KR20110087081A - High-injectable calcium based cement composition - Google Patents

Abstract

PURPOSE: A highly injectable calcium based cement composition is provided to secure biodegradation properties and dynamic viscosity. CONSTITUTION: A highly injectable calcium based cement composition is constituted as follows. A bone cement composed of liquid cement and powder cement is mixed with anionic polyamino acid. Powder calcium compound is comprised of amorphous calcium phosphate, dibasic calcium phosphate, tetrabasic calcium phosphate, alpha type tribasic calcium phosphate, beta type tribasic calcium phosphate, and calciumsulfate. A curing accelerator promotes the production of hydroxyapatite. The curing accelerator is comprised of NaH2PO4, K2HPO4, NH4H2PO4, and Na2SO4. An anionic polyamino acid is comprised of poly-gamma-glutamic acid or a salt thereof, a polyaspartic acid salt, a polyalkyl aspartic acid salt, and an aspartic acid-alkyl aspartic acid copolymer.

Description

High-injectable calcium based cement composition

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. 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. In clinical applications, when calcium phosphate and aqueous solution are mixed, the calcium phosphate partially ionizes in water and slowly dissolves, and then precipitates with calcium-based compounds such as hydroxy apatite (HA), causing the particles to aggregate and harden. Happens. As the curing accelerator, compounds that promote the precipitation reaction and compounds that promote the ionization of calcium phosphate are used. After that, cements with improved physical properties were developed. In US Patent No. 4880610, α-type TCP, monocalcium phosphate monohydrate (MCPM), calcium carbonate (calcium carbonate, CC) and the like were mixed with water to prepare cement. In US Patent No. 5338356, α-type TCP, TTCP, DCPA, HA, etc. were mixed with water to prepare cement. In US Patent 4619655, calcium sulphate hemihydrate (CSH) was introduced into cement. In International Publication No. 04-00374, calcium sulphate dihydrate (CSD) was introduced into cement. In Korean Patent Registration No. 0371559, polyphosphate was introduced into cement.

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:

2 CaSO ₄ 2 H ₂ 0 → 2 CaSO ₄ 0.5 H ₂ 0 + 3 H ₂ 0.

When water is added to the calcined gypsum, 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 ㎛. 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.

On the other hand, when the amount of the liquid is increased to improve the fluidity, the viscosity of the paste is significantly reduced, and when injected into the affected area, the bone cement is not lost and hardened. That is, bone cement is washed out by the body fluid. In addition, a filter-pressing phenomenon occurs and a layer separation phenomenon occurs between the liquid phase and the solid phase, so that the problem of injection is often not good. On the other hand, if a large amount of liquid is used, porosity is increased in cement, and thus there is a problem that the strength is significantly reduced.

As a result, when using calcium-based bone cement in actual clinical practice, the steps of mixing, transferring to syringes, and injecting are performed. If all processes are not performed quickly, bone cement cannot be completely implanted into the affected part, which is very inconvenient. I feel it.

In order to solve the above problems, studies have been conducted to improve the implantability by introducing sodium citrate into bone cement (Uwe Gbureck, Jake E. Barralet, Kerstin Spatz, Liam M. Grover, Roger Thull, Ionic modification of calcium phosphate cement viscosity.Part I: hypodermic injection and strength improvement of apatite cement, Biomaterials, 25, 2187-2195, 2004; JE Barralet, LM Grover, U. Gbureck, Ionic modification of calcium phosphate cement viscosity.Part II : hypodermic injection and strength improvement of brushite cement, 25, 2197-2203, 2004; Xiaopeng Qi, Jiandong Ye, Ying Wang, Improved injectability and in vitro degradation of a calcium phosphate cement containing poly (lactide-co-glycolide) microspheres, Acta Biomaterialia, 4, 1837-1845, 2008). In addition, hydroxypropyl methyl cellulose (HPMC) was introduced into the liquid phase of bone cement to improve the implantability (EF Burguera, Hockin HK Xu, MD Weir, Injectable and rapid setting calcium phosphate bone cement). with dicalcium phosphate dihydrate, J. Biomed. Mater.Res. Part B: Appl. Biomater., 77B, 126-134, 2006). When about 15% of sodium citrate is dissolved in the liquid phase, it has been reported that the implantability of bone cement is about 96 to 97% .However, when such a large amount of sodium citrate is used, the amount of sodium citrate interferes with the formation of apatite, thereby lowering the strength. The disadvantage is that. In addition, sodium citrate does not increase the viscosity of the bone cement does not have a function to prevent the loss of bone cement. On the other hand, HPMC is a cellulose-based polymer is known to be hardly biodegradable because there is no enzyme to decompose it in the human body. Therefore, when transplanted into the human body is not decomposed in the liver, the molecular weight is large, it is difficult to be excreted through the kidneys can accumulate in the kidneys and cause side effects. In addition, 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 =-△ P _n πD _n ⁴ / 128μ _f L _n

At this time, Q _f is the flow rate, ΔP _n is the injection pressure, D _n is the needle inner diameter, μ _f is the viscosity of the cement paste, L _n is the needle length. In other words, if the viscosity of the cement paste is too large, the flow rate is reduced, rather the injection property is lowered.

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.

In order to achieve the above object, 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;
2 is a graph showing the results of the implantability measurement of Example 1 and Example 2 according to the present invention;
3 is a graph showing the results of the implantability measurement of Example 3 and Example 4 according to the present invention;
4 is a graph showing the results of the implantability measurement of Example 5 according to the present invention;
5 is a graph showing the results of the implantability measurement of Comparative Example 2 according to the present invention;
6 is a graph showing the change in biodegradability of anionic polyamino acids according to the present invention;
7 is a graph showing the results of measuring the dynamic viscosity of bone cement 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.

Hereinafter, the present invention will be described in detail.

The calcium-based bone cement powder of the present invention is amorphous calcium phosphate (Amorphous caclium phosphate), dicalcium phosphate (Dicalcium phosphate anhydrous, DCPA), tetracalcium phosphate (Tetracalcium phosphate, TTCP), α-type tricalcium phosphate ( It is preferably at least one powdered calcium compound selected from the group consisting of α-Tricalcium phosphate (α-TCP), β-Tricalcium phosphate (β-TCP) and calcium sulfate (gypsum, calcium sulfate). Do.

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 HPO ₄ , NH ₄ H ₂ PO ₄ And at least one phosphoric acid compound and sulfate compound selected from the group consisting of 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 (γ-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):

(Wherein 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 polyalkyl aspartic acid salt is preferably a compound represented by the following general formula (1):

(In 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):

(In Formula 3, 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. 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. .

When the anionic polyamino acid is adsorbed to the bone cement powder particles, 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.

By increasing the amount of anionic polyamino acid to be mixed in the bone cement, the sensitivity or fluidity of the bone cement can be improved. In addition, when an appropriate amount of anionic polyamino acid is 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. However, in the case of using an excessive amount of anionic polyamino acid, 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.

In this case, 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 curing 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. When the liquid phase is used in less than 20 parts by weight, the implantability of bone cement may be lowered. When 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.

Hereinafter, the present invention will be described in detail through Examples and Experimental Examples. However, the following examples are merely to illustrate the present invention, but the content of the present invention is not limited by the following examples.

< Example  1> High Injectionability  Calcium Bone cement  Preparation of the composition 1

As a powdered calcium compound of bone cement, α-tricalcium phosphate (α-Tricalcium phosphate, α-TCP) is used, and polygamma glutamic acid 0, 0.5, 1, 2 mass% is 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  2> High granularity  Calcium Bone cement  Preparation of the Composition 2

Example 1 was carried out in the same manner as in Example 1, except that 0, 3, 5, 7, 10 mass% of polyaspartic acid sodium salt was used instead of polygammaglutamic acid.

< Example  3> High granularity  Calcium Bone cement  Preparation of the Composition 3

As a powdered calcium compound of bone cement, α-tricalcium phosphate (α-Tricalcium phosphate, α-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 anionic polyamino acid introduced was 0, 1, 2, 3, 5 mass% 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  4> High Injectionability  Calcium Bone cement  Preparation of the Composition 4

Example 3 was carried out in the same manner as in Example 2, except that polygammaglutamic acid was used instead of polyaspartic acid-methylaspartic acid salt.

< Example  5> High Injectionability  Calcium Bone cement  Preparation of the Composition 5

As a powdered calcium compound of bone cement, α-tricalcium phosphate (α-TCP) is used, and tetracalcium phosphate (TTCP) / dicalcium phosphate (Dicalcium phosphate anhydrous) is used here. , DCPA) 1: 1 mixed powder was introduced. At this time, the mixing ratio was 10, 20, 30, 50, 100 mass%. As the bone cement liquid phase, 5% by mass polygamma glutamic acid was dissolved in 2.5% by mass disodium hydrogen phosphate 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 for 1 minute.

< Example  6> High Injectionability  Calcium Bone cement  Preparation of the Composition 6

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  7> High Injectionability  Calcium Bone cement  Preparation of the Composition 7

Example 6 was carried out in the same manner as in Example 5, except that methyl aspartic acid salt was used instead of polyaspartic acid salt.

< Example  8> High Injectionability  Calcium Bone cement  Preparation of the Composition 8

Example 6 was carried out in the same manner as in Example 5, except that polygammaglutamic acid was used instead of polyaspartic acid salt.

< Comparative example  1> Calcium Bone cement  Preparation of the composition

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.

< Comparative example  2> calcium-based polymer Bone cement  Preparation of the composition

As a powdered calcium compound of bone cement, α-tricalcium phosphate (α-Tricalcium phosphate, α-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 mass% 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.

< Comparative example  3> calcium-based polymer Bone cement  Preparation of the composition

As a powdered calcium compound of bone cement, α-tricalcium phosphate (α-Tricalcium phosphate, α-TCP) was used, and 1 mass% of chondroitin sulfate was added thereto, and the mixture was uniformly mixed using a ball mill. As the liquid phase of the bone cement, an aqueous solution of 2.5 wt% disodium hydrogen phosphate (Na ₂ HPO ₄ ) 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  4> Calcium based polymer Bone cement  Preparation of the composition

Except for using alginate instead of sulfateduritin sulfate in Comparative Example 2 was carried out in the same manner as in Comparative Example 2.

< Comparative example  5> Calcium system containing polymer Bone cement  Preparation of the composition

Except for using hyaluronic acid in place of chondroitin sulfate in Comparative Example 3 was carried out in the same manner as in Comparative Example 3.

< Comparative example  6> Calcium system containing polymer Bone cement  Preparation of the composition

In Comparative Example 3 was carried out in the same manner as in Comparative Example 3 except for using HPMC instead of chondroitin sulfate.

< Comparative example  7> Calcium Bone cement  Preparation of the composition

Α-tricalcium phosphate (α-TCP) is used as the calcium compound in bone cement powder, and 2.5 wt% 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.

< Experimental Example  1> Injection  Measure

In order to determine the implantability of the calcium-based bone cement composition mixed with anionic polyamino acid according to the present invention, the following experiment was performed.

Injectability of Examples 1 to 8 and Comparative Examples 1 to 6 according to the present invention was measured as shown in FIG. 1 using a universal testing machine (Instron 4482). At this time, the crosshead speed was 20 mm / min, the maximum load was 300 N, and the syringe used a 13G needle. Injectability was calculated by the following equation.

M ₀ = empty syringe volume

M ₁ = Filled syringe volume.

M ₂ = load volume after injection

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 2 are shown in FIG. 5.

Polyamino acid concentration (mass%) Injectionability (%) Example 1


0 37 0.5 59 One 97 2 96 Example 2



0 37 3 69 5 85 7 96 10 96 Example 3



0 55 One 58 2 60.5 3 62 5 67 Example 4



0 55 One 64.5 2 74 3 80.5 5 94 Example 5



10 * 96 20 * 92.5 30 * 90.5 50 * 77.5 100 * 69.5 Example 6 0.01 50 Example 7 0.01 67 Example 8 0.01 86 Comparative Example 1 0 35 Comparative Example 2

0** 55 One** 49 2** 49.5 3 ** 47 5 ** 46 Comparative Example 3 One** 49 Comparative Example 4 One** 48 Comparative Example 5 One** 12 Comparative Example 6 One** 57 Comparative Example 7 0 55 *:% concentration of DCPA mixed powder on α-TCP
**:% of polymer

Referring to Table 1 and Figure 2, Example 1 and Example 2 according to the present invention can both improve the implantability. Particularly, 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, and 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.

Referring to Table 1 and FIG. 3, it can be seen that both Example 3 and Example 4 according to the present invention have improved implantability. In particular, 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, and 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.

Referring to Table 1 and FIG. 4, 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.

Referring to Table 1, 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%, while the implantability of Comparative Example 1 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.

Referring to Table 1 and Figure 5, Comparative Example 2 according to the present invention can be seen that the injection property decreases as the amount of chondroitin sulfate used as a thickener increases. In addition, the injection of Comparative Example 3 is about 49%, the Injection of Comparative Example 4 is about 18%, the Injection of Comparative Example 5 is about 12%, and the injection of Comparative Example 6 is about 57%, whereas the injection of Comparative Example 7 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.

From this it can be seen that 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.

< Experimental Example  2> biodegradability measurement

In order to determine the biodegradability of the anionic polyamino acid used in the present invention, the following experiment was performed.

The 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 ℃ by the OECD 301C method, the results are shown in FIG.

As shown in Figure 6, it can be seen that both the biodegradability of the polyaspartic acid-methyl aspartic acid salt and the polyaspartic acid salt according to the present invention increases with time. In particular, after 28 days, 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.

From this it can be seen that 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.

< Experimental Example  3> Dynamic viscosity  Measure

In order to determine the dynamic viscosity of the calcium-based bone cement composition mixed with anionic polyamino acid according to the present invention, the following experiment was performed.

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 ℃. As a control, the calcium-based bone cement composition of Comparative Example 7 was not mixed with anionic polyamino acid. The results are shown in FIG.

As shown in Figure 7, it can be seen that Examples 3 and 4 according to the present invention has a high dynamic viscosity compared to Comparative Example 7. In addition, Examples 3 and 4 according to the present invention can be seen that the viscosity rise is faster than Comparative Example 7.

From this it can be seen that 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.

Therefore, 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, and thus can be usefully used as bone cement.

Claims (10)

A high injection calcium bone cement composition comprising anionic polyamino acid mixed with bone cement composed of powder and liquid phase.
According to claim 1, wherein the powder is amorphous calcium phosphate (Amorphous caclium phosphate), dicalcium phosphate (Dicalcium phosphate anhydrous, DCPA), tetracalcium phosphate (Ttetracalcium phosphate, TTCP), α-type tricalcium phosphate (α- Tricalcium phosphate, α-TCP), β-tricalcium phosphate (β-TCP) and calcium sulfate (gypsum, calcium sulfate) characterized in that it comprises one or more powdered calcium compounds selected from the group consisting of Highly injectable calcium-based bone cement composition.
The high injection calcium bone cement composition of claim 1, wherein the liquid phase comprises a curing accelerator for promoting precipitation of ionized calcium and phosphate ions to promote hydroxyapatite production.
According to claim 3, wherein the curing accelerator NaH ₂ PO ₄ , K ₂ HPO ₄ , NH ₄ H ₂ PO ₄ And at least one phosphoric acid compound and a sulfate compound selected from the group consisting of Na ₂ SO ₄ , or at least one organic acid selected from the group consisting of citric acid, maleic acid and propionic acid.
The method of claim 1, wherein the anionic polyamino acid is poly-gamma-glutarmic acid (γ-PGA) or a salt thereof, polyaspartate, polyalkyl aspartic acid salt and aspartic acid-alkyl aspartic acid. A high injection calcium bone cement composition, characterized in that at least one member selected from the group consisting of ticic acid copolymers.
The method of claim 5, wherein the polyalkyl aspartic acid salt is a high injection calcium-based bone cement composition, characterized in that the compound represented by the formula (1):
[Formula 1]

(In Formula 1,
R is hydrogen, methyl, ethyl or propyl,
M is lithium ion (Li ⁺ ), beryllium ion (Be ^{2 +} ), sodium ion (Na ⁺ ), potassium ion (K ⁺ ), ammonia ion (NH ₄ ⁺ ), magnesium ion (Mg ^{2 +} ) or calcium ion ( and Ca ^{2 +),}
n is an integer from 20 to 50).
The high injection calcium-based bone cement composition according to claim 5, wherein the aspartic acid-alkyl aspartic acid copolymer is a compound represented by the following Chemical Formula 2:
(2)

(In Formula 2,
R is hydrogen, methyl, ethyl or propyl,
M is lithium ion (Li ⁺ ), beryllium ion (Be ^{2 +} ), sodium ion (Na ⁺ ), potassium ion (K ⁺ ), ammonia ion (NH ₄ ⁺ ), magnesium ion (Mg ^{2 +} ) or calcium ion ( and Ca ^{2 +),}
x is an integer from 10 to 100,
y is an integer from 10 to 100).
The high-injection calcium-based bone cement composition according to claim 1, wherein the anionic polyamino acid is mixed and used in any one or both of powder or liquid phase of bone cement.
The high-injection calcium-based bone cement composition according to claim 1, wherein the anionic polyamino acid is used in an amount of 0.01 to 5 parts by weight based on 100 parts by weight of the powdered calcium compound.
[Claim 2] The high injection calcium-based bone cement composition according to claim 1, wherein the liquid phase of the bone cement is used in an amount of 30 to 45 parts by weight based on 100 parts by weight of powder.

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