WO1991017722A1 - Rapid setting hydroxylapatite and plaster formulation - Google Patents
Rapid setting hydroxylapatite and plaster formulation Download PDFInfo
- Publication number
- WO1991017722A1 WO1991017722A1 PCT/US1991/003208 US9103208W WO9117722A1 WO 1991017722 A1 WO1991017722 A1 WO 1991017722A1 US 9103208 W US9103208 W US 9103208W WO 9117722 A1 WO9117722 A1 WO 9117722A1
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- WO
- WIPO (PCT)
- Prior art keywords
- composition
- weight
- blood
- sodium sulfate
- calcium sulfate
- Prior art date
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- 239000000203 mixture Substances 0.000 title claims abstract description 41
- 229910052588 hydroxylapatite Inorganic materials 0.000 title claims abstract description 21
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 title claims abstract description 21
- 239000011505 plaster Substances 0.000 title description 10
- 238000009472 formulation Methods 0.000 title description 7
- ZOMBKNNSYQHRCA-UHFFFAOYSA-J calcium sulfate hemihydrate Chemical compound O.[Ca+2].[Ca+2].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O ZOMBKNNSYQHRCA-UHFFFAOYSA-J 0.000 claims abstract description 32
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims abstract description 24
- 229910052938 sodium sulfate Inorganic materials 0.000 claims abstract description 24
- 235000011152 sodium sulphate Nutrition 0.000 claims abstract description 24
- 239000008280 blood Substances 0.000 claims abstract description 23
- 210000004369 blood Anatomy 0.000 claims abstract description 23
- 239000000463 material Substances 0.000 claims description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 8
- 239000007943 implant Substances 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 239000001506 calcium phosphate Substances 0.000 claims description 5
- 235000011010 calcium phosphates Nutrition 0.000 claims description 5
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims description 5
- 239000011780 sodium chloride Substances 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 3
- 229910000389 calcium phosphate Inorganic materials 0.000 claims 3
- 239000000080 wetting agent Substances 0.000 claims 2
- CGMRCMMOCQYHAD-UHFFFAOYSA-J dicalcium hydroxide phosphate Chemical group [OH-].[Ca++].[Ca++].[O-]P([O-])([O-])=O CGMRCMMOCQYHAD-UHFFFAOYSA-J 0.000 claims 1
- 230000000977 initiatory effect Effects 0.000 claims 1
- 238000009736 wetting Methods 0.000 claims 1
- 210000000988 bone and bone Anatomy 0.000 abstract description 5
- 210000001124 body fluid Anatomy 0.000 abstract description 3
- 239000010839 body fluid Substances 0.000 abstract description 3
- 238000002513 implantation Methods 0.000 abstract description 3
- 239000010440 gypsum Substances 0.000 description 11
- 229910052602 gypsum Inorganic materials 0.000 description 11
- 239000000126 substance Substances 0.000 description 7
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Inorganic materials [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 6
- 239000011507 gypsum plaster Substances 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 5
- 229910052939 potassium sulfate Inorganic materials 0.000 description 5
- 235000011151 potassium sulphates Nutrition 0.000 description 5
- 230000001133 acceleration Effects 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 230000007547 defect Effects 0.000 description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 150000004683 dihydrates Chemical group 0.000 description 2
- IRXRGVFLQOSHOH-UHFFFAOYSA-L dipotassium;oxalate Chemical compound [K+].[K+].[O-]C(=O)C([O-])=O IRXRGVFLQOSHOH-UHFFFAOYSA-L 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 230000000399 orthopedic effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000003416 augmentation Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000008468 bone growth Effects 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- PASHVRUKOFIRIK-UHFFFAOYSA-L calcium sulfate dihydrate Chemical compound O.O.[Ca+2].[O-]S([O-])(=O)=O PASHVRUKOFIRIK-UHFFFAOYSA-L 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 239000004053 dental implant Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000011790 ferrous sulphate Substances 0.000 description 1
- 235000003891 ferrous sulphate Nutrition 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000003239 periodontal effect Effects 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000011800 void material Substances 0.000 description 1
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
Definitions
- This invention relates to formulations useful in bone and dental implant, repair and reconstruction.
- the formulations include mixtures of calcium sulfate hemihydrate, hydroxylapatite and sodium sulfate.
- the sodium sal ate has been found to greatly accelerate the hardening of the mixture in the presence of blood.
- U. S. Patent 4,619,655 discloses animal implants comprising a binder lattice or scaffold of calcium hemihydrate (plaster of paris) and a non- bioresorbable calcium material such as hydroxylapatite.
- a binder lattice or scaffold of calcium hemihydrate plaster of paris
- a non- bioresorbable calcium material such as hydroxylapatite.
- calcium sulfate hemihydrate is described as hardening in water in about thirty (30) minutes.
- Calcium sulfate hemihydrate (plaster of Paris) has been known for years to have excellent reparative qualities in bone defects, but ordinarily it is quickly resorbed.
- a composite of a dense form of plaster of Paris and hydroxylapatite provides nonresorbable hydroxylapatite particles for bone to form around and within during the phase of plaster absorption.
- the invention provides a composition useful in dental, orthopedic and neurological procedures 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.
- "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 acceleration in the presence of blood. It is employed in the range of 1.5 to 4 % by dry weight based on the weight of calcium sulfate hemihydrate.
- Potassium sulfate at 0.85% by weight of the calcium sulfate hemihydrate provided acceleration. However, questions concerning its toxicity eliminated its use as an accelerator in vivo. Also, at these levels the potlife is not optimum. "Potlife” refers to the working time of the mixture. When the plaster begins to set the mixture becomes cohesive and putty ⁇ like. At the end of its useful potlife, the material becomes gritty and does not hold together well. The potlife expires when the material loses its smooth, soft nature or when the material becomes gritty and does not stick together.
- the individual chemicals present in a potassium oxalate blood tube were suspected of being accelerants. Testing of the chemicals found that sodium sulfate is an accelerant in the presence of blood. Although sodium sulfate is not an additive to the blood tubes, both the sodium and sulfate ion are present. The inventors recognized that the contributions of the ions in the blood tube could be reproduced by employing sodium sulfate in the plaster formulation. Sodium sulfate had not been tested previously since it was known to be an inferior accelerator for plaster of paris as compared to potassium sulfate, gypsum and potassium chloride based on literature reviews and laboratory bench work.
- HA Hydroxylapatite
- HA Hydroxylapatite
- HA is a biocompatible substance functioning as a non-resorbable scaffold for new bone growth.
- 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 in conjunction with HA to produce a more deliverable and i plantable composition which minimizes migration of particles from the site to an undesired location.
- Calcium sulfate hemihydrate hardens into a dihydrate form known as gypsum. Gypsum is completely 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 of implant volume during plaster resorption. Lower plaster levels result in a less cohesive mass of particles for delivery.
- resorbable or non-resorbable forms of calcium phosphates may be employed in this invention.
- Set is the crystallization of calcium sulfate dihydrate (gypsum) from calcium sulfate hemihydrate in the presence of water.
- Hardening is a measure 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.
- 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.
- Hydroxylapatite/calcium sulfate hemihydrate compositions were prepared in a 65:35 ratio by weight and were wetted with 0.9% saline solution. The material immediately softened upon implantation and did not harden 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 with a swab, which instead drew the plaster-portion up further. The nearly set (hardened) mixture softened immediately even in contact with minimal blood.
- Hydroxylapatite/calcium sulfate hemihydrate compositions were prepared in a 65:35 ratio by weight and were wetted with 0.9% 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.
- the following table shows the set time and potlife of compositions using varying levels of sodium sulfate. As shown, sodium sulfate levels of less than about 1.5% or greater than about 4.0% have potlives which are not desirable.
- 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.
- the preferred range increases to as much as 3.5%.
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Dermatology (AREA)
- Cardiology (AREA)
- Engineering & Computer Science (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Dental Preparations (AREA)
- Materials For Medical Uses (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (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
RAPID SETTING HYDROXYLAPATITE AND PLASTER FORMULATION
Background of the Invention
1. Field of the Invention This invention relates to formulations useful in bone and dental implant, repair and reconstruction. The formulations include mixtures of calcium sulfate hemihydrate, hydroxylapatite and sodium sulfate. The sodium sal ate has been found to greatly accelerate the hardening of the mixture in the presence of blood.
2. Description of the Related Art
U. S. Patent 4,619,655 discloses animal implants comprising a binder lattice or scaffold of calcium hemihydrate (plaster of paris) and a non- bioresorbable calcium material such as hydroxylapatite. In U.S. Patent 4,681,644 calcium sulfate hemihydrate is described as hardening in water in about thirty (30) minutes.
Calcium sulfate hemihydrate (plaster of Paris) has been known for years to have excellent reparative qualities in bone defects, but ordinarily it is quickly resorbed. A composite of a dense form of plaster of Paris and hydroxylapatite provides nonresorbable hydroxylapatite particles for bone to form around and within during the phase of plaster absorption.
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
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 water to be supersaturated. Salt crystal formation on the nuclei of crystallization of 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 retardants. One of the inventors of U.S. Patent
4,619,655 has published a paper which states that set retardation in blood may be controlled by the addition of 10% potassium sulfate or 16.7% sodium chloride. These high concentrations may cause salt crystal formation due to the increased potassium ion levels. Additionally, the concentrations employed may be harmful to the body. The sterilized gypsum-accelerated product is not fully 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.
The art described in this section is not intended to constitute an admission that any patent, publication or other information referred to herein is "prior art" with respect to this invention, unless
specifically designated as such. In addition, this section should not be construed to mean that a search has been made or that no other pertinent information 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 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. "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 acceleration in the presence of blood. It is employed in the range of 1.5 to 4 % by dry weight based on the weight of calcium sulfate hemihydrate.
Screening studies were undertaken to seek an accelerant that would be stable in the presence of blood. Potassium oxalate and sodium heparin blood 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 blood. Ferrous sulfate provided acceleration but has an inadequate shelflife.
Potassium sulfate at 0.85% by weight of the calcium sulfate hemihydrate provided acceleration.
However, questions concerning its toxicity eliminated its use as an accelerator in vivo. Also, at these levels the potlife is not optimum. "Potlife" refers to the working time of the mixture. When the plaster begins to set the mixture becomes cohesive and putty¬ like. At the end of its useful potlife, the material becomes gritty and does not hold together well. The potlife expires when the material loses its smooth, soft nature or when the material becomes gritty and does not stick together.
The individual chemicals present in a potassium oxalate blood tube were suspected of being accelerants. Testing of the chemicals found that sodium sulfate is an accelerant in the presence of blood. Although sodium sulfate is not an additive to the blood tubes, both the sodium and sulfate ion are present. The inventors recognized that the contributions of the ions in the blood tube could be reproduced by employing sodium sulfate in the plaster formulation. Sodium sulfate had not been tested previously since it was known to be an inferior accelerator for plaster of paris as compared to potassium sulfate, gypsum and potassium chloride based on literature reviews and laboratory bench work.
Description of the Preferred Embodiments
Hydroxylapatite (HA) has been commonly used in dental applications of periodontal defect filling and ridge augmentation since the 1970*s. HA is a biocompatible substance functioning as a non-resorbable scaffold for new bone growth.
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 in conjunction with HA to produce a more deliverable and i plantable composition which minimizes migration of particles from the site to an undesired location.
Calcium sulfate hemihydrate hardens into a dihydrate form known as gypsum. Gypsum is completely 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 of implant volume during plaster resorption. Lower plaster levels result in a less cohesive mass of particles for delivery. Again, resorbable or non-resorbable forms of calcium phosphates may be employed in this invention.
"Set" is the crystallization of calcium sulfate dihydrate (gypsum) from calcium sulfate hemihydrate in the presence of water. "Hardening" is a measure 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 thirty seconds, and transferrable to the defect site within one minute.
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 and thus i plantable 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 of placement.
EXAMPLE
Hydroxylapatite/calcium sulfate hemihydrate compositions were prepared in a 65:35 ratio by weight and were wetted with 0.9% saline solution. The material immediately softened upon implantation and did not harden 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 with a swab, which instead drew the plaster-portion up further. The nearly set (hardened) mixture softened immediately even in contact with minimal blood.
EXAMPLE II Hydroxylapatite/calcium sulfate hemihydrate compositions were prepared in a 65:35 ratio by weight and were wetted with 0.9% 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.
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 material was mixed with the blood also affected the end result. It has been found that the inclusion of sodium sulfate in the range of 1.5 to about 4.0 % by weight based on weight of calcium sulfate hemihydrate will provide a superior product. The compositions of the invention maintain 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
described in detail herein specific preferred embodiments of the invention. The present disclosure is an exemplification of the principles of the invention and is not intended to limit the invention to the particular embodiments illustrated.
This completes the description of the preferred 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
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.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP91509419A JPH05507862A (en) | 1990-05-11 | 1991-05-09 | Fast-curing hydroxylapatite and gypsum formulation |
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 |
|---|---|
| WO1991017722A1 true WO1991017722A1 (en) | 1991-11-28 |
Family
ID=24079727
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1991/003208 WO1991017722A1 (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) |
Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5366507A (en) * | 1992-03-06 | 1994-11-22 | Sottosanti John S | Method for use in bone tissue regeneration |
| US5462722A (en) * | 1991-04-17 | 1995-10-31 | Liu; Sung-Tsuen | Calcium phosphate calcium sulfate composite implant material |
| EP0807432A2 (en) * | 1996-05-18 | 1997-11-19 | Corimed Kundenorientierte Medizinprodukte GmbH | Process for the production of a medical preparation containing calcium sulphate and a medical preparation containing calcium sulphate |
| WO2002005861A1 (en) * | 2000-07-17 | 2002-01-24 | Bone Support Ab | A composition for an injectable bone mineral substitute material |
| ES2178556A1 (en) * | 2000-06-30 | 2002-12-16 | Univ Catalunya Politecnica | CEMENT OF CALCIUM SULPHATE WITH CONTROLLED BIODEGRADATION. |
| WO2003053488A1 (en) * | 2001-12-20 | 2003-07-03 | Bone Support Ab | A new bone mineral substitute |
| US7250550B2 (en) | 2004-10-22 | 2007-07-31 | Wright Medical Technology, Inc. | Synthetic bone substitute material |
| WO2007132026A1 (en) * | 2006-05-12 | 2007-11-22 | Martin-Nieto Camacho Christoba | Bone-regenerating substance composed of semi-hydrated calcium sulphate and calcium phosphate |
| US7754246B2 (en) | 2005-09-09 | 2010-07-13 | Wright Medical Technology, Inc. | Composite bone graft substitute cement and articles produced therefrom |
| US7767226B2 (en) * | 2007-01-30 | 2010-08-03 | The Research Foundation Of State University Of New York | Calcium sulfate based nanoparticles |
| US7935121B2 (en) | 2003-11-11 | 2011-05-03 | Bone Support Ab | Device for providing spongy bone with bone substitute and/or bone reinforcing material, bone substitute and/or bone reinforcing material and method |
| US7938572B2 (en) | 2004-06-22 | 2011-05-10 | Bone Support Ab | Device for producing a hardenable mass |
| US8025903B2 (en) | 2005-09-09 | 2011-09-27 | Wright Medical Technology, Inc. | Composite bone graft substitute cement and articles produced therefrom |
| US9180137B2 (en) | 2010-02-09 | 2015-11-10 | Bone Support Ab | Preparation of bone cement compositions |
| US9446170B2 (en) | 2013-12-13 | 2016-09-20 | Agnovos Healthcare, Llc | Multiphasic bone graft substitute material |
| US10294107B2 (en) | 2013-02-20 | 2019-05-21 | Bone Support Ab | Setting of hardenable bone substitute |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Citations (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 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 JP JP91509419A patent/JPH05507862A/en active Pending
- 1991-05-09 AU AU79033/91A patent/AU7903391A/en not_active Abandoned
- 1991-05-09 EP EP19910910075 patent/EP0537180A4/en not_active Withdrawn
Patent Citations (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 |
Non-Patent Citations (1)
| Title |
|---|
| Proceedings of the 44th Annual Meeting of the Electron Microscopy Society of America, issued 1986, HANKER et al., "Setting of Composite Hydroxylapatite/Plaster Implants with Blood for Bone Reconstruction", pages 328-329, see the entire document. * |
Cited By (27)
| 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 |
| EP0807432A2 (en) * | 1996-05-18 | 1997-11-19 | Corimed Kundenorientierte Medizinprodukte GmbH | Process for the production of a medical preparation containing calcium sulphate and a medical preparation containing calcium sulphate |
| EP0807432A3 (en) * | 1996-05-18 | 1998-01-07 | Corimed Kundenorientierte Medizinprodukte GmbH | Process for the production of a medical preparation containing calcium sulphate and a medical preparation containing calcium sulphate |
| ES2178556A1 (en) * | 2000-06-30 | 2002-12-16 | Univ Catalunya Politecnica | CEMENT OF CALCIUM SULPHATE WITH CONTROLLED BIODEGRADATION. |
| US7417077B2 (en) | 2000-07-17 | 2008-08-26 | Bone Support Ab | Composition for an injectable bone mineral substitute material |
| WO2002005861A1 (en) * | 2000-07-17 | 2002-01-24 | Bone Support Ab | A composition for an injectable bone mineral substitute material |
| WO2003053488A1 (en) * | 2001-12-20 | 2003-07-03 | Bone Support Ab | A new bone mineral substitute |
| EP1829565A1 (en) * | 2001-12-20 | 2007-09-05 | Bone Support AB | A new bone mineral substitute |
| AU2002359206B2 (en) * | 2001-12-20 | 2008-04-10 | Bone Support Ab | A new bone mineral substitute |
| US7935121B2 (en) | 2003-11-11 | 2011-05-03 | Bone Support Ab | Device for providing spongy bone with bone substitute and/or bone reinforcing material, bone substitute and/or bone reinforcing material and method |
| US8297831B2 (en) | 2004-06-22 | 2012-10-30 | Bone Support Ab | Device for producing a hardenable mass |
| US7938572B2 (en) | 2004-06-22 | 2011-05-10 | Bone Support Ab | Device for producing a hardenable mass |
| US7766972B2 (en) | 2004-10-22 | 2010-08-03 | Wright Medical Technology, Inc. | Synthetic, malleable bone graft substitute material |
| US7250550B2 (en) | 2004-10-22 | 2007-07-31 | Wright Medical Technology, Inc. | Synthetic bone substitute material |
| US9180224B2 (en) | 2005-09-09 | 2015-11-10 | Agnovos Healthcare, Llc | Composite bone graft substitute cement and articles produced therefrom |
| US8025903B2 (en) | 2005-09-09 | 2011-09-27 | Wright Medical Technology, Inc. | Composite bone graft substitute cement and articles produced therefrom |
| US8685464B2 (en) | 2005-09-09 | 2014-04-01 | Agnovos Healthcare, Llc | Composite bone graft substitute cement and articles produced therefrom |
| US8685465B2 (en) | 2005-09-09 | 2014-04-01 | Agnovos Healthcare, Llc | Composite bone graft substitute cement and articles produced therefrom |
| US7754246B2 (en) | 2005-09-09 | 2010-07-13 | Wright Medical Technology, Inc. | Composite bone graft substitute cement and articles produced therefrom |
| WO2007132026A1 (en) * | 2006-05-12 | 2007-11-22 | Martin-Nieto Camacho Christoba | Bone-regenerating substance composed of semi-hydrated calcium sulphate and calcium phosphate |
| US7767226B2 (en) * | 2007-01-30 | 2010-08-03 | 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 |
| US10294107B2 (en) | 2013-02-20 | 2019-05-21 | Bone Support Ab | Setting of hardenable bone substitute |
| US10994998B2 (en) | 2013-02-20 | 2021-05-04 | Bone Support Ab | Setting of hardenable bone substitute |
| US9446170B2 (en) | 2013-12-13 | 2016-09-20 | Agnovos Healthcare, Llc | Multiphasic bone graft substitute material |
| US10973949B2 (en) | 2013-12-13 | 2021-04-13 | Agnovos Healthcare, Llc | Multiphasic bone graft substitute material |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0537180A1 (en) | 1993-04-21 |
| AU7903391A (en) | 1991-12-10 |
| EP0537180A4 (en) | 1993-04-28 |
| JPH05507862A (en) | 1993-11-11 |
| CA2082632A1 (en) | 1991-11-12 |
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