CN102390941B - Medical alpha-hemihydrate calcium sulfate artificial bone repairing material and preparation method thereof - Google Patents
Medical alpha-hemihydrate calcium sulfate artificial bone repairing material and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a medical alpha-hemihydrate calcium sulfate artificial bone repairing material and a preparation method thereof. The material has uniform particle size distribution, regular shape, favorable biocompatibility and wide market application prospect in the field such as a bone transplanting material and the like. In addition, the invention relates to the application of the bone repairing material and the like.
Description
Technical field
The invention belongs to the medical product field, particularly, the present invention relates to medical alpha-hemihydrate calcium sulfate artificial bone repairing material and preparation method thereof.In addition, the invention still further relates to the application of this bone renovating material.
Background technology
Along with growth and the aging of population, be one of modal disease clinically because the bone that causes behind wound, infection and the tumor resection is damaged.According to the recent statistics of the U.S., relate to the surgical operation of bone defect repair its every year above 1,000,000 person-times.And China, existing limbs the disabled is about 7,550,000 people, and the accidental injury that causes because of traffic, industrial injury and sports etc. is with annual 7.3% speed increase, and the urgent needs of a large amount of clinical practices has driven growing continuously and fast of bone renovating material.
Clinical various bone renovating materials are mainly titanium, aluminium oxide ceramics, bio-vitric, tricalcium phosphate (TCP), polymethyl methacrylate (PMMA), bone cement, various take the biomaterial of hydroxyapatite (HAP) as the basis at present.Above-mentioned these materials are owing to the defectives such as biocompatibility, osteoinductive limit its application.
The nineties in 20th century U.S. Wright medical skill company limited take calcium sulfate as the substrate development and production go out bone transplantation substitute product OsteoSet of new generation, be the half-H 2 O calcium sulphate (CaSO that uses special method to make
41/2H2O).Have good biocompatibility and bone inductive effect, through the authentication of U.S. FDA (U.S. food and FAD), get permission a kind of bone graft substitute in clinical use.
Correspondingly, Chinese patent 00100673 discloses the Osteological material of half-H 2 O calcium sulphate, but does not study particle diameter character, does not also contain the calcium succinate composition; Chinese patent 0180866 discloses the setting granule of sulfur acid calcium, the complicated means preparation but it need to pressurize etc., nor contain the calcium succinate composition; Chinese patent 02125346 discloses the composite biological material of sulfur acid calcium, but does not study particle diameter character, does not also contain the calcium succinate composition; Chinese patent 02809194 discloses a kind of bone transplantation group compound based on calcium phosphate/calcium sulfate, phosphoric acid calcium wherein, but do not contain calcium succinate; Chinese patent 02817063 discloses the implant compositions that contains calcium sulfate compound and polymer, but does not study particle diameter character, does not also contain the calcium succinate composition; Chinese patent 200480009791 discloses and has contained particle diameter less than the Injectable composition of 0.1 micron granular hardened calcium sulfate material, is used for the bone mineral substitution material, but does not wherein have the calcium succinate composition; Chinese patent 200510103264 discloses citric acid half-H 2 O calcium sulphate bone substitute, but does not study particle diameter character, does not also contain the calcium succinate composition; Chinese patent 200510131093 has mentioned that bone substitute can comprise calcium sulphate dihydrate granule and at least a calcium carbonate, bata-tricalcium phosphate, calcium hydrogen phosphate, dicalcium phosphate dehydrate, magnesium carbonate, tricresyl phosphate magnesium, magnesium hydroxide or the magnesian granule of being selected from, but does not point out all the time the use of calcium succinate; Chinese patent 200610014733 discloses controllable cured calcium sulfate bone-cementing agent and preparation method thereof, but its controllable be not the size of particle diameter, nor contain calcium succinate; Chinese patent 200610029066 and 200610029067 discloses bio-activity tricalcium silicate/semi water calcium sulphate composite self-solidification material, but does not study particle diameter character, does not also contain the calcium succinate composition; Chinese patent 200810301291 discloses calcium sulfate composite material, and it is comprised of the chemical compound that contains strontium and calcium sulfate, but does not study particle diameter character, does not also contain calcium succinate.
The inventor is through long-term and arduous research, find unexpectedly, in the process of preparation α-half-H 2 O calcium sulphate, add the composition that forms calcium succinate, can be so that not only the crystal grain that finally obtains be subjected to the impact of blending constituent, and pattern is more regular, and particle size distribution is homogeneous comparatively, can become the paddy repair materials by direct pressing fully; More surprisingly, the preparation method that the inventor studies, the size that can regulate the crystal grain particle diameter by regulating these simple means of amount of alcohol added, and in preparation process, avoided pressure process and too high temperature (as, 140 ℃) so that preparation operates more easily, cost is lower.
Summary of the invention
Technical problem to be solved by this invention just provides the regular α of pattern-half-H 2 O calcium sulphate artificial bone repair materials and preparation method thereof, remedying the defective of prior art, and additional the deficiencies in the prior art.
Particularly, in first aspect, the invention provides the preparation method of artificial bone repair materials, it comprises:
(1) add ethanol in the solution that mixes succinic acid, calcium hydroxide and water, then add sulfuric acid reaction, filtering successively more also, drying obtains powder; With
(2) heating mixes the solution of succinic acid, calcium chloride and water, then adds the resulting powder of step (1) and insulation reaction, filters successively, dries and obtain powder, and this powder compaction is become artificial bone renovating material.
Stirring is for disperseing solute, and the effects such as accelerated reaction are known in those skilled in the art.Therefore preferred in the preparation method of first aspect present invention, all can stir in the process of mixing, adding and/or reacting, such as magnetic agitation.The speed that stirs can be 100-400rpm, as 200-400rpm(as, in step (1)) or 100-300rpm(as, in step (2)).
Because therefore succinic acid indissoluble solution can mix with water first in the process of mixing succinic acid, ultra-sonic dispersion 5-60min to dissolve complete, and then adds other materials.
Dry usually use heat up dry (that is, oven dry), this knows to those skilled in the art.Baking temperature can be 30-120 ℃, usually is dried to no longer loss of weight of powder.For example, baking temperature can be 30-50 ℃, is generally 2-6 hour drying time, and and for example, baking temperature is 100-120 ℃, is generally 0.5-3 hour drying time.
In the preparation method of first aspect present invention, the powder that step (2) obtains can become artificial bone renovating material by direct pressing, also can with other materials (as, polymer, binding agent, antibiotic, bone morphogenetic protein and/or chemotherapeutics) mix after compacting, preferred direct pressing.The form that is pressed into can be general lamellar morphology (that is, tablet), so that cut and correction of the flank shape when using, and the form that also can direct pressing becomes to use.
Preferably in the preparation method of first aspect present invention,
Ethanol in the step (1) is dehydrated alcohol;
Solution and ethanol volume ratio in the step (1) are 1:0.5-5, are preferably 1:0.7-3.5, most preferably are 1:0.75-3, such as 1:3, and 1:1.5,1:1, or 1:0.75;
Step (2) is carried out under normal pressure; And/or
The particle diameter of the resulting powder of step (2) preferably less than 80 microns, is more preferably less than 50 microns less than 100 microns, as between the 25-55 micron, and 20-35,17-25, perhaps 14-18 micron.
It is also preferred in the preparation method of first aspect present invention,
Succinic acid in the step (1) and the mol ratio of calcium hydroxide are 1:0.5-2, are preferably 1:0.85-1.25, most preferably are 1:1;
Calcium hydroxide in the step (1) and the mol ratio of sulphuric acid are 1:1-3, and preferably 1:1.5-2.5 most preferably is 1:2;
Succinic acid in the step (1) and the weight ratio of water are 0.25-0.6:150, are preferably 0.3-0.45:150, most preferably are 0.3872:150;
Solution in the step (2) contains 20-40%(w/w) calcium chloride, preferably contain 25-35%(w/w) calcium chloride, most preferably contain 30% calcium chloride; And/or
Succinic acid in the step (2) and the weight ratio of water are 0.5-0.8:35, are preferably 0.6-0.75:35, most preferably are 0.686:35.
It is also preferred in the preparation method of first aspect present invention,
Other processes in the step (1) except the process of drying are carried out at 0-50 ℃, preferably carry out at 10-40 ℃, are more preferably at 20-30 ℃ to carry out, and most preferably carry out in room temperature (25 ℃);
The temperature of heating is 90-100 ℃ in the step (2), is preferably 95-100 ℃, most preferably is 100 ℃; And/or
The temperature of insulation is 100-130 ℃ in the step (2), is preferably 105-125 ℃, most preferably is 110-120 ℃.
It is preferred in the preparation method of first aspect present invention in addition,
The time of reaction is 1-4 hour in the step (1), is preferably 1.5-2.5 hour, most preferably is 2 hours; And/or
The time of reaction is 2-6 hour in the step (2), is preferably 3-5 hour, most preferably is 4 hours;
Can also be preferred in the preparation method of first aspect present invention,
Sulphuric acid in the step (1) is that the form with sulfuric acid solution provides, and the concentration of preferably sulfuric acid solution is 0.5-2mol/L, is preferably 0.8-1.5mol/L, most preferably is 1.2mol/L; And/or
Slowly add sulphuric acid in the step (1), the speed that preferably adds sulphuric acid is 10-50mmol/ hour, preferably 20-30mmol/ hour, most preferably is 24mmol/ hour.
In the preparation method in the specific embodiment of the invention,
Solution in the step (1) and ethanol volume ratio are 1:3, and the particle diameter of the resulting powder of step (2) is between the 29.9-52.1 micron thus;
Solution in the step (1) and ethanol volume ratio are 1:1.5, and the particle diameter of the resulting powder of step (2) is between the 23.6-33.2 micron thus;
Solution in the step (1) and ethanol volume ratio are 1:1, and the particle diameter of the resulting powder of step (2) is between the 17.8-23.6 micron thus; And/or
Solution in the step (1) and ethanol volume ratio are 1:0.75, and the particle diameter of the resulting powder of step (2) is between the 14.2-17.5 micron thus.
In second aspect, the invention provides the artificial bone repair materials of the preparation method preparation of first aspect present invention, wherein contain calcium sulfate and calcium succinate.
In the third aspect, the artificial bone repair materials that the invention provides second aspect present invention is for the preparation of the application in the medical product of bone repair, and preferred wherein artificial bone repair materials and a surname are from one or more material compound use of antibiotic, bone morphogenetic protein and chemotherapeutics.
In yet another aspect, the invention provides the method for regulating powder diameter size in the artificial bone renovating material, it comprises solution in the step (1) of the preparation method of regulating first aspect present invention and the volume ratio of ethanol.That is, the invention provides the method for regulating powder diameter size in the artificial bone renovating material, it comprises:
(1) solution of mixing succinic acid, calcium hydroxide and water, the volume ratio of regulator solution and ethanol adds the ethanol through the adjusted volume ratio, then adds sulfuric acid reaction, and filtering successively more also, drying obtains powder; With
(2) heating mixes the solution of succinic acid, calcium chloride and water, then adds the resulting powder of step (1) and insulation reaction, filters successively, dries and obtain powder, and this powder compaction is become artificial bone renovating material.Identical described in the preparation method of each preferred aspect and first aspect present invention wherein.
The present invention has obtained following beneficial effect:
1, preparation method of the present invention need not to carry out compressive reaction, can prepare.
2, powder diameter is more regular in the artificial bone repair materials of preparation method preparation of the present invention, so that constant product quality, clinical use has no side effect, and more can replace clinically other repair materials.
3, under preparation method framework of the present invention, according to the different volumes of finding than the affect rule of ethanol/solution on crystallite dimension, pattern, can active adjustment artificial bone repair materials in the size of powder.Along with improving constantly of dehydrated alcohol/solution proportion in the reaction solution, to reduce crystallite dimension, length is narrowed down to about 17um by 50um, and width is narrowed down to about 7um by 13um, draw ratio narrows down to 2.4 by 3.1, make crystal formation by needle-like, thin wall shape to bar-shaped, heavy wall shape transition.
For the ease of understanding, below will the present invention be described in detail by concrete drawings and Examples.It needs to be noted that instantiation and accompanying drawing only are in order to illustrate, not consist of limitation of the scope of the invention.Obviously those of ordinary skill in the art can illustrate according to this paper, within the scope of the invention the present invention is made various corrections and change, and these corrections and change are also included in the scope of the present invention.In addition, the present invention has quoted open source literature, and these documents also are in order more clearly to describe the present invention, and their full text content is all included the present invention in and carried out reference, just look like they full text in description of the present invention repeated description excessively the same.
Description of drawings:
The artificial bone repair materials finished product that Fig. 1 prepares for preparation technology according to the present invention;
Fig. 2 is for preparing the SEM photo of the powder of step (1) with different proportion ethanol/solution, (a)-(d) corresponding embodiment 1-4 successively wherein, and wherein crystal habit, size are comparatively mixed and disorderly;
Fig. 3 is for preparing the SEM photo of the powder of step (2) with different proportion ethanol/solution, (a)-(d) corresponding embodiment 1-4 successively wherein, and wherein crystal habit is regular;
Fig. 4 has wherein measured respectively the length (length) of crystal, wide (width) and length-width ratio (ratio) for prepare the measurement result of the crystalline size (Crain size) of the powder of step (2) with different proportion ethanol (Ethanol amount).
Concrete embodiment:
Below in conjunction with specific embodiment, further illustrate the present invention.Should be understood that these embodiment only are used for explanation the present invention, limit the scope of the invention and be not used in.
Embodiment 1 prepares bone renovating material with ethanol at high proportion
(1) preparation of amorphous powder:
Under the room temperature (25 ℃), take by weighing succinic acid 0.3872g, ultra-sonic dispersion is 5 minutes in the 150ml distilled water, and adding with the succinic acid mol ratio is the calcium hydroxide 0.24g of 1:1, ultrasonic 5 minutes again, mentioned solution is pressed the 1:3 volume ratio add dehydrated alcohol, when utilizing magnetic stirrer, drip the dilute sulfuric acid 5.4ml of 1.2mol/L in the solution, rate of addition is 20mL/h, then, reaction 2h filters, dries and to get amorphous powder.
(2) preparation of micron order crystal powder:
Take by weighing succinic acid 0.6860g, ultra-sonic dispersion is 3 minutes in the 35ml distilled water, adds calcium chloride, (making it become mass fraction is 30% calcium chloride solution), mentioned solution is poured in the there-necked flask, place oil bath pan, the top is equipped with recirculated water, magnetic agitation, rotating speed is 200 rev/mins, be preheated to the powder that adds step (1) preparation gained after 100 ℃, the control reaction temperature is 110 ℃, reaction 4h, filter, oven dry obtains crystalline powder (powder detects through scanning electron microscope and is micron powder, and powder diameter is between the 29.9-52.1 micron), carry out tabletting, make the bone renovating material tablet, sterilization, envelope.
Embodiment 2 prepares bone renovating material with middle ratio ethanol
(1) preparation of amorphous powder:
Under the room temperature (25 ℃), take by weighing succinic acid 0.3872g, ultra-sonic dispersion is 5 minutes in the 150ml distilled water, and adding with the succinic acid mol ratio is the calcium hydroxide 0.24g of 1:1, ultrasonic 5 minutes again, mentioned solution is pressed the 2:3 volume ratio add dehydrated alcohol, when utilizing magnetic stirrer, drip the dilute sulfuric acid 5.4ml of 1.2mol/L in the solution, rate of addition is 20mL/h, reaction 2h filters, dries and to get amorphous powder.
(2) preparation of micron order crystal powder:
Take by weighing succinic acid 0.6860g, ultra-sonic dispersion is 3 minutes in the 35ml distilled water, add calcium chloride, (making it become mass fraction is 30% calcium chloride solution) pours mentioned solution in the there-necked flask into, place oil bath pan, the top is equipped with recirculated water, magnetic agitation, and rotating speed is 200 rev/mins, be preheated to the powder that adds step (1) preparation gained after 100 ℃, the control reaction temperature is 120 ℃, and reaction 4h filters, oven dry, obtain crystalline powder (powder detects through scanning electron microscope and is micron powder, and powder diameter is between the 23.6-33.2 micron) and carry out tabletting, make the bone renovating material tablet, sterilization, envelope.
Embodiment 3 prepares bone renovating material with equal proportion ethanol
(1) preparation of amorphous powder:
Under the room temperature (25 ℃), take by weighing succinic acid 0.3872g, ultra-sonic dispersion is 5 minutes in the 150ml distilled water, and adding with the succinic acid mol ratio is the calcium hydroxide 0.24g of 1:1, ultrasonic 5 minutes again, mentioned solution is pressed the 1:1 volume ratio add dehydrated alcohol, when utilizing magnetic stirrer, drip the dilute sulfuric acid 5.4ml of 1.2mol/L in the solution, rate of addition is 20mL/h, reaction 2h filters, dries and to get amorphous powder.
(2) preparation of micron order crystal powder:
Take by weighing succinic acid 0.6860g, ultra-sonic dispersion is 3 minutes in the 35ml distilled water, add calcium chloride, (making it become mass fraction is 30% calcium chloride solution) pours mentioned solution in the there-necked flask into, place oil bath pan, the top is equipped with recirculated water, magnetic agitation, and rotating speed is 200 rev/mins, be preheated to the powder that adds step (1) preparation gained after 100 ℃, the control reaction temperature is 118 ℃, and reaction 4h filters, oven dry, obtain crystalline powder (powder detects through scanning electron microscope and is micron powder, and powder diameter is between the 17.8-23.6 micron) and carry out tabletting, make the bone renovating material tablet, sterilization, envelope.
Embodiment 4 prepares bone renovating material with low ratio ethanol
(1) preparation of amorphous powder:
Under the room temperature (25 ℃), take by weighing succinic acid 0.3872g, ultra-sonic dispersion is 5 minutes in the 150ml distilled water, and adding with the succinic acid mol ratio is the calcium hydroxide 0.24g of 1:1, ultrasonic 5 minutes again, mentioned solution is pressed the 4:3 volume ratio add dehydrated alcohol, when utilizing magnetic stirrer, drip the dilute sulfuric acid 5.4ml of 1.2mol/L in the solution, rate of addition is 20mL/h, reaction 2h filters, dries and to get amorphous powder.
(2) preparation of micron order crystal powder:
Take by weighing succinic acid 0.6860g, ultra-sonic dispersion is 3 minutes in the 150ml distilled water, add calcium chloride, (making it become mass fraction is 30% calcium chloride solution) pours mentioned solution in the there-necked flask into, place oil bath pan, the top is equipped with recirculated water, magnetic agitation, and rotating speed is 200 rev/mins, be preheated to the powder that adds step (1) preparation gained after 100 ℃, the control reaction temperature is 112 ℃, and reaction 4h filters, oven dry, obtain crystalline powder (powder detects through scanning electron microscope and is micron powder, and powder diameter is between the 14.2-17.5 micron) and carry out tabletting, make the bone renovating material tablet, sterilization, envelope.
The clinical efficacy of embodiment 5 bone renovating materials of the present invention
Zhao so-and-so (numbering 0079XX), the man, 23 years old, before January under without obvious inducement left side ilium pain appearred, limitation of activity, the X sheet shows: left ilium bone cyst, about 3cm * 3cm size, row left ilium cyst excision bone grafting operation, wherein used artificial bone is to prepare according to the embodiment of the invention 4 methods.The postoperative wound healing is good, has no inflamed.In 1 week behind the operation in patients, left lower extremity can carry out simple telescopic movable in bed, and 2 weeks can be leant on to turn lowerly and be walked.Allergy and general toxic reaction are not found in postoperative check in January, and the X sheet shows: the artificial bone of implantation has a small amount of degraded, have very thin trabecular bone structure to form on every side, and bone density increases; 3 months after operation, the most of degraded of artificial bone, cavity area is substituted by freshman bone tissue; Postoperative June, artificial bone is absorbed fully, and bone cavity has formed good trabecular bone structure, and new bone is through reinventing deformation and surrounding normal bone Nature Link, patient's freedom of movement.
Claims (44)
1. the preparation method of artificial bone repair materials, it comprises:
(1) add ethanol in the solution that mixes succinic acid, calcium hydroxide and water, then add sulfuric acid reaction, filtering successively more also, drying obtains powder; With
(2) heating mixes the solution of succinic acid, calcium chloride and water, then adds the resulting powder of step (1) and insulation reaction, filters successively, dries and obtain powder, and this powder compaction is become artificial bone renovating material.
2. preparation method claimed in claim 1, wherein,
Ethanol in the step (1) is dehydrated alcohol;
Solution in the step (1) and ethanol volume ratio are 1:0.5-5;
Step (2) is carried out under normal pressure; And/or
The particle diameter of the resulting powder of step (2) is less than 100 microns.
3. preparation method claimed in claim 2, wherein, the solution in the step (1) and ethanol volume ratio are 1:0.7-3.5.
4. preparation method claimed in claim 3, wherein, the solution in the step (1) and ethanol volume ratio are 1:0.75-3.
5. preparation method claimed in claim 4, wherein, the solution in the step (1) and ethanol volume ratio are 1:3,1:1.5,1:1, or 1:0.75.
6. preparation method claimed in claim 2, wherein, the particle diameter of the resulting powder of step (2) is less than 80 microns.
7. preparation method claimed in claim 6, wherein, the particle diameter of the resulting powder of step (2) is between the 25-55 micron.
8. preparation method claimed in claim 6, wherein, the particle diameter of the resulting powder of step (2) is less than 50 microns.
9. preparation method claimed in claim 8, wherein, the particle diameter of the resulting powder of step (2) is between the 20-35 micron.
10. preparation method claimed in claim 8, wherein, the particle diameter of the resulting powder of step (2) is between the 17-25 micron.
11. preparation method claimed in claim 8, wherein, the particle diameter of the resulting powder of step (2) is between the 14-18 micron.
12. preparation method claimed in claim 1, wherein,
Succinic acid in the step (1) and the mol ratio of calcium hydroxide are 1:0.5-2;
Calcium hydroxide in the step (1) and the mol ratio of sulphuric acid are 1:1-3;
Succinic acid in the step (1) and the weight ratio of water are 0.25-0.6:150;
Solution in the step (2) contains 20-40%(w/w) calcium chloride; And/or
Succinic acid in the step (2) and the weight ratio of water are 0.5-0.8:35.
13. the described preparation method of claim 12, wherein, the succinic acid in the step (1) and the mol ratio of calcium hydroxide are 1:0.85-1.25.
14. the described preparation method of claim 13, wherein, the succinic acid in the step (1) and the mol ratio of calcium hydroxide are 1:1.
15. the described preparation method of claim 12, wherein, the calcium hydroxide in the step (1) and the mol ratio of sulphuric acid are 1:1.5-2.5.
16. the described preparation method of claim 15, wherein, the calcium hydroxide in the step (1) and the mol ratio of sulphuric acid are 1:2.
17. the described preparation method of claim 12, wherein, the succinic acid in the step (1) and the weight ratio of water are 0.3-0.45:150.
18. the described preparation method of claim 17, wherein, the succinic acid in the step (1) and the weight ratio of water are 0.3872:150.
19. the described preparation method of claim 12, wherein, the solution in the step (2) contains 25-35%(w/w) calcium chloride.
20. the described preparation method of claim 19, wherein, the solution in the step (2) contains 30%(w/w) calcium chloride.
21. the described preparation method of claim 12, wherein, the succinic acid in the step (2) and the weight ratio of water are 0.6-0.75:35.
22. the described preparation method of claim 21, wherein, the succinic acid in the step (2) and the weight ratio of water are 0.686:35.
23. preparation method claimed in claim 1, wherein,
Other processes in the step (1) except the process of drying are carried out at 0-50 ℃;
The temperature of heating is 90-100 ℃ in the step (2); And/or
The temperature of insulation is 100-130 ℃ in the step (2).
24. the described preparation method of claim 23, wherein, other processes in the step (1) except the process of drying are carried out at 10-40 ℃.
25. the described preparation method of claim 24, wherein, other processes in the step (1) except the process of drying are carried out at 20-30 ℃.
26. the described preparation method of claim 25, wherein, other processes in the step (1) except the process of drying are carried out at 25 ℃.
27. the described preparation method of claim 23, wherein, the temperature of heating is 95-100 ℃ in the step (2).
28. the described preparation method of claim 27, wherein, the temperature of heating is 100 ℃ in the step (2).
29. the described preparation method of claim 23, wherein, the temperature of insulation is 105-125 ℃ in the step (2).
30. the described preparation method of claim 29, wherein, the temperature of insulation is 110-120 ℃ in the step (2).
31. preparation method claimed in claim 1, wherein,
The time of reaction is 1-4 hour in the step (1); And/or
The time of reaction is 2-6 hour in the step (2).
32. the described preparation method of claim 31, wherein, the time of reaction is 1.5-2.5 hour in the step (1).
33. the described preparation method of claim 32, wherein, the time of reaction is 2 hours in the step (1).
34. the described preparation method of claim 31, wherein, the time of reaction is 3-5 hour in the step (2).
35. the described preparation method of claim 34, wherein, the time of reaction is 4 hours in the step (2).
36. preparation method claimed in claim 1, wherein,
Sulphuric acid in the step (1) is that the form with sulfuric acid solution provides; And/or
The speed that adds sulphuric acid in the step (1) is 10-50mmol/ hour.
37. the described preparation method of claim 36, wherein, the concentration of sulfuric acid solution is 0.5-2mol/L.
38. the described preparation method of claim 37, wherein, the concentration of sulfuric acid solution is 0.8-1.5mol/L.
39. the described preparation method of claim 38, wherein, the concentration of sulfuric acid solution is 1.2mol/L.
40. the described preparation method of claim 36, wherein, the speed that adds sulphuric acid in the step (1) is 20-30mmol/ hour.
41. the described preparation method of claim 40, wherein, the speed that adds sulphuric acid in the step (1) is 24mmol/ hour.
42. the artificial bone repair materials of the arbitrary described preparation method preparation of claim 1-41 wherein contains calcium sulfate and calcium succinate.
43. the described artificial bone repair materials of claim 42 is for the preparation of the application in the medical product of bone repair.
44. the described application of claim 43, wherein artificial bone repair materials and one or more the material compound use that is selected from antibiotic, bone morphogenetic protein and chemotherapeutics.
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| CN105169470B (en) * | 2015-09-02 | 2018-04-06 | 北京益而康生物工程开发中心 | A kind of method that gravity Method prepares Injectable bone repair material |
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|---|---|---|---|---|
| WO1996039203A1 (en) * | 1995-06-06 | 1996-12-12 | Gensci Regeneration Laboratories, Inc. | Modified osteogenic materials |
| CN1470247A (en) * | 2002-07-24 | 2004-01-28 | 清华大学 | Bone repairing material |
| US20050208094A1 (en) * | 2003-09-05 | 2005-09-22 | Armitage Bryan M | Bone cement compositions having fiber-reinforcement and/or increased flowability |
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| CN102390941A (en) | 2012-03-28 |
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