This application is a Divisional of application Ser. No. 12/841,667, filed Jul. 22, 2010, which is a Continuation of PCT/CN2009/000336, filed Mar. 30, 2009, which applications are incorporated herein by reference.
FIELD OF THE INVENTION
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The present invention relates to a foldable capsular vitreous body, and its mould design, method for manufacturing, product appearance, drug delivery property, surgical applications, and so on.
BACKGROUND OF THE INVENTION
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Currently, national and international studies on substitutes for vitreous body are numerous, mainly including inert gas, silicone oil, heavy silicone oil, perfluorocarbon liquids, and hydrogels composed of high molecular weight hydrophilic polymers being the national or international research focus in the 1990s. However, their therapy results are not satisfying, some of which could result in serious complications, for example, inert gas for instance C3F8 may cause cataract easily and lose the effect of tamponade at about two weeks after the surgery such that it could not generate sustained top-pressure on the retina; Perfluorocarbon liquids is toxic to the retina such that it could not settle in the cavity of vitreous body for a long time and could be utilized in surgery only. Additionally, perfluorocarbon liquids is easy to remain in the eyes and difficult to remove after reaction with water; Present substitutes for silicon oils widely used in clinic could result in glaucoma and cataract and will self-emulsify within a particular time. The emulsified substitutes had to be removed. However, upon removing, the retina is easy to detach again. Repetitive surgeries not only aggravated the burden of patients but also seriously impaired the vision of the patients; Even though the surgery is successful, the vision of the patients is very poor resulting from that low refractive index of silicon oil could not generate adequate top pressure on the breaks underlying the retina, and that the diopter in eyeball shifted to high hyperopia after filling; Additionally, after surgeries, patients had to lie on stomach for a long time to prevent silicon oil from flowing into the anterior chamber, thus making the patients very agonized. Hydrogels mainly included PVP hydrgels, PVA hydrogels, PAM hydrogels and Poly (1-vinyl-2-pyrrolidone) hydrogels, and so on. However, these hydrogels are still at the experimental stage in ophthalmology, and so far no one of these hydrogels is performed in clinic application resulting in lack of observation on the long-term therapeutic effect on the toxicity to the eyes and the price is very high. The patients could not afford it. Finding out vitreous substitutes which met physiological needs and are more economical is required, which is one of problems disturbing the doctors for vitreous retinal disorders in the century.
How to make an artificial vitreous body of which both structure and function are the same as those of the natural vitreous body is one of the keys to ensure the success of vitrectomy. Up to now, the components of vitreous body are not fully known. Based on the conditions of modern science and technology, the need to make an artificial vitreous body of which both structure and function are perfect is impractical. The current substitutes for vitreous body are sometimes called as artificial vitreous body. Implantation methods are performed by directly injecting the substitutes for vitreous body into the cavity of vitreous body to support the retina to prevent the retina from detaching again.
Therefore, without pursuing to make a fully physiological artificial vitreous body, the research thinking is changed to restore the most important function of vitreous body, i.e. support of retina so as to avoid repetitive retinal detachment, which is also a method to resolve the problem. Here we design a novel therapy method as using foldable capsular vitreous body (FCVB) to substitute the natural vitreous body. The FCVB consist of a thin capsule, drainage tube and valve. And it also equipped with auxiliary tools: the ejector handle. Chinese Patent No. ZL 03126845.5 discloses a technical scheme and manufacture method for FCVB. Chinese Patent Publication No. CN1810301 (A) and US Patent Publication No. US2007173933 (A1) further limit the material and manufacturing process (dip-molding) of FCVB. The present patent application further extends the material and another manufacturing process of FCVB. New mould design method and capsule pressure regulating drainage valve are added.
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OF THE INVENTION
The object of the present invention is to provide a foldable capsular vitreous body (FCVB) for artificial vitreous body with high biocompatibility and excellent flexibility, advanced and stable technology. The invention also provides a capsule pressure regulating drainage valve, the manufacturing process and the mould thereof.
The object of the present invention is carried out as follows:
A mould for the manufacture of FCVB includes three major parts, an upper mould, a lower mould, and a core between these two moulds. A drainage tube pin is connected to the core and to the plastic injection channel. Heating holes are provided on the upper mould and/or the lower mould. The mold is further connected to a temperature control equipment to control the manufacture to be carried out within a suitable temperature.
The upper mould has a slide block, the core is connected to a positioning plate, and the positioning plate can be positioned in the slide block. The principal axis of the positioning plate is at right angle with respect to the principal axis of the drainage tube pin, the positioning plate and the centre of the core are on the same plane. The drainage tube pin is connected with the drainage valve via the plastic injection channel.
The invention also provides a method using the mould above to manufacture the FCVB. Materials are injected into the mould and vulcanized to form the FCVB. The method including following steps:
(1) mixing evenly natural or modified macromolecule materials, vacuumizing and setting aside;
(2) coating a proper amount of processing materials on the drainage valve and laying a rigid sheet;
(3) putting the core between the upper mould and the lower mould, closing and locking the mould;
(4) injecting the processing materials obtained in the step (1) into the mould cavity from the plastic injection channel;
(5) heating the mould via the heating holes and solidifying the material in the mould cavity;
(6) opening the mould, taking out the core after cooling, and peeling out the capsular bag.
To extend the life of the mould and to prepare for the next manufacturing, the mould must be cleaned each time after the products are stripped out.
The capsular bag for FCVB is mainly made of one selected from the group consisting of polysiloxane, polyurethane, styrene triblock copolymer thermoplastic elastomers, hydroxyethyl methacrylate (HEMA), polyvinyl alcohol (PVA), poly (lactide-co-glycolide) (PLGA) and hyaluronic acid ester.
As an improvement to the present invention, materials of the FCVB, such as polysiloxane or polyurethane are modified by adding hydroxy(—OH)-containing hydrophilic groups, to control water rate in the capsular bag such that the water rate is 5-30%; fluoro group-containing materials are added into the materials of polysiloxane or polyurethane to increase oxygen permeability of the capsular bag.
Preferably, the materials are absorbable materials, so that the implanting FCVB will be absorbed slowly over disease treatment period, to avoid secondary removal of the foldable intraocular vitreous body. Dilution is added into the processing material to alter the physical state of the processing materials. Volatile dilution is preferable, in order to enable the natural volatilization.
In the step (2), by coating a proper amount of processing materials on the drainage valve and fixing on a rigid sheet, the rigid sheet prevents the FCVB from being perforated by the injector pins to ensure the gas-tightness of the body. When artificial plastic injection approach is used, a proper amount of materials may be pre-coated on the upper and lower molds.
After the step (6), the obtained capsule can be further processed: a proper amount of processing materials is coated on the peeling opening of the capsular bag, then put the capsular bag in a sealing device which matches with the peeling opening of the capsular bag to realize the post forming of the peeling opening, and trim the peeling opening by trimmer after agglutination. The operating temperature of the sealing device is in a range of 60° C.-300° C., preferably at 110° C., with working time of more than 2 seconds, preferably 6 seconds.
The capsule products obtained in the step (6) may be processed by the following process:
a proper amount of diluted processing materials is coated on the peeling opening of the capsular bag obtained in the step (6), then the peeling opening of the capsular bag is vulcanized and sealed by heating with an infrared lamp; or a proper amount of room temperature solidified gel materials is coated to seal the peeling opening directly as the gel materials solidified in room temperature.
In the step (5), the heating temperature is controlled in a range of 80° C.-300° C., and preferably at 160° C.
In the method for manufacturing a foldable artificial vitreous body, the permeability of capsular bag is controlled by changing the aperture, wall thickness of capsular bag, osmotic pressure of medium in capsular bag or using nanotechnology, and therapeutic drug, nutritional factors or natural vitreous effective composition are injected via the drainage valve to make the capsular bag product to become a sustained drug deliver system (DDS).
The manufacture method allows batch production of the FCVB by connecting multiple cores with the plastic injection channel simultaneously.
The invention also provides a FCVB produced by the manufacturing method and manufacturing mould as described above. The FCVB includes a capsule, a drainage tube and a drainage valve. The drainage tube has an inner opening and an outer opening connected to the capsule and the drainage valve respectively, and a small recess is provided on the capsule.
The bottom of the drainage valve has the same curvature as the ocular surface. A rigid sheet is disposed at the bottom of the valve to prevent it from being pierced and to maintain its air tightness. Actually, the valve is still air tightness after puncturing for many times. The valve has cracks to regulate the pressure inside the capsule. The valve can be in any shape such as triangular, trapezoidal, rectangular or irregular shape.
The FCVB can be used as a drug delivery system (DDS) inside or around the eye ball, such as eye wall, retrobulbar, peribulbar, eye muscle, orbital wall, by injecting therapeutic drugs, nutritional factors, biological agents, cell, radioisotope, makers, natural active ingredients of vitreous body and so on, which could cure eye diseases including ametropia, uveitis, ocular tumors, degenerative eye diseases, vascular disease, optic neuropathy and so on.
The size or shape of the FCVB can be changed depending on the different implant site. The shape including circle, fan, oval, triangle, quadrilateral, trapezoid, polygon, tubular, sphere, ellipsoid, cylindrical, ring, semi-ring and so on.
Some harmless medium such as physiological saline, silicone oil, heavy silicone oil, hydrogel, can be injected into the FCVB, and the fluid is in liquid or gel state after injection.
The FCVB can also be used as an orbital implant.
Comparison of current technologies, the invention has the following advantages:
(1) Safety with low toxicity. Since restricted by the capsule, the substitutes for vitreous body are not in comprehensive contact with the ophthalmic tissues, thus avoiding the effect of current substitutes for vitreous body on anterior segment. The capsule is easy to be removed completely. Even the patient could not endure the serious reaction in eyes, it could be removed easily, and thus avoiding the current substitutes for vitreous body remaining in the eyes due to difficult removing.
(2) Good result of top pressure on the retina. Because expanding evenly, the capsule could generate sustained top pressure on retinal breaks in any position so as to decrease the recrudescent chances of retinal detachment and increase the cure rate of the operation, which largely alleviated the patients' financial burden due to avoiding repetitive operations;
(3) The drainage valve of FCVB can control the pressure inside the capsule, and to avoid the frequent optic nerve damages caused by high intraocular pressure.
(4) The post Operative visual acuity is better. As the optical parameters of the FCVB are closer to the normal vitreous body, so the patients will gain better vision.
(5) The FCVB is skillfully integrated with the sustained drug release system. By controlling the permeability of the capsule, a DDS is formed to control the sustained release result of the FCVB. Treatment of eye disease or eye nutrition can be achieve by injecting therapeutic drugs, nutritional factors, biological agents, cell, radioisotope, makers, natural active ingredients of vitreous body and so on.
(6) There are lots of differences in comparison with the previous patents (Chinese Patent No. ZL 03247199.8, Chinese Patent No. ZL 03126845.5), such as basic materials, manufacturing method, mold design and drainage valve.