U.S. patent application number 17/258579 was filed with the patent office on 2021-06-03 for disinfectant composition.
This patent application is currently assigned to OTSUKA PHARMACEUTICAL FACTORY, INC.. The applicant listed for this patent is OTSUKA PHARMACEUTICAL FACTORY, INC.. Invention is credited to Akihumi HAGI, Kazumasa HASHIMOTO, Kaoru IMAI, Motoya KIKUCHI, Hisae NISHIOKA, Shinji ODA.
Application Number | 20210161143 17/258579 |
Document ID | / |
Family ID | 1000005407154 |
Filed Date | 2021-06-03 |
United States Patent
Application |
20210161143 |
Kind Code |
A1 |
IMAI; Kaoru ; et
al. |
June 3, 2021 |
DISINFECTANT COMPOSITION
Abstract
An antiseptic composition with a more extended applicable range
by further enhancing the efficacy of olanexidine gluconate, which
has been used as a highly safe dermal bactericidal disinfectant,
and extending antibacterial spectrum. The antiseptic composition
includes and has a more extended bactericidal spectrum than
conventional disinfectants.
Inventors: |
IMAI; Kaoru; (Tokushima,
JP) ; NISHIOKA; Hisae; (Tokushima, JP) ; HAGI;
Akihumi; (Tokushima, JP) ; ODA; Shinji;
(Tokushima, JP) ; HASHIMOTO; Kazumasa; (Tokushima,
JP) ; KIKUCHI; Motoya; (Tokushima, JP) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
OTSUKA PHARMACEUTICAL FACTORY, INC. |
Tokushima |
|
JP |
|
|
Assignee: |
OTSUKA PHARMACEUTICAL FACTORY,
INC.
Tokushima
JP
|
Family ID: |
1000005407154 |
Appl. No.: |
17/258579 |
Filed: |
July 12, 2019 |
PCT Filed: |
July 12, 2019 |
PCT NO: |
PCT/JP2019/027803 |
371 Date: |
January 7, 2021 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A01N 47/44 20130101;
A01N 31/02 20130101 |
International
Class: |
A01N 47/44 20060101
A01N047/44; A01N 31/02 20060101 A01N031/02 |
Foreign Application Data
Date |
Code |
Application Number |
Jul 18, 2018 |
JP |
2018-135190 |
Claims
1. An antiseptic composition comprising olanexidine gluconate,
wherein the antiseptic composition is basic.
2. The antiseptic composition according to claim 1, having a pH
within a range from 8 to 11.
3. The antiseptic composition according to claim 1, wherein a
concentration of olanexidine gluconate is 0.01 to 20% (WV).
4. The antiseptic composition according to claim 1, comprising
water and/or an antiseptic alcohol.
5. The antiseptic composition according to claim 4, wherein a
concentration of the antiseptic alcohol concentration is 10 to 85%
(V/V).
6. The antiseptic composition according to claim 4, wherein the
antiseptic alcohol is selected from ethanol and isopropyl
alcohol.
7. A rubbing agent comprising the antiseptic composition according
to claim 1.
8. The antiseptic composition according to claim 2, wherein a
concentration of olanexidine giuconate is 0.01 to 20% (W/V).
9. The antiseptic composition according to claim 2, comprising
water and/or an antiseptic alcohol.
10. The antiseptic composition according to claim 3, comprising
water and/or an antiseptic alcohol.
11. The antiseptic composition according to claim 8, comprising
water and/or an antiseptic alcohol.
12. The antiseptic composition according to claim 5, wherein the
antiseptic alcohol is selected from ethanol and isopropyl
alcohol.
13. The antiseptic composition according to claim wherein the
antiseptic alcohol is selected from ethanol and isopropyl
alcohol.
14. The antiseptic composition according to claim 10, wherein the
antiseptic alcohol is selected from ethanol and isopropyl
alcohol.
15. The antiseptic composition according to claim 11, wherein the
antiseptic alcohol is selected from ethanol and isopropyl
alcohol.
16. A rubbing agent comprising the antiseptic composition according
to claim 2.
17. A rubbing agent comprising the antiseptic composition according
to claim 3.
18. A rubbing agent comprising the antiseptic composition according
to claim 4.
19. A rubbing agent comprising the antiseptic composition according
to claim 5.
20. A rubbing agent comprising the antiseptic composition according
to claim 6.
Description
TECHNICAL FIELD
[0001] The present invention relates to an antiseptic composition
(disinfectant composition) containing olanexidine gluconate and
having a broader bactericidal spectrum.
BACKGROUND ART
[0002] Olanexidine, chemical name
1-(3,4-dichlorobenzyl)-5-octylbiguanide, is a compound with a high
bactericidal activity. Olanexidine gluconate has sufficient water
solubility, a broad bactericidal spectrum, demonstrates a
bactericidal effect in a short time, further sustains such an
effect for an extended period of time, and is highly safe, thereby
to be useful as a medical disinfectant (Patent Document 1). Dermal
bactericidal disinfectants containing olanexidine gluconate have
good efficacy on various bacteria which are considered as normal
bacteria on skin and enveloped viruses, while substantially have no
efficacy on feline calicivirus which has no envelope (Non-patent
Document 1). For this reason, in the fields such as medical and
nursing, and food and drink industries, olanexidine
gluconate-containing disinfectants having more efficacies with a
broader bactericidal spectrum are in demand.
[0003] Olanexidine belongs to monobiganide-based compounds which
have 1 biganide structure. Examples of the disinfectant having the
same biganide structure representatively include chlorhexidine,
which is a bisbiganide-based compound, and polyhexamethylene
biguanide, which is a polybiganide-based compound.
[0004] Chlorhexidine is a bisbiganide-based compound having 2
biganide structures in a molecule. As with olanexidine,
chlorhexidine is hardly water-soluble and becomes soluble in the
form of gluconate, for the reason of which it is mainly used in the
form of chlorhexidine gluconate as a pharmaceutical product
(Non-patent Document 2). Chlorhexidine gluconate, as with
olanexidine gluconate, shows a viricidal action on enveloped
viruses, while having no efficacy on non-enveloped viruses
(Non-patent Document 3). Further, chlorhexidine gluconate is stable
at pH 4 to 6.5 and is known to cause precipitation when a dilute
aqueous solution is basic of pH 8 or more and cause no difference
in the bactericidal efficacies even when pH is increased (Patent
Document 2, Non-patent Document 2, and Non-patent Document 4).
[0005] On the other hand, polyhexamethylene biganide, classified as
a polybiganide-based compound, is a polymer of hexamethylene
biganide having 1 biganide structure in a unit. Polyhexamethylene
biganide is extremely easily soluble in water and has a broad
bactericidal spectrum, for the reason of which a mild acidic
solution thereof is commonly available as a low toxic sterilizing
agent (Non-patent Documents 5 and 6). Further, commercial
polyhexamethylene biganide disinfectants are reported as having
viricidal activities on non-enveloped viruses (Non-patent Document
7) and further reported as increasing bactericidal efficacy and
viricidal efficacy when pH is further increased (Non-patent
Document 4 and Patent Documents 3 and 4).
Prior Art Documents
Patent Documents
[0006] [Patent Document 1] Japanese unexamined Patent Application
Publication No. 2005-289959 [0007] [Patent Document 2] Japanese
unexamined Patent Application Publication No. 2007-217394 [0008]
[Patent Document 3] Japanese unexamined Patent Application
Publication No. 2007-045732 [0009] [Patent Document 4] Japanese
unexamined Patent Application Publication No. 2017-171606
Non-Patent Documents
[0009] [0010] [Non-patent Document 1] Attached document
"Olanexidine solution 1.5% antiseptic applicator 10 mL/25 mL"
(August, 2015 Revised) [0011] [Non-patent Document 2]
Pharmaceutical Product Interview Form "Clorhexidine gluconate
solution" (July, 2010 Revised)
[0012] [Non-patent Document 3] Clin Microbiol Rev.; 12(1): 147-179
(January, 1999) [0013] [Non-patent Document 4] Skin Pharmacol
Physiol.; 28(3): 147-158 (2015) [0014] [Non-patent Document 5]
Scientific Committee on Consumer Safety "Opinion on the safety of
poly(hexamethylene) biguanide hydrochloride (PHMB)" (July, 2015)
[0015] [Non-patent Document 6] VANTOCIL IB Antimicrobial Technical
information materials [0016] [Non-patent Document 7] Website "Arch
Chemicals Reports that Studies Confirm that Vantocil (.TM.) Product
Controls Norovirus, a Leading Cause of Acute Gastroenteritis"
(https://www.businesswire.com/news/home/20060113005294/en/Arch-Chemicals--
Reports-Studies-Confirm-Vantocil-.TM.)
SUMMARY OF THE INVENTION
Object to be Solved by the Invention
[0017] An object of the present invention is to provide an
antiseptic composition with a more extended applicable range by
further enhancing the efficacy of olanexidine gluconate, which has
been used as a highly safe dermal bactericidal disinfectant, and
extending bactericidal spectrum.
Means to Solve the Object
[0018] The present inventors continued extensive studies to solve
the above object. Conventional bactericides containing olanexidine
gluconate were formulated to be pH (Non-patent Document 1) because
compositions applied to skins are generally mildly acidic according
to pH (pH 4 to 7) of skins and olanexidine deposits in the form of
a free compound when neutralized with an alkaline aqueous solution
(Patent Document 1), however, the present inventors intentionally
prepared a basic solution of olanexidine gluconate to test
activities thereof and found that bactericidal efficacies are not
only unexpectedly enhanced but efficacies are demonstrated on
non-enveloped viruses against which a mildly acidic formulation
thereof had substantially no efficacy. Further, the present
inventors confirmed that further addition of a surfactant to a
basic solution containing olanexidine gluconate enhances the
stability. The present invention is based on the above
findings.
[0019] More specifically, the present invention is as follows.
[0020] (1) An antiseptic composition comprising olanexidine
gluconate, wherein the antiseptic composition is basic. [0021] (2)
The antiseptic composition according to (1), having a pH within a
range from 8 to 11. [0022] (3) The antiseptic composition according
to (1) or (2), wherein a concentration of olanexidine gluconate is
0.01 to 20% (W/V). [0023] (4) The antiseptic composition according
to any one of (1) to (3), comprising water and/or an antiseptic
alcohol. [0024] (5) The antiseptic composition according to (4),
wherein a concentration of the antiseptic alcohol concentration is
10 to 85% (V/V). [0025] (6) The antiseptic composition according to
(4) or (5), wherein the antiseptic alcohol is selected from ethanol
and isopropyl alcohol. [0026] (7) A rubbing agent comprising the
antiseptic composition according to any one of (1) to (6).
Effect of the Invention
[0027] According to a composition of the present invention, a
disinfectant usable in the fields such as medical and nursing, and
food and drink industries and having higher efficacy with a broader
bactericidal spectrum can be produced.
BRIEF DESCRIPTION OF DRAWINGS
[0028] FIG. 1 is a chart showing bactericidal powers of olanexidine
gluconate-containing compositions (pH 5, 8 to 10) of Example 1
against Mycobacterium fortuitum JCM 6387.
[0029] FIG. 2 is a chart showing bactericidal powers of olanexidine
gluconate-containing compositions (pH 5, 8 to 10) of Example 1
against Mycobacterium chelonae JCM 6388.
[0030] FIG. 3 is a chart showing bactericidal powers of olanexidine
gluconate-containing compositions (pH 5, 8 to 10) of Example 1
against Microsporum canis NBRC 32464.
[0031] FIG. 4 is a chart showing viricidal (phage) activities of
olanexidine gluconate-containing compositions (pH 5, 7 to 12) of
Example 2 on phage.
[0032] FIG. 5 is a chart showing a viricidal (phage) activity of
ethanol-containing olanexidine formulation of Example 3 on
phage.
MODE OF CARRYING OUT THE INVENTION
[0033] The present invention relates to an antiseptic composition
which comprises olanexidine gluconate and is basic. Being basic
used herein may be any composition of pH being more than 7 but
examples include, in view of toxicity and a bactericidal activity
to skins, pH being more than 7 to 12, pH being more than 7 to 11.5,
pH being more than 7 to 11, pH being more than 7 to 10.5, and pH
being more than 7 to 10; preferably pH 7.5 to 12, pH 7.5 to 11.5,
pH 7.5 to 11, pH 7.5 to 10.5, and pH 7.5 to 10; more preferably pH
8 to 11.5, pH 8 to 11, pH 8 to 10.5, pH 8 to 10; further preferably
pH 8.5 to 11.5, pH 8.5 to 11, pH 8.5 to 10.5, and pH 8.5 to 10; and
furthermore preferably pH 9 to 12, pH 9 to 11.5, pH 9 to 11, pH 9
to 10.5, and pH 9 to 10. Note that the composition of the present
invention is an aqueous solution. Further, in the present
Description, the "disinfection" and "bactericidal" mean to kill
bacteria, fungi and/or viruses.
[0034] Any known pH adjuster can be used to adjust the pH, but
examples include a basic solution such as sodium hydroxide,
potassium hydroxide, calcium hydroxide, ammonium carbonate, and
potassium carbonate, of which sodium hydroxide is preferable.
Further, the composition of the present invention is optionally
prepared using a basic buffer, and examples of the buffer used
include a boric acid-sodium carbonate buffer, a CAPS-NaOH buffer, a
Bicine-NaOH buffer, a Glycine-NaOH buffer, a Tricine-NaOH buffer, a
HEPPS-NaOH buffer, a TAPS-NaOH buffer, a Bicine-NaOH buffer, and a
HEPES-NaOH buffer.
[0035] The concentration of olanexidine gluconate is not
particularly limited as long as it has sufficient bactericidal
efficacy, but examples include 0.01 to 20% (W/V), preferably 0.1 to
10% (W/V), and more preferably 0.5 to 5% (W/V). When the antiseptic
alcohol to be described later is used concurrently, examples of
such a concentration include 0.01 to 10% (W/V), preferably 0.1 to
7% (W/V), more preferably 0.5 to 5% (W/V), and further preferably
0.5 to 3% (W/V).
[0036] A composition of the present invention has more promoted
bactericidal activities on filamentous fungi and acid-fast
bacteria, particularly bacteria of the genus Microsporum and
bacteria of the genus Mycobacterium. Further, the present
composition also has good viricidal activities even on
non-enveloped viruses, particularly viruses of the family
Caliciviridae (viruses of the genus Norovirus), against which the
conventional olanexidine gluconate-containing disinfectants failed
to inactivate.
[0037] A composition of the present invention further optionally
contains an antiseptic alcohol to potentiate bactericidal
activities and impart quick-dryness. Examples of the antiseptic
alcohol herein preferably include ethanol and isopropyl alcohol,
and examples of the antiseptic alcohol concentration include 10 to
85% (V/V), 20 to 85% (V/V), 30 to 85% (V/V), 40 to 85% (V/V), 50 to
85% (V/V), 10 to 80% (V/V), 20 to 80% (V/V), 30 to 80% (V/V), 40 to
80% (V/V), 50 to 80% (V/V), 10 to 70% (V/V), 20 to 70% (V/V), 30 to
70% (V/V), 40 to 70% (V/V), and 50 to 70% (V/V). A composition of
the present invention may not substantially contain an antiseptic
alcohol. Containment of the antiseptic alcohol enables to prepare a
quick-drying disinfectant having both potentiating effects of
bactericidal activities due to the antiseptic alcohol and sustained
effects of bactericidal activities due to olanexidine gluconate.
Further, as bactericidal activities are potentiated due to the
antiseptic alcohol, a concentration of olanexidine gluconate can be
reduced. Examples of the concentration ratio of the olanexidine
gluconate to the antiseptic alcohol include 1:400 to 1:20,
preferably 1:300 to 1:30, and more preferably 1:200 to 1:40.
[0038] A composition of the present invention can further contain a
known bactericide. Examples of the bactericide include a
benzalkonium salt such as benzalkonium chloride and benzalkonium
alkyl phosphate, benzethonium chloride, triclosan, isopropyl
methylphenol, cetylpyridinium chloride, resorcin,
trichlorocarbanilide, chlorhexidine hydrochloride, chlorhexidine
gluconate, polyhexamethylene biganide, sodium hypochlorite,
hydrogen peroxide, povidone iodine, and iodine tincture. These
bactericides are optionally used singly or 2 or more may be used in
combination.
[0039] A composition of the present invention can further contain a
known solubilizer. Examples of the solubilizer include a nonionic
surfactant, an ionic surfactant, ethylenediamine, sodium benzoate,
nicotinamide, cyclodextrin, ethanol, benzyl alcohol, and propylene
glycol. Examples of the ionic surfactant preferably include an
alkyl dimethylamine oxide such as an oleyl dimethylamine oxide, a
stearyl dimethylamine oxide, a palmityl dimethylamine oxide, a
myristyl dimethylamine oxide, a lauryl dimethylamine oxide, and a
coconut oil alkyl dimethylamine oxide, of which a lauryl
dimethylamine oxide is preferable. Examples of the nonionic
surfactant include a sorbitan fatty acid ester, a polyoxyethylene
sorbitan fatty acid ester, a polyoxyethylene alkyl ether, a
polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene
polyoxypropylene glycol, a polyglyceryl fatty acid ester, a
polyoxyethylene hydrogenated castor oil, and a sucrose fatty acid
ester, of which polyoxyethylene polyoxypropylene glycol, a
polyoxyethylene alkyl ether, and a polyoxyethylene polyoxypropylene
alkyl ether are preferable. Examples of the polyoxyethylene
polyoxypropylene glycol include polyoxyethylene(42)
polyoxypropylene(67) glycol (Pluronic (R) P-123),
polyoxyethylene(54) polyoxypropylene(39) glycol (Pluronic (R)
P-85), polyoxyethylene(196) polyoxypropylene (67) glycol (Pluronic
(R) F-127), polyoxyethylene(3) polyoxypropylene(17) glycol
(Pluronic (R) L-31), polyoxyethylene(20) polyoxypropylene(20)
glycol (Pluronic (R) L-44), polyoxyethylene(120)
polyoxypropylene(40) glycol (Pluronic (R) F-87), and
polyoxyethylene(160) polyoxypropylene(30) glycol (Pluronic (R)
F-68), of which polyoxyethylene(20) polyoxypropylene(20) glycol
(Pluronic (R) L-44) is preferable. Examples of the polyoxyethylene
alkyl ether include a polyoxyethylene cetylether, a polyoxyethylene
oleyl ether, and a polyoxyethylene lauryl ether (lauromacrogol),
with a polyoxyethylene lauryl ether (lauromacrogol) being
particularly preferable. Further, examples of the polyoxyethylene
polyoxypropylene alkyl ether include a polyoxyethylene(20)
polyoxypropylene(4) cetylether, a polyoxyethylene(30)
polyoxypropylene(6) decyltetradecyl ether, a polyoxyethylene(25)
polyoxypropylene(25) lauryl ether, with a polyoxyethylene(20)
polyoxypropylene(4) cetylether being particularly preferable. The
concentration of a solubilizer may be a concentration which
prevents olanexidine gluconate from precipitating and does not
reduce the bactericidal activity and is usually determined in
accordance with a concentration of olanexidine gluconate within a
concentration range of 0.1 to 30% (W/V).
[0040] A composition of the present invention optionally contains
an anti-inflammatory agent, a moisturizer, an emollient agent, a
touch improver, and a thickener.
[0041] Examples of the anti-inflammatory agent include a licorice
extract, glycyrrhetinic acid, dipotassium glycyrrhizinate, stearyl
glycyrrhetinate, tocopherol acetate, allantoin, and an aloe
extract.
[0042] Example of the moisturizer include an amino acid, a fatty
acid ester, pyrrolidone carboxylic acid, sodium pyrrolidone
carboxylate, sodium lactate, hyaluronic acid, sodium hyaluronate,
N-cocoyl-L-arginine ethyl ester-DL-pyrrolidone carboxylate, urea,
sorbitol, trehalose, 1,3-butylene glycol, propylene glycol,
poloxamer (Pluronic (R) F-68, etc.), and glycerin.
[0043] Examples of the emollient include a fatty acid ester such as
isopropyl myristate, isopropyl palmitate, isopropyl stearate,
isobutyl oleate, and isobutyl maleate, and 1 fatty acid ester
singly or 2 or more of these can be contained.
[0044] Examples of the touch improver include a silicone-based
compound such as dimethylpolysiloxane and cyclic silicone.
[0045] Examples of the thickener include a cellulose derivative
such as hydroxyethyl cellulose, hydroxypropyl cellulose,
hydrophobic hydroxypropyl methylcellulose, methyl cellulose, and
carboxymethyl cellulose, a (meth)acrylic acid base copolymer,
polyvinyl alcohol, polyvinylpyrrolidone, a methyl vinyl
ether-maleic anhydride copolymer, polyacrylamide, alginic acid,
sodium alginate, propylene glycol alginate, gelatin, a gum arabic,
a gum tragacanth, a locust bean gum, a guar gum, a tamarind gum, a
xanthan gum, a gellan gum, and carrageenan.
[0046] A composition of the present invention can preferably be
used for the purpose of disinfecting the instrument surfaces of
medical instruments, cookware, and nursing equipment, and skin
surfaces such as hands and fingers. A composition of the present
invention is optionally used as soaked in paper, cloth, non-woven
fabric, cotton swab, or absorbent cotton, or as filled in an
applicator for application, or in the form of a rubbing agent or a
scrubbing agent, but a composition of the present invention is
preferably used as a rubbing agent. The rubbing agent herein means
a quick-drying rubbing-type formulation, and the scrubbing agent
means a formulation obtained by mixing a bactericide/disinfectant
and a surfactant having detergency. Note that when a composition of
the present invention is used for disinfecting fingers of both
hands, an amount usually used per disinfection is 1 to 5 ml,
preferably 1.5 to 4.5 ml, more preferably 2 to 4 ml, and further
preferably 2.5 to 3.5 ml, and examples of the number of times used
per day include, in view of dermal toxicity, within 100 times,
preferably within 80 times, more preferably within 60 times, and
further preferably within 40 times.
[0047] Hereinafter, the present invention will be described more
specifically in reference to examples, but technical ranges of the
present invention are not limited thereto.
EXAMPLE 1
[0048] 1. Bactericidal Power Against Fungi and Non-Tuberculous
Mycobacteria
[0049] Bactericidal power of olanexidine gluconate
containing-compositions (pH5, 8 to 10) against filamentous fungi
and non-tuberculous mycobacteria, which are known to cause
infections, was evaluated by Time-kill test. [0050] 1-1 Test
Material and Method [0051] 1-1-1 Test Substances
TABLE-US-00001 [0051] (1) Substance to be tested 1 Name:
Olanexidine formulation pH 5 Composition: Olanexidine gluconate
1.5% (W/V) Pluronic L-44 1.08% (W/V) pH Adjuster (sodium hydroxide,
glucono-.delta.-lactone) qs Pure water qs pH 5 (2) Substance to be
tested 2 Name: Olanexidine formulation pH 8 Composition:
Olanexidine gluconate 1.5% (W/V) Pluronic L-44 1.08% (W/V) HEPES
0.1% (W/V) pH Adjuster (sodium hydroxide, glucono-.delta.-lactone)
qs Pure water qs pH 8 (3) Substance to be tested 3 Name:
Olanexidine formulation pH 9 Composition: Olanexidine gluconate
1.5% (W/V) Pluronic L-44 4.08% (W/V) Glycine 0.1% (W/V) pH Adjuster
(sodium hydroxide, glucono-.delta.-lactone) qs Pure water qs pH 9
(4) Substance to be tested 4 Name: Olanexidine formulation pH 10
Composition: Olanexidine gluconate 1.5% (W/V) Pluronic L-44 16.08%
(W/V) Glycine 0.1% (W/V) pH Adjuster (sodium hydroxide,
glucono-.delta.-lactone) qs Pure water qs pH 10 (5) Control
substance Name: Base pH 10 Composition: Pluronic L-44 1.08% (W/V)
Glycine 0.1% (W/V) pH Adjuster (sodium hydroxide,
glucono-.delta.-lactone) qs Pure water qs pH 10
[0052] 1-1-2 Medium [0053] (1) 7H10 Plate
[0054] To 19 g of Difco Middlebrook 7H10 Agar (product number:
262710, manufactured by Becton, Dickinson and Company), 5 mL of
glycerol (product number: 070-04941, manufactured by Wako Pure
Chemical Industries, Ltd.) and 900 mL of pure water were added and
stirred. The medium was steam-sterilized under pressure
(121.degree. C., 20 minutes). After sterilization, the medium was
taken out from the pressure steam sterilizer, cooled to 50 to
55.degree. C. with stirring, and subsequently 100 mL of BBL
Middlebrook OADC Enrichment (product number: 212240, manufactured
by Becton, Dickinson and Company) was added and stirred. About 20
mL each of the agar, before set, was dispensed in petri dishes and
allowed to be solidified. [0055] (2) SAB Plate
[0056] To 65 g of a Sabouraud agar medium "Nissui" (product number:
05701, manufactured by NISSUI PHARMACEUTICAL CO., LTD.), 1000 mL of
pure water was added and stirred. The medium was steam-sterilized
under pressure (121.degree. C., 20 minutes). About 20 mL each of
the agar, before set, was dispensed in petri dishes and allowed to
be solidified. [0057] (3) SABLP Plate
[0058] To 73 g of a Sabouraud-Dextrose LP Agar medium "DAIGO"
(product code: 392-01875, manufactured by NIHON PHARMACEUTICAL CO.,
LTD.), 1000 mL of pure water was added and stirred. The medium was
steam-sterilized under pressure (121.degree. C., 20 minutes). About
20 mL each of the agar, before set, was dispensed in petri dishes
and allowed to be solidified. [0059] 1-1-3 Neutralizer
[0060] To about 800 mL of distilled water, 100 g of polysorbate 80,
5.0 g of a sodium thiosulfate hydrate, 0.4 g of potassium
dihydrogen phosphate, 1 mL of Triton X-100, 10.1 g of disodium
hydrogen phosphate anhydrous, and 11.7 g of soy lecithin were added
and stirred. Further, 10.0 g of Tamol (R) NN8906 was added, and
heated and stirred until dissolved. After dissolution, a 1 mol/L
sodium hydroxide solution was added to adjust pH to 7.8 to 7.9.
Distilled water was added until the total amount was 1000 mL, and
then steam-sterilization under pressure was carried out. [0061]
1-1-4 Test Microorganisms
[0062] For test microorganisms, filamentous fungus Microsporum
canis NBRC 32464, acid-fast bacteria Mycobacterium chelonae JCM
6388 and Mycobacterium fortuitum JCM 6387 were used. Each of the
test microorganisms was cultured on the 7H10 plate (Mycobacterium
chelonae and Mycobacterium fortuitum) or the SAB plate (Microsporum
canis), and then suspended in distilled water to prepare test
microorganism solutions of McFarland No.1 (Mycobacterium chelonae
and Mycobacterium fortuitum) or of McFarland No.5 (Microsporum
canis). [0063] 1-2 Bactericidal Power Evaluation Test [0064] 1-2-1
Measurement of Initial Viable Cell Counts (Mycobacterium chelonae
and Mycobacterium fortuitum) [0065] (1) To 3 mL of distilled water,
150 .mu.L of the test microorganism solution was added and mixed.
[0066] (2) Immediately, 50 .mu.L of the bacterium mixture was added
to 4.95 mL of the neutralizer and mixed. The mixture was prepared
to be a 10.sup.2-fold dilution. [0067] (3) 0.3 mL of the
10.sup.2-fold dilution was added to 2.7 mL of the neutralizer to
dilute 10 times. Dilution was further repeated by the same
operation to produce 10-fold dilution series (3 stages in total
from 10.sup.2- to 10.sup.4-fold dilutions). [0068] (4) 100 .mu.L
each of the 10.sup.2- to 10.sup.4-fold dilutions was dispensed onto
the 7H10 plate and smeared. Steps (2) to (4) were carried out
within 30 minutes. [0069] (5) The smear plate was inverted and the
cells were cultured until a colony count can be carried out. [0070]
(6) The colonies grown in the smear plate were visually counted and
the number of colonies was multiplied by a dilution factor to
calculate a viable cell count (CFU/mL). However, the smear plates
in which the number of colonies is too numerous to distinguish
colonies from each other were defined as TNTC (too numerous to
count) and not counted. [0071] 1-2-2 Measurement of Viable Cell
Count After the Test Substances Acted (Mycobacterium chelonae and
Mycobacterium fortuitum) [0072] (1) To 3 mL of the test substance,
150 .mu.L of the test microorganism solution was added and mixed.
Using this mixture as a reaction solution, the reaction was carried
out at room temperature. [0073] (2) After allowing the reaction to
proceed for a predetermined period of time, 50 .mu.L of the
reaction solution was extracted, to which 4.95 mL of the
neutralizer was added and mixed. This mixture was prepared to be a
10.sup.2-fold dilution. [0074] (3) 0.3 mL of the 10.sup.2-fold
dilution was added to 2.7 mL of the neutralizer to dilute 10 times.
Dilution was further repeated by the same operation to produce
10-fold dilution series (3 stages in total from 10.sup.2- to
10.sup.4-fold dilutions). [0075] (4) 100 .mu.L each of the
10.sup.2- to 10.sup.4-fold dilutions was dispensed onto the 7H10
plate and smeared. [0076] (5) The smear plate was inverted and the
cells were cultured until a colony count can be carried out. [0077]
(6) The colonies grown in the smear plate were visually counted and
the number of colonies was multiplied by a dilution factor to
calculate a viable cell count (CFU/mL). [0078] 1-2-3 Measurement of
Initial Viable Cell Count (Microsporum canis) [0079] (1) To 3 mL of
distilled water, 150 .mu.L of the test microorganism solution was
added and mixed. [0080] (2) Immediately, 500 .mu.L of the
microorganism mixture solution was added to 4.5 mL of the
neutralizer and mixed. This mixture was prepared to be a
10.sup.1-fold dilution. [0081] (3) 0.3 mL of the 10.sup.1-fold
dilution was added to 2.7 mL of the neutralizer to dilute 10 times.
Dilution was further repeated by the same operation to produce
10-fold dilution series (3 stages in total from 10.sup.1- to
10.sup.3-fold dilutions). [0082] (4) 100 .mu.L each of the
10.sup.1- to 10.sup.3-fold dilutions was dispensed onto the SABLP
plate and smeared. Steps (2) to (4) were carried out within 30
minutes. [0083] (5) The smear plate was inverted and the cells were
cultured until a colony count can be carried out. [0084] (6) The
colonies grown in the smear plate were visually counted and the
number of colonies was multiplied by a dilution factor to calculate
a viable cell count (CFU/mL). However, the smear plates in which
the number of colonies is too numerous to distinguish colonies from
each other were defined as TNTC and not counted. [0085] 1-2-4
Measurement of Viable Cell Count After the Test Substance Acted
(Microsporum canis) [0086] (1) To 3 mL of the test substance, 150
.mu.L of the test microorganism solution was added and mixed. Using
this mixture as a reaction solution, the reaction was carried out
at room temperature. [0087] (2) After allowing the reaction to
proceed for a predetermined period of time, 500 .mu.L of the
reaction solution was extracted, to which 4.5 mL of the neutralizer
was added and mixed. This mixture was prepared to be a
10.sup.1-fold dilution. [0088] (3) 0.3 mL of the 10.sup.1-fold
dilution was added to 2.7 mL of the neutralizer to dilute 10 times.
Dilution was further repeated by the same operation to produce
10-fold dilution series (3 stages in total from 10.sup.1- to
10.sup.3-fold dilutions). [0089] (4) 100 .mu.L each of the
10.sup.1- to 10.sup.3-fold dilutions was dispensed onto the SABLP
plate and smeared. [0090] (5) The smear plate was inverted and the
cells were cultured until a colony count can be carried out. [0091]
(6) The colonies grown in the smear plate were visually counted and
the number of colonies was multiplied by a dilution factor to
calculate a viable cell count (CFU/mL). [0092] 1-2-5 Calculation
Formula of Log.sub.10 Reduction (LR)
[0092] LR=A-B [0093] A: Average value of initial viable cell count
(common logarithm value) [0094] B: Viable cell count after each of
the test substances acted (common logarithm value)
[0095] With Mycobacterium chelonae and Mycobacterium fortuitum, the
mixing ratio of the reaction solution to the neutralizer is 1:99
and the smear amount is 100 .mu.L, because of which the minimum
limit of detection of a viable cell count is 1000 CFU/mL (3 in
common logarithm value). Further, with Microsporum canis, the
mixing ratio of the reaction solution to the neutralizer is 1:9 and
the smear amount is 100 .mu.L, because of which the minimum limit
of detection of a viable cell count is 100 CFU/mL (2 in common
logarithm value). When a colony was not detected, the minimum limit
of detection was adopted and LR is indicated with a sign of
inequality ">". [0096] 1-3 Results
[0097] The results are shown in Tables 1 to 3 and FIGS. 1 to 3
below.
TABLE-US-00002 TABLE 1 Bactericidal power against acid-fast
bacterium Mycobacterium fortuitum JCM 6387 Log.sub.10 reduction
(mean .+-. SD) Test substance 5 min (n = 3) 10 min (n = 6) 15 min
(n = 3) Olanexidine 0.83 .+-. 0.24 1.28 .+-. 0.33 1.94 .+-. 0.26
formulation pH 5 Olanexidine 2.08 .+-. 0.38 3.18 .+-. 0.25 3.40
.+-. 0.00 formulation pH 8 Olanexidine 2.18 .+-. 0.28 2.51 .+-.
0.16 3.06 .+-. 0.60 formulation pH 9 Olanexidine 1.67 .+-. 0.24
2.13 .+-. 0.30 2.51 .+-. 0.55 formulation pH 10 Base pH 10 0.00
.+-. 0.02 0.02 .+-. 0.15 0.06 .+-. 0.13
TABLE-US-00003 TABLE 2 Bactericidal power against acid-fast
bacterium Mycobacterium chelonae JCM 6388 Log.sub.10 reduction
(mean .+-. SD, n = 3) Test substance 5 min 10 min 15 min
Olanexidine 0.12 .+-. 0.38 0.24 .+-. 0.32 0.62 .+-. 0.53
formulation pH 5 Olanexidine 1.62 .+-. 0.65 2.02 .+-. 0.55 2.24
.+-. 0.17 formulation pH 8 Olanexidine 0.68 .+-. 0.40 1.00 .+-.
0.24 2.24 .+-. 0.17 formulation pH 9 Olanexidine 0.08 .+-. 0.10
0.53 .+-. 0.42 0.94 .+-. 0.22 formulation pH 10 Base pH 10 -0.37
.+-. 0.23 -0.09 .+-. 0.22 -0.17 .+-. 0.20
TABLE-US-00004 TABLE 3 Bactericidal power against filamentous
fungus Microsporum canis NBRC 32464 Log.sub.10 reduction (mean .+-.
SD, n = 3) Test substance 15 sec 30 sec 60 sec Olanexidine 0.29
.+-. 0.04 0.44 .+-. 0.03 0.86 .+-. 0.05 formulation pH 5
Olanexidine 2.23 .+-. 0.35 >2.57 >2.57 formulation pH 8
Olanexidine 2.47 .+-. 0.17 >2.57 >2.57 formulation pH 9
Olanexidine 2.23 .+-. 0.35 2.37 .+-. 0.35 >2.57 formulation pH
10 Base pH 10 -0.07 .+-. 0.04 0.02 .+-. 0.06 0.07 .+-. 0.03
[0098] The above results revealed that, in all test microorganisms,
bactericidal powers of the olanexidine formulations at pH 8 to 10
are more intense than the olanexidine formulation at pH 5. Note
that the bactericidal power of the olanexidine formulation at pH 10
is more reduced than the olanexidine formulation at pH 8, but this
is considered that the activity was prohibited by Pluronic L-44
added as the solubilizer.
EXAMPLE 2
[0099] 2. Action of Olanexidine Formulations on Bacteriophage
MS2
[0100] Bacteriophage MS2 is known to be resistant to disinfectants
and is used for an alternative test such as the norovirus killing
action of disinfectants. For this reason, viricidal effects of the
olanexidine formulations prepared by changing pH and a commercial
disinfectant on a virus were evaluated by a test using
bacteriophage MS2. [0101] 2-1 Test Material and Method [0102] 2-1-1
Test Substances
TABLE-US-00005 [0102] (1) Substance to be tested 1 Name:
Olanexidine formulation pH 5 Composition: Olanexidine gluconate
1.5% (W/V) Pluronic L-44 1.08% (W/V) pH Adjuster (sodium hydroxide,
glucono-.delta.-lactone) qs Pure water qs pH 5 (2) Substance to be
tested 2 Name: Olanexidine formulation pH 7 Composition:
Olanexidine gluconate 1.5% (W/V) Pluronic L-44 1.08% (W/V) HEPES
0.1% (W/V) pH Adjuster (sodium hydroxide, glucono-.delta.-lactone)
qs Pure water qs pH 7 (3) Substance to be tested 3 Name:
Olanexidine formulation pH 8 Composition: Olanexidine gluconate
1.5% (W/V) Pluronic L-44 1.08% (W/V) HEPES 0.1% (W/V) pH Adjuster
(sodium hydroxide, glucono-.delta.-lactone) qs Pure water qs pH 8
(4) Substance to be tested 4 Name: Olanexidine formulation pH 8.5
Composition: Olanexidine gluconate 1.5% (W/V) Pluronic L-44 1.08%
(W/V) L-Histidine 0.1% (W/V) pH Adjuster (sodium hydroxide,
glucono-.delta.-lactone) qs Pure water qs pH 8.5 (5) Substance to
be tested 5 Name: Olanexidine formulation pH 9 Composition:
Olanexidine gluconate 1.5% (W/V) Pluronic L-44 4.08% (W/V) Glycine
0.1% (W/V) pH Adjuster (sodium hydroxide, glucono-.delta.-lactone)
qs Pure water qs pH 9 (6) Substance to be tested 6 Name:
Olanexidine formulation pH 9.5 Composition: Olanexidine gluconate
1.5% (W/V) Pluronic L-44 10.08% (W/V) Glycine 0.1% (W/V) pH
Adjustor (sodium hydroxide, glucono-.delta.-lactone) qs Pure water
qs pH 9.5 (7) Substance to be tested 7 Name: Olanexidine
formulation pH 10 Composition: Olanexidine gluconate 1.5% (W/V)
Pluronic L-44 16.08% (W/V) Glycine 0.1% (W/V) pH Adjustor (sodium
hydroxide, glucono-.delta.-lactone) qs Pure water qs pH 10 (8)
Substance to be tested 8 Name: Olanexidine formulation pH 12
Composition: Olanexidine gluconate 1.5% (W/V) Pluronic L-44 26.08%
(W/V) L-Arginine 0.1% (W/V) pH Adjustor (sodium hydroxide,
glucono-.delta.-lactone) qs Pure water qs pH 12 (9) Control
substance Name/Abbreviated name: Antiseptic ethanol "Kenei"/70%
EtOH Manufacturer and distributor: KENEI Pharmaceutical Co., Ltd.
Composition: Ethanol (C.sub.2H.sub.6O) content is 76.9 to 81.4%
(V/V).
[0103] 2-1-2 Medium [0104] (1) 702 Liquid Medium
[0105] To 1 L of pure water, 10 g of Polypepton, 2 g of a Yeast
extract, and 1 g of MgSO.sub.4.7H.sub.2O were added and
steam-sterilized under pressure (121.degree. C., 20 minutes).
[0106] (2) Soft Agar Medium
[0107] To 0.5 L of pure water, 5 g of Polypepton, 1 g of a Yeast
extract, 0.5 g of MgSO.sub.4.7H.sub.2O, and 3.5 g of agar for a
medium were added and steam-sterilized under pressure (121.degree.
C., 20 minutes). [0108] (3) Agar Plate
[0109] To 64 g of a trypto-soya agar medium (SCD agar medium)
"Nissui", 1.6 L of pure water was added and stirred. The medium was
steam-sterilized under pressure (121.degree. C., 20 minutes). About
20 mL each of the agar, before set, was dispensed in petri dishes
and allowed to be solidified. [0110] 2-1-3 Neutralizer
[0111] To about 800 mL of distilled water, 100 g of polysorbate 80,
5.0 g of a sodium thiosulfate hydrate, 0.4 g of potassium
dihydrogen phosphate, 1 mL of Triton X-100, 10.1 g of disodium
hydrogen phosphate anhydrous, and 11.7 g of soy lecithin were added
and stirred. Further, 10.0 g of Tamol (R) NN8906 was added, and
heated and stirred until dissolved. After dissolution, a 1 mol/L
sodium hydroxide solution was added to adjust pH to 7.8 to 7.9.
Distilled water was added until the total amount was 1000 mL, and
then steam-sterilization under pressure was carried out. [0112]
2-1-4 Bacteriophage and Host [0113] (1) Bacteriophage [0114]
Name/Abbreviated name: Escherichia coli phage MS2/MS2 phage [0115]
Supply source: National Institute of Technology and Evaluation
Biotechnology Center (NBRC) [0116] NBRC No.: 102619 [0117] (2) Host
[0118] Name/Abbreviated name: Escherichia coli (Migula 1895)
Castellani and Chalmers 1919/E. coli NBRC13965 [0119] Supply
source: NBRC [0120] NBRC No.: 13965 [0121] 2-2 Test Method [0122]
2-2-1 Host [0123] E. coli NBRC 13965 preserved in a casitone medium
was inoculated in 5 mL.times.4 of a 702 liquid medium and cultured
by shaking at 35.degree. C. overnight. The cells were added to 180
mL of the 702 liquid medium and further cultured by shaking for 3
hours to use the obtained culture by shaking as a host culture
liquid. [0124] 2-2-2 Phage Solution
[0125] A phage solution prepared to about 6.times.10.sup.12 PFU/mL
in accordance with a routine method was used. [0126] 2-2-3
Viricidal (Phage) Test [0127] (1) To 475 .mu.L of the test
substance, 25 .mu.L of the phage solution was added. Further, 25
.mu.L of the phage solution was added to 475 .mu.L of distilled
water as a control action solution. [0128] (2) The action was
allowed to proceed at room temperature for 30 seconds, 1 minute and
3 minutes. The control action solution only had the action time of
about 3 minutes. [0129] (3) After the action, 50 .mu.L of the
action solution was collected and then 450 .mu.L of the neutralizer
was added and stirred. This mixture was prepared to be a
10.sup.1-fold dilution. [0130] (4) 20 .mu.L of each of the
10.sup.1-fold dilutions was added to 180 .mu.L of the neutralizer
and stirred. This mixture was prepared to be a 10.sup.2-fold
dilution. Same dilution operation was repeated to produce 10-fold
dilution series to 10.sup.9-fold. [0131] (5) To 100 .mu.L of
10.sup.2- to 10.sup.9-fold dilutions series, 0.2 mL of the host
culture liquid was added and stirred. About 5 mL of a soft agar
medium preserved at about 47.degree. C. was added, gently stirred,
and then overlaid on the agar plate. [0132] (6) The soft agar
medium, after solidified, was cultured at 35.degree. C. overnight.
[0133] (7) The number of plaques caused was counted. [0134] (8) A
titer (log.sub.10 PFU/mL) was calculated using weighted average
method [(Equation 1) below]. Further, a Log.sub.10 reduction was
calculated. [0135] 2-2-5 Data Analysis [0136] (1) Phage Titer
[0137] Phage titer was calculated using the following (Equation
1).
PFU/t=(.SIGMA.c.sub.1+c.sub.2+ . . . +c.sub.n)
((n.sub.1+n.sub.2.times.v.sub.2+ . . .
+n.sub.n.times.v.sub.n).times.d) (Equation 1) [0138] t: A dilution
amount added to the plate (0.1 mL in the present test) [0139]
c.sub.1: Total number of plaques of all plates of the minimum
dilution factor countable [0140] c.sub.2: Total number of plaques
of all plates of dilution factor after c.sub.1 [0141] c.sub.n:
Total number of plaques of all plates of the maximum dilution
factor [0142] n.sub.1: Number of plates of c.sub.1 [0143] n.sub.2:
Number of plates of c.sub.2 [0144] v.sub.2: Ratio of the dilution
factors of c.sub.1 to c.sub.2 (10.sup.-1 in the present test)
[0145] n.sub.n: Number of plates of c.sub.n [0146] v.sub.n: Ratio
of the dilution factors of c.sub.1 to c.sub.n [0147] d: Dilution
factor of c.sub.1
[0148] A titer (PFU/mL) was converted to common logarithm
(log.sub.10 PFU/mL) and indicated to the first decimal place by
rounding off. When a titer (PFU/mL) was 1 or less, its common
logarithm value was 0. [0149] (2) Log.sub.10 Reduction (LR)
[0150] The viricidal (phage) action was evaluated by a Log.sub.10
reduction value.
LR=A-B [0151] A: Average value of control action solution phage
titer (common logarithm value) [0152] B: Phage titer of each of the
test substances after acted (common logarithm value)
[0153] LR is indicated to the first decimal place by rounding off.
Note that when a titer (common logarithm value) of the test
substance after acted was 0, LR is indicated as ">(A-3)" because
the phage titer has the minimum limit of detection of 3-log.sub.10.
[0154] 2-3 Results
[0155] Evaluation results on the viricidal actions of the test
substances are shown in Table 4 and FIG. 4.
TABLE-US-00006 TABLE 4 Phage killing effect of test substances
Log.sub.10 reduction Test substance 30 sec 60 sec 180 sec
Olanexidine 0.6 0.9 1.2 formulation pH 5 Olanexidine 1.6 2 3
formulation pH 7 Olanexidine 2.3 3.1 4.3 formulation pH 8
Olanexidine 3 3.6 5 formulation pH 8.5 Olanexidine 3.1 4 5.3
formulation pH 9 Olanexidine 3.4 4 4.5 formulation pH 9.5
Olanexidine 3 4.1 5.2 formulation pH 10 Olanexidine 7.6 8.5 >8.5
formulation pH 12 70% EtOH 1.9 2.9 3.9
[0156] The olanexidine formulation at pH 5 did not substantially
show the viricidal action, and the viricidal action of the
olanexidine formulation at pH 7 was equal to 70% ethanol used as
the control substance, whereas the olanexidine formulations with
the pH changed to basic tended to have larger LR as pH increased.
The formulations at pH 8 or more had an LR of 3 or higher at 60
seconds and the formulation at pH 8.5 or more had an LR of 3 or
higher at 30 seconds thereby to meet a requirement for the
viricidal action of an ideal disinfectant of LR 3 or higher. Thus,
a basic solution of olanexidine gluconate was revealed to have a
practical viricidal activity and such a viricidal activity is
intensified as pH increases.
EXAMPLE 3
[0157] 3. Action of Ethanol-Containing Basic Olanexidine
Formulation on Bacteriophage MS2
[0158] In the present Example, ethanol was added to a basic
olanexidine formulation of pH 9.5 to evaluate a viricidal effect by
a test using bacteriophage MS2 for the purpose of confirming the
quick-dryness imparting effect and the potentiating effect of the
bactericidal activity by an antiseptic alcohol to a basic
olanexidine formulation. [0159] 3-1 Test Substance
[0160] Substances to be tested 1 to 3, Comparative Example 1, and
Base (control substance) were prepared by the compositions of the
following Table 5.
TABLE-US-00007 TABLE 5 Amount (in g/100 mL) Substance Substance
Substance to be to be to be Comparative Ingredient tested 1 tested
2 tested 3 Example 1 Base Olanexidine 1.5 1 0.5 1.5 -- gluconate
Pluronic L-44 1.08 0.72 0.36 1.08 1.08 Benzyl 3.5 3.5 3.5 -- 3.5
alcohol Hexyldecanol 0.01 0.01 0.01 -- 0.01 Pluronic F-68 1 1 1 --
1 Glycyrrhetinic 0.1 0.1 0.1 -- 0.1 acid Glycine 0.1 0.1 0.1 -- 0.1
Glucono-.delta.- qs qs qs -- qs lactone Sodium qs qs qs -- qs
hydroxide Ethanol 70 77 83 70 70 Purified qs qs qs qs qs water pH
9.5 9.5 9.5 6.89 9.5
[0161] Further, the following antiseptic ethanol was used as a
control. [0162] Name: Antiseptic ethanol "Kenei" [0163]
Manufacturer and distributor: KENEI Pharmaceutical Co., Ltd. [0164]
Composition: Ethanol (C.sub.2H.sub.6O) content is 76.9 to 81.4%
(V/V). [0165] 3-2 Test Method
[0166] Viricidal effects were evaluated by the method using the
bacteriophage MS2 described in the above Example 2, 2-1 and 2-2.
Note that a phage solution prepared to about 4.times.10.sup.12
PFU/mL was used. [0167] 3-3 Results
[0168] Evaluation results on viricidal actions of the test
substances are shown in Table 6 and FIG. 5.
TABLE-US-00008 TABLE 6 Log.sub.10 reduction Test substance 30 sec
60 sec Substance to be tested 1 6 6.7 (Olanexidine gluconate 1.5%)
Substance to be tested 2 5.2 5.8 (Olanexidine gluconate 1.0%)
Substance to be tested 3 4.4 5 (Olanexidine gluconate 0.5%)
Comparative Example 1 2.6 3.5 (Olanexidine gluconate 1.5%, pH 6.89)
Base 3.8 4.5 Antiseptic ethanol 2.2 3.4
[0169] The above results showed that the viricidal action increases
in a concentration dependent manner of olanexidine gluconate even
in the basic olanexidine formulation containing ethanol whereby the
viricidal action by olanexidine gluconate is not impeded even when
ethanol is added to impart quick-dryness. Further, the basic
olanexidine formulation containing ethanol has a higher viricidal
action compared with a basic olanexidine formulation which does not
contain ethanol, for the reason of which the ethanol-containing
basic olanexidine formulation showed to have a practical viricidal
action even when an olanexidine gluconate concentration is reduced.
Furthermore, a practical viricidal activity (LR or higher) was not
found in the ethanol-containing olanexidine formulation having pH
of less than 7 (Comparative Example 1), thereby suggesting that, in
the basic olanexidine formulation containing ethanol, olanexidine
gluconate, ethanol, and basicity synergistically contribute to the
viricidal action. Note that, in the present Example, Pluronic F-68
was added for relieving rough skin and moisturization, and no
difference in the effect was found even when Pluronic F-68 was 0.5
g/100 mL.
INDUSTRIAL APPLICABILITY
[0170] The composition of the present invention, when used, can
produce an olanexidine gluconate-containing disinfectant having an
improved bactericidal spectrum and an effect on non-enveloped
viruses and is thus highly useful in the fields such as medical and
nursing, and food and drink industries.
* * * * *
References