CN103656759A - composite bone cement - Google Patents
composite bone cement Download PDFInfo
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- CN103656759A CN103656759A CN201210396521.4A CN201210396521A CN103656759A CN 103656759 A CN103656759 A CN 103656759A CN 201210396521 A CN201210396521 A CN 201210396521A CN 103656759 A CN103656759 A CN 103656759A
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- Prior art keywords
- bone cement
- bone
- collagen protein
- calcitonin
- water preparation
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- 239000002131 composite material Substances 0.000 title abstract description 4
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- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims abstract description 18
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Images
Abstract
The invention provides composite bone cement, which comprises a powder and an aqueous solution, wherein the powder comprises calcium sulfate and calcium phosphate; the aqueous preparation comprises water, collagen and an effective amount of a medicinal component. By adding collagen and the medicinal component into the aqueous solution of bone cement, the medicinal component has a slow-release effect and is beneficial to the differentiation of sclerosteous cells and the repair of bone defects.
Description
Technical field
The present invention is about a kind of bone cement, espespecially a kind of plyability bone cement that can be used as medical components carrier.
Background technology
Commonly clinically by wound or tumor, remove caused bone defect, and the bone matrix that osteoporosis causes runs off, all can allow bone lose the intensity of support, and then affect patient's daily life.For the problems referred to above can be resolved, developed at present bone supplementing material for implantable bone defect with accelerated bone tissue repairing, reach the object of the osseous tissue normal function of getting well.
Good bone substitute should possess bone conductibility, osteoinductive, bio-compatibility, biological absorbable,, easily use similar with bone structure, and cheap.The ceramic material being comprised of calcium salt class is applied to dentistry and orthopaedics since the 1980's, and good bio-compatibility and engineering properties are its major advantages.The calcium salt class of wherein more often being used comprises tricalcium phosphate (tricalciumphosphate), oxyhydrogen-base apatite (hydroxylapatite) and calcium sulfate (calcium sulfate).It can be carried and release of bioactive substances, for example somatomedin and medicine for the solid apertured structure of pottery.At present existing document demonstration can be used calcium phosphate bone cement as the carrier of cancer therapy drug (cisplatinum and methotrexate).As the calcium phosphate bone cement of carrier, being generally considered to medicine is to be adsorbed on its pore space structure surface, reaches the effect that extends release time.
The macromolecule of tool biological degradability, for example polylactic acid, gelatin, chitin, can be used as the interpolation adjuvant of ceramic bone cement.By adding adjuvant, can adjust degraded and the drug release ability of ceramic bone cement.Because the constituent of natural bone tissue comprises mineral and protein, so the bone cement of compound protein is extensively studied.The protein wherein the most often being used is collagen protein (collagen).Collagen protein is the protein that people's in-vivo content is maximum, also has many researcheres to utilize merely collagen protein to develop bone substitute, and the more common practice is that bone cement is mixed with collagen protein, reaches preferably application and biological activity.Wherein, the interpolation of the first collagen type can promote bone to rebuild (bone remodeling), and strengthen the engineering properties of bone cement, if osteoblast is incubated on the bone cement of compound the first collagen type, the hypertrophy that can observe cell will change to some extent with differentiation.
Add the method for collagen protein in bone cement, what the most simply can be used at present is that collagen protein powder is directly made an addition in bone cement powder, yet this collagen protein powder lacks restructuring ability, is similar to gelatin (collagen protein of degeneration).Another kind of newer addition manner, is that calcium salt mineralising is deposited on the collagen fabric of having recombinated, and by centrifugal concentrating, lyophilization again, the mineralized collagen of gained is sieved through grinding again, can make an addition in the powder of bone cement.See through above-mentioned two kinds of bone cements prepared by method, collagen content is had to 22.5wt% by 2.5wt%, but neither possesses and the fibre structure that in human body, the collagen protein of restructuring is identical naturally, so its biological activity is poor.
Osteoporosis is the abnormal disease of a kind of chronic bone metabolism, and with age growth, the effect between Osteoclasts and osteoblast is unbalance, causes skeleton density to reduce and formation osteoporosis.There is main cause and have three classes in it, is respectively that thyroxine and the secretion of parathormone fat absorption uneven, calcium reduces and the deficiency of active vitamin D, and wherein a kind of common Therapeutic Method is and uses calcitonin.
Calcitonin is the hormone that a kind of thyroxine is manufactured, can prevent that calcium runs off in skeleton, and promote gastrointestinal tract and renal tubules to absorb calcium and reduce blood calcium concentration, also can suppress Osteoclasts effect, prevent sclerotin from absorbing again and increase bone density, for being widely used in the medical components for the treatment of osteoporosis.The use of calcitonin is carried out with muscle injection mode conventionally clinically, and this mode is except operation is more inconvenient, and the fluctuation of concentration of medicine in blood is also easier to cause side effect.Therefore,, if calcitonin can be combined with specific bone supplementing material, in the treatment of its or osteoporosis damaged in bone, will there are certain potentiality.Yet the past is for the many management about cardiovascular disease or diabetes of the research using implant as drug delivery system, it is in the relevant application of orthopaedics stage in the early stage still.
In sum, still need a kind of can be as the carrier of orthopaedics medical components, possess height biological activity, and can effectively shorten the plyability bone cement of bone defect healing time.
Summary of the invention
This case proposes a kind of plyability bone cement, and it comprises a powder and a water preparation, and wherein this powder comprises calcium sulfate and a calcium phosphate; The medical components that this water preparation comprises water, collagen protein and effective dose.
According to above-mentioned conception, wherein this medical components is preferably a polypeptide.
According to above-mentioned conception, wherein this medical components is more preferred from calcitonin.
According to above-mentioned conception, the form that wherein this medical components discharges with long-acting release or control is disengaged in this plyability bone cement.
Aforementioned long-acting release refers to that the release time of this medical components is higher than action time oral or injection; Control release and refer to the rate of release capable of regulating of this medical components, and maintain steady rate a period of time.
According to above-mentioned conception, wherein the concentration expressed in percentage by weight of collagen protein in this water preparation is 0.01% to 0.1%.
According to above-mentioned conception, wherein the ratio of this powder weight and this water preparation volume is 2 g of weights: 1 milliliter to 3 g weight: 1 milliliter.
According to above-mentioned conception, wherein this water preparation further comprises normal saline solution.
A kind of bone cement with bone defect repairing ability of the another proposition of this case, it comprises a powder and a water preparation, and wherein this powder comprises calcium sulfate and a calcium phosphate; This water preparation comprises water and collagen protein.
According to above-mentioned conception, wherein the concentration expressed in percentage by weight of collagen protein in this water preparation is 0.01% to 0.1%.
According to above-mentioned conception, wherein the ratio of this powder weight and this water preparation volume is 2 g of weights: 1 milliliter to 3 g weight: 1 milliliter.
According to above-mentioned conception, wherein collagen protein is preferably the first collagen type.
According to above-mentioned conception, wherein this water preparation further comprises a medical components of effective dose.
According to above-mentioned conception, wherein this medical components is preferably a polypeptide.
According to above-mentioned conception, wherein this polypeptide is preferably calcitonin.
According to above-mentioned conception, the form that wherein calcitonin discharges with long-acting release or control is disengaged in this bone cement.
According to above-mentioned conception, wherein this calcium phosphate selects the group that free oxyhydrogen-base apatite, calcium phosphate, dicalcium phosphate, tricalcium phosphate, tetracalcium phosphate, OCP and combination thereof form.
According to above-mentioned conception, wherein this calcium phosphate is preferably oxyhydrogen-base apatite.
The present invention makes an addition to collagen protein in the water preparation of bone cement in advance as the carrier of medical components, be present in the fibre structure that collagen molecules possesses with in human body, the collagen protein of restructuring is identical naturally in water preparation, so its biological activity is higher.By aforementioned water preparation and powder mixing cured after, the bone supplementing material of gained is similar on the one hand skeleton and forms, and also can have on the other hand the effect of medical components in the middle of slow release.
See through interpolation collagen protein and calcitonin in the water preparation of bone cement, after mixing with powder, formed bone cement can make calcitonin possess the effect of slow release, and contribute to the repairing that os osseum cell differentiation and bone are damaged, its therapeutic effect, higher than general bone cement, has the potentiality of clinical practice.
Bone cement provided by the present invention can be used as the bone supplementing material that carries calcitonin, in the process of slowly decomposing at this bone supplementing material, can produce hole grows into by osteocyte, the simultaneously slow release of calcitonin can long-lasting activatable osteocyte and is suppressed the effect of erosion bone, the efficiency of calcium deposition is improved, the effectively healing of accelerated bone defect.
Accompanying drawing explanation
Fig. 1 shows the external degradation test result of each bone cement sample.
Fig. 2 shows the X-ray diffraction collection of illustrative plates of each bone cement sample.
Fig. 3 A shows the curve that calcitonin discharges in bone cement sample.
Fig. 3 B is converted to by the 3rd figure A the result presenting on logarithmic coordinates axle.
Fig. 4 A shows with each its WST-1 test result of bone cement sample extract cultured cells.
Fig. 4 B shows with each bone cement sample extract cultured cells ALP active.
Fig. 5 A is the os osseum section outside drawing of zoopery collagen protein group in the time of the 4th week.
Fig. 5 B is the area of new bone Fluirescence observation result figure of zoopery collagen protein group in the time of the 4th week.
Fig. 5 C is the partial enlarged drawing of zoopery area of new bone Fluirescence observation result of collagen protein group in the time of the 4th week.
Fig. 5 D is the section X light analysis result figure of zoopery collagen protein group in the time of the 4th week.
Fig. 5 E is the os osseum section outside drawing of zoopery compound calcitonin group of collagen protein in the time of the 4th week.
Fig. 5 F is the area of new bone Fluirescence observation result figure of zoopery compound calcitonin group of collagen protein in the time of the 4th week.
Fig. 5 G is the partial enlarged drawing of zoopery area of new bone Fluirescence observation result of the compound calcitonin group of collagen protein in the time of the 4th week.
Fig. 5 H is the section X light analysis result figure of zoopery compound calcitonin group of collagen protein in the time of the 4th week.
Fig. 5 I is the os osseum section outside drawing of zoopery collagen protein group in the time of the 12nd week.
Fig. 5 J is the area of new bone Fluirescence observation result figure of zoopery collagen protein group in the time of the 12nd week.
Fig. 5 K is the partial enlarged drawing of zoopery area of new bone Fluirescence observation result of collagen protein group in the time of the 12nd week.
Fig. 5 L is the section X light analysis result figure of zoopery collagen protein group in the time of the 12nd week.
Fig. 5 M is the os osseum section outside drawing of zoopery compound calcitonin group of collagen protein in the time of the 12nd week.
Fig. 5 N is the area of new bone Fluirescence observation result figure of zoopery compound calcitonin group of collagen protein in the time of the 12nd week.
Fig. 5 O is the partial enlarged drawing of zoopery area of new bone Fluirescence observation result of the compound calcitonin group of collagen protein in the time of the 12nd week.
Fig. 5 P is the section X light analysis result figure of zoopery compound calcitonin group of collagen protein in the time of the 12nd week.
Fig. 6 shows the os osseum calcification degree with radiation analysis zoopery tissue slice.
The specific embodiment
This case " plyability bone cement " can see through following embodiment explanation and allow those skilled in the art understand its creation spirit, and can complete according to this.The enforcement of this case is not limited it and implements kenel by following embodiment.
For confirming that bone cement constituent proposed by the invention has bone inducibility and other profitable matter, physical property for bone cement, such as setting time, mechanical strength, porosity, crystal structure, water absorbing force, external degradation speed etc., carries out experimental verification.And the rate of release of calcitonin in bone cement, with and extract the impact of stem cell os osseum differentiation is also inquired into some extent.Finally carry out zoopery, by bone cement without calcitonin and compound calcitonin simultaneously and respectively implantable bone damaged in, after certain hour, take out the speed that osseous tissue assessment os osseum is repaired.Wherein the configuration mode of each bone cement sample is as described below.
As physical property and biological activity test, each sample has been used and has not contained the first collagen type (Type I Collagen) normal saline solution agent of calcitonin, difference according to collagen protein concentration expressed in percentage by weight in water preparation, can be divided into and not add, add several groups of collagen protein 0.01%, 0.05% and 0.1% etc., and collagen protein (concentration expressed in percentage by weight 0.1%) the normal saline solution agent that contains calcitonin (3200IU/ml equals 0.5mg/ml).In powder, contain 75% calcium sulfate and 25% oxyhydrogen-base apatite.Wherein the particle diameter of oxyhydrogen-base apatite is 5 to 15 microns, and the particle diameter of calcium sulfate is 15 to 35 microns.The mixed ratio of powder and water preparation is that 2.2 grams of powder add 1 milliliter of water preparation.
Setting time test
Setting time test is that the standard of formulating according to American Society for Testing Materials (ASTM C266-08e1) operates.First the bone cement mixing is applied on flat glass sheet, approximately 0.5 centimeter of thickness, re-uses the test initial set of Fred Gilmore coomb's test Coomb instrument and final setting time.Presetting period is used bodkin (0.3MPa) test, and the initial time occurring without impression in bone cement plane is the presetting period, and 3 diverse locations of follow-on test are confirmed.Final setting time is with fine needle (5MPa) test, and the initial time occurring without impression in bone cement plane is final setting time, and 3 diverse locations of follow-on test are confirmed.Test environment is 25 ℃ of temperature, humidity 60%.The setting time test result of each bone cement sample is as shown in following table one, wherein mark the project of a and be less than 0.001 without the P value (P-value) between same-sign person, mark the project of b and be less than 0.05 without the P value between same-sign person, mark the project of c and be less than 0.001 without the P value between same-sign person.
The setting time test result of table one, each bone cement sample
| Test event | Presetting period (minute) | Final setting time (minute) |
| Do not add collagen protein | 5.33±0.27 | 9.33±0.27 |
| Containing 0.01% collagen protein | 5.42±0.32 | 9.42±0.42 |
| Containing 0.05% collagen protein | 5.42±0.17 | 10.17±0.58(b) |
| Containing 0.1% collagen protein | 8.75±0.32(a) | 19.75±0.92(b,c) |
| Containing 0.1% collagen protein and calcitonin | 9.00±0.27(a) | 20.00±0.86(b,c) |
At collagen protein, add less in the situation that (in water preparation containing 0.01% and 0.05%), the setting time of bone cement is very approaching, influenced hardly with the control group of not adding collagen protein.Yet when in water preparation, collagen concentration brings up to 0.1%, no matter initial set or final setting time all significantly increase, and are almost the twice of not adding collagen protein group.Can find in addition, the interpolation of calcitonin does not affect setting time yet.Although bone cement can extend it after adding collagen protein, solidify required time, on clinical manipulation, the setting time of 20 minutes still within the acceptable range.
The test of bone cement porosity
Bone cement is packed into mould and after its sclerosis, lyophilization one day, with true high density instrument (Pycnometer) test bone cement porosity, can obtain the data of following table two.
Table two, bone cement porosity test result
By data, can be learnt, add the bone cement sample of collagen protein, its porosity all drops in 46% to 48% scope, and its porosity of bone cement that additionally adds calcitonin drops to 44.4% a little, but with other group difference little.
The test of bone cement water absorbing force
By bone cement be packed into mould and until its sclerosis after, lyophilization one day, weighing weight, is called dry weight.Again dry bone cement is inserted in intermediate water and soaked three hours, with tweezers, pick up and remove weighing after excessive moisture, be called weight in wet base.The weight difference of dry weight and weight in wet base is its water weight absorbing, and the percentage ratio that the water absorbing heavily accounts for original dry weight is water suction ratio, can obtain the data of following table three, wherein marks the project of a and is less than 0.001 without the P value between same-sign person.
The water absorbing force test result of table three, bone cement
Data can be found out thus, have the bone cement that adds collagen protein, and its water suction ratio all drops in 23% to 26% scope, and to each other without significant difference, that is the amount of collagen protein not affects the principal element of water suction ratio.
The test of bone cement stress intensity
Bone cement is injected to mould, after 37 ℃ of waits are solidified 24 hours, become 6 mm dias, 12 millimeters of high cylinders, and the demoulding.Material Testing Machine is used in sample test, at room temperature carries out, and compression speed is 1 centimetre per minute.Data occur that the highest intensity level is maximum stress, linear stress-strain curve that the test initial stage occurs, and its slope is modulus of elasticity.Result is as shown in following table four.
Table four, stress intensity (Compressive Strength) test result
Data by table four can be learnt, add the bone cement of collagen protein and the bone cement that additionally adds again calcitonin, after sclerosis twenty four hours, measured stress intensity declines a little, but there is no significant difference (the P value between each group is all greater than 0.05), and its modulus of elasticity also changes not quite, can think that thus the interpolation of collagen protein and calcitonin does not affect the engineering properties of final bone cement.
External degradation test
Each bone cement sample is soaked in (not comprising calcitonin group) in the PBS aqueous solution of 37 ℃, in the time point of setting, sample is taken out and 37 ℃ dry 24 hours after weighing.The PBS aqueous solution that the complete sample of weighing is inserted preparation again is again maintained at 37 ℃, test time-histories 2 totally months (not containing drying time).The weight that degraded percentage ratio is loss is multiplied by absolutely divided by original weight.
Fig. 1 shows the external degradation curve of each bone cement sample, and wherein transverse axis is elapsed time (day), the percentage ratio that the longitudinal axis is residuals weight.By the 1st figure, can be found, add 0.1% collagen protein in water preparation, can allow bone cement degradation speed ease up, in the time of the 8th week, also retain 93.5%, add 0.05% collagen protein similar with the degradation rate of control group bone cement (remaining respectively 90.8% and 90.2%), and add 0.01% collagen protein, in water preparation, can allow on the contrary bone cement degraded accelerate, in the time of the 8th week, also retain 88.3%.
The experiment of X-ray diffraction
Sample powder by simple bone cement powder and five groups of experimental grouies (37 ℃, curing 24 hours), carries out crystal structure analysis with X-ray diffractometer.Adopt the filtered Cu target of monocrystalline K α layer ray (λ=1.5405E, 120mA, 40kV), continuous sweep (8 °/min, 2 θ scopes are from 10 ° to 60 °).
Fig. 2 shows the X-ray diffraction collection of illustrative plates of each bone cement sample.As shown in Figure 2, utilize X-ray diffraction to measure the crystal structure of bone cement, can find to add collagen protein and calcitonin not to affect the crystalline texture of bone cement.
The release of calcitonin test in bone cement
The bone cement sample of coated calcitonin is soaked in normal saline solution and sealing, wherein adds 0.01% sodium azide (sodium azide) and prevent bacterial growth.Sample in above-mentioned immersion is placed under 37 ℃, 100rpm concussion frequency.Each time point is got 80 μ L and is carried out calcitonin measurement of concetration, and sample continues to soak until next time point after covering 80 μ L normal saline solutions.The 80 μ L release liquid elder generations that extract centrifugal 20 minutes with 42000g, get supernatant 50 μ L and measure calcitonin concentration with the high-effect chromatograph of liquid of anti-phase (HPLC).HPLC is used C8 tubing string, is placed in 35 ℃ of constant temperature, and eluate is detected with wavelength 210nm.Each sample repeat number is three.The burst size of last gained, according to Korsmeyer – Peppas model (M
t/ M
∞=kt
n) analyze its medical components release behavior, wherein M
tfor the cumulative release amount of certain time point, M
∞for original total coated dose.
Fig. 3 A is the curve that calcitonin discharges in bone cement sample, the cumulative release ratio that the longitudinal axis is calcitonin, and transverse axis is the time.Fig. 3 B for to present the results conversion of Fig. 3 A to logarithmic coordinates axle, and wherein the longitudinal axis is that calcitonin burst size is applied mechanically equational M
t/ M
∞value, transverse axis is for take ten logarithms that are the truth of a matter.
As shown in Fig. 3 A and Fig. 3 B, calcitonin is covered by after the bone cement containing collagen protein, and its release behavior can be divided into two stages, take the 3rd day be boundary.A few days ago can first discharge fast about 4.6% content, speed is approximately 2.33%/sky, and the 1 gram of bone cement (approximately containing 227.27 μ g calcitonin) of take is example, and being scaled calcitonin burst size is 5.3 μ g/ days.The 3rd day starts, it is 0.33%/sky that rate of release slows down, be about a few days ago 1/7th, the 1 gram of bone cement (approximately containing 227.27 μ g calcitonin) of take is example, being scaled calcitonin burst size is 750ng/ days, thereafter up to approximately discharging 22.4% of covering amount altogether till the 8th week, curve also shows the effect of long-acting release.To discharge nest with after equation calculating, can find that its release is that two kinds of modes of mating surface diffusion and carrier erosion are carried out simultaneously.
Hyperplasia and the test of bone inducibility
The promotion hyperplasia ability of bone cement and os osseum inductivity are that the extract of getting bone cement is tested.After respectively organizing bone cement sample and solidifying, under ultraviolet light, irradiate and within two hours, guarantee asepticly, then sample is soaked in to 30 milliliters of DMEM (containing 1% antibiotic, containing FBS), 37 ℃ three days.Extract is got to supernatant with 3000rpm after centrifugal 15 minutes, with 0.45 micron of fracture filtration, then add 10%FBA.Sample group total (1) is not containing additive bone cement group; (2) water preparation contains 0.01% collagen protein group; (3) water preparation contains 0.5% collagen protein group; (4) water preparation contains 0.1% collagen protein group; (5) water preparation contains 0.1% collagen protein and calcitonin group; (6) forward control group; And (7) negative sense control group.Wherein only forward control group is used os osseum division culture medium, and other group is used general hyperplasia culture medium.Test adopts 48 porose discs, and extract is with ten times of dilutions of culture medium, and cell is used the Medulla Sus domestica interstital stem cell of each hole 5x103, and cell seeding second day after 48 porose discs changes the culture medium of adding containing dilution extract into.Add containing after the culture medium of extract the 1st, 3,7,11,15 days, with WST1 and ALP (Alkaline phosphatase) reagent set test cell hypertrophy and os osseum differentiation degree respectively.Wherein WST-1 cell proliferation detection method is used for test cell in activity and the growth differences of different bone cement sample extracts; And in bone metabolism anabolic effect, ALP, as the Biological indicators in bone metabolism, can reflect the metabolism state of osteocyte.
Fig. 4 A demonstration is with each its WST-1 test result of bone cement sample extract cultured cells, and the longitudinal axis is the light absorption value of wavelength 450nm, and numerical value is higher represents that its cytoactive is stronger.As shown in Figure 4 A, add collagen protein and contribute to hyperplasia, and the most obvious to add 0.1% effect.And have the experimental group that adds calcitonin, because calcitonin has the effect that promotes os osseum differentiation, so hyperplasia speed is lower, but compared with forward control group, be still high.
Fig. 4 B shows with each bone cement sample extract cultured cells ALP active, the longitudinal axis be ALP activity divided by DNA concentration, represent that the ALP of per unit DNA is active.As shown in Figure 4 B, bone cement extract containing calcitonin is carried out after 10 times of dilutions, be added in stem cell os osseum inducing culture, ALP specific activity in the time of the 15th day is only added the group of collagen protein for high, infers the effect that truly has short os osseum differentiation adding containing calcitonin bone cement extract.
Zoopery
Utilize operation in New Zealand white rabbit both sides Thigh bone lateral epicondyles (femoral condyle) manufacturing defect, control its defect size and shape, implantable bone material for repairing subsequently, and with same rabbit to side seam defect as a control group, carry out the experiment (to three months) of different time course, condition is as shown in following table five:
Table five, zooperal condition are set
Experiment rabbit was alternately injected fluorescent agent calcein (Calcein) and xylenol orange (Xylenol Orange) after operation every two weeks.After sacrificing rabbit, the osseous tissue of regeneration is carried out to pathological section analysis, process is first fixing with 10% neutral buffered formalin (neutral buffered formalin), with diamond microtome, sample is cut into equal thickness thin slice, and take pictures to analyze knitting density with X-ray machine, and take area of new bone fluorescence with fluorescence anatomic microscope.After sample decalcification being completed, be embedded in the upper machine section of paraffin, use the effectiveness of assessment bone supplementing material, and analyze remaining material for repairing, judge its biolytic degree, and whether cause immunoreation thereafter.
Fig. 5 A is the os osseum section outside drawing of zoopery collagen protein group in the time of the 4th week; Fig. 5 B is the area of new bone Fluirescence observation result figure of zoopery collagen protein group in the time of the 4th week; Fig. 5 C is the partial enlarged drawing of zoopery area of new bone Fluirescence observation result of collagen protein group in the time of the 4th week; Fig. 5 D is the section X light analysis result figure of zoopery collagen protein group in the time of the 4th week.Fig. 5 E is the os osseum section outside drawing of zoopery compound calcitonin group of collagen protein in the time of the 4th week; Fig. 5 F is the area of new bone Fluirescence observation result figure of zoopery compound calcitonin group of collagen protein in the time of the 4th week; Fig. 5 G is the partial enlarged drawing of zoopery area of new bone Fluirescence observation result of the compound calcitonin group of collagen protein in the time of the 4th week; Fig. 5 H is the section X light analysis result figure of zoopery compound calcitonin group of collagen protein in the time of the 4th week.Fig. 5 I is the os osseum section outside drawing of zoopery collagen protein group in the time of the 12nd week; Fig. 5 J is the area of new bone Fluirescence observation result figure of zoopery collagen protein group in the time of the 12nd week; Fig. 5 K is the partial enlarged drawing of zoopery area of new bone Fluirescence observation result of collagen protein group in the time of the 12nd week; Fig. 5 L is the section X light analysis result figure of zoopery collagen protein group in the time of the 12nd week.Fig. 5 M is the os osseum section outside drawing of zoopery compound calcitonin group of collagen protein in the time of the 12nd week; Fig. 5 N is the area of new bone Fluirescence observation result figure of zoopery compound calcitonin group of collagen protein in the time of the 12nd week; Fig. 5 O is the partial enlarged drawing of zoopery area of new bone Fluirescence observation result of the compound calcitonin group of collagen protein in the time of 12 weeks; Fig. 5 P is the section X light analysis result figure of zoopery compound calcitonin group of collagen protein in the time of the 12nd week.Every picture group is all usingd same a slice section as representative.Known according to Fig. 5 A ~ Fig. 5 P, no matter be the bone cement that adds merely collagen protein or contain calcitonin and collagen protein, there is the growth (fluorescence staining) of obvious freshman bone tissue.
Fig. 6 shows the os osseum calcification degree with radiation analysis zoopery tissue slice, the calcification percentage ratio that the representative of longitudinal axis numerical value is relative with normal bone.As shown in Figure 6, fill containing the bone of calcitonin bone cement damagedly, its osseous tissue is all high compared with other group in the repairing of 4th week and the 12 week, confirms that the bone cement of composite collagen and calcitonin can allow the damaged repairing of bone quicker really.
Comprehensive above-mentioned experimental result shows, add after collagen protein and calcitonin, only collagen protein can extend the hardening time of bone cement, and no matter the interpolation of collagen protein and calcitonin whether, does not all make significant difference for stress intensity, porosity, crystal structure and the moisture content of bone cement.And can find to add in water preparation 0.1% collagen protein by external degradation experiment, and can allow the degradation speed of bone cement slow down, to the 8th week, still possess 93.5% material bodies, be conducive to the long-acting release of calcitonin.The release profiles of calcitonin also shows until only have 22.4% calcitonin to be released on the 8th week.Bone cement extract is added in the culture fluid of stem cell os osseum, and can be observed the extract that contains calcitonin only has better short os osseum differentiation effect containing the extract of collagen protein.Finally according to zooperal result, show that the bone of filling containing calcitonin bone cement is damaged, its osseous tissue is all high compared with other group in the repairing of 4th week and the 12 week, confirms that the bone cement of composite collagen and calcitonin can the damaged repairing of accelerated bone.
By the plyability bone cement containing calcitonin provided by the present invention, its physical property is with the bone cement containing additive is not almost identical, also can be with general bone cement in same condition and under needing operation use, and the release of calcitonin also can reach more than eight weeks, possesses the effect of slow release.Via cell and zoopery test, confirm that the bone cement that adds calcitonin contributes to os osseum cell differentiation and the damaged repairing of bone really in addition.
The present invention, except can generally the mode of smearing is used, if be filled in syringe before sclerosis after material mixing, can inject the damaged hole of os osseum that be difficult to filling via injection system, and can be applicable to the fields such as orthopaedics and dentistry doctor material, bone substitute.
Above carrying is only the better embodiment of this case, is not intended to limit the practical range of this case, and any technical staff in this field changes and modifies not departing from as do under the spirit of this case and scope all, de-as protector that attached claim is wanted.
Claims (17)
1. a plyability bone cement, it comprises a powder and a water preparation, and wherein this powder comprises calcium sulfate and a calcium phosphate; The medical components that this water preparation comprises water, collagen protein and effective dose.
2. plyability bone cement as claimed in claim 1, is characterized in that, this medical components is a polypeptide.
3. plyability bone cement as claimed in claim 1, is characterized in that, this medical components is calcitonin.
4. the plyability bone cement as described in arbitrary claim in claims 1 to 3, is characterized in that, the form that this medical components discharges with long-acting release or control is disengaged in this plyability bone cement.
5. plyability bone cement as claimed in claim 4, is characterized in that, the concentration expressed in percentage by weight of collagen protein in this water preparation is 0.01% to 0.1%.
6. plyability bone cement as claimed in claim 4, is characterized in that, the ratio of this powder weight and this water preparation volume is 2 g of weights: 1 milliliter to 3 g weight: 1 milliliter.
7. plyability bone cement as claimed in claim 4, is characterized in that, this water preparation further comprises normal saline solution.
8. a bone cement with bone defect repairing ability, it comprises a powder and a water preparation, and wherein this powder comprises calcium sulfate and a calcium phosphate; This water preparation comprises water and collagen protein.
9. bone cement as claimed in claim 8, is characterized in that, the concentration expressed in percentage by weight of collagen protein in this water preparation is 0.01% to 0.1%.
10. bone cement as claimed in claim 8, is characterized in that, the ratio of this powder weight and this water preparation volume is 2 g of weights: 1 milliliter to 3 g weight: 1 milliliter.
11. bone cements as claimed in claim 8, is characterized in that, collagen protein is the first collagen type.
12. bone cements as described in arbitrary claim in claim 8 to 11, is characterized in that, this water preparation further comprises a medical components of effective dose.
13. bone cements as claimed in claim 12, is characterized in that, this medical components is a polypeptide.
14. bone cements as claimed in claim 13, is characterized in that, this polypeptide is calcitonin.
15. bone cements as claimed in claim 14, is characterized in that, the form that calcitonin discharges with long-acting release or control is disengaged in this bone cement.
16. bone cements as claimed in claim 12, is characterized in that, the group that this calcium phosphate selects free oxyhydrogen-base apatite, calcium phosphate, dicalcium phosphate, tricalcium phosphate, tetracalcium phosphate, OCP and combination thereof to form.
17. bone cements as claimed in claim 16, is characterized in that, this calcium phosphate is oxyhydrogen-base apatite.
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| CN104523341A (en) * | 2014-12-18 | 2015-04-22 | 中国人民解放军第四军医大学 | Method for manufacturing immediately implanted tooth with periodontal bioactivity |
| CN104771785A (en) * | 2015-04-03 | 2015-07-15 | 周宏志 | Preparation method of bone repair material with neuropeptide inductive osteogenic activity |
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| CN1192700A (en) * | 1995-06-06 | 1998-09-09 | 基因科学再生实验室有限公司 | Modified osteogenic materials |
| CN1961973A (en) * | 2005-11-09 | 2007-05-16 | 同济大学 | A novel nano bone repair material and preparation method thereof |
| CN101843918A (en) * | 2010-05-27 | 2010-09-29 | 甘少磊 | Composite bone repairing material based on nano-hydroxyapatite and hemihydrate calcium sulfate and preparation method thereof |
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| SE0300620D0 (en) * | 2003-03-05 | 2003-03-05 | Bone Support Ab | A new bone substitute composition |
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| CN1192700A (en) * | 1995-06-06 | 1998-09-09 | 基因科学再生实验室有限公司 | Modified osteogenic materials |
| CN1961973A (en) * | 2005-11-09 | 2007-05-16 | 同济大学 | A novel nano bone repair material and preparation method thereof |
| CN101843918A (en) * | 2010-05-27 | 2010-09-29 | 甘少磊 | Composite bone repairing material based on nano-hydroxyapatite and hemihydrate calcium sulfate and preparation method thereof |
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| CN104523341A (en) * | 2014-12-18 | 2015-04-22 | 中国人民解放军第四军医大学 | Method for manufacturing immediately implanted tooth with periodontal bioactivity |
| CN104523341B (en) * | 2014-12-18 | 2017-06-20 | 中国人民解放军第四军医大学 | The manufacture method of the immediate implantation teeth with periodontal bioactivity |
| CN104771785A (en) * | 2015-04-03 | 2015-07-15 | 周宏志 | Preparation method of bone repair material with neuropeptide inductive osteogenic activity |
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