Gelatin and silica hybrid material and the formation method thereof

Abstract

This invention relates to a gelatin-silica bridging material and a method for forming the same, comprising the following steps: first, preparing a gelatin aqueous solution and adding 3-glycidoxypropyltrimethoxysilane (GPTMS) for modification; then hydrolyzing tetraethoxysilane; subsequently, mixing antibiotics into the aforementioned modified gelatin aqueous solution; and finally, mixing the hydrolyzed tetraethoxysilane with the antibiotic-containing modified gelatin aqueous solution to synthesize the gelatin-silica bridging material.

Description

Technical Field

[0001] This invention discloses a bridging material and a method for forming the same, particularly a gelatin-silica bridging material and a method for forming the same. Prior Technology

[0002] With the increasing demand for various orthopedic surgeries, including bone fracture treatments, and despite the high success rate of orthopedic surgery, surgical site infections (SSIs) can still occur post-operatively due to factors such as the patient's health condition and surgical indications. SSIs are a highly complex and clinically challenging issue, often requiring additional orthopedic surgery, increased hospitalization time, and higher medical costs. Furthermore, if left untreated, early fracture infections can develop into chronic, persistent infections, such as chronic osteomyelitis or prosthetic joint infections, both of which are difficult to treat and eradicate.

[0003] One of the treatment steps for fracture infection is debridement surgery. This surgery must thoroughly and effectively remove necrotic and infected tissue and remove internal fixation devices associated with the infection, such as loose or infected bone screws or plates, or artificial joints, to eradicate the infection. Subsequently, depending on the specific bacteria causing the infection, a bridging material that can be used as an antibiotic carrier should be selected to provide a comprehensive treatment effect.

[0004] In the treatment of traditional orthopedic infections, polymethyl methacrylate (PMMA) balls loaded with antibiotics are often used as carriers to release the antibiotics. These PMMA balls are implanted in the hip and knee joints to release gentamicin. However, it has been observed that during the first week after implantation, there can be a sudden surge in drug release, and after two weeks, the concentration of the loaded antibiotic gradually decreases. Sudden surges in drug release can overburden the kidneys, leading to acute kidney injury (AKI). Conversely, prolonged exposure to low concentrations of antibiotics can cause pathogens to develop drug resistance.

[0005] Furthermore, and more importantly, when polymethyl methacrylate (PMMA) is used as a release carrier for antibiotics, not only can the drug release rate not reach 5% of the total drug, but because PMMA is a bioinert material, it cannot be degraded by the human body. Moreover, a second surgery is required to remove the PMMA spheres from the patient's body. Summary of the Invention

[0006] This invention relates to a method for forming a gelatin-silica bridging material, comprising the following steps: modifying a gelatin aqueous solution with 3-glycidoxypropyltrimethoxysilane (GPTMS); hydrolyzing tetraethoxysilane; subsequently mixing an antibiotic into the modified gelatin aqueous solution; and mixing the hydrolyzed tetraethoxysilane with the antibiotic-containing modified gelatin aqueous solution to synthesize the gelatin-silica bridging material.

[0007] This invention discloses a gelatin-silica bridging material and a method for its formation, aiming to replace polymethyl methacrylate (PMMA) currently used in clinical practice as a carrier for antibiotics. Furthermore, this invention can carry any different materials, not only antibiotics up to 50 wt%, but also potentially various other drugs.

[0008] One of the advantages of the gelatin-silica bridging material and its formation method in this invention is that, unlike general composite materials, it can form covalent bonds at the molecular scale and simultaneously possesses the characteristics of both organic and inorganic materials.

[0009] One of the advantages of the gelatin and silicon dioxide bridging material and its formation method of the present invention is that its organic components have drug-carrying capacity, plasticity and biodegradability, while the inorganic components can provide the integrity of the overall structure and mechanical strength, while slowing down the degradation rate, making the drug release slow and long-lasting.

[0010] One of the advantages of the gelatin-silica bridging material and its formation method of the present invention is that, through the coordinated action of organic and inorganic substances, the material can be completely degraded, achieving complete release of antibiotics and effectively controlling the dosage of antibiotics.

[0011] One of the advantages of the gelatin and silicon dioxide bridging material and the method for forming the present invention is that by adjusting the composition ratio of the material, the mechanical strength can even be controlled by adjusting the ratio to meet the needs of different situations. For example, the mechanical strength can be adjusted to be harder around bone, while it can be adjusted to be softer next to soft tissue, thus the mechanical properties can be controlled.

[0012] One of the advantages of the gelatin-silica bridging material and the method for forming the present invention is that the mechanical properties of the material can be adjusted, and compared with polymethyl methacrylate (PMMA) material, the method of the present invention does not produce an exothermic reaction during the formation process.

[0013] One advantage of the gelatin-silica bridging material and its formation method of the present invention is that it can be molded or artificially shaped to meet the needs of clinical use.

[0014] One of the advantages of the gelatin and silicon dioxide bridging material and its formation method in this invention is that it is an organic-inorganic bridging material for long-acting antibiotic release, which is expected to replace the currently used polymethyl methacrylate (PMMA) material as an antibiotic drug carrier in orthopedic surgery.

[0015] One of the advantages of the gelatin-silica bridging material and the method for forming the present invention is that it can provide better drug release control, reduce the risk of infection, and reduce hospitalization time and medical expenses caused by postoperative infection.

[0016] One of the advantages of the gelatin-silica bridging material and its formation method of the present invention is that the material of the present invention has good plasticity and biodegradability, and can be adjusted to cure within a few minutes to half an hour. During the curing period, it can be freely shaped by hand, which is convenient for clinical use and provides greater operational flexibility and selectivity. It is expected to play an important role in various infection control treatments. Simple Explanation of the Diagram

[0017] Figure 1 illustrates a method for bridging gelatin and silicon dioxide according to the present invention.

[0018] Figure 2 shows an image of a gelatin-silica bridging material of the present invention displayed by a scanning electron microscope (SEM). Implementation

[0019] This invention relates to a gelatin-silica bridging material and a method for forming the same. As shown in Figure 1, one method for forming a gelatin-silica bridging material involves step 10, which modifies a gelatin solution. There are three embodiments of this method. In the first embodiment (not shown in the figure), 50 wt% silica and 50 wt% gelatin are mixed, with a combined weight of approximately 2.7 to 6.7 grams. The gelatin is added to approximately 7.3 to 11.3 ml of deionized water at 30°C to 50°C and stirred until dissolved. After dissolution, approximately 0.37 to 0.17 ml of 3-glycidoxypropyltrimethoxysilane (GPTMS) is added and stirred for 20 to 40 minutes to initiate a ring-opening reaction. The aforementioned GPTMS acts as a coupling agent. Specifically, 3-epoxypropoxypropyltrimethoxysilane (GPTMS) serves as a coupling agent to facilitate the formation of covalent bonds between gelatin and tetraethoxysilane, thus making it a bridging material. The initial and intermediate stages may also involve an epoxy-amine reaction, where amine and epoxy groups form a cross-linked network structure, ultimately resulting in a ring-opening reaction. This process endows the material with excellent mechanical properties and chemical stability.

[0020] This invention discloses a gelatin-silica bridging material and a method for forming the same. As shown in Figure 1, the first step, step 10, involves modifying the gelatin solution. In the second embodiment (not shown in the figure), this involves mixing 60 wt% silica and 40 wt% gelatin, or 40 wt% silica and 60 wt% gelatin, with a total weight of approximately 1.1 g to 5.1 g. The gelatin is then added to approximately 8.2 mL to 4.2 mL of deionized water at 30°C to 50°C and stirred until dissolved. After dissolution, approximately 0.37 mL to 0.17 mL of 3-epoxypropoxypropyltrimethoxysilane (GPTMS) is added and stirred for 20 to 40 minutes to initiate a ring-opening reaction.

[0021] This invention discloses a gelatin-silica bridging material and a method for forming the same. As shown in Figure 1, the first step, step 10, involves modifying the gelatin solution. In the third embodiment (not shown in the figure), this involves mixing 70 wt% silica with 30 wt% gelatin, or mixing 30 wt% silica with 70 wt% gelatin, with a total weight of approximately 3 to 1 gram. The gelatin is then added to approximately 2 to 6 ml of deionized water at 30°C to 50°C and stirred until dissolved. After dissolution, approximately 0.37 to 0.17 ml of 3-epoxypropoxypropyltrimethoxysilane (GPTMS) is added and stirred for 20 to 40 minutes to initiate a ring-opening reaction.

[0022] The present invention discloses a gelatin-silica bridging material and a method for forming the same. As shown in Figure 1, step 12 involves hydrolyzing tetraethyl orthosilicate (TES), in which deionized water and hydrogen chloride (HCl) are sequentially added to the tetraethyl orthosilicate to perform hydrolysis.

[0023] The present invention discloses a gelatin and silicon dioxide bridging material and a method for forming the same, as shown in Figure 1, and includes step 14 of the synthesis of mixed antibiotics and materials, which includes the following steps 1401, 1402 and 1403.

[0024] The present invention discloses a gelatin and silicon dioxide bridging material and a method for forming the same. As shown in FIG1, step 14 of the synthesis of mixed antibiotics and materials is performed. As shown in step 1401 of FIG1, the gelatin produced by the aforementioned step of modifying the gelatin solution and the tetraethoxysilane produced by the aforementioned step of hydrolyzing tetraethoxysilane are mixed and stirred evenly to form a mixed material.

[0025] This invention discloses a gelatin and silica bridging material and a method for its formation. As shown in Figure 1, step 14, similar to step 1402, involves adding the aforementioned mixed material, and adding vancomycin hydrochloride antibiotic at a total weight percentage of 0 wt% to 50 wt% of the aforementioned mixed material, and ceftazidime antibiotic powder at a total weight percentage of 0 wt% to 50 wt% of the aforementioned mixed material, followed by mixing and stirring until homogeneous. This invention's method for forming a gelatin and silica bridging material allows for the mixing of any combination of antibiotics at weight percentages of 0 wt% to 50 wt%. When the modified gelatin is mixed with hydrolyzed tetraethoxysilane (TEOS), all reactions begin. Typically, the antibiotics are mixed before the tetraethoxysilane hydrolysis step to achieve better homogeneity.

[0026] The present invention discloses a gelatin and silicon dioxide bridging material and a method for forming the same. As shown in Figure 1, step 14 involves the synthesis of a mixture of antibiotics and materials. In step 1403, a molding step is performed whereby the aforementioned mixed materials and antibiotics are poured into a large container and placed at room temperature to dry, thus becoming a gelatin and silicon dioxide bridging material.

[0027] The gelatin used in this invention is a partially hydrolyzed collagen protein derived from the skin and bones of animals such as pigs and cattle. The amino acid composition of gelatin is similar to that of collagen, specifically the Ala-Gly-Pro-Arg-Gly-Glu-Hyp-Gly-Pro amino acid sequence, which effectively promotes cell adhesion, proliferation, diffusion, and differentiation. Silicon dioxide (SiO2) possesses the properties and structure of glass, exhibiting both strength and brittleness. Coupling agents can be used to develop gelatin-silica bridging materials to create tough materials suitable for bone regeneration. Furthermore, utilizing natural polymers such as chitosan, chitin, or gelatin, their biodegradability and malleability allow the gelatin-silica bridging material to possess the flexibility of natural polymers and the strength of glassy silicon dioxide.

[0028] Figure 2 shows an image of a gelatin-silica bridging material of the present invention displayed by a scanning electron microscope (SEM). Part a of Figure 2 shows an image of pure gelatin, and it can be seen that the surface of pure gelatin has pores of different sizes.

[0029] This invention discloses a gelatin-silica bridging material. The image shown in Figure 2, obtained using a scanning electron microscope (SEM), illustrates a composition of 70% silica and 30% gelatin by weight. The gelatin-silica bridging material utilizes 3-epoxypropoxypropyltrimethoxysilane (GPTMS) as a coupling agent. Through ring-opening and epoxy-amine reactions, covalent bonds are generated to modify the gelatin. The other end of the coupling agent consists of silyl groups (Si-OH) and hydrolyzed tetraethoxysilane (TEOS). After condensation / polymerization, a covalently bonded silica network is formed, resulting in good bonding and structural stability in the gelatin-silica bridging material. However, the higher the silica content, the more brittle the structure of the gelatin-silica bridging material becomes, meaning that brittle fracture cracks are more likely to appear on the surface.

[0030] This invention discloses a gelatin-silica bridging material. The image shown in Figure 2, obtained using a scanning electron microscope (SEM), illustrates a composition of 60 wt% silica and 40 wt% gelatin. The increased gelatin content transforms the overall structure into a tough, natural polymer structure, significantly reducing brittle fracture.

[0031] This invention discloses a gelatin-silica bridging material. The image shown in Figure 2, obtained using a scanning electron microscope (SEM), illustrates this material as a mixture of 50 wt% silica and 50 wt% gelatin. The increased gelatin content further strengthens the original structure, making it more dominated by natural polymers, resulting in a very smooth surface.

[0032] The present invention discloses a gelatin and silicon dioxide bridging material. The image shown in Figure 2 is obtained by scanning electron microscopy (SEM). Part e of Figure 2 shows a pure gelatin surface and antibiotics, in which the pores on the gelatin surface are filled with mixed antibiotics.

[0033] This invention discloses a gelatin-silica bridging material. The image shown in Figure 2, obtained using a scanning electron microscope (SEM), illustrates this material as comprising 70% by weight silica, 30% by weight gelatin, and a mixture of antibiotics. Due to the higher silica content, the surface of the gelatin-silica bridging material is more prone to cracking.

[0034] This invention discloses a gelatin-silica bridging material. The image shown in Figure 2, obtained by scanning electron microscopy (SEM), is as follows: Part g of Figure 2 shows that the material consists of 60 wt% silica, 40 wt% gelatin, and mixed antibiotics. The surface of the material is relatively rough and granular because the gelatin itself is already dissolved in water. However, the addition of mixed antibiotics competes with the water in the gelatin, causing agglomeration. However, the increased amount of gelatin makes the overall structure more continuous, thus preventing cracks from forming.

[0035] This invention discloses a gelatin and silicon dioxide bridging material. The image shown in Figure 2, obtained by scanning electron microscopy (SEM), is as follows: Figure 2, part h, shows a mixture of 50 wt% silicon dioxide, 50 wt% gelatin, and antibiotics. The surface of the material is relatively rough and granular because more gelatin dissolves in water. After the antibiotics are added, they compete with the water in the gelatin, causing agglomeration. However, the increased total amount of natural polymer gelatin maintains a continuous structure without cracks, even under these conditions.

[0036] Because the silane coupling agents of this invention can form covalent bonds, bridging the organic material gelatin and the inorganic material silicon dioxide, they possess the properties of both materials. The organic material, gelatin, exhibits excellent biocompatibility, plasticity, and biodegradability, making it suitable for drug delivery. The inorganic material, silicon dioxide, possesses good biocompatibility and a strong structure that slows degradation, thus delaying the overall degradation rate and the release rate of mixed antibiotics. Utilizing silane coupling agents allows for chemical interactions between the organic and inorganic materials at the nanoscale, resulting in a more uniform material distribution compared to other physically mixed composites. This results in a more uniform and controllable degradation rate while improving mechanical properties. The properties can be controlled without affecting the physical and chemical properties of the material. Furthermore, the good interaction between cells and materials allows for wider application in tissue engineering.

[0037] The present invention discloses a method for forming a gelatin-silica bridging material, comprising modifying a gelatin solution, hydrolyzing tetraethoxysilane, and mixing any antibiotic with a synthetic material.

[0038] A gelatin-silica bridging material comprising 30 wt%, 40 wt%, 50 wt%, 60 wt%, and 70 wt% silica by weight, and 70 wt%, 60 wt%, 50 wt%, 40 wt%, and 30 wt% gelatin by weight, and any mixture of antibiotics, wherein the weight percentage ranges from 0 wt% to 50 wt%.

[0039] The above description is merely a preferred embodiment of the present invention and is not intended to limit the scope of the patent application of the present invention; all other equivalent changes or modifications made without departing from the spirit disclosed in the present invention should be included in the scope of the patent application below.

[0040] 10: Steps 12: Steps 14: Steps 1401: Steps 1402: Steps 1403: Steps

Claims

1. A method for forming a gelatin-silica bridging material with antibiotic carrier function, comprising at least: modifying a gelatin solution, comprising: mixing 50 wt% silica and 50 wt% gelatin, the mixed weight being approximately 2.7 g to 6.7 g; adding gelatin to approximately 7.3 mL to 11.3 mL of deionized water at 30°C to 50°C, stirring until dissolved; and adding approximately 0.37 mL to 0.17 mL of 3-epoxypropoxypropyltrimethoxysilane, stirring for 20 min to 40 min to carry out a ring-opening reaction; hydrolyzing tetraethoxysilane, comprising: sequentially adding deionized water and hydrogen chloride to tetraethoxysilane to carry out hydrolysis; and mixing any antibiotic with a synthetic material, comprising: The gelatin produced by the modified gelatin solution step and the tetraethoxysilane produced by the hydrolysis of tetraethoxysilane step are mixed and stirred evenly to form a mixed material. Add the mixed material, and add any antibiotic of the mixed material in a total weight range of 0% to 50% by weight, and mix and stir until homogeneous; The molding process involves pouring the mixture and any antibiotic into a container, placing it at room temperature, and waiting for it to dry to form a gelatin-silica bridging material.

2. The method for forming a gelatin-silica bridging material having antibiotic carrier function as described in claim 1, wherein the step of modifying the gelatin solution involves an antibiotic selected from the group consisting of vancomycin hydrochloride and bactericidal cephalosporin antibiotics.

3. The method for forming a gelatin and silica bridging material with antibiotic carrier function as described in claim 1, wherein the step of modifying the gelatin solution further comprises: mixing 60 wt% silica and 40 wt% gelatin, the mixed weight being approximately 1.1 g to 5.1 g; adding gelatin to approximately 8.2 mL to 4.2 mL of deionized water at 30°C to 50°C, stirring until dissolved; and adding approximately 0.37 mL to 0.17 mL of 3-epoxypropoxypropyltrimethoxysilane, stirring for 20 min to 40 min to carry out a ring-opening reaction.

4. The method for forming a gelatin and silica bridging material having antibiotic carrier function as described in claim 1, wherein the mixing of 50 wt% silica and 50 wt% gelatin further comprises mixing 40 wt% silica and 60 wt% gelatin.

5. The method for forming a gelatin and silica bridging material with antibiotic carrier function as described in claim 1, wherein the step of modifying the gelatin solution further comprises: mixing 70 wt% silica and 30 wt% gelatin, the mixed weight being approximately 3 g to 1 g; adding the gelatin to approximately 2 mL to 6 mL of deionized water at 30°C to 50°C, and stirring until dissolved; and adding approximately 0.37 mL to 0.17 mL of 3-epoxypropoxypropyltrimethoxysilane, and stirring for 20 to 40 minutes to carry out a ring-opening reaction.

6. The method for forming a gelatin and silica bridging material having antibiotic carrier function as described in claim 1, wherein the step of mixing 50 wt% of the silica and 50 wt% of the gelatin further comprises mixing 30 wt% of the silica and 70 wt% of the gelatin.

7. A gelatin-silica bridging material having antibiotic carrier function, comprising at least: silica, wherein the weight percentage of silica is selected from the group consisting of 30 wt%, 40 wt%, 50 wt%, 60 wt%, and 70 wt%; gelatin, wherein the weight percentage of gelatin is selected from the group consisting of 70 wt%, 60 wt%, 50 wt%, 40 wt%, and 30 wt%; and a mixture of any antibiotic, wherein the mixture of any antibiotic is from 0 wt% to 50 wt%, wherein the antibiotic is selected from the group consisting of vancomycin hydrochloride antibiotic and bactericidal cephalosporin antibiotic.

8. The gelatin-silica bridging material having antibiotic carrier function as described in claim 6, wherein the antibiotic is selected from the group consisting of vancomycin hydrochloride antibiotic and bactericidal cephalosporin antibiotics.

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