US 20070149945 A1
An intradermal delivery device for delivery a substance into the skin of a patient has a fluid chamber for containing the substance, at least one micro skin penetrating member, and a valve controlling the flow of the substance from the fluid chamber to the micro skin penetrating member. An adhesive releasably attaches the device to the skin of the patient, the fluid chamber can be sized to hold a unit dose of the substance, and, in some embodiments, the fluid chamber can be releasably coupled to a housing of the device.
1. A method for delivering a substance into the skin of a patient, comprising:
positioning on the skin of a patient a delivery device including a housing, a fluid chamber having an outlet, a substance in the fluid chamber, a manually operated valve for controlling movement of the substance through the outlet of said fluid chamber, and at least one skin penetrating member in fluid communication with said channel;
applying a pressure sufficient for said skin penetrating members to penetrate said skin to a depth sufficient to deliver said substance to the patient; and
opening said valve to enable the substance to move from said fluid chamber, through said skin penetrating members, and into the skin of the patient.
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This Application is a divisional of U.S. patent application Ser. No. 10/112,756, filed on Apr. 2, 2002, now U.S. Pat. No. X,XXX,XXX.
The present invention relates to an intradermal delivery device having a fluid chamber to contain a substance to be delivered intradermally to a patient in a target area of the skin. The present invention also relates to a method of delivering a substance into the skin of a patient.
Drugs and pharmaceutical agents are delivered to patients by a variety of methods. A typical method delivers the drug or pharmaceutical agent subcutaneously by a stainless steel cannula. Although the subcutaneous sampling and delivery methods using a cannula are effective for many applications, the pain normally induced by the cannula has prompted the development of less painful delivery methods.
The skin is made up of several layers, with the upper composite layer being the epithelial layer. The outermost layer of the skin, the stratum corneum, is a waterproof membrane with well known barrier properties that prevent the influx of undesirable molecules and various foreign substances while preventing the outflux of various analytes. The stratum corneum is a complex structure of compacted keratinized cell remnants having a thickness of about 10-30 microns.
The natural impermeability of the stratum corneum prevents the administration of most pharmaceutical agents and other substances through the skin. Numerous methods and devices have been proposed to enhance the permeability of the skin and to increase the diffusion of various drugs through the skin for utilization by the body. Typically, the delivery of drugs through the skin is enhanced by increasing either the permeability of the skin or the force or energy used to direct the drug through the skin.
Another method of sampling and delivering various substances through the skin is by forming micropores or cuts through the stratum corneum. By piercing the stratum corneum and delivering a drug to the skin in or below the stratum corneum, many drugs can be administered effectively. In a similar manner, some substances can be extracted from the body through cuts or pores formed in the stratum corneum. The devices for piercing the stratum corneum generally include a plurality of micron size needles or blades having a length to pierce the stratum corneum without passing completely through the epidermis. Examples of these devices are disclosed in U.S. Pat. No. 5,879,326 to Godshall et al.; U.S. Pat. No. 5,250,023 to Lee et al., and WO 97/48440.
The above-noted devices that include micron-sized needles or blades can be effective in delivering substances to the body. However, these needles and blades having a length of a few microns to a few hundred microns typically do not penetrate skin to a uniform depth. The natural elasticity and resilience of the skin will often result in the skin being deformed by the needles rather than pierced. A microneedle array when pressed against the skin often results in the outermost needles penetrating the skin while the innermost needles do not penetrate or only penetrate to depth less than the outermost needles.
The prior methods and devices for the intradermal administration of substances have exhibited limited success. Accordingly, an unmet need exists in the industry for an improved device for the sampling and administration of various drugs and other substances to the body.
The present invention is directed to a method and device for the intradermal sampling or delivery of a substance into the skin of a patient. More particularly, the invention is directed to a method and device for controlling the flow of a pharmaceutical agent, such as a drug or vaccine, through the device for delivery into or below the stratum corneum of the skin to a depth sufficient for the pharmaceutical agent to be absorbed and utilized by the body.
Accordingly, it is an object of the invention to provide a sampling or delivery device having at least one skin penetrating member having a length that provides an increased comfort level to the patient.
A further object of the invention is to provide a method of penetrating the skin for sampling or delivering a substance through the skin substantially without pain to the patient.
Another object of the invention is to provide a delivery device having a plurality of micro skin penetrators, such as microtubes, needles, microneedles, blades or lancets, selected for piercing the stratum corneum of the skin to a depth that is short of the nerve endings.
Still another object of the invention is to provide a delivery device having a manually operated valve to control the delivery of a substance to the at least one micro skin penetrating member of the delivery device.
A further object of the invention is to provide a pre-filled delivery device having a reservoir containing a substance, at least one micro skin penetrating member, and a reservoir outlet for supplying a substance to the micro skin penetrating member for delivery to the patient.
Another object of the invention is to provide a delivery device having a reservoir containing a substance to be delivered to a patient, wherein the reservoir is defined, at least in part, by a movable wall that is depressed to dispense the substance to the patient.
Still another object of the invention is to provide a delivery device having at least one micro skin penetrating member for delivering a substance to a target area on the skin of a patient and a ridge encircling the micro skin penetrating members to form a containment area around the target area.
These and other aspects of the invention are substantially achieved by providing a device for delivering a substance into the skin of a patient. The device comprises a housing having a fluid chamber having an outlet. A valve member is coupled to the housing for controlling the flow of the substance through the outlet of the chamber. A skin penetrating device is coupled to the housing and is in fluid communication with the fluid chamber for delivering the substance to the patient.
The objects and advantages of the invention are further attained by providing a device for intradermally delivering a substance to a patient. The device comprises a housing having a bottom face dimensioned to contact the skin of the patient. The housing has a fluid chamber with an outlet, and a manually operated valve coupled to the housing for controlling the flow of the substance through the outlet of the chamber. A micro skin penetrating member is coupled to the housing and is in fluid communication with the chamber. An arrangement is provided for applying to the substance a pressure sufficient to deliver the substance into the skin of a patient.
A yet further object of the invention is to provide a method for delivering a substance into or through the skin of a patient. The method comprises positioning on the skin of a patient a delivery device including a housing; a fluid chamber on the housing for containing the substance, said chamber having an outlet for the substance; a valve member connected to said housing to control the flow of the substance through the outlet; and a skin penetrating device on the housing and in fluid communication with the chamber for delivering the substance into the skin of the patient. A sufficient pressure is applied for the micro skin penetrating members to penetrate the skin to a depth sufficient to deliver the substance to the patient. The valve is opened, the substance is introduced from the fluid chamber to the micro skin penetrating members under pressure, and the substance is delivered to the patient. In some embodiments, the fluid chamber is removably coupled to the housing before the delivery device is positioned on the skin.
The aspects, advantages and other salient features of the invention will become apparent from the following detailed description which, taken in conjunction with the annexed drawings, discloses preferred embodiments of the invention.
The following is a brief description of the drawings in which:
The present invention is directed to a device for sampling, monitoring or delivering a substance into the skin of a patient. More particularly, the invention is directed to a delivery device and to a method for administering a substance to below the stratum corneum of the skin of a patient.
As used herein, the term “penetrate” refers to entering a layer of the skin without passing completely through. The term “pierce” refers to passing completely through a layer of the skin.
The device and method of the present invention are suitable for use in administering various substances, including pharmaceutical agents, to a patient, and especially to a human patient. As used herein, a pharmaceutical agent includes a substance having biological activity that can be delivered through the body membranes and surfaces, and particularly into the skin. Examples include antibiotics, antiviral agents, analgesics, anesthetics, anorexics, antiarthritics, antidepressants, antihistamines, anti-inflammatory agents, antineoplastic agents, vaccines, including DNA vaccines, and the like. Other substances that can be delivered intradermally to a patient include proteins, peptides and fragments thereof. The proteins and peptides can be naturally occurring, synthesized or recombinantly produced.
The device of the invention is primarily for delivering a substance into selected layers of the skin. In alternative embodiments of the invention, the device is suitable for withdrawing a substance or monitoring the level of a substance in the body. Examples of substances that can be monitored or withdrawn include blood, interstitial fluid or plasma that can then be analyzed for analytes, glucose, drugs and the like.
Referring to the drawings, body 12 forms a housing that has a generally flat profile when attached to the skin of a patient. The flat profile provides an ease of attachment to the skin and less obstruction to the patient. As shown in the embodiment of
As shown in
Base 18 is dimensioned and configured to be placed against the skin of a patient for delivering a substance such as a drug or pharmaceutical. As shown in
Reservoir 28 has an outer wall 40 integrated with the body 12 and spaced from top wall 36 of base 18 to define an internal chamber 42. Chamber 42 is dimensioned to contain a sufficient volume, for example, a predetermined unit dose, of a substance to be delivered to a patient. The chamber 42 is prefilled with the substance. In the embodiment illustrated, outer wall 40 of reservoir 28 has a generally dome shape with a convex outer surface 44 and a concave inner surface 46. Outer wall 40 is coupled to top face 26 of base 18 by a suitable adhesive or a weld to form a fluidtight seal for enclosing reservoir 28.
Reservoir 28 includes an end wall 48 having a channel 50 extending between cavity 38 and chamber 42, the channel 50 defining an outlet of the chamber 42. Outer wall 40 includes a movable dispensing member 52 for applying sufficient pressure to the chamber 42 to dispense a substance from chamber 42 through channel 50 to cavity 38. In the embodiment illustrated, dispensing member 52 is a flexible member that can be depressed inwardly toward chamber 42 to dispense the substance. Dispensing member 52 initially has a concave inner surface 54 to form a generally bubble shape. Preferably, dispensing member 52 is made of a resilient, flexible plastic material that can be depressed and deflected inward by manual pressure by the user. In this embodiment, outer wall 40 is substantially rigid.
Valve assembly 16 is positioned in channel 50 to control the flow of the substance from chamber 42 through channel 50. In this embodiment, valve assembly 16 is a rotatable valve having a valve element, or valve body 56, having a portion exposed to the exterior of the delivery device 10 for manipulation between a closed position and an open position. In the illustrated embodiment, the exposed portion has an actuator handle 58. Referring to
Valve body 56 includes an axial passage 66 extending from lower end 64. A radial passage 68 extends through valve body 56 and intersects axial passage 66. Radial passage 68 is aligned with channel 50 in end wall 48 of reservoir 28 to provide fluid communication between reservoir 28 and cavity 38. Valve body 56 is rotatable within aperture 60 as depicted in
In the illustrated embodiment, micro skin penetrating members 74 are hollow needles each having a beveled tip 76 for penetrating the skin of a patient and an axial passage 78 extending between tip 76 and a top face 80 of base 72. Base 72 has a bottom face 82 supporting micro skin penetrating members 74. Preferably, bottom face 82 of base 72 has a substantially planar configuration and is oriented in the plane of bottom face 24 of base 18.
Skin penetrating device 14, having at least one micro skin penetrating member 74, can be made from various materials. In one embodiment, a plurality of micro skin penetrating members 74 are spaced apart from each other a uniform distance and have a uniform length. The skin penetrating device 14 is made from silicon by, for example, suitable silicon etching or micromachining steps. In other embodiments, device 14 is made from stainless steel, tungsten steel, or alloys of nickel, molybdenum, chromium, cobalt and titanium. Alternatively, the micro skin penetrating members can be made of ceramic materials, polymers and other non-reactive materials.
The micro skin penetrating members 74 have a length suitable to achieve the desired depth of penetration in the skin. The length and thickness of the micro skin penetrating members 74 are selected based on the substance being administered or withdrawn and the thickness of the skin in the location where the device is to be applied. The micro skin penetrating members can be microneedles, microtubes, solid or hollow needles, lancets and the like. Generally, the micro skin penetrating members have a length, measured from the base to the tip of the member, of about 50 microns to about 4,000 microns and preferably, about 250 microns to 1,000 microns. The needles are typically mounted in a suitable base and have a substantially uniform length. In some embodiments, the micro skin penetrating members are about 30-gauge to about 50-gauge needles having a length of about 500 microns to about 1,000 microns. The micro skin penetrating members have a substantially square cross-sectional shape. Alternatively, the micro skin penetrating members can be triangular, cylindrical, or pyramid-shaped, or they can be flat blades.
The skin penetrating members 74 can be in an array covering an area of from about one cm.sup.2 to about 10 cm.sup.2. The array can have a width and length of about one centimeter to about five centimeters. The base 40 has a thickness of about 200 to 400 microns, and typically about 250 microns.
Generally, when the device is used as a delivery device, a pharmaceutical agent or drug solution is provided in the reservoir 28. In alternative arrangements, a dried or lyophilized drug or pharmaceutical agent can be provided in the cavity 38 or in the axial passages 78 of the skin penetrating member 74. A diluent such as distilled water or saline solution can be provided in the reservoir 28 and selectively allowed to flow by manipulation of the valve handle 58 into the cavity 38 and the axial passages 78 of the micro skin penetrating members 74 to dissolve and reconstitute the drug or pharmaceutical agent and then deliver the drug to the patient.
Bottom face 24 of base 18 in the embodiment of
Device 10 is primarily intended to be a prefilled delivery device containing a pharmaceutical agent or drug to be delivered to a patient. In use, device 10 is removed from its protective packaging and positioned on the surface of skin 86 as shown in
After device 10 is positioned on skin 86, valve assembly 16 is rotated to the open position shown in
Device 10, including body 12 and valve assembly 16, is preferably made of a polymeric material that is non-reactive with the substance being delivered to the patient and non-irritating to the patient. Typically, base 12 is made of a suitable plastic material that allows some flexibility to conform to the contour of the skin of the patient while being sufficiently rigid to maintain the structural integrity of device 10. Examples of suitable polymers include polyethylene, polypropylene, polystyrene, polyesters, polyamides, polycarbonates, and copolymers thereof.
Top surface 98 of body 92 includes a recess 102 defined by a bottom surface 104 and a side wall 106. A flexible closure member 108 is coupled to top face 98 to close recess 102. Closure member 108 defines a reservoir having a chamber 110 between bottom surface 104 and closure member 108. As shown in
Side wall 106 of recess 102 includes a channel 116 extending radially outward from side wall 106. An aperture 118 defining a cylindrical channel extends between top surface 98 of body 92 and bottom surface 100. As shown in
Bottom surface 100 of body 92 includes a recess 120 dimensioned to receive skin penetrating device 94. Recess 120 includes a ledge 122 having a side wall 124 for receiving skin penetrating device 94. As shown in
Recess 120 has a bottom surface 106 that is spaced from bottom surface 100 by a distance greater than the thickness of skin penetrating device 94 to define a cavity 128. Aperture 118 communicates with cavity 128 to provide fluid communication between chamber 110 and cavity 128.
Skin penetrating device 94 includes a base 130 having at least one micro skin penetrating member 132 extending outwardly therefrom. As shown in
Valve assembly 96 includes a cylindrical element body 134 dimensioned to fit in aperture 118. An actuating handle 136 is coupled to a top end 138 of valve body 134. Valve body 134 has a bottom end 140 with an axial passage 142. A radial passage 144 extends through a side face 146 of valve body 134 and intersects with axial passage 142. As shown in
Device 90 is used in a manner similar to the embodiment of
Housing 162, as shown in the embodiment of
A supply tube 192 is coupled to collar 180 and extends radially outward from collar 180 in a direction generally parallel to top surface 168 of housing 162. Supply tube 192 includes an axial passage 194 extending radially through collar 180 and intersecting axial passage 182 of collar 180. Supply tube 192 has an outer end with a coupling member 196 for removably coupling a supply device or container 198 to the delivery device 160.
Supply device 198 is removably coupled to coupling member 196. Coupling member 196 can be a luer-type fitting, friction fit or other suitable coupling member capable of forming a fluid coupling with supply device 198.
Supply device 198 is preferably a single use disposable device containing a unit dose of the substance to be delivered to the patient. In the embodiment illustrated, supply device 198 includes a collar 200 and a compressible hollow body 202 containing the substance to be delivered to the patient. Collar 200 complements coupling member 196 for coupling supply device 198 to device 160. In the embodiment illustrated, body 202 is a bladder formed from a flexible material that can be compressed to dispense the contents of supply device 198. In other embodiments, supply device 198 can be a commercially available device containing a predetermined unit dose of a substance to be delivered and being squeezable to deliver the substance. One such device is sold under the trademark UNIJECT by Becton Dickinson and Company. Other unit dose delivery devices can be used instead.
As in the previous embodiments, skin penetrating device 164 includes a base 202 having a top face 206 and a planar bottom face 208. At least one micro skin penetrating member 210 in the form of a microneedle extends outwardly from bottom face 208. Micro skin penetrating members 210 have an axial passage extending between top face 206 in communication with cavity 178 and the tip of skin penetrating member 210. Bottom surface 170 of body 162 includes a rib 212 extending outwardly from body 162. Rib 212 surrounds skin penetrating device 164 and has a substantially annular shape as shown in
In the embodiment illustrated, rib 212 is spaced outwardly from micro skin penetrating members 210 and is impressed on the skin to define a target area on the skin for the micro skin penetrating members 210. Preferably, micro skin penetrating members 210 have an axial length slightly greater than the height of rib 212 as shown in
Device 160 is placed on the skin 220 of a patient and pressed downwardly. The downward pressure on device 160 causes rib 212 to contact skin 220 and stretch the skin in a target area 222 surrounded by rib 212. Stretching the skin in target area 222 enables micro skin penetrating members 210 to pierce the surface of the skin. The normal elasticity of the skin provides a penetrating resistance to micro skin penetrating members 210. By stretching the skin in the target area 222, micro skin penetrating members 210 are better able to pierce the surface of the skin. In addition, rib 212 forms a seal against the surface of skin 220 to contain the substance that can leak from target area 222.
After device 160 is positioned on skin 220, valve body 166 is rotated to the open position shown in
Device 160 is preferably designed and constructed to be a disposable, single use device. The device is prepackaged in a sterile condition for immediate use. In the illustrated embodiment, bottom face 170 of body 162 includes a protective cover sheet 226. Cover sheet 226 is attached to bottom surface 170 in a manner that can be peeled easily from device 160 at the time of use. Cover sheet 226 is preferably a flexible sheet material such as Tyvek.RTM. Cover sheet 226 has a dimension to cover skin penetrating device 164 to maintain skin penetrating device 164 in sterile conditions until ready for use. Cover sheets similar to cover sheet 226 can be used in connection with other embodiments according to the present invention.
The illustrated embodiments of the device can be used safely and effectively for the intradermal delivery of a pharmaceutical agent or other substance to a patient. The device is particularly suitable for introducing a vaccine intradermally for efficiently delivering a small amount of a vaccine antigen. The length, width and spacing of the microneedles can vary depending on the pharmaceutical agent being administered and the desired depth of penetration for delivery. When delivering a vaccine, the microneedles are dimensioned to target the optimum intradermal delivery site to promote the desired immune response.
While several exemplary embodiments have been chosen to illustrate the invention, it will be appreciated by those skilled in the art that various additions and modifications can be made to the invention without departing from the scope of the invention as defined in the appended claims.