WO1999052567A1

WO1999052567A1 - Catalytic chamber

Info

Publication number: WO1999052567A1
Application number: PCT/EP1999/002440
Authority: WO
Inventors: Marc Harlan Minter; Leslie Frank Stebbins; Martha Jane Graham; Robert Allen Janssen
Original assignee: Novartis Ag; Novartis-Erfindungen Verwaltungsgesellschaft Mbh
Priority date: 1998-04-14
Filing date: 1999-04-12
Publication date: 1999-10-21
Also published as: EP1071478A1; NO20004960L; CA2326895A1; AU3605999A; JP2002511333A; NO20004960D0

Abstract

A method of preserving and/or disinfecting a continuous-flow aqueous stream in a health care product manufacturing facility and a catalytic chamber for decomposition of peroxide in a continuous flow conduit. The method and device are especially useful in the preservation of aqueous streams used in contact lens production, contact lens care and ophthlamic drug production processes.

Description

CATALYTIC CHAMBER

This invention relates generally to the preservation or inhibition of microbial growth in aqueous streams in a health care manufacturing operation. In a preferred embodiment, this invention relates to preservation of streams in pharmaceutical or ophthalmic production facilities, such as contact lens production facilities.

Manufacturing facilities which produce health care products are under ethical and legal requirements to maintain exceptionally clean production facilities. For example, contact lens manufacturing facilities are subject to strict cleanliness protocols in order to ensure consumer safety. Typically, manufacturing facilities focus on using highly pure raw materials and avoiding introduction of microorganisms during the storage or manufacturing processes. In particular, aqueous environments such as process flowpipes, present a problem because of the enhanced likelihood of bacteria growing in any moist, dark environment.

Ideally, the methods used to prevent introduction of microorganisms into the manufacturing environment will entirely eliminate any potential for contamination. However, in a real manufacturing setting, there is inevitably some finite possibility of contamination. In addition, the controls on water supplies in some countries are not sufficiently stringent to reduce the probability of contamination to an acceptable level. Accordingly, a method of preserving aqueous flow streams in health care production facilities is desirable, in order to inhibit growth of any microorganisms which inadvertently contaminate aqueous raw material streams.

A large number of antimicrobials and preservatives exist, which may be added to an aqueous solution in order to inhibit microbial growth or erradicate any microorganisms present. However, many of these antimicrobials and preservatives cannot remain in a final health care product because of the incompatibility with human tissue. For example, benzalconium chloride (BAK or BAC) has been used as an antimicrobial in ophthalmic drug products and lens care disinfection products. However, BAK causes stinging and redness in many patients when contacted with the eye. Furthermore, BAK is incompatible with some drugs.

Similarly, a number of patents disclose the use of hydrogen peroxide to disinfect contact lenses. A fundamental patent in this area is US-A-3,912,451 , issued to Gaglia. In addition, the use of low concentrations of peroxide to preserve lens care or ophthalmic drug solutions has been disclosed. Two fundamental patents claiming this technology are US-A-5,576,028 and US-A-5,607,698, issued to Martin, et al.

However, there is a need for compositions and processes which preserve and/or disinfect production flow streams without resulting in products which cause discomfort when used or incompatibility with other components of the product. In particular, there remains a need to preserve continuous flow streams in production processes and to remove substantially all of the preservative before product sale to the consumer. There is a particular need to preserve continuous-flow aqueous streams used in ophthalmic production processes and to remove substantially all of the preservative before the ophthalmic product is distributed to the consumer.

It is therefore an object of the invention to provide a process for preserving and/or disinfecting continuous-flow aqueous streams in health care product manufacturing facilities.

Another object of the invention is to provide methods and devices for removing a peroxide preservative and/or disinfectant from a continuous-flow stream.

A further object of the invention is to provide a means for in-line decomposition of hydrogen peroxide in a ophthalmic lens production facility.

These objects and other advantages of the invention will become apparent from an examination of the invention as summarized below and as defined in detail hereinafter.

An embodiment of the invention is a method of preserving and/or disinfecting a continuous- flow aqueous stream in a health care product manufacturing facility. The method involves preserving an aqueous solution with a preservative, providing a continuous flow stream of said preserved solution, and continuously or semi-continuously decomposing substantially all of the preservative in said preserved stream prior to dispensing the aqueous solution. A preferred preservative is hydrogen peroxide.

Another embodiment of the invention is a catalytic chamber for decomposition of peroxide in a continuous flow conduit. The catalytic chamber includes an external housing adapted to be disposed within or as part of a fluid-conveying conduit, and a catalytic element disposed within the housing having catalytic material disposed therein or thereon. The catalytic chamber defines openings therethrough to allow passage of fluid. The catalytic chamber forces contact between fluid passing therethrough and the catalytic element, thereby accelerating decomposition of any peroxide present in any fluid passing therethrough.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a side sectional exploded view of an exemplary catalytic chamber of the present invention.

FIG. 2 is a side sectional view of a tool useful in assembling the catalytic chamber of FIG. 1.

FIG. 3 is a plan view of a support member for a perforated disk.

FIG. 4 is a bottom view of a catalytic chamber.

FIG. 5 illustrates a catalytic element retention means in a cross-sectional view.

An embodiment of the invention is a method of preserving and/or disinfecting a continuous- flow aqueous stream in a health care product manufacturing facility. The method is particularly useful in preserving saline solutions in piping and storage networks within contact lens production facilities, although the scope of the invention is not so limited. A particularly useful preservative is a peroxide, preferably hydrogen peroxide or an additive which generates hydrogen peroxide in solution (e.g., sodium perborate).

The method generally involves the steps of preserving an aqueous solution with a preservative, providing a continuous flow stream of the preserved solution; and continuously or semi-continuously decomposing substantially all of the preservative in said preserved stream prior to dispensing said aqueous solution.

Another embodiment of the invention is a device for decomposing peroxide in a continuous- flow conduit. The decomposition of the peroxide preferably occurs immediately prior to dispensing of the aqueous solution into the product package, in order to minimize any area of piping which is not preserved.

The decomposition device generally includes an external housing adapted to be disposed within or as part of a fluid-conveying conduit, including inlet and outlet openings and a catalytic element disposed within the housing having catalytic material disposed therein or - 4 -

thereon. The device includes openings therethrough to allow passage of fluid. The device forces contact between fluid passing therethrough and the catalytic element, thereby accelerating decomposition of peroxide present in fluid passing therethrough.

As used herein, the device for decomposing preservative is termed a "catalytic chamber". The catalytic chamber includes an external housing which is adapted to be disposed within or as part of a fluid-conveying conduit and a catalytic element disposed within the external housing. The catalytic element may have catalytic material disposed within the element or coated on portions of the element, or both. The catalytic chamber has an inlet opening for receiving upstream flow of solution and an outlet opening for allowing solution to pass out of the chamber. The design of the catalytic chamber forces contact between the passing fluid and the catalytic element, thereby accelerating decomposition of any peroxide present in the passing fluid.

One embodiment of the catalytic chamber includes (a) an external housing adapted to be removably affixed to solution-carrying piping, (b) a catalytic element having inlet and outlet openings, (c) a first catalytic element retention means positioned near the inlet opening and (d) a second catalytic element retention means positioned near the outlet opening.

One preferred embodiment of a catalytic chamber is illustrated in exploded sectional view in FIG. 1 , in which the solution flow direction is shown by the arrow. Catalytic chamber 10 includes an external housing 12 which provides the ultimate support for all other components. External housing 12 is adapted to be releasably affixed to piping (not shown) via standard sanitary clamps (not shown) which are releasably secured to inlet and outlet end flanges 14. Further sealing is provided by o-rings 16 imbedded in the flanges.

The downstream catalyst retention means includes perforated disk 18 held in place by castellated collar 20. During assembly, perforated disk 18 is inserted into external housing 12. Next, castellated collar 20 is inserted and threaded via external threading 22 into internal threading 24 of external housing 12. Manipulation of castellated collar 20 within external housing 12 is accomplished with an appropriate tool, such as collar key 42 of FIG. 2. After castellated collar 20 has been secured, piston 26 is inserted into external housing 12. Two o-rings 28 positioned on the external wall, near each opening of the piston, guide the piston as it is moved into a resting position within external housing 12. A catalytic element or catalytic material (not shown) is then placed or poured into the cavity defined by piston 26. Perforated disk 30 is subsequently positioned on top of the catalytic element and castellated collar 32 is secured to piston 26 by threaded engagement.

Piston 26 includes perforations 34 in downstream support member 36 which provides structural support for perforated disk 30 while minimizing resistance to flow. In a similar manner, external housing 12 includes downstream support member 38 with perforations 40 designed to minimize fluid resistance while providing support for perforated disk 18. All of the perforations are preferably substantially aligned in order to reduce pressure drop.

FIG. 3 is a plan view of support member 50 which retains a perforated disk in place within the catalytic chamber. Support member 50 has a plurality of substantially uniformly spaced, uniformly sized circular openings which allow fluid to pass through the support member. Clearly, a wide variety of designs of a support member could be envisioned (e.g., variations in opening shape, size and spacing) which would provide substantially the same function as the design of FIG. 3, and such designs are within the scope of the present invention.

The catalytic element which increases the rate of decomposition of preservative may be formed in a wide variety of shapes and sizes. A preferred catalytic element includes a plurality of beads of catalytic material having catalytic material disposed thereon. Another preferred catalytic element includes a granular mass of catalytic material (e.g. powder form).

A preferred catalytic material for decomposing peroxide is platinum. The platinum may be used in several forms or combinations of forms. For example, the platinum may be coated onto metallic, ceramic or polymeric structures (e.g., spheres or beads) disposed within the catalytic element. For example, platinum black or a platinum alloy may be used to decompose peroxide. However, one preferred catalyst form is a powdered or granular platinum or platinum-containing material. An advantage of a powdered form is a higher surface area per volume, while a disadvantage is that the pressure drop increases and fouling may be more likely. While the mesh size of the powder can be varied depending on the particular application, powder having a mesh size of less than 400 microns, preferably less than 325 microns has been found to be useful.

Thus, powder is preferred in order to maximize the ratio of exposed surface area to weight of catalytic material. A preferred ratio of catalyst surface area to weight is about 100 to 1000 m² / gram, more preferably about 250 to 330 m²/g.

In addition, it should be noted that properly selected catalytic elements themselves may serve as a bacteriostat. The platinum catalyst which accelerates decomposition of the peroxide preservative will also simultaneously act as an antimicrobial.

For example, a preferred catalytic material for decomposing peroxide is platinum-coated alumina powder. A weight percentage of platinum of about 1 to 10% has been found to be suited to the application. While the mass of catalytic material to be used may depend on several factors, it has been found that a mass of about 250 to 450 grams, preferably about 310 to 350 grams, is useful in streams having a flow rate of about 350 to 700 ml/min.

The catalytic element may include catalytic particulates having exposed surfaces of platinum or platinum-containing material and inert packing. A preferred inert packing material is alumina powder. For example, a catalytic element may include about 1 to 10 weight percent catalytic particulates having exposed surfaces of platinum or platinum- containing material and about 99 to 90 weight percent inert packing.

Alternatively, the powder or bead catalytic material may be formed into a solid element. The catalytic element may be a rigid, sintered disc formed by fusing particles having exposed surfaces of platinum or platinum-containing material. In yet another alternative, the catalytic element includes a solid support meshwork defining a plurality of substantially uniform openings therethrough and a coating of platinum or platinum-containing material deposited on said meshwork. These embodiments illustrate that there are a number of designs which may accomplish the desired result of the invention and are within the scope of the invention.

When a powdered catalytic material is used, a means for retaining the catalytic material is needed in the catalytic chamber. A preferred location for placement of the catalytic element retention means is adjacent the upstream and downstream ends of the piston, preferably - 7 -

structurally supported by the perforated disks. A suitable catalytic element retention means is a felt material, in particular, a stainless steel felt material. The porosity of the felt is determined, in part, by the size of the catalytic powder being retained by the felt and by the effluent particle concentration and size requirements. A suitable felt porosity has been determined to be about 1 to 50 microns, preferably about 5 to 20 microns. In a preferred embodiment, the upstream felt has a 20 micron porosity, while the downstream felt has a 5 micron porosity.

FIGs. 4 and 5 illustrate a useful design of a catalytic element retention means formed from a felt material. The catalytic element retention means may be formed from plastic, glass, stainless steel or other material which may be made suitably porous (e.g., in a felted, knitted or woven manner). FIG. 4 shows catalytic element retention means 60 having molded felted material 62 molded into it, with support on both sides by a screen. The bottom surface features O-ring 64 which seals against the inner surface of the catalytic chamber body. A similar disk is placed into the piston body. In both cases, the disks are topped with the perforated disks of FIG 3 and held in place by castellated collars.

The external housing, catalytic element housing, and catalytic element retaining means of the catalytic chamber may be composed of a number of rigid materials, but a preferred group of materials are those which are resistant to corrosion in the presence of the process solution (e.g., 50 ppm hydrogen peroxide in saline). A preferred group of materials are the stainless steels (e.g., 316 stainless steel) and rigid, machinable polymers such as polyvinylidene fluoride (PVDF).

Polymers, such as polyvinylidene fluoride, are particularly preferred in order to avoid any possible corrosion problems. While stainless steels may be appropriate for some applications, it has been found that polymeric materials are preferred for long term durability in the presence of 40 to 50 ppm hydrogen peroxide.

Hydrogen peroxide, a preferred preservative, decomposes into water and oxygen under certain conditions. It is known that application of light or heat, or contact with a catalyst such as platinum, will accelerate the decomposition of hydrogen peroxide. In accordance with the present invention, a preferred method of decomposing peroxide in an aqueous processing - 8 -

stream before dispensing is to pass the peroxide-containing solution over a catalytic chamber having platinum coated surfaces therein or thereon.

Preferably, the catalytic chamber is positioned in the flow stream, such that the aqueous process solution continuously or semi-continuously passes through the catalytic chamber. Locating the catalytic chamber in the flow path forces contact of the peroxide in the solution with catalyst in the chamber, thereby causing accelerated peroxide decomposition.

In particular, it is preferred to position the catalytic chamber near the end of the flow stream, quite close to the dispensing end. Preferably, the catalytic chamber is located immediately before the valve which controls dispensing, in order to maximize the length of piping which is preserved.

The peroxide concentration in the flow stream should be sufficiently high to handle potential microbial burden. However, the concentration should be minimized in order to minimize the cost associated with preservative use and the burden upon the catalytic chamber. A preferred concentration of hydrogen peroxide in a flow stream is about 20 to 100 ppm, more preferably about 40 to 60 ppm.

In order to use the solution from the flow stream in an ophthalmic product, the peroxide concentration must be reduced to a level which does not cause any substantial irritation to the consumer. In use as contact lens saline storage solution, the peroxide concentration is preferably reduced to below about 10 ppm, more preferably below about 2 ppm, and, in certain circumstances, below about 0.2 ppm.

The characteristics of the flow stream may vary substantially, depending on the particular production requirements. Generally, the flow rate may be about 100 to 1000 ml/minute, and in a preferred embodiment, the flow rate is about 350 to 700 ml/min. The inner diameter of the piping may be about 1 to 8 inches, and is preferably about 2 to 6 inches. The pressure may be about 5 to 100 psig, and is preferably about 10 to 30 psig.

The design of the catalytic chamber may vary substantially, depending on the requirements of the particular production needs. Some of the factors which impact the design of the catalytic chamber include a balance of the goals of: 1. minimizing pressure drop across the chamber,

2. maximizing solution / catalyst contact within the chamber,

3. ensuring ease of replacement / change-over,

4. reducing the rate of fouling or clogging, and

5. maximizing catalyst useful life.

In order to minimize pressure drop across the catalytic chamber, the overall internal dimensions preferably conform substantially with the internal dimensions of the adjacent piping. Accordingly, a preferred catalytic chamber has a cylindrical shape in conformance with production plant piping. Further, in order to promote convenient servicing and replacement, the exterior structural support for the catalytic chamber is preferably a standard piece of threaded piping. A preferred external housing for the catalytic chamber is a straight pipe having external threading on either end and internal dimensions roughly the same as the surrounding piping.

An exemplary catalytic chamber has a PVDF external housing composed of a nominal four inch diameter cylinder containing a PVDF catalytic piston which retains catalytic elements therein. Inside the piston is a first catalyst retaining means which is composed of a circular piece of BekiportE> 20 AL3 SS AISI 316L-WNR 1.4404 material (Bekaert Corporation, Marietta, Georgia) fused into a polyethylene ring and equipped with o-rings. This seals against the inner surface of the face of the piston. It is covered with a disk and clamped into place using a castellated collar. Both the disk covering the catalyst retaining means and the face of the piston are perforated with a series of large holes which allows saline to flow through the center of the piston. The piston is equipped with a double Viton® o-ring seal. Downstream of the piston face is a cavity for retaining catalytic elements therein, formed by the void within the cylinder between the first catalyst retention means and a second catalyst retention means (i.e., another circular piece of Bekipor® material of different porosity [5 AL3 SS AISI 316L-WNR 1.4404]). This second catalyst retention disk is held in place in a fashion identical to that of the first. The chamber itself is filled with about 310 to 350 grams of -325 mesh platinum on alumina powdered catalyst (Pt 5%) having a surface area in excess of 250 m²/g. The device is equipped with standard sanitary flanges at both ends.

The device is advantageous in that it is able to retain the large number of small catalyst particles required to reduce the hydrogen peroxide concentration from the 40 to 50 ppm to - 10 -

the <0.2 ppm level in a process stream flowing in excess of 700 ml/minute. Preferably, the stream will contain no more than about 50 particles/ml which are equal to or greater than 10 mm, no more than 5 particles equal to or greater than 25 mm, and no more than 1 particle greater than or equal to 50 mm.

The device is also advantageous in that it is completely passive (i.e., it has no power requirements) and can also be designed to operate at modest pressures (e.g., 10 to 30 psi). In addition, it is relatively easy to refurbish. The Bekipor® disc retaining the catalyst may restored to its originally rated flow rate by simply reversing the flow through it to remove fouling.

This device allows the addition of hydrogen peroxide as an ingredient in saline without its introduction into the final product. Thus, the bacteriostatic benefits of hydrogen peroxide can be realized in the saline distribution loop piping and in various intermediate steps in the manufacturing process requiring saline. The catalytic chamber then removes the hydrogen peroxide at the final packaging step, resulting in a final product that has benefited from the bacteriostatic effect yet is functionally identical, in ophthalmic compatibility, to product manufactured using saline without hydrogen peroxide.

In order to accelerate the decomposition rate of peroxide, the solution may be heated in addition to being exposed to catalytic elements. Accordingly, in another embodiment of the invention the catalytic chamber is equipped with a heating element, internally and/or externally, in order to accelerate or better control the peroxide decomposition rate.

Clearly, there are a number of factors to consider in designing of the catalytic chambers of the present invention. However, given the teachings herein, a person having ordinary skill in the art should be able to design a wide range of systems performing substantially the same function, in substantially the same way to achieve substantially the same result, taking into account factors, which include without limitation, the following:

• feed peroxide concentration

• target effluent peroxide concentration

• maximum flow rate

• piping dimensions - 11

Reynold's number acceptable pressure drop catalyst material purity / activity stream temperature range (including amount of added heat, location, duration) exposed surface area of catalyst fouling rate of catalyst configuration of calaytic elements difficulty and cost of manufacture of catalytic element durability and servic life of catalytic element competiting chemical reactions (e.g. presence of chemical species which inhibit peroxide decomposition)

The invention has been described in detail, with reference to certain preferred embodiments, in order to enable the reader to practice the invention without undue experimentation. However, a person having ordinary skill in the art will readily recognize that many of the components and parameters may be varied or modified to a certain extent without departing from the scope and spirit of the invention. Furthermore, titles, headings, definitions or the like are provided to enhance the reader's comprehension of this document, and should not be read as limiting the scope of the present invention. Accordingly, the intellectual property rights to this invention are defined only by the following claims and appropriate extensions and equivalents thereof.

Claims

- 12 -CLAIMS

1. A catalytic chamber for decomposition of peroxide in a continuous flow conduit, comprising: a) an external housing adapted to be disposed within or as part of a fluid-conveying conduit, including inlet and outlet openings; and b) a catalytic element disposed within said housing having catalytic material disposed therein or thereon, wherein said catalytic chamber includes openings therethrough to allow passage of fluid, and wherein said catalytic chamber forces contact between fluid passing therethrough and said catalytic element, thereby accelerating decomposition of peroxide present in any fluid passing therethrough.

2. A catalytic chamber of claim 1 , wherein said catalytic element comprises a substantial surface area exposing platinum or a platinum-containing material as the catalytic material.

3. A catalytic chamber of claim 1 , further comprising: a) a first catalytic element retention means positioned on the upstream end of said catalyst material, and b) a second catalytic element retention means positioned on the downstream end of said catalyst material.

4. A catalytic chamber of claim 3, wherein the catalytic element retention means include stainless steel felt material.

5. A catalytic chamber of claim 4, wherein the felt material has a porosity of 1 to 50 microns.

6. A catalytic chamber of claim 1 , wherein said catalytic element comprises: a) a solid support meshwork defining a plurality of substantially uniform openings therethrough; and b) a coating of platinum or platinum-containing material deposited on said meshwork. - 13 -

7. A catalytic chamber of claim 1 , wherein said catalytic element includes a porous retention chamber comprising: a) catalytic particulates having exposed surfaces of platinum or platinum-containing material; and b) inert packing.

8. A catalytic chamber of claim 7, wherein said catalytic particulates include less than 400 mesh platinum particulates.

9. A catalytic chamber of claim 8, wherein said inert packing includes alumina powder.

10. A catalytic chamber of claim 9, wherein said catalytic element comprises about 1 to 10 weight percent platinum.

11. A catalytic chamber of claim 10, comprising: a) about 1 to 10 weight percent catalytic particulates having exposed surfaces of platinum or platinum-containing material; and b) about 99 to 90 weight percent inert packing.

12. A catalytic chamber of claim 1 , wherein said catalytic element is a rigid, sintered disc formed by fusing particles having exposed surfaces of platinum or platinum-containing material.

13. A catalytic chamber of claim 1 , further including a heating element.

14. A catalytic chamber of claim 1 , which is capable of continuously or semi-continuously reducing peroxide concentration of 40 ppm at the inlet to below 2 ppm at the outlet.

15. A catalytic chamber of claim 1 , which is capable of operation in fluid communication with a piping system providing a continuously flowing solution stream at 10 to 30 psig.

16. A catalytic chamber of claim 1 , comprising: a) an external housing adapted to be disposed within or as part of a fluid-conveying conduit, including inlet and outlet openings; and - 14 -

b) a catalytic element disposed within said housing, including: i) a first catalytic element retention means positioned at the inlet of the catalytic element, ii) powdered catalytic material including platinum, iii) a second catalytic element retention means positioned at the outlet of the catalytic element wherein said catalytic chamber forces contact between fluid passing therethrough and said catalytic element, thereby accelerating decomposition of any peroxide present in any fluid passing therethrough.

17. A method of preserving and/or disinfecting a continuous-flow aqueous stream in a health care product manufacturing facility, comprising the steps of: a) preserving an aqueous solution with a preservative; b) providing a continuous flow stream of said preserved solution; and c) continuously or semi-continuously decomposing substantially all of the preservative in said preserved stream prior to dispensing said aqueous solution.

18. A method of claim 17, wherein the preservative is a peroxide.

19. A method of claim 18, wherein the preservative is hydrogen peroxide.

20. A method of claim 17, further comprising the step of subsequently instilling a quantity of the solution in the stream into a health care product container.

21. A method of claim 18, wherein said decomposing is accomplished by positioning a fixed catalytic element in the flow stream near the dispensing end of said flow stream.

22. A method of claim 21 , wherein said catalytic element includes platinum or a platinum- containing material.

23. A method of claim 17, further comprising the step of increasing the temperature of said preserved stream to accelerate the decomposition of peroxide.

24. A method of claim 18, wherein the preserved solution has a peroxide concentration of about 10 to 100 ppm. - 15 -

25. A method of claim 22, wherein the preserved solution has a peroxide concentration of about 30 to 60 ppm.

26. A method of claim 17 wherein the step of decomposing is accomplished by contacting preservative with a catalytic element.

27. A method of claim 26, wherein the catalytic element comprises a platinum-containing powder.

28. A method of claim 27, wherein the aqueous solution subsequent to the step of decomposing stream contains no more than about 50 particles/ml which are equal to or greater than 10 mm