1. Field of the Invention
The present invention relates to syringes (manual, automatic and/or cartridge type), and more particularly to a double chambered syringe having a pair of pistons including an upper piston that is operable by the user and another piston that "floats" in between the upper piston and the distal, dispensing end of the syringe. Even more particularly, the present invention relates to a dual chamber syringe that has a pair of chambers positioned respectively in between the first and second pistons and in between the first "floating piston" and the distal, dispensing end of the syringe and wherein a plurality of longitudinally extending channels are provided at a middle portion of the syringe barrel so that when the first floating piston is positioned adjacent to the channels, liquid contained in the upper chamber can flow around the first piston and through the channels to the second chamber wherein a dry medicine is contained. A mixing of the liquid and dry medicine takes place in the second chamber. Continued downward movement of the two pistons dispenses the combined liquid and dry components (to an I.V. line, intermediary bottle, patient, etc.). The closure can be a closure cap, a Luer lock, or a needle/condom. For these dispensing and closure arrangements, a user simply inverts the syringe during dispensing.
2. General Background of the Invention
It is known that many drugs cannot be administered by the oral route because of gastrointestinal intolerance, irregularity in absorption, and metabolic breakdown in the gut wall and liver (first pass effects). In particular, first pass loss abolishes oral bioavailability of all polypeptide and protein medications [e.g. sermorelin acetate, follitropin beta growth hormone, insulin, glucagon, alteplase, erythropoietin, alglucerase (glucocerebrosidase-B-glucosidase), etc.]. This necessitates their administration through various parenteral routes, i.e., intravenous, intramuscular, subcutaneous, intrathecal, etc. Further, parenteral delivery of such drugs will expand with future mapping and functional understanding of the human genome. Pharmaceutical recombinant DNA synthesis of new peptide-protein moieties will concomitantly increase [e.g. megakaryocyte growth and development factor, tumor necrosis binding receptor, angiogenic growth factor, stem cell factor, neurotrophin-3, leptin, glial cell line-derived neurotrophic factor, nerve growth factor, etc.], and make a cost-contained, safe, effective and simple to use delivery device essential for both patients and medical professionals.
Functionally, stability of an injectable drug may be defined as its capability to retain chemical, sterile, toxicological and therapeutic specifications within 90% of its original potency. By tradition, expiration dates denote the last day of a month and year a particular preparation retains such stability under recommended conditions. In case of a dry or lyophilized medication to be reconstituted prior to use, expiration dates are designated for both the dry and reconstituted product. When compared to drug solutions ready for injection, dry soluble medications ready to be reconstituted with solvent just prior to use are well known to have greater stability and longer expiration dates.
Time related deterioration in ready to use parenteral drug preparations include interactions between combined active, and between active and inactive ingredients. Aqueous solvents in particular, potentiated by heat and radiation, initiate or accelerate time dependent drug degradation through oxidation, reduction, hydrolysis, racemization, decarboxylation, photolysis, and, autooxidative free radical chain reactions.
Notwithstanding such chemical breakdown, buffers, antioxidants, preservatives and other stabilizers oftentimes cannot be used in formulations containing water because of their reactivity with the active ingredient(s) or, direct patient hypersensitivity. Moreover, water itself has a profound effect on hydrolysis and denaturation of drugs possessing ester or amide chemical bonds, e.g. tetracaine, physostigmine, anagrelide, growth hormone, benzylpenicillin, calcitonin, epoetin alfa, menotropins, placental gonadotropin, interferons, pituitary releasing hormones (gonadorelin, cosyntropin, etc.) and numerous others.
A cost effective, simple, self contained dual-chamber syringe which isolates dry-wet drug components and mixes them immediately prior to injection is highly desirable. Furthermore, such a device would eliminate extra standard syringes, medication and diluent containers required for mixing the individual drug constituents. The device would permit accurate drug reconstitution, reduce time required for drug preparation, eliminate waste and possible introduction of contaminants through human error.
Various types of two compartment injection syringes have been patented to address such concerns and are known. U.S. Pat. No. 5,395,326 describes a medication jell-liquid two compartment syringe fitted with side-by-side chambers for mixing and injecting via a dilating O-ring piston assembly; U.S. Pat. No. 4,983,164 utilizes a two chambered syringe barrel created by a non-movable, separating membrane which ruptures when displaced toward the plunger.
Other patents, U.S. Pat. Nos. 4,413,991, 4,202,314 and 4,214,584 either possess dual chambers interconnected with side openings through an injection needle, or two driving systems for mixing and injecting, or have concentric dual chambers which upon manual rotation, untighten and permit mixing with subsequent standard injection.
Dual chamber syringes are known for administering medicinal preparations wherein it is desired to isolate a first medicinal preparation from a second medicinal preparation until it is time to administer the combination of the two preparations to a patient.
An example of a device for administering such first and second medicinal preparations is seen in the Smirnov et al. U.S. Pat. No. 4,214,584. The Smirnov device is provided for administering medicinal preparations that includes an isolated capsule divided into a chamber for a first medicinal preparation and a chamber for a second medicinal preparation. Coaxially inside the isolated capsule and concentrically therewith is the piston which bounds the chamber for the first medicinal preparation. Made fast on the piston is an injection needle having a hole located at the base of the piston. Provision is made in the device for a mechanical actuator of the piston, which is a spring-opposed pushrod located inside the housing which also accommodates the retaining member for the spring-opposed pushrod. The chamber for the second medicinal preparation is arranged concentrically with the chamber for the first medicinal preparation so as to embrace the latter. The isolated capsule is mounted traversably inside the housing, while communication between both of the chambers is established upon a positive extension of the isolated capsule from the housing outwards.
Another Smirnov patent is U.S. Pat. No. 4,202,314 entitled "Device For Injection Of Medicinal Preparations". The device for injection of medicinal preparations, comprises a changeable isolated capsule, an injection needle, and a drive to move pistons, made in the form of a spring-loaded pusher located inside the housing which supports the changeable isolated capsule. The housing has a stopping member to arrest said spring-loaded pusher. Inside said isolated capsule, installed coaxially therewith and with each other are a main piston closed by a partition on the side facing the chamber holding the first medicinal preparation and an additional piston. The partition is movable. The injection needle is installed inside the isolated capsule, fixed on the additional piston, and it in use passes through said partition, and has an aperture in the zone of the partition on the side of the chamber holding the first medicinal preparation. The additional piston is located in the channel of the main piston and limits the chamber for the second medicinal preparation. The drive of the pistons has an additional spring-loaded pusher interacting with the additional piston and is located coaxially with the spring-loaded pusher. The housing of the drive of the pistons has an additional stopping member for the additional spring-loaded pusher.
The Kamstra U.S. Pat. No. 4,529,403, entitled "Automatic Injection Syringe", relates to a syringe for injecting two or more different injection liquids which may not be contact with each other for long periods of time. For that purpose, the ampoule between the piston and the needle connection includes one or more stoppers which keep the injection liquids separated from each other, while at a point a short distance before the needle connection a by-pass means is present through which the injection liquid or injection liquids present behind the stopper or stoppers can pass the stopper or stoppers during use of the syringe.
In the Hook U.S. Pat. No. 4,983,164, an automatic two-chamber injector for mixing and injecting a medicinal solution is disclosed. The injector comprises a barrel having a first end with a receiving portion for an injection needle, that portion being sealed prior to use, and a second end with a displaceable plunger. The barrel comprises two chambers separated by a migration proof membrane, the membrane being adapted to rupture when the plunger is displaced towards the first end of the barrel. The '164 patent also discloses a method for mixing and injecting a solution by means of an automatic two-chamber injector and to a cartridge for a two-chamber injector.
European Patent Application No. 0 072 057 relates to an automatic syringe for injecting two or more different injection liquids which may not be in contact with each other for longer periods of time. For that purpose the ampoule between piston and needle connection comprises one or more stoppers which keep the injection liquids separated from each other, while at a short distance before the needle connection a by-pass means is present past which the injection liquid or injection liquids present behind the stopper or stoppers can pass the stopper or stoppers during use of the syringe.
One of the problems with dual chamber syringes is that of achieving a complete mixture of the medicinal components while at the same time perfecting a complete and total dispensing of the combined medicinal portions into the patient after mixing has been completed.
The syringes disclosed in the above-discussed patents do not provide a plurality of ribs that define flow channels therebetween and dampening slots that hold the first, lower piston until the diluent has completely mixed with the dry drug.
Many of the above-discussed prior art patents are highly complex structures comprising multiple interlocking and telescoping portions, some requiring springs for operation. The present invention is an improvement over these prior art patents. Unlike prior art dual chamber syringes, the apparatus of the present invention has only two moving parts, each being a piston sliding within a single one piece syringe barrel. Yet the present invention effectively isolates first and second medicinal portions before use, perfects mixture immediately prior to administration, and contains the mixed medicinal components below a lower piston in the syringe barrel to ensure complete discharge of the mixed medicinal components during administration to the patient.