Abstract:
Injection devices, systems and methods are disclosed for injecting two or more medicaments to a patient at a single injection site while preferably minimizing any mixing of the medicaments prior to delivery to the patient. The invention can also be used to sequentially deliver the medicaments to the patient in a repetitive manner. For example, the injection apparatus can sequentially provide a first medicament and then a second medicament to the patient during a first injection procedure. During a second injection procedure, the injection apparatus can again sequentially provide the first medicament and the second medicament to the patient either at the injection site of the first injection procedure or at a different injection site. Multi-lumen manifolds are disclosed for coupling to conventional drug ampoules, to permit the user to sequentially delivery different medicaments via a single skin penetration. Systems including multiple drug reservoirs and filling adaptors are also disclosed.

Description:
FIELD OF THE INVENTION  
       [0001]     The technical field of the invention concerns medicament injection methods and apparatus, and more particularly to injection techniques and devices for injecting two or more medicaments to a patient at a single injection site (or closely spaced sites).  
       BACKGROUND OF THE INVENTION  
       [0002]     Various devices have been developed for the subcutaneous delivery of medications or other treatment agents to a patient. For example, conventional injection devices include a syringe and a hollow needle. The needle is inserted under the skin of the patient and a syringe plunger delivers a medicament, typically a liquid medicament, contained within the syringe through the needle and into the skin.  
         [0003]     There are various situations where it is desirable to deliver two medicaments. For example, injection devices are used to deliver wrinkle-reducing agents, such as botulism toxin (e.g., BOTOX) or collagen, to facial areas of a patient. Subcutaneous injection of such cosmetic agents, however, typically is painful. To minimize the pain associated with such injections, it may be advantageous to administer a local anesthetic at the target site prior to injection of the therapeutic or cosmetic agent.  
         [0004]     In such applications, two separate injection devices would be needed: a first injection device containing an anesthetic compound and a second injection device containing the cosmetic agent. The needle of the first injection device must penetrate the target skin region so that the anesthetic agent can delivered to the patient, and then is withdrawn. Next, the needle of the second injection device penetrates the same site so that the cosmetic agent can be delivered.  
         [0005]     This procedure would need to be repeated numerous times during a facial cosmetic treatment. While the use of the anesthetic can reduce pain during treatment, each injection site of the patient usually requires two separate needle insertions or needle “sticks”. Multiple needle insertions can traumatize the injection site and cause the patient&#39;s skin to become discolored (e.g., black-and-blue) at the site.  
         [0006]     Registration of the first and second injections can also be difficult unless the target sites are marked in advance (e.g., by drawing dots on the patient&#39;s face with a marker). Moreover, the overall time to perform the treatment procedure is lengthened by the need for separate and sequential delivery of the different medicaments.  
         [0007]     Simultaneous deliver of two medicaments may be desirable but is usually not practical. Even if two drugs could be mixed without side effects, the nature of the formulations (e.g., solvents, pH, and storage temperature constraints), would typically preclude direct co-administration  
         [0008]     Thus, there is a need for improved medicament delivery systems that allow independent subcutaneous delivery of multiple medicaments to a patient during a single injection while limiting mixing of the medicaments prior to delivery to the patient.  
       SUMMARY OF THE INVENTION  
       [0009]     Injection devices, systems, and methods are disclosed for injecting two or more medicaments to a patient at a single injection site. The injection apparatus is preferably adapted to minimize mixing of the medicaments prior to delivery to the patient.  
         [0010]     The injection apparatus can be used to sequentially deliver two or more medicaments to the patient in a repetitive manner. For example, the injection apparatus can sequentially provide a first medicament and then a second medicament to the patient during a first injection procedure. The injection apparatus can then sequentially provide the first medicament and the second medicament to the patient during a second injection procedure either at the injection site of the first injection procedure or at a different injection site.  
         [0011]     In one aspect of the invention, multi-lumen manifolds are disclosed for coupling to conventional drug syringes or other drug delivery sources, to permit the user to sequentially delivery different medicaments via a single skin penetration. A manifold according to the invention can included a manifold body, at least one injector adapted to penetrate skin, and at least two lumens disposed within the manifold body to provide fluidic coupling between separate medicament sources and a target tissue site. The injector can further include a hollow needle having a single or multiple lumens, e.g., concentric tubular needle elements or nested needle elements to deliver the different medicaments.  
         [0012]     In another aspect of the invention, injection systems are disclosed that can include a hollow inner needle defining a first lumen fluidically couplable to a first medicament reservoir and a first fluid delivery actuator and a hollow outer needle having a distal end that at least partially surrounds the inner needle, the outer needle defining a second lumen fluidically couplable to a second medicament reservoir and a second fluid delivery actuator. The injection apparatus can be used to penetrate tissue and independently deliver at least two separate medicaments from the first and second medicament reservoirs to a patient.  
         [0013]     In another aspect of the invention, filling adaptors are provided for filling a multi-lumen injection apparatus with a medicament. The filling adaptor can include a fitting for fluidically coupling the adaptor to container of a medicament and a body defining a fluid passageway from a coupled medicament container to a lumen of a multi-lumen injection apparatus. The filling adaptor can also include a lumen engagement portion configured to engage at least one lumen of a multi-lumen injection apparatus and block access of the medicament to the one lumen while the passageway is aligned with another lumen of the multi-lumen injection apparatus to allow passage of the medicament to the other lumen.  
         [0014]     In another aspect of the invention, an injection kit is provided. The injection kit can include an injection apparatus for independently delivering a plurality of medicaments and one or more filling adaptors. The apparatus can include an inner needle coupled to a first medicament reservoir and an outer needle having a distal end that at least partially surrounds the inner needle, the outer needle coupled to a second medicament reservoir and a second fluid delivery actuator. The filling adaptor can include a first adaptor configured to fill the first medicament reservoir and a second adaptor configured to fill the second medicament reservoir.  
         [0015]     In another aspect of the invention, a method delivering a plurality of medicaments is disclosed. A multi-lumen injection apparatus can be disposed adjacent to a target skin region, the injection apparatus having at least a first reservoir containing a first medicament and a second reservoir containing a second medicament. The apparatus can also include a hollow inner needle defining a first lumen fluidically couplable to a first medicament reservoir and a hollow outer needle having a distal end that at least partially surrounds the inner needle and defining a second lumen fluidically couplable to a second medicament reservoir. The skin region can then be penetrated with the injection apparatus and the first medicament and the second medicament applied. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0016]     The invention will be more fully understood from the following detailed description taken in conjunction with the accompanying drawings, in which:  
         [0017]      FIG. 1  is a cross-sectional schematic side view of a multi-lumen injection apparatus according to the invention.  
         [0018]      FIG. 2  is a schematic illustration of a concentric dual plunger arrangement for an injection apparatus.  
         [0019]      FIG. 3  is a cross-sectional top view of the apparatus of  FIG. 1  along section line  3 - 3 .  
         [0020]      FIG. 4  is a schematic illustration of an alternative embodiment of the invention employing a split plunger arrangement.  
         [0021]      FIG. 5  is a schematic view of a distal needle-coupling end cap for use within the embodiment of  FIG. 4 .  
         [0022]      FIG. 6  is a schematic diagram of an automated injection system according to an embodiment of the invention.  
         [0023]      FIG. 7  is a cross-sectional view of the injection manifold of  FIG. 1  along section line  7 - 7  according to an embodiment of the invention.  
         [0024]      FIG. 8  is a cross-sectional view of the injection manifold of  FIG. 1  along section line  8 - 8  according to another embodiment of the invention.  
         [0025]      FIG. 9  is a cross-sectional view of an injection manifold according to an embodiment of the invention.  
         [0026]      FIG. 10  is a schematic side view of a filling adaptor for filling a multi-lumen injection apparatus with medicaments.  
         [0027]      FIG. 11  is a cross-sectional view of an adaptor as shown schematically in  FIG. 10  for filling an inner lumen of a multi-lumen injection apparatus.  
         [0028]      FIG. 12  is a cross-sectional view of an adaptor as shown schematically in  FIG. 10  for filling an outer lumen of a multi-lumen injection apparatus.  
         [0029]      FIG. 13  is a cross-sectional view of an injection manifold having a single needle according to an embodiment of the invention.  
         [0030]      FIG. 14  is a cross-sectional view of an injection manifold having a single needle according to another embodiment of the invention. 
     
    
     DETAILED DESCRIPTION  
       [0031]     For a fuller appreciation of the invention, various terms used in this specification are defined. The term “medicament” as used herein is intended to encompass not only prescription and over-the-counter drugs, but also various other therapeutic and cosmetic agents, including, not limited to anesthetic agents, toxins, nerve relaxing agents, vitamins, collagen and other biocompatible fillers, sunscreens, pigmentation and/or skin bleaching agents, synthetic and natural agents, including small molecules and larger molecules, such as peptides, proteins, lymphokines, growth factors, hormones, antibodies, conjugates of antibodies with other agents, and other chemical or biological molecules that can provide desired effects when injected into biological tissue. The term “medicament” as used herein further encompasses water, saline, and lumen-cleaning or purging solutions.  
         [0032]      FIG. 1  illustrates an injection apparatus  10  in accordance with the present invention having a medicament delivery portion  12  and an injection manifold  14  in fluid communication with the medicament delivery portion  12 . The medicament delivery portion  12  is configured to provide independent delivery of at least two separate medicaments to a patient via the injection manifold  14 . The injection manifold  14  is configured to penetrate tissue of a patient and allow independent transmission of separate medicaments while limiting or preventing mixing of the medicaments prior to delivery to the patient.  
         [0033]     The medicament delivery portion  12  can include a number of medicament reservoirs that contain and allow delivery of separate medicaments to a patient. As illustrated in  FIG. 1 , the medicament delivery portion  12  can include a first reservoir assembly  13  having a first reservoir  16  defining a first lumen  17  and a first actuator  20 . The medicament delivery portion  12  can also include a second reservoir assembly  15  having a second reservoir  18  defining a second lumen  19  and a second actuator  22 . In one embodiment, the first reservoir assembly  13  and the second reservoir assembly  15  can be configured as syringes where the first  16  and second  18  reservoirs are formed as substantially cylindrical syringe chambers and the first  20  and second  22  actuators are formed as syringe plungers.  
         [0034]     Each of the first  16  and second  18  reservoirs can be configured to contain separate medicaments for delivery to the injection manifold  14 . For example, the first reservoir  16  can be configured to contain a first medicament within the first lumen  17 , such as an agent used in cosmetic surgery (e.g., BOTOX, collagen, RESTYLANE) and a second reservoir  18  can be configured to contain a second medicament within the second lumen  19 , such as an anesthetic agent (e.g., Novocain, lidocaine).  
         [0035]     Each of the first  20  and second  22  actuators can also be configured to provide independent delivery of the medicaments from each of the respective reservoirs  16 ,  18  to the injection manifold  14 . For example, operation of the first actuator  20  (e.g., depression of the first syringe plunger) can deliver a portion of the medicament contained within the first reservoir  16  to the injection manifold  14  while operation of the second actuator  22  (e.g., depression of the second syringe plunger) can deliver a portion of the medicament contained in the second reservoir  18  to the injection manifold  14 . With each actuator  20 ,  22  configured to operate independently from the other, the injection apparatus  10  can provide independent subcutaneous delivery of multiple medicaments to a patient during a single injection (i.e., at a single injection site).  
         [0036]     The injection manifold  14  can couple to the medicament delivery portion  12  via a connector  26 . For example, the connector  26  can be a threaded connector, a Luer locking element, or some other connecting element useful for providing a sealed fluidic coupling between the injection manifold  14  and the medicament delivery portion  12 . In one embodiment, the connector  26  can align the lumens  17 ,  19  of the medicament reservoirs  16 ,  18  with corresponding hollow needles associated with the injection manifold  14  to provide fluid communication between the medicament delivery portion  12  and the injection manifold  14 .  
         [0037]     The injection manifold  14  can include a number of hollow needles configured to transmit medicaments from the medicament delivery portion  12  to a tissue while limiting mixing of the medicaments prior to delivery to the tissue. For example, in one embodiment, the injection manifold  14  can include an inner needle  28  in fluid communication with the first reservoir  16  and an outer needle  30  that at least partially surrounds the inner needle  28  and in fluid communication with the second reservoir  18 . In another embodiment, the injection manifold  14  can include more than two needles. For example, the injection manifold  14  can include a two inner needles disposed within the outer needle  28 , each inner needle in fluid communication with a corresponding (e.g., separate) reservoir assembly.  
         [0038]     In one embodiment, the outer needle  30  includes a first end  36  that can couple to the second reservoir  18  via the connector  26 , a second end  38  configured to insert within a tissue of a patient, and a lumen  40  extending between the first end  36  and the second end  38  and in fluid communication with the lumen  19  of the second reservoir  18 . In one embodiment, the outer needle  30  can be smaller than a 28 gauge needle. For example, the outer needle can be a 30 gauge needle having an outer diameter  33  of approximately 0.31 mm and an inner (e.g., lumen) diameter  34  of approximately 0.19 mm.  
         [0039]     In one embodiment, the inner needle  28  includes a first end  42  that can couple to the first reservoir  16  via the connector  26 , a second end  44  configured to insert within a tissue of a patient, and a lumen  46  extending between the first end  42  and the second end  44  and in fluid communication with the lumen  17  of the first reservoir  16 . In one embodiment, the inner needle  28  can be smaller than a 30 gauge needle. For example, the inner needle  28  can be a 36 gauge needle having an outer diameter of approximately 0.11 mm and an inner (e.g., lumen) diameter  32  of approximately 0.06 mm. In another example, the needle can be a 34.5 gauge needle having an outer diameter  31  of approximately 0.15 mm and an inner (e.g., lumen) diameter  32  of approximately 0.08 mm.  
         [0040]     The relatively small sizes of the lumens  46 , 40  of the needles  28 , 30 , combined with the positioning of the needles  28 ,  30  relative to each other (e.g., such as when the outer needle  30  surrounds a portion of the inner needle  28 ) can minimize an effect of capillary action within the lumens  46 ,  40  of the needles  28 ,  30 . As such, the gauge size and relative positioning of the needles  28 ,  30  can minimize or prevent mixing or the exchange of medicaments between the needles  28 ,  30 .  
         [0041]     For example, regarding the capillary properties of a lumen or tube, generally the narrower the tube the further a liquid can be drawn within the tube. Referring to  FIG. 1 , assume a 36 gauge inner needle  28  inserts within a lumen  40  of a 30 gauge outer needle  30 . Because the lumen  40  of the outer needle  30  can be relatively larger than the lumen  46  of the inner needle  28  (i.e., the lumen  46  of the inner needle  28  is narrower than the lumen  40  of the outer needle  30 ), the lumen  40  can draw a medicament to a lower (i.e., more proximal) level  50  within the injection manifold  14  relative to a higher (i.e., more distal) level  52  of the medicament drawn by the lumen  46 . Such positioning of the medicaments within the lumens  46 ,  40  can minimize or prevent mixing of the medicaments carried by the needles  28 ,  30 .  
         [0042]     In one embodiment, one of the needles  28 ,  30  of the injection manifold  14  can be configured with a cutting surface to allow the injection manifold  14  to penetrate the tissue of a patient. For example, the second end (e.g., distal tip)  38  of the outer needle  30  can be configured with a beveled edge  48  that can cut into tissue and allow insertion of the outer needle  30  and the inner needle  28  into the tissue of a patient. In another embodiment, one of the needles  28 ,  30  of the injection manifold  14  can be configured with a non-cutting surface. For example, the second end (e.g., distal tip)  44  of the inner needle  30  can be configured as having a blunt (e.g., non-cutting) surface.  
         [0043]     In one embodiment, the second end  44  of the inner needle  28  can be recessed (e.g., shorter) relative to the distal tip  38  of the outer needle  30  to minimize contact between the inner needle  28  and the tissue of a patient as the outer needle  30  inserts within the tissue of the patient during an injection procedure. As such, the recess limits axial loading of the inner needle  28  by the tissue and thereby minimizes the possibility of the inner needle  28  bending or fracturing during an injection procedure.  
         [0044]     During operation, the injection apparatus  10  can deliver medicaments carried by the injection apparatus  10  to a patient. For example, the injection apparatus  10  can penetrate a skin region of a patient, such as at an injection site. In one embodiment, the distal tip  38  of the outer needle  30  can pierce the tissue of the patient at the injection site such that the distal tip  38  of the outer needle  30  and the distal tip  44  of the inner needle  28  insert within the tissue. The injection apparatus  10  can then deliver a first medicament to the patient at the injection site. For example, the second actuator  22  associated with the second reservoir  18  can be actuated to deliver a portion of the medicament contained in the second reservoir  18 , such as an anesthetic agent, through the lumen  40  of the outer needle  30  and into the tissue.  
         [0045]     Following injection of the first medicament, the injection apparatus  10  can then deliver a second medicament to the injection site either at substantially the same depth as the first medicament or at a different depth than the first medicament. In one embodiment, the position of the injection apparatus can be maintained relative to the injection site, thereby maintaining the relative position of the inner needle within the tissue. In another embodiment, the injection apparatus  10  can advance into the tissue such that the inner needle  28  positions at a different depth than the outer needle  30 . The first actuator  20  associated with the first reservoir  16  can then be actuated, independently from the second actuator  22 , to deliver a portion of the medicament contained in the first reservoir  16 , such as a cosmetic agent, through the lumen  46  of the inner needle  28  and into the tissue.  
         [0046]     Also during operation, the medicament delivery process described above can be repeated to deliver additional doses of the medicaments to the patient. In one embodiment, each medicament from the first  16  and second  18  reservoirs can be repeatedly delivered to the patient at the same injection site. For example, after the apparatus  10  has delivered doses of the first and second medicaments to the tissue, the apparatus  10  can deliver a second dose of the first and second medicaments to the tissue. In another embodiment, after delivery of the first and second medicaments to the patient at a first injection site, the injection manifold  14  can be removed from the first injection site and inserted within a second (e.g., different) injection site of the patient. Alternating delivery of the first and second medicaments from the first  16  and second  18  reservoirs can then be repeated for the second, and subsequent, injection sites of the patient.  
         [0047]     As indicated above, the injection apparatus  10  can allow independent subcutaneous delivery of multiple medicaments to a patient during a single injection while limiting mixing of the medicaments prior to delivery to a patient. The injection apparatus  10  can be configured in a variety of ways to allow such medicament delivery to the patient.  
         [0048]     In one example, the reservoir assemblies  13 ,  15  can be positioned relative to each other in various configurations. In one embodiment as illustrated in  FIG. 1 , the first reservoir assembly  13  is disposed within the second reservoir assembly  15 . For example, the first reservoir assembly  13  can be positioned concentrically relative to the second reservoir assembly  15  such that the first actuator  20  and the second actuator  22  align along a common longitudinal axis  25 , as also illustrated in  FIG. 2 . With such a configuration, the second actuator  22  can define an opening  23  through which the second first actuator  20  can extend, thereby allowing independent actuation of the first  20  and second  22  actuators.  
         [0049]     Returning to  FIG. 1 , with the first reservoir assembly  13  is disposed within the second reservoir assembly  15 , the medicament delivery portion  12  can include structures that couple the fluid reservoirs  16 ,  18  to each other. For example, the medicament delivery portion  12  can include an end cap  24 , such as disposed at a first or proximal end  25  of the medicament delivery portion  12  and one or more struts  33 , such as disposed at a second or distal end  27  of the medicament delivery portion  12 .  
         [0050]     The end cap  24  can couple the first reservoir  16  and the second reservoir  18  to provide a degree of rigidity or stability to the apparatus  10 . The end cap  24  can also maintain a spaced-apart relationship between the first reservoir  16  and the second reservoir  18  at the proximal end  25  of the medicament delivery portion  12 . For example, the end cap  24  orients the first reservoir  16  relative to the second reservoir  18  to define a toroid-shaped lumen  19  between the walls of the reservoirs  16 ,  18  for containment of a medicament within the second reservoir  18 .  
         [0051]     As shown in  FIGS. 1 and 3 , the struts  36  are disposed between the first reservoir  16  and the second reservoir  18  and can couple the first reservoir  16  and the second reservoir  18  to provide a degree of rigidity or stability to the apparatus  10 . The struts  36  can also maintain a spaced-apart relationship between the first reservoir  16  and the second reservoir  18  at the distal end  25  of the medicament delivery portion  12 . For example, the struts  36  can divide the lumen  19  formed between the walls of first reservoir  16  and the second reservoir  18  into subsections, such as a first lumen  19 - 1 , a second lumen  19 - 2 , a third lumen  19 - 3 , and a fourth lumen  19 - 4  to maintain a fluid pathway between the second reservoir  18  and the injection manifold  14 .  
         [0052]     While the reservoir assemblies  13 ,  15  can be positioned within one another, as described above, the reservoir assemblies  13 ,  15  can also be positioned in a side-by-side or adjacent relationship. For example,  FIGS. 4 and 5  illustrate an embodiment of the injection apparatus  10 ′ configured with a first reservoir assembly  13 ′, having a first reservoir  16 ′ and a first actuator  20 ′, positioned adjacent to a second reservoir assembly  15 ′ having a second reservoir  18 ′ and a second actuator  22 ′. As shown in  FIG. 4 , the actuators  20 ′,  22 ′ can be configured as independently actuatable in a “split plunger” arrangement to allow independent delivery of medicaments to an injection site.  
         [0053]     With the reservoir assemblies  13 ′,  15 ′ positioned in a side-by-side or adjacent relationship, the injection manifold can be configured to attach to the adjacent reservoir assemblies  13 ′,  15 ′ to provide fluid communication between the associated reservoirs  16 ′,  18 ′ and the needles of the injection manifold. For example, the injection apparatus  10 ′, as shown in  FIG. 5 , can include an injection manifold  14 ′ coupled to the first  16 ′ and second  18 ′ reservoirs and having an inner needle  28 ′ and an outer needle  30 ′. While the needles  28 ′,  30 ′ are illustrated as being substantially aligned (e.g., aligned along a longitudinal axis) with the first reservoir  16 ′, the needles  28 ′,  30 ′ can be offset relative to the second reservoir  18 ′ (e.g., offset relative to a longitudinal axis of the second reservoir  18 ′). Such an offset provides fluid communication between the adjacently positioned reservoirs  16 ′,  18 ′ and the respective needles  28 ′,  30 ′.  
         [0054]     The actuators  20 ,  22  of the injection assembly  10  can be manually operated to deliver medicaments from the reservoirs  16 ,  18  to the injection manifold  14 . However in one embodiment, operation of the actuators can be automated.  FIG. 6  illustrates an embodiment of a medicament delivery portion  12 ′ of an injection assembly  10  having automated actuators.  
         [0055]     The medicament delivery portion  12 ′ can include a controller  80  in electrical communication with actuators  90 ,  92  and electrically couples to a power supply  86 , such as either an internal power supply (e.g., a battery) or an external power supply. The first actuator  90 , such as a valve, can position in fluid communication with the first reservoir  16  and with the inner needle  28 . The second actuator  92 , such as a valve, can position in fluid communication with the second reservoir  18  and the outer needle  30 .  
         [0056]     The controller  80  can include a memory  82  and a processor  84 . The memory  82  can be any type of computer readable medium such as electronic semiconductor memory (e.g., Random Access Memory or Read Only Memory), programmable memory (e.g., EEPROM), or another storage or enclosable medium such magnetic or optical disk storage. The processor  84  can be any type of central processing unit, microprocessor, programmable gate array (PGA) or other circuitry that are capable of executing, interpreting, operating, being configured with, or otherwise performing sets of logic instructions such as computer program code. A data bus  83  or other circuitry can interconnect the memory  82  and the processor  84 .  
         [0057]     The controller  80 , in one embodiment, is configured to control delivery of a proscribed dosage (e.g., volume) of the medicaments contained within the reservoirs  16 ,  18  to an injection site. For example, based upon instructions stored in the memory  82  and executed by the processor  84 , at a first time, the controller  80  can send a first signal to the first actuator  90  and to the second actuator  92 . The first signal can cause the first actuator  90  to prevent the flow of medicament from the first reservoir  16  to the inner needle  28  and can cause the second actuator  92  to allow a flow of medicament from the second reservoir  18  to the outer needle  30 . After delivery of a proscribed dosage of the medicament from the first reservoir  16 , the controller  50  can then send a second signal to the first  90  and second  92  actuators that can cause the first actuator  90  to allow a flow of medicament from the first reservoir  16  to the inner needle  28  and can cause the second actuator  92  to prevent a flow of medicament from the second reservoir  18  to the outer needle  30 . Such automated delivery can provide sequential delivery of medicaments to a single injection site and can allow delivery of substantially precise dosages of the medicaments to the site.  
         [0058]     As indicated above, the injection manifold  14  can deliver multiple medicaments to a patient during a single injection while limiting or preventing mixing of the medicaments prior to delivery to the patient. The injection manifold  14  can be configured in a variety of ways to allow such medicament delivery to the patient.  
         [0059]     In one embodiment, the needles  28 ,  30  are oriented substantially coaxially relative to each other. For example,  FIG. 7  illustrates an embodiment of a 30 gauge inner needle  28  coaxially disposed within a 36 gauge outer needle  30 . The 30 gauge inner needle  28  defines a lumen  46  having cross-sectional area of approximately 2800 μm 2 . The annular cross-sectional area of a lumen  40  formed between an outer wall  52  of the inner needle  28  and an inner wall  54  of the outer needle  30  is approximately 18,800 μm 2 . The relatively large lumen  40  formed between the outer needle  28  and the inner needle  28  reduces the capillary properties of the lumen  40  and minimizes mixing of the medicaments carried by the needles  28 ,  30 .  
         [0060]     In another embodiment, the needles  28 , 30  are oriented in a substantially eccentric manner relative to each other.  FIG. 8  illustrates an embodiment of a 34.5 gauge inner needle  28 ′ eccentrically disposed within the 36 gauge outer needle  30  (e.g., a longitudinal axis of the inner needle  28 ′ is offset from a longitudinal axis of the outer needle  30 ). The 30 gauge inner needle  28 ′ has a lumen  50 ′ having a cross-sectional area of approximately 5000 μm 2 . The annular cross-sectional area of a lumen  58 ′ formed between an outer wall  52 ′ of the inner needle  28 ′ and an inner wall  54 ′ of the outer needle  30 ′ is approximately 10,700 μm 2 . The relatively large lumen  58 ′ formed between the outer needle  28 ′ and the inner needle  28 ′ reduces the capillary properties of the lumen  58 ′, compared to the relatively small lumen  50 ′ of the inner needle  28 ′, and minimizes mixing of the medicaments carried by the needles  28 ′,  30 ′.  
         [0061]     In one embodiment, the injection manifold  14  can include connection elements that allow one or more reservoir assemblies to attach to the injection manifold  14 . For example,  FIG. 9  illustrates an embodiment of the injection manifold  14 ″ having hubs  140  configured to allow attachment of medicament reservoirs to the injection manifold  14 ″. In one embodiment, the injection manifold  14 ″ includes a first hub  140 - 1  and a second hub  140 - 2  for attachment of a first medicament reservoir  16  and a second medicament reservoir  18 , respectfully.  
         [0062]     The injection manifold  14 ″ can include fluid pathways formed between the hubs  40  and corresponding needles. In one embodiment, the injection manifold  14 ″ can include a first fluid pathway  142  between the first hub  140 - 1  and the inner needle  28  for transmission of a first medicament from the first reservoir  16  to the inner needle  28  and can also include a second fluid pathway  144  between the second hub  140 - 2  and the outer needle  30  for transmission of a second medicament from the second reservoir  18  to the outer needle  30 . In one embodiment, the injection manifold  14 ″ can include a distributor  147  positioned between the second fluid pathway  144  and the outer needle  30 . The distributor  147  can be configured to provide a substantially uniform distribution of the second medicament from the second fluid pathway  144  to the outer needle  30 .  
         [0063]     The injection apparatus  10  can be provided prior to use (e.g., such as by a manufacturer) with each of the medicament reservoirs filled with a separate (e.g., distinct) medicament. However, in certain cases, the injection apparatus  10  can be provided with substantially empty medicament reservoirs that require filling prior to use of the injection apparatus  10 . As indicated above, however, the injection assembly  10  can include two or more needles, each in fluid communication with a medicament reservoir. In one embodiment, a filling adaptor can be provided to allow the medicament reservoirs of the injection apparatus  10  to be selectively filled prior to use using the needles of the apparatus  10 .  
         [0064]      FIG. 10  illustrates a filling adaptor  70  that can provide the medicament reservoirs (e.g., lumens  17 ,  19  of the reservoirs  16 ,  18 ) with access to a medicament, such as contained within a container  72 . In one embodiment, the adaptor  70  can include a fitting portion  74  and a body portion  76 . The fitting portion  74  can be configured to couple the adaptor  70  to the container  72  and the body portion  76  can be configured to provide selective access to the medicament within the container. As will be described with respect to  FIGS. 11 and 12 , the body portion  76  can define a fluid passageway that provides a first lumen of the injection assembly  10  access to the medicament and can also include a lumen engagement portion, such as formed as an elastomeric pad, that can block a second lumen of the injection assembly  10  access to the medicament.  
         [0065]      FIG. 11  illustrates an embodiment of the adaptor  70  configured to provide medicament access to an inner needle  28 , and an associated reservoir  16  of the injection assembly  10 . The body portion  76  can define an opening  79  oriented substantially at a central location of the adaptor  70  and configured to align with the lumen  46  of the inner needle  28 . The body portion  76  can also include an engagement portion  78  oriented substantially about a circumference of the adaptor  70  and configured to align with or engage the lumen  40  between the inner needle  28  and the outer needle  30 .  
         [0066]     During operation, as the injection manifold  14  inserts within the adaptor, the inner needle  28  can insert within the opening  79  and the outer needle  30  can engage the engagement portion  78 . As a result, the lumen  46  of the inner needle  28  can access the medicament contained in the container  72 , thereby allowing the associated medicament reservoir  16  to be filled with the medicament. Additionally, the material forming the engagement portion  78  can fill or substantially encompass a cross-sectional area of the lumen  40  between the inner needle  28  and the outer needle  30  thereby limiting or preventing the lumen&#39;s  40  access to the medicament contained in the container  72  and preventing the associated medicament reservoir  18  from being filled with the medicament.  
         [0067]      FIG. 12  illustrates an embodiment of the adaptor  70  configured to provide medicament access to an outer needle  30 , and an associated reservoir  18  of the injection assembly  10 . The body portion  76  can define one or more openings  79 ′ positioned substantially about a circumference of the adaptor  70  and configured to align with the lumen  40  between the inner needle  28  and the outer needle  30 . The body portion  76  can also include an engagement portion  78 ′ oriented substantially at a central location of the adaptor  70  and configured to align with the lumen  46  of the inner needle  28 .  
         [0068]     During operation, as the injection manifold  14  inserts within the adaptor, the outer needle  30  can insert within the opening  79 ′ and the inner needle  28  can engage the engagement portion  78 ′. As a result, the lumen  40  between the inner needle  28  and the outer needle  30  can access the medicament contained in the container  72 , thereby allowing the associated medicament reservoir  18  to be filled with the medicament. Additionally, the material forming the engagement portion  78 ′ can fill or substantially encompass a cross-sectional area the lumen  46  of the inner needle  28  thereby limiting or preventing the lumen&#39;s  46  access to the medicament contained in the container  72  and preventing the associated medicament reservoir  16  from being filled with the medicament.  
         [0069]     As indicated above, the injection manifold  14  is configured to penetrate tissue of a patient and allow independent transmission of separate medicaments while limiting or preventing mixing of the medicaments prior to delivery to the patient. As described in  FIGS. 7-9 , the injection manifold can include a number of concentric or otherwise nested needles configured to transmit medicaments from the medicament delivery portion  12  to the patient. However, in other embodiments, the injection manifold  14  includes a single needle that allows independent transmission of separate medicaments while limiting or preventing mixing of the medicaments prior to delivery to the patient.  
         [0070]      FIG. 13  illustrates an embodiment of an injection manifold  100  having ports  102 , a needle  104 , and fluid pathways  106  disposed between the needle  104  and the ports  102 . The injection manifold  100  can include a first port  102 - 1  and a second port  102 - 2  that can be configured to couple to drug sources, e.g. drug-loaded syringes, containing distinct medicaments. The fluid pathways can include a first pathway  106 - 1  and a second fluid pathway  106 - 2  in fluid communication with the first port  102 - 1  and the second port  102 - 2  and in fluid communication with a lumen  108  defined by the needle  104 . The needle lumen  108  can have a diameter that minimizes or prevents the medicaments sequentially delivered from the first port  102 - 1  and the second port  102 - 2  from mixing within the needle  104 . For example, in one embodiment the needle  104  can be configured as a 30 gauge needle (e.g., having a diameter of approximately 0.19 mm).  
         [0071]     While the embodiment of the injection manifold  100  illustrated in  FIG. 13  is shown as having two ports  102  and two fluid pathways  106 , the injection manifold  100  can have more than two ports  102  and two fluid pathways  106 . For example,  FIG. 14  illustrates another embodiment of an injection manifold  100  having a first port  102 - 1 , a second port  102 - 2 , and a third port  102 - 3  configured to couple to a third reservoir. The injection manifold  100  can also have a third fluid pathway  106 - 3  disposed between the third port  106 - 3  and the lumen  108  of the needle  104 .  
         [0072]     In one embodiment, the third port  102 - 3  can couple to a reservoir containing a saline solution. In such an embodiment, the third fluid pathway  106 - 3  is configured to direct saline from the reservoir and through the lumen  104  of the needle  108  prior to delivery of a first medicament from the first port  102 - 1  to the needle  104  and prior to delivery of a second medicament from the second port  102 - 2  to the needle  104 . The saline can flush the lumen  108  of the needle prior to delivery of the medicament from either port  102 - 1 ,  102 - 2 , thereby minimizing mixing of medicaments within the needle  104 .  
         [0073]     One skilled in the art will appreciate further features and advantages of the invention based on the above-described embodiments. Accordingly, the invention is not to be limited by what has been particularly shown and described, except as indicated by the appended claims. All publications and references cited herein are expressly incorporated by reference in their entirety.