ex~-~.i",e,1lal results also indicated that dense hydroxyapatite is non-bio,~:,orl,sb'r; while other porous calcium pl~r,:",l1dl~ ceramics are 1 0 bioresorbable.
The surgeon is most interested in implant materials that can be shaped and harden in situ, but such biOC~Ial,lic prt:pa,dlions are not yet available. Most of the calcium phos~,~laL~ ceramics for medical r, ~' Lions are prepared either in granule form or block form. The granule form has poor manipulatio~ cllala~ while the block form is very brittle and difficult to shape. In order to solve the above problems, many attempts have been made to prepare binder systems for b;oce, dll 1;~ . Plaster of Paris, collagen, polylactate, polyacrylate, calcium pho~ hdL~ ~rout and hydroxyapatite cement have been used.
Ideally, a useful binder system for bi~c~rallli~s should have good b;OCOl~ aLiLliliLy~ (including a near neutral pH), a suitable t .t:~or~.lion rate, be moldable at surgical sites, and have good setting .,lldldl,lt:ri~ .a. The acidity of the setting cement is dependent on the type of calcium phosphate A bioactive glass material whose major ,u...~u~ aro CaO, SiO2 and P20~. Minor ~"-~.u,~ may be Na20, M~O, Al203, B20, and CaF2. A bioactive ~lass can form a surface layer of ~yd, u~ , when soa ~ed in the aqueous ~:" . :. u~
2 1 7~3~
sait used, the scidity of the setting rea~ent, and the reaction rate. Typical cements are formed from dissolution and recry~ of salts with Ca/P
mole ratio > 1 after Collluilldlio" with acidic reagents.
When the calcium pho:"uhal~ salt reacts with the acid setting reagent 5 to form a cement, the calcium phos?hdle dissolves and new calcium compounds are formed during the setting stage. The extent of the reaction, the setting time and setting cl~a~d~ , are sensitive to the nature of calcium ph~ lldl~ powder, the pH and the type of setting reagents. Even when excess calcium phosplldl~ powder is used to form a paste with highly 10 soluble acidic setting reagent, the setting cement will nevertheless contain some unreacted acid setting reagent trapped in the cement. The result is low surface pH of the setting cement. If the calcium phosphate cementing powder is near neutral and has a very slow; !~ltion rate, the surface pH
will stay low for a lon~ time. This low pH cement is ~"deDi, ' ' since it 15 may cause irritation and illrla,l,lllalury reactions. Addiliull~ !y setting times of this cement are difficult to control and it has poor l~a", ~lAfinn al d~ Lil,5 .
Most binders have disadvantages. Plaster of Paris has a I t:asonable setting ~ a~ a~ lics but the re~or,uliol l rate is too fast. Collagen-20 hydroxyapatite co"l~,o:-iL~ and polylactatehydroxyapatite can serve as a useful delivery system for hydroxyapatite or other calcium ~ ospl~aL~
granular ceramics, but these Colll~,G .iL~ materials must be premolded; they cannot be molded at the surgical site.
Calcium phG:I~JhdLI: grout does not set well in the in situ aqueous 25 envi,unlllenl. For example, a recentiy reported calcium pllG~ dL~ cement WO 95/13835 r ~ ~ 2 ~ 7 6 3 3 4 PCTIUS93111071 combined with bifunctional acids as setting reagents (U.S. patent 4,668,295) was very acidic, ~ ld~l:d very fast in the in situ aqueous env;,~"-,-e-~, and lacked good setting cl~ala~,L~ .s. Pure hydroxyapatite cement prepared by reacting tetracalcium pl~o~ al~ and other calcium 5 phGsphaLt:~ is no l~ .olL ' ' and does not have good setting cl~ala~ liD~i(;s (U.S. patents 4,-18,430 and 4,612,053).
Oonishi2 reported a bioactive ~r-tricalcium phO:>tJhal~ cement. This calcium pho ",hal~: cement has a ~asol-abl~ setting time and strong l,,e.,l,al.i~,dl strength, but is very acidic. More recently, a bioglass cement 10 containing calcium phosphate using phosphoric acid or calcium hydroxide as the setting reaç ent has been reported.3 The bioglass cement with phosphoric acid has low pH. No setting cl-a-d.,~ , of this bioglass cement has beer reported.
SUMMARY OF THE INVENTION
This invention relates to surgical cements formed by combining calcium alkali ph~p~,a~e ceramics with acidic citrate setting reagents which shortly after setting have near neutral surface pH (pH 7) and are highly b;ocolll~a~iL~ n'oldable~andl~solbabl~ Sincethematerialofthisinvention 20 may be mixed to vary the reaction rates, greater flexibility of use may be expected because the medical ~ idl~ could apply this invention in paste form in situ or premold the implant.
2 H. Oonishi, et at., 'Studies on Du;.', of o-TCP Bioactive Bone Cement~ Posted Paper, En~inecrin~ Foundat on Conferences, Bioceramics, Santa Barbara, CA 1986.
BACKGROUND OF THE INVENTION
1. Field of the Invention This invention relates to a surgical cement, also known as bone 5 cement or bi~ sol LaLlr~ i" ")la"lalion material, and its process of formation.
The cements of this invention are formed from calcium alkali pl~,uhaLe ceramics and acidic citrate setting reagents, which when combined with an aqueous solution form a moldable paste having high biOcOlll~Jai :' Ly. The paste is easy to Illdll', ~"tQ and reaches neutral pH or higher shortly after 10 lla~ . The resulting cements are useful in o,Ll,opedic and Illa~ oral~ial sur~eries and in dental .~r r : S.
2. Desc,iuLion of the Prior Art In the last two decades, many artificial hard tissue implant materials have been made. since the Major inorganic c~l"pone"l of human hard tissue l5 le.g. bone, teeth) is a calcium phOslJha~a compound, which is biological apatite, hydroxy-apatite and other calcium phO:~JllaL~ ceramics were logically selected for hard tissue implant materials.
Most of the previous calcium phospllal~ cements developed used hydroxyapatite or tricalcium pl-O~ lalt: as the c~"~"Li"~ ceramic and 20 phosphoric acid, bifunctional organic acids or other polyfunctional organic acids as setting reagents. These cements are normally very acidic in nature and take a very long time to reach neutral pH. After illl~lallLdLion, these cements may cause irritation and illrlallllllalury reactions.
Bioc~" lua i ' " :y has been the limiting factor in successful .~ ions 25 of implant materials. The most successful artificial implant materials to WO 95/13835 2 ~ 7 6 3 3 4 PCT/US93111071 achieve the excellent b;oco~ Jai ' "~y have been hydroxyapatite, bioglass', and other calcium phOs~haL~ ceramics. Hydroxyapatite and B-tricalcium pho:~lla~e cerarrics and calcium pho~,halt: co"l..;., ,9 g~ass have been extensively studied. Clinical studies co,lri""~d that most of the calcium pllo~,ullale cerarics such as hydroxyapatite, tricalcium phOspha~, ~ d~ ;um p~lu:~hale and dicalcium phG .~Jhdl~ have excellent bioco"~, ' ."b~ and are well accepted by both hard tissue and soft tissue.
The ex~-~.i",e,1lal results also indicated that dense hydroxyapatite is non-bio,~:,orl,sb'r; while other porous calcium pl~r,:",l1dl~ ceramics are 1 0 bioresorbable.
The surgeon is most interested in implant materials that can be shaped and harden in situ, but such biOC~Ial,lic prt:pa,dlions are not yet available. Most of the calcium phos~,~laL~ ceramics for medical r, ~' Lions are prepared either in granule form or block form. The granule form has poor manipulatio~ cllala~ while the block form is very brittle and difficult to shape. In order to solve the above problems, many attempts have been made to prepare binder systems for b;oce, dll 1;~ . Plaster of Paris, collagen, polylactate, polyacrylate, calcium pho~ hdL~ ~rout and hydroxyapatite cement have been used.
Ideally, a useful binder system for bi~c~rallli~s should have good b;OCOl~ aLiLliliLy~ (including a near neutral pH), a suitable t .t:~or~.lion rate, be moldable at surgical sites, and have good setting .,lldldl,lt:ri~ .a. The acidity of the setting cement is dependent on the type of calcium phosphate A bioactive glass material whose major ,u...~u~ aro CaO, SiO2 and P20~. Minor ~"-~.u,~ may be Na20, M~O, Al203, B20, and CaF2. A bioactive ~lass can form a surface layer of ~yd, u~ , when soa ~ed in the aqueous ~:" . :. u~
2 1 7~3~
sait used, the scidity of the setting rea~ent, and the reaction rate. Typical cements are formed from dissolution and recry~ of salts with Ca/P
mole ratio > 1 after Collluilldlio" with acidic reagents.
When the calcium pho:"uhal~ salt reacts with the acid setting reagent 5 to form a cement, the calcium phos?hdle dissolves and new calcium compounds are formed during the setting stage. The extent of the reaction, the setting time and setting cl~a~d~ , are sensitive to the nature of calcium ph~ lldl~ powder, the pH and the type of setting reagents. Even when excess calcium phosplldl~ powder is used to form a paste with highly 10 soluble acidic setting reagent, the setting cement will nevertheless contain some unreacted acid setting reagent trapped in the cement. The result is low surface pH of the setting cement. If the calcium phosphate cementing powder is near neutral and has a very slow; !~ltion rate, the surface pH
will stay low for a lon~ time. This low pH cement is ~"deDi, ' ' since it 15 may cause irritation and illrla,l,lllalury reactions. Addiliull~ !y setting times of this cement are difficult to control and it has poor l~a", ~lAfinn al d~ Lil,5 .
Most binders have disadvantages. Plaster of Paris has a I t:asonable setting ~ a~ a~ lics but the re~or,uliol l rate is too fast. Collagen-20 hydroxyapatite co"l~,o:-iL~ and polylactatehydroxyapatite can serve as a useful delivery system for hydroxyapatite or other calcium ~ ospl~aL~
granular ceramics, but these Colll~,G .iL~ materials must be premolded; they cannot be molded at the surgical site.
Calcium phG:I~JhdLI: grout does not set well in the in situ aqueous 25 envi,unlllenl. For example, a recentiy reported calcium pllG~ dL~ cement WO 95/13835 r ~ ~ 2 ~ 7 6 3 3 4 PCTIUS93111071 combined with bifunctional acids as setting reagents (U.S. patent 4,668,295) was very acidic, ~ ld~l:d very fast in the in situ aqueous env;,~"-,-e-~, and lacked good setting cl~ala~,L~ .s. Pure hydroxyapatite cement prepared by reacting tetracalcium pl~o~ al~ and other calcium 5 phGsphaLt:~ is no l~ .olL ' ' and does not have good setting cl~ala~ liD~i(;s (U.S. patents 4,-18,430 and 4,612,053).
Oonishi2 reported a bioactive ~r-tricalcium phO:>tJhal~ cement. This calcium pho ",hal~: cement has a ~asol-abl~ setting time and strong l,,e.,l,al.i~,dl strength, but is very acidic. More recently, a bioglass cement 10 containing calcium phosphate using phosphoric acid or calcium hydroxide as the setting reaç ent has been reported.3 The bioglass cement with phosphoric acid has low pH. No setting cl-a-d.,~ , of this bioglass cement has beer reported.
SUMMARY OF THE INVENTION
This invention relates to surgical cements formed by combining calcium alkali ph~p~,a~e ceramics with acidic citrate setting reagents which shortly after setting have near neutral surface pH (pH 7) and are highly b;ocolll~a~iL~ n'oldable~andl~solbabl~ Sincethematerialofthisinvention 20 may be mixed to vary the reaction rates, greater flexibility of use may be expected because the medical ~ idl~ could apply this invention in paste form in situ or premold the implant.
2 H. Oonishi, et at., 'Studies on Du;.', of o-TCP Bioactive Bone Cement~ Posted Paper, En~inecrin~ Foundat on Conferences, Bioceramics, Santa Barbara, CA 1986.
3 W.S. Chcn, Y. Chen, J.P. Rausch. E.A. Monroe, ~Phosphate Glass Bone Graft~, page 241, Thc 1 5th Annual Mcctin~ o' thc Society for ~ ial~, april 28-May 2, 1989, t~ke Buena Vista, The present invention uses a highly alkaline and rapidly ~i;.;,olv;.,g calcium alkali phOa~Jhdlc ceramic, such as calcium sodium phO~ laLt: or calcium potassium pho~hcLc ceramics which result in the increased surface pH of the surgical cement and hence the greater tii~COIl, " ""y.
Ad~iLio~1 'y, the present invention provides increased L ~ ",li~n and improved "~d~ tion I~a~d~ .s. This invention permits manipulation of the c-c",t:"lilious paste at the surgical site for hard tissue rcplac~lllelll within a ,casor 'e setting time. It can also be prepared in ~, c" ,ol~ed shapes.
Rt:sor~,Lion rates can be varied by p,~dt:Lc,,,,;,,ed mixtures of b;OCOIII,udi" 'e filler compounds added to the cclll~llLillg powders. These cements are only slightly acidic after mixing into a paste. After setting in the liquid environment, the surface pH of the cements raises rapidly to near 7 or higher.
In summary, the advantages of these cements are relatively high surface pH, good L- ~~ " ~t ~ :y, l~ cs~,i ~' y, ~casol~ s setting time and good manipulation I,a,d. l~ s. Consequently, these cements have greater usefulness as implants for hard tissue ~cplacrc~ l materials over prior art. They can be used for bone graft, bone fracture fixation, bone 20 defect fillers, ",_ 'Icrcial surgery, spinal fusion, bone cements, dental cements and drug delivery systems. They can also be used as a binder system for the granule form of calcium phosphate ceramics.
lll ~` ,` 2 ~ 76334 WO 95/13~135 _ 6 PCT/US93111071 ~, DETAILED DESCRIPTION OF THE
P~t~tll~tu '~'-OS~ TS
Among the pure calcium phos~lla l~ salts, only tetracalcium phosphate is alkaline in nature. In a p,~pa,aliun of calcined pl~ ale fertilizer, Ando4 and Ando and Matsuno5 reported the formation of mixed ceramics. This mixed ceramic is a crystalline solid solution Gon , ,9 tricalcium pllO~ dlt:, Ca5Na2(PO4)4 and I~ llallli~e (a and ,B form of CaNaPO~). In general, these calcium sodium ~I1GS~JI la~ ceramics are alkaline in nature, and have relatively high solubility. Similarly, the calcium potassium phosphate ceramics are also alkaline and have high ~; o'ution rates. The present invention uses these calcium alkaii C~lllaill;llg phosphate ceramics for the cementing powder. Because of the alkaline nature and high lis~o!utinn rates, these ceramics are able to react with acidic citrate compounds yielding cements with relatively short setting times ranging from several minutes to about a half an hour, and having high surface pH.
The setting reagents used in this invention are acidic citrate compounds, including citric acid, dihydrogen citrate salts or monohydrogen citrate salts. In tle present cement system, the weight ratio of c~",e"li"g powder to settin~ reagent varies from 1.2:1 to 10:1. When the ratio is as high as 10, the final set cement contains reaction products and high amounts of ~iolc:~olLld~l~ unreacted calcium alkali pho~ alt:.
A further i~crease of the surface pH of the setting cement may be achieved by usin~ hydrogen citrate salts or citric acid with alkaline reagents
Ad~iLio~1 'y, the present invention provides increased L ~ ",li~n and improved "~d~ tion I~a~d~ .s. This invention permits manipulation of the c-c",t:"lilious paste at the surgical site for hard tissue rcplac~lllelll within a ,casor 'e setting time. It can also be prepared in ~, c" ,ol~ed shapes.
Rt:sor~,Lion rates can be varied by p,~dt:Lc,,,,;,,ed mixtures of b;OCOIII,udi" 'e filler compounds added to the cclll~llLillg powders. These cements are only slightly acidic after mixing into a paste. After setting in the liquid environment, the surface pH of the cements raises rapidly to near 7 or higher.
In summary, the advantages of these cements are relatively high surface pH, good L- ~~ " ~t ~ :y, l~ cs~,i ~' y, ~casol~ s setting time and good manipulation I,a,d. l~ s. Consequently, these cements have greater usefulness as implants for hard tissue ~cplacrc~ l materials over prior art. They can be used for bone graft, bone fracture fixation, bone 20 defect fillers, ",_ 'Icrcial surgery, spinal fusion, bone cements, dental cements and drug delivery systems. They can also be used as a binder system for the granule form of calcium phosphate ceramics.
lll ~` ,` 2 ~ 76334 WO 95/13~135 _ 6 PCT/US93111071 ~, DETAILED DESCRIPTION OF THE
P~t~tll~tu '~'-OS~ TS
Among the pure calcium phos~lla l~ salts, only tetracalcium phosphate is alkaline in nature. In a p,~pa,aliun of calcined pl~ ale fertilizer, Ando4 and Ando and Matsuno5 reported the formation of mixed ceramics. This mixed ceramic is a crystalline solid solution Gon , ,9 tricalcium pllO~ dlt:, Ca5Na2(PO4)4 and I~ llallli~e (a and ,B form of CaNaPO~). In general, these calcium sodium ~I1GS~JI la~ ceramics are alkaline in nature, and have relatively high solubility. Similarly, the calcium potassium phosphate ceramics are also alkaline and have high ~; o'ution rates. The present invention uses these calcium alkaii C~lllaill;llg phosphate ceramics for the cementing powder. Because of the alkaline nature and high lis~o!utinn rates, these ceramics are able to react with acidic citrate compounds yielding cements with relatively short setting times ranging from several minutes to about a half an hour, and having high surface pH.
The setting reagents used in this invention are acidic citrate compounds, including citric acid, dihydrogen citrate salts or monohydrogen citrate salts. In tle present cement system, the weight ratio of c~",e"li"g powder to settin~ reagent varies from 1.2:1 to 10:1. When the ratio is as high as 10, the final set cement contains reaction products and high amounts of ~iolc:~olLld~l~ unreacted calcium alkali pho~ alt:.
A further i~crease of the surface pH of the setting cement may be achieved by usin~ hydrogen citrate salts or citric acid with alkaline reagents
4 J. Ando, ~Phase Dial~rams of Ca,(PO~12-M~,(PO412 and Ca,(PO412 -CaNaPO~ Systems~, Bull.
Chem. Soc., Japan, 31, 2û' (1958~.
Chem. Soc., Japan, 31, 2û' (1958~.
5 J. Ando and S. Matsuno, "Ca,(PO4)2-CaNaPO~ System,~ Bull. Chem. Soc., Japan, 41, 342 (1 968).
~W09S/13835 PCT/US93111071 instead of usin~ pure citric acid as the setting rea~cnt. Amon~ the suitable hydrogen citrate salts are: sodium dihydrogen citrate, disodium hydrogen citrate, ammonium dihydrogen citrate, .lic,,,,,,,ol, lrn hydrogen citrate, potassium dihydrogen citrate and dipotassium hydrogen citrate. The pH
5 may also be raised by using citric acid with alkaline reagents. Suitable alkaline reagents include NaOH, KOH, KH40H, sodium citrate, potassium citrate, ammonium citrate, sodium pl~G:"JhclLt:, disodium hydrogen phosphate, potassium phosphate, and dipotassium hydrogen pllospl~
While the pH of concehL,c,~ed pure citric acid is normally at 2, the pH
10 modified setting reagent should provide an initial solution pH which is much hi~her than the pure citric acid, reaching a pH of 3 to 5. Therefore, after setting, the surface pH of the setting cement will initially be near 5 and quickly reach 7 or higher upon hardening.
The surgical cement of this invention relates to a flexible CG"~pOSi~ion 15 by changin~ the CaO:Na20 or CaO:K20 mole ratios in the calcium alkali pllo~ e ceramics. The dissolution rate as well as the bio,~o,yliun rate of the cement changes accordingly. The overall chemical CGIllpO~ilioll of these ceramics can be changed from 2.9 CaO-0.1 Na20-P205 to 0.8 CaO-2.2 Na20-P205. The calcium potassium pllG ~,uh~ ceramics can be varied 20 in composition in the same manner. While these mixed ceramics cover a wide variety of chemical c~",posi~ions and a wide range of dissolution rates, in general, the dicsQl~ltion rates increase by increasing the alkali element content. As a result, the ~ nici~" can achieve greater bio,~iG" ~iol- rate control with the mixed ceramics than with the pure single component 25 calcium phOa~Jhell~ cements.
WO95/13835 ~ ' ~ 2 ~ PCT/US93/11071 Further control of the L~ 50r,u~ioll rate in this invention is achieved by incorporating a biocol~,uaL~ e filler material in the form of fine powder or granule, havin~ a particle size rangin~q from a few microns to 20 mesh. Filler material must be bioco,,,,udLiL,l~ without Si~lliri~.alllly effectin~ the integrity 5 and settin~q behavior of the cement. Fillers useful for this purpose include tetracalcium pl~:"JhaL~, tricalcium pllG:",h~Le, calcium phosphal~ apatite, dicalcium pl~GS~JhdL~, calcium carbonate, calcium sulfate dehydrate, calcium sulfate hemihydrate, calcium sulfate anhydrous, calcium fluoride, calcium oxide, calcium hyoroxide, calcium citrate, magnesium hydroxide, ma~nesium 10 oxide, collagen and other sparingly calcium organic salts. The wei~qht ratio of filler to calcium alkali pl~o~ laL~ c~",~,llil,g powder can be up to 5:1.
In the present invention the c~",t:"~i"g powder was premixed with filler material to form a homo~eneous mixed powder. The settin~q reaction can be initiated e ther by dissolving the setting reagent and pH adjustment 15 reagents in water or saline water to form an aqueous settin~q solution and.
adding it to the Fremixed powder, or premixing the solid setting reagents with the c~",e"Li"g powder and using sterili~ed pure water or saline water as the setting aqueous solution.
The cements of the present invention may be used as implant 20 materials for: (1) ~one grafts as filler or It:pld~,~rll~llL of bone that has been removed surgically or traumatically; (2) rid9e au~ w~ ~LdLi~ns~ (3) jaw repairs:
(4) cranial and " . " ~d~ial surgeries; (5) luting cement in dentistry and orthopedic surgery; (6) spinal fusions; (7) endodontic ',F': Lions, (8) root cements; (9) repl3cing or plullluLillg ,~gen~ldLiun of bone mineral lost due 25 to pe~iodo,lLdl disease; and (10) drug release systems. Antibiotics (up to wo 95113835 2 ~ 7 6 3 3 4 PCT/US93J11071 20% of cement by weight) and bone growth proteins lup to 10% of cement by weight) are the preferred drugs to be released by the cement of this invention .
The strength as well as the setting time of the present cements are directly dependent on the nature and particle size of the calcium alkali phr~ :~phdLt: ceramics, the nature of the filler powder, the type and amount of the setting reagent, and the solid powder to liquid ratio. In ~eneral, with other factors constant, the strength increases as the particle size of the powder de~ .35~. The setting time increases as the cementing powder to setting reagent weight ratio dec,t:ases.
The cement can be molded to any shape before use. For example, when used as a drug delivery system, the required amount of the drug is mixed with the cementing powder and setting reagent to form paste first.
After setting, the hardened cement may be broken into a suitabiy sized granules. This drug containing cement is then dried and stored before use.
For more convenient ~ Lions at the surgical site, the cement can then be prepared as a paste first. The paste can be introduced into the bone defects or illl,UldllldLiOIl site before it becomes hardened.
This invention may be prepared as a kit, c~" ,pris;"9 a selected cementing powder and setting reagent which when admixed with aqueous solution will form a paste. This paste will harden in a short time and will reach a pH near 7 or higher.
Pure CaNaP04 (calcium sodium phosphate) ceramic was prepared by W095113835 ,` t i ~ 2 ~ 76334 pCT/US93/11071 solid state reaction at hi~qh temperature. S~uiCI~iu~lcLli~, amounts of CaHPO4 snd Na2CO3 c~ ~ ci~uor ' 19 to the formation of CaNaPO4 were h~",oueneously mixed. The mixed powder was then sintered at high temperature to form CaNaPO4 ceramic. The ceramic was then ground to 5 fine powder. 2 9 of the CaNaPO~ powder was mixed with 0.8 9 of solid citric acid. A few drops of pure water was then added to form a sticky paste. After mixing, the paste set within several minutes. Shortly after setting, the surface pH of the set cement was tested with pH indicator paper. Initially, the surface pH was near 5; it reached 7 or higher in less 10 than a half hour. The hardened cement aged in pure water did not show any sign of d;~ cgldliu,~.
2 9 of CaNaPO4 fine ceramic powder prepared from Example 1 was premixed with J.3 9 of citric acid and 0.3 9 of trisodium citrate. The premixed powder was then mixed with few drops of pure water to form a h~",o~el~eous priste. This paste set in a few minutes. After setting, the initial surface pH was near 6 and reached 7 or higher in less than half hour.
CaNaPO4 mixed ceramics haYing an overall chemical co,,lpoi,iLiùn of 2.7 CaO-0.3 Na,O-P205 were prepared by solid state reaction at high temperatures. Required amounts of CaHPO4, Na2CO3 and CaCO3 were mixed l1o",o~el1eously and sintered. After sintering, the prepared mixed 25 ceramics were ~ round to fine powder, and 2 9 of the prepared ceramics 2 ~ 76334 ~WO 95/13835 ~ . PCT/US93/1 1071 powder was mixed with 0.6 ~ of anhydrous citric acid. This mixed powder was then mixed with few drops of 10% saline water. The paste hardened within five minutes. The set cement had a surface pH near 5. The surface pH reached to near 7 within less than half hour after setting.
CaNaPO4 pure ceramic was prepared by solid reaction at high temperatures. Required amounts of (NH4)zHPO4, Na2CO3 and CaC03 were mixed h~",oç,elleously and sintered. The sintered ceramic has the same 10 x-ray pattern as those prepared from Example 1. The sintered solid was then ground to fine powder. 1.5 9 of anhydrous citric acid and 1.5 9 of trisodium citrate was dissolved in 5 ml of pure water to form the settinQ
solution. 1 9 of prepared CaNaPO4 ceramic powder was mixed with 1 9 of anhydrous calcium sulfate. This mixed powder was then mixed with a few 15 drops of the setting solution to form a paste which set in a few minutes.
The surface pH was near 6 at the beginning, and increased to 7 or higher within a half hour after setting. No signs of surface disintegration were slnown after soaking the set cement in pure water.
Mixed ceramics of CaNaPO4 with the chemical C~ .osiliu" of 1.2 CaO-1.8 Na20-P205 were prepared by solid state reaction at hi~h temperatures. Required amounts of (NH,)2HPO4, CaC03 and Na2CO3 co"~:~pond;.,g to the above chemical culll~Josilion were mixed 25 homogeneously and sintered. The sintered ceramic was then ground to fine wo ss/l383s - 1 2 -powder. This pre ~ared ceramic has high alkalinity and dissolves much faster than other calcium ceramics. 2 9 of the above prepared ceramic fine powder was mixed with 0.4 9 of anhydrous citric acid and 0.4 9 of trisodium citrate. This mixed powder was then mixed with few drops of pure water to form a paste. The surface pH of the set cement was near 7.
Examples 1-5 use calcium and sodium phG~JhaLt: ceramics but calcium potassium phosphdL~ ceramics can be used i~L~ l,d"~ably with the calcium sodium pho:"~haL~ ceramics and thus also react with citric acid or acidic citrate salts to form b;oco",~.dLiLI~ and ,~:so,Lable cements. It 10 should be understood that the foregoing disclosure emphasizes certain ~",~o~i."e"L~ of the invention and that all Illo~i~i. dLiolls or alternatives thereto are within the spirit and scope of the invention.
~W09S/13835 PCT/US93111071 instead of usin~ pure citric acid as the setting rea~cnt. Amon~ the suitable hydrogen citrate salts are: sodium dihydrogen citrate, disodium hydrogen citrate, ammonium dihydrogen citrate, .lic,,,,,,,ol, lrn hydrogen citrate, potassium dihydrogen citrate and dipotassium hydrogen citrate. The pH
5 may also be raised by using citric acid with alkaline reagents. Suitable alkaline reagents include NaOH, KOH, KH40H, sodium citrate, potassium citrate, ammonium citrate, sodium pl~G:"JhclLt:, disodium hydrogen phosphate, potassium phosphate, and dipotassium hydrogen pllospl~
While the pH of concehL,c,~ed pure citric acid is normally at 2, the pH
10 modified setting reagent should provide an initial solution pH which is much hi~her than the pure citric acid, reaching a pH of 3 to 5. Therefore, after setting, the surface pH of the setting cement will initially be near 5 and quickly reach 7 or higher upon hardening.
The surgical cement of this invention relates to a flexible CG"~pOSi~ion 15 by changin~ the CaO:Na20 or CaO:K20 mole ratios in the calcium alkali pllo~ e ceramics. The dissolution rate as well as the bio,~o,yliun rate of the cement changes accordingly. The overall chemical CGIllpO~ilioll of these ceramics can be changed from 2.9 CaO-0.1 Na20-P205 to 0.8 CaO-2.2 Na20-P205. The calcium potassium pllG ~,uh~ ceramics can be varied 20 in composition in the same manner. While these mixed ceramics cover a wide variety of chemical c~",posi~ions and a wide range of dissolution rates, in general, the dicsQl~ltion rates increase by increasing the alkali element content. As a result, the ~ nici~" can achieve greater bio,~iG" ~iol- rate control with the mixed ceramics than with the pure single component 25 calcium phOa~Jhell~ cements.
WO95/13835 ~ ' ~ 2 ~ PCT/US93/11071 Further control of the L~ 50r,u~ioll rate in this invention is achieved by incorporating a biocol~,uaL~ e filler material in the form of fine powder or granule, havin~ a particle size rangin~q from a few microns to 20 mesh. Filler material must be bioco,,,,udLiL,l~ without Si~lliri~.alllly effectin~ the integrity 5 and settin~q behavior of the cement. Fillers useful for this purpose include tetracalcium pl~:"JhaL~, tricalcium pllG:",h~Le, calcium phosphal~ apatite, dicalcium pl~GS~JhdL~, calcium carbonate, calcium sulfate dehydrate, calcium sulfate hemihydrate, calcium sulfate anhydrous, calcium fluoride, calcium oxide, calcium hyoroxide, calcium citrate, magnesium hydroxide, ma~nesium 10 oxide, collagen and other sparingly calcium organic salts. The wei~qht ratio of filler to calcium alkali pl~o~ laL~ c~",~,llil,g powder can be up to 5:1.
In the present invention the c~",t:"~i"g powder was premixed with filler material to form a homo~eneous mixed powder. The settin~q reaction can be initiated e ther by dissolving the setting reagent and pH adjustment 15 reagents in water or saline water to form an aqueous settin~q solution and.
adding it to the Fremixed powder, or premixing the solid setting reagents with the c~",e"Li"g powder and using sterili~ed pure water or saline water as the setting aqueous solution.
The cements of the present invention may be used as implant 20 materials for: (1) ~one grafts as filler or It:pld~,~rll~llL of bone that has been removed surgically or traumatically; (2) rid9e au~ w~ ~LdLi~ns~ (3) jaw repairs:
(4) cranial and " . " ~d~ial surgeries; (5) luting cement in dentistry and orthopedic surgery; (6) spinal fusions; (7) endodontic ',F': Lions, (8) root cements; (9) repl3cing or plullluLillg ,~gen~ldLiun of bone mineral lost due 25 to pe~iodo,lLdl disease; and (10) drug release systems. Antibiotics (up to wo 95113835 2 ~ 7 6 3 3 4 PCT/US93J11071 20% of cement by weight) and bone growth proteins lup to 10% of cement by weight) are the preferred drugs to be released by the cement of this invention .
The strength as well as the setting time of the present cements are directly dependent on the nature and particle size of the calcium alkali phr~ :~phdLt: ceramics, the nature of the filler powder, the type and amount of the setting reagent, and the solid powder to liquid ratio. In ~eneral, with other factors constant, the strength increases as the particle size of the powder de~ .35~. The setting time increases as the cementing powder to setting reagent weight ratio dec,t:ases.
The cement can be molded to any shape before use. For example, when used as a drug delivery system, the required amount of the drug is mixed with the cementing powder and setting reagent to form paste first.
After setting, the hardened cement may be broken into a suitabiy sized granules. This drug containing cement is then dried and stored before use.
For more convenient ~ Lions at the surgical site, the cement can then be prepared as a paste first. The paste can be introduced into the bone defects or illl,UldllldLiOIl site before it becomes hardened.
This invention may be prepared as a kit, c~" ,pris;"9 a selected cementing powder and setting reagent which when admixed with aqueous solution will form a paste. This paste will harden in a short time and will reach a pH near 7 or higher.
Pure CaNaP04 (calcium sodium phosphate) ceramic was prepared by W095113835 ,` t i ~ 2 ~ 76334 pCT/US93/11071 solid state reaction at hi~qh temperature. S~uiCI~iu~lcLli~, amounts of CaHPO4 snd Na2CO3 c~ ~ ci~uor ' 19 to the formation of CaNaPO4 were h~",oueneously mixed. The mixed powder was then sintered at high temperature to form CaNaPO4 ceramic. The ceramic was then ground to 5 fine powder. 2 9 of the CaNaPO~ powder was mixed with 0.8 9 of solid citric acid. A few drops of pure water was then added to form a sticky paste. After mixing, the paste set within several minutes. Shortly after setting, the surface pH of the set cement was tested with pH indicator paper. Initially, the surface pH was near 5; it reached 7 or higher in less 10 than a half hour. The hardened cement aged in pure water did not show any sign of d;~ cgldliu,~.
2 9 of CaNaPO4 fine ceramic powder prepared from Example 1 was premixed with J.3 9 of citric acid and 0.3 9 of trisodium citrate. The premixed powder was then mixed with few drops of pure water to form a h~",o~el~eous priste. This paste set in a few minutes. After setting, the initial surface pH was near 6 and reached 7 or higher in less than half hour.
CaNaPO4 mixed ceramics haYing an overall chemical co,,lpoi,iLiùn of 2.7 CaO-0.3 Na,O-P205 were prepared by solid state reaction at high temperatures. Required amounts of CaHPO4, Na2CO3 and CaCO3 were mixed l1o",o~el1eously and sintered. After sintering, the prepared mixed 25 ceramics were ~ round to fine powder, and 2 9 of the prepared ceramics 2 ~ 76334 ~WO 95/13835 ~ . PCT/US93/1 1071 powder was mixed with 0.6 ~ of anhydrous citric acid. This mixed powder was then mixed with few drops of 10% saline water. The paste hardened within five minutes. The set cement had a surface pH near 5. The surface pH reached to near 7 within less than half hour after setting.
CaNaPO4 pure ceramic was prepared by solid reaction at high temperatures. Required amounts of (NH4)zHPO4, Na2CO3 and CaC03 were mixed h~",oç,elleously and sintered. The sintered ceramic has the same 10 x-ray pattern as those prepared from Example 1. The sintered solid was then ground to fine powder. 1.5 9 of anhydrous citric acid and 1.5 9 of trisodium citrate was dissolved in 5 ml of pure water to form the settinQ
solution. 1 9 of prepared CaNaPO4 ceramic powder was mixed with 1 9 of anhydrous calcium sulfate. This mixed powder was then mixed with a few 15 drops of the setting solution to form a paste which set in a few minutes.
The surface pH was near 6 at the beginning, and increased to 7 or higher within a half hour after setting. No signs of surface disintegration were slnown after soaking the set cement in pure water.
Mixed ceramics of CaNaPO4 with the chemical C~ .osiliu" of 1.2 CaO-1.8 Na20-P205 were prepared by solid state reaction at hi~h temperatures. Required amounts of (NH,)2HPO4, CaC03 and Na2CO3 co"~:~pond;.,g to the above chemical culll~Josilion were mixed 25 homogeneously and sintered. The sintered ceramic was then ground to fine wo ss/l383s - 1 2 -powder. This pre ~ared ceramic has high alkalinity and dissolves much faster than other calcium ceramics. 2 9 of the above prepared ceramic fine powder was mixed with 0.4 9 of anhydrous citric acid and 0.4 9 of trisodium citrate. This mixed powder was then mixed with few drops of pure water to form a paste. The surface pH of the set cement was near 7.
Examples 1-5 use calcium and sodium phG~JhaLt: ceramics but calcium potassium phosphdL~ ceramics can be used i~L~ l,d"~ably with the calcium sodium pho:"~haL~ ceramics and thus also react with citric acid or acidic citrate salts to form b;oco",~.dLiLI~ and ,~:so,Lable cements. It 10 should be understood that the foregoing disclosure emphasizes certain ~",~o~i."e"L~ of the invention and that all Illo~i~i. dLiolls or alternatives thereto are within the spirit and scope of the invention.
Claims (20)
1. A surgical cement for orthopedic, dental, and maxillofacial applications comprising:
a cementing powder selected from the group of calcium alkali phosphate ceramics consisting of calcium sodium phosphate or calcium potassium phosphate ceramics;
a setting reagent selected from the group of acidic citrates consisting of citric acid or acidic citrate salts wherein the weight ratio of cementing powder to setting reagent lies between 1.2:1 and 10:1, and sufficient aqueous setting solution selected from the group consisting of sterilized pure water and saline water to form a cementitious paste, said paste reaching a neutral pH of 7 shortly after setting.
a cementing powder selected from the group of calcium alkali phosphate ceramics consisting of calcium sodium phosphate or calcium potassium phosphate ceramics;
a setting reagent selected from the group of acidic citrates consisting of citric acid or acidic citrate salts wherein the weight ratio of cementing powder to setting reagent lies between 1.2:1 and 10:1, and sufficient aqueous setting solution selected from the group consisting of sterilized pure water and saline water to form a cementitious paste, said paste reaching a neutral pH of 7 shortly after setting.
2. The surgical cement of claim 1 wherein the cementing powder is selected from the group consisting of CaNaPO4 or Ca5Na2(PO4)4.
3. The surgical cement of claim 1 wherein the cementing powder selected from the group of calcium alkali phosphate ceramics consists of mixed ceramics as a crystalline solution containing Ca3(PO4)2, CaNaPO4 and Ca5Na2(PO4)4, and has an overall chemical composition ranging from 2.9 CaO0.1 Na2O-P2O6 to 2.0 CaONa2P2O5 prepared from solid state reaction at high temperatures.
4. The surgical cement of claim 1 wherein the calcium alkali phosphate ceramic further comprises mixed ceramics of CaNaPO4 and Na3PO4 having an overall chemical composition ranging from 2.0 CaONa2OP2O5 to 0.8 CaO-2.2 Na2OP2O5 prepared from solid state reaction at high temperatures.
5. The surgical cement of claim 1 wherein the calcium alkali phosphate ceramic comprises CaKPO4.
6. The surgical cement of claim 1 wherein the calcium alkali phosphate ceramic is a mixed ceramic as a crystalline solution of Ca3(PO4)2 and CaKPO4, and has an overall chemical composition ranging from 2.9 CaOO.1 K2OP2O6 to 2.0 CaO1.0 K2OP2O5 prepared from solid state reaction at high temperatures.
7. The surgical cement of claim 1 wherein the calcium alkali phosphate ceramic further comprises a mixed ceramic of CaKPO4 and K3PO4 having an overall chemical composition ranging from 2.0 CaOK2OP2O5 to 0.8 CaO2.2 K2OP2O5 prepared from solid state reaction at high temperatures.
8. The surgical cement of claim 1 wherein the setting reagent selected from the group of acidic citrates comprises citric acid and at least one of the following citrate compounds: NaH2 citrate, Na2H citrate, KH2 citrate, K2H citrate, NH4H2 citrate, and (NH4)2H citrate.
9. The surgical cement of claim 1 further including a soluble pH
adjusting reagent.
adjusting reagent.
10. The surgical cement of claim 9 wherein said soluble pH
adjusting reagents are selected from the group consisting of: NaOH, KOH, NH4OH, Na3 citrate, K3 citrate, (NH4)3 citrate, Na3PO4, Na2HPO, K3PO4, or K2HPO4.
adjusting reagents are selected from the group consisting of: NaOH, KOH, NH4OH, Na3 citrate, K3 citrate, (NH4)3 citrate, Na3PO4, Na2HPO, K3PO4, or K2HPO4.
11. The surgical cement of claim 9 wherein said soluble pH
adjusting reagent is premixed with said cementing powder and said setting reagent.
adjusting reagent is premixed with said cementing powder and said setting reagent.
12. The surgical cement of claim 9 wherein said soluble pH
adjusting reagent is dissolved in said aqueous setting solution.
adjusting reagent is dissolved in said aqueous setting solution.
13. The surgical cement of claim 1 wherein the cementing powder further comprises up to approximately 5:1 by weight of filler to cementing powder.
14. The surgical cement of claim 13 wherein the filler is selected from the group consisting of tetracalcium phosphate, a-tricalcium phosphate, .beta.-tricalcium phosphate, calcium phosphate apatite, octacalcium phosphate, dicalcium phosphate, calcium carbonate, calcium oxide, calcium hydroxide, calcium sulfate dihydrate, calcium sulfate hemihydrate, calcium sulfate anhydrous, calcium fluoride, calcium citrate, magnesium oxide, magnesium hydroxide, and collagen.
15. The surgical cement of claim 13 wherein said filler is a powder of granule form having a particle size ranging from 1 micron to 20 mesh.
16. The surgical cement of claim 1 further comprising up to approximately 20% of an antibiotic.
17. The surgical cement of claim 1 further comprising up to approximately 10% bone growth protein.
18. A process for forming the surgical cement of claim 1 in which the setting reagent and pH adjusting reagents are dissolved in aqueous solution consisting of water or saline water to form an aqueous setting solution prior to intermixing with the cementing powder to form a paste capable of hardening into a cement.
19. A process for forming the surgical cement of claim 1 in which the setting reagent and pH adjusting reagents are premixed with the cementing powder prior to its intermixture with the aqueous solution consisting of water or saline water to form a paste capable of hardening into a cement.
20. A kit for making a surgical cement for orthopedic, dental, and maxillofacial applications comprising:
a cementing powder consisting of calcium alkali phosphate ceramics; and a setting reagent;
said cementing powder and said setting reagent, when admixed with sufficient aqueous solution forms a cementitious paste, which after setting, will attain a pH of at least 7.
a cementing powder consisting of calcium alkali phosphate ceramics; and a setting reagent;
said cementing powder and said setting reagent, when admixed with sufficient aqueous solution forms a cementitious paste, which after setting, will attain a pH of at least 7.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002176334A CA2176334A1 (en) | 1993-11-15 | 1993-11-15 | Resorbable bioactive phosphate containing cements |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002176334A CA2176334A1 (en) | 1993-11-15 | 1993-11-15 | Resorbable bioactive phosphate containing cements |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2176334A1 true CA2176334A1 (en) | 1995-05-26 |
Family
ID=4158181
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002176334A Abandoned CA2176334A1 (en) | 1993-11-15 | 1993-11-15 | Resorbable bioactive phosphate containing cements |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2176334A1 (en) |
-
1993
- 1993-11-15 CA CA002176334A patent/CA2176334A1/en not_active Abandoned
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Effective date: 20031117 |