Antibacterial gel for obstetrical department and preparation method thereof

Abstract

The invention belongs to the technical field of medical gel, and particularly relates to antibacterial gel for obstetrics and a preparation method of the antibacterial gel. The antibacterial gel is prepared from the following raw materials in parts by weight: 0.3 to 0.5 part of nuciferine derivatives, 0.5 to 1.5 parts of hydroxyethyl cellulose, 0.5 to 1 part of glycerol, 1.5 to 2 parts of propylene glycol, 0.5 to 1.5 parts of carbomer, 70 to 80 parts of ethanol and 15 to 20 parts of water. The nuciferine derivative has the following structural formula. The antibacterial gel provided by the invention has good antibacterial performance and moisturizing effect.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical gels, in particular to a bacteriostatic gel for obstetrics and a preparation method thereof. BACKGROUND

[0002] Natural childbirth refers to the process of the fetus being delivered from the mother's uterus to the outside world through the birth canal. During the process of natural childbirth, the puerpera will experience severe pain and fear, which is a common physiological response during natural childbirth. Reducing the pain of the puerpera during natural childbirth is not only a humanistic care for the puerpera, but also an important measure to protect the safety of mother and infant.

[0003] In the operation of midwifery, the hands of the midwife need to directly contact the birth canal of the puerpera. The immune defense function of the puerpera during childbirth is relatively weak, and the birth canal is in an open state, which is extremely easy to become a breakthrough for the invasion of exogenous pathogenic microorganisms. Once the pathogenic microorganisms invade, not only can it cause puerperal infection of the puerpera, but also can increase the risk of serious complications such as vertical transmission of mother and infant and perinatal infection, endangering the life and health of mother and infant. Therefore, maintaining the antibacterial efficiency of the hand operation interface is a core element to ensure the safety of puerpera during childbirth.

[0004] Nuciferine is an aporphine alkaloid in lotus leaves, which is the main lipid-lowering active ingredient of lotus leaves, has the effects of lowering blood lipids, resisting free radicals and inhibiting bacteria. Its antibacterial mechanism involves inhibiting bacterial reproduction, damaging cell membranes and affecting energy metabolism. However, the single antibacterial principle of nuciferine is easy to be disturbed by the outside world, and the long-acting antibacterial property is challenged.

[0005] In view of the above situation, the present application makes in-depth research on nuciferine, and combines the characteristics of obstetric bacteriostatic gel to provide an obstetric bacteriostatic gel which has safety and long-acting antibacterial efficiency and moisturizing properties. SUMMARY

[0006] In view of the shortcomings of the prior art, the first purpose of the present application is to provide a bacteriostatic gel for obstetrics, which has excellent long-acting antibacterial property and moisturizing property, and is safe and non-irritating.

[0007] The second purpose of the present application is to provide a preparation method of the bacteriostatic gel for obstetrics, which is simple in process and controllable in cost.

[0008] In order to achieve the above purpose, the technical scheme adopted by the present application is as follows:

[0009] A bacteriostatic gel for obstetrics comprises the following raw materials by weight: nuciferine derivative 0.3-0.5 parts, hydroxyethyl cellulose 0.5-1.5 parts, glycerol 0.5-1 part, propylene glycol 1.5-2 parts, carbomer 0.5-1.5 parts, ethanol 70-80 parts, and water 15-20 parts; the structure formula of the nuciferine derivative is as follows:

[0010]

[0011] Further, the preparation method of the nuciferine derivative comprises the following steps:

[0012] (1) under an inert gas atmosphere, dibenzyl diselenide and sodium borohydride are added into anhydrous N, N-dimethylformamide and stirred for 15-25 min, then nuciferine solution is added, and heating reaction is carried out; after the reaction is completed, the reaction liquid is purified to obtain compound 1; the structural formula of the compound 1 is as follows:

[0013]

[0014] (2) under an inert gas atmosphere at-10-0℃, the compound 1, 4-hydroxy-2-butanone, triphenyl phosphine, and diethyl azodicarboxylate are added into tetrahydrofuran, and stirred for 20-30 min, then the reaction liquid is raised to room temperature for reaction; after the reaction is completed, the reaction liquid is treated to obtain compound 2; the structural formula of the compound 2 is as follows:

[0015]

[0016] (3) 1-phenylbiguanide, compound 2, and concentrated hydrochloric acid are added into ethanol for heating reaction, and after the reaction is completed, the nuciferine derivative is obtained through treatment.

[0017] Further, the molar ratio of the dibenzyl diselenide, sodium borohydride, and nuciferine in step (1) is (0.7-0.9) : (7-9) : 1.

[0018] Further, the heating reaction temperature in step (1) is 130-150℃, and the time is 8-12 h.

[0019] Further, the molar ratio of the compound 1, 4-hydroxy-2-butanone, triphenyl phosphine, and diethyl azodicarboxylate in step (2) is 1: (1.1-1.5) : (1.1-1.5) : (1.3-1.5); and the reaction time is 16-24 h.

[0020] Further, the amount ratio of 1-phenylbiguanide, compound 2, and concentrated hydrochloric acid in step (3) is 1 mmol: (1-1.05) mmol: 0.08 mL; wherein the concentration of the concentrated hydrochloric acid is 12 mol / L.

[0021] Further, the heating reaction temperature in step (3) is 85-95℃, and the time is 24-36 h.

[0022] Further, the preparation method of the carbomer is: mixing acrylic monomer, 2-methacryloyloxyethyl phosphoryl choline, azobisisobutyronitrile, allyl pentaerythritol ether, emulsifier Hypermer-B246, ethyl acetate and n-hexane at 80-85 DEG C for 3-5 h, filtering, concentrating and drying after the reaction to obtain the carbomer.

[0023] Further, the mass ratio of the acrylic monomer, 2-methacryloyloxyethyl phosphoryl choline, azobisisobutyronitrile, allyl pentaerythritol ether, emulsifier Hypermer-B246, ethyl acetate and n-hexane is (90-95):(8-12):(0.4-0.6):(0.5-1.0):(0.5-0.8):(400-600):(400-600).

[0024] The preparation method of the antibacterial gel for obstetrics comprises the following steps:

[0025] (a) according to the weight parts of each raw material, dispersing the carbomer in water at 50-60 DEG C, and cooling to room temperature to obtain a carbomer liquid;

[0026] (b) adding glycerol, propylene glycol and hydroxyethyl cellulose into the carbomer liquid and stirring uniformly, then adding ethanol and norepinephrine derivative in sequence and stirring, and the solution can be gelled.

[0027] Compared with the prior art, the application has the following beneficial effects:

[0028] 1. The antibacterial gel for obstetrics provided by the application comprises norepinephrine derivative and carbomer and the like. The norepinephrine derivative is prepared from natural compound norepinephrine through a series of modifications such as acid catalysis hydrolysis, etherification and nucleophilic substitution. The norepinephrine derivative not only has the function of destroying cell wall and cell membrane of norepinephrine, but also has the effect of interfering metabolism and destroying biological membrane of triazine compounds. Meanwhile, the norepinephrine derivative contains multiple amino groups, so that the whole norepinephrine derivative is positively charged and has certain adsorption performance on bacterial protein shell. The above-mentioned multiple properties synergistically act to give the product excellent long-acting antibacterial effect. In addition, the carbomer is prepared from acrylic monomer and 2-methacryloyloxyethyl phosphoryl choline in the application. After adding 2-methacryloyloxyethyl phosphoryl choline in the carbomer, the substance forms a firm hydration layer with water molecules through the phosphoryl choline group on the side chain, and the hydration layer has stable film-forming performance due to the biocompatibility and hydrophilicity of the substance, so as to reduce the water loss of hand skin and keep the hand skin moist.

[0029] 2. The application also provides the preparation method of the above-mentioned bacteriostatic gel for obstetrics, which is simple in preparation process, low in material cost, and capable of neutralizing the excessive carboxylic acid in carbomer due to the amino group carried by the nuciferine derivative, so that no additional pH regulator needs to be added to neutralize the acidity of carbomer, and is suitable for large-scale preparation. BRIEF DESCRIPTION OF DRAWINGS

[0030] Figure 1 The synthesis route of the nuciferine derivative of the application. DETAILED DESCRIPTION

[0031] The application will be further described below in combination with the drawings and specific embodiments. It should be noted that the embodiments described below or the technical features thereof can be combined in any manner to form new embodiments without conflict. The specific conditions not mentioned in the embodiments are carried out according to the conventional conditions or the conditions recommended by the manufacturer. The reagents or instruments used, if not specifically mentioned, are conventional products obtained through commercial channels.

[0032] (I) Embodiments

[0033] Embodiment 1

[0034] Embodiment 1 provides a bacteriostatic gel for obstetrics, which comprises the following raw materials in parts by weight: nuciferine derivative 0.4 parts, hydroxyethyl cellulose 250M 1 part, glycerol 0.8 part, propylene glycol 1.8 part, carbomer 1 part, ethanol 75 parts, and water 18 parts.

[0035] The structural formula of the nuciferine derivative is as follows:

[0036]

[0037] The preparation process of the above-mentioned nuciferine derivative is as shown in Figure 1 The specific preparation process comprises the following steps:

[0038] (1) Under a nitrogen atmosphere, dibenzyl diselenide (1.36 g, 4 mmol) and sodium borohydride (1.51 g, 40 mmol) are added to 50 mL of anhydrous N,N-dimethylformamide, and then a nuciferine (1.48 g, 5 mmol) solution in anhydrous N,N-dimethylformamide (150 mL) is added. The reaction is carried out at 140°C for 10 h. After the reaction, the reaction solution is concentrated, and water is added thereto until the reaction solution is stable at room temperature without intense heat release. Then, the pH of the reaction solution is adjusted to 7 with a 5 wt% sulfuric acid solution, and the reaction solution is extracted with dichloromethane. The dichloromethane phase is dried and concentrated, and then purified by column chromatography (volume ratio of dichloromethane to methanol is 80:20) to obtain compound 1 with a yield of 74%;

[0039] The preparation process of compound 1 is as shown in 1H NMR (CDCI3, 400 MHz), δ: 7.77-7.15 (m, 4H, Ar H), 6.96 (s, 1H, Ar H), 4.27-4.22 (m, 3H), 3.82 (s, 3H), 3.35 (t, 2H), 3.08-2.65 (m, 6H), 2.28 (s, 3H), 2.10 (s, 3H). 18 H 19 H NMR (CDCI3, 400 MHz), δ: 7.77-7.15 (m, 4H, Ar H), 6.96 (s, 1H, Ar H), 4.27-4.22 (m, 3H), 3.82 (s, 3H), 3.35 (t, 2H), 3.08-2.65 (m, 6H), 2.28 (s, 3H), 2.10 (s, 3H).

[0040] (2) In 50 mL of tetrahydrofuran, compound 1 (2.81 g, 10 mmol), 4-hydroxy-2-butanone (1.06 g, 12 mmol) and triphenylphosphine (3.41 g, 13 mmol) were added and stirred, then diethyl azodicarboxylate (2.44, 14 mmol) was added and stirred at 0°C for 30 min, then the temperature was raised to room temperature and stirred for 20 h; the reaction solution was concentrated, 15 mL of n-hexane was added, stirred and filtered, then the filtrate was purified by column chromatography (volume ratio of ethyl acetate to n-heptane was 8:92) to obtain compound 2, yield 92%;

[0041] H NMR (CDCI3, 400 MHz), δ: 7.77-7.15 (m, 4H, Ar H), 6.96 (s, 1H, Ar H), 4.27-4.22 (m, 3H), 3.82 (s, 3H), 3.35 (t, 2H), 3.08-2.65 (m, 6H), 2.28 (s, 3H), 2.10 (s, 3H). 1 H NMR (CDCI3, 400 MHz), δ: 7.77-7.15 (m, 4H, Ar H), 6.96 (s, 1H, Ar H), 4.27-4.22 (m, 3H), 3.82 (s, 3H), 3.35 (t, 2H), 3.08-2.65 (m, 6H), 2.28 (s, 3H), 2.10 (s, 3H). 22 H 25 H NMR (CDCI3, 400 MHz), δ: 7.77-7.15 (m, 4H, Ar H), 6.96 (s, 1H, Ar H), 4.27-4.22 (m, 3H), 3.82 (s, 3H), 3.35 (t, 2H), 3.08-2.65 (m, 6H), 2.28 (s, 3H), 2.10 (s, 3H).

[0042] (3) In 200 mL of ethanol, 1-phenylbiguanide (2.11 g, 10 mmol), compound 2 (3.86 g, 10.25 mmol) and concentrated hydrochloric acid (0.8 mL, 12 mol / L) were added and reacted at 90°C for 30 h; after the reaction was completed, the reaction solution was concentrated and purified by column chromatography (volume ratio of chloroform, methanol and acetic acid was 80:15:5), the fraction obtained after purification was concentrated, then free with triethylamine, then concentrated to obtain the nuciferine derivative, yield 28%.

[0043] H NMR (CDCI3, 400 MHz), δ: 7.77-7.15 (m, 4H, Ar H), 6.96 (s, 1H, Ar H), 4.27-4.22 (m, 3H), 3.82 (s, 3H), 3.35 (t, 2H), 3.08-2.65 (m, 6H), 2.28 (s, 3H), 2.10 (s, 3H). 1 H NMR (CDCI3, 400 MHz), δ: 7.77-7.15 (m, 4H, Ar H), 6.96 (s, 1H, Ar H), 4.27-4.22 (m, 3H), 3.82 (s, 3H), 3.35 (t, 2H), 3.08-2.65 (m, 6H), 2.28 (s, 3H), 2.10 (s, 3H). 30 H 34N6O2, 400 MHz, DMSO), δ: 7.77-7.12 (m, 6H, Ar H), 6.96 (s, 1H, Ar H), 6.84 (s, 2H, NH2), 6.74-6.57 (m, 3H), 6.50 (s, 2H, NH2), 4.27 (t, 1H), 3.92 (t, 2H), 3.82 (s, 3H), 3.08-2.65 (m, 6H), 2.28 (s, 3H), 1.92 (t, 2H), 1.21 (s, 3H). ESI-MS (m / z): 511.35 [M+H] + .

[0044] The preparation process of the carbomer is as follows:

[0045] At 82℃, 93 parts of acrylic monomer, 10 parts of 2-methyl acryloyl ethyl phosphocholine, 0.5 parts of azobisdimethylvaleronitrile, 0.8 parts of allyl pentaerythritol ether, and 0.6 parts of emulsifier Hypermer-B246 are added into 500 parts of ethyl acetate and 500 parts of n-hexane, and after the feeding is completed, the reaction is carried out for 4 hours; the reaction solution is filtered while hot, the filtrate is concentrated, and after drying in an oven at 65℃ for 10 hours, the carbomer is obtained.

[0046] Example 1 also provides a preparation method of the above antibacterial gel for obstetrics, and the specific preparation process is as follows:

[0047] S1. The raw materials are weighed according to the above weight parts, water is heated to 55℃, then the carbomer is uniformly dispersed in the water surface and left to cool to room temperature to obtain a carbomer solution;

[0048] S2. The glycerol, propylene glycol, and hydroxyethyl cellulose 250M are added into the carbomer solution and stirred uniformly, then ethanol is added, and the nuciferine derivative is added during the stirring process, and the solution is obtained in the form of a gel.

[0049] Example 2

[0050] Example 2 provides an antibacterial gel for obstetrics, which comprises the following raw materials in weight parts: nuciferine derivative 0.3 parts, hydroxyethyl cellulose 250M 0.5 parts, glycerol 0.5 parts, propylene glycol 1.5 parts, carbomer 0.5 parts, ethanol 70 parts, and water 15 parts; the structural formula of the nuciferine derivative is the same as that of Example 1.

[0051] The preparation method of the above nuciferine derivative comprises the following steps:

[0052] (1) Under nitrogen atmosphere, dibenzyl diselenide (1.19 g, 3.5 mmol) and sodium borohydride (1.32 g, 35 mmol) were added into 50 mL of anhydrous N,N-dimethylformamide, then a solution of the honokiol (1.48 g, 5 mmol) in anhydrous N,N-dimethylformamide (150 mL) was added, and the reaction was carried out at 130 °C for 8 h; after the reaction, the reaction solution was concentrated, and water was added thereto until the reaction solution was stable at room temperature without intense heat release; then 5 wt% sulfuric acid solution was used to adjust the pH of the reaction solution to 6.8, and the reaction solution was extracted with dichloromethane, and the dichloromethane phase was dried and purified by column chromatography (volume ratio of dichloromethane to methanol was 80:20) to obtain the compound 1 with a yield of 73%; the H NMR result was consistent with that of Example 1. 1 The H NMR result was consistent with that of Example 1.

[0053] (2) Under nitrogen atmosphere at 0 °C, compound 1 (2.81 g, 10 mmol), 4-hydroxy-2-butanone (0.97, 11 mmol) and triphenylphosphine (2.88 g, 11 mmol) were added into 50 mL of tetrahydrofuran, and then diazodicarbonic acid diethyl ester (2.26, 13 mmol) was added after stirring to be uniform, and stirring was carried out at 0 °C for 20 min, and the reaction was carried out at room temperature for 16 h after being raised to room temperature; the reaction solution was concentrated, 15 mL of n-hexane was added thereto, and stirring was carried out after filtration, and the filtrate was purified by column chromatography (volume ratio of ethyl acetate to n-heptane was 8:92) to obtain compound 2 with a yield of 91%; the H NMR result of compound 2 was consistent with that of Example 1. 1 The H NMR result was consistent with that of Example 1.

[0054] (3) 1-phenylbiguanide (2.11 g, 10 mmol), compound 2 (3.76 g, 10 mmol) and concentrated hydrochloric acid (0.8 mL, 12 mol / L) were added into 200 mL of ethanol, and the reaction was carried out at 85 °C for 24 h; after the reaction, the reaction solution was concentrated and purified by column chromatography (volume ratio of chloroform to methanol to acetic acid was 80:15:5), and the fraction obtained after purification was concentrated, freed with triethylamine, and then concentrated to obtain the honokiol derivative with a yield of 27%; the H NMR and ESI-MS (m / z) results of the honokiol derivative were consistent with those of Example 1. 1 The H NMR and ESI-MS (m / z) results were consistent with those of Example 1.

[0055] The preparation process of the above carbomer is as follows:

[0056] At 80 °C, 90 parts of acrylic monomer, 8 parts of 2-methacryloyloxyethyl phosphocholine, 0.4 parts of azobis isobutyronitrile, 0.5 parts of allyl pentaerythritol ether and 0.5 parts of emulsifier Hypermer-B246 were added into 400 parts of ethyl acetate and 400 parts of n-hexane, and after the addition was completed, the reaction was carried out for 3 h; the reaction solution was filtered hot, the filtrate was concentrated, and after being dried in an oven at 65 °C for 10 h, the carbomer was obtained.

[0057] Example 2 also provides the preparation method of the above antibacterial gel for obstetrics, and the specific preparation process is as follows:

[0058] S1. According to the above weight parts, each raw material is weighed, water is heated to 50℃, then carbomer is uniformly dispersed in the water surface and left to stand, and cooled to room temperature to obtain a carbomer liquid;

[0059] S2. Glycerol, propylene glycol and hydroxyethyl cellulose 250M are added to the carbomer liquid and stirred uniformly, then ethanol is added, and during the stirring process, the nuciferine derivative is added, and the solution is obtained in the form of a gel to obtain the antibacterial gel for obstetrics.

[0060] Example 3

[0061] Example 3 provides an antibacterial gel for obstetrics, which comprises the following raw materials in parts by weight: nuciferine derivative 0.3 parts, hydroxyethyl cellulose 250M 1.5 parts, glycerol 1 part, propylene glycol 2 parts, carbomer 1.5 parts, ethanol 80 parts, and water 20 parts; the structural formula of the nuciferine derivative is consistent with that of Example 1.

[0062] The preparation method of the above nuciferine derivative comprises the following steps:

[0063] (1) Under a nitrogen atmosphere, dibenzyl diselenide (1.53 g, 4.5 mmol) and sodium borohydride (1.70 g, 45 mmol) are added to 50 mL of anhydrous N,N-dimethylformamide, then a nuciferine (1.48 g, 5 mmol) solution in anhydrous N,N-dimethylformamide (150 mL) is added, and the reaction is carried out at 150℃ for 12 h; after the reaction, the reaction solution is concentrated, and water is added until the reaction solution is stable at room temperature without intense heat release; then the reaction solution is adjusted to pH = 7.2 with a 5wt% sulfuric acid solution, extracted with dichloromethane, and the dichloromethane phase is dried and concentrated, then purified by column chromatography (volume ratio of dichloromethane to methanol is 80:20) to obtain compound 1 with a yield of 70%; the H NMR result of compound 1 is consistent with that of Example 1. 1 H NMR result is consistent with that of Example 1.

[0064] (2) Under a nitrogen atmosphere at 0℃, compound 1 (2.81 g, 10 mmol), 4-hydroxy-2-butanone (1.32 g, 15 mmol) and triphenylphosphine (3.93 g, 15 mmol) are added to 50 mL of tetrahydrofuran, stirred uniformly, then diethyl azodicarboxylate (2.61, 15 mmol) is added and stirred, after stirring for 30 min at 0℃, the reaction is carried out at room temperature for 24 h; the reaction solution is concentrated, 15 mL of n-hexane is added, stirred, then filtered, and the filtrate is purified by column chromatography (volume ratio of ethyl acetate to n-heptane is 8:92) to obtain compound 2 with a yield of 91%; the H NMR result of compound 2 is consistent with that of Example 1. 1The H NMR result is consistent with that of Example 1.

[0065] (3) 1-phenylbiguanide (2.11 g, 10 mmol), compound 2 (3.95 g, 10.5 mmol), concentrated hydrochloric acid (0.8 mL, 12 mol / L) were added into 200 mL of ethanol and reacted at 95°C for 36 h. After the reaction was completed, the reaction solution was concentrated and purified by column chromatography (the volume ratio of chloroform, methanol and acetic acid was 80:15:5). The purified fraction was concentrated, freed with triethylamine, and then concentrated to obtain the nuciferine derivative, with a yield of 26%; the H NMR and ESI-MS (m / z) results of the nuciferine derivative were consistent with those of Example 1. 1 The H NMR and ESI-MS (m / z) results of the nuciferine derivative were consistent with those of Example 1.

[0066] The preparation process of the above carbomer is as follows:

[0067] At 85°C, 95 parts of acrylic monomer, 12 parts of 2-methacryloyloxyethyl phosphorylcholine, 0.6 parts of azobisisobutyronitrile, 1.0 part of allyl pentaerythritol ether, and 0.8 part of emulsifier Hypermer-B246 were added into 600 parts of ethyl acetate and 600 parts of n-hexane. After the addition was completed, the reaction was carried out for 5 h. The reaction solution was filtered while hot, and the filtrate was concentrated and dried in an oven at 65°C for 10 h to obtain the carbomer.

[0068] Example 3 also provides a preparation method of the above antibacterial gel for obstetrics, and the specific preparation process is as follows:

[0069] S1. The raw materials were weighed according to the above weight parts, water was heated to 60°C, then the carbomer was uniformly dispersed in the water surface and left to stand, and cooled to room temperature to obtain a carbomer solution;

[0070] S2. The glycerol, propylene glycol, and hydroxyethyl cellulose 250M were added to the carbomer solution and stirred uniformly, then ethanol was added, and the nuciferine derivative was added during stirring. When the solution became a gel state, the antibacterial gel for obstetrics was obtained.

[0071] (II) Comparative Example

[0072] Comparative Example 1

[0073] Comparative Example 1 is basically the same as Example 1, except that the nuciferine derivative is replaced by nuciferine.

[0074] Comparative Example 2

[0075] Comparative Example 2 is basically the same as Example 1, except that the carbomer is replaced by carbomer 947P.

[0076] (III) Experimental Example

[0077] Experimental Example 1: Bacteriostatic experiment

[0078] 1. Bacteriostatic stability test: According to the method of GB 15979-2002 "Hygienic Standard for Disposable Hygienic Products" Appendix C, the products obtained in Examples 1-3 and Comparative Examples 1-2 were tested for antibacterial effect against Staphylococcus aureus (ATCC 6538), Escherichia coli (8099) and Candida albicans (ATCC 10231); the antibacterial effect of each group of products was detected again after being placed at 54°C and 75% relative humidity for 14 days, and the above test results are shown in Table 1.

[0079] Table 1

[0080]

[0081] From the test data in Table 1, it can be seen that the gel products of Examples 1-3 still have good bacteriostatic rate after being placed at room temperature for 14 days.

[0082] 2. Long-term bacteriostatic test: Staphylococcus aureus (ATCC 6538) was selected as the test strain, and the concentration of the Staphylococcus aureus suspension was adjusted to 1x10 4 CFU / mL with PBS, 5mL of the gel prepared in Examples 1-3 and Comparative Examples 1-2 was taken, sterilized and added to a sterile test tube, 100μL of the Staphylococcus aureus suspension was added to the sterile test tube, mixed quickly, and after 2min, 0.5mL of the liquid in the above sterile test tube was taken with a sterile pipette and added to 4.5mL of sterilized PBS in a test tube, mixed evenly, and after 10min, 200μL of the sample liquid was placed in a sterile plate, two sterile plates were inoculated with each sample liquid, 15mL of nutrient agar medium at 45°C was used for pouring, the plate was rotated to make it fully and evenly, after the agar was solidified, the plate was turned over, and at 1, 4 and 8h of culture at 37°C, the number of viable bacteria colonies was counted; the gel was replaced with PBS and the same treatment was performed as a blank control group.

[0083] The bacteriostatic rate was calculated, bacteriostatic rate = (average number of colonies in the blank control group - average number of colonies in the experimental group) / average number of colonies in the blank control group x 100%; each group was tested in triplicate, the bacteriostatic rate values were averaged, and the results are shown in Table 2.

[0084] Table 2

[0085]

[0086] Result analysis: As shown in Table 2, the gel products prepared in Examples 1-3 of the present application have excellent long-acting antibacterial properties. In Comparative Example 1, the nuciferine derivative is replaced by nuciferine, and the antibacterial effect and long-acting antibacterial properties are decreased. The reason is that the nuciferine derivative of the present application not only retains the function of nuciferine to destroy cell walls and cell membranes, but also has the effect of triazine compounds to interfere with bacterial metabolism and destroy biofilms. In addition, the nuciferine derivative contains multiple amino groups, which are positively charged as a whole, and can adsorb bacterial protein shells. The synergistic effect of the above-mentioned properties makes the nuciferine derivative have excellent antibacterial effect and excellent long-acting antibacterial effect.

[0087] Experiment 2: Moisturizing property test

[0088] The moisturizing effect of the antibacterial gels of Examples 1-3 and Comparative Examples 1-2 was determined as follows:

[0089] Randomly selected 50 volunteers aged 18-35 years old as test personnel, using each group of gel hand washing 5 min, select the back of the hand 3x3cm test area, using skin moisture test probe to determine the water content of the test site, take 5 times measurement average, after 30 min, again measurement moisture content. Calculate the water loss rate = (initial skin surface moisture content-later skin surface moisture content) / initial skin surface moisture content * 100%, the test results are shown in Table 3.

[0090] Table 3

[0091] Group Rate of water loss Example 1 9％ Example 2 12％ Example 3 14％ Comparative Example 1 15％ Comparative Example 2 23％

[0092] Result analysis: As shown in Table 3, the gel products prepared in Examples 1-3 of the present application have good moisturizing properties.

[0093] Compared with Example 1, Comparative Example 2 replaces carbomer with carbomer 947P, and the water loss increases and the moisturizing property becomes poor, which may be because the addition of 2-methacryloyloxyethyl phosphorylcholine in the carbomer of the present application forms a firm hydration layer with water molecules through the phosphorylcholine group on its side chain, and by virtue of its biocompatibility and hydrophilicity, the hydration layer has stable film-forming properties, thereby reducing the water loss of the skin of the hand and keeping the skin of the hand moist.

[0094] Experiment 3: Irritation test

[0095] Test method: The human skin patch test was carried out according to the "2022 Cosmetics Safety Technical Specifications", and the specific steps were as follows: the gels prepared in Examples 1-3 and Comparative Examples 1-2 were placed in the patch tester chamber, and then tightly attached to the inner arm skin of the test subjects (25-40 years old). After 24 hours of attachment, the patch tester was removed, and the skin condition was observed at 30 min, 24 h, and 48 h. If no adverse reactions (such as redness, itching, tingling, rash, etc.) occurred on the skin of all test subjects, the test result was determined to be negative, and the experimental results are shown in Table 4.

[0096] Table 4

[0097] Group 30 min 24h 48h Example 1 Negative, 10 people Negative, 10 people Negative, 10 people Example 2 Negative, 10 people Negative, 10 people Negative, 10 people Example 3 Negative, 10 people Negative, 10 people Negative, 10 people Comparative Example 1 Negative, 10 people Negative, 10 people Negative, 10 people Comparative Example 2 Negative, 10 people Negative, 10 people Negative, 10 people

[0098] Result analysis: As can be seen from Table 4, the gels prepared in Examples 1-3 of the present application have no irritation.

[0099] In summary, the obstetric bacteriostatic gel prepared by the present application not only has excellent long-acting bacteriostatic effect, but also has excellent moisturizing performance, and is mild and non-irritating to use.

[0100] The above embodiments are only preferred embodiments of the present application, and cannot be used to limit the scope of protection of the present application. Any non-substantial changes and substitutions made by those skilled in the art on the basis of the present application are within the scope of protection of the present application.

Claims

1. An antibacterial gel for use in obstetrics, characterized in that, The raw materials include the following parts by weight: 0.3-0.5 parts of lotus leaf alkaloid derivative, 0.5-1.5 parts of hydroxyethyl cellulose, 0.5-1 part of glycerol, 1.5-2 parts of propylene glycol, 0.5-1.5 parts of carbomer, 70-80 parts of ethanol, and 15-20 parts of water; the structural formula of the lotus leaf alkaloid derivative is as follows:

2. The antibacterial gel for obstetric use according to claim 1, characterized in that, The preparation method of the lotus leaf alkaloid derivative includes the following steps: (1) Under an inert gas atmosphere, dibenzyl diselenide and sodium borohydride were added to anhydrous N,N-dimethylformamide and stirred for 15–25 min, followed by the addition of lotus leaf alkali solution and heating. After the reaction was completed, the reaction solution was purified to obtain compound 1. The structural formula of compound 1 is: (2) Under an inert gas atmosphere at -10 to 0°C, compound 1, 4-hydroxy-2-butanone, triphenylphosphine, and diethyl azodicarbonate were added to tetrahydrofuran. After stirring for 20 to 30 minutes, the reaction solution was brought to room temperature for further reaction. After the reaction was completed, the reaction solution was post-treated to obtain compound 2. The structural formula of compound 2 is: (3) Add 1-phenylbiguanide, compound 2 and concentrated hydrochloric acid to ethanol and heat to react. After the reaction is completed, the lotus leaf alkaloid derivative is obtained by treatment.

3. The antibacterial gel for obstetric use according to claim 2, characterized in that, The molar ratio of dibenzyl diselenide, sodium borohydride, and lotus leaf alkaloid in step (1) is (0.7-0.9):(7-9):

1.

4. The antibacterial gel for obstetric use according to claim 2, characterized in that, The heating reaction in step (1) is carried out at a temperature of 130-150°C for 8-12 hours.

5. The antibacterial gel for obstetric use according to claim 2, characterized in that, In step (2), the molar ratio of compound 1, 4-hydroxy-2-butanone, triphenylphosphine, and diethyl azodicarbonate is 1:(1.1-1.5):(1.1-1.5):(1.3-1.5); and the reaction time is 16-24 h.

6. The antibacterial gel for obstetric use according to claim 2, characterized in that, The ratio of 1-phenylbiguanide, compound 2 and concentrated hydrochloric acid used in step (3) is: 1 mmol: (1-1.05) mmol: 0.08 mL; wherein the concentration of concentrated hydrochloric acid is 12 mol / L.

7. The antibacterial gel for obstetric use according to claim 2, characterized in that, The heating reaction in step (3) is carried out at a temperature of 85–95°C for 24–36 hours.

8. The antibacterial gel for obstetric use according to claim 1, characterized in that, The method for preparing carbomer is as follows: at 80-85°C, acrylic acid monomer, 2-methacryloyloxyethyl phosphocholine, azobisisobutyronitrile, allyl pentaerythritol ether, emulsifier Hypermer-B246, ethyl acetate and n-hexane are mixed and reacted for 3-5 hours. After the reaction is completed, the mixture is filtered, concentrated and dried to obtain carbomer.

9. The antibacterial gel for obstetric use according to claim 8, characterized in that, The mass ratio of the acrylic monomer, 2-methacryloyloxyethyl phosphocholine, azobisisobutyronitrile, allyl pentaerythritol ether, emulsifier Hypermer-B246, ethyl acetate and n-hexane is (90-95):(8-12):(0.4-0.6):(0.5-1.0):(0.5-0.8):(400-600):(400-600).

10. The method for preparing the antibacterial gel for obstetric use according to any one of claims 1 to 9, characterized in that, Includes the following steps: (a) Weigh each raw material according to the stated weight proportions, disperse carbomer in water at 50-60°C, and allow it to stand and cool to room temperature to obtain a carbomer solution; (b) Add glycerol, propylene glycol and hydroxyethyl cellulose to carbomer solution and stir until homogeneous. Then add ethanol and lotus leaf alkaloid derivative in sequence and stir until the solution becomes gel-like.

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