(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)
`(19) World Intellectual Property
`Organization
`International Bureau
`
`UOUTA ATAYA
`
`(43) International Publication Date
`23 August 2012 (23.08.2012)
`
`WIPO!IPCT
`
`\=
`
`(10) International Publication Number
`WO 2012/111029 A2
`
`Designated States (unless otherwise indicated, for every
`kind of national protection available): AE, AG, AL, AM,
`AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ,
`CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO,
`DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN,
`HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR,
`KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME,
`MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI NO, NZ,
`OM,PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SC, SD,
`SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR,
`TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW.
`
`GD)
`
`International Patent Classification:
`A61K 31/46 (2006.01)
`A61K 31/137 (2006.01)
`
`(81)
`
`(21)
`
`International Application Number:
`
`PCT/IN2012/000114
`
`(22)
`
`International Filing Date:
`
`17 February 2012 (17.02.2012)
`
`(25)
`
`(26)
`
`(30)
`
`(71)
`
`(72)
`(75)
`
`(74)
`
`Filing Language:
`
`Publication Language:
`
`Priority Data:
`170/CHE/2011 18 February 2011 (18.02.2011)
`
`English
`
`English
`
`IN
`
`Applicant (for all designated States except US): M/S. AP-
`PASAMY ASSOCIATES [IN/IN]; 20, SBI Officer's
`Colony, First Street, Arumbakkam, Chennai
`- 600 106,
`Tamil Nadu (IN).
`
`Inventor; and
`(for US only): RENGASAMY,
`Inventor/Applicant
`Krishnasamy [IN/IN]; 20, SBI Officer's Colony, First
`Street, Arumbakkam, Chennai-600 1060, Tamil Nadu (IN).
`
`Agent: JHABAKH, Kalyan; Surana & Surana Interna-
`tional Attorneys,
`International Law Center, 61-63, Dr.
`Radhakrishanan Salai, Mylapore, Chennai
`- 600 004,
`Tamil Nadu (IN).
`
`(84)
`
`Designated States (unless otherwise indicated, for every
`kind of regional protection available): ARIPO (BW, GH,
`GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ,
`UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU,
`TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE,
`DK,EE,ES, FI, FR, GB, GR, HR, HU,IE, IS, IT, LT, LU,
`LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK,
`SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ,
`GW, ML, MR, NE, SN, TD, TG).
`Declarations under Rule 4.17:
`
`of inventorship (Rule 4.17(iv))
`Published:
`
`without international search report and to be republished
`uponreceipt ofthat report (Rule 48.2(g))
`
`(54) Title: OPHTHALMIC COMPOSITION FOR ENABLING DILATION OF PUPILS
`
`
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`FIGURE 7
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`(57) Abstract: The present invention discloses an ophthalmic composition for ophthalmic application (s) inclusive of Eye examina-
`tion, surgeries carried out in the posterior chamber of the Eye like cataract surgery. The said composition comprises at least three
`active ingredients. The said ingredients may be inclusive of, but not restricted to, Epinephrine Bitartrate, Atropine Bisuiphate, Xylo-
`caine Hydrochloride and additives like, antioxidant compounds, buffers and the like. The said composition comes in a packaging
`container inclusive ofsterile package such as vial / ampoule/pretilled syringes. The said composition can be directly injected in the
`Fye in order to bring about effective and speedy dilation of the pupil(s), in particular pupil(s) of relatively smaller dimension than
`normal pupil. The three active ingredients are mixed in a predefined percentage range in a predefined volumeand the composition is
`supplied in a sterile package.
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`2012/111029A2IIITNATATIATTNAIATA
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`WO 2012/111029
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`PCT/IN2012/000114
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`TITLE OF THE INVENTION: OPHTHALMIC COMPOSITION FOR ENABLING DILATION OF PUPILS
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`Field of the Invention
`
`The present invention relates to, an ophthalmic composition. More particularly, the present invention
`
`relates to an ophthalmic composition, to enable dilation of Pupil(s), during ophthalmic application(s),
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`inclusive of Eye examination andfor increasing the overall efficacy of surgeries carried out in the posterior
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`chamberof the Eye.
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`The ophthalmic composition as exemplified by the present invention is especially useful, whenitis
`deployed for Eye examination and surgeries, that are performedin the posterior chamber, exemplified by
`Cataract surgery, Glaucoma, Retinal surgery, Vitreous Surgery and Implant of other devices in Posterior
`Chamberof the Eye, wherein,it is required to widen the dimension ofthe Iris by dilating the pupil(s) so
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`that, the surgery can be performedefficiently.
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`Stil! further,
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`the compositian as exemplified by the present invention is especially useful when it
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`is
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`deployedin the patient's whose pupils do net respond to the conventional ophthalmic composition
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`and take a relatively longertime to dilate, said pupils being termed as "sluggish pupils” by personsskilled
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`in the art.. he ophthalmic composition as exemplified in the present invention enables even the sluggish
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`pupils to dilate in a quickened manner compared to conventional compositions.
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`structurally, the Eye comprises Anterior and Posterior chambers. Behind theiris (I}, is a
`In this context,
`cavity called the anterior chamber(AC),filled with fluid, and behind that,
`is the lens (L). The anterior
`chamber(AC)is the fluid-filled space inside the Eye betweentheiris and the cornea's innermostsurface,
`the endothelium. Behind the lens (L) is a second fluid-filled area called the posterior chamber (PC). It
`makes up most of the Eye's (F) entire size. The retina (R) is the surface that bordersit in a large curve
`extending almostto the Ciliary Muscle around the lens. Retinal cells are highly light-sensitive and receive
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`the images in incoming light.
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`Backgroundofthe Invention
`
`It is known that, in the pre-industrial era, manufacturing of products was performed by manual operation,
`or by mechanical means. The economy wasalso predominantly restricted fo territories such as,the village
`and/or town of inhabitation. The nutrition consumed by people, was also natural, and without artificial
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`additives. However, with the advent of industrial era, the scenario of day-to-dayliving and ihe general
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`lifestyle of people have undergonea transformation.
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`Environmental pollution has increased due to the establishment of factories, and industrial entities. The
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`modesof nutrition have also changed with people consuming foods with processed ingredients as against
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`natural ingredients in the past.
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`The changing lifestyle and consumption of poor nutrients, has caused a plethora of health problems. In
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`particular, it has been observed that, due to the environmental! pollution, Eye-related disorders have been
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`on the rise. Some of the Eye-related disorders that have been observed are cataract, glaucoma and the
`like,
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`In the above-mentioned context,
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`it has been further observed that, although, some of the Eye-related
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`disorders are curable by instrumentation, such as, spectacles and contact
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`lenses, others require
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`medication to be used.
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`At an advanced stage, someof the disorders are curable only by Eye surgery. With particular focus to
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`cataract, in medical terminology, a “cataract” is defined as opacity of the lens of the Eye that causes a
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`progressive, painless loss of vision. The symptoms through which, cataract
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`is recognizable are,
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`in
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`20°
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`general, vision may be blurred, contrast may be losi, and halos maybevisible aroundlights.
`
`it is known that, Cataracts are the leading cause of blindness worldwide. Cataracts are
`in this context,
`commen, mostly in the older adults. They usually develop without any apparent cause. Even though,
`Cataracts usually cannot be attributed to any apparent cause, however, certain factors have been
`identified as contributing factors. The identified contributing factors are inclusive of, but are not restricted
`‘ to, injury to the Eye, prolonged use of certain drugs (such as corticosteroids), prolonged exposure to x-
`rays (such as with radiation therapy to the Eye),inflammatory andinfectious Eye diseases, diseases such
`as diabetes, dark Eyes, prolonged exposure to direct sunlight, poor nutrition, smoking, alcoho! use and
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`heat from infrared exposure.
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`in the medicalfield, it is generally observed by Eye surgeons and the knowledgeableoptical professionals
`that, people who have had a cataract in one Eye are morelikely to develop one later in the other Eye.
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`Sometimes, cataracts can develop in both Eyes at the same time. Babies can be born with them
`(congenital cataracts), and children can also develop cataracts, usually as a result of injury orillness. An
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`ophthalmic professional is generally aware of the symptomsthat may confirm the existence of a cataract.
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`In this context, becauseall light entering the Eye passes through the lens, clouding of the lens can block,
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`distort, or diffuse light and cause poor vision. Thefirst symptom of a cataract may be seeing halos and
`starbursts around lights (glare). Sometimes, the first symptom is blurred vision. Less commonly, double
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`vision is an early symptom. A person may also notice that colors seem more yellow andless vibrant.
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`Reading may become more difficult because of a worsening ability to distinguish the contrast between the
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`light and darkof printed letters on a page. The extentofvariation in vision due to the formation of cataract
`
`dependsontheintensity oflight entering the Eye and on the location of the cataract.
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`With a cataract near the backof the lens (posterior sub capsularcataract), visual acuity is worse when the
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`pupil constricts (for example, in bright light or during reading). Posterior sub capsular cataracts are also
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`more likely to cause loss of contrast, as well as glare from bright lights or car headlights, while driving at
`night. People with cataracts who take drugs that constrict their pupils, (certain glaucoma Eye drops, for
`
`example) may also have greatervision loss.
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`After the condition of cataract is determined, a doctor can usually detect a cataract, while examining the
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`Eye with an ophthalmoscope. A doctor can identify the exact location of the cataract and the extent to
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`which it blocks light by using an instrumentcalled a slit lamp, which allows examination of the lens and
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`other parts of the Eye in more detail. The only treatment that provides a cure for cataracts is surgery.
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`There are no Eye drops or drugs that will make cataracts go away. Occasionally, cataracts cause
`_ changes (such as swelling of the cataract or glaucoma) thal lead doctors to recommend the cataract be
`removed quickly. However, mosttimes people, should have surgery only whentheir vision is so impaired
`by cataracts that, they feel unsafe, uncomfortable, or unable to perform daily tasks. There is no advantage
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`to having cataracts removed before then.
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`Cataract surgery can be performed on a person of any age andis generally safe even for people with
`illnesses such as heart disease and diahetes. Usually, the doctor makes a small incision in the Eye and
`removes the cataract by breaking it up with ultrasound and taking out the pieces (phaco-emulsification).
`Whenall the cataract pieces have been removed, the surgeon places anartificial lens (intraocular lens)
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`within the lens capsule left behind, when the cataract was removed.
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`Cataract surgery has been mentioned only for the purposesofillustration and Eye surgery is inclusive of
`_ but not restricted to surgeries carried out in the Posterior Chamberof the Eye like. Glaucoma, Retinal
`surgery, Vitreous Surgery and Implant of other devices in Posterior Chamberof the Eye.
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`It is known to an ophthalmic professional, that Eye surgery is an intricate procedure, and requiresa lot of
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`meticulousness and care, when the surgery is under progress.
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`it is amply clear to a person skilled in the art that cataract surgery
`To examine the process in detail,
`involves removalof the natural lenses of the patient's Eye,followed by implantation of replacement lenses
`termed as Intraocular lenses (IOL's) which are implanted behind theiris. In order to achieve such an
`Intraocular lens transplant, the Eye surgeontypically dilates the Eye,installs instrumentation to maintain
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`the iris in an expanded position, and makesan incision in the anterior wall of the capsule, so as to permit
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`removal of the patient's natural lens. At this point, the LOL is inserted and properly emplaced, followed by
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`necessary final sutures in the cornea.
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`As can be appreciated, surgery of this type involves working in extraordinarily close quarters with theIris.
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`The Iris widens in fow fight conditions and contracts in bright light conditions in the natural scheme of
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`things without manual intervention. But during surgery dueto the brightness of microscopelight, itis found
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`that the Iris contracts, but it can be adverse to the results of the surgery, since there is a requirementfor
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`dilation of pupils during the surgery. To achieve the said dilation of pupils, certain pupil dilatory
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`instruments are available. The said instruments are termed as “Iris Retractors".
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`For instance, US Patent No. 5,174,279 entitled “Iris retractor for use in operations on the Eye of a living
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`creature" reveals anIris retractor for use in operating on the Eye of a living creature, by means of which
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`the iris: is drawn outwards for widening the pupil and is held at the outer edge, which is essentially formed
`by the transition from the cornea to the sclera. Theiris retractor essentially comprises a suspended part
`having a hook portion and a guide part and on which a platelet-like clamping part is displaceable relative
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`to the hook portion.
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`iris retaining
`Similarly, US Patent No. 4,782,820 entitled "Iris retaining device” reveals an improved,
`device adapted for placement within the pupillary opening of a human Eye so as to engage the inner
`margin of the iris, so as to enlarge and maintain the pupillary opening during Eye surgery. The device
`preferably comprises an elongated, arcuate, flexible, resilient body including a generally U-shaped in
`cross section iris-receiving sidewall; the lattér presents an inboard central bight portion and a pair of
`spaced apart wall sections extending outwardly therefrom. The ends of
`the body are slidably
`interengaged, and a drawstring is provided for manually contracting the body forinitial placement thereof.
`After such contraction andinitial placement, the drawstring and may be released sothatthe resilient bady
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`expands to engage, expand andprotectthe margin oftheiris.
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`As indicated, the conventional technique is to employ iris-expanding instrumentation, but this is only
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`partially effective. Due to the usage of the instrumentation, the iris may be readily traumatized during Eye
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`surgery, resulting from irrigation solutions used to wash out the cortex of the Eye, and instrumentation
`necessary to retract the iris during surgery. Finally, the iris can also be damaged during implantation of an
`iOL.
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`Manya time these retractors are cumbersometo insert into small incisions and resuit in faulty positioning.
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`As a result of their relatively small size, the surgeon has oftentimes great difficulty to see the individualiris
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`retractors during the process of inserting the retractors into the anterior chamber and attaching the
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`tetractors to the iris or removing them from the Eye. Sometimes,
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`this problem generally requires a
`
`surgeonto interrupt the surgery to re-grasp and retracttheiris.
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`Alternatively,
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`to save time, surgeons must simply pull
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`the iris retractor. This latter method can be
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`dangerous because of possible lacerations to the delicateiris. This may potentially adversely affect the
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`surgery.
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`Alternatively there are devices being used in Eye surgery today whichretract theiris, strctching for 360
`degrees aroundtheiris, thereby enlarging the pupil, but these retractors must be held by someone, such
`as a surgeon or a nurse. Furthermore, the iris retractors currently in use do not provide equal stretching
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`for 360 degrees aroundtheiris.
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`Whenthe related procedures requiring dilation are finished, the reverse procedure is carried out.It is
`found that the Iris does not return back to its original profile because of the apertures madein theIris to
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`insert the Iris Retractor.
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`Therefore, it is observed that a chemical composition when used to dilate a pupil is much more safer to
`avoid injury to theiris, a critical but weak and delicate organ. In procedures passing through or nearthe
`iris,
`it is desirable to dilate the pupil to keep theiris out of harm's way and to give the surgeon a wider
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`opening through which to work and view the posterior segments of the Eye
`
`Campositions are available in the art, which is employed for treatment of Eye-related disorders.
`A proposal in the art is available, namely, US 6,218,428, entitled “Optilhalmic composition”. The said
`proposal reveals an ophthalmic composition that combines multiple agents necessary to perform a routine
`Eye examination. The said composition is a mixture of a topical local anesthetic, a pupillary dilating agent,
`and a dye, all in solution. The composition may also include a preservative, a wetting agent, a diluting
`agent, and/or a buffer. The preferred composition provides a meansto: 1) anesthetize the cornea to allow
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`for pain relief, manipulation and the measurement of intraocular pressure, 2) dye the comea and
`conjunctiva to allow for the detection of pathology and for the measurementofintraocular pressure, and 3)
`dilate the pupil to allow for examination of the’ optic nerve, macula, retina, retinal vasculature, and
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`peripheral fundus.
`
`the posterior pole are
`The typical dilating agent used to dilate the pupils for examination of
`sympathomemetic or parasympatholytic
`agent,
`or
`both,
`including
`phenylephrine,
`tropicamide,
`cyclopentolate, hydroxyamphetamine, atropine, homatropine and/or otherdilating agents. Most preferably,
`the total dilating agent should be in an amount between about0.1% and about 5% of the solution. Also an
`embodiment of this composition may be used preoperatively before ophthalmic surgery (e.g., cataract
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`surgery).
`
`is available, namely, US 7,229,961, entitled “Compositions and methods for
`in the art
`A proposal
`enhancing drug delivery across and into ocular tissues”. The said proposal reveals Sympathomimetic
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`agents, which are useful for treating, e.g., glaucoma and mydriasis. Exemplary sympathomimetic agents
`include, e.g., dipivefrin, epinephrine, phenylephrine, apraclonidine, cocaine, hydroxyamphetamine,
`
`naphazoline, and tetrahydrozoline. Muscaric antagonists are useful
`for
`treating, e.g., cycloplegic
`retinoscopy and cycloplegia. They are also useful in dilated fundoscopic exams. Exemplary muscaric
`antagonists include, e.g., atropine, scopolamine, homatropine, cyclopentolate, and tropicamide.
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`is available, namely, US 5,227,372 entitled “Method for retaining
`in the art
`Yet another proposal
`ophthalmological agents in ocular tissues’. The proposal reveals Ophthalmological agents which may be
`used in combination with glucan sulfate as a vehicle readily may be determined bytheskilled artisan by a
`numberof techniques and include: therapeutic agents for the treatment of glaucoma such as epinephrine
`orits salt, therapeutic agents for the treatment of cataracts such as pirenoxine; anti-allergic agents such
`as sodium nomoglicate, cromolyn and amlexanox;anesthetics such as xylocaine, tetracaine and thelike.
`
`Anotherproposalin the art is available, namely, US 6,268,359, entitled “Preventives or remediesfor vision
`disorders”. The said proposal reveals a pharmaceutical composition for preventing or treating visual
`functional disorders caused by ocular circulatory disorders (for example, ocular hypertension and
`glaucoma) and visual function disorders, based onciliary tension, (for example, myopia) whoseactive
`component is a vasopressin antagonist.
`In addition to the vasopressin antagonist, the pharmaceutical
`composition of the present invention may optionally contain, or may be used together with one or more
`other pharmacological active agents. Examples of such pharmacological active agents include,
`parasympathomimetic drugs (for example, pilocarpine and carbachol), cholinesterase inhibitors (for
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`example, physostigmine salicylate, distigmine brornide and echothiopate iodide), sympathomimetic drugs
`
`(for example, epinephrine, dipivalyl epinephrine, clonidine, paraamino clonidine and brimonidine), and
`sympathomimetic Beta.
`- Blockers
`(for example, betaxolol,
`levobunolol,
`timolol and carteolol),
`
`prostaglandine derivatives (for example, isopropyl! unoprostone and latanoprost) for diseases caused by
`
`ocular circulatory disorders, and tropicamide for diseases caused byciliary muscle tension.
`
`Still further, another proposalin the art is available, namely, US 5,079,253 entitled, “Composition for the
`topical treatment of glaucoma or ocular hypertension. The said proposal reveals a method for the topical
`
`treatment of glaucoma or ocular hypertension, which comprises contacting the surface of the Eye with a
`
`composition, consisting essentially of an effective intra-ocular pressure reducing amount of a mixture of:
`
`an adrenergic agonist selected from the group consisting of epinephrine, dipivalylepinephrine,
`
`norepinephrine, phenylephrine, clonidine, isoproterenol, salbutamol, metaproterenol and terbutaline, and;
`a phosphodiesterase
`inhibitor
`selected from the group consisting of
`isobutylmethylxanthine,
`
`theophyllamine, Rolipram and RO-2017624, in an ophthalmically compatible carrier.
`
`Still further, another proposal in the art is available, namely, US 4,190,642 entitled, “Ocular therapeutic
`
`system for dispensing a medication formulation”. The said proposal reveals an ocular system, which is
`disclosed for dispensing a medication formulation to the Eye. The system comprises a formulation,
`consisting of a pilo-carpine osmotic solute and an epinephrine osmotic solute, dispersed in a polymer
`such that, the formulation is surrounded substantially,
`individually by the polymer. The system, when
`placed in the Eye, dispenses the formulation at a controlled rate, over time. A methud also, is disclosed
`
`for the managementof intraocular pressure using the ocular system.
`
`It is observed that, the said proposals available in
`Someother similar proposals are available in the art.
`the art, describe usage of a chemical composition or a mechanical instrumentation, both of which are
`deployed to dilate the pupil
`lo lhe required dimension for the duration of the surgery. The available
`proposals have some inherent deficiencies, however, for an Eye surgeon performing an intricate Eye
`surgery,it is required to dilate the pupil of the Eye during the duration in which, the surgery is performed.
`
`It will be well understood by a personskilled in the art that, the pupil(s) are dilated not only for the purpose
`of Eye surgery inclusive of Cataract surgery, Glaucoma, Retinal surgery, Vitreous Surgery and Implant of
`other devices in Posterior Chamber of the Eye but also for the examination of the Eye for purposes other
`
`than eye surgery.
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`There is therefore, a needin the art, for an alternative to an instrumentillustratively embodied by an Ivis
`
`Retractor deployed conventionally to dilate the Iris, and widening the pupil within the Iris for the purpose
`
`..
`
`.Of.Eye surgery and also for the examination of the Eye for purposes other than Eye surgery..
`It is further observed by personsskilled in the art that, dilating the pupil depends on the nature of the pupil
`
`_ and its responsiveness due to age and other factors. Also many at time certain pupils termed by
`
`ophthalmic professionals as "sluggish pupils" take a longer time to dilate than "normal pupils” when
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`conventional ophthalmic compositions are used.
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`In such a scenario there is a need in the art for an
`
`opthalmic composition which enables quickening the process ofdilating even in the “sluggish pupils".
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`Thereis therefore, also a further needin the art, for an Ophthalmic Composition, in which,it is possible to
`dilate the pupil(s) for the required duration, especialiy for people who have pupil(s) whicharerelatively
`
`smaller in dimension than the normal pupil(s), and then, reverse it to its normal dimension without any
`
`detrimental side effects to the structure of the Iris which is a critical component for vision but which is
`fragile due to which, any laceration in the Iris structure will
`result
`in long-term permanent vision
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`impairment.
`
`Summary ofthe Invention:
`
`- The present invention is embodiedin the ophthalmic composition in a manner, so asto fulfill the above-
`mentioned need(s)
`in the art.
`In addition,
`the present
`invention also,.has further objective(s) as
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`enumerated and described in the present disclosure. A person skilled in the art, is very well aware that,
`the enumerated objective(s) of the composition, as embodied in the present invention, are merely
`illustrative of the scope and purview of the present invention, as described in the present disclosure.
`However, such anillustration may not be construed to restrict the present invention in any manner.It will
`be very clear to a person skilled in the art that, any variation and/or combination in the said objective(s)
`fulfilled hy the present invention, may also be understood to be within the scope and purview of the
`present invention, as described in the present disclosure. The present invention may be embodied in
`other specific forms without departing from the spirit or essential attributes thereof.
`
`to provide an ophthalmic
`In the above-mentioned context, an objective of the present invention is,
`composition, using which, it is passible to dilate the pupil(s) during ophthalmic application(s) inclusive of
`Eye examination and surgeries carried out in the posterior chamberof the Eye like calaracl surgery.
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`An objective of the present invention is to dilate even sluggish pupil(s) and therefore, conventionally take
`~ a longer time duration to dilate in a quick manner, so as to make the process of surgery non-cumbersome
`
`and more comfortable to the patient.
`
`An objective of the present inventionis to dilate pupil{s) which are relatively smaller in dimension than the
`
`normal pupil(s).
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`Yet another objective of the present invention is, to provide an ophthalmic composition, using which, it is
`
`possible to dilate the pupil during ophthalmic application(s) inclusive of Eye examination and surgeries
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`10
`
`carried out in the posterior chamberof the Eye like cataract surgery , in a mannerthat the dilated pupil(s)
`
`are capable of being restored to its original dimensions without deformities, after the surgery has been
`
`completed.
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`Still another objective of the present invention is, to provide an ophthalmic composition, using which, it is
`
`15
`
`possible to dilate the pupil during ophthalmic application(s) inclusive of Eye examination and surgeries
`
`carried out in the posterior chamberof the Eyelike cataract surgery, in a mannerso that, the composition
`
`is nontoxic to the Eye.
`
`Furtherstill, an objective of the present invention is to provide an ophthalmic composition, using which, it
`is possible to dilate the pupil during ophthalmic application(s) inclusive of eye examination and surgeries
`
`20
`
`in a manner such that, the
`in the posterior chamber of the Eye like cataract surgery,
`carried out
`composition retains the pupil in the same dimension, during the duration of the surgery or examination.
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`25
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`30
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`35
`
`A further objective of the present invention is, to provide an ophthalmic composition, using which,it is
`possible to dilate the pupil without affecting the position or condition of the surrounding parts of the Eye,
`the Eye being an intricate and delicate organ, wherein, any minor changein positioning and/or condition
`of the surrounding parts of the Eye is capable of affecting the outcome of the surgery.
`
`A further objective of the present invention is, to provide an ophthalmic composition, using which,it is
`possible to dilate the pupil without causing any laceration to the pupil resulting in deformities due to which
`there may be long term and permanentvision impairment due to usage of pupil dilatory instrumentation.
`
`Furtherstill, an objective of the present invention is to provide an ophthalmic composition, using which,it
`is possible to dilate the pupil during Eye surgery, without the requirementof the personeffecting the pupil
`dilatory composition/instrumentation to be a very highly skilled ophthalmic professional for instance a
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`personin the league of an Eye surgeon.
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`

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`WO 2012/111029
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`PCT/IN2012/000114
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`Furtherstill, an cbjective of the present invention is to provide an ophthalmic composition, in which, it is
`
`possible to dilate the pupil during ophthalmic application(s) inclusive of Eye examination and surgeries
`
`carried out in the posterior chamberof the Eye like cataract surgery, without the requirement of a very
`costly instrument, since Iris Retractors are very expensive in comparison to Compositions.
`
`Furtherstill, an objective of the present invention is to provide an ophthalmic composition, in which,
`
`the Iris returnsto its original configuration without any ruptures in its structure resulting in deformities, after
`
`the surgery is completed.
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`10
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`In view of the above-mentioned objectives, the present invention discloses an ophthalmic composition for
`
`enabling dilation of pupil(s),
`
`in ophthalmic application(s) inclusive of Eye examination and surgeries
`
`carried out in the posterior chamber of the Eye like cataract surgery. The ophthalmic composition as
`
`embodied in the present invention comes in a packaging container inclusive of sterile package such as
`
`vial/ampoule/ prefilled syringes. The ophthalmic composition as embodied by the present invention is an
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`15
`
`Intacameral Mydriatic solution (ICM) Injected for pupil dilation, during Eye examination and surgeries
`
`carried out in the posterior chamberof the Eye.
`
`In medical parlance, an !ntacameral Mydriatics (ICM) Injection enables injection of preservative free
`
`ophthalmic composition of 0.5m! to tml, without using any Preoperative to induce pupil dilation so thatits
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`20
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`diameter increases to a maximum of 4-6 mm within 30-90 secondsof injection given. This pupil dilation
`
`effect will hold up to30-120 minutes , which is safe time for phaco-emulsification and Intraocular lens (IOL)
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`Implantation. The mean pupil diameterwill be significantly greater than the than its normal dimension. No
`additional Mydriatics are needed up to the end of the surgery. The ophthalmic composition as embodied
`by the present invention can be directly injected in the Eye.
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`25
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`The said composition as embodied in the present invention comprises: at least three active ingredients.
`
`The said ingredients may beinclusive of, but not restricted to, Epinephrine Bitartrate, Atropine Bisulphate,
`Xylocaine Hydrochloride and additives
`like, antioxidant compounds, buffers and the Sike. The
`corresponding range of percentage(s) of Epinephrine Bitartrate in 1 ml
`is 0.07-0.21%, Atropine
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`30
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`Bisulphate in 1 ml is 0.005-0.12%, and Xylocaine Hydrochloride in 1 ml is 92-99.9%. The three
`
`active ingredients are mixed in a predefined percentage range, and the composition is supplied
`
`in a sterile packaging containers such as vial / ampoule/ prefilled syringes.It is very safe and
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`effective for human subjects..
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`35
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`The composition as revealed in the present disclosure,
`
`is injected into the pupil, by employing a
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`Intacameral Mydriatics (ICM).
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`

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`WO 2012/111029
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`PCT/IN2012/000114
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`Brief Description of Drawings
`
`The description of the present invention in conjunction with the drawingsillustrating the present invention
`
`and in application(s) illustrative of the present invention, explain in detail, the working of the present
`
`invention.
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`It will be amply clear to a person skilled in the art, that the application as disclosed in the
`
`drawings are merelyillustrative of the scope of the present invention and not exhaustive of the scope of
`the presentinvention in its entirety. The advantagesarising out oftheillustrated application in conjunction
`with the enclosed drawings are merely indicative and are not to be construed to be restricting the scope of
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`10
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`the present invention in any manner.
`
`FIG. 1
`
`showsthe structure of the human Eye.
`
`FIG. 2 showsthe division of the Eye into the Anterior and Posterior Chambers (AC, PC).
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`FIG. 3 shows the variation in dimension of tris under normal conditions, viz., widening of Iris under low-
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`15
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`light conditions and contraction of Iris under