Invented by Brian John Bellhouse, John Bell, Huw Richard Millward, Monisha Jane Phillips, Samih M. Nabulsi, Powderject Research Ltd
The Powderject Research Ltd invention works as followsA needleless-syringe is provided that can accelerate particles onto a target surface. The syringe has a body with a lumen and a diaphragm adjacent to its terminus. The diaphragm is shaped to deliver particles from its external surface by using the force generated by the shockwave that impacts the inner surface. “A method of delivering particles using the needleless syringe” is also provided.
Background for Particle delivery
No. No. In U.S. Patent No. 5,630,796, an needleless syringe is used to deliver particles. The syringe can be used to deliver particles (powdered compositions and compounds) into skin, muscles, blood, or lymph. The syringe may also be used during surgery to deliver particles (powdered compounds and compositions) to solid tumors, organ surfaces or surgical cavities.
The needleless syringe is a U.S. Patent. No. The 5,630,796 is usually constructed as an elongated tubular nozzle with a rupturable barrier that initially closes the passage through the tube adjacent to the downstream end of the nozzle. The membrane is surrounded by particles, which are usually powdered pharmaceutical agents. The particles are 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 high-velocity gas flow.
The needleless syringe described above is used to deliver particles with an approximate size of between 0.1 and 240?m. The optimal particle size for drug delivery is typically between 10 and 15 m (the same size as a cell). In general, the optimal particle size for gene delivery is smaller than 10 micrometers. The device can deliver particles larger than 250 m. However, the maximum size is the point where the particle would damage the target tissue. The distance that the particles penetrate is dependent on the size of the particles (e.g. the nominal diameter, assuming a roughly cylindrical particle geometry), the particle density, initial velocity, and density and viscosity (e.g. skin) of the target tissues. The optimal particle density for needleless injection is between 0.1 and 25g/cm3, preferable between 0.5 and 2.0g/cm3, with injection speeds ranging between 100-3,000m/sec.
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. In operative combination, the syringe includes a body with a lumen that extends through it. The lumen has two termini, one upstream and one downstream. Its upstream end is connected to an energizing device such as a volume filled with a pressurized gas. The syringe also includes a diaphragm adjacent to the downstream end of the lumen. This diaphragm is arranged with an internal surface facing into the lumen and a surface that faces outwardly away from the syringe. The diaphragm can be moved between an initial position where a concavity appears on the external diaphragm surface, and a position dynamic in which the external diaphragm surface is substantially convex.
In certain aspects, the diaphragm consists of an eversible membrane in the form of a dome 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, the therapeutic agent-containing particles are usually housed inside the concavity created by the outer surface. The needleless syringe body can be designed as a tubular elongated structure with the diaphragm placed over the downstream end of a lumen that extends along the major axis. Or, the diaphragm can be positioned over an opening next to the downstream terminal, oriented in a direction substantially parallel to the major tubular axis.
In another embodiment, the diaphragm is a dome shape for use with an needleless syringe. The diaphragm includes a concavity which sealably holds particles containing a therapeutic agent.
In a further embodiment of the invention, an needleless syringe with a body that has a lumen running through it is provided. The lumen includes an upstream and downstream terminus. The upstream end of the lumen interfaces with an energizing device such as a volume containing a pressurized gas. The syringe also includes a diaphragm adjacent to the downstream end of the lumen. This diaphragm is arranged with an internal surface facing into the lumen and a surface that faces outwardly. The diaphragm can be moved between an initial position where a concavity appears on the external diaphragm surface, and a position dynamically in which this external diaphragm surface is substantially convex. The diaphragm’s external surface is characterized by one or more topographical elements that selectively retain particles when the diaphragm in its initial “loaded” position. position.
In a further embodiment, a method of transdermal particle delivery is provided. The method involves providing a needleless diaphragm according to the invention. It has a concave and convex diaphragm, with particles disposed on its concave side. The gaseous shockwave is directed in the direction of the convex diaphragm. This shockwave provides enough motive force to push the diaphragm into an everted position.
In certain aspects of the present invention, particles are accelerated towards the target surface substantially in the same direction as the travel direction of the gaseous wave. In some aspects of the invention the particles are accelerated towards the target surface in an opposite direction to the travel direction of the gaseous wave.
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? The singular forms?a?,?an? Plural referents are acceptable unless content dictates otherwise. Referring to “a therapeutic agent” is an example. Referring to “a therapeutic agent” includes mixtures of two or three such agents. Also, referring to “a gas?” includes mixtures of two or three gases. Includes mixtures of at least two gases and similar substances.
The following terms are used in this document: “Unless defined differently, all technical and science terms used herein shall have the same meaning that is commonly understood by a person of ordinary skill within the art to which it pertains.
The following terms will be defined below.
The term “needleless syringe” is used to describe a device that does not require a needle. “The terms ‘needleless device’ and ‘needleless syringe,? As used in this document, the term “particle delivery system” refers to a device that can be used for delivering particles into or across tissue. The particles should have an average particle size between 0.1 and 250 m, preferable 10 to 70 m. These devices can deliver particles larger than 250 m, but the maximum size is the size at which the particles cause pain or damage to target tissue. Particles are delivered with high speed, typically 250-300 m/s. The first description of such needleless syringes was found in a commonly owned U.S. Patent. No. No. All of these publications are also incorporated by reference. These devices are used for transdermal drug delivery into skin or mucosal tissues, in vitro or in situ. They can also be used to deliver generally inert particle samples in order to sample analytes from biological systems in a minimally or non-invasive manner. The term “needleless” only refers to devices that are capable of delivering particulate materials. Devices such as liquid jet injectors, for example, are excluded from this definition.
The term “transdermal” is used to describe the delivery of intradermal, transdermal (or ‘percutaneous? “The term ‘transdermal? Transmucosal is the term used to describe administration by passing a therapeutic agent through or into skin tissue. Transdermal Drug Deliver: Developmental Issues and Research Initiatives (eds. ), Hadgraft and Guy Marcel Dekker, Inc., 1989; Controlled Drug Deliver: Fundamentals and Application, Robinson and Lee, (eds. Marcel Dekker Inc. (1987); Transdernal Drug Delivery, Vols. Kydonieus & Berner (eds. ), CRC Press, (1987). CRC Press (1987). The invention is described in this document as ‘transdermal’. Delivery, unless specified otherwise, is meant to be applied to intradermal delivery, transdermal delivery, and transmucosal. The devices, systems and methods should, unless otherwise stated, be assumed to be equally applicable for intradermal, Transdermal and Transmucosal delivery.
As used in this document, the term ‘therapeutic agent’ is defined as: “As used herein, the terms?therapeutic agent? The term is used to describe any substance or composition of matter that, when administered by local or systemic action, induces the desired pharmacologic or immunogenic effect on an organism (human or otherwise). The term encompasses all compounds and chemicals that are traditionally considered drugs, vaccines and biopharmaceuticals, including proteins, peptides hormones biological response modulators, nucleic acid, gene constructs, etc. The term “therapeutic agent” is used more specifically. The term?therapeutic agent’ is used to describe compounds or compositions that are intended for use across all major therapeutic areas, including but not limited, to: adjuvants.
The term “analyte” is used herein in its broadest sense to denote any specific substance or component that one desires to detect and/or measure, whether it be through a physical, chemical, biochemical electrochemical photochemical spectrophotometric polarimetric calorimetric radiometric analysis. The term “analyte” is used in this document in its broadest meaning to refer to any substance or component which one wishes to detect or measure, whether it be in a physical or chemical analysis, or if it’s a biochemical or electrochemical analysis, spectrophotometric or polarimetric or calorimetric or radiometric. This material can produce a detectable signal, either directly, or indirectly. In some applications the analyte can be a physiologically active substance (e.g. glucose) or a chemical with a physiological effect, such as a drug.Click here to view the patent on Google Patents.