Patent Grant
10940087
This invention relates generally to methods for medical procedures involving liquid transfer, sterilization and mixing in a field environment to produce a sterile autologous blood eye drop product. It is also particularly related to kits and to methods which employ preassembled parts to provide a sterile product without requiring confines of a laminar flow hood.
Conventionally, mixing and formulation of medications is a pharmacy or other medical environment performed function most often involving use of laminar flow hoods and strict aseptic technique to maintain sterility. In pharmacies, medical solutions are often passed through a medical grade sterilizing filter to assure an aseptic condition. Resulting products from these facilities are highly regarded and widely used in hospitals and other clinical facilities.
However, today, a significant portion of medical practice takes place outside sophisticated medical institutions. As an example, a new and very effective eye-treatment technology is based upon mixing autologous blood serum with normal saline in exacting proportions. Commonly, blood is drawn from patients in a wide range of areas remote from pharmacies and laboratories. The expense and inconvenience of relying on such facilities to sterilize and mix is prohibitive, negatively affecting broader application of this promising technology. Thus, there exists a severe contemporary need for a process or methodology, not currently available commercially, which can, with appropriate safety and efficacy, provide such sterilizing, dispensing and mixing to produce sealed containers of autologous blood eye drops in a field capability.
Convenience kits have become commonly used appliances for a number of reasons. First, a convenience kit is specifically made for a given application. Contents of each such kits are prepared and provided in a form which generally reduces procedure steps and improves efficiency. Second, such kits can provide additional safety such as the kit disclosed in U.S. Pat. No. 9,449,521, titled METHODS FOR MAKING AND USING A VIAL SHIELDING CONVENIENCE KIT, issued May 28, 2013, which proved effective in providing additional safety to technicians and patients by keeping hazardous drug fumes and liquid fully contained.
Vial and bottle filling into containers disposed within a plastic bag is also known in medical art. An example of such a process is provided in U.S. Pat. No. 9,140,939, allowed Oct. 6, 2015 to Jean-Pascal Zambaux (Zambaux) titled DISPOSABLE ISOLATOR COMPARING MEANS FOR FILLING CONTAINERS. However, the process, as disclosed in Zambaux, has been abandoned in the United States due to experience of contamination in source liquid used for filling without further sterilization. Such contamination has been found to be in liquid distributed to a plurality of containers, resulting in a spread of infection. For this reason, the Applicants understand that compounding pharmacies are now commonly employed for filling medical vials and bottles through sterilizing filters. Relative to the instant method of the current invention, Zambaux is also deficient for being used for a portable all environment convenience kit because no method for capping and thereby protecting sterile state of liquid in bottles and vials is taught.
As indicated supra, use of sterilizing filters in now well known and accepted. U.S. Pat. No. 9,636,444 titled FILTRATION SYSTEM FOR PREPARATION OF FLUIDS FOR MEDICAL APPLICATIONS allowed to Jeffrey H. Burbank, et al. (Burbank) allowed May 2, 2017 discloses such use, but, as is the case of Zambaux, does not disclose filling and capping within a bag to protect a sterile state when removed there from.
Following is a list of terms and associated definitions which are provided for clarity and understanding when used to disclose precepts of the instant invention:
contaminating environment, n: substance surrounding comprising freely moving masses which communicate with an unshielded substance to negatively affect the substance SAL
dead space, n: a volume of inaccessible fluid which is retained within a device after a procedure
digital, adj: relating to, or done with thumb or fingers
distal, adj: a distance relative to a cited object or person; opposite of proximal
ETO, n: acronym for ethylene oxide, a powerful sterilizing agent
field of use, n: a location in an uncontrolled environment in which potentially contaminating health-hazardous materials are present.
filter, n: a product material having a sufficiently small porous matrix to impede passage there through of a particulate of predetermined size; a medical grade sterilizing filter generally has a 0.2 micron pore size
filter assembly, n: apparatus comprising one or more filters and a sealed bag interface
filter component, n: A housing for a filter having a pair of opposing fittings providing communicating conduits to and from the filter.
fitting, n: a medical connector
insulated wrap, n: a flexible container which may be a bag or folded shield which is sealed to provide a container in which enclosed parts can be maintained at a reduced temperature
kit, n: a group of parts, provided within a single package for a designated use laminar flow hood, n: (a fume hood) a work-place enclosure in which purified air flow is directed so as to prevent contamination of sterile materials by airborne organisms. It should be noted that special training and technique is required to prevent contamination by such physical manipulations as touch and breathing.
luer fitting, n: a medical connector having a frustoconical-shaped connecting geometry which is in common use in medical practice
luer lock fitting, n: a luer fitting having a locking mechanism whereby a male and female connector are securely, but releasably affixed one to the other
plastic bag, n: a sturdy container made of clear pliant material which comprises an opening initially available at one end for product insertion and which is sealed thereafter to provide a totally enclosed product shroud, the material being sufficiently pliant to permit digital, in-bag product handling from outside the container
interface gasket, n: an elongated hollow tube that is sized, shaped and disposed to be affixed to along a filter component conduit about a hole in a plastic bag and thereby provide a fluid tight seal between the bag and component conduit
gasket support, n; a rigid component which has an outer diameter which is similar to an outer diameter of a gasket and an inner diameter which interfaces with a luer connecting fitting to thereby transfer force from the connecting fitting to an interface gasket to provide a seal
port or portal, n: an orifice site where through fluid is communicated (generally associated with a conduit sealingly disposed there through)
proximal, adj: an indicator of a segment of a device being normally closest to an object of a sentence describing its position
radiation, n: generally gamma radiation imposed with sufficient intensity and time to sterilize a product to a desired SAL.
SAL n: Sterilized Assurance Level
sub-kit, n: a group of parts provided as a unit and considered to be a kit when provided alone but a lesser kit form when provided as a part of a more inclusive kit which is packaged with additional items
tray, n: a convenience kit container wherein kit parts are stored and transported; for the case of the current invention the tray is considered to provide a special interface with kit parts
unitized, adj: a plurality of separate parts permanently joined to be handled and used as a single unit
In brief summary, this novel invention alleviates all of the known problems related to mixing, dispensing and providing a sterile liquid product for delivery into a field environment. It is important to note that preparation of autologous blood eye drops simply involves mixing a measured volume of patient serum with a volume of normal saline determined by prescribed serum/saline concentration and acquired patient serum volume. Though other methods may be employed within the scope of the instant invention, preferred devices and processes are disclosed hereafter for clarity of enablement.
Commonly, medical products, as mentioned supra, are often produced by being sterilized by filtration and mixed under a fume or laminar flow hood in a pharmacy or laboratory facilities. For products which are acquired for sterilizing and mixing in a field environment, remote from such facilities, lack of a fume hood or laminar flow capability currently prohibits wide-spread production of autologous blood eye drops. It is for the purpose of fulfilling this need that an inventive methodology based upon a novel sub-kit is disclosed herein.
The core items of this sub-kit are a conventional commercial plastic bag, having an accessible opening, which is closed and sealed after sub-kit assembly, a sterilizing filter assembly which is affixed to the bag via a sealed portal to provide a solitary sterilizing fluid pathway to components inside the so closed bag and a tray for providing bottle containment and retention throughout the eye drop preparation process. To assure product sterility, the bag and articles are sterilized after assembly and prior to use. Once sterilized, the only passageway inside the sealed bag is through the filter assembly. Therefore, all product inside the bag remains sterile for all subsequent procedures until the bag is opened.
Generally, the preferred embodiment of the filter assembly comprises a first sterilizing filter comprising a body which holds and surrounds a filter part to provide for fluid flow only through the filter. The filter body also comprises a pair of opposing conduits which provide a pathway to and from the filter. One of the conduits with a male Luer fitting (the internal conduit) is disposed through a hole in the bag and sealed thereat to assure retention of a predetermined SAL within the bag. A sealing grommet, disposed about the conduit and bag hole is affixed to assure competence of the seal. A nozzle part may be affixed to the end of the internal conduit for directing liquid flow there through. The preferred embodiment also comprises a second sterilizing filter, having similar structure to the first filter, serially securely, but releasably affixed outside the bag to the first filter (e.g. via a male/female Luer fitting interface). It has been commonly demonstrated that. when delivering volumes of particulate contaminated liquid (as derived from a biological source) a first filter can clog and obstruct flow. Under such conditions, no further flow is possible through the first filter resulting in kit failure due to flow obstruction. Providing a second filter cascaded with the first filter aggregates clogging material in the second filter. Thus, when flow is obstructed by clogging, the second filter can be removed and, if necessary, replaced.
For the instant invention, the sub-kit is delivered as part of a larger kit which may additionally comprise two empty conventional medical syringes having male luer fittings, a female/female luer fitting component which is affixed to one of the two empty syringes, a blood collection tube transfer barrel and an accessible volume of normal saline (preferably provided as pre-filled saline syringes). All of the additional parts may be provided clean, rather than sterile as all fluid which passes into the plastic bag is sterilized by passing through the filter which provides the only entry pathway into the bag. Note that all parts of both the sub-kit and larger kit meet a current FDA Convenience Kit Standard which requires all components involved with a medical procedure be previously approved for medical use.
An exemplary, more detailed description of components of the sub-kit made according to the instant invention may be as follows:
1. The plastic bag is sufficiently supple and impenetrable to permit digital manipulation of items disposed therein via digital contact only with the bag exterior and has an accessible opening for displacement of the articles into the bag before the opening is closed and sealed, sufficient material disposed about the opening to permit sealing and an exterior surface which completely envelopes and protects sterility of articles disposed therein. Bag and articles therein should be predisposed to digital manipulation via the bag exterior and should be radiation stable.
2. A filter component comprising at least one sterilizing grade filter (and preferably two cascaded filters (a first filter and a second filter) each having two opposing elongated conduits having connecting fittings at ends remote from each filter housing. One of the conduits of the first filter, is displaced through a tight fitting hole in the bag. A gasket seal is disposed about the conduit/hole interface, providing a hollow conduit as the only fluid access pathway into the bag after the bag opening is sealed. Note that the pathway leads to at least one filter through which all fluid must pass, thereby assuring that no non-sterile material can be introduced into the bag beyond the filter.
3. At least one bottle comprising an open orifice provided for dispensing eye drop liquid there through.
4. A cap for each at least one bottle, the cap being able to be affixed to the bottle while in protective enclosure of the bag to provide a protective seal about the bottle orifice, such that when attached to the bottle and thereafter removed from the bag, following liquid transfer, product sterility is assured. As cap to interior bag surface may not have an exterior surface frictional interface which promotes easy digital access and handling within the bag, each cap is provided with a treatment about a grasping surface which increases the coefficient of friction between bag and cap and thereby permits facile digital displacement of each cap.
5. A tray having cavities for each bottle and associated cap. The bottle cavities are sized and shaped to securely engage the bottles during transport and kit displacement and to strictly restrict bottle rotation while caps are affixed thereto. Further, the cavities are disposed to affix retention forces at each bottle bottom permitting bottles to be “popped” free after the tray is displaced from the bag. Similarly, cap cavities are sized and shaped to retain each cap until digitally accessed for capping a bottle while having retaining forces disposed at the bottom thereof to permit each cap to be “popped” free for easy access.
One of the compelling purposes for basic convenience kits resulting from this invention is providing fluid flow through a sterilizing filter. As liquids to be mixed in a field environment can be expected to be compromised and/or contaminated, it is critical that every so-employed liquid be passed through such a filter and sterilized while being displaced into the bag. In the case of the instant invention, retention of sterility throughout dispensing is extremely important. For this reason, all kit mixing, sterilization and subsequent packaging functions are performed within the plastic bag which retains such sterility until reopened. It is important to note that digital facility of kit use is also very important. As a consequence, it is preferred to use a bag which comprises a snap or peel open seal for access after product transfer and sealing in capped bottles. However, it is not enough to maintain liquid sterility only while the product is inside the bag. The product must be shielded and disposed in a closed and sealed container before being displaced from the bag.
Given the sub-kit contents and additional parts which make up the larger kit, the method for preparing autologous blood eye drops is as summarized in table 1, below:
To show by example, a comparison of advantages and disadvantages relative to employing a convenience kit used according to the present invention versus using a laminar flow hood, for a sterile transfer process, distinctions are summarized in the following two tables (i.e Tables 2 & 3).
Table 2 summarizes a comparison of general factors related to preparing an eye-wash product using a laminar flow hood and the convenience kit.
Table 3 compares a current process of producing an eye treatment product to a like product production using a convenience kit made according to the present invention.
Accordingly, it is a primary object to provide convenience kit methods and apparatus for transferring and sterilizing mixed eye drop liquids to, thereby, provide a packaged, sealed, aseptic product which can be produced in a potentially contaminating environment.
It is a major object to provide a kit which can be used to sterilize, mix and protectively seal, for safety, a sterilized product for delivery into a contaminating environment without use of a laminar flow hood.
It is a principle object to provide methods for a portable apparatus which can be used for preparing and delivering prescribed concentration eye drops sterilized to a predetermined SAL within a contaminating environment.
It is an object to provide methods and apparatus for preparing and using convenience kits which can be used for sterilizing and delivery of autologous blood-based eye drops in home care situations.
It is a very important object to provide a kit and methods, for sterilizing liquids to be dispensed into bottles within an internally sterile kit, by which contaminating particles are filtered before entry into a sterile field and for assuring aggregated particles do not prematurely clog the first filter and prematurely impede or obstruct bottle filling.
It is an object that the sub-kit comprises a sectioned bottle and cap holding tray which has at least two cavities wherein eye drop bottles and caps are disposed and securely affixed therein for eye drop liquid dispensing and bottle capping whereby bottles are filled and capped in a sterile state within a plastic bag before distribution into a non-sterile environment.
It is a fundamental object to provide a bag which is sealable for maintaining contents sterile therein and able to be opened for access to products mixed and sterilized therein.
It is another major object that bagged parts of a convenience kit made according to the present invention be digitally accessible and displaceable such that liquid sterility protecting caps can be securely affixed to vessels before perforating the bag barrier.
It is yet another critical object to select items which are gamma stable for purposes of sterilization within the bag.
It is still another object to provide a means for transporting and storing filled eye drop bottles in a controlled environment for stability of product sterility and medical efficacy.
These and other objects and features of the present invention will be apparent from the detailed description taken with reference to accompanying drawings.
Reference is now made to the embodiments illustrated in
This inventive method is specifically dedicated to preparing autologous blood serum eye drops. While inventive properties disclosed may be applied throughout a wide variety of applications, the following description is singly focused on eye drop production.
Kit Preparation Steps
In
Reference is now made to
However, filtering of biological materials, such as serum, yields a wide variety of particles and other separated products which must be retained within the filter component to produce a filtered product sterilized to the predetermined SAL. The unpredictable nature and bulk can clog to produce sufficient obstruction to flow that an undesirable pressure is required to continue dispensing through filter component 60. Such obstruction of filter component 60 is catastrophic to device such as kit 10, which depends upon continued flow for proper performance. For this reason, a second filter component 60′ is securely, but releasably affixed to filter component 60 to cascade flow through both filters, as seen in
Reference is made to
As seen in
Also as seen in
Referring once more to
Selection of an effective eye drop bottle is critical to the safety and effectiveness of the instant invention. As such, the eye drop bottle must be able to be securely capped and closed to preserve sterility while still being disposed within bag 20. Also, because a prolonged period of time (e.g. four to six weeks) may pass from time of mixing and bottle filling until use, a desired product SAL must be maintained until use. In addition, as the eye drops are used at a prescribed rate, eye drop accuracy and precision is important. For this reason, an eye drop bottle (called Novelia® (Novelia)) commercially available from Nemera, an international company originated in France, is preferred for use in products made by the instant invention. Nemera states the following concerning Novelia:
Reference is now made to
Cap 6, seen in
Reference is now a made to
To complete kit 10 assembly, tray 2 filled with bottles 4 and caps 6 is displaced into bag 20 as seen in
Eye Drop Preparation Steps
Blood is preferably accessed from a patient for preparing autologous blood eye drops; using Becton Dickinson Vacutainers™, samples of which are commonly numbered 150 and seen in
Items which are provided as part of a larger kit are seen in
1. A first conventional medical syringe 200 which is specified to have a capacity for accessing and containing the total liquid volume of all vessels 108 of bottles 4 in convenience kit 10.
2. A second medical syringe 210 having the same liquid volume as syringe 200 and having a female/female fitting 212 affixed thereto.
3. A Vacutainer™ access barrel 220.
4. A plurality of conventional pre-filled normal saline syringes, generally numbered 230.
Each of items listed in 1-3, above, can be provided clean (as opposed to sterile) because all fluid which contacts these items is sterilized upon being dispensed through pathway 70 of filter component 60 into bag 20. For the same reasons, filter component 60′ can be provided clean. For safety, prefilled syringes 230 should be pre-sterilized.
Preparation for filling bottles 4 involves:
1. Prescribing a ratio of serum to saline to be mixed and form a desired mixture which is used as autologous blood eye drops.
2, Following conventional procedures for:
3. Using conventionally provided indicia (not shown in
4. Referencing the prescribed saline/serum ratio, determining the amount of saline which must be added to the acquired blood volume to formulate each predetermined dose. Two methods for determining saline volume are currently preferred. However, other methods may be used within the scope of the instant invention. A first method is via a chart 242 such as the one seen, by example, in
mLsal=mLser (100−% ser)/(% ser)
5. Drawing determined required dose volume of saline (mLsal) into syringe 220 (see
6. Affixing syringe 200 to communicate with syringe 210 as seen in
7. Detaching filled syringe from fitting 212.
8. Acquiring kit 10, which may be disposed as seen in
9. Then, affixing, as seen in
10. Capping each bottle 4. Once each bottle 4 is filled with a prescribed dose sterilized to a predetermined SAL, perhaps the most important step still remains, capping and sealing each bottle 4 for delivering bottles into an open environment would otherwise likely detrimentally affect SAL of bottle content. To cap each bottle, each cap 6 (see
11. Providing a protected product for use outside bag 20. Once all bottles 4 are filled and capped, bag 20 is accessed for delivering eye drops to a patient, additional care should be provided for, while the product is sterile to a given SAL, the product contains material which is life based. To aid in maintaining at a predetermined SAL, it is highly recommended that a means for keeping eye drop liquids at a low temperature throughout transport and storage. For this purpose, an insulated bag 300 and an associated ice pack 310 (seen in
The invention may be embodied in many other specific forms without departing from the spirit or essential characteristics thereof. The presently disclosed embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.
This Patent Application is a CONTINUATION-IN-PART of U.S. patent application Ser. No. 16/501,534 filed Apr. 25, 2019 by Gale H. Thorne, et al. and titled METHODS FOR PREPARING AUTOLOGOUS BLOOD EYE DROPS which is a CONTINUATION-IN-PART of Ser. No. 16/350,279 filed by Gale H. Thorne, et al. (Thorne 279). Oct. 25, 2018 and titled CONVENIENCE KITS FOR ASEPTIC STERILIZING AND DISPENSING.
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| Number | Date | Country | |
|---|---|---|---|
| 20200337946 A1 | Oct 2020 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 16501534 | Apr 2019 | US |
| Child | 16501974 | US |
