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Description  |
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BACKGROUND OF THE INVENTION
The present invention concerns a liquid dispenser for sterile solutions.
More particularly, the present invention relates to a multidose dispenser
for sterile solutions, particularly in a dropwise form, which keeps the
solutions aseptic without the use of preservatives.
A number of solutions which are sold and administered as over-the-counter
("OTC") and/or prescription preparations must be kept sterile to prevent
bacterial or other microbial growth. The conventional means of Preventing
microbial growth is to add a preservative or other antibacterial agent to
the solution during packaging. Although these preservatives keep the
enclosed solution sterile, the bottle itself may harbor external bacterial
growth which is carried along with the outflow of fluid. In addition, the
preservatives themselves are often toxic not just to bacteria but also to
the cells which are being treated by the bottled preparation. For example,
the preservatives used in most eye drops are toxic to goblet cells and
other cells in the eye. Because of this toxicity level, continued use can
cause more long term problems then the solutions solve.
Filter bottles have been used to store the solutions in aseptic condition
after cold sterilization for many years. Antimicrobial filters, e.g., 0.2
micron filters, are often used for this purpose. However, in many of these
previous designs, removal of the fluid required removal of the filter. In
other cases, the limitations of flow caused by the small pore size of the
microbial filters are not important because the solution is not dispensed
through the filters or high pressures are available for dispersing.
Because of these and the other problems with filter bottles, the use of
preservatives or single dose packaging have been the rule in dispensing
OTC and other liquid products such as eye medicants or drops.
Accordingly, an object of the invention is to provide a multidose liquid
dispenser which can keep solutions aseptic under prolonged use without the
use of an antibacterial or antimicrobial additive.
A further object of the invention is to provide a filter bottle for use in
cold sterilization processes which provides good flow properties and
protection against bacterial contamination.
Another object of the invention is to provide a bottle which can be used
for eye drops and similar solutions which do not contain preservatives.
These and other objects and features of the invention will be apparent from
the following description and the drawing.
SUMMARY OF THE INVENTION
The present invention features a multidose dispenser for sterile liquids
which provides antimicrobial action without need for preservatives or
other antibacterial additives. The invention is based, in part, on a dual
filter assembly which provides good flow rate of fluids, protection
against contamination after filter breakage, and assists in prevention of
bacterial growth on the external dispersing tip of the bottle.
The liquid dispenser of the present invention, which is particularly useful
for dispensing sterile liquids or solutions, has a reservoir compartment
adapted for storing the sterile solutions. The reservoir is in fluid
communication, through a flow passage, to a tip adapted to dispense the
sterile solution. A filter assembly is sealed across the entire expanse of
the flow of passage to prevent fluid delivery except through the filter
assembly. The filter assembly contains both a hydrophobic and a
hydrophilic filter, the filters being arranged such that the hydrophilic
filter is closer to the reservoir while the hydrophobic filter is closer
to the liquid dispensing end of the tip. Both the hydrophobic and
hydrophilic filters have pores which are of a size sufficient to prevent
bacteria from traversing the filter, e.g., the pores act as microbial
filters.
In preferred embodiments of the invention, the filter assembly has the
hydrophobic and hydrophilic filters separated, e.g., by a support ring. A
more preferred embodiment has a filter structure whereby there are a
plurality of support rings between, and on opposite sides of, the filters
to provide structural support and filter separation. In the most preferred
embodiment, the filter assembly is located in the flow passage such that
the hydrophobic filter is substantially at the dispensing end of the
liquid dispensing tip. The filter assembly can be sealed in the flow
passage by any means. Preferred methods of sealing the filter assembly in
the flow passage are non-flaking adhesives, ultrasonic sealing, and heat
sealing.
BRIEF DESCRIPTION OF THE DRAWING
The sole figure of the drawing shows a cut-away view of a liquid dispenser
of the invention.
DESCRIPTION OF THE INVENTION
The present invention features a multidose dispenser for sterile liquids
which is capable of preserving sterility of the contained solution without
the use of chemical preservatives or antibacterial additives. The dual
filter assembly of the present apparatus provides excellent flow
properties, inhibits bacterial contamination of the bottle, and preserves
the sterility of the contained solution.
The sole figure of the drawing more clearly illustrates that present
invention. Flexible squeeze bottle 10 has a reservoir chamber 20 connected
by flow path 30 to tip 40. Standard dispersing bottles with removable tip,
e.g., low density polypropylene such as those made by Wheaton Scientific,
Melville, N.J. can be used. The bottles were modified by addition of
filter assembly 50 located across flow path 30 near tip 40. Filter
assembly 50 contains a hydrophobic filter 52, for example a TF (PTFE) 0.2
micron pore size filter such as is obtainable from Gelman Sciences, Inc.,
Ann Arbor, Mich. Hydrophilic filter 54 is a microbial filter, preferably
having a pore size of 0.2 microns or less. The FP Vericel filter, also
obtainable from Gelman Sciences, Inc., is exemplary of this type of
filter. The hydrophilic filter may have a laminated polypropylene web
support on one side for reinforcement and durability. Support disks 56 are
placed to further support and separate filters 52 and 54. Silicone rings
punched from Silicone sheeting, e.g., Silastic Brand Sheeting from Dow
Corning, Midland, Mich., can be formed into a preferred ring for use to
provide both support and separation functions. The rings are bound to the
filters, and to the plastic of the bottle, by standard techniques, e.g.,
ultrasonic binding, heat sealing, or adhesive sealing. If an adhesive is
used, it must be non-flaking. A preferred adhesive is Silastic Brand
Medical Adhesive Silicone-type A, also from Dow Corning. The adhesive must
be kept off the active portions of the filters to prevent contamination
and maintain flow.
The dual filter assembly of the invention has a variety of purposes. First,
if there is a break in either filter, sterility is maintained by having
two distinct filters. Second, the hydrophobic filter does not retain water
so bacteria are inhibited from growing on the outside surface of the
filter assembly. Third, the hydrophilic filter closer to the reservoir
wets better than the hydrophobic filter, and since flow rate is improved
by better wetting, the use of the hydrophilic filter permits a higher flow
rate from the bottle without high pressure.
The following non-limiting Examples further illustrate the efficacy of the
invention.
EXAMPLE 1
This Example, 15 ml Wheaton bottles with snap-tips are fitted with filter
assemblies of the invention. This filter assembly has a 0.2 micron FP
Vericel Membrane Filter (Gelman Sciences, Inc.) glued between two punched
Silastic rings using Silastic Brand Medical Adhesive Silicone-type A (Dow
Corning). The filter disks are 8 mm in diameter and Silastic support rings
are also 8 mm disks of Silastic Brand Sheeting (0.02 inches) (Dow Corning)
with 5.5 mm essentially central holes punched-out. The assembly further
includes a 0.2 micron PTFE membrane filter (Gelman Sciences, Inc.) which
is bonded between one of the Silastic rings and a third Silastic ring. The
assembly is glued to the snap-tip dropper such that the Silastic support
ring is bonded directly to the dispensing end of the snap-tip dropper and
the Vericel filter is closest to the solution in the bottle.
Five bottles made with the filter assembly and another bottle, identical
except lacking the filter assembly, were filled with substantially the
same amount of a test solution under cold sterilization procedures. The
solution is an eye drop solution such as described in U.S. Pat. No.
4,775,531, issued on an application of the present inventor. All the
bottles were used to dispense fluid to the eyes of human volunteers
between one and two times daily for one month, excluding weekends. At the
end of the period, the snap-tip assembly was removed and 1 ml of the
remaining fluid was placed in fluid thioglycollate broth for fourteen days
at 30-35.degree. C. An additional 1 ml of the remaining fluid was placed
in soybean-casein digest medium for fourteen days at a temperature of
20-25.degree. C. After the fourteen days, the fluid thioglycollate broth
was plated out on soybean-casein digest medium and incubated at
20-25.degree. C. for an additional fourteen days.
At the end of the period, all of the solutions contained within the bottles
having the filter assembly were sterile. However, the solution from the
bottle without the filter system was contaminated with bacteria as
indicated by turbidity of the thioglycollate broth. Further investigation
indicated that the bacteria was pseudomonas.
EXAMPLE 2
For this Example, forty-nine filter bottles were made using the filter
assembly described in Example 1. The bottles were all filled with the same
eye drop solution. Eleven patients were given the bottles at separate time
intervals as needed. The patients were instructed to use the drops
contained at least six times a day. The bottles were returned with a
portion of the solution remaining and compliance was monitored by
measuring the volume remaining upon the return of the bottles. Mean
duration of usage was 23.4+/-1.2 (SEM) days. Twenty-three of the bottles
were used for twenty-eight days or longer. Upon return, all forty-nine
solutions tested sterile by USP guidelines, using the testing described in
USP XXI, Section 71.
As is clearly indicated by the Examples, the present invention provides a
means of maintaining the sterility of solutions without the use of
additives such as preservatives or other antibacterial agents. Because of
the toxic effects of such agents on certain cells, this has numerous
advantages.
The invention is not limited by the foregoing Examples but may be practiced
in other obvious variations. Such other variations of the claimed
invention are included within the following claims.
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