CN1079401A - Cmposite artificial bone and production technology thereof - Google Patents
Cmposite artificial bone and production technology thereof Download PDFInfo
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- CN1079401A CN1079401A CN 92104430 CN92104430A CN1079401A CN 1079401 A CN1079401 A CN 1079401A CN 92104430 CN92104430 CN 92104430 CN 92104430 A CN92104430 A CN 92104430A CN 1079401 A CN1079401 A CN 1079401A
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- 210000000988 bone and bone Anatomy 0.000 title claims abstract description 69
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 7
- 238000005516 engineering process Methods 0.000 title claims description 7
- 239000003102 growth factor Substances 0.000 claims abstract description 39
- 230000009645 skeletal growth Effects 0.000 claims abstract description 39
- 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 abstract description 23
- 239000000243 solution Substances 0.000 claims description 17
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 14
- 108010010803 Gelatin Proteins 0.000 claims description 12
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 229920000159 gelatin Polymers 0.000 claims description 12
- 239000008273 gelatin Substances 0.000 claims description 12
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- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 241001484259 Lacuna Species 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
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- 208000006735 Periostitis Diseases 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
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- 108010077465 Tropocollagen Proteins 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
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- 210000000544 articulatio talocruralis Anatomy 0.000 description 1
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- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
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- VSIIXMUUUJUKCM-UHFFFAOYSA-D pentacalcium;fluoride;triphosphate Chemical compound [F-].[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 VSIIXMUUUJUKCM-UHFFFAOYSA-D 0.000 description 1
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- Materials For Medical Uses (AREA)
Abstract
The present invention relates to a kind of cmposite artificial bone and production method thereof, its principal character is: this cmposite artificial bone is to be flooded skeletal growth factor solution and formed by the phosphate tricalcium artificial bone.This novel artificial bone is transplanted in the human body, skeletal growth factor is slowly discharged and induce new bone formation, promptly induce typical cephacoria differentiation mesenchymal cell to enter cartilage and bone, cause that chromatin ossify and the formation area of new bone in the body, can be applicable to that bone is damaged, multiple operations such as bone does not connect, bone remodelling, cranium are outer, shaping, and biologically active forms synostosis, no immunoreation with body.
Description
The invention belongs to a kind of prosthetic material, relate in particular to a kind of cmposite artificial bone and production technology thereof.
Past, when on hospital clinical, running into the damaged or nonunion of bone, general employing patient replaces or filling from body bone or corpse bone, the former is owing to the hardship that deficiency and patient from the body bone are subjected to once to operate on more impels the medical personnel to look for another way, latter Ze Yin corpse bone is the material that does not have life, can not induce and produce new bone, can't be used for old fracture and nonunion case, 90 years Decembers of Chinese patent disclosed a kind of " hydroox apatite artificial bone material preparation method " on the 12nd, though the preparation technology of this material is simple, raw material cheaply is easy to get, be displaced to human body after skeletonization not good, do not possess biological activity, effect is not satisfactory.
In recent years, research about skeletal growth factor has become one of important topic of orthopedics circle, there is the research report to confirm, skeletal growth factor is the non-collagen tissue in the decalcified bone matrix, be a kind of acid glycoconjugates albumen, for being prevalent in a kind of osteogenic induction factor in the vertebrates bone matrix, it can induction of vascular around in the periosteum, to be converted into the irreversibility bone be cell for the mesenchymal cell that moves about in the bone marrow, thereby can be at the bone marrow position or any position beyond the skeleton produce bone and osseous tissue.
The physicochemical property of skeletal growth factor, skeletal growth factor are a kind of hydrophobic glycoproteins, tightly are enclosed in the tropocollagen molecule.Also have and think that skeletal growth factor is stored in the lacuna wall of osteocyte, mainly contain albumen (in the albumen again based on aspartic acid, aminoacetic acid and serine) hydroxyproline in the molecule, amidohexose, calcium, compositions such as phosphorus.Its molecular weight is in 20,000 to 63,000 scope.Skeletal growth factor is insoluble in water, is soluble in non-polar solven, and it has the ability of certain anticollagenase, but is vulnerable to the influence of endogenous enzymes or foreign protein hydrolytic enzyme.The active optimum temperature of skeletal growth factor is 20～37 ℃, and PH 7.0～7.4, loses biological activity greater than 70 ℃ the time.The extraction of skeletal growth factor according to skeletal growth factor hydrophobic, can not be high temperature resistant and guanidine hydrochloride albumen saccharide, glycoprotein and other proteic characteristic can be proposed, under solution state, handle the decalcification bones and extract skeletal growth factors with neutral salt solution and dissolution factor etc.
Purpose of the present invention arises from the basis of above-mentioned research and a kind of novel artificial bone that proposes just, and promptly skeletal growth factor and phosphate tricalcium artificial bone's synthesizes.
Cmposite artificial bone of the present invention floods skeletal growth factor solution by the phosphate tricalcium artificial bone and forms, and the phosphate tricalcium artificial bone is preferably porous matter.Its specific embodiment is: the phosphate tricalcium artificial bone is immersed in the skeletal growth factor solution, and the molten long-pending ratio of its weight is 1mg: 1ml, stirs 5～22 hours under 18 °～20 ℃ temperature with magnetic stirrer, promptly gets cmposite artificial bone through freezing draining again.
Phosphate tricalcium artificial bone among the present invention makes by the following method: with tertiary sodium phosphate with anhydrous calcium chloride and add ammonium water and mix, temperature is controlled at 70 °～100 ℃, reacted 2～6 hours, vacuum filtration goes out solid matter, be dried pulverizing adding 20～100 purpose naphthalenes or hydrogen peroxide, bonding agent, water mediation more evenly, be processed into required form, promptly got the phosphate tricalcium artificial bone in 3～6 hours through 900～1300 ℃ of sintering.Its technical specification Ca/P 1.4～1.67, porosity 〉=40%, aperture 100～500 microns/〉=15%, side pressure strength 30kg.
Skeletal growth factor among the present invention adopts following method to extract: the skeletal grain that the rabbit long bone is crushed to 1～10 cubic millimeter, add 0.4～0.6N mixed in hydrochloric acid, make the complete decalcification of skeletal grain, after removing by filter cellulose and residue by 0.11～0.22 micron cellulose acetate membrane in aperture, chloroform with 1: 1: methanol reaches complete defat dehydration, reuse 1～2M calcium oxide, 0.5～1M EDTANa(editic acid sodium), 4～6M lithium chloride is transformed into gelatin to ossein respectively, 4～6M carbamide and 0.3～0.5M calcium oxide aqueous solution will be added again in this bone matrix gelatin, stirred 24～72 hours with magnetic stirrer, skeletal growth factor promptly extracts from gelatin with the form of skeletal growth factor/carbamide, use the cellulose acetate membrane filtration in 0.22 micron in aperture at last, dialyse through the 5mmol/L sodium azide, promptly get skeletal growth factor solution purely, for ease of long preservation, can skeletal growth factor solution is centrifugal 20～30 minutes with 36000 rev/mins, precipitate is a skeletal growth factor, drain through the freezing machine of draining, deepfreeze is standby through cobalt 60 irradiation or after with oxirane disinfection.
This cmposite artificial bone is transplanted in the human body, skeletal growth factor is slowly discharged and induce new bone formation, promptly induce typical cephacoria differentiation mesenchymal cell to enter cartilage and bone, cause that chromatin ossify and the formation area of new bone in the body, it is damaged to can be applicable to bone, bone does not connect, bone remodelling, outside the cranium, multiple operation such as shaping and dentistry, it becomes the transplanting that can generate biological tissue to the transplanting of xenobiotic in the past, and there is not an immunoreation, it makes bone does not connect, bone is damaged, past such as bone remodelling, the many problems that can't improve solution were readily solved, and its application will make orthopedics circle step greatly forward and go a step further.
Embodiment 1:
1, the preparation method of skeletal growth factor
(1), gets bone, pulverizing, decalcification
Get the rabbit limb long tubular bone, remove soft tissue and bone marrow, bone meal is broken to skeletal grain about 1～10 cubic millimeter, with ice-cold water washing for several times, in (weight ratio) 1: 10 ratio, with the mixed in hydrochloric acid of bone meal and 0.6N, temperature is at 4 ℃, mixture is packed into (the bag filter molecular weight ranges is 5000～10000) in the acetate fiber bag filter, be immersed in the 0.6N hydrochloric acid solution 36 hours, make the complete decalcification of skeletal grain.
(2), filtration treatment
Remove by filter residue with the 0.22 micron cellulose acetate membrane in aperture, the solid-based pledge is moved in the large beaker, with 1: 1 chloroform: methanol reached complete defat and dewaters, reuse 2M calcium chloride, and 0.5M EDTANa, the 6M lithium chloride is transformed into gelatin to ossein.
(3), stir, filter, dialyse
Getting bone matrix gelatin joins and contains in 6M carbamide and the 0.5M calcium chloride 500ml aqueous solution, stirred 48 hours with magnetic stirrer, skeletal growth factor is extracted from gelatin, with the 0.22 micron cellulose acetate membrane filtration in aperture, through 5mmol/L sodium azide dialysis 50 hours, the solution in this bag filter was skeletal growth factor solution.
(4), centrifugal, lyophilizing, preservation
With skeletal growth factor solution with 36000 rev/mins centrifugal 30 minutes, precipitate is a skeletal growth factor, drains with the freezing machine of draining, deepfreeze is standby after cobalt 60 irradiation.
2, phosphate tricalcium artificial bone's preparation method
(1), raw material specification a, tertiary sodium phosphate analytical pure, b, anhydrous calcium chloride analytical pure, c, ammonium water analysis are pure
(2), the 2+NaCL of chemical equation Na3PO+CaCL2 → Ca3(PO4)
(3), technical process:
Tertiary sodium phosphate 200 gram is dissolved in is heated to 100 ℃ in 600 ml waters, other takes by weighing 70 gram anhydrous calcium chlorides and is dissolved in and is heated to 100 ℃ in the 400ml water.Add 5ml ammonium water in trisodium phosphate solution, the calcium chloride solution with heat under stirring adds tertiary sodium phosphate, aqueous ammonium reaction 2～6 hours, and vacuum filtration goes out solid matter (being tricalcium phosphate), drying and crushing.The 50 purpose naphthalenes, bonding agent, the water that add screening afterwards in this powder are in harmonious proportion evenly, use mould molding, and 50 ℃ of dryings 24 hours down, the temperature sintering with 1200 ℃ promptly got the phosphate tricalcium artificial bone in 5 hours in high temperature furnace then with article shaped.
3, the preparation of cmposite artificial bone
The phosphate tricalcium artificial bone who has made is dipped in the dissolved skeletal growth factor solution (dissolving with carbamide) again, its weight is molten to be amassed than 1mg: 1ml, stirs 15 hours under 20 ℃ of temperature through magnetic stirrer, drains, sterilizes, packs through freezing, deepfreeze, long preservation is standby.
Embodiment 2:
1, the preparation method of skeletal growth factor
(1), gets bone, pulverizing, decalcification
Get the rabbit limb long tubular bone, remove soft tissue and bone marrow, bone meal is broken into skeletal grain about 3～8, with the about 4 ℃ ice-cold water washing of temperature 3 times, in 1: 10 ratio (weight ratio), with 1 part of skeletal grain and 10 parts of 0.4N mixed in hydrochloric acid, temperature is at 4 ℃, mixture is packed in the acetate fiber bag filter, be immersed in the 0.4N hydrochloric acid solution 48 hours, make the skeletal grain decalcification.
(2), filtration treatment
Remove by filter residue with the 0.22 micron cellulose acetate membrane in aperture, the solid-based pledge is moved in the large beaker, with 1: 1 chloroform: methanol 50ml reached complete defat and dewaters, reuse 1M calcium chloride, and 1M EDTANa, the 4M lithium chloride is transformed into gelatin to ossein.
(3), stir, filter, dialyse
Getting bone matrix gelatin joins and contains in 4M carbamide and the 0.3M calcium chloride water, stirred 60 hours with magnetic stirrer, skeletal growth factor is extracted from gelatin, with the 0.22 micron cellulose acetate membrane filtration in aperture, through the dialysis of 5mmol/L sodium azide, promptly get skeletal growth factor solution.
2, the preparation method of phosphate tricalcium artificial bone and cmposite artificial bone:
The preparation of tricalcium phosphate raw material is with embodiment 1, the hydrogen peroxide, bonding agent, the water that add 2% in the tricalcium phosphate raw material for preparing are in harmonious proportion evenly, be pressed into 2 * 2 * 2 or 1 * 1 * 2 cubic decimeters little bar-shaped with mould, with article shaped 100 ℃ of dryings 48 hours, then in high temperature furnace with 1100 ℃ of following sintering 6 hours, get the phosphate tricalcium artificial bone, the ethane via epoxyethane sterilization is after 6 hours, with 20 milligrams of phosphate tricalcium artificial bone 10 gram and dissolved skeletal growth factors again, be in harmonious proportion evenly, place aseptic following half an hour, can be directly used in surgical patient.
In the past few years, my institute's clinical practice cmposite artificial bone is totally 31 routine patients, old fracture of shaft of femur disunion patient 13 examples wherein, old fracture of femoral neck disunion patient 6 examples; Tibia and femur fibrous dysplasia patient 2 examples; Damaged patient's 1 example of distal radius bone; Idiopathic scoliosis orthopedic procedure posterior spinal fusion patient 2 examples, right hand fifth metacarpal bone enchondroma patient 1 example, two ankle joint old fracture patient 1 examples of right foot; Toes old fracture disunion patient 2 examples.Maximum 57 years old of 31 routine patient age, minimum 7 years old, women's 4 examples, male's 27 examples.Wherein the old fracture disunion time the longest 2 years, the shortest two months, 9 * 4 * 3 cubic centimetres of the damaged maximum areas of fibrous dysplasia patient bone.31 routine patient's perioperativelies have all been made the mensuration of biochemistry, potassium, sodium, calcium, chlorine, zinc, copper, ferrum, magnesium and hepatic and renal function, all in normal range value.Example: old fracture disunion patient, make internal fixation operation of cutting and resetting 3 times in local hospital, wherein use the ilium bone grafting in 2 operations, the bone that postoperative was planted in 3 months absorbs fully, hardens fully in the fracture two ends, and medullary cavity disappears, pseudoarticulation formation, the damaged 2.5cm that reaches of bone comes to use in the operation after my institute cmposite artificial bone of the present invention, and postoperative 5 all X-ray films show growth of spur, decay appears in the phosphate tricalcium artificial bone behind 3 first quarter moons, decay is finished after 6 months, and callus plasticity is good, and effect is fine.
Claims (5)
1, a kind of cmposite artificial bone, it is to be composited by skeletal growth factor and phosphate tricalcium artificial bone.The invention is characterized in: cmposite artificial bone soaks skeletal growth factor solution by phosphate tricalcium artificial bone's stain and forms.
2, cmposite artificial bone according to claim 1 is characterized in that: used phosphate tricalcium artificial bone is for porous matter.
3, the technology of the described cmposite artificial bone of a kind of production claim 1, it is characterized in that: the phosphate tricalcium artificial bone is immersed in the skeletal growth factor solution, the molten long-pending ratio of its weight is 1mg: 1ml, stirred 5～22 hours down at 18 ℃～20 ℃ with magnetic stirrer, promptly get cmposite artificial bone through freezing draining again.
4, production technology according to claim 3, it is characterized in that: the phosphate tricalcium artificial bone is by tertiary sodium phosphate and adds the mixing of ammonium water, temperature is controlled at 70 °～100 ℃, reacted 2～6 hours, vacuum filtration goes out solid matter, be dried again pulverize to add 20～100 purpose naphthalenes or hydrogen peroxide, bonding agent, water is in harmonious proportion evenly, is processed into required form through 900 °～1300 ℃ sintering 3～6 hours, promptly gets the phosphate tricalcium artificial bone.
5, production technology according to claim 3, it is characterized in that: skeletal growth factor is to be made by following method, the rabbit long bone is crushed to 1～10 cubic millimeter skeletal grain, add 0.4～0.6N mixed in hydrochloric acid, make the complete decalcification of skeletal grain, after cellulose acetate membrane by 0.11～0.22 micron in aperture removes by filter cellulose and residue, chloroform with 1: 1: methanol reaches complete defat dehydration, reuse 1～2M calcium oxide, 0.5～1M EDTANa(editic acid sodium), 4～6M lithium chloride is transformed into gelatin to ossein respectively, 4～6M carbamide and 0.3～0.5M calcium oxide aqueous solution will be added again in this bone matrix gelatin, stirred 24～72 hours with magnetic stirrer, skeletal growth factor promptly extracts from gelatin with the form of skeletal growth factor/carbamide, use the cellulose acetate membrane filtration in 0.22 micron in aperture at last,, promptly get skeletal growth factor solution through the dialysis of 5mmol/L sodium azide.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 92104430 CN1079401A (en) | 1992-06-04 | 1992-06-04 | Cmposite artificial bone and production technology thereof |
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| CN 92104430 CN1079401A (en) | 1992-06-04 | 1992-06-04 | Cmposite artificial bone and production technology thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102284082A (en) * | 2011-07-01 | 2011-12-21 | 董萍 | Facial fibrous protein composite filled and positioned in subcutaneous soft tissues, and preparation method thereof |
| CN108904891A (en) * | 2018-07-26 | 2018-11-30 | 西南医科大学附属医院 | A kind of multiporous biological active bone cement and preparation method thereof |
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1992
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102284082A (en) * | 2011-07-01 | 2011-12-21 | 董萍 | Facial fibrous protein composite filled and positioned in subcutaneous soft tissues, and preparation method thereof |
| CN102284082B (en) * | 2011-07-01 | 2014-03-26 | 董萍 | Facial fibrous protein composite filled and positioned in subcutaneous soft tissues, and preparation method thereof |
| CN108904891A (en) * | 2018-07-26 | 2018-11-30 | 西南医科大学附属医院 | A kind of multiporous biological active bone cement and preparation method thereof |
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