WO2011090255A2 - Composition de ciment osseux facilement injectable a base de calcium - Google Patents

Composition de ciment osseux facilement injectable a base de calcium Download PDF

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WO2011090255A2
WO2011090255A2 PCT/KR2010/007157 KR2010007157W WO2011090255A2 WO 2011090255 A2 WO2011090255 A2 WO 2011090255A2 KR 2010007157 W KR2010007157 W KR 2010007157W WO 2011090255 A2 WO2011090255 A2 WO 2011090255A2
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bone cement
calcium
acid
cement composition
ion
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PCT/KR2010/007157
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Korean (ko)
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WO2011090255A3 (fr
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김승수
권순용
김용식
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한국화학연구원
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    • C—CHEMISTRY; METALLURGY
    • C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
    • C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
    • C04B28/00—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements
    • C04B28/34—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements containing cold phosphate binders
    • C04B28/344—Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements containing cold phosphate binders the phosphate binder being present in the starting composition solely as one or more phosphates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/0047—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L24/0073—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material with a macromolecular matrix
    • A61L24/0089—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material with a macromolecular matrix containing inorganic fillers not covered by groups A61L24/0078 or A61L24/0084
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2400/00—Materials characterised by their function or physical properties
    • A61L2400/06—Flowable or injectable implant compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
    • C—CHEMISTRY; METALLURGY
    • C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
    • C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
    • C04B2111/00—Mortars, concrete or artificial stone or mixtures to prepare them, characterised by specific function, property or use
    • C04B2111/00474—Uses not provided for elsewhere in C04B2111/00
    • C04B2111/00836—Uses not provided for elsewhere in C04B2111/00 for medical or dental applications

Definitions

  • the present invention relates to a high injection calcium-based bone cement composition.
  • Calcium-based bone cement is a type of biomedical material used in orthopedic, dental, and plastic surgery as bone bonding, bone filler, and bone tissue growth promoting agent.It can be injected into the affected area using a syringe to minimize incisions (non-invasive theraphy). This is possible and has been widely practiced recently. Clinically, it is mainly used for bone filling and splicing when fractures or bone defects occur in the vicinity of joints such as wrist and knee, skull, lumbar spine, etc. The bone cement injected into the affected area is slowly biodegraded and disappeared, and the living bone tissue grows and is replaced in place, and the bone tissue is treated. Such calcium-based bone cement should be excellent injectability on paste and not lost in the body for minimal incision.
  • the calcium-based bone cement is mainly composed of a powder form such as calcium phosphate compound or gypsum and a liquid phase containing a curing accelerator.
  • a powder form such as calcium phosphate compound or gypsum
  • a liquid phase containing a curing accelerator When the calcium-based bone cement is clinically applied, when the powder and liquid are mixed with each other and injected into the affected part, the calcium-based bone cement is cured at room temperature to have a bone bonding or bone filling effect.
  • the calcium phosphate bone cement which is mainly composed of calcium phosphate, was first developed in 1983 by mixing phosphate solution with TTCP, DCP and the like by Brown and Chow (WE Brown and LC Chow, “A new calcium phosphate water setting cement, "in Cements Research Progress, American Ceramic Society, Westerville, Ohio, 1986, pp. 352-379).
  • the calcium phosphate cement is mainly composed of an aqueous solution containing calcium phosphate powder and a curing accelerator.
  • the calcium phosphate partially ionizes in water and slowly dissolves, and then precipitates with calcium-based compounds such as hydroxy apatite (HA), causing particles to aggregate and harden. happenss.
  • Plasma-based bone cements which are made of gypsum, are mainly composed of plaster of Paris (US Patent No. 448885, US Patent No. 179533, US Patent No. 872564).
  • the gypsum is prepared by heating gypsum at about 150 ° C. to evaporate water as follows:
  • the reaction proceeds in the opposite direction to the chemical reaction and the crystals of the particles are combined to cause hardening. Therefore, when the gypsum-based cement cement is injected into the affected part, it acts as a bone filler.
  • Calcium-based bone cement is generally used inorganic particles having a particle size of about 1 to 20 ⁇ m. Such small particles have a high surface area but absorb a lot of water because they have a large surface area. Therefore, when a liquid phase containing mostly powder and water is mixed, it becomes difficult to obtain a uniform paste due to a poor kneading. This has a disadvantage of poor injection properties. In addition, during injection, the initial fluidity decreases over time, making injection difficult.
  • HPMC can prevent the filter-pressing phenomenon, but since the material is too high viscosity, it may play a role of lowering the injectability by the following Hagen-Poiseuille formula.
  • Q f is the flow rate
  • ⁇ P n is the injection pressure
  • D n is the needle inner diameter
  • ⁇ f is the viscosity of the cement paste
  • L n is the needle length.
  • the inventors of the present invention while studying to develop bone cement with improved implantability, bone cement because the calcium-based bone cement composition mixed with anionic polyamino acid not only shows excellent biodegradability, but also shows excellent dynamic viscosity and implantability.
  • the present invention was found to be useful as it was completed.
  • An object of the present invention is to provide a high injection calcium-based bone cement composition with improved implantability.
  • the present invention provides a high injection calcium-based bone cement composition in which anionic polyamino acid is mixed with bone cement composed of powder and liquid phase.
  • the high-injectability calcium-based bone cement composition in which the anionic polyamino acid is mixed according to the present invention not only shows excellent biodegradability, but also shows excellent dynamic viscosity and injectability, and thus can be usefully used as bone cement.
  • 1 is an actual image showing a method of measuring the implantability of bone cement according to the present invention
  • Example 2 is a graph showing the results of the implantability measurement of Example 1 and Example 2 according to the present invention.
  • Example 3 is a graph showing the results of the implantability measurement of Example 3 and Example 4 according to the present invention.
  • Example 4 is a graph showing the results of the implantability measurement of Example 5 according to the present invention.
  • Example 8 is a graph showing the results of the implantability measurement of Example 9 according to the present invention.
  • Example 9 is a graph showing the measurement results of the initial curing time of Example 9 according to the present invention.
  • Example 10 is a graph showing the measurement results of the compressive strength of Example 9 according to the present invention.
  • Figure 11 is a graph showing the cell affinity measurement results of Example 9 according to the present invention.
  • the present invention provides a high injection calcium-based bone cement composition in which anionic polyamino acid is mixed with bone cement composed of powder and liquid phase.
  • the calcium-based bone cement powder according to the present invention is amorphous calcium phosphate (Amorphous caclium phosphate), dicalcium phosphate (Dicalcium phosphate anhydrous, DCPA), tetracalcium phosphate (Tetracalcium phosphate, TTCP), ⁇ -type tricalcium phosphate ( It is preferably at least one powdered calcium compound selected from the group consisting of ⁇ -Tricalcium phosphate ( ⁇ -TCP), ⁇ -Tricalcium phosphate ( ⁇ -TCP) and calcium sulfate (gypsum, calcium sulfate).
  • ⁇ -TCP ⁇ -Tricalcium phosphate
  • ⁇ -TCP ⁇ -Tricalcium phosphate
  • ⁇ -TCP calcium sulfate
  • the liquid phase of the calcium-based bone cement according to the present invention preferably comprises a curing accelerator for promoting the precipitation reaction of ionized calcium and phosphate ions to promote the production of hydroxyapatite, the curing accelerator NaH 2 PO 4 , K 2 It is preferably at least one phosphoric acid compound and sulfate compound selected from the group consisting of HPO 4 , NH 4 H 2 PO 4 and Na 2 SO 4 or at least one organic acid selected from the group consisting of citric acid, maleic acid and propionic acid.
  • the anionic polyamino acid mixed in the calcium-based bone cement composition according to the present invention is poly-gamma-glutarmic acid ( ⁇ -PGA) or salts thereof, polyaspartate, polyalkyl aspartic acid salt and It is preferable that it is at least 1 type selected from the group which consists of an aspartic acid-alkyl aspartic acid copolymer.
  • the polygamma glutamic acid may be prepared by fermenting soybean with Bacillus subtilis bacteria.
  • the polyaspartic acid salt may be prepared by the following method (US Patent No. 5543490, Republic of Korea Patent No. 764933):
  • M is lithium ion (Li + ), beryllium ion (Be 2+ ), sodium ion (Na + ), potassium ion (K + ), ammonia ion (NH 4 + ), magnesium ions (Mg 2+ ), calcium ions (Ca 2+ ), and the like, n is an integer of 20 to 100).
  • the polyalkyl aspartic acid salt is preferably a compound represented by the following general formula (1):
  • R is hydrogen, methyl, ethyl, propyl, etc.
  • M is lithium ion (Li + ), beryllium ion (Be 2 + ), sodium ion (Na + ), potassium ion (K + ), ammonia ion (NH 4 + ), magnesium ions (Mg 2+ ), calcium ions (Ca 2+ ), and the like
  • n is an integer of 20 to 100).
  • the aspartic acid-alkyl aspartic acid copolymer is preferably a compound represented by the following formula (2):
  • R is hydrogen, methyl, ethyl, propyl, and the like
  • M is a lithium ion (Li + ), Beryllium Ion (Be 2+ ), Sodium ion (Na + ), Potassium ion (K + ), Ammonia ion (NH 4 + ), Magnesium ions (Mg 2+ ), Calcium ion (Ca 2+ ), x is an integer from 10 to 100, y is an integer from 10 to 100).
  • Building cement uses a water reducing agent such as lignin sulfonate, naphthalene sulfonate, melamine sulfonate, and polycarboxylic acid to reduce cohesion and improve fluidity.
  • the water reducing agent has an anionic functional group and has a chemical structure that is smoothly adsorbed onto the cement particles.
  • the water sensitizer adsorbs to the cement particles, thereby generating a negatively charged electric double layer on the surface of the particles, thereby causing electrostatic repulsion between adjacent particles to disperse the cement particles and prevent reaggregation.
  • the sensitizer is expected to increase the fluidity of the calcium-based bone cement because it improves the dispersibility of the particles, but they are highly toxic and there is a risk that the biodegradation does not occur well in the body and remain in the body. Since the anionic polyamino acid according to the present invention has an anionic functional group to not only increase the dispersibility of the particles, but also biodegrade in the body and do not exhibit toxicity, it can effectively perform the role of a reducing agent used in building cement. .
  • the electrostatic repulsion force is generated by an anionic side chain to increase the interparticle spacing, thereby reducing the cohesion force of the bone cement powder particles, thereby mixing even in a small amount of liquid phase. It exhibits excellent sensitivity (fluid reducing the amount of the appropriate liquid phase required for mixing) or fluidity. That is, by adding a small amount of the anionic polyamino acid according to the present invention, a good homogeneous paste can be obtained in a small liquid phase without clumping.
  • the sensitivity or fluidity of the bone cement can be improved.
  • an appropriate amount of anionic polyamino acid when used, it exhibits a viscosity enough to prevent loss of bone cement in the body, and has the advantage of not using an additional thickener in the bone cement.
  • the viscosity of the bone cement becomes too high, rather, it may lower the implantability.
  • the anionic polyamino acid according to the present invention can be used by mixing either or both of the powder or liquid phase of the bone cement.
  • the anionic polyamino acid is preferably used in an amount of 0.01 to 10 parts by weight, and more preferably 0.01 to 5 parts by weight, based on 100 parts by weight of the powdered calcium compound. If the anionic polyamino acid is used in less than 0.01 parts by weight, the water sensitization effect may not appear properly, and when it is used in excess of 10 parts by weight, the viscosity of the bone cement is too high, so that the implantability may be lowered or the hardening may be inhibited. Can be.
  • the liquid phase of the calcium-based bone cement according to the present invention is preferably used in an amount of 20 to 50 parts by weight, and more preferably in an amount of 30 to 45 parts by weight, based on 100 parts by weight of powder.
  • the liquid phase is used in less than 20 parts by weight, the implantability of bone cement may be lowered.
  • the liquid phase is used in excess of 50 parts by weight, the strength of bone cement may be lowered and the viscosity may be lowered. Can be.
  • ⁇ -tricalcium phosphate As a powdered calcium compound of bone cement, ⁇ -tricalcium phosphate ( ⁇ -Tricalcium phosphate, ⁇ -TCP) was used, and 0.5, 1, and 2 mass% of polygamma glutamic acid was added thereto as an anionic polyamino acid. The ball mill was used to mix uniformly. As a liquid phase of the bone cement, an aqueous solution of 2.5% by mass disodium hydrogen phosphate (Na 2 HPO 4 ) was used. The weight ratio of the powdered phase and the liquid phase of the bone cement was 10: 3.5 and hand-mixed for 1 minute.
  • Example 1 was carried out in the same manner as in Example 1, except that 3, 5, 7, and 10% by mass of polyaspartic acid sodium salt were used instead of polygammaglutamic acid.
  • ⁇ -tricalcium phosphate As a powdered calcium compound of bone cement, ⁇ -tricalcium phosphate ( ⁇ -Tricalcium phosphate, ⁇ -TCP) was used.
  • the liquid liquid of bone cement was prepared by dissolving polyaspartic acid-methyl aspartic acid salt (60:40) in an aqueous solution of 2.5% by mass disodium hydrogen phosphate (Na 2 HPO 4 ).
  • the amount of the anionic polyamino acid introduced was 1, 2, 3, 5 mass%, respectively, relative to the aqueous solution.
  • the weight ratio of the powdered phase and liquid phase of the bone cement was 10: 4.5, which was prepared by direct mixing (hand-mixing) for 1 minute.
  • Example 3 was carried out in the same manner as in Example 3, except that polygammaglutamic acid was used instead of polyaspartic acid-methylaspartic acid salt.
  • ⁇ -TCP ⁇ -tricalcium phosphate
  • TTCP tetracalcium phosphate
  • DCPA dicalcium phosphate
  • calcined gypsum As a calcium compound of bone cement powder, calcined gypsum was used, and 0.01 mass% of polyaspartic acid powder was added thereto, and it prepared by mixing enough using a ball mill. A 2 mass% sodium sulfate aqueous solution was used as a bone cement liquid phase. The weight ratio of the powdered phase and the liquid phase of the cement cement was 10: 4, which was prepared by direct mixing for 1 minute.
  • Example 6 was carried out in the same manner as in Example 6, except that methyl aspartic acid salt was used instead of polyaspartic acid salt.
  • Example 6 was carried out in the same manner as in Example 6, except that polygammaglutamic acid was used instead of the polyaspartic acid salt.
  • ⁇ -tricalcium phosphate ⁇ -TCP
  • calcium carbonate ⁇ -tricalcium phosphate monohydrate
  • MCPM phosphate monocalcium phosphate monohydrate
  • the liquid phase of the bone cement was prepared by adding polygamma glutamic acid in an aqueous solution of 2.5 mass% disodium hydrogen phosphate (Na 2 HPO 4 ) at 0.1, 0.5, and 1.0 mass%, respectively.
  • the weight ratio of the powdered phase and liquid phase of the bone cement was 10: 4.5, which was prepared by direct mixing (hand-mixing) for 1 minute.
  • a calcium-based bone cement composition was prepared in the same manner as in Example 1, except that the anionic polyamino acid was not added in Example 1.
  • a calcium-based bone cement composition was prepared in the same manner as in Example 3, except that the anionic polyamino acid was not added in Example 3.
  • Plasma gypsum was used as the powdered calcium compound of bone cement, and 2 mass% sodium sulfate aqueous solution was used as the liquid liquid of bone cement.
  • the weight ratio of the powdered phase and the liquid phase of the cement cement was 10: 4, which was prepared by direct mixing for 1 minute.
  • ⁇ -tricalcium phosphate As a powdered calcium compound of bone cement, ⁇ -tricalcium phosphate ( ⁇ -Tricalcium phosphate, ⁇ -TCP) was used.
  • the liquid phase of bone cement was prepared by dissolving chondroitin sulfate, which is widely used as a thickener, in an aqueous solution of 2.5% by mass disodium hydrogen phosphate (Na 2 HPO 4 ).
  • the amount of chondroitin sulfate introduced was 0, 1, 2, 3, 5% by mass relative to the aqueous solution, respectively.
  • the weight ratio of the powdered phase and liquid phase of the bone cement was 10: 4.5, which was prepared by direct mixing (hand-mixing) for 1 minute.
  • ⁇ -tricalcium phosphate As a powdered calcium compound of bone cement, ⁇ -tricalcium phosphate ( ⁇ -Tricalcium phosphate, ⁇ -TCP) was used, and 1 mass% of chondroitin sulfate was added thereto, and the mixture was uniformly mixed using a ball mill.
  • ⁇ -Tricalcium phosphate As a liquid phase of the bone cement, an aqueous 2.5 mass% disodium hydrogen phosphate (Na 2 HPO 4 ) solution was used.
  • the weight ratio of the powdered phase and liquid phase of the bone cement was 10: 4.5, which was prepared by direct mixing (hand-mixing) for 1 minute.
  • Comparative Example 5 Except for using alginate instead of sulfateduritin sulfate in Comparative Example 5 was carried out in the same manner as in Comparative Example 5.
  • Comparative Example 5 was carried out in the same manner as in Comparative Example 5 except for using HPMC instead of chondroitin sulfate.
  • ⁇ -tricalcium phosphate ( ⁇ -TCP) is used as the powdered calcium compound in bone cement, and 2.5 mass% disodium hydrogen phosphate (Na 2 HPO 4 ) aqueous solution is used as the liquid phase of bone cement. It was. The weight ratio of the powdered phase and liquid phase of the bone cement was 10: 4.5, which was prepared by direct mixing (hand-mixing) for 1 minute.
  • M 1 filled syringe volume.
  • Example 1 The results are shown in Table 1 and FIGS. 2 to 5. More specifically, the implantability measurement results of Examples 1 and 2 according to the present invention are shown in Figure 2, and the implantability measurement results of Examples 3 to 4 are shown in Figure 3, the main of Example 5 The particle size measurement results are shown in FIG. 4, and the injection property measurement results of Comparative Example 4 are shown in FIG. 5.
  • Example 1 and Example 2 according to the present invention can be improved in the injection.
  • Example 1 exhibits about 97% or more of injectability when 0.5 mass% of polygamma glutamic acid is mixed on the powder of the bone cement composition
  • Example 2 shows 7 mass of polyaspartic acid sodium salt on the powder of the bone cement composition. It can be seen that the injection ratio is about 96% or more when mixed with%. Therefore, it can be seen that the implantability of the bone cement composition in which the anionic polyamino acid is mixed on the powder according to the present invention is improved.
  • Example 3 shows the injection properties of 67% when 5% by mass of polyaspartic acid-methyl aspartic acid is mixed in the liquid phase of the bone cement composition
  • Example 4 shows 5% polygamma glutamic acid in the liquid phase of the bone cement composition. It can be seen that when the mass% is mixed, the injection property is about 94%. Therefore, it can be seen that the implantability of the bone cement composition in which the anionic polyamino acid is mixed in the liquid phase is improved.
  • Example 5 according to the present invention shows that when the mixing ratio of the fourth calcium phosphate / dicalcium phosphate 1: 1 mixed powder is 30% by mass or less, the injection property is 90% or more. Able to know. Therefore, it can be seen that the bone cement composition using the mixed calcium compound in the powder form according to the present invention exhibits excellent injectability.
  • the implantability of Example 6 according to the present invention is about 50%
  • the implantability of Example 7 is about 67%
  • the implantability of Example 8 is about 86%
  • the implantability of Comparative Example 3 It can be seen that it represents about 35%. Therefore, it can be seen that the implantability of the bone cement composition in which the anionic polyamino acid is mixed on the powder according to the present invention is improved.
  • Example 9 the injectability of Example 9 according to the present invention is expressed as about 83% when about 0.1% by mass of polygamma glutamic acid, about 88% when about 0.5% by mass, and 1.0. Since the mass% is about 90%, it can be seen that the injection property is improved as the amount of polygamma glutamic acid increases.
  • Comparative Example 4 is chondroitin sulfate used as a thickener It can be seen that as the amount of is increased, the injectability decreases. In addition, while the implantability of Comparative Example 5 is about 49%, the implantability of Comparative Example 6 is about 18%, the implantability of Comparative Example 7 is about 12%, and the implantability of Comparative Example 8 is about 57%, whereas the injection of Comparative Example 9 It can be seen that the sex is about 55%. Therefore, it can be seen that the chondroitin sulfate and the polymer material used as the thickener do not improve the implantability compared to the anionic polyamino acid according to the present invention.
  • the calcium-based bone cement composition according to the present invention can be usefully used as bone cement because it shows excellent injectability by mixing anionic polyamino acid in powder or liquid phase.
  • microorganisms (10 6 CFU / mL or more) extracted from the sludge of the biodegradable change of the polyaspartic acid-methyl aspartic acid salt (60:40) used in Example 2 and the polyaspartic acid salt used in Example 6 according to the present invention was measured for 28 days at 25 °C by the OECD 301C method, the results are shown in FIG.
  • both the biodegradability of the polyaspartic acid-methyl aspartic acid salt and the polyaspartic acid salt according to the present invention increases with time.
  • the biodegradability of polyaspartic acid-methylaspartic acid salt (60:40) was about 73%, and the biodegradability of polyaspartic acid salt was about 85%, resulting in the introduction of a hydrophobic functional methyl group. It can be seen that the biodegradability decreases accordingly.
  • the anionic polyamino acid of the bone cement composition according to the present invention can be safely used as bone cement because it does not remain in the body by showing excellent biodegradability.
  • Example 3 After mixing the powder phase and liquid phase of Example 3 (5% by mass of anionic polyamino acid relative to aqueous solution) and 4 (5% by mass of anionic polyamino acid relative to aqueous solution) at room temperature for 1 minute, paste 5 g was taken and measured using a rheometric dynamic spectrometer (Rheometric RDA-III, Rheometric scientific TM ). At this time, the measurement conditions were measured by setting the frequency 10 Hz, 5% constant strain (constant strain). In addition, in order to meet the clinical application temperature, the measurement temperature was measured while maintaining the same 37 °C. As a control, the calcium-based bone cement composition of Comparative Example 9, in which anionic polyamino acid was not mixed, was used. The results are shown in FIG.
  • Examples 3 and 4 according to the present invention has a high dynamic viscosity compared to Comparative Example 9.
  • Examples 3 and 4 according to the present invention has a faster viscosity increase than Comparative Example 9.
  • the bone cement composition according to the present invention can be usefully used as bone cement is not lost in the body by showing an excellent dynamic viscosity.
  • Initial curing time was measured according to Gilmore method. After mixing the powder phase and the liquid phase of the cement for about 1 minute, the 24-well plate (cell culture vessel) was filled with 5 wells per sample and measured using a glass syringe. The weight of the syringe was adjusted to 100 g and the time taken for the needle to stick to the cement surface by less than 1 mm was measured.
  • the initial curing time was about 28 minutes when the concentration of polygamma glutamic acid was 0 mass%, about 24 minutes when the concentration of polygamma glutamic acid was 0.1 mass% in Example 9 according to the present invention. It takes about 23 minutes at 0.5% by mass, and about 21 minutes at 1.0% by mass. It can be seen that the initial curing time decreases as the amount of polygamma glutamic acid increases.
  • the compressive strength was about 12 MPa when the concentration of polygamma glutamic acid was 0 mass%, and the concentration of poly gamma glutamic acid was 0.1 mass% and 0.5 mass in Example 9 according to the present invention. In%, about 13.5 MPa, and in 1.0 mass%, about 19 MPa, it can be seen that the strength is improved as the amount of polygamma glutamic acid increases.
  • the cell number was about 6 ⁇ 10 4 cells after 48 hours of culture at 0% by mass of polygamma glutamic acid, and about 0.1% by mass of polygamma glutamic acid in Example 9 according to the present invention. It is 10.1 ⁇ 10 4 , about 14.5 ⁇ 10 4 at 0.5% by mass, and about 17.5 ⁇ 10 4 at 1.0% by mass, so that the number of attached cells increases as the amount of polygammaglutamic acid increases. It can be seen that cell affinity improves with the introduction of polygamma glutamic acid.
  • the highly injectable calcium-based bone cement composition mixed with anionic polyamino acid according to the present invention not only shows excellent biodegradability, but also shows excellent dynamic viscosity and injectability, so that it can be usefully used as bone cement.

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Abstract

L'invention concerne une composition de ciment osseux à base de calcium facilement injectable comprenant au moins un type d'acide polyamino anionique choisi dans le groupe constitué d'acide poly-gamma-glutamique (γ-PGA) ou des sels de celui-ci, de polyaspartate, polyalkylaspartate, et d'un copolymère aspartate-alkylaspartate, mélangés à un liquide et/ou une poudre de ciment osseux. La composition de ciment osseux à base de calcium facilement injectable mélangée à un acide polyamino anionique selon l'invention présente non seulement de bonnes propriétés de biodégradabilité mais également une bonne viscosité et une bonne injectabilité et convient donc à l'utilisation en tant que ciment osseux.
PCT/KR2010/007157 2010-01-25 2010-10-19 Composition de ciment osseux facilement injectable a base de calcium WO2011090255A2 (fr)

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KR102361469B1 (ko) * 2019-12-02 2022-02-10 단국대학교 천안캠퍼스 산학협력단 구리가 도핑된 생활성 유리 나노입자를 포함하는 나노시멘트 및 이의 제조 방법

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