Abstract:
A compact, nonelectric fluid dispenser for use in controllably dispensing beneficial agents such as propofol and dexmedetomidine hydrochloride to patients. The dispenser includes a fluid flow control assembly that precisely controls the flow of the medicament solution to the patient and embodies a collapsible, pre-filled drug container that contains the beneficial agents to be delivered to the patient. The unit-dose fluid dispenser of the invention is presented in a sterile and aseptic manner, where the drug has been pre-filled in the system, so that the practitioner cannot mistakenly give the wrong drug to the patient. The dispenser uniquely provides a more efficient medicament delivery system for procedure rooms, such as the endoscopy center, so that a greater number of patients can be treated per day at a higher standard of care with increased profits for the healthcare provider.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This is a Continuation-In-Part Application of co-pending U.S. Ser. No. 12/288,115 filed Oct. 15, 2008. 
    
    
     STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT 
     Not applicable 
     INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ON A COMPACT DISC 
     Not applicable 
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates generally to fluid dispensing devices. More particularly, the invention concerns a novel dispenser for dispensing propofol, as well as analogous sedation agents, to patients with increased safety and efficiency, while reducing the probability of hospital acquired infections. 
     2. Description of Related Art Including Information Disclosed Under 37 CFR 1.97 and 1.98 
     A number of different types of medicament dispensers for dispensing various types of medicaments to patients have been suggested in the past. The traditional prior art infusion methods make use of a flexible infusion bag suspended above the patient. Such gravametric methods are cumbersome, imprecise, require many time consuming steps by clinicians, are susceptible to medication errors and require bed confinement of the patient. Periodic monitoring of the apparatus by the nurse or doctor is required to detect malfunctions of the infusion apparatus. Accordingly, the prior art devices are not well suited for use in those instances where the patient must be transported from one part of the healthcare facility to another. 
     Many of the state-of-the-art medicament delivery devices involve the use of electronic pumps to dispense the medicament from the dispenser reservoir. In the past, these types of devices have been the devices of choice for dispensing propofol (and other injectable sedation agents) and this equipment requires significant effort to prepare and administer the drug. 
     Propofol is a highly protein bound in vivo and is metabolized by conjugation in the liver. Its rate of clearance exceeds hepatic blood flow, suggesting an extrahepatic site of elimination as well. Its mechanism of action is uncertain, but it is postulated that its primary effect may be potentiation of the GABA—a receptor, possibly by slowing the closing channel time. Recent research has also suggested the endocannabinoid system may contribute significantly to propofol&#39;s anesthetic action and to its unique properties. 
     In recent years propofol has been widely used as an anesthetic agent for the induction of general anesthesia in adult patients and pediatric patients older than 3 years of age, for use in the maintenance of general anesthesia in adult patients and pediatric patients older than 2 months of age, for use in sedation for intubated, mechanically ventilated adults, and in procedures such as colonoscopy. 
     At the present time, propofol is commonly delivered through an electronic pump that is preset with the patient&#39;s weight (in kg) and a dosage increment measured in micrograms/kg/min. One prior art electronic pump that is presently in use is a pump sold by Baxter International, Inc, of Deerfield, Ill. under the name and style “.InfusO.R.”. This pump contains four separate dials. The first dial is to set the patient weight; the second dial is to set the dosage; the third dial is to set a bolus volume to initiate sedation; and the fourth dial is used to purge the syringe if there is any remaining propofol after the procedure. The Baxter pump has a magnetic plate that contains all the increments of the dials and the plates can be changed for different medications. By having removable plates, there is an increased possibility of medication error if the magnetic plate is not checked for increments for the correct medication or the correct concentration. The Baxter pump is typically used in the surgicenter setting where the anesthesiologist gives the patient an initial bolus of propofol for inducing sedation and the preset dosage is given in addition to gas anesthesia to keep the patient asleep during the operation. 
     Another pump that is presently in use is a pump sold by the Cardinal Health Company of Dublin, Ohio under the name and style “ALARIS PL”. The ALARIS PL syringe pump or ALARIS IVAC pump is used in conjunction with a Diprifusor syringe that is pre-filled with propofol. The Diprifusor is a target controlled infusion (TCI) system that was developed to enhance the control of IV anesthesia. With a TCI pump, a microprocessor manages the infusion rate and controls the syringe. The anesthesiologist enters the body weight of the patient, the age of the patient, and the dosage in microgram/ml. The Alaris pumps rely on the anesthesiologist entering the correct data minimizing the possibility of medication error but the dosage form is not the commonly used increment, (microgram/ml instead of microgram/kg/min) which relies on the anesthesiologist to convert the dosage and potentially increases the risk of medication error through miscalculation. The Diprifusor and TCI pumps are typically used in Europe where the pump is used to control sedation and anesthesia, but are thus far not dominant in the American surgical market. 
     Many current disposable infusion pump modalities also require the disposable pump to be filled by an attending clinician. These filling and preparation protocols present a number of serious challenges that can lead to serious medication errors, patient injury, or patient death. For example, a medication error can result from the clinician accidentally putting the wrong medicine into the delivery system. Additionally, filling an infusion pump in a non-aseptic environment (e.g. the operating room) can also pose challenges in maintaining drug and device sterility. 
     As will be discussed in greater detail hereinafter, the propofol dispenser of the present invention allows the anesthesiologist to create a basic “recipe” for propofol based sedation that could prevent patient complications. The dispenser of the present invention is particularly well-suited for use in the administration of propofol by non-anesthesiologists in low risk procedures, such as colonoscopies. 
     Another pharmaceutical agent appropriate for use in this novel dispenser technology is dexmedetomidine hydrochloride (Precedex), and related compounds. Precedex is indicated for sedation of initially intubated and mechanically ventilated patients during treatment in an intensive care setting. Precedex is typically administered by continuous infusion using a syringe of the drug fluid (drawn up in a non-aseptic environment by the anesthesiologist) and dispensed by an electronic pump. Precedex is being used with patients in the intensive care unit (ICU), during neurosurgery and for children during MRI. 
     Precedex is delivered via intravenous infusion over a selected amount of time through a controlled infusion with the use of an electronic or battery operated pump or with a “smart pump”. A pre-filled and non-electric pump that is therapy specific could allow more widespread use of novel sedation agents (such as Precedex), because of the ability to administer the therapy in a safer and more efficient manner without the need for multiple steps and sophisticated software routines. 
     The novel dispenser of the present invention provides numerous advantages over prior art devices including the following: 
     Creation of a standard operating procedure for the administration of propofol by anesthesiologists and non-anesthesiologists alike. 
     Elimination of the need for filling syringes, thereby reducing the potential for medication errors due to filling (i.e. using the wrong concentration of propofol) or use of a drug that is similar in appearance to propofol. 
     Elimination of the need for an electronic pump, thereby reducing the potential for medication error due to incorrect settings. 
     Reducing costs to healthcare providers and practitioners by eliminating expensive electronic capital equipment that requires continuous maintenance, calibration and cleaning. 
     Elimination of the requirement for electricity in austere or chaotic environments (e.g. during military engagements, natural disasters). 
     Presentation of the sedation agent at the point of care in an aseptic manner as a single self-contained unit-dose pre-filled delivery system should also minimize the probability of hospital acquired infection. 
     As previously mentioned, a significant market for the pre-filled unit-dose small volume dispenser of the present invention is the endoscopy center market. In this regard, one form of the dispenser of the present invention is specially designed for relatively short procedures (i.e. 20-30 minutes), such as colonoscopies and endoscopies. More particularly, the dispenser of the invention, which is non-electric and disposable following use, can provide an extremely cost effective means of increasing efficiency in the endoscopy center. The dispenser uniquely provides an alternative to expensive electronic pumps that are often complicated and time consuming to operate. In addition, low cost disposable devices for use in outpatient clinics are consistent with a broader theme in healthcare that is aimed at lowering costs while improving quality of care and patient outcomes. Because physicians in the endoscopy center are searching for a cost effective means to increase patient throughput within the center, the dispenser of the present invention provides a natural fit for a standardized sedation process for colonoscopies and endoscopies, without compromising the quality and safety of the procedure. 
     In another form of the present invention, the dispenser comprises a mid-volume propofol delivery systems technology (65 ml) that is specially designed for use in the surgicenter for procedures that require sedation times of 1-2 hours. In this application a novel dispenser can serve as a safe and effective means for patients that are to be fitted with orthopedic and cardiac implants. Similarly, this novel mid-volume dispenser can function well with minimum discomfort for general surgeries such as hernia repairs and the like. Because physicians in the surgicenter market are often quite time conscious, the dispenser of the present invention comprises a natural fit for a standardized sedation process that could potentially increase patient throughput within the market without compromising the quality and safety of the procedure. Additionally, patients prefer propofol as an anesthetic agent because there is no “hangover” effect, which stems from its ease of titration and rapid elimination half-life. By way of comparison, traditional anesthesia with gas has a very slow elimination half-life and patients require long recovery times that are typically complicated by nausea and vomiting. Conversely, propofol has inherent antiemetic properties, which chemically combats feelings of nausea. 
     In yet another form of the present invention, the dispenser comprises a large volume propofol dispenser (250 ml) that is specially designed for use in military applications, including total W anesthesia (TIVA) by the Forward Surgical Team at the battlefield, as well as for sedation of the patient during transport from one echelon of care to the next. This form of the invention can provide a safe and effective means to sedate a patient during an operation and throughout transport without relying on bulky medical equipment or expensive equipment that is transported with the patient and never returned to the original care facility. 
     As will be fully appreciated from the discussion that follows, the devices of the present invention-are also particularly useful in ambulatory situations. The ability to quickly and efficaciously treat wounded soldiers, especially in unpredictable or remote care settings, can significantly improve chances for patient survival and recovery. Accurate intravenous (IV) drug and fluid delivery technologies for controlling pain, preventing infection, and providing a means for IV access for rapid infusions during patient transport are needed to treat almost all serious injuries. 
     It is imperative that battlefield medics begin administering life saving medications as soon as possible after a casualty occurs. The continuous maintenance of these treatments is vital until higher echelon medical facilities can be reached. A compact, portable and ready to use infusion device that could be easily brought into the battlefield would allow medics to begin drug and resuscitation agent infusions immediately. Additionally, it would free them to attend to other seriously wounded patients who may require more hands-on care in the trauma environment following triage. In most serious trauma situations on the battlefield, IV drug delivery is required to treat fluid resuscitation, as well as both pain and infection. Drug infusion devices currently available can impede administration of IV infusions in remote care settings. 
     Expensive electronic infusion pumps are not a practical field solution because of their weight and cumbersome size. Moreover, today&#39;s procedures for starting IV infusions on the battlefield are often dangerous because the attending medic must complete several time consuming steps. The labor intensive nature of current gravity solution bag modalities can prevent medics from attending to other patients also suffering from life threatening injuries. In some cases, patients themselves have been forced to hold flexible infusion bags elevated, in order to receive the medication by gravity drip. 
     BRIEF SUMMARY OF THE INVENTION 
     By way of brief summary, one form of the dispensing device of the present invention for dispensing the beneficial agent, such as propofol, to a patient comprises a housing, a carriage assembly disposed within the housing, a pre-filled drug reservoir assembly carried by the carriage, a stored energy means operably associated with the carriage for moving the carriage between a first position and a second position to expel from the reservoir the fluid medicament contained therein, and flow control means to control the flow of fluid from the reservoir, the flow control means uniquely comprising dose control means for controlling the dose of medicament to be delivered to the patient and rate control means for controlling the rate of medicament flow to the patient. This novel design would therefore allow the physician to set a medicament flow rate based on the patient&#39;s body weight in kg and the patient appropriate dose in micrograms per kg per hour. 
     With the forgoing in mind, it is an object of the present invention to provide a compact, nonelectric fluid dispenser in which the stored energy source is cooperatively associated with the collapsible container of the dispensing device and functions to deliver a variable force to the container that tends to urge fluid flow therefrom at a variable rate. In one form of the invention the stored energy source uniquely comprises an elongated, pre-stressed strip of spring material that is formed into coils and exhibits a cross-sectional mass that varies along its length. In another form of the invention, the band portion of the spring is coiled about its spring drum in predetermined varying degrees of tightness to achieve highly specific and desirable linear and non-linear force-distention curves to meet the fluid delivery requirements of the invention. 
     Another object of the invention is to provide a compact dispensing device of the character described in the preceding paragraph in which variation in cross-sectional mass along the length of the retractable spring can be achieved by varying the width of the pre-stressed spring along its length. 
     Another object of the invention is to provide a compact dispensing device of the character described in which variation in cross-sectional mass along the length of the retractable spring can be achieved by providing spaced-apart apertures in the pre-stressed spring along its length. 
     Another object of the invention is to provide a compact dispensing device of the character described in which the band portion of the spring is coiled about its spring drum in predetermined varying degrees of tightness to achieve highly specific and desirable linear and non-linear force-distention curves to meet the fluid delivery requirements of the invention. 
     Another object of the invention is to provide a fluid dispenser of the class described for use in controllably dispensing propofol to patients. 
     Another object of the invention is to provide a fluid dispenser of simple construction that can be used in the field with a minimum amount of training. 
     Another object of the invention is to allow infusion therapy to be initiated quickly and easily on the battlefield so that the attending medic or medical professional can more efficiently deal with triage situations in austere environments. 
     Another object of the invention is to provide a dispenser of the class described which includes a fluid flow control assembly that precisely controls the flow of the medicament solution to the patient. 
     Another object of the invention is to provide a dispenser that includes precise variable flow rate selection. 
     Another object of the invention is to provide a fluid dispenser of simple construction, which embodies a collapsible, pre-filled drug container that contains the beneficial agents to be delivered to the patient. 
     Another object of the invention is to provide a fluid dispenser of the class described which is compact, lightweight, is easy and safe for providers to use, is fully disposable, transportable, and is extremely reliable in operation. 
     Another object of the invention is to provide a unit-dose fluid dispenser of the class described that is presented in a sterile and aseptic manner, where the drug has been pre-filled in the system, so that the practitioner cannot mistakenly give the wrong drug to the patient. 
     Another object of the invention is to provide a medicament dispenser that improves the process efficiency of the healthcare setting by streamlining the tasks associated with the preparation, administration and monitoring of drug delivery of regimen. 
     Another object of the invention is to provide a low cost single-use alternative to expensive electronic pumps that have to be continually cleaned, calibrated and maintained at tremendous costs to healthcare providers. 
     Another object of the invention is to provide a dispenser that can administer anesthesia and sedation agents to patients without problematic side effects, such as nausea and vomiting, typically encountered with traditional gas anesthesia. 
     Another object of the invention is to provide a more efficient medicament delivery system for procedure rooms, such as the endoscopy center, so that a greater number of patients can be treated per day at higher standard of care with increased profits for the healthcare provider. 
     Another object of the invention is to provide a fluid dispenser as described in the preceding paragraphs that is easy and inexpensive to manufacture in large quantities. 
    
    
     
       BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS 
         FIG. 1  is a generally perspective view of one form of the fluid dispensing device of the present invention for dispensing medicaments to a patient. 
         FIG. 2  is a generally perspective view of the fluid dispensing device shown in  FIG. 1 , but broken away to show internal construction. 
         FIG. 3  is a longitudinal cross-sectional view of the rear, fluid delivery portion of the fluid dispensing device shown in  FIG. 1 . 
         FIG. 4  is a foreshortened, longitudinal cross-sectional view similar to  FIG. 3 , but showing the advancement of the carriage and fluid reservoir components of the fluid dispensing device. 
         FIG. 5  is an enlarged, fragmentary cross-sectional view similar to  FIGS. 3 and 4 , but showing the advancement of the carriage by the stored energy means of the invention in a manner to collapse the side walls of the reservoir defining assembly. 
         FIG. 6  is an enlarged, fragmentary cross-sectional view of the fluid flow actuation locking device portion of the fluid flow actuation subsystem. 
         FIG. 7  is an enlarged, fragmentary cross-sectional view similar to  FIG. 6 , but showing the fluid flow actuation locking device in a release configuration permitting rotation of the reservoir housing to advance the penetrating member of the fluid flow actuation subsystem. 
         FIG. 8  is an enlarged, fragmentary cross-sectional view of the penetrating member housing of the fluid flow actuation subsystem. 
         FIG. 9  is an enlarged, cross-sectional view of the penetrating member. 
         FIG. 10  is a generally perspective, exploded view of the rear, fluid delivery portion of the fluid dispensing device shown in  FIG. 1   
         FIG. 11  is an enlarged front view of the reservoir carriage of the fluid flow actuation subsystem. 
         FIG. 12  is a cross-sectional view taken along lines  12 - 12  of  FIG. 11 . 
         FIG. 13  is a view taken along lines  13 - 13  of  FIG. 12 . 
         FIG. 14  is an enlarged, front view of the reservoir and advancement housing subassembly of the fluid delivery portion of the fluid dispensing device shown in  FIG. 1 . 
         FIG. 15  is a cross-sectional view taken along lines  15 - 15  of  FIG. 14 . 
         FIG. 16  is a view taken along lines  16 - 16  of  FIG. 15 . 
         FIG. 17  is an enlarged, front view of the carriage release component of the fluid delivery portion of the fluid dispensing device. 
         FIG. 18  is a cross-sectional view taken along lines  18 - 18  of  FIG. 17 . 
         FIG. 19  is a view taken along lines  19 - 19  of  FIG. 18 . 
         FIG. 20  is a longitudinal cross-sectional view similar to  FIG. 4 , but showing the advancement of the piercing needle component of the fluid dispensing device into piercing engagement with the elastomeric seal provided in the neck of the fluid reservoir component and into piercing engagement with the closure wall of the fluid reservoir component. 
         FIGS. 21A and 21B  when considered together comprise an enlarged, longitudinal cross-sectional view of the fluid dispensing device shown in  FIG. 2 . 
         FIG. 22  is a cross-sectional view taken along lines  22 - 22  of  FIG. 21B . 
         FIG. 23  is an enlarged top plan view of the patient weight selector subassembly of the fluid dispensing device. 
         FIG. 24  is a cross-sectional view taken along lines  24 - 24  of  FIG. 23 . 
         FIG. 25  is an enlarged, generally perspective exploded view of the patient weight selector subassembly of the fluid dispensing device. 
         FIG. 26  is a bottom plan view of the upper rate control plate of the patient weight selector subassembly illustrated in  FIG. 25  and showing in phantom lines the main fluid pickup housing of the device. 
         FIG. 27  is a cross-sectional view taken along lines  27 - 27  of  FIG. 26  showing the main fluid pickup housing device in greater detail. 
         FIG. 28  is a fragmentary view taken along lines  28 - 28  of  FIG. 27  showing only one half of the main fluid pickup housing and illustrating the construction of the anti-rotational grooves thereof. 
         FIG. 29  is a cross-sectional view taken along lines  29 - 29  of  FIG. 28 . 
         FIG. 30  is a generally diagrammatic view illustrating the main fluid pickup housing of the device shown in the upper portion of  FIG. 27  as it would appear in flat configuration. 
         FIG. 31  is a top plan view of the fluid connector boss of the fluid delivery device illustrated in  FIG. 25 . 
         FIG. 32  is a side elevation view of the fluid connector boss shown in  FIG. 31  illustrating the configuration of the fluid micro pickup of the connector boss. 
         FIG. 33  is a cross sectional view taken along lines  33 - 33  of  FIG. 31 . 
         FIG. 34  is a top plan view of the upper rate control plate of the patient weight selector subassembly illustrated in  FIG. 25 . 
         FIG. 35  is a cross-sectional view taken along lines  35 - 35  of  FIG. 34 . 
         FIG. 36  is a cross-sectional view taken along lines  36 - 36  of  FIG. 34 . 
         FIG. 37  is a view taken along lines  37 - 37  of  FIG. 34 . 
         FIG. 38  is a cross-sectional view taken along lines  38 - 38  of  FIG. 34 . 
         FIG. 39  is a top plan view of the rate control plate of the fluid delivery device illustrated in  FIG. 25 . 
         FIG. 40  is a cross-sectional view taken along lines  40 - 40  of  FIG. 39 . 
         FIG. 41  is a view taken along lines  41 - 41  of  FIG. 39 . 
         FIG. 41A  is a view taken along lines  41 A- 41 A of  FIG. 39 . 
         FIG. 42  is a top plan view of the bottom rate control plate of the fluid delivery device illustrated in  FIG. 25 . 
         FIG. 43  is a top elevation view of the rate control assembly retaining cover of the fluid delivery device. 
         FIG. 44  is a cross-sectional view taken along lines  44 - 44  of  FIG. 43 . 
         FIG. 45  is a cross-sectional view taken along lines  45 - 45  of  FIG. 43 . 
         FIG. 46  is a view taken along lines  46 - 46  of  FIG. 43 . 
         FIG. 47  is a view taken along lines  47 - 47  of  FIG. 43 . 
         FIG. 48  is a view taken along lines  48 - 48  of  FIG. 21B . 
         FIG. 49  is a view taken along lines  49 - 49  of  FIG. 21B . 
         FIG. 50  is a top plan view of the patient weight selector knob of the patient weight selector subassembly of the fluid delivery device. 
         FIG. 51  is a cross-sectional view taken along lines  51 - 51  of  FIG. 50 . 
         FIG. 51A  is a generally diagrammatic view illustrating the portion of the patient weight selector knob shown in the lower portion of  FIG. 51  as it would appear in flat configuration. 
         FIG. 52  is a cross-sectional view taken along lines  52 - 52  of  FIG. 51 . 
         FIG. 53  is a view taken along lines  53 - 53  of  FIG. 51 . 
         FIG. 53A  is a view taken along lines  53 A- 53 A of  FIG. 53 . 
         FIG. 54  is a top plan view of the patient dose selector knob of the patient dose selector subassembly of the fluid delivery device. 
         FIG. 55  is a view partly in cross-section taken along lines  55 - 55  of  FIG. 54 . 
         FIG. 56  is a view taken along lines  56 - 56  of  FIG. 55 . 
         FIG. 57  is a generally diagrammatic view illustrating the portion of the patient dose selector knob shown in the lower portion of  FIG. 55  as it would appear in flat configuration. 
         FIG. 58  is a top plan view of the patient weight selector knob and the patient dose selector knob components of the fluid dispensing device. 
         FIG. 59  is a cross-sectional view taken along lines  59 - 59  of  FIG. 58 . 
         FIG. 60  is a cross-sectional view taken along lines  60 - 60  of  FIG. 58 . 
         FIG. 61  is a generally perspective, diagrammatic view illustrating the path of fluid flow through the device during the fluid delivery step. 
         FIG. 62  is a generally perspective, diagrammatic view illustrating the path of fluid flow through the device in a direction toward the bolus reservoir of the device. 
         FIG. 63  is a generally perspective, diagrammatic view illustrating the path of fluid flow outwardly of the bolus reservoir and toward the administration line of the device. 
         FIG. 64  is an end view of the fluid delivery device shown in  FIG. 1 . 
         FIG. 65  is a cross-sectional view taken along lines  65 - 65  of  FIG. 64  illustrating the construction of the bolus operating mechanism of the fluid delivery device. 
         FIG. 66  is a fragmentary cross-sectional view illustrating the construction of the bolus interlock mechanism of the fluid delivery device. 
         FIG. 67  is a generally perspective, exploded view of the bolus operating mechanism. 
         FIG. 68  is a top plan view of the bolus reservoir of the apparatus. 
         FIG. 69  is a cross-sectional view taken along lines  69 - 69  of  FIG. 68 . 
         FIG. 70  is a view taken along lines  70 - 70  of  FIG. 69 . 
         FIG. 71  is a top plan view of the bolus selector subassembly of the apparatus. 
         FIG. 72  is a cross-sectional view taken along lines  72 - 72  of  FIG. 71  illustrating the construction of the main bolus and secondary plunger assembly portion of the bolus operating mechanism. 
         FIG. 73  is a view taken along lines  73 - 73  of  FIG. 72 . 
         FIG. 74  is a top view of the main reservoir operating shaft. 
         FIG. 75  is a cross-sectional view taken along lines  75 - 75  of  FIG. 74 . 
         FIG. 76  is a cross-sectional view taken along lines  76 - 76  of  FIG. 74 . 
         FIG. 77  is a cross-sectional view taken along lines  77 - 77  of  FIG. 74 . 
         FIG. 78  is a cross-sectional view taken along lines  78 - 78  of  FIG. 72 . 
         FIG. 79  is a cross-sectional view taken along lines  79 - 79  of  FIG. 78 . 
         FIG. 80  is a cross-sectional view similar to  FIG. 78 , but showing the operating spring of the bolus plunger assembly in a compressed condition. 
         FIG. 81  is a cross-sectional view taken along lines  81 - 81  of  FIG. 78 . 
         FIG. 82  is a cross-sectional view taken along lines  82 - 82  of  FIG. 78 . 
         FIG. 83  is a top view of the secondary reservoir operating shaft of the bolus plunger assembly. 
         FIG. 84  is a cross-sectional view taken along lines  84 - 84  of  FIG. 83 . 
         FIG. 85  is a view taken along lines  85 - 85  of  FIG. 84 . 
         FIG. 86  is a view taken along lines  86 - 86  of  FIG. 84 . 
         FIGS. 87 ,  88  and  89  are generally perspective views of the bolus operating mechanism of the invention illustrating the sequential steps to be followed in operating the mechanism to accomplish the delivery to the patient of bolus doses. 
         FIGS. 90 and 90A  when considered together comprise an enlarged, longitudinal cross-sectional view of an alternate form of the dispensing device of the invention. 
         FIG. 91  is a cross-sectional view taken along lines  91 - 91  of  FIG. 90 . 
         FIG. 92  is a fragmentary, longitudinal cross-sectional view similar to  FIG. 90 , but showing the configuration of the device following delivery of the fluid contained within the collapsible container. 
         FIG. 93  is a generally perspective view of a prior art retractable constant force spring as it appears in a partially expanded configuration. 
         FIG. 94  is a generally illustrative view of the configuration of a modified retractable spring that would deliver a force that decreases by a factor of w 1 /w 2  as a spring returned from its fully extended configuration to its fully coiled configuration. 
         FIG. 94A  is a generally graphical representation plotting pressure versus the length of the reservoir container when a constant force spring is used to compress a bellows-like reservoir container. 
         FIG. 94B  is a generally graphical representation, similar to FIG.  94 A, plotting pressure versus the degree of compression for the reservoir container when the container is compressed by a constant force spring. 
         FIG. 95  is a generally perspective view illustrating an alternate form of variable force spring of the invention. 
         FIG. 95A  is a generally graphical representation plotting force exerted by the alternate form of variable force spring illustrated in  FIG. 94  as a function of the length of the spring. 
         FIG. 96  is a generally perspective view illustrating still another form of variable force spring of the invention. 
         FIG. 97  is a fragmentary, longitudinal cross-sectional view similar to  FIG. 90 , but showing the configuration of the collapsible container portion of still another form of the dispensing device of the invention. 
         FIG. 97A  is an enlarged longitudinal cross-sectional view of the control portion of the alternate form of the dispensing device of the invention. 
         FIG. 97B  is a greatly enlarged cross-sectional view of the area designated as “ 97 B” in  FIG. 97 . 
         FIG. 97C  is a greatly enlarged cross-sectional view taken along lines  97 C- 97 C of  FIG. 97A . 
         FIG. 97D  is a cross-sectional view taken along lines  97 D- 97 D of  FIG. 97C . 
         FIG. 98  is a cross-sectional view taken along lines  98 - 98  of  FIG. 97 . 
         FIG. 99  is a fragmentary, longitudinal cross-sectional view similar to  FIG. 97 , but showing the configuration of the device following delivery of the fluid contained within the collapsible container. 
         FIG. 100  is a greatly enlarged cross-sectional view of yet another form of the variable force spring of the invention. 
         FIG. 100A  is a view taken along lines  100 A- 100 A of  FIG. 100 . 
         FIG. 100B  is a view taken along lines  100 B- 100 B of  FIG. 100 . 
         FIG. 101  is a generally perspective view of still another form of variable spring of the invention. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     Definitions—As used herein the following terms mean: 
     Unitary Container: 
     A closed container formed from a single component. 
     Continuous/Uninterrupted Wall: 
     A wall having no break in uniformity or continuity. 
     Hermetically Sealed Container: 
     A container that is designed and intended to be secure against the entry of microorganisms and to maintain the safety and quality of its contents after pressurizing. 
     Aseptic Processing: 
     The term ‘aseptic processing’ as it is applied in the pharmaceutical industry refers to the assembly of sterilized components and product in a specialized clean environment. 
     Sterile Product: 
     A sterile product is one that is free from all living organisms, whether in a vegetative or spore state. 
     Blow-Fill-Seal Process: 
     The concept of aseptic blow-fill-seal (BFS) is that a container is formed, filled, and sealed as a unitary container in a continuous manner without human intervention in a sterile enclosed area inside a machine. The process is multi-stepped, pharmaceutical grade resin is extruded into a tube, which is then formed into a container. A mandrel is inserted into the newly formed container and filled. The container is then sealed, all inside a sterile shrouded chamber. The product is then discharged to a non-sterile area for packaging and distribution. 
     Integrally Formed: 
     An article of one-piece construction or several parts that are rigidly secured together and is smoothly continuous in form and that any such components making up the part have been then rendered inseparable. 
     Frangible: 
     An article, item or object that is capable of being ruptured or broken, but does not necessarily imply any inherent materials weakness. A material object under load that demonstrates a mechanical strain rate deformation behavior, leading to disintegration. 
     Spring: 
     A mechanical element that can be deformed by a mechanical force such that the deformation is directly proportional to the force or torque applied to it. An elastic machine component able to deflect under load in a prescribed manner and to recover its initial shape when unloaded. The combination of force and displacement in a deflected spring is energy which may be stored when moving loads are being arrested. 
     Referring to the drawings and particularly to  FIGS. 1 and 2 , one form of the fluid dispensing apparatus of the present invention for dispensing medicaments including sedatives such as propofol, dexmedetomidine hydrochloride and related compounds is there shown. This novel apparatus, which is generally designated in the drawings by the numeral  80 , is particularly well suited for use in the sedation of initially intubated and mechanically ventilated patients during treatment in an intensive care unit. The apparatus here comprises a device housing  82  having a forward portion  84 , a rear portion  86  having a base  86   a  and a central portion  88 . Housing  82  can be constructed from metal, plastic or any suitable material. 
     Disposed within the rear portion  86  of the device housing is the important fluid delivery portion and disposed within the central portion  88  thereof is the novel fluid flow control means, which functions to control the flow of fluid from reservoir  94  ( FIGS. 2 and 3 ) of the fluid delivery portion of the device toward the patient. Disposed within the forward portion  84  of the device housing is the bolus operating means of the invention which functions to permit selected bolus doses of medicaments to be delivered from reservoir  94  to the patient as may be required. 
     Considering first the fluid delivery portion of the fluid dispensing apparatus, this portion comprises a carriage  98  that carries and acts upon reservoir  94 . Carriage  98  is movable between a first rearward position shown in  FIG. 3  and a second advanced position shown in  FIG. 5 . As best seen by referring to  FIGS. 3 ,  10  and  11  through  13 , carriage  98  includes a carriage flange  98   a  and a reduced diameter portion  98   b  that receives the novel stored energy means of the present invention. Carriage  98  is releasably locked in its first position by a novel locking means the character of which will be described in the paragraphs which follow. 
     Carried by carriage flange  98   a , from which a generally hexagonal shaped protuberance  99  extends, is a reservoir defining assembly  100 . Reservoir defining assembly  100  here comprises an integrally formed, hermetically sealed container, which as illustrated in  FIGS. 3 and 15 , includes a front portion  100   a , a rear portion  100   b  and a collapsible accordion-like, continuous, uninterrupted side wall  100   c  that interconnects the front and rear portion of the assembly so as to define the fluid reservoir  94 . As illustrated in the drawings, the accordion like side wall  100   c  comprises a multiplicity of adjacent generally “V” shaped interconnected folds, while rear portion  100   b  includes a generally cup shaped recess  104  having a wall  104   a . As best seen in  FIG. 3 , hexagonal shaped protuberance  99  is closely received within the cup-shaped recess  104 . Extending from wall  104   a  is an ullage defining protuberance  106 , the purpose of which will presently be described. 
     Reservoir defining assembly  100  is constructed in accordance with aseptic blow-fill seal manufacturing techniques the character of which is well understood by those skilled in the art. Basically, this technique involves the continuous plastic extrusion through an extruder head of a length of parison in the form of a hollow tube between and through two co-acting first or main mold halves. The technique further includes the step of cutting off the parison below the extruder head and above the main mold halves to create an opening which allows a blowing and filling nozzle assembly to be moved downwardly into the opening in the parison for molding and then filling the molded container in a sterile fashion. 
     Containers for use in dispensing beneficial agents in specific dosages, such as the reservoir assembly of the present invention present unique requirements. For example, it is important that as much of the beneficial agents contained within the reservoir assembly be dispensed from a container to avoid improper dosage, waste and undue expense. Accordingly, the previously identified ullage defining protuberance  106  is provided, which functions to fill the interior space of the collapsible container when it is collapsed. 
     In a manner presently to be described, fluid medicament reservoir  102  of the reservoir defining assembly  100  is accessible via a penetrating member  108  that is adapted to pierce a closure wall  110  as well as a pierceable membrane  112  ( FIGS. 3 and 15 ). Pierceable membrane  112  is positioned over closure wall  110  of by means of a closure cap  114  which is affixed to the neck portion  116  of reservoir defining assembly  100  ( FIG. 15 ). As previously described, the reservoir defining assembly  100  is formed using the earlier described aseptic blow fill technique and the reservoir portion of the container is sealed by the thin closure wall  110 . The piercable membrane  112  is then positioned over the closure wall and the internally threaded closure cap  114  is positioned over the piercable membrane and threadably secured to the externally threaded neck portion  116  in a conventional manner. 
     The first step in using the apparatus of the invention, is to remove the tear off spacer  116  that is disposed between the reservoir outer shell  118  and a shoulder  120   a  provided on the reservoir connector housing  120  of the apparatus ( FIG. 3 ). Tear off spacer  116  functions to prevent the threadable advancement of the reservoir advancement housing  122  from the position shown in  FIG. 3  of the drawings to the position shown in  FIG. 4 . Once the tear off spacer is removed, rotation of the reservoir outer shell  118  will cause the threads  122   a  formed on the reservoir advancement housing  122  to advance over the threads  120   b  formed on the reservoir connector housing  120  (see  FIG. 4 ). As the assemblage made up of the reservoir outer shell  118  and the reservoir advancement housing  122  is advanced as the assemblage is rotated, a locking tab  118   b  formed on the reservoir outer shell  118  will move into locking engagement with a locking groove  120   c  formed in the reservoir connector housing  120 . In this way, the reservoir connector housing  120  is interconnected with the assembly made up of the reservoir outer shell  118  and the reservoir advancement housing  122  so that rotation of the reservoir outer shell  118  will cause advancement of the pierceable member  108 . 
     It is to be observed that as the assemblage made up of the reservoir outer shell  118  and the reservoir advancement housing  122  is advanced, the neck portion  114  of the reservoir defining assembly  100  moves from the position shown in  FIG. 3  to the position shown in  FIG. 5  wherein it resides within a cavity  124   a  formed in the bearing shaft  124 . With the neck portion  114  of the reservoir defining assembly  100  in position within cavity  124   a , the fluid delivery step can commence by rotating the entire rearward portion of the housing. However, in order to enable this rotation, the locking means, or locking member  128  must be manipulated in the manner illustrated in  FIGS. 6 and 7  of the drawings. As best seen in  FIGS. 6 and 7 , locking member  128 , which is received within a cavity  130  formed in reservoir connector housing  120 , includes a locking finger  128   a  that is received within a cavity  132   a  ( FIG. 7 ) that is formed within a mounting block  132  (see also  FIG. 8 ). Locking member  128  also includes an outwardly extending, finger engaging plunger  132   b . As indicated in  FIG. 7 , a downward pressure exerted on the finger engaging plunger  132   b  will yieldably deform the lower portion of the locking member in a manner to move locking finger  128  out of cavity  132   a  in the manner shown in  FIG. 7 , thereby permitting rotation of the rearward portion of the housing along with the mounting block  132 . As the mounting block  132  rotates, the internal threads  132   b  formed on the mounting block will engage the external threads  108   a  formed on the penetrating member ( FIG. 9 ) causing the penetrating member to advance into the position shown in  FIG. 5 . As the penetrating member advances, the piercing point  108   b  of the penetrating member will first pierce the elastomeric member  112  and will then pierce closure wall  110  (see also  FIG. 15 ) so as to open communication between the fluid reservoir  102  and the internal passageway  108   c  of the penetrating member. 
     With communication between the fluid reservoir and the internal passageway of the penetrating member having been established in the manner thusly described, the fluid contained within the fluid reservoir can be expelled by rotating the carriage release knob  134 , which is held within base portion  86   a  by a retaining ring  135  ( FIG. 10 ). This is accomplished by grasping the finger engaging rib  134   a  ( FIG. 19 ) and rotating the knob until the threaded end  134   b  is free from the internally threaded cavity  98   c  formed in the carriage  98  ( FIG. 5 ). Once the carriage release knob is freed from the carriage, the stored energy source, here shown as a coil spring  136  that is movable from the first compressed position shown in  FIG. 3  to a second extended position shown in  FIG. 5 , will urge the carriage forwardly in the manner illustrated in  FIG. 5  of the drawings. As the carriage moves forwardly the circumferentially spaced guide tabs  98   d  formed on the carriage will slide within and be guided by guide channels  122   g  formed in reservoir advancement housing  122 . As the accordion side walls collapse, the fluid will be forced outwardly of the reservoir into internal passageway  108   c  of the penetrating member. In a manner presently to be described, the fluid will then flow toward the fluid flow control means of the invention, which functions to control the flow of fluid from the fluid reservoir of the fluid delivery portion of the device toward the patient. 
     The fluid flow control means, which is carried by the central portion  88  of the housing, here comprises dose control means for controlling the dose of medicament to be delivered to the patient and rate control means for controlling the rate of medicament flow from collapsible reservoir toward the dose control means. 
     Considering first the rate control component of the fluid flow control means, as best seen in  FIGS. 21 through 51 , this novel means here comprises a flow rate control assembly  156  ( FIGS. 24 and 25 ) for controlling the rate of fluid flow toward the dose control means. Flow rate control assembly  156  includes a first, or lower rate control plate  158  and a second, or upper, rate control plate  160  ( FIGS. 24 ,  25 ,  39 ,  40  and  42 ). As best seen in  FIG. 42 , the bottom side of rate control plate  160  is uniquely provided with a plurality of fluidic micro-channels identified in the drawings as  162 ,  164 ,  166 ,  168 ,  170 ,  172 ,  174 ,  176 ,  178 ,  180 ,  182 ,  184 ,  186 ,  188 ,  190 ,  192 ,  194  and  196 . Each of the fluidic micro-channels is also provided with an outlet  162   a ,  164   a ,  166   a ,  168   a ,  170   a ,  172   a ,  174   a ,  176   a ,  178   a ,  180   a ,  182   a ,  184   a ,  186   a ,  188   a ,  190   a ,  192   a ,  194   a  and  196   a , respectively. 
     As best seen in  FIG. 39 , upper side of rate control plate  160  is also uniquely provided with a plurality of fluidic micro-channels of different lengths that are identified in the drawings as  202 ,  204 ,  206 ,  208 ,  210 ,  212 ,  214 ,  216 ,  218 ,  220 ,  222 ,  224 ,  226 ,  228 ,  230 ,  232 ,  234  and  236 . Each of the fluidic micro-channels is also provided with an outlet  202   a ,  204   a ,  206   a ,  208   a ,  210   a ,  212   a ,  214   a ,  216   a ,  218   a ,  220   a ,  222   a ,  224   a ,  226   a ,  228   a ,  230   a ,  232   a ,  234   a  and  236   a , respectively. Upper control plate  160  is also provided with inlet ports  250 ,  252 ,  254 ,  256 ,  258 ,  260 ,  262 ,  264 ,  266 ,  268 ,  270 ,  272 ,  274 ,  276 ,  278 ,  280 ,  282  and  284  that communicate with the outlet ports  162   a  through  196   a  of lower side of control plate  160 . 
     As best seen in  FIG. 25 , the inlet ports of the upper control plate as well as the outlet ports thereof communicate with a multiplicity of spaced apart fluid ports  290  formed in rate control distribution plate  292 . From fluid ports  290 , the fluid flows toward the novel fluid pickup housing  294  of the invention. As illustrated in  FIGS. 23 and 24 , fluid pickup housing  294  includes a base  294   a  and tower portion  294   b  that is provided with a multiplicity of circumferentially spaced apart, generally vertically extending fluid passageways  296  of varying lengths. 
     With the construction described in the preceding paragraphs, fluid flowing from the fluid reservoir will fill fluidic micro channels  162  through  196  as well as fluidic micro channels  202  through  236  via an inlet port  297  carried by rate control distribution plate  292  (see  FIGS. 25 and 34 ). Fluid flowing through the outlet ports of these fluidic micro-channels will flow into spaced apart fluid ports  290  formed in rate control distribution plate  292 . From fluid ports  290 , the fluid will flow into and fill the circumferentially spaced apart, generally vertically extending fluid passageways  296  of fluid pickup housing  294  ( FIGS. 26 ,  27 ,  28  and  29 ). Referring to  FIG. 30 , which is a depiction of the inner surface of fluid pickup housing  294  when viewed in a planar configuration, it is to be noted that fluid passageways  296  are arranged in six spaced part groups of passageways  298 ,  300 ,  302 ,  304 ,  306  and  308  respectively. Each group of passageways is made up of six spaced apart passageways of a different length, each passageway having an outlet located at a different height with respect to base  294   a  of the fluid pick-up housing ( FIG. 27 ). From a selected one of the six groups of fluid passageways  296 , the fluid will flow into a group of six vertically and circumferentially spaced apart inlets  310  ( FIGS. 53 and 53A ) formed in the skirt portion  312   a  of a patient weight selector knob  312  (see also  FIG. 30 , which is a depiction of the inner surface of the skirt portion when viewed in a planar configuration). For a purpose presently to be described, the skirt portion  312   a  of patient weight selector knob  312  is also provided with six circumferentially spaced apart outlet groups  314 , each group having six vertically spaced apart outlet ports  316 . From inlets  310 , the fluid will flow into a plurality of vertically spaced apart, circumferentially extending fluid passageways  320  formed in a fluid pickup housing  322  ( FIGS. 28 ,  29  and  30 ) that is housed interiorly of the downwardly depending skirt  312   a  of the patient weight selector knob  312  (see  FIGS. 21B ,  22 , and  23 ). Retaining tabs  325  are disposed interiorly of skirt  312   a  ( FIG. 51 ). The fluid pickup housing  322  is bonded to pickup housing  294 , forming a rigid support to snap the retaining tabs  325  into pickup housing  322 . 
     With the construction described in the preceding paragraphs, fluid flowing from the fluid reservoir will fill fluidic micro channels  162  through  196  ( FIG. 42 ) as well as fluidic micro channels  202  through  236  ( FIG. 39 ), will fill the fluid passageways  296  of fluid pickup housing  294  ( FIG. 27 ) and will fill the circumferentially extending fluid passageways  320  formed in a fluid pickup housing  322  ( FIG. 25 ). From fluid passageways  320  the fluid will flow into the vertically spaced apart outlet passageways  316  formed in patient weight selector knob  312  ( FIG. 24 ). 
     When the patient weight selector knob  312  is rotated into the position shown in  FIG. 24 , fluid will flow from outlet ports  316  into the six vertically spaced apart, transversely extending fluid passageways  330  formed in fluid pickup housing  294 . As will presently be described, fluid passageways  330  communicate with the dose control means of the invention which, as previously mentioned, functions to control the dose of medicament to be delivered to the patient. 
     With the patient weight selector knob  312  in position ( FIG. 24 ) wherein inlets  310  ( FIG. 53A ) align with one of the groups  298  through  308  ( FIG. 30 ) of fluid passageways  296 , fluid will flow from the fluid reservoir through inlet  297  ( FIG. 25 ) into the fluidic micro-channels of different lengths formed in upper and lower surfaces of lower rate control plate  160  ( FIGS. 39 and 42 ), into vertically extending fluid passageways  296  of fluid pickup housing  294  ( FIG. 27 ), into inlets  310  ( FIG. 25 ), into passageways  320  formed in the fluid pickup assembly  322 , into passageways  316  of the patient weight selector knob  312 , into passageways  330  of the fluid pickup assembly  294  and finally into passageways  332  of body portion  334   a  of the dose control assembly  334 . It is apparent that the rate of fluid flow toward the dose control means depends upon the configuration of the rate control passageways formed in the rate control plate  160  that are in communication with inlets  310  via vertically extending fluid passageways  296 . By way of example, assume that the patient weight selector knob  312  is rotated into a position wherein inlets  310   a ,  310   b ,  310   c ,  310   d ,  310   e  and  310   f  ( FIG. 51A ) align with the passageways  296   a ,  296   b ,  296   c ,  296   d ,  296   e  and  296   f  of group  298  ( FIG. 30 ). Assume further, that the six passageways  296   a ,  296   b ,  296   c ,  296   d ,  296   e  and  296   f  are in communication with fluid passageways  162 ,  164 ,  166 ,  168 ,  170  and  172  respectively of rate control plane  160  ( FIG. 42 ). In this situation, fluid will flow from fluid passageway  162  into passageway  296   a , then into passageway  310   a  and finally into the lower most circumferentially extending passageway  320   a  formed in the fluid pickup assembly  322  ( FIG. 21B ). Similarly, in this situation, fluid will flow from fluid passageway  164  into passageway  296   b , then into passageway  310   b  and finally into circumferentially extending passageway  320   b  formed in the fluid pickup assembly  322  ( FIG. 24 ). The fluid will flow in a similar manner from passageways  166 ,  168 ,  170  and  172  into the remaining circumferentially extending passageway  320  formed in the fluid pickup assembly  322 . 
     As illustrated in  FIGS. 58 and 59  of the drawings, rate control indexing means are provided to position the locking knob  312  in a selected rotational position. In the present form of the invention, this rate control indexing means comprises a locking plunger  333  that is received within a bore  104   a  formed in the forward portion  104  of housing  102 . Locking plunger  333  is continuously biased outwardly by a coiled spring  335  into locking engagement with a selected one of a plurality of circumferentially spaced apart cutouts  312   c  formed in the flange portion  312   b  of the locking knob assembly  312 . With this construction, in order to rotate the locking knob from the selected rotational position, the locking plunger  333  must be manually pushed inwardly against the urging of spring  335 . 
     Turning now particularly to  FIGS. 21B and 54  through  56 , rotatably mounted within body portion  334   a  of the dose control assembly  334  is the patient dose selector knob  338  and formed within a body portion  338   a  of the dose selector knob vertically spaced-apart radially outwardly extending fluid passageways  340 ,  342 ,  344 ,  346 ,  348  and  350  ( FIGS. 55 ,  56  and  57 ). As shown in  FIG. 48 , dose selector knob  338  rests on a base support  339 . By rotating the dose selector knob within body portion  334   a , the radially outwardly extending fluid passageways can be selectively brought in to communication with the passageways  332  that are, in turn, in communication with the circumferentially extending passageway  320  formed in the fluid pickup assembly  322  of the rate control means of the invention. By way of example, in  FIG. 21  of the drawings radially outwardly extending fluid passageway  340  is shown in communication with the uppermost passageway  332  of the dose control means. 
     As illustrated in  FIG. 55 , each of the radially outwardly extending fluid passageways is in communication with an axially extending passageway  352  that is, in turn, in communication with the bolus operating mechanism of the invention, the character of which will presently be described. 
     By way of example, further rotation of the dose selector knob within body portion  334   a  can bring radially outwardly extending fluid passageway of fluid pickup assembly  322  via the lower-most passageway  332 . In this situation, it can be seen that fluid passageway  350  is in communication with fluid passageway  162  of the lower surface of rate control plate  160  via the lower most passageway  332 , the lower most passageway  330 , the lower most passageway  316 , circumferentially extending passageway  320   a  and passageway  296   a . Similarly, in this example, by controlled rotation of the dose selector knob, each of the fluid passageways formed in the dose selector knob can be brought into communication with a selected one of the passageways  164  through  172  formed in the rate control plate  160 . In this way, the rate of fluid flow toward the patient of the medicinal fluid contained within the device reservoir can be closely controlled. 
     As illustrated in  FIGS. 58 and 60  of the drawings, dose control indexing means are provided to lock the patient dose selector knob  338  in any selected position. In the present form of the invention this dose control indexing means comprises a locking plunger  353  that is received within a bore  104   b  formed in the forward portion  104  of housing  102 . Locking plunger  353  is continuously biased outwardly by a coiled spring  355  into locking engagement with a selected one of a plurality of circumferentially spaced apart cutouts  338   c  formed in the flange portion  338   b  of the patient dose selector knob assembly  338 . With this construction, in order to rotate the patient dose selector knob  338  from a selected position, the locking plunger  353  must be manually pushed inwardly against the urging of spring  355 . 
     Considering further the bolus delivery means of the invention, this novel means, which is housed within forward portion  104  of housing  102 , includes a double bolus reservoir  360  ( FIGS. 68 ,  69  and  70 ) that is disposed within a cavity  359  formed in forward portion  104  of housing  102 . The double bolus reservoir  360  is defined by interconnected, collapsible bellows structures  360   a  and  360   b  that are in communication with passageway  352  of the dose control means via a longitudinally extending passageway  362 , a vertical stub passageway  364 , a conventional umbrella check valve  366 , a vertical stub passageway  368  and a longitudinal passageway  370  (see  FIGS. 21 and 61 ). Umbrella check valve  366 , which is carried-with an internal housing  372 , functions to permit fluid flow toward reservoir  360 , but blocks fluid flow in the opposite direction. Reservoir  360  is in fluid communication with the administration set  153  ( FIG. 1 ) via passageway  374 , a second conventional umbrella check valve  376 , a vertical passageway  378  and longitudinally extending passageway  380 . With this construction, low flow from the dose control means any selected dose, to bolus reservoir  360  and then on to the patient via the administration set  153  which here comprises a conventional “Y” site injection septum or port  153   a , a conventional gas vent and particulate filter  153   b , a line clamp  153   c  and a conventional luer connector  153   d.    
     Referring particularly to  FIGS. 61 , and  63  through  67 , the important bolus operating mechanism of the invention is there shown and generally designated by the numeral  384 . This mechanism permits selected bolus doses of medicaments to be delivered to the patient from reservoir  360  as may be required. As best seen in  FIGS. 65 and 67  of the drawings, this novel mechanism here comprises a first, or main operating shaft  386  for controllably collapsing the bellows structure  360   a  and a second operating shaft  387  ( FIGS. 71 ,  72 ,  83  and  84 ) for controllably collapsing the bellows structure  360   b  (see  FIG. 69 ). By way of non limiting example, bellows structure  360   a  can have a first volume of between approximately 3 ml and approximately 6.0 ml while bellows structure  360   b  can have a second, lesser volume of approximately 0.5 ml and approximately 2.0 ml. Main operating shaft  386  controllably collapses bellows structure  360   a  by pushing inwardly on the shaft against the urging of a coiled operating spring  388  that circumscribes bellows structure  360   a . In the manner illustrated in  FIG. 65 , main operating shaft  386  is movable within the reduced diameter portion  390   a  of the bolus selector housing  390  that is carried within the forward portion  104  of housing  102 . Following rotation of the bolus selector in a manner presently to be described, the main operating shaft can be moved inwardly against the urging of coiled operating spring  388  from an extended to an inward position. Inward movement of the main operating shaft causes inward movement of a pusher member  394  which, in turn, causes the collapse of the bellows portion  360   a . It is to be noted that pusher member  394  is provided with a yieldably deformable locking tab  394   a  (see also  FIG. 72 ) that is adapted to engage a plurality of generally saw-toothed shaped protuberances  396  that are formed on the inner wall of cavity  359 . Locking tab  394   a  is so constructed and arranged as to ride over protuberances  396  as the main operating shaft is pushed inwardly of cavity  359 . However, the saw-toothed protuberances  396  are configured so that the locking tab will engage the vertical faces  396   a  of the protuberances in a manner to prevent movement of the pusher member in a direction toward its starting position. With this construction, once the reservoir bellows portion  360   a  is collapsed, it will remain in a collapsed configuration. 
     Following rotation of the operating knob  399  of the bolus operating mechanism  384  in a manner presently to be described, second operating shaft  387  can be moved inwardly within a bore  386   a  provided in main operating shaft  386  against the urging of a second coil spring  400 . Second operating shaft  387  operates against bellows portion  360   b  in a manner to collapse the bellows portion as the second operating shaft is urged inwardly against the urging of spring  400 . As the bellows portion  360   b  collapses, medicinal fluid contained there within will be urged outwardly of the reservoir via outlet passageway  378 . However, upon the release of inward pressure exerted against second operating shaft  387 , spring  400  will urge the operating shaft into its original starting position so that subsequent smaller bolus doses of medicament can be delivered to the patient. 
     Turning now to  FIGS. 87 ,  88  and  89 , in delivering bolus doses of medicament to the patient, a locking member  404  that is carried by housing  102  in the manner shown in  FIG. 66  of the drawings must be pushed inwardly in order to permit rotation of the reduced diameter portion  390   a  of the bolus selector housing  390 . As indicated in  FIG. 66 , inward movement of the locking member causes the locking shoulder  404   a  to move out of locking engagement with a cavity  390   c  formed in the enlarged diameter portion  390   b  of the bolus selector housing  390  so as to permit rotation of the bolus selector housing  390 . With the locking member pushed inwardly, the bolus selector housing  390  can be rotated from the “off” position shown in  FIG. 87  of drawings to the “5.0 ml” position. This done, the main operating shaft can be pushed inwardly causing plunger  394  to collapse bellows  360   a , resulting in the delivery of a bolus dose of a predetermined volume of medicament to the patient (in this case 5.0 ml). As previously mentioned, once the main operating shaft is pushed inwardly, it will be locked in position by locking tab  394   a.    
     When it is desired to deliver a smaller bolus dose of medicament to the patient, as, for example 2.5 ml, it is necessary to first rotate cap  399  from the “off” position shown in  FIG. 87  to the “2.5 ml” position shown in  FIG. 88 . As best seen in  FIG. 83  second operating shaft  387  is provided with a rotational stop  387   a  that engages a stop wall  410  provided on the main operating shaft  390  (see  FIGS. 74 through 77 ). As the second operating shaft is rotated, a coiled spring  412  carried a spring shelf  414  ( FIGS. 83 ,  84  and  86 ) will resist the rotation and will be compressed in the manner in  FIG. 80 . 
     This done, the secondary operating shaft  387  can be pushed inwardly in the manner illustrated in  FIG. 89 . This inward movement of the second operating shaft will collapse bellows portion  360   b  causing the fluid contained there within (in this instance 2.5 ml) to be delivered to the patient via outlet passageway  374 . 
     With the construction described in the preceding paragraph, when the rotational forces exerted on cap  399  cease, spring  412  will urge the cap to return to its starting position and at the same time, spring  400  will urge shaft  387  into its starting position, thereby permitting a repeated application of a smaller bolus dose of medicament to the patient as may be required. 
     Turning now to  FIGS. 90 and 90A , these views when considered together illustrate an alternate form of the apparatus of the invention which is generally identified by the numeral  420 . This form of the apparatus is similar in many respects to the embodiment illustrated in  FIGS. 20 through 89  of the drawings and like numerals are used in  FIGS. 90 ,  90 A,  91  and  92  to identify like components. The primary difference between this alternate embodiment of the invention and the earlier described embodiments resides in the differently configured stored energy means. More particularly, in this latest form of the invention, the stored energy means comprise a plurality of circumferentially spaced variable force springs  424  that are somewhat similar in construction to prior art constant force springs, but have been modified to produce highly specific and desirable linear and non-linear force-distention curves to meet the fluid delivery requirements of the invention. For example, as will be discussed in greater detail in the paragraphs that follow, in this latest form of the invention the elongated band or strip portion  424   a  of the spring has been modified to exhibit a cross-sectional mass that varies along the length of the band. 
     Referring particularly to  FIGS. 90 and 90A , like the earlier described embodiments of the invention, this latest form of the fluid dispensing apparatus of the invention is used for dispensing various types of medicaments, including sedatives such as propofol, dexmedetomidine hydrochloride and related compounds. The apparatus here comprises a device housing  426  having a forward portion  84 , a central portion  88  and a rear portion  430  having a base  430   a . Housing  426  can be constructed from metal, plastic or any suitable material. 
     Disposed within the rear portion  430  of the device housing is the important fluid delivery portion of the apparatus and, as in the earlier described embodiment of the invention, the novel fluid flow control means is disposed within the central portion  88 . As before, the fluid flow control means functions to control the flow of fluid from the reservoir  94  of the reservoir defining assembly  100  of the invention. In this latest embodiment of the invention, the reservoir defining assembly  100  is substantially identical in construction and operation to that illustrated in  FIGS. 2 and 3  of the drawings and previously described herein. Disposed within the forward portion  84  of the device housing is the bolus operating means of the invention, which is also substantially identical in construction and operation to that previously described and which functions to permit selected bolus doses of medicaments to be delivered from reservoir  94  to the patient as may be required. 
     Considering first the fluid delivery portion of the fluid dispensing apparatus, this portion, which is somewhat different in construction and operation to that previously described, comprises a carriage  434  that carries and acts upon reservoir defining assembly  100 . Carriage  434  is movable between a first rearward position shown in  FIG. 90  and a second advanced position shown in  FIG. 92 . 
     As best seen by referring to  FIGS. 90 and 92 , carriage  434  includes a body portion  434   a  that carries the novel stored energy means of the invention and a reduced diameter portion  434   b . Carriage  434  is releasably locked in its first position by a novel locking means the character of which will be described in the paragraphs which follow. 
     Reduced diameter portion  434   b  of the carriage is received within a cavity  95  provided an ullage defining protuberance  95   b  of reservoir defining assembly  100  which, as before, comprises an integrally formed, hermetically sealed container of the character previously described. Fluid medicament reservoir  94  of the hermetically sealed container is accessible via a penetrating member  108  that is adapted to pierce a closure wall  110  as well as a pierceable membrane  112  (see  FIG. 15 ). 
     In using the apparatus of this latest form of the invention, rotation of the reservoir outer shell  118  in the manner previously described will cause the threads  122   a  formed on the reservoir advancement housing  122  to advance over the threads  120   b  formed on the reservoir connector housing  120 . As the assemblage made up of the reservoir outer shell  118  and the reservoir advancement housing  122  is advanced, a locking tab  118   b  formed on the reservoir outer shell  118  will move into locking engagement with a locking groove  118   b  formed in the reservoir connector housing  120 . In this way, the reservoir connector housing  120  is interconnected with the assembly made up of the reservoir outer shell  118  and the reservoir advancement housing  122  so that rotation of the reservoir outer shell  118  will cause advancement of the pierceable member  108 . 
     As the assemblage made up of the reservoir outer shell  118  and the reservoir advancement housing  122  is advanced, the neck portion  114  of the container  100  moves to the position shown in  FIG. 90  wherein it resides within a cavity  124   a  formed in the bearing shaft  124 . With the neck portion  114  of the reservoir defining assembly  100  in position within cavity  124   a , the fluid delivery step can commence by rotating the entire rearward portion of the housing. However, as before, in order to enable this rotation, the locking means, or locking member  128  must be manipulated in the manner previously described. As the mounting block  132  rotates, the internal threads  132   b  formed on the mounting block will engage the external threads  108 a formed on the penetrating member causing the penetrating member to advance into the position shown in  FIG. 92 . As the penetrating member advances, the piercing point  108   b  of the penetrating member will first pierce the elastomeric member  112  and will then pierce closure wall  110  (see also  FIG. 15 ) so as to open communication between the fluid reservoir  94  and the internal passageway  108   c  of the penetrating member. 
     With communication between the fluid reservoir and the internal passageway of the penetrating member having been established in the manner thusly described, the fluid contained within the fluid reservoir can be expelled by rotating the carriage release knob  440 , which is held within base portion  430   a  by a retaining ring  135  (see  FIG. 10 ). This is accomplished by grasping the finger engaging rib  440   a  and rotating the knob until the threaded end  440   b  is free from the internally threaded cavity  440   c  formed in the carriage  434 . Once the carriage release knob is freed from the carriage, the stored energy means will urge the carriage forwardly in the manner illustrated in  FIG. 92  of the drawings. As the accordion side walls of the reservoir defining assembly  100  collapse, the fluid will be forced outwardly of the reservoir into internal passageway  108   c  of the penetrating member. In the manner previously described, the fluid will then flow toward the fluid flow control means of the invention which, as before, functions to control the flow of fluid from the fluid reservoir of the fluid delivery portion of the device toward the patient. 
     The fluid flow control means, which is carried by the central portion  88  of the housing and which is substantially identical in construction and operation to that previously described, comprises dose control means for controlling the dose of medicament to be delivered to the patient and rate control means for controlling the rate of medicament flow from collapsible reservoir toward the dose control means. 
     The rate control component of the fluid flow control means, which is substantially identical in construction and operation to that previously described, comprises the flow rate control assembly  156  illustrated in  FIGS. 24 and 25  of the drawings. Similarly, the dose control means, which is substantially identical in construction and operation to that previously described, comprises the construction previously described and illustrated in  FIGS. 53 through 62 . The bolus delivery means of the invention, which is also substantially identical in construction and operation to that previously described, comprises the construction previously described herein and illustrated in  FIGS. 61 through 89 . 
     A more detailed consideration of the stored energy sources, or variable force springs of this latest form of the invention will now be undertaken. At the outset it is to be understood that the objective of many prior art fluid and drug delivery system is to deliver fluid at a constant flow rate. One method for achieving a constant flow rate over time involves ensuring that the pressure driving the fluid through the device is constant, i.e., the pressure inside the fluid reservoir of the apparatus is constant In this latest form of the invention, achieving constant pressure in the bellows-like fluid reservoir  94  of the device is accomplished in a unique manner by modifying a typical constant force spring, such as a Negator spring “NS” of the character shown in  FIG. 93 . Negator springs are readily commercially available from a number of sources including Stock Drive Products/Sterling Instruments of New Hyde Park, N.Y. 
     The prior art Negator extension spring comprises a pre-stressed flat strip “FS” of spring material that is formed into virtually constant radius coils around itself or on a drum “Z” having a radius R-1 ( FIG. 93 ). The area identified in  FIG. 93  of the drawings as “FGR” designates the “active region” or “the force generating region” of the constant force spring. It should be understood that in this “active region” the radius of curvature of the spring changes and it is this change in radius of curvature of the spring that is responsible for the generation of the force. In fact, the radius of curvature changes from essentially infinity to a value equal to the radius R-1 of the spool on which the spring is wound. As will be discussed in greater detail hereinafter, increasing the mass of material in this “force generating region” will increase the force provided by the spring. Conversely, decreasing the mass of material in the “force generating region” will result in a reduction of the force generated by the spring. The mass in the active region can be changed by changing the thickness of the spring, the width of the spring, the density of material of the spring, or any combination of these. It should be further noted that because the force generating region takes up some portion of the length of the spring it will tend to average any point-by-point changes in physical or structural properties of the spring. The variable L shown in  FIG. 93  of the drawings is defined to be the distance from the force generating region to the end of the spring. When deflected, the spring material straightens as it leaves the drum (see  FIG. 93 ). This straightened length of spring actually stores the spring&#39;s energy through its tendency to assume its natural radius. 
     The force delivered by a typical prior art constant force spring, such as the Negator extension spring, depends on several structural and geometric factors. Structural factors include material composition and heat treatment. Geometric factors include the thickness of the spring ‘T’, the change in radius of curvature of the spring as the spring is extended, and the width “W” of the spring. 
     Turning now to a consideration of the novel variable force springs of the present invention, these springs can be constructed from various materials, such as metal, plastic, ceramic, composite and alloys, that is, intermetallic phases, intermetallic compounds, solid solution, metal-semi metal solutions including but not limited to Al/Cu, Al/Mn, Al/Si, Al/Mg, Al/Mg/Si, Al/Zn, Pb/Sn/Sb, Sn/Sb/Cu, Al/Sb, Zn/Sb, In/Sb, Sb/Pb, Au/Cu, Ti/Al/Sn, Nb/Zr, Cr/Fe, non-ferrous alloys, Cu/Mn/Ni, Al/Ni/Co, Ni/Cu/Zn, Ni/Cr, Ni/Cu/Mn, Cu/Zn, Ni/Cu/Sn. These springs comprise a novel modification of the prior art constant force springs to provide variable springs suitable for use in many diverse applications. 
     With the forgoing in mind, if one wanted to produce a spring that delivered a force that increased by a factor of two as the spring returned from its fully extended conformation to its equilibrium, or fully coiled conformation, one would require that, as illustrated in  FIG. 94  of the drawings, the width of the spring change by a factor of two along its length. In the example illustrated in  FIG. 94A , the force will decrease by a factor of w 1 /w 2  as the spring changes from a fully extended configuration to a fully retracted configuration. 
     With the forgoing in mind, one form of the modified spring of the present invention can be described algebraically as follows: 
     If x denotes the position of a point along a line that is parallel to the longitudinal axis of the spring and w(x) denotes the width of the spring at that point then:
 
 w ( x )=(constant) x  
 
This describes the case wherein the width varies linearly with x as is shown in  FIG. 94  of the drawings.
 
     However, it is to be observed that the relationship between a position along the longitudinal axis of the spring and the width of the spring at that position need not be linear as shown in  FIG. 94 . Further, the width of the spring could be any arbitrary function of x. Thus:
 
 w ( x )= f ( x )
 
where (x) denotes an arbitrary function of x.
 
     Using this concept, a spring can be designed that can be used to controllably compress a bellows type reservoir, such as reservoir  94 , which when compressed by the modified spring exhibits a pressure vs. degree of compression curve of the character shown in  FIG. 94B . Stated another way, it is apparent that the concept can be employed to design a spring that generates a pressure that is independent of the degree of compression of the bellows-type reservoir. 
     By way of example, suppose that the pressure vs. degree of compression curve for a bellows-like container when compressed by a constant force spring is exemplified by the curve P(x) and the force of the constant force spring is identified as FCFS”. Further assume that the drop in pressure as the container is compressed is due to the force “BF(x)”, which is the force required to compress the container. Then the net force producing the pressure in the container can then be written:
 
 F ( x )= FCFS−BF ( x )
 
     Assume for simplicity that the area on which the force F acts is constant and is represented by “A”. Then the pressure in the bottle is:
 
 P ( x )=( FCFS−BF ( x ))/ A  
 
This equation describes, in functional form, the curve labeled P(x) in  FIG. 94B , and includes explicitly the contributions of the two forces generating the pressure within the reservoir  94  of the bellows-like container, that is the force due to the spring and the force due to the bellows-like container.
 
     The forgoing analysis allows one to design a spring, the force of which changes in such a way that the sum of all forces generating the pressure in the container is independent of the degree of the compression of the container, i.e., independent of the variable x. The force delivered by such a spring can be stated as:
 
 F   ms ( x )= FCFS+AF ( x )
 
Where “FCFS” is the force delivered by the original constant force spring and AF(x) is an additional force whose functional form is to be determined. Thus, the modified spring can be thought of as being composed of two parts, one part delivers the force of the original constant force spring (a force independent of x) and the other delivers a force that depends on the variable x.
 
     For this system the net force generating the pressure in the reservoir of the bellows-like container is stated as:
 
 FS ( x )= F   ms ( x )− BF ( x )= FCFS+AF ( x )− BF ( x )
 
Assuming that:
 
 AF ( x )= BF ( x ) for all  x.  
 
Then the total force compressing the container is:
 
 FS ( x )= FCFS+AF ( x )− AF ( x )= FCFS  
 
which force is independent of the degree of compression of the container, and wherein the pressure within the container is independent of the degree of compression of the container.
 
 P   ms ( x )=( FCFS+AF ( x )− AF ( x ))/ A=FCFS/A  
 
Where P ms (x) denotes the pressure in the fluid reservoir when the modified spring of the invention is used.
 
     In designing the modified spring of the present invention, the information contained in the pressure vs. displacement curve when the container is compressed by a constant force spring can be used to determine how the cross-sectional mass, in this case the width of the spring, must vary as a function of x in order that the pressure in the container when compressed with the modified spring remains constant. 
     The force delivered by the spring being linearly dependent on the width of the spring if all other things remain constant, thus:
 
 AF ( x )=(constant) w ( x )
 
Substituting this into equation:
 
 P ( x )=( FCFS−BF ( x ))/ A , then:
 
 P ( x )=( FCFS−AF ( x ))/ A =( FCFS −constant) w ( x ))/ A  
 
However, it is to be observed that FCFS/A−P(x) is just the difference between the two curves shown in  FIG. 94B , FCFS/A being the horizontal line. Thus, the modification to the width, denoted w(x), of the original constant force spring is proportional to the difference between the two curves shown in  FIG. 94B . In other words, the shape of the change in the width of the spring as a function of x is similar to the difference between the two curves as a function of x. Furthermore, one can simply “read off” the shape of the curve w(x) from the pressure vs. displacement curve.
 
     The broader utility of a variable force spring whose width defines the specific force may be that the spring design can be appropriately constructed to deliver a non-linear and highly variable force to meet a specific requirement. In this way, a spring that has a width that simply decreases as it is unrolled could be used. Alternatively, the spring could have an increasing width, followed by a width that decreases again during its distention. The spring force provided is therefore highly tunable to meet a variety of applications and requirements, simply by constructing a spring of specific width at the desired distension. 
     Referring to  FIGS. 95 and 95A  of the drawings, still another form of variable force spring having varying cross-sectional mass along its length is there illustrated. In this instance, the varying cross-sectional mass is achieved by a constant force spring wherein the force generating region of the spring has been modified to include a plurality of spaced-apart apertures “AP” along its length. As shown in  FIG. 95A , which is a schematic plot (not to scale) of force versus cross-sectional mass, the spring uniquely provides an increasing force in a stair step fashion as it is retracted. It is to be understood, that the apertures formed in the pre-stressed strip of spring material can be located in any desired configuration and can be both transversely and longitudinally spaced-apart to provide the desired force as the spring is retracted. 
       FIG. 96  is a generally perspective view of still another form of the retractable spring of a modified configuration that can be used in an apparatus of the character illustrated in  FIGS. 90 and 90A  of the drawings. This latter form of the retractable spring of a modified configuration is somewhat similar to that shown in  FIG. 95  of the drawings, but here comprises a novel laminate construction made up of a first laminate FL and a second interconnected laminate SL. The varying cross-sectional mass is once again achieved by providing a plurality of the elongated transversely and longitudinally spaced-apart aperes, or slits. 
     Turning now to  FIGS. 97 and 97A , these views when considered together illustrate yet another form of the apparatus of the invention which is generally identified by the numeral  450 . This form of the apparatus is similar in many respects to the embodiment illustrated in  FIGS. 90 and 90A  of the drawings and like numerals are used in  FIGS. 97 and 97A  to identify like components. The primary difference between this latest embodiment of the invention and the earlier described embodiments resides in the differently configured reservoir defining assembly and the differently configured stored energy means. More particularly, in this latest form of the invention, the stored energy means comprise a plurality of circumferentially spaced variable force spring assemblies  454  that are somewhat similar in construction to prior art constant force spring assemblies, but have been modified to produce highly specific and desirable linear and non-linear force-distention curves to meet the fluid delivery requirements of the invention. For example, as will be discussed in greater detail in the paragraphs that follow, in this latest form of the invention the elongated band or strip portion  454   a  of the spring is coiled about a spring drum  456  in predetermined varying degrees of tightness. Accordingly, like the earlier described variable force springs in which the elongated band or strip portion of the spring has been modified to exhibit a cross-sectional mass that varies along the length of the band, springs with a variation of coil tightness such as illustrated in  FIGS. 100 and 100A , can produce highly specific and desirable linear and non-linear force-distention curves to meet the fluid delivery requirements of the invention. This type of “inter-wound negative gradient” spring has no slot. In fact, it is that the winding process is done precisely to create a “negative gradient” so that as the spring retracts, it provides a higher force. 
     Like the earlier described embodiments of the invention, this latest form of the fluid dispensing apparatus of the invention is also used for dispensing various types of medicaments, including sedatives such as propofol, dexmedetomidine hydrochloride and related compounds. The apparatus here comprises a device housing  426  having a forward portion  84 , a central portion  88  and a rear portion  430  having a base  430   a . Housing  426  can be constructed from metal, plastic or any suitable material. 
     Disposed within the rear portion  430  of the device housing is the important fluid delivery portion of the apparatus and, as in the earlier described embodiment of the invention, the novel fluid flow control means is disposed within the central portion  88 . The fluid flow control means which is identical in construction and operation to that previously described, functions to control the flow of fluid from the reservoir  458  of the reservoir defining assembly  460  of the invention. In this latest embodiment of the invention, the reservoir defining assembly  460  is somewhat similar in construction and operation to that illustrated in  FIGS. 2 and 3  of the drawings and previously described herein, but uniquely comprises a laminate construction. Disposed within the forward portion  84  of the device housing is, the bolus operating means of the invention, which is also substantially identical in construction and operation to that previously described and which functions to permit selected bolus doses of medicaments to be delivered from reservoir  458  to the patient as may be required. 
     With regard to the reservoir defining assembly  460  of this latest form of the invention, this assembly uniquely comprises a co-extrusion formed by the blow-fill-seal process. As shown in  FIG. 97B , assembly  460  here comprises a novel laminate wall made up of laminates L-1, L-2, L-3 and L-4. With regard to the blow-fill-seal process, co-extrusion in the blow-fill-seal process is typically used in the prior art to package liquids that are either oxygen or moisture sensitive. Further, oxygen sensitive products, as well as compounds that need a longer shelf life, are frequently packaged using co-extruded plastic. Blow-Fill-Seal is a preferred drug packaging modality because polypropylene (PP) and polyethylene are typically used. Compared to a traditional flexible solution bag made from PVC, a PP or PE, the blow-fill-seal container is much less permeable. 
     With suitable resins, co-extruded plastic blow-fill-seal containers can readily be constructed to prevent water vapor loss out of container, and ingress of oxygen into the container contents. The typical co-extruded material is a five layer system that exhibits substantially the same thickness as a comparable container constructed from a single layer resin material. That is, each layer is ⅕ of the equivalent container that is homogeneous (non-laminate). However, it should be recognized that, at a minimum a three layer system is required to suit the purposes of the present invention, while a system having up to about 10 layers would be feasible for certain applications. 
     In a typical five layer co-extruded blow-fill-seal container, the laminate material may comprise an inert internal polyolefin, such as PP. The barrier material in the center of the five layer laminate may be selected to exhibit gas or water barrier properties, or both. The barrier material is affixed to the inert hydrophobic plastic layer (e.g. PP) via a binder layer. 
     Although a variety of plastic resins may be used for the co-extrusion of blow-fill-seal containers, polyolefins (e.g. PP of LDPE) are desirable to be in contact with the parenteral solution, as this material is inert and hydrophobic. 
     It is well know in the food packaging industry that Ethylene-Vinyl Alcohol Copolymer (EVOH) is an excellent gas barrier. Additionally, a variety of nylon based materials (also referred to as polyamides (PA)) can act as strong vapor barriers. Those skilled in the art will also recognize cyclic polyolefin copolymers (COP) for their effectives as water barriers, and therefore there use in co-extruded blow-fill-seal containers. 
     Other suitable barrier materials may included, but are not limited to, polyvinyl chloride, oriented polyvinyl chloride (OPVC), biaxially oriented PET, silica-deposited resins, sequentially biaxially oriented polyvinyl alcohol, biaxially oriented polyester, vinylidene chloride (or copolymers of vinylidene chloride and methyl methacrylate), polyacrylonitrile (PAN), oriented polyethylene terephthalate (OPET), polystyrene (PS), ethylene methyl acrylate copolymer (EMA), and other polymer resins known to those skilled in the art which are generally termed “high gas barrier polymers” HBP. Additionally, those skilled in the art will recognize multi-lamellar barrier materials, such as those based on the blends of high-density polyethylene (HDPE) and co-polyester (PETG) prepared via melt extrusion, and poly(ethylene-co-acrylic acid) (EAA) as a compatibilizer incorporated into the blends, as possible barrier materials as well. 
     A variety of binder materials may be used to “tie” the dissimilar polyolefin and the barrier materials together. These include, but are not limited to agents of the formula AMXP in which AM is a backbone copolymer prepared by copolymerizing propylene with α-olefins and where X is selected from among citraconic anhydride, fumaric acid, mesaconic acid, the anhydride of 3-allylsuccinic acid and maleic anhydride, and P is a polyamide oligomer prepared from caprolactam, 11-aminoundecanoic acid or dodecalactam; ethylene vinyl acetate copolymer (EVA); a coextrusion binder comprising a metallocene polyethylene (A1), a cografting monomer said cografting monomer being an unsaturated carboxylic acid grafting monomer or functional acid derivative thereof, and an ethylene homopolymer; an ethylene copolymer wherein the comonomer is (a) an alpha-olefin, (b) an ester of an unsaturated carboxylic acid or (c) a vinyl ester of a saturated carboxylic acid; and a hydrocarbon elastomeric copolymer; and Celanex (polybutylene terephthalate (PBT) copolymer binder). 
     Although the most common coextrusion systems seem to be a 5 layer laminate, a variety of different “size” laminate materials would be workable in BioQ dispensers and fit the spirit of the expanded invention. At a minimum, a three layer sandwich would be required (i.e. inert polyolefin, binder and barrier) would be required. At a maximum, many repeated layers that comprise both oxygen and moisture barriers would be feasible. 
     The fluid delivery portion of this latest form of the fluid dispensing apparatus is somewhat different in construction and operation to that previously described. More particularly, as previously mentioned, the three circumferentially spaced variable force spring assemblies  554  are of a slightly different construction. The variable force spring assemblies are carried by a carriage  434  that is substantially identical in construction and operation to that previously described. Carriage  434 , which also carries and acts upon the reservoir defining assembly  460 , is movable between a first rearward position shown in  FIG. 97  and a second advanced position shown in  FIG. 99 . 
     In using the apparatus of this latest form of the invention, rotation of the reservoir outer shell  118  in the manner previously described will cause the threads  122   a  formed on the reservoir advancement housing  122  to advance over the threads  120   b  formed on the reservoir connector housing  120 . As the assemblage made up of the reservoir outer shell  118  and the reservoir advancement housing  122  is advanced, the neck portion  464  of the container  460  moves to the position shown in  FIG. 97  wherein it resides within a cavity  124   a  formed in the bearing shaft  124 . With the neck portion  464  of the reservoir defining assembly  460  in position within cavity  124   a , the fluid delivery step can commence by rotating the entire rearward portion of the housing. However, as before, in order to enable this rotation, the locking means, or locking member  128 , must be manipulated in the manner previously described. As the penetrating member advances, the piercing point  108   b  of the penetrating member will first pierce the elastomeric member  112  and will then pierce closure wall  466  (see also  FIG. 99 ) so as to open communication between the fluid reservoir  458  and the internal passageway  108   c  of the penetrating member. 
     With communication between the fluid reservoir and the internal passageway of the penetrating member having been established in the manner thusly described, the fluid contained within the fluid reservoir can be expelled by rotating the carriage release knob  440 , which is held within base portion  430   a  by a retaining ring  135  (see  FIG. 97 ). This is accomplished by grasping the finger engaging rib  440   a  and rotating the knob until the threaded end  440   b  is free from the internally threaded cavity  440   c  formed in the carriage  434 . Once the carriage release knob is freed from the carriage, the stored energy means will urge the carriage forwardly in the manner illustrated in  FIG. 99  of the drawings. As the accordion side walls of the reservoir defining assembly  460  collapse, the fluid will be forced outwardly of the reservoir into internal passageway  108   c  of the penetrating member. In the manner previously described, the fluid will then flow toward the fluid flow control means of the invention which, as before, functions to control the flow of fluid from the fluid reservoir of the fluid delivery portion of the device toward the patient via the delivery line  461  of the administration set. As illustrated in  FIGS. 97C and 97D , delivery line  461  here includes a novel side wall construction comprising an elongated extruded body  461   a  within which is encapsulated two elongated spaced-apart reinforcing lines, or filaments  461   b . Filaments  461   b  substantially reinforce and strengthen the administration line  461 . 
     With regard to the stored energy sources or variable force spring assemblies  454  of this latest form of the invention, the elongated band or strip portion  454   a  of the spring  455  is coiled about a spring drum  456  and in predetermined varying degrees of tightness. More particularly, as depicted in  FIGS. 100 and 100A  of the drawings where one example of the coiling method is illustrated, the band portion of the spring is initially wound tightly about the drum  456  to produce a first segment  467  having a diameter “D-1”. This done, the band portion is then coiled, or wound more loosely about the drum  456  to produce a second segment  469  having a diameter “D-2”. Finally, the band portion is coiled, or wound even more loosely about the drum  456  to produce a third segment  471  having a diameter “D-3”. 
     By coiling the springs about their respective drums with a variation of coil tightness in the manner described in the preceding paragraph and as illustrated in  FIGS. 100 and 100A , springs having highly specific and desirable linear and non-linear force-distention curves can be produced which will meet the fluid delivery requirements of the invention. 
     Spring assemblies, such as those depicted in  FIGS. 100 and 100A  of the drawings, that exhibit a variation of coil tightness that produce highly specific and desirable linear and non-linear force-distention curves to meet the fluid delivery requirements of the invention, are available by custom order from various sources, including Vulcan Mfg. &amp; Spring Company of Telford, Pa. 
     Turning now to  FIG. 101  of the drawings, still another form of variable force spring that can be used with the apparatus illustrated in  FIGS. 97 and 97A  is there shown. This spring, which is generally identified by the numeral  474 , is of a novel laminate construction. This latter form of the retractable spring of a modified configuration is somewhat similar to that shown in  FIG. 96  of the drawings, but here comprises a novel laminate construction made up of a first laminate FL and a second interconnected laminate SL. As in the spring of  FIGS. 100 and 100A , the elongated band or strip portion  474   a  of the spring is coiled about a spring drum Z in predetermined varying degrees of tightness. Accordingly, like the earlier described variable force springs in which the elongated band or strip portion of the spring has been modified to exhibit a cross-sectional mass that varies along the length of the band, springs with a variation of coil tightness such as illustrated in  FIGS. 100 and 100A , can produce highly specific and desirable linear and non-linear force-distention curves to meet the fluid delivery requirements of the invention. As before, this type of “inter-wound negative gradient” spring has no slot. In fact, it is that the winding process is done precisely to create a “negative gradient” so that as the spring retracts, it provides a higher force. Springs with a variation of coil tightness that produce highly specific and desirable linear and non-linear force-distention curves to meet the fluid delivery requirements of the invention, are available by custom order from various sources, including Vulcan Mfg. &amp; Spring Company of Telford, Pa. 
     Having now described the invention in detail in accordance with the requirements of the patent statutes, those skilled in this art will have no difficulty in making changes and modifications in the individual parts or their relative assembly in order to meet specific requirements or conditions. Such changes and modifications may be made without departing from the scope and spirit of the invention, as set forth in the following claims.