FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule13)
1. TITLE OF THE INVENTION:
DEVICE FOR MICRONEEDLE ATTACHMENT TO INJECTION PEN
2. APPLICANT (S)
(a) NAME: WOCKHARDT LTD.
(b) NATIONALITY: INDIAN
(c) ADDRESS: D-4, M.I.D.C. Area, Chikalthana, Aurangabad - 431210
(M.S.) India
3. PREAMBLE TO THE DESCRIPTION
The present invention provides a device for the delivery of biological material across the biological tissue with minimal or no pain, damage and irritation to the tissue. The device comprises at least one microneedle attached to a needle cap and optionally an adapter wherein the needle cap is attached to an injection pen device.
The following specification particularly describes the invention and the manner in which it is to be performed.
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4. Description
The present invention provides a device for the delivery of biological material across the biological tissue with minimal or no pain, damage and irritation to the tissue. The device comprises at least one microneedle attached to a needle cap and optionally an adapter wherein the needle cap is attached to an injection pen device.
Dosed biological material delivery devices, often referred to as "injection pen device" are commonly used for routine injection of biologic materials.
Dosed biological material delivery devices are a preferred means of delivery wherever the volume of biological material delivered needs to be variable but accurate, critical, small and needs to be administered very frequently. Hence, "injection pen device" refer generally to any and all free- standing portable device containing a plurality of doses of a biological material liquid which can be operated by a patient for self injection to deliver metered doses of the liquid to the patient's body on a plurality of occasions.
The term "microneedle" refers to a device for transdermal or Intradermal delivery or removal of fluids without many of the risks associated with standard syringes. Microfabricated microneedle arrays are designed to pierce the stratum corneum skin barrier layer in a minimally invasive and pain-free manner to provide transient pathways for the delivery of macromolecules to the underlying skin epidermis. Since the needles are short, they do not reach the nerve-rich regions of the lower parts of the skin. As a consequence, the stimulus caused by microneedle insertion into the skin is weak and cause less pain. Such devices use arrays of small diameter needles that each deliver relatively small flow rates of fluid across or into a biological barrier, which together with the fluid delivered by other needles in the array, provide a clinically useful alternative to standard syringes.
Usage of microneedle with conventional biological material dosage delivery systems can be either directly or indirectly attached and the indirect attachment can be a suitable
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adapter for transfer of biological material substance from the standard syringe or pen devices to the microneedle. The prevalent microneedle attached adapter designed for delivery of biological material dosage from the "injection pen device" allows excessive biological material being delivered accidentally or otherwise during the usage of the device.
US Patent No. 6,533,949 discloses a method for processing a wafer to form a plurality of hollow microneedles projecting from a substrate.
PCT Application No. 2007066341 discloses an adapter for achieving Intradermal dosed delivery of a liquid by use of a dosed biological material delivery device, the dosed biological material delivery device including a reservoir having a pierceable septum.
PCT Application No. 2003074102 and 2005049107 disclose device and method for transporting fluids across biological barriers.
US Application 20050209566 discloses a method for delivering a fluid into a flexible biological barrier.
US Application 20030050602 discloses a system and method for an injectable substance delivery pen comprising a microneedle hub assembly removably engaged with a pen device body which includes a cartridge, a plunger, and a drive mechanism.
US Application 20030181863 discloses an adapter for the transport of fluids with a microneedle device.
The present inventors while working for suitable micro needle device design have found that there is a need for a device that allows not only easy attachment to biological material delivery injection pen device but also that the once set dosage is delivered to the patient without resorting to extra delivery due to any other factors when the biological material is delivered. The present invention provides a device wherein at least one
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microneedle can be directly or indirectly attached to a needle cap or an adapter attached to a injection pen device. The device comprises an adapter and a mechanism for biological material delivery wherein the device comprises at least one micro needle and a reservoir to receive and hold selected dose of biological material from a biological material delivery injection pen device such that the device prevents the excessive delivery of biological material during storage or use.
One of the aspects of present invention provides device for transport of biological materials across biological barrier wherein the device comprises at least one microneedle attached to a needle cap and optionally an adapter wherein the needle cap is attached to an injection pen device.
In one of the embodiment, the adapter comprises
(i) a reservoir to receive and hold selected dose of biological material from a
biological material delivery injection pen device to which it is attached at its
biological material dosage end,
(ii) a flow passage which is integrally attached or molded to the reservoir of the
adapter,
(iii) a closure mechanism such as a flap or disk is provided on the flow passage
which closes or opens the flow passage.
"Biological Material Storage" may mean a syringe or cartridge containing suitable pharmaceutical substance.
As used herein, the term " biological material " refers to an agent which possesses therapeutic, prophylactic, or diagnostic properties in vivo, for example when administered to an animal, including mammals, such as humans. The biological material is selected from the group comprising of peptides, proteins, carbohydrates, nucleic acid molecules, lipids and other pharmaceutically active ingredients or combinations thereof.
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The pharmaceutically active ingredients may be one or more of anesthetics, analgesics, anti bacterials, anti virals, antiadrenergics, antiamebics, antianginals, antiarrhythmics, antibiotics, anticoagulants, anticonvulsants, antidepressants, antidiabetics, antidiuretics, antidyskinetics, antiemetics, antifungals, antihistaminics, antihyperparathyroids, antihypertensives, antiinflammatories, antimigraines, antineoplastics, antineoplastics, antiprotozoals, antipsychotics, antispasmodics, antithrombotics, antiulceratives, anxiolytics, astringents, bone resorption inhibitors, bronchodilators, cardiotonics, cholinergics, diaprostic agents, diuretics, hormones, steriods, hydrochloride as anineoplastic, hypnotics, immunomodulators, immunosuppresants, mucolytics, muscle relaxants, neuromuscular blocking agents, oxytocics, vasodilator and the like.
The pharmaceutically active ingredients may further include one or more ketamine, chloroprocaine hydrochloride, alfentanil, amikacin, abacavir, bretylium tosylate, metronidazole, diltiazem hydrochloride, ciprofloxacin, dextran sulfate sodium, fosphenytoin sodium, rubidium chloride, insulin, desmopressin acetate, haloperidol lactate, dimenhydrinate, abelcet, diphenhydramine hydrochloride, paricalcitol, diltiazem hydrochloride, ketorolac, dihydroergotamine mesylate, mitoxantrone hydrochloride, leuprolide acetate, metronidazole, aripiprazole, dicyclomine hydrochloride, dipyridamole, cimetidine hydrochloride, diazepam, zinc chloride, zoledronic acid, aminophyllin, digoxin, pyridostigmine bromide, diatrizoate sodium, furosemide, estrogen, androgen and the like, steriods such as glucocorticoid and the like, mechlorethamine hydrochloride, etomidate, mitoxantrone hydrochloride, tacrolimus, acetylcysteine, baclofen, vecuronium bromide, oxytocin nitroglyceine and the like.
In another embodiment of the invention, the adapter can be attached by mating of threads of the adapter and the biological material delivery injection pen device.
In another embodiment of the invention, the microneedle can either integrally be attached to needle cap or by mating of threads of the microneedle to the needle cap.
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In another embodiment of the invention, microneedles can be arranged in one or more predetermined array system.
In another embodiment of the invention, microneedles can be hollow, solid, biological material coated hollow or solid, porous and the like.
As used herein, the term "porous" means having pores or voids throughout at least a portion of the micro needle structure, sufficiently large and sufficiently interconnected to permit passage of fluid and/or solid materials through the micro needle.
As used herein, the term "hollow" means having one or more substantially annular bores or channels through the interior of the micro needle structure, having a diameter sufficiently large to permit passage of fluid and/or solid materials through the micro needle. A solid or porous micro needle can be hollow. One of skill in the art can select the appropriate porosity and/or bore features required for specific applications. For example, one can adjust the pore size or bore diameter to permit passage of the particular material to be transported through the micro needle device.
In another embodiment of the invention, the geometrical shape of microneedles can be selected from the group comprising of cylindrical, pyramidal, frustoconical and frustopyramidal.
The microneedles can be formed with shafts that have a circular cross-section in the perpendicular, or the cross-section can be non-circular. For example, the cross-section of the micro needle can be polygonal (e.g. star-shaped, square, triangular, pyramidal), oblong, or another shape such as frusto conical and frusto pyramidal. The shaft can have one or more bores.
In another embodiment of the invention, the outer diameter of microneedle varies from about 10 microns to 100 microns and length of the microneedle is at least 100 microns.
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The cross-sectional dimensions typically are between about lum and 500 um, and preferably between 10 and 100 um. The outer diameter is typically between about 10 um and about 100 um, and the inner diameter is typically between about 3 um and about 80 um.
The length of the microneedles typically is between about 10 um and 1 mm, preferably between 100 um and 500 um, and more preferably between 150 um and 350 um. The length is selected for the particular application, accounting for both an inserted and un inserted portion. An array of microneedles can include a mixture of microneedles having, for example, various lengths, outer diameters, inner diameters, cross-sectional shapes, and spacing between the microneedles. In transdermal applications, the "insertion depth" of the microneedles is preferably less than about 500 um, so that insertion of the microneedles into the skin does not penetrate into the dermis, thereby avoiding contacting nerves which may cause pain. In such applications, the actual length of the microneedles typically is longer, since the portion of the microneedles distal the tip may not be inserted into the skin; the uninserted length depends on the particular device design and configuration. The actual (overall) height or length of microneedles should be equal to the insertion depth plus the un inserted length.
Suitable materials for manufacturing microneedles include one or more metals, ceramics, semiconductors, organics, non biodegradable polymer, biodegradable polymer, or composites.
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The metals can be selected from the group comprising of pharmaceutical grade stainless steel, gold, titanium, nickel, iron, tin, chromium, copper, palladium, platinum, alloys, silicon, silicon dioxide, and combinations thereof.
Suitable non-biodegradable polymers include one or more cellulose, polycarbonate, polyester, or polyacrylamides.
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Suitable biodegradable polymers include one or more lactic acid and glycolic acid polylactide polymer, polyglycolide, polylactide-co-glycolide, and copolymers with PEG, polyanhydrides, poly(ortho)esters, polyurethanes, poly(butyric acid), poly(valeric acid), and poly(lactide-co-caprolactone).
In another embodiment of the present invention, the reservoir is formed of a material which is deformable or elastic. Elastic material includes elastomeric polymer, rubber or combination thereof.
Adapter can be made up of metal, plastic or polymeric material. Representative metals include stainless steel, nickel, gold, Chromium, copper, palladium, alloys of these metals, silicon, silicon dioxide etc. Non degradable polymers include one or more of polycarbonate, polyester, cellulose and polyacrylamide.
In another embodiment of the present invention, the biological material is selected from the group comprising of peptides, proteins, carbohydrates, nucleic acid molecules, lipids and other pharmaceutically active ingredients and combinations thereof.
A pen device that would be used for the administration of set dose of the biological material is detailed below. The pen used for precise administration of dose is described in detail with references to the drawing.
Figure 1 shows mechanism for discharge of biological material through micro needle
attached to a pen device - Existing attachment of needle and needle cap
Figure 2 shows mechanism for discharge of biological material through micro needle
attached to a pen device - Proposed microneedle attachment to pen cap
Figure 3 shows micro needle and injection pen adapter attachment mechanism
Figure 1 shows the pen device (1) where in present needle and a cap (5) that would be associated with a pen. Needle cap (5) has an internal thread (6) that mates with the cartridge or syringe (2) and needle (9) extends on both sides of the needle cap (5). On
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attachment of needle cap (5) to the cartridge or syringe (2) by screw mechanism, needle (9) which extends on to the internal of the cap pierces the rubber seal 93) of the cartridge or syringe (2) and establishes contact with the biological material in the cartridge or syringe (2). Needle cap (5) is removed and set dosage of the biological material is administered to a patient.
Figure 2 shows the proposed system wherein instead of needle (9) which protrudes out of the cap is replaced by array of micro needle (7). An array of micro needle is either screwed on to the needle cap (5) externally or bonded. On attachment of the needle cap (5) to cartridge or syringe (2), needle (9) which is internal to the cap pierces the cartridge rubber and establishes contact with the biological material. Micro needle establishes contact with the biological material through the needle.
A pen device (1), needle cap (5) and a number of micro needle (7) array system would be in a package. To start with a needle cap (5) is screwed on to pen device (1). One micro needle array is attached to a needle cap by a screw mechanism in one direction from the package and detached on the patient skin surface by unscrewing in the opposite direction.
Figure 3 shows another embodiment of the present invention. The pen device (l)of the present invention comprises a biological material flow passage that interfaces the biological material storage or the pen device (1) and the adapter reservoir (6). The orifice at the interface of the biological material storage and the biological material flow passage has a flap or disc (5) which serves to block the flow of biological material to the adapter (3). The flow passage may be integrally molded to the reservoir (6)of the adapter(3). The adapter reservoir (6) is designed in such a way that it holds the dose of the biological material which is set using a pen device(l). Adapter is provided with an internal screw thread that mates with the external screw thread of the "injection pen device" as shown in Figure 3.
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A dose of biological material is set by a dose setting mechanism of " injection pen device" and the dose setting mechanism is activated to allow discharge of the biological material to pass through the biological material passage into the reservoir of the adapter.
A suitable closure mechanism such as a flap or disk (5) is provided on the flow passage which closes or opens, and such closure or opening of the orifice caused by flap or disk (5) coming in line with orifice opening by virtue of rotation of the flow passage that is integrally attached to the reservoir (6) of the adapter, when at least one microneedle is attached to the adapter of the injection pen device by a suitable mechanical mechanism by rotation in one direction.
Flow passage for the biological material flow from the biological material delivery injection pen device is opened up when at least one microneedle (7) is detached for administration of biological material to a patient by rotating the same in a direction which is opposite to the direction used for attaching the microneedle with adapter (3).
Biological delivery from biological material delivery injection pen device (1) to adaptor reservoir corresponding to the set dosage of the dosage setting system is affected by a suitable trigger mechanism so as to allow the next dose of biological material to the reservoir for delivery to a patient.
Biological material is set by a suitable dose setting mechanism and delivered by an actuating a triggering mechanism. Delivered biological material falls into the reservoir provided in the adapter. The flow passage is integrally attached to the adapter reservoir. Bottom of the reservoir could be porous membrane through which the biological material flows into at least one microneedle or an array of micro needle (1). At least one micro needle or an array of micro needle is mated with the screws provided in the reservoir. Attachment of micro needle to biological delivery injection pen device by rotation movement causes the flap or disc provided in the flow passage coming in line with the orifice portion at the interface between the biological material reservoir and the flow
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passage causing the closure of the biological material passage. This prevents the accidental delivery of the biological material from the "injection pen device".
Previously transferred and stored biological material substance in the micro needle is removed for delivery to a patient. The removal of this micro needle (7) is accomplished by unscrewing the micro needle (7) in the opposite direction. In the embodiment described, the attachment of micro needle (7) to adapter (3) is by rotation in a clockwise rotation and detachment is by anti-clockwise direction. During this process the orifice closure flap (5) or disc is opened up making way for the release of the biological material from the "injection pen device" to the reservoir (6) of the adapter (3).
A pre determined biological material dosage is set for the next delivery and the dosage is delivered by triggering an actuating mechanism.
The microneedles must have the mechanical strength to remain intact and to deliver biological materials, or collect biological fluid, while being inserted into the skin, while remaining in place for up to a number of days, and while being removed. The microneedles should be sterilizable using standard methods.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
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WE CLAIM:
1. A device for transport of biological materials across biological barrier wherein the device comprises at least one microneedle attached to a needle cap and optionally an adapter wherein the needle cap is attached to an injection pen device.
2. The device as claimed in claim 1, wherein the adapter comprises
(i) a reservoir to receive and hold selected dose of biological material from a
biological material delivery injection pen device to which it is attached at its
biological material dosage end,
(ii) a flow passage which is integrally attached or molded to the reservoir of the
adapter,
(iii) a closure mechanism such as a flap or disk is provided on the flow passage
which closes or opens the flow passage.
3. The device as claimed in claim 1, wherein the adapter can be attached by mating of threads of the adapter and the injection pen device.
4. The device as claimed in claim 1, wherein the microneedle can either integrally be attached to needle cap or by mating of threads of the microneedle to the needle cap.
5. The device as claimed in claim 1, wherein the microneedles can be arranged in one or more predetermined array system.
6. The device as claimed in claim 1, wherein the microneedles can be hollow, solid, biological material coated hollow or solid, porous and the like.
7. The device as claimed in claim 1, wherein the geometrical shape of microneedles can be selected from the group comprising of cylindrical, conical, tapered, pyramidal, frustoconical and frustopyramidal.
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8. The device as claimed in claim 1, wherein the outer diameter of microneedle varies from about 10 microns to 100 microns and length of the microneedle is at least 100 microns.
9. The device as claimed in claim 1, wherein the suitable material for manufacturing microneedles include one or more metals, ceramics, semiconductors, organics, non¬biodegradable polymer, biodegradable polymer or composites.
10. The device of claim 1, wherein the biological material is selected from the group comprising one or more of peptides, proteins, carbohydrates, nucleic acid molecules, lipids and other pharmaceutically active ingredients.
Dated this 14TH day of May, 2008 For Wockhardt Limited

(Mandar Kodgule) Authorized Signatory
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