CN113101263A

CN113101263A - Skin disinfection microemulsion gel and preparation method thereof

Info

Publication number: CN113101263A
Application number: CN202110327118.5A
Authority: CN
Inventors: 柴金岭; 韩颖; 李德杰
Original assignee: Shandong Normal University
Current assignee: Shandong Normal University
Priority date: 2021-03-26
Filing date: 2021-03-26
Publication date: 2021-07-13

Abstract

The invention belongs to the technical field of disinfection gel, and particularly relates to skin disinfection microemulsion gel and a preparation method thereof. The skin disinfection microemulsion gel comprises the following components in percentage by mass: 50% -60% of ethanol, 0.5% -3% of methyl salicylate, 0.006% -0.1% of eugenol and other skin-acceptable carriers. The skin disinfection microemulsion gel provided by the invention is not added with any surfactant, and adopts the compounding of ethanol, methyl salicylate and eugenol to play a synergistic bactericidal and bacteriostatic role, so that the bactericidal and bacteriostatic effects are excellent. Meanwhile, the sodium hyaluronate with high moisture retention component is added, so that the irritation to the skin is reduced, the skin is kept moist, and the skin is moistened and maintained.

Description

Skin disinfection microemulsion gel and preparation method thereof

Technical Field

The invention belongs to the technical field of disinfection gel, and particularly relates to a skin disinfection micro-emulsion gel without a surfactant and a preparation method thereof.

Background

The information in this background section is only for enhancement of understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art that is already known to a person of ordinary skill in the art.

People often contact with various pathogenic microorganisms in daily life, and part of the pathogenic microorganisms influence human health and even threaten life safety, so that the disinfection gel products become indispensable daily supplies in people's life. Most of disinfection gel products on the market at present select triclosan, ethanol and the like as effective sterilization components. Triclosan is an international topical antibacterial disinfectant and can kill Staphylococcus aureus, Escherichia coli, Candida albicans, pyococcus and intestinal pathogenic fungi. However, the publication in PNAS in 2014 reported that triclosan acts as a liver tumor promoter. The hepatotoxic effects of triclosan were reported in 2016, the journal of Science. A study published in the journal of Science relative Medicine in the United states shows that triclosan, an antibacterial agent widely used in daily life, alters the intestinal microbiota, aggravates the inflammatory response of the intestine, and increases the incidence of intestinal cancer.

Ethanol is also widely used for skin surface disinfection, and studies show that 75% ethanol has the best disinfection effect. However, 75% alcohol is evaporated too quickly and easily causes dry skin, and the skin tolerance is low, and meanwhile, most of disinfection gel products using alcohol as a disinfection active ingredient are added with a surfactant, and the addition amount of the surfactant in part of the products is high. The surfactant not only has a large stimulation effect on the skin, but also can permeate into the skin. About 0.5% of gel applied on skin can permeate into blood, and the permeability of skin with wound is increased by more than 10 times. The surfactant entering human body can reduce calcium ion concentration in blood, acidify blood, and make human body feel tired. In addition, the surfactant also reduces the detoxifying function of the liver, so that the toxins originally discharged from the body accumulate in the body, which reduces the immunity of the human body, possibly damages liver cells and induces cancer. Therefore, the research on the disinfectant gel product without the surfactant has very important practical significance and application prospect.

Disclosure of Invention

In order to solve the defects of the prior art, the invention provides the skin disinfection microemulsion gel and the preparation method thereof. Meanwhile, the sodium hyaluronate with high moisture retention component is added, so that the irritation to the skin is reduced, the skin is kept moist, and the skin is moistened and maintained.

In order to achieve the above object, the invention provides a skin disinfection microemulsion gel in a first aspect, which comprises the following components in percentage by mass: 50% -60% of ethanol, 0.5% -3% of methyl salicylate, 0.006% -0.1% of eugenol and other skin-acceptable carriers.

The other dermatologically acceptable carrier comprises water.

The skin disinfection microemulsion gel also contains 0.5 to 1.5 percent of moisturizing substances;

preferably, the moisturizing substance is sodium hyaluronate, glycerol, amino acid, squalane or other natural moisturizing factors;

further preferably, the moisturizing substance is sodium hyaluronate.

The second aspect of the invention provides a preparation method of the skin disinfection microemulsion gel, which comprises the following steps:

(1) mixing ethanol, methyl salicylate and eugenol, stirring to obtain solution A, and standing;

(2) mixing sodium hyaluronate with water, stirring to obtain solution B, and standing;

(3) slowly adding the solution A into the solution B, stirring, and performing ultrasonic treatment to obtain a skin disinfection microemulsion gel product.

One or more embodiments of the present invention have at least the following advantageous effects:

(1) the skin disinfection microemulsion gel provided by the invention does not contain a surfactant, and the ethanol, the methyl salicylate and the eugenol are compounded to achieve a synergistic bactericidal and bacteriostatic effect, so that the bactericidal and bacteriostatic effects are excellent.

(2) The components such as methyl salicylate, eugenol, ethanol, sodium hyaluronate, water and the like can form transparent, homogeneous and stable microemulsion gel without surfactant, the defect that the existing disinfection gel products are volatile is overcome, the volatilization failure of ethanol in the gel can be avoided, and the skin discomfort caused by ethanol stimulation can be avoided to a certain extent.

(3) The microemulsion gel has good adhesiveness, clarity and transparency, is easy to spread on skin, is not greasy, and has good use feeling.

Detailed Description

It is to be understood that the following detailed description is exemplary and is intended to provide further explanation of the invention as claimed. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of exemplary embodiments according to the invention. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, and it should be understood that when the terms "comprises" and/or "comprising" are used in this specification, they specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof, unless the context clearly indicates otherwise.

As described in the background art, most of the skin disinfection gels in the prior art, which use ethanol as a main active ingredient, contain surfactants, so that the skin disinfection gels are harmful to the skin and even human bodies, and the ethanol in the ethanol-based disinfection gels volatilizes too fast, so that the skin is easily dried, and the skin tolerance is low.

In order to solve the technical problems, the invention provides a skin disinfection microemulsion gel which comprises the following components in percentage by mass: 50% -60% of ethanol, 0.5% -3% of methyl salicylate, 0.006% -0.1% of eugenol and other skin-acceptable carriers.

Methyl salicylate, also known as birch oil, betula oil, methyl salicylate, tea seed oil, etc., has strong fragrance of wintergreen oil. Methyl salicylate is used as a medicine, is called a non-steroidal anti-inflammatory drug, has the effects of diminishing inflammation, relieving pain, sterilizing and the like when being externally applied, and is easy to be absorbed when being applied to the skin.

Eugenol has strong fragrance of flos Caryophylli, strong bactericidal effect, and local antiseptic effect. Has inhibitory effect on pathogenic fungi at a concentration of 1:8000-1: 16000; in the concentration range of 1:2000-1:8000, it has inhibitory effect on Staphylococcus aureus and Bacillus of pneumonia, dysentery, large intestine, deformation, and tuberculosis.

The invention provides a skin disinfection microemulsion gel, which is prepared by adding methyl salicylate, eugenol and ethanol into a gel system to synergistically play a disinfection antibacterial role, wherein in order to avoid adverse effects of a surfactant in the traditional disinfection gel on human skin, blood and liver, the inventor introduces methyl salicylate, eugenol and ethanol to synergistically play a disinfection antibacterial role, methyl salicylate and eugenol in a certain addition ratio can relieve the dry skin feeling caused by adding pure alcohol, and can further assist ethanol in sterilization and antibiosis through the antibacterial effect of the methyl salicylate and eugenol, and the methyl salicylate, the eugenol, the ethanol and the ethanol are synergistically used for sterilization and bacteriostasis.

The invention sets the addition amount of the methyl salicylate to be 0.5-3 percent and the addition amount of the eugenol to be 0.006-0.1 percent, because under the addition amount, the methyl salicylate can just replace part of ethanol to play a role in disinfection and antibiosis, the addition amount of the methyl salicylate and the eugenol is too much, the proportion of the ethanol is reduced, the whole bactericidal effect of the disinfection microemulsion gel is influenced, and the addition amount of the methyl salicylate and the eugenol is too little, the phenomenon that the skin is not tolerant due to the large amount of ethanol is formed.

In one or more embodiments of the present invention, the skin sanitizing microemulsion gel further comprises from 0.5% to 1.5% of a moisturizing substance;

further preferably, the moisturizing substance is sodium hyaluronate.

The sodium hyaluronate is a natural macromolecular polymer and is rich in mammalian tissues. It is in loose state in water solution, occupies large space, and combines with surrounding water molecules which are 1000 times of its own weight through hydrogen bonds. Due to this conformational characteristic, the polysaccharide solution has strong viscosity and elasticity. In the microemulsion gel, the sodium hyaluronate plays a role in moisturizing the skin, and can keep the skin moist while ensuring the sterilization and disinfection effects of the microemulsion gel, and has the effects of moistening and maintaining the skin.

The sodium hyaluronate is added for nourishing the skin and avoiding the problem of skin dryness caused by ethanol volatilization, and the components such as methyl salicylate, eugenol, ethanol, sodium hyaluronate, water and the like can form transparent, homogeneous and stable microemulsion gel without surfactant, thereby overcoming the defect that the existing disinfection gel products are volatile.

In one or more embodiments of the invention, the additional dermatologically acceptable carrier comprises water.

In one or more embodiments of the present invention, the skin sanitizing microemulsion gel comprises the following components in percentage by mass: 55 to 60 percent of ethanol, 1.5 to 3 percent of methyl salicylate, 0.02 to 0.1 percent of eugenol, 0.5 to 1.5 percent of sodium hyaluronate and the balance of water.

The molecular weight of the sodium hyaluronate is in the range of 200-1200 kDa.

Preferably, the molecular weight of sodium hyaluronate is 400-800kDa, more preferably 400 kDa.

In one or more embodiments of the present invention, the skin sanitizing microemulsion gel comprises the following components in percentage by mass: 60% of ethanol, 2% of methyl salicylate, 0.05% of eugenol, 1.0% of sodium hyaluronate and the balance of water.

According to the invention, researches show that the skin disinfection microemulsion gel has the best effect. If the addition amounts of ethanol, methyl salicylate and eugenol are reduced, the antibacterial effect is reduced. On the other hand, if the addition amounts of ethanol, methyl salicylate and eugenol are increased, the antibacterial effect may be better, but the addition amount of sodium hyaluronate is reduced, the moisturizing performance of the disinfection gel is also reduced, and certain side effects are brought to the human body.

In one or more embodiments of the invention, in the step (1), the stirring process is performed in a stirrer, the fixed rotation speed is 1000r/min, and the stirring time is 15-30 min.

In one or more embodiments of the invention, in the step (2), the stirring process is performed in a stirrer, the fixed rotation speed is 500r/min, and the stirring time is 12-24 h.

In one or more embodiments of the invention, in the step (3), the solution a is added into the solution B while stirring, the stirring fixed rotation speed is 500r/min, and after the addition, the stirring is continued for 1 to 1.5 hours, and the ultrasonic time is 10 to 15 minutes.

In order to make the technical solutions of the present invention more clearly understood by those skilled in the art, the technical solutions of the present invention will be described in detail below with reference to specific embodiments.

Example 1

The skin disinfection microemulsion gel comprises the following components in percentage by mass: 50% of ethanol, 0.5% of methyl salicylate, 0.006% of eugenol, 1.5% of sodium hyaluronate and the balance of water. The molecular weight of the sodium hyaluronate is 1200 kDa.

A method of preparing the microemulsion gel comprising the steps of:

step one, sequentially putting 50% of ethanol, 0.5% of methyl salicylate and 0.006% of eugenol in a stirrer, stirring at a fixed rotation speed of 1000r/min for 15min to obtain a solution A, and standing for later use;

step two, adding 1.5 mass percent of moisturizing ingredient sodium hyaluronate and 47.99 mass percent of water into another stirrer, fixing the rotating speed at 500r/min, stirring for 12 hours to obtain solution B, and standing for later use;

and step three, slowly adding the solution A into the solution B, stirring while adding, keeping the fixed rotation speed at 500r/min, continuing stirring for 1h after adding, and performing ultrasonic treatment for 15min to obtain the microemulsion gel without the surfactant.

Example 2

The skin disinfection microemulsion gel comprises the following components in percentage by mass: 55% of ethanol, 1.0% of methyl salicylate, 0.01% of eugenol, 1.0% of sodium hyaluronate and the balance of water. The molecular weight of the sodium hyaluronate is 800 kDa.

A method of preparing the microemulsion gel comprising the steps of:

step one, sequentially putting 55% of ethanol, 1.0% of methyl salicylate and 0.01% of eugenol in a stirrer at a fixed rotation speed of 1000r/min, stirring for 20min to obtain a solution A, and standing for later use;

step two, adding 1.0 mass percent of moisturizing ingredient sodium hyaluronate and 42.99 mass percent of water into another stirrer, stirring for 15 hours at a fixed rotation speed of 500r/min to obtain solution B, and standing for later use;

Example 3

The skin disinfection microemulsion gel comprises the following components in percentage by mass: 55% of ethanol, 1.5% of methyl salicylate, 0.02% of eugenol, 1.0% of sodium hyaluronate and the balance of water. The molecular weight of the sodium hyaluronate is 400 kDa.

A method of preparing the microemulsion gel comprising the steps of:

step one, sequentially putting 55% of ethanol, 1.5% of methyl salicylate and 0.02% of eugenol in a stirrer at a fixed rotation speed of 1000r/min, stirring for 20min to obtain a solution A, and standing for later use;

step two, adding 1.0 mass percent of moisturizing ingredient sodium hyaluronate and 42.48 mass percent of water into another stirrer, stirring for 20 hours at a fixed rotating speed of 500r/min to obtain solution B, and standing for later use;

and step three, slowly adding the solution A into the solution B, stirring while adding at the rotating speed of 500r/min, continuously stirring for 1h after adding, and performing ultrasonic treatment for 15min to obtain the microemulsion gel without the surfactant.

Example 4

The skin disinfection microemulsion gel comprises the following components in percentage by mass: 60% of ethanol, 2% of methyl salicylate, 0.05% of eugenol, 1.0% of sodium hyaluronate and the balance of water. The molecular weight of the sodium hyaluronate is 400 kDa.

A method of preparing the microemulsion gel comprising the steps of:

step one, sequentially putting 60% of ethanol, 2.0% of methyl salicylate and 0.05% of eugenol in a stirrer, stirring at a fixed rotation speed of 1000r/min for 30min to obtain a solution A, and standing for later use;

step two, adding 1.0 mass percent of moisturizing ingredient sodium hyaluronate and 36.95 mass percent of water into another stirrer, stirring for 20 hours at a fixed rotating speed of 500r/min to obtain solution B, and standing for later use;

Example 5

The skin disinfection microemulsion gel comprises the following components in percentage by mass: 60% of ethanol, 3% of methyl salicylate, 0.1% of eugenol, 0.5% of sodium hyaluronate and the balance of water. The molecular weight of the sodium hyaluronate is 200 kDa.

A method of preparing the microemulsion gel comprising the steps of:

step one, sequentially putting 60% of ethanol, 3.0% of methyl salicylate and 0.1% of eugenol in a stirrer at a fixed rotation speed of 1000r/min, stirring for 30min to obtain a solution A, and standing for later use;

step two, adding 0.5 mass percent of moisturizing component sodium hyaluronate and 36.40 mass percent of water into another stirrer, stirring for 24 hours at a fixed rotating speed of 500r/min to obtain solution B, and standing for later use;

The microemulsion gels for skin disinfection described in the examples were subjected to a microbial kill test, and the results are shown in table 1.

And (3) microorganism killing test: the bacteria content is 5.0 × 10 according to 2002 edition' Disinfection technical Specification⁵-1.0×10⁶The killing test was carried out on cfu/mL of bacterial suspension. 0.5mL of test bacterial suspension is added into a large sterile test tube, and is placed in a water bath with the temperature of 20 +/-1 ℃ for 5min, 4.0mL of disinfectant with the concentration is absorbed by a sterile pipette and is injected into the sterile test tube, and the sterile test tube is quickly mixed and immediately timed. After the test bacteria and the disinfectant interact for 3min, 0.5mL of the mixed solution of the test bacteria and the disinfectant is respectively sucked and added into 4.5mL of the sterilized neutralizer, and the mixture is uniformly mixed. Adding neutralizing agent into the mixed solution of test bacteria and disinfectant, reacting for 10min, respectively sucking 1.0mL of sample solution, determining viable bacteria number by viable bacteria culture counting method, and inoculating 2 plates to each tube of sample solution.

Meanwhile, the diluent is used for replacing disinfectant, and a parallel test is carried out to be used as a positive control. The positive control sample and the test sample are cultured in a constant temperature incubator at 37 ℃ for 48 hours, and the viable bacteria concentration (cfu/mL) of each group is observed.

The sterilization rates (%) of the sterilization gels of examples 1-5 were calculated after 3min of action on Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, and Pseudomonas aeruginosa, respectively.

Sterilization rate ═ average number of colonies in control sample-average number of colonies in test sample)/average number of colonies in control sample × 100%

TABLE 1 Sterilization rates (%), for Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, and Pseudomonas aeruginosa, of the disinfectant gels of examples 1 to 5

Test bacterium	Example 1	Example 2	Example 3	Example 4	Example 5
						Staphylococcus aureus	＞99.97	＞99.97	＞99.98	＞99.98	＞99.98
Pseudomonas aeruginosa	＞99.97	＞99.97	＞99.98	＞99.98	＞99.98
						Escherichia coli	＞99.97	＞99.98	＞99.98	＞99.98	＞99.98
Candida albicans	＞99.96	＞99.97	＞99.98	＞99.98	＞99.98
						Pseudomonas aeruginosa	＞99.97	＞99.98	＞99.98	＞99.98	＞99.98

Quantitative sterilization tests show that the sterilization rates of the microemulsion gel in the examples 1 to 5 on staphylococcus aureus, pseudomonas aeruginosa, escherichia coli, candida albicans and pseudomonas aeruginosa are all more than 99.96%.

The microemulsion gels for skin disinfection described in the examples were subjected to a human skin surface bacteria killing experiment, and the results are shown in table 2.

The preparation of the bacterial suspension is carried out according to the method and requirements specified in the "Disinfection technical Specification" 2002 edition. Selecting Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, and Pseudomonas aeruginosa with bacteria content of 2.0 × 10⁸-2.0×10⁹Bacterial suspensions of cfu/mL were tested for bacterial kill on the skin surface.

Washing the inner side of forearm of the subject with liquid soap for 1min, washing off residual soap solution with tap water, and wiping with sterile gauze to remove natural bacteria contaminated on the inner surface of forearm. A glass tube dipped with 3.0cm ink at one end is attached to the middle part of each forearm of the subject to divide a test area. mu.L of the bacterial suspension was sampled by a sample applicator, inoculated on the forearm test area, and applied to a circle at a distance of 4-5mm from the edge of the test area by a disposable inoculating loop, and naturally dried in the air.

The right forearm was disinfected with the microemulsion gel of examples 1-5, generally for an action time of 1-3 min. After sterilization the inoculated area on the forearm was sampled with a neutralizer. During sampling, the metal cylinder is placed in the middle of the test area to cover the bacteria staining area without contacting the edge covered with the printing ink. 1.0mL of the neutralizing agent was pipetted into a metal cylinder, the skin in the area covered with the metal cylinder was scraped off with a nylon swab for 60 seconds, the liquid in the cylinder was pipetted into the test tube, 1.0mL of the neutralizing agent was added to scrape off the skin in this area for a second 30 seconds, and the liquid scrubbed for the second time was injected into the test tube containing the liquid scraped off for the first time to prepare a test group sample.

The middle left forearm was treated with distilled water instead of disinfectant as a control sample.

The test uses the unused neutralizer of the same batch and 1.0mL of diluent respectively as negative control group samples.

1.0mL of each of the test group, the control group and the negative control group samples with appropriate dilution was taken, plates were inoculated by the agar pour method, 2 plates were inoculated for each sample, the plates were placed in an incubator at 37 ℃ for 48 hours, the viable cell concentration (cfu/mL) of each group was calculated and converted to a logarithmic value (N), and a logarithmic value (KL) of the reduction in the number of bacteria on the skin surface was calculated.

Log Kill (KL) is the log of the mean viable bacteria concentration of the control group (No) -log of the viable bacteria concentration of the test group (Nx).

TABLE 2 log values (KL) for bacterial kill on the surface of human skin using the microemulsion gel products described in examples 1-5

Test bacterium	Example 1	Example 2	Example 3	Example 4	Example 5
						Staphylococcus aureus	6.00	6.02	6.02	6.10	6.02
Pseudomonas aeruginosa	5.72	5.75	5.80	5.80	5.80
						Escherichia coli	5.80	5.85	5.87	5.90	5.90
Candida albicans	5.85	5.90	5.92	5.92	5.90
						Pseudomonas aeruginosa	5.95	6.02	6.05	6.10	6.05

The experimental result of the human skin surface bacteria killing shows that after the microemulsion gel of the embodiment 1 to 5 is used, the average killing log values of the human skin surface bacteria are all more than or equal to 5.72, the standard killing log values of the disinfection technical specification are all more than or equal to 3.00, and the disinfection effect is reliable. Meanwhile, the microemulsion gel contains moisturizing components such as sodium hyaluronate and the like, has moisturizing and nourishing effects on skin, and is a good choice for skin disinfection.

The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A skin disinfection microemulsion gel, which is characterized in that: comprises the following components in percentage by mass: 50% -60% of ethanol, 0.5% -3% of methyl salicylate, 0.006% -0.1% of eugenol and other skin-acceptable carriers.

2. The skin sanitizing microemulsion gel as set forth in claim 1, wherein: the other dermatologically acceptable carrier comprises water.

3. The skin sanitizing microemulsion gel as set forth in claim 2, wherein: the skin disinfection micro-emulsion gel also contains 0.5-1.5% of moisturizing substances.

4. A skin sanitizing microemulsion gel as set forth in claim 3, wherein: the moisturizing substance is sodium hyaluronate, glycerol, amino acid, squalane or other natural moisturizing factors;

preferably, the moisturizing substance is sodium hyaluronate.

5. The skin sanitizing microemulsion gel as set forth in claim 4, wherein: the skin disinfection microemulsion gel comprises the following components in percentage by mass: 55 to 60 percent of ethanol, 1.5 to 3 percent of methyl salicylate, 0.02 to 0.1 percent of eugenol, 0.5 to 1.0 percent of sodium hyaluronate and the balance of water.

6. The skin sanitizing microemulsion gel as set forth in claim 5, wherein: the molecular weight of the sodium hyaluronate is in the range of 200-1200kDa, preferably 400-800kDa, and more preferably 400-kDa.

7. The skin sanitizing microemulsion gel as set forth in claim 5, wherein: the skin disinfection microemulsion gel comprises the following components in percentage by mass: 60% of ethanol, 2% of methyl salicylate, 0.05% of eugenol, 1.0% of sodium hyaluronate and the balance of water.

8. A method of preparing a skin sanitizing microemulsion gel as set forth in claim 5, wherein: comprises the following steps:

9. The method of claim 8, wherein: in the step (1), the stirring process is carried out in a stirrer, the fixed rotating speed is 1000r/min, and the stirring time is 15-30 min.

10. The method of claim 8, wherein: in the step (2), the stirring process is carried out in a stirrer, the fixed rotating speed is 500r/min, and the stirring time is 12-24 h;

or, in the step (3), the solution A is added into the solution B while stirring, the stirring fixed rotation speed is 500r/min, and the stirring is continued for 1 to 1.5 hours after the addition, and the ultrasonic time is 10 to 15 minutes.