HIGH EFFICIENCY POLYMERIC STERILANT CONTAINER ASSEMBLY

Abstract

The present invention relates to a method for sterilizing an article inside a sealed container by placing a polyoxymethylene melt formable co-polymer that has been irradiated between about 1 and 200 kGy and then heated at from about 20° C. to about 90° C. for a selected period of time.

Description

This application is a continuation-in-part of U.S. non-provisional application Ser. No. 12/881,276 filed on Sep. 14, 2010 which claims priority to provisional application No. 61/276,944 filed on Sep. 18, 2009 and is incorporated herein in its entirety by reference.

COPYRIGHT NOTICE

A portion of the disclosure of this patent contains material that is subject to copyright protection. The copyright owner has no objection to the reproduction by anyone of the patent document or the patent disclosure as it appears in the Patent and Trademark Office patent files or records, but otherwise reserves all copyright rights whatsoever.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to sterilized packages and containers. In particular, the present invention relates to sterilized packaging containing a highly efficient formaldehyde releasing composition.

2. Description of Related Art

There is a wide array of medical devices that must be sterilized prior to their use. In the medical field it is common to have articles that can be re-sterilized or disposable articles that are only used one time but are provided to the user already sterilized. The art uses a wide variety of methods to sterilize or re-sterilize medical articles including, ethylene oxide, formaldehyde, low temperature steam-formaldehyde, gamma/e-beam irradiation, steam autoclave, dry heat, and the like.

While gaseous sterilization is very effective, the handling and long periods of time needed to diffuse and remove the sterilant gas from the chamber containing large pallets of heavy cardboard boxes/packages is a problem. Because of the long contact times and purge cycles required for gaseous sterilization, most gaseous sterilizations take place mainly in industrial settings where the requirement for expensive equipment is more cost effective and careful control can take place during the sterilization cycle by someone experienced in the sterilization process. Also, high energy irradiation methods require expensive radiation facilities and certified personnel skilled in the use of radiation isotopes for the purpose of sterilization of medical products. Plastic components of medical products are often embrittled or damaged by the destructive nature of the irradiation process. In the non-industrial setting, such as a hospital or physician's office, historically one of the most widely used methods for sterilization is the use of high temperature steam autoclaves. Unfortunately, the temperature of an autoclave is not conducive for use with many of today's plastics or other heat sensitive medical products which are commonplace in the medical environment of today. Accordingly, many medical offices throw away reusable medical devices because there are currently no techniques that are suitable for the non-industrial setting that are both cost effective and easy to use in small medical facilities.

Some twenty-five years ago an attempt to solve the problem was made in U.S. Pat. No. 4,050,576 to Williams et al. In that patent a sterilant package included a relatively thick piece of poly acetal (which contains oxymethylene groups and stabilizing groups) which had been irradiated to effect chain cleavage of the polymer without depolymerization. The package, upon subsequent heating, caused the poly acetal to slightly depolymerize which caused a release of trace amounts of formaldehyde gas. Unfortunately, the irradiation doses required to achieve sufficient gas release for sterilization using this method were so high that the insert became very brittle and difficult to manage as indicated by low film breaking angles in embrittlement tests.

During the prior art timeframe, thermoplastic polyoxymethylenes were only commercially available as extremely viscous melts that limited the thermoformability into simple geometries, such as thick films, slabs, and rods, which required prolonged crystallization times that caused even further embrittlement of the material. Severe plastic embrittlement caused by the combination of thicker part limitations and higher irradiation doses required to achieve sufficient gas release resulted in the prior art never being adopted commercially.

BRIEF SUMMARY OF THE INVENTION

The present invention relates to the discovery that if a low melt viscosity and melt formable (such as by melt blowing) polyoxymethylene or copolymer of polyoxymethylene is formed into a relatively thin fiber or other thin article with a sufficient high surface to mass ratio and irradiated, it can be included in a package for purposes of sterilization of the contents of the container by low heat release of formaldehyde without becoming too brittle yet still releasing sufficient formaldehyde to sterilize the article.

Accordingly, one embodiment of the present invention relates to a container of a selected volume on the inside suitable for low heat sterilizing a selected article positioned in the inside of the container comprising a container insert on the inside of the container comprising a melt formable polyoxymethylene or co-polymer of polyoxymethylene that has been melt formed into a container insert and has been irradiated sufficient to cause chain cleavage without depolymerization or brittleness of the insert such that formaldehyde is released upon subsequent application of low heat to the insert by any manner.

In yet another embodiment of the present invention, there is a process for producing a container of a selected volume on the inside suitable for low heat sterilizing a selected article positioned on the inside of the container comprising positioning in the inside of the container, a container insert comprising a melt formable polyoxymethylene or co-polymer polyoxymethylene which has been melt formed into a container insert and has been irradiated sufficient to cause chain cleavage without depolymerization or brittleness such that formaldehyde is released upon subsequent application of low heat to the insert.

In yet another embodiment of the present invention there is a method of sterilizing an article at low heat in a container of a selected volume on the inside comprising:

• • a. positioning the article in the container;
  • b. positioning a container insert in the container which comprises a melt formable polyoxymethylene or polyoxymethylene co-polymer which has been melt formed into a container insert and has been irradiated sufficient to cause chain cleavage without depolymerization or brittleness such that formaldehyde is released upon subsequent heating of the insert; and
  • c. heating the insert to a temperature of about 20° C. to about 90° C. for a time sufficient to release formaldehyde and sterilize the article.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a medical device in a container with the polymer insert of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

While this invention is susceptible to embodiment in many different forms, there is shown in the drawings and will herein be described in detail specific embodiments, with the understanding that the present disclosure of such embodiments is to be considered as an example of the principles and not intended to limit the invention to the specific embodiments shown and described. In the description below, like reference numerals are used to describe the same, similar or corresponding parts in the several views of the drawings. This detailed description defines the meaning of the terms used herein and specifically describes embodiments in order for those skilled in the art to practice the invention.

Definitions

The terms “a” or “an”, as used herein, are defined as one or as more than one. The term “plurality”, as used herein, is defined as two or as more than two. The term “another”, as used herein, is defined as at least a second or more. The terms “including” and/or “having”, as used herein, are defined as comprising (i.e., open language). The term “coupled”, as used herein, is defined as connected, although not necessarily directly, and not necessarily mechanically.

The terms “about” and “essentially” mean ±10 percent.

Reference throughout this document to “one embodiment”, “certain embodiments”, and “an embodiment” or similar terms means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, the appearances of such phrases or in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments without limitation.

The term “or” as used herein is to be interpreted as an inclusive or meaning any one or any combination. Therefore, “A, B or C” means any of the following: “A; B; C; A and B; A and C; B and C; A, B and C”. An exception to this definition will occur only when a combination of elements, functions, steps or acts are in some way inherently mutually exclusive.

The drawings featured in the figures are for the purpose of illustrating certain convenient embodiments of the present invention, and are not to be considered as limitation thereto. Term “means” preceding a present participle of an operation indicates a desired function for which there is one or more embodiments, i.e., one or more methods, devices, or apparatuses for achieving the desired function and that one skilled in the art could select from these or their equivalent in view of the disclosure herein and use of the term “means” is not intended to be limiting.

As used herein, the term “container” refers to any package, bag, or the like in which a desired item for sterilization can be enclosed and sealed and having a selected volume on the inside. The container must be capable of withstanding the low heat of the present invention and be essentially impermeable to formaldehyde to prevent its leakage during the sterilization process. In one embodiment the humidity on the inside of the container is about 5-100 percent relative humidity. In one embodiment, the containers are plastic bags made of polyethylene, polypropylene, Saran, aluminum foil or foil coated plastic, and the like. In one embodiment, they are essentially flat bags of the shape and style of food sandwich bags with an appropriate closure (sandwich zip lock). The flat bags will have a selected length and width with an area defined by the product of the length times the width. The bags can be sealed, for example, by an adhesive seal, zipper lock seal, or other methods for sealing the bag. In another embodiment, the article is placed in the bag and the bag heat sealed shut, thus making the bag a onetime disposable bag since the bag must be torn, cut open, or the like to obtain the enclosed sterilized item. In still another embodiment, a combination of zip lock and heat seals are used as tamper-proof seal configurations. In still another embodiment, a chevron seal is provided at the opposite end of the bag to maintain sterility when opening in a sterile field, such as an operating room. The container of the present invention can be any size necessary to contain the item to be sterilized. Accordingly, most any size container can be utilized, but for efficiency sake, the bag would be the minimum size that the article to be sterilized would fit inside the closed portion of the container. For example, a flat, polymeric bag for sterilizing a scalpel would only need to be 4 or 5 inches long and 3 or 4 inches wide while surgical instruments might need to be several feet long.

As used herein “low heat” refers to the ability to apply heat to the insert in the range of about 20° C. to about 90° C. The heat can be applied by any convenient means, such as a gas or electric oven, electric heating wires, heatlamp, chemical reaction, sunlight, or the like. The container could be heated in order to heat the insert in one embodiment. Other embodiments of heating include heating the insert prior to placement in the container incorporating a heating device (e.g. heating wires) inside the insert, internal, or external heating packs (wire heaters or hand warmers). In another embodiment, the insert can be accessed through the container (e.g. a tube that extends through the container wall that can contain a heating element. The exact heat will vary but will depend on the size of the article and the time at the particular heat. In view of the present disclosure, one could easily match the exact heat temperature and time to obtain a sufficient time for heating to release formaldehyde. In one embodiment, the time period of heating is from about 5 minutes to 600 minutes and in another embodiment it is about an hour. In one embodiment the heating could be at room temperature and could be sustained over an extended period of time (days to weeks).

The “selected article” as used herein, is the article that one wishes to sterilize. Since the maximum heat is in the ranges noted above, the article can be made of plastic or other materials that normally would not handle higher heats. Once again, if an article would not survive say, 90° C., the article can be heated at a lower temperature for a longer time and achieve the same result of sterilization though a longer time would be necessary.

As used herein, a “melt formable polyoxymethylene (POM)” or “co-polymer of polyoxymethylene” are any polymers which can be melt blown or otherwise melt formable into thin products. The POM polymeric materials of the present invention have a very high melt flow rate and consequently are very fluid in the molten state, unlike historical POM's that were extremely viscous in the melt. High melt flow rate polymers are generally used in industry for forming high surface area fibers or melt processing and forming into non-woven fabric or mat type articles. Other shapes could be formed as well, but generally having a diameter or thickness of no more than 500 microns are utilized in one embodiment. Generally, the radiation dosage to accomplish the proper chain cleavage without depolymerization or brittleness, such that formaldehyde is released upon subsequent heating of the insert, is from about 1 to about 200 kGy. In one embodiment the insert is irradiated from about 35 to about 70 kGy.

As used herein a “container insert” is a piece of high melt flow POM melt formed copolymer that has been irradiated sufficiently to cause chain cleavage without depolymerization or brittleness, but sufficiently that formaldehyde is released upon the subsequent low heat sterilizing of the insert for a select period of time. The insert can be in many shapes, for example, it can be a fiber (with a high surface area) or a non-woven mat which can be melt formed or the like. In one embodiment it can be pod shaped while in another it can be part of the container itself (e.g. the wall material). The insert needs to be of a sufficient weight and surface area that upon low heat application the container the insert will release sufficient formaldehyde to reach a concentration of at least 0.1 mg/L in the container volume inside. In one embodiment it is of at least 0.3 mg/L formaldehyde. The insert can be a loose piece inside the container, or in other embodiments, it can be attached to or part of the inside surface of the container, for example, by layering the POM co-polymer on the inside of the container especially where the container is a polymeric bag. In some embodiments the POM co-polymer can be mixed with other polymers or substances to create a larger insert or a multi-component insert for particular additional purposes. In one embodiment, a thermochromic material is added to the POM co-polymer so that when it is heated it will change color at the end of the sterilization heating. The inset is placed in the container prior to the heating or at the time of heating, as necessary or desired.

In general, the process of sterilizing an article at low heat in a container comprises placing the container insert and article to be sterilized (in any order) inside the container. The insert is heated to a temperature of about 25° C. to about 90° C. for a time sufficient to release formaldehyde from the container insert and sterilize the article either before placing in the container or afterwards. The container is sealed after insert placement therein. The package can then be opened and if resealable, reused. The article is then sterilized and ready for the desired sterilized use.

Now referring to the drawing. FIG. 1 is an embodiment of the present invention. There is shown a container 11 suitable for low heat sterilizing. Inside container 11 is a high surface area inset 12 which in this embodiment is a thin rod. Also, in container 11 is an article to be sterilized, a surgical tool 13. In this embodiment the container 11 is a zip lock 14 closable container made from a clear polyester material.

EXAMPLE 1

A 10 mil thick sample of POM dense film and an equivalent weight of melt blown POM of the present invention were gamma irradiated to a nominal dose of 70 kGy followed by heating both samples at 70° C. for a period of 60 minutes in a convection oven. The thick film yielded a 0.18% formaldehyde release while the melt blown sample of the present invention yielded a 2.12% release of formaldehyde which is over a ten-fold increase compared to the thick film. In separate experiments, the same level of sterility could be achieved with one-tenth the weight of melt blown material compared to thick film.

Comparative embrittlement bending tests indicated that the thick film failed at a 21 degree bending angle while the melt blown sample could undergo a full 180 degree bend without failure.

Example 2

A 10 mil thick sample of POM film and an equivalent weight fiber of melt blown POM of the present invention were both gamma irradiated to a nominal dose of 30 kGy followed by heating both samples at 70° C. for a period of 60 minutes in a convection oven. The film yielded 0.6 mg of formaldehyde while the melt blown sample of the present invention yielded 3.1 mg of formaldehyde or over five-fold more sterilant for equal sample comparison. In separate experiments, the same level of sterility could be achieved with one-fifth the weight of melt blown material compared to thick film.

Comparative embrittlement bending tests indicated that the thick film failed at a 20 degree bending angle while the melt blown sample could undergo a full 180 degree bend without failure.

Example 3 to Example 11

Three melt blown samples of high melt flow rate POM were prepared on a melt-blown processing line at the University of Tennessee with average weights per square meter (GSM) of 100, 150, and 200 GSM. All melt blown mats had average fiber diameters of 10 microns. Stock rolls of the melt blown mats were irradiated to 20, 35, and 50 kGy in a cobalt-60 gamma facility. Following irradiation, 4″×6″ samples of each weight melt blown mat were placed into separate 5″×8″ zip-lock bags along with a strip of a biological indicator inoculated with either 10⁵ Geobacillus Stearothermophilus or 10⁶ Bacillus Atrophoeous. All samples after heating to 70° C. for 15 minutes were found to be sterile as shown below:

Example	GSM	Dose (kGy)	G. Stearothermophilus	B. Atrophoeous
3	100	20	Sterile	Sterile
4	100	35	Sterile	Sterile
5	100	50	Sterile	Sterile
6	150	20	Sterile	Sterile
7	150	35	Sterile	Sterile
8	150	50	Sterile	Sterile
9	200	20	Sterile	Sterile
10	200	35	Sterile	Sterile
11	200	50	Sterile	Sterile

Even the lowest weight 100 GSM mat yielded sufficient sterilant to render the contents of the bag sterile even at the lowest dose of 20 kGy.

Example 12

A bone screw with dimensions of 9×23 mm (part #AR-1590BC made by Arthrex Inc, Naples, Fla.) was removed from its package and inoculated with 10⁵ Bacillus atrophaeus spores. The item was then placed into a 6″×11″ self-sterilizing bag containing 5 sheets (6″×9″) of aged 200 GSM meltblown material irradiated at 35 kGy in 2008 along with a BI containing 10⁶ B. atrophaeus organisms. The bag was incubated at 37° C. for 24 hours for sterilization. Afterwards, the item was aseptically removed from the bag and placed in a tube of TSB for sterility testing at a incubation of 30-35° C. for 7 days: tubes were checked daily for sterility. All bone screws and cultured BI were sterile after 7 days.

Example 13

A 5.5 mm BioComposite Corkscrew FT Suture Anchor with one #2 FiberWire and one #2 TigerWire (White/Black) 38″ long, Inserter with Handle (part #PB1927BF01-11 made by Anthrex, Inc., Naples, Fla.) is used. Using the procedure of EXAMPLE 12, the Corkscrew was inoculated, and cultured in TSB for 7 days. All corkscrews and cultured BI were sterile after 7 days.

Example 14

A simulated contact lens container was made from a 25mm petri dish fitted with a 1″ piece of the irradiated Antimicrobial plastic in the top and a second 1″ piece in the bottom of the container. A rigid contact lens was inoculated with 0.1 ml of a 24-hour TSB culture of S. aureus or P. aeruginosa diluted in TSB to yield 1.3×105 cells/0.1 ml. The inoculum was allowed to dry on the lenses in an operating Biohazard hood. A lens, with the dried inoculum of the test organism in TSB, was placed on the Antimicrobial material in the case, inoculated side up, and the lid replaced. This sample preparation was repeated, adding multipurpose lens cleaning solution in the same manner. The sample lenses were stored in the case at room temperature for 18 hours. The lens was then aseptically sterility tested in TSB and incubated at 35-40° C. Appropriated positive and negative controls were also included and the results are summarized in Table 1 below.

TABLE 1
Antimicrobial effectiveness of the test material with indirect contact with
microbial contamination.
	S.	P.
Test Sample	aureus	aeruginosa
1) Inoculated lens on antimicrobial material	S	S
2) Inoculated lens on material with multipurpose lens	S	S
solution
3) Inoculated lens on material with sterile	S	S
buffer solution
4) Negative control 1	S	S
5) Negative control 2	S	S
6) Positive control 1	NS	NS
7) Positive control 2	NS	NS
Sterility Test Results: S = sterile, NS = non-sterile with positive growth of the test organism

All test samples (1-5) were sterile in 24 hours or less with the exception of the positive controls (6-7).

Example 15

Size of Insert vs. Bag Volume 0.3 mg/L

The following bags were heated for 60 minutes at 70° C. where the insert was irradiated at 35 kGy-70 KGy.

Bag Size	Bag Volume (mL)	35kGy mg of insert	mg insert at 70kGy
4″ × 6″	200	20	5
6″ × 9″	700	70	17.5
7″ × 12″	1600	160	40

Those skilled in the art to which the present invention pertains may make modifications resulting in other embodiments employing principles of the present invention without departing from its spirit or characteristics, particularly upon considering the foregoing teachings. Accordingly, the described embodiments are to be considered in all respects only as illustrative, and not restrictive, and the scope of the present invention is, therefore, indicated by the appended claims rather than by the foregoing description or drawings. Consequently, while the present invention has been described with reference to particular embodiments, modifications of structure, sequence, materials and the like apparent to those skilled in the art still fall within the scope of the invention as claimed by the applicant.

Claims

1. A container of a selected volume on the inside, suitable for low heat sterilizing a selected article positioned in the inside of the container comprising a container insert on the inside of the container comprising a melt formable polyoxymethylene or co-polymer of polyoxymethylene that has been melt formed into a container insert and has been irradiated sufficient to cause chain cleavage without depolymerization or brittleness of the insert such that formaldehyde is released upon subsequent application of low heat to the insert.

2. The container according to claim 1 wherein the thickness of the insert is no more than 20 mm.

3. The container according to claim 2 wherein the insert is a high surface area fiber or a non-woven mat.

4. The container according to claim 1 wherein the polyoxymethylene polymer contains ethylene oxide copolymerized to a suitable level for melt blowing into fibers or non-woven mats.

5. The container according to claim 1 wherein the melt forming process is melt blowing.

6. The container according to claim 1 wherein the insert is melt formed by spin bonding.

7. The container according to claim 1 wherein the radiation dosage is in a range of from about 1 to 200 kGy.

8. The container according to claim 1 wherein the insert is part of or attached to the inside of the container.

9. The container according to claim 1 wherein the insert is heated in a atmosphere of about 5 to 100 percent relative humidity.

10. The container according to claim 1 wherein the insert is one component of a multi component insert.

11. The container according to claim 1 wherein the insert further comprises a thermochromic material.

12. The container according to claim 1 wherein the container insert is of sufficient weight and surface area that upon low heating the insert the insert releases enough formaldehyde to reach a concentration of at least about 0.1 mg/L in the selected volume.

13. The container according to claim 1 wherein the bag is an essentially flat bag having a selected length and width.

14. The container according to claim 13 wherein the insert is a non-woven mat having a mat length and width and wherein the mat length and width is selected such that the mat fits in the bag and is of a size at least about half the product of the length times the bag width.

15. A process for producing a container of a selected volume on the inside suitable for low heat sterilizing a selected article positioned on the inside of the container comprising positioning in the inside of the container, a container insert comprising a melt formable polyoxymethylene or co-polymer which has been melt formed into a container insert and has been irradiated sufficient to cause chain cleavage without depolymerization or brittleness such that formaldehyde is released upon subsequent application of low heat to the insert.

16. The process according to claim 15 wherein the insert is melt formed into a high surface area fiber or non-woven mat.

17. The process according to claim 15 wherein the container insert is of sufficient weight and surface area that upon low heating the container the insert releases enough formaldehyde to reach a concentration of at least about 0.1 mg/L in the selected volume.

18. A method of sterilizing an article at low heat in a container of a selected volume on the inside comprising:

a) positioning the article in the container;

b) positioning a container insert in the container which comprises a melt formable polyoxymethylene or polyoxymethylene co-polymer which has been melt formed into a container insert and has been irradiated sufficient to cause chain cleavage without depolymerization or brittleness such that formaldehyde is released upon subsequent heating of the insert; and

c) heating the insert to a temperature of about 20° C. to about 90° C. for a time sufficient to release formaldehyde and sterilize the article.

19. The method according to claim 18 wherein the heating of the insert is accomplished by a method selected from the group consisting essentially of:

a) heating the container with the insert inside;

b) heating the insert and placing it in the container;

c) heating the container with external or internal heating pads;

d) heating the insert with heating wires placed in or on the insert; and

e) heating the container with an externally placed heating element.

20. The method according to claim 18 wherein the formaldehyde is sustained release at ambient temperature.