KR20200077818A - Alcoholic disinfectant with enhanced antibacterial durability stability comprising chlorhexidine or derivatives thereof - Google Patents

Abstract

The present invention relates to alcoholic disinfectants with improved antibacterial persistence, which comprises: chlorhexidine or derivatives thereof; alcoholic solvents; amphiphilic thickeners; and polyglyceryl fatty acid esters as amphiphilic stabilizers.

Description

ALCOHOLIC DISINFECTANT WITH ENHANCED ANTIBACTERIAL DURABILITY STABILITY COMPRISING CHLORHEXIDINE OR DERIVATIVES THEREOF}

The present invention relates to an alcoholic disinfectant with improved antimicrobial persistence comprising chlorhexidine or a derivative thereof.

Chlorhexidine has a wide range of bactericidal and bacteriostatic effects against Gram-negative and Gram-positive bacteria. This material is a bisbiguanide material and is widely used as acetate, gluconate and hydrochloride. The chemical name mainly uses 1,1'-hexamethylenebis[5-(4-chlorphenyl)biguanide]acetate digloconate and dihydrochloride salts, and is composed of a material stabilized with each organic acid salt.

Among them, the substance tested to be the most stable as an organic acid salt is gluconate, and this salt is widely used as a sterilizing preservative. Depending on its content, it has a strong sterilizing effect at high concentrations, and Pseudomonas and Mycobacterium bacteria at low concentrations. It shows low sensitivity, but also shows excellent bacteriostatic action against these strains. Commercially, gluconate is a 20% aqueous solution stock, and its standard is listed in the pharmacopoeia worldwide.

As described above, studies on alcoholic disinfectants including chlorhexidine or derivatives thereof have been made in various ways, but there is a problem in that its antibacterial activity is not sustained.

The present invention is chlorhexidine or a derivative thereof; Alcoholic solvents; Amphipathic thickener; And as an amphipathic stabilizing agent, it is intended to provide an alcoholic disinfectant with improved antimicrobial persistence, which comprises a polyglyceryl fatty acid ester.

However, the technical problem to be achieved by the present invention is not limited to the above-mentioned problems, and other problems not mentioned will be clearly understood by those skilled in the art from the following description.

The present invention is chlorhexidine or a derivative thereof; Alcoholic solvents; Amphipathic thickener; And as an amphiphilic stabilizer, it characterized in that it comprises a polyglyceryl fatty acid ester, provides an antimicrobial persistence improved alcoholic disinfectant.

The chlorhexidine or derivative thereof may be one or more selected from the group consisting of chlorhexidine, chlorhexidine gluconate, chlorhexidine dihydrochloride and chlorhexidine diacetate.

The amphipathic thickener may include hydroxyalkylcellulose or polyvinylpyrrolidone.

The polyglyceryl fatty acid ester may have a hydrophile-lipophile balance (HLB) value of 8 to 12.

The polyglyceryl fatty acid ester is at least one PEG system selected from the group consisting of PEG-23 glyceryl cocoate, PEG-7 glyceryl cocoate, PEG-20 glyceryl triisostearate and PEG-15 glyceryl monostearate. Glyceryl fatty acid esters.

For 100 mL of the alcoholic disinfectant, 0.10 g to 5.00 g of the chlorhexidine or its derivatives; 50.00 g to 100.00 g of the alcoholic solvent; 1.00 g to 50.00 g of the amphipathic thickener; And 0.01 g to 50.00 g of the polyglyceryl fatty acid ester.

The alcoholic disinfectant may be maintained at pH 5.5 to pH 6.5.

The viscosity at 25°C of the alcoholic disinfectant can be maintained between 10 cps and 2,500 cps.

With respect to the total content of chlorhexidine or a derivative thereof, iv) the alcoholic disinfectant is stored for 3 months in a long-term (25°C temperature and 60% relative humidity) condition, and the content of chlorhexidine or a derivative thereof is 99% by weight or more, Ii) After storing the alcoholic disinfectant under accelerated conditions (temperature of 40° C. and relative humidity of 75%) for 3 months, the content of chlorhexidine or a derivative thereof may be 93% by weight or more.

Alcoholic disinfectants having improved antibacterial persistence according to the present invention include chlorhexidine or derivatives thereof; Alcoholic solvents; Amphipathic thickener; And as an amphiphilic stabilizer, it characterized in that it comprises a polyglyceryl fatty acid ester, due to the use of the amphiphilic thickener, to adjust the viscosity, as well as high residual amount after application does not occur, chlorhexidine or There is an advantage that can control the release amount of its derivatives. In addition, as the amphiphilic stabilizer, due to the use of polyglyceryl fatty acid ester, it is possible to sustain the antibacterial activity by enabling sustained release of chlorhexidine or its derivatives, as well as protecting chlorhexidine or its derivatives for long-term and accelerated conditions. It has the advantage of improving stability over time.

1 is a graph comparing the evaluation of cumulative chlorhexidine gluconate release behavior of alcoholic disinfectants prepared in Examples 3, 8, and 15-18.

The present inventors were studying amphiphilic thickeners during research to improve the antibacterial persistence of an alcoholic disinfectant containing chlorhexidine or a derivative thereof; And as an amphiphilic stabilizer, by adding a polyglyceryl fatty acid ester, it was confirmed that it is possible to maintain the antibacterial activity, and to improve stability over time in long-term and accelerated conditions, and completed the present invention.

Hereinafter, the present invention will be described in detail.

The present invention is chlorhexidine or a derivative thereof; Alcoholic solvents; Amphipathic thickener; And as an amphiphilic stabilizer, characterized in that it comprises a polyglyceryl fatty acid ester, provides an antibacterial persistence improved alcoholic disinfectant.

The "alcoholic disinfectant" in the present specification is an external preparation containing an alcoholic solvent, and then applied to the human body such as skin to be disinfected, and then the alcoholic solvent volatilizes and serves to increase comfort, while the rest of the non-volatile components such as skin to be disinfected It forms a stable film and acts as a disinfectant.

First, the alcoholic disinfectant whose antibacterial persistence is modified according to the present invention includes chlorhexidine or a derivative thereof. The chlorhexidine or derivative thereof is preferably one or more selected from the group consisting of chlorhexidine, chlorhexidine gluconate, chlorhexidine dihydrochloride and chlorhexidine diacetate, but is not limited thereto. On the other hand, a chlorohexidine salt such as the chlorohexidine gluconate is present in an aqueous solution state, and the chlorohexidine is preferably 10% to 30% by weight, and 20% by weight based on the total weight of the aqueous solution. % Is preferred, but is not limited thereto.

In this case, the content of chlorhexidine or a derivative thereof may be 0.10 g to 5.00 g, and preferably 0.10 g to 1.00 g, with respect to 100 mL of the alcoholic disinfectant.

Next, the alcoholic disinfectant with improved antimicrobial persistence according to the present invention includes an alcoholic solvent. The alcoholic solvent is applied to the human body, such as the skin to be disinfected, and then volatilized to increase the comfort. The alcoholic solvent may be C1-C4 alcohol, preferably ethanol, but is not limited thereto.

At this time, the content of the alcoholic solvent, with respect to 100 mL of the alcoholic disinfectant, may be 50.00 g to 100.00 g, preferably 60.00 g to 70.00 g, but is not limited thereto. At this time, when the content of the alcoholic solvent is too small, there is a problem that the volatility is too low, and when the content of the alcoholic solvent is too large, there is a problem that the stickiness becomes too severe, and thus it is impossible to have excellent comfort.

Next, the alcoholic disinfectant with improved antimicrobial persistence according to the present invention includes an amphipathic thickener. The amphiphilic thickener has both a hydrophobic end portion and a hydrophilic end portion, and may exist at the interface between the aqueous solution containing the chlorhexidine or a derivative thereof and the alcoholic solvent, thereby increasing solubility and miscibility and promoting stability of the active ingredient. can do. In addition, the viscosity of the alcoholic disinfectant can be adjusted, and after application, the residual amount is high and no drop occurs, and the release amount of the chlorhexidine or its derivatives can be controlled. The amphipathic thickener may include hydroxyalkylcellulose or polyvinylpyrrolidone. Specifically, the hydroxyalkyl cellulose may be hydroxymethyl cellulose, hydroxyethyl cellulose or hydroxypropyl cellulose.

At this time, the content of the amphipathic thickener may be 1.00 g to 50.00 g, and preferably 2.00 g to 15.00 g, with respect to 100 mL of the alcoholic disinfectant.

Next, the alcoholic disinfectant with improved antimicrobial persistence according to the present invention is an amphipathic stabilizer, and includes a polyglyceryl fatty acid ester. The polyglyceryl fatty acid ester may have a glyceryl fatty acid ester group corresponding to a hydrophobic end portion, and a PEG (polyethylene glycol) group corresponding to a hydrophilic end portion. Specifically, the polyglyceryl fatty acid ester may have a hydrophile-lipophile balance (HLB) value of 8 to 12, preferably 9 to 11, but is not limited thereto. Therefore, the polyglyceryl fatty acid ester may be present at the interface between the aqueous solution containing the chlorhexidine or its derivative and the alcoholic solvent. Thus, even if the alcoholic solvent is applied to the human body, such as the skin to be disinfected, and then volatilized, the polyglyceryl fatty acid ester can form a stable film to protect the chlorhexidine or its derivatives, so that the alcoholic disinfectant is vulnerable to long-term and accelerated conditions. Stability can be improved. In addition, it is possible to sustain sustained release of the chlorhexidine or a derivative thereof to maintain antibacterial activity. The polyglyceryl fatty acid ester is at least one PEG system selected from the group consisting of PEG-23 glyceryl cocoate, PEG-7 glyceryl cocoate, PEG-20 glyceryl triisostearate and PEG-15 glyceryl monostearate. It may be a glyceryl fatty acid ester, and is preferably PEG-23 glyceryl cocoate, but is not limited thereto.

At this time, the content of the polyglyceryl fatty acid ester, with respect to 100 mL of the alcoholic disinfectant, may be 0.01 g to 50.00 g, preferably 0.1 g to 20.00 g, but is not limited thereto.

Therefore, the viscosity at 25° C. of the alcoholic disinfectant according to the present invention can maintain 10 cps to 2,500 cps, and it is preferable to maintain 10 cps to 1,000 cps, but is not limited thereto. At this time, when the viscosity of the alcoholic disinfectant is too low to show characteristics close to water, there is a problem in that drop occurs, and if the viscosity of the alcoholic disinfectant is too high, there is a problem in that the residual amount after application is low and drops are generated. Therefore, in order to maintain the viscosity of the alcoholic disinfectant within the above-described range, it is necessary to use a certain amount of amphiphilic thickener.

In addition, the alcoholic disinfectant according to the present invention is characterized by improving stability over time in long-term and accelerated conditions. This is because the alcoholic disinfectant is an amphipathic stabilizer and is based on the results of using polyglyceryl fatty acid esters.

Specifically, the alcoholic disinfectant is the content of chlorhexidine or its derivatives after storage for 3 months under conditions of long-term (25°C temperature and 60% relative humidity) conditions for the total amount of chlorhexidine or its derivatives. This is 99% by weight or more (preferably, 99.9% or more), and ii) the content of chlorhexidine or a derivative thereof is 93 after storing the alcoholic disinfectant under accelerated conditions (temperature of 40°C and relative humidity of 75%) for 3 months. It may be more than weight percent (preferably, 98% or more).

In addition, the alcoholic disinfectant according to the present invention may further include other additives. The other additives may be, for example, one or more selected from the group consisting of emollients, pH adjusting agents, flavoring agents, preservatives, solubilizers, emulsifiers, antioxidants and colorants.

Specifically, the emollient imparts flexibility to the alcoholic disinfectant and can be used, for example, allantoin, diisobutyl adipic acid, and the like. At this time, the content of the softener may be 0.001% by weight to 50% by weight, and preferably 0.005% by weight to 30% by weight, based on the total amount of the alcoholic disinfectant, but is not limited thereto.

In addition, the pH adjusting agent is for adjusting the acidity of the alcoholic disinfectant to an appropriate level, for example, an acidic substance such as hydrochloric acid or a basic substance such as sodium hydroxide can be used. At this time, the content of the pH adjusting agent may be an appropriate amount to maintain the alcoholic disinfectant at pH 5.5 to pH 6.5, and is preferably an appropriate amount to maintain pH 5.9 to pH 6.1, but is not limited thereto.

In addition, the flavoring agent improves compliance by allowing the scent to be felt when the alcoholic disinfectant is applied, for example, apple flavor, cherry flavor, orange flavor, strawberry flavor, banana flavor, grape flavor, mango flavor, peach flavor, etc. Various fruit flavors or comprehensive fruit flavors; Vanilla flavor; Mint flavor; And one or more selected from the group consisting of honey scent. At this time, the content of the flavoring agent, based on the total amount of the alcoholic disinfectant, may be 0.1% to 5% by weight, preferably 0.2% to 3% by weight, but is not limited thereto.

In addition, the preservative inhibits the growth of microorganisms during storage of the alcoholic disinfectant, for example, paraoxybenzoic acids such as methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, and butyl paraoxybenzoate; Benzoic acids such as benzoic acid and sodium benzoate; And sorbic acids such as sorbic acid and potassium sorbate. At this time, the content of the preservative, relative to the total content of the alcoholic disinfectant, may be 0.01% to 2% by weight, preferably 0.02% to 1% by weight, but is not limited thereto.

In addition, the dissolution aid improves solubility of the active substance in the alcoholic disinfectant, and for example, one or more selected from the group consisting of meglumine, arginine and lysine may be used. At this time, the content of the dissolution aid may be 0.001% by weight to 1% by weight, and preferably 0.005% by weight to 0.5% by weight, based on the total amount of the alcoholic disinfectant, but is not limited thereto.

As described above, the alcoholic disinfectant having improved antibacterial persistence according to the present invention is chlorhexidine or a derivative thereof; Alcoholic solvents; Amphipathic thickener; And as an amphiphilic stabilizer, it characterized in that it comprises a polyglyceryl fatty acid ester, due to the use of the amphiphilic thickener, to adjust the viscosity, as well as high residual amount after application does not occur, chlorhexidine or There is an advantage that can control the release amount of its derivatives. In addition, as the amphiphilic stabilizer, due to the use of polyglyceryl fatty acid ester, it is possible to sustain the antibacterial activity by enabling sustained release of chlorhexidine or its derivatives, as well as protecting chlorhexidine or its derivatives for long-term and accelerated conditions. It has the advantage of improving stability over time.

Hereinafter, preferred embodiments are provided to help understanding of the present invention. However, the following examples are only provided to more easily understand the present invention, and the contents of the present invention are not limited by the following examples.

[ Example ]

Example 1-6 and Comparative example One

To evaluate the solubility of chlorhexidine gluconate, an alcoholic disinfectant was prepared with the composition of Table 1 below. Specifically, after adding and dissolving chlorhexidine cluconate solution (20%), ethanol, emollient, and pH adjusting agent, purified water is added so that the final volume is 100 ml, and then filtered through a 0.2 μm membrane filter to remove the alcoholic disinfectant. It was prepared. At this time, the alcoholic disinfectant was maintained at pH 5.9 to pH 6.1.

　
　 Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Comparative Example 1 chief ingredient Chlorhexidine cloconate solution (20%) (g) 1.07 1.07 1.07 1.07 1.07 1.07 1.07 Alcoholic solvent Ethanol (g) 50.00 60.00 70.00 80.00 90.00 100.00 - Amphipathy
Thickener Hydroxypropylcellulose (0.1-1.0 MDa) (g) - - - - - - - Polyvinylpyrrolidone (0.1-2.0 MDa) (g) - - - - - - - Amphipathy
Stabilizer PEG-23 glyceryl cocoate (g) - - - - - - - Softener Allantoin Proper Proper Proper Proper Proper Proper Proper Diisobutyl adipic acid Proper Proper Proper Proper Proper Proper Proper pH regulator Hydrochloric acid Proper Proper Proper Proper Proper Proper Proper Sodium hydroxide Proper Proper Proper Proper Proper Proper Proper solvent Purified water Proper Proper Proper Proper Proper Proper Proper

Experimental Example One: Amphipathy Thickener And Amphipathy In the alcoholic disinfectant with the stabilizer omitted Chlorhexidine Gluconate Solubility and Comfort evaluation

In order to evaluate the solubility of chlorhexidine gluconate in the alcoholic disinfectants prepared in Examples 1 to 6 and Comparative Example #1, the undissolved precipitate was filtered, and the total content of chlorhexidine gluconate (injection amount) through a high-purity liquid chromatography method. ) The relative content of chlorhexidine gluconate was measured after the precipitate was filtered, and the results are shown in Table 2. In addition, for 20 adults (users), 5 mL of the alcoholic disinfectant prepared in Examples 1 to 6 and Comparative Example #1 was dropped on the surface of the palm or back of the hand to perform sensory evaluation for comfort (volatility and stickiness). , The results are shown in Table 2. At this time, the sensory evaluation for comfort was set as 5 points for higher volatility and 0 points for higher stickiness, and was examined based on 0 to 5 points according to the user, and the average was shown.

Relative content of chlorhexidine gluconate (% by weight) after sediment is filtered Comfort volatility Stickiness Comparative Example 1 100.1 2.8 3.4 Example 1 99.9 4.1 3.1 Example 2 100.0 4.2 2.8 Example 3 99.9 4.8 1.5 Example 4 100.2 4.6 0.8 Example 5 99.9 5.0 0.5 Example 6 100.0 0.0 4.4

As shown in Table 2, both the alcoholic disinfectants prepared in Examples 1 to 6 and Comparative Example #1 were confirmed to dissolve chlorhexidine gluconate without precipitation. However, despite the fact that the content of the main component in the alcoholic disinfectants prepared in Examples 1 to 6 and Comparative Example #1 was the same, it was confirmed that the results of evaluation of comfort were different according to the change in the content of ethanol. Since the feeling of comfort is excellent in being highly volatile and having little stickiness, when the content of ethanol per 100 mL of alcohol disinfectant is 60.00 g to 70.00 g, such as the alcoholic disinfectants prepared in Examples 2 to 3, it is considered to have the best feeling. Can.

Example 7-18

Alcoholic disinfectants were additionally prepared with the composition of Table 3 below. Specifically, after adding and dissolving chlorhexidine cluconate solution (20%), ethanol, amphiphilic thickener, amphiphilic stabilizer, emollient, and pH adjusting agent, after adding purified water to a final volume of 100 ml, 0.2 Alcoholic disinfectants were prepared by filtration through a membrane filter of µm. At this time, the alcoholic disinfectant was maintained at pH 5.9 to pH 6.1.

Example
7 Example
8 Example
9 Example
10 Example
11 Example
12 Example
13 Example
14 Example
15 Example
16 Example
17 Example
18 chief ingredient Chlorhexidine cloconate solution (20%) (g) 1.07 1.07 1.07 1.07 1.07 1.07 1.07 1.07 1.07 1.07 1.07 1.07 Alcoholic solvent Ethanol (g) 70.00 70.00 70.00 70.00 70.00 70.00 70.00 70.00 70.00 70.00 70.00 70.00 Amphipathy
Thickener Hydroxypropylcellulose (0.1-1.0 MDa) (g) 2.50 5.00 10.00 20.00 - - - - 5.00 5.00 5.00 5.00 Polyvinylpyrrolidone (0.1-2.0 MDa) (g) - - - - 2.50 5.00 10.00 20.00 - - - - Amphipathy
Stabilizer PEG-23 glyceryl cocoate (g) - - - - - - - - 0.01 0.10 1.00 10.00 Softener Allantoin Proper Proper Proper Proper Proper Proper Proper Proper Proper Proper Proper Proper Diisobutyl adipic acid Proper Proper Proper Proper Proper Proper Proper Proper Proper Proper Proper Proper pH regulator Hydrochloric acid Proper Proper Proper Proper Proper Proper Proper Proper Proper Proper Proper Proper Sodium hydroxide Proper Proper Proper Proper Proper Proper Proper Proper Proper Proper Proper Proper solvent Purified water Proper Proper Proper Proper Proper Proper Proper Proper Proper Proper Proper Proper

Experimental Example 2: Amphipathy Thickener Viscosity of alcoholic disinfectant depending on whether added, residual amount after application and Drop Evaluation of occurrence

The viscosity of the alcoholic disinfectants prepared in Examples 3 and 7 to 14 was measured under appropriate test conditions (25°C, Spindle No. 18) using a rotary viscometer (Brookfield Digital Viscometer, Model DV-1), and the results It is shown in Table 4. In addition, 5 mL of the alcoholic disinfectant prepared in Examples 3 and 7 to 14 was applied to a pig skin surface similar to that of human skin, and then weighed after about 30 seconds to evaluate the weight reduction rate after application. Table 4 shows. In addition, 500 ml of the pumping vessel contained the alcoholic disinfectants prepared in Examples 3 and 7 to 14, and after pumping three times, it was observed whether or not a drop occurred at the distal end of the nozzle, and the results are shown in Table 4. Shown.

Viscosity (cps) Weight reduction rate after application (%) Whether a drop occurs Example 3 2.4 88.4 O Example 7 19.0 84.2 X Example 8 85.2 75.6 X Example 9 441.1 62.8 X Example 10 3992.0 45.9 O Example 11 15.8 87.7 X Example 12 47.5 77.9 X Example 13 261.2 66.7 X Example 14 2897.0 54.4 O

As shown in Table 2, when an amphiphilic thickener is not added, such as the alcoholic disinfectant prepared in Example 3, the viscosity is too low to show properties close to water, and accordingly, there is a problem in that drop occurs Is confirmed. In addition, it is confirmed that, like the alcoholic disinfectants prepared in Examples 10 and 14, when the content of the amphipathic thickener is too high, the viscosity is too high, the weight reduction rate after application is large, and the drop occurs. Therefore, when the content of the amphiphilic thickener per 100 mL of the alcohol disinfectant is 2.50 g to 10.00 g, such as the alcoholic disinfectants prepared in Examples 7 to 9 and Examples 11 to 13, the appropriate viscosity is maintained. It can be seen that the weight reduction rate is small and no drop occurs.

Experimental Example 3: Amphipathy Accumulated alcoholic disinfectants depending on whether stabilizers are added Chlorhexidine Gluconate Emission behavior evaluation

After applying 10 mL of the alcoholic disinfectant prepared in Examples 3, 8, and 15 to 18 to a pig skin surface (2 X 2 cm ² ) similar to human skin, and then drying for about 1 minute, about 10 mL of 0.01 M PBS, immersed in 37 °C, samples were collected over time, and fresh eluate was added. The sample collected according to each time point was analyzed for the main component content through a high-purity liquid chromatography method to calculate the cumulative release amount of chlorhexidine gluconate (%, compared to the input amount), and the results are shown in Table 5 and FIG. 1. Did.

Early
(%) 0.5 minutes later
(%) 1 minute later
(%) 2 minutes later
(%) 5 minutes later
(%) 10 minutes later
(%) 15 minutes later
(%) 30 minutes later
(%) 60 minutes later
(%) Example 3 0 7.8 12.1 13 13 13 13 13 13 Example 8 0 60.9 72.4 76.4 78.8 80.8 80.9 80.9 80.9 Example 15 0 60.2 68.7 74.4 78.8 81.4 83.4 83.4 83.4 Example 16 0 34.4 48.9 58.9 68.8 76.8 82.4 82.4 82.4 Example 17 0 24.4 36.8 47.4 55.9 64.6 70.9 79.8 88.1 Example 18 0 20.2 31.2 38.8 48.4 57.6 65.4 76.9 87.7

As shown in Table 5 and Figure 1, when the alcoholic disinfectant prepared in Example 3 does not contain both amphiphilic thickeners and amphiphilic stabilizers, the problem of significantly reduced cumulative release amount of chlorhexidine gluconate It is confirmed that there is. However, when the amphiphilic thickener was included, such as the alcoholic disinfectants prepared in Examples 8 and 15 to 18, it was confirmed that the cumulative release amount of chlorhexidine gluconate increased significantly. In particular, when additionally including an amphiphilic stabilizer, such as the alcoholic disinfectant prepared in Examples 15 to 18 (preferably, Examples 16 to 18), cumulative chlorhexidine while reducing the initial release amount of chlorhexidine gluconate By further increasing the amount of gluconate released, sustained release is possible and the antibacterial activity can be maintained for a long time. At this time, the PEG-23 glyceryl cocoate used as an amphiphilic stabilizer is characterized by having an HLB value of 10, which may exist at the interface between water and ethanol, thereby protecting chlorhexidine cluconate, thereby allowing sustained release. Antibacterial activity can be maintained for a long time.

Experimental Example 4: Amphipathy Evaluation of stability of alcoholic disinfectants over time in long-term and accelerated conditions depending on whether stabilizers are added

To evaluate the stability over time of the alcoholic disinfectants prepared in Examples 3, 8, 16 to 17 under long-term and accelerated conditions, the alcoholic disinfectants prepared in Examples 3, 8, 16 to 17 were filled and packaged in a polypropylene container. Samples were prepared and each sample was evaluated for stability for about 3 months in a stability chamber with long-term (25° C. temperature and 60% relative humidity) and accelerated (40° C. temperature and 75% relative humidity) conditions. Specifically, the relative content of chlorhexidine gluconate was measured after storage for about 3 months compared to the total content (dosage) of chlorhexidine gluconate through a high purity liquid chromatography method, and the results are shown in Table 6.

Relative content of chlorhexidine gluconate after storage for about 3 months (% by weight) Early Long term conditions Acceleration
Condition Example 3 100.1 98.4 92.4 Example 8 100.1 99.9 94.2 Example 16 100.0 99.9 98.9 Example 17 99.9 100.0 99.6

As shown in Table 6, when the alcoholic disinfectant prepared in Example 3 does not include both an amphiphilic thickener and an amphiphilic stabilizer, it is confirmed that there is a problem of deterioration of stability over time in long-term and accelerated conditions. . However, when the amphiphilic thickener is included, such as the alcoholic disinfectants prepared in Examples 8, 16, and 17, it has been found that stability over time is improved in long-term and accelerated conditions, in particular, in Examples 16 and 17. When an amphiphilic stabilizer, in addition to an amphiphilic thickener, such as an alcoholic disinfectant, is further included, it is confirmed that stability over time in long-term and accelerated conditions is further improved. At this time, the PEG-23 glyceryl cocoate used as an amphiphilic stabilizer is characterized by having an HLB value of 10, which may exist at the interface between an aqueous solution containing chlorhexidine cluconate and ethanol, thereby protecting chlorhexidine cluconate. Can.

The above description of the present invention is for illustration only, and a person having ordinary knowledge in the technical field to which the present invention pertains can understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, it should be understood that the embodiments described above are illustrative in all respects and not restrictive.

Claims (9)

Chlorhexidine or derivatives thereof;
Alcoholic solvents;
Amphipathic thickener; And
As an amphiphilic stabilizer, characterized in that it comprises a polyglyceryl fatty acid ester, alcoholic disinfectant with improved antibacterial persistence.
The method of claim 1.
The chlorhexidine or a derivative thereof is an alcoholic disinfectant with improved antimicrobial persistence, selected from the group consisting of chlorhexidine, chlorhexidine gluconate, chlorhexidine dihydrochloride and chlorhexidine diacetate.
The method of claim 1.
The amphiphilic thickener comprises hydroxyalkyl cellulose or polyvinylpyrrolidone, an alcoholic disinfectant with improved antimicrobial persistence.
According to claim 1,
The polyglyceryl fatty acid ester is characterized in that the hydrophile-lipophile balance (HLB) value is 8 to 12, an alcoholic disinfectant with improved antibacterial persistence.
According to claim 1,
The polyglyceryl fatty acid ester is at least one PEG system selected from the group consisting of PEG-23 glyceryl cocoate, PEG-7 glyceryl cocoate, PEG-20 glyceryl triisostearate and PEG-15 glyceryl monostearate. Alcoholic disinfectant with improved antibacterial persistence, a glyceryl fatty acid ester.
According to claim 1,
For 100 mL of the alcoholic disinfectant, 0.10 g to 5.00 g of the chlorhexidine or its derivatives; 50.00 g to 100.00 g of the alcoholic solvent; 1.00 g to 50.00 g of the amphipathic thickener; And characterized in that it comprises 0.01 g to 50.00 g of the polyglyceryl fatty acid ester, alcoholic disinfectant with improved antimicrobial persistence.
According to claim 1,
The alcoholic disinfectant is maintained at pH 5.5 to pH 6.5, an alcoholic disinfectant with improved antimicrobial persistence.
According to claim 1,
Viscosity at 25 ℃ the alcoholic disinfectant is characterized in that to maintain 10 cps to 2,500 cps, alcoholic disinfectant with improved antimicrobial persistence.
According to claim 1,
With respect to the total content of chlorhexidine or a derivative thereof,
Iv) The content of chlorhexidine or a derivative thereof is 99% by weight or more after storing the alcoholic disinfectant for 3 months in a long-term (25°C temperature and 60% relative humidity) condition,
Ii) The alcoholic disinfectant is an alcoholic disinfectant with improved antimicrobial persistence, characterized in that the content of chlorhexidine or a derivative thereof is at least 93% by weight after being stored for 3 months under accelerated conditions (temperature of 40°C and relative humidity of 75%). .

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