An endoscopic cleaning compound disinfectant and its preparation method

Abstract

The present invention provides an endoscopic cleaning composite disinfectant and a preparation method thereof, belonging to the technical field of disinfectants. It has the following structural formula; the present invention prepares an asymmetric quaternary ammonium base, which is compounded with natamycin to form an endoscopic cleaning composite disinfectant. The preparation method is simple, the reaction conditions are mild, the prepared asymmetric quaternary ammonium base has good disinfection and bactericidal effects, strong decontamination ability, good antibacterial and bacteriostatic effects, and good killing ability against viruses, and has broad application prospects.

Description

Technical Field

[0001] The present invention relates to the technical field of disinfectants, and particularly relates to an endoscopic cleaning composite disinfectant and a preparation method thereof. Background Art

[0002] Quaternary ammonium hydroxide is an organic strong base with a general molecular structure formula of R4N + OH - (where R is the same or different hydrocarbon groups), similar to ammonium hydroxide. Quaternary ammonium hydroxide itself is prone to deliquescence and absorption of carbon dioxide in the air, and has good water solubility. The mass fraction of its aqueous solution is generally 10% or 25%. As a special type of quaternary ammonium salt, quaternary ammonium hydroxide has important applications in the fields of surfactants, antistatic agents, emulsifiers, etc. And as an important organic base, quaternary ammonium hydroxide has unique properties that inorganic bases do not have, and has broad application prospects in chemical engineering, silicone synthesis, molecular sieve preparation, as a phase transfer catalyst, and in the treatment of daily chemicals.

[0003] Quaternary ammonium hydroxide has advantages that traditional inorganic strong bases do not have and has become a key basic fine chemical in many fields. Currently, long-chain quaternary ammonium hydroxide, adamantane quaternary ammonium hydroxide, etc. are widely used as surfactants in the fields of sterilization, decontamination, etc. And quaternary ammonium hydroxide itself can change the cationic group or the number of carbon chains to endow itself with more functions. Therefore, the research on quaternary ammonium hydroxide has very good application and development prospects. Asymmetric quaternary ammonium hydroxide, also known as chiral quaternary ammonium hydroxide, has good applications in the fields of asymmetric catalysis, surfactants, antibacterial and bacteriostatic. Summary of the Invention

[0004] The purpose of the present invention is to provide an endoscopic cleaning composite disinfectant and a preparation method thereof. An asymmetric quaternary ammonium hydroxide is prepared, which is compounded with natamycin to form an endoscopic cleaning composite disinfectant. The preparation method is simple, the reaction conditions are mild, the prepared asymmetric quaternary ammonium hydroxide has good disinfection and sterilization effects, strong decontamination ability, good antibacterial and bacteriostatic effects, and good killing ability against viruses, and has broad application prospects.

[0005] The technical solution of the present invention is realized as follows:

[0006] The present invention provides an asymmetric quaternary ammonium hydroxide having a structural formula shown in Formula I:

[0007]

[0008] Formula I;

[0009] Wherein, R1 and R2 are alkyl chains of C6-C12.

[0010] The present invention further protects a preparation method of the above-mentioned asymmetric quaternary ammonium base, comprising the following steps:

[0011] S1. React 1-adamantylamine with a haloalkane to obtain intermediate 1, with the structure as follows: ;

[0012] S2. React a long-chain fatty alcohol with epichlorohydrin to obtain intermediate 2, with the structure as follows: ;

[0013] S3. React intermediate 1 with intermediate 2 to obtain intermediate 3, with the structure as follows: ;

[0014] S4. React intermediate 3 with butanesultone to obtain the product.

[0015] As a further improvement of the present invention, in step S1, the molar ratio of 1-adamantylamine to the haloalkane is 1:1.1 - 1.2, and a base is also added. The base is NaOH or KOH, the reaction temperature is 50 - 60 °C, and the time is 3 - 5 h.

[0016] As a further improvement of the present invention, the haloalkane is selected from at least one of 1-chlorohexane, 1-chloroheptane, 1-chlorooctane, 1-chlorononane, 1-chlorodecane, 1-chloroundecane, and 1-chlorododecane.

[0017] As a further improvement of the present invention, in step S2, the molar ratio of the long-chain fatty alcohol to epichlorohydrin is 1:1.2 - 1.3, and a base is also added. The base is NaOH or KOH, the reaction temperature is 45 - 55 °C, and the time is 5 - 7 h.

[0018] As a further improvement of the present invention, the long-chain fatty alcohol is selected from at least one of hexanol, heptanol, octanol, nonanol, decanol, and dodecanol.

[0019] As a further improvement of the present invention, in step S3, the molar ratio of intermediate 1 to intermediate 2 is 1:1 - 1.1, the reaction temperature is 30 - 40 °C, and the time is 8 - 12 h.

[0020] As a further improvement of the present invention, in step S4, the molar ratio of intermediate 3 to butanesultone is 1:1.1 - 1.3, the reaction temperature is 30 - 40 °C, and the time is 10 - 12 h.

[0021] As a further improvement of the present invention, it specifically comprises the following steps:

[0022] S1. Add 1 molar equivalent of 1 - adamantylamine, 1.1 - 1.2 molar equivalents of haloalkane, and 3 - 5 molar equivalents of base to acetonitrile. Heat the mixture to 50 - 60 °C and stir for 3 - 5 h. Remove the solvent under reduced pressure, recrystallize with acetone, filter, wash, and dry to obtain Intermediate 1.

[0023] S2. Add 1 molar equivalent of long - chain fatty alcohol, 1.2 - 1.3 molar equivalents of epichlorohydrin, and 2 - 3 molar equivalents of base to methanol. Heat the mixture to 45 - 55 °C and stir for 5 - 7 h. Remove the solvent under reduced pressure, recrystallize with acetone, filter, wash, and dry to obtain Intermediate 2.

[0024] S3. Add 1 molar equivalent of Intermediate 1 and 1 - 1.1 molar equivalents of Intermediate 2 to dichloromethane. Heat the mixture to 30 - 40 °C and stir for 8 - 12 h. Remove the solvent under reduced pressure, recrystallize with ethanol, filter, wash, and dry to obtain Intermediate 3.

[0025] S4. Add 1 molar equivalent of Intermediate 3 and 1.1 - 1.3 molar equivalents of butanesultone to dichloromethane. Heat the mixture to 30 - 40 °C and stir for 10 - 12 h. Remove the solvent under reduced pressure, recrystallize with ethanol, filter, wash, and dry to obtain the product.

[0026] The present invention further protects an endoscopic cleaning compound disinfectant, which comprises the above - mentioned asymmetric quaternary ammonium base and natamycin, and the mass ratio is 10 - 15:2 - 5.

[0027] The present invention further protects a preparation method of the above - mentioned endoscopic cleaning compound disinfectant, which comprises the following steps: Mix the asymmetric quaternary ammonium base and natamycin evenly according to the mass ratio of 10 - 15:2 - 5 to obtain the endoscopic cleaning compound disinfectant.

[0028] The present invention has the following beneficial effects:

[0029] The synthetic route of the present invention is as follows:

[0030]

[0031] The present invention prepares an asymmetric quaternary ammonium base, which forms an endoscopic cleaning compound disinfectant in combination with natamycin. The preparation method is simple, the reaction conditions are mild, the prepared asymmetric quaternary ammonium base has good disinfection and sterilization effects, strong decontamination ability, good antibacterial and bacteriostatic effects, and good killing ability against viruses, and has broad application prospects. Specific embodiments

[0032] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention. Example 1

[0033] This embodiment provides a method for preparing an asymmetric quaternary ammonium base, including the following steps:

[0034] S1. Add 1 mol of 1 - adamantylamine, 1.1 mol of 1 - chlorohexane, and 3 mol of NaOH to 500 mL of acetonitrile, heat to 50 °C, stir and react for 3 h, remove the solvent under reduced pressure, recrystallize with acetone, filter, wash, and dry to obtain Intermediate 1. The calculated value of ESI - MS: C 16 H 30 N(M + H) + 236.23, the measured value: 236.2, and the yield is 89%.

[0035] S2. Add 1 mol of hexanol, 1.2 mol of epichlorohydrin, and 2 mol of NaOH to 500 mL of methanol, heat to 45 °C, stir and react for 5 h, remove the solvent under reduced pressure, recrystallize with acetone, filter, wash, and dry to obtain Intermediate 2. The calculated value of ESI - MS: C9H 19 O2(M + H) + 159.13, the measured value: 159.1, and the yield is 92%;

[0036] S3. Add 1 mol of Intermediate 1 and 1 mol of Intermediate 2 to 500 mL of dichloromethane, heat to 30 °C, stir and react for 8 h, remove the solvent under reduced pressure, recrystallize with ethanol, filter, wash, and dry to obtain Intermediate 3. The calculated value of ESI - MS: C 25 H 48 NO2(M + H) + 394.36, the measured value: 394.4, and the yield is 77%;

[0037] S4. Add 1 mol of Intermediate 3 and 1.1 mol of butanesultone to 500 mL of dichloromethane, heat to 30 °C, stir and react for 10 h, remove the solvent under reduced pressure, recrystallize with ethanol, filter, wash, and dry to obtain the product. The calculated value of ESI - MS: C 29 H 56 NO5S(M + H) + 530.38, the measured value: 530.4, and the yield is 74%. Example 2

[0038] This embodiment provides a method for preparing an asymmetric quaternary ammonium base, comprising the following steps:

[0039] S1. Add 1 mol of 1 - adamantylamine, 1.2 mol of 1 - chloroheptane, and 5 mol of KOH to 500 mL of acetonitrile, heat to 60 °C, stir and react for 5 h, remove the solvent under reduced pressure, recrystallize with acetone, filter, wash, and dry to obtain intermediate 1;

[0040] S2. Add 1 mol of heptanol, 1.3 mol of epichlorohydrin, and 3 mol of KOH to 500 mL of methanol, heat to 55 °C, stir and react for 7 h, remove the solvent under reduced pressure, recrystallize with acetone, filter, wash, and dry to obtain intermediate 2;

[0041] S3. Add 1 mol of intermediate 1 and 1.1 mol of intermediate 2 to 500 mL of dichloromethane, heat to 40 °C, stir and react for 12 h, remove the solvent under reduced pressure, recrystallize with ethanol, filter, wash, and dry to obtain intermediate 3;

[0042] S4. Add 1 mol of intermediate 3 and 1.3 mol of butanesultone to 500 mL of dichloromethane, heat to 40 °C, stir and react for 12 h, remove the solvent under reduced pressure, recrystallize with ethanol, filter, wash, and dry to obtain the product. Example 3

[0043] This embodiment provides a method for preparing an asymmetric quaternary ammonium base, comprising the following steps:

[0044] S1. Add 1 mol of 1 - adamantylamine, 1.15 mol of 1 - chlorooctane, and 4 mol of KOH to 500 mL of acetonitrile, heat to 55 °C, stir and react for 4 h, remove the solvent under reduced pressure, recrystallize with acetone, filter, wash, and dry to obtain intermediate 1;

[0045] S2. Add 1 mol of nonanol, 1.25 mol of epichlorohydrin, and 2.5 mol of NaOH to 500 mL of methanol, heat to 50 °C, stir and react for 6 h, remove the solvent under reduced pressure, recrystallize with acetone, filter, wash, and dry to obtain intermediate 2;

[0046] S3. Add 1 mol of intermediate 1 and 1.05 mol of intermediate 2 to 500 mL of dichloromethane, heat to 35 °C, stir and react for 10 h, remove the solvent under reduced pressure, recrystallize with ethanol, filter, wash, and dry to obtain intermediate 3;

[0047] S4. Add 1 mol of intermediate 3 and 1.2 mol of butanesultone to 500 mL of dichloromethane, heat to 35 °C, stir and react for 11 h, remove the solvent under reduced pressure, recrystallize with ethanol, filter, wash, and dry to obtain the product. Example 4

[0048] A preparation method of an endoscopic cleaning compound disinfectant: Mix 10 g of the asymmetric quaternary ammonium base prepared in Example 1 and 2 g of natamycin evenly to obtain the endoscopic cleaning compound disinfectant. Example 5

[0049] A preparation method of an endoscopic cleaning compound disinfectant: Mix 15 g of the asymmetric quaternary ammonium base prepared in Example 2 and 5 g of natamycin evenly to obtain the endoscopic cleaning compound disinfectant. Example 6

[0050] A preparation method of an endoscopic cleaning compound disinfectant: Mix 12.5 g of the asymmetric quaternary ammonium base prepared in Example 3 and 3.5 g of natamycin evenly to obtain the endoscopic cleaning compound disinfectant.

[0051] Test Example 1

[0052] Perform performance tests on the asymmetric quaternary ammonium bases prepared in Examples 1-3. The results are shown in Table 1.

[0053] Use an automatic surface tension meter to measure the surface tension. The test temperature is (25 ± 0.5) °C. Test its critical micelle concentration cmc and the surface tension γ at this concentration according to the national standard GB / T22237-2008 method. cmc 。

[0054] According to the national standard GB / T7462-1994, use a Ross foam meter to measure the foam by the solution dropping method. Record the initial foam volume, and at the same time record the time when the foam collapses to half of the initial height, that is, the foam half-life. The solution concentration is 0.1 wt%.

[0055] Table 1

[0056]

[0057] As can be seen from the above table, the asymmetric quaternary ammonium bases prepared in Examples 1-3 of the present invention have good surface activity.

[0058] Test Example 2

[0059] Use the disk diffusion method (K-B method) to measure the MIC value. According to the different concentrations of the drug in the circular filter paper, use the tube two-fold dilution method to prepare the drug stock solution (the endoscopic cleaning compound disinfectants prepared in Examples 4-6 and commercially available similar products). Dilute the stock solution into different concentrations respectively, soak the circular filter paper with the different concentration liquid medicines, dry, and make drug sensitivity test papers. Take 100 μL of the test bacterial solution (including Escherichia coli ATCC25922, Staphylococcus aureus ATCC25923, and the concentration of the bacterial solution is 10 10(cfu / mL) onto the formed blank agar plate, spread evenly with a bacterium spreading rod. After the bacterial suspension on the plate is completely absorbed, filter paper disks soaked with different drug concentrations are successively and flatly attached to the agar plate, and cultured in an incubator for 24 h. The lowest drug concentration of the culture solution that produces an inhibition zone is the minimum inhibitory concentration (MIC) of the drug against the test bacteria. The culture solution concentrations that all produce inhibition zones are successively inoculated onto the blank agar plate, and the lowest drug concentration with no more than 5 colony counts on the agar plate is the minimum bactericidal concentration (MBC) of the drug. The results are shown in Table 2.

[0060] Table 2

[0061]

[0062] As can be seen from the above table, the endoscopic cleaning compound disinfectant prepared in Examples 4-6 of the present invention has good antibacterial and bactericidal properties.

[0063] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. An asymmetric quaternary ammonium base, characterized in that It has the structural formula shown in Formula I: ； Wherein, R1 and R2 are C6-C12 alkyl chains.

2. A method for preparing an asymmetric quaternary ammonium base as claimed in claim 1, characterized in that: The following steps are involved: S1. 1-adamantanamine is reacted with an alkyl halide to obtain intermediate 1, the structure of which is as follows: ; S2. A long-chain fatty alcohol is reacted with epichlorohydrin to obtain intermediate 2, the structure of which is as follows: ; S3. Intermediate 1 is reacted with intermediate 2 to obtain intermediate 3, the structure of which is as follows: ; S4. The intermediate 3 is reacted with butane sultone to obtain the product.

3. The preparation method according to claim 2, characterized in that: In step S1, the molar ratio of 1-adamantanamine to alkyl halide is 1:1.1-1.2, a base is added, and the base is NaOH or KOH. The reaction temperature is 50-60° C. and the reaction time is 3-5 h.

4. The preparation method according to claim 3, characterized in that: The alkyl halide is selected from at least one of 1-chlorohexane, 1-chloroheptane, 1-chlorooctane, 1-chlorononane, 1-chlorodecane, 1-chloroundecane and 1-chlorododecane.

5. The preparation method according to claim 2, characterized in that: In step S2, the molar ratio of the long-chain fatty alcohol to epichlorohydrin is 1:1.2-1.3, and a base is added, which is NaOH or KOH. The reaction temperature is 45-55° C. and the reaction time is 5-7 hours.

6. The preparation method according to claim 5, characterized in that: The long-chain fatty alcohol is at least one selected from hexanol, heptanol, octanol, nonanol, decanol and dodecanol.

7. The preparation method according to claim 2, characterized in that: In step S3, the molar ratio of intermediate 1 to intermediate 2 is 1:1-1.1, the reaction temperature is 30-40° C., and the reaction time is 8-12 h.

8. The preparation method according to claim 2, characterized in that: In step S4, the molar ratio of the intermediate 3 to butanesultone is 1:1.1-1.3, the reaction temperature is 30-40°C, and the reaction time is 10-12h.

9. A composite disinfectant for cleaning endoscopes, characterized in that: The invention comprises the asymmetric quaternary ammonium base according to claim 1 and natamycin, wherein the mass ratio of the asymmetric quaternary ammonium base to natamycin is 10-15:2-5.

10. A method for preparing the composite disinfectant for cleaning endoscopes as claimed in claim 9, characterized in that: The method comprises the following steps: uniformly mixing asymmetric quaternary ammonium base and natamycin according to a mass ratio of 10-15:2-5 to prepare an endoscope cleaning composite disinfectant.

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