CN116396412B - Novel quinoline/isoquinoline quaternary ammonium salt modified chitosan and preparation method and application thereof - Google Patents
Novel quinoline/isoquinoline quaternary ammonium salt modified chitosan and preparation method and application thereof Download PDFInfo
- Publication number
- CN116396412B CN116396412B CN202211613229.3A CN202211613229A CN116396412B CN 116396412 B CN116396412 B CN 116396412B CN 202211613229 A CN202211613229 A CN 202211613229A CN 116396412 B CN116396412 B CN 116396412B
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- Prior art keywords
- quaternary ammonium
- ammonium salt
- quinoline
- isoquinoline
- novel
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- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title claims abstract description 116
- 229920001661 Chitosan Polymers 0.000 title claims abstract description 87
- AWJUIBRHMBBTKR-UHFFFAOYSA-N iso-quinoline Natural products C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 title claims abstract description 71
- -1 isoquinoline quaternary ammonium salt Chemical class 0.000 title claims abstract description 64
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 230000000844 anti-bacterial effect Effects 0.000 claims abstract description 35
- 238000006243 chemical reaction Methods 0.000 claims abstract description 21
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 20
- 238000000034 method Methods 0.000 claims abstract description 19
- 239000002994 raw material Substances 0.000 claims abstract description 9
- 238000006482 condensation reaction Methods 0.000 claims abstract description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 46
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 16
- 239000007788 liquid Substances 0.000 claims description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- 230000000845 anti-microbial effect Effects 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- 239000007810 chemical reaction solvent Substances 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- 206010046865 Vaccinia virus infection Diseases 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 208000007089 vaccinia Diseases 0.000 claims description 6
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical group Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 5
- 241000222122 Candida albicans Species 0.000 claims description 5
- 229940095731 candida albicans Drugs 0.000 claims description 5
- 239000000047 product Substances 0.000 claims description 5
- 238000009987 spinning Methods 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 241000191967 Staphylococcus aureus Species 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Chemical group 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 229910052740 iodine Chemical group 0.000 claims description 4
- 239000011630 iodine Chemical group 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
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- 241000588724 Escherichia coli Species 0.000 claims description 3
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- 230000012010 growth Effects 0.000 claims description 3
- 239000008213 purified water Substances 0.000 claims description 3
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 3
- 230000036573 scar formation Effects 0.000 claims description 3
- 238000004062 sedimentation Methods 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 238000004809 thin layer chromatography Methods 0.000 claims description 3
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 2
- 150000001350 alkyl halides Chemical class 0.000 claims description 2
- 125000002843 carboxylic acid group Chemical group 0.000 claims description 2
- 239000002537 cosmetic Substances 0.000 claims description 2
- 239000012043 crude product Substances 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- 239000002798 polar solvent Substances 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims description 2
- 239000004599 antimicrobial Substances 0.000 claims 1
- 238000011282 treatment Methods 0.000 abstract description 5
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- 241000192125 Firmicutes Species 0.000 abstract description 2
- 241000233866 Fungi Species 0.000 abstract description 2
- 231100000956 nontoxicity Toxicity 0.000 abstract description 2
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- 206010061218 Inflammation Diseases 0.000 abstract 1
- 238000010923 batch production Methods 0.000 abstract 1
- 230000003467 diminishing effect Effects 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 230000004054 inflammatory process Effects 0.000 abstract 1
- 230000001737 promoting effect Effects 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 26
- 238000010521 absorption reaction Methods 0.000 description 12
- 238000001228 spectrum Methods 0.000 description 12
- 239000003242 anti bacterial agent Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 238000001819 mass spectrum Methods 0.000 description 6
- 230000005311 nuclear magnetism Effects 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 206010052428 Wound Diseases 0.000 description 4
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- 150000001875 compounds Chemical class 0.000 description 4
- 229920002101 Chitin Polymers 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 239000000835 fiber Substances 0.000 description 3
- 230000035876 healing Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 229910021645 metal ion Inorganic materials 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- RAYMXZBXQCGRGX-UHFFFAOYSA-N quinoline-5-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=N1 RAYMXZBXQCGRGX-UHFFFAOYSA-N 0.000 description 3
- 229910052709 silver Inorganic materials 0.000 description 3
- 239000004332 silver Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000001348 alkyl chlorides Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 239000008367 deionised water Substances 0.000 description 2
- 229910021641 deionized water Inorganic materials 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- ZIPLFLRGHZAXSJ-UHFFFAOYSA-N isoquinoline-5-carboxylic acid Chemical compound N1=CC=C2C(C(=O)O)=CC=CC2=C1 ZIPLFLRGHZAXSJ-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 230000004224 protection Effects 0.000 description 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 239000004753 textile Substances 0.000 description 2
- MLRVZFYXUZQSRU-UHFFFAOYSA-N 1-chlorohexane Chemical compound CCCCCCCl MLRVZFYXUZQSRU-UHFFFAOYSA-N 0.000 description 1
- CNDHHGUSRIZDSL-UHFFFAOYSA-N 1-chlorooctane Chemical compound CCCCCCCCCl CNDHHGUSRIZDSL-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 108010077805 Bacterial Proteins Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- 206010048038 Wound infection Diseases 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
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- 239000007853 buffer solution Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
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- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 1
- JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 description 1
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- 238000007865 diluting Methods 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
- C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
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Abstract
The invention belongs to the technical field of organic chemical synthesis, and particularly relates to novel quinoline/isoquinoline quaternary ammonium salt modified chitosan, a preparation method thereof and application thereof in the field of medical antibacterial dressings and the field of masks. The invention provides novel quinoline/isoquinoline quaternary ammonium salt modified chitosan, which is prepared from chitosan and carboxyl-containing quinoline/isoquinoline quaternary ammonium salt compound serving as main raw materials through condensation reaction, and has the advantages of high yield, mild reaction conditions and easiness in batch production. The medical antibacterial dressing prepared by the method has good mechanical strength and excellent gel forming performance, has remarkable antibacterial performance on gram-negative bacteria, gram-positive bacteria and fungi, and has the effects of diminishing inflammation, promoting wound healing and repairing. The invention has the advantages of rich raw materials, low price, mild reaction conditions, simple post-treatment, safety, no toxicity and good application prospect.
Description
Technical Field
The invention belongs to the technical field of organic chemical synthesis, and particularly relates to novel quinoline/isoquinoline quaternary ammonium salt modified chitosan, a preparation method thereof and application thereof in the field of medical antibacterial dressings and the field of masks.
Background
The chitosan is a product of removing partial acetyl of natural polysaccharide chitin, the chitin is widely distributed in nature, and the reserve is only behind cellulose and is a second large natural polymer. The amino group in the chitosan molecular structure has stronger reactivity than the acetamido group in the chitin molecule, so that the polysaccharide has excellent biological functions and can carry out chemical modification reaction. Chitosan has various physiological functions such as biodegradability, biocompatibility, nontoxicity, bacteriostasis, anticancer, lipid-lowering, immunity enhancement and the like, and is widely applied to various fields such as food additives, textiles, agriculture, environmental protection, beauty and health care, cosmetics, antibacterial agents, medical fibers, medical dressings, biomedical fields, medical absorbable materials, tissue engineering carrier materials, medical treatment, drug development and the like and other daily chemical industries, so that chitosan is considered as a functional biological material with a larger application potential than cellulose.
Most studies suggest that the bacteriostasis of chitosan is mainly derived from the positively charged substituent amino groups on the molecular chain. Cells of general bacteria are often negatively charged, and positively charged groups bind to bacterial proteins to modify them and flocculate and coagulate the bacteria, thereby inhibiting their reproductive capacity. This means that chitosan should exert its antibacterial properties in a weak acid environment, but when used as a dressing in the medical field, the wound part of the patient is weakly alkaline, so that the antibacterial properties of the chitosan dressing are greatly impaired. At present, the antibacterial modification of medical dressings mainly comprises two forms: 1. metal ions are added as antibacterial agents, such as silver ions. However, silver ions and zinc ions are used as a heavy metal antibacterial agent, the antibacterial mechanism is not clear enough, and a large amount of silver ions and zinc ions enter human bodies to have certain toxicity and larger cytotoxicity. 2. Adding organic antibacterial agent such as guanidine antibacterial agent. The method has a large risk of dissolution of the antibacterial agent, influences cell growth and tissue repair, and also has a certain risk of entering the human metabolic system.
Therefore, development of a chemical grafting method for modifying chitosan, and grafting quaternary ammonium salt molecules onto chitosan molecular chains, so that chitosan still has better antibacterial performance even in alkaline environment, is a future development direction.
Disclosure of Invention
The invention aims to provide novel quinoline/isoquinoline quaternary ammonium salt modified chitosan and a preparation method thereof. The modified chitosan has better antibacterial property. Meanwhile, an application method of the modified chitosan is also provided. The invention has the advantages of abundant raw materials, low raw material price, mild reaction conditions, simple post-treatment, safety and innocuity, and has good application prospect in the medical field.
In order to achieve the above purpose, the present invention provides the following technical solutions:
the invention provides novel quinoline/isoquinoline quaternary ammonium salt modified chitosan which is characterized in that chitosan and carboxyl-containing quinoline/isoquinoline quaternary ammonium salt compound are used as main raw materials, and the novel quinoline/isoquinoline quaternary ammonium salt modified chitosan is prepared through condensation reaction, has antibacterial performance, and has any one of the following molecular structural formulas:
wherein n is a positive integer; r is saturated alkane or unsaturated alkane with carbon chain of 1-16; x is fluorine, chlorine, bromine or iodine.
Further, the carboxyl-containing quinoline/isoquinoline quaternary ammonium salt compound is prepared by taking carboxyl-containing quinoline/isoquinoline as a starting material and reacting with halogenated alkane, and has any one of the following molecular structural formulas:
wherein R is saturated alkane or unsaturated alkane with a carbon chain of 1-16; x is fluorine, chlorine, bromine or iodine.
Further, the haloalkane which is a preparation raw material of the carboxyl-containing quinoline/isoquinoline quaternary ammonium salt compound can be chlorinated alkane, and can have any one of the following molecular structural formulas:
wherein R1 is an alkyl chain with a carbon chain of 1; r2 is an alkyl chain with a carbon chain of 6; r3 is an alkyl chain with a carbon chain of 8.
Further, the invention also provides a preparation method of the novel quinoline/isoquinoline quaternary ammonium salt modified chitosan, which is characterized by comprising the following steps:
step 1, preparing a carboxyl quinoline/isoquinoline quaternary ammonium salt compound, which specifically comprises the following steps: adding carboxyl-containing quinoline/isoquinoline and halogenated alkane into a reaction solvent in proportion, heating and refluxing for reaction for a certain time, determining a reaction process by a thin layer chromatography, removing the solvent after the reaction is finished, and preparing by a sedimentation method;
step 2, preparing novel quinoline/isoquinoline quaternary ammonium salt modified chitosan, which specifically comprises the following steps: mixing the carboxyl-containing quinoline/isoquinoline quaternary ammonium salt compound prepared in the step 1 with chitosan in proportion, adding a reaction solvent and a catalyst, and reacting at 70-90 ℃ for 1-3 h to obtain a crude product; is prepared by washing with purified water and drying at 50-80 ℃ for 2-4 h.
Further, the halogenated alkane in the step 1 is any one of chlorinated alkane or brominated alkane; the reaction solvent is a polar solvent and comprises any one of acetonitrile, tetrahydrofuran, dimethyl sulfoxide and N, N-dimethylformamide; the reaction temperature is 80-120 ℃ and the reaction time is 6-8 h.
Further, in the step 1, the molar ratio of carboxyl-containing quinoline/isoquinoline to halogenated alkane is 1:0.95-1:1.2.
Further, the mass ratio of the quinoline/isoquinoline with carboxylic acid groups to the chitosan in the step 2 is 0.5-1:1, the reaction solvent is tetrahydrofuran, and the catalyst is EDCl (1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride).
Further, the invention also discloses an application method of the novel quinoline/isoquinoline quaternary ammonium salt modified chitosan, which is characterized in that according to the novel quinoline/isoquinoline quaternary ammonium salt modified chitosan and unmodified chitosan 0.02: and (3) spinning according to the mass ratio of 1 to prepare the novel antibacterial dressing.
Furthermore, the novel antibacterial dressing has antibacterial property on staphylococcus aureus, escherichia coli and candida albicans, and the antibacterial rate can reach 99.99 percent.
Furthermore, the novel antibacterial dressing has good gelling performance, large liquid absorption and average liquid absorption of 20-40 times.
Furthermore, the novel antibacterial dressing has anti-inflammatory and analgesic effects on vaccinia skin and skin after cosmetology, and can effectively inhibit the growth of vaccinia and reduce scar formation.
The beneficial effects of the invention are as follows:
1. the novel quinoline/isoquinoline quaternary ammonium salt modified chitosan provided by the invention has a safe and long-acting contact antibacterial effect, and has a wide application prospect in the field of medical dressings and the field of masks.
2. The preparation method of the carboxyl quinoline/isoquinoline quaternary ammonium salt compound provided by the invention has the advantages of mild chitosan condensation grafting reaction condition, simplicity in operation, high production efficiency, yield up to more than 95% and convenience in mass production; the antibacterial agent is fixed on a chitosan molecular chain through a chemical bond, can not be released freely, has no dissolution risk compared with a metal ion antibacterial agent, has no cytotoxicity, and is safer.
3. The invention provides an application method of novel quinoline/isoquinoline quaternary ammonium salt modified chitosan, which comprises the following steps of: 1 spinning, and carrying out subsequent treatments such as conventional dehydration, acid washing, dehydration, drying and the like, the prepared novel antibacterial dressing has the advantages of large liquid absorption and good gel forming property, and the average liquid absorption rate is between 20 and 40, so that wound seepage can be effectively absorbed. And according to the wet healing theory, a durable and effective healing environment can be provided for the wound to promote the healing of the wound.
4. The invention provides an application method of novel quinoline/isoquinoline quaternary ammonium salt modified chitosan, and the novel antibacterial dressing prepared by the method has remarkable antibacterial property on gram-negative bacteria, gram-positive bacteria and fungi, and the antibacterial property can reach 99.99%. Effectively prevent wound infection and promote wound healing and repair. Has anti-inflammatory and analgesic effects on vaccinia skin and skin after caring skin, and can effectively inhibit vaccinia growth and reduce scar formation.
5. The invention has the advantages of abundant raw materials, low raw material price, mild reaction conditions, simple post-treatment, safety and innocuity, and has good application prospect in the medical field.
Drawings
In order to more clearly illustrate the technical solution of the present invention, the drawings that are used in the embodiments will be briefly described below.
FIG. 1 is a molecular structural formula of a novel quinoline/isoquinoline quaternary ammonium salt modified chitosan; wherein the left side is a molecular structural formula of quinoline quaternary ammonium salt modified chitosan, and the right side is a molecular structural formula of isoquinoline quaternary ammonium salt modified chitosan.
FIG. 2 is a schematic diagram of a preparation method of novel quinoline/isoquinoline quaternary ammonium salt modified chitosan.
FIG. 3 is an infrared spectrum of the novel quinoline/isoquinoline quaternary ammonium salt modified chitosan.
FIG. 4 is a photograph of a novel antimicrobial dressing product comprising novel quinoline/isoquinoline quaternary ammonium salt modified chitosan.
FIG. 5 shows nuclear magnetic resonance hydrogen spectrum of C1-quinoline-5-carboxylic acid quaternary ammonium salt.
FIG. 6 is a nuclear magnetic resonance carbon spectrum of a C1-quinoline-5-carboxylic acid quaternary ammonium salt.
FIG. 7 shows nuclear magnetic resonance hydrogen spectrum of C6-quinoline-5-carboxylic acid quaternary ammonium salt.
FIG. 8 is a nuclear magnetic resonance carbon spectrum of a C6-quinoline-5-carboxylic acid quaternary ammonium salt.
FIG. 9 is a nuclear magnetic resonance hydrogen spectrum of a C8-quinoline-5-carboxylic acid quaternary ammonium salt.
FIG. 10 is a nuclear magnetic resonance carbon spectrum of a C8-quinoline-5-carboxylic acid quaternary ammonium salt.
FIG. 11 is a nuclear magnetic resonance hydrogen spectrum of a C1-isoquinoline-5-carboxylic acid quaternary ammonium salt.
FIG. 12 is a nuclear magnetic resonance carbon spectrum of a C1-isoquinoline-5-carboxylic acid quaternary ammonium salt.
FIG. 13 is a nuclear magnetic resonance hydrogen spectrum of a C6-isoquinoline-5-carboxylic acid quaternary ammonium salt.
FIG. 14 is a nuclear magnetic resonance carbon spectrum of a C6-isoquinoline-5-carboxylic acid quaternary ammonium salt.
FIG. 15 is a nuclear magnetic resonance hydrogen spectrum of a C8-isoquinoline-5-carboxylic acid quaternary ammonium salt.
FIG. 16 is a nuclear magnetic resonance carbon spectrum of a C8-isoquinoline-5-carboxylic acid quaternary ammonium salt.
Detailed Description
The embodiments of the present invention will be described in detail below, and the embodiments are all implemented on the premise of the technical solution of the present invention, and detailed implementation procedures are given, but it should be stated that the scope of protection of the present invention is not limited to the following embodiments.
Examples
Taking quinoline-5-carboxylic acid and isoquinoline-5-carboxylic acid as examples, the structural formulae are shown as follows:
quinoline-5-carboxylic acid (left) and isoquinoline-5-carboxylic acid (right)
Firstly, preparing a carboxyl-containing quinoline/isoquinoline quaternary ammonium salt compound; secondly, mixing the prepared quaternary ammonium salt compound with chitosan according to a proportion, adding a reaction solvent and a catalyst, and preparing novel quinoline/isoquinoline quaternary ammonium salt modified chitosan under proper reaction conditions; and finally, mixing the modified chitosan and the unmodified chitosan in proportion for spinning to prepare the novel antibacterial dressing.
The specific implementation process is as follows:
1. preparation of carboxyl-containing quinoline/isoquinoline quaternary ammonium salt compound
Quinoline-5-carboxylic acid (2 mmol,346 mg) was weighed into a round bottom flask and acetonitrile 10 mL was added. Chloroalkanes (wherein the three chloroalkanes were selected from 1-chloromethane, 1-chloron-hexane, 1-chlorooctane) (1.2 mmol) were weighed into a round bottom flask. The reaction was run by thin layer chromatography with reflux 6 h. After the reaction is finished, the solvent is removed, and the sedimentation method is used to obtain the carboxyl quinoline-5-carboxylic acid quaternary ammonium salt, and the yield is up to 95%. The structural formula is as follows:
nuclear magnetism and mass spectrum data of compound a: 1 H NMR (400 MHz, DMSO) δ13.21(s, 1 H)，δ9.12(d, 1 H), 8.89(d, 1H), 8.21(t, 1 H), 8.18(d, 1 H), 7.66(d, 1 H), 7.56(t, 1 H), 4.39(s, 3 H)。
13 C NMR (101 MHz, DMSO) δ167.7, 149.8, 139.5, 134.8, 130.6, 130.3, 128.1, 126.3, 126.0, 121.7, 45.3。
HRMS(ESI) m/z: calc for[C 11 H 10 ClNO 2 ] + :223.0400，Found:223.0408。
nuclear magnetism and mass spectrum data of compound B: 1 H NMR (400 MHz, DMSO) δ13.21(s, 1 H)，δ9.12(d, 1 H), 8.89(d, 1H), 8.21(t, 1 H), 8.18(d, 1 H), 7.66(d, 1 H), 7.56(t, 1 H), 5.01(t, 2 H), 2.01(m, 2 H), 1.28(m, 6 H), 0.88(t, 3 H)。
13 C NMR (101 MHz, DMSO) δ167.7, 146.0, 139.5, 134.8, 130.6, 130.3, 128.1, 126.3, 126.0, 121.7, 60.5, 31.3, 29.9, 27.6, 22.7, 14.1。
HRMS(ESI) m/z: calc for[C 16 H 20 ClNO 2 ] + :293.1183，Found:293.1189。
nuclear magnetism and mass spectrum data of compound C: 1 H NMR (400 MHz, DMSO) δ13.21(s, 1 H)，δ9.12(d, 1 H), 8.89(d, 1H), 8.21(t, 1 H), 8.18(d, 1 H), 7.66(d, 1 H), 7.56(t, 1 H), 5.01(t, 2 H), 2.01(m, 2 H), 1.26(m, 10 H), 0.88(t, 3 H)。
13 C NMR (101 MHz, DMSO) δ167.7, 146.0, 139.5, 134.8, 130.6, 130.3, 128.1, 126.3, 126.0, 121.7, 60.5, 31.9, 29.9, 27.9, 22.7, 14.1。
HRMS(ESI) m/z: calc for[C 18 H 24 ClNO 2 ] + :321.1496，Found:321.1492。
the carboxyl-containing isoquinoline-5-carboxylic acid quaternary ammonium salt is prepared by the same method and has the following structural formula:
nuclear magnetism and mass spectrum data of compound D: 1 H NMR (400 MHz, DMSO) δ13.21(s, 1 H)，δ10.24 (s, 1 H), 8.89(d, 1H), 8.62(d, 1 H), 7.77(d, 1 H), 7.66(d, 1 H), 7.56(t, 1 H), 4.42(s, 3 H)。
13 C NMR (101 MHz, DMSO) δ167.7, 148.4, 146.1, 146.0, 131.0, 130.3, 130.0, 126.2, 125.6, 123.9, 49.5。
HRMS(ESI) m/z: calc for[C 11 H 10 ClNO 2 ] + :223.0400，Found:223.0405。
nuclear magnetism and mass spectrum data of compound E: 1 H NMR (400 MHz, DMSO) 1 H NMR (400 MHz, DMSO) δ13.21(s, 1 H)，δ10.24 (s, 1 H), 8.89(d, 1H), 8.62(d, 1 H), 7.77(d, 1 H), 7.66(d, 1 H), 7.56(t, 1 H), 5.01(t, 3H), 2.01(m, 2H),1.28(m, 6H), 0.88(t, 3H)。
13 C NMR (101 MHz, DMSO) δ167.7, 148.4, 146.1, 146.0, 131.0, 130.3, 130.0, 126.2, 125.6, 123.9, 72.4, 31.5, 30.4, 27.7, 22.7, 14.1。
HRMS(ESI) m/z: calc for[C 16 H 20 ClNO 2 ] + :293.1183，Found:293.1188。
nuclear magnetism and mass spectrum data of compound F: 1 H NMR (400 MHz, DMSO) 1 H NMR (400 MHz, DMSO) δ13.21(s, 1 H)，δ10.24 (s, 1 H), 8.89(d, 1H), 8.62(d, 1 H), 7.77(d, 1 H), 7.66(d, 1 H), 7.56(t, 1 H), 5.01(t, 2H), 2.01(m, 2H),1.26(m, 10H), 0.88(t, 3H)。
13 C NMR (101 MHz, DMSO) δ167.7, 148.4, 146.1, 146.0, 131.0, 130.3, 130.0, 126.2, 125.6, 123.9, 72.4, 31.9, 30.4, 29.3, 28.0, 22.7, 14.1。
HRMS(ESI) m/z: calc for[C 18 H 24 ClNO 2 ] + :321.1496，Found:321.1492。
the nuclear magnetic patterns are shown in fig. 5 to 16, and are as follows: the deuterating agent used is deuterated dimethyl sulfoxide.
2. Novel quinoline/isoquinoline quaternary ammonium salt modified chitosan and application thereof
Carboxyl quinoline-5-carboxylic acid quaternary ammonium salt and chitosan are mixed according to the proportion of 0.5-1:1 into a round bottom flask, tetrahydrofuran is added as a catalyst, EDCl with the concentration of 0.5% is added as a catalyst, and the mixture is heated and refluxed for 2 h. Washing with purified water after the reaction is finished, and drying 3 h at 50-80 ℃ to obtain the novel quinoline-5-carboxylic acid quaternary ammonium salt modified chitosan.
The mass ratio of the modified chitosan to the unmodified chitosan of the quinoline-5-carboxylic acid quaternary ammonium salt containing carboxyl is 0.02:1, spinning and post-treating to prepare novel antibacterial dressing which are respectively named as C1+ chitosan dressing, C6+ chitosan dressing and C8+ chitosan dressing.
The novel isoquinoline quaternary ammonium salt modified chitosan dressing is prepared by using the carboxyl-containing isoquinoline-5-formic quaternary ammonium salt according to the same method, and is respectively named as isoc 1+ chitosan dressing, isoc 6+ chitosan dressing and isoc 8+ chitosan dressing.
And carrying out infrared test on the prepared quinoline/isoquinoline quaternary ammonium salt chitosan, wherein an infrared spectrogram of the infrared test is shown in figure 3. As apparent from the spectrogram, compared with unmodified chitosan, the modified chitosan has 750cm -1 Up to 1750cm -1 Is significantly changed, wherein 1593cm -1 To 1411cm -1 The new absorption peak is the telescopic vibration peak of-COO formed after quinoline/isoquinoline modification, which shows that the quinoline/isoquinoline quaternary ammonium salt is successfully grafted on the chitosan molecular chain.
Fig. 4 is a diagram of the novel antibacterial dressing product containing quinoline/isoquinoline quaternary ammonium salt chitosan, and it can be seen from the diagram that the prepared antibacterial dressing has good mechanical strength and excellent gel forming performance.
In addition, the prepared novel antibacterial dressing containing quinoline/isoquinoline quaternary ammonium salt chitosan has the following antibacterial performance and liquid absorption performance tested:
(1) Antibacterial property
Bacterial and fungal test subjects included: staphylococcus aureus, escherichia coli, candida albicans, the experiment followed the evaluation of the antimicrobial properties of textiles according to GB/T20944.3-2008 part 3: the oscillation method. Coli 8099, staphylococcus aureus ATCC 6538, candida albicans ATCC 10231 were purchased from shanghai luzhi micro-tech limited, the test medium was purchased from beijing obbo biotechnology limited, and the other reagents were all analytically pure. An unmodified chitosan dressing served as a control.
The testing steps are as follows: sterilizing the sample in the embodiment, putting the sample into an Erlenmeyer flask, adding PBS buffer solution and inoculating bacterial liquid, oscillating on a constant temperature oscillator, diluting, sucking the liquid in the flask, transferring the liquid into a sterilizing plate, pouring nutrient agar medium or sand agar medium, solidifying at room temperature, inverting the plates, culturing at 37+/-1 ℃ for 24-48 h (candida albicans 48-72 h), recording the colony number in each plate, and calculating the bacteriostasis rate of the embodiment and the control sample according to a formula in a standard table 1.
(2) Liquid absorption
The solution A is prepared according to the pharmacopoeia requirement, and the steps are as follows: weigh 8.3 g sodium chloride and 0.277 g calcium chloride deionized water to dissolve thoroughly, and place in a volumetric flask to 1000 mL volume with deionized water. The solution mimics the major metal ion content of human blood. A certain amount of the novel antibacterial dressing and an unmodified chitosan dressing are placed in an open environment for 24h, so that the moisture regain reaches balance, and the dry weight of the dressing is measured to be W (g). The solution a was weighed 50 times heavier than the dressing, the dressing and solution a were placed in a beaker, lowered at 37 ℃ for 30 min, and hung in the air with forceps holding one corner of the dressing until no drop was dropped, for about 30 s. Weigh dressing wet weight W 1 (g) The moisture absorption per unit mass of the dressing was (W 1 W)/W, the results are shown in Table 1.
According to the data in table 1, the antibacterial property and the liquid absorption amount of the modified chitosan dressing are greatly improved compared with those of the unmodified chitosan dressing, and the substitution degree of the chitosan is increased under the same reaction condition along with the increase of the dosage of the quinoline/isoquinoline quaternary ammonium salt in the reaction, so that the liquid absorption capacity of the modified chitosan is further enhanced.
The experiment shows that the quinoline quaternary ammonium salt modified chitosan fiber has better antibacterial property and liquid absorption, and the novel medical dressing product prepared by using the chitosan fiber has very broad market prospect.
Table 1: antibacterial property and liquid absorption experimental test results of unmodified chitosan dressing and various chitosan dressings prepared in examples
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims (11)
1. A novel quinoline/isoquinoline quaternary ammonium salt modified chitosan is characterized in that chitosan and a quinoline/isoquinoline quaternary ammonium salt compound containing carboxyl are used as main raw materials, and the novel quinoline/isoquinoline quaternary ammonium salt modified chitosan is prepared through condensation reaction, has antibacterial performance and has any one of the following molecular structural formulas; wherein n is a positive integer; r is saturated alkane or unsaturated alkane with carbon chain of 1-16; x is fluorine, chlorine, bromine or iodine;
2. the novel quinoline/isoquinoline quaternary ammonium salt modified chitosan according to claim 1, wherein the carboxyl-containing quinoline/isoquinoline quaternary ammonium salt compound is prepared by taking carboxyl-containing quinoline/isoquinoline as a starting material through reaction with halogenated alkane, and has any one of the following molecular structural formulas; wherein R is saturated alkane or unsaturated alkane with a carbon chain of 1-16; x is fluorine, chlorine, bromine or iodine;
3. the novel quinoline/isoquinoline quaternary ammonium salt modified chitosan according to claim 2, wherein the carboxyl-containing quinoline/isoquinoline quaternary ammonium salt compound has any one of the following molecular structural formulas; wherein R is 1 Is an alkyl chain with a carbon chain of 1; r is R 2 Is an alkyl chain with a carbon chain of 6; r is R 3 Is an alkyl chain with a carbon chain of 8;
4. a method for preparing the novel quinoline/isoquinoline quaternary ammonium salt modified chitosan according to any one of claims 1 to 3, which is characterized by comprising the following steps:
step 1, preparing a carboxyl quinoline/isoquinoline quaternary ammonium salt compound, which specifically comprises the following steps: adding carboxyl-containing quinoline/isoquinoline and halogenated alkane into a reaction solvent in proportion, heating and refluxing for reaction for a certain time, determining a reaction process by a thin layer chromatography, removing the solvent after the reaction is finished, and preparing by a sedimentation method;
step 2, preparing novel quinoline/isoquinoline quaternary ammonium salt modified chitosan, which specifically comprises the following steps: mixing the carboxyl-containing quinoline/isoquinoline quaternary ammonium salt compound prepared in the step 1 with chitosan in proportion, adding a reaction solvent and a catalyst, and reacting at 70-90 ℃ for 1-3 h to obtain a crude product; is prepared by washing with purified water and drying at 50-80 ℃ for 2-4 h.
5. The method for preparing the novel quinoline/isoquinoline quaternary ammonium salt modified chitosan according to claim 4, wherein the haloalkane in the step 1 is any one of chloralkane or bromoalkane; the reaction solvent is a polar solvent and comprises any one of acetonitrile, tetrahydrofuran, dimethyl sulfoxide and N, N-dimethylformamide; the reaction temperature is 80-120 ℃ and the reaction time is 6-8 h.
6. The method for preparing the novel quinoline/isoquinoline quaternary ammonium salt modified chitosan according to claim 4, wherein the addition molar ratio of the carboxyl-containing quinoline/isoquinoline to the halogenated alkane in the step 1 is 1:0.95-1:1.2.
7. The preparation method of the novel quinoline/isoquinoline quaternary ammonium salt modified chitosan according to claim 4, wherein the addition mass ratio of the quinoline/isoquinoline with carboxylic acid groups to the chitosan in the step 2 is 0.5-1:1, the reaction solvent is tetrahydrofuran, and the catalyst is EDCl (1-ethyl- (3-dimethylaminopropyl) carbodiimide hydrochloride).
8. A novel antibacterial dressing prepared by using the novel quinoline/isoquinoline quaternary ammonium salt modified chitosan according to any one of claims 1 to 3, which is characterized in that the novel quinoline/isoquinoline quaternary ammonium salt modified chitosan and unmodified chitosan are 0.02:1 mass ratio, and spinning to obtain the product.
9. The novel antimicrobial dressing of claim 8, wherein the novel antimicrobial dressing has antimicrobial properties against staphylococcus aureus, escherichia coli and candida albicans with an antimicrobial rate of up to 99.99%.
10. The novel antimicrobial dressing of claim 8, wherein the novel antimicrobial dressing has good gelling properties, a large liquid uptake, and an average liquid uptake of between 20-40 times.
11. The novel antimicrobial dressing according to claim 8, wherein the novel antimicrobial dressing has an anti-inflammatory and analgesic effect on vaccinia skin and post-cosmetic skin, and is effective in inhibiting the growth of vaccinia and reducing scar formation.
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