Patent Publication Number: US-8124165-B2

Title: Pressurized dip coating system

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     The present application claims the benefit of and priority to U.S. Provisional Application Ser. No. 60/777,055, filed on Feb. 27, 2006, the entire disclosure of which is incorporated herein by reference. 
    
    
     BACKGROUND 
     1. Technical Field 
     The present disclosure relates to a method for coating a medical device such as a braided suture and an apparatus for coating a medical device. 
     2. Background of Related Art 
     Medical devices intended for the repair of body tissues must meet certain requirements: they must be substantially non-toxic, capable of being readily sterilized, they must have good tensile strength and if they are of the absorbable or biodegradable variety, the absorption or biodegradation of the device must be closely controlled. An example of a particularly useful medical device is sutures. 
     Sutures have been constructed from a wide variety of materials including surgical gut, silk, cotton, a polyolefin such as polypropylene, polyamide, polyglycolic acid, polyesters such as polyethylene terephthalate and glycolide-lactide copolymer, etc. Some materials are suitable for preparing monofilament sutures, while sutures manufactured from other materials are provided as braided structures. For example, sutures manufactured from silk, polyamide, polyester and bioabsorbable glycolide-lactide copolymer are usually provided as multifilament braids. 
     Currently available braided suture products are acceptable in terms of their tensile strength and ability to be sterilized. However, they can be difficult to coat from a processing standpoint due to the small interstitial spaces present between each individual filament that may be difficult to penetrate. 
     It would be advantageous to have more effective methods for coating medical devices, especially multifilament medical devices. 
     SUMMARY 
     Methods are described wherein medical devices are coated in a pressurized system. The process includes the steps of placing one or more medical devices to be coated into a coating vessel and reducing the pressure within the vessel. A coating composition is added to the vessel to contact the medical device with the coating composition. Next, the pressure inside the vessel is increased. The coating composition is optionally withdrawn from and re-introduced into the vessel via a circulation pump. After the medical device contacts the coating composition for a predetermined amount of time, the vessel is drained and any excess coating composition is collected in a reservoir. Pressure within the vessel is again reduced and, optionally, a heated inert gas is passed through the vessel to cure the coating and/or dry the medical device. The coated medical device can then be removed from the vessel. Apparatus for performing the present methods are also described herein. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  illustrates one embodiment of a coating apparatus suitable for coating a medical device in accordance with this disclosure. 
         FIG. 2  is a flowchart illustrating a method of forming a coating onto a surface of a medical device in accordance with one embodiment described herein. 
     
    
    
     DETAILED DESCRIPTION 
     The present methods can be used to coat any medical device. Some examples include, but are not limited to, sutures, staples, meshes, stents, grafts, clips, pins, screws, tacks, slings, drug delivery devices, wound dressings, woven devices, non-woven devices, braided devices, and other implants. In certain embodiments, the medical device is formed from one or more filaments. The filaments can be knitted, braided, woven or non-woven. In a particularly useful embodiment, the medical device is a braided suture. 
     The medical device can be formed from any sterilizable material that has suitable physical properties for the intended use of the medical device. The medical device can be bioabsorbable or non-bioabsorbable. Some specific examples of suitable absorbable materials which may be utilized to form the medical device include trimethylene carbonate, caprolactone, dioxanone, glycolic acid, lactic acid, glycolide, lactide, homopolymers thereof, copolymers thereof, and combinations thereof. Some specific examples of suitable non-absorbable materials which may be utilized to form the medical device include polyolefins, such as polyethylene, polypropylene, copolymers of polyethylene and polypropylene, and blends of polyethylene and polypropylene. 
     Referring now to  FIG. 1 , one embodiment of an apparatus  100  for coating a medical device includes a coating vessel  110  into which a medical device to be coated is placed. (See, step  210  in  FIG. 2 .) Vessel  110  includes a sealable door  112  through which one or more medical devices to be coated can be placed into vessel  110  and the coated medical device can be removed from vessel  110 . While the medical device can be placed into the coating vessel  110  in any manner or position, the greater the surface area of the medical device that is accessible to the coating solution, the more thorough a coating the medical device will receive. Thus, a rack (not shown) adapted to hold the one or more medical devices may be placed within vessel  110 . In some embodiments, sutures wound on a spool or a rack are placed within vessel  110 . 
     The interior of vessel  110  can be advantageously made from or lined with a material that is non-reactive with the medical device and the coating composition. Such non-reactive materials include stainless steel, glass and the like. It is also contemplated that the interior of vessel  110  can be passivated to make the interior surface less reactive. Passivation techniques are within the purview of those skilled in the art. 
     Once the coating vessel contains the medical device, the medical device is subjected to reduced pressure. (See, step  220  in  FIG. 2 .) The pressure within the vessel  110  can be reduced by any means known to one skilled in the art. In the embodiment shown in  FIG. 1 , a vacuum pump  120  is connected to the coating vessel  110 . The vacuum pump  120  can be used to withdraw air from the coating vessel  110  through line  122  if valve  124  is open. The pressure within vessel  110  can be reduced to a pressure in the range of about 740 to 1 mmHg, more typically in the range of 100 to 10 mmHg. The pressure inside the coating vessel  110  is monitored during this step and other steps of the coating process by pressure indicator  130 . Providing a reduced pressure environment within vessel  110  prepares the medical device placed therein to better receive the coating composition, especially where the medical device includes small interstices. In addition, hygrometer  135  can be provided to monitor the level of humidity in vessel  110  during this and other steps of the process. 
     Optionally, an inert gas, (such as, for example xenon, neon, argon or nitrogen), can be flowed through the vessel during the evacuation step. To this end, line  172  connects vessel  110  to a nitrogen source  175 . An inert gas flush will help remove any air from vessel  110 , thereby assisting in drying the medical device and insuring a non-reactive environment for the coating process. 
     Once the desired pressure is attained within vessel  110 , a coating composition is introduced into vessel  110 . (See, step  230  in  FIG. 2 .) The coating composition can be added to the coating vessel  110  in any manner within the purview of one skilled in the art. In the embodiment depicted in  FIG. 1 , a coating composition is stored in reservoir  160  and enters the coating vessel  110  via lines  163 ,  164 ,  165  once valve  167  is opened and with the assistance of pump  150 . The amount of coating composition added to the coating vessel  110  should be sufficient to cover the medical devices to be coated. As those skilled in the art will appreciate, because medical devices to be coated can vary in size and surface area, and the manner in which the medical devices to be coated can be positioned within the vessel in various ways (e.g., on racks, spools, etc.), the amount of the coating solution added to the vessel will vary accordingly. 
     Any coating composition known to be used to coat medical devices may be applied to a medical device using the present methods and apparatus. The coating composition can be a solution, dispersion, emulsion containing, for example, one or more polymeric materials and/or one or more bioactive agents. 
     In some embodiments, the coating composition includes a polymer, or a combination of polymers. The polymer is most suitably biocompatible, including polymers that are non-toxic, non-inflammatory, chemically inert, and substantially non-immunogenic in the applied amounts. The polymer may be either bioabsorbable or biostable. A bioabsorbable polymer breaks down in the body. Bioabsorbable polymers are gradually absorbed or eliminated by the body by hydrolysis, metabolic process, bulk, or surface erosion. Examples of bioabsorbable materials include but are not limited to polycaprolactone (PCL), poly-D, L-lactic acid (DL-PLA), poly-L-lactic acid (L-PLA), poly(lactide-co-glycolide), poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), polydioxanone, polyorthoester, polyanhydride, poly(glycolic acid), poly(glycolic acid-cotrimethylene carbonate), polyphosphoester, polyphosphoester urethane, poly (amino acids), cyanoacrylates, poly(trimethylene carbonate), poly(iminocarbonate), copoly(ether-esters), polyalkylene oxalates, polyphosphazenes, polyiminocarbonates, and aliphatic polycarbonates. Biomolecules such as heparin, fibrin, fibrinogen, cellulose, starch, and collagen are typically also suitable. A biostable polymer does not break down in the body, and thus a biostable polymer is present in the body for a substantial amount of time after implantation. Examples of biostable polymers include Parylene™, Parylast™, polyurethane (for example, segmented polyurethanes such as Biospan™), polyethylene, polyethlyene teraphthalate, ethylene vinyl acetate, silicone, polyethylene oxide, and polytetrafluoroethylene (PTFE). 
     The coating composition may also include a solvent. Suitable solvents include, but are not limited to, organic solvents, volatile solvents, alcohols, e.g., methanol, ethanol, propanol, chlorinated hydrocarbons (such as methylene chloride, chloroform, 1,2-dichloro-ethane, 1,1,2-trichloro-ethane), aliphatic hydrocarbons (such as hexane, heptene, ethyl acetate), aromatic solvents (such as toluene, benzene, xylene) and combinations thereof. 
     In some embodiments, the coating compositions of the present disclosure may also include a fatty acid component that contains a fatty acid or a fatty acid salt or a salt of a fatty acid ester. Suitable fatty acids may be saturated or unsaturated, and include higher fatty acids having more than about 12 carbon atoms. Suitable saturated fatty acids include, for example, stearic acid, palmitic acid, myristic acid and lauric acid. Suitable unsaturated fatty acids include oleic acid, linoleic acid, and linolenic acid. In addition, an ester of fatty acids, such as sorbitan tristearate or hydrogenated castor oil, may be used. 
     Suitable fatty acid salts include the polyvalent metal ion salts of C 6  and higher fatty acids, particularly those having from about 12 to 22 carbon atoms, and mixtures thereof. Fatty acid salts including the calcium, magnesium, barium, aluminum, and zinc salts of stearic, palmitic and oleic acids may be useful in some embodiments of the present disclosure. Particularly useful salts include commercial “food grade” calcium stearate which consists of a mixture of about one-third C 16  and two-thirds C 18  fatty acids, with small amounts of the C 14  and C 22  fatty acids. 
     Suitable salts of fatty acid esters which may be included in the coating compositions applied in accordance with the present disclosure include calcium, magnesium, aluminum, barium, or zinc stearoyl lactylate; calcium, magnesium, aluminum, barium, or zinc palmityl lactylate; calcium, magnesium, aluminum, barium, or zinc olelyl lactylate; with calcium stearoyl-2-lactylate (such as the calcium stearoyl-2-lactylate commercially available under the tradenameVERV from American Ingredients Co., Kansas City, Mo.) being particularly useful. Other fatty acid ester salts which may be utilized include those selected from the group consisting of lithium stearoyl lactylate, potassium stearoyl lactylate, rubidium stearoyl lactylate, cesium stearoyl lactylate, francium stearoyl lactylate, sodium palmityl lactylate, lithium palmityl lactylate, potassium palmityl lactylate, rubidium palmityl lactylate, cesium palmityl lactylate, francium palmityl lactylate, sodium olelyl lactylate, lithium olelyl lactylate, potassium olelyl lactylate, rubidium olelyl lactylate, cesium olelyl lactylate, and francium olelyl lactylate. 
     Where utilized, the amount of fatty acid component can range in an amount from about 5 percent to about 50 percent by weight of the total coating composition. Typically, the fatty acid component may be present in an amount from about 10 percent to about 20 percent by weight of the total coating compositions. 
     In some embodiments, the coating composition contains one or more bioactive agents. The term “bioactive agent”, as used herein, is used in its broadest sense and includes any substance or mixture of substances that have clinical use. Consequently, bioactive agents may or may not have pharmacological activity per se, e.g., a dye. Alternatively a bioactive agent could be any agent which provides a therapeutic or prophylactic effect, a compound that affects or participates in tissue growth, cell growth, cell differentiation, a compound that may be able to invoke a biological action such as an immune response, or could play any other role in one or more biological processes. 
     Examples of classes of bioactive agents which may be utilized in accordance with the present disclosure include antimicrobials, analgesics, antipyretics, anesthetics, antiepileptics, antihistamines, anti-inflammatories, cardiovascular drugs, diagnostic agents, sympathomimetics, cholinomimetics, antimuscarinics, antispasmodics, hormones, growth factors, muscle relaxants, adrenergic neuron blockers, antineoplastics, immunogenic agents, immunosuppressants, gastrointestinal drugs, diuretics, steroids, lipids, lipopolysaccharides, polysaccharides, and enzymes. It is also intended that combinations of bioactive agents may be used. 
     Suitable antimicrobial agents which may be included as a bioactive agent in the bioactive coating of the present disclosure include triclosan, also known as 2,4,4′-trichloro-2′-hydroxydiphenyl ether, chlorhexidine and its salts, including chlorhexidine acetate, chlorhexidine gluconate, chlorhexidine hydrochloride, and chlorhexidine sulfate, silver and its salts, including silver acetate, silver benzoate, silver carbonate, silver citrate, silver iodate, silver iodide, silver lactate, silver laurate, silver nitrate, silver oxide, silver palmitate, silver protein, and silver sulfadiazine, polymyxin, tetracycline, aminoglycosides, such as tobramycin and gentamicin, rifampicin, bacitracin, neomycin, chloramphenicol, miconazole, quinolones such as oxolinic acid, norfloxacin, nalidixic acid, pefloxacin, enoxacin and ciprofloxacin, penicillins such as oxacillin and pipracil, nonoxynol 9, fusidic acid, cephalosporins, and combinations thereof. In addition, antimicrobial proteins and peptides such as bovine lactoferrin and lactoferricin B may be included as a bioactive agent in the bioactive coating of the present disclosure. 
     Other bioactive agents which may be included as a bioactive agent in the coating composition applied in accordance with the present disclosure include: local anesthetics; non-steroidal antifertility agents; parasympathomimetic agents; psychotherapeutic agents; tranquilizers; decongestants; sedative hypnotics; steroids; sulfonamides; sympathomimetic agents; vaccines; vitamins; antimalarials; anti-migraine agents; anti-parkinson agents such as L-dopa; anti-spasmodics; anticholinergic agents (e.g. oxybutynin); antitussives; bronchodilators; cardiovascular agents such as coronary vasodilators and nitroglycerin; alkaloids; analgesics; narcotics such as codeine, dihydrocodeinone, meperidine, morphine and the like; non-narcotics such as salicylates, aspirin, acetaminophen, d-propoxyphene and the like; opioid receptor antagonists, such as naltrexone and naloxone; anti-cancer agents; anti-convulsants; anti-emetics; antihistamines; anti-inflammatory agents such as hormonal agents, hydrocortisone, prednisolone, prednisone, non-hormonal agents, allopurinol, indomethacin, phenylbutazone and the like; prostaglandins and cytotoxic drugs; estrogens; antibacterials; antibiotics; anti-fungals; anti-virals; anticoagulants; anticonvulsants; antidepressants; antihistamines; and immunological agents. 
     Other examples of suitable bioactive agents which may be included in the coating composition include viruses and cells, peptides, polypeptides and proteins, analogs, muteins, and active fragments thereof, such as immunoglobulins, antibodies, cytokines (e.g. lymphokines, monokines, chemokines), blood clotting factors, hemopoietic factors, interleukins (IL-2, IL-3, IL-4, IL-6), interferons (β-IFN, (α-IFN and γ-IFN), erythropoietin, nucleases, tumor necrosis factor, colony stimulating factors (e.g., GCSF, GM-CSF, MCSF), insulin, anti-tumor agents and tumor suppressors, blood proteins, gonadotropins (e.g., FSH, LH, CG, etc.), hormones and hormone analogs (e.g., growth hormone), vaccines (e.g., tumoral, bacterial and viral antigens); somatostatin; antigens; blood coagulation factors; growth factors (e.g., nerve growth factor, insulin-like growth factor); protein inhibitors, protein antagonists, and protein agonists; nucleic acids, such as antisense molecules, DNA and RNA; oligonucleotides; and ribozymes. 
     A single bioactive agent may be utilized to form the coating composition or, in alternate embodiments, any combination of bioactive agents may be utilized to form the coating composition applied in accordance with the present disclosure. 
     After the coating composition is introduced into coating vessel  110 , the pressure inside the coating vessel  110  is increased. (See, step  240  in  FIG. 2 .) The pressure can be raised using any technique within the purview of one skilled in the art. In the embodiment shown in  FIG. 1 , inert gas (nitrogen) from source  175  is introduced into the coating vessel  110  via lines  171 ,  172  to increase the pressure within vessel  110 . Pressure control valve  141  is used for controlling the flow of the inert gas through line  171  and a pressure safety valve  142  is used to release pressure from the line when the pressure in the line is higher than needed or for safety purposes. 
     It is also contemplated that in other embodiments, the pressure within vessel  110  can be raised using a structure (not shown) that provides a static head of the coating composition. Techniques for producing pressure using a static head are within the purview of those skilled in the art. 
     The pressure can be increased to any super-atmospheric level. Thus, the pressure may range from about 761 mmHg to 2 atmospheres or more. Typically, pressures in the range of from about 770 to about 900 mmHg are used. The pressure inside the vessel is monitored and measured by the pressure indicator  130 . 
     The increased pressure inside the coating vessel  110  will also increase the temperature inside the coating vessel  110 . The temperature is measured and monitored by the temperature indicator  180  that is also directly attached to the coating vessel  110 . 
     Once the system is pressurized, the coating composition is circulated. (See, step  250  in  FIG. 2 ). The coating composition can be circulated in any manner known to one skilled in the art. In the embodiment shown in  FIG. 1 , pump  150  is used to circulate the coating composition. The coating composition exits vessel  110  through line  154 , and with valve  152  open passes through line  164  and is pumped by pump  150  through line  165  back into vessel  110 . 
     The coating composition is circulated for a predetermined amount of time ranging from about 10 seconds to about 60 minutes. Typically, the coating composition is circulated for about 2 minutes to about 10 minutes. 
     Once the predetermined amount of time expires, the coating composition is drained from vessel  110 . (See, step  260  in  FIG. 2 .) Before emptying the excess coating composition, the pressure inside the coating vessel can advantageously be returned back to atmospheric pressure. Any method within the purview of those skilled in the art may be to drain the coating composition from the vessel  110 . For example, the excess coating composition can be drained from the coating vessel  110  using gravity. In the embodiment shown in  FIG. 1 , coating composition flows through line  154  through open valve  162  into drain tank  160 . 
     Following the removal of the excess coating composition, the coated medical device is dried. The drying of the coated medical device can be done using any drying method within the purview of those skilled in the art. For example, the pressure within vessel  110  can be again reduced. (See, step  270  in  FIG. 2 .) Vacuum pump  120  is turned on, thereby, sweeping the medical device with air or inert gas. Optionally, heated inert gas may be swept over the coated medical device. For example, as shown in the embodiment of  FIG. 1 , heater  170  warms inert gas which is pulled by vacuum pump  120  through line  177  and open valve  179  into vessel  110  where it passes over the coated medical device. The heater contains its own temperature indicator  173  to measure and monitor the temperature of the gas before entering the coating vessel  110 . 
     It is also contemplated that a solvent tank and/or master batch of coating composition (not shown) can be provided to refresh the coating composition to ensure the desired concentrations of coating components are maintained in the coating composition. For example, if solvent volatilizes and is vented trough a hood or to the atmosphere, additional solvent can be mixed into the coating composition to maintain the desired formulation. 
     It is also contemplated that a control system (e.g., a computer control system (not shown)) can be provided to automate the operation of the present coating apparatus. 
     It will be understood that various modifications may be made to the embodiments described herein. Therefore, the above description should not be construed as limiting, but merely as exemplifications of preferred embodiments. Those skilled in the art will envision other modifications within the scope and the spirit of the claims appended hereto.