CN103843808A - Macromolecular guanidinium antibacterial agent with hyperbranched structure and preparation method thereof - Google Patents
Macromolecular guanidinium antibacterial agent with hyperbranched structure and preparation method thereof Download PDFInfo
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- CN103843808A CN103843808A CN201210555319.1A CN201210555319A CN103843808A CN 103843808 A CN103843808 A CN 103843808A CN 201210555319 A CN201210555319 A CN 201210555319A CN 103843808 A CN103843808 A CN 103843808A
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Abstract
The invention relates to a macromolecular guanidinium antibacterial agent with a hyperbranched structure and a preparation method thereof. Phenyl and acylamino with antimicrobial activity are led to a poly-guanidine salt by a novel molecular design, so as to form a novel macromolecular guanidinium antibacterial agent with the hyperbranched structure. The macromolecular guanidinium antibacterial agent is formed by a midbody, polyamine, guanidine hydrochloride or hydrochloric acid biguanide with a branched structure. The hyperbranched macromolecular guanidinium antibacterial agent disclosed by the invention is simple in synthetic process, and the antibacterial effect is more significant by leading of a plurality of active groups. The antibacterial agent has long-term antibacterial action, is stable in property, easy to dissolve in water, free of a side effect, free of corrosivity, and free of pollution to environment, can be used at wider temperature and pH value ranges, is a novel environmental antibacterial agent, can be widely applied to the fields such as medical treatment and public health, food processing, daily-use chemical industry, daily life, agriculture, aquatic products, livestock breeding and the like.
Description
Technical field
The invention belongs to antibacterial agent technical field, be specifically related to a kind of hyperbranched macromolecular guanidinesalt antibacterial agent and preparation method thereof.
Background technology
As far back as 1861, Strecke just found guanidine, had in succession found subsequently the existence of guanidine in a series of natural productss and various plants; In humans and animals body, also contain micro-guanidine.From structure, guanidine is carbotriamine, its structure have as follows three resonant:
Guanidine is accepted the stable guanidine radicals cation forming after proton, makes the hydrate of guanidine have significant alkalescence.Utilize this principle, guanidine radicals cation and organic acid ion can be in conjunction with forming guanidinesalt.Guanidinesalt is an important component part in guanidine compound, can derive miscellaneous guanidine compound.Common commodity are all generally guanidinesalts on the market, as Guanidine Phosphates, hydrochloric acid guanidinesalt, sulfuric acid guanidinesalt, carbonic acid guanidinesalt, nitric acid guanidinesalt, stearic acid guanidinesalt etc.
Guanidine is the organic compound that a class has significant application value and good biological activity, and has good anti-microbial property.For a long time, guanidine compound is widely used in medicine, agricultural chemicals and chemical field as disinfection sanitizer, catalyzer, nutritional agents, feed and cosmetic additive agent etc.
Large molecule guanidinesalt antibacterial agent is to apply in recent years a more class disinfectant, and soluble in water, easy to use, has antimicrobial spectrum, low toxicity, non-stimulated widely, to human body and environmentally friendly simultaneously.As antibacterial agent, obtained general use accreditation in Europe, except for the industrial disinfection such as food and alcoholic beverage, also can be used for the sterilization of fibre paper, food and towel, sweater, mouth mask etc.But it also exists, and polymerization guanidinesalt molecular weight is lower, product is single, thermally-stabilised poor, need could show the shortcomings such as antibacterial effectiveness longer action time.
The sterilization mechanism of guanidine class disinfectant belongs to cationic antibacterial agent sterilization mechanism.Think that at present the Antibacterial Mechanism of cationic antibacterial agent is:
Guanidine radicals in guanidine compound is water-soluble rear positively charged, is easily adsorbed on electronegative microorganism surface, and first the CHARGE DISTRIBUTION on destroy microorganisms surface and the permeability of film are micromolecular K
+, Na
+, the small molecular weight material such as ATP flows out externally, then the macromolecule material such as nucleic acid flows out, and causes microbial death.Guanidinesalt can be penetrated in microbial body simultaneously, and the cell structure of destroy microorganisms body and metabolism of energy substances, make bacterium and virus lose activity.
We know, the pesticide resistance of bacterium is because little molecule anti-biotic material can enter bacterial nucleus (cytoplasm), cause the change of indivedual nucleotide on DNA of bacteria chain to produce.And large molecule guanidinesalt is while being adsorbed onto microbial cell surface, its molecular network forming will be stopped up the respiration channel of microorganism, makes microorganism be choked to death and die rapidly.Because large molecule anti-biotic material is different from the Antibacterial Mechanism of little molecule anti-biotic material, and be difficult to enter bacterium inside, be also difficult to the DNA of bacterium, direct effect occurring, thereby bacterium be difficult to large molecule guanidinesalt to develop immunity to drugs.
From table 1 (Biomacromolecules 2000,1,473-480) known, the charge density of dendrimer, dendritic polymer antibacterial agent is the highest, but the low molecule of resistance ratios of dendrimer, dendritic polymer antibacterial agent and polymer antibacterial agent penetration cell wall is large, but dendrimer, dendritic polymer antibacterial agent is than general polymer antibacterial agent compactness, the resistance ratios being subject to is little, and with regard to resultant effect, the anti-microbial property of dendrimer, dendritic polymer organic antibacterial agent is best.The object of the invention is by hyperbranched technology, in increasing product relative molecular weight, increase substantially the density of the antibacterial group of large molecule guanidinesalt, make large molecule guanidinesalt have the antibacterial advantage of large molecule and little molecule antibacterial agent concurrently simultaneously, become high efficiency, a high performance class novel antibacterial processing.
The comparison of table 1 cationic antibacterial agent anti-microbial property
| Performance | Little molecular cation antibacterial agent | Macromolecule cation antibacterial agent | Dendrimer cationic antibacterial agent |
| Adsorption capacity | A little less than | By force | By force |
| Be combined with cell membrane | Low | In | High |
| Upset cell membrane | Low | In | High |
| Penetration cell | High | Low | In |
Summary of the invention
Technical problem to be solved by this invention is to overcome the technical disadvantages such as existing polymerization guanidinesalt molecular weight is lower, product is single, is keeping, under the prerequisite of the antibacterial advantage of large molecule guanidinesalt, further improving anti-microbial property and the service efficiency of guanidinesalt.The present invention, by the structuring MOLECULE DESIGN to large molecule guanidinesalt, adopts the centronucleus with bactericidal activity to realize the hyperbranched framework to large molecule guanidinesalt antibacterial agent, thereby can provide a class to have high-performance, high efficiency, water miscible novel antibacterial material concurrently.Another object of the present invention, is to provide the method for preparing this class antibacterial agent.
Technical scheme of the present invention is summarized as follows:
A kind of hyperbranched macromolecular guanidinesalt antibacterial agent (I), its structure comprises hyperbranched intermediate (II) and large molecule guanidinesalt (III), and wherein hyperbranched intermediate (II) is acid amide type or ester type (being X=N or O); Large molecule guanidinesalt (III) comprises large molecule list guanidinesalt and large molecule guazatine.
Symbol in formula represents following implication:
X: be N or O;
L:C
2～12methylene or there is the Oxymethylene of different numbers;
n＝2～12。
The preparation method of above-mentioned hyperbranched macromolecular guanidinesalt antibacterial agent (I) comprising:
(1) preparation of hyperbranched intermediate (II);
By 1 part of trimesic acid trimethyl and 3～15 parts of diamines (NH
2-L-NH
2) in organic solvent, back flow reaction 8～24h makes, wherein organic solvent is methyl alcohol and/or ethanol.
(2) preparation of hyperbranched macromolecular guanidinesalt antibacterial agent (I)
(a) one-step method: add 1 part of hyperbranched intermediate (II), 0～15 part of aliphatic diamine (NH2-L-NH2) and 3～15 parts of guanidine hydrochlorides or dicyanodiamine in reaction system, 60～120 DEG C are stirred frit reaction 1～4h hour, be warming up to 130～180 DEG C, stirring reaction 1～10h, after cooling product.This product is water-soluble.
(b) two-step method:
1) in reaction system, add 3～15 parts of aliphatic diamines (NH2-L-NH2) and 3～15 parts of guanidine hydrochlorides or dicyanodiamine, stir frit reaction 1～4h at 60～120 DEG C, be warming up to 130～180 DEG C, stirring reaction 1～10h.Wherein diamines (NH
2-L-NH
2) with the rate of charge of guanidine hydrochloride or dicyanodiamine be 1～1.5: 1, optimum charging ratio is 1～1.1: 1, optimum reaction condition is 80～100 DEG C of stirring reaction 1～2h, is warming up to 130～160 DEG C, stirring reaction 2～8h.
2) 1 part of hyperbranched intermediate (II) is added to reaction system, under 140～180 DEG C of conditions, continue reaction 1～4h.
Optimum condition is that temperature is 150～160 DEG C, and the reaction time is 2～3h, after cooling product.This product is water-soluble.
Compared with prior art, its gain effect is novel hyperbranched macromolecular guanidinesalt antibacterial agent of the present invention:
1, due to the present invention adopt be organic guanidinesalt, organic guanidinesalt has long-term antibacterial action, stable in properties, soluble in water, can under wide temperature and pH value scope, use, have no side effect, non-corrosiveness, environmentally safe, be a kind of antibacterial agent of novel environment-friendly;
2, because the present invention is hyperbranched macromolecular guanidinesalt, its charge density is the highest, and hyperbranched macromolecular guanidinesalt antibacterial agent is than general polymer antibacterial agent compactness simultaneously, and the resistance ratios being subject to is little, and the anti-microbial property having is best;
3, because the present invention adopts hyperbranched technology, in increasing product relative molecular weight, increase substantially the density of the antibacterial group of large molecule guanidinesalt, make large molecule guanidinesalt have the antibacterial advantage of large molecule and little molecule antibacterial agent concurrently simultaneously, become high efficiency, a high performance class antibacterial agent.
4, due to the introducing of rigid radical in dissaving structure of the present invention, make the thermal stability excellence of synthetic antibacterial agent, can in the preparation technology of high temperature antibacterial product, apply.
5, because hyperbranched macromolecular guanidinesalt provided by the invention can be widely used in each fields such as health care, food processing, daily-use chemical industry, daily life, agricultural, aquatic products, livestock breeding.
In order to verify advantage of the present invention, we have done inhibition zone test to staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, the results are shown in Table 1.
Table 1: the Bactericidal test result of antibacterial agent to staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa
Note: [1] is satellite rings phenomenon
The scraps of paper are 6mm filter paper
As can be seen from Table 1: the inhibition zone with the large molecule guanidinesalt antibacterial agent of branched structure is obviously greater than the inhibition zone of the large molecule guanidinesalt of straight chain, simultaneously, the inhibition zone of the branched product of one-step method is less than the inhibition zone of the branched product of two-step method, and therefore we can learn qualitatively: the anti-microbial property optimum of the large molecule guanidinesalt of branching of two step synthesis.
Concrete embodiment
Provide example below so that the present invention will be described in more detail, better to understand content of the present invention.It is important to point out; following examples can not be interpreted as limiting the scope of the invention; some nonessential improvement that the person skilled in the art in this field makes the present invention according to the invention described above content, adjustment, amendment, replacement etc., must belong to protection scope of the present invention.
Comparative example: hexamethylene diamine and guanidine hydrochloride, at 120 DEG C of reaction 6h, obtain the large molecule guanidinesalt of straight chain (1).
Embodiment 1
Under 25 DEG C of room temperatures, by 1 part of benzenetricarboxylic acid trimethyl add with stir and the three-necked bottle of the 500ml of condensing unit in, then add 200 parts of ethanol to be heated to backflow.10 parts of hexamethylene diamines are added dropwise to reaction system, and reaction 18h, removes solvent, and excessive hexamethylene diamine decompression is steamed, and the product obtaining is faint yellow thick.
Synthesizing of hyperbranched macromolecular (I)
Embodiment 2
One-step method: by 1 part of hyperbranched intermediate (II, L=-CH
2cH
2-), 3 parts of guanidine hydrochlorides add in the three-necked bottle with the 250ml of agitating device, 60 DEG C of stirring reactions 1 hour, are warming up to 130 DEG C, stirring reaction 1 hour, after cooling product (2).This product is water miscible.
Embodiment 3
One-step method: by 1 part of hyperbranched intermediate (II, L=-(CH
2)
6-), 15 parts of hexamethylene diamines, in the three-necked bottle of the 250ml that 15 parts of dicyanodiamines add, 100 DEG C are stirred frit reaction 2 hours, are warming up to 180 DEG C, stirring reaction 10h, after cooling flaxen hyperbranched macromolecular guazatine.This product is water miscible.
Embodiment 4
Two-step method: by 3.3 parts of hexamethylene-diamine hydrochlorides, 3 parts of dicyanodiamines add in the three-necked bottle with the 250ml of agitating device, mix and are heated to 120 DEG C of stirring reaction 1h, are warming up to 180 DEG C, stirring reaction 8h.Then, by 1 part of hyperbranched intermediate (II, L=-CH
2cH
2-) join in reaction system, at 150 DEG C of temperature, continue reaction 4h, coolingly obtain flaxen hyperbranched macromolecular guazatine.This resin-like product is water miscible.
Embodiment 5
Two-step method: by 15 hexamethylene diamines, 15 parts of guanidine hydrochlorides add in the three-necked bottle with the 250ml of agitating device, mixes and is heated to 100 DEG C, and reaction 2h, is then warming up to 150 DEG C, stirring reaction 2h.Then by 1 part of hyperbranched intermediate (II, L=-(CH
2)
6-) join reaction system, at 160 DEG C of temperature, in reaction, react 2h, after cooling flaxen hyperbranched macromolecular list guanidinesalt (3).This product is water miscible.
Claims (10)
1. a hyperbranched macromolecular guanidinesalt antibacterial agent (I), it is characterized in that: described hyperbranched macromolecular guanidinesalt structure comprises hyperbranched intermediate (II) and large molecule guanidinesalt (III), and wherein hyperbranched intermediate (II) is acid amide type or ester type (being X=N or O); Large molecule guanidinesalt (III) comprises large molecule list guanidinesalt and large molecule guazatine,
Symbol in formula represents following implication:
X: be N or O;
L:C
2～12methylene or there is the Oxymethylene of different numbers;
n＝2～12。
2. a method of preparing hyperbranched macromolecular guanidinesalt antibacterial agent according to claim 1 (I), is characterized in that: the preparation of (1) hyperbranched intermediate (II); (2) preparation of hyperbranched macromolecular guanidinesalt (I).
3. the preparation method of hyperbranched macromolecular guanidinesalt antibacterial agent according to claim 2 (I), is characterized in that, the preparation method of described hyperbranched intermediate (II) is 1 part of trimesic acid trimethyl and 3～15 parts of diamines (NH
2-L-NH
2) back flow reaction 8～24h in organic solvent, remove after organic solvent and excessive diamines, obtain hyperbranched intermediate (II).
4. the preparation method of hyperbranched macromolecular guanidinesalt antibacterial agent according to claim 3 (I), is characterized in that, organic solvent is methyl alcohol and/or ethanol.
5. the preparation method of hyperbranched macromolecular guanidinesalt antibacterial agent according to claim 2 (I), it is characterized in that, in reaction system, add 1 part of hyperbranched intermediate (II), 0～15 part of diamines (NH2-L-NH2) and 3～15 parts of guanidine hydrochlorides or dicyanodiamine, 60～120 DEG C are stirred frit reaction 1～4h hour, be warming up to 130～180 DEG C, stirring reaction 1～10h, after cooling product, this product is water-soluble.
6. the preparation method of hyperbranched macromolecular guanidinesalt antibacterial agent according to claim 2 (I), is characterized in that comprising the following steps:
1) in reaction system, add 3～15 parts of diamines (NH2-L-NH2) and 3～15 parts of guanidine hydrochlorides or dicyanodiamine, stir frit reaction 1～4h at 60～120 DEG C, be warming up to 130～180 DEG C, stirring reaction 1～10h;
2) 1 part of hyperbranched intermediate (II) is added to reaction system, under 140～180 DEG C of conditions, continues reaction 1～4h, after cooling product, this product is water-soluble.
7. the preparation method of hyperbranched macromolecular guanidinesalt antibacterial agent according to claim 6 (I), is characterized in that, described diamines (NH
2-L-NH
2) with the rate of charge of guanidine hydrochloride or dicyanodiamine be 1～1.5: 1, the best is 1～1.1: 1.
8. the preparation method of hyperbranched macromolecular guanidinesalt antibacterial agent according to claim 6 (I), it is characterized in that, aliphatic diamine (NH2-L-NH2) is 80～100 DEG C of stirring reaction 1～2h with the optimum condition of reacting of guanidine hydrochloride or dicyanodiamine, be warming up to 130～160 DEG C, stirring reaction 2～8h.
9. the preparation method of hyperbranched macromolecular guanidinesalt antibacterial agent according to claim 6 (I), is characterized in that, adding the post-reacted optimum condition of hyperbranched intermediate (II) is that temperature is 150～160 DEG C, and the reaction time is 2～3h.
10. hyperbranched macromolecular guanidinesalt antibacterial agent according to claim 1 (I), it is characterized in that, this antibacterial agent has long-term antibacterial action, stable in properties, soluble in water, the feature that can use under wide temperature and pH value scope, can be widely used in health care, food processing, daily-use chemical industry, daily life, agricultural, aquatic products, livestock breeding field.
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| CN114181389A (en) * | 2021-05-31 | 2022-03-15 | 杭州聚合顺新材料股份有限公司 | Antibacterial nylon 6 containing guanidino group and preparation method thereof |
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Cited By (4)
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| CN110121548A (en) * | 2017-01-03 | 2019-08-13 | 陈煌兴 | Branched polymeric biguanide compound and application thereof |
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| CN114181389A (en) * | 2021-05-31 | 2022-03-15 | 杭州聚合顺新材料股份有限公司 | Antibacterial nylon 6 containing guanidino group and preparation method thereof |
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Application publication date: 20140611 |