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:
A SYSTEM FOR DELIVERY OF BIODEGRADABLE MICRONEEDLES
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
A device for delivery of a biodegradable microneedle comprising of a therapeutically active principle and a biodegradable polymer across a biological barrier, wherein the device comprises a microneedle strip consisting of a biodegradable microneedle, and a mechanism to cut the selected portion of biodegradable needle corresponding to the dose of the biodegradable microneedle to be delivered, wherein the microneedle strip comprising at least one biodegradable microneedle.

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The following specification particularly describes the invention and the manner in which it is to be performed.

4. Description
The present invention provides a device for delivering the biodegradable microneedle across a biological barrier, wherein the device comprises a microneedle strip comprising of biodegradable microneedles and a mechanism to cut the selected portion of biodegradable microneedle corresponding to the selected dose of the biodegradable microneedles. The present invention also relates to method of delivering the biodegradable microneedle.
The term "microneedle" refers to a device for transdermal delivery or removal of fluids without many of the risks associated with standard syringes. Such devices use arrays of small diameter microneedles and these small diameter microneedles can be non biodegradable or biodegradable. The term "biodegradable microneedle" refers to microneedles made of biodegradable polymers which include polymers of hydroxy acids such as lactic acid and glycolic acid polylactide, polyglycolide, polylactide-co-glycolide, and copolymers with PEG, poly anhydrides, poly (ortho)esters, polyurethanes, poly(butyric acid), poly (valeric acid), and poly (lactide-co-caprolactone) comprising a biological material 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.
Biological material delivered by these biodegradable microneedles provide a clinically useful alternative to standard syringes. The devices comprising biodegradable microneedles are known in the art for delivering a wide variety of biological materials. The amount of selected portion of biodegradable microneedle corresponding to the dose to be delivered varies from individual to individual. Adjusting the selected portion of biodegradable needle corresponding to the dose according to individual need is a challenging task with biodegradable
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microneedles as the biological material that needs to be delivered is fixed per microneedle and there is no reservoir attached for increasing the dose.
US Patent No. 7,056,495, 6,586,006, 6,565,871, 6,331,310, 6,290,991, 6,811,792 and 6,893,657 disclose a solid dose delivery systems for administration of guest substances and bioactive material to subcutaneous and intradermal tissue, the delivery vehicle being sized and shaped for penetrating the epidermis.
US Patent No 7,141,034 relates to transdermal drug delivery device for forming a micropore in a tissue membrane of an animal comprising a substrate and a porator that is located on or within the substrate.
US Patent No 7,083,592 relates to apparatus for delivering or withdrawing fluid, e.g. a drug, through the skin.
US Application No. 20050008683 relates to a method for administration of a substance to a subject's skin comprising delivering the substance into an intra dermal compartment of the subject's skin, wherein the substance results in an immune response no greater than when the substance is delivered intramuscularly.
US Application No. 20050010193 relates to a method for administration of a substance into a subject's skin, comprising delivering the substance into a junctional layer of the subject's skin.
While developing a system for delivering the desired dose of a pharmaceutically active ingredient coated or embedded in biodegradable microneedle, it was observed that if a mechanism for cutting a selected portion of the biodegradable microneedle corresponding to the dose was used along with a microneedle strip containing biodegradable microneedle, it was able to provide a selected dose of
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biodegradable microneedle according to individual's need. The device is simple in design and involves simple mechanism for the delivery of the selected portion of the biodegradable microneedle corresponding to the desired dose of the biodegradable microneedle. The device has user friendly features.
One of the aspects of the present invention provides a device for delivery of a biodegradable microneedle comprising of a therapeutically active principle and a biodegradable polymer across a biological barrier, wherein the device comprises
a. a microneedle strip comprising of biodegradable microneedle, and
b. a mechanism to cut the selected portion of biodegradable
microneedle corresponding to the selected dose of the
biodegradable microneedle to be delivered
wherein the microneedle strip comprising at least one biodegradable microneedle.
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
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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.
The term "non biodegradable polymers" include polycarbonate, polyester, and poly acryl amides.
In embodiments where the microneedles are formed of biodegradable polymers, however, the mechanical requirement is less stringent, since the microneedles or tips thereof can break off, for example in the skin, and will biodegrade. Nonetheless, even a microneedle comprising a biodegradable microneedle still needs to remain intact at least long enough for the microneedle to serve its intended purpose (e.g., its conduit function). Therefore, microneedles comprising biodegradable microneedle can provide an increased level of safety, as compared to non biodegradable ones.
In one of the embodiments the device further comprises a main piston and an auxiliary piston for positioning and applying the microneedles comprising the biodegradable microneedles to the skin surface, a roll for loading the microneedle strip comprising biodegradable microneedles; a flexible wall comprising an opening for discharge of microneedles and housing holding all the components of the device.
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In one of the embodiments the geometrical shape of biodegradable microneedles can be selected from the group comprising of cylindrical, conical, tapered .pyramidal, frustoconical and frustopyramidal.
The microneedles strip comprising biodegradable microneedles can be formed with shafts that have a circular cross-section in the perpendicular, or cross-section can be non-circular. For example, the cross-section of the microneedle comprising the biodegradable microneedle can be polygonal (e.g. star-shaped, square, triangular, pyramidal), oblong, or another shape such as to frusto conical and frusto pyramidal. The shaft can have one or more bores.
In one of the embodiments the cutting mechanism can be a cutter, a razor, a known claw mechanism made of a sharp edged metal.
In one of the embodiments the main piston, auxiliary piston, and the roll can be made of metal, plastic, polymeric material and combination thereof.
The metals for both of the above embodiments 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.
In one of the embodiments the biodegradable microneedles has an outer diameter of from about 10 microns to 100 microns and length of at least 100 microns.
The cross-sectional dimensions biodegradable microneedles typically are between about 1µm and 500 µm, and preferably between 10 and 100 µm. The outer diameter is typically between about 10 µm and about 100 µm, and the inner diameter is typically between about 3 µm and about 80 µm.
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The length of the microneedles typically is between about 10 urn and 1 mm, preferably between 100 urn and 500 urn, and more preferably between 150 urn and 350 urn.
In one of the embodiments the flexible wall is made of flexible polymeric material.
In one of the embodiments a method for delivering the biodegradable microneedle wherein the method comprises
(a) setting up the portion of the biodegradable microneedle corresponding to the dose of the biodegradable microneedle to be delivered,
(b) rotating the main piston by half or one rotation in one direction to cut the select portion of the biodegradable microneedle corresponding to set dose of biodegradable microneedle,
(c) rotating the main piston by half or one rotation for the next operation in the same direction to position the auxiliary piston for the next operation,
(d) applying force on the main piston to position the biodegradable microneedle on the flexible wall and to deliver the portion of the biodegradable microneedle corresponding to set dose of biodegradable microneedle on to the skin surface, and
(e) a release mechanism to re-position the main piston to its original position
In one of the embodiments the dose setting involves vertical movement of the microneedle strip comprising of biodegradable microneedles by a known mechanism.
In one of the embodiments the application .of force on the main piston either for positioning the biodegradable microneedle or delivery on to the skin surface uses energy stored in a spring or any other known mechanism.
In one of the embodiments the release mechanism is a known mechanism.
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"Biodegradable microneedle" used in the present invention include bio degradable polymer and one or more of the diagnostic substance, prophylactic substance, therapeutic substance and the like comprising the pharmaceutically active ingredients.
Figure 1 shows mechanism for dose setting and system for discharge of biodegradable microneedle
Figure 2 shows mechanism for cutting microneedle strip comprising of biodegradable microneedle
In Figure 1, a microneedle strip comprising of biodegradable microneedles are (3) wound round a roll (1). The roll is made of either a metal or non biodegradable polymer. The roll and microneedle strip comprising of biodegradable microneedle are located inside the housing (7). Housing is also made of either a metal or non biodegradable polymer. A known mechanism is used to select the number of biodegradable microneedle strips corresponding to the set dosage of the biodegradable microneedles. When the dose is selected by the known mechanism, there would be a corresponding vertical down ward movement of the biodegradable microneedle over the roll.
In one of the embodiments the position of the main piston (2) would be in a reference position to start with. This reference position would correspond to the reference position of the biodegradable microneedle in its unused condition. The main piston(2) is made of either metal or non biodegradable polymer.
A cutter (8) is attached to the main piston (2) either integrally or by other means. The cutter (8) is positioned circumferentially on the main piston(2) in any of its vertical length. The position of cutter(8) attachment to main piston(2) correspond to reference position. The cutter is made of suitable sharp edged metal.
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The main piston (2) is both rotatable and moveable in the longitudinal direction. The main piston (2) can travel only in one longitudinal direction and restrained to move in the opposite direction. The main piston (2) travels only in the downward direction in the embodiment shown in Figure 1. A known mechanical mechanism or other means is used to fulfill the movement in the longitudinal direction and rotation.
An auxiliary piston (4) is attached to main piston (2) at its distal end. The auxiliary piston (4) is made either of metal or non biodegradable polymer. It is attached either integrally or by other means. Further auxiliary piston (4) attachment position is at an angle to main piston(2) attachment circumferentially. This angle can vary between 30° to 180°. In the Figure 1, it is shown to be positioned at 180°. Attachment of auxiliary piston (4) at an angle is to ensure prevention of delivery of the biodegradable microneedle by accidental application of force and also prevent the hindrance of auxiliary piston (4) from free fall when the biodegradable microneedles are cut.
Both main piston(2) and auxiliary piston(4) can be of any shape such as circular, rectangular , square etc. The Figure 1 shows the auxiliary piston of circular shape.
Once the dose of biodegradable microneedle is set, the main piston(2) is rotated by either 180 ° or 360 ° . When it is rotated by the predetermined rotation, the set dose of biodegradable microneedle is cut and falls on to the sloping flexible wall. After this operation, the auxiliary piston (4) which is located opposite the main piston (2), need to be repositioned before the next operation. A further equal rotation 180 ° or 360 ° is performed so as to position the auxiliary piston (4) for the next operation.
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Now a suitable force is applied on the main piston (2) either manually or by other mechanical or electrical means or a combination of both. This force application is necessary to make ready the position of the biodegradable microneedle for discharge as shown in Figure 1. Further application of force dischargesv the biodegradable microneedle on to the skin.
Once the biodegradable microneedle is discharged, a known release mechanism reverts back the main piston (2) to its original position for the next dose setting and operation.
In Figure 2, yet another mechanism for cutting a microneedle strip comprising of biodegradable needle is shown. A microneedle strip comprising of biodegradable microneedles (2) is placed over grooves (3) of a kit (1). Biodegradable microneedles are projecting inside the kit (1). There are perforations between a select number of bio degradable microneedles. A tool for pick up of select number of bio degradable microneedles having claws (5) fits into the grooves (7). A spring (6) provides necessary force to dislodge the select strip of bio degradable needles along the perforations. Since the substrate containing the perforated microneedles are rested and supported on grooves (3), removal of a microneedle strip comprising of bio degradable microneedle keeps the remaining biodegradable microneedles intact.
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WE CLAIM:
1 A device for delivery of a biodegradable microneedle comprising of a
therapeutically active principle and a biodegradable polymer across a biological
barrier, wherein the device comprises
c. a microneedle strip comprising of biodegradable microneedle, and
d. a mechanism to cut selected portion of biodegradable microneedle
corresponding to the selected dose of the biodegradable
microneedle to be delivered
wherein the microneedle strip comprising at least one biodegradable microneedle.
2 The device as claimed in claim 1, further comprises a main piston and an auxiliary piston for positioning and applying the biodegradable microneedles to the skin surface, a roll for loading the microneedle strip of biodegradable microneedles; a flexible wall comprising an opening for discharge of microneedles and housing holding all the components of the device.
3 The device as claimed in claim 1, wherein the geometrical shape of biodegradable microneedles can be selected from the group consisting of cylindrical, conical, tapered, pyramidal, frustoconical and frustopyramidal.
4 The device as claimed in claim 1, wherein the cutting mechanism can be a cutter, a razor, a known claw mechanism made of a sharp edged metal.
5 The device as claimed in claim 2, wherein main piston, auxiliary piston, and the roll can be made of metal, plastic, polymeric material and combination thereof.
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6 The device as claimed in claim 1, wherein biodegradable microneedles has an outer diameter of from about 10 microns to 100 microns and length of at least 100 microns.
7 The device as claimed in claim 2, wherein the flexible wall is made of flexible polymeric material.
8 A method for delivering the biodegradable microneedle wherein the method comprises

(a) setting up the portion of the biodegradable microneedle corresponding to the dose of the biodegradable microneedle to be delivered,
(b) rotating the main piston by half or one rotation in one direction to cut the portion of the biodegradable microneedle corresponding to set dose of biodegradable microneedle,
(c) rotating the main piston by half or one rotation for the next operation in the same.direction to position the auxiliary piston for the next operation,
(d) applying force on the main piston to position the biodegradable
microneedle on the flexible wall and to deliver the portion of the
biodegradable microneedle corresponding to set dose of biodegradable
microneedle on to the skin surface, and
(e) a release mechanism to re-position the main piston to its original position.
9 The method as claimed in claim 8, wherein the portion of the biodegradable
microneedle corresponding to the dose setting involves vertical movement of
the microneedle strip comprising of biodegradable microneedles by a known
mechanism.
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10 The method as claimed in claim 8, wherein the application of force on the main piston either for positioning the biodegradable microneedle or delivery on to the skin surface uses energy stored in a spring or any other known mechanism.
Dated this 05th day of June 2008 For Wockhardt Limited

(Mandar Kodgule) Authorized Signatory
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