Bactericide against vancomycin resistant enterococcus

Drug – bio-affecting and body treating compositions – Plant material or plant extract of undetermined constitution... – Containing or obtained from camellia

Reexamination Certificate

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C424S744000, C424S750000, C424S405000, C424S725000

Reexamination Certificate

active

06387417

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a bactericide against vancomycin resistant Enterococcus for use in such applications as sterilization of vancomycin resistant Enterococcus (hereinafter referred to as “VRE” simply) that is resistant to vancomycin hydrochloride, disinfection of a site contaminated with VRE, and intestinal sterilization of VRE in animals (human, bovine, chicken, and the like) in which VRE is possible to grow at their intestines.
2. Description of the Related Art
The vancomycin hydrochloride exhibits bactericidal activity on most of bacteria and bacteriostatic activity on Enterococcus. The vancomycin hydrochloride is effective even against methicillin resistant
Staphylococcus aureus
(hereinafter referred to as “MRSA” simply) which has been at issue particularly recently as a bacterium causing nosocomial infection, and hence has been approved as an antibiotic against MRSA in many countries including Japan.
As the vancomycin hydrochloride has been increasingly used as a remedy for diseases caused by the MRSA, there have appeared bacteria having a resistance to the vancomycin hydrochloride. Accordingly, a substance exhibiting bactericidal or antibacterial activity on VRE has now been desired.
SUMMARY OF THE INVENTION
The inventor of the present invention has discovered a fact that hinokitiol known as a bactericidal substance having a relatively extensive antibacterial spectrum is also effective against VRE. The present invention has been attained based on this discovery.
One object of the present invention is to provide a method of sterilizing a vancomycin resistant Enterococcus. The method comprises use of a bactericide containing hinokitiol, a metal complex thereof or their salt as an effective component.
Another objection of the present invention is to provide a method comprising administering an effective amount of a composition containing hinokitiol, a metal complex thereof or their salt to an animal infected with a vancomycin resistant Enterococcus.
Another object of the present invention is to provide a method of disinfecting, the method comprising administering an effective amount of a composition containing hinokitiol, a metal complex thereof or their salt to a site contaminated with a vancomycin resistant Enterococcus.
The foregoing and other objects, features and attendant advantages of the present invention will be more fully appreciated from the reading of the following detailed description.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
A composition for use of sterilizeing a vancomycin resistant Enterococcus, or a bactericide against VRE used in the present invention, contains hinokitiol, a metal complex thereof or their salt as an effective component.
One method of the present invention comprises administering an effective amount of the composition to an animal (e.g. human, bovine, chicken, and pet such as cat and dog) infected with the vancomycin resistant Enterococcus, thereby treating the animal.
Another method of the present invention comprises administering an effective amount of the composition to a site contaminated with the vancomycin resistant Enterococcus, thereby disinfecting the site.
Hereinafter, the composition (i.e. bactericide against VRE) used in the present invention is described in detail.
An effective component in the composition is Hinokitiol, which is otherwise termed &bgr;-Thujaplicin. Hinokitiol is contained in essential oils extracted from such plants as Taiwan hinoki cypress (
Chamaecyparis obtusa
var
formosana
), Aomori hiba (
Thulopsis dolabrata
var
hondai
) and a species of incense cedar (
Calocedrus decurrens
). Not only natural hinokitiol, but also synthetic hinokitiol may be used. Such natural or synthetic hinokitiol is commercially available, for example, from TAKASAGO PERFUME CO., LTD. and OSAKA ORGANIC CHEMICAL IND., LTD.
Examples of metal complexes of hinokitiol include those complexes of hinokitiol with zinc, copper, iron, calcium, magnesium, barium, tin, cobalt, titanium and vanadium. The ratio of hinokitiol to such a metal is not particularly limited, but 2:1 or 3:1 in molar ratio is generally preferable.
Examples of specific salts of hinokitiol or salts of metal complexes of hinokitiol include alkali metal salts such as sodium salts and potassium salts; alkali earth metal salts such as calcium salts and magnesium salts; transition metal salts such as copper salts and zinc salts; alkanolamine salts such as diethanolamine salts, 2-amino-2-ethyl-1,3-propanediol salts and triethanolamine salts; heterocyclic amine salts such as morpholine salts, piperazine salts and piperidine salts; and basic amine salts such as ammonium salts, arginine salts, lysine salts and histidine salts.
Hinokitiol, metal complexes thereof or their salts may be used either alone or in combination of two or more of them depending on the type of a composition to be prepared. In the case of administering the composition into a human body directly, e.g. oral administration, it is preferable to use hinokitiol as it is. On the other hand, metal complexes of hinokitiol or salts of these metal complexes have higher resistance to light than hinokitiol as it is and hence are preferable when the metal complex or the salt of hinokitiol is adapted for applications requiring resistance to light.
Hinokitiol, a metal complex thereof or their salt (hereinafter referred to as “hinokitiol or its analog” unless referred to distinctively) exhibits potent antibacterial activity on VRE. Though hinokitiol is known to exhibit wide antibacterial activity on aerobic bacteria such as tubercle bacillus and typhoid bacillus, anaerobic bacteria such as clostridium, food poisoning pathogens such as Salmonella, and other bacteria including
E. colli
, the inventor of the present invention has made the first discovery that hinokitiol possesses bactericidal activity on VRB.
When hinokitiol or its analog is used alone, hinokitiol in an amount of about 50 to about 100 &mgr;g can exhibit an effective bactericidal action against VRE.
According to the present invention, a preferable composition for the bactericide against VRE further contains at least one selected from the group consisting of respective extracts of aloe, green tea, low striped bamboo and dokudami (hereinafter referred to as “aloe extract and like extracts” unless referred to distinctively). These extracts serve to enhance the antibacterial activity against VRE of hinokitiol and hence contribute to a reduction in the amount of hinokitiol to be required to inhibit the growth of VRE. Where the bactericide is used in the form of an aqueous solution, coexistence of at least one of the aloe extract and like extracts with hinokitiol is particularly preferable. This is because the aloe extract and like extracts can readily provide for an aqueous solution of about 1% by mass hinokitiol, although the limit of the solubility of hinokitiol in water without the aloe extract and like extracts is generally 0.2% by mass.
The aloe extract is made by press extracting aloe leaves, particularly a jelly-like flesh thereof, and heating the aloe juice thus extracted for concentration and stabilization. Instead of such an aloe extract, it is possible to use aloin, which is an anthraquinone derivative forming a principal component of the aloe extract, or barbaloin. The aloe extract contains aloe-emodin, aloesin, aloenin and the like, in addition to aloin and barbaloin.
The green tea extract is a liquid prepared by extracting ground green tea with hot water, followed by purification and concentration. The main component of the green tea extract is tea polyphenol, which is a general term of compounds having a phenolic hydroxyl group in a molecule thereof and contains, as principal components, catechin, epi-catechin, gallo-catechin, epi-gallo-catechin, epi-catechin-gallerte, epi-gallo-catechin-gallerte and the like.
The low striped bamboo extract can be obtained by extracting low striped bamboo with a low temperature/high pressure extracting method. This method utilizes machine equipment s

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