A method for the separation of ofloxacin chiral drugs by two-phase recognition extraction

Abstract

The present invention belongs to the field of drug splitting technology, and in particular to a method for splitting ofloxacin chiral drugs by two-phase identification extraction. The present invention mixes ofloxacin racemate, cyclodextrin and water to obtain ofloxacin racemate aqueous phase solution; Cyclodextrin includes β-cyclodextrin and / hydroxypropyl β-cyclodextrin, and the mass concentration of cyclodextrin in ofloxacin racemate aqueous phase solution is 0.005~0.015g / mL; Tartaric acid and organic solvent are mixed to obtain organic phase solution; Tartaric acid includes L / D-di-p-methylbenzoyltartaric acid, L / D-dibenzoyltartaric acid and L / D-diethyl tartrate; Ofloxacin racemate aqueous phase solution and organic phase solution are mixed, and the obtained mixed solution is subjected to chiral extraction. The splitting method provided by the present invention not only has higher selectivity, and low cost, is suitable for industrial application.

Description

Technical Field

[0001] The invention belongs to the technical field of drug separation, and particularly relates to a method for separating the chiral drug ofloxacin by two-phase recognition extraction. Background Art

[0002] Ofloxacin is a third-generation fluoroquinolone antibacterial agent widely used clinically to treat acute and chronic infections of the respiratory tract, urinary tract, eyes, ears, skin, and soft tissue. As a chiral drug, L-ofloxacin has an antibacterial activity 8 to 128 times that of D-ofloxacin and has lower toxic side effects.

[0003] Currently, methods for obtaining single-enantiomer chiral drugs can be primarily categorized into two types: chiral synthesis and racemate resolution. Chiral synthesis, however, is limited in its application due to its numerous steps, high substrate requirements, slow reaction times, and difficulty in product separation. Racemate resolution is an important method for obtaining single-enantiomer chiral drugs, and several methods have been developed, including crystallization, chromatography, membrane separation, simulated moving bed, and chiral liquid-liquid extraction.

[0004] Among them, chiral liquid-liquid extraction is a method with great industrial application potential. In chiral liquid-liquid extraction, selectivity is an important factor in the chiral separation effect, which is defined as the ratio of the distribution coefficients of the two isomers. Zhang Weiyang et al. (Zhang Weiyang, Cui Xing, Jiang Shuxian et al. Study on the separation of ofloxacin enantiomers by extraction with diethyl L-tartrate [J]. Journal of Chemical Engineering of Colleges and Universities, 2017, 31(04): 769-775.) used diethyl L-tartrate to separate the ofloxacin racemate with a selectivity of 1.39. On this basis, Zhang Weiyang et al. (Zhang Weiyang. Study on the separation of ofloxacin enantiomers by chiral liquid-liquid extraction [D]. Zhejiang University, 2017.) used diethyl L-tartrate and L-dibenzoyltartaric acid as mixed extractants for separation, with a selectivity of 1.58. The above two separation methods have low selectivity.

[0005] Chinese patent CN103664998A discloses a reagent and method for resolving the ofloxacin racemate. A biphasic recognition extraction system is constructed using a chiral ionic liquid (alkyl imidazole L-tartrate) and D-dibenzoyltartaric acid to resolve the ofloxacin racemate. The constructed biphasic recognition extraction system can significantly enhance the separation performance of the chiral liquid-liquid extraction system. However, the alkyl imidazole L-tartrate ionic liquid used is expensive, which is not conducive to its application in industrial production. Summary of the Invention

[0006] The object of the present invention is to provide a method for the separation of ofloxacin chiral drug by two-phase recognition extraction. The separation method provided by the present invention has high selectivity and low cost, and is suitable for industrial application.

[0007] In order to achieve the above object, the present invention provides the following technical solutions:

[0008] The present invention provides a method for the separation of ofloxacin chiral drug by two-phase recognition extraction, comprising the following steps:

[0009] Mixing ofloxacin racemate, cyclodextrin and water to obtain an ofloxacin racemate aqueous solution; the cyclodextrin comprises β-cyclodextrin and / or hydroxypropyl-β-cyclodextrin, and the mass concentration of the cyclodextrin in the ofloxacin racemate aqueous solution is 0.005 to 0.015 g / mL;

[0010] Mixing a tartaric acid substance and an organic solvent to obtain an organic phase solution; the tartaric acid substance includes one or more of L-di-p-methylbenzoyl tartaric acid, D-di-p-methylbenzoyl tartaric acid, L-dibenzoyl tartaric acid, D-dibenzoyl tartaric acid, L-diethyl tartrate, and D-diethyl tartrate, and the mass concentration of the tartaric acid substance in the organic phase solution is 0.01 to 0.02 g / mL;

[0011] The aqueous phase solution of the ofloxacin racemate and the organic phase solution are mixed, and the obtained mixed solution is subjected to chiral extraction to obtain an organic phase enriched in L-ofloxacin and an aqueous phase enriched in D-ofloxacin, wherein the enantiomeric excess of L-ofloxacin in the organic phase enriched in L-ofloxacin is ≥4.4%.

[0012] Preferably, when the cyclodextrin substance is β-cyclodextrin, the mass concentration of β-cyclodextrin in the aqueous solution of ofloxacin racemate is 0.006 g / mL.

[0013] Preferably, when the tartaric acid substance is L-di-p-methylbenzoyl tartaric acid, the mass concentration of L-di-p-methylbenzoyl tartaric acid in the organic phase solution is 0.012 g / mL.

[0014] Preferably, the organic solvent includes one or more of n-octanol, n-hexanol and decanol.

[0015] Preferably, the mass concentration of the ofloxacin racemate in the ofloxacin racemate aqueous solution is 1 to 1.5 g / L; and the volume ratio of the ofloxacin racemate aqueous solution to the organic phase solution is 1:1.

[0016] Preferably, the mixing temperature is 20-50° C. and the mixing time is 1-5 hours.

[0017] Preferably, the mixing is oscillating mixing, and the rotation speed of the oscillating mixing is 500-1000 rpm.

[0018] Preferably, the temperature of the chiral extraction is 20-50° C., and the time is 4-12 hours.

[0019] Preferably, the chiral extraction is performed under static conditions.

[0020] Preferably, the selectivity of the method for resolving the chiral drug ofloxacin by biphasic recognition extraction is ≥1.1.

[0021] The invention provides a method for the biphasic identification extraction and separation of ofloxacin chiral drugs, comprising the following steps: mixing ofloxacin racemate, cyclodextrin substances and water to obtain an ofloxacin racemate aqueous phase solution; the cyclodextrin substances include β-cyclodextrin and / or hydroxypropyl-β-cyclodextrin, and the mass concentration of the cyclodextrin substances in the ofloxacin racemate aqueous phase solution is 0.005-0.015 g / mL; mixing a tartaric acid substance and an organic solvent to obtain an organic phase solution; the tartaric acid substance includes L-di-p-methylbenzoyltartaric acid, D-di-p-methylbenzoyltartaric acid, and the like. One or more of p-methylbenzoyltartaric acid, L-dibenzoyltartaric acid, D-dibenzoyltartaric acid, L-tartrate diethyl ester and D-tartrate diethyl ester, wherein the mass concentration of the tartaric acid substance in the organic phase solution is 0.01-0.02 g / mL; the aqueous phase solution of the ofloxacin racemate and the organic phase solution are mixed, and the obtained mixed solution is subjected to chiral extraction to obtain an organic phase enriched in L-ofloxacin and an aqueous phase enriched in D-ofloxacin, and the enantiomeric excess of L-ofloxacin in the organic phase enriched in L-ofloxacin is ≥17.8%. The present invention introduces low-cost cyclodextrins (such as β-cyclodextrin and / or hydroxypropyl-β-cyclodextrin) into the aqueous phase to selectively identify D-ofloxacin; introduces low-cost tartaric acid substances (such as one or more of L-di-p-methylbenzoyltartaric acid, D-di-p-methylbenzoyltartaric acid, L-dibenzoyltartaric acid, D-dibenzoyltartaric acid, L-diethyl tartrate and D-diethyl tartrate) into the organic phase to selectively identify L-ofloxacin, utilizes cyclodextrins and tartaric acid substances to respectively play a chiral resolution role in the aqueous phase and the organic phase, successfully constructs a two-phase recognition chiral extraction system for ofloxacin enantiomer drugs, and successfully achieves an improvement in separation performance compared to single-phase recognition chiral extraction, showing higher selectivity. Therefore, the separation method provided by the present invention not only has high selectivity, but also is low in cost and suitable for industrial application. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 The present invention provides a flowchart of the chiral drug separation of ofloxacin. DETAILED DESCRIPTION

[0023] The present invention provides a method for the separation of ofloxacin chiral drug by two-phase recognition extraction, which is characterized by comprising the following steps:

[0024] Mixing ofloxacin racemate, cyclodextrin and water to obtain an ofloxacin racemate aqueous solution; the cyclodextrin comprises β-cyclodextrin and / or hydroxypropyl-β-cyclodextrin, and the mass concentration of the cyclodextrin in the ofloxacin racemate aqueous solution is 0.005 to 0.015 g / mL;

[0025] Mixing a tartaric acid substance and an organic solvent to obtain an organic phase solution; the tartaric acid substance includes one or more of L-di-p-methylbenzoyl tartaric acid, D-di-p-methylbenzoyl tartaric acid, L-dibenzoyl tartaric acid, D-dibenzoyl tartaric acid, L-diethyl tartrate, and D-diethyl tartrate, and the mass concentration of the tartaric acid substance in the organic phase solution is 0.01 to 0.02 g / mL;

[0026] The aqueous phase solution of the ofloxacin racemate and the organic phase solution are mixed, and the obtained mixed solution is subjected to chiral extraction to obtain an organic phase enriched in L-ofloxacin and an aqueous phase enriched in D-ofloxacin, wherein the enantiomeric excess of L-ofloxacin in the organic phase enriched in L-ofloxacin is ≥4.4%.

[0027] In the present invention, unless otherwise specified, all preparation raw materials / components are commercially available products well known to those skilled in the art.

[0028] The present invention mixes ofloxacin racemate, cyclodextrin substances and water (hereinafter referred to as first mixing) to obtain an ofloxacin racemate aqueous solution; the cyclodextrin substances include β-cyclodextrin and / or hydroxypropyl-β-cyclodextrin, and the mass concentration of the cyclodextrin substances in the ofloxacin racemate aqueous solution is 0.005-0.015 g / mL.

[0029] In the present invention, the cyclodextrin substance is preferably β-cyclodextrin. The mass concentration of the cyclodextrin substance in the aqueous phase solution of the ofloxacin racemate is preferably 0.006 g / mL or 0.01 g / mL, more preferably 0.006 g / mL. In a specific embodiment of the present invention, the mass concentration of the ofloxacin racemate in the aqueous phase solution of the ofloxacin racemate is preferably 1 to 1.5 g / L, more preferably 1 to 1.3 g / L. In the present invention, the first mixing is preferably: dissolving the cyclodextrin substance in water to obtain an aqueous solution of the cyclodextrin substance; and mixing the ofloxacin racemate and the aqueous solution of the cyclodextrin substance.

[0030] The invention mixes tartaric acid substances and an organic solvent to obtain an organic phase solution; the tartaric acid substances include one or more of L-di-p-methylbenzoyl tartaric acid, D-di-p-methylbenzoyl tartaric acid, L-dibenzoyl tartaric acid, D-dibenzoyl tartaric acid, L-diethyl tartrate and D-diethyl tartrate; and the mass concentration of the tartaric acid substances in the organic phase solution is 0.01-0.02 g / mL.

[0031] In the present invention, the tartaric acid substance is preferably L-di-p-methylbenzoyltartaric acid.

[0032] In the present invention, the organic solvent preferably comprises one or more of n-octanol, n-hexanol, and decanol, more preferably n-octanol, n-hexanol, or decanol, and further preferably n-octanol. When the tartaric acid is preferably L-di-p-methylbenzoyltartaric acid, the mass concentration of L-di-p-methylbenzoyltartaric acid in the organic phase solution is preferably 0.012 g / mL.

[0033] After obtaining an aqueous phase solution of the ofloxacin racemate and an organic phase solution, the present invention mixes the aqueous phase solution of the ofloxacin racemate and the organic phase solution (hereinafter referred to as the second mixture), and the obtained mixed solution is subjected to chiral extraction to obtain an organic phase enriched in L-ofloxacin and an aqueous phase enriched in D-ofloxacin, wherein the enantiomeric excess of L-ofloxacin in the organic phase enriched in L-ofloxacin is ≥4.4%.

[0034] In the present invention, the volume ratio of the ofloxacin racemic aqueous solution to the organic phase solution is preferably 1:1.

[0035] In the present invention, the second mixing temperature is preferably 20-50°C, more preferably 25-35°C; the time is preferably 1-5 hours, more preferably 3 hours. The second mixing is preferably oscillating mixing, and the rotation speed of the oscillating mixing is preferably 500-1000 rpm, more preferably 500 rpm.

[0036] In the present invention, the chiral extraction temperature is preferably 20-50°C, more preferably 25-35°C; the time is preferably 4-12 hours, more preferably 4 hours. The chiral extraction is preferably performed under static conditions.

[0037] In the present invention, the enantiomeric excess of L-ofloxacin in the L-ofloxacin-enriched organic phase is ≥4.4%, more preferably 4.4-26.2%, further preferably 17.8-26.2%, and specifically preferably 4.4%, 10.4%, 15.2%, 6.9%, 18.8%, 17.8%, 26.2%, 21.5%, or 21.9%. The selectivity of the method for the biphasic recognition extraction and resolution of the chiral drug ofloxacin is preferably ≥1.1, more preferably 1.1-2.38, further preferably 1.78-2.38, and specifically preferably 1.1, 1.28, 1.5, 1.25, 1.51, 1.78, 2.38, 2.08, or 2.12.

[0038] In order to further illustrate the present invention, the technical solutions provided by the present invention are described in detail below in conjunction with the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0039] The following examples are all based on Figure 1 The splitting process shown is carried out.

[0040] Example 1

[0041] 0.1059 g of the ofloxacin enantiomer (racemate) was dissolved in 100 mL of a 0.01 g / mL β-cyclodextrin aqueous solution as the aqueous phase. Separately, a 0.01 g / mL solution of L-dibenzoyltartaric acid (L-DBTA) in n-octanol was prepared as the organic phase. 3 mL of each of the aqueous and organic phases were mixed and shaken in a thermostatic metal bath at 25°C and 500 rpm for 3 hours. The mixture was then allowed to stand at the same temperature for 4 hours to allow the phases to separate. After extraction, the partition coefficients (organic / aqueous) for L-ofloxacin and D-ofloxacin were 0.218 and 0.198, respectively, with a selectivity of 1.10. The enantiomeric excess of L-ofloxacin in the organic phase was 4.4%.

[0042] Example 2

[0043] 0.1059 g of the ofloxacin enantiomer (racemate) was dissolved in 100 mL of a 0.01 g / mL β-cyclodextrin aqueous solution as the aqueous phase. Separately, a 0.01 g / mL solution of L-diethyl tartrate (L-DE) in n-octanol was prepared as the organic phase. 3 mL of each of the aqueous and organic phases were mixed and shaken in a thermostatic metal bath at 25°C and 500 rpm for 3 hours. The mixture was then allowed to stand at the same temperature for 4 hours to allow the two phases to separate. After extraction, the partition coefficients for L-ofloxacin and D-ofloxacin were 0.289 and 0.225, respectively, with a selectivity of 1.28. The enantiomeric excess of L-ofloxacin in the organic phase was 10.4%.

[0044] Example 3

[0045] 0.1059 g ofloxacin enantiomer (racemate) was dissolved in 100 mL of a 0.01 g / mL β-cyclodextrin aqueous solution as the aqueous phase. Separately, a 0.01 g / mL solution of L-di-p-methylbenzoyltartaric acid (L-DTTA) in n-octanol was prepared as the organic phase. 3 mL of each of the aqueous and organic phases were mixed and shaken in a thermostatic metal bath at 25°C and 500 rpm for 3 hours. The mixture was then allowed to stand at the same temperature for 4 hours to allow the two phases to separate. After extraction, the partition coefficients for L-ofloxacin and D-ofloxacin were 0.440 and 0.294, respectively, with a selectivity of 1.50. The enantiomeric excess of L-ofloxacin in the organic phase was 15.2%.

[0046] Example 4

[0047] 0.1059 g of the ofloxacin enantiomer (racemate) was dissolved in 100 mL of a 0.01 g / mL β-cyclodextrin aqueous solution as the aqueous phase. Separately, a 0.01 g / mL solution of L-di-p-methylbenzoyltartaric acid (L-DTTA) in n-hexanol was prepared as the organic phase. 3 mL of each of the aqueous and organic phases were mixed and shaken in a thermostatic metal bath at 25°C and 500 rpm for 3 hours. The mixture was then maintained at the same temperature and allowed to stand for 4 hours to allow the two phases to separate. After extraction, the partition coefficients for L-ofloxacin and D-ofloxacin were 0.917 and 0.736, respectively, with a selectivity of 1.25. The enantiomeric excess of L-ofloxacin in the organic phase was 6.9%.

[0048] Example 5

[0049] 0.1059 g ofloxacin enantiomer (racemate) was dissolved in 100 mL of a 0.01 g / mL β-cyclodextrin aqueous solution as the aqueous phase. Separately, a 0.01 g / mL solution of L-di-p-methylbenzoyltartaric acid (L-DTTA) in decanol was prepared as the organic phase. 3 mL of each of the aqueous and organic phases were mixed and shaken in a thermostatic metal bath at 25°C and 500 rpm for 3 hours. The mixture was then allowed to stand at the same temperature for 4 hours to allow the two phases to separate. After extraction, the partition coefficients for L-ofloxacin and D-ofloxacin were 0.166 and 0.110, respectively, with a selectivity of 1.51. The enantiomeric excess of L-ofloxacin in the organic phase was 18.8%.

[0050] Example 6

[0051] 0.1059 g ofloxacin enantiomer (racemate) was dissolved in 100 mL of a 0.01 g / mL β-cyclodextrin aqueous solution as the aqueous phase. Separately, a 0.012 g / mL solution of L-di-p-methylbenzoyltartaric acid (L-DTTA) in n-octanol was prepared as the organic phase. 3 mL of each of the aqueous and organic phases were mixed and shaken in a thermostatic metal bath at 25°C and 500 rpm for 3 hours. The mixture was then allowed to stand at the same temperature for 4 hours to allow the two phases to separate. After extraction, the partition coefficients for L-ofloxacin and D-ofloxacin were 0.919 and 0.515, respectively, with a selectivity of 1.78. The enantiomeric excess of L-ofloxacin in the organic phase was 17.8%.

[0052] Example 7

[0053] 0.1059 g of the ofloxacin enantiomer (racemate) was dissolved in 100 mL of a 0.006 g / mL β-cyclodextrin aqueous solution as the aqueous phase. Separately, a 0.012 g / mL solution of L-di-p-methylbenzoyltartaric acid (L-DTTA) in n-octanol was prepared as the organic phase. 3 mL of each of the aqueous and organic phases were mixed and shaken in a thermostatic metal bath at 25°C and 500 rpm for 3 hours. The mixture was then allowed to stand at the same temperature for 4 hours to allow the two phases to separate. After extraction, the partition coefficients for L-ofloxacin and D-ofloxacin were 1.032 and 0.433, respectively, with a selectivity of 2.38. The enantiomeric excess of L-ofloxacin in the organic phase was 26.2%.

[0054] Example 8

[0055] 0.1237 g of the ofloxacin enantiomer (racemate) was dissolved in 100 mL of a 0.006 g / mL β-cyclodextrin aqueous solution as the aqueous phase. Separately, a 0.012 g / mL solution of L-di-p-methylbenzoyltartaric acid (L-DTTA) in n-octanol was prepared as the organic phase. 3 mL of each of the aqueous and organic phases were mixed and shaken in a thermostatic metal bath at 25°C and 500 rpm for 3 hours. The mixture was then allowed to stand at the same temperature for 4 hours to allow the two phases to separate. After extraction, the partition coefficients for L-ofloxacin and D-ofloxacin were 0.998 and 0.480, respectively, with a selectivity of 2.08. The enantiomeric excess of L-ofloxacin in the organic phase was 21.5%.

[0056] Example 9

[0057] 0.1059 g ofloxacin enantiomer (racemate) was dissolved in 100 mL of a 0.006 g / mL β-cyclodextrin aqueous solution as the aqueous phase. Separately, a 0.012 g / mL solution of L-di-p-methylbenzoyltartaric acid (L-DTTA) in n-octanol was prepared as the organic phase. 3 mL of each of the aqueous and organic phases were mixed and shaken in a thermostatic metal bath at 35°C and 500 rpm for 3 hours. The mixture was then allowed to stand at the same temperature for 4 hours to allow the two phases to separate. After extraction, the partition coefficients for L-ofloxacin and D-ofloxacin were 1.097 and 0.517, respectively, with a selectivity of 2.12. The enantiomeric excess of L-ofloxacin in the organic phase was 21.9%.

[0058] Comparative Example 1

[0059] No recognition agent was added to either of the n-octanol-water phases, and extraction was performed at 25°C. After extraction, the partition coefficients for L-ofloxacin and D-ofloxacin were 0.366 and 0.358, respectively, with a selectivity of 0.98. The enantiomeric excess of L-ofloxacin in the organic phase was only 1.3%. This suggests that the introduction of a chiral recognition agent to provide a chiral environment is essential for the liquid-liquid extraction resolution of ofloxacin enantiomers.

[0060] Comparative Example 2

[0061] Only L-di-p-methylbenzoyltartaric acid was added to n-octanol at a concentration of 0.01 g / mL, and the extraction was performed at 25°C. After extraction, the partition coefficients of L-ofloxacin and D-ofloxacin were 0.772 and 0.704, respectively, the selectivity was 1.10, and the enantiomeric excess of L-ofloxacin in the organic phase was 3.0%.

[0062] Comparative Example 3

[0063] β-cyclodextrin was added only to the aqueous phase at a concentration of 0.01 g / mL, and extraction was performed at 25°C. After extraction, the partition coefficients for L-ofloxacin and D-ofloxacin were 0.215 and 0.179, respectively, with a selectivity of 1.20. The enantiomeric excess of L-ofloxacin in the organic phase was 8.1%. Comparing Control Experiments 2 and 3 with Example 3, the separation performance of the dual-phase recognition extraction system constructed with L-di-p-methylbenzoyltartaric acid and β-cyclodextrin was significantly improved compared to the respective single-phase recognition extraction systems.

[0064] The results of the above examples and comparative examples show that in Example 7 of the present invention, ofloxacin racemate and β-cyclodextrin are dissolved in water to form an aqueous phase, wherein the concentration of ofloxacin racemate is 1 g / L and the concentration of β-cyclodextrin is 0.006 g / mL; L-di-p-methylbenzoyl tartaric acid is dissolved in n-octanol to form an organic phase at a concentration of 0.012 g / mL; the two phases after full dissolution are taken in equal volumes, shaken at 25° C. and 500 rpm for 3 hours, and then allowed to stand at 25° C. for 4 hours to reach phase equilibrium. In Example 7, the enantiomeric selectivity after single-stage extraction can reach 2.38, and the enantiomeric excess of L-ofloxacin in the organic phase can reach 26.2%. Thus, the L-di-p-methylbenzoyl tartaric acid and β-cyclodextrin selected by the present invention play a chiral resolution role in the organic phase and the aqueous phase, respectively, and the constructed two-phase recognition chiral extraction system shows higher selectivity. Moreover, the operating conditions of the process are mild, and the extraction process can achieve good separation effects at room temperature and normal pressure, which has the advantages of energy saving and economy.

[0065] Although the above embodiment provides a detailed description of the present invention, it is only a part of the embodiments of the present invention, not all of the embodiments. Other embodiments can be obtained based on this embodiment without creativity, and these embodiments all fall within the scope of protection of the present invention.

Claims

1. A method for the separation of ofloxacin chiral drugs by two-phase identification extraction, characterized in that: The following steps are involved: Mixing ofloxacin racemate, β-cyclodextrin and water to obtain an ofloxacin racemate aqueous solution; the mass concentration of β-cyclodextrin in the ofloxacin racemate aqueous solution is 0.006-0.01 g / mL; Mixing a tartaric acid substance and an organic solvent to obtain an organic phase solution; the tartaric acid substance is L-di-p-methylbenzoyltartaric acid, the organic solvent is n-octanol or decanol, and the mass concentration of the tartaric acid substance in the organic phase solution is 0.01-0.012 g / mL; The aqueous phase solution of the ofloxacin racemate and the organic phase solution are mixed, and the obtained mixed solution is subjected to chiral extraction to obtain an organic phase enriched in L-ofloxacin and an aqueous phase enriched in D-ofloxacin, wherein the enantiomeric excess of L-ofloxacin in the organic phase enriched in L-ofloxacin is ≥10.4%.

2. The method according to claim 1, characterized in that The mass concentration of the ofloxacin racemate in the ofloxacin racemate aqueous phase solution is 1-1.5 g / L; and the volume ratio of the ofloxacin racemate aqueous phase solution to the organic phase solution is 1:

1.

3. The method according to claim 1, characterized in that The mixing temperature is 20-50° C. and the mixing time is 1-5 hours.

4. The method according to claim 1 or 3, characterized in that The mixing is oscillating mixing, and the rotation speed of the oscillating mixing is 500-1000 rpm.

5. The method according to claim 1, wherein The chiral extraction temperature is 20-50° C., and the time is 4-12 hours.

6. The method according to claim 1 or 5, characterized in that The chiral extraction is carried out under static conditions.

7. The method according to claim 1, characterized in that The selectivity of the method for biphasic recognition extraction and resolution of ofloxacin chiral drug is greater than or equal to 1.28.

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