Title of Invention

LOW INTENSITY DEVICE FOR SEPARATING EPITHELIAL CELLS

Abstract

In various surgical procedures, it is necessary to effectively separate cells which adhere to basement membranes or capsules due to various reasons. There are several devices and means in the prior art like mechanical, chemicals, heat, electricity, laser and, mechenical to achieve this. The chief limitation of these methods is the possibility of injury to the surrounding tissue. The present invention relates to a device emitting light of selected low intensity wavelengths for separating epithelial cells and an optical carrying system that carries the light energy so that the epithelial cells lining the capsule or base membrane are exposed to the said light device directly (Figs 1, 7) and various methods for using the device. The device can be employed in a number of procedures for effective separation of epithelial cells without causing any damage to the tissues.

Full Text

FORM 2 THE PATENTS ACT : 1970 (39 OF 1970) COMPLETE SPECIFICATION SECTION: 10 LOW-INTENSITY DEVICE FOR SEPARATING EPITHELIAL CELLS Dr. Rajeev Maruti Raut 27, Manisha 2 A, Moledina Road, Pune 411 001, Maharashtra Indian National The following specifications particularly describe the nature of this invention and the manner in which it is to be performed. 07-04-2005 2 FIELD OF INVENTION In various surgical procedures, it is necessary to effectively remove cells which adhere to basement membranes or capsules due to various reasons. Such removal has to be effective to prevent further complications or deterioration of the membrane or tissues. There are several devices and methods as disclosed in the prior art, which aim to separate cells which adhere to the cell membranes. The present invention relates to a device and a method, which overcomes the various problems associated with prior Art. The invention embodies a device emitting light of selected low intensity wavelengths for separating epithelial cells. The device can be employed in a number of procedures. Li the present complete specification, the invention is described with reference to an ophthalmologic procedure. BACKGROUND OF THE INVENTION In a mammal, lens epithelial cells of eye proliferate after the rest of the lens material is removed during cataract surgery. They may become opaque, and cause "after cataract" which affects vision. Some epithelial cells get injured and devitalised during cataract surgery, or as a result of injury or irritation to them from the intraocular lens, which may be implanted. These cells attract mediators of inflammation and cause inflammatory response after cataract surgery. 3 Some of these cells change their character after surgery, become fibroblasts, and may cause fibrous scar formation in the capsule, giving rise to capsule contraction syndrome. It is desirable to remove these cells during cataract surgery to avoid all these problems in the postoperative period. The cell membrane such as eye capsule is very thin and fragile. The space in which the surgeon has to work is very limited, and the capsule must be spared along with the surrounding tissue, at all cost. The inner structures of the eye do not tolerate any high-energy insults like chemicals, heat, electricity, laser, mechanical abrasions, etc. The lens epithelial cells are attached to the capsule. They do not come out by simple washing as the attachment between the cells and the capsule is very strong. If this attachment is loosened or severed, the cells can be washed out easily, or may be sucked out by a simple tubular irrigating cannula attached to a syringe. The prior Art in the field discloses various means for overcoming the problem of removing the epithelial cells .. 4 Some of the prior art discloses use of mechanical means to remove unwanted cells. The chief limitation of these methods is the possibility of injury to the surrounding tissue. International Patent Publication WO 00/49976, PCT/USOO/04339 describes a Nicapsulorhexis Valve. This is a silastic valve which will attach to the capsulorhexis opening, in a water tight fashion. This excludes the rest of the inner surface of the eye from contact with certain cytotoxic substances, which may be introduced into the capsular bag, to destroy the epithelial cells. International Patent Publication WO 99/04729 , deals with an Intraocular Ring as a device. This disclosure deals with a physical gadget called intra ocular ring, which kills the cells or prevents their proliferation, by the pressure effect caused by its contact with the cells. ffitefnafiofial Patent Publication WO 2004/039295 deseriBes a method of making a capsulorhexis in the lens capsule. The lens is removed from the lens capsule of an eye and the capsulorhexis is sealed with a sealing means/device, to provide gas leakage proof sealing. The lens capsule is expanded with a gas and desired operation is performed inside the said expanded lens capsule. 5 Here, the inventor discloses a air tight sealing device seals the capsular bag from the rest of the eye so that toxic gases or liquids may be introduced into the bag to kill the cells. U.S. patent No. 6,432,078 describes a System and Method for removing cataract or other cells in an eye using water jet and a suction. It discloses a mechanical device to abrase, and then to suck the cells out of the eye, using water jet, mechanical brushes, etc. International Patent Publication WO 98/25610 / PCT/CA97/00949, discloses use of green porphyrins for the manufacture of a medicament for the treatment of secondary cataracts .In this document, researchers from the University of Columbia disclose certain chemical substances called green porphyrins. These chemical substances are applied to the epithelial cells, and then irradiated with light, so that they destroy the cells to which the substance is applied. This has called photodynamic therapy of the lens capsule. Porphyrins are chemical substances, which must be introduced into the eye. The method is therefore not desirable. International Patent Publication WO 99/39722 ,PCT/IB99/00905 discloses compositions and methods for separating lens epithelial cells and preventing posterior capsular opacification This is achieved by modulating focal contacts, which mediate adhesion between lens epithelial cells and the lens capsule, using 6 a treating solution containing a focal contact-modulating substance or a proenzyme, such as Lys-plasminogen, which is introduced into the eye. Intemational Patent Publication WO 02/047728 , PCT/GBO1/05465 discloses treatment of posterior capsule opacification . This disclosure deals with killing the cells with a chemical ligand. The ligand is preferably Fas ligand. A spacer is preferably polyethylene glycol. The polymer preferably constitutes an intraocular lens. Intemational Patent Publication WO 02/43632, PCT/AUOl/01554 discloses a device for sealing the capsular bag of an eye and a method for delivering fluid or treatment substances to the lens of an eye . A method is disclosed to seal the capsular bag from the rest of the eye, at the same time allowing delivery of strong chemicals into the bag, to kill the cells. US patent 4,966,577 discloses a composition for preventing secondary cataract formation in the eye following removal of the lens, comprising an antibody specific to particular lens cells related to secondary cataract formation, which antibody is conjugated to an antiproliferative agent. The particularly preferred antiproliferative agents require activation after binding of the antibody to the target cells, and activation may be accomplished by addition of a second composition or by exposure of the eye to electromagnetic energy. Also disclosed is a method of using the composition by administering it directly to 7 the site from which the lens was removed to kill or prevent proliferation of lens cells. This disclosure again specifies first, introduction of a chemical substance, then introduction of another chemical substance, and then activation of this combination by use of electromagnetic energy, to destroy the cells of the capsule. US patents US 5,620,013 US 5,843,893, US 5,627,162 disclose chemical agents to destroy the cells of the capsule. The chief limitation to chemical methods disclosed above is toxicity and adverse effects of the chemicals to the surrounding tissue. International Patent Publication WO 01/54603 , PCT/USOl/03052 discloses a system and method for treating cells of a site in the body, such as at a lens capsule of an eye . The system and method employs an energy emitting device, and a positioning device, adapted to position the energy emitting device at a position in relation to the cells at the site in the body, such as the cells of the lens capsule , such that energy emitted from the energy emitting device heats the cells to a temperature which is above body temperature and below a temperature at which protein denaturation occurs in the cells, to kill the cells or impede multiplication of the cells. The energy emitting device can include a 8 container containing a heated fluid which heats the cells to the desired temperature. The disclosures here deal with a method that heats the cells to denature or coagulate them, thereby destroying them. International Patent Publication WO 98/18392 , PCT/US96/17322 discloses an instrument for destroying residual lens epithelial cells in a lens capsule of an eye. The said instrument comprising of an electrical energy source, a probe comprising an electrode ,electrically coupled to said electrical energy source, and the said probe having a distal end portion configured for insertion into said eye between an iris of said eye and said lens capsule; and an insulating sleeve. In this disclosure, the inventor discloses a method to electrically cauterise the capsule cells, so as to kill them. The chief limitation of electrical methods is that the delicate tissue around the cells may also get cauterised U.S. Patent No. 6,669,694 discloses medical instruments and techniques for highly-localized thermally-mediated therapies. It describes delivery of high thermal energy to the tissue to achieve an ablative effect on the cells. U.S. Patent No. 4,963,142 discloses an apparatus for endolaser microsurgery . A method and apparatus for performing endolaser microsurgery is disclosed, the apparatus including a laser delivery system coupled to a probe capable of 9 transmitting the laser energy through a suitable medium such as sapphire. The probe includes a coaxial canal for aspiration of ablated tissue and/or fluids. The method involves steps of ablating tissue by laser and aspirating the ablated tissue and/or fluids, the method being useful for sclerostomy, vitrectomy and as a substitute for ultrasonic phacoemulsification among others. A probe for performing endolaser microsurgery and removing ablated tissues is described. The apparatus disclosed here is meant to deliver laser energy, and to ablate the tissue, followed by removing the ablated tissue. The term ablation, is a geological term. By definition, it means "melting away" or removal away by melting or evaporation. The laser energy described here is a means to achieve a high energy level, high enough to melt the tissue, and then to remove the ablated or melted products. The achievement of high energy is done by using laser, which allows very high energy concentration at a small area, for a short time, and achieves the melting with out damaging the surrounding tissue. U.S. Patent Nos. 6,238,386, 6,554,824, 6,582,421, 6,712,808, 6,726,680 disclose an instrument that applies laser energy to human tissue. U.S. Patent No 6,454,762 discloses an instrument for applying light, especially laser light, to the human or animal body. It describes an instrument which consists of a movable tip, which enables light energy or laser energy from an external source to be directed to the desired part of the human body. 10 U.S. Patent No 6,238,386 discloses application of sound energy and laser energy to internal body cavities by endoscope. The application of energy inside the human body by fiber optic delivery system. The laser used is therapeutic laser and supplies laser radiation at an optical power at said distal end which is at least 5 Watts or at an intensity at said distal end which is at least 1 kW cm.sup.-2. The power is disclosed to be such as is required for coagulating tissue. Muller discloses a device for using laser energy and sound energy for treating inner body parts endoscopically, but the device uses energy, as stated above, to coagulate tissue. The minimum energy disclosed in the said invention is 5 watts. As 1 watt = 408 lux ,the magnitude of energy used will be 2040 lux The lasers involve high energy, and may cause thermal damage or thermal coagulation of the tissue by raising the temperature of the tissue to high levels for a fraction of a second. However, the surrounding tissue can also get ablated when high energy systems like lasers are used. Such energy will certainly damage the underlying capsule, if the epithelial cells were to be coagulated. It is well known that the capsule breaks at energy levels of 1.2 millijoules, therefore, the disclosed device in the said invention can not be used in ophthalmology to separate epithelial cells from the capsule. This damages the cornea and the capsule itself. 11 LIMITATIONS OF PRIOR ART The prior art cited above attempts to stop the problems associated with the capsular epithelial cells by destroying them and then removing the cells by the following general means :-- A. Mechanical means These methods disclose mechanical devices for the removing the unwanted cells. The chief limitation of these methods is the possibility of injury to the surrounding tissue. B Chemical means . These methods use chemicals for removing the cells. The chief limitation to this method is toxicity of these chemicals to surrounding tissue. C. Electrical means. The chief limitation is again, the delicate tissue around the cells may also get cauterised. D. Laser or Sonic methods .The lasers involve high energy, and achieves thermal damage or thermal coagulation of the tissue by raising the temperature of the tissue to high levels for a fraction of a second. However, the surrounding tissue can also get ablated when high energy systems like lasers are used. This damages the cornea and the capsule itself. 12 SUMMARY OF THE INVENTION The invention embodies a device emitting light of selected low intensity wavelengths as a low intensity device for separating epithelial cells. The present invention overcomes the various shortcomings of the prior art by providing a device embodying a low intensity light source and method/s to expose the epithelial cells in such manner as to loosen the attachment between the epithelial cells and the capsule . This is achieved by directly exposing the target cells to a pre-selected very low intensity light of wavelengths between 300 to 850 nanometers by a device and a method. The light is directed onto the cells from inside. The light is delivered to the cells from inside, by actually touching the tip of the light source carrier to the capsule, and the distance between the epithelial cells and the light source is zero. The time to achieve this is a few seconds. The light specified here is from the visible spectrum, and the intensity specified here of 0.001 to 100 lux. This intensity is very low and the light is almost invisible. The cells are extremely resistant to this light, if it comes from the normal outer side, but extremely sensitive to this light if it is directed to them from the inner side in the manner provided in the invention. 13 BRIEF DESCRIPTION OF THE DRAWINGS Fig 1 is a diagrammatic representation of low intensity device for separating epithelial cells. Fig 2 shows the device using external light, passing through the cornea, which is directed under the anterior capsule by a reflecting mirror, placed inside the eye, where the mirror collects the light and directs it onto the epithelial cells. Fig. 3 shows a tiny light source carried into the bag directly without fiber optics, by attaching it to a handle. Fig. 4 shows device with dual source of light, where the second source outside the bag. Fig. 5 shows smooth tip either in contact or close to the capsule. Fig. 6 shows curved tip, dual source device, with correct method of exposure and placement of the device tip. Fig. 7 shows single light source with two transport systems, the second transport system bypassing the filters. The invention will now be described with reference to the figures 1 to 7 described above. The low intensity device for separating epithelial cells consists of a light source ( 1), and a transport system ( 2) to carry this light into the specific site, into the 14 capsular bag, through the surgical opening made into the bag. The tip of the transport system ( 9 ) where the instrument comes in contact with the capsule (basement membrane ) is smooth, and atraumatic. In another embodiment, two light pipes carry light into the eye, one goes into the inside of the capsular bag, and the other illuminates the capsular bag from outside. LIGHT SOURCE Single light source with filters may be used to create pure color wavelengths and the inside of the capsule bag may be exposed to pure colors. A mixed light source of white light may also be used. Wavelength selected is between 300 to 850 nanometers. Intensity is the critical part of the device. The intensity of the light source used in the invention must be such that the final incident light which falls on the cells must be of very low intensity to produce illuminance of 0.001 lux to about 100 lux. It may be noted that a 40 watts domestic light bulb produces illuminance of thousands of lux if measured very close to the surface of the bulb. The light source may be switched or pulsed on and off several times a second, in one of the preferred embodiments, to increase the effectiveness of the device to incise bonds between the cells and basement membranes 15 The light source may be more than one, so that cells are exposed to different wavelengths of light, alternately. Second light source for delivery on the surface of the capsule-In combination with the first light source, there may be a second light source used (7,10 ) to see inside the eye properly. This may be an external light source of the surgical microscope, or a totally different light source, by which, light is carried into the eye, and it falls on the anterior surface of the capsule from under the cornea. hi one of the preferred embodiments, such a light source is used with an intensity of 1 lux to 1,000 lux. This second light source facilitates the surgical procedure. The second light source is white, but may be of different colors, in the same region of the spectrum as the first light source. If the first light source is white light, and if filters are used to produce pure wavelengths to be delivered into the inside of the capsule, the first light source may be used also as the second light source, by bypassing the filters as shown in Figure 7. 16 DELIVERY SYSTEM Fiber optic cable ( 2 ), or reflecting mirrors (5 ) are used to deliver the light energy to the cells directly. The fiber optic cable may be enclosed in a transparent water tight tubular cannula ( 9 ), to avoid its contact with the tissues of the eye. The tip of the cannula (9,11 ) is smooth, rounded, so that when it comes in contact with the under surface of the capsule, it does not tear or damage it. METHOD During cataract surgery, after handling the nucleus of the cataract and after removal of the cortex the light is carried through the device into the capsular bag, and the cells are exposed to it from inside and outside for a few seconds. The cells freed / separated by the low intensity device for separating epithelial cells can be removed by known methods such as simple wash and suction. The device may be made more effective by exposing the capsule cells to light from both sides at the same time. One beam of light falls on the anterior capsule from outside. This beam is either from the source of light used by the surgeon as an operating microscope, or a source of light located outside, and brought on to the anterior surface of the capsule by a light pipe made of fiberoptic as shown in 17 Figure 7. The light which falls on the anterior capsule from outside may be of an intensity from 1 lux to 1,00, 000 lux. However this outer beam of light alone does not form the device, the device must essentially contain the inner beam of light which falls onto the cells from inside, with specified low illumination. For purpose of convenience, the light from the source which is used to treat the cells of the capsule may be turned on and off one to fifteen times a second. This helps to minimise energy further, and gives time to move the light from one area of the capsule to another. In another embodiment of the invention the light energy is transported to the inside of the anterior capsule by a set of mirrors placed in a bent pipe, so mat instead of a fiber optic carrier, the light travels through the hollow pipe and is turned into required path by these reflecting mirrors and prisms. In another embodiment of the invention the light source is directly carried to the point where exposure of capsule cells is possible without passing this light through anterior or posterior capsules, by the use of reflecting mirrors as shown in figure 5. IS The present invention, however, is not limited to any particular application ox environment Instead, those skilled in the art will find that the present invention may be advantageously applied to any application or environment using different low intensity light sources or combinations in multiple thereof , methods for applying such low intensity light sources by any other direct or indirect methods or means ,the use of mirrors or any other reflecting device. The description of the exemplary embodiments, which follows, is therefore, for the purpose of illustration and not limitation. MOST PREFERRED EMBODIMENT A. THE DEVICE Light source consisting of a white bulb (1,15), where the bulb is a full spectrum bulb, A transformer or a dimmer to dim the bulb, as is known to those skilled in the ar* A band pass filter (13 ) and or cut off filter (13 ), which alternately allow the light of wavelengths between 360 to 420 nm and above 620 nm to pass through, mounted on a wheel (14 ) in front of the bulb. The wheel is rotated by a motor so that each filter comes in front of the bulb 1 to 200 times a second. 19 The light coming out of the system is picked up by a fiber optic light pipe, which carries it to the inside of the eye. The end piece of the fiber optic is a cannula (9,11 ) whose tip is transparent, and allows this light to be delivered to the capsule. Another fiber optic pipe (7,10 ), which picks up the light from the said bulb, before it passes through the filters, from the side. This light pipe is finished into another cannula, with a transparent tip, which allows the light to be incident on the outer side, or anterior to the anterior capsule. B. PREFERRED EMBODIMENT - METHOD For the application of the low intensity device for separating epithelial cells, the first cannula is applied inside the capsular bag emptied of the nucleus and the cortex, and the second above the bag. The capsule is touched from inside, with the first cannula at many places, allowing the light from the device to fall momentarily on different regions of the capsule. Cells are loosened and may even already start floating in the fluid in the anterior chamber. These may be removed by known methods such as washing with gentle irrigation and 20 aspiration, either with a hand held syringe and cannula, or with the automated system available with most phacoemulsification machines. The particular feature of the present invention is that the width of the intraocular ring is sufficient to overlie the band of living cells so as to suffocate such cells. Thereby preventing cell growth onto an intraocular optic system inserted into the lens capsule after the intraocular ring has been inserted. This device is different from the mechanical devices disclosed in the prior art. The device of the invention does not contain any movable parts, does not transmit any laser light, and /transmits light of only certain well defined wavelengths, for a well defined intensity and for a well defined period of time, specifically to a well defined part of the human body. The device described in the application uses plain light energy, with specified energy levels which are several thousand times lower than those used by Muller. The energy delivery in the invention does not aim to "coagulate" tissue, The device disclosed in this application uses very low light energy to gently separate or loosen the cells, so that they can be washed out. The typical laser energies used in the prior art disclose energies several thousand times more than the energy delivered as specified in this application. The device disclosed in the application uses illuminance levels of 0.001 lux to I claim: 1 A device for separating epithelial cells comprising a light source or sources, with specific wavelengths varying from 194 nanometers to 850 nanometers selected by a standard band pass and a cut off filter, with a transport system such as an optic cable, which simultaneously expose cell surface and basement membrane surface of the cell basement membrane complex to two different levels of light energy with the energy exposure on the cell side of the complex being very low in intensity, and an optical carrying system such as a fiber optic cable or a reflecting mirror placed in front of light source that carries this light energy so that the epithelial cells lining the capsule or base membrane are exposed to the light emanating from the device directly without passing through the basement membrane or when two light beams are used, atleast one of mem applies light energy from the device to the epithelial cells directly, without the energy having to pass through anterior and /or posterior capsule. 2 The device of claim 1 where the light source that directly illuminates the capsule cells emits low light energy of a magnitude so low that the final available energy where it acts on the capsule epithelial cells, is between 0.001 lux and 100 lux. 3 The device of claim 1 where the light source is external and the light is carried to the capsule cells by a fiber optic pipe, which allows passage of light energy between 194 nanometers and 850 nanometers. / 23 4 The device of claim 1 where the light source is directly carried to the point where exposure of capsule cells is possible without passing this light through anterior or posterior capsules, by the use of reflecting mirrors. 5 The device of claim 1 where the light energy is transported to the inside of the anterior capsule by a set of mirrors placed in a bent pipe, so that instead of a fiber optic carrier, the light travels through the hollow pipe and is turned into required path by these reflecting mirrors and prisms. 6 The device of claim 1 where the light source itself is fitted into the hollow pipe so that it directly irradiates the interior of the capsular bag. 7 The device of claim 1-6 with an additional light source which illuminates the capsular bag from outside, so that the capsular bag is illuminated from both inside and outside at the same time. 8 The device of claim 7 where the additional second light source is that of an operating microscope or any other external light, that passes down.. 9 The device of claim 7 where the second light source is carried by a fiber optic light source, directly onto the anterior surface of the capsule. 23 24 10 The device of claim 7 where the second hght source is carried onto the outer surface of the anterior capsule by using reflecting mirrors placed. 11 The device of claims 1 to 10 where the part of the device that goes into the capsular bag is smoothly turned into a round tip. 12 The device of claims 1 to 10 where the part of the device that goes into the capsular bag is turned into a round loop. Dated this 23rd day of August 2004 (Dr. Avinash Shivade ) 24

Documents:

905-mum-2004-abstract(07-04-2005).doc

905-mum-2004-abstract(07-04-2005).pdf

905-mum-2004-cancelled pages(07-04-2005).pdf

905-mum-2004-claims(granted)-(07-04-2005).doc

905-mum-2004-claims(granted)-(07-04-2005).pdf

905-mum-2004-correspondence(24-06-2005).pdf

905-mum-2004-correspondence-(ipo)-(08-02-2007).pdf

905-mum-2004-drawing(07-04-2005).pdf

905-mum-2004-form 1(23-08-2004).pdf

905-mum-2004-form 19(23-08-2004).pdf

905-mum-2004-form 2(granted)-(07-04-2005).doc

905-mum-2004-form 2(granted)-(07-04-2005).pdf

905-mum-2004-form 26(23-08-2004).pdf

905-mum-2004-form 3(23-08-2004).pdf

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