The present invention relates to a drug eluting member, a method of attaching the drug eluting member and a method of fabricating the drug eluting member. In addition, the present invention provides a device for holding the drug eluting member and a drug eluting device.
Cataract may be the first and a major cause for reversible blindness and the cataract-affected population has been on the rise globally due to increasing life expectancy. Intraocular lens (IOL) market accounted for the largest share, which was 77.7%, of the overall cataract devices market at $3.4 billion in year 2009, and this number is expected to reach $5.2 billion in year 2014.
IOL can restore the patients' vision, nevertheless, post-operative infection, such as bacterial endophthalimitis may result in devastating permanent vision loss. A typical current solution to manage the post-operative infection is to administer a short course of antibiotics topically or deliver the antibiotics intracamerally at the end of the operation. However, due to the low level of intraocular penetration (less than 0.3%) from topical application, a very high concentration of antibiotics needs to be applied, which is costly and toxic to the ocular tissues. Moreover, patient non-compliance with frequent administration of the eye drops becomes a major issue that potentially leads to suboptimal therapeutic effect.
Only in recent years, researchers started to recognise this problem and focus on the potential development of a drug loaded IOL to overcome the problems generated by the use of eye drops. One attempt in achieving a drug loaded IOL was to soak the commercial IOLs in gatifloxacin and levofloxacin solutions, which only achieved therapeutic concentration in 72 hours. Other attempts were to adopt the soaking method, but none of them were able to release the active agents for a period longer than a week. In addition to a limited period of drug release, the soaking method may also generate an undesirable huge initial burst release of the antibiotics which may be toxic to the surrounding ocular tissues. Another approach was developed utilising a biodegradable drug loaded tube on the haptic/s of the IOL. Despite of the longer period of release, the orientation and centration of the lens may be distorted upon the IOL insertion due to unbalanced weight. Therefore, none of these approaches are able to achieve a sustained release over a period of two weeks, without potential affecting the optical properties and distorting the orientation of the implanted IOL.
Topical administration of antibiotics post-cataract surgery needs to be frequent. Generally, antibiotic eye drop is applied 4-6 times daily over two weeks after the natural crystal lens has been replaced by synthetic IOL due to cataract. Preservative in the eye drop and non-compliance by patients may lead to serious problems. Current research on the drug eluting intraocular lens does not seem to achieve a sustained release over the required minimum administration period, e.g. fourteen days, without affecting the optical properties of the IOLs or the configuration of the IOLs post-implantation.
The present invention provides a drug eluting member adapted to be attachable onto a perimeter edge of a lens portion of an intraocular lens, the drug eluting member includes an interfacing portion adapted to receive a portion of the perimeter edge.
According to various embodiments, the interfacing portion includes a channel that is adapted to receive the portion of perimeter edge therein.
According to various embodiments, the channel conforms to the profile of the portion of the perimeter edge.
According to various embodiments, the interfacing portion includes an adhesive surface adapted to adhere the drug eluting member to the lens portion.
According to various embodiments, the drug eluting member is bio-degradable.
According to various embodiments, the drug eluting member is arcuated.
According to various embodiments, the drug eluting member surrounds the lens portion along the perimeter edge of the lens portion.
According to various embodiments, the drug eluting member is ring-shaped.
The present invention provides a drug eluting device that includes a first drug eluting member and a second drug eluting member of any one of drug eluting members referred to above such that the first drug eluting member is being adapted to be attached to a portion of a perimeter edge of a lens portion of an intraocular lens, and the second drug eluting member is being adapted to be attached to another portion of the perimeter edge.
According to various embodiments, when attached to the lens portion, the first drug eluting member is substantially opposite the second drug eluting member.
According to various embodiments, the first drug eluting member and second drug eluting member meet to form a through hole capable of surrounding the lens portion of the intraocular lens thereby attaching the first eluting member and second eluting member to the lens portion.
The present invention provides a device for holding any one of the drug eluting members referred to above to a portion of a perimeter edge of a lens portion of an intraocular lens, the device includes a holder being adapted to hold the drug eluting member; and a handling portion for a user to handle the holder.
According to various embodiments, the holder includes a receiving channel for receiving the drug eluting member therein.
According to various embodiments, the handling portion includes a handle extending from the holder.
The present invention provides a method of attaching any one of the drug eluting members referred to above to a perimeter edge of a lens portion of an intraocular lens using any one of the devices referred to above, the method includes positioning the device with the drug eluting member held therein against a portion of the perimeter edge; and releasing the drug eluting member from the device to attach the drug eluting member to the lens portion.
According to various embodiments, the method further includes the step of adhering the drug eluting member to the lens portion.
The present invention provides a method of fabricating any one of the drug eluting member referred to above, the method includes providing a mold for molding the drug eluting member; discharging a forming solution from a nozzle onto the mold; and forming the drug eluting member.
According to various embodiments, the step of forming the drug eluting member includes displacing the mold with respect to the nozzle; and coating the mold with the forming solution.
According to various embodiments, the step of displacing the mold includes rotating the mold at about an axis; and/or translating the mold along the axis.
According to various embodiments, the method further includes the step of shaping the drug eluting member.
According to various embodiments, the mold is a disc-shaped plate.
According to various embodiments, the mold is a disc-shaped plate with an augmented perimeter portion such that the thickness of the mold at the augmented perimeter portion is larger than the thickness of the mold at the centre portion.
According to various embodiments, the forming solution includes a polymer and drug solution.
The drug eluting member of the present invention may be attached or adhered to the existing commercially available IOLs; and may be completely biodegradable with drug elution locally over the required administration period. Unlike other approaches, the drug eluting member of the present invention does not seem to affect the optical properties of the IOL, nor change the mass of the entire IOL (including the haptics). The design may be applicable to any intra-ocular lens design, regardless of the intraocular lens material, degree of the intraocular lens, dimension of the intraocular lens.
a-4c show various view of an exemplary embodiment of a drug eluting member;
a-7b show various views of the drug eluting member in
a-8c show various views of another exemplary embodiment of a drug eluting member;
a-9c show various views of the drug eluting member in
a-12b show perspective views of the device in
a-13d show perspective views of the steps to attach a drug eluting member using the device in
a-15c shows elevation views of the steps to fabricate a drug eluting member in any one of
a shows a sectional view of an exemplary embodiment of a mold for a drug eluting member in any one of
b shows a partial sectional view of a drug eluting member formed on the mold in
In other words, drug eluting member 100 may be attached onto the perimeter edge 512 of intraocular lens 500. Drug eluting member 100 has interfacing portion 102 which is able to receive a portion of the perimeter edge 512.
As shown in
Drug eluting member 100 has an interfacing portion 102. Interfacing portion 102 may be a portion of the drug eluting member 100 that contacts or interfaces with the lens portion 510 when the drug eluting member 100 is attached to the lens portion 510 of the intraocular lens 500. Interfacing portion 102 may include a channel 150 (see
As shown in
Drug eluting member 100 may include an outer surface 110. Outer surface 110 may be connected to the facing side 104. Surface 110 may extend from the facing side 104 to the outer rim 108. As outer surface 110 extends from the facing side 104 to the outer rim 108, surface 110 may be tapered towards the outer rim 108. In other words, outer surface 110 may form a semi-circular or the profile of an acute end of an elliptical, e.g. egg-shaped, cross section profile.
Channel 150 may be formed on the facing side 104 of the drug eluting member 100 such that facing side 104 is divided by the channel 150 thus forming a pair of lips 152 such that the channel is formed between the pair of lips 152. Channel 150 may include an inner surface 156 which connects to the facing side 104. Inner surface 156 may conform to and substantially parallel to the outer surface 110 such that the thickness of the drug eluding member 100 between the outer surface 110 and the inner surface 110 from one lip 152 to the other lip 152 may be substantially uniform.
Pair of lips 152 may be adapted to receive the lens portion 510 between them and within the channel 150. Lens portion 510 may be secured to the drug eluting member 100 by securing the lens portion 510 to the pair of lips 152 mechanically, e.g. by clamping the lens portion 510.
Interfacing portion 102 may include an adhesive surface 154 adapted to adhere the drug eluting member 100 to the lens portion 510. Adhesive surface 154 may be formed between the pair of lips 152. Adhesive surface 154 may be formed within channel 150 by coating the inner surface 156 with a layer of bio-adhesive.
Referring to
Drug eluting member 100 may be made from a bio-degradable material. As such, drug eluting member 100 may be bio-degradable.
a-4c shows another exemplary embodiment of the drug eluting member 100. As shown in
A drug eluting device 200 is shown in
a-7b show various views of the embodiment of drug eluting device 200 in
a-8c show various views of another exemplary embodiment of drug eluting member 300. As shown in
Drug eluting member 300 may be formed by two semi-circular drug eluting members, a first drug eluting member and a second drug eluting member, joined together to form the ring-shape. First drug eluting member and second drug eluting member may meet to form a through hole capable of surrounding the lens portion 510 of the intraocular lens 500 thereby attaching the first drug eluting member and second drug eluting member to the lens portion 510. It can be understood by a skilled person that the ring-shaped drug eluting member 300 may be formed by three or more drug eluting members. First drug eluting member and second drug eluting member may each include at least one opening 360 for a haptic of the intraocular lens (not shown in
a-9b show a side view and front view of the drug eluting member 300 attached to the lens portion 510. As seen in
As shown in
Handling portion 620 may be a portion or part of the holder 610. A user may hold the holder 610 at the handling portion 620 to attach drug eluting member 100 to the lens portion 510. Handling portion 620 may include a handle extending from the holder 610 as shown in
a-12b show device 600 receiving arcuated drug eluting member 100. Drug eluting member 100 may be ring-shaped drug eluting member 300.
Drug eluting member 100 may be attached onto the perimeter edge 512 of the lens portion 510 of the intraocular lens 500 (not shown in
A thin layer of bio-adhesive may be coated onto the inner surface 156 of the drug eluting member 100 for securing the drug eluting member 100 onto the lens portion 510.
Drug eluting member may be made from bio-stable polymers or similar polymer. Bio-stable polymer may include poly 2-phenethyl methacrylate (poly(PhEMA)), poly ethyl-methacrylate (PEMA), poly 2,2,2-trifluoroethyl methacrylate (PTFEMA), poly dimethylsiloxane (PDMS), poly diphenylsiloxane (PDPhS), poly ethylene vinyl acetate (PEVA), polyurethanes or poly ethylene terephthalate.
Drug eluting member may be made from biodegradable polymers e.g. a poly(a-hydroxy ester) or a biodegradable polyurethane which contains a PLA/PCL copolymer or a PCL/PTMC copolymer as the soft blocks. Biodegradable polymers may have substantial mass loss starting at around 1 month to 6 months, and being substantially absorbed within 3-12 months. The base material used for the drug eluting member may be bio-degradable elastomer.
a-13d shows a method 1000 of attaching a drug eluting device 200 to the lens portion 510 of an intraocular lens 500 using device 600. Drug eluting device 200 may include two drug eluting members 100 as shown in
Two devices 600 may be used hold the two drug eluting members 100 of drug eluting device 200. As shown in
a-15c show a method 2000 of fabricating a drug eluting member as mentioned in any one of the embodiments above, e.g. drug eluting member 300 having a ring-shaped profile.
Referring to
Mandrel 730 may be set to move in both rotational and translational motion. (see arrows in
Forming solution 730 may include a dissolved/dispersed polymer and a drug solution. Forming solution 730 may be sprayed from nozzle 710 onto mold 700. Forming solution 730, or drug dispersed polymer solution, would dry upon being coated onto the mold 700.
As shown in
Displacing the mold 700 may include rotating the mold 700 at about an axis and/or translating the mold 700 along the axis. A number of cycles of rotational and/or translational movement may be pre-determined to fabricate drug eluting member 300 with a desired thickness of the coating, i.e. desired thickness of drug eluting member 100.
Drug eluting member 300 may be dried. Drug eluting member may be dried in a vacuum oven (not shown in
Referring to
Mold 700 may have augmented perimeter portion 704.
b shows a partial sectional view of a drug eluting element 300 formed on mold 700 with augmented perimeter portion 704. As shown, drug eluting element 300 that is formed on mold 700 with augmented perimeter portion 704 may have a pair of jaws 320 which extends inwards towards each other so that drug eluting member 300 may provide better hooking or attaching property to the lens portion 510 of intraocular lens 500.
Drug eluting member 300 may be evaluated in vitro for drug release and degradation. A set of the drug eluting member 300 may then be attached, e.g. adhered, to the intraocular lens 500 and sterilized using ethylene oxide. The drug eluting member 300 may be able to bend and be implant together with the intraocular lens 500 by an intraocular lens injector, without being detached from the intraocular lens 500.
Drug eluting member 300 may be fabricated by the spray coating technique due to the delicate nature and stringent dimension of the drug eluting member 300. Drug eluting member 300 may be fabricated by dip coating techniques, or ultra-sonic spray coating technique. Such a method allows dimension of drug eluting member to be in micron scale.
As shown above, drug eluting member may be attached mechanically or using a bio-adhesive to the edge of an intraocular lens. A skilled person would appreciate that drug eluting member would not affect the optical properties of the intraocular lens or distort the lens orientation post-operatively.
Drug eluting member may be formulated to have drugs dispersed or dissolved throughout the polymer (“matrix” system). Drugs commonly used to treat postoperative infection include: (1) Levofloxacin; (2) Moxifloxacin; and (3) Gatifloxacin.
Levofloxacin is a synthetic antibiotic of the fluoroquinolone drug and is used to treat bacterial eye infections by oral or topical administration. It works to treat bacterial infections by interfering with an enzyme that the bacteria need to multiply.
Moxifloxacin and gatifloxacin belongs to the fourth generation of the fluoroquinolones, which are commonly used in the United States. Clinically, these two drugs showed better ocular tissue penetration and improved spectrum of bacteria coverage. It also appears that moxifloxacin is superior to gatifloxacin in terms of penetration.
Approximately 0-50% of a drug, such as levofloxacin, moxifloxacin and gatifloxacin may be dispersed or dissolved in the polymer matrix body.
Drugs may include anti-inflammatories, anti-cancer drugs, as well as antibiotics with both hydrophobic and hydrophilic properties.
When the drugs are formulated into drug eluting member, a loading of 5% to 50% by weight may be proposed. Such drugs are released in a controlled fashion from the “matrix”, as shown in
A typical composition for a fully-degradable drug eluting member with drugs surrounds the edge of the IOL would be as follows:
The present application claims the benefit of the U.S. provisional patent application No. 61/683,438 filed on 15 Aug. 2012, the entire contents of which are incorporated herein by reference for all purposes.
Filing Document | Filing Date | Country | Kind |
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PCT/SG2013/000346 | 8/14/2013 | WO | 00 |
Number | Date | Country | |
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61683438 | Aug 2012 | US |