WO1998007458A1 - Surface coating method for metal implants - Google Patents

Surface coating method for metal implants Download PDF

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Publication number
WO1998007458A1
WO1998007458A1 PCT/KR1997/000153 KR9700153W WO9807458A1 WO 1998007458 A1 WO1998007458 A1 WO 1998007458A1 KR 9700153 W KR9700153 W KR 9700153W WO 9807458 A1 WO9807458 A1 WO 9807458A1
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WO
WIPO (PCT)
Prior art keywords
polymer
antiinfective
organic solvent
group
polylactic acid
Prior art date
Application number
PCT/KR1997/000153
Other languages
French (fr)
Inventor
Seo-Young Jeong
Kuiwon Choi
Ick-Chan Kwon
Yong-Hee Kim
Jae-Bong Choi
Original Assignee
Korea Institute Of Science And Technology
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Korea Institute Of Science And Technology filed Critical Korea Institute Of Science And Technology
Priority to DE19781971A priority Critical patent/DE19781971B4/en
Priority to JP10510607A priority patent/JP2000501318A/en
Priority to DE19781971T priority patent/DE19781971T1/en
Priority to AU39528/97A priority patent/AU3952897A/en
Publication of WO1998007458A1 publication Critical patent/WO1998007458A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08—Materials for coatings
    • A61L31/10—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/606—Coatings

Definitions

  • the present invention relates to a surface coating method of metal implants which are widely in use in medical fields such as general surgery, orthopedics surgery, cosmetic surgery and dental surgery. More particularly, the present invention relates to a surface coating method of metal implants, wherein the surface of the implant is coated with an antiinfective polymer film obtained by mixing a polymer and an antiinfective agent with dissolution, suspension, or emulsification method, thereby the antiinfective agent is continuously discharged therefrom and accordingly prevents or treats infection and inflammation of a subject body.
  • Metallic implants for insertion into a living body which have been generally employed for medical treatments are made of stainless steel, Cr-Co alloy, pure titanium or titanium alloy. Those materials are mostly applied to general surgical treatments including orthopedics surgery, cosmetic surgery and dental surgery: Pins, wires, screws, plates and the like have been used for fracture treatments and bone fixture in surgical operation; screws, pins, and artificial joints for cosmetic surgery; and, dental implants for dental treatments.
  • a clinical problem so far incurred by the use of such conventional metallic implants is that it is not certain how an implant inserted into a body infects body tissues and what routes the infection takes.
  • an infection may occur due to an area of the body in contact with the exterior environment.
  • 5 Directly delivered antibiotics into an infected area or continuous oral administration of antiinfective agents have been used to prevent and treat infections.
  • the above treatment not only requires a continuous checkup and treatment process of the doctor in charge, but also side effects incurrs or the o body weakness due to the antibiotic resistance caused by the continuous dose thereof.
  • a surface coating method of metal implants for accomplishing an effective and economical prevention and/or treatment than that of the conventional method.
  • a surface coating method of metal implants according to the present invention wherein the metal implants being inserted into the body are immersed in an antiinfective polymer solution obtained by dissolving, suspending, or 5 emulsifying an an antiinfective agent in polymer solution to coat the implants with a desired thickness and then dried at room temperature or vacuum dried.
  • a method of coating metal implants according to the present invention o was established from a study of prevention and treatment of infection caused by metal implants inserted into a body, such as operational materials: Pins, wires, screws, plates and the like for fracture treatments and bone fixture in surgical operation; screws, pins, and artificial joints for cosmetic surgery; and, dental implants for dental treatments.
  • the present invention 5 provides a coating method of a metallic material inserted into the body, wherein an antiinfective agent is dissolved, suspended or emulsified in a polymer solution. The metal implants are immersed into the solution so as to coat with the antiinfective polymer film to a predetermined thickness, and then the solvent is eliminated therefrom, by use of a gradual drying at room 0 temperature or a vacuum drying.
  • the polymer used in the present invention are polylactic acid homopolymer of molecular weight (M.W.) of 5,000 to 300,000, a copolymer of lactic acid and glycolic acid of molecular weight of 5,000 to 300,000. Due to their bio-degradability, these polymers are widely used in the medical field.
  • An L type, D type, or their racemate LD type polylactic acid may be used in the present invention.
  • the polylactic acid homopolymer manufactured by Polysciences, Inc., U.S.A.
  • polylactic acid and glycolic acid poly (DL-lactide-co-glycolide)] (50:50), manufactured by Sigma Chemical, Co., MO, U.S.A.
  • poly (DL-lactide-co-glycolide) 50:50
  • the amount of the polymer is generally 0.1 to 10 wt./vol.% of the organic solvent used.
  • the antiinfective agent applicable to the present invention is not limited, so that, antibiotic, including anti-bacterial agent, anti-fungal agents and antiviral agents may be used.
  • the antibiotic applied to the present invention includes: sulfonamides such as sulfisoxazole, sulfadiazine, sulfasalazine, sulfacetamide, sulfadoxine; cjuinolones such as nalidixic acid, cinoxacin, norfloxacin; penicillins such as penicillin G, penicillin V, methicillin, ampicillin, amoxicillin, bacampicillin, carbenicillin, ticarcillin; cephalosporins such as cephalothin, cefazolin, cefalexin, cefaladin, cefaclor, cefoxitin, cefotaxime, ceftizoxime; aminoglycosides such as streptomycin, gentamicin, tobramycin, amikoc
  • the antiinfective agent is generally added to an amount of 1 to 50 wt.% based on the amount of the polymer.
  • Organic solvents employed in the present invention to dissolve polymers are butyl alcohol, chloroform, cyclohexane, acetonitrile, dichloromethane, dichlorethane, ethylacetate, ethylether, dipropylether, and toluene.
  • the b thickness of the coat after immersing the metal implant in the antiinfective polymer film may be adjusted depending on user's purpose. However, the thickness of the coating is confined to 5 - 500 ⁇ m for the continuous elution of the antiinfective agent, whereby the antiinfective agent is eluted for 2 to 3 months from a antiinfective polymer film containing a 10% of the antiinfective o agent.
  • the thickness of the film can be varied depending on the desired elution period of the antiinfective agent.
  • AMP-100K-PLLA denotes a film admixture containing ampicillin and polylactic acid having a molecular weight of 100,000.
  • AMP-300K-PLLA denotes a film admixture containing ampicillin and polylactic acid of M.W. 300,000.
  • GM-100K-PLAA denotes a film admixture containing gentamicin and 0 polylactic acid of M.W.100,000.
  • Drug loading (%) (amount of antiinfective agent contained in the film) / (film weight) x 100
  • Loading efficiency (%) (amount of the antiinfective agent contained in the film) / (initially additional amount of the antiinfective agent) x 100.
  • EXAMPLE 1 5 Polylactic acids of 0.9g having molecular weights 100,000 and 300,000, respectively, were completely dissolved in 6.0ml of dichloromethane. 0.1 g of ampicillin powder was gradually added to the polylactic acid/dichloromethane solution and agitated using a homogenizer. The air bubbles were removed by letting the solution stand for about five minutes. Screws used in orthopedic l o treatments were immersed in the antiinfective polymer solution and taken out, and the solvent was removed by gradually drying the screws at room temperature.
  • Screws coated with a polylactic acid film containing ampicillin using the same method as in Example 1 are left in a physiological saline solution of pH 7.4 for two weeks, and its release profile was measured.
  • the release of ampicillin as a function of time is as shown in the following table: Time Accumulated relase amount of ampicillin ( ⁇ g) (days) AMP-100K-PLLA * AMP-300K-PLLA *
  • Screws coated with a polylactic acid film containing gentamicin using the same method as in Example 3 were left in a physiological saline solution of pH 7.4 for 20 days, and a release profile of the gentamicin was measured.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biomedical Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Transplantation (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Vascular Medicine (AREA)
  • Surgery (AREA)
  • Dermatology (AREA)
  • Molecular Biology (AREA)
  • Cardiology (AREA)
  • Materials For Medical Uses (AREA)

Abstract

A surface coating method for metal implants which provides a prevention and treatment of implant associated infection. An antiinfective agent is dissolved, suspended or emulsified in a solution of polylactic acid homopolymer or a copolymer of a lactic acid and glycolyc acid to which the metal implant is immersed whereby the metal implant is coated with the antiinfective-polymer film to a predetermined thickness.

Description

SURFACE COATING METHOD FOR METAL IMPLANTS
Technical Field The present invention relates to a surface coating method of metal implants which are widely in use in medical fields such as general surgery, orthopedics surgery, cosmetic surgery and dental surgery. More particularly, the present invention relates to a surface coating method of metal implants, wherein the surface of the implant is coated with an antiinfective polymer film obtained by mixing a polymer and an antiinfective agent with dissolution, suspension, or emulsification method, thereby the antiinfective agent is continuously discharged therefrom and accordingly prevents or treats infection and inflammation of a subject body.
Background of the Invention
Metallic implants for insertion into a living body which have been generally employed for medical treatments are made of stainless steel, Cr-Co alloy, pure titanium or titanium alloy. Those materials are mostly applied to general surgical treatments including orthopedics surgery, cosmetic surgery and dental surgery: Pins, wires, screws, plates and the like have been used for fracture treatments and bone fixture in surgical operation; screws, pins, and artificial joints for cosmetic surgery; and, dental implants for dental treatments.
A clinical problem so far incurred by the use of such conventional metallic implants is that it is not certain how an implant inserted into a body infects body tissues and what routes the infection takes.
In particular, when such an implant or surgical device are exposed to an external environment of the body, an infection may occur due to an area of the body in contact with the exterior environment. 5 Directly delivered antibiotics into an infected area or continuous oral administration of antiinfective agents have been used to prevent and treat infections.
The above treatment not only requires a continuous checkup and treatment process of the doctor in charge, but also side effects incurrs or the o body weakness due to the antibiotic resistance caused by the continuous dose thereof.
With regard to the above-described prevention and treatment for infections caused by the metal implants, generally known surgical treatment methods are involved as follows: (1) maintaining implants and surgical devices s thereof in a sterilized condition; (2) administering antiinfective agents into probable areas of infection in advance or continuouly administrating such agents; or (3) oral administration of antibiotic. However, these treatments have been considerable burdens to both doctors and patients in terms of cost, time and effectiveness. 0
DISCLOSURE OF THE INVENTION Accordingly, it is an object of the present invention to provide a surface coating method of metal implants for accomplishing an effective and economical prevention and/or treatment than that of the conventional method. To achieve the above-described object, there is provided a surface coating method of metal implants according to the present invention, wherein the metal implants being inserted into the body are immersed in an antiinfective polymer solution obtained by dissolving, suspending, or 5 emulsifying an an antiinfective agent in polymer solution to coat the implants with a desired thickness and then dried at room temperature or vacuum dried.
METHOD FOR CARRYING OUT THE INVENTION A method of coating metal implants according to the present invention o was established from a study of prevention and treatment of infection caused by metal implants inserted into a body, such as operational materials: Pins, wires, screws, plates and the like for fracture treatments and bone fixture in surgical operation; screws, pins, and artificial joints for cosmetic surgery; and, dental implants for dental treatments. Specifically, the present invention 5 provides a coating method of a metallic material inserted into the body, wherein an antiinfective agent is dissolved, suspended or emulsified in a polymer solution. The metal implants are immersed into the solution so as to coat with the antiinfective polymer film to a predetermined thickness, and then the solvent is eliminated therefrom, by use of a gradual drying at room 0 temperature or a vacuum drying.
The polymer used in the present invention are polylactic acid homopolymer of molecular weight (M.W.) of 5,000 to 300,000, a copolymer of lactic acid and glycolic acid of molecular weight of 5,000 to 300,000. Due to their bio-degradability, these polymers are widely used in the medical field. An L type, D type, or their racemate LD type polylactic acid may be used in the present invention. In the embodiment of the present invention, the polylactic acid homopolymer (manufactured by Polysciences, Inc., U.S.A.) having a molecular weight 100,000 to 300,000 and copolymers of lactic acid and glycolic acid (poly (DL-lactide-co-glycolide)] (50:50), manufactured by Sigma Chemical, Co., MO, U.S.A.) are preferably employed.
The amount of the polymer is generally 0.1 to 10 wt./vol.% of the organic solvent used.
The antiinfective agent applicable to the present invention is not limited, so that, antibiotic, including anti-bacterial agent, anti-fungal agents and antiviral agents may be used. The antibiotic applied to the present invention includes: sulfonamides such as sulfisoxazole, sulfadiazine, sulfasalazine, sulfacetamide, sulfadoxine; cjuinolones such as nalidixic acid, cinoxacin, norfloxacin; penicillins such as penicillin G, penicillin V, methicillin, ampicillin, amoxicillin, bacampicillin, carbenicillin, ticarcillin; cephalosporins such as cephalothin, cefazolin, cefalexin, cefaladin, cefaclor, cefoxitin, cefotaxime, ceftizoxime; aminoglycosides such as streptomycin, gentamicin, tobramycin, amikocin, kanamycin, neomycin; tetracyclines such as tetracycline, chloramphenicol, erythromycin, clindamycin, vancomycin, bacitracin; anti-fungal agents such as amphotericin B, flucytosine, miconazole, fluconazole, and griseofulvin; anti-viral agents such as azidothymidine, acyclovir, gencyclovir, vidarabine, idoxuridine, trifluridine, foscarnet, amantadine, ribavirin, and ofloxacin.
The antiinfective agent is generally added to an amount of 1 to 50 wt.% based on the amount of the polymer.
Organic solvents employed in the present invention to dissolve polymers are butyl alcohol, chloroform, cyclohexane, acetonitrile, dichloromethane, dichlorethane, ethylacetate, ethylether, dipropylether, and toluene. The b thickness of the coat after immersing the metal implant in the antiinfective polymer film may be adjusted depending on user's purpose. However, the thickness of the coating is confined to 5 - 500 μm for the continuous elution of the antiinfective agent, whereby the antiinfective agent is eluted for 2 to 3 months from a antiinfective polymer film containing a 10% of the antiinfective o agent. Here, the thickness of the film can be varied depending on the desired elution period of the antiinfective agent.
With reference to the following examples according to the present invention, the surface coating method of the metal implants according to the present invention will be described in further detail. 5 When it comes to terminology and abbreviation employed in the examples, AMP-100K-PLLA denotes a film admixture containing ampicillin and polylactic acid having a molecular weight of 100,000. AMP-300K-PLLA denotes a film admixture containing ampicillin and polylactic acid of M.W. 300,000. GM-100K-PLAA denotes a film admixture containing gentamicin and 0 polylactic acid of M.W.100,000. The following expression means:
Drug loading (%) = (amount of antiinfective agent contained in the film) / (film weight) x 100 Loading efficiency (%) = (amount of the antiinfective agent contained in the film) / (initially additional amount of the antiinfective agent) x 100.
EXAMPLE 1 5 Polylactic acids of 0.9g having molecular weights 100,000 and 300,000, respectively, were completely dissolved in 6.0ml of dichloromethane. 0.1 g of ampicillin powder was gradually added to the polylactic acid/dichloromethane solution and agitated using a homogenizer. The air bubbles were removed by letting the solution stand for about five minutes. Screws used in orthopedic l o treatments were immersed in the antiinfective polymer solution and taken out, and the solvent was removed by gradually drying the screws at room temperature.
SAMPLES Drug loading(w/w%) Loading efficiency (%)
AMP-100L-PLLA* 9.89 ±0.39" 98.9 l b AMP-300L-PLLA* 9.87±0.30** 89.7
* denotes a polylactic acid film containing ampicillin, ** denotes average ± standard deviation (n=6).
20 EXAMPLE 2
Screws coated with a polylactic acid film containing ampicillin using the same method as in Example 1 are left in a physiological saline solution of pH 7.4 for two weeks, and its release profile was measured. The release of ampicillin as a function of time is as shown in the following table: Time Accumulated relase amount of ampicillin (μg) (days) AMP-100K-PLLA* AMP-300K-PLLA*
1 19.7±0.20** 16.8±0.19**
2 20.7±0.20 16.9±0.20
3 21.6±0.21 17.1 ±0.26
5 23.5±0.27 17.7±0.27
6 24.5±0.23 18.2±0.41
7 25.5±0.24 18.7±0.46
10 24.4±0.75 20.3 ±1.00
14 28.3+0.50 21.6± 1.02
denotes a polylactic acid film containing ampicillin, denotes average ± standard deviation (n=6).
EXAMPLE 3
150mg of polylactic acid having a molecular weight of 100,000 was completely dissolved in 30.0ml of dichloromethane. 15mg of powder gentamicin was gradually added to the polylactic acid/dichloromethane solution and agitated therein using a homogenizer for thereby forming a homogeneous state therein. The air bubbles were removed by letting the solution stand for about five minutes. Screws used in orthopedic treatments were immersed in the antiinfective polymer solution and taken out and the solvent was removed by gradually drying the screws at room temperature. An appropriate thickness of the film was obtained by repeatedly immersing the screws into the polymer solution 20 times. The drug loading (%) of the polylactic acid film coated on the screws is listed in the following table:
Sample Drug loading (%)
GM-100K-PLLA* 8.79 ±1.43**
denotes a polylactic acid film containing gentamicin, denotes average ± standard deviation (n=6).
EXAMPLE 4
Screws coated with a polylactic acid film containing gentamicin using the same method as in Example 3 were left in a physiological saline solution of pH 7.4 for 20 days, and a release profile of the gentamicin was measured.
The accumulate release gentamicin on the screws as a function of time is as shown in the following table:
Time(day) Accumulated release amount of gentamicin(μg)
0.125 742.9±205.63*
0.25 751.8±207.30
0.417 752.7 ±204.63
1 761.0±209.70
3 821.2±212.81
7 876.3±223.37
10 908.0±223.65
15 620.4±227.97
20 978.0±225.05
denotes average ± standard deviation (n=6). EXAMPLE 5
300mg of a copolymer (M.W. 50,000-75,000) of lactic acid and glycolic acid was completely dissolved in 30 ml of acetonitrile at room temperature. 15mg of gentamicin powder was gradually added to the copolymer/acetonitriie solution and sufficiently agitated therein using a homogenizer for thereby forming a homogeneous state therein. The air bubbles were removed by letting the solution stand for about five minutes. Screws employed in orthopedic treatments were immersed in the polymer-antiinfective agent solution and taken out and the solvent was removed by gradually drying the screws at room temperature. An appropriate thickness of the polymer-antiinfective agent film was obtained by repeatedly immersing the screws into the polymer solution 20 times.
EXAMPLE 6 300 mg of polylactic acid (M.W. 100,000) was completely dissolved in
30.0 mL of dichloromethane at a temperature of 20±5°C. 15mg of ofloxacin was gradually added to the solution and dissolved therein for thereby obtaining a transparent solution. Screws employed in orthopedic treatments were immersed in the polymer-antiinfective solution and taken out and the solvent was removed by gradually drying for 24 hours under a pressure of 30mmHg. Then, an appropriate thickness of film was obtained by repeatedly immersing the screws into the polymer solution 20 times.

Claims

What is claimed is:
1. A surface coating method for metal implants, wherein the metal implant is immersed into a polymer solution obtained by dissolving, suspending or emulsifying an antiinfective agent and a polymer in an organic solvent, and then dried to remove the organic solvent.
2. The method of Claim 1 , wherein the polymer is selected from the group consisting of polylactic acid homopolymer of molecular weight of 5,000 to 300,000, and a copolymer of a lactic acid, and a glycolic acid of molecular weight of 5,000 to 300,000.
3. The method of Claim 1 , wherein the polylactic acid homopolymer is selected from the group consisting of L type, D type, or LD type.
4. The method of Claim 1 , wherein the antiinfective agent is selected from the group consisting of sulfisoxazole, sulfadiazine, sulfasalazine, sulfacetamide, sulfadoxine, nalidixic acid, cinoxacin, norfloxacin, penicillin G, penicillin V, methicillin, ampicillin, amoxicillin, bacampicillin, carbenicillin, ticarcillin, cephalothin, cefazolin, cephalexin, cephaladin, cefaclor, cefoxitin, cefotaxime, ceftizoxime, streptomycin, gentamicin, tobramycin, amikacin, kanamycin, neomycin, tetracycline, chloramphenicol, erythromycin, clindamycin, vancomycin, bacitracin, amphotericin B, flucytosine, miconazole, fluconazole, griseofulvin, azidothymidine, acyclovir, gencyclovir, vidarabine, idoxuridine, trifluridine, foscarnet, amantadine, ribavirin, and ofloxacin.
5. The method of Claim 1 , wherein the organic solvent is selected from the group consisting of butylalcohol, chloroform, cyclohexane, acetonitrile, dichloromethane, dichloro-ethane, ethylacetate, ethylether, dipropyilether, and toluene.
6. The method of Claim 1 , wherein the polymer is contained in an amount of 0.1 to 10 wt./vol.% based on the organic solvent.
7. The method of Claim 1 , wherein the antiinfective agent is contained in an amount of 1 to 50 wt.% based on the amount of the polymer.
PCT/KR1997/000153 1996-08-19 1997-08-18 Surface coating method for metal implants WO1998007458A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
DE19781971A DE19781971B4 (en) 1996-08-19 1997-08-18 Process for coating surfaces of metal implants
JP10510607A JP2000501318A (en) 1996-08-19 1997-08-18 Metal graft surface coating method
DE19781971T DE19781971T1 (en) 1996-08-19 1997-08-18 Process for coating surfaces of metal implants
AU39528/97A AU3952897A (en) 1996-08-19 1997-08-18 Surface coating method for metal implants

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1996/34213 1996-08-19
KR1019960034213A KR0176334B1 (en) 1996-08-19 1996-08-19 Coating method of endogenous infectious insert metal surface and its treatment technology

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KR (1) KR0176334B1 (en)
AU (1) AU3952897A (en)
DE (2) DE19781971T1 (en)
WO (1) WO1998007458A1 (en)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000045803A2 (en) * 1999-02-08 2000-08-10 Cedars-Sinai Medical Center Use of 5-aminosalicylates as antimicrobial agents
JP2002524208A (en) * 1998-09-11 2002-08-06 シュミドマイヤー，ゲルハルド Biologically active implant
US6443942B2 (en) 1996-11-01 2002-09-03 Minimed, Inc. Medication device with protein stabilizing surface coating
US7813780B2 (en) 2005-12-13 2010-10-12 Medtronic Minimed, Inc. Biosensors and methods for making and using them
US8660628B2 (en) 2009-12-21 2014-02-25 Medtronic Minimed, Inc. Analyte sensors comprising blended membrane compositions and methods for making and using them
US8834772B2 (en) 2011-12-07 2014-09-16 Biomet Manufacturing, Llc Antimicrobial methacrylate cements
US9237865B2 (en) 2002-10-18 2016-01-19 Medtronic Minimed, Inc. Analyte sensors and methods for making and using them
US9492111B2 (en) 2002-04-22 2016-11-15 Medtronic Minimed, Inc. Methods and materials for stabilizing analyte sensors
US9541519B2 (en) 2002-10-18 2017-01-10 Medtronic Minimed, Inc. Amperometric sensor electrodes
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US6443942B2 (en) 1996-11-01 2002-09-03 Minimed, Inc. Medication device with protein stabilizing surface coating
JP2002524208A (en) * 1998-09-11 2002-08-06 シュミドマイヤー，ゲルハルド Biologically active implant
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WO2000045803A2 (en) * 1999-02-08 2000-08-10 Cedars-Sinai Medical Center Use of 5-aminosalicylates as antimicrobial agents
US9492111B2 (en) 2002-04-22 2016-11-15 Medtronic Minimed, Inc. Methods and materials for stabilizing analyte sensors
US9541519B2 (en) 2002-10-18 2017-01-10 Medtronic Minimed, Inc. Amperometric sensor electrodes
US9163273B2 (en) 2002-10-18 2015-10-20 Medtronic Minimed, Inc. Biosensors and methods for making and using them
US9237865B2 (en) 2002-10-18 2016-01-19 Medtronic Minimed, Inc. Analyte sensors and methods for making and using them
US7813780B2 (en) 2005-12-13 2010-10-12 Medtronic Minimed, Inc. Biosensors and methods for making and using them
US8660628B2 (en) 2009-12-21 2014-02-25 Medtronic Minimed, Inc. Analyte sensors comprising blended membrane compositions and methods for making and using them
US8834772B2 (en) 2011-12-07 2014-09-16 Biomet Manufacturing, Llc Antimicrobial methacrylate cements
US10588862B2 (en) 2018-02-02 2020-03-17 Ripple Therapeutics Corporation Dexamethasone prodrug compositions and uses thereof
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DE19781971T1 (en) 1999-09-30
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DE19781971B4 (en) 2004-04-15
KR0176334B1 (en) 1999-04-01

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