KR102666722B1 - Composition of a drug carrier, pharmaceutical composition thereof, preparation method and use method thereof - Google Patents

Abstract

Compositions of drug carriers, pharmaceutical compositions thereof, methods of making them, and uses thereof are provided. The composition of the drug carrier includes a first mixture and a second mixture. The first mixture includes a hydrophilic polymer, tricalcium phosphate, and a water-soluble dispersant. The second mixture includes a moisture-absorbing material and a divalent cation salt. The pharmaceutical composition includes a composition of the drug carrier and a drug for preparing an anti-inflammatory agent or antibiotic. The method for producing the drug carrier composition includes mixing the first mixture and the second mixture. Use of the composition of the drug carrier includes mixing the first mixture with a drug and then adding the second mixture. Therefore, when the pharmaceutical composition is applied topically to the surgical site, the drug can be effectively released thereon.

Description

Composition of drug carrier, pharmaceutical composition thereof, method of production and method of use thereof {COMPOSITION OF A DRUG CARRIER, PHARMACEUTICAL COMPOSITION THEREOF, PREPARATION METHOD AND USE METHOD THEREOF}

The present disclosure relates to compositions and pharmaceutical compositions for preparing drug carriers, and methods of making and using the same. In particular, this disclosure relates to drug carriers that can effectively release drugs at the surgical site.

In the current field of drug release technology, one of the main research directions is to achieve the predicted drug release effect through the design of drug carriers. Most of the prior art uses proteins, amino acids and some other biopolymers to prepare drug carriers, and such biopolymers are the commonly used materials among them. Biopolymers need to be biocompatible and biodegradable. “Biocompatible” means that a material is compatible with biological entities and will not cause immune rejection or pathological changes. At the same time, it will not cause or cause cardiovascular embolism, toxic reactions, allergic reactions, tissue destruction and carcinogenesis during use. “Biodegradability” refers to the phenomenon in which a material hydrolyzes or oxidizes in a biological environment, causing the material to break down or decompose into other products when implanted into or otherwise utilized within an organ. Additionally, products of decay or decomposition can be further broken down and released from the organ through the organ's basic metabolism. Biopolymers can be divided into natural polymers and synthetic polymers. Common natural polymers include chitosan, alginate, chitin, collage, hyaluronic acid and other substances.

On the other hand, in orthopedic surgery, drug release is also an important issue. For example, in artificial joint replacement surgery, the probability of postoperative infection is about 2 to 3%. Among these, the greatest risk of postoperative infection is deep infection of the surgical site. If not managed properly, multiple surgeries or long-term antibiotic treatment may be necessary. To reduce the risk of inflammation caused by deep infection, there is currently a method of adding antibiotics to the implanted bone filling material, which is released through the implanted bone filling material to areas where deep infection can occur. do.

However, releasing antibiotics through implanted bone filling material to reduce the risk of inflammation caused by deep infection would cause other problems. After antibiotics are added to the bone filler material, the durability of the bone filler material is significantly reduced. This may lead to the risk of the implant being shaken or displaced during the later recovery stage. To solve the problem of reduced durability of bone filler materials after addition of antibiotics, another alternative method uses a conventional injection method to administer antibiotics. Typically, antibiotics are injected into a patient's wrist vein and are then transported through the systemic blood circulation to the surgical site. However, these methods may not completely and effectively deliver antibiotics to the surgical site.

In light of the foregoing problems, embodiments of the present invention provide a composition for preparing a drug carrier comprising a first mixture and a second mixture. The first mixture includes 300 to 3600 parts by weight of hydrophilic polymer, 300 to 3600 parts by weight of tricalcium phosphate, and 100 to 1800 parts by weight of a water-soluble dispersant. The second mixture comprises 100 to 7200 parts by weight of a water-absorbing material, and 10 to 1800 parts by weight of a divalent cation salt. The water-absorbing material has high biocompatibility, high hygroscopicity, and biodegradability.

In the composition for preparing the drug carrier as described above, the tricalcium phosphate is α-phase tricalcium phosphate or β-phase tricalcium phosphate.

In the composition for preparing the drug carrier as described above, the water-soluble dispersant is methyl cellulose (MC), carboxymethyl cellulose (CMC), hydroxyethyl cellulose (HEC), hydroxypropyl methyl cellulose (HPMC), and any combination thereof. is selected from the group consisting of

In compositions for preparing drug carriers as described above, the water-absorbing material is selected from the group consisting of hyaluronic acid (HA), sodium hyaluronate, collagen, gelatin, polydextrose and any combinations thereof.

In the composition for preparing the drug carrier as described above, the divalent cation salt is calcium chloride (CaCl ₂ ), calcium carbonate (CaCO ₃ ), barium chloride (BaCl ₂ ), strontium chloride (SrCl ₂ ), magnesium chloride (MgCl ₂ ) and any combination thereof.

To achieve the above and other aspects, another embodiment of the present invention provides a pharmaceutical composition for preparing an anti-inflammatory or antibiotic drug using a drug carrier prepared by the above-described composition for preparing a drug carrier. do.

To achieve the foregoing and other aspects, another embodiment of the present invention provides a method for preparing a pharmaceutical composition. Such a method includes the following steps. A first mixture is prepared by mixing 300 to 3600 parts by weight of a hydrophilic polymer, 300 to 3600 parts by weight of tricalcium phosphate, and 100 to 1800 parts by weight of a water-soluble dispersant. A second mixture is prepared by mixing 100 to 7200 parts by weight of a water-absorbing material and 10 to 1800 parts by weight of a divalent cation salt, the water-absorbing material being biocompatible and biodegradable. The precursor mixture is then prepared by mixing the drug and the first mixture in water. The second mixture and the precursor mixture are then mixed to obtain the pharmaceutical composition.

To achieve the foregoing and other aspects, another embodiment of the present invention provides a pharmaceutical composition prepared by the method for preparing a pharmaceutical composition described above.

In the pharmaceutical composition as described above, the drug may be an anti-inflammatory drug or an antibiotic. The anti-inflammatory drug may be selected from the group consisting of adalimumab, certolizumab, etanercept, golimumab, abatacept, tocilizumab, rituximab, infliximab, and any combinations thereof. The antibiotic may be selected from the group consisting of gentamicin, vancomycin, mezlocillin, cloxacillin, methicillin, cephalothin, lincomycin, polymyxin E, bacitracin, fusidic acid, and any combinations thereof. .

In light of the foregoing, when the pharmaceutical composition is applied to the surgical site, the drug can be effectively released from the surgical site.

Figure 1 shows the appearance of the drug carrier of Example 1 in a syringe.
Figure 2 is an optical image showing the distribution of particles of the drug carrier of Example 1 observed with an inverted microscope.
Figure 3 shows the analysis results of cell viability of the drug carrier in the biocompatibility test.
Figures 4a and 4b show the results of drug release rates in the experimental and control groups within 3 and 180 hours, respectively.

DETAILED DESCRIPTION Reference will now be made specifically to this embodiment of the invention, examples of which are shown in the accompanying drawings. For clarity of explanation, details regarding many embodiments are set forth in the description below. However, it should be understood that these details regarding the embodiments are not intended to limit the scope of the invention. That is, these details regarding the embodiments do not necessarily become part of the embodiments of the present invention. Additionally, to simplify the drawings, some of the typical structures and elements are shown in schematic drawings.

Composition for preparing drug carriers

In this embodiment, the composition for making the drug carrier includes a first mixture and a second mixture. Such compositions are prepared by the following method.

The first mixture includes 300 to 3600 parts by weight of a hydrophilic polymer, 300 to 3600 parts by weight of tricalcium phosphate (Ca ₃ (PO ₄ ) ₂ ), and 100 to 1800 parts by weight of a water-soluble dispersant. The second mixture comprises 100 to 7200 parts by weight of a water-absorbing material, and 10 to 1800 parts by weight of a divalent cation salt. The water-absorbing material is biocompatible and biodegradable.

In some embodiments of this invention, the hydrophilic polymer has at least one anionic group, such as a carboxylate group. The hydrophilic polymer may be a salt of alginate acid, polyacrylic acid, gelatin, carboxymethyl cellulose (CMC), polyglutamatic acid (γ-PGA), or any combination thereof, with a monovalent metal cation such as Na+ or K+. . However, in some other embodiments of the invention, the hydrophilic polymer may also be replaced by other hydrophilic polymers with similar properties and is therefore not limited thereto. The parts by weight of the hydrophilic polymer may be 300, 400, 600, 1000, 1200, 1500, 1800, 2000, 2500, 2800, 3000, or 3600, but the parts by weight of the hydrophilic polymer are not limited to the specific values described above.

In some embodiments of the invention, the tricalcium phosphate is α-phase tricalcium phosphate or β-phase tricalcium phosphate. The parts by weight of tricalcium phosphate may be 300, 600, 1000, 1200, 1500, 1800, 2000, 2500, 2800, 3000, or 3600, but the parts by weight of tricalcium phosphate are not limited to the specific values described above.

In some embodiments of the invention, the water-soluble dispersant may be methyl cellulose (MC), carboxymethyl cellulose (CMC), hydroxyethyl cellulose (HEC), hydroxypropyl methyl cellulose (HPMC), or any combination thereof. However, in some other embodiments, the water-soluble dispersant may also be replaced with another water-soluble dispersant having similar properties and is therefore not limited thereto. The parts by weight of the water-soluble dispersant may be 100, 200, 300, 400, 800, 1200, 1600, or 1800, but the parts by weight of the water-soluble dispersant are not limited to the specific values described above.

In some embodiments of this invention, the water-absorbing material may be hyaluronic acid (HA), sodium hyaluronate, collagen, gelatin, polydextrose, or any combination thereof. Water-absorbing materials are not only capable of absorbing large amounts of water, but are also biocompatible and biodegradable. However, in some other embodiments, the water-absorbing material may also be replaced by other water-absorbing materials with similar properties and is therefore not limited thereto. The parts by weight of water-absorbing material may be 100, 500, 1000, 1500, 2000, 3000, 4000, 5000, 6000, or 7200, but the parts by weight of water-absorbing material are not limited to the specific values described above.

In some embodiments of this invention, the divalent cation salt is calcium chloride (CaCl2), calcium carbonate (CaCO3), strontium chloride ( _SrCl2 ), barium chloride ( _BaCl2 ), magnesium chloride ( _MgCl2 ), or any of these. It may be a combination of However, in some other embodiments, the divalent cation salt may also be replaced with other divalent cation salts having similar properties and is therefore not limited thereto. The parts by weight of the divalent cation salt may be 10, 50, 100, 200, 300, 400, 500, 1000, 1200, 1600, or 1800, but the parts by weight of the divalent cation salt are not limited to the specific values described above. The divalent cation of the divalent cation salt can act as a crosslinking agent in the form of a salt of a hydrophilic polymer.

In some other embodiments, the first mixture and the second mixture may further comprise 5,000 to 90,000 and 2,000 to 180,000 parts by weight of water, respectively.

Method for preparing compositions for preparing drug carriers

In this method, the above-described first mixture is prepared by the following steps. 300 to 3600 parts by weight of a hydrophilic polymer, 300 to 3600 parts by weight of tricalcium phosphate (Ca3(PO4)2), and 100 to 1800 parts by weight of a water-soluble dispersant are dispersed and mixed in water. Water-soluble dispersants can promote uniform mixing of the hydrophilic polymer and tricalcium phosphate. After mixing, hydrogen bonds can be created within single molecules of the hydrophilic polymer, between different molecules of the hydrophilic polymer, and between the hydrophilic polymer and the phosphate anion of tricalcium phosphate, forming a network structure.

After the first mixture is prepared, the first mixture can be further dried to make it more stable for storage. For example, the first mixture can be further dried into a dry batt block material by freeze drying. However, the first mixture can also be stored in the original solution form, and thus the storage form of the first mixture is not limited, as long as the storage stability of the first mixture is acceptable.

The second mixture is prepared by the following steps. 100 to 7200 parts by weight of the water-absorbing material and 10 to 1800 parts by weight of the divalent cation salt may each be dissolved in water and then mixed. Alternatively, the water-absorbing material can also be dissolved directly in the solution of the divalent cation salt.

drug carrier

In some embodiments, a drug carrier is also provided. The composition of the drug carrier includes 300 to 3600 parts by weight of a hydrophilic polymer, 300 to 3600 parts by weight of tricalcium phosphate, 100 to 1800 parts by weight of a water-soluble dispersant, 100 to 7200 parts by weight of a water-absorbing material, and 10 to 1800 parts by weight of a divalent cation salt. Includes. Details regarding hydrophilic polymers, water-soluble dispersants, water-absorbing materials, and divalent cation salts have been described above and are therefore omitted here.

In some other embodiments, the composition of the drug carrier may further include 7,000 to 270,000 parts by weight of water.

Manufacturing method of drug carrier

In this method, the above-described drug carrier is prepared by the following steps. First, the first mixture and the second mixture are each prepared as described above. Then, the first mixture and the second mixture are mixed more uniformly so that the hydrophilic polymer in the first mixture is cross-linked with the divalent cations in the second mixture to form a gel-like drug carrier to obtain the above-described drug carrier.

Examples 1 to 3 for the preparation of drug carriers

In this example, drug carriers with different compositions were prepared by the drug carrier preparation method as described above.

In the first mixture of Examples 1-3, the hydrophilic polymer was alginate and the water-soluble dispersant was methyl cellulose. The mixing ratios of alginate, tricalcium phosphate, and methyl cellulose in Examples 1 to 3 are listed in Table 1 below. Table 1 expresses the weight parts of each component in the first mixture of Examples 1 to 3. Accordingly, alginate, tricalcium phosphate, and methyl cellulose in the proportions listed in Table 1 were first dispersed in water and then mixed to prepare the first mixtures of Examples 1 to 3, respectively.

alginate tricalcium phosphate methyl cellulose Example 1 1200 1200 200 Example 2 600 600 200 Example 3 300 300 200

Unit: parts by weight

#Examples 1 to 3 were each dispersed in 6500 parts by weight of water.

In the second mixture of Examples 1 to 3, the water-absorbing material was sodium hyaluronate and the divalent cation salt was calcium chloride in the form of an aqueous solution with a concentration of 30 mg/mL. The mixing ratios of sodium hyaluronate and calcium chloride are listed in Table 2 below. Table 2 expresses the weight parts of each component in the second mixture of Examples 1 to 3. Accordingly, sodium hyaluronate was dissolved in the aqueous solution of calcium chloride in the proportions listed in Table 2, thereby preparing the second mixtures of Examples 1 to 3, respectively.

sodium hyaluronate Calcium chloride (aqueous)* Example 1 1000 400 Example 2 1000 400 Example 3 1000 400

Unit: parts by weight

* Concentration: 30 mg/mL

#Examples 1 to 3 were each dispersed in 13000 parts by weight of water.

Finally, in Examples 1 to 3, the first mixture and the second mixture were each uniformly mixed, and then a drug carrier in gel form was obtained.

Figure 1 shows the appearance of the drug carrier of Example 1 in a syringe. In Figure 1, the drug carrier prepared in Example 1 was in the form of a white gel similar to milk. The appearance of the drug carrier prepared in Examples 2 and 3 was also identical to that of the drug carrier prepared in Example 1.

Figure 2 is an optical image showing the distribution of particles of the drug carrier of Example 1 observed with an inverted microscope (ECLIPSE Ts2, NIKON) at a magnification of 10x eyepiece and 20x objective lens. In Figure 2, the particles in the drug carrier of Example 1 were uniformly dispersed.

Biocompatibility testing of compositions of drug carriers:

First, the gel-type drug carriers of Examples 1 to 3 were each prepared by the above-described manufacturing method.

Next, four 6-well plates were prepared. In each of the 6-well plates, 2 ml of cell culture solution containing NIH/3T3 cells in culture medium was added to three wells of each 6-well plate. The culture medium was DMEM medium, and the concentration of NIH/3T3 cells was 1×105 cells/ml.

Next, the drug carriers of Examples 1, 2, and 3 were added to three wells of the first, second, and third 6-well plates, respectively, and the amount of drug carrier added was 20 μL. The first, second, and third 6-well plates with added drug carrier were experimental groups 1, 2, and 3, respectively. No drug carrier was added to three wells of the fourth plate, thus serving as the control group. Table 3 shows the added amounts of drug carrier and cell medium solutions.

drug carrier Example One Example 2 Example 3 1×10⁵ NIH/3T3 cells/1 mL DMEM medium Experiment One 20 μL - - 2mL Experiment 2 - 20 μL - 2mL Experiment 3 - - 20 μL 2mL contrast - - - 2mL

Finally, the 6-well plates of experimental groups 1 to 3 and control group were placed in a cell incubator and incubated at 37°C for 48 hours. At 24 and 48 hours, 100 μl of cell culture solution was sampled from each well of experimental groups 1 to 3 and control group. For sampled cell culture solutions of experimental groups 1 to 3 and control group, tetramethylazolium salt solution (MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide) was used to conduct the MTT test. Based on the results of the MTT test, the average cell survival rate of experimental groups 1 to 3 and control group was calculated.

Figure 3 shows the analysis results of cell viability of the drug carrier in the biocompatibility test. In Figure 3, after culturing for 24 hours (hrs) or 48 hours, the number of cells in experimental groups (sample) 1 to 3 was greater than the number of cells in the control group (control). Compared to the cell number obtained at 24 hours, the cell number at 48 hours was decreased in all experimental groups 1 to 3, because the increase in cell concentration worsened the culture environment. Accordingly, it can be confirmed that the drug carriers of Examples 1 to 3 are not only highly biocompatible and non-toxic, but are also capable of promoting cell growth.

Method for preparing medicinal compositions

In some embodiments, the pharmaceutical composition is further provided and prepared by the following method. The pharmaceutical composition includes a drug and a composition of the drug carrier described above.

First, the above-described first mixture is prepared by mixing 300 to 3600 parts by weight of a hydrophilic polymer, 300 to 3600 parts by weight of tricalcium phosphate, and 100 to 1800 parts by weight of a water-soluble dispersant.

Next, the above-mentioned second mixture is prepared by mixing 100 to 7200 parts by weight of the water-absorbing material and 10 to 1800 parts by weight of the divalent cation salt.

The precursor mixture is then prepared by mixing the drug and the first mixture in water.

Finally, the second mixture and the precursor mixture are mixed to form the pharmaceutical composition.

Although the drug is first mixed with the first mixture to embed the drug more effectively, the drug can also be mixed with the first mixture and the second mixture simultaneously. Accordingly, the mixing order is not limited to the method described above.

In some embodiments, the aforementioned drug may be an anti-inflammatory drug or antibiotic. The anti-inflammatory drug may be adalimumab, certolizumab, etanercept, golimumab, abatacept, tocilizumab, rituximab, infliximab, and any combination thereof. The antibiotic is selected from the group consisting of gentamicin, vancomycin, mezlocillin, cloxacillin, methicillin, cephalothin, lincomycin, polymyxin E, bacitracin, fusidic acid, and any combinations thereof. However, in some other embodiments, the drug may also be replaced by another drug with similar properties and is therefore not limited thereto. The weight part of the drug may be 30 to 300, for example 80 to 200. For example, the weight parts of drug may be 30, 40, 60, 80, 100, 120, 140, 160, 180, 200, 220, 240, 260, 280, or 300. The weight parts of the drug are not limited to the specific values described above.

Because the hydrophilic polymer and tricalcium phosphate in the first mixture form a network structure through hydrogen bonding, the drug can be dispersed and entangled within the network structure. Additionally, since the divalent cations provided by the divalent cation salt in the second mixture are further cross-linked with the hydrophilic polymer to create a gel-like pharmaceutical composition, the drug can be more effectively retained within the network structure of the drug carrier. . Therefore, the drug can be transported by the drug carrier and released within the human body.

Drug release rate testing of pharmaceutical compositions

In this test, a total of 3 ml of a solution of the first and second mixtures (sodium alginate: tricalcium phosphate: methylcellulose: sodium hyaluronate; the weight ratio of calcium chloride was 36:36:15:80:20) and 50 mg of gentamicin was mixed to prepare a pharmaceutical composition containing gentamicin, which served as the experimental group. The pharmaceutical composition containing gentamicin was then placed into the dialysis bag. At the same time, as a control group, 50 mg of gentamicin was dissolved in 3 ml of water.

Next, 200 ml of phosphate buffered saline (PBS) solution was added to each of the two 500 ml beakers. The prepared solutions of the experimental and control groups were each placed in a dialysis bag, and then they were placed in a PBS solution. Afterwards, the beaker containing the dialysis bag and the PBS solution was slightly shaken at 37° C. to allow the drug to be released from the dialysis bag into the PBS solution. Within the drug release period, the PBS solutions of the experimental and control groups were shaken at 15 minutes, 30 minutes, 45 minutes, 60 minutes, 75 minutes, 90 minutes, 105 minutes, 120 minutes, 150 minutes, and 180 minutes from the start of shaking. Samples were taken on days 1, 1, 2, 3, 4, 5, 6, and 7. The sampled volume of the PBS solution in the beaker was 1 mL, and 1 mL of fresh PBS solution was added to the sampled beaker again. The concentration of gentamicin released from the dialysis bag into the PBS solution was analyzed by high-performance liquid chromatography (HPLC).

Figures 4a and 4b show the results of drug release rates in the Experimental group and Control group within 3 and 180 hours, respectively. In Figure 4a, within the first 3 hours (hr), the drug release rate (cumulative release) of the control group was much faster than that of the experimental group. In the first 3 hours, the release rate of gentamicin in the experimental group was very slow within the first 3 hours.

In Figure 4b, within 180 hours, the drug release rate of the Control group was still much faster than the drug release rate (Cumulative release) of the Experimental group. In the case of the control group, the cumulative released amount of gentamicin in the PBS solution reaches almost 100% within 30 hours. For the experimental group, the cumulative released amount of gentamicin released in the PBS solution gradually reaches about 80% after 70 hours. Accordingly, the pharmaceutical composition of this embodiment can prolong the release time and residence time of the drug in the human body.

In view of the foregoing, the pharmaceutical composition comprising the above-described drug carrier can be applied topically to the required part of the human body so as to slowly release the drug in the pharmaceutical composition to the required part of the human body over a relatively long period of time. It can be applied, for example, to the surgically affected area of the patient. Accordingly, the effect of the drug on the needed part of the body can be greatly increased over a relatively long period of time, compared to conventional injection methods, without affecting other parts surrounding the needed part of the body. Other areas around the required part of the body may be the site of implantation of the prosthesis, for example in bone tissue. Therefore, the medicinal composition is safer for the human body.

In addition to being applied directly to the affected area of a patient undergoing orthopedic surgery, the pharmaceutical composition may also be used in applications such as implantable prostheses, metal implants, and implantable fixed medical devices used in orthopedic surgery. , can be coated on the surface of an implantable medical device. The method for coating the above-described medical device with a pharmaceutical composition includes the following steps. The degree of crosslinking of the hydrophilic polymer can be increased by immersing the medical device in the aforementioned pharmaceutical composition and then in a 10 to 30 mg/mL solution of a divalent cation salt such as calcium chloride. Accordingly, the hardness of the pharmaceutical composition on the surface of the medical device can be further increased.

In addition, because the water-absorbing material of the drug carrier is biodegradable and other components of the drug carrier are also biocompatible, the drug carrier can be decomposed and released from the human body within a certain period of time without affecting human health. It can be.

Although the present invention has been disclosed in the foregoing preferred embodiments, those skilled in the art will understand that the embodiments are used only to illustrate the invention and should not be regarded as limiting the scope of the invention. It is to be noted that all changes and substitutions equivalent to these embodiments are to be included within the scope of the present invention. Accordingly, the scope of protection of the present invention will be determined by the scope of the patent application.

Claims (9)

delete According to claim 1,
A composition wherein the hydrophilic polymer is selected from the group consisting of salts of alginate acid, polyacrylic acid, gelatin, carboxymethyl cellulose (CMC), and polyglutamic acid (γ-PGA). According to claim 1,
A composition wherein the tricalcium phosphate is α-phase tricalcium phosphate or β-phase tricalcium phosphate. According to claim 1,
A composition wherein the water-soluble dispersant is selected from the group consisting of methyl cellulose (MC), carboxymethyl cellulose (CMC), hydroxyethyl cellulose (HEC), and hydroxypropyl methyl cellulose (HPMC). According to claim 1,
A composition wherein the water-absorbing material is selected from the group consisting of hyaluronic acid (HA), sodium hyaluronate, collagen, gelatin, polydextrose, high moisture content and degradable properties. According to claim 1,
The divalent cation salt is selected from the group consisting of calcium chloride (CaCl ₂ ), calcium carbonate (CaCO ₃ ), barium chloride (BaCl ₂ ), strontium chloride (SrCl ₂ ), and magnesium chloride (MgCl ₂ ). Composition for preparing a pharmaceutical composition:
The composition of claim 1; and
A composition containing a drug. According to claim 7,
The drug is an anti-inflammatory drug or antibiotic,
The anti-inflammatory drug is selected from the group consisting of adalimumab, certolizumab, etanercept, golimumab, abatacept, tocilizumab, rituximab, and infliximab; and
A composition wherein the antibiotic is selected from the group consisting of gentamicin, vancomycin, mezlocillin, cloxacillin, methicillin, cephalothin, lincomycin, polymyxin E, bacitracin, and fusidic acid. A method for preparing a pharmaceutical composition using the composition of claim 1:
Preparing a first mixture by mixing 300 to 3600 parts by weight of a hydrophilic polymer, 300 to 3600 parts by weight of tricalcium phosphate, and 100 to 1800 parts by weight of a water-soluble dispersant;
Preparing a second mixture by mixing 100 to 7200 parts by weight of a water-absorbing material and 10 to 1800 parts by weight of a divalent cation salt, wherein the water-absorbing material has high biocompatibility, moisture content and degradable properties. Steps having;
preparing a precursor mixture by mixing a drug and the first mixture in water; and
A method comprising mixing the second mixture and the precursor mixture.