Invented by Brian John Bellhouse, John Bell, John Christopher Greenford, David Francis Sarphie, Powderject Research Ltd
The Powderject Research Ltd invention works as followsThe needleless syringe is capable of accelerating therapeutic agents across the skin or mucosal tissues of vertebrate subjects. The syringe includes an elongate tube nozzle with a bend down its length. It is connected or connectable to a suitable energy source for producing a supersonic state in the nozzle that will cause the delivery of particles to the target surface. The needleless syringe can also be used to deliver particles containing a therapeutic agent.
Background for Trans-mucosal particle delivery
No. No. In U.S. Patent No. 5,630,796, an noninvasive delivery system that uses a needleless-syringe is described. The syringe can be used to deliver powdered compositions and therapeutic compounds transdermally into skin, muscle, or blood. The syringe may also be used with surgery in order to deliver therapeutics on organ surfaces, solid tumours, and/or surgical cavities.
The needleless tube syringe has an elongated tubular nozzle with a rupturable nozzle membrane that initially closes the passageway through the nozzle near the downstream end. The membrane is surrounded by particles containing a powdered drug. The therapeutic agent can be delivered by an energizing device that applies gaseous pressure on the membrane’s upstream side. This is enough to rupture the membrane and produce a supersonic flow of gas through the nozzle.
As explained in U.S. Pat. No. No. When delivering powdered agents, such as agents that are delivered without a carrier particle or a carrier particle’s aid, the general parameters for delivery include a size of the particles preferably between 10-40?m and a density of the particles preferably between 0.5-2.0g/cm3 with an initial velocity of the order of 200-2500m/sec, with a momentum densities preferably within the range 4-7kg/sec/m.
In one embodiment, the invention provides a needleless-syringe. The needleless device is capable of accelerating therapeutic agents across the skin or mucosal tissues of vertebrates. The syringe consists of an elongated tubular nozzle with an upstream end and a downstream end, and a bend in between. The upstream end of the nozzle can be used to interface with an energizing device, such as a volume filled with a pressurized gas. The syringe also includes a release mechanism for releasing a force energetic from the energizing gas into the upstream end of the nozzle. This force creates supersonic conditions within the nozzle (e.g. a gaseous gas flow or shock wave) that are sufficient to deliver therapeutic agents from the syringe into the target tissue.
In certain aspects of this invention, the diameter between the bend in the nozzle and the downstream end is smaller than the diameter between the upstream terminal and the bend. This configuration allows for a supersonic flow of gas to only be achieved in the downstream section of the nozzle. That is, the portion between the bend of the nozzle and the downstream terminal. The downstream portion of a nozzle can be smaller than the upstream portion to allow for supersonic flow only in the downstream section. This particular construction allows a driving-gas to pass through the upstream section of the bend at a moderate speed before it is rapidly accelerated into supersonic speeds at the downstream portion of nozzle. This narrower, downstream portion of the nozzle can also have a convergent portion, such as where the portion of the nozzle has a convergent/cylindrical or convergent/divergent shape, with the convergent portion of the nozzle being of greater conicity than the cylindrical or divergent portion.
In another aspect of the invention, a syringe can be used to deliver therapeutic agents in particles. The particles are entrapped in a gas stream created in the upstream section of the nozzle, and accelerated supersonic speeds as they pass into and out of a downstream portion of nozzle to reach the target surface. The syringe may include upstream- and downstream-rupturable membranes extending across the interior of a nozzle. The nozzle can house particles containing a therapeutic agent between these membranes. If the release mechanism includes a rupturing surface, the membranes upstream and downstream can be used to create a supersonic environment within the nozzle in order to deliver the particles.
In one embodiment, the syringe can only be used to deliver therapeutic agents, where the particles are not entrained in a gas flow. The syringe in this embodiment includes a diaphragm over the downstream end of the needle, with an internal surface facing into the interior of nozzle and an exterior surface facing away from the syringe. The diaphragm can be moved between an initial position where a concavity appears on the external diaphragm surface, and a dynamic positioning in which the diaphragm’s external surface is substantially convex.
In certain aspects, a diaphragm can be a dome-shaped membrane made of flexible polymeric materials. In some aspects, the membrane is bistable and can be moved between an initial inverted position, as well as a dynamic everted position. When the diaphragm is in its initial position, particles containing a therapeutic agent can be housed within the concavity created by the outer surface of the membrane.
The particles can be given a sufficient amount of energy by creating a shockwave at the portion of nozzle which is upstream from the bend, and therefore away from the target surface. For example, the mucosal tissues in the patient’s mouth. The downstream portion of a nozzle can then be reduced in size to make it easier to position the syringe inside the mouth cavity.
In a still further embodiment, the invention provides a method of delivering therapeutic agents to a surface target. The method involves providing a needleless, syringe that has a bend in the nozzle between its upstream and downstream ends. The downstream end of the nozzle, which is adjacent to the target area, is then positioned and the release mechanism actuated in order to create supersonic conditions sufficient to accelerate particles into skin or mucosal tissues.
In certain aspects, the method can be used to deliver an agent that is topically active and local anesthetic. The method can, for example, be used to deliver anesthetics such as lignocaine hydrochloride or lignocaine bases, procaine hydrochloride or prilocaine base, and bupivacaine. The local anaesthetic may be mixed with adrenaline if desired. Epinephrine, or adrenaline, causes vasoconstriction of the tissue targeted, which prolongs the anaesthetic effects of the local anaesthetic. Other aspects of the invention use the method to deliver a therapeutic agent that is systemically active, such as, for example, systemically-active small molecules (organic or inorganic), peptides and proteins, vaccine compositions oligonucleotides and/or metals ions. Some examples of therapeutic agents are insulin, testosterone and growth hormones. Other examples include glucagon atropine alprazolam calcitonin desmopressin 5HT dihydroergotamine interleukins.
In yet another aspect of the invention, the method used is to deliver particles containing a therapeutic agent on a mucosal surfaces such as gum mucosa or cheek mucosa. It can also be applied to the mucosas in the vaginal area, the rectal region, the nasal mucosa and the ocular surface.
The disclosures here will lead those with ordinary knowledge of the art to easily recognize these and other embodiments.
Before describing this invention in details, please note that it is not restricted to any particular pharmaceutical formulations, or process parameters, as these can, of course vary. The terminology used in this document is intended only to describe particular embodiments of invention and not to limit.
All publications, Patents, and Patent Applications cited in this document, whether in the preceding or following paragraphs, are hereby included by reference to their entire content.
The singular forms “a”, “an” and “the” are plural, unless the context clearly indicates otherwise. For example, a reference to “a therapeutic agent” can include a mixture of more than one such agent, a reference to “a gas” can include mixtures of more than two gases, etc.
All technical and scientific terms are used in this document with the same meaning that a person of ordinary knowledge would understand. “The following terms are intended as defined below.
The term “transdermal” delivery encompasses both transdermal administration (also known as ‘percutaneous”), and transmucosal delivery, which is the passage of a drug through mucosal or skin tissue. Transdermal Drug Deliver: Developmental Issues and Research Initiatives (eds. Hadgraft and Guy) is one example. Marcel Dekker, Inc., 1989; Controlled Drug Deliver: Fundamentals and Application, Robinson and Lee, (eds. Marcel Dekker Inc. (1987); Transdermal Drug Delivery, Vols. Kydonieus & Berner (eds. ), CRC Press, (1987). CRC Press (1987). The aspects of the invention described in this document as “transmucosal”, unless otherwise stated, are intended to apply both to transdermal delivery and transmucosal. It is assumed that the compositions and systems of the invention are equally applicable to both transdermal and tranmucosal delivery modes, unless otherwise stated.
As The The
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