Abstract:
Treating absorbable sutures that have been sterilized using ethylene oxide with carbon dioxide at or near its supercritical pressure and temperature conditions to remove any residual ethylene oxide.

Description:
BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates to using carbon dioxide, at or near its supercritical pressure and temperature conditions, to remove residual ethylene oxide (EtO) from absorbable surgical sutures. EtO, although an effective sterilant, is a carcinogenic and mutagenic chemical with direct impact on wound healing. 
     2. Description of the Related Art 
     It is common to sterilize absorbable surgical sutures using ethylene oxide as set forth in U.S. Pat. No. 6,440,364. However, the process disclosed in the &#39;364 patent has been found to leave residual ethylene oxide on the sutures. This residual ethylene oxide has been found to cause irritation suture induced inflammation when used in some patients. It has also been found that ethylene oxide is carcinogenic. Still further, it has been found the residual ethylene oxide compromises mechanical properties of the suture. Therefore, it would be desirable to remove all ethylene oxide after sterilization. It is towards fulfilling such a need that the present invention is directed. 
     SUMMARY OF THE INVENTION 
     The method of the present invention is directed to treating absorbable sutures, after they are sterilized using ethylene oxide, with supercritical carbon dioxide to remove all residual ethylene oxide. In accordance with a preferred embodiment, absorbable sutures in a gas permeable package are placed in a basket which is inserted into a reactor vessel. Carbon dioxide is then introduced into the reactor vessel while being pressurized and heated to supercritical levels above 1099 psi and 31.1 C. The sutures, depending upon the number, are allowed to sit in the pressurized and heated reactor vessel from 1 second to 4 hours while the supercritical fluid is stirred, preferably 30 to 60 minutes. Upon completion of the specified time, the reactor vessel is depressurized. Depressurization times can range from 15 seconds to 30 minutes. The basket containing the packaged sutures is removed and the sutures are ready for shipping or repackaged for shipping. 
     Other objects and advantages of the present invention will become apparent from the following detailed description when viewed in conjunction with the accompanying drawings, which set forth certain embodiments of the invention. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a schematic view of a preferred apparatus used for treatment. 
         FIG. 2  is a detailed schematic view of the reactor vessel employed in the apparatus of  FIG. 1 . 
         FIG. 3  shows the reactor vessel open with packaged sutures in baskets placed into the reactor vessel. 
         FIG. 4  shows a basket containing treated sutures in a plurality of packages. 
     
    
    
     DESCRIPTION OF THE PREFERRED EMBODIMENT 
     The detailed embodiment of the present invention is disclosed herein. It should be understood, however, that the disclosed embodiment is merely exemplary of the invention, which may be embodied in various forms. Therefore, the details disclosed herein are not to be interpreted as limiting, but merely as a basis for teaching one skilled in the art how to make and/or use the invention. 
     With reference to  FIG. 1 , an apparatus according to the present invention is depicted. The apparatus  10  includes a standard compressed gas cylinder  12  containing carbon dioxide, and a standard air compressor  14  used in operative association with a carbon dioxide booster  16  (e.g., Haskel Booster ALG-32). Alternatively, it is appreciated the air compressor and booster can be replaced with a single carbon dioxide compressor. 
     The carbon dioxide is introduced to a reactor vessel  20  from supply line  17  via valve  18 . A pressure gauge  30  is provided in supply line  17  to allow the pressure to be monitored. In order to prevent an overpressure condition existing in line  17 , a pressure relief valve  29  may be provided. An outlet line  40  through valve  22  allows the reactor vessel  20  to be depressurized. 
     The reactor vessel  20  is most preferably constructed of stainless steel (e.g., 316 stainless steel) and has a total internal volume sufficient to accommodate the materials being treated either on a laboratory or commercial scale. For example, in laboratory studies, an internal volume of 20 L (e.g., approximately 22 inches long by about 10 inches inside diameter) was deemed adequate. The reactor vessel  20  includes a temperature control unit  62  and a mechanical stirring system most preferably comprised of an impeller  64  and a magnetic driver  66 . The reactor vessel  20  contains a conventional basket  65  which is also preferably constructed of stainless steel. The basket  65  serves to hold the sutures  72  to be treated as well as to direct the carbon dioxide in a predetermined manner. The top  28  of the reactor vessel  20  may be removed when depressurized to allow access to the reactor vessel&#39;s interior  24 . 
     In use, the sutures  72  to be treated are placed in basket  65  while still in their commercial gas permeable pouch or “as sold” packaging  70  and introduced into the interior space  24  of the reactor vessel  20 . The “as sold” packaging is the packaging in which the sutures are originally packaged when treated with ethylene oxide and intended for commercial sale. The temperature control unit  62  is operated so as to set the desired initial temperature between 31.1 and 45 C for treatment. The reactor vessel  20  may then be pre-equilibrated with carbon dioxide from gas cylinder  12  at atmospheric pressure. Thereafter, the magnetic driver  66  is operated so as to activate the impeller  64 . The reactor vessel  20  may then be pressurized to a desired pressure of greater than 1099 psi by introducing additional carbon dioxide gas from cylinder  12  via the air compressor  14  linked to booster  16 . The reactor vessel  20  is pressurized and heated to supercritical levels above 1099 psi and 31.1 C. The sutures are allowed to sit in the pressurized and heated chamber for 1 second to 4 hours while the supercritical fluid is being stirred. Optimally, a time period between 30 to 60 minutes has been found to be effective in removing all residuals of EtO, though treating for more than 60 minutes may be required depending upon the number of sutures and amount of residual EtO needing to be removed. Upon completion of the desired time period, an outlet line  40  controlled by a valve  22  allows the reactor vessel to be depressurized. Depressurization times can range from 15 seconds to 30 minutes. 
     Results show an untreated control suture has a cytotoxicity score of a 2 or 3 (out of 4). A suture treated in accordance with the present invention has a score of 0, indicating removal of all residual EtO. Scores are obtained through an established ISO standard protocol where c2c12 mouse cells are exposed to the suture extract. A score of zero means all or most of the cells did not die from the direct exposure. A score of 2 means the exposure had to be diluted twice for the cells to survive. Cytotoxicity is a major side effect in today&#39;s absorbable sutures. Although EtO has currently acceptable levels of residual gas from 1 to 10+ ppm, optimally the complete removal or absence of chemical residuals would be preferable. Sutures, as well as other medical items, are allowed residuals, because it&#39;s the only current acceptable way to sterilize half or most of medical products in the world. Currently in the U.S. 10 ppm EtO residuals in steroidal drugs is acceptable, whereas in the EU and accordance with the Kyoto Treaty only 1 ppm of residuals is acceptable. 
     While the preferred embodiment has been shown and described, it will be understood that there is no intent to limit the invention by such disclosure, but rather, is intended to cover all modifications and alternate constructions falling within the spirit and scope of the invention.