GB2176192A - Bone filling composition - Google Patents
Bone filling composition Download PDFInfo
- Publication number
- GB2176192A GB2176192A GB08611603A GB8611603A GB2176192A GB 2176192 A GB2176192 A GB 2176192A GB 08611603 A GB08611603 A GB 08611603A GB 8611603 A GB8611603 A GB 8611603A GB 2176192 A GB2176192 A GB 2176192A
- Authority
- GB
- United Kingdom
- Prior art keywords
- bone
- calcium phosphate
- phosphate compound
- prepared
- hap
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/475—Growth factors; Growth regulators
- C07K14/51—Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
-
- 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
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/227—Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
-
- 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
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/46—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Transplantation (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Gastroenterology & Hepatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Composite Materials (AREA)
- Materials Engineering (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Inorganic Chemistry (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Molecular Biology (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Materials For Medical Uses (AREA)
Abstract
The filler composition contains a calcium phosphate compound having the apatite crystalline structure of the general formula Cam(PO4)nOH (1.50 </= m/m ??? 1.70) and a bone morphogenetic protein. The protein is extracted from by a multi-stage process. The two components have a synergistic effect which promotes faster bone formation than use of the calcium phosphate compound alone.
Description
SPECIFICATION
Bone fillers
The invention relates to a fillerfor repair of bone tissue lost by operation to remove tumour or by external injury.
The variety of metal alloys and organic materials have conventionally been used as a material for substituting for a hard tissue in a living body. However, these material have disadvantages in that some of them dissolve or otherwise deteriorate in the environment ofthe living body, while others are harmful to the living body or cause foreign body reactions. In recent years, ceramic materials have been developed forthis purpose, since they are excellent in compatibility with living tissues and do not have the aforementioned disadvantages. From the ceramic materials, artificial bones and teeth made of aluminia, carbon, tricalcium phosphate or a sintered body or a monocrystal of hydroxyapatite have been developed, and have attracted public attention because of their excellent compatibility with living tissues.
However, these known artificial bones and teeth are significantly harderthan surrounding bone tissue to stimulate the vicinal living tissue surrounding the implanted artificial bone or tooth, leading to absorption of bone, whereby loosening of the implanted artificial bone or tooth results. Because of this problem, the ceramic materials have not yet been applied for practical uses.
The invention provides a fillerforfilling defects and hollow portions of bone, the filler comprising a calcium phosphate compound having the apatite crystalline structure and represented bythe general formula:
Cam(PO4)nOH (1.50 S min < 1.70) and a bone morphogenetic protein.
In view ofthefactthat new bone isformed in the vicinity of a calcium phosphate compound implanted in a defect or hollow portion of bone, we have first aimed to utilize the characteristics of calcium phosphate compounds for promoting bone formation. The calcium phosphate compound used in the invention is, as stated, a calcium phosphate compound having the apatite crystalline structure and represented by the general formula Cam(PO4)nOH(1 .50 S m/n s 1.70). This calcium phosphate compound has a tendency, due to the inherent structural characteristics of its apatite crystalline structure, of easily introducing various different ions at the Ca site, PO4site or OH site thereof.In the invention,the calcium phosphate compounds containing different ions may be used as far as they have compatibility with living tissues and their compositions are within the range indicated by 1.50 < min S 1.70 (m/n being the molar ratio of Ca to P04). If the ratio of min is out of the defined range, compatibility with the living body is lowered and the effect of promoting formation of new bone is also reduced. In addition, adsorption ofthe bone morphongenetic protein to the calcium phosphate compound is so lowered as to lessen the synergistic effect of the composite filler of the invention, if the ratio of m/n is out of the defined range.
The calcium phosphate compound used in the composite filler of the invention may be artificially synthesized through a wet process, a dry process ora hydrothermal process, or may be a material of natural origin, such as human or animal bones. Irrespective of whetherthe calcium phosphate compound is an artificially synthesized material or a material of natural origin, it is desirable that it be baked at a temperature of not lower than 400 C, preferably not lowerthan 600 C, in order to adsorb the bone morphogenetic protein and thereby prepare the composite filler of the invention. If the baking temperature is lower than 4000C, the amount of the bone morphogenetic protein adsorbed by the baked calcium phosphate becomes too small promptly to form new bone.The upper limit of the baking temperature is not particularly restricted, but should be lower than the decomposition temperature of the calcium phosphate compound.
The calcium phosphate compound used in the invention may be in the form of powder, granule or porous body as long as it adsorbs the bone morphogenetic protein to form the composite filler. Porous bodies are particularly preferred, since the bone morphogenetic protein is carried in the pores in such a mannerthatthe bone morphogenetic protein is held in situ internally ofthe calcium phosphate compound, without being dispersed, for a long time after the filler is implanted into a defect or hollow portion of bone. It isfurther preferable that the porous body has an average pore diameter of not more than 320 microns, more preferably not more than 200 microns, forthe rapid formation of new bone.The porous body of the calcium phosphate compound may be prepared by impregnating a slurry of calcium phosphate compound into a porous carrier of an organic material, and then baking to burn offthe porous carrierofthe organic material.
A calcium phosphate compound having the apatite crystalline structure and having a zeta potential of not more than -0.1 mV may be particularly preferred, since such a compound has improved adsorption of the bone morphogenetic protein and improved effect of promoting formation of new bone. The zeta potential is determined by the streaming potential determination method. In detail, a sample to be determined is finely pulverized and filled in a test cell to form a diaphragm through which a liquid (distilled water) is forcibly passed using an inert gas, such as nitrogen, as the pressure source to detect the potential difference between the end faces ofthe diaphragm-shaped sample.The zeta potential is calculated by substituting the values ofthe applied pressure and the detected potential difference in the following equation (Helmholtz-Smoluchowski's equation): Zeta
EP
wherein 11 is the coefficient of viscosity (poise) of the liquid, A is the specific conductivity (Q~lcm~ ) of the liquid, #isthe dielectric constant (-) of the liquid in air, E is the detected potential difference (mV) and P is the applied
gas pressure (cm H2O).
An important aspect of the invention resides in the utilization ofthe synergistic effect ofthe calcium
phosphate compound and the bone morphogenetic protein carried bythe calcium phosphate compound to
promote remarkablyfasterformation of bone as compared with a filler composed only ofthe calcium
phosphate compound. The bone morphogenetic protein used in the invention may be prepared,forexample, by a process described by Urist et al.This process comprises the steps of removing soft tissues, such as muscular periosteum,from a human bone or a bone of cattle, pig or rabbit, crushing the bone into small
pieces, removing bone-marrowfrom the crushed bone pieces, defatting the crushed bone with a mixture of
chloroform and methanol (1:1), deliming with 0.6N HCI, defatting again with a mixture of chloroform and methanol (1:1), adding 8M lithium chloride solution to the defatted and delimed bone, washing with water, heating and then freeze-drying.
The thus obtained freeze-dried bone pieces are added to a 4M guanidinohydrochloric acid solution
(containing 10 millimoles of N-ethylmaleimide and 1 millimole of phenyl-methylsulphonylfluoride), and the
soluble fraction is filtered and then subjected to centrifugal separation to obtain a supernatantwhich is
dialyzed with seven times its volume of deionized water. Thewater-insolublefraction formed during the
dialysis is collected by centrifugal separation, washed with water and then freeze-dried to prepare the bone
morphogenetic protein. The thus prepared bone morphogenetic protein is preferably purified by the gel
filtration method.It is, of course, desirable that bone morphogenetic protein prepared from human bones is
used in a filler to be implanted into a human body, and that a bone morphogenetic protein prepared from
animal bone is used as a fillerto be implanted into that animal.
In preparation of a composite filler according to the invention, wherein the bone morphogenetic protein is
carried bythe calcium phosphate compound having the apatite crystalline structure, the thus prepared bone
morphogenetic protein may be again dissolved in a 4M guanidinohydrochloricacid solution, added to the
calcium phosphate compound, dialyzed through a dialyzing tube, and then freeze-dried.
In the following Examples, which illustrate the invention, the bone morphogenetic protein will be referred to
briefly as BMP and the calcium phosphate compound having the apatite crystalline structure will be referred to
briefly as HAp. The powder-form HAp was prepared by synthesis through the wet process, followed by baking
and pulverization. The granular HAp was prepared by granulating the powder-form HAp using a rolling granulator, followed by baking. The porous HAp was prepared by impregnating a slurry of HAp powder,
followed by baking. The BMPwas prepared from rabbit bonethrough Urist's process. Each HAp was added to
a solution of BMP in a 4M guanidinohydrochloric acid solution, followed by dialysis through a dialyzing tube and freeze-drying, to prepare each ofthefillers.
Example 1 Cylindrical defects were formed in femurs of rabbits by using a 4.5 mm diameter drill, and the defects were
filled with BMP-HAp porous bodies and HAp porous bodies (each having the dimensions of 4 mm diameter
and 8 mm length, being baked at900 C, having a ratio of Ca/P = 1.67, and having an average pore diameter of
90 microns, 200 microns, 320 microns and 410 microns). The conditions ofthe defects after implantation with thefillerswere observed.
The results were that formation of new bones was found in all of the defects after a lapse of 2 weeks from the
implantation. Particularly, growth of new bone in the defects implanted with the BMP-HAp porous bodies
reached a greater level, and the greatest growth of bone was observed in the defects implanted with the BMP-HAp porous bodies each having an average pore diameter of not more than 320 microns. The results
observed after a lapse of 4 weeks and 8 weeks were similartothe results after the lapse of weeks in thatthe growth of new bones reached remarkedly higher levels in the defects implanted with the BMP-HAp porous
bodies.
Example 2 Agranular BMP-HAp and a granular HAp (each having a granule diameter of 1.0 to 0.5 mm and a ratio of Ca/P i =1.67 and being prepared by baking at 1 000 C) were implanted in defects in bones of rabbits, the defects being
formed as described in Example 1, and the conditions ofthe defects after implantation with the fillers were
observed.
The results werethatformation of new bones was found in both ofthe defects after a lapse of 2 weeksfrom
the implantation, and that growth of new bone in the defects implanted with the granular BMP-HAp reached a higher level.
Example 3
Porous bodies of HAp, respectively having Ca/P ratios of 1.35,1.50,1.67 and 1.85, were prepared by baking at
a baking temperature of 6000C, and porous bodies of BMP-HAp (each having an average pore diameter of 90 microns) were prepared therefrom.
Respective porous bodies of BMP-HAp were implanted in defects of bones of rabbits, the defects being formed as described in Example 1, and the conditions of the defects after implantation with the fillers were observed. The results were that growth of new bones in the defects implanted with the fillers having the Ca/P ratios of 1.50 and 1.67 reached appreciable levels after a lapse of 2 weeks from the implantation, and that only a little growth of new bones was observed in the defects implanted with the fillers having the Ca/P ratios of 1.35 and 1.85.
Porous bodies made only of HAp were implanted in defects, generally in accordance with similar procedures, as the controls. The defects implanted with the control HAp porous bodies were observed after the lapse of 2 weeks from the implantation. The resu Its were that the formation of new bones in the defects implanted with the control HAp porous bodies were less than those in the defects implanted with the corresponding BMP-HAp porous bodies, and the differences were considerably significant in cases where the ratios of Ca/P were 1.50 and 1.67.
Example4
HAp porous bodies each having a Ca/P ratio of 1.67 and being baked, respectively, at 300 C,400 C,600 C, 900"C, 1 200"C and 1 300"C, were prepared, from which BMP-HAp porous bodies were prepared. Thethus prepared BMP-HAp porous bodies were implanted in defects offemurs of rabbits, the defects being formed as described in Example 1, and the conditions of the defects after the implantation were observed.The results were that appreciable formation of new bones were observed in the defects implanted with the fillers prepared by baking at600 C or a highertemperature, and that the growth of new bone in the defect implanted with the filler prepared by baking at400'C was at a level slightly lower than those in the defect implanted with thefillers prepared by baking at 6000C or a higher temperature. In contrastthereto, very little growth of new bone as observed in the defect implanted with the filler prepared by baking at300 C.
Porous bodies made of HAp alone were implanted in defects, generally in accordance with similar procedures, as controls. The conditions of the defects implanted with the control HAp porous bodies were observed afterthe lapse of weeks from implantation. The results were that the formation of new bones in the defects implanted with the control HAp porous bodies were less than those in the defects implanted with the corresponding BMP-HAp porous bodies, and the differences were considerably significant in cases wherethe fillers were prepared by baking at 6000C or at higher baking temperatures.
Example 5 HAp powders having, respectively, Ca/P ratios of 1.55, 1.68 and 1.74were baked at 600 C, and the zeta potentials ofthe HAp powders were determined using distilled water as the forcibly passed liquid. The zeta potential of the powder having the ratio of Ca/P = 1.55 was - 0.5 5 0.4 mV, the zeta potential of the powder having the ratio of Ca/P = 1.68 was -0.8 # 0.5 mV, a and the zeta potential of the powder having the ratio of Ca/P = 1.74was - 0.05 + 0.01 mV.
The BMP was adsorbed by each of the powders to prepare a BMP-HAp powder which was implanted in a bone defect formed as described in Example 1. As a control, each of the HAp powders was implanted in a similar defect.
The results were that formation of new bones were observed in all of the defects implanted with the
BMP-HAp powders, and that the growth of new bone in the defect implanted with the BMP-HAp powder having the Ca/P ratio of 1.74 is less than those in the defects implanted with the other two BMP-HAp powders.
The growth of new bone in each ofthe defects implanted with the BMP-HAp powders was greaterthan that in the defect implanted with the corresponding control HAp powder, and the differences were considerably significant in cases were the ratios of Ca/P were 1.55 and 1.68.
Claims (8)
1. Afillerforfilling defects and hollow portions of bone, thefiller comprising a calcium phosphate compound having the apatite crystalline structure and represented bythe general formula: Cam(PO4)nOH (1.50 s m/n < 1.70) and a bone morphogenetic protein.
2. Afiller according to claim 1 in which the calcium phosphate compound is prepared by baking at a temperature of not lower than 400 C.
3. Afiller according to claim 1 or claim 2 in which the calcium phosphate compound has a zeta potential of not more than -0.1 mV determined using distilled was as the forcibly passed fluid.
4. Afiller according to any preceding claim in which the calcium phosphate compound is in the form of a porous body.
5. Afiller according to claim 4 in which the body has an average pore diameter of not more than 320 microns.
6. Afilleraccording to any preceding claim in which the bone morphogenetic protein is prepared by a process comprising the steps of defatting a bone, deliming the defatted bone, defatting again the delimed bone, admixing lithium chloride with the defatted and delimed bone, heating and then freezing the admixture, drying the frozen admixture to obtain a freeze-dried admixture, adding the freeze-dried admixture to a solution of guanidino-hydrochloric acid to dissolve the soluble ingredients therein, separating the supernatant containing the soluble ingredients, dialyzing the supernatantwith deionized water, and freeze-drying a phase insoluble in water.
7. Afilleraccording to any preceding claim prepared by dissolving the morphogenetic protein in a solution ofguanidinohydrochloric acid, adding the calcium phosphate, dialysing and freeze-drying.
8. A filler according to claim 1, the filler being substantially as described herein with reference to anyofthe Examples.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60101193A JPS61259675A (en) | 1985-05-15 | 1985-05-15 | Bone lost part and cavity part filling material |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| GB8611603D0 GB8611603D0 (en) | 1986-06-18 |
| GB2176192A true GB2176192A (en) | 1986-12-17 |
| GB2176192B GB2176192B (en) | 1989-07-05 |
Family
ID=14294111
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB8611603A Expired GB2176192B (en) | 1985-05-15 | 1986-05-13 | Bone fillers |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JPS61259675A (en) |
| DE (1) | DE3616365A1 (en) |
| GB (1) | GB2176192B (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0271668A1 (en) * | 1986-10-22 | 1988-06-22 | Gesellschaft für Biotechnologische Forschung mbH (GBF) | Growth stimulating material, process for its production, and therapeutic composition |
| EP0366029A2 (en) * | 1988-10-25 | 1990-05-02 | Takao Yamamuro | Bone repairing material and artificial bone fixing agent |
| EP0520237A2 (en) * | 1991-06-26 | 1992-12-30 | MERCK PATENT GmbH | Bone replacement material containing fibroblast growth factors |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH01151461A (en) * | 1987-12-08 | 1989-06-14 | Koransha Co Ltd | Prosthesis material for organism |
| JPH01158965A (en) * | 1987-12-16 | 1989-06-22 | Tokuyama Soda Co Ltd | Curable composition |
| JPH0231749A (en) * | 1988-07-20 | 1990-02-01 | Mitsubishi Mining & Cement Co Ltd | Filler for bone depleted part and osteoporosis part |
| JP2725387B2 (en) * | 1989-07-12 | 1998-03-11 | 三菱マテリアル株式会社 | Filling material for bone defect and bone void |
| JP2008132303A (en) * | 2006-10-27 | 2008-06-12 | Mmt:Kk | Biological member |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2164042A (en) * | 1984-05-28 | 1986-03-12 | Kyocera Corp | Artificial bone forming composition |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5654841A (en) * | 1979-10-08 | 1981-05-15 | Mitsubishi Mining & Cement Co | Bone broken portion and filler for void portion and method of treating bone of animal using said filler |
| DE3203957A1 (en) * | 1982-02-05 | 1983-08-18 | Chemokol Gesellschaft zur Entwicklung von Kollagenprodukten, 5190 Stolberg | Method for the production of fine-pore collagen sponges |
| JPS59131347A (en) * | 1983-01-18 | 1984-07-28 | 科学技術庁無機材質研究所長 | Production of artificial bone or artificial dental implant material |
| JPS6014860A (en) * | 1983-07-06 | 1985-01-25 | 三菱鉱業セメント株式会社 | Inorganic implant material |
| JPS6018174A (en) * | 1983-07-09 | 1985-01-30 | 住友セメント株式会社 | New bone inducing method and ceramic material |
| DE3414924A1 (en) * | 1984-04-19 | 1985-10-31 | Klaus Dr.med. Dr.med.habil. 8000 München Draenert | COATED ANCHORAGE PART FOR IMPLANTS |
-
1985
- 1985-05-15 JP JP60101193A patent/JPS61259675A/en active Granted
-
1986
- 1986-05-13 GB GB8611603A patent/GB2176192B/en not_active Expired
- 1986-05-15 DE DE19863616365 patent/DE3616365A1/en active Granted
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2164042A (en) * | 1984-05-28 | 1986-03-12 | Kyocera Corp | Artificial bone forming composition |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0271668A1 (en) * | 1986-10-22 | 1988-06-22 | Gesellschaft für Biotechnologische Forschung mbH (GBF) | Growth stimulating material, process for its production, and therapeutic composition |
| WO1993012803A1 (en) * | 1986-10-22 | 1993-07-08 | Krueger Wolfgang | Growth-simulating material, process for preparing the same and therapeutical composition |
| EP0366029A2 (en) * | 1988-10-25 | 1990-05-02 | Takao Yamamuro | Bone repairing material and artificial bone fixing agent |
| EP0366029A3 (en) * | 1988-10-25 | 1991-01-09 | Takao Yamamuro | Bone repairing material and artificial bone fixing agent |
| EP0520237A2 (en) * | 1991-06-26 | 1992-12-30 | MERCK PATENT GmbH | Bone replacement material containing fibroblast growth factors |
| EP0520237A3 (en) * | 1991-06-26 | 1993-05-19 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Bone replacement material containing fibroblast growth factors |
Also Published As
| Publication number | Publication date |
|---|---|
| DE3616365A1 (en) | 1986-11-20 |
| JPH0533062B2 (en) | 1993-05-18 |
| DE3616365C2 (en) | 1989-09-14 |
| GB8611603D0 (en) | 1986-06-18 |
| JPS61259675A (en) | 1986-11-17 |
| GB2176192B (en) | 1989-07-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4981451B2 (en) | Composite biomaterial comprising calcium phosphate material, collagen and glycosaminoglycan | |
| Yuan et al. | Osteoinduction by calcium phosphate biomaterials | |
| CN101417145B (en) | Bracket material for bone tissue engineer and preparation method thereof | |
| JP5201510B2 (en) | Osteoinducible calcium phosphate | |
| KR100807108B1 (en) | Preparation method of porous ?-tricalcium phosphate granules | |
| US9642934B2 (en) | Bone regeneration material kit, paste-like bone regeneration material, bone regeneration material, and bone bonding material | |
| Sivakumar et al. | Preparation, characterization, and in vitro release of gentamicin from coralline hydroxyapatite‐alginate composite microspheres | |
| AU2020202702A1 (en) | Semi-synthetic powder material, obtained by modifying the composition of a natural marine biomaterial, method for producing same, and applications thereof | |
| AU2009208807B2 (en) | Porous biomaterial on hydropatite | |
| GB2176192A (en) | Bone filling composition | |
| EP3111967A1 (en) | High strength synthetic bone for bone replacement for increasing compressive strength and facilitating blood circulation, and manufacturing method therefor | |
| Zyman et al. | Nonstoichiometric hydroxyapatite granules for orthopaedic applications | |
| US20100233269A1 (en) | Mineralized polymer particles and the method for their production | |
| Barbeck et al. | The effect of temperature treatment of xenogeneic bone substitute on the tissue response: a mini review | |
| Vrânceanu et al. | Development and characterization of novel porous collagen based biocomposite for bone tissue regeneration | |
| CN100366301C (en) | Coral hydroxyapatite artificial bone with betatype tricalcium phosphate coating and its preparation | |
| Petronis et al. | New biphasic calcium phosphate in orthopedic surgery: first clinical results | |
| Passuti et al. | Experimental data regarding macroporous biphasic calcium phosphate ceramics | |
| JPH0575427B2 (en) | ||
| JPS60256460A (en) | Composition for filling bone defficient part and gap part containing fibrin and calcium phosphate | |
| ES2961866T3 (en) | Mineralization procedure of a biopolymer membrane and membranes thus obtained | |
| EP2814521B1 (en) | Bone repair material | |
| CN115317663B (en) | Continuous anti-infection composite bone powder and preparation method and application thereof | |
| JPS60256461A (en) | Kit for preparing composition for filling bone lost part andgap part | |
| KR101769019B1 (en) | Guided bone regeneration composition, guided bone regeneration membrane and method for manufacturing the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 20020513 |