JP5359059B2 - Antibacterial film forming agent for outer skin - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a novel antifungal film-forming agent for epidermis, capable of forming a highly durable film on the skin, excellent in the fungal adhesion preventive property, and capable of inhibiting adhesion of fungi itself. <P>SOLUTION: The antifungal film-forming agent for epidermis is characterized by including copolymers 0.01-10 mass% , whose weight average molecular weight is 50,000-5,000,000, composed of 2-methacryloyloxy ethyl phosphoryl choline and a hydrophobic group-containing monomer expressed by the formula (1) (in the formula, L<SP>1</SP>is a group selected from a group consisting of -C<SB>6</SB>H<SB>4</SB>-, -(C=O)-NH-, -O-, -(C=O)-O-, and -O-(C=O)-O-, L<SP>2</SP>is a 1C-18C alkyl group, and R<SP>1</SP>is a hydrogen atom or methyl group.), at least one of low alcohol of 15-95 mass% selected from methanol, ethanol, isopropanol and normal propanol, and water. The antifungal film-forming agent is dried after application to be used. <P>COPYRIGHT: (C)2010,JPO&amp;INPIT

Description

  The present invention relates to a completely new antibacterial film-forming agent for outer skin that can form a highly durable film on the skin, has excellent antibacterial adhesion prevention properties, and suppresses bacterial adhesion itself.

  In recent years, there is concern about the spread of infectious diseases caused by pathogenic viruses and bacteria, and various infection prevention related products are being developed. Among them, hand sterilizers have the advantage that they can be sterilized and disinfected by simply applying or spraying them on the fingers during use, and do not need to be wiped off with towels. However, the above-mentioned disinfectant contains alcohol, reverse soap, etc. as disinfecting ingredients, so it induces skin damage to patients who are sensitive to these ingredients and nurses who use them on a daily basis. There was a case. In addition, many of the bactericidal components have an immediate effect and have no antibacterial activity.

  According to Patent Document 1, a copolymer of 2-methacryloyloxyethyl phosphorylcholine and a hydrophobic group-containing monomer is applied to a coating agent for biochemical plates, and has the effect of suppressing the adhesion of proteins and microorganisms. As is known, this exhibits a lubricating function when the surface of a material coated with a copolymer of 2-methacryloyloxyethyl phosphorylcholine and a hydrophobic group-containing monomer is wetted by a liquid such as a buffer solution or a medium. The present invention relates to a medical substrate.

  In addition, as an invention characterized by the formation of antibacterial film, Patent Document 2 discloses an antibacterial and antibacterial feature characterized by mixing 80% to 97% of inorganic material powder and 20% to 3% of inorganic copper powder. There is a composition. However, it cannot be used on the skin. Patent Document 3 discloses a dental composition for preventing caries for forming a film made of a water-soluble and / or aqueous emulsion polymer, but it cannot be used for outer skins such as fingers. Patent Document 4 describes a film-forming composition that can form a transparent and highly durable film on the surface of a substrate by drying, but it uses a photocatalyst and does not use it on the skin. There wasn't.

Under such circumstances, doctors and nurses working at medical institutions strongly demand a new type of antibacterial agent that can be used safely and constantly on the skin without causing skin problems. It was.
JP 2003-180801 A JP 2006-249041 A JP 2006-124293 A JP 2005-154750 A

  When using the antibacterial film forming agent for outer skins for fingers, it is required not only that the film formation is excellent, but also that the formed film is excellent in flexibility and follows the bending and stretching of fingers. If the film formation is inferior, the skin surface of the finger cannot be sufficiently covered, and if the film is inferior in flexibility, the film is damaged and the bacterial adhesion preventing property is insufficient. An object of the present invention is to provide an antibacterial film-forming agent for outer skin that contains a MPC polymer and exhibits high antibacterial adhesion after being applied to the skin.

  That is, a copolymer of 2-methacryloyloxyethyl phosphorylcholine (hereinafter sometimes abbreviated as MPC monomer) and a hydrophobic group-containing monomer (hereinafter abbreviated as MPC polymer) as a fungus adhesion preventing component. And a completely new antibacterial film forming agent for outer skin that suppresses bacterial adhesion itself.

  As a result of diligent investigations to solve the above problems, the present inventors have developed an antibacterial film forming agent for outer skin using a copolymer composed of an MPC monomer and a hydrophobic group-containing monomer. As a result, the present inventors have found that it exhibits high film-forming ability and excellent flexibility, and also exhibits high antibacterial adhesion prevention properties when applied on the skin, thereby completing the present invention.

That is, the present invention includes the following [1] and [2].
[1]
2-Methacryloyloxyethyl phosphorylcholine and formula (1)

(In the formula, L ¹ represents —C ₆ H ₄ —, — (C═O) —NH—, —O—, — (C═O) —O— and —O— (C═O) —O—). A group selected from the group consisting of: L ² represents an alkyl group having 1 to 18 carbon atoms, and R ¹ represents a hydrogen atom or a methyl group.) A coating containing 0.01 to 10% by mass of a copolymer having a weight average molecular weight of 50000 to 5000000, 15 to 95% by mass of one or more lower alcohols selected from methanol, ethanol, isopropanol, and normal propanol, and water, followed by drying. An antibacterial film-forming agent for outer skin,

[2]
Furthermore, the antibacterial film-forming agent for an outer skin according to the item [1], further comprising 0.01 to 5.0% by mass of a bactericide.

  According to the present invention, not only the film-forming property is excellent, but also the formed film is excellent in flexibility, excellent in anti-bacterial adhesion prevention following the bending and stretching of fingers, and can be used after drying. An antibacterial film-forming agent could be provided.

Hereinafter, the present invention will be described in more detail.
The antibacterial film-forming agent for the outer skin of the present invention contains an MPC polymer, has a high film-forming ability, is excellent in flexibility, and exhibits a high anti-bacterial adhesion preventing function when applied on the skin. it can.
The MPC polymer used in the present invention is obtained by copolymerizing MPC monomer and LA monomer.
As the MPC monomer, commercially available 2-methacryloyloxyethyl phosphorylcholine can be suitably used.
As the LA monomer, the following formula (1)

(In the formula, L ¹ represents —C ₆ H ₄ —, — (C═O) —NH—, —O—, — (C═O) —O— and —O— (C═O) —O—). A commercially available LA monomer represented by the following formula is used: L ² represents an alkyl group having 1 to 18 carbon atoms, and R ¹ represents a hydrogen atom or a methyl group.

  Specific examples of the LA monomer of the formula (1) include methyl (meth) acrylate, ethyl (meth) acrylate, butyl (meth) acrylate, lauryl (meth) acrylate, stearyl (meth) acrylate, and 2-ethylhexyl. (Meth) acrylate, benzyl (meth) acrylate, phenoxyethyl (meth) acrylate, cyclohexyl (meth) acrylate, polypropylene glycol mono (meth) acrylate, polytetramethyleneethylene glycol mono (meth) acrylate, polypropylene glycol di (meth) acrylate , Polytetramethyleneethylene glycol di (meth) acrylate, polypropylene glycol polyethylene glycol mono (meth) acrylate and the like. Of these monomers, butyl (meth) acrylate, lauryl (meth) acrylate, and stearyl (meth) acrylate are more preferable from the viewpoint of film forming ability, film flexibility, and adhesion to the skin. These LA monomers can be used alone or as a mixture of two or more in the production of the MPC polymer.

  The LA monomer plays an important role in adhering the MPC polymer onto the skin when it constitutes the MPC polymer. This is because inclusion of the LA monomer improves the film-forming property and film flexibility of the MPC polymer, and the hydrophobic group in the LA monomer exhibits an anchoring effect on the skin. This is for improving the adhesion between the MPC polymer film and the skin.

  The MPC polymer used in the present invention may be a commercially available product, but a known method such as solution polymerization, emulsion polymerization, suspension polymerization or the like for a monomer composition containing an MPC monomer and an LA monomer. Can also be obtained by polymerization according to For example, in the case of solution polymerization, the monomer composition is dissolved in an organic solvent such as lower alcohol, and a radical polymerization initiator such as an azo compound or a peroxide is added under an atmosphere of an inert gas such as nitrogen or argon. The MPC polymer used in the present invention can be obtained by heating and stirring.

  The MPC polymer used for the antibacterial film-forming agent for outer skin of the present invention is composed of MPC monomer and LA monomer, but preferably has a copolymer composition ratio derived from MPC monomer. A copolymer having a copolymer composition ratio of 90 to 10 mol% derived from 10 to 90 mol% and LA monomer is used. That is, the copolymer composition ratio of each monomer in the MPC polymer can be appropriately selected within the range of 10:90 to 90:10 (MPC monomer: LA monomer, mol%). The copolymer composition ratio derived from each monomer is more preferably in the range of 30:70 to 80:20 (mol%) from the viewpoints of film-forming properties and fungus adhesion prevention function. When the copolymerization composition ratio of the MPC monomer is less than 10 mol%, sufficient ability to prevent bacterial adhesion may not be obtained, and when the copolymerization composition ratio of the LA monomer is less than 10 mol%, sufficient Since film forming ability may not be obtained, it is not preferable.

The weight average molecular weight of the MPC polymer used for the antibacterial film-forming agent for the outer skin of the present invention can be appropriately selected within the range of 50,000 to 5000000, but from the viewpoint of film forming property and ease of handling, 100,000 to 3000000. The range of is more preferable.
The blending amount of the MPC polymer in the antibacterial film forming agent for the outer skin can be appropriately selected within a range of 0.01 to 10% by mass. The range of 05-5 mass% is more preferable.
The form of the MPC polymer used for the production of the antibacterial film-forming agent for the outer skin of the present invention may be any of powder, solution or uniformly dispersed liquid.

  The antibacterial film-forming agent for outer skin of the present invention contains a lower alcohol for the purpose of facilitating uniform application to the skin. By containing a lower alcohol, the interfacial tension of the preparation is lowered and easily spreads on the skin, so that the feeling in use is improved and the uniformity during film formation is also improved. Examples of the lower alcohol used in the present invention include methanol, ethanol, isopropanol, and normal propanol. When used, one or more kinds of lower alcohols may be mixed. Among these, ethanol and / or isopropanol are more preferable from the viewpoints of odor and usability. The content rate of a lower alcohol is 15-95 mass% in the antibacterial film-forming agent for outer skins of this invention, Preferably it is the range of 25-85 mass%. When the content is less than 15% by mass, unevenness occurs in the obtained film. Further, even if the content ratio exceeds 95% by mass, the effect on the uniformity of the film does not change.

  The antibacterial film-forming agent for outer skin of the present invention contains water in addition to the MPC polymer and the lower alcohol. By using a mixed solvent of lower alcohol and water, the adhesion of the MPC polymer to the skin can be improved. This is because the transpiration rate of lower alcohol and water is different when the preparation is dried, and the phosphorylcholine group in the MPC polymer is oriented closely to the air interface, and the hydrophobic group is effective at the skin interface. This is for the purpose of orientation. The water used in the present invention is not particularly limited, but it is preferable to use ion-exchanged water, purified water, water for injection, or the like having a low impurity content. The content rate of water is 5-85 mass% in the antibacterial film-forming agent for outer skins of this invention, Preferably it is the range of 15-75 mass%. When the content ratio is less than 5% by mass or when the content exceeds 85% by mass, the adhesion of the MPC polymer to the skin is undesirably reduced.

  Moreover, the antibacterial film-forming agent for outer skin of the present invention may contain a wetting agent without departing from the object of the present invention. Examples of the wetting agent include ethylene glycol, propylene glycol, dipropylene glycol, 1,3-butylene glycol, 1,4-butylene glycol, pentylene glycol, hexylene glycol, isoprene glycol, ethylhexanediol, and isopentyldiol. And polyol compounds such as glycerin, diglycerin, polyglycerin, sorbitol, xylitol, maltitol, mannitol, erythritol and the like, and can be used alone or as a mixture of two or more. Among these wetting agents, propylene glycol, dipropylene glycol, 1,3-butylene glycol and glycerin are more preferable because of their familiarity with the outer skin. The ratio when the wetting agent is contained is usually 0.1 to 5.0% by mass with respect to the total amount of the antibacterial film forming agent for the outer skin as long as the desired effect of the present invention is not impaired.

  The antibacterial film-forming agent for outer skin of the present invention may preferably further contain a bactericidal agent in order to reduce the bacteria originally present on the outer skin. As the bactericidal agent used in the present invention, those that do not inhibit the film-forming property of the MPC polymer can be used. Cationic surfactants such as benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, chlorhexidine gluconate, hydrochloric acid A biguanide compound such as chlorhexidine, an iodine compound such as iodine ion, iodoform, and povidone iodine, an inorganic compound such as silver ion, and a phenol compound such as cresol and isopropylmethylphenol can be blended. In using these, 1 type or 2 types or more can be mixed and used in the range of 0.01-5.0 mass% in the antibacterial film-forming agent for outer skins.

  In addition, the antibacterial film-forming agent for outer skin of the present invention may contain additives used for known external preparations in addition to the above components. Examples of the additive include a thickener, a foaming agent, an aerosol agent, an organic acid, an antioxidant, a stabilizer, an antiseptic, a sequestering agent, a fragrance, a dye, and a coloring material. It can mix | blend in the range which is not impaired.

In the production of the antibacterial film forming agent for an outer skin of the present invention, the respective components may be appropriately mixed. For example, it can also be produced as follows. When the MPC polymer is in the form of powder, it is added to water and mixed well with stirring to dissolve it uniformly. When the MPC polymer is in the form of a solution or a uniformly dispersed liquid, it is made uniform by stirring and mixing in addition to water. By adding a lower alcohol to the MPC polymer solution thus obtained and mixing it, a bacteriostatic film-forming agent for the outer skin can be easily obtained.
When adding other components such as bactericides and additives, add these components to water or alcohol in advance, stir and mix, dissolve well, and then mix with the MPC polymer solution to prevent bacteriolysis for the skin. A film-forming agent can be easily obtained.

  Regarding the shape of the antibacterial film forming agent for the outer skin of the present invention, from the viewpoint of convenience and safety during use, a liquid discharge type filled in a container with a dispenser pump, a spray type filled in a container with a spray pump, a former A foam discharge type filled in a container with a pump or an aerosol container is desirable. In any case, in use, the effect can be obtained by taking an appropriate amount of about 1 to 3 mL of the antibacterial film-forming agent for the skin, applying it while rubbing it into the hand, and drying. In particular, if the antibacterial film forming agent for the outer skin does not dry and the skin is still wet, the drug is wiped off from the coated surface by contact with the article, etc. It is preferable to dry the antibacterial film-forming agent for the skin on the skin. Care must be taken since the effect of preventing adhesion of bacteria may not be sufficiently exerted if the drying is insufficient after application to the skin.

Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples.
Example 1
A 5% aqueous solution of 2-methacryloyloxyethyl phosphorylcholine (MPC) and n-butyl methacrylate (BMA) copolymer (MPC / BMA = 8/2) (hereinafter abbreviated as MPC polymer A) in 73.0 g of purified water. 2.0 g (polymer solid content 0.1 g, containing purified water 1.9 g) was added and stirred until the system was uniform. Next, 25.0 g of ethanol was added and stirred until the system was uniform to prepare 100 g of an antibacterial film forming agent for outer skin. About this, the following (evaluation of the film-forming property of the antibacterial film-forming agent for skin), (evaluation of the film flexibility and film uniformity of the anti-bacterial film-forming agent for skin), Evaluation of fungus adhesion prevention function) was performed, and the determination results are shown in Table 1.

(Evaluation of film forming property of antibacterial film forming agent for outer skin)
The film forming property of the antibacterial film forming agent for outer skin of the present invention was evaluated by the following method. That is, a predetermined amount of the antibacterial film-forming agent for the outer skin was taken, spread on a fluororesin-treated petri dish, dried at room temperature, and then dried at 40 ° C. under reduced pressure. After drying, when the solid was obtained in the form of a film, it was judged that there was film-forming property, and when it was not obtained as a film (such as paste or powder), it was judged that there was no film-forming property.
<Judgment result; film-forming property>
Filmed: ○, not filmed: ×

(Evaluation of film flexibility and film uniformity of antibacterial film forming agent for skin)
The film flexibility of the antibacterial film forming agent for outer skin of the present invention was evaluated by the following method. That is, after taking a predetermined amount of the antibacterial film-forming agent for outer skin of the present invention, applying it to artificial leather (white) and drying at room temperature, it was placed in an environment with an air temperature of 30 ° C. and a relative humidity of 65% for 15 minutes. The film was bent at a right angle to evaluate whether a crack occurred in the coating layer. It was determined that there was flexibility when no crack occurred, and that there was no flexibility when crack occurred.
The film uniformity was evaluated by the following method. That is, using an antibacterial film forming agent for outer skin colored in advance in advance, it was applied to artificial leather by the same method as described above, and after drying, color unevenness was visually judged to evaluate film formation uniformity.
<Judgment result; film flexibility>
No crack occurred: ○, Crack occurred: ×
<Judgment result; film uniformity>
No unevenness: ○, unevenness: ×

(Evaluation of antibacterial function of antibacterial film forming agent for outer skin)
Take 3 mL of commercially available disinfectant ethanol and rub it for 20 seconds twice. After the fingers are sufficiently dried, put the palm on the palm stamp (Niken Biomedical Research Institute, General Bacterium (SCD) Medium). Stamped. Next, the operation of taking 3 mL of the antibacterial film-forming agent for outer skin of the present invention with a finger and rubbing for 20 seconds was performed twice, and the subject was allowed to live as usual, and after 3 hours, stamping was similarly performed. For each preparation, the same operation was performed by 5 subjects. Each medium after stamping was cultured in an incubator at 37 ° C. for 24 hours, and the number of fungal colonies was counted on the medium. The number of colonies immediately after disinfection (A) and the number of colonies (B) after 3 hours from the application of the antibacterial film-forming agent for outer skin were counted, and the respective logarithmic values (logA, logB) were calculated. A value obtained by subtracting log A from log B was defined as “log increase value”, and an average of 5 subjects was calculated to calculate “average log increase value”. Regarding the fungus adhesion prevention function, the average log increase value was determined to be significantly less than 0.3, 0.3 to less than 1.0 was effective, and 1.0 or more was determined to be invalid.
<Judgment result; fungus adhesion prevention function>
Remarkable: ◎, valid: ○, invalid: ×

(Explanation of the table)
* Polymer component MPC polymer A: copolymer of 2-methacryloyloxyethyl phosphorylcholine (MPC) and n-butyl methacrylate (BMA) (MPC / BMA = 8/2)
MPC polymer B: copolymer of MPC and BMA (MPC / BMA = 3/7)
MPC polymer C: copolymer of MPC and lauryl methacrylate (LMA) (MPC / LMA = 3/7)
MPC polymer D: copolymer of MPC and stearyl methacrylate (SMA) (MPC / SMA = 3/7)

** Average log increase (5 subjects)
= {Log (number of colonies after 3 hours after application) -log (number of colonies immediately after disinfection)} / 5
Criteria: Less than 0.3: Excellent, 0.3 or more and less than 1.0: Valid, 1.0 or more: Invalid

Examples 2-7
100 g of the antibacterial film-forming agent for outer skins of Examples 2 to 7 were prepared according to the method described in Example 1 except that the types and amounts of the ingredients were changed as shown in Table 1. About this, it is the same as Example 1 (evaluation of the film forming property of the antibacterial film forming agent for the outer skin), (evaluation of the film flexibility and film uniformity of the antibacterial film forming agent for the outer skin), Evaluation of the function of the film-forming agent for preventing bacterial adhesion was performed, and the determination results are shown in Table 1.

Example 8
To 64.9 g of purified water, 0.1 g of glycerin was added and stirred until the system was uniform. Next, 10.0 g of a 5% aqueous solution of MPC polymer A (containing 0.5 g of polymer solids and 9.5 g of purified water) was added and stirred until the system was uniform. Next, 25.0 g of ethanol was added and stirred until the system was uniform to prepare 100 g of an antibacterial film forming agent for outer skin. About this, it is the same as Example 1 (evaluation of the film forming property of the antibacterial film forming agent for the outer skin), (evaluation of the film flexibility and film uniformity of the antibacterial film forming agent for the outer skin), Evaluation of the function of the film-forming agent for preventing bacterial adhesion was performed, and the determination results are shown in Table 1.

Examples 9-11
Using the chlorhexidine gluconate, hydroxypropyl cellulose, polysorbate 80 instead of glycerin, and changing the blending amount as shown in Table 1, according to the method described in Example 8, the outer skin of Examples 9-11 100 g of each antibacterial film forming agent was prepared. About this, it is the same as Example 1 (evaluation of the film forming property of the antibacterial film forming agent for the outer skin), (evaluation of the film flexibility and film uniformity of the antibacterial film forming agent for the outer skin), Evaluation of the function of the film-forming agent for preventing bacterial adhesion was performed, and the determination results are shown in Table 1.

Comparative Examples 1-5
Samples of Comparative Examples 1 to 5 and 100 g of each were prepared according to the method described in Example 1 except that the types and amounts of the ingredients were changed as shown in Table 2. About this, it is the same as Example 1 (evaluation of the film forming property of the antibacterial film forming agent for the outer skin), (evaluation of the film flexibility and film uniformity of the antibacterial film forming agent for the outer skin), Evaluation of the anti-fungus adhesion function of the film-forming agent) was performed, and the determination results are shown in Table 2.

  From the above Examples and Comparative Examples, it was revealed that the antibacterial film forming agent for outer skin of the present invention is superior in the uniformity of the film than the sample used in the Comparative Example, and further excellent in the function of preventing bacterial adhesion. . When the uniformity of the film is not maintained, the antibacterial film is not formed, and the function of preventing the adhesion of bacteria is not exhibited. Therefore, it is important for the present invention to obtain the film uniformity. In the antibacterial film-forming agent for outer skin of the present invention, since the blending ratio of MPC polymer, lower alcohol and water is appropriately controlled, the phosphorylcholine group can be densely oriented at the air interface, and the skin It was possible to maintain the uniformity of the film having phosphorylcholine groups and to exert antibacterial effects.

Claims (2)

It is an antibacterial film-forming agent for the skin that is used after being applied and dried,
A copolymer having a weight average molecular weight of 50,000 to 5,000,000, composed of 2-methacryloyloxyethyl phosphorylcholine and a hydrophobic group-containing monomer represented by the following formula (1);

(In the formula, L ¹ represents —C ₆ H ₄ —, — (C═O) —NH—, —O—, — (C═O) —O— and —O— (C═O) —O—). A group selected from the group consisting of: L ² represents an alkyl group having 1 to 18 carbon atoms, and R ¹ represents a hydrogen atom or a methyl group.)
15 to 95% by mass of one or more lower alcohols selected from methanol, ethanol, isopropanol, and normal propanol ;
15-75% by weight of water
An antibacterial film-forming agent for outer skin containing   Furthermore, the antibacterial film-forming agent for outer skins of Claim 1 containing 0.01-5.0 mass% of bactericides.