TWI364301B - Implantable drug delivery system - Google Patents

Description

</ RTI> </ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; The present invention relates to a drug delivery system; more particularly, the invention relates to an implantable small drug delivery device for use in humans or other animals. C Prior Art; j Background of the Invention By using - or more agents, several symptoms or diseases occurring in the human or animal body are effectively treated. 1 Logistic symptoms and diseases are taken orally. Once swallowed, the agent moves through the gastrointestinal system and finally moves to the location of the symptoms or disease. In other cases, the drug is delivered to the location of the condition or disease via blood flow. In particular, a medicament is injected into a muscle or soft tissue by a hypodermic syringe, and then loaded by blood flow. In its case, the IV drip method can be used to directly place the agent in the blood vessel. In other cases, some types of surgical treatments are used to place a particular agent at or near the location of a symptom or disease in the body. It has been discovered that by using techniques developed for the generation of integrated circuits, it is possible to make small drug delivery devices for containing and then delivering the agent to a location of a symptom or disease in the human body. Examples of such small-sized drug-implanting devices are disclosed in the following U.S. Patent Nos. 1,364,301, 5,770,076; U.S. Patent No. 5,797,898; U.S. Patent No. 5,985,328; U.S. Patent No. 6,123,861; 6,331,313. Several of these small drug implant devices are highly complex and, therefore, difficult and expensive to manufacture. Therefore, there is a need in the industry for a small, low-cost, easy-to-manufacture implantable small drug delivery device that can be used for implantation in the human body or other animals to transmit the drug to a wide range of drugs. s position.

SUMMARY OF THE INVENTION The simple, low cost, and easy to manufacture implantable drug delivery system of the present invention enables a mechanism to be implanted in a human body for transporting the agent to a wide range of locations. The disclosed system includes at least one pool, well or open space. The pool, well or open space is framed, enclosed, packaged or constructed in a core body. The pool, well or open space or 15 cell shell portion of the core body is of sufficient size to hold the desired amount of medicament required for prolonged in vivo treatment of chronic symptoms or diseases. These typical chronic symptoms or diseases are known to be chronic symptoms or diseases that occur in the eye. A screen 20, a well or an open space is surrounded by a screen 20 at the top or bottom of the core body, or at the top and bottom. The screen is used to control the release of drugs or medicines in tablets, powders or slurries placed in pools, wells or open spaces into the human body or animal body. The number, size, location, and configuration of the pores in the sieve are the solubility of the drug contained in the cell, well or open space, the dissolution rate of the agent, the concentration of the drug, and the form of the drug - 6 1364301 5

10 15

20 Tablets, powders, slurries or a combination of these, etc. Once one or more of the medicaments are placed in a pond, well or opening, and the pond, well or opening is covered with a screen, the entire drug or combination of medicaments, the body of the constituent pool, and the screen are implanted in the body. For example, one technique is to embed the disclosed drug delivery system into the eye via the scleral portion for symptoms or diseases that occur in the eye. Once the disclosed drug delivery device is properly positioned at its desired location, it can be secured in place using several methods, including passing the suture through a hole formed in the core body. The agent disperses from the pool, well or open space as it moves from the body through the perforations in the screen into the pool. This fluid flows through the screen and begins to dissolve the agent in the cell. The dissolved medicament will thus slowly ooze out through the pores in the screen, as long as the dosage is maintained in the pool of the disclosed drug delivery device to provide continuous treatment for symptoms or diseases. BRIEF DESCRIPTION OF THE DRAWINGS A preferred understanding of the implantable drug delivery system of the present invention can be obtained by reference to the drawings. 1 is a side view of a specific embodiment of the present invention embedded in a human eye; FIG. 2A is an exploded perspective view of a preferred embodiment; and FIG. 2B is similar to that shown in FIG. 2A A perspective view of a core body; Figure 2C is a perspective view of a screen similar to that shown in Figure 2A; Figure 2D is an enlarged plan view of a portion of the screen such as shown in Figure 2C; 7 1364301 Figure 3 is an exploded perspective view of a first alternate embodiment; Figures 4A and 4B are perspective views of a second and a third alternate embodiment of the disclosed drug delivery system; Figure is a side view of a drug delivery system attached to a support; 5 Figure 6A is a perspective view of a drug delivery system including a sharpened edge or a scalpel portion; Figure 6B is a 6A is an exploded view of the embodiment shown in the drawing; FIG. 6C is a perspective view of the drug delivery system including a sharpened edge 10 similar to that shown in FIG. 6A; FIG. 6D is An exploded view of the specific embodiment shown in Figure 6C; Figure 7 is a A perspective view of an alternate embodiment of the core body of the drug delivery system of the present invention, further comprising a channel for refilling the drug into the cell; Figure 7A is the drug shown in Figure 7 An alternate embodiment of the core body of the delivery system comprising a flange portion; and Figure 8 is a perspective view of another alternate embodiment of the drug delivery system comprising a plurality of smaller cells 20 Figure 9 is a transmission of a drug delivery system with a three-zone pool

a view wherein an internal passage is included between the divisions for medicament movement; Figure 10 is a perspective view of a drug delivery system in which two smaller pools are included in a larger pool; A cross-sectional view of a specific embodiment of the drug delivery system shown in Fig. 10; Fig. 12 is a perspective view of a drug delivery system having a single cell, and Fig. 13 is for Figure 12 is a perspective view of a first embodiment of the drug delivery system shown in Figure 12; Figure 14 is a second alternate embodiment of the drug delivery system shown in Figure 12 a perspective view;

Figure 15 is a perspective view of a third alternate embodiment of the drug delivery system shown in Figure 12; 10 Figure 16 is a first embodiment of the drug delivery system shown in Figure 12 4 is a perspective view of an alternate embodiment; FIG. 17 is a perspective view of a fifth alternate embodiment of the drug delivery system shown in FIG. 12; FIG. 18 is a view of FIG. A sixth perspective view of a sixth embodiment of the drug delivery system shown in the alternative embodiment;

Figure 19 is a perspective view of a seventh alternate embodiment of the drug delivery system shown in Figure 12; Figure 20 is an eighth embodiment of the drug delivery system shown in Figure 12 A perspective view of an alternate embodiment can be alternated; 20 Figure 21 is a perspective view of a first alternate embodiment of the drug delivery system shown in Figure 10; Figure 22 is in Figure 10. A perspective view of a second alternate embodiment of the drug delivery system shown; Figure 23 is an in vitro study using betaxolol hydrochloride tablets (in 9 vitm study) to determine 'drug concentration versus time A curve; and Figure 24 is a plot of drug concentration versus time in an in vitro study using nepafenac tablets. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT(S) DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT The representative symbols used in the following description of preferred and alternate embodiments are intended to illustrate the disclosed invention. Throughout the description, the same parts as in each of the specific embodiments are denoted by the same ones and tens. The representations of the hundreds and thousands digits are used to indicate an alternate embodiment. As seen in Figure 1, a handful of implantable drug delivery systems of the present invention are shown for treating a condition or disease that affects the intrinsic portion of the eye. Such diseases include, but are not limited to, age-related macular degeneration (ARMD), proliferative diabetic retinopathy (pDR), neovascular glaucoma, ischemic and iatrogenic retinopathy, posterior eye inflammation, and retinal edema. DETAILED DESCRIPTION OF THE INVENTION The preferred embodiments of the present invention are described herein in terms of their use in treating endophthalmia, but those skilled in the art will appreciate that the present invention can be used in any animal. It is suitable for use in a position to treat symptoms or diseases in a small-sized drug delivery device. In addition to treating diseases of the eye, the drug delivery device of the present invention can be placed close to the prostate for the treatment of prostate cancer or by taking the exposed device, usually accompanied by The deputy that occurs during treatment, such as hot flashes, changes in sound, or chest 1364301 5 can be significantly reduced, or even eliminated. Moreover, those skilled in the art will appreciate that the cost of the patient can be significantly reduced by reducing the cost of the patient. Therapeutic-type adherence to patients is improved with the need to effectively eliminate frequent dosing. The pharmacist's workload and exposure to dangerous or toxic preparations will be combined. It can effectively avoid the opportunity for drugs to interact with each other. Also, increase the chances of providing drug-binding therapies.

10 If the disclosed device includes a contraceptive that is implanted in a woman, it has similar advantages. Other potential applications include the treatment of a foreign mold infection with an antifungal agent.

Patients with Parkinson's disease are also awaiting the implantation of the disclosed drug delivery device into the brain: to slowly release the agent to reduce tremors. A digestive system with a stagnation of the colon or a number of different digestive diseases can also be alleviated by implanting the disclosed device in the digestive tract. 15 As seen in Figure 2A, the drug delivery system 10 includes a pool 14. The pool is formed in the pool enclosure, the frame or the outer casing portion 12. For simplicity of explanation, the pool enclosure, the frame or the outer casing portion is referred to as the core body 12. In a preferred embodiment, the core body 12 is formed from a generally flat piece of material. The pool 14 shown in Fig. 2A has a top portion 16 and a bottom portion 18. The top 16 of the pool 14 intersects the upper surface 20 of the core body 12. In the preferred embodiment, the bottom 18 of the cell 14 intersects the lower surface 22 of the core body 12. The illustrated pool 14 is in fact a hole through which the core body 12 passes. If the top 16 is larger than the bottom 18', the pool 14 can have a push-out wall 17. 11 1364301 A better understanding of the construction of the core body 12 can be obtained by referring to FIG. 2B. Among them, the core body 12 is shown to have an arched modified runway outer periphery. The pool 14 contained therein passes completely through the upper surface 20 to the lower surface 22, and is surrounded approximately parallel to the outer periphery of the core body. For a better understanding of the disclosed small size drug delivery system, the core body 12 has a length of about 9.5 mm and a width of about 5.3 mm.

As shown in FIG. 2B, the pool 14 can be located at the center of the core body 12 or closer to one end of the core body 12. The size of the pool 14 is sufficient to accommodate a plurality of different medicaments. Such agents may include such direct or indirect 10 neuroprotective agents, antioxidants, anti-apoptotic agents, soluble growth factor promoters or antagonists, anti-proliferative agents, angiogenic inhibitors, anti-edema agents, blood vessels A standard, anti-inflammatory or antibiotic, whether it is a small organic molecule or organism, such as a protein, a nucleic acid type enzyme, an antibody, an antibody fragment, an aptameter, or a nucleotide deficiency. More specifically, suitable agents include, but are not limited to, signal transduction inhibitors, protein catalyzed antagonists, tyrosine catalyzed antagonists, vascular endothelial growth factor receptor antagonists, integrin antagonists, matrix metalloproteinases Inhibitors, plasma glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDS), epoxidase (COX-1 and / or COX-2) inhibitors and angiostatic steroids. Each of the 20 pharmaceutical systems can be in the form of a powder, a serum or a tablet. Depending on the type and severity of the disease, a prescription for the drug is prescribed for a period of time sufficient to provide adequate treatment for the disease. If desired, a plurality of different additives can be added to the agent to increase its effectiveness. For example, a hydrophilic additive, such as an adjuvant humectant, can be added to the medicament to attract 12 1364301 water molecules into the area of the delivery device where the delivery device is inserted, either to aid in the dissolution of the agent or to transport the agent away. The pool 14. In order to minimize the small bubbles formed in the pool 14, the size and shape of the pool 14 is preferably substantially the same as the size and shape 5 of the medicament placed in the tank 14 to minimize the amount of free air.

As shown in Fig. 2C, a first screen 24 is attached to the upper surface 20 of the core body 12 for covering the top 16 of the pool 14. Optionally, a second screen 26 is attached to the lower surface 22 of the core body 12 to cover the bottom portion 18 of the pool 14. In a preferred embodiment, the screen 24 is shown as 1 in Figure 2C. In particular, the screen 24 has an arched modified runway perimeter 36 that is approximately parallel to the circumference of the pool 14 and the periphery of the core body 12. The portion 23' of the screen constituting the hole 28 has a thickness which is the same as the thickness of the periphery 25 depending on the configuration of the device 1' or a different thickness.

As can be seen in Figure 2D, the screen 24 or screens 24, 26 are formed to accommodate the 15 plurality of apertures 28. The number, size, location, and configuration of the apertures 28 in the screen 24 or screens 24, 26 are a function of various factors, including the solubility of the drug placed in the cell 4, and the dissolution rate of the drug placed in the cell 14. And the concentration of the drug placed in the pool 14. Typically, the size of the apertures 28 is generally from about 2 microns to 1 (8) microns at any location. However, the disclosed invention is capable of using different aperture sizes in other applications. Although it should be understood that the 大体上 'substantially the pores 28 are evenly distributed to cover the surface of the screen 24 or the screens 24, 26' to enable maximum dissolution of the agent, as will be explained below, the uneven distribution of the other holes 28 can be achieved. effect. It will also be appreciated by those skilled in the art that when the drug delivery system of the present invention is used in the eye, the apertures must be small enough to prevent the passage of any undissolved drug particles that would interfere with vision. Cold “For each sieve (4) thickness, depending on the dosage of the drug intended to be administered to the target implant site, is from about 0.05 mm to 0.5 mm, while the core body 12

Appropriate thickness ', from about 5 mm to 3 G cm, preferably from about 〇 八 至 to 2.0 mm β A field using metal or non-metallic materials to expose the drug delivery device 'Screen 24 or screens 24, 26 can be fixed to core body 12 using a plurality of different adhesives, including gums, cyanoacrylic acid, or room temperature adhesives commonly used for human body use, Thermal adhesives and epoxy bites are UV-curable adhesives. In a preferred embodiment, the screen 24 or (four), 26 formed as the core body 12' is generally planar. A plurality of different materials can be used to make the core body core a screen 24'26. The 笙 from t times (four) Φ, η 4 can be self-complexed for a variety of suitable for human use, including enamel, glass, ruby, sapphire, diamond or ceramic. If desired, materials suitable for human use may be used to form the core - body 12 and screens 24, 26. These materials suitable for human use include gold, silver, platinum, non-recorded steel, tungsten and titanium. When using a material suitable for human use, the screen 24 or the screens 24, 26 can be spliced to the core body 12 using a plurality of different 2 techniques, including lightning joints, thermoelectric joints, if not first, or Glue and adhesive. It will be appreciated by those skilled in the art that the disclosed drug delivery platform/stage is effective during the segmentation process by passing the appropriate number of medicaments/knifes so that the sum of the apertures 28 in the sieve must be capable of 1364301 Pool 14 achieves the desired drug transfer rate. Generally, this is considered as the pore density. For this disclosure, the pore density is the total pore area divided by the total surface area of the device, or even the area not covered by a screen.

The number of holes in the surface of a screen, its size, its position, and its general appearance, constitute a pattern of holes. This pattern of holes is adjusted to ensure that the desired amount of medicament is delivered at the desired flow rate. When a plurality of pools are formed in the core body, a plurality of pore patterns in the sieve can be used to control the flow of the medicament. For example, a pattern of holes concentrating at one end of the cell will begin to cause a rapid flow of the agent. However, when the medicament is used up, the medicament travels a longer path before it is expelled from the pool 14; therefore, the release rate of the medicament from the drug delivery reservoir 14 will drop sharply over time. In an alternate embodiment shown in FIG. 3, the bottom portion 118 of the pool 114 may itself be constructed as a screen, thereby eliminating the need to use and attach a second screen 26 as shown in FIG. 2A. . In other applications, as shown in Figure 3, it is also possible to have the pool 114 have a solid bottom. When the pool 114 has a solid bottom, only a single screen 124 is used on the top 116 of the pool 114. Although the preferred embodiment shows a modified runway periphery 36, the pool 14 is closer to the end 15, and a slit 30 is disposed at the proximal end 13, it is understood by those skilled in the art that a plurality of species The design of other implantable drug delivery platforms is feasible without departing from the scope of the invention. For example, the drug delivery platform can be constructed with a plurality of slits 30 or a straight side, such as the triangular shape 310 shown in Figure 4A. Alternatively, the square shape, the annular shape, the paddle shape, or any other suitable shape may be embedded in the eye or in the portion of the body - a small incision, which is the most The location that is used effectively. Since the adaptability of the disclosed invention can be configured into a plurality of different shapes, in particular, if the core body and the screen are made of a material suitable for human use, the disclosed device can be constructed as shown in the first side. It is a ring or a cylinder 380. f When assembled in this manner, the device can be crimped around a portion of the button, ligament, muscle fiber tube, nerve bundle, or any other portion of the body that responds well to local administration. Similarly, the cylinder (10) can be placed in a tubular tube placed in the body, expanded or sutured to secure its position. Different types of agents can be placed in different cores of different shapes or different colors, if desired. The use of different meanings in core bodies of different shapes or colors allows the surgeon to distinguish between different agents by the shape and color of the device containing the device, reducing the confusion of the agent. 15 (d) The condition, which may be related to the symptom or disease being treated, is to orient the drug delivery device in a - position. In this case, as shown in Fig. 5, the drug delivery device 410 can be attached to a support member 432 with the core body 412 positioned in the desired direction. In another specific embodiment of the drug transfer platform 51A shown in Figures 6A and 6B, a core body 512, an upper screen 524, and a lower screen 525 are formed to form a sharpened edge 534. Although a thin planar embodiment as shown in Figures 2A, 3, and 4A is suitable for insertion into the vitreous of the eye, other applications require penetration through the soft tissue. When the core body 512 is configured to cause a portion of the peripheral edge 536 of the core body 512 to be formed, including a sharpened edge 16 534, the core body itself can be used to make a beginning incision, or the knife edge can be enlarged to allow the drug The transfer device 51G is placed through. Here, the implementation of H5_Lf$524 "the edge is a part of the sharpening edge, which is used to create an initial 5 touch for an opening that can cause the exposed drug delivery device to pass through. Another alternate implementation In Example 610, as shown in Figures 6C and 6D, the sharpened edge system can be placed on a portion of the edge of a solid member 625 that sits below the pool 614. Although sufficient medicament can be placed in the pool of the core body. In order to treat the symptoms of 10 treatments or the duration of the disease - the shortest period or the extended period, but if the symptoms or diseases are stubborn, then it must be actually replaced. Although the entire device can be replaced, it is found that When the device is used in a patient for an extended period of time, such as one year or longer, as shown in Figure 7, the pool 714 in the core body 712 can be surrounded by a circumference 15 from the core body 712. The edge 736 is refilled by a passage 738 into the pool 714. Due to the small size of the core body 712, it is not possible to drill a channel from the peripheral edge 736 to the pool 714. In these conditions, the two-phase fitting 712 is required. 712B constitutes the core subject 712, each phase fitting includes a portion of the passage. When one of the portions is placed on top of the other portion, the two portions of the passage, whether horizontal or 2, are vertically formed together to form an aperture 738 from the peripheral edge 736 to the pool. 714. In another embodiment 810, the end of the channel 838 can be attached to a flange 840. The flange 840 is adapted to facilitate the position of the opening by using a hypodermic syringe (not shown) to treat the pool with a medicament. 814 is refilled. Further, the use of the flange 84 can prevent or reduce contamination. The flange 840 can be disposed on the side of the core body 812, or a short distance from the segment, and by a small tube 842 Connection. As shown in Figure 7A, the channel 838 can be constructed as a tortuous path. In complex situations, multiple agents must be placed in close proximity to the symptoms or disease. Under these conditions, in the core body 943, % may constitute a pool of plurals. As shown in Fig. 8, the core body commits at least a smaller proximal end pool 943, and a smaller end pool 945. Due to different medicaments, it is necessary to a screen covering the proximal end 943 and End 945, including a different number and size of apertures, covers each of the proximal end 943 and the smaller end of the pool 945. Other embodiments of the disclosed drug delivery platform illustrated in Figures 9 through 23 are described below. Figure 9 shows a specific embodiment of a drug delivery device 1010 that includes a proximal end cell 1043, an intermediate cell 1045, and an end cell 1047. The proximal side 4 cell 1043 utilizes a first separator 1 〇 41 The intermediate pool 1045 is separated from the end tank 1047 by using a second partition 1049. If necessary, the passage formed in the partitions 1〇41, 1〇49 The 1048 'system helps the agent to transfer or move between different pools. It is also noted that 'the first screen on the top surface of the core body 1012 and the second screen on the lower surface 1024 of the core body 1012 are made to control the release of the medicament. . Specifically, at the end 1〇15 2〇, a U-shaped pattern 1〇5〇 is included, and an arched shape 1052 is included at the proximal end 1〇13. In this embodiment, three medicaments mi, M2 and M3 are particularly useful when placed in a scorpion animal. Alternatively, the dividers 1〇41 and 1〇49 may be solid or impervious to separate the medicament mi, m2 18 1364301 and M3. Figure 10 is a diagram showing a specific embodiment 1110 for dissipating the two medicaments M1 and M2 in vivo. Thus, the core body m2 utilizes a solid or impervious partition 1141 divided therebetween into a proximal end cuvette 5 1143 ' and an end cuvette 1147. The release of the agent M2 is by sieving

A U-shaped pattern of 1124 and screen openings 1150 in the lower screen 1126 covers the end tank 1147 for control. A trapezoidal pattern of screen openings 1154 is configured to cover the proximal end pool 1143 for controlling the release of the medicament M1. In Figure 11, the other two-zone implantable drug delivery 10 platform 121 is shown. It should be noted that a first mesh pattern 1256 covers the entire end cell 1247, and a second mesh pattern 1258 covers the entire proximal end cell 1243' to accommodate the medicaments M2 and M1, respectively. As shown in Fig. 12, a specific embodiment π has a single cell 1314 for containing a drug cartridge. The single cell 1314 is constructed by combining two core main body members 1312 and 1312. Each of the core body members 1312A, 1312B includes a complete mesh pattern 1360 for covering the pool 1314 formed between the two portions 1312A, 1312B of the core body. Also shown in Fig. 13 is another specific embodiment 141 of a single cell 1414. In this embodiment 1410, the core body 1412 includes a lower screen 1426 that is covered by an upper screen 1424. It should be noted that the upper screen 1424 completely covers the core body 1412 and is fitted with a complete screen pattern 1460 for covering the entire pool 1414. The one shown in Figure 14 is another single pool embodiment 151. 19 1364301

In this particular embodiment, the upper screen 1524 has a one-week length 1536 that mates with the interior of the pool 1514 that is formed within the core body 1512. Another specific embodiment 1610 having a single well 1614 is shown in FIG. In this embodiment 1610, the upper screen 1634 includes a downwardly depending flange 662 that is constructed and configured to be press fit into the interior of the pool 1614 formed in the core body 1612. Alternatively, a flange system, as shown in Fig. 18, may be disposed on the core body 1612 for upwardly extending into a recessed portion of a screen 1624. 10 15

20

Another specific embodiment 1710 having a single cell 1714 is shown in FIG. The unit of the single pool 1714 is formed in a core body 1712 that is further mated with a core body support 1712 (the inner body support 1712C includes a -pg release portion 1712C丨 in which the core body 1712 is securely held therein. The upper screen 1724 covers the pool (7) 4 in the core body 1712. The bottom portion of the core d body! 712 is a wire mesh screen. As shown in Fig. 17, it is shown in the figure - and the specific figure shown in Fig. 16 Embodiment 17 is similar to the specific embodiment. However, the core body bracket 1812D is configured to have a right-handed branch with an open space 1812D.1 therebetween, rather than a shoulder-to-go, a continuous surrounding core body. Bracket 1812D. The opening and closing chamber 18120.1' is configured to receive the core body 1812. A groove 1864 receives the two branches of the /body body bracket 1812D. Again, the core body 1812 is externally configured as 1 The teacher 1824 covers 'and the core' of the body 1812 is shown in Fig. 18, and the disclosed embodiment 1910 includes a core body 1912 having an upwardly extending flange 1966. Cooperate with the upper screen 1924 20' Thus, the upper screen 1924 can be disposed over the core body 1912 to cover the pool 1914. As shown in Figure 19, a particular embodiment 2010 includes a generally hollow core body 2012. The lower screen 2026 is configured to be generally hollow. The bottom surface 2022 of the core body 2012, and an upper screen 2026 are positioned on the top surface 2〇2 of the core body. As shown in Fig. 20, a specific embodiment 211 includes a proximal end cell 2143' And a terminal cuvette 2147. The partition 2141 separating the proximal end cuvette 2143 from the end cuvette 2147 has a channel 2148' configured to move therethrough. By arching in the upper screen 2124 and the lower screen 2126 The hole pattern 2152 controls the release of the medicaments M1, M2. Alternatively, the spacers 2141 may be distributed along the long axis of the pool 2114 to form a juxtaposed pool. As shown in Fig. 21, another embodiment 2210 A proximal end 2243 is included, and an end cuvette 2247. A divider 2241 separates the proximal end cuvette 2243 in the core body 2212 from the end cuvette 2247. Both the upper screen 2224 and the lower screen 2226 are at the end 2215 At A hole pattern 2250' comprising a shape; and a complete hole pattern 2260 is included at the proximal end 2213. As shown in FIG. 22, it is an elliptical thickened embodiment 2310 comprising an annular screen 2324 2326 is disposed on the upper surface 2320 and the lower surface 2322 of the core body 2312. Examples These devices similar to those shown in Fig. 15 are implanted in eight New Zealand white rabbits. The screen is attached to the core body with a 矽 adhesive. The contralateral 1364301 eye was used as a control. On the second day, a rabbit was taken out of the study. At one month, three rabbits were tested and the remaining four rabbits were tested at three months. Histopathological observations were performed at one month and three months. At one month, three of the rabbits showed a small number of cells inflamed in the vitreous. One of the three rabbits also developed inflammation in the serrated margin. Finally, the rabbit has the minimum growth of the lens fiber. The toxicological observations of this group were not significant.

In an in vitro study, betaxolol hydrochloride, a relatively high water-soluble substance, is a total weight of 22 mg tablets with 10% microcrystalline cellulose and 4% stearic acid. magnesium. The betaxolol hydrochloride tablets are embedded in a pool of drug delivery devices similar to the specific embodiment shown in Figure 15. These devices use an 8 micron 丨% porosity on one side of the cell. The ratio of the area of all the pores to the area of the sieve is about 〇18%. The ratio of the area of all the pores on the β drug transfer device to the area of all the surfaces is about 15 〇.〇2%. The loaded drug delivery device of the present invention is placed at a height of 4 mL

欵Liquid liquid chromatography (HPLC) in a small glass bottle with 'with phosphate/physiological saline buffer' followed by stirring with a small stir bar. These small glass bottles are regularly targeted at the drug concentration by high performance liquid chromatography. (HPLC) sampling and analysis. As shown in Fig. 24, the graph is a graph of drug concentration versus time, indicating the release curve.

In a second in vitro study, another second pharmaceutical formulation having a relatively low water soluble shell, nepafenac tablet, was also used in a device similar to the specific embodiment illustrated in Figure 15 the study. The tablets also contained 10% microcrystalline cellulose and 4% magnesium stearate. One tablet is tied 22 1364301

Placed in a two-sided 14 micron 25% porosity device. The ratio of the area of all the holes to the area of the sieve is about 4.5%. The ratio of the area of all the holes in the drug delivery device to the area of all surfaces is about 0.48%. A second tablet was placed in a two-sided 14 micron 1% device. The ratio of the area of all the holes to the surface area of the sieve is about 〇18%. The ratio of the area of all the holes in the drug delivery device to the area of all surfaces is about 0.02%. Drug release studies were performed as described above. As shown in Fig. 25, the curve "A" shows a release amount curve derived from a two-sided 14 μm 25% porosity device. Curve "B" shows the release profile curve from a two-sided 14 micron 1% porosity device. A third experiment was performed by replacing the disc acid/saline buffer from a two-sided 14 micron porosity device and the experiment was restarted. This experiment is indicated by the curve "C". Once the symptoms or disease in the surgery have been confirmed and located, the physician will determine if the drug can be treated in a manner that is very close to the symptoms or disease. If it is decided to treat a symptom or disease in a manner that is very close to the symptoms or disease, it is necessary to actually place the agent near the symptom or the disease site. In other applications, it is necessary to use - &amp; New Zealand to treat symptoms or diseases. The brachytherapy requires a continuous flow of medicament from the drug delivery device. The specific embodiment shown in Fig. 1 presents that the symptoms or diseases are present in the eyes of the patient. For example, a surgeon can embed a 'can be implanted' device in the sclera into the patient's glassy room. The music transfer platform 10 is then embedded via a slit and secured in place by stitching through the slits 30 in the core main body 12 and attaching the other portions of the stitch to the eye. Orienting the platform causes the implantable platform to maintain a path of light that deviates from the lens to the omentum. In order to prevent the implanted device from being covered by cells and hindering the flow of the drug from the cell through the pores, an anti-proliferative coating can be applied to the sieve and the core body. Similarly, a material such as tantalum can constitute a wafer that prevents the screen from being flattened and can cover the core body with a substance to prevent flattening. As just mentioned, although the preferred embodiment shown is directed to embedding a medicament for treating symptoms or diseases in the eye, those skilled in the art will understand that the disclosed implantable drug delivery is disclosed. The platform 10 can be used at any location in an animal's body where an implanted agent is optimally treated for symptoms or diseases. The present invention will now be appreciated by those skilled in the art in light of the <RTIgt; Other embodiments of the present invention will be apparent to those skilled in the art and may be embodied by the foregoing disclosure. These other specific embodiments are intended to be included within the scope and meaning of the appended claims. BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a side view of a specific embodiment 20 of the present invention embedded in a human eye; Fig. 2A is an exploded perspective view of a preferred embodiment; A perspective view of a core body similar to that shown in Figure 2A; Figure 2C is a perspective view of a screen similar to that shown in Figure 2A; 24 1364301 Figure 2D is shown in Figure 2C. An enlarged plan view of a portion of a screen; FIG. 3 is an exploded perspective view of a first alternate embodiment; FIGS. 4A and 4B are a second and fifth to third disclosed drug delivery system A perspective view of an alternate embodiment; Figure 5 is a side view of a drug delivery system attached to a support; Figure 6A is a perspective view of a drug delivery system including a sharpened edge or a scalpel nose portion Figure

Figure 6B is an exploded view of the embodiment shown in Figure 6A; Figure 6C is a perspective view of a drug delivery system including a sharpened edge similar to that shown in Figure 6A. Figure 6D is an exploded view of the specific embodiment shown in Figure 6C

15 Figure 7 is a core body of the drug delivery system of the present invention.

A perspective view of an alternate embodiment, further comprising a channel for resupplying the agent into the cell; Figure 7A is an alternate embodiment of the core body of the drug delivery system shown in Figure 7, It comprises a flange portion; and 20 Figure 8 is a perspective view of another alternate embodiment of the drug delivery system comprising a plurality of smaller cells; Figure 9 is a three-zone pool A perspective view of a drug delivery system, wherein an internal channel is included between the zones for drug movement; Figure 10 is a perspective view of a drug delivery system including a second in a pool larger than 25 1364301 a small pool; Fig. 11 is a perspective view of an alternate embodiment of the drug delivery system shown in Fig. 10; Fig. 12 is a perspective view of a drug delivery system having a single cell Figure 13 is a perspective view of a first alternate embodiment of the drug delivery system shown in Figure 12;

Figure 14 is a perspective view of a second alternate embodiment of the drug delivery system shown in Figure 12; 10 Figure 15 is a first embodiment of the drug delivery system shown in Figure 12 3 is a perspective view of an alternate embodiment; FIG. 16 is a perspective view of a fourth alternate embodiment of the drug delivery system shown in FIG. 12; and FIG. 17 is a view of FIG. A fifth aspect of the drug delivery system shown in the alternate embodiment of the fifth embodiment;

Figure 18 is a perspective view of a sixth alternate embodiment of the drug delivery system shown in Figure 12; Figure 19 is a seventh embodiment of the drug delivery system shown in Figure 12 A perspective view of an alternate embodiment can be alternated; 20 Figure 20 is a perspective view of an eighth alternate embodiment of the drug delivery system shown in Figure 12; Figure 21 is in Figure 10. A perspective view of a first alternate embodiment of the drug delivery system shown in FIG. 22; a second embodiment of a second embodiment of the drug delivery system shown in FIG. Perspective view; Figure 23 is a plot of drug concentration versus time using an in vitro study of betaxolol hydrochloride tablets; and Figure 24 is an in vitro study using nepafenac tablets (in Vitr〇study), a curve of drug concentration versus time β

[Main component symbol description] 10...implantable drug delivery system 12, 412, 512, 712, 812, 912, 1012, 1112, 1412, 1512, 1612, 1712, 1812, 1912, 2012, 2212, 2312...core Main body 13, 1013, 2213... proximal end 14, 114, 614, 714, 814, 1314, 1414, 1514, 1914, 2114... pool 15, 1015, 2215... end 16, 116... item 17 ... push wall 18 , 118... bottom 20, 1020, 2320... upper surface 22, 2322... lower surface 23... screen portion 24, 1024... first screen 25, 36, 1536... peripheral 26... second screen 28... hole 30... seam Holes 38, 838, 1048, 2148... channels 110, 610... alternate embodiments 124, 1624, 1824... sieve 310... triangular shape 380... cylinder 410, 1010... drug delivery device 432... support members 510, 1210... Drug delivery platforms 524, 1124, 1424, 1524, 1634, 1724, 1924, 2124, 2224... upper screens 525, 1126, 1426, 2026, 2126, 2226... lower screen 534... sharpen edges 536, 736. 27 1364301

625··· Solids 712 Α, Β...phase fittings 810, 1110'1310'1410, 1510, 1610, 1710, 1810, 1910, 2010, 2110, 2210, 2310... Specific Examples 840, 1662, 1966·. Flange 842...tubules 943, 1043, 1243... proximal end pools 945, 1047, 1247... end pools 1041···first partitions 1045.·· intermediate pools 1049...second partitions 1050.··υ Shape pattern 1052...arched pattern

28

Claims (1)

1364301 Patent Application No. 096,128,653, Application for Patent Renewal, February 16, 101 What is claimed is: 1. An ophthalmic implantable drug delivery device comprising: a reservoir constructed and configured to contain a medicament, the pool being surrounded by a pool receiving portion; a screen constructed and configured for The top of the cell is covered when secured to the cell receiving portion, which is formed of tantalum and contains a plurality of holes. 2. The ophthalmic implantable drug delivery device of claim 1, further comprising a screen covering the bottom of the cell. 3. The ophthalmic implantable drug delivery device of claim 1, wherein the cell passes through the cell receiving portion and a second screen is positioned at the bottom of the cell, which is constructed and configured to be secured Cover the bottom of the pool to the receiving portion of the pool. 4. The ophthalmic implantable drug delivery device of claim 1, wherein the cell receiving portion is substantially planar. 5. The ophthalmic implantable drug delivery device of claim 1, wherein the cell comprises a plurality of portions separated by an impermeable barrier. 6. The ophthalmic implantable drug delivery device of claim 1, wherein the size and number of holes in the screen covering a portion of the cell are in contact with the mesopores in the other portion of the cell The size and number are different. 7. An ophthalmic device for delivering a medicament to an animal body in close proximity to a symptom treatable by the medicament, the ophthalmic device comprising: a pool receiving portion having a first surface, a a second surface, a periphery, and a medicament pool between the first surface and the second surface; a first screen fixed to the first surface of the pool receiving portion, 29 1364301 No. 096128653 Patent Application Patent No. </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; 8. The ophthalmic device of claim 7, further comprising a second screen fixed to the lower surface of the pool receiving portion, proximate to an intersection of the pool and the lower surface of the pool receiving portion . 9. If applying for a full-time (4) 8 device, the pool in which the t is in the tank receiving portion includes a plurality of smaller cells separated by an impermeable wall (4). A method of manufacturing an ophthalmically implantable drug delivery platform comprising the steps of: a) constituting a pool containing portion of a pool that is constructed and configured to contain the drug; b) will be - -! (d) to the pool receiving portion for covering the pool, the first screen is formed of tantalum and contains a plurality of holes. 15 U. The method of claim 10, further comprising the step of disposing a second screen on opposite sides of the cell. 12. The method of claim </RTI> wherein the second screen is secured to the pool receiving portion. The method of claim 10, wherein the pool receiving portion is substantially planar. 14. The method of claim 10, wherein the first screen is substantially planar. 15. A method of applying for a full-time correction, wherein the second screen is generally planar. </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; . 17. The method of claim 10, further comprising the step of dividing the pool into at least two smaller pools. The method of claim 17, further comprising the step of forming the size and number of the apertures in the screen covering the smaller pool. 31