The present invention is related to a method of manufacturing an intraocular lens, and more particularly, to a method of manufacturing an intraocular lens with a poly-p-xylylene film.
Biomedical optics devices require specific parameters that meet both optical and bio-interfacial properties. The development of intraocular lenses (IOLs) has resulted in both research investigations and clinical products because of the enormous need to treat cataract patients (approximately 10 million IOLs are implanted yearly worldwide). In the search for relevant materials for fabricating IOLs, surface modifications on existing materials are currently being exploited; however, device associated problems, including postoperative calcification, dislocation, and the proliferation and migration of epithelial cells, which cause posterior capsular opacification or secondary cataracts, are lingering challenges. Some approaches solve one problem while compromising another issue, and current synthetic IOLs are still far from ideal.
Nevertheless, synthetic IOL products provide an effective solution for the immediate needs of cataract patients. In the design of future IOLs, it is desirable to obtain (i) enhanced compatibility with the environment of the posterior capsule in terms of position and chemical/biological properties, (ii) stability and durability to avoid leaching of potentially harmful substances to the surrounding biological environment, (iii) customizable optical and biological properties for diverse patient needs, and (iv) effective and simple procedures for delivery and implantation.
It is still a need to provide an intraocular lens which can meet the above requirements.
The present invention therefore provides an intraocular lens and a method of forming the same, so as to meet the current requirements.
According to one embodiment, the present invention provides an intraocular lens, including a first poly-p-xylylene film, a second poly-p-xylylene film and a liquid drop. The liquid drop is disposed between the first poly-p-xylylene film and the second poly-p-xylylene.
According to another embodiment, the present invention further provides a method of forming an intraocular lens. First, a chemical vapor deposition (CVD) process is performed to form a first poly-p-xylylene film, following by placing a solution drop on the first poly-p-xylylene film. A chemical vapor deposition encapsulation process is performed to form a second poly-p-xylylene film on the first poly-p-xylylene film and the solution drop.
An innovative intraocular lens (IOL) device is fabricated based on a chemical vapor deposition encapsulation process using functionalized poly-p-xylylenes. The advanced IOL device provides noncompromised design parameters for both its optical and biological properties.
These and other objectives of the present invention will no doubt become obvious to those of ordinary skill in the art after reading the following detailed description of the preferred embodiment that is illustrated in the various figures and drawings.
To provide a better understanding of the present invention, preferred embodiments are detailed as follows. The preferred embodiments are also illustrated in the accompanying drawings to clarify the contents and effects of the present invention.
Please refer to
Step 300: performing a chemical vapor deposition (CVD) process to form a first poly-p-xylylene film;
Step 302: placing a solution drop on the first poly-p-xylylene film; and
Step 304: performing a chemical vapor deposition encapsulation process to form a second poly-p-xylylene film on the first poly-p-xylylene film and the solution drop.
To clearly describe the above steps, please refer to
The method of manufacturing an intraocular lens, as shown in
The paracyclophane in the present invention can have various functional group so as to form the functionalized first PPX film 502. In one embodiment, the first PPX film 502 includes the following structure with formula (1):
wherein R1 and R2 is selected from a group consisting of hydrogen, —C(═O)H, —C(═O)—CFH2, —C(═O)—CF3, —C(═O)—C2F5, —C(═O)—C8F17, —C(═O)—OH, —C(=O)-Ph, —C≡CH, —CH═CH2, —CH2—OH, —CH2—NH2, —NH2, —C(═O)—O—CH3, —C(═O)—O—C2H5, —CH2—O—C(═O)—C—(CH3)2Br, —CH2—O—C(═O)—C≡CH, a chemical structure of formula (1-1), a chemical structure of formula (1-2) and a chemical structure of formula (1-3), and R1 and R2 are not simultaneous hydrogen, and m and n refer to an integral greater than 750,000:
wherein in formula (1-1), R3 refer to —CH2—, —CH2—CH2—OC(═O)—, —CH2—CH2—NH—C(═O)—, —C(═O)— or —O—CH2—; and R4 and R5 refer to hydrogen, methyl or chloride.
In another embodiment, the first PPX film 502 includes the following structure:
wherein m and n refer to an integral greater than 750,000.
In one preferred embodiment, the first PPX film 502 is a vinyl PPX film, in which the monomer thereof is 4-vinyl-[2,2]paracyclophane.
For the CVD process, please see
Subsequently, as shown in
Next, as shown in
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As shown in
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It is noted that the abovementioned embodiments of the IOL 530 can be combined arbitrarily to form various types of IOL 530. For example, the IOL with two curved surface shown in
The shape and curvature of the PPX-IOL were controlled by varying the liquid wettability to produce varied optical properties. Prior to the encapsulation process, strategies for changing the liquid wettability were demonstrated by three different approaches: (i) by choosing liquids with varying wetting properties, (ii) by fine-tuning a mixture of two liquids with contrasting wettabilities, and (iii) by conducting plasma modification of the underlying surface wettability.
In the first approach, liquid droplets with a low vapor pressure, including silicone oil, poly(ethylene glycol) (PEG), 1,2,6-trihydroxyhexane, and glycerol, were placed on the previously deposited surface of the vinyl-PPX film. Prior to the encapsulation process, the wettability of each liquid was determined by placing a 2-μL droplet on the vinyl-PPX surface, and the static contact angle was measured by using a contact angle goniometer. As shown in
In the second approach, a mixture of two of the above liquids (if mixable) is created and the ratio is adjusted during mixing to form droplets with a tunable wettability. Please refer to
In the third approach, the plasma treatment with various gas for the supporting vinyl-PPX surfaces is performed. The plasma treatment was carried out via a radio frequency (13.56 MHz) plasma source that was used to discharge argon, oxygen, or C4F8 for treatment of the vinyl-PPX surfaces. The gas flow was 50 sccm for both argon and oxygen, and 50 sccm C4F8 was used together with 25 sccm of argon. A power of 15 W was maintained during the plasma process, and the processing time was 30 s for all plasma treatments. Please refer to
A summary of the effective focal lengths and refractive indices with respect to the liquid wettability is provided in Table 1. As shown in column 2 of Table 1, the refractive indices of the device range from 1.575 to 1.610. Though there is a great range of the wettability of the film, the variation of the refractive indices is small. High refractive indices were obtained for all of the combinations of PPX-IOL devices tested, which is attributed to the intrinsic index of refraction for vinyl-PPX (nD=1.611). Since the advanced PPX-IOL has a high refractive, the total volume of the solution drop can be lowered, and an ultra-thin PPX-IOX can be fabricated by using the chemical vapor deposition encapsulation process.
The effective focal lengths of PPX-IOL can be verified by using an OptiSpheric® instrument. As shown in column 3 of Table 1, the effective focal lengths of PPX-IOL can range from 4.394±01012 mm of C4F8 plasma treatment to >100 mm of silicon oil, showing a great tunable value. The corresponding changes in the effective focal length were confirmed to have a high dependency on the wetting properties of the encapsulated liquid. A low CA was correlated with a high focal length and vice versa. A desirable effective focal length can be obtained by fine-tuning the wettability.
The optical properties were examined with respect to the transmittance of the PPX-IOL device by UV-vis analysis. Please refer to
The device/material-associated potency of calcium precipitation was examined in the PPX-IOLs. A simulated calcifying environment based on a highly concentrated calcium-potassium solution was used to examine the PPX-IOL, and control experiments were performed by comparing the IOLs with commercial IOLs, including Hydroview MI60 (Bausch & Lomb), PMMA MZ30BD (Alcon), and AcrySof SN60WF (Alcon) devices, which were all investigated in parallel. The IOL devices were immersed in a calcium-phosphate solution containing calcium chloride dihydrate, sodium phosphate monobasic monohydrate, and bovine serum albumin (BSA). Two calcifying solutions were prepared: one solution containing 100 mg/mL calcium chloride dehydrate, 100 mg/mL sodium phosphate monobasic monohydrate, and 200 mg/mL BSA and a second solution containing 200 mg/mL calcium chloride dehydrate, 50 mg/mL sodium phosphate monobasic monohydrate, and 200 mg/mL BSA. The IOL devices were alternately exposed to the two calcifying solutions (freshly prepared) every 2 days. The experiment was conducted at a constant temperature of 37° C. After 48 days of exposure, the samples were retrieved, washed with deionized water. Please refer to
With respect to the surface chemical properties, the PPX-IOL provided additional ethylene anchoring sites to enable an orthogonal thiol-ene click reaction that can be activated photochemically. These anchoring sites were used to attach thiol-PEGs and cysteine containing peptides (Arg-Glu-Asp-Try-Try-Cys) (RGDYYC). The attachment of these molecules on selected areas is important in providing guided cell attachment cues for epithelial cells and is directed by a photoimmobilization procedure during the photochemically activated thiol-ene click reaction. Because of the curved surface of the IOL, a flat transparency photomask cannot be utilized for the photoimmobilization step. Instead, a microscopic patterning technique that is capable of precisely projecting desired patterns onto nonplanar surfaces was used for photoimmobilization of the IOL device. In this experiment, Human lens epithelial cells (HLECs) are seeded at a density of 1.5×104 cells/cm2 onto PPXIOL devices with previously immobilized thiol-PEG and RGDYYC. After a 24-h incubation, the resulting HLECs cells were fixed with 10% formalin, permeabilized with 0.1% Triton X-100 for 30 and 5 min, respectively, and then stained with 1 μg/mL 4′,6-diamidino-2-phenylindole and 50 μg/mL rhodamine-phalloidin for 15 and 30 min, respectively. The samples were then examined and photographed using a fluorescence microscope. Please refer to
In summary, an innovative intraocular lens (IOL) device was fabricated based on a chemical vapor deposition encapsulation process using functionalized poly-p-xylylenes. The advanced IOL device provides noncompromised design parameters for both its optical and biological properties. As an excellent optical device, it provides a high refractive index and a tunable effective focal length that is realized by manipulating the wetting properties of the encapsulated liquids; the device also offers protection from UV radiation. As a key medical device, it exhibits excellent biocompatibility and reduced postoperative calcification through the intrinsic properties of poly-p-xylylenes. In addition, these synergic functions are provided with precise surface chemistry for location to a guided attachment or repellent properties for eye epithelial cells, which is important in preventing device-associated complications.
Those skilled in the art will readily observe that numerous modifications and alterations of the device and method may be made while retaining the teachings of the invention. Accordingly, the above disclosure should be construed as limited only by the metes and bounds of the appended claims.
Number | Date | Country | Kind |
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104143053 | Dec 2015 | TW | national |
This application is a Divisional of application Ser. No. 14/997,591 filed on Jan. 18, 2016, and included herein by reference.
Number | Date | Country | |
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Parent | 14997591 | Jan 2016 | US |
Child | 15963048 | US |