PARK SUNG-HUI (KR)
| KR20070023910A | 2007-03-02 | |||
| US6777420B2 | 2004-08-17 | |||
| US5057520A | 1991-10-15 | |||
| KR20020003220A | 2002-01-10 |
WHAT IS CLAIMED IS:
1. A reactive antibiotic containing reactive groups bonded to fluoroquinolone based antibiotic.
2. The reactive antibiotic according to Claim 1, wherein the reactive antibiotic has a structure represented by the following chemical formula 1 :
(chemical formula 1)
wherein A is a reactive group covalently bondable to natural fiber, R 1 is hydrogen or methyl group, R2 is ethyl group or cyclopropane, and R3 is hydrogen or fluorine.
3. The reactive antibiotic according to Claim 1, wherein the fluoroquinolone based antibiotic is one selected from a group consisting of norfloxacin, ciprofloxacin, enoxacin, lomefloxacin, sparfloxacin and grepafloxacin.
4. The reactive antibiotic according to Claim 1 or 2, wherein the reactive group covalently bondable to natural fiber is one selected from a group consisting of cyanuric chloride group, vinyl sulfone group and α-bromoacrylamide group.
5. An antibacterial fiber processed by using the reactive antibiotic as defined in Claim 1. |
REACTIVE ANTIBIOTICS AND ANTIBACTERIAL FIBER TREATED
THEREBY
TECHNICAL FIELD The present invention relates to reactive antibiotics having structure of reactive groups bonded to fluoroquinolone based antibiotics with strong anti-bacterial properties, the reactive groups of which are covalently bondable to natural fibers, and antibacterial fibers treated with the same. Generally, a fabric product used in garment or bedclothes needs to undergo a fiber material dyeing process with desired colors to satisfy different tastes of consumers.
Such manufactured fabric product often becomes habitable for microorganisms due to poor care, allowing the microorganisms to inhabit and grow with normal bodily secretions as nutrient when the microorganisms contact directly with a human body so that it threatens health of the human body and/ or results bad odor, contamination, discoloration, brittleness of fiber, etc., thereby being a major cause to deteriorate quality of the fabric product such as durability, color fastness or the like.
Accordingly, the fabric product may become a medium or habitat for pathogenic bacteria to invade the human body. However, if the fabric product has anti-bacterial properties, it will become a functional fabric product that inhibits inhabitation or growth of microorganisms and, as a result, protects against contagious disease
and bad odor, and prevents staining and brittleness of fiber of the fabric product.
BACKGROUND ART It is well known that anti-bacterial and deodorization processes are generally classified into post-treatment processes and fiber improving processes. The post- treatment processes include: as disclosed in Korean Patent Laid-Open No. 2000-007593, a method for giving anti-bacterial properties to fibers, which includes extraction of dyeing ingredient from a natural material such as Saururus chinensis (Lour.) Baill with anti-bacterial properties; a method which cross-links an anti-bacterial material such as organometallic compound or organic material with fibers and thermally fixes the bonded product to surface of the fibers by using a reactant resin; a method which fixes an anti- bacterial material to surface of fibers by adsorption and so on. On the other hand, the fiber improving processes include: a method which comprises introducing an inorganic anti-bacterial agent within fibers by blend- spinning the inorganic anti-bacterial agent into polymer in a process of manufacturing synthetic fibers; a method which disperses a copper compound into fibers during coagulating and regenerating in a process of manufacturing regenerated fibers; a method for synthesizing polymer, which comprises organic copolymer ingredients with antibacterial properties and so on.
The anti-bacterial and deodorization processes have not a purpose of sterilization or treatment of diseases but are to inhibit
inhabitation and growth of microbes and/or fungi on fibers. Therefore, the processes require that an anti-bacterial effect is continuously maintained at least a predetermined level rather than only exhibiting high anti-bacterial properties for a short time and must safe to human bodies. Under these circumstances, although organic mercury compound, organic tin compound, organic copper compound and organic zinc compound among the organometallic compounds used in the post-treatment processes have very superior anti-bacterial properties, they also have a problem of safety to a human body such as toxicity. As a result, most of the organometallic compounds for garments are prohibited by countries such as Japan, U.S.A., etc. but are partially used in applications that do not involve direct contact with the human body, for example, production of carpet or wallpaper, or other industrial fields. Furthermore, such organometallic compounds that have demonstrated problems of undesired adhesion to fibers and low laundry durability are restricted in their permanent anti-bacterial effect.
Also, general organic an ti- bacterial materials that could be easily processed compared with inorganic materials and do not affect mechanical properties, transparency, color, etc., as much are widely used at present. However, use of the organic anti-bacterial materials is limited because their anti-bacterial effect is not continued for a long term as described above and they have inferior heat- resistance. Alternatively, some of the organic anti-bacterial materials often have disadvantages of causing skin irritation, tearing property and so on.
Dyes extracted from natural materials have a merit that anti-bacterial properties are early given to fibers in a dyeing process. But, they have a restriction in extracting the dyes due to seasonal limitation and a disadvantage that mordant dyeing accompanied with additional heavy metals is required to improve color fastness as a defect of natural dyes.
Inorganic anti-bacterial materials are obtained by substitution of an inorganic carrier such as zeolite, silica, alumina, etc. with metal ions such as silver, copper, zinc, etc. having excellent anti-bacterial properties. The inorganic anti-bacterial materials that have three- dimensional structure formed with micro-fine pores demonstrate a large surface area and excellent heat-resistance. It is believed as of now that silver, copper and zinc belong to a few metals with superior antibacterial effect and safety, and are harmless to the human body. The inorganic anti-bacterial materials have higher heat-resistance and stability sufficient not to cause volatilization and decomposition thereof in comparison to conventional organic anti-bacterial materials, thereby being used in a wide variety of applications. In addition, since they express anti-bacterial effect via activated oxygen ions, the inorganic anti-bacterial materials have an excellent anti-bacterial effect superior to the organic anti-bacterial materials. However, such metal ions, for example, silver, copper or zinc that are apt to deteriorate resin or cause yellowing have a possibility of significantly lowering value of goods containing the same. There is another concern with the inorganic antibacterial materials in that they may cause cutting of thread if the inorganic anti-bacterial materials are added to micro-fine fibers during
blend-spinning, since they generally have a larger average particle diameter above micron units and a wider distribution of particle size.
DISCLOSURE OF THE INVENTION (TECHNICAL PROBLEM)
Accordingly, the present invention is directed to solve the problems of conventional anti-bacterial materials used as dyes as described above and, an object of the present invention is to provide reactive antibiotics containing strong anti-bacterial reactant groups with safety but neither deterioration nor yellowing condition.
Specifically, the present invention provides reactive antibiotics with introduction of reactive groups into fluoroquinolone based antibiotics having excellent anti-bacterial properties, for example, norfloxacin, ciprofloxacin, enoxacin, lomefloxacin, sparfloxacin, grepafloxacin and the like, the reactive groups of which are covalently bondable to natural fibers.
Another object of the present invention is to provide antibacterial fibers treated with the above reactive antibiotics, which have antibacterial properties that are continuously maintained for a long period of time.
(TECHNICAL MEANS TO SOLVE THE PROBLEM)
In order to accomplish the above described objects, the present invention provides reactive antibiotics having structure of reactive groups bonded to fluoroquinolone based antibiotics with strong anti- bacterial properties, the reactive groups of which are covalently
bondable to natural fibers.
The present invention will be described in detail below.
Anti-bacterial materials generally used include, for example, penicillin, sulfonamide, fluoroquinolone, tetracycline, aminoglucoside and the like. Among them, preferred are tetracycline, sulfonamide, quinolone, etc. which are widely and commercially available as intermediates of dyes. The present invention especially uses fluoroquinolone based antibiotics capable of inhibiting metabolic function of enzymes in microorganisms to endow anti-bacterial properties to a subject matter.
Fluoroquinolone based antibiotics are one of novel anti-bacterial agents with a wide range of applications, which have excellent tissue penetration and relatively long duration of action. The above antibiotics have a reaction mechanism that prevents DNA replication by combining the antibiotics with DNA of the human body. The fluoroquinolone antibiotics are called '4-quinolone fluoride' because they contain fluorine atoms at 6th position of 4-quinolone ring structure, and some of them have 1 -piperazinyl group at 7th position of the structure. The fluoroquinolone based antibiotics are effective to treat a variety of microorganisms including, for example, Escherichia coli, Klebsiella, Enterobacter, Serratia sp., Proteus mirabilis, Proteus Indole positive bacteria, Citrobacter, Salmonella, Shigella, Hemophilus, Staphylococcus, Streptococcus, Gonococcus, S. pneumoniae, Pseudomonas sp., Acinetobacter sp., Clostridium perfringens (or Clostridium welchii), Micoplasma, Chlamidia trachomatis, etc. and are totally synthetic
chemotherapy agents which exhibit stronger anti-bacterial activity in a wider range of applications than that of typical quinolone agents or nalidixic acid.
Conventional fluoroquinolone based antibiotics which are at present continuously studied and widely employed, have important features that are very effective to treat bacterial diseases, have strong anti-bacterial ability and wide spectrum, are prepared by total synthesis unlike to penicillin or cephalosporin based antibiotics which are formed by semi-synthesis, and applicable to oral administration thereof. Furthermore, the above antibiotics possess specific anti-bacterial functions absolutely different from that of other formulations generally known at present. Also, there exist rare drug-resistant bacteria in relation to the above antibiotics because the antibiotics do not have anti-bacterial activity attained by plasmid. The fluoroquinolone based antibiotics make DNA gyrase inactivate, which is an enzyme necessary to replicate DNA of bacteria for supercoiling such as joining DNA cut pieces with other DNA after cutting circular DNA, distortion, relaxation, and ATP hydrolysis, etc. Thus, such enzyme inactivation causes abnormal chromosome conditions which results in impossible division and growth of bacteria, thereby showing sterilization effect.
Derivatives with introduction of fluorine atom at C-6th position of the fluoroquinolone based antibiotics can increase antibacterial activity with respect to DNA gyrase by about 2 to 17 times and cell penetration by about 2 to 70 times depending on the type of substituents at C-7th position of the antibiotics. Also, the derivatives
show maximum efficacy when piperazinyl group is added to C-7th position.
The fluoroquinolone based antibiotic used in the present invention includes a variety of kinds, for example, that are selected from a group consisting of norfloxacin, ciprofloxacin, enoxacin, lomefloxacin, sparfloxacin and grepafloxacin, and, most preferably, comprises lomefloxacin which has the convenience of being synthetic.
The fluoroquinolone based antibiotic with strong anti-bacterial properties used in the present invention includes, but is not limited to: Norfloxacin
Ciprofloxacin
Enoxacin
Lomefloxacin
Sparfloxacin
Grepafloxacin
All of the antibiotics mentioned in the detailed description are useable as intermediates of the present invention. As a particular embodiment, if using lomefloxacin among the fluoroquinolone based antibiotics as the intermediate, and bonding it with various reactive groups which are covalently bondable to natural fibers, there is provided a reactive antibiotic represented by chemical formula 1 :
(Chemical formula 1)
wherein A is a reactive group covalently bondable to natural fiber, R 1 is hydrogen or methyl group, R2 is ethyl group or cyclopropane and R3 is hydrogen or fluorine.
In the chemical formula 1, the reactive group covalently bondable to natural fiber is selected from a group consisting of cyanuric chloride group, vinyl sulfone group and α-bromoacrylamide group.
In a preferred embodiment of the present invention, there is provided a reactive antibiotic represented by chemical formula 2 obtained by condensation of lomefloxacin represented by general formula 1 with cyanuric chloride dispersion represented by general formula 2:
(General formula 1) Lomefloxacin
(General formula 2) Cyanuric chloride
(Chemical formula 2)
In another preferred embodiment of the present invention, there is provided a reactive antibiotic represented by chemical formula 3 obtained by condensation of lomefloxacin represented by the general formula 1 with α,β-dibromopropionyl chloride dispersion represented by general formula 3:
(General formula 1) Lomefloxacin
(General formula 3) α,β-dibromopropionyl chloride
(Chemical formula 3)
In another preferred embodiment of the present invention, there is provided a reactive antibiotic represented by chemical formula 4 obtained by first condensation of lomefloxacin represented by the
general formula 1 with cyanuric chloride represented by the general formula 2, then, second condensation of the first reactive product with P-aminobenzene vinyl sulfone represented by general formula 4 or m- aminobenzene vinyl sulfone represented by general formula 5: (General formula 4) P-aminobenzene vinyl sulfone
wherein x is H or Na.
(General formula 5) m-aminobenzene vinyl sulfone
wherein x is H or Na. (Chemical formula 4)
wherein x is H or Na.
(ADVANTAGEOUS EFFECTS)
As described in detail above, the present invention can prepare functional antibacterial fibers by covalently bonding specific reactive groups to natural fibers to give anti-bacterial and anti-fungal properties to the fibers without adverse effect to color of the fibers. Features of the present invention described above and other advantages will be more clearly understood by the following non-limited examples, which are not intended to restrict the scope of the invention but are instead illustrative embodiments of the present invention. Accordingly, it will be obvious to those skilled in the art that the present invention is not restricted to the specific matters stated above and the examples below.
BEST MODE FOR CARRYING OUT THE INVENTION
[Example 1: Preparation of a reactive antibiotic represented by the chemical formula 2]
0.01 moles of cyanuric chloride represented by the general formula 2 is mixed with small amount of acid, fed into 100ml of distilled water under agitation, and uniformly dispersed in the distilled water while maintaining the solution at 0 to 5°C. After feeding 45.7 parts by weight of lomefloxacin represented by the general formula 1 into distilled water then adding small amount of acid to the solution, the prepared solution is dissolved while maintaining the solution at 5 0 C or below. The dissolved lomefloxacin solution is slowly added to the cyanuric chloride solution to proceed condensation for 2 hours. After completing the reaction, the obtained product is subjected to cooling,
neutralization and dehydration, and dried under vacuum conditions to produce the reactive antibiotic represented by the chemical formula 2:
[Example 2: Preparation of a reactive antibiotic represented by the chemical formula 3]
0.01 moles of lomefloxacin represented by the general formula 1 is fed into distilled water, mixed with small amount of acid and dissolved in the distilled water while maintaining the solution at 5°C and below. In an alternative burette, 0.01 moles of α,β- dibromopropionyl chloride represented by the general formula 3 is fed and subjected to condensation for 2 hours while slowly adding the lomefloxacin solution thereto. After completing the first reaction, the reactive product is mixed with 10% KOH solution while maintaining the solution at about 20 0 C to keep pH 12 and proceed debromination. After completing the debromination, the obtained product is subjected to
neutralization and dehydration, and dried under vacuum conditions to produce the reactive antibiotic represented by the chemical formula 3:
[Example 3: Preparation of a reactive antibiotic represented by the chemical formula 4]
0.01 moles of cyanuric chloride represented by the general formula 2 is mixed with small amount of acid, fed into 100ml of distilled water under agitation, and uniformly dispersed in the distilled water while maintaining the solution at 0 to 5°C. After feeding 45.7 parts by weight of lomefloxacin represented by the general formula 1 into distilled water then adding small amount of acid to the solution, the
prepared solution is dissolved while maintaining the solution at 5°C or below. The dissolved lomefloxacin solution is slowly added to the cyanuric chloride solution to proceed condensation for 2 hours to prepare first condensed product:
After completing the first condensation, 0.01 moles of p- aminobenzene vinyl sulfone is dissolved in an alternative beaker and the obtained solution is slowly added to the first condensed solution to proceed second condensation. Herein, the temperature of a reaction vessel is kept to about 40 0 C. After completing the second condensation, the obtained solution is subjected to neutralization and dehydration, and dried under vacuum conditions to produce the reactive antibiotic represented by the chemical formula 4:
0.1% o.w.f. solution is produced by using the prepared reactive antibiotic represented by the chemical formula 2 in water and glacial acetic acid is added thereto to obtain an anti-bacterially treated solution. To the treated solution, cotton fiber is introduced and treated at 40 0 C for 30 minutes, soaped and dried to form the antibacterial fiber.
In another embodiment, 0.1% o.w.f. solution is produced by using the prepared reactive antibiotic represented by the chemical formula 3 in water and glacial acetic acid is added thereto to obtain the anti-bacterially treated solution. To the treated solution, cotton fiber is introduced and treated at 98°C for 30 minutes, soaped and dried to form the antibacterial fiber.
In a further embodiment, 0.1% o.w.f. solution is produced by using the prepared reactive antibiotic represented by the chemical formula 4 in water and sodium carbonate is added thereto to obtain the anti-bacterially treated solution. To the treated solution, cotton fiber is
introduced and treated at 60 0 C for 30 minutes, soaped and dried to form the antibacterial fiber.
Following experiments for determining anti-bacterial properties of the above treated antibacterial fiber, the result is shown in Table 1 below:
[Test of anti-bacterial properties]
Conditions of the test for determining anti-bacterial properties of the antibacterial fiber according to the present invention are as follows:
1. Test method : KSK 0693-2001
2. Test types of strain
1) Strain I : Straphylococcus aureus ATCC 6538
2) Strain II : Klebsiella pneumoniae ATCC 4352
3. Concentration of challenged strain of bacteria
1) Strain I : 1.3 x 10 5 numbers/ ml
2) Strain II : 1.5 x 10 5 numbers/ ml
TABLE 1
Test result for anti-bacterial properties of colored antibacterial fiber
INDUSTRIAL APPLICABILITY
As described in detail above, the present invention provides functional antibacterial fibers by covalently bonding specific reactive groups to natural fibers to give anti-bacterial and anti-fungal properties to the fibers without adverse effect to color of the fibers.
While the present invention has been described with reference to exemplary embodiments thereof, it will be understood by those skilled in the art that various modifications and variations may be made therein without departing from the scope of the present invention as defined by the appended claims.
Next Patent: REACTIVE ANTIBIOTIES AND A METHOD OF PREPARING THE SAME AND ANTIBACTERIAL FIBER TREATED THEREBY