JP6304506B2 - Gel for external use - Google Patents

Description

  The present invention relates to an external gel agent that does not require an alcohol-based component and / or a hypochlorous acid-based component, and that can maintain the gel state for a certain period of time after the gel state is formed.

  In the present invention, “external use” means that the gel of the present invention is applied by means other than “internal use and injection” (Yodogawa Pharmaceutical University Dictionary, 5th edition, 268 pages, 2013, (See Yodogawa Shoten). As long as it is applied by means other than “internal use and injection”, the subject, method and means to which the gel of the present invention is applied are not particularly limited. The gel agent of the present invention can be suitably applied to the skin surface, mucous membrane, and the like by means of application, gargling, spraying, spraying, etc., for the purpose of disinfection and cleaning, for example.

  With the recent consumer trend (cleanliness orientation), there is an increasing need for antibacterial and antibacterial agents for external use on the entire skin external surface including fingers, arms and legs. In particular, since the summer of 1996, when pathogenic Escherichia coli (enteric hemorrhagic Escherichia coli) O-157 has become violent, the number and types of sanitized products have increased.

  Although it is data of a private research company, the scale of the deodorizing, deodorizing and sanitizing market exceeded 100 billion yen (based on sales amount) in FY2005, and then the economy deteriorated to 113.9 billion yen in 2008 Although the growth rate slowed down due to the impact of the new flu, the number increased in 2009, when there was a new influenza turmoil, and the subsequent market has also been improving. Furthermore, according to a survey by the JPO, “Inorganic antibacterial agents and natural organic antibacterial agents are expected to grow, and when antibacterial products are applied with inorganic antibacterial agents, a huge market of about 800 billion yen market. It is.

  In addition to the above, recently there have been many news of new infectious diseases such as O-157 and bird flu, and the bacteria and viruses that cause them are "invisible to the eye". For this reason, there is a tendency that the need for “sanitization” and “antibacterial” products is even higher.

  Furthermore, with the recent support of natural thinking, antibacterial and antifungal agents are safer and less toxic than synthetic organic antibacterial and antifungal agents, and gradually release antibacterial components to prolong antibacterial properties. There is an increasing need for inorganic antibacterial and antifungal agents with durability to maintain, as well as natural sanitizing and antibacterial agents with high safety.

  There are, of course, a very large number of sanitized products currently on the market. For example, Patent Document 1 (Japanese Patent Laid-Open No. 11-302146) describes an external gel agent containing an alcohol component. Patent Document 2 (Japanese Patent Application Laid-Open No. 2014-114291) describes an external gel agent containing a hypochlorous acid component. As described above, some “non-alcoholic” products exist, but most are gels for external use mainly composed of “alcohol” or “sodium hypochlorite”. Both “alcohol” and “sodium hypochlorite” have an excellent disinfecting effect, but there are points that should be “cautioned in use”.

(About alcohol)
Conventionally, “alcohol” is a general term for ethanol (ethyl alcohol), methanol (methyl alcohol), isopanol (isopropyl alcohol), and the like. Traditionally, the alcohols used for disinfection were ethanol and isopropanol, which are said to have relatively low toxicity to humans. Among conventional gels for external use, pure ethanol increases the cost due to taxation under the Liquor Tax Law, so that 2-propanol, a kind of secondary alcohol, is added to ethanol for tax reduction purposes, Some products were combined with 2-propanol or benzalkonium chloride.

Here, the use of alcohol has the following advantages and disadvantages. The merit is that it is excellent in quick-drying and fast-acting properties, is highly safe, and has an antibacterial effect against various bacteria (excluding spores). On the other hand, the disadvantages include the following.
・ Ineffective against bacteria and noroviruses that form spores.
・ Stimulation on skin, leather and artificial leather is strong, causing rough hands and leather surface deterioration.
・ Since it evaporates immediately, there is no continuous sterilization effect.
-When used in a wet state (that is, with a reduced alcohol concentration), the effect is diminished.
・ It is flammable due to high volatility (easily vaporized)
・ There is a strong odor of alcohol.

(Sodium hypochlorite)
The use of sodium hypochlorite has the following advantages and disadvantages. The merit is that it is fast acting and has antibacterial effects against various bacteria (expectation can be expected for spores and noroviruses). On the other hand, the disadvantages include the following.
-Expert elements of handling such as dilution concentration by the object are high.
Strong irritation to skin, leather and artificial leather, causing rough hands and deterioration of the leather surface.
-There are restrictions on the objects of use, such as deterioration of plastic and rubber products, corrosion of metals, bleaching action (use precautions for color and patterned linens).
・ Chlorine gas is generated when there is a chlorine odor and acidic substances are mixed.
(Non-alcohol disinfectant)
Regarding the need for non-alcohol-based disinfectants (for example, disinfecting gels), there are the following possibilities.
(1) About “alcohol” allergy It is said that about half of Japanese people do not have ALDH2 (aldehyde dehydrating enzyme) or its function is weak and may cause alcohol allergy. The method by which alcohol is absorbed in the body is not limited to drinking. For example, it may be ingested from the skin by noticing and touching things that have been wiped with alcohol or mixed things (sanitized sheets, wet tissues, disinfectants, detergents, makeup, etc.).

(2) About the expanding halal market (discipline of halal and Muslim) In the Islamic norm “Islamic law”, alcohol is considered to disturb the spirit, and it is prohibited to use it. Contained seasonings must also be avoided. Halal's strict rules are established not only for food, but also for the manufacturing process of cosmetics and pharmaceuticals that touch the skin.

Regarding the “halal” market, the following can be mentioned.
・ The population of ASEAN countries is 600 million, of which 40% are Muslims.
-40% of the population of ASEAN, whose population and economy are growing rapidly, is Muslim, and the majority is concentrated in Indonesia (88% of the population of 250 million, and 28 million in Malaysia is Muslim). doing.
・ There are 500 million Muslims in South Asia, 180 million in India, 1.7 billion in Pakistan, 140 million in Bangladesh, a total of 500 million Muslims doing. There are 300 million people in West Asia such as the Middle East. In Asia, more than 1 billion people are Muslims, accounting for 40% of the Asian population.

・ The halal market is 60 trillion yen. Of that, Asia is 35 trillion yen.
・ The Muslim food market (halal market) around the world is $ 580 billion (60 trillion yen). Asia's total is 345 billion dollars (35 trillion yen), which is 60% of the world.
・ The number of Muslims in Japan is 100,000 and the halal market in Japan is 54 billion yen.
・ About 100,000 Muslims in Japan. The largest number is about 20,000 in Indonesia.
・ About 50,000 Muslims are Japanese. A total of 150,000 people live (the halal market is approximately 54 billion yen).

・ There are 350,000 Muslims visiting Japan. The halal food market in Japan is approximately 2.5 billion yen, and accommodation and souvenirs are 10 billion yen (12.5 billion yen in total).
-With the increase in the Olympics and international conferences, Muslims visiting Japan are expected to double in 1 or 2 years.
(Source: Brand Research Institute materials)

JP-A-11-302146 JP 2014-114291 A

  The object of the present invention is to eliminate the above-mentioned drawbacks of the prior art and maintain the gel state for a certain period of time after the gel state is formed without requiring an alcohol component and / or a hypochlorous acid component. An object of the present invention is to provide a gel for external use.

  As a result of diligent research, the present inventor has found that an external gel containing at least water, a hydroxide and a thickener, even in the case of not using an alcohol component and / or a hypochlorous acid component as in the prior art. And the gel state of the external gel agent lasts for a certain period of time (specifically, when the external gel agent is in a gel state and then left in a sealed container at 25 ° C., the gel state is 24. It has been found that it is extremely effective to achieve the above-mentioned purpose.

  The external gel agent of the present invention is based on the above findings, and more specifically, an external gel agent containing at least water, a hydroxide, and a thickener; and after the gelling of the external gel, 25 ° C.) The gel state can be maintained for 24 hours or more when left in a closed container.

  The present invention can include, for example, the following aspects.

[1] An external gel agent containing at least water, a hydroxide and a thickener; and 24 hours when left in a closed container at room temperature (25 ° C.) after gelling the external gel agent The gel state can be maintained.
It said hydroxide, topical gels, characterized in that selected hydroxides of alkali metals, hydroxides of alkaline earth metals, and hydroxides of tetraalkylammonium.

[2] before Kisui oxide, calcium hydroxide (Ca _{(OH) 2)} Lithium hydroxide (LiOH), sodium hydroxide (NaOH), potassium hydroxide (KOH), rubidium hydroxide (RbOH), and water The gel agent for external use according to [1], which is selected from cesium oxide (CsOH).

[3] The alkaline earth metal hydroxide is strontium hydroxide (Sr (OH) ₂ ), barium hydroxide (Ba (OH) ₂ ), europium hydroxide (II) (Eu (OH) ₂ ), And the gel for external use according to [1], which is selected from thallium hydroxide (I) (TlOH).

[4] In [1], the tetraalkylammonium hydroxide is selected from tetramethylammonium hydroxide (N (CH ₃ ) ₄ OH) and tetraethylammonium hydroxide (N (C ₂ H5) ₄ OH). The gel for external use as described.

  [5] In any one of [1] to [4], the calcium hydroxide is calcium hydroxide generated from a shell, coral, egg shell, limestone (for example, marble, stalactite, chalk) or the like. The gel for external use as described.

  As described above, according to the present invention, an external gel agent that does not require an alcohol component and / or a hypochlorous acid component and can maintain the gel state for a certain time after the gel state is formed. Can be obtained.

  According to the present invention, it is possible to obtain an external gel agent that has an appropriate viscosity, can be uniformly applied onto the skin, and is substantially free from stickiness when dried.

  Further, according to the present invention, it is possible to obtain a gel agent for external use that does not require a “rinsing” operation after gel application.

It is a graph which shows an example of the viscoelasticity measurement result of the gel for external use of this invention.

  Hereinafter, the present invention will be described more specifically with reference to the drawings as necessary. In the following description, “parts” and “%” representing the quantity ratio are based on mass unless otherwise specified.

(External gel)
The external gel agent of the present invention can maintain the gel state for a certain period of time after the gel state is formed without requiring an alcohol-based component and / or a hypochlorous acid-based component. Here, in the present invention, “without requiring an alcoholic component” means that the “alcohol component” is not essential (that is, in an embodiment not containing an alcoholic component) and is externally applied to the present invention. It means that the original effect of the gel agent (that is, having an appropriate antibacterial property and capable of maintaining the gel state for a certain time after the gel state is formed) can be exhibited.

(Alcohol component)
In the present invention, the “alcohol component” refers to an alcohol compound having 1 to 10 carbon atoms and 1 to 4 “OH groups”. The content of such an alcohol component can be measured, for example, by gas chromatograph mass spectrometry or GC / MS (SIM) analysis. For details of the alcohol component analysis, for example, the following URL can be referred to as necessary.
http://www.ube-ind.co.jp/usal/documents/f074_142.htm
http://www.an.shimadzu.co.jp/gcms/support/faq/fundamentals/index.htm
Regarding the details of the alcohol analysis, for example, “trimethylsilylation → GC-MS analysis method” at the following URL can be suitably used as necessary.
http://www.jsac.or.jp/bunseki/pdf/bunseki2008/200807nyumon.pdf (derivatization for GC / MS, LC / MS)

(Hypochlorous acid component)
The external gel agent of the present invention is capable of maintaining the gel state for a certain period of time after the gel state is formed without requiring a hypochlorous acid component. Here, in the present invention, “without requiring a hypochlorous acid-based component” means that the “hypochlorous acid” is not essential (that is, in a mode not containing a hypochlorous acid-based component). In addition, the original effect of the gel preparation for external use of the present invention (that is, having an appropriate antibacterial property and capable of maintaining the gel state for a certain period of time after the gel state is formed) can be exhibited. Say.

In the present invention, the “hypochlorous acid component” is sodium hypochlorite (chemical formula is NaClO) obtained through chlorine in an aqueous solution of sodium hydroxide, an aqueous solution obtained by electrolyzing a sodium chloride aqueous solution or hydrochloric acid. Says certain hypochlorous acid water. The content of such a hypochlorous acid component can be measured by, for example, gas chromatography mass spectrometry when the amount is small, and syringaldazine method when the amount is large. In addition, it can be measured by an ion chromatography and a quantitative analysis method of “sodium hypochlorite sample solution for ammonium test”. For details of the hypochlorous acid analysis, for example, the following URL can be referred to as necessary.
http://www.an.shimadzu.co.jp/hplc/ic/ic.htm
http://www.jaima.or.jp/jp/basic/chromatograph/ion-chromatography.html
Article "Hypochlorous acid" in the "11th revision Japanese Pharmacopoeia Commentary" (Yodogawa Shoten, 1986)

For trace analysis of hypochlorous acid components using the GC-MS method, for example, the following URL (quantitative determination of hypochlorous acid in foods by GC-MS) can be suitably used.
http://www.pref.okinawa.jp/site/hoken/eiken/syoho/documents/s34_12gc-ms.pdf

(Change in gel condition)
In the gel for external use of the present invention, the gelled state is maintained for a long time when the gelled state is formed by (predetermined concentration of calcium hydroxide aqueous solution + thickener) and then left in a closed container. (For specific conditions, refer to Example 4 described later).

  When the gel for external use of the present invention is left in a closed container as described above, it is preferable that the gel state can be maintained for 24 hours or more. This “gel state” holding time is preferably 30 hours or longer, more preferably 48 hours or longer, further preferably 72 hours or longer, further preferably 96 hours or longer, more preferably 120 hours or longer, particularly It is preferably 144 hours or longer.

(Change in gel condition)
In the gel for external use of the present invention, the change in the gelled state can be confirmed more specifically by viscoelasticity measurement (refer to Example 2 described later for viscoelasticity measurement). it can). When viscoelasticity at the initial stage of gelation (for example, 24 hours after gelation) is V1 (mPa · S) and viscoelasticity after t time (hr) has elapsed from gelation is V2 (mPa · S) Furthermore, at the time of t = 48 hours, it is preferable that the viscoelastic reduction rate Rv = 100 × (V1−V2) / V1 (%) is 50% or less. The value of Rv is further preferably 45% or less, further preferably 40% or less, further preferably 35% or less, and further preferably 25% or less, Furthermore, it is preferably 20% or less, more preferably 18% or less, further preferably 16% or less, further preferably 14% or less, and further preferably 12% or less. It is preferable that it is 10% or less. In the case of V2 ≧ V1 (that is, when the viscosity increases after gelation), these numerical values satisfy the condition of the reduction rate Rv (assuming that Rv = zero).

(Change in pH)
In the gel for external use of the present invention, when the pH immediately after gelation is P1, and the pH after elapse of t time (hr) is P2, the rate of decrease in pH at t = 48 hours. Pv = 100 × (P1−P2) / P1 (%) is preferably 20% or less. The value of Rv is further preferably 18% or less, more preferably 16% or less, further preferably 14% or less, and further preferably 12% or less, Further, it is preferably 10% or less, more preferably 8% or less, further preferably 7% or less, further preferably 6% or less, particularly 5% or less. It is preferable. In the case of P2 ≧ P1, these numerical values satisfy the above-described decrease rate Pv (assuming that Pv = zero).

(Thickener)
In the present invention, the thickener is not particularly limited. That is, the thickener that can be used in the present invention is not particularly limited as long as it provides a suitable gelation state in combination with (water + hydroxide) which is an essential component of the external gel composition of the present invention. Moreover, in this invention, it is also possible to use 2 or more types of thickeners by combining by mixing etc. as needed. Thus, "whether it gives suitable gel state in combination with (water + hydroxide product)" may be the screening of Example 4 described later, to confirm easily.

(Preferred thickener)
(Water-soluble cellulose thickener)
In the present invention, from the viewpoint of compatibility in the combination of (water + hydroxide), a water-soluble cellulose-based thickener can be preferably used. Examples of such water-soluble cellulose-based thickeners include the following.
CMC (carboxymethylcellulose), HEC (hydroxyethylcellulose), HPMC (hydroxypropylmethylcellulose), CVP (carboxyvinylpolymer / carbomer), decyltetradeceth-20 / HDI copolymer

In the present invention, a nonionic water-soluble cellulose ether-based thickener can be preferably used. Examples of such nonionic water-soluble cellulose ether-based thickeners include the following.
HEC (hydroxyethylcellulose), HEMC (hydroxyethylmethylcellulose), HPMC (hydroxypropylmethylcellulose), MC (methylcellulose)

In the present invention, from the viewpoint of compatibility in the combination with (water + hydroxide) as described above, a water-soluble cellulose-based thickener can be preferably used. Examples of the system thickener (for example, a water-soluble cellulose ether-based thickener) include the following.
CMC (carboxymethylcellulose), HEC (hydroxyethylcellulose), HPMC (hydroxypropylmethylcellulose), CVP (carboxyvinylpolymer / carbomer), decyltetradeceth-20 / HDI copolymer, HEMC (hydroxyethylmethylcellulose), overlapping HPMC (hydroxypropyl) Methylcellulose), MC (methylcellulose) overlap HPMC (hydroxypropylmethylcellulose).

(Especially preferred thickener)
In the present invention, as the “nonionic water-soluble cellulose ether-based thickener”, various etherifying agents (for example, after natural or synthetic cellulose is treated with an alkali (for example, sodium hydroxide)). , Methyl chloride, ethylene oxide, propylene oxide, etc.) and “methylcellulose-based” (MCE type) and “hydroxypropylmethylcellulose-based” (HPMC type) thickeners which can be suitably used.

As the MCE type, for example, a methoxy (—OCH ₃ ) group = about 25 to 33% (for example, a compound having CAS No. = 9004-67-5) can be suitably used. On the other hand, as the HPMC type, for example, the following can be preferably used.
<Methoxy group><Hydroxypropoxygroup>
(-OCH ₂ CHOHCH ₃₎
27-30% 4-7.5%
(For example, compound of CAS No. = 9004-65-3)
27-30% 7-12%
19-24% 4-12%

In the present invention, it is preferable to use a thickener that satisfies one or more of the following conditions. The thickener further preferably satisfies two or more of the following conditions, and further preferably satisfies three of the following conditions.
(A) methyl (--CH3) or methoxy (--OCH3) providing a hydrophobic prompting a reduction in the cellulosic hydroxyl hydrogen bonding, and / or that has a group replaced with hydroxycarboxylic propoxy group.
(B) Nonionic properties that are not easily affected by salts and metal ions.
(C) The viscosity standard value (for example, the viscosity standard value described in the “catalog” of the product) is 3,500 to 15,000 mPa · s.
Examples of the thickener that satisfies the above conditions include SH65-4000, SH65-15000, SH90-15000, manufactured by Shin-Etsu Chemical Co., Ltd.

(Preferred thickener)
In the present invention, a cellulose-based thickener having a methoxy (—OCH ₃ ) group and a hydroxypropoxy group (—OCH ₂ CHOHCH ₃ ) is preferable. Here, the content of the methoxy group in the thickener is preferably 15 to 40%, more preferably 18 to 35%, and further preferably 19 to 33%. It is preferable that it is 19 to 31% (for details of the content of such a methoxy group, for example, a table of “Metroze” (trade name) described later can be referred to). On the other hand, the content of the hydroxypropoxy group is preferably 3 to 18%, more preferably 3.5 to 16%, further preferably 4 to 15%, particularly 4 to 13%. (For details of the content of such a hydroxypropoxy group, for example, the “Metroze” table described later can be referred to).

(hydroxide)
The hydroxide that can be used in the present invention is not particularly limited as long as it is selected from an alkali metal hydroxide, an alkali metal earth metal hydroxide, and a tetraalkylammonium hydroxide. That is, as long as a suitable gelation state is given in combination with (water + thickening agent) which is an essential component of the external gel agent of the present invention, “alkali metal hydroxides, alkali metal earths” usable in the present invention can be used. The “hydroxide selected from metal hydroxides and tetraalkylammonium hydroxides” is not particularly limited. It should be noted that guanidine that exhibits strong alkalinity in water is a molecular cation that has protonated cations that are resonance-stabilized, so the above-mentioned “alkali metal hydroxides, alkali metal earth metal hydroxides, And tetraalkylammonium hydroxide "can be used in the present invention.

  In the present invention, as the hydroxide, two or more kinds of hydroxides may be used in combination by mixing or the like, if necessary.

  As described above, “whether or not it is a hydroxide that gives a suitable gelation state in combination with (water + thickener)” can be easily determined by a method similar to the screening in Example 4 described later. Can be confirmed. That is, in “Screening of Example 4”, the thickener may be fixed to the “specific thickener” used in “Example 1” and the “hydroxide” may be varied.

  Examples of the alkali metal hydroxide include calcium hydroxide (Ca (OH) 2), lithium hydroxide (LiOH), sodium hydroxide (NaOH), potassium hydroxide (KOH), rubidium hydroxide (RbOH), and One or more selected from cesium hydroxide (CsOH) can be suitably used. Examples of the alkaline earth metal hydroxide include strontium hydroxide (Sr (OH) 2), barium hydroxide (Ba (OH) 2), europium hydroxide (II) (Eu (OH) 2), And one or more selected from thallium hydroxide (I) (TlOH) can be preferably used. Further, as the alkali metal hydroxide, one or more selected from alkali metal earth metal hydroxides and tetraalkylammonium hydroxides can be suitably used.

(Calcium hydroxide)
The calcium hydroxide may be added to the gel agent of the present invention in the form of calcium oxide (CaO) (for example, in the form of calcined calcium). This is because this calcium oxide is neutral in powder, has a hydroxyl group, becomes calcium hydroxide and exhibits strong alkalinity. As the naturally derived calcined calcium, calcined shell calcium, coral, calcium oxide purified from chicken eggs, calcium oxide produced from limestone called lime, and the like can also be used.

(Calcium hydroxide content)
In the present invention, even when “CaO” (calcium oxide; molecular weight = 56) is added to the gel for external use, the content is calculated as “Ca (OH) ₂ ” (calcium hydroxide; molecular weight = 74). It shall be. This is because CaO usually exists in the state of Ca (OH) ₂ in a system containing water as in the gel for external use of the present invention. One mole of “CaO” corresponds to one mole of “Ca (OH) ₂ ”. Therefore, for example, when 1 mol (56 g) of “CaO” is added to the gel for external use of the present invention, the content is calculated as 1 mol (74 g) of “Ca (OH) ₂ ” added. To do.

(Optional component)
The gel for external use of the present invention contains the above-mentioned water, hydroxide and thickener as essential components, but may contain other optional components as necessary. Examples of such “arbitrary components” include the following.
-Food additives such as sweeteners (eg glycerin), hyaluronic acid, chitosan, fragrance extract, etc. Details of such "food additives" can be confirmed, for example, at the following URL (Ministry of Health, Labor and Welfare website).
http://www.mhlw.go.jp/stf/seisakunitsuite/bunya/kenkou_iryou/shokuhin/syokuten/
-Quasi-drug additive such as chamomile extract The details of such "quasi-drug additive" can be confirmed, for example, at the following URL (Independent Administrative Institution Pharmaceuticals and Medical Devices Agency website).
http://www.pmda.go.jp/index.html

  However, from the viewpoint of suitably exhibiting the effect of the external gel agent of the present invention, when the total of the essential components (that is, water + calcium hydroxide + thickening agent) is 100 parts by mass, the “arbitrary component” "(However, excluding the following" antibacterial agent "and the above-mentioned" alcohol-based component "and" hypochlorous acid-based component ") is preferably 100 parts by mass or less. The total of the “arbitrary components” is preferably 80 parts by mass or less, more preferably 60 parts by mass or less, and further preferably 40 parts by mass or less with respect to 100 parts by mass of the total of essential components. Preferably, it is preferably 30 parts by mass or less, more preferably 20 parts by mass or less, and particularly preferably 10 parts by mass or less.

(Antimicrobial agent)
The gel for external use of the present invention does not require an antibacterial agent. That is, in the present invention, an antibacterial agent is not necessarily required. However, you may mix | blend an antibacterial agent as needed. Examples of such “antibacterial agents” include the following.

1. Low-level disinfectant 1) Quaternary ammonium salt (1) Benzalkonium chloride (2) Benzethonium chloride 2) Chlorhexidine (1) Chlorhexidine gluconate 3) Amphoteric surfactant (1) Alkyldiaminoethylglycine hydrochloride 2. Medium level disinfectant 1) Alcohol (1) Ethanol (2) Isopropanol (3) Isopropanol-added ethanol solution (4) Disinfectant based on alcohol 2) Iodohol-iodine (1) Povidone iodine (2) Iodo tincture 3 ) Hypochlorous acid (1) Sodium hypochlorite (2) Other hypochlorous acid disinfectant 4) Phenol (1) Cresol (2) Phenol High-level disinfectant 1) Aldehydic (1) Glutaral (2) Phthalal 2) Other high-level disinfectant (1) Peracetic acid (2) Hydrogen peroxide (3) Chlorine dioxide Other disinfectants 1) Acrinol hydrate 2) Oxole 3) Triclosan 4) Formalin etc.

The details of the “antibacterial agent” can be confirmed, for example, at the following URL (Yoshida Pharmaceutical homepage; disinfectant text 4th edition “from the standpoint of infection control based on evidence”).
http://www.yoshida-pharm.com/category/countermeasure/texts/

  However, from the viewpoint of suitably exerting the effect of the external gel agent of the present invention, when the total of the essential components (that is, water + calcium hydroxide + thickener) is 100 parts by mass, the “antibacterial agent” Is preferably 82 parts by mass or less. The amount of the “antibacterial agent” is preferably 70 parts by mass or less, more preferably 60 parts by mass or less, further preferably 50 parts by mass or less, and further 40 parts by mass. Is preferably 30 parts by mass or less, more preferably 20 parts by mass or less, further preferably 15 parts by mass or less, and further preferably 10 parts by mass or less. Preferably, it is preferably 8 parts by mass or less, more preferably 6 parts by mass or less, and particularly preferably 5 parts by mass or less.

(Cellulose nanofiber)
In the present invention, cellulose nanofibers can be used as necessary as the above-mentioned “thickening agent” without departing from the spirit of the present invention. This cellulose can be used as all of the above mentioned “thickeners” or as part of a “thickener” (ie cellulose nanofibers and other “non-nanofiber” thickeners described above. In combination). Moreover, it is also possible to use 2 or more types of cellulose nanofibers as a thickener by combining them by mixing or the like as necessary. Regarding the cellulose nanofibers, for example, Tetsuo Kondo, “A New World Opened by Nanofibers”, Chemistry, February 2016, pp. 33-38, (Chemical Doujin) can be referred to as necessary. . Here, “a range that does not contradict the gist of the present invention” means that as long as a suitable gelled state is given in combination with (water + hydroxide) which is an essential component of the gel for external use of the present invention, It means that it can be used.

(Preferable manufacturing method)
The method for producing the gel for external use of the present invention is not particularly limited. ** From the viewpoint of simplicity and efficiency **, for example, the following “Production Method A” and / or “Production Method B” can be suitably used. When a thickener containing a carboxy group is used, when a salt (hydroxide) is added to the solution of the thickener (production method A), and when a thickener is added to the salt solution With (Manufacturing method B), there exists a tendency for those thickening effects to come out. Usually, the former method (Production Method A) tends to give a gel agent having a higher viscosity.

(Production method A; thickener is added to the salt solution)
(1) Using purified water, prepare a solution of 0.1% hydroxide (for example, shellel = shell calcined calcium) powder.
(2) A hydroxide gel containing 1% thickener is prepared based on the 0.1% hydroxide solution obtained above. That is, the thickener is dissolved little by little in a 0.1% hydroxide aqueous solution and stirred for about 1 minute with a blender machine while paying attention not to “dama”. At this time, “foaming” is observed, but the produced “foam + mixture” is immediately put into a sealed container. At this time (immediately before putting in a closed container), it is confirmed that the pH of the mixture is 12 or more.

(Manufacturing method B; salt is added to the thickener dispersion solution)
(1) A 1% thickener aqueous solution is prepared by blending a thickener with purified water.
(2) A 0.1% calcium hydroxide-containing gel is prepared based on the 1% thickener aqueous solution obtained above. That is, while dissolving calcium hydroxide (for example, shellel = shell calcined calcium) powder little by little in a 1% thickener aqueous solution, it is stirred for about 1 minute with a blender machine, taking care not to cause “dama”. Bond. At this time, “foaming” is observed, but the produced “foam + mixture” is immediately put into a sealed container. At this time (immediately before putting in a closed container), it is confirmed that the pH of the mixture is 12 or more.

(Measurement of antibacterial properties)
The gel for external use of this invention can show a moderate antibacterial effect. More specifically, when measured under the conditions of “Example 5” described later (that is, using a viable cell solution adjusted to 1 × 10 exp (8) / mL), the pour plate A preferable range of the “viable cell count (N ₁₅ ) 15 minutes after the start of measurement” when the gel for external use of the present invention is used as a sample in the state after culturing can be defined as follows.

(Number of viable bacteria 15 minutes after the start of measurement)
That is, when N ₀ = the initial viable cell count and N ₁₅ = the viable cell count after 15 minutes, in the present invention, the ratio Nn = N ₀ / N ₁₅ = 100 or more (that is, 1 × 10 exp (2) Or more). The ratio Nn is further preferably 3 × 10 exp (2) or more, more preferably 6 × 10 exp (2) or more, and further preferably 8 × 10 exp (2) or more. Further, it is preferably 1 × 10 exp (3) or more, more preferably 3 × 10 exp (3) or more, further preferably 6 × 10 exp (3) or more, and further 8 × 10 exp. It is preferably (3) or more, more preferably 1 × 10 exp (4) or more, further preferably 3 × 10 exp (4) or more, further 6 × 10 exp (4) or more. Preferably, it is preferably 8 × 10 exp (4) or more, more preferably 1 × 10 exp (5) or more, and further 3 × 10 exp (5) or more. DOO preferably, more preferably at 6 × 10exp (5) or more, more preferably at 8 × 10exp (5) or more, and particularly preferably 1 × 10exp (6) above.

(Number of viable bacteria 30 minutes after the start of measurement)
That is, when N ₀ = the initial viable cell count and N ₁₅ = the viable cell count after 30 minutes, in the present invention, the ratio Nn = N ₀ / N ₃₀ = 100 or more (that is, 1 × 10exp (2) Or more). The ratio Nn is further preferably 3 × 10 exp (2) or more, more preferably 6 × 10 exp (2) or more, and further preferably 8 × 10 exp (2) or more. Further, it is preferably 1 × 10 exp (3) or more, more preferably 3 × 10 exp (3) or more, further preferably 6 × 10 exp (3) or more, and further 8 × 10 exp. It is preferably (3) or more, more preferably 1 × 10 exp (4) or more, further preferably 3 × 10 exp (4) or more, further 6 × 10 exp (4) or more. Preferably, it is preferably 8 × 10 exp (4) or more, more preferably 1 × 10 exp (5) or more, and further 3 × 10 exp (5) or more. DOO preferably, more preferably at 6 × 10exp (5) or more, more preferably at 8 × 10exp (5) or more, and particularly preferably 1 × 10exp (6) above.

(Antimicrobial properties 15 minutes after the start of measurement)
Regarding the above-mentioned antibacterial effect, under the conditions of “Example 5” described later (that is, using a living bacterial solution adjusted to 1 × 10 exp (8) / mL), the “Shelyl aqueous solution” sample according to the present invention. Nr (Nr ₁₅ = Nr ₁₅₎ = “viable cell count” = Naq 15 minutes after the start of measurement, and “viable cell count” = Ng when the gel for external use of the present invention is used as a sample. Naq / Ng) is preferably 1.5 or more 15 minutes after the start of measurement. The Nr ₁₅ is preferably 1.6 or more, more preferably 1.7 or more, further preferably 1.8 or more, and further 1.9 or more. Preferably, it is preferably 2 or more, more preferably 2.1 or more, further preferably 2.2 or more, further preferably 2.3 or more, Is preferably 2.4 or more, more preferably 2.5 or more, further preferably 2.6 or more, further preferably 2.7 or more, and further 2 Is preferably 2.8 or more, more preferably 2.9 or more, further preferably 3 or more, further preferably 3.1 or more, and further on 3.2. It is preferable that there is also 3.3 or more Preferably, it is preferably 3.4 or more, more preferably 3.5 or more. The greater this ratio Nr, the greater the antibacterial effect “gelled” in the present invention.

(Antimicrobial properties 30 minutes after the start of measurement)
Regarding the antibacterial properties 30 minutes after the start of measurement, the “ratio Nr ₃₀ ” defined in the same manner as the ratio Nr ₁₅ is preferably 1.5 or more 30 minutes after the start of measurement. The Nr is preferably 1.6 or more, more preferably 1.7 or more, further preferably 1.8 or more, and further 1.9 or more. Preferably, it is preferably 2 or more, more preferably 2.1 or more, further preferably 2.2 or more, and further preferably 2.3 or more. Preferably, it is preferably 2.4 or more, more preferably 2.5 or more, further preferably 2.6 or more, and further preferably 2.7 or more, Furthermore, it is preferably 2.8 or more, more preferably 2.9 or more, further preferably 3 or more, further preferably 3.1 or more, and further 3. 2 is preferable, and further Is preferably .3 or more, more preferably 3.4 or more, and particularly preferably 3.5 or more.

The “antibacterial effect” in “Example 5” mentioned above refers to the values 15 minutes after the start of measurement and 30 minutes after the start of measurement, but the “antibacterial” of the gel for external use of the present invention. The “effect” can be measured in the same manner as the measurement in “Example 5” even at a time point in the range of 5 minutes to less than 15 minutes after the start of measurement. In other words, even at the time points in these ranges, values similar to the above-described “Nn” and “Nr” (for example, the ratio Nn = N ₀ / N ₅ and Nr _{5 at} the time point 5 minutes after the start of measurement) = Naq / Ng) can be calculated, and a numerical value in the “preferred range” similar to that described above can be given.

(Aspects corresponding to “halal”)
In an embodiment that should correspond to “halal”, it is important to reduce as much as possible the content of “alcohol component” (for example, ethanol) in the gel for external use of the present invention. Needless to say, the use of “alcohol” is strictly restricted in Islam.

(Aspect prepared at the time of use)
The gel for external use of the present invention can also be used in a so-called “preparation before use” mode. In facilities and institutions where “sanitization” is important, such as medical institutions, beauty salons, barbers, etc., the gel for external use of the present invention should be prepared and used “in situ” immediately before its use. This is because, for example, it may be preferable from the viewpoint of reducing the probability of preventing deterioration of the product due to the storage method and conditions as much as possible.

  In such an external gel preparation “prepared at the time of use” of the present invention, it is preferable that the “gel state” can be maintained for 5 minutes or more. This “gel state” holding time is further preferably 20 minutes or longer, more preferably 25 minutes or longer, further preferably 30 minutes or longer, further preferably 40 minutes or longer, more preferably 50 minutes or longer, particularly It is preferable that it is 60 minutes or more.

(Aspect used for oral care)
Since the gel for external use of the present invention is “external use” (that is, applicable by means other than internal use and injection), it should be used in oral care of humans and animals (for example, pets such as dogs and cats). Can do. Even in such an aspect, for example, from the viewpoint of facilitating application to the oral cavity, as needed (for example, changing / reducing the type and amount of thickener) than the aspect used for human fingers. The viscosity can be made slightly lower.

(Aspect used for animals)
The gel for external use of the present invention can be suitably used for various cares such as oral care for animals other than humans (for example, pets such as dogs and cats).

  Hereinafter, the present invention will be described more specifically with reference to examples.

Example 1
(Preparation of gel preparation by production method A)
In a Pyrex (registered trademark) beaker having a capacity of 3000 ml, 999 g of “purified water” (trade name: Trusco purified water, manufactured by Trusco Nakayama Co., Ltd.) in accordance with Japanese Pharmacopoeia standards was put. Next, 1 g of calcium hydroxide (Ca (OH) 2) powder, shell calcined calcium powder; made by Shin Functional Science Co., Ltd., trade name: Cheryl powder) is put into the purified water, and a stirrer (portable type) The blender machine: manufactured by Tescom Co., Ltd., model: THM320, trade name: stick blender; rotation speed = 9000-15,000 rpm) was stirred for about 1 minute, and then allowed to stand for 12 hours.

  After the standing, the supernatant of the precipitated portion was collected to obtain a 0.1% calcium hydroxide aqueous solution for gel preparation of the present invention.

  Next, a calcium hydroxide gel containing 1% thickener was prepared based on the 0.1% calcium hydroxide solution obtained above. That is, in a Pyrex container having a capacity of 3000 ml, the above-obtained 0.1% calcium hydroxide aqueous solution (1000 g) was stirred (portable blender machine: manufactured by Tescom Co., Ltd., model: THM320 , Trade name: stick blender; rotational speed = 9,000 to 15,000 rpm), "nonionic water-soluble cellulose ether" as a thickener (manufactured by Shin-Etsu Chemical Co., Ltd., trade name: Metroles 65SH-4000) While gradually dissolving the thickener in the above 0.1% aqueous calcium hydroxide solution, 101 g of was gradually added over about 5 minutes, taking care not to “dama”. Furthermore, stirring by the blender machine was continued for about 3 minutes under the same conditions, and then allowed to stand for 24 hours.

At this time, “foaming” is observed in the gel preparation mixture, but this generated “foam + mixture” is immediately sealed in a sealed container (made by Pyrex glass: capacity = about 1000 mL (milliliter), Nippon Genetics). Product, product name: Hiroguchi Mesame bottle). By this operation, the obtained 0.1% calcium hydroxide aqueous solution-thickener mixture was gelled, and the gel composition of the present invention (external gel agent) was obtained.

As described above, it was confirmed that the pH of the mixture was 12 or more immediately before the “foam + mixture” was put in the sealed container. The measurement conditions used for pH measurement at this time are as follows.
pH measuring device: Hanna Instruments Japan Co., Ltd., Model: HI 98128, Product name: pHep5 (Pep 5)

Example 1a
(Confirmation of viscosity change over time)
In the gel composition obtained in Example 1, the presence or absence of a change in viscosity over time was confirmed.
<Storage conditions>
The gel composition in the sealed container obtained in Example 1 was stored under conditions of 25 ° C. and normal pressure.
<Confirmation method of viscosity change>
Confirmation method: The viscosity of the gel composition after each lapse of time was confirmed by a visual method.
Confirmed elapsed time: After the preparation of the gel composition, it was observed for 24 hours, 48 hours, or up to about 1 week.

<Confirmation result of viscosity change>
No change in viscosity was observed in the period of 24 to 48 hours after preparation of the gel composition. In addition, when a thickener other than the above “Metroze” was used, a phenomenon in which the viscosity increased was also observed. Even when the viscosity increased in this way, there was no substantial adverse effect on the use / effect of the gel agent of the present invention.

Example 1b
The same as in Example 1 except that the thickening agent for preparing a gel composition shown in the following “Table 1” was used instead of the “Metroze 65SH-4000” as the thickening agent used in Example 1 above. Thus, a total of 11 types of gel compositions were obtained.

＊１：２０℃、２％水溶液，
＊２：２５℃、１％水溶液３０ｒｐｍ，
＊３：２５℃、１％水溶液６０ｒｐｍ，
＊４：乾量１％
＊５：１%未中和分散液 (Table 1)
<Thickener for preparing gel composition>

* 1: 20 ° C, 2% aqueous solution,
* 2: 25 ° C., 1% aqueous solution 30 rpm,
* 3: 25 ° C., 1% aqueous solution 60 rpm,
* 4: 1% dry weight
* 5: 1% non-neutralized dispersion

  Detailed specifications of various thickeners described in Table 1 are shown in Tables 2 to 6 below. In the “Results” section of Tables 2 to 6 below, “determining method” means “manufacturing method A”, and “after thickener dispersion” is “manufacturing method B”. ".

<Functional group of Metroze>
65SH-4000: Methoxy group = 28.1 (27-30)
Hydroxy * propoxy group * = 6.1 (4.0-7.5)
Viscosity (mPa · S): 3500-5600
65SH-1500: methoxy group = 28.2 (27-30)
Hydroxy * propoxy group * = 6.14.0-7.5
Viscosity (mPa · S): 1200 to 1800
65SH-15000: methoxy group = 28.1 (27-30)
Hydroxy * propoxy group * = 6.0 (4.0-7.5)
Viscosity (mPa · S): 12000-18000
90SH-15000: methoxy group = 23.0 (19-24)
Hydroxy * propoxy group * = 9.6 (4.0-12)
Viscosity (mPa · S): 12000-18000

<Functional group of HEC Daicel>
・ (Product name unknown): hydroxyethyl group = 1.0 to 1.3
Viscosity (mPa · S): 100 to 300
· SP900: hydroxyethyl = unknown <br/> viscosity (mPa · S): 4000~5500
<Functional group of CMC Daicel>
CMC 2260: Carboxymethyl group Viscosity (mPa · S): 4000 to 6000
Etherification degree: 0.89 (0.8-1.0)

<Functional group of kicolate>
F-120: Carboxymethyl group Viscosity (mPa · S): 150-200
Degree of substitution: 0.56 (0-3)

<Functional group of Hibiswako>
Hibiswaco 103: Carboxy group = 59.9 (57.7-63.4%)
Viscosity (mPa · S): 17800 (13,000 to 27000)
(1% unneutralized 400)
Hibiswaco 104: Carboxy group = 59.9 (57.7-63.4%)
Viscosity (mPa · S): 25800 (22000-40000)
(1% unneutralized 2500)
Hibiswaco 105: Carboxy group = 59.9 (57.7-63.4%)
Viscosity (mPa · S): 10200 (7000-14000)
(1% unneutralized 5000)

<Functional group of EMALEX>
EMALEX 2420: hydroxyl group = 47.97%
HLB value: 12

(Table 2)

(Table 3)

(Table 4)

(Table 5)

(Table 6)

In addition, the value shown in the above “standard thickening value (mPa · s)” is obtained from the website of each manufacturer.
Shin-Etsu Chemical Co., Ltd .: http://www.metolose.jp/industrial/index.shtml; etc. Daicel Finechem Co., Ltd .: ** http: //www.daicelfinechem.jp/products/chemical.html **
Nichirin Chemical Industry Co., Ltd .: ** http: //www.nichirin-chem.co.jp/31seihin.html **
Wako Pure Chemical Industries, Ltd .: ** http://www.wako-chem.co.jp/kaseihin/hiviswako/index.htm **
Nippon Emulsion Co., Ltd .: ** https: //www.nihon-emulsion.co.jp/products/emalex **

With respect to the various thickeners described above, the following results were obtained.
<Metroze>
(General) It was relatively less affected by acids and bases, and exhibited a predetermined viscosity in the range of pH 3.0 to 11.0. In addition, in the case of Metrouse use, even if it preserve | saved for one year or more, the fall of the viscosity was not seen.
Metroze 65SH-4000: Viscosity related data was generally good.
・ Metroze 65SH-1500:
(Manufacturing method A) The viscosity related data showed a value close to “Metroze 65SH-4000”.
(Manufacturing method B) The viscosity related data showed a value close to “Metroze 65SH-4000”.
・ Metroze 65SH-15000:
(Manufacturing method A) The viscosity related data was “honey-like → good after 24 hours”.
(Manufacturing method B) The viscosity related data was “honey ⇒good after 24 hours”.
・ Metroze 90SH-15000:
(Manufacturing method A) The viscosity related data was “honey-like → good after 24 hours”.
(Manufacturing method B) The viscosity related data was “honey ⇒good after 24 hours”.

<HEC Daicel>
(General) It was not easily affected by salts and metal ions, and was highly compatible with salts and other drugs.
-Unknown product name (hydroxyethyl group: 1.0 to 1.3):
(Manufacturing method A) The viscosity related data was "viscosity relaxation".
(Manufacturing method B) The viscosity-related data was “viscosity-relaxed white turbidity → transparent after 48 hours”.
・ SP900:
(Manufacturing method A) The viscosity related data was "high viscosity".
(Manufacturing method B) The viscosity related data were "viscosity strong cloudiness".

<CMC Daicel>
-CMC 2260:
(Manufacturing method A) The viscosity related data was "jelly-like".
(Manufacturing method B) The viscosity related data was "jelly-like and hard gel separation".

<Chicolate>
(General) There was a tendency to be susceptible to metal ions and salt contamination. Some divalent salt metals are good and bad. When the pH is 10 or more, the viscosity decreases.
・ F120:
(Manufacturing method A) The viscosity related data was "water state".
(Production method B) The viscosity-related data was “water”.

<Hibis Wako>
(General) Effective pH range (1% thickener):
Hibiswako 103: 5.5-10,
Hibiswako 104: 5 to 10.5,
Hibiswako 105: 4-11
Stability against metal ions:
Hibis Wako 103: Slightly unstable Hibis Wako 104: Slightly unstable Hibis Wako 105: Stable / Hibis Wako 103
(Manufacturing method A) The viscosity related data was “jelly-like / damaged / pH decreased”.
(Production method B) Viscosity-related data was “no viscosity / depleted white turbidity-separated sulfur-smelling pH drop”.
・ Hibiswako 104
(Manufacturing method A) The viscosity related data was “jelly-like / damaged / pH decreased”.
(Production method B) Viscosity-related data was “no viscosity / depleted white turbidity-separated sulfur-smelling pH drop”.
・ Hibiswako 105
(Manufacturing method A) The viscosity related data was “jelly-like / damaged / pH decreased”.
(Production method B) Viscosity-related data was “no viscosity / depleted white turbidity-separated sulfur-smelling pH drop”.

<EMALEX>
(General) Etherified product obtained by addition polymerization of ethylene oxide to iso-branched higher alcohol. Since the alkyl group has an iso-branch, it has a lower melting point than the straight chain type.
EMALEX 2420: “Component: Polyoxyethylene decyl tetradecyl ether (Production method A) Viscosity is very low.
(Production Method B) Lightly cloudy and very weak in viscosity

Example 1c
(Preparation of gel agent by production method B; salt added to thickener dispersion)
Pyrex beaker with a capacity of 3000 ml was charged with 1000 g of “purified water” (trade name: Trusco purified water, manufactured by Trusco Nakayama Co., Ltd.) according to Japanese Pharmacopoeia standards. Next, under stirring (portable blender machine: manufactured by Tescom Co., Ltd., model: THM320, trade name: stick blender; rotation speed = 9,000 to 15,000 rpm) To avoid “dama” while 101 g of “ionic water-soluble cellulose ether” (manufactured by Shin-Etsu Chemical Co., Ltd., trade name: Metrol's 65SH-4000) is gradually dissolved in the purified water. Carefully added over about 5 minutes. Furthermore, stirring with the blender machine was continued for about 3 minutes under the same conditions, and then allowed to stand for 12 hours.

  A 1% thickener aqueous solution was prepared by the above operation.

Next, a 0.1% calcium hydroxide-containing gel was prepared based on the 1% thickener aqueous solution obtained above. That is, in a Pyrex (registered trademark) container having a capacity of 3000 ml, the above-obtained 1% thickener aqueous solution (1000 g) [ 1101 g of thickener 101 g of purified water 1101 g ] was stirred (portable type). Blender machine: manufactured by Tescom Co., Ltd., model: THM320, product name: stick blender; rotation speed = 9,000 to 15,000 rpm), calcium hydroxide (Ca (OH) 2) powder, shell calcined calcium 1 g of powder: New Functional Science Co., Ltd., trade name: Cheryl Powder) was gradually added over about 5 minutes, and then stirring was continued for about 3 minutes under the same conditions, and then allowed to stand for 24 hours.

  When this calcium hydroxide powder is mixed, “foaming” is observed in the gel preparation mixture. The generated “foam + mixture” is immediately sealed in a sealed container (made of Pyrex glass; capacity = about 1000 mL). , Manufactured by Nippon Genetics Co., Ltd. By this operation, the mixture of 1% thickener aqueous solution-0.1% calcium hydroxide was gelled, and the gel composition of the present invention (external gel agent) was obtained.

As described above, it was confirmed that the pH of the mixture was 12 or more immediately before the “foam + mixture” was put in the sealed container. The measurement conditions used for pH measurement at this time are as follows.
pH measuring device: Hanna Instruments Japan Co., Ltd., Model: HI 98128, Product name: pHep5 (Pep 5)

  Instead of “nonionic water-soluble cellulose ether” (manufactured by Shin-Etsu Chemical Co., Ltd., trade name: Metroles 65SH-4000), which is a thickener used in the above operation, each “thickening” shown in Table 1 above. Except for using “agent”, a gel composition (external gel agent) using each “thickener” shown in Table 1 was obtained in the same manner as described above.

  The evaluation results of the various gel agents obtained above are shown in Tables 2-6 and Tables 7-8 below.

(Table 7)

(Table 8)

Example 1d
(Confirmation of viscosity change over time)
Of the various gel compositions shown in Tables 2 to 8 (external gel agents), those using the following “thickeners” are good immediately after gel formation (for example, 5 minutes after gel formation). A gel state was exhibited, and a good gel state was exhibited even after storage for 24 hours in a sealed container.
<Production method A>
Metroise: Hydroxypropyl methylcellulose 65SH-15000, 65SH-15000, 90SH-15000
<Production method B>
Metroise: Hydroxypropyl methylcellulose 65SH-15000, 65SH-15000, 90SH-15000

Example 2
(Viscoelasticity measurement)
Viscoelasticity was measured under the following conditions for eight specimens of “gel composition according to the present invention” obtained in Example 1 (manufacturing dates differ; storage at room temperature) (measurement date and time: January 2016) 28th (Thursday) 13: 00 to 16:00).
・ Test place: Tochigi Prefectural Industrial Technology Center (1-20-20 Yuinomori, Utsunomiya City)
-Measuring machine manufacturer: HAAKE (Haake) [Germany]; Model: Rheostress RS600
・ <Measurement sample>
-Specimen 1: Sample number 201501818 Sample after 1 year (Production date: February 18, 2015)
Specimen 2: Sample number 20150720 Sample after 6 months (manufacturing date: July 20, 2015)
Specimen 3: Sample number 20151209 Sample after 2 months (Production date: December 9, 2015)
Sample 4: Sample No. 2016160115 Sample after 2 weeks (Production date: January 15, 2016)
Specimen 5: Sample number 201601121 Sample after one week (Production date: January 21, 2016)
Specimen 6: Sample number 20160126 Sample after 1 day (Production date: evening of January 26, 2016)
Specimen 7: Sample number 20160128 Sample immediately after production (Production date: January 28, 2016)
Specimen 8: Sample number tepika — 4C10 Commercially available alcoholic gel sample (manufactured by Kenei Pharmaceutical Co., Ltd.)
-Viscoelasticity measuring apparatus The following measurement conditions were set in the rheostress RS600, a measuring instrument was mounted, and samples 1 to 8 were measured.
Sensor: C35 / 1 ° CE (sample amount 0.200 cm 3; measurement range 100 to 106 Pa · S)
* With reference to the viscosity standard, the sensor was selected within the measurement range, assuming that the viscosity was between salad oil (60-80) and shampoo (2,000-3,000).
Measurement temperature: 25 ° C
It was determined on the assumption of storage at room temperature (referring to “cosmetic evaluation method” in JP 2011-185950 A).
Shear rate: continuously increasing from 0 to 200 (1 / S) in 60 seconds, then continuously decreasing from 200 (1 / S) to 0.
dγ / dt [1 / s]: Reference was made to “Cosmetics Evaluation Method” in JP2011-185950A.

  The obtained results are shown in Table 9.

(Table 9)

Example 3
(PH measurement)
1. Implementation date January 28, 2016 (Thursday) 10: 00 to 11:30
2. Place Tochigi Industrial Technology Center (1-20-20 Yuinomori, Utsunomiya City)
3. Measuring machine Manufacturer: HORIBA Model: 6366C
4). <Sample>
Specimen 1: Sample number 201501818 Sample after one year (Production date: February 18, 2015)
Specimen 2: Sample number 20150720 Sample after 6 months (manufacturing date: July 20, 2015)
Specimen 3: Sample number 20151209 Sample after 2 months (production date: December 9, 2015)
Specimen 4: Sample number 201601115 Sample after 2 weeks (Production date: January 15, 2016)
Specimen 5: Sample number 201601121 Sample after one week (production date: January 21, 2016)
Specimen 6: Sample number 20160126 Sample after 1 day (Production date: evening of January 26, 2016)
Specimen 7: Sample No. 20160128 Sample immediately after production (Production date: January 28, 2016)
Specimen 8: Cheryl powder aqueous solution (before adding thickener)
5. Method: Wash and correct the electrode before measuring the sample with “pH standard solution 100-9” (Ph: 9) manufactured by Horiba.
-After correction, samples 1 to 8 are measured. Before each sample measurement, the electrode is washed with “pH standard solution 100-9”.
-The measurement time was 3 minutes after electrode insertion.

  The obtained results are shown in Table 10.

(Table 10)

Example 4
(Thickener screening)
In the present invention, the “thickener” suitable for the preparation of the gel composition of the present invention can be easily screened by the following method. As is apparent from the following procedure, a significant number (eg, about 10-50 samples of different thickeners) can be screened in parallel.

Specifically, the following procedure is used.
(1) Similar to that in Example 1, a “0.1%” concentration Ca (OH) 2 aqueous solution is prepared.
(2) As in Example 1, the “thickening agent” to be screened is added to the Ca (OH) 2 aqueous solution, and the gelation state of the resulting mixture is visually checked (for example, Depending on the type of “thickener”, it may be in a solution state).
(3) Furthermore, the persistence of the gelled state is visually checked for a long time (for example, after 24 hours).
(4) Check the gelation state for a longer time (for example, about one week).

Example 5
(Measurement of antibacterial effect of gel composition)
The antibacterial effect of the gel composition of the present invention was measured by the following method.
・ Test place: Kaken Test Center (Osaka Office; Nishi-ku, Osaka City)
・ Microorganism: Escherichia coli NBRC 3972
Test method: 0.1 mL of a bacterial solution adjusted to a viable cell count of 108 cells / mL (ie, 1 × 10 exp (8) cells / mL) is added to a sample solution of 10 mL, and a specified time (ie, 15 minutes, 30 For a minute). Thereafter, 1 mL of the test solution was inactivated with 9 mL of SCDLP broth medium, and the viable cell count was measured by pour plate culture. Moreover, the same process was performed with distilled water as object.

  The results obtained above are shown in Table 11. That is, when distilled water (control) is used as a sample, the initial viable cell count is 8.3 × 10 exp (4), the viable cell count after 15 minutes is 1.1 × 10 exp (5), The number of viable bacteria after 30 minutes was 1.0 × 10exp (5).

  On the other hand, when a Sherry (Sherry ⇒ Shellyl) aqueous solution (that is, an aqueous solution of “water + hydroxide”) was used as a sample, the viable count after 6.0 minutes was 6.0 and after 30 minutes The number of viable bacteria was 3.5.

  Furthermore, when the shelly gel (that is, the gel of “water + hydroxide + thickener” obtained in Example 1) was used as a sample, the viable count after 15 minutes was less than 1.0, The viable count after 30 minutes was also less than 1.0.

(Table 11)

Claims (3)

A gel for external use containing at least water, a hydroxide , and a thickener; and when the gel for external use is made into a gel at room temperature (25 ° C.) and allowed to stand in a closed container for at least 24 hours State can be maintained,
The thickener is hydroxypropyl methylcellulose having a viscosity standard value of 3,500 to 18,000 mPa · s,
The hydroxide is calcium hydroxide (Ca (OH) ₂ ), and
A gel for external use characterized by not containing an anionic surfactant .   The gel for external use according to claim 1, wherein the calcium hydroxide is calcium hydroxide produced from shells, corals, egg shells, or limestone.   The gel for external use according to claim 2, wherein the limestone is marble, stalactite, or chalk.

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