CN111925527B

CN111925527B - Long-chain alkyl grafted quaternized silicone and preparation method and application thereof

Info

Publication number: CN111925527B
Application number: CN202010846307.9A
Authority: CN
Inventors: 侯桂革; 王春华; 苏长鸣; 高中飞
Original assignee: Binzhou Medical College
Current assignee: Binzhou Medical College
Priority date: 2020-08-21
Filing date: 2020-08-21
Publication date: 2022-05-24
Anticipated expiration: 2040-08-21
Also published as: CN111925527A

Abstract

The invention relates to long-chain alkyl substituted quaternized silicone (N-long-chain alkyl-N, N-dihydroxyethyl-N-hexyl) -silicone with antibacterial, anti-inflammatory, moisturizing and scar removing effects and a preparation method thereof. The method comprises the steps of taking polymethyl hydrogen siloxane as a raw material, taking 6-bromo-1-hexene as a coupling agent, firstly carrying out side chain derivatization on the polymethyl hydrogen siloxane through hydrosilylation reaction to obtain bromoalkyl substituted polymethyl hydrogen siloxane, and then carrying out quaternization reaction on the bromoalkyl substituted polymethyl hydrogen siloxane and diethanolamine substituted by long-chain alkyl to obtain (N-long-chain alkyl-N, N-dihydroxyethyl-N-hexyl) -silicone. The prepared silicone has obviously increased antibacterial performance and can make up the defect that polymethyl hydrogen siloxane has no antibacterial effect.

Description

Long-chain alkyl grafted quaternized silicone and preparation method and application thereof

Technical Field

The invention relates to a medical antibacterial material, in particular to a long-chain alkyl grafted quaternized silicone material.

Background

Silicones, also known as polysiloxanes, are frequently found in many fields, such as food and medicine, electronics and electrical, engineering and construction, and are hot spots of research due to their excellent water resistance, non-toxicity and non-irritation. The main raw material of the commercially available silicone product is Polydimethylsiloxane (PDMS), and the PDMS has certain clinical application due to the advantages of stable chemical properties and moisturizing capability of promoting rapid softening of horny layer and inhibiting scars, and can be used as a main drug of scar repairing products, such as Shuxieling and Beixieling. Silicone also has defects, and the silicone scar inhibitor cannot ensure the scar treatment and resist the infection of external bacteria, and in addition, the preparation has strong inflammatory effect, so that the clinical application is limited, such as the preparation is forbidden to be applied to unclosed or infected wounds. Therefore, improving the antibacterial properties of silicones has become an important issue to be solved.

The clinically used silicone products for treating scars are PDMS, and the application of Polymethylhydrosiloxane (PMHS) with higher activity in medicine is very rare. Because the chain segment polymerized by PMHS contains active Si-H bond, the chain segment is easy to be interacted with moisture in the air and converted into stable Si-OH. PMHS has large steric hindrance due to the self-polymerization degree, and is difficult to directly modify the structure. The invention creatively introduces halogenated alkyl and dihydroxyl into the side chain of PMHS to further synthesize the quaternized silicone derivative. The antibacterial performance of the prepared silicone is obviously improved, and the defect that PMHS has no antibacterial effect can be overcome.

Disclosure of Invention

The invention provides long-chain alkyl substituted quaternized silicone and a preparation method thereof, in order to obtain an antibacterial material with excellent antibacterial property, scar repairing property, water retention property and toxicity reduction property.

The invention is realized by the following technical scheme:

a long chain alkyl grafted quaternized silicone named (N-long chain alkyl-N, N-dihydroxyethyl-N-hexyl) -silicone, QP, structure:

(1) wherein R is dodecyl, and the name of the specific compound is (N-dodecyl-N, N-dihydroxyethyl-N-hexyl) -silicone, namely QP 12;

(2) Wherein R is tetradecyl, the specific compound name is (N-tetradecyl-N, N-dihydroxyethyl-N-hexyl) -silicone, i.e., QP 14.

The synthetic route of the long-chain alkyl grafted quaternized silicone disclosed by the invention is as follows:

the preparation route of the long-chain alkyl grafted quaternized silicone provided by the invention is that polymethyl hydrogen siloxane (PMHS) is used as a raw material, 6-bromo-1-hexene is used as a coupling agent, side chain derivatization is firstly carried out on the polymethyl hydrogen siloxane through hydrosilylation reaction to obtain bromoalkyl substituted polymethyl hydrogen siloxane (MHSB), and then quaternization reaction is carried out on the bromoalkyl substituted polymethyl hydrogen siloxane and long-chain alkyl substituted diethanol amine to obtain (N-long-chain alkyl-N, N-dihydroxyethyl-N-hexyl) -silicone.

The laboratory preparation method of the long-chain alkyl grafted quaternized silicone of the invention is as follows:

(1) laboratory preparation of MHSB: under the protection of inert gas (argon or nitrogen), dissolving PMHS and a proper amount of 6-bromo-1-hexene in anhydrous toluene in a dry experimental device to form a mixed solution, dropwise adding a proper amount of catalyst into the mixed solution at normal temperature, reacting for 24-48 hours at 40-80 ℃, mixing the obtained solution with cold anhydrous methanol, standing overnight in a refrigerator at-50 ℃, pouring out supernatant, performing ultrafiltration on residues by using a 0.20-0.60 mu m filter membrane, and performing reduced pressure evaporation on filtrate to remove the solvent to obtain an intermediate MHSB;

(2) Laboratory preparation of QP: dissolving the intermediate MHSB and the long-chain alkyl diethanol amine in a chloroform/N, N-dimethyl formamide mixed solution with a volume ratio of 1:1, stirring and reacting at 60-80 ℃ for 12-24 hours, cooling to room temperature after the reaction is finished, pouring the mixture into anhydrous ether for precipitation, performing suction filtration on the precipitate, washing with cold anhydrous ether for three times, and performing vacuum drying to obtain the target product QP.

The pilot plant preparation of the long chain alkyl grafted quaternized silicone of the present invention was as follows:

(1) pilot plant preparation of MHSB: under the protection of inert gas (argon or nitrogen), sequentially adding 3L of toluene, 230g of PMHS and a proper amount of 6-bromo-1-hexene into a dry 10L reaction kettle at normal temperature, uniformly stirring, then dropwise adding a proper amount of catalyst, reacting at 60-80 ℃ for 24-48 hours, then adding a proper amount of anhydrous methanol, mixing, continuously stirring for 0.5 hour, decompressing and steaming out most of solvent in the mixture, adding a proper amount of activated carbon into residues, decoloring at 60-80 ℃ for 0.5 hour, performing suction filtration, decompressing and steaming out the solvent in the filtrate to obtain an intermediate MHSB;

(2) pilot plant preparation of QP: and dissolving the obtained intermediate MHSB and the long-chain alkyl diethanol amine in 3L of N, N-dimethylformamide, stirring and reacting at 60-80 ℃ for 12-24 hours, cooling to room temperature after the reaction is finished, evaporating the solvent from the mixture under reduced pressure, washing the residue with cold anhydrous methanol for three times, and drying in vacuum to obtain the target product QP.

The addition amount of the 6-bromine-1-hexene is 1.0-2.0 times of the mole number of the silicon-hydrogen bond in the PMHS.

The catalyst is a xylene solution of 1, 3-divinyl-1, 1,3, 3-tetramethyldisiloxane platinum, wherein the content of platinum element is 2%.

The long-chain alkyl diethanolamine is N-dodecyl diethanolamine or N-tetradecyl diethanolamine.

The long-chain alkyl grafted quaternized silicone disclosed by the invention is applied to antibacterial agents and antibacterial materials.

The long chain alkyl grafted quaternized silicone of the present invention is useful in tissue repair or scar repair.

The long chain alkyl grafted quaternized silicone of the present invention is useful as a wound dressing, a tissue engineering dressing, and in other medical devices.

Drawings

FIG. 1: infrared spectra of PMHS, QP12, QP 14;

FIG. 2: of PMHS, QP12, QP14¹H NMR spectrum.

Detailed Description

The following is a detailed embodiment of the present invention and is provided to supplement the description of the present invention. The preparation method of the long-chain alkyl grafted quaternized silicone comprises the following steps:

example 1: laboratory preparation of (N-dodecyl-N, N-dihydroxyethyl-N-hexyl) -silicone (QP12)

(1) Synthesis of MHSB

Taking 245 mu L of PMHS (1 time equivalent) in a three-neck flask after high-temperature drying, filling dry argon for protection by using a Schlenk step, sequentially adding 0.8g (equivalent to 1.6 times of a silicon-hydrogen bond of the PMHS) of 6-bromo-1-hexene and 5mL of anhydrous toluene, stirring for 5min for fully mixing, adding 50 mu L of a catalyst, heating and stirring for 48h at 65 ℃, mixing the obtained solution with 20mL of cold anhydrous methanol, standing overnight in a refrigerator at-50 ℃, pouring out a supernatant, carrying out ultrafiltration on the residue by using a filter membrane of 0.20-0.60 mu m, and carrying out reduced pressure distillation to obtain pale yellow or colorless MHSB.

(2) Synthesis of quaternized Silicone QP12

Putting the PMHS and the N-dodecyl diethanol amine (1.4g, 4.9mmoL) obtained in the above into a reaction bottle, adding 5mL of chloroform/N, N-dimethylformamide mixed solvent (volume ratio is 1:1), heating and stirring at 70 ℃ for refluxing for 22h, precipitating by using cold anhydrous ether, and washing by using the cold anhydrous ether for three times to obtain a light yellow invention product QP 12.

Example 2: laboratory preparation of (N-tetradecyl-N, N-dihydroxyethyl-N-hexyl) -silicone (QP14)

(1) Synthesis of MHSB

The procedure for the preparation of MHSB in example 1 was used.

(2) Synthesis of quaternized Silicone QP14

One equivalent of derivatized PMHS and N-tetradecylethanolamine (1.4g, 4.9mmoL) are placed in a reaction bottle, 5mL of chloroform/N, N-dimethylformamide mixed solvent (volume ratio is 3:2) is added, heating and stirring are carried out for 18h at 70 ℃, precipitate is washed by cold anhydrous ether, and the precipitate is washed by the cold anhydrous ether for three times to obtain a light yellow product QP 14.

Example 3: pilot plant preparation of (N-dodecyl-N, N-dihydroxyethyl-N-hexyl) -silicone (QP12)

(1) Pilot scale preparation of MHSB

Under the protection of inert gas (argon or nitrogen), 3L of anhydrous toluene, 230g of PMHS and a certain amount of 6-bromo-1-hexene (equivalent to 1.1 times of a silicon-hydrogen bond of the PMHS) are sequentially added into a dry 10L reaction kettle at normal temperature, stirred for 5min to be fully and uniformly mixed, a certain amount of catalyst is added, the mixture reacts for 48 hours at 65 ℃, then 1L of anhydrous methanol is added for mixing, the mixture is continuously stirred for 0.5 hour, most of solvent is evaporated under reduced pressure, 100g of activated carbon is added into residues, decolorization is carried out for 0.5 hour at 80 ℃, suction filtration is carried out, and filtrate is evaporated under reduced pressure to remove the solvent to obtain a faint yellow or colorless intermediate MHSB.

(2) Pilot plant preparation of quaternized Silicone QP12

And (2) placing the PMHS and the N-dodecyl diethanolamine (equivalent to 1.1 times of the silicon-hydrogen bond of the PMHS) obtained in the previous step into a 10L reaction kettle, adding 3L of N, N-dimethylformamide, heating, stirring and refluxing for 22h at 75 ℃, cooling to room temperature after the reaction is finished, evaporating the solvent from the mixture under reduced pressure, washing the residue with 2L of cold anhydrous methanol for three times, and drying in vacuum to obtain a light yellow target product QP 12.

Example 4: pilot plant preparation of (N-tetradecyl-N, N-dihydroxyethyl-N-hexyl) -silicone (QP14)

(1) Pilot scale preparation of MHSB

The procedure for the preparation of MHSB in example 3 was used.

(2) Pilot plant preparation of quaternized Silicone QP14

And (2) placing the PMHS and the N-dodecyl diethanolamine (equivalent to 1.1 times of the silicon-hydrogen bond of the PMHS) obtained in the previous step into a 10L reaction kettle, adding 2.5L of N, N-dimethylformamide, heating, stirring and refluxing for 18h at 75 ℃, cooling to room temperature after the reaction is finished, evaporating the solvent from the mixture under reduced pressure, washing the residue with 2L of cold anhydrous methanol for three times, and drying in vacuum to obtain a light yellow target product QP 14.

The long-chain alkyl grafted quaternized silicone of the invention is proved to be correct in synthetic route and measure the substitution degree thereof by methods such as elemental analysis, infrared spectrum, nuclear magnetic resonance and the like.

(1) Elemental analysis and degree of substitution

The measured contents of each element of QP12 and QP14 were measured by an element analyzer, and the degree of substitution was calculated to be 22.99%. The same calculation gave a degree of substitution of 17.68% for QP14 (Table 1) and a different degree of substitution for the quaternized silicone QP product, possibly due to steric hindrance of the N-long alkyl ethanolamine to which it was grafted. As the alkyl chain length increases, the QP product decreases in degree of substitution due to the increased steric hindrance of the N-long chain alkyl ethanolamine.

TABLE 1 Synthesis conditions, elemental analysis and degree of substitution of quaternized silicones

(2) Infrared spectroscopic analysis

QP12 as representative analysis object, PMHS through siliconAnd (3) extending a side chain by hydrogen addition reaction, and successfully reacting the active group at the tail end of the side chain with a tertiary amine LA12 to prepare QP 12. As shown in FIG. 1, 2162cm in PMHS^-1Ascribed to a Si-H bond vibration peak of 2966cm^-1Attribution as-CH₃Peak of stretching vibration, 1038cm^-1The strain is attributed to the Si-O-Si bond stretching vibration peak. 2854cm in MHSB map^-1Is attributed as-CH₂-peak of stretching vibration, and 564cm^-1The C-Br bond stretching vibration peak is present at 2100cm^-1The nearby Si-H bond disappeared, indicating successful grafting of 6-bromo-1-hexene onto PMHS. QP12 map, 3316cm^-1shows-OH stretching vibration peak at 560cm ^-1The peak intensity of nearby C-Br is greatly reduced compared with the MHSB intensity, and is 730cm^-1The long-chain alkyl characteristic peak appears, and the successful reaction of the dodecyl diethanol tertiary amine and the MHSB is proved. The same structure is also embodied in QP 14.

(3)¹H NMR spectroscopic analysis

Of the starting materials Polymethylhydrosiloxane (PMHS) and two quaternized silicones (QP12, QP14)¹H NMR analysis was performed on a Bruker 600 instrument using deuterated DMSO as the solvent. The QP12 is taken as a representative analysis result, the modified PMHS is represented by a nuclear magnetic resonance hydrogen spectrum, and the representation result shows that the bulk drug PMHS belongs to hydrogen directly connected with silicon at 4.5ppm, and other hydrogen belongs to hydrogen connected with carbon; on one hand, after quaternization modification, the QP12 nuclear magnetic spectrum shows that the original Si-H peak of 4.5ppm disappears, and Si-CH 2-hydrogen addition appears at the position of 0.5ppm instead, and the result shows that the hydrosilylation reaction is successfully carried out; on the other hand, the QP12 map shows hydrogen with the position similar to that of LA12, for example, 1.3ppm of angelica belongs to-CH in the dodecyl chain₂Hydrogen on-demonstrates successful quaternization of PMHS, a conclusion consistent with the infrared results, indicating the correctness of the synthetic route.

(4) Antibacterial performance test and result analysis

Tests of antimicrobial tests of quaternized silicones are divided into qualitative and quantitative tests.

Qualitative test method-bacteriostasis loop method

The bacteriostatic circle method is a method for qualitatively testing the antibacterial performance of the quaternized silicone (QP12, QP14), and the experimental scheme is as follows: cutting filter paper into round pieces (diameter 6mm), sterilizing and drying for later use; the concentration of the test bacterial liquid is 10⁸CFU/mL, and a corrected absorbance at a wavelength of 625nm of 0.08 to 0.1 (corresponding to a 0.5 McLeod standard concentration). After 0.1mL of test bacterial liquid is fully and uniformly coated on a solid culture medium, a filter paper wafer is flatly paved on the solid culture medium, quaternized silicone solutions to be tested with different concentrations are prepared, the final concentration gradients are respectively 0 mu g/mL, 100 mu g/mL, 500 mu g/mL, 1000 mu g/mL and 2500 mu g/mL, the quaternized silicone solutions are dropwise added onto paper sheets of the culture medium, and Polymethylhydrosiloxane (PMHS) with the same concentration gradient is set as a negative control group according to the same method; benzalkonium Bromide (BZK) and Chlorhexidine (CA) as positive control group, and culturing in 37 deg.C incubator for 24 hr. And (5) counting the diameter of the bacteriostatic circle after culture, and taking the diameter as the basis for evaluating the bacteriostatic performance of the quaternized silicone.

TABLE 2 zone of inhibition diameter of quaternised silicones (QP12, QP14) (diameter units: mm, concentration units. mu.g/mL)

In the qualitative test experiment, the quaternary ammonium silicone (QP12, QP14) has certain antibacterial capacity for the selected strain. As shown in Table 2, for gram-positive staphylococcus aureus, when the concentration is increased to 500 mug/mL, the inhibition zone is shown, and when the concentration is continuously increased, the inhibition zone tends to be gradually increased; similarly, the same experimental results were shown for the fungus Candida albicans, which showed a zone of inhibition when the concentration increased to 1000. mu.g/mL; the results of other gram-negative bacteria experiments show that the quaternary silicone (QP12, QP14) has far less effect on the bacteria than staphylococcus aureus and candida albicans. In general, the quaternary silicone (QP12, QP14) has stronger action on gram-positive bacteria and fungi than gram-negative bacteria.

Quantitative test experiment-two-fold dilution method

The double dilution method is a method for quantitatively testing the antibacterial performance of the quaternized silicone (QP12, QP14), and the experimental scheme is as follows: preparing 2mL of liquid medicine to be detected with mother liquor concentration of 1600 mu g/mL, adding equal volume of culture solution for dilution by multiple times to make the final concentration of the liquid medicine to be detected 800 mu g/mL, 400 mu g/mL, 200 mu g/mL, 100 mu g/mL, 50 mu g/mL, 25 mu g/mL, 12.5 mu g/mL, 6.25 mu g/mL and 3.125 mu g/mL, and setting Polymethylhydrosiloxane (PMHS) with the same concentration gradient as a negative control group according to the same method; benzalkonium Bromide (BZK) and Chlorhexidine (CA) were used as positive controls. Adding 0.1mL of bacterial suspension into the groups, fully mixing uniformly, culturing at 37 ℃ for 18h, recording the Minimum Inhibitory Concentration (MIC), taking 0.1mL of culture solution of a clarification test tube, fully coating the culture solution on a solid culture medium, culturing for 24h, recording the number of colonies, and taking the colonies with the number less than 5 in a culture dish as the Minimum Bactericidal Concentration (MBC).

TABLE 3 MIC and MBC (μ g/mL) for Quaternary ammonium silicones (QP12, QP14)

Quaternary ammonium silicone (QP12) is modified by a high molecular polymer, and in the whole, the MBC and MIC values of QP12 are lower than those of a positive drug group in the same operation, and the antibacterial activity is weaker. For the antibacterial capacity of different strains, QP12 has lower activity of inhibiting gram-negatives such as escherichia coli, pseudomonas aeruginosa and the like, the MIC value is 200 mu g/mL or 400 mu g/mL, the proliferation of staphylococcus aureus of gram-positive bacteria and candida albicans of fungi with the action of QP12 can be inhibited under lower medicine concentration, the MIC value can reach 50 mu g/mL at the lowest, and the data show that the action capacity of QP12 for inhibiting the gram-negative bacteria is lower than that of the gram-positive bacteria and the fungi which are treated in the same way; compared with the same genus, QP12 has the strongest effect on inhibiting staphylococcus aureus, the MIC value is 1/4 of alpha hemolytic streptococcus, the inhibiting capability is 4 times of that of alpha hemolytic streptococcus, and the lowest value of all strain testing values shows the effect of QP12 on staphylococcus aureus. There was no significant difference in the ability of QP12 to act on the selected gram-negative strains. According to the results shown in Table 3, the antibacterial ability of QP14 for different bacterial species was similar to QP 12. However, compared with QP12, the concentration of the drug required for effectively inhibiting the proliferation of bacteria is higher than that of QP12, for example, the MIC of Staphylococcus aureus is 100 mug/mL, and the like, and the main reason of the drug is probably that the reduction of the substitution degree of the quaternary ammonium salt reduces the bacteriostatic and bactericidal capacity of QP.

(5) Antimicrobial challenge experiments and results analysis

Antimicrobial invasion assay three representative strains (s. aureus, e.coli, Candida albicans) were cultured on a surface coated with QP12, QP14, and the ability of the nanomembrane to resist bacteria was observed. The specific experimental operations were as follows: firstly, cutting sterile filter paper into square small blocks with the size of 1cm multiplied by 1cm, placing the small blocks into a culture medium after sterilization, enabling one side of each small block to be tightly attached to the culture medium, and smearing QP12 or QP14 on the other side of each small block; next, a suspension of the bacterial suspension (concentration 1.5X 10) was prepared⁸CFU/mL), and 100 mu L of inoculation is dripped on the outer side of the filter paper, and the inverted culture is carried out for 8h, 12h and 24h at the temperature of 37 ℃; after treatment, the growth of bacteria on both sides of the filter paper was observed. The experimental group without QP12 or QP14 was the control group. The experimental results showed that in the control group, both sides of the filter paper were full of the bacteria of S.aureus, E.coli and Candida albicans, and the number of bacteria was greatly increased with the increase of time, and a biofilm was formed. In the experimental groups coated with QP12 or QP14, the side of the filter paper was full of bacteria, while the side coated with QP12 or QP14 showed almost no bacteria to survive and showed good resistance. The QP12 or the QP14 are proved to be effective in resisting the invasion of microorganisms and have remarkable antibacterial performance.

(6) Cytotoxicity test and results analysis

Quaternary ammonium silicones (QP12, QP14) were tested for cytotoxicity against human normal hepatocytes (LO2), human immortalized epidermal cells (Hacat) using the MTT method. The concentration of the mother liquor to be tested is 10000 mug/mL, the mother liquor is prepared to be the final concentration of 1000 mug/mL, 800 mug/mL, 600 mug/mL, 400 mug/mL, 200 mug/mL, 100 mug/mL, 50 mug/mL and 25 mug/mL, and the small molecule antibacterial medicine benzalkonium Bromide (BZK) and Chlorhexidine (CA) are used as positive references. Culturing cells to logarithmic phase, digesting with pancreatin, resuspending the culture medium and inoculating into 96-well plate with 0.1mL of 5X 10 concentration per well³Culturing in single/mL cell suspension for 24 hr, changing into different concentrations of medicinal liquid to be tested, culturing for 24 hr, and changing into MTT reagent-containing culture solutionAnd 4h, testing the absorbance at 570nm, and calculating the cell survival rate, so as to evaluate the cytotoxicity of the solution to be tested on the test cells.

TABLE 4 Quaternary ammonium silicones (QP12, QP14) cytotoxicity (μ g/mL) against LO2, Hacat

In cytotoxicity testing experiments, the quaternary silicones (QP12, QP14) were much less cytotoxic to both cells than the positive drug group. As shown in Table 4, IC of QP12 for human normal hepatocytes (LO2)₅₀A value of 515.6. mu.g/mL, which is much lower than 2.23. mu.g/mL for Chlorhexidine (CA); IC of QP12 for human immortalized epidermal cells (Hacat) ₅₀The value is only 324.3 mug/mL, which is much lower than 2.69 mug/mL of CA; similarly, the cytotoxicity of QP14 is far lower than that of two positive medicine groups, and the result shows that the quaternized silicones (QP12 and QP14) have lower cytotoxicity, and also shows the potential of QP12 and QP14 in the field of novel low-toxicity and antibacterial medicines.

(7) Scar removal performance test and result analysis

Quaternary ammonium silicones (QP12, QP14) were evaluated for scar removal performance by establishing a rabbit ear wound-scar repair model. The animal model is used for removing the full-layer skin and the perichondrium of the wound at the ventral side of the rabbit ear, coating quaternized silicones (QP12 and QP14) on the wound after modeling is completed, and establishing a negative control group without treatment and a positive control group coated with commercially available scar removing products Shuxiling and double-scar ling according to the same operation method as reference to evaluate the scar removing effect of the quaternized silicones (QP12 and QP 14). The experimental result shows that the hyperplastic scar beyond the wound range is generated after the wound is self-repaired within 28 days of the negative control group experiment, and the animal model is proved to be effective; the wounds of the positive control group Shuxieling and the double scar panacea are basically repaired after being treated for 14 days, the repaired tissues protrude out of the surface of the skin to form scar tissues similar to those of the negative control group, and the scar tissues are not obviously improved in 28 days of the experiment, which indicates that the commercial products have no scar removing effect or have no scar removing effect within 28 days; after the QP12 and QP14 experiments are carried out for 28 days, no obvious scar tissue protrudes out of the skin surface after the wound is repaired, and the color and the thickness of the scar tissue are similar to those of the surrounding normal tissues. The experimental results show that QP12 and QP14 can achieve excellent scar removing effects superior to those of the Shuxiling and Bixiling which are commercial products within 28 days of rabbit ear wound-scar repair experiments, and scar removing tissues are similar to normal tissues, which indicates that the quaternized silicones (QP12 and QP14) have the potential in the aspect of scar removing.

(8) Anti-inflammatory performance testing and results analysis

Hypertrophic scars are morphologically characterized by hyperplasia of tissues that does not extend beyond the wound, and pathologically characterized by an inflammatory response in the tissues that persists with the hyperplasia of the scar. Thus, the status of scar tissue can be indirectly reflected by detecting the level of inflammatory factors within the scar tissue. According to the invention, in the model in (7), the TNF-alpha level in scar tissues is evaluated through immunohistochemistry, and the result shows that the TNF-alpha level in the tissues is obviously increased within 14 days of the negative control group experiment, no reduction sign exists when the experiment time lasts to 28 days, and the inflammatory reaction in the tissues is heavy; the commercial products of shuxiscar ling and double scar ling have higher TNF-alpha level in tissues in 14 days of experiments and show obvious inflammatory reaction. When the experimental time reaches 28 days, although the TNF-alpha level in the tissue is slightly reduced compared with that of a negative control group, a large amount of TNF-alpha still exists, namely scars cannot be obviously removed; QP12, QP14 showed similar results, and the expression of TNF-alpha in the tissue is less in 14 days of experiment and has no increasing trend along the experiment time, which shows that the quaternized silicone (QP12, QP14) can inhibit the expression of TNF-alpha in scar tissue. The experimental results show that QP12 and QP14 can obviously inhibit the expression of TNF-alpha within 28 days of the experiment and are superior to the Shuxieling and the Beijing which are commercial products, the results are consistent with the results obtained in the step (6), and the potential of QP12 and QP14 in the aspect of scar removal is shown.

Claims

1. A long chain alkyl substituted quaternized silicone characterized by: the long chain alkyl substituted quaternized silicones are prepared by the following method: taking polymethyl hydrogen siloxane as a raw material and 6-bromo-1-hexene as a coupling agent, firstly performing side chain derivatization on the polymethyl hydrogen siloxane through hydrosilylation reaction to obtain bromoalkyl substituted polymethyl hydrogen siloxane, and then performing quaternization reaction on the bromoalkyl substituted polymethyl hydrogen siloxane and long-chain alkyl substituted diethanol amine to obtain (N-long-chain alkyl-N, N-dihydroxyethyl-N-hexyl) -silicone;

when the (N-long alkyl-N, N-dihydroxyethyl-N-hexyl) -silicone is (N-dodecyl-N, N-dihydroxyethyl-N-hexyl) -silicone, the degree of substitution is 22.99%;

when the (N-long chain alkyl-N, N-dihydroxyethyl-N-hexyl) -silicone was (N-tetradecyl-N, N-dihydroxyethyl-N-hexyl) -silicone, the degree of substitution was 17.68%.

2. A method of preparing a long chain alkyl substituted quaternized silicone of claim 1 characterized in that: the method comprises the steps of taking polymethyl hydrogen siloxane as a raw material, taking 6-bromo-1-hexene as a coupling agent, firstly carrying out side chain derivatization on the polymethyl hydrogen siloxane through hydrosilylation reaction to obtain bromoalkyl substituted polymethyl hydrogen siloxane, and then carrying out quaternization reaction on the bromoalkyl substituted polymethyl hydrogen siloxane and diethanolamine substituted by long-chain alkyl to obtain (N-long-chain alkyl-N, N-dihydroxyethyl-N-hexyl) -silicone.

3. A method of preparing a long chain alkyl substituted quaternised silicone as claimed in claim 2 characterised in that: the specific method comprises the following steps:

(1) laboratory preparation of bromoalkyl-substituted polymethylhydrosiloxanes: under the protection of inert gas, in a dry experimental device, dissolving polymethylhydrosiloxane and 6-bromo-1-hexene in anhydrous toluene to form a mixed solution, dropwise adding a catalyst into the mixed solution at normal temperature, reacting at 40-80 ℃ for 24-48 hours, mixing the obtained solution with cold anhydrous methanol, standing in a refrigerator at-50 ℃ for overnight, pouring out supernatant, performing ultrafiltration on residues with a 0.20-0.60 mu m filter membrane, and performing reduced pressure evaporation on the filtrate to remove the solvent to obtain intermediate bromoalkyl substituted polymethylhydrosiloxane;

(2) laboratory preparation of QP: dissolving the intermediate bromoalkyl-substituted polymethylhydrosiloxane and long-chain alkyl diethanol amine obtained in the step (1) in a mixed solution of chloroform and N, N-dimethylformamide in a volume ratio of 1:1, stirring and reacting at 60-80 ℃ for 12-24 hours, cooling to room temperature after the reaction is finished, pouring the mixture into anhydrous ether for precipitation, performing precipitation and suction filtration, washing with cold anhydrous ether for three times, and performing vacuum drying to obtain a target product QP;

Wherein the addition amount of the 6-bromine-1-hexene is 1.0-2.0 times of the mole number of the silicon-hydrogen bond in the polymethylhydrosiloxane;

4. A method of preparing a long chain alkyl substituted quaternized silicone according to claim 2, characterized in that: the specific method comprises the following steps:

(1) pilot plant preparation of bromoalkyl-substituted polymethylhydrosiloxanes: under the protection of inert gas, sequentially adding 3L of toluene, 230 g of polymethylhydrosiloxane and 6-bromo-1-hexene into a dry 10L reaction kettle at normal temperature, uniformly stirring, dropwise adding a catalyst, reacting at 60-80 ℃ for 24-48 hours, adding anhydrous methanol, mixing, continuously stirring for 0.5 hour, evaporating most of the solvent from the obtained product under reduced pressure, adding activated carbon into the residue, decolorizing at 60-80 ℃ for 0.5 hour, performing suction filtration, and evaporating the solvent from the filtrate under reduced pressure to obtain an intermediate bromoalkyl substituted polymethylhydrosiloxane;

(2) pilot plant preparation of QP: dissolving the intermediate bromoalkyl-substituted polymethylhydrosiloxane and the long-chain alkyl diethanol amine obtained in the step (1) in 3L of N, N-dimethylformamide, stirring and reacting at 60-80 ℃ for 12-24 hours, cooling to room temperature after the reaction is finished, evaporating the solvent from the mixture under reduced pressure, washing the residue with cold anhydrous methanol for three times, and drying in vacuum to obtain a target product QP;

Wherein the addition amount of the 6-bromine-1-hexene is 1.0 to 2.0 times of the mole number of the silicon hydrogen bonds in the polymethylhydrosiloxane;

5. A method of preparing a long chain alkyl substituted quaternised silicone as claimed in claim 3 or 4 characterised in that: the long-chain alkyl diethanolamine is N-dodecyl diethanolamine or N-tetradecyl diethanolamine.

6. Use of a long chain alkyl substituted quaternized silicone according to claim 1 in the preparation of antibacterial agents and antibacterial materials.

7. Use of a long chain alkyl substituted quaternized silicone according to claim 1 in the preparation of a tissue repair or scar repair material.

8. Use of a long chain alkyl substituted quaternised silicone as claimed in claim 1 in the preparation of wound dressings, tissue engineering dressing materials.