NOVEL DEVICE FOR OPHTHALMIC DELIVERY

Abstract

Described herein is an intracameral therapeutic agent delivery device in the form of a pen-injector comprising a cartridge container for dispensing multiple doses of a medicament, coupled to an actuation assembly within a housing. A needle assembly is coupled to the distal end of the cartridge container, provided with a removable cap received within the housing will be in optional pre-sterile or no-sterile condition. Use of such device for the prevention or treatment of ocular conditions or diseases is also disclosed.

Claims

1. A novel cable-free, motor driven ophthalmic device in the form of a pen-injector comprising: (a) A cartridge assembly at the distal end of the device; (b) An actuation assembly at the proximal end of the device covered with top and bottom housing covers; and (c) An over cap covering the cartridge assembly locked with the housing of the actuation assembly.

2. The ophthalmic device of claim 1, wherein the cartridge assembly comprises a cartridge holder with a pre-sterile multiple dose glass cartridge having an opening therein comprising the medicament, confined at the proximal end by a piston slidably received within the rearward opening of the cartridge.

3. The ophthalmic device of claim 2, wherein the cartridge assembly constitutes a separate isolated unit and may be sterilized and readily fixed to the device during operation.

4. The ophthalmic device of claim 1, wherein the actuation assembly comprises a plunger rod, a motor, a printed circuit board (PCB) with dose setting buttons on it and a rechargeable/replaceable battery mechanically and electronically supported by the PCB.

5. The ophthalmic device of claim 4, wherein the battery provides the energy for driving the motor and thereby the piston within the cartridge for dispensing the medicament by means of the plunger rod extending from the motor towards the piston of the cartridge within the housing of the device.

6. The ophthalmic device of claim 1, wherein the over cap covers the cartridge assembly held in locked position with the actuation assembly.

7. The ophthalmic device of claim 1, wherein the over cap is replaced and a needle assembly is fixed to the opening of cartridge during administration.

8. An ophthalmic device comprising a needle that is single or double pointed and mounted on a pen device coupled with a sterile cartridge chamber.

9. An ophthalmic device comprising a needle that is single or double pointed with a curved or with a flat edge and mounted on a pen device coupled with a sterile cartridge chamber.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0040] FIG. 1a is a perspective exploded view of an injection device in accordance with one aspect of the invention.

[0041] FIG. 1b is a cross sectional view of the housing assembly of a device in accordance with some embodiments.

[0042] FIG. 2 shows a cartridge assembly for use with some embodiments.

[0043] FIG. 3 is a view showing the assembly of a delivery device in accordance with some embodiments.

[0044] FIG. 4 is an exploded view of a delivery device in accordance with some embodiments.

[0045] FIG. 4a is an exploded view of the device of FIG. 4 showing a dorsal view of the top housing cover.

[0046] FIG. 4b is an exploded view of the device of FIG. 4 showing a ventral view of the top housing cover.

[0047] FIGS. 5a and 5b are front and side views of a novel drug delivery device according to some embodiments.

[0048] FIG. 6 shows needles which may be affixed to the device during operation.

DETAILED DESCRIPTION OF THE INVENTION

[0049] The present invention provides a novel ophthalmic device for intracameral delivery of therapeutic agents in the form a pen-injector for the treatment of ocular diseases and conditions in subject in need thereof.

[0050] It is to be understood that the terminology used herein is for the purpose of describing particular embodiments of the invention and is not intended to be limiting.

[0051] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one having ordinary skill in the art to which the invention pertains.

[0052] As used herein, the term “ocular” or “ophthalmic” refers to any area of eyeball including without limitation, the anterior chamber, the posterior chamber, the vitreous cavity, the choroid, the suprachoroidal space, the conjunctiva, the subconjunctival space, the episcleral space, the intracorneal space, the epicorneal space, the sclera, the pars plana, surgically-induced avascular regions, the macula, and the retina.

[0053] The term “ocular condition” as used herein refers to a disease, ailment or a condition which affects or involves the eye or one of the parts or regions of the eye. Particularly, the present invention provides a pen type auto injector for the treatment of ocular conditions associated with anterior chamber of the eye.

[0054] As used herein the term “anterior ocular condition” refers to a disease, ailment or a condition which affects or involves an anterior ocular region or site, such as a cataract of the lens, or an ailment of the periocular muscle, an eye lid or an eye ball tissue or fluid which is located anterior to the posterior wall of the lens capsule or ciliary muscles.

[0055] The terms “medicament”, “therapeutic agent”, “active agent”, “drug” used interchangeably herein refer to and include, an agent, drug, compound, composition of matter, or mixture thereof, including its formulation, which provides some beneficial effect.

[0056] It is to be understood that more than one agent can be combined or mixed together and incorporated into or used by the present invention, and that the use of the terms “medicament”, “therapeutic agent”, “active agent” in no way excludes the use of two or more such “medicaments”, “therapeutic agents”, “active agents”.

[0057] The term “intracameral delivery” as used herein refers to the delivery of medicament in to the anterior chamber of the eye.

[0058] As used herein, the term “distal” shall designate the end or direction of the injection. The term “proximal” shall designate the end or direction towards the rear of the injection.

[0059] The intracameral delivery device of the present invention is a pen-injector comprising a housing for a pre-sterile cartridge container and an actuation assembly secured together within the housing by a locking system.

[0060] In an embodiment of the invention, the body of the housing is preferably cylindrical, oval or elliptical in shape, such that it is ergonomic. Such design prevents the device from rolling off a table or a flat surface, while providing a greater surface area for printing user instructions. The outer body of the housing is preferably formed from a synthetic material such that it can be easily molded. The outer body of the housing may be transparent so as to easily view the inner components through the outer body. It is also contemplated that the outer body may be opaque such that the interior components are not visible through the outer body. It is also contemplated that a label may be affixed to the outer body, which may increase the rigidity of the outer body.

[0061] Some embodiments of the invention may be explained with reference to the figures.

[0062] FIG. 1a represents a perspective view of the drug delivery device of the present invention.

[0063] In another embodiment, the device comprises a cartridge container disposed within the housing. The cartridge container has a generally elongated, hollow body sized to receive within the housing. The elongated hollow body has a hollow interior sized to receive the cartridge therein. The hollow body has an opening such that a pre-sterile cartridge can be located in the hollow interior and to permit the plunger rod to be slidably received within the cartridge. The cartridge container is designed so as to accommodate various sized cartridges. The cartridge housing may be made of moldable materials such as metal or plastic to ensure sterility, particularly during surgery. In some embodiments, the cartridge housing may be modified so as to incorporate other surgical modules like optical fibres; surgical cauterys.

[0064] In preferred embodiments of the invention, the device comprises a cartridge holder made of polypropylene disposed within the housing.

[0065] In another embodiment, the whole assembly comprising the cartridge within the housing may be sterile or optionally non sterile.

[0066] In the present context, a pre-sterile cartridge is received within the cartridge holder comprising single or multiple doses of a medicament, having an opening at the proximal end for receiving the injection material, rearwardly confined by a piston made of polypropylene to be acted upon by a plunger rod by means of a motor driven force of the device. The cartridge container has a closed front end having an opening therein sized to receive only the needle there through during a medicament dispensing operation and a circumferential flange at the rear adaptable for engaging with the actuation assembly within the housing.

[0067] The cartridge of the present invention may be well described with reference to FIG. 2, wherein the cartridge (201) comprising a cylindrical wall (202) has a distal end (210), which terminates in a neck part ending in circumferential flange (203) against which a piercable and flexible membrane (204) is held sealingly by a cap (205). At a central part of the membrane (204) the cap (205) has an opening (206) through which the membrane (204) is exposed. A hollow conduit (207), such as an injection needle can be stuck through the membrane (204) to communicate with the inner space of the cartridge (201) in which the medicament is stored between the membrane (204) and a front wall (208) of a piston (209) which fits into the cartridge (201). The piston (209) is usually made from a suitable material, such that it is tightly sealed against the inside of the cylindrical wall (202).

[0068] In another embodiment, the cartridge is adapted to be attached to a needle assembly at its distal end to dispense the medicament there through during operation. The cartridge housing may be sterile or non-sterile, further attached to routine plunger rods, further with motor driven electrically from a rechargeable/replaceable battery. In preferred embodiments, the needle assembly may comprise bent or straight needles of various lengths and sized customized for delivering the medicament into the eye.

[0069] In yet another embodiment, the ophthalmic delivery device of the present invention may further comprise a removable cap or a needle cover covering the needle assembly, received within the housing. The needle cover is so designed that it is held in a locked position to prevent the cover from being retracted to expose the needle. The removable cap or needle cover can be replaced by the user during operation of the device. Preferably, the outer dimensions of the needle cover are similar or identical to the dimensions of the outer body of the housing. Such construction provides an impression of a unitary whole when the removable cap is in position covering the needle assembly.

[0070] In a further embodiment of the invention, the present invention provides an intracameral delivery device in the form of a pen-injector (300) comprising a spring (301) of compressed or open type which drives the motor (302). In some embodiments, the actuation assembly may comprise a rechargeable/replaceable battery (303), connected to a motor and a compressible spring. The actuation assembly further may comprises a movable plunger rod (304) adjacent to the proximal end portion of the cartridge container. The actuation assembly may be configured within the housing (305) such that it is extendable in a distal direction to cause the extrusion of the injectable medicament from the cartridge and through the needle (306) when the cartridge is coupled to the actuation assembly. The device may also contain a printed circuit board (307) coupled to the motor and to buttons (308) for delivering accurate doses of a medicament. FIG. 3 illustrates the features of this embodiment.

[0071] In some embodiments of the invention, the actuation assembly (110) within the housing has a proximal end and distal end. The actuator shown has an outer body (111). The distal end portion of the actuation assembly may have a coupler (112) with two hinges (113) that are disposed approximately equidistance circumferentially about the coupler (112), configured to engage the flange of the cartridge container (115) of the cartridge (114) at two distinct circumferential locations where the coupler (112) is hinged to the cartridge container. In preferred embodiments of the invention, the actuation assembly is wrapped in a flexible sterile silicon wrap that protects from breaching the sterile barrier. The features of this embodiment are illustrated in FIG. 1b.

[0072] In a further embodiment of the invention, the pen-injector of present invention further may comprise the housing encompassing end of the cartridge holder and the inner body of the actuation assembly.

[0073] In the present context, the actuation assembly comprises a battery (116) which may be provided as an alkaline, a lithium or any other type of battery, for single use or rechargeable in nature. It is also contemplated that the power source consists in a non-rechargeable battery of specific size and power specifically adapted for use in this device. This allows to realize a particularly simple solution of a cable-free operable device, with significantly less constraints both on the manufacturer's side, e.g. in terms of compliance with legal regulations in the medical sector concerning power sources and chargers, as well as on the user's side, e.g. in terms of keeping multiple pieces which otherwise would have to be furnished with the device, like a battery charger for rechargeable batteries.

[0074] The power source may consist of a single cell unit or of multiple cell units working in series or in parallel. Alternatively, the power source may also be provided as a capacitor or super capacitor capable of storing electrical energy. The injection device according to the present invention thus does not require any cables outside its casing, i.e. it is a cable-free electrically actuated device. The battery supplies electrical power for triggering the injection of medicament which drives the motor (117) to apply an extrusion force or the spring (118) itself compels the force to drive the rod or compressible spring causing the pushing of the plunger rod (119) in the distal direction of the cartridge towards the needle. In the embodiment shown in FIG. 1b, a piston (120) is further provided at the proximal end (121) of the cartridge (114). Positioned at the distal end (122) of the cartridge are a regulator (123), coupler (124), hub (125), and needle (126).

[0075] As illustrated in FIG. 4, a novel drug delivery (400) device according to some embodiments comprises an over cap (401) covering the cartridge assembly which may be locked with actuation assembly, when not in use. The over cap is made of polypropylene and is designed in such a way so as to lock itself with the body of the housing containing the actuation assembly, such that it gives the appearance of a unitary whole when in locked position. During operation, the over cap may be removed and a needle assembly is attached for dispensing the medicament. After use, the over cap may be replaced in its position.

[0076] The cartridge assembly comprises a cartridge holder (402) preferably made of polypropylene constructed for housing a cartridge (403) comprising the medicament to be delivered. The cartridge holder (402) has as opening at its distal end allowing for insertion of a needle assembly and a circumferential flange at its proximal end, facilitating the locking of the cartridge with the actuation assembly, closed at the proximal end by a piston (410) made of polypropylene. In preferred embodiments, the cartridge is a multiple dose glass cartridge.

[0077] In preferred embodiments of the invention, the cartridge holder and a pre-sterile cartridge constitute a separate isolated unit, which may be easily attached during operation or detached when not in use. The isolated unit is so designed as to facilitate easy and firm locking of the said unit with the device at the time of dispensing the medication. The isolated unit may be sterilized and fixed to the device so that the medicament may be used during surgery or post-surgery as and when required.

[0078] Further, the device is designed to accommodate an actuation assembly comprising a rechargeable/replaceable battery (404), electrically supported by and connected to a PCB (405), followed by a motor (406) providing the driving force for dispensing the medicament through the cartridge aided by a plunger rod (411) passing from the motor towards the piston. The actuation assembly is also provided with buttons (407) on the PCB for delivering accurate doses of the medicament.

[0079] In some embodiments of the invention, the actuation assembly at the proximal end is covered by housing covers on both the sides (e.g. top cover (408) and bottom cover (409)), made of a thermoplastic polymer, namely ABS (acrylonitrile butadiene styrene) which account for the resistance, toughness and shiny impervious surface of the body of the housing.

[0080] In some embodiments, the battery is mechanically and electronically supported by one or more printed circuit boards (PCBs). A PCB generally consists of a copper sheet laminated on a non-conductive substrate, etched with conductive pathways or tracks to connect electronic components.

[0081] FIG. 4a shows an exploded view of the novel ophthalmic device of the present invention illustrating the alignment and arrangement of actuation assembly comprising a power source in the form of a battery, electronically supported by a PCB, followed by a motor providing the driving force for delivery of the medicament through the cartridge by means of plunger rod extending from the motor through the piston at the rearward opening of the cartridge. The PCB is provided with buttons on it for delivering desired dosage of medicament. FIG. 4a also illustrates a dorsal view of the housing cover of the device with provision for engaging the buttons PCB board with the housing cover of the device.

[0082] FIG. 4b also represents an exploded view of the ophthalmic delivery device of the present invention with emphasis on the ventral view of the top cover of the housing of actuation assembly.

[0083] FIGS. 5a and 5b are representative of the front and side views of the entire assembly of the pen-injector of the present invention.

[0084] FIG. 6 represents the needles for dispensing the medicament during use. The needles comprise a cylindrical body made of polypropylene and a stainless steel syringe for passing the medicament there through. The needles are so designed to facilitate easy locking with the cartridge during use.

[0085] In another embodiment, the present invention provides a novel, intracameral device in the form of a pen injector which is electronically controlled, or cable-free motor driven, or combinations thereof, so constructed to be handheld, mobile, easily chargeable, flexible to operate with or without a cable. Preferably, the intracameral pen injector of the present invention may be carried for surgical camps.

[0086] According to the present invention, the intracameral drug delivery device is configured for the prevention or treatment of diseases or conditions, including without limitation, aphakia; pseudophakia; astigmatism; blepharospasm; cataract; conjunctival diseases; conjunctivitis; corneal diseases; corneal ulcer; dry eye syndromes; eyelid diseases; lacrimal apparatus diseases; lacrimal duct obstruction; myopia; presbyopia; pupil disorders; refractive disorders and strabismus. Glaucoma can also be considered to be an anterior ocular condition because a clinical goal of glaucoma treatment can be to reduce a hypertension of aqueous fluid in the anterior chamber of the eye (i.e. reduce intraocular pressure).

[0087] According to present invention, the intracameral for ophthalmic delivery may carry balanced salt solution as supplement and also not limited to a solution containing solution of electrolytes as supplement as well.

[0088] According the present invention, the Intracameral for ophthalmic delivery may carry various actives for administration into eye selected from those of antibiotics, steroids, monoclonal antibodies, hyaluronic acid compounds or derivatives thereof and may also be useful to carry hydroxyl propyl methyl cellulose or derivatives or related compounds as inactive. The term antibiotic is not limited to antibacterials, are a type of antimicrobial used in the treatment and prevention of bacterial infection.

[0089] They may either kill or inhibit the growth of bacteria. Antibiotics may also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the common cold or influenza Erythromycin, Clindamycin, Gentamycin, Tetracycline, Meclocycline, and (Sodium) sulfacetamide or combinations thereof. Most of the eye infections are treated with combination of antibiotics and steroids. Thus term antibiotic is also related to combination of steroid and antibiotics. The type of combination is chosen based on the type of eye infection all about. The combinations may be selected from dexamethasone, tobramycin, loteprednol, sulfacetamide sodium, neomycin, polymyxin B, prednisolone, bacitracin, hydrocortisone, flurometholone, gentamicin or combinations thereof.

[0090] The term ‘HA’ is not limited to Hyaluronic Acid (HA) or its derivatives or combinations thereof, HA is also known as hyaluronan or hyaluronate, is a carbohydrate, more specifically a mucopolysaccharide occurring naturally throughout the human body. It can be several thousands of sugars (carbohydrates) long. When not bound to other molecules, it binds to water giving it a stiff viscous material. This viscous Gel is one of the most heavily researched substances, the inventors of the present application have attempted to deliver the same using the device in eye surgery. Its function in the body is, amongst other things, to bind water and to lubricate movable parts of the body, such as eye muscles.

[0091] The term MAB (mono clonal antibody) is not limited to the following otherwise selected from wherein the monoclonal antibody is selected from the group consisting of abagovomab, afelimomab, anatumomab mafenatox, arcitumomab, bectumomab, besilesomab, capromab, edobacomab, edrecolomab, elsilimomab, enlimomab, enlimomab pegol, epitumomab cituxetan, ibritumomab tiuxetan, imciromab, inolimomab, mitumomab, oregovmab, satumomab, sulesomab, technetium (99mTc) nofetumomab merpentan, tositurnomab, vepalimomab, zolimomab aritox, adalimumab, adecatumumab, belimumab, bertilimumab, denosumab, efungumab, golimumab, ipilimumab, iratumumab, lerdelimumab, lexatumumab, mapatumumab, metelimumab, ofatumumab, panitumumab, pritumumab, raxibacumab, sevirumab, stamulumab, ticilimumab, tuvirumab, votumumab, zalutumumab, zanolimumab, abciximab, basiliximab, bavituximab, cetuximab, ecromeximab, galiximab, infliximab, keliximab, lumiliximab, pagibaximab, priliximab, rituximab, teneliximab, volociximab, alemtuzumab, apolizumab, aselizumab, bapineuzumab, bevacizumab, bivatuzumab, cantuzumab mertansine, certolizumab pegol, daclizumab, eculizumab, efalizurnab, epratuzumab), fontolizumab, gemtuzumab, inotuzumab ozogamicin, labetuzumab, lintuzumab, matuzumab, mepolizumab, motavizumab, natalizumab, nimotuzumab, ocrelizumab, omalizumab, palivizumab, pascolizumab, pertuzumab, pexelizumab, ranibizumab, reslizumab, rovelizumab, ruplizumab, sibrotuzumab, siplizumab, sontuzumab, tadocizumab, talizumab, tefibazumab, tocilizumab, toralizumab, trastuzumab, tucotuzumab celmoleukin, urtoxazumab, visilizumab, yttrium (90Y) tacatuzumab tetraxetan, and IgG or combinations thereof.

[0092] The present invention involves the delivery of the mono clonal antibody delivery using the novel device, the term MAB is not limited to the following or otherwise selected from wherein the monoclonal antibody is selected from the group consisting of: abagovomab, afelimomab, anatumomab mafenatox, arcitumomab, bectumomab, besilesomab, capromab, edobacomab, edrecolomab, elsilimomab, enlimomab, enlimomab pegol, epitumomab cituxetan, ibritumomab tiuxetan, imciromab, inolimomab, mitumomab, oregovomab, satumomab, sulesomab, technetium (.sup.99mTc) nofetumomab merpentan, tositumomab, vepalimomab, zolimomab aritox, adalimumab, adecatumumab, belimumab, bertilimumab, denosumab, efungumab, golimumab, ipilimumab, iratumumab, lerdelimumab, lexatumumab, mapatumumab, metelimumab, ofatumumab, panitumumab, pritumumab, raxibacumab, sevirumab, stamulumab, ticilimumab, tuvirumab, votumumab, zalutumumab, zanolimumab, abciximab, basiliximab, bavituximab, cetuximaba ecromeximab, galiximab, infliximab, keliximab, lumiliximab, pagibaximab, priliximab, rituximab, teneliximab, volociximab, alemtuzumab, apolizumab, aselizumab, bapineuzumab, bevacizumab, bivatuzumab, cantuzumab mertansine, certolizumab pegol, daclizumab, eculizumab, efalizumab, epratuzumab), fontolizumab, gemtuzumab, inotuzumab ozogamicin, labetuzumab, lintuzumab, matuzumab, mepolizumab, motavizumab, natalizumab, nimotuzumab, ocrelizumab, omalizumab, palivizumab, pascolizumab, pertuzumab, pexelizumab, ranibizumab, reslizumab, rovelizumab, ruplizumab, sibrotuzumab, siplizumab, sontuzumab, tadocizumab, talizumab, tefibazumab, tocilizumab, toralizumab, trastuzumab, tucotuzumab celmoleukin, urtoxazumab, visilizumab, yttrium .sup.90Y tacatuzumab tetraxetan, IgG-1, IgG-2, IgG-3, and IgG-4 or combinations thereof.

[0093] The term antibody refer to “Antibody” or “antibody peptide(s)” refer to an intact antibody, or a binding fragment thereof that competes with the intact antibody for specific binding. Binding fragments are produced by recombinant DNA techniques, or by enzymatic or chemical cleavage of intact antibodies. Binding fragments include Fab, Fab′, F(ab′)2, Fv, and single-chain antibodies. An antibody other than a “bispecific” or “bifunctional” antibody is understood to have each of its binding sites identical. An antibody substantially inhibits adhesion of a receptor to a counter receptor when an excess of antibody reduces the quantity of receptor bound to counter receptor by at least about 20%, 40%, 60% or 80%, and more usually greater than about 85% (as measured in an in vitro competitive binding assay).

[0094] The present invention involves the delivery of the mono clonal antibody delivery using the novel device, the term ‘polypeptide’ is not limited to the following or otherwise selected from wherein the Examples of polypeptides include insulin like growth factor-I (IGF-I or Somatomedin-C), insulin, calcitonin, leptin, hGH, human parathyroid hormone (PTH) or active fragments thereof, such as but not limited to PTH 1-31, PTH 1-34 and PTH 3-34, melatonin, GLP-1 or Glucagon-like peptide-1, GiP, OB-3 peptide, pituitary adenylate cyclase neuropeptide-activating polypeptide, GM-1 ganglioside, nerve growth factor (NGF), D-tryp6)-LHRH, nafarelin, FGF, VEGF, VEGF antagonists, Leuprolide, interferon-alpha, interferon-beta, interferon-gamma, low molecular weight heparin, PYY, LHRH, LH, GDNF, G-CSF, Ghrelin antagonists, Ghrelin, KGF, Integrelin, Nesiritide, cetrorelix acetate, ganirelix acetate, bivalirudin, zafirlukast, Exanitide, pram lintide acetate, vasopressin, desmopressin, glucagon, ACTH, GHRH and analogs, oxytocin, corticotropin releasing hormone, TRHrh, atrial natriuretic peptide, thyroxine releasing hormone, FSH, prolactin, Tobramycin, Triptorelin, Goserelin, Buserelin, Octreotide, Gonadorelin, Felypressin, Deslorelin, Vasopressin, 8-L-Arg, Eptifibatide, GM-CSF, EPO, Interleukin-11, Endostatin, Angiostatin, N-acetyl oxyntomodulin 30-37, Oxyntomodulin, Ularitide, Xerecept, Apo A-IV, rNAPc2, Secretin, Thymopentin, Neuromedin U, Neurotensin, Thrombospondin-1 inhibitors, FGF-18, FGF-20, FGF-21, Elcatonin Acetate, Antide Acetate, Dynorphin A (1-13) Acetate, Sincalide, Thymopentin Acetate, Thymosin alpha1 acetate (Thymalfasin), Fertirelin Acetate, CRF Acetate, CRF (ovine), Hisrelin, Thymalfasin, Ecallantide, Oxycortin, Urocortin, Spiegelmer nucleotide aptamers, CGRP (calcitonin gene related protein), Urocortin, Amylin, IL-21, melanotan, valpreotide, ACV-1 neuropathic pain peptide, gastrin, gastrin releasing peptide (GRP), gastrin releasing peptide-like peptides, or epidermal growth factor or combinations thereof.

[0095] The term HPMC (Hydroxyl propyl methyl cellulose) is not limited to an average molecular weight between about 10,000 and 13 million. Preferred cellulosic polymers include: hydroxypropyl methyl cellulose (HPMC), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC) and methyl cellulose (MC). In general, these cellulosic polymers are present in the compositions of the present invention at a concentration between about 0.05 and about 5.0 percent by weight (wt %), preferably between about 0.25 and about 1.0 wt %. It is especially preferred to use the cellulosic polymers at a concentration of about 0.5 wt %.

[0096] The invention having been disclosed in connection with the foregoing embodiments, additional variations will now be apparent to persons skilled in the art. Various modifications and variations to the above described pen-injector can be made without departing from the scope of the invention.

[0097] From the foregoing it will be understood that the embodiments of the present invention described above are well suited to provide the advantages set forth, and since many possible embodiments may be made of the various features of this invention and as the device herein described may be varied in various parts, all without departing from the scope of the invention, it is to be understood that all matter hereinbefore set forth or shown in the accompanying drawings is to be interpreted as illustrative and that in certain instances some of the features may be used without a corresponding use of other features, all without departing from the scope of the invention.

[0098] Further, the present invention has be illustrated in the different figures. The following specific and non-limiting steps for functioning need to be construed as merely illustrative, and do not limit the present disclosure in any way whatsoever.