Medical sterilizing, antagonistic-free and fat-retaining disinfectant hand sanitizer and preparation method thereof

Abstract

The invention discloses a medical sterilizing, antagonistic-free and fat-retaining disinfectant hand sanitizer and a preparation method thereof, and relates to the technical field of hand sanitizers. CHG is used as a main bactericide, sophorolipid, CAB and alpha-glucan oligosaccharide are used as a composite surfactant, and the antagonistic effect of sterilization effect reduction caused by CHG wrapping after a conventional surfactant forms micelles is eliminated; meanwhile, phytosterol ester, glycosylglycerol and madecassoside are introduced as skin fat-retaining components, so that the sebum retention rate is greater than or equal to 95%, meanwhile, the antibacterial rate on staphylococcus aureus is still kept 100%, and the hand washing liquid is suitable for high-frequency hand washing of medical staff.

Description

Technical Field

[0001] This invention relates to the field of hand sanitizer technology, specifically to a bactericidal, non-antagonistic, oil-retaining medical disinfectant hand sanitizer and its preparation method. Background Technology

[0002] Medical hand sanitizers are essential infection control products in healthcare settings. Currently, commercially available medical hand sanitizers typically contain antibacterial agents and surfactants. Chlorhexidine gluconate (CHG) is a commonly used broad-spectrum antibacterial agent with good bactericidal effects against both Gram-positive and Gram-negative bacteria.

[0003] However, the existing technology has the following technical problems: Traditional hand sanitizer formulations often use cocamidopropyl betaine (CAB) as a surfactant. However, studies have found a significant antagonistic effect when CAB is combined with CHG. Zeta potential analysis and scanning electron microscopy revealed that the antagonistic mechanism involves CAB forming micelles that encapsulate CHG molecules, preventing them from contacting bacterial cell membranes and thus reducing antibacterial efficacy. Furthermore, existing surfactants (such as CAB and AEO-9) lack selectivity, dissolving skin lipids while removing dirt, leading to excessive sebum removal. Experiments show that after five consecutive uses of traditional hand sanitizer formulations, the sebum content on the hands decreases by more than 40%, and long-term use can lead to dry skin and a damaged skin barrier.

[0004] To address the aforementioned issues, existing technologies have attempted some improvements. For example, Chinese invention patent CN112351684A discloses a disinfectant composition, but it mainly involves a combination of potassium persulfate complex salt and a biosurfactant, without addressing the combination of CHG and sophorolipids. Chinese invention patent CN118556692A discloses a synergistic bacterial inhibitory composition based on sophorolipids, but it uses a quaternary ammonium salt surfactant instead of CHG. US invention patent US5776430A discloses an antibacterial cleaner containing CHG, but its formulation contains a high concentration of alcohol (50-60%), making it unsuitable for use as a hand sanitizer.

[0005] Therefore, there is a need for a high-frequency medical hand sanitizer that has a stable and efficient bactericidal function and protects the skin's lipids while removing stains. Summary of the Invention

[0006] The technical problem to be solved by this invention is to overcome the shortcomings of the prior art and provide a bactericidal and non-antagonistic lipid-retaining medical hand sanitizer and its preparation method. CHG is used as the main bactericide, and sophorolipid, CAB and α-glucan oligosaccharide are used as composite surfactants. This eliminates the antagonistic effect of conventional surfactants forming micelles and encapsulating CHG, which leads to a decrease in bactericidal effect. At the same time, phytosterol esters, glyceryl glucoside and asiaticoside are introduced as skin lipid-retaining components, so that the sebum retention rate is ≥95% and the antibacterial rate against Staphylococcus aureus is still 100%, which is suitable for medical staff to wash their hands frequently.

[0007] The technical solution of this invention is as follows: On the one hand, the present invention provides a bactericidal, non-antagonistic, and lipid-retaining medical hand sanitizer, which is made of the following components in weight percentage: 0.2-0.5% chlorhexidine gluconate, 0.5-5% sophorolipid, 0.5-5% cocamidopropyl betaine, 0.01-0.05% α-glucan oligosaccharide, 1-4% isopropanol, 1-2% glycerol, 0.3-1% phytosterol ester, 0.1-0.5% glyceryl glucoside, 0.05-0.2% asiaticoside, and the balance being deionized water.

[0008] Preferably, the phytosterol ester is one or both of β-sitosterol oleate and campesterol palmitate.

[0009] Preferably, the mass ratio of chlorhexidine gluconate, sophorolipid and cocamidopropyl betaine is 1:(5-10):(5-10).

[0010] Preferably, it is made from the following components in the indicated weight percentages: 0.5% chlorhexidine gluconate, 5% sophorolipid, 5% cocamidopropyl betaine, 0.05% α-glucan oligosaccharide, 4% isopropanol, 2% glycerol, 1% phytosterol ester, 0.5% glycerol glucoside, 0.2% asiaticoside, with the balance being deionized water.

[0011] On the other hand, the present invention provides a method for preparing the above-mentioned antibacterial, non-antagonistic, and oil-retaining medical hand sanitizer, comprising the following steps: S1 Dissolves chlorhexidine gluconate in a portion of deionized water, mixes thoroughly, and obtains solution A; S2 is prepared by mixing sophorolipid, cocamidopropyl betaine, α-glucan oligosaccharide and the remaining deionized water, stirring and letting it stand to defoam, and then using it as solution B. S3 is a mixture of isopropanol, glycerol, phytosterol esters, glyceryl glucoside, and asiaticoside, which is used as solution C. Under stirring conditions S4, solution B is added to solution A, and stirring continues after the addition is complete. The pH is adjusted to 5-6 using a pH adjuster to obtain a mixed solution. Solution C is then added to the mixed solution and mixed thoroughly. The pH is then adjusted to 5-6.5 using a pH adjuster to obtain a bactericidal, non-antagonistic, and lipid-retaining medical hand sanitizer. Adjusting the pH in stages avoids sudden pH changes that could lead to component aggregation and improves product stability.

[0012] Compared with the prior art, the present invention has the following advantages: 1. This invention reveals for the first time the antagonistic mechanism between CAB and CHG, and innovatively uses sophorolipids, CAB, and α-glucan oligosaccharides as a composite surfactant. Experiments show that when sophorolipids, CAB, and α-glucan oligosaccharides are combined as a composite surfactant, the branched structure of the α-glucan oligosaccharides can dynamically embed itself into the intermolecule gaps of CAB, disrupting the thermodynamic stability of micelle formation and maintaining a dynamic equilibrium of "dispersed state - weakly aggregated state" in the system. Simultaneously, sophorolipids, as a biosurfactant, possess stronger interfacial activity and steric hindrance effects due to its molecular structure (disaccharide head and long-chain hydroxy fatty acid tail). It can form mixed micelles or compete for adsorption sites with CAB molecules in solution, interfering with and disrupting CAB's ability to form dense, orderly micelle structures, thereby completely blocking the encapsulation pathway of CHG molecules by CAB and increasing the antibacterial rate to 100%. Moreover, sophorolipids are a "glycolipid" hybrid molecule with a disaccharide head and a hydroxy oleic acid tail. The hydroxyl-rich head can form directional hydrogen bonds with hydrophobic pollutants at the oil-water interface, and the long tail prevents the intercalation with squalene and cholesterol esters in the skin. Therefore, it can form a stable complex with oils, proteins and other substances in dirt, while having a low affinity for the skin's own lipid components, which can prevent the washing process from removing too much sebum.

[0013] 2. This invention introduces phytosterol esters, glyceryl glucoside, and asiaticoside as skin-protecting components, further improving sebum retention. Among them, phytosterol esters have a "cyclopentane polyhydrophenanthrene backbone + fatty acid side chain", which is highly similar to the spatial conformation of cholesterol, cholesterol esters, and wax esters in human sebum, resulting in high interfacial compatibility and effectively maintaining sebum thickness during frequent hand washing. Glyceryl glucoside and asiaticoside further promote the self-repair process of surface sebum and reduce irritation to the hands. Attached Figure Description

[0014] Figure 1 This is a test chart showing the antibacterial properties of 0.2wt.% CHG combined with different medical hand sanitizer ingredients against Staphylococcus aureus and Escherichia coli in this invention.

[0015] Figure 2 This is a graph showing the antibacterial performance test of 0.2 wt.% CHG combined with different concentrations of CAB against Staphylococcus aureus in this invention.

[0016] Figure 3 This is a diagram showing the zeta grain size of the 3.5 wt.% CAB sample aqueous solution in this invention.

[0017] Figure 4 This is a zeta grain size diagram of the aqueous sample of 3.5% CAB + 0.2wt.% CHG in this invention.

[0018] Figure 5 These are SEM images of the 3.5wt.% sophorolipid + 3.5wt.% CAB + 0.2wt.% CHG sample and the 3.5wt.% CAB + 0.2wt.% CHG sample in this invention. Figures a and c correspond to the 3.5wt.% sophorolipid + 3.5wt.% CAB + 0.2wt.% CHG sample, and figures b and d correspond to the 3.5wt.% CAB + 0.2wt.% CHG sample. Detailed Implementation

[0019] To enable those skilled in the art to better understand the technical solutions of this invention, the technical solutions of this invention will be clearly and completely described below in conjunction with the embodiments of this invention.

[0020] Experiment on the antagonistic mechanism of CAB and CHG: (1) Experimental materials: Strains: Staphylococcus aureus (ATCC6538), Escherichia coli (ATCC25922, CMCC44102); Reagents: CHG (Panjin Jiaheshengshi Pharmaceutical Technology Co., Ltd., content 20%); Alkyl glycoside (APG, Shanghai Fakai Chemical Co., Ltd., content 50%); Fatty alcohol polyoxyethylene ether (AEO-9, Wanhua Chemical Group Co., Ltd., content ≥99%); Cocamidopropyl betaine (CAB, Shanghai Jianghong Biotechnology Co., Ltd., content 35%); Glycerin (INTEGRATEDFORTUNE, content ≥99.9%); Sorbitol (Shouguang Huali Litangol Co., Ltd., solid content ≥69%); Urea (Tianjin Kemio Chemical Reagent Co., Ltd., content ≥99%); Phenoxyethanol (Wuhan Xindadi Environmental Protection Materials Co., Ltd., content ≥99.5%).

[0021] (2) Experimental methods As shown in Table 1, prepare a mixed aqueous solution of 0.2 wt.% CHG with different raw materials in the hand sanitizer, and conduct an antibacterial test according to Appendix E of GB15979-2024 "Hygienic Standard for Disposable Sanitary Products", with an action time of 2 min and repeated 3 times for each group.

[0022] Table 1. Compound formulations of 0.2wt.% CHG with different ingredients in hand sanitizer

[0023] Medical hand sanitizers contain CHG and CAB, as well as other ingredients such as glycerin, APG, and AEO-9. To investigate the reason for CHG antagonism, 0.2 wt.% CHG was used alone and compounded with different ingredients to test its antibacterial properties against Staphylococcus aureus and Escherichia coli. The experimental results are as follows: Figure 1 As shown, when CHG is combined with other components, it has no effect on its antibacterial activity; however, when combined with CAB, the antibacterial rate of Staphylococcus aureus drops significantly to below 80%, while the antibacterial rate of Escherichia coli remains at 100%. This indicates that the antagonistic effect of CAB on CHG is species-selective. This may be because the cell wall surface of Staphylococcus aureus has more negatively charged sites, resulting in stronger electrostatic attraction between it and the positively charged CAB micelles or CAB-CHG complex, promoting the adsorption and encapsulation of micelles on the cell surface, thereby hindering the bactericidal effect of CHG. In contrast, the lipopolysaccharide layer on the surface of Escherichia coli may produce different steric hindrance or charge distribution, making it difficult for CAB micelles to approach and encapsulate CHG molecules, thus the antibacterial rate is not affected.

[0024] To further investigate the effect of CAB concentration, CHG concentration was fixed at 0.2 wt.%, and mixed with different concentrations of CAB (as shown in Table 2) to prepare mixed aqueous solutions. Antibacterial tests were conducted according to Appendix E of GB 15979-2024 "Hygienic Standard for Disposable Sanitary Products". The contact time was 2 min, and each group was repeated 3 times to test the antibacterial performance against Staphylococcus aureus.

[0025] Table 2. 0.2wt.% CHG and CAB compound formulation

[0026] Test results are as follows Figure 2 As shown, when CHG is combined with CAB, the effect of CAB on CHG gradually increases with the increase of CAB concentration. When the CAB concentration is >1.7wt.%, the antibacterial rate of 0.2wt.% CHG against Staphylococcus aureus decreases significantly.

[0027] Zeta potential test: Aqueous solutions of 3.5 wt.% CAB and 3.5% CAB + 0.2 wt.% CHG were prepared and tested using a Zeta potential analyzer. The results are as follows: Figure 3-4 As shown.

[0028] Figure 3In the 3.5 wt.% CAB sample, the main peak position was 5.615 nm, the peak concentration was 29.63%, the particles were concentrated in a small size range of 4.187-10.100 nm, and there was a significant secondary peak of 5.73% at 4.187 nm and a strong peak of 20.05% at 4.849 nm. There was no distribution in the 200-600 nm region, and ultra-large particles >4000 nm had a trace distribution of 0.0085%.

[0029] Figure 4 In the sample containing 3.5 wt.% CAB and 0.2 wt.% CHG, the main peak position shifted to 7.531 nm (an increase of 34%), the peak concentration increased to 34.12%, and the main peak shifted to a larger size range of 5.615-11.696 nm; the distribution at 4.187 nm and 4.849 nm completely disappeared, and the signal in the small size region <5 nm disappeared completely; the distribution continued to appear in the 200-600 nm range (such as 220.19 nm, 255.00 nm, 341.99 nm, etc.), and the distribution of ultra-large particles >4000 nm disappeared.

[0030] In summary, the addition of CHG resulted in the formation of larger CAB-CHG composite particles within the system. Small-sized CAB particles participated in encapsulating CHG, forming secondary aggregates. Furthermore, the encapsulation of CHG by CAB suppressed disordered aggregation, leading to a more concentrated distribution, consistent with the single-layer / multi-layer encapsulation model. The change in particle size distribution is a typical characteristic of CAB encapsulation of CHG, consistent with the colloidal encapsulation mechanism.

[0031] Morphological characteristics: Aqueous solutions of 3.5 wt.% sophorolipid + 3.5 wt.% CAB + 0.2 wt.% CHG and 3.5 wt.% CAB + 0.2 wt.% CHG were prepared, respectively. After freeze-drying, the freeze-dried samples were directly adhered to conductive adhesive, and their morphology was observed using a ZEISS Gemini SEM360 scanning electron microscope. The results are as follows: Figure 5 As shown.

[0032] Microstructure of the 3.5wt.% CAB + 0.2wt.% CHG sample: (e.g.) Figure 5 As shown in b and 5d, a more fused, relatively uniform, and larger overall structure appears. Combined with the encapsulation mechanism mentioned earlier, this is because CHG is encapsulated by CAB. The originally free small-sized CAB particles adsorb CHG and aggregate into composite particles. The corresponding result is that the main peak of the particle size distribution shifts to 7.531 nm and the small-size peak disappears, which directly presents microscopic evidence of the formation of composite particles by CAB encapsulating CHG.

[0033] Microstructure of sample containing 3.5 wt.% sophorolipid + 3.5 wt.% CAB + 0.2 wt.% CHG: (See image below) Figure 5As shown in a and 5c, the surface exhibits a relatively regular and dispersed granular structure, with small particle size and relatively uniform distribution, indicating that the composite particles have changed from an encapsulated state to a dispersed state.

[0034] The above experiments confirm that CAB forms micelles that encapsulate CHG molecules, preventing them from contacting bacterial cell membranes (especially affecting Staphylococcus aureus), thereby affecting antibacterial properties.

[0035] Examples 1-4 The formulations of the bactericidal, non-antagonistic, and lipid-retaining medical hand sanitizers in Examples 1-4 (excluding deionized water) are shown in Table 3. In Examples 1 and 4, the phytosterol ester is β-sitosterol oleate; in Example 2, the phytosterol ester is campesterol palmitate; and in Example 3, the phytosterol ester is a 1:1 mass ratio of β-sitosterol oleate and campesterol palmitate. Table 3. Formulations of antibacterial, non-antagonistic, and lipid-preserving medical hand sanitizers from Examples 1-4

[0036] The preparation methods of the bactericidal, non-antagonistic, and lipid-preserving medical hand sanitizers in Examples 1-4 include the following steps: S1 Dissolves chlorhexidine gluconate in half of the deionized water under stirring, and mixes well to obtain solution A; S2 is prepared by mixing sophorolipid, cocamidopropyl betaine, α-glucan oligosaccharide and the remaining deionized water, stirring at 30°C for 25 minutes, and allowing it to stand to defoam before using it as solution B. S3 is a mixture of isopropanol, glycerol, phytosterol esters, glyceryl glucoside, and asiaticoside, which is used as solution C. Under stirring conditions S4, solution B is added to solution A, and stirring is continued for 10 minutes after the addition is complete. The pH is adjusted to 5 with a pH adjuster to obtain a mixed solution. Solution C is added to the mixed solution and mixed evenly. Stirring is continued for 20 minutes, and the pH is adjusted to 6 with a pH adjuster to obtain a bactericidal, non-antagonistic, and lipid-preserving medical hand sanitizer.

[0037] Comparative Examples 1-7 The formulations of the medical disinfectant hand sanitizers (excluding deionized water) in Comparative Examples 1-7 are shown in Table 4. In Comparative Examples 1, 4, 6, and 7, the phytosterol ester is β-sitosterol oleate. The preparation method of the medical disinfectant hand sanitizer is the same as in the examples. Table 4. Medical hand sanitizer formulations for Comparative Examples 1-7

[0038] Performance tests were conducted on the medical hand sanitizers of Examples 1-4 and Comparative Examples 1-7: Artificial sebum film-stain biphasic model: Materials: Simulated sebum: Formulated according to the composition of human sebum, 10 wt.% squalene, 25 wt.% wax esters, 25 wt.% triglycerides, 15 wt.% cholesterol esters, 5 wt.% cholesterol, with the remainder being deionized water. Simulated stains: Carbon black particles (hydrophobic stains), olive oil (oily stains), and bovine serum albumin (protein stains), in a mass ratio of 1:1:1.

[0039] Procedure: Apply simulated sebum onto a glass slide, then cover it with simulated stains.

[0040] Solution treatment: After washing the glass slides five times consecutively with the medical disinfectant hand sanitizers of Examples 1-4 and Comparative Examples 1-7, the sebum retention rate on the slides was determined as: residual simulated sebum mass / initial simulated sebum mass. Antibacterial testing was also performed, following the methods outlined in GB 15979-2024 "Hygienic Requirements for Disposable Sanitary Products". The test results are shown in Table 5. Table 5 Performance test results of medical hand sanitizers in Examples 1-4 and Comparative Examples 1-7

[0041] As shown in Table 5, Comparative Example 1 lacked sophorolipids to disrupt the CAB micelle structure, resulting in a significant antagonistic effect of CAB on CHG encapsulation, leading to a substantial decrease in the antibacterial rate to 71.3%. The lipid-retaining components remained intact, thus the sebum retention rate was acceptable (90%), but still lower than that of the embodiments of this invention.

[0042] In Comparative Example 2, the complete complex surfactant system resulted in an antibacterial rate of 100%; however, due to the complete lack of lipid-retaining components such as phytosterol esters, glyceryl glucoside, and asiaticoside, sebum was excessively removed during the washing process, resulting in a low sebum retention rate (85%).

[0043] Comparative Example 3 lacks both sophorolipids and lipid-retaining components, resulting in both CAB antagonism against CHG, reducing the antibacterial rate to 71.2%, and the absence of any lipid-retaining measures, thus exhibiting the worst sebum retention rate (78%).

[0044] Comparative Example 4 lacked the disruptive effect of α-glucan oligosaccharides on the stability of CAB micelles. Sophorolipid alone was insufficient to completely block encapsulation, and the antagonistic effect was partially reproduced, resulting in a decrease in the antibacterial rate to 75.5%. The lipid-retaining components were intact, and the sebum retention rate was relatively good (92%).

[0045] Comparative Example 5, lacking the core sebum analogue supplement phytosterol esters, maintained a 100% antibacterial rate, but its ability to directly repair and maintain the sebum film was weakened, and its sebum retention rate (88%) was lower than that of the example containing a complete sebum-retaining system.

[0046] Comparative Example 6 lacked glyceryl glucoside, a component that promotes sebum self-repair. Although the antibacterial rate remained at 100%, the rapid recovery ability of the sebum film was affected, and the sebum retention rate (90%) decreased slightly.

[0047] Comparative Example 7 lacks the soothing and repairing component asiaticoside. Although the antibacterial rate remains at 100%, the skin barrier protection ability is slightly weaker under long-term and high-frequency use, and the sebum retention rate (89%) is slightly lower than the complete formula of the Example.

Claims

1. A bactericidal, non-antagonistic, and oil-retaining medical hand sanitizer, characterized in that: Made from the following components by weight percentage: 0.2-0.5% chlorhexidine gluconate, 0.5-5% sophorolipid, 0.5-5% cocamidopropyl betaine, 0.01-0.05% α-glucan oligosaccharide, 1-4% isopropanol, 1-2% glycerol, 0.3-1% phytosterol esters, 0.1-0.5% glyceryl glucoside, 0.05-0.2% asiaticoside, balance deionized water.

2. The bactericidal, non-antagonistic, and lipid-retaining medical hand sanitizer as described in claim 1, characterized in that, The phytosterol ester is one or both of β-sitosterol oleate and campesterol palmitate.

3. The bactericidal, non-antagonistic, and lipid-retaining medical hand sanitizer as described in claim 1, characterized in that, The mass ratio of chlorhexidine gluconate, sophorolipid and cocamidopropyl betaine is 1:(5-10):(5-10).

4. The bactericidal, non-antagonistic, and oil-retaining medical hand sanitizer as described in claim 1, characterized in that, Made from the following components by weight percentage: 0.5% chlorhexidine gluconate, 5% sophorolipid, 5% cocamidopropyl betaine, 0.05% α-glucan oligosaccharide, 4% isopropanol, 2% glycerol, 1% phytosterol ester, 0.5% glycerol glucoside, 0.2% asiaticoside, balance deionized water.

5. The method for preparing the bactericidal, non-antagonistic, and lipid-retaining medical hand sanitizer according to any one of claims 1-4, characterized in that, Includes the following steps: S1 Dissolves chlorhexidine gluconate in a portion of deionized water, mixes thoroughly, and obtains solution A; S2 is prepared by mixing sophorolipid, cocamidopropyl betaine, α-glucan oligosaccharide and the remaining deionized water, stirring and letting it stand to defoam, and then using it as solution B. S3 is a mixture of isopropanol, glycerol, phytosterol esters, glyceryl glucoside, and asiaticoside, which is used as solution C. Under stirring conditions S4, add solution B to solution A, continue stirring after addition, and adjust the pH to 5-6 with a pH adjuster to obtain a mixed solution; add solution C to the mixed solution and mix well, stir, and adjust the pH to 5-6.5 with a pH adjuster to obtain a bactericidal, non-antagonistic, lipid-preserving medical hand sanitizer.

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