Linezolid glucose injection and preparation process thereof

Abstract

The invention discloses a linezolid glucose injection and a preparation process thereof.The linezolid glucose injection is prepared from linezolid, sodium citrate, citric acid, anhydrous dextrose, an ethylene complex and poloxamer. Phospholipid and cholesterol serve as raw materials, lipidosome is prepared through ultrasonic dispersion, and then the lipidosome is added into the injection; after the liposome is mixed with a linezolid solution, the linezolid is coated in the liposome through dialysis, so that the slow release effect of the linezolid is realized, the effect that the side effect is aggravated due to quick release of the drug effect is avoided, and the safety of the injection is improved; the ethylene complex and the poloxamer are added to serve as stabilizers of the injection, the stability of the medicine is improved, meanwhile, the sodium citrate and the citric acid are matched to adjust the pH value and the osmotic pressure of the injection, and the bioavailability of the medicine after injection is guaranteed; in the liquid preparation treatment process, activated carbon is added, decarburization stirring is carried out, impurities and particles suspended in the solution are adsorbed, and the purity of the prepared injection is guaranteed.

Description

Technical Field

[0001] The present invention relates to the technical field of medical preparations, in particular to a linezolid glucose injection and a preparation process thereof. Background Art

[0002] Linezolid is a synthetic oxazolidinone antibiotic. Its main mechanism of action is to inhibit bacterial protein synthesis. It acts on the bacterial 50S ribosomal subunit, preventing the connection between mRNA and ribosomes, thereby inhibiting bacterial protein synthesis. The linezolid glucose injection prepared with linezolid as raw material is mainly used to treat infections caused by sensitive strains of specific microorganisms. Linezolid is different from other antibiotics. Its unique site and mode of action make it less likely to develop cross-resistance with other antimicrobial drugs that inhibit protein synthesis in positive bacteria with intrinsic or acquired resistance characteristics, and it has been widely used in the medical field. The existing linezolid glucose injection and its preparation process can basically meet the daily use needs, but due to the influence of linezolid itself, allergic reactions or signs of infection are prone to occur after injection. The existing injection does not have a sustained-release effect, and the side effects are easily aggravated during the rapid release of the drug effect, affecting the safety of the injection; at the same time, the preparation materials are single, and the osmotic pressure and pH differences after the drug preparation will affect the stability and bioavailability of the drug; and the impurities generated during the preparation process are easily suspended in the injection, affecting the purity of the injection. Therefore, it is very necessary to design a linezolid glucose injection and its preparation process. Summary of the invention

[0003] The object of the present invention is to provide a linezolid glucose injection and a preparation process thereof, so as to solve the problems raised in the above background technology.

[0004] To achieve the above-mentioned purpose, the present invention provides the following technical scheme: a linezolid glucose injection, comprising: linezolid, sodium citrate, citric acid, anhydrous glucose, ethylene complex and poloxamer; the weight proportions of the components are: 50-60 parts of linezolid, 0.8-1 parts of sodium citrate, 2-2.6 parts of citric acid, 15-21 parts of anhydrous glucose, 0.6-1.5 parts of ethylene complex and 2-4 parts of poloxamer.

[0005] A preparation process of linezolid glucose injection, comprising the following steps: step 1, raw material preparation; step 2, pretreatment; step 3, coating treatment; step 4, liquid preparation treatment; step 5, pH adjustment; step 6, mixing and filtering; step 7, filling and sterilization; step 8, packaging and storage;

[0006] In the above step 1, 50-60 parts of linezolid, 0.8-1 parts of sodium citrate, 2-2.6 parts of citric acid, 15-21 parts of anhydrous glucose, 0.6-1.5 parts of ethylene complex and 2-4 parts of poloxamer are weighed according to the weight of each component and set aside;

[0007] In the above step 2, the anhydrous glucose prepared in the above step 1 is placed in a beaker, and then water for injection and activated carbon are added to the beaker, and then the beaker is heated with an alcohol lamp, and then continuously boiled after heating to boiling, and after boiling, the pre-treatment liquid is decarbonized and placed in a liquid preparation tank to obtain a pre-treatment liquid for standby use;

[0008] Wherein in the above step 3, phospholipids and cholesterol are added to deionized water for thorough mixing, the thoroughly mixed solution is added to an ultrasonic disperser for dispersion treatment, a liposome solution is obtained after the dispersion treatment, and the liposome solution is set aside, then the linezolid prepared in the above step 1 is put into water for injection, and the linezolid solution is obtained after stirring, and then the linezolid solution and the liposome solution are poured into a stirrer for mixing and stirring, and the mixing and stirring are put into a dialysis bag, and the dialysis bag is immersed in PBS dialysate for dialysis treatment, and the linezolid coating solution is obtained after the dialysis treatment, and the linezolid coating solution is set aside;

[0009] In the above step 4, water for injection and pretreatment liquid are added to the liquid preparation tank in the above step 2 to mix with each other, and then the sodium citrate and citric acid prepared in the above step 1 are added to the liquid preparation tank for stirring, and after stirring, the linezolid coating liquid prepared in step 3 is added for stirring again, and after stirring again, activated carbon is added to the solution and stirred for decarbonization, and after decarbonization and stirring, the drug stock solution is obtained by standing and separating for standby;

[0010] In the above step 5, the prepared reagent stock solution in the above step 4 is placed in a regulating tank, and then the pH value in the regulating tank is adjusted to 4.7-4.9 to obtain a regulating solution for standby use;

[0011] In the above step 6, the adjustment solution prepared in the above step 5 is put into a blender, and then the ethylene complex and poloxamer prepared in the step 1 are added, followed by continuous stirring in the blender, and after continuous stirring, filtering is performed to remove any insoluble particles or impurities to obtain an injection stock solution for standby use;

[0012] In the above step 7, the injection stock solution obtained in the above step 6 is discharged into a disinfection tank and then subjected to wet heat treatment using high-pressure saturated steam, and then continuously sterilized after the wet heat treatment, and then filled into a sterile infusion bag after sterilization to obtain a sterile injection solution for standby use;

[0013] In the above step eight, the sterile injection solution obtained in the above step seven is subjected to quality inspection, including appearance, pH value and microbial limit, and qualified products are packaged and marked with product information to obtain linezolid glucose injection.

[0014] As a further technical solution of the present invention, in step 2, the amount of water for injection added is 300% to 450% of the mass fraction of anhydrous glucose, the concentration of activated carbon in the beaker is 0.012 to 0.015 mg / mL after the activated carbon is added, and the boiling treatment time is 15 to 30 minutes.

[0015] As a further technical solution of the present invention, in the step three, phospholipids and cholesterol are added to deionized water so that the concentration of phospholipids in the deionized water is 0.5-0.6 mg / mL, and the concentration of cholesterol in the deionized water is 3-6 mg / mL; the operating frequency of the ultrasonic disperser during the dispersion treatment is 5-13 kHz, and the dispersion treatment time is 3-7 min.

[0016] As a further technical solution of the present invention, in the step three, the concentration of linezolid in the linezolid solution after stirring is 45-52 mg / mL, the volume ratio of the linezolid solution to the liposome solution during the mixing and stirring process is 1:2, the stirring speed during the mixing and stirring is 30-60 r / min, and the mixing and stirring time is 18-25 min, and the dialysis treatment time in the PBS dialysate is 60-90 min.

[0017] As a further technical solution of the present invention, in step 4, the amount of additional injection water is 10% to 30% of the volume of the pretreatment liquid, the temperature during stirring treatment is 50 to 60°C, the stirring speed during stirring treatment is 18 to 25 r / min, and the stirring treatment time is 7 to 10 min.

[0018] As a further technical solution of the present invention, in the step four, the temperature during the second stirring is 50-60°C, the stirring speed during the second stirring is 28-35r / min, and the stirring time is 15-20min; the activated carbon concentration in the solution after the addition of activated carbon is 0.003mg / mL-0.0075mg / mL, the temperature during decarbonization stirring is 50-60°C, the stirring speed during decarbonization stirring is 38-45r / min, and the decarbonization stirring time is 4-5min, and the standing time after decarbonization stirring is 15-30min.

[0019] As a further technical solution of the present invention, in step five, the regulator used in the pH adjustment process is a hydrochloric acid solution with a molar concentration of 10 mol / ml or a sodium hydroxide solution with a molar concentration of 15 mol / ml.

[0020] As a further technical solution of the present invention, in step six, the temperature in the stirrer during continuous stirring is 55-60°C, the stirring speed during continuous stirring is 28-35 r / min, and the continuous stirring time is 10-15 min.

[0021] As a further technical solution of the present invention, in step seven, the temperature during continuous sterilization is 121-123° C., and the continuous sterilization time is 30-45 minutes.

[0022] Compared with the prior art, the beneficial effects of the present invention are as follows: the linezolid glucose injection and the preparation process thereof use phospholipids and cholesterol as raw materials to prepare liposomes through ultrasonic dispersion, and then mix with a linezolid solution to encapsulate linezolid inside the liposomes through dialysis, thereby achieving a sustained release effect of linezolid, avoiding the effect of rapid release of drug efficacy and aggravating side effects, and improving the safety of the injection; by adding ethylene complexes and poloxamer as stabilizers of the injection, compounds that can bind metal ions through hydrogen bonds improve drug stability, and by adding sodium citrate and citric acid to adjust the pH value and osmotic pressure of the injection, the bioavailability of the drug after injection is guaranteed; in the process of liquid preparation, activated carbon is added and decarbonization stirring is performed to adsorb impurities and particulate matter suspended in the solution, thereby ensuring the purity of the injection after preparation. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 It is a flow chart of the preparation process of the present invention. DETAILED DESCRIPTION

[0024] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0025] See also Figure 1 , the present invention provides a technical solution:

[0026] Embodiment 1:

[0027] A linezolid glucose injection comprises: linezolid, sodium citrate, citric acid, anhydrous glucose, ethylene complex and poloxamer; the weight proportions of the components are: 60 parts of linezolid, 1 part of sodium citrate, 2.6 parts of citric acid, 21 parts of anhydrous glucose, 1.5 parts of ethylene complex and 4 parts of poloxamer.

[0028] A preparation process of linezolid glucose injection, comprising the following steps: step 1, raw material preparation; step 2, pretreatment; step 3, coating treatment; step 4, liquid preparation treatment; step 5, pH adjustment; step 6, mixing and filtering; step 7, filling and sterilization; step 8, packaging and storage;

[0029] In the above step 1, 60 parts of linezolid, 1 part of sodium citrate, 2.6 parts of citric acid, 21 parts of anhydrous glucose, 1.5 parts of ethylene complex and 4 parts of poloxamer are weighed according to the weight of each component and set aside;

[0030] In the above step 2, the anhydrous glucose prepared in the above step 1 is placed in a beaker, and then water for injection and activated carbon are added to the beaker, and then the beaker is heated with an alcohol lamp, and then continuously boiled after heating to boiling, and then decarbonized into a liquid preparation tank after boiling to obtain a pre-treated liquid for standby use; the amount of water for injection added is 450% of the mass fraction of anhydrous glucose, and the concentration of activated carbon in the beaker is 0.015 mg / mL after the activated carbon is added, and the boiling time is 30 min;

[0031] In the above step 3, phospholipids and cholesterol are added to deionized water for thorough mixing, and the thoroughly mixed solution is added to an ultrasonic disperser for dispersion treatment, and a liposome solution is obtained after the dispersion treatment, and the liposome solution is set aside, and then the linezolid prepared in the above step 1 is added to water for injection, and the linezolid solution is obtained after stirring, and then the linezolid solution and the liposome solution are poured into a stirrer for mixing and stirring, and the mixing and stirring are put into a dialysis bag, and the dialysis bag is immersed in PBS dialysis solution for dialysis treatment, and the linezolid coating solution is obtained after the dialysis treatment, and the phospholipids and cholesterol are added to After deionizing the water, the phospholipid concentration in the deionized water is 0.6 mg / mL, and the cholesterol concentration in the deionized water is 6 mg / mL; the working frequency of the ultrasonic disperser during the dispersion treatment is 13 kHz, and the dispersion treatment time is 7 minutes; after stirring, the linezolid concentration in the linezolid solution is 52 mg / mL, the volume ratio of the linezolid solution to the liposome solution during the mixing and stirring process is 1:2, the stirring speed during the mixing and stirring is 60 r / min, and the mixing and stirring time is 25 minutes, and the dialysis treatment time in the PBS dialysate is 90 minutes;

[0032] In the above step 4, water for injection is added to the liquid preparation tank in the above step 2 and mixed with the pretreatment liquid, and then the sodium citrate and citric acid prepared in the above step 1 are added to the liquid preparation tank for stirring, and after stirring, the linezolid coating liquid prepared in step 3 is added for stirring again, and after stirring again, activated carbon is added to the solution and stirred for decarbonization, and after decarbonization and stirring, the drug stock solution is obtained by standing and separating for standby; the amount of water for injection added is 30% of the volume of the pretreatment liquid, and the temperature during the stirring treatment is 60℃, the stirring speed during the stirring treatment is 25r / min, and the stirring time is 10min; the temperature during the second stirring is 60℃, the stirring speed during the second stirring is 35r / min, and the stirring time is 20min; the activated carbon concentration in the solution after the addition of activated carbon is 0.0075mg / mL, the temperature during decarbonization stirring is 60℃, the stirring speed during decarbonization stirring is 45r / min, and the decarbonization stirring time is 5min, and the standing time after decarbonization stirring is 30min;

[0033] In the above step 5, the prepared reagent stock solution in the above step 4 is placed in a regulating tank, and then the pH value in the regulating tank is adjusted to 4.9 to obtain a regulating solution for standby use; the regulating agent used in the pH adjustment process is a hydrochloric acid solution with a molar concentration of 10 mol / ml or a sodium hydroxide solution with a molar concentration of 15 mol / ml;

[0034] In the above step 6, the adjustment solution prepared in the above step 5 is put into a mixer, and then the ethylene complex and poloxamer prepared in the step 1 are added, followed by continuous stirring in the mixer, and after continuous stirring, filtering is performed to remove any insoluble particles or impurities to obtain an injection stock solution for standby use; during the continuous stirring process, the temperature in the mixer is 60° C., the stirring speed during the continuous stirring is 35 r / min, and the continuous stirring time is 15 min;

[0035] In the above step 7, the injection stock solution obtained in the above step 6 is discharged into a disinfection tank and then subjected to wet heat treatment using high-pressure saturated steam, and then continuously sterilized after the wet heat treatment, and then filled into a sterile infusion bag after sterilization to obtain a sterile injection solution for standby use; the temperature during continuous sterilization is 123°C, and the continuous sterilization time is 45 minutes;

[0036] In the above step eight, the sterile injection solution obtained in the above step seven is subjected to quality inspection, including appearance, pH value and microbial limit, and qualified products are packaged and marked with product information to obtain linezolid glucose injection.

[0037] Embodiment 2:

[0038] A linezolid glucose injection comprises: linezolid, sodium citrate, citric acid, anhydrous glucose, ethylene complex and poloxamer; the weight proportions of the components are: 50 parts of linezolid, 0.8 parts of sodium citrate, 2 parts of citric acid, 15 parts of anhydrous glucose, 0.6 parts of ethylene complex and 2 parts of poloxamer.

[0039] A preparation process of linezolid glucose injection, comprising the following steps: step 1, raw material preparation; step 2, pretreatment; step 3, coating treatment; step 4, liquid preparation treatment; step 5, pH adjustment; step 6, mixing and filtering; step 7, filling and sterilization; step 8, packaging and storage;

[0040] In the above step 1, 50 parts of linezolid, 0.8 parts of sodium citrate, 2 parts of citric acid, 15 parts of anhydrous glucose, 0.6 parts of ethylene complex and 2 parts of poloxamer are weighed according to the weight of each component and set aside;

[0041] In the above step 2, the anhydrous glucose prepared in the above step 1 is placed in a beaker, and then water for injection and activated carbon are added to the beaker, and then the beaker is heated with an alcohol lamp, and then continuously boiled after heating to boiling, and then decarbonized into a liquid preparation tank after boiling to obtain a pre-treated liquid for standby use; the amount of water for injection added is 300% of the mass fraction of anhydrous glucose, and the concentration of activated carbon in the beaker is 0.012 mg / mL after the activated carbon is added, and the boiling time is 15 min;

[0042] In the above step 3, phospholipids and cholesterol are added to deionized water for thorough mixing, and the thoroughly mixed solution is added to an ultrasonic disperser for dispersion treatment, and a liposome solution is obtained after the dispersion treatment, and the liposome solution is set aside, and then the linezolid prepared in the above step 1 is added to water for injection, and the linezolid solution is obtained after stirring, and then the linezolid solution and the liposome solution are poured into a stirrer for mixing and stirring, and the mixing and stirring are put into a dialysis bag, and the dialysis bag is immersed in PBS dialysis solution for dialysis treatment, and the linezolid coating solution is obtained after the dialysis treatment, and the phospholipids and cholesterol are added to After deionizing the water, the phospholipid concentration in the deionized water is 0.5 mg / mL, and the cholesterol concentration in the deionized water is 3 mg / mL; the working frequency of the ultrasonic disperser during the dispersion treatment is 5 kHz, and the dispersion treatment time is 3 min; after stirring, the linezolid concentration in the linezolid solution is 45 mg / mL, the volume ratio of the linezolid solution to the liposome solution during the mixing and stirring process is 1:2, the stirring speed during the mixing and stirring is 30 r / min, and the mixing and stirring time is 18 min, and the dialysis treatment time in the PBS dialysate is 60 min;

[0043] wherein in the above step 4, water for injection is added to the liquid preparation tank in the above step 2 and mixed with the pretreatment liquid, then the sodium citrate and citric acid prepared in the above step 1 are added to the liquid preparation tank for stirring, after stirring, the linezolid coating liquid prepared in step 3 is added for stirring again, after stirring again, activated carbon is added to the solution and decarbonized and stirred, after decarbonized and stirred, the drug stock solution is obtained by standing and separating for standby; the amount of water for injection added is 10% of the volume of the pretreatment liquid, the temperature during stirring is 50°C, the stirring speed during stirring is 18r / min, and the stirring time is 7min; the temperature during stirring again is 50°C, the stirring speed during stirring again is 28r / min, and the stirring time is 15min; after the addition of activated carbon, the activated carbon concentration in the solution is 0.003mg / mL, the temperature during decarbonization stirring is 50°C, the stirring speed during decarbonization stirring is 38r / min, and the decarbonization stirring time is 4min, and the standing time after decarbonization stirring is 15min;

[0044] In the above step 5, the prepared reagent stock solution in the above step 4 is placed in a regulating tank, and then the pH value in the regulating tank is adjusted to 4.7 to obtain a regulating solution for standby use; the regulating agent used in the pH adjustment process is a hydrochloric acid solution with a molar concentration of 10 mol / ml or a sodium hydroxide solution with a molar concentration of 15 mol / ml;

[0045] In the above step 6, the adjustment solution prepared in the above step 5 is put into a mixer, and then the ethylene complex and poloxamer prepared in step 1 are added, followed by continuous stirring in the mixer, and after continuous stirring, filtering is performed to remove any insoluble particles or impurities to obtain an injection stock solution for standby use; during the continuous stirring process, the temperature in the mixer is 55° C., the stirring speed during the continuous stirring is 28 r / min, and the continuous stirring time is 10 min;

[0046] In the above step 7, the injection stock solution obtained in the above step 6 is discharged into a disinfection tank and then subjected to wet heat treatment using high-pressure saturated steam, and then continuously sterilized after the wet heat treatment, and then filled into a sterile infusion bag after sterilization to obtain a sterile injection solution for standby use; the temperature during continuous sterilization is 121° C., and the continuous sterilization time is 30 minutes;

[0047] In the above step eight, the sterile injection solution obtained in the above step seven is subjected to quality inspection, including appearance, pH value and microbial limit, and qualified products are packaged and marked with product information to obtain linezolid glucose injection.

[0048] Embodiment 3:

[0049] A linezolid glucose injection comprises: linezolid, sodium citrate, citric acid, anhydrous glucose, ethylene complex and poloxamer; the weight proportions of the components are: 60 parts of linezolid, 0.8 parts of sodium citrate, 2.6 parts of citric acid, 15 parts of anhydrous glucose, 1.5 parts of ethylene complex and 2 parts of poloxamer.

[0050] A preparation process of linezolid glucose injection, comprising the following steps: step 1, raw material preparation; step 2, pretreatment; step 3, coating treatment; step 4, liquid preparation treatment; step 5, pH adjustment; step 6, mixing and filtering; step 7, filling and sterilization; step 8, packaging and storage;

[0051] In the above step 1, 60 parts of linezolid, 0.8 parts of sodium citrate, 2.6 parts of citric acid, 15 parts of anhydrous glucose, 1.5 parts of ethylene complex and 2 parts of poloxamer are weighed according to the weight of each component and set aside;

[0052] In the above step 2, the anhydrous glucose prepared in the above step 1 is placed in a beaker, and then water for injection and activated carbon are added to the beaker, and then the beaker is heated with an alcohol lamp, and then continuously boiled after heating to boiling, and then decarbonized into a liquid preparation tank after boiling to obtain a pre-treated liquid for standby use; the amount of water for injection added is 450% of the mass fraction of anhydrous glucose, and the concentration of activated carbon in the beaker is 0.012 mg / mL after the activated carbon is added, and the boiling time is 30 min;

[0053] In the above step 3, phospholipids and cholesterol are added to deionized water for thorough mixing, and the thoroughly mixed solution is added to an ultrasonic disperser for dispersion treatment, and a liposome solution is obtained after the dispersion treatment, and the liposome solution is set aside, and then the linezolid prepared in the above step 1 is added to water for injection, and the linezolid solution is obtained after stirring, and then the linezolid solution and the liposome solution are poured into a stirrer for mixing and stirring, and the mixing and stirring are put into a dialysis bag, and the dialysis bag is immersed in PBS dialysis solution for dialysis treatment, and the linezolid coating solution is obtained after the dialysis treatment, and the phospholipids and cholesterol are added to After deionizing water, the phospholipid concentration in the deionized water is 0.5 mg / mL, and the cholesterol concentration in the deionized water is 6 mg / mL; the working frequency of the ultrasonic disperser during the dispersion treatment is 5 kHz, and the dispersion treatment time is 7 minutes; after stirring, the linezolid concentration in the linezolid solution is 45 mg / mL, the volume ratio of the linezolid solution to the liposome solution during the mixing and stirring process is 1:2, the stirring speed during the mixing and stirring is 60 r / min, and the mixing and stirring time is 18 minutes, and the dialysis treatment time in the PBS dialysate is 90 minutes;

[0054] wherein in the above step 4, water for injection is added to the liquid preparation tank in the above step 2 and mixed with the pretreatment liquid, then the sodium citrate and citric acid prepared in the above step 1 are added to the liquid preparation tank for stirring, after stirring, the linezolid coating liquid prepared in step 3 is added for stirring again, after stirring again, activated carbon is added to the solution and decarbonized and stirred, after decarbonized and stirred, the drug stock solution is obtained by standing and separating for standby; the amount of water for injection added is 30% of the volume of the pretreatment liquid, the temperature during stirring is 50°C, the stirring speed during stirring is 25r / min, and the stirring time is 7min; the temperature during stirring again is 60°C, the stirring speed during stirring again is 28r / min, and the stirring time is 20min; after the addition of activated carbon, the activated carbon concentration in the solution is 0.003mg / mL, the temperature during decarbonization stirring is 60°C, the stirring speed during decarbonization stirring is 38r / min, and the decarbonization stirring time is 5min, and the standing time after decarbonization stirring is 15min;

[0055] In the above step 5, the prepared reagent stock solution in the above step 4 is placed in a regulating tank, and then the pH value in the regulating tank is adjusted to 4.9 to obtain a regulating solution for standby use; the regulating agent used in the pH adjustment process is a hydrochloric acid solution with a molar concentration of 10 mol / ml or a sodium hydroxide solution with a molar concentration of 15 mol / ml;

[0056] In the above step 6, the adjustment solution prepared in the above step 5 is put into a mixer, and then the ethylene complex and poloxamer prepared in the step 1 are added, followed by continuous stirring in the mixer, and after continuous stirring, filtering is performed to remove any insoluble particles or impurities to obtain an injection stock solution for standby use; during the continuous stirring process, the temperature in the mixer is 55° C., the stirring speed during the continuous stirring is 35 r / min, and the continuous stirring time is 10 min;

[0057] In the above step 7, the injection stock solution obtained in the above step 6 is discharged into a disinfection tank and then subjected to wet heat treatment using high-pressure saturated steam, and then continuously sterilized after the wet heat treatment, and then filled into a sterile infusion bag after sterilization to obtain a sterile injection solution for standby use; the temperature during continuous sterilization is 123°C, and the continuous sterilization time is 30 minutes;

[0058] In the above step eight, the sterile injection solution obtained in the above step seven is subjected to quality inspection, including appearance, pH value and microbial limit, and qualified products are packaged and marked with product information to obtain linezolid glucose injection.

[0059] The linezolid and glucose injections obtained in the above examples were tested for performance and compared with common injections on the market. The results are shown in the following table:

[0060] Doping rate Blood samples were collected 2 hours after injection to measure the concentration of linezolid Example 1 0.14％ 0.054mg / mL Example 2 0.18％ 0.048mg / mL Example 3 0.23％ 0.054mg / mL Comparative Example 2.35％ 0.003mg / mL

[0061] Based on the above, the advantages of the present invention are that, when used, the present invention uses phospholipids and cholesterol as raw materials to prepare liposomes through ultrasonic dispersion, mixes with linezolid solution, and then dialysis is performed to coat linezolid inside the liposomes, thereby achieving a sustained release effect of linezolid, avoiding the effect of rapid release of drug efficacy and aggravating side effects, and improving the safety of the injection; by adding ethylene complexes and poloxamer as stabilizers for the injection, compounds that can bind to metal ions through hydrogen bonds improve drug stability, and by adding sodium citrate and citric acid to adjust the pH value and osmotic pressure of the injection, the bioavailability of the drug after injection is guaranteed; during the liquid preparation process, activated carbon is added and decarbonization stirring is performed to adsorb impurities and particulate matter suspended in the solution, thereby ensuring the purity of the injection after preparation.

[0062] It will be apparent to those skilled in the art that the invention is not limited to the details of the exemplary embodiments described above and that the invention can be implemented in other specific forms without departing from the spirit or essential features of the invention. Therefore, the embodiments should be considered exemplary and non-limiting in all respects, and the scope of the invention is defined by the appended claims rather than the foregoing description, and it is intended that all variations falling within the meaning and scope of the equivalent elements of the claims be included in the invention. Any reference numeral in a claim should not be considered as limiting the claim to which it relates.

Claims

1. A linezolid and glucose injection, the formula comprising: Linezolid, sodium citrate, citric acid, anhydrous glucose, ethylene complex and poloxamer; characterized in that the weight proportions of the components are: 50-60 parts of linezolid, 0.8-1 parts of sodium citrate, 2-2.6 parts of citric acid, 15-21 parts of anhydrous glucose, 0.6-1.5 parts of ethylene complex and 2-4 parts of poloxamer.

2. A preparation process of linezolid glucose injection, comprising the following steps: Step 1, raw material preparation; Step 2, pretreatment; Step 3, coating treatment; Step 4, liquid preparation treatment; Step 5, pH adjustment; Step 6, mixing and filtration; Step 7, filling and sterilization; Step 8, packaging and storage; It is characterized by: In the above step 1, 50-60 parts of linezolid, 0.8-1 parts of sodium citrate, 2-2.6 parts of citric acid, 15-21 parts of anhydrous glucose, 0.6-1.5 parts of ethylene complex and 2-4 parts of poloxamer are weighed according to the weight of each component and set aside; In the above step 2, the anhydrous glucose prepared in the above step 1 is placed in a beaker, and then water for injection and activated carbon are added to the beaker, and then the beaker is heated with an alcohol lamp, and then continuously boiled after heating to boiling, and after boiling, the pre-treatment liquid is decarbonized and placed in a liquid preparation tank to obtain a pre-treatment liquid for standby use; Wherein in the above step 3, phospholipids and cholesterol are added to deionized water for thorough mixing, the thoroughly mixed solution is added to an ultrasonic disperser for dispersion treatment, a liposome solution is obtained after the dispersion treatment, and the liposome solution is set aside, then the linezolid prepared in the above step 1 is put into water for injection, and the linezolid solution is obtained after stirring, and then the linezolid solution and the liposome solution are poured into a stirrer for mixing and stirring, and the mixing and stirring are put into a dialysis bag, and the dialysis bag is immersed in PBS dialysate for dialysis treatment, and the linezolid coating solution is obtained after the dialysis treatment, and the linezolid coating solution is set aside; In the above step 4, water for injection and pretreatment liquid are added to the liquid preparation tank in the above step 2 to mix with each other, and then the sodium citrate and citric acid prepared in the above step 1 are added to the liquid preparation tank for stirring, and after stirring, the linezolid coating liquid prepared in step 3 is added for stirring again, and after stirring again, activated carbon is added to the solution and stirred for decarbonization, and after decarbonization and stirring, the drug stock solution is obtained by standing and separating for standby; In the above step 5, the prepared reagent stock solution in the above step 4 is placed in a regulating tank, and then the pH value in the regulating tank is adjusted to 4.7-4.9 to obtain a regulating solution for standby use; In the above step 6, the adjustment solution prepared in the above step 5 is put into a blender, and then the ethylene complex and poloxamer prepared in the step 1 are added, followed by continuous stirring in the blender, and after continuous stirring, filtering is performed to remove any insoluble particles or impurities to obtain an injection stock solution for standby use; In the above step 7, the injection stock solution obtained in the above step 6 is discharged into a disinfection tank and then subjected to wet heat treatment using high-pressure saturated steam, and then continuously sterilized after the wet heat treatment, and then filled into a sterile infusion bag after sterilization to obtain a sterile injection solution for standby use; In the above step eight, the sterile injection solution obtained in the above step seven is subjected to quality inspection, including appearance, pH value and microbial limit, and qualified products are packaged and marked with product information to obtain linezolid glucose injection.

3. The preparation process of linezolid and glucose injection according to claim 2, characterized in that: In the step 2, the amount of water for injection added is 300% to 450% of the mass fraction of anhydrous glucose, the concentration of activated carbon in the beaker is 0.012 to 0.015 mg / mL after the activated carbon is added, and the boiling treatment time is 15 to 30 minutes.

4. The preparation process of linezolid and glucose injection according to claim 2, characterized in that: In the step three, phospholipids and cholesterol are added to deionized water so that the concentration of phospholipids in the deionized water is 0.5-0.6 mg / mL, and the concentration of cholesterol in the deionized water is 3-6 mg / mL; the operating frequency of the ultrasonic disperser during the dispersion treatment is 5-13 kHz, and the dispersion treatment time is 3-7 min.

5. The preparation process of linezolid and glucose injection according to claim 2, characterized in that: In the step three, the concentration of linezolid in the linezolid solution after stirring is 45-52 mg / mL, the volume ratio of the linezolid solution to the liposome solution during the mixing and stirring process is 1:2, the stirring speed during the mixing and stirring is 30-60 r / min, and the mixing and stirring time is 18-25 min, and the dialysis treatment time in the PBS dialysate is 60-90 min.

6. The preparation process of linezolid and glucose injection according to claim 2, characterized in that: In the step 4, the amount of injection water added is 10% to 30% of the volume of the pretreatment liquid, the temperature during the stirring treatment is 50 to 60° C., the stirring speed during the stirring treatment is 18 to 25 r / min, and the stirring treatment time is 7 to 10 min.

7. The preparation process of linezolid and glucose injection according to claim 2, characterized in that: In the step 4, the temperature during the second stirring is 50-60°C, the stirring speed during the second stirring is 28-35 r / min, and the stirring time is 15-20 min; After the activated carbon is added, the activated carbon concentration in the solution is 0.003 mg / mL to 0.0075 mg / mL, the temperature during decarbonization stirring is 50 to 60°C, the stirring speed during decarbonization stirring is 38 to 45 r / min, the decarbonization stirring time is 4 to 5 minutes, and the standing time after decarbonization stirring is 15 to 30 minutes.

8. The preparation process of linezolid and glucose injection according to claim 2, characterized in that: In the step 5, the regulator used in the pH adjustment process is a hydrochloric acid solution with a molar concentration of 10 mol / ml or a sodium hydroxide solution with a molar concentration of 15 mol / ml.

9. The preparation process of linezolid and glucose injection according to claim 2, characterized in that: In the step six, the temperature in the stirrer during the continuous stirring process is 55-60° C., the stirring speed during the continuous stirring is 28-35 r / min, and the continuous stirring time is 10-15 min.

10. The preparation process of linezolid and glucose injection according to claim 2, characterized in that: In the step 7, the temperature during continuous sterilization is 121-123° C., and the continuous sterilization time is 30-45 minutes.

Images