33 results about "Tobramycinum" patented technology

The invention provides a method for simultaneously determining eight aminoglycoside antibiotics in cosmetics, and belongs to the technical field of medicines. By optimizing an HPLC-MS / MS (High Performance Liquid Chromatography-Mass Spectrometry / Mass Spectrometry) method, a method capable of simultaneously determining spectinomycin, tobramycin, kanamycin B, kanamycin, hygromycin B, streptomycin, dihydrostreptomycin and amikacin in cosmetics is established. The method is good in specificity, the eight aminoglycoside antibiotics can be effectively separated, interference of solvents and matrixes in cosmetics is avoided, and the accuracy of a detection result is ensured; within the range of 5-500 ng.mL <-1 >, a good linear relation is achieved, and the content of antibiotics in cosmetics can be accurately reflected; target antibiotics can still be reliably detected and quantified at low concentration; the method is good in precision and high in recovery rate and repeatability. The method provides reliable technical support for cosmetic risk monitoring, and provides scientific basis for perfecting related detection standards and supervision policies.

This invention provides a method and a production strain for increasing the yield of carbamoyl tobramycin, belonging to the field of genetic engineering technology. By knocking out the tobR gene, which encodes an Lrp / AsnC family transcriptional regulator, within the tobramycin synthesis gene cluster region of the *Streptoalloteichus tenebrarius* genome, and by overexpressing the tobO gene, which encodes a TauD / TfdA family oxidase directly acted upon by TobR, using a constitutive strong promoter, a hybrid mutant strain was obtained, exhibiting a significantly increased fermentation yield of carbamoyl tobramycin. The shake-flask fermentation level of carbamoyl tobramycin by this hybrid mutant strain reached 3.76 g / L, a 42.5% increase compared to the 2.64 g / L of the starting strain. The advantages of this invention are: by inactivating the tobR gene and simultaneously overexpressing the tobO gene in *S. tenebrarius*, a high-yielding carbamoyl tobramycin strain was constructed. This strain can increase the fermentation yield of carbamoyl tobramycin without increasing the cost of additional culture medium, thus reducing production costs and showing significant industrial application potential.

The invention relates to the technical field of high polymer materials, in particular to a preparation method of antibacterial hydrogel for infectious diabetes wound healing, chitosan and tobramycin are used as dynamic physical cross-linking agents, and the hydrogel is prepared through free radical polymerization of N-acryloyl triester (hydroxymethyl) aminomethane and acrylic acid under the irradiation of an ultraviolet lamp. Through electrostatic interaction between carboxyl of the copolymer and amino of the tobramycin, the tobramycin is incorporated into a hydrogel network, so that the mechanical strength is increased, and drug release is controlled. Chitosan exists as another cross-linking agent, so that the mechanical strength of the hydrogel can be adjusted. The hydrogel has an easy-to-synthesize process and sufficient mechanical strength and adhesion, and has the potential of providing a promising and practical combined treatment method for effectively treating chronic infectious diabetes wounds.

The invention relates to the technical field of biological medicine, and discloses a tobramycin nano transfer body as well as a preparation method and application thereof. The invention provides a preparation method of a tobramycin nano transfer body, which specifically comprises the following steps: uniformly mixing lipid, a surfactant, xylooligosaccharide and an alcohol solvent, evaporating to remove the alcohol solvent to obtain a film, and hydrating the film with a tobramycin-PBS buffer solution to obtain a suspension; and then carrying out ultrasonic treatment and graded filtration on the suspension to obtain the tobramycin nano transfer body. The tobramycin nano transfer body has the advantages of high stability, capability of effectively improving the permeability of a hydrophilic drug penetrating through a biological barrier, small particle size, small PDI and the like. The tobramycin-in-situ gel prepared by using the tobramycin nano transfer body has good biocompatibility, stable drug loading capacity and controllable drug release performance, can penetrate cornea to reach a focus to play a targeting role, and can be applied to preparation of external preparations for treating ocular inflammation.

The invention relates to a method for determining the content of tobramycin in tobramycin eye drops, which comprises the following steps: 1) preparation of a reference substance solution: taking a tobramycin reference substance, and adding water and sulfuric acid to dissolve the tobramycin reference substance to prepare the reference substance solution; 2) preparation of a test solution: diluting tobramycin eye drops with water to prepare a reference solution; 3) preparation of derivatization solutions: respectively adding the reference substance solution and the test substance solution into a 2, 4-dinitrofluorophenethyl alcohol solution and a tris (hydroxymethyl) aminomethane solution for reaction, and adding acetonitrile after the reaction is completed to prepare a reference substance derivatization solution and a test substance derivatization solution; and 4) determination: taking the reference substance derivatization solution and the test sample derivatization solution, respectively injecting into a high performance liquid chromatograph to obtain chromatograms, and calculating the tobramycin content by using an external standard method according to the peak area of the chromatograms.

The invention discloses a fixing material for a medical device implant and a preparation method of the fixing material. The fixing material comprises a degradable polymer base material with a porous structure and a drug sustained-release coating uniformly loaded on the degradable polymer base material, holes in the degradable polymer are uniformly distributed in a staggered array manner, the holes are circular, the aperture of each hole is 0.5-3.0 mm, and the distance between every two adjacent holes is 0.5-3.0 mm; the drug sustained-release coating contains antibiotics; the antibiotics comprise rifampicin, minocycline hydrochloride, vancomycin, tobramycin, gentamicin and the like. The fixing material disclosed by the invention takes the degradable polymer as a base material, and the drug-loading coating containing antibiotics and anti-inflammatory substances is loaded on the surface, so that slow release of antibiotic drugs can be realized, and the fixing material has excellent antibacterial and anti-inflammatory performance and complete absorbability in a biological environment; and the problems of biocompatibility, infection risk and secondary operation removal of the implant for a long time are solved.

The invention discloses a method for detecting tobramycin based on an organic-inorganic hybrid copper cluster ratio fluorescent probe. A metal doped cluster CuCoNCs (at) PVP emitting blue fluorescence is synthesized, on the basis, a second fluorescent dye probe fluorescein sodium is introduced through physical and chemical interaction, an organic-inorganic hybrid copper cluster ratiometric fluorescent probe (CuCoNCs (at) PVP / FluNa) is constructed, the ratio F513 / F417 of the fluorescence intensity of the system at 513 nm to the fluorescence intensity of the system at 417 nm is used as an output signal, and the fluorescence intensity of the CuCoNCs (at) PVP and the fluorescence intensity of the CuCoNCs (at) PVP are detected. The precise detection on the tobramycin is realized.

The present invention relates to a pharmaceutical composition for preventing or treating flavivirus infections. The invention provides a pharmaceutical composition. The pharmaceutical composition comprises at least one of gentamicin sulfate, netilmicin, tobramycin, paromomycin, amikacin, capreomycin, triflurazine, dihydrostreptomycin, hydroxychloroquine, thiolidazine hydrochloride, efavirenz, mitefonew, nystatin, micafungin, bleomycin, remistat, montelukast, norfloxacin, nedaplatin and cephalosporin, and the pharmaceutical composition is prepared from the following raw materials in parts by weight. It is possible to exhibit an excellent growth inhibition or inactivation effect on different species of flavivirus.

The invention discloses an intelligent antibacterial hydrogel and a preparation method thereof, wherein the specific steps of the preparation method are as follows: mixing a tannic acid aqueous solution with 3-formylphenylboronic acid, adjusting the pH value to 8.0-9.0, obtaining a first solution, then adding an aqueous solution of tobramycin of equal volume to the first solution, and standing for 5-30 minutes to form a TA / BA / TOB hydrogel. The TA / BA / TOB hydrogel of the invention is a bifunctional anchoring structure composed of an aldehyde group and boric acid, and gelled with natural structural monomers (tobramycin and tannic acid), to construct a fully small molecule dynamic covalent intelligent hydrogel, which not only embodies the traditional advantages of the hydrogel, but also has soft and adjustable mechanical properties, solution stability, good biocompatibility, controllable drug release and in vivo antibacterial activity.

This invention relates to the field of pharmaceutical analysis technology, and more particularly to a method for detecting tobramycin-related substances in tobramycin products. The detection method provided by this invention utilizes HPLC-CAD to detect tobramycin-related substances. Based on the concept of quality analysis originating from design, it establishes a stable and reliable analytical method operation design region by systematically identifying and optimizing key method parameters. This overcomes the problems of low sensitivity, complex operation, and insufficient robustness in existing technologies, achieving rapid, accurate, and repeatable detection of related substances in tobramycin raw materials and their preparations.

The invention belongs to the field of chemical analysis and testing, and particularly relates to a quinoline derivative coumarin fluorescent probe targeting tobramycin and a preparation method of the quinoline derivative coumarin fluorescent probe. The preparation method comprises the following steps: dissolving N1-(7-chloroquinoline-4-yl) ethane-1, 2-diamine and 7-(diethylamino) coumarin-3-formic acid in dichloromethane, adding condensing agents of 1-hydroxybenzotriazole (HOBT), 1-ethyl-(3-dimethylamino aldehyde) carbodiimide hydrochloride (EDCI) and triethylamine, carrying out a stirring reaction at room temperature, carrying out separation and purification on an obtained crude product through silica gel column chromatography, and carrying out recrystallization to obtain the 7-(diethylamino) coumarin-3-carboxylic acid-N-(7-chloroquinoline-4-yl) coumarin-3-carboxylic acid-N-(7-chloroquinoline-4-yl) coumarin-3-carboxylic acid-N-(7-chloroquinoline-4-yl) coumarin-3-carboxylic acid. The coumarin fluorescent probe DL containing the quinoline derivatives is obtained. The prepared coumarin fluorescent probe forms a complex under the participation of Cu < 2 + >, and tobramycin can be specifically and rapidly detected in deionized water.

The application discloses an analysis method of tobramycin sulfate injection and application thereof, and the analysis method comprises the following steps: performing a pre-column derivatization reaction on a sample containing tobramycin and impurities by using a derivatization reagent, and then performing high performance liquid chromatography analysis on the sample after derivatization. The analysis is performed by gradient elution of a mobile phase A and a mobile phase B composed of water, acetonitrile and phosphoric acid, wherein the content of acetonitrile in the mobile phase B is higher than that in the mobile phase A, and effective separation of tobramycin and related impurities is realized by multi-stage gradient elution. The method can simultaneously separate and detect process impurities, degradation impurities and unknown impurities, has good separation degree and stability indicating capacity, and is suitable for quality control and drug stability research of tobramycin sulfate injection.

This invention relates to a tobramycin eye drop. Specifically, this invention provides a tobramycin eye drop comprising tobramycin, polyethylene glycol 400, glycerin, sorbitol, alanine, hydroxypropyl cellulose, sodium dihydrogen phosphate, disodium hydrogen phosphate, and water. The tobramycin eye drop of this invention has the advantage of low ocular irritation, significantly improving ocular drug administration compliance. Furthermore, the tobramycin eye drop of this invention exhibits excellent light and high-temperature stability, ensuring the quality and safety of the tobramycin eye drop, thereby enhancing its application value.

The invention provides a method for improving the fermentation yield of a carbamoyl tobramycin production strain. According to the method, a culture medium in the fermentation process of a carbamoyl tobramycin producing strain is improved, a glucose isomerization product is added into the improved fermentation culture medium, or the glucose isomerization product is used for partially replacing glucose in an original fermentation culture medium. After the method is used, the shake flask fermentation yield of carbamoyl tobramycin of the same strain is increased to 3.91 g / L from 3.5 g / L, and is increased by 11.7%. On the basis of finely adjusting the formula of the fermentation culture medium, the fermentation yield of carbamoyl tobramycin is increased while the additional fermentation cost is basically not increased, and the method has important industrial application prospects.

The present invention discloses a tobramycin detection system and a detection method based on CRISPR-Cas12a and hybridization chain reaction, including an identification probe TOB-AP-5, hybridization chain reaction amplification elements H1 and H2, LbCas12a protein, crRNA, and F-Q reporter probe. This method uses the identification probe TOB-AP-5 to recognize tobramycin, trigger the hybridization chain reaction, and then activate the nuclease activity of LbCas12a-crRNA to cleave the F-Q reporter probe and output a fluorescence signal. The system designs and optimizes the position of the tobramycin aptamer sequence in the identification probe, improving the detection sensitivity. The system designs part of the activation sequence of CRISPR-Cas12a in the loop region of the hybridization chain reaction element H1, effectively improving the signal-to-noise ratio. The detection linear range of this method is relatively wide, being 0.125 nM - 25 nM and 25 nM - 2500 nM, with high detection sensitivity, the lowest detection limit being 25 pM, and it can detect tobramycin in milk and beef samples, having broad application prospects in the fields of food safety and environmental monitoring.

The application provides a method for improving the fermentation yield of a carbamoyl tobramycin production strain. The method improves the fermentation medium of the carbamoyl tobramycin production strain, and the improved fermentation medium is added with a glucose isomerization product or uses the glucose isomerization product to partially replace the glucose in the original fermentation medium. After the method is used, the shake flask fermentation yield of the same strain is increased from 3.5 g / L to 3.91 g / L, and the yield is increased by 11.7%. The application improves the fermentation yield of carbamoyl tobramycin on the basis of fine-tuning the fermentation medium formula, and does not increase the additional fermentation cost, so the application has important industrial application prospects.

The invention relates to a compound medicine for treating vulva lichen sclerosus. The compound medicine is prepared from methylrosanilinium chloride, aminoglycoside antibiotics, glucocorticoid, pyrrole broad-spectrum antifungal drugs and pharmaceutic adjuvants. The aminoglycoside antibiotic is tobramycin, the glucocorticoid is dexamethasone, and the pyrrole broad-spectrum antifungal drug is clotrimazole. The compound medicine is ointment or water aqua.

This invention relates to a method for preparing tobramycin sulfate, comprising: S1, acidifying carbamoyl tobramycin fermentation broth, adsorbing it with a first cation exchange resin, sieving and washing it, packing it into a column, then eluting it with a first ammonia solution, while simultaneously decolorizing it with a decolorizing resin column in series, and collecting the eluent rich in carbamoyl tobramycin; S2, hydrolyzing the eluent rich in carbamoyl tobramycin under alkaline conditions to obtain a tobramycin hydrolysate; S3, adjusting the pH of the tobramycin hydrolysate to neutral, adsorbing it with a second cation exchange resin column, washing it with water, and then sequentially eluting it with a second ammonia solution of first, second, and third concentrations, collecting the eluent rich in tobramycin, concentrating it by nanofiltration, salting it, decolorizing it with activated carbon, and spray drying it to obtain the tobramycin sulfate; the first concentration is 0.05~0.1 mol / L, the ratio of the second concentration to the first concentration is 1.5~2, and the ratio of the third concentration to the second concentration is 1.2~1.5. The tobramycin sulfate prepared by the method of this invention has a purity ≥99% and a yield ≥50%.

The invention relates to an ophthalmic medicament for neurotrophic eye diseases of pets and a preparation method and application thereof.The ophthalmic medicament comprises the active ingredients of cat nerve growth factors and tobramycin, and in the ophthalmic medicament, the concentration of the cat nerve growth factors is 60-150 micrograms / mL; the weight percentage of the tobramycin is 0.2-0.5%, the nucleotide sequence for coding the cat nerve growth factor is shown as SEQ ID NO: 1 or SEQ ID NO: 7, the cat nerve growth factor has better stability and biological activity, and compared with a traditional extraction type nerve growth factor, the production cost is lower, large-scale production is more facilitated, and the method is suitable for industrial production. The invention has important application significance and application prospect in the field of preparation and application of therapeutic agents for pet neurotrophic keratitis and neurotrophic corneal ulcer.

The invention relates to a fluorescence sensor for detecting kanamycin and tobramycin in milk based on two-color fluorescent silver nanoclusters, and belongs to the field of food safety detection. The preparation method comprises the following steps: linking an aptamer and a silver nano-cluster template fragment by using a carbon 12 spacer arm, and synthesizing the double-color fluorescent silver nano-cluster. The synthesized silver nanocluster can generate strong red fluorescence and yellow fluorescence which do not interfere with each other at the wavelength of 570 nm and the wavelength of 677 nm, synthesis of the silver nanocluster is promoted through introduction of a C12 spacer group, the fluorescence intensity is enhanced, and cross reaction in the quenching process is reduced. After the aptamer fragment is combined with kanamycin and tobramycin, the structure and conformation of the aptamer fragment are changed, so that the fluorescence of the corresponding silver nano-cluster is quenched. The fluorescence sensor has good sensitivity, the detection limits of kanamycin and tobramycin are 180 pM and 860 pM respectively, the recovery rates of labeled milk are 93.6%-110.1% and 91.4%-98.6% respectively, and meanwhile, the specificity is good. It is proved that the method can be applied to detection of kanamycin and tobramycin in a milk sample and has important application prospects in simultaneous detection and analysis of various antibiotics in food safety application.

The present invention discloses a dressing for skin wounds, its preparation method and application, belonging to the technical field of hydrogels; the dressing for skin wounds provided by the present invention comprises the following raw materials: carboxymethyl cellulose, polyvinyl alcohol, metal chelate, cannabidiol and tobramycin; the metal chelate is a TA / Fe chelate formed by the chelation reaction of trivalent iron ions and tannic acid. The dressing for skin wounds provided by the present invention has excellent mechanical properties, adhesion properties, hemostatic, antibacterial and anti-inflammatory properties, and the effect of promoting wound healing, and can be widely applied to the preparation of drugs for treating trauma. Moreover, the preparation method of the dressing for skin wounds provided by the present invention is simple in operation and is beneficial to practical application.

The embodiment of the invention provides a nanofiltration membrane and a preparation method thereof. The nanofiltration membrane provided by the embodiment of the invention comprises a base membrane and a separation layer arranged on the base membrane, and the separation layer comprises a polymer formed based on tobramycin. Therefore, a large number of amino groups and hydroxyl groups can be provided for the nanofiltration membrane through the tobramycin, lithium ions and other ions are selectively separated through electrostatic interaction generated by the amino groups, the other ions can be effectively intercepted, and the selectivity of the nanofiltration membrane is improved. Meanwhile, an amino group and a hydroxyl group provided by the tobramycin are used for controlling the nanofiltration membrane to form a relatively loose separation layer, so that the permeability of the nanofiltration membrane can be improved, and the treatment efficiency of the nanofiltration membrane is effectively improved.

Compositions and methods are provided for the treatment and degradation of biofilms. In some aspects, engineered polypeptides are provided that can both degrade extracellular polysaccharides (EPS) in biofilm matrix and breaks down quorum-sensing signal molecules that can contribute to formation of biofilms. The engineered polypeptides may synergize with antibiotics such as tobramycin to reduce biofilms. Uses of the engineered polypeptides to treat biofilm infections in medical and other settings are also provided.

The invention discloses a tobramycin polymyxin conjugated compound as well as a preparation method and application thereof. The tobramycin and polymyxin conjugated compound comprises tobramycin and polymyxin which are connected through a chemical bond, and specifically, the tobramycin and the polymyxin are connected through an amido bond or triazole. The tobramycin polymyxin conjugated compound disclosed by the invention can be used for efficiently killing persistent bacteria under the condition of independently using the tobramycin polymyxin conjugated compound; particularly, the modified tobramycin and polymyxin B are connected through an amido bond to obtain the compound AKPB1, high-retention-level mutant strains of escherichia coli can be efficiently killed under the condition of independent medication, the dosage is small, and the compound AKPB1 obviously has potential important application value in the aspect of clinical antibacterial infection treatment and has a broad application prospect. The compound is expected to be used for treating bacterial infection diseases including but not limited to pneumonia, blood flow infection, urinary tract infection, respiratory tract infection, intestinal infection and the like, and is expected to be used for treating bacterial infection of animals.

The invention relates to the field of eye drops, and discloses a tobramycin eye drop preparation process which comprises the following steps: adding 80% of water for injection into a liquid preparation tank, adding sodium chloride, sodium sulfate and boric acid, stirring until the materials are completely dissolved, adding tobramycin, stirring until the materials are completely dissolved, weighing benzalkonium chloride by using a beaker, adding water for dispersing, adding the materials into the liquid preparation tank, and stirring until the materials are completely dissolved; the preparation method comprises the following steps: weighing teloxpol by using a beaker, slowly adding the teloxpol into a liquid preparation tank, washing the beaker by using water for injection, completely transferring the teloxpol into the liquid preparation tank, and stirring until the teloxpol is completely dissolved; the pH value of the liquid medicine is measured and should be 7.0-7.8, if not, 1 mol / L sulfuric acid is used for adjusting the pH value of the liquid medicine to a target value, water for injection is supplemented to the full amount, and stirring is conducted till the liquid medicine is mixed evenly; the culture medium growth promoting ability verification samples all have bacterial growth and are target strains, the negative control samples all have sterile growth and have no turbid phenomenon, and the sensitivity of a microbial challenge method of the product is determined to be 10 microns by taking a 100% intrusive aperture as the sensitivity.

The invention relates to the technical field of CIK cell cryopreservation, in particular to a gel preparation for CIK cell cryopreservation and a preparation method and application thereof. The skin care solution is specifically prepared from sodium hyaluronate, sodium carboxymethyl cellulose, guaiacol, human serum albumin, ornithine, L-proline, low-molecular dextran, dimethyl sulfoxide, 1-aniline, isomaltose oligosaccharide, glutathione, propylene glycol alginate tobramycin, povidone and the balance of water. The skin care solution is prepared from the following raw materials: sodium hyaluronate, sodium carboxymethylcellulose, guaiacol, human serum albumin, ornithine, L-proline, low-molecular dextran, dimethyl sulfoxide, 1-aniline, isomaltose oligosaccharide, glutathione, propylene glycol alginate tobramycin, povidone and the like. The gel preparation provided by the invention can be used for long-time cryopreservation of CIK cells, and the survival rate of immune cells can still reach 96.4% after the CIK cells are preserved for 12 months.

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a liquid preparation containing tobramycin and dexamethasone as well as a preparation method and application of the liquid preparation. The liquid preparation containing tobramycin and dexamethasone takes water as a solvent, and contains tobramycin, dexamethasone, hydroxyethyl cellulose, edetate disodium, sodium sulfate, teloxpol, sodium chloride and benzalkonium chloride. Wherein the weight-average molecular weight of the hydroxyethyl cellulose is 0.3 * 10 < 6 > Dalton to 1.3 * 10 < 6 > Dalton. According to the liquid preparation containing tobramycin and dexamethasone provided by the invention, the long-term storage safety and stability of the liquid preparation in terms of sensitization can be remarkably improved.

The present invention relates to a pharmaceutical composition for preventing or treating flavivirus infections. The invention provides a pharmaceutical composition. The pharmaceutical composition comprises at least one of gentamicin sulfate, netilmicin, tobramycin, paromomycin, amikacin, capreomycin, triflurazine, dihydrostreptomycin, hydroxychloroquine, thiolidazine hydrochloride, efavirenz, mitefonew, nystatin, micafungin, bleomycin, remistat, montelukast, norfloxacin, nedaplatin and cephalosporin, and the pharmaceutical composition is prepared from the following raw materials in parts by weight. It is possible to exhibit an excellent growth inhibition or inactivation effect on different species of flavivirus.

The application relates to the field of analysis and detection, and relates to preparation of a composite silver film coupled with surface plasmons and application of the composite silver film in SERS detection of tobramycin. The preparation of the composite silver film comprises preparation of two layers of silver films, one layer being a self-assembled silver nanoparticle film loaded on the front surface of PDMS, and the other layer being a silver cube film loaded on the back surface of the PDMS. The surface plasmons of the two layers of silver films are coupled with each other by controlling the thickness of the PDMS, and the two layers of silver films are used as a SERS substrate for analysis and detection, so that the sensitivity of detection can be greatly improved. The detection limit of tobramycin can be as low as 2.36*10 ‑12 M, and the linear detection range is 10 ‑5 ~10 ‑11 M, and the relative standard deviation of SERS intensity is less than 10%. The composite silver film prepared by the application has high sensitivity, good universality and practical prospect.

The present invention provides a method for preparing an injectable hydrogel for repairing infectious bone defects, wherein chitosan CS and 4-formylphenylboronic acid 4-FPBA are dissolved in an alcohol-water mixed solution and stirred evenly to obtain a 4-FPBA-CS mixed solution; rosmarinic acid RosA is dissolved in a 4-FPBA-CS mixed solution and stirred evenly to obtain a 4-FPBA-CS / RosA mixed solution; tobramycin solution and 4-FPBA-CS / RosA mixed solution are mixed and allowed to stand to obtain an injectable hydrogel for repairing infectious bone defects. The present invention utilizes rosmarinic acid, chitosan, tobramycin and 4-formylphenylboronic acid to develop an injectable hydrogel with strong structural adaptability, strong antibacterial activity and continuous / stable immunomodulatory function of inducing M2 macrophage polarization. With the gradual degradation of the 4-FPBA-CS / RosA / Tob hydrogel, RosA and Tob can be continuously released at the interface where the hydrogel contacts the bone defect to play a role.