EP0955947B1

EP0955947B1 - Pharmaceutical delivery system

Info

Publication number: EP0955947B1
Application number: EP98900505A
Authority: EP
Inventors: Richard Harland; Stephen D. Acres
Original assignee: MetaMorphix International Inc
Current assignee: MetaMorphix International Inc
Priority date: 1997-01-24
Filing date: 1998-01-20
Publication date: 2003-01-02
Anticipated expiration: 2018-01-20
Also published as: DE69810442D1; CA2276414A1; AU734703B2; EP0955947A1; WO1998032397A1; BR9808876A; AU5546398A; AR011431A1; NZ336847A

Description

Technical Field:

The present invention relates to the administration of drugs or vaccines to vertebrate subjects. More particularly, the invention relates to a pharmaceutical delivery system for use with a variety of delivery devices, wherein the system prevents, or reduces the incidence of, inappropriate or accidental administration of a drug or vaccine to a person operating the delivery system.

Background of the Invention:

Drugs and vaccines are routinely administered to vertebrate subjects by needle and syringe, and the accidental administration of drugs or vaccines to technicians, for example by needle stick, is not uncommon. Devices that deliver drugs or vaccines via air injection, jet injection or particle bombardment can also be accidently discharged, thereby delivering a drug or vaccine to an inappropriate recipient. The administration of veterinary drugs and vaccines is often carried out under less than ideal conditions, which greatly increases the potential for such inappropriate administrations. WO90/13270 describes a medicated ear tag. FR-A-2599976 describes a transdermal therapeutic device.

In the context of veterinary medicine, many vaccines and drugs are administered to vertebrates that could result in undesirable or harmful effects if accidentally administered to the person delivering the vaccine or drug, or to another person for whom delivery was not intended. This is especially true of drugs and vaccines used in domestic animals. For example, the antibiotic tilmicosin (available under the tradename MICOTIL®), used in the treatment of bovine respiratory disease, can cause severe adverse reactions or possibly even death if accidently. administered to humans. Also, a number of vaccines are under development for use in domestic animals to induce immunity against native hormones in the vaccinated subject. These vaccines can be used to alter growth, productivity and/or reproductive function in treated subjects. However, since vertebrates share the same or similar hormones targeted by such vaccines, the accidental vaccination of a human could produce the same effect. For example, a vaccine intended to prevent reproductive maturation in a domestic animal could, if accidently administered to a human, prevent reproductive maturation in the human.

Several mechanisms are known which can be used to reduce accidental administration of drugs and vaccines. These mechanisms have been developed for use with conventional needle and syringe delivery devices. For example, telescoping sheaths or housings that encompass a needle can be used to avoid common accidental administrations due to needle-sticks.

However, there remains a need to provide a delivery system which can be used with a variety of drug and vaccine delivery methods to prevent or reduce the incidence of accidental administration.

EP-A-376 143 discloses a device for prolonged medicine application corresponding the preamble of claim 1 of the invention.

Summary of the Invention:

The invention relates to a pharmaceutical delivery system. The delivery system has first and second substantially planar opposing arms that are connected to each other at one end of a housing, and open at an opposite end to define a gap. The gap is sized to receive a body part of a vertebrate. A delivery means is disposed on one of the opposing arms of the housing, and is capable of delivering a pharmaceutical to a vertebrate body part inserted within the gap. Delivery of the pharmaceutical is carried out along a direction substantially normal to the plane of the opposing arms.

In one embodiment, the invention relates to a pharmaceutical delivery system comprising a housing formed from opposing arms that are held together by a dynamic fastener at a closed end of the housing. At an opposite end of the housing, the arms are open to define a gap into which a vertebrate body part can be inserted for administration of a pharmaceutical. The system also includes a delivery means arranged on one arm. A pharmaceutical can be delivered from the delivery means to a vertebrate body part disposed within the housing.

In preferred embodiments of the invention, the gaps provided at the open ends of the system housings are preferably sized to accommodate a skin flap, ear, tail, fin or wing of a vertebrate, but small enough to reduce the possibility of accidently inserting an adult human appendage into the gap. The delivery systems can employ any known pharmaceutical delivery mechanism, such as, but not limited to, a needle syringe, an air injector, a jet injector or a particle injector.

In related embodiments, the above pharmaceutical delivery systems can also include means for applying tracking indicia on body parts inserted within the system housings. Such indicia can include dye marks, tattoos, scars, brands, tags, or fin or ear notches. The delivery systems can further include means for positioning and maintaining a vertebrate body part within the delivery system, such as mechanical, hydraulic, inflatable, or other adjustable means that reduce the size of the gap provided by the opposing arms of the housing.

These and other embodiments of the subject invention will readily occur to those of ordinary skill in the art in view of the disclosure herein.

Brief Description of the Figures:

Figure 1 is an isometric view of one embodiment of the pharmaceutical delivery system of the invention.

Figure 2 is a side view, in partial cut-away, showing the delivery system of Figure 1.

Figure 3 is a side view, in partial cut-away, showing a delivery system having two substantially opposing delivery means located on the opposing arms of the system.

Figure 4 is a side view, in partial cut-away, showing another embodiment of the delivery system of the present invention having a housing that can be operated by dynamic fastening means.

Figure 5 is a side view of an embodiment of the present invention having an optional pad arranged on one of the arms of the system.

Figure 6 is a side view of another embodiment of the invention having pads arranged on both arms of the system.

Detailed Description:

Before describing the present invention in detail, it is to be understood that this invention is not limited to particular pharmaceuticals, drug delivery routes, or delivery mechanisms as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments of the invention only, and is not intended to be limiting.

It must be noted that, as used in this specification and the appended claims, the singular forms "a", "an" and "the" include plural referents unless the content clearly dictates otherwise. Thus, for example, reference to "a pharmaceutical" includes a mixture of two or more pharmaceutical agents, reference to "a delivery means" includes two or more delivery means, and the like.

A. Definitions

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although a number of materials similar or equivalent to those described herein can be used in the practice of the present invention, the preferred materials are described herein.

In describing the present invention, the following terms will be employed, and are intended to be defined as indicated below.

As used herein, a "pharmaceutical" intends any compound or composition of matter which, when administered to a vertebrate subject, induces a desired pharmacologic, immunologic, and/or physiologic effect by local and/or systemic action. The term therefore encompasses those compounds or chemicals traditionally regarded as drugs, vaccines, growth promotants, and biopharmaceuticals, including, without limitation: proteins, peptides and fragments thereof (whether naturally occurring, chemically synthesized or recombinantly produced); nucleic acid molecules (polymeric forms of two or more nucleotides, either ribonucleotides (RNA) or deoxyribonucleotides (DNA) including both double- and single-stranded molecules, gene constructs, and expression vectors); carbohydrates; polysaccharides; growth promoting or enhancing steroids and chemicals; steroid and non-steroid hormones; cytokines and other biological response modifiers and/or intercellular messengers; and the like. Thus, the term "pharmaceutical" includes compounds or compositions for use in all of the major therapeutic areas, and is particularly defined herein to include vaccine compositions containing an antigen capable of initiating lymphocyte activation resulting in an antigen-specific immune response, adjuvants, immunomodulators, cytokines, and the like.

By "vertebrate subject" is meant a member of the subphylum chordata, including, without limitation, mammals such as rodents, cattle, pigs, sheep, goats, horses and non-human primates; domestic animals such as dogs and cats; birds, including domestic, wild and game birds such as cocks and hens including chickens, turkeys and other gallinaceous birds; and fish. The term does not denote a particular age. Thus, adults, newborns, and fetuses are intended to be covered.

Referring now to Figure 1, one embodiment of the pharmaceutical delivery system is generally indicated at 2. The delivery system includes a housing 4, having first and second substantially planar opposing arms, 6 and 8, respectively, connected to each other at a closed end 10 of the housing 4.
The opposing arms are open at an end 12 opposite from the closed end 10, thereby defining a gap 14 into which a vertebrate body part can be inserted. Typically, the gap is sized to receive a skin flap, ear, tail, fin, or wing of a vertebrate.

The housing 4 can be comprised of any suitable material, for example a resilient metal or polymeric material, and can be formed by conventional methods such as casting, injection molding, milling, or the like. In the embodiment shown in Figure 1, the housing has an overall shape and outer dimension designed to fit comfortably within an operator's grasp to facilitate single-hand operation of the delivery system. In another embodiment, the delivery system 2 comprises a protrusion or extension attached to the housing 4 that enables the delivery system to be operated from a more remote location. Suitable protrusions include handles or grips, and suitable extensions for use in the invention include, but are not limited to, wands, booms or poles. If desired, the extension can have an adjustable length, such as wherein the extension is a telescoping pole, or the like. In the device depicted in Figure 1, opposing

arms

6 and 8 are fixed relative to each other such that the size of the gap 14 does not change appreciably during operation of the device.

In an alternative embodiment, the housing 4 can be partially inflatable. When in a deflated state, the housing can be readily positioned about an vertebrate's body part. Once in place, the housing can be inflated to hold the body part in position for subsequent delivery of a drug or vaccine from the delivery system 2. The partially inflatable housing includes structural elements that maintain the overall shape of the housing, and deformable or elastic elements that allow the structure to be inflated and deflated within a selected range. The partially inflatable housing further comprises means for communicating with a source of compressed gas, for example a valve body or the like.

The ability to hold the body part in position using the inflatable housing provides a higher degree of control over the delivery of the pharmaceutical. When the body part is held in place by the housing, tissue into which the pharmaceutical is to be delivered can be substantially stabilized at a selected pressure, and a targeted delivery area will not be brought out of its position within the device due to movements by the vertebrate subject or the operator.

Referring still to Figure 1, the delivery system 2 includes a delivery means 16 arranged on the housing arm 6 at a selected position proximal to the closed end 10 of the housing. The present delivery system is designed for use with any type of pharmaceutical delivery means known in the art, for example, conventional needle syringes, spring or compressed gas (air) injectors (U.S. Patent Nos. 1,605,763 to Smoot; 3,788,315 to Laurens; 3,853,125 to Clark et al.; 4,596,556 to Morrow et al.; and 5,062,830 to Dunlap), liquid jet injectors (U.S. Patent Nos. 2,754,818 to Scherer; 3,330,276 to Gordon; and 4,518,385 to Lindmayer et al.), and particle injectors (U.S. Patent Nos. 5,149,655 to McCabe et al. and 5,204,253 to Sanford et al.).

The delivery means 16 can be used for single use delivery of a pharmaceutical, such as wherein the delivery system 2 is a disposable unit.
Alternatively, the delivery means can be used for repeated delivery, in which case a controlled or metered supply of pharmaceutical and/or motive force (e.g., compressed gas) can be associated with the delivery system, either remotely or directly, by way of a suitable interface. Further, a plurality of discrete delivery means can be employed within the housing, such as wherein it is desirable to simultaneously deliver a number of different pharmaceuticals to the vertebrate subject using a single delivery system. In some embodiments, the delivery system can be configured to provide at least a partial vacuum with a body part inserted into the housing.

Referring now to Figure 3, a delivery system 2' is shown having a first delivery means 16' on one opposing arm 6' of the housing 4', and a second delivery means 20 disposed on the other opposing arm 8'. The first and second delivery means can be positioned such that they substantially oppose each other across the interior of the housing, or the delivery means can be positioned such that they are offset from each other.

Referring back to Figure 2, the delivery means 16 is used to deliver a pharmaceutical to a vertebrate body part placed within the gap 14 at the open end 12 of the housing 4. Parenteral delivery of the pharmaceutical is generally preferred, for example wherein the pharmaceutical is delivered into muscle tissue, dermis, epidermis, or subcutaneous space of the vertebrate body part inserted into the housing. Other modes of delivery can also be practiced, such as topical delivery from the delivery means. In addition, delivery of the pharmaceutical is carried out within the housing, and proceeds in a transverse direction relative to the plane of the opposing

arms

6 and 8 of the housing. More particularly, the direction of pharmaceutical delivery is generally within the range of about 5 to about 90 degrees relative to the plane of the opposing arms. In a preferred embodiment, the delivery means can be configured to deliver the pharmaceutical into the dermis, epidermis or subcutaneous space of the body part. The delivery means 16 can also be adjusted within the above range when switching between different modes of delivery with the delivery system 2. Thus, when intramuscular delivery is to be carried out, the direction of delivery can be set substantially normal to the plane of the opposing arms. When subcutaneous or subdermal delivery is to be carried out using a needle syringe, the direction of delivery can be reset closer to about 5 degrees relative to the plane of the opposing arms. The selected angle or direction of delivery from the delivery means 16 will depend upon the mode of delivery used, and can be readily determined by those of ordinary skill in the art.

Use of the delivery system 2 helps prevent or reduce the incidence of accidental administration to an adult human. As best seen in Figure 2, the gap 14 defined by the opposing arms of the housing can be dimensioned to readily receive a skin flap, ear, tail, fin or wing (e.g., a wing web) of a vertebrate, but help prevent accidental insertion of a human appendage into the gap. More particularly, the gap 14 at the open end 12 of the housing has a small enough width (w) to preclude insertion of human fingers into the body of the housing, thus preventing contact with the delivery means which could lead to inadvertent delivery of the pharmaceutical to a human operator or technician.

Referring still to Figure 2, an additional level of protection can be provided by arranging the delivery means 16 at, or near to, the closed end 10 of the housing 4. In this configuration, the distance (ℓ), between the open end 14 of the housing and the delivery means 16, is sufficiently long enough to prevent a human appendage inserted into the gap 14 from contacting the delivery means.

Yet further safety features that can be added to the delivery system 2 include, but are not limited to, pressure sensitive locking mechanisms that prevent actuation of the delivery means when a body part is incorrectly positioned within the gap in the housing. For example, a trip-arm, that projects into the space within the housing, can be provided to prevent actuation of the device unless a body part is contacting the arm, indicating proper positioning of the body part within the housing.

Referring now to Figure 4, another embodiment of the pharmaceutical delivery system is generally indicated at 22. The delivery system includes a housing 24, having first and second substantially planar opposing arms, 26 and 28, respectively, connected to each other at a closed end 30 of the housing. The opposing arms are open at an end 32 opposite from the closed end 30, thereby defining a gap 34 into which a skin flap, ear, tail, fin, wing, or wing web can be inserted. A delivery means 36 is disposed on the first opposing arm, 26, and allows for the delivery of pharmaceuticals to a body part inserted into the gap 34. The delivery means can comprise any known delivery mechanism, such as conventional needle syringes, air injectors, jet injectors or particle injectors. As described above, delivery of the pharmaceutical is carried out within the confines of the housing 24, and proceeds along a transverse direction relative to the plane of the opposing arms.

The opposing arms are held together by a moveable, dynamic fastener 38 that allows the opposing

arms

26 and 28 to move towards, or away from, each other about the fastener. In this way, the size of the gap 34 can be increased or decreased. The fastener can be pivotable, for example, hinged, thereby allowing the opposing arms to articulate about a pivot point supplied by the hinge. Alternatively, the fastener can comprise a slidable member that allows the opposing arms to move upwards-downwards relative to each other, such as wherein the fastener is compressible.

Both pivotable and compressible fasteners allow the housing 24 to be positioned about a vertebrate subject's body part in an initial position, e.g., wherein the opposing

arms

26 and 28 are spread apart from each other to define a maximum gap 34. Once the body part is positioned within the housing, the opposing arms can be brought together to define a smaller gap, holding the body part in position for delivery of a pharmaceutical from the delivery means 36. As described above, the ability to position and hold the targeted body part within the housing provides a high degree of control over the delivery of the pharmaceutical.

In one particular embodiment, movement of the opposing

arms

26 and 28 toward each other actuates the delivery means 36. In other embodiments, the above-described safety features can be included with the delivery system 22, such as by restricting the maximum gap size, and/or separating the delivery means from the open end of the housing, to prevent insertion of human appendages into the gap 34, or accidental contact with the delivery means 36.

The

pharmaceutical delivery systems

2 and 22, can also include one or more pads disposed on an inner surface of the first or second opposing arms of the housing. Referring now to Figure 5, a delivery system 42 is shown with a pad 58 disposed on an opposing arm 48 of the housing 44. The pad faces a delivery means 56, and reduces the size of a gap defined by the surface of the pad, and the inner surface of a second opposing arm 46. In an alternative embodiment, the pad 58 can be adjustably connected to the arm 48, allowing movement of the pad relative to the arm so as to reduce or increase the size of the gap between the surface of the pad and the inner surface of the opposing arm. The adjustable pad can be used to maintain the position of a body part inserted into the housing for subsequent delivery of a pharmaceutical from the delivery means. The pad 58 can alternatively be inflatable, wherein the pad does not move relative to the arm 48, but can increase in size to reduce the gap between the pad and the opposing arm.

In Figure 6, a different delivery system 62 is depicted. The system is shown with a first pad 78 disposed on a first opposing arm 68 of the housing 64. A second pad 80 is disposed on the second opposing arm 66, and a delivery means 76 projects through the arm 66 and second pad 80 for delivery of pharmaceutical to a body part inserted within the housing as described above. The pads reduce the size of a gap defined by the inner surfaces thereof. Further, one, or both of the pads can be adjustably connected to the arm of the housing, allowing movement relative to the arm so as to reduce or increase the size of the gap.

In related embodiments of the invention, the

delivery systems

2, 2', 22, 42 and/or 62 can further include means for applying tracking indicia on a body part inserted into the housing for delivery of the pharmaceutical. For example, the housing can include one or more mechanisms for providing dye marks, tattoos, scars, brands, tags, ear or fin notches, or like indicia, to body parts inserted into the housing, thereby providing visual confirmation of pharmaceutical delivery in individual subjects. If desired, the tracking mechanism can be actuated by actuation of the delivery means, or individually actuated by appropriate controls. Alternatively, dyes or like materials can be included with a pharmaceutical composition delivered from the delivery system, thereby providing visual confirmation of pharmaceutical delivery.

When the pharmaceutical delivery systems of the present invention are operated under field conditions to deliver pharmaceuticals to vertebrate subjects, the risk of accidental delivery of the pharmaceutical to the operator or other human technicians is greatly reduced or eliminated. In systems configured for repetitive delivery of pharmaceuticals, associated components such as a pharmaceutical supply and/or a source of motive force (e.g., compressed gas), can be carried in a backpack, or on the operator's belt. The associated components can be connected to the delivery system via an appropriate interface, thereby allowing for safe and simplified operation of the system.

In yet further related embodiments of the invention, the delivery system housings can be reconfigured for use in delivery of a pharmaceutical to human subjects. In such devices, the gap defined by the opposing jaws of the housing are sized to accommodate human body parts, for example arms of infants, children, adolescents or adult humans. The embodiments of the invention that comprise means for adjusting, positioning and holding inserted body parts are particularly well adapted for use in this context. The ability to position and hold the body part within the housing provides a high degree of control over delivery parameters, since targeted tissue can be substantially stabilized at a selected pressure, and a targeted delivery area maintained in position.

Thus, novel pharmaceutical delivery systems and methods for obtaining and using the same are disclosed. Although preferred embodiments of the subject invention have been described in some detail, it is understood that obvious variations can be made without departing from the scope of the invention as defined by the appended claims.

Claims

A pharmaceutical delivery system (2, 2', 22, 42, 62), comprising:

(a) a housing (4, 4', 24, 44, 64) having first (6, 6', 26, 46, 66) and second (8, 8', 28, 48, 68) substantially planar opposing arms connected to each other on one end (10, 30) and open on an opposite end (12, 32), wherein the opposing arms define a gap (14, 34) into which a vertebrate body part can be inserted; and

(b) delivery means (16, 16', 36, 56) disposed on an arm of the housing, wherein the delivery means is capable of delivering a pharmaceutical to a body part disposed within the gap in a transverse direction relative to the plane of the opposing arms and further characterised in that the delivery means is selected from the group consisting of a needle syringe, an air injector, a jet injector and a particle injector.
The delivery system of claim 1, characterized in that the gap defined by the opposing arms can receive a skin flap, ear, tail, fin or wing of a vertebrate subject, but is small enough to reduce or eliminate the possibility of inserting a human finger into the gap.
The delivery system of anyone of the preceding claims, characterized in that the delivery means is arranged on the arm such that the distance between the open end of the housing and the delivery means prevents contact between the-delivery means and any human appendage inserted into the gap.
The delivery system of anyone of the preceding claims, characterized in that the delivery means is configured to deliver a pharmaceutical into the dermis, epidermis, or subcutaneous space of a body part placed within the gap defined by the opposing arms.
The delivery system of claim 1 further comprising a pad (58, 78) disposed on an inner surface of an arm of the housing and facing the delivery means, characterized in that said pad and an inner surface of the opposing arm define a gap into which a vertebrate body part can be inserted.
The delivery system of claim 5, characterized in that the pad is adjustably connected to the arm, thereby allowing movement of the pad relative to said arm so as to reduce or enlarge the gap defined by the pad and the inner surface of the opposing arm.
The delivery system of anyone of claims 5-6, characterized in that the gap defined by the pad and the inner surface of the opposing arm can receive a skin flap, ear, tail, fin or wing of a vertebrate subject, but is small enough to reduce or eliminate the possibility of inserting a human appendage into the gap.
The delivery system of anyone of claims 5-7, characterized in that the delivery means is configured to deliver a pharmaceutical into the dermis, epidermis, or subcutaneous space of a body part placed within the gap defined by the pad and the inner surface of the opposing arm.
The delivery system of any one of the preceding claims, characterized in that the housing is inflatable and comprises means for communicating with a source of compressed gas.
The delivery system of any one of the preceding claims further comprising means for applying tracking indicia to a body part inserted within the gap.
The delivery system of claim 10, characterized in that the indicia is selected from the group consisting of a dye mark, a tattoo, a scar, a brand, a tag and an ear or fin notch.
A pharmaceutical delivery system according to any one of the preceding claims wherein said first and second substantially planar opposing arms are held together at a dynamic fastener (38) disposed at the closed end (30) of the housing.
A delivery system according to claim 12 wherein the delivery means is disposed on the first arm of the housing.
The delivery system of claim 12 or claim 13, characterized in that the fastener is pivotable.
The delivery system of any one of claims 12 to 14, characterized in that the arms can be moved toward, away from, each other about the fastener, thereby decreasing or increasing the size of the gap.
The delivery system of claim 15, characterized in that movement of the arms toward each other actuates the delivery means.
The delivery system of claim 12 when dependent on claim 5, characterized in that the pad is inflatable so as to reduce, or deflatable so as to enlarge, the gap defined by the pad and the inner surface of the opposing arm.
A delivery system according to any one of the preceding claims wherein a second delivery means (20) is disposed on the other arm of the housing.
A delivery system according to any one of the preceding claims when dependent on claim 5 wherein the delivery system further comprises a second pad (80) disposed on the other arm of the housing.