Abstract:
A capsular bag for artificial vitreous body is made up of one selected from the group comprising polysiloxane, polyurethane, styrene triblock copolymer thermoplastic elastomers, hydroxyethyl methacrylate, polyvinyl alcohol, poly(lactide-co-glycolide) and hyaluronic acid ester. A method for manufacturing the capsular bag for artificial vitreous body is performed with dip-molding, effectively improving the smoothness of inner surface of the capsule, comprising: an eye die is dipped into gel solution until the surface adsorbs gel and then lifted, repeating the step 3-6 times; the dipped eye is hardened into shape; a shaped spherical outer capsule is peeled out of the eye die. The capsular bag for artificial vitreous body had high biocompatibility and excellent flexibility.

Description:
FIELD OF THE INVENTION 
       [0001]    The present invention relates to a medical biomaterial, particularly to a capsular bag for artificial vitreous body and a method for manufacturing the same. 
       BACKGROUND OF THE INVENTION 
       [0002]    Modern vitrectomy is a great revolution in ophthalmic therapy, thus allowing many ophthalmic disorders which would have previously been regarded as incurable to be cured. The operation indications thereof enlarge to several dozens kind of ophthalmic disorders. It plays a great role in ophthalmic clinic and saved innumerable eyes which would be blind. 
         [0003]    The normal vitreous body is a kind of gelatinous tissue which could not regenerate. After vitrectomy, substitutes for vitreous body are required to fill the cavity of vitreous body to support or plug the retina to prevent retinal detachment. 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. 
         [0004]    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. 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. 
         [0005]    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. Chinese patent No. ZL 03126845.5 discloses a technical scheme about capsular artificial vitreous body, which utilizes a system of artificial vitreous body comprising a capsular bag made of high molecular weight film filled with water and having a drainage valve to achieve the object of supporting the retina and preventing the retina from detaching again. Wherein, the capsular bag accommodated with the shape and volume of the cavity of the human eyes. A drainage tube provided with a drainage valve is connected to the top of the capsular bag. The capsular bag and the drainage tube are hidden inside an assistant implanting means, i.e. an ejector handle. The head of the ejector handle could clamp the capsular bag. However, since the capsular bag is manufactured manually with acetic acid and vinyl acetate copolymer, the technical scheme still has drawbacks, such as low biocompatibility and poor flexibility. 
       SUMMARY OF THE INVENTION 
       [0006]    The object of the present invention is to overcome the drawbacks of the prior art, and to provide a capsular bag for artificial vitreous body with high biocompatibility and excellent flexibility, and a method for manufacturing the same. 
         [0007]    The object of the present invention is carried out as follows: 
         [0008]    The capsular bag for artificial vitreous body is mainly made up of one selected from the group comprising polysiloxane, polyurethane, styrene triblock copolymer thermoplastic elastomers, hydroxyethyl methacrylate (HEMA), polyvinyl alcohol (PVA), poly(lactide-coglycolide) (PLGA) and hyaluronic acid ester. 
         [0009]    The capsular bag for the artificial vitreous body has an anteroposterior diameter of 14-18 mm, a horizontal diameter of 20-25 mm and a vertical diameter of 20-25 mm; The front face had a concave with a curvature radius of 4-8 mm. 
         [0010]    The wall of the capsular bag for artificial vitreous body is 10-50 μm thick. The shore hardness of the capsular bag is 5-40 degree. The tensile strength is 4-12 Mpa. The hemolysis rate of material is not more than 5%. The transmission rate is not less than 90%. The fog density is not more than 0.1%. The elongation is not less than 1000%. The tear strength is 10-40 kN/m. 
         [0011]    The top capsular bag for artificial vitreous body is connected to a drainage tube. The drainage tube provided a drainage valve made up of one selected from the group comprising polysiloxane, polyurethane, styrene triblock copolymer thermoplastic elastomers, hydroxyethyl methacrylate (HEMA) polyvinyl alcohol (PVA), poly(lactide-co-glycclide) (PLGA) and hyaluronic acid ester. The drainage tube had 2-5 mm of length and 0.1-0.3 mm of the inner diameter as well as 0.4-0.7 mm of outer diameter. The diameter of the body of the drainage valve is 2-4 mm with 1-3 mm of height. 
         [0012]    The styrene triblock copolymer thermoplastic elastomers may be selected from the group comprising styrene-ethylene/butadiene-styrene triblock copolymer(SEBS) or styrene-isoprene butadiene-styrene triblock copolymer(SIS) or styrene-ethylene/propylene-styrene triblock copolymer (SEPS) or styrene-butadiene-styrene triblock copolymer (SBS). 
         [0013]    Preferably, the capsular bag for artificial vitreous body and the drainage tube are made up of polysiloxane. 
         [0014]    As an improvement to the present invention, materials of the capsular bag for artificial vitreous body, 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. A drug sustained release system (DDS) are formed by changing the thickness and crosslink density of the materials of the capsular bag for artificial vitreous body and increasing osmotic pressure inside the capsular bag to control the sustained release result of the capsular bag and by injecting therapeutic drugs via the drainage valve. 
         [0015]    The method for manufacturing the capsular bag for artificial vitreous body is performed with dip-molding, comprising the following steps: 
         [0016]    (1) an eye die is dipped into the gel solution until the surface adsorbed gel and then lifted, repeating the step 3-6 times; 
         [0017]    (2) the dipped die is hardened to shape; 
         [0018]    (3) the shaped spherical outer capsule is peeled out of the eye die. 
         [0019]    The capsular bag for artificial vitreous body of the present invention is of the following advantages: 
         [0020]    (1) Safety with low toxicity. Since restricted by the capsular bag, 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 capsular bag is easy to remove completely. Even the patient could not endure the serious reaction in eyes, it could be removed easily, thus avoiding the current substitutes for vitreous body remaining in the eyes due to difficultly removing. 
         [0021]    (2) Good result of top pressure on the retina. Because expanding evenly, the capsular bag 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&#39; financial burden due to avoiding repetitive operations; 
         [0022]    (3) The drainage valve of artificial vitreous body could control the pressure inside the capsular bag. Upon the pressure is more than 20 mmHg, the liquid in the capsular bag flew out automatically such that the pressure inside the capsular bag is adjusted at 12-20 mmHg. 
         [0023]    (4) The artificial vitreous body is skillfully integrated with the drug sustained release system. 
         [0024]    (5) The capsular bag for artificial vitreous body and the drainage valve manufactured by application of absorbable materials such as poly(lactide-co-glycolide) (PLGA), and hyaluronic acid could be degraded within 60-90 days and absorbed completely. 
         [0025]    In conclusion, according to the present invention, the capsular bag for artificial vitreous body made of modified polysiloxane elastomers has high biocompatility and excellent flexibility. After implantation of the artificial vitreous body system, animal experiments proved that it could be implanted and removed easily without significant histological toxicology reaction examined by electrophysiology, light microscopy and electron microscopy. The intraocular pressure could be adjusted via drainage valve which is fixed underlaying the conjunctiva after operation. The fabricating procedure is carried out with the method for dipped-molding, effectively improving the smoothness of the inner surface of capsular bag. This manufacture is easy to operate and repeatability is attractive. 
     
    
     DESCRIPTION OF THE PREFERRED EMBODIMENT 
     EXAMPLE 1 
       [0026]    According to the present example, the capsular bag for artificial vitreous body and the drainage tube on it and the drainage valve are made up of polysiloxane. The anteroposterior diameter of the artificial vitreous body is 16 mm and the horizontal diameter is 22 mm thereof and the vertical diameter thereof is 23 mm. The front surface thereof had a concave with a curvature radius of 6 mm. The thickness of the wall of the capsular bag for artificial vitreous body is 50 μm. Shore hardness of the material for the artificial capsular bag is 30 degree. The tensile strength is 5 Mpa. The elongation is more than 1000%. The tear strength is about 35 kN/m. The hemolysis rate of the material is about 4%. The transmission rate is 95%. The fog density is less than 0.1%. The drainage tube on the capsular bag for artificial vitreous body is 3 mm long and the inner diameter is 0.2 mm and the outer diameter is 0.57 mm. The body of the drainage valve is of a diameter of 3 mm and a height of 2 mm. 
         [0027]    Polysiloxane is a transparent high molecular weight polymer with high biocompatibility and excellent forming technology and flexibility and without generation and escape of low molecular weight during formation of sulfide crosslink. The biological evaluation experiments showed negative reaction. The material has not significant toxicity No potential sensitive substances are contained in the material. Pyrogen content therein is in accordance with the requirement of organism. Polysiloxane is a satisfying candidate material for artificial vitreous body. The manufactured artificial vitreous body could be infused with physiological saline solution via the drainage valve to fill the capsular bag and simultaneously adjust the pressure inside the capsular bag. 
         [0028]    The present capsular bag for artificial vitreous body is manufactured by the following steps: 
         [0029]    A die specific for human eyes is used. The surfaces and corners of the die should be as smooth as possible to facilitate to achieve the smoothness of inner surface of capsule; the die is slowly dipped into the polysiloxane gel solution and lifted until the surface thereof absorbed gel. The dipping and lifting procedures are repeated 5 times with moderate force of action and speed to prevent generation of bubbles: then, it is placed into oven to be heated to harden into shape; the hardening conditions are: at a temperature of 100 degree, two hours. Finally, the shaped outer capsule is peeled out of the die, thus obtaining the capsular bag for artificial vitreous body. 
         [0030]    The drainage valve is manufactured according to the prior art press moulding. The bottom of the body is embeded with a steel barrier to prevent the body from being perforated by the injector pin s to ensure the gas-tightness of the body. 
       EXAMPLE 2 
       [0031]    According to the present example, the capsular bag for artificial vitreous body and the drainage tube on it and the drainage valve are made up of poly(lactide-co-glycolide). The anteroposterior diameter of the artificial vitreous body is 18 mm and the horizontal diameter thereof is 25 mm and the vertical diameter thereof is 25 mm. The front face thereof has a concave with 7 mm of curvature radius. The thickness of the wall of the capsular bag for artificial vitreous body is 50 μm. Shore hardness of the material for the artificial capsular bag is 40 degree. The tensile strength is 5 Mpa. The elongation is more than 1000%. The tear strength is about 35 kKN/m. The hemolysis rate of the material is about 2%. The transmission rate is 93%. The fog density is less than 0.1%. The drainage tube on the capsular bag for artificial vitreous body is 5 mm long and the inner diameter is 0.25 mm and the outer diameter is 0.65 mm. The diameter of the body of the drainage valve is 3.5 mm and the height is 2.5 mm. 
         [0032]    The present capsular bag for artificial vitreous body is manufactured by the following steps: 
         [0033]    A die specific for human eyes is used. The surfaces and corners of the die should be as smooth as possible to facilitate to achieve the smoothness of inner surface of capsule; The die is slowly dipped into the poly(lactide-co-glycolide) gel solution and lifted until the surface thereof absorbed gel. The dipping and lifting procedures are repeated 5 times with moderate force of action and speed to prevent generation of bubbles; Then it is placed into oven to heat to harden to shape; The hardening conditions are: at a temperature of 85 degree, three hours. Finally, the shaped outer capsule is peeled out of the die, thus obtaining the capsular bag for artificial vitreous body. 
         [0034]    The drainage valve is manufactured according to the method described in example 1. 
       EXAMPLE 3 
       [0035]    According to the present example, the capsular bag for artificial vitreous body and the drainage tube on it and the drainage valve are made of styrene-ethylene/butadiene-styrene triblock copolymer (SEBS). The anteroposterior diameter of the artificial vitreous body is 14.5 mm and the horizontal diameter  20  thereof and the vertical diameter thereof 21 mm. The front surface thereof had a concave with 4.5 mm of curvature radius. The thickness of the wall of the capsular bag for artificial vitreous body is 50 μm. Shore hardness of the material for the artificial capsular bag is 15 degree. The tensile strength is 5 Mpa. The elongation is more than 1000%. The tear strength is about 35 kN/m. The hemolysis rate of the material is about 2%. The transmission rate is 95%. The fog density is less than 0.1%. The drainage tube on the capsular bag for artificial vitreous body is 3 mm long and the inner diameter is 0.15 mm and the outer diameter is 0.45 mm. The diameter of the body of the drainage valve is 2 mm and the height is 1.5 mm. 
         [0036]    The present capsular bag for artificial vitreous body is manufactured by the following steps: 
         [0037]    A special die for human eyes is used. The surfaces and corners of the die should be as smooth as possible to facilitate to achieve the smoothness of inner surface of capsule; The die is slowly dipped into the polysiloxane gel solution and lifted until the surface thereof absorbed gel. The dipping and lifting procedures are repeated 5 times with moderate force of action and speed to prevent generation of bubbles; Then it is placed into oven to heat to harden to shape; The hardening conditions are, at a temperature of 110 degree, three hours. Finally, the shaped outer capsule is peeled out of the die, thus obtaining the capsular bag for artificial vitreous body. 
       EXAMPLE 4 
       [0038]    According to the present example, the capsular bag for artificial vitreous body and the drainage tube on it and the drainage valve are made of modified polyurethane containing hydroxy(—OH) hydrophilic groups. The anteroposterior diameter of the artificial vitreous body is 15 mm and the horizontal diameter thereof is 22 mm and the vertical diameter thereof is 23 mm. The front face thereof has a concave with a curvature radius of 5 mm. The thickness of the wall of the capsular bag for artificial vitreous body is 40 μm. Shore hardness of the material for the artificial capsular bag is 25 degree. The tensile strength is 6 Mpa. The elongation is more than 1000%. The tear strength is about 35 kN/m. The hemolysis rate of the material is about 3%. The transmission rate is 95%. The fog density is less than 0.1%. The drainage tube on the capsular bag for artificial vitreous body is 3.5 mm long and the inner diameter is 0.2 mm and the outer diameter is 0.5 mm. The diameter of the body of the drainage valve is 2.5 mm and the hight is 2 mm. The water content in the capsular bag is 10%. 
         [0039]    The present capsular bag for artificial vitreous body is manufactured by the following steps: 
         [0040]    A special die for human eyes is used. The surfaces and corners of the die should be as smooth as possible to facilitate to achieve the smoothness of inner surface of capsule; the die is slowly dipped into the gel solution composed of modified polyurethane containing hydroxy(—OH) hydrophilic groups and lifted until the surface thereof absorbed gel. The dipping and lifting procedures are repeated 5 times with moderate force of action and speed to prevent generation of bubbles; then, it is placed into oven to heat to harden to shape, the hardening conditions are: at a temperature of 105 degree, 3.5 hours. Finally, the shaped outer capsule is peeled out of the die, thus obtaining the capsular bag for artificial vitreous body. 
         [0041]    According to the present invention, the capsular bag for artificial vitreous body could be full of physiological saline solution via the drainage valve and adjust the top pressure on retina inside the capsular bag at an appropriate level. 
         [0042]    After implantation of the artificial vitreous body system prepared by the capsular bag according to the prevent invention, animal experiment proved that it could be implanted and removed easily without significant histological toxicology reaction examined by electrophysiology, light microscopy and electron microscopy. 
         [0043]    The capsular bag for the artificial vitreous body manufactured by the said examples 1-4 could control the sustained release result of the capsular bag by methods for changing the thickness and crosslink density of the materials of the capsular bag for artificial vitreous body and increasing osmotic pressure inside the capsular bag and can be infused with drugs via the drainage valve such that the capsular bag for the artificial vitreous body becomes a drug sustained release system (DDS). 
         [0044]    Since restricted by the capsular bag, 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. Even a patient could not endure the serious reaction in eyes, it could be removed easily, thus avoiding the current substitutes for vitreous body remaining in the eyes due to difficultly removing. 
         [0045]    Because expanding evenly, the capsular bag could generate sustained top pressure on retinal breaks in any position so as to decrease the recrudescent chances of retinal detachment and increased the cure rate of the operation, which largely alleviate the patients&#39; financial burden due to avoiding repetitive operations.