CA2082632A1 - Rapid setting hydroxylapatite and plaster formulation - Google Patents
Rapid setting hydroxylapatite and plaster formulationInfo
- Publication number
- CA2082632A1 CA2082632A1 CA002082632A CA2082632A CA2082632A1 CA 2082632 A1 CA2082632 A1 CA 2082632A1 CA 002082632 A CA002082632 A CA 002082632A CA 2082632 A CA2082632 A CA 2082632A CA 2082632 A1 CA2082632 A1 CA 2082632A1
- Authority
- CA
- Canada
- Prior art keywords
- composition
- weight
- calcium sulfate
- blood
- hydroxylapatite
- 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
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/02—Inorganic materials
- A61L27/12—Phosphorus-containing materials, e.g. apatite
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/28—Bones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00005—The prosthesis being constructed from a particular material
- A61F2310/00179—Ceramics or ceramic-like structures
- A61F2310/00293—Ceramics or ceramic-like structures containing a phosphorus-containing compound, e.g. apatite
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Cardiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Inorganic Chemistry (AREA)
- Vascular Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Dental Preparations (AREA)
- Materials For Medical Uses (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Compositions for use in bone implantation, repair and reconstruction comprising calcium sulfate hemihydrate, hydroxylapatite and sodium sulfate. The sodium sulfate enables the composition to be used in the presence of blood or other body fluids.
Description
2 P~T/US91/0320~
-~ 2~2~3~, RAPID SETTING HYDROXYLAPATITE AND PLAS~ER FORMULATION
'~ l. Field of the Invention This invention relates to ~ormulations useful `1 in bone and dental implant, repair and reconstruc~ion, ,'', The formulations include mixtures of calcium sulfate ,,, '~ hemihydrate, hydroxylapatite and sodium sul~ate. The sodium sulfate has been ~ound to greatly,accelerate the ' ' hardening of,the mixture in the presence o~ blood.
', , 2. Description of the ~elated Art , U. S. Patent 4,61~,655 discloses animal ,', implants comprising a binder lattice or scaffold of ~, calcium hemihydrate (plaster of paris) and a non~
' bioresorbable calcium material such as hydroxylapatite.
i In U.S. Patent 4,681,644 calcium sulfate hemihydrate is described as hardening in water in about thirty ~30) ~, minutes.
, -;""
i Calcium sulfate hemihydrate tplaster of ,~
;1 Paris) has been known for years to have excellent ;'~
M reparative qualities in bone defects, but ordinarily '~
' it is quickly resorbed. A composite of a 25 dense form of plaster of Paris ,and ,~
~ hydroxylapatite provides nonresorbable .'1 hydroxylapatite particles for bone to form around ~-, and within during the phase of plaster absorptlon.
'~ 30 - 'It is known that calcium sulfate hemihydrate ~.
compositions set poorly in the presence of blood and other-proteinaceous body fluids. Outside of the'body, ' many chemical additives may be used to deliberately ~'~ ~ , ~ i . ' ' ' ': : , `3 ~`
". : ~
'`l - :
WO91~17722 PCT/US~1/03208 2 ~ '.3 ~ -. , .
, .
accelerate or retard setting. In the body, however, body fluids contribute chemicals which upset the delicate balance between retardation and acceleration of plaster setting.
, !
As the dihydrate forms, the concentration of chemicals such as sodium chloride increases. This causes the remaining watar to be supersaturated. Salt crystal formation on the nuclei oP crystallization of ; lO the gypsum "poisons" the nuclei. This retards further - crystallization, upsetting the delicate balance.
:, ~
Thus, although some compounds are listed as known accelerators, in the body they may act as set ` ~ 15 re~ardants. Ona of *he inventors of U.S. Patent :~
4,6l9,655 has published a paper which states that set retardation in blood may be controlled by the addition .1 of lO~ potassium sulfate or 16.7~ sodium chloride. ~ -These high concentrations may cause salt crystal . `.
;1 20 formation due to the increased potassium ion levels.
iJ ~ Additionally, the concentrations employed may be harmful to the body. The sterilized gypsum-accelerated product is not ~ully acceptable because the shelf-live is only eight months due to pre-implantation characteristics. Also, since gypsum is not water soluble, the gypsum must be mixed into the dry powders. ,~
Since very little gypsum is needed, it is difficult to assure a uniform and homogeneous mixture with gypsum.
30 .i - The art described in this-section is not intended to constitute-an admission that any patent, ~`, pubIication or other information referred to herein is ~, ~ ; "prior art" with respect to this invention, unless ';
i . ~ I
"
'.: ''' ' I .:",.
~ WO9l/17722 P~r/US9l/03208 20~2~32 -3~
speclfically designated as such. In addition, this section should not be construed to mean that a search has been made or that no other pertinent informatlon as defined in 37 C.F~R. 1.56(a~ exists.
SummarY of the Invention ., The invention provides a composition useful in dental, orthopedic and neurological procedures }0 involving bone implant, repair or reconstruction. The composition includes calcium sulfate hemihydrate (plaster of paris), hydroxylapatite and sodium sulfate ~ to accelerate and control the setting.
i "Hydroxylapatite" as used herein may include variations of resorbable and non-resorbable calcium phosphates, including the resorbable trichloryl phosphate form.
The sodium sulfate provides superior accelera~ion in I the presence of blood. It is employed in the range of -~
`l 1.5 to 4 % by dry weight based on the weight of calcium sulfate hemihydrate.
Screening studies were undertaken to seek an I accelerant that would be stable in the presence of ;~ blood. Potassium oxalate and sodium heparin blood i 25 tubes were found to be useful. It was found that sodium citrate and EDTA acted as a setting retardant.
Calcium hydroxide and deionized water did not function as an accelerant in the presence of ~lood. Ferrous ~ -j sulfate provided acceleration but has an inadequate ;t 30 shelflife. - - - ` -j , , Potassium sulfate at 0.85~ by weight of the l ~ calcium sulfate hemihydrate provided acceleration.
.1, ~':
`'1 . . ~ ... .... , . ~
WO91/17722 PCT/US91/03208 ~
2 ~ ~ 2 ~ 3 2 -HA alone is not readily used in orthopedic applications because it does not maintain a cohesive mass during delivery and placement in the implant site.
Calcium sulfate hemihydrate (plaster of paris) is used 5 in conjunction with HA to produce a more d~liverable ~
and implantable composition which minimizes migration ~-o~ particles from the site to an undesired location.
'~
Calcium sulfate hemihydrate hardens into a dihydrate form known as qypsum. Gypsum is cumpletely resorbed from the site in the body in about four to six weeks. HA is preferably used in about a 65% to 35%
calcium sulfate hemihydrate mixture to provide enough plaster to fill the gaps between the HA particles. -~-Higher plaster levels results in loss o~ implant volume during plaster resorption. Lower plaster levels result in a less cohesive mass of particles for delivery.
Again, resorbable or non-resorba~le forms of calcium phosphates may be employed in this invention.
` "Set" is the crystallization of calcium sulfate dihydrate (gypsum) ~rom calcium sulfate hemihydrate;in the presence of~water. t'Hardening" is a mèasure of compressive strength development in calcium sulfate hemihydrate as set occurs. It is dependent on the chemical crystallization "set" process. Hardening may be~gauged by a Vicat set test, ASTM C-472.
EASE OF USE
~ Following combination of the~dry ingredients and water, the components must be thoroughly mixable within about ~hirty seconds, and transferrable to the defect site within one minute.
~,''~ :
~: :
".~," ",." ., ~"",,~ , ,",~
WO91/17722 PCT/~S9J/03208 3~
-6- :
. POT LIFE
; . The ~o~mulati~n should provide a working ~ime of.be~ween two and five minutes. This ~s defined as the length of time that the product remains moldable and thus implantable in a defect site.
MOLDABILITY
The product must be able to be molded down and packed into an implant site, such that the void is completely filled. The material should not fall out of the site due to the effects of gravity. ~ :
SETTING TIME IN SITE
In order to achieve the control of particle migration, the product must lose its.moldability in the site within about ten minutes of placement. In .
addition, it must harden within about one hour o~
placement.
EXAMPLE .
Hydroxylapatite/calcium sulfate hemih~drate-compositions were prepared in a 65:35 ràtio by weight :~
and were wetted with o.g~ saline solution. The :~
material immediately softened upo~ implantati.on.and did not harden within the desired time li.mit. It appeared ; as though the plaster portion was dissolving in contact with the blood. "Tamping" of the mixture into the site .~
only resulted in ~urther flowage of HA particles from ,. ~`
the site. LiXewise, the material could not be wiped up .
: 30 with a swab, which:instead drew the plaster-portion ùp ~;;`
fuxther. The nearly:set (hardened) mixture.softened' '~
immediately-even in contact.with minimal blood..
, ~
, ~
~ :, - ~
W091/17722 PCr/US91/03208 --.
~a~ 3~ :
POT LIFE
The formulation should provide a working time of between two and five minutes. This is defined as , the length of time that the product remains moldable 5 and thus implantable in a defect site. ~
MOLDABILITY ~, , The product must be able to be molded down and packed into an implant site, such that the void is completely filled. The material should not fall out of the ~ite due to the effects of gravity.
:' -SETTING TIME IN SITE
In order to achieve the controi of particle migration, the product must lose its moldability in the site within about ten minutes of placement. In addition, it must harden within about one hour o~
placement. ~
2 0 EXAMPLE ~ ; . n Hydroxylapatite/calcium sulfate hemih~drate compositions were prepared in a 65:35 ratio by weight ~
and were wetted with 0.9% saline solution. The , material immediately so~tened upon implantation and did not h~rden within the desired time limit. It appeared as though the plaster portion was dissolving in contact with the blood. "Tamping" of the mixture into the site only resulted in further flowage of HA particles from ," ,~
the site. Likewise, the material could not be wiped up 30 with a swab,,which instead drew the plaster-portion up ;, `
further. The nearly set (hardened) mixture softened~
,immediately even in contact with minimal blood. ~-~. . .~ .
`.'.'`~,'.'.,','''.,'',',;,'',`''''''.' ;.' ,;, ,, .,.. ,.. ........... . . . . -. -- ~
2 ~ 2 ' ' ' , ~7~
EXAMPLE II
Hydroxylapatite/calcium sul~ate hemihydrate compositions were prepared in a 65:35 ratio by weight and were wetted with O.9% saline solution. Sodium sulfate was added by weight percent by weight of calcium sulfate hemihydrate.
Sodium sulfate accelerated compositions provided better set times in blood than the use of potassium sulfate. It could be uniformly supplied to the original powder unlike the addition of gypsum as an accelerant. The following table compares sodium sulfate to potassium sulfate as an accelerant.
_ . . ,:: :
15 J Minutes Potassium Sulfate Sodium Sulfate ~-Potlife ¦ < 2 2 < x < 4 ~
, Set Time 1 > 45 4 < x < 45 (in blood) l , The following table shows the set time and potlife o~ compositions using varying levels of sodium `;
sulfate. As shown, sodium sulfate levels of less than about l.5~ or greater than about 4.0% have potlives which are no~ desirable.
':
.
. " ' ' ' .j ' ' ~ '' ~
:, ,', ,: -:. '' ' ' ' , , ' ' , ~ ~
WO91/17722 PCr/US91/03208 . . , . --Sodium Sulfate Potlife 1 Blood Set Time (Dry~ (minutes) 1 (minut~s) -_ . _ .
9.25 > 45 I ._ . .__ _ 1 105 _ 1-75 30 2.4 2.25 30 . .
~ 3.4 3.030 < x < 45 I . . _. ... . . _ --4.0 5.0 30*
~ Se~ #ith t~ ë e~ception of nr~ns ~here~~i Id had poo~ed 1 0 , Further studies with the 2.4% and 3.4% -~
formulas showed that blood set times are dependent on the consistency of the material when it is added to the blood, the harder the better. The extent to which the 15 material was mi~ed with the blood also affected the end -~
result. It has been found that the inclusion of sodium sulfate in the range of l.5 to about 4.0 % by weight based on weight of calcium sulfate hemihydrate will provide a superior product. The compositions of the 20 invention main~ain their cohesiveness in blood better `~
than previous formulations.
''~ '' Presently, the preferred level of sodium sulfate is between about 2.35 and about 2.45~ by weight per calcium sulfate hemihydrate by weight for dry sodium sulfate. However, when sodium sulfate is added as a solution, the preferred range increases to as much as 3.5~.
.:
While this invention may be embodied in many ~
different forms, there are shown in the drawings and ~ -- ~ ~. - .: . .: . :,... ... . . , : - -.: : : .:: - :: .. : : : : . - . : - - . ~ . - - .-. . : .. . . - -' ' ... . ' ' ; ' ~ ;................ '!. . , . ; ', ' , ' . ' ' '`' ' " ' .' ' .. '' : '"'' ' i'.: ' . ... . ' i': '.1..... .
2~82~32 _9_ describad in detail herein specific preferred embodiments of the invention. The present disclosure is an exemplification o~ the principles of the invention and is not intended to limit the invention to ~ -~
the particular embodiments illustrated.
This completes the des~ription of the pre~erred and alternate embodiments of the invention.
Those skilled in the art may recognize other equivalents to the specific embodiment described herein which equivalents are intended to be encompassed by the claims attached hereto.
,. ..
~.~. ....
,, '; ~
: ~. :
: ''' .` ':
~ ~. '' ;:' ,: ' :
, ~:
.
.. .. ~ ~.
'~ ~
,~,: ,',,~',-,
-~ 2~2~3~, RAPID SETTING HYDROXYLAPATITE AND PLAS~ER FORMULATION
'~ l. Field of the Invention This invention relates to ~ormulations useful `1 in bone and dental implant, repair and reconstruc~ion, ,'', The formulations include mixtures of calcium sulfate ,,, '~ hemihydrate, hydroxylapatite and sodium sul~ate. The sodium sulfate has been ~ound to greatly,accelerate the ' ' hardening of,the mixture in the presence o~ blood.
', , 2. Description of the ~elated Art , U. S. Patent 4,61~,655 discloses animal ,', implants comprising a binder lattice or scaffold of ~, calcium hemihydrate (plaster of paris) and a non~
' bioresorbable calcium material such as hydroxylapatite.
i In U.S. Patent 4,681,644 calcium sulfate hemihydrate is described as hardening in water in about thirty ~30) ~, minutes.
, -;""
i Calcium sulfate hemihydrate tplaster of ,~
;1 Paris) has been known for years to have excellent ;'~
M reparative qualities in bone defects, but ordinarily '~
' it is quickly resorbed. A composite of a 25 dense form of plaster of Paris ,and ,~
~ hydroxylapatite provides nonresorbable .'1 hydroxylapatite particles for bone to form around ~-, and within during the phase of plaster absorptlon.
'~ 30 - 'It is known that calcium sulfate hemihydrate ~.
compositions set poorly in the presence of blood and other-proteinaceous body fluids. Outside of the'body, ' many chemical additives may be used to deliberately ~'~ ~ , ~ i . ' ' ' ': : , `3 ~`
". : ~
'`l - :
WO91~17722 PCT/US~1/03208 2 ~ '.3 ~ -. , .
, .
accelerate or retard setting. In the body, however, body fluids contribute chemicals which upset the delicate balance between retardation and acceleration of plaster setting.
, !
As the dihydrate forms, the concentration of chemicals such as sodium chloride increases. This causes the remaining watar to be supersaturated. Salt crystal formation on the nuclei oP crystallization of ; lO the gypsum "poisons" the nuclei. This retards further - crystallization, upsetting the delicate balance.
:, ~
Thus, although some compounds are listed as known accelerators, in the body they may act as set ` ~ 15 re~ardants. Ona of *he inventors of U.S. Patent :~
4,6l9,655 has published a paper which states that set retardation in blood may be controlled by the addition .1 of lO~ potassium sulfate or 16.7~ sodium chloride. ~ -These high concentrations may cause salt crystal . `.
;1 20 formation due to the increased potassium ion levels.
iJ ~ Additionally, the concentrations employed may be harmful to the body. The sterilized gypsum-accelerated product is not ~ully acceptable because the shelf-live is only eight months due to pre-implantation characteristics. Also, since gypsum is not water soluble, the gypsum must be mixed into the dry powders. ,~
Since very little gypsum is needed, it is difficult to assure a uniform and homogeneous mixture with gypsum.
30 .i - The art described in this-section is not intended to constitute-an admission that any patent, ~`, pubIication or other information referred to herein is ~, ~ ; "prior art" with respect to this invention, unless ';
i . ~ I
"
'.: ''' ' I .:",.
~ WO9l/17722 P~r/US9l/03208 20~2~32 -3~
speclfically designated as such. In addition, this section should not be construed to mean that a search has been made or that no other pertinent informatlon as defined in 37 C.F~R. 1.56(a~ exists.
SummarY of the Invention ., The invention provides a composition useful in dental, orthopedic and neurological procedures }0 involving bone implant, repair or reconstruction. The composition includes calcium sulfate hemihydrate (plaster of paris), hydroxylapatite and sodium sulfate ~ to accelerate and control the setting.
i "Hydroxylapatite" as used herein may include variations of resorbable and non-resorbable calcium phosphates, including the resorbable trichloryl phosphate form.
The sodium sulfate provides superior accelera~ion in I the presence of blood. It is employed in the range of -~
`l 1.5 to 4 % by dry weight based on the weight of calcium sulfate hemihydrate.
Screening studies were undertaken to seek an I accelerant that would be stable in the presence of ;~ blood. Potassium oxalate and sodium heparin blood i 25 tubes were found to be useful. It was found that sodium citrate and EDTA acted as a setting retardant.
Calcium hydroxide and deionized water did not function as an accelerant in the presence of ~lood. Ferrous ~ -j sulfate provided acceleration but has an inadequate ;t 30 shelflife. - - - ` -j , , Potassium sulfate at 0.85~ by weight of the l ~ calcium sulfate hemihydrate provided acceleration.
.1, ~':
`'1 . . ~ ... .... , . ~
WO91/17722 PCT/US91/03208 ~
2 ~ ~ 2 ~ 3 2 -HA alone is not readily used in orthopedic applications because it does not maintain a cohesive mass during delivery and placement in the implant site.
Calcium sulfate hemihydrate (plaster of paris) is used 5 in conjunction with HA to produce a more d~liverable ~
and implantable composition which minimizes migration ~-o~ particles from the site to an undesired location.
'~
Calcium sulfate hemihydrate hardens into a dihydrate form known as qypsum. Gypsum is cumpletely resorbed from the site in the body in about four to six weeks. HA is preferably used in about a 65% to 35%
calcium sulfate hemihydrate mixture to provide enough plaster to fill the gaps between the HA particles. -~-Higher plaster levels results in loss o~ implant volume during plaster resorption. Lower plaster levels result in a less cohesive mass of particles for delivery.
Again, resorbable or non-resorba~le forms of calcium phosphates may be employed in this invention.
` "Set" is the crystallization of calcium sulfate dihydrate (gypsum) ~rom calcium sulfate hemihydrate;in the presence of~water. t'Hardening" is a mèasure of compressive strength development in calcium sulfate hemihydrate as set occurs. It is dependent on the chemical crystallization "set" process. Hardening may be~gauged by a Vicat set test, ASTM C-472.
EASE OF USE
~ Following combination of the~dry ingredients and water, the components must be thoroughly mixable within about ~hirty seconds, and transferrable to the defect site within one minute.
~,''~ :
~: :
".~," ",." ., ~"",,~ , ,",~
WO91/17722 PCT/~S9J/03208 3~
-6- :
. POT LIFE
; . The ~o~mulati~n should provide a working ~ime of.be~ween two and five minutes. This ~s defined as the length of time that the product remains moldable and thus implantable in a defect site.
MOLDABILITY
The product must be able to be molded down and packed into an implant site, such that the void is completely filled. The material should not fall out of the site due to the effects of gravity. ~ :
SETTING TIME IN SITE
In order to achieve the control of particle migration, the product must lose its.moldability in the site within about ten minutes of placement. In .
addition, it must harden within about one hour o~
placement.
EXAMPLE .
Hydroxylapatite/calcium sulfate hemih~drate-compositions were prepared in a 65:35 ràtio by weight :~
and were wetted with o.g~ saline solution. The :~
material immediately softened upo~ implantati.on.and did not harden within the desired time li.mit. It appeared ; as though the plaster portion was dissolving in contact with the blood. "Tamping" of the mixture into the site .~
only resulted in ~urther flowage of HA particles from ,. ~`
the site. LiXewise, the material could not be wiped up .
: 30 with a swab, which:instead drew the plaster-portion ùp ~;;`
fuxther. The nearly:set (hardened) mixture.softened' '~
immediately-even in contact.with minimal blood..
, ~
, ~
~ :, - ~
W091/17722 PCr/US91/03208 --.
~a~ 3~ :
POT LIFE
The formulation should provide a working time of between two and five minutes. This is defined as , the length of time that the product remains moldable 5 and thus implantable in a defect site. ~
MOLDABILITY ~, , The product must be able to be molded down and packed into an implant site, such that the void is completely filled. The material should not fall out of the ~ite due to the effects of gravity.
:' -SETTING TIME IN SITE
In order to achieve the controi of particle migration, the product must lose its moldability in the site within about ten minutes of placement. In addition, it must harden within about one hour o~
placement. ~
2 0 EXAMPLE ~ ; . n Hydroxylapatite/calcium sulfate hemih~drate compositions were prepared in a 65:35 ratio by weight ~
and were wetted with 0.9% saline solution. The , material immediately so~tened upon implantation and did not h~rden within the desired time limit. It appeared as though the plaster portion was dissolving in contact with the blood. "Tamping" of the mixture into the site only resulted in further flowage of HA particles from ," ,~
the site. Likewise, the material could not be wiped up 30 with a swab,,which instead drew the plaster-portion up ;, `
further. The nearly set (hardened) mixture softened~
,immediately even in contact with minimal blood. ~-~. . .~ .
`.'.'`~,'.'.,','''.,'',',;,'',`''''''.' ;.' ,;, ,, .,.. ,.. ........... . . . . -. -- ~
2 ~ 2 ' ' ' , ~7~
EXAMPLE II
Hydroxylapatite/calcium sul~ate hemihydrate compositions were prepared in a 65:35 ratio by weight and were wetted with O.9% saline solution. Sodium sulfate was added by weight percent by weight of calcium sulfate hemihydrate.
Sodium sulfate accelerated compositions provided better set times in blood than the use of potassium sulfate. It could be uniformly supplied to the original powder unlike the addition of gypsum as an accelerant. The following table compares sodium sulfate to potassium sulfate as an accelerant.
_ . . ,:: :
15 J Minutes Potassium Sulfate Sodium Sulfate ~-Potlife ¦ < 2 2 < x < 4 ~
, Set Time 1 > 45 4 < x < 45 (in blood) l , The following table shows the set time and potlife o~ compositions using varying levels of sodium `;
sulfate. As shown, sodium sulfate levels of less than about l.5~ or greater than about 4.0% have potlives which are no~ desirable.
':
.
. " ' ' ' .j ' ' ~ '' ~
:, ,', ,: -:. '' ' ' ' , , ' ' , ~ ~
WO91/17722 PCr/US91/03208 . . , . --Sodium Sulfate Potlife 1 Blood Set Time (Dry~ (minutes) 1 (minut~s) -_ . _ .
9.25 > 45 I ._ . .__ _ 1 105 _ 1-75 30 2.4 2.25 30 . .
~ 3.4 3.030 < x < 45 I . . _. ... . . _ --4.0 5.0 30*
~ Se~ #ith t~ ë e~ception of nr~ns ~here~~i Id had poo~ed 1 0 , Further studies with the 2.4% and 3.4% -~
formulas showed that blood set times are dependent on the consistency of the material when it is added to the blood, the harder the better. The extent to which the 15 material was mi~ed with the blood also affected the end -~
result. It has been found that the inclusion of sodium sulfate in the range of l.5 to about 4.0 % by weight based on weight of calcium sulfate hemihydrate will provide a superior product. The compositions of the 20 invention main~ain their cohesiveness in blood better `~
than previous formulations.
''~ '' Presently, the preferred level of sodium sulfate is between about 2.35 and about 2.45~ by weight per calcium sulfate hemihydrate by weight for dry sodium sulfate. However, when sodium sulfate is added as a solution, the preferred range increases to as much as 3.5~.
.:
While this invention may be embodied in many ~
different forms, there are shown in the drawings and ~ -- ~ ~. - .: . .: . :,... ... . . , : - -.: : : .:: - :: .. : : : : . - . : - - . ~ . - - .-. . : .. . . - -' ' ... . ' ' ; ' ~ ;................ '!. . , . ; ', ' , ' . ' ' '`' ' " ' .' ' .. '' : '"'' ' i'.: ' . ... . ' i': '.1..... .
2~82~32 _9_ describad in detail herein specific preferred embodiments of the invention. The present disclosure is an exemplification o~ the principles of the invention and is not intended to limit the invention to ~ -~
the particular embodiments illustrated.
This completes the des~ription of the pre~erred and alternate embodiments of the invention.
Those skilled in the art may recognize other equivalents to the specific embodiment described herein which equivalents are intended to be encompassed by the claims attached hereto.
,. ..
~.~. ....
,, '; ~
: ~. :
: ''' .` ':
~ ~. '' ;:' ,: ' :
, ~:
.
.. .. ~ ~.
'~ ~
,~,: ,',,~',-,
Claims (9)
1. A composition for use as an animal implant comprising calcium sulfate hemihydrate, calcium phosphate and between about 1.5 to about 4.0 percent sodium sulfate by weight based on calcium sulfate hemihydrate.
2. The composition of Claim 1 wherein said sodium sulfate comprises between about 2.35 to about 3.5 percent by weight of the composition.
3. The composition of Claim 1 further including a wetting agent selected from the group consisting of water, saline, blood and mixtures thereof.
4. The composition of Claim 1 wherein said calcium phosphate is hydroxylapatite, and the hydroxylapatite and calcium sulfate hemihydrate are in a ratio of about 65 to 35 percent by weight.
5. A composition for use as an animal implant consisting essentially of calcium sulfate hemihydrate and hydroxylapatite at a weight to weight ratio of about 35 to 65, and between about 1.5 to about 4.0 percent sodium sulfate by weight based on calcium sulfate hemihydrate.
6. The composition of Claim 5 wherein said sodium sulfate comprises between about 2.35 to about 2.45 percent by weight of the composition.
7. The composition of Claim 6 further including a wetting agent selected from the group consisting of water, saline, blood and mixtures thereof
8. A method for hardening calcium sulfate hemihydrate compositions in the presence of blood which comprises adding from about 1.5 to about 4.0 percent by weight sodium sulfate to the composition, contacting the composition with a wetting solution, initiating the hardening reaction and thereafter placing the wetted composition in contact with blood or other proteinaceous material from an animal.
9. A composition for use as an animal implant having a set time of less than about 30 minutes and a pot life of between about two to five minutes comprising calcium sulfate hemihydrate, calcium phosphate and between about 1.5 to about 4.0 percent sodium sulfate by weight based on calcium sulfate hemihydrate.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US52216790A | 1990-05-11 | 1990-05-11 | |
| US522,167 | 1990-05-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2082632A1 true CA2082632A1 (en) | 1991-11-12 |
Family
ID=24079727
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002082632A Abandoned CA2082632A1 (en) | 1990-05-11 | 1991-05-09 | Rapid setting hydroxylapatite and plaster formulation |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0537180A4 (en) |
| JP (1) | JPH05507862A (en) |
| AU (1) | AU7903391A (en) |
| CA (1) | CA2082632A1 (en) |
| WO (1) | WO1991017722A1 (en) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5462722A (en) * | 1991-04-17 | 1995-10-31 | Liu; Sung-Tsuen | Calcium phosphate calcium sulfate composite implant material |
| US5366507A (en) * | 1992-03-06 | 1994-11-22 | Sottosanti John S | Method for use in bone tissue regeneration |
| DE19620117C1 (en) * | 1996-05-18 | 1997-07-24 | Corimed Kundenorientierte Medi | Preparation of medicinal composition containing calcium sulphate |
| ES2178556B1 (en) * | 2000-06-30 | 2004-07-16 | Universitat Politecnica De Catalunya | CEMENT OF CALCIUM SULPHATE WITH CONTROLLED BIODEGRADATION. |
| SE517168C2 (en) | 2000-07-17 | 2002-04-23 | Bone Support Ab | A composition for an injectable bone mineral replacement material |
| SE522098C2 (en) * | 2001-12-20 | 2004-01-13 | Bone Support Ab | Artificial bone mineral substitute material useful as an X-ray contrast medium comprises ceramic and water soluble non-ionic X-ray contrast agent |
| WO2003053488A1 (en) * | 2001-12-20 | 2003-07-03 | Bone Support Ab | A new bone mineral substitute |
| SE0302983D0 (en) | 2003-11-11 | 2003-11-11 | Bone Support Ab | Apparatus for providing spongy bone with bone replacement and / or bone strengthening material and associated method |
| SE527528C2 (en) | 2004-06-22 | 2006-04-04 | Bone Support Ab | Apparatus for the preparation of curable pulp and use of the apparatus |
| US7250550B2 (en) | 2004-10-22 | 2007-07-31 | Wright Medical Technology, Inc. | Synthetic bone substitute material |
| US8025903B2 (en) | 2005-09-09 | 2011-09-27 | Wright Medical Technology, Inc. | Composite bone graft substitute cement and articles produced therefrom |
| BRPI0617086B8 (en) | 2005-09-09 | 2021-06-22 | Agnovos Healtcare Llc | bone graft substitute composite cement and articles originated from it |
| WO2007132026A1 (en) * | 2006-05-12 | 2007-11-22 | Martin-Nieto Camacho Christoba | Bone-regenerating substance composed of semi-hydrated calcium sulphate and calcium phosphate |
| WO2008094585A1 (en) * | 2007-01-30 | 2008-08-07 | The Research Foundation Of State University Of New York | Calcium sulfate based nanoparticles |
| US9180137B2 (en) | 2010-02-09 | 2015-11-10 | Bone Support Ab | Preparation of bone cement compositions |
| ES2671122T3 (en) | 2013-02-20 | 2018-06-05 | Bone Support Ab | Enhanced hardening of hardenable bone substitute |
| TWI651103B (en) | 2013-12-13 | 2019-02-21 | 萊特醫技股份有限公司 | Multiphase bone graft replacement material |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2862829A (en) * | 1956-07-18 | 1958-12-02 | Nat Foam Systems Inc | Manufacture of foamed gypsum and the like |
| US3303030A (en) * | 1963-06-20 | 1967-02-07 | Dentists Supply Co | Refractory mold |
-
1991
- 1991-05-09 JP JP91509419A patent/JPH05507862A/en active Pending
- 1991-05-09 EP EP19910910075 patent/EP0537180A4/en not_active Withdrawn
- 1991-05-09 WO PCT/US1991/003208 patent/WO1991017722A1/en not_active Application Discontinuation
- 1991-05-09 CA CA002082632A patent/CA2082632A1/en not_active Abandoned
- 1991-05-09 AU AU79033/91A patent/AU7903391A/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AU7903391A (en) | 1991-12-10 |
| EP0537180A4 (en) | 1993-04-28 |
| JPH05507862A (en) | 1993-11-11 |
| EP0537180A1 (en) | 1993-04-21 |
| WO1991017722A1 (en) | 1991-11-28 |
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