KR102209945B1 - A powder composition for preparing bone cement providing tunnels for moving bone-forming cells - Google Patents

Abstract

The present invention relates to a powdery composition for producing bone cement containing calcium sulfate and calcium phosphate, and to bone cement prepared by mixing the composition and a liquid, and more particularly, to provide a passage through which bone tissue producing cells can smoothly move. It relates to a calcium phosphate/calcium sulfate bone cement containing at least 10 wt% of gypsum or calcium sulfate having a particle size of 100 um or more, and a manufacturing and packaging method capable of producing the same.

Description

A powder composition for preparing bone cement providing tunnels for moving bone-forming cells}

The present specification relates to a powdery composition for producing bone cement containing calcium sulfate and calcium phosphate, and to bone cement prepared from the composition, and more particularly, in order to provide a passage through which bone tissue producing cells can smoothly move, the particle size is It relates to calcium phosphate/calcium sulfate bone cement containing 100 um or more gypsum or calcium sulfate, and a composition, kit, and packaging method capable of producing the same.

Bone bonding cement is used for fixing artificial joints such as artificial hip joints and artificial knee joints, as a filler after bone tumor removal surgery, for replenishment of bone defects after head surgery, and for fracture treatment, plastic surgery, dental treatment, etc. It is widely used.

As such a conventional cement for bone bonding, an acrylic cement mainly composed of polymethyl methacrylate (PMMA) is used. This acrylic cement has an advantage of excellent mechanical strength, but has a disadvantage in that it cannot regenerate bone tissue because it is not biodegradable. In addition, acrylic cement has recently been applied to spinal reinforcement in osteoporotic patients, but there is a problem in that it can damage the spinal nerves due to a high exothermic reaction, thereby making the patient hemiplegic.

Therefore, in 1983, Brown and Chow developed calcium phosphate cement for the first time by mixing TTCP, DCP, and phosphate aqueous solution. This calcium phosphate cement is mainly composed of an aqueous solution containing calcium phosphate powder and a hardening accelerator. In clinical application, when calcium phosphate and an aqueous solution are mixed, the calcium phosphate is partially ionized in water and dissolved slowly, and then precipitated as a calcium-based compound such as hydroxy apatite (HA), and the particles are aggregated and the curing reaction occurs. It happens. As the curing accelerator, a compound that accelerates the precipitation reaction and a compound that promotes the ionization of calcium phosphate are used.

This calcium phosphate cement produces hydroxyapatite or brushite (Dicalcium phosphate dihydrate; DCPD) in the body. Hydroxy apatite has a solubility product of 58.4, which is very slow, which has a problem that interferes with the regeneration of new bones in patients. Brucite has a solubility product of 6.59, which decomposes very quickly compared to hydroxyapatite, but this bone cement uses strong acids such as phosphoric acid or sulfuric acid during the reaction, thus causing necrosis of surrounding bone tissue or interfering with the proliferation of osteoblasts, delaying new bone regeneration There is. Table 1 below is the solubility product of major calcium-based chemicals used as bone substitute materials.

compound Solubility product (pKsp=-log(Ksp) at 35℃) Hydroxyapatite (HA) 58.4 β-Tricalcium phosphate (β-TCP) 28.9 Dicalcium phosphate dihydrate (DCPD) 6.59 Calcium sulfate dihydrate (CSD) 4.62

*pKsp: solubility product; Ksp: dissolution rate constant.

Therefore, calcium sulfate-based bone cement is widely used. Calcium sulfate, or gypsum, has a solubility product of 4.62, which has the advantage that biodegradation occurs smoothly in the body. However, the biodegradation rate of this material is so fast that it is absorbed in the body before bone regeneration is complete, leaving an empty space, a nonunion phenomenon, in bone tissue, causing fractures or requiring reoperation. Therefore, when the biodegradation rate of bone cement almost matches the regeneration rate of new bone, bone cement has bone conduction and promotes the regeneration of new bone.

Accordingly, research and commercialization are being conducted to control the decomposition rate of bone substitutes or bone cement by compounding calcium sulfate and slow calcium phosphate with high decomposition rate. Liu et al. developed a technique to form a calcium sulfate/calcium phosphate complex by partially converting calcium sulfate particles into calcium phosphate (US 5,462,722 No. 10/31/1995).

Moseley et al. mixed calcium sulfate dihydrate powder (calcium sulfate hemihydrate) with monocalcium phosphate monohydrate (MCPM) and beta-tricalcium phosphate (b-TCP) to form gypsum and brucite. Bone cement from which (brushite) is produced was developed (US 8,685,464 B2, 04/01/2014; KR 10-2016-0113594). This invention is characterized in that the MCPM and b-TCP react with each other to generate brucite, but it takes more than 30 minutes and does not harden well, causing inconvenience to the clinician.

Cooper developed a composition containing calcium sulfate powder and beta-tricalcium phosphate powder with a particle diameter of 0.4-5.0 mm as the main raw material, and a mixture of substances that generate calcium and hydroxide ions, substances for treatment, etc. (US 8,496,955 B2, 07/30 /2013). The large particles of beta-tricalcium phosphate have a very slow decomposition rate, so the particles themselves are decomposed and cannot provide a space for cell movement, and the reason for using this is to facilitate the adhesion of osteogenic cells. If it is large, it is not easy to inject with a syringe.

On the other hand, in order for tissue cells to grow, there must be a substrate that can be supported, and in order to make a three-dimensional tissue, there must be a passage through which they can grow and enter. Therefore, the scaffold used in tissue engineering has a porous structure. It is reported that a porous material is used in the bone substitute as well, and the appropriate pore size is 100-800 um (Byeongtaek Lee, et al., KR 10-1168121; Heeseok Yang, et al., KR 10-2016-0121726; Sous et al., Biomaterials 19, 2147-53, 1998).

In bone cement, since it is not a porous structure, there is a disadvantage in that there is no passage of cells, and a porous cement was developed to solve this problem (Real, Biomaterials 23, 3673, 2002; Ginebra, JBMR 80A, 351, 2007). However, due to the porosity of this method, the mechanical properties of cement are too weak from the initial stage of implantation, so it is difficult to apply directly to clinical applications, and it is difficult to apply clinically due to difficulties in handling due to the late hardening time.

Therefore, there is a need for research on a composition for producing bone cement that solves the above problems.

US Patent No. 5,462,722 Korean Patent Publication No. 10-2016-0113594 U.S. Patent No. 8,685,464 U.S. Patent No. 8,496,955

Accordingly, the present inventors seek to solve the problem that new bone formation is not smooth because it is difficult for bone-forming cells to penetrate into the bone cement due to the non-porosity, which is the weakness of bone cement, as described above.

An aspect of the present invention is to provide a powdery composition for producing bone cement that acts as a support to which osteogenic cells can attach, and makes a passage of 100 um or more so that the cells can move through biodegradation so that bone tissue regeneration can occur smoothly. .

Another aspect of the present invention is to provide a bone cement comprising a reaction product formed by mixing a liquid composition with the powdery composition.

Another aspect of the present invention is to provide a kit for bone cement having the above characteristics.

The object of the present invention is not limited to the object mentioned above. The object of the present invention will become more apparent from the following description, and will be realized by the means described in the claims and combinations thereof.

One aspect of the present invention is i) a particle size of 80 um-450 um, calcium sulfate hemihydrate powder; Ii) calcium sulfate hemihydrate powder having a particle size of 60 um or less; And iii) having a particle size of 60 um or less, calcium phosphate powder; containing, forming a bone graft substitute when mixed with an aqueous solution, provides a powdery composition for producing bone cement.

In one aspect of the present invention, the calcium sulfate hemihydrate powder of i) provides a powdery composition for producing bone cement, having a particle size of 100 um-400 um.

In one aspect of the present invention, the calcium sulfate hemihydrate powder of i) or ii) includes any one or more of a beta-type calcium sulfate hemihydrate powder and an alpha-type calcium sulfate hemihydrate powder, and the calcium phosphate powder of iii) It provides a beta-type tricalcium phosphate, a powdery composition for producing bone cement.

In one aspect of the present invention, the calcium sulfate hemihydrate powder of ii) and the calcium sulfate hemihydrate powder of ii) are included in a weight ratio of 1: 0.5 to 1.5, providing a powdery composition for producing bone cement.

In one aspect of the present invention, the ii) calcium sulfate hemihydrate powder and the iii) calcium phosphate powder are contained in a weight ratio of 1: 1.5-2.5, providing a powdery composition for producing bone cement.

In one aspect of the present invention, the calcium sulfate hemihydrate powder of ii), the calcium sulfate hemihydrate powder of ii) and the calcium phosphate powder of iii) are included in a weight ratio of 1: 0.5-1.5: 1.5-2.5, bone It provides a powdery composition for producing cement.

In one aspect of the present invention, based on the total weight of the powdery composition for producing bone cement

The calcium sulfate hemihydrate powder of i) is contained in an amount of 10% to 40% by weight,

The calcium sulfate hemihydrate powder of ii) is contained in an amount of 10% to 30% by weight,

The iii) calcium phosphate powder is contained in an amount of 20% to 60% by weight, providing a powdery composition for producing bone cement.

Another aspect of the present invention provides a bone cement comprising a reaction product formed by mixing a liquid composition with a powdery composition according to any one of the above.

In another aspect of the present invention, the liquid composition provides a bone cement, which is an aqueous solution containing at least one of sodium chloride, sodium sulfide and potassium sulfide.

Another aspect of the present invention, a first unit containing the powdery composition according to any one of the above; And a second unit containing the liquid composition; wherein the first unit and the second unit are separated by a switch, but when the switch is removed or opened, the powdery composition included in the first unit and the second unit are included. It provides a kit for bone cement, in which the liquid composition is mixed.

Calcium sulfate/calcium phosphate bone cement according to the present invention is a calcium sulfate/calcium phosphate bone cement that provides a passage for bone tissue-producing cells to act as a support to which bone-forming cells can attach, and biodegradation occurs so that cells can move. It has the effect of making a passage of 100 um or more so that bone tissue regeneration can occur smoothly.

The effects of the present invention are not limited to the effects mentioned above. It should be understood that the effects of the present invention include all effects that can be inferred from the following description.

FIG. 1 is a SEM photograph of a calcium sulfate hemihydrate powder separated using a column having a size of 100-400 um according to Experimental Example 1, and FIG. 1A is a 200-fold enlarged picture, and FIG. 1B is a 500-fold enlarged picture.
FIG. 2 is a graph of particle distribution of calcium sulfate and bone cement of 100-400 um large particles prepared in Example 1. FIG.
3 is a SEM photograph of the surface of bone cement investigated for 2 weeks in 1N hydrochloric acid aqueous solution according to Experimental Example 4, and FIG. 3A is a 200-fold enlarged photograph, and FIG. 3B is a 1000-fold enlarged photograph.
Figure 4 is a bone cement kit according to another aspect of the present invention.

Unless otherwise specified, all numbers, values, and/or expressions expressing ingredients, reaction conditions, and content of ingredients used herein are the variety of measurements that occur in obtaining such values, among other things, in which these numbers are essentially different. Since they are approximations that reflect uncertainty, they should be understood as being modified in all cases by the term "about". In addition, when numerical ranges are disclosed herein, these ranges are continuous and, unless otherwise indicated, include all values from the minimum value of this range to the maximum value including the maximum value. Furthermore, when this range refers to an integer, all integers from the minimum value to the maximum value including the maximum value are included, unless otherwise indicated.

In the present specification, when a range is described for a variable, it will be understood that the variable includes all values within the stated range, including the stated endpoints of the range. For example, a range of "5 to 10" includes values of 5, 6, 7, 8, 9, and 10, as well as any subranges such as 6 to 10, 7 to 10, 6 to 9, 7 to 9, etc. Inclusive, and it will be understood to include any values between integers that are reasonable in the scope of the stated range, such as 5.5, 6.5, 7.5, 5.5 to 8.5 and 6.5 to 9, and the like. Also, for example, the range of "10% to 30%" is 10% to 15%, 12% to 10%, 11%, 12%, 13%, etc., as well as all integers including up to 30%. It will be understood to include any subranges such as 18%, 20% to 30%, and the like, and include any values between reasonable integers within the scope of the stated range, such as 10.5%, 15.5%, 25.5%, and the like.

Hereinafter, the present invention will be described in detail.

Calcium sulfate has been used as bone cement for a long time in the field of dentistry and orthopedic surgery, but it can be seen as very biocompatible because no biological reactions such as foreign body reactions or immune reactions have occurred. However, the biodegradation rate is so fast that there is a problem that the bone cement, which should serve as a base, often disappears before bone regeneration completely occurs. Accordingly, studies on delaying the decomposition rate of bone cement by compounding calcium phosphate, which has a relatively slow absorption rate, have been conducted since the 1990s, and have recently been widely used in clinical practice.

This calcium sulfate/calcium phosphate bone cement has the advantage of slowing down the decomposition rate compared to calcium sulfate cement, but there are few pores over 100 μm for the growth of bone-forming cells, which hinders the growth of bone tissue, and thus bone regeneration is not smooth. It often happens. Accordingly, in the present invention, bone cement capable of generating large pores was developed by using a predetermined amount or more of 100 um or more of calcium sulfate. In other words, small particles of calcium phosphate and calcium sulfate are mixed with each other, so even if calcium sulfate is decomposed first, calcium phosphate particles remain, so that there are no pores or passages that allow tissue cells to grow. On the other hand, in the case of calcium sulfate having a large particle diameter of 100 um or more, when it is dissolved, pores or passages with a diameter of 100 um or more are generated in the vacancy, through which osteogenic cells can grow and enter.

Hereinafter, various aspects of the present invention will be described.

One aspect of the present invention is i) a particle size of 80 um-450 um, calcium sulfate hemihydrate powder; Ii) calcium sulfate hemihydrate powder having a particle size of 60 um or less; And iii) having a particle size of 60 um or less, calcium phosphate powder; containing, forming a bone graft substitute when mixed with an aqueous solution, provides a powdery composition for producing bone cement.

Calcium sulfate used in the present invention is the chemical name of gypsum, and there are calcium sulfate hemihydrate, anhydrous, dihydrate, etc., and the solubility product is close to 4.6, which is very similar to each other, as in bone cement. When it comes into contact with, all of it becomes calcium sulfate dihydrate. Therefore, either calcium sulfate or gypsum can be applied.

In one embodiment, calcium sulfate is prepared by removing water by heating a gypsum gemstone, which is a calcium sulfate dihydrate, in the atmosphere or in a pressure vessel, as is generally well known. The prepared calcium sulfate is crushed using a grinder, and the particles are put in a vibrating separator, and the particles are sorted by size. The large-particle calcium sulfate used in the present invention is used by selecting particles between 100 and 400 um using a 100 um square and a 400 um square. In one embodiment, as a result of SEM analysis, in reality, small particles were adsorbed on the particle surface, so that the particles were not completely 100 um or more, and as a result of particle distribution analysis, about 10% of the particles were 100 um or less.

In one embodiment, the small particles of calcium sulfate use calcium sulfate hemihydrate, which in contact with water turns into calcium sulfate dihydrate and solidifies, which is the main hardening mechanism of bone cement. Small particles of calcium sulfate hemihydrate were screened using a stick having a size of about 60 um, and the average particle size was about 20-40 um.

In one embodiment, the calcium phosphate is beta-tricalcium phosphate. This is selected by using a stick having a size of about 60 um, and particles having an average particle size of 20-40 um are used. Particles with an average particle size of 40 um or more are not uniformly combined with calcium sulfate, and in order to obtain particles with an average particle size of 20 um or less, there is a problem of low screening efficiency and high cement viscosity.

In one aspect of the present invention, the calcium sulfate hemihydrate powder of i) provides a powdery composition for producing bone cement, having a particle size of 100 um-400 um.

In one aspect of the present invention, the calcium sulfate hemihydrate powder of i) or ii) includes any one or more of a beta-type calcium sulfate hemihydrate powder and an alpha-type calcium sulfate hemihydrate powder, and the calcium phosphate powder of iii) It provides a beta-type tricalcium phosphate, a powdery composition for producing bone cement.

In one aspect of the present invention, the calcium sulfate hemihydrate powder of ii) and the calcium sulfate hemihydrate powder of ii) are included in a weight ratio of 1: 0.5 to 1.5, providing a powdery composition for producing bone cement.

In one aspect of the present invention, the ii) calcium sulfate hemihydrate powder and the iii) calcium phosphate powder are contained in a weight ratio of 1: 1.5-2.5, providing a powdery composition for producing bone cement.

In one aspect of the present invention, the calcium sulfate hemihydrate powder of ii), the calcium sulfate hemihydrate powder of ii) and the calcium phosphate powder of iii) are included in a weight ratio of 1: 0.5-1.5: 1.5-2.5, bone It provides a powdery composition for producing cement.

When the weight ratio is satisfied, when the composition is applied to the human body, the composition acts as a support to which osteogenic cells can be attached, and when biodegradation occurs, a passage of 100 um or more is created so that the cells can move so that bone tissue regeneration can occur smoothly. A powdery composition for producing cement can be provided.

In one aspect of the present invention, based on the total weight of the powdery composition for producing bone cement

The calcium sulfate hemihydrate powder of i) is contained in an amount of 10% to 40% by weight,

The calcium sulfate hemihydrate powder of ii) is contained in an amount of 10% to 30% by weight,

The iii) calcium phosphate powder is contained in an amount of 20% to 60% by weight, providing a powdery composition for producing bone cement.

In one embodiment, the calcium sulfate of i) was used in 10-40 wt% of the total powder. When it exceeds 40 wt%, the strength of bone cement may be weakened, and when it is less than 10 wt%, there are fewer pores and thus, there is a problem that the cell passage is small.

In one embodiment, the calcium sulfate hemihydrate powder of ii) has a problem in that the strength of bone cement may be weak when 10 wt% or less, and the decomposition rate of bone cement is accelerated when it is 30 wt% or more.

Another aspect of the present invention provides a bone cement comprising a reaction product formed by mixing a liquid composition with a powdery composition according to any one of the above.

The liquid composition may be an aqueous solution obtained by dissolving salt, sodium sulfate, potassium sulfide, and the like in tertiary distilled water. These components are substances that accelerate the hardening of cement, and may be used in a concentration of 4 wt% or less. If the concentration exceeds 4 wt%, there is a problem that may cause side effects to the patient during surgery.

In another aspect of the present invention, the liquid composition provides a bone cement, which is an aqueous solution containing at least one of sodium chloride, sodium sulfide and potassium sulfide.

Another aspect of the present invention, a first unit containing the powdery composition according to any one of the above; And a second unit containing the liquid composition; wherein the first unit and the second unit are separated by a switch, but when the switch is removed or opened, the powdery composition included in the first unit and the second unit are included. It provides a kit for bone cement, in which the liquid composition is mixed.

It is very difficult to maintain complete sterilization even in the operating room. Therefore, clinicians are always striving to maintain sterile conditions and prevent bacterial infection. Therefore, in the present invention, in order to maintain the sterilization state of cement during mixing, a closure capable of opening and closing is installed in one plastic pack as shown in FIG. 4, so that the cement liquid is put in one side and the powdery form is put in the other side, and a fusing machine is used. The plastic pack was sealed. As shown in Figure 4, the opening and closing can be replaced with a plastic zipper such as a zipper bag. This zipper can be installed in duplicate as necessary to improve the reliability of sealing. This pack can be equipped with connectors to connect or connect syringes, tubes, needles, etc., as needed.

When using cement in the operating room, open the switch and combine the liquid and powder phases, and then mix the packaging pack by hand from the outside of the pack. If necessary, the switch is re-installed on the upper part of the pack to maintain an appropriate mixing space before mixing, and then mixing is performed. When installing a zipper, close the zipper and hand-mold to mix. It can be used by cutting one end of the pack with scissors and transferring it to a syringe. Or, if you install a connector that can connect to the syringe, it can be transferred directly from the pack to the syringe, further preventing the risk of infection.

Hereinafter, the present invention will be described in more detail through specific examples. The following examples are only examples to aid understanding of the present invention, and the scope of the present invention is not limited thereto.

Example 1

Gypsum ore stone is crushed to a size of 10-20 mm, and then dried in air for 12 hours in a drying oven at 120° C. to prepare beta-type calcium sulfate hemihydrate, and then crushed using a pulverizer, and the particles are placed in a vibrating separator. And sort the particles by size. At this time, sticks of 60, 100, and 400 um size are used. The powder of calcium sulfate hemihydrate obtains particles of 60 um or less and particles between 100 and 400 um.

To prepare a powdery form of calcium sulfate/calcium phosphate bone cement, 20 g of beta-type tricalcium phosphate (Acros organics) with an average particle size of about 26 mm and 10 g of calcium sulfate hemihydrate with a size of less than 60 um and particle sizes of 100-400 um Add 10 g of calcium sulfate hemihydrate to the ball mill and rotate for 12 hours at a rotation speed of 150 rpm to mix. The liquid form of calcium sulfate/calcium phosphate bone cement is prepared by dissolving 0.6 g of salt in 20 ml of ultrapure water.

Example 2

Gypsum ore stone is crushed to a size of 10-20 mm, and then dried in a high pressure reactor at 120°C for 2 hours under high pressure to prepare an alpha-type calcium sulfate hemihydrate, and then crushed using a pulverizer, and the particles are placed in a vibrating separator. And sort the particles by size. At this time, sticks of 60, 100, and 400 um size are used. The powder of alpha-type calcium sulfate hemihydrate (light gypsum) yields particles of 60 um or less and particles between 100 and 400 um.

To prepare a powdery form of calcium sulfate/calcium phosphate bone cement, 20 g of beta-type calcium phosphate (Acros organics) having an average particle size of about 26 mm and 10 g of alpha-type calcium sulfate hemihydrate having a size of less than 60 um and 100-400 um Add 10 g of alpha-type calcium sulfate hemihydrate of particle size to a ball mill and rotate for 12 hours at a rotation speed of 150 rpm to mix. The liquid form of calcium sulfate/calcium phosphate bone cement is prepared by dissolving 0.8 g of sodium sulfide in 20 ml of ultrapure water.

Example 3

After crushing the gypsum stone into 10-20 mm size, put it in 30 wt% calcium chloride aqueous solution and boil for 2 hours, thoroughly wash it with 100 ^o C ultrapure water, and dry it sufficiently in a 100 ^o C drying oven to produce alpha-type calcium sulfate. To prepare half-water (ultra-hard gypsum). Next, it is crushed using a pulverizer, and the particles are put in a vibrating separator and sieved to sort the particles by size. At this time, sticks of 60, 100, and 400 um size are used. The powder of alpha-type calcium sulfate hemihydrate (ultra-hard gypsum) yields particles of 60 um or less and particles between 100 and 400 um.

To prepare a powdery form of calcium sulfate/calcium phosphate bone cement, 20 g of beta-type calcium phosphate (Acros organics) having an average particle size of about 26 mm and 10 g of alpha-type calcium sulfate hemihydrate having a size of less than 60 um and 100-400 um Add 10 g of particle-sized cemented carbide to a ball mill and rotate for 12 hours at a rotation speed of 150 rpm to mix. The liquid form of calcium sulfate/calcium phosphate bone cement is prepared by dissolving 0.4 g of potassium sulfide in 20 ml of ultrapure water.

Experimental Example 1

The beta-type calcium sulfate hemihydrate powder having a particle size of 100-400 um used in the present invention was analyzed using SEM.

1A is a 200-fold SEM image, and FIG. 1B is a 500-fold SEM image. As shown in the picture, it was confirmed that particles of 100 um or more exist. However, since smaller particles were adsorbed or dispersed, they were separated by using a 100-400 um screen, but it was confirmed that only particles of 100 um or more did not exist.

Experimental Example 2

The particle distribution of the calcium sulfate hemihydrate and bone cement prepared in Example 1 was investigated using a particle size analyzer (Microtrac Inc., Bluewave).

Experimental results were as shown in Figure 2 below.

The particle size of calcium sulfate separated by 60 um cells was 29.8 ± 23.5 um, and the calcium sulfate separated by 100-400 um cells was 106.4 ± 102.2 um.

Therefore, it was confirmed that more than 100 um of calcium sulfate was present. In addition, the average particle size of bone cement was 29.0 ± 23.0 um.

Experimental Example 3

After mixing the powdery and liquid phases of calcium sulfate/calcium phosphate bone cement prepared in Example 1-3, it was put into a 30 ml syringe to evaluate the injectability, and the initial curing time was measured using the Gilmore needle method.

The experimental results were shown in Table 2. As shown in Table 2, the injectability was generally good at 90% or more, and the initial curing time was also within 15 minutes, and it was confirmed that clinical application was possible because there was no major problem in clinical application.

Sample name Injectability (%) Initial curing time (min) Example 1 96 10 Example 2 99 12 Example 3 94 14

Experimental Example 4

Because osteoclasts degrade bone tissue in vivo by secreting aqueous hydrochloric acid solution of pH 5.5, experiments were conducted in aqueous hydrochloric acid solution to investigate the decomposition behavior of bone cement.

The bone cement cured body of Example 1 prepared in Experimental Example 3 was crushed into an appropriate size, placed in 1 N hydrochloric acid aqueous solution, and after 2 weeks elapsed, the surface of the cured body was examined by SEM.

The experimental results were as shown in FIG. 3 below. As shown in FIG. 3, a particle decomposition trace of 100 um or more was observed. Therefore, the powdery composition according to the present invention and the bone cement prepared from the composition can provide a path through which osteogenic cells, which are passages having a size of 100 um or more, can grow and enter, so that bone tissue regeneration can occur smoothly. Confirmed.

In the above, embodiments of the present invention have been described with reference to the accompanying drawings, but those of ordinary skill in the art to which the present invention pertains can be implemented in other specific forms without changing the technical spirit or essential features. You can understand that there is. Therefore, it should be understood that the embodiments described above are illustrative in all respects and not limiting.

Claims (10)

I) calcium sulfate hemihydrate powder having a particle size of 80 um-450 um;
Ii) calcium sulfate hemihydrate powder having a particle size of 60 um or less; And
Iii) calcium phosphate powder having a particle size of 60 um or less;
Including,
The calcium sulfate hemihydrate powder of i), the calcium sulfate hemihydrate powder of ii), and the iii) calcium phosphate powder are included in a weight ratio of 1: 0.5-1.5: 1.5-2.5,
Powdered composition for producing bone cement to form a bone graft substitute upon mixing with an aqueous solution.
The method of claim 1,
The calcium sulfate hemihydrate powder of i) has a particle size of 100 um-400 um, a powdery composition for producing bone cement.
The method of claim 1,
The calcium sulfate hemihydrate powder of i) or ii) includes any one or more of a beta-type calcium sulfate hemihydrate powder and an alpha-type calcium sulfate hemihydrate powder,
The calcium phosphate powder of iii) is beta-type tricalcium phosphate, a powdery composition for producing bone cement.
delete delete delete The method of claim 1,
Based on the total weight of the powdery composition for producing bone cement
The calcium sulfate hemihydrate powder of i) is contained in an amount of 10% to 40% by weight,
The calcium sulfate hemihydrate powder of ii) is contained in an amount of 10% to 30% by weight,
The iii) calcium phosphate powder is contained in an amount of 20% to 60% by weight, a powdery composition for producing bone cement.
A bone cement comprising a reaction product formed by mixing a liquid composition with the powdery composition according to any one of claims 1 to 3 and 7.
The method of claim 8,
The liquid composition is an aqueous solution containing at least one of sodium chloride, sodium sulfide and potassium sulfide, bone cement.
A first unit containing the powdery composition according to any one of claims 1 to 3 and 7; And a second unit containing a liquid composition; and
The first unit and the second unit are separated by a switch, but when the switch is removed or opened, the powdery composition contained in the first unit and the liquid composition contained in the second unit are mixed, the bone cement kit.

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