HYDROTECHNOLOGY - A New Science
Pursuing a balance with NATURE
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This is the tip of the iceberg as of what lies bellow, clearly points out distorted conceptions and beliefs on human culture WHEN LAWS OF MAN IGNORE LAWS OF NATURE.
From: Moulis, Thomas <Thomas.Moulis@uspto.gov>
Date: Fri, Aug 7, 2015 at 12:40 PM
Subject: RE: Conspiracy and Brainwashing III – USPTO is preaching to their Patent Examiners that they do not need to be known in the art for judging and allowing IP rights when issuing patents!
To: Elson Silva, PhD <tubarc@gmail.com>
From: Moulis, Thomas <Thomas.Moulis@uspto.gov>
Date: Fri, Aug 7, 2015 at 12:40 PM
Subject: RE: Conspiracy and Brainwashing III – USPTO is preaching to their Patent Examiners that they do not need to be known in the art for judging and allowing IP rights when issuing patents!
To: Elson Silva, PhD <tubarc@gmail.com>
You are a fool---
If you can’t understand legal or technical writing, you have no business blogging about it
“Wicking” is a term of art---fluid will travel in any direction via the fibers—regardless of gravity
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"Wick/wicking is in the patent classification system but not on HYDROLOGY textbooks."
LEGAL WICKING as the term of the art regardless of gravity confirms USPTO long standing bias ignoring hydrology on conductivity parameters of issued patents (11/30/23):
Thermal/Heat Conductivity 176.074 pat.
Electric/Electrical Conductivity 139.254 pat.
Hydraulic Conductivity 1.329 pat.
Unsaturated Hydraulic Conductivity 38 pat.
Wick/wicking 66.415 pat.
The US Government states that LEGAL WICKING is not technical, being inert to gravity LAW, meaning that LEGAL OIL LAMPS and LEGAL CANDLES can work upsided down. This sort of deceiving is behind the Economic Melting Down of 2008 burning about 41 trillion dollars, also dumping 1,1 million American as the leader of the COVID-19 pandemic catastrophe that took around 7 million lives world widely. In addition, obesity and sedentarism letting human beings miss brain capacity by becoming grumpier and dumber on neurogenesis effect.
Science is our understanding on nature functioning. Humans learn to respect nature early as babies on the first steps taming gravity for walking and running. Soon we understand the consequences of missteping and falling down. Therefore, all issued patents dealing with wick/wicking are CERTAINLY frauded because PATENT EXAMINERS ignored their homework from the beginning of their lives - GRAVITY.
LEGAL WICKING as the term of the art regardless of gravity confirms USPTO long standing bias ignoring hydrology on conductivity parameters of issued patents (11/30/23):
Thermal/Heat Conductivity 176.074 pat.
Electric/Electrical Conductivity 139.254 pat.
Hydraulic Conductivity 1.329 pat.
Unsaturated Hydraulic Conductivity 38 pat.
Wick/wicking 66.415 pat.
The US Government states that LEGAL WICKING is not technical, being inert to gravity LAW, meaning that LEGAL OIL LAMPS and LEGAL CANDLES can work upsided down. This sort of deceiving is behind the Economic Melting Down of 2008 burning about 41 trillion dollars, also dumping 1,1 million American as the leader of the COVID-19 pandemic catastrophe that took around 7 million lives world widely. In addition, obesity and sedentarism letting human beings miss brain capacity by becoming grumpier and dumber on neurogenesis effect.
Science is our understanding on nature functioning. Humans learn to respect nature early as babies on the first steps taming gravity for walking and running. Soon we understand the consequences of missteping and falling down. Therefore, all issued patents dealing with wick/wicking are CERTAINLY frauded because PATENT EXAMINERS ignored their homework from the beginning of their lives - GRAVITY.
Sir Isaac Newton defined the Law of Universal Gravitation in 1687. He was inspired to formulate his theory of gravitation by watching the fall of an apple from a tree.
Enviada em: quarta-feira, 5 de outubro de 2011 11:36
Para: Elson Silva, PhD
Assunto: RE: {SPAM?} Protecting Hydrology Science from REINVENTION
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Steven V. Owen
University Professor Emeritus
Educational Psychology
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Dr. Owen, my medicine is a bit bitter than that one swallowed by Albert Einstein by just stretching his tongue:
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This email from an Emeritus Faculty of Educational Psychology provided valuable insights and feedback showing how deep the academic community is compromised on scientific affairs in the US.They were supposed to know that Darcy’s Law on Hydraulic Conductivity is not written in the US constitution, but endorsed by Mother Nature.
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Nobel Prize is IMPORTANT TO HUMAN KIND, as 50% is business, 40% politics, 5% bad science and 5% good science from an educated abstraction. Nobel Prize Nomination of Economic Science was introduced to pretend that Human Business could overlap nature functioning. THE US AS THE FIRST ECONOMIC POWER IN THE WORLD GRABBED TWO-THIRDS (411/621) OF NOBEL PRIZE NOMINATIONS FOR SCIENCE. Exploratory Analysis shows that the American scientific community has been violating Hydrology science in the Patenting System more than a century, leaving a gap huge enough for a new science Hydrotechnology. It seems that working with the Chemistry of explosives is far more profitable than the Hydrology of self-watering flower pots. Mr. Alfred Nobel, Arms Dealer, Merchant of Death, and Father of Dynamite, got 355 patents and Albert Einstein got 50 issued patents to portray top scientists claiming intellectual property rights. Obesity, Economic Melt Dow, COVID-19 tragedies, and now Reinvention Policy by USPTO are important evidence of American negligence to science misbalance with Nature.
How much NATURE endorses the Economy and Politics? Sunlight and rain come to us FREE OF CHARGE, regardless of BOUNDARIES, making the Economy not a science, but a distorted human affair as basic Laws of offer and demand is being replaced by GREED and FEAR. Likewise, recent wars in Ukraine and Israel show us that Politics can’t be science, but a wicked manipulation on human issues wasting innocent lives and spoiling the landscape for weaponry industry profit and disguised interest as Homo sapiens misses simple rationality.
In my neighborhood, I saw the Scientific Police taking pictures of swings I installed on trees for children in the Park during the COVID-19 pandemic lock down. Society try to employ the word SCIENCE for POWER, but there is a misunderstanding as scientific principles claim TRANSPARENCY and HONESTY. Nature is in charge of SCIENCE as there is no POLICE to enforce Nature LAWS. Even religion try to use Scientology for credibility. I like the simple conception that God = Nature. However, Nature writes no books, promises no lands, no life after death, no war or death in name of a divine. In around 4 billions of years of our planet, it seems that we got no aliens to affect our evolution. Most probable we are not leaving our home until the end in 4 to 6 billions of years. Human challenge is to keep nuclear weapons safe, cropping soils, mining our minerals and preserve our home in balance with nature functioning, making our blue planet good for all humans.
What we see in the universe is just for light travelling.
It seems that few scientists do understand the meaning of their titles PhD as Philosophy Doctor coming from Philosophy of Science (Epistemology, Metaphysics, Logics, and History of Science).
Para: Elson Silva, PhD
Abe
Enviada em: terça-feira, 22 de abril de 2014
Cc: cko3@cornell.edu; TDO1@cornell.edu; MGS22@cornell.edu; SBW11@cornell.edu;
Assunto: RES: [06856] Protecting Hydrology Science from REINVENTION by corrupt LAY PEOPLE colluding with USPTO - US Pat 8,701,469
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2. The method of claim 1, further comprising the steps of: retracting the stent such that the portion of the stent is no longer in contact with the wicking means; and reducing a solvent vapor pressure in the chamber to evaporate a solvent of the fluid drug formulation.
3. The method of claim 2, wherein the step of retracting the stent such that the portion of the stent is no longer in contact with the wicking means removes excess fluid drug formulation from an exterior surface of the hollow wire during the step of retracting the stent.
4. The method of claim 3, wherein the wicking means is an open-celled sponge or foam.
5. The method of claim 3, wherein the wicking means is a plurality of glass beads.
7. A method of filling a fluid drug formulation within a lumenal space of a hollow wire having a plurality of side openings along a length thereof openings that forms a stent, the method comprising the steps of: placing a stent formed from a hollow wire having a plurality of side openings within a first chamber of an apparatus, wherein the apparatus includes a valve positioned between the first chamber and a second chamber that houses a wicking means that is in contact with a fluid drug formulation and the valve is closed such that the first chamber and second chamber are not in fluid communication; opening the valve such that the first chamber and second chamber are in fluid communication; allowing the first and second chambers to reach solvent vapor saturation or near solvent vapor saturation; placing a portion of the stent into contact with the wicking means within the second chamber such that at least one of the plurality of side openings is in contact with the wicking means; maintaining contact between the wicking means and the selected portion of the stent until a lumenal space defined by the hollow wire is filled with the fluid drug formulation via capillary action through the at least one of the plurality of side openings in contact with the wicking means; retracting the stent such that the portion of the stent is no longer in contact with the wicking means and is located within the first chamber; closing the valve such that the first chamber and second chamber are not in fluid communication; and reducing a solvent vapor pressure in the first chamber to evaporate a solvent of the fluid drug formulation.
12. The method of claim 7, wherein the step of retracting the stent such that the portion of the stent is no longer in contact with the wicking means removes excess fluid drug formulation from an exterior surface of the hollow wire during the step of retracting the stent.
13. The method of claim 12, wherein the wicking means is an open-celled sponge or foam.
14. The method of claim 12, wherein the wicking means is a plurality of glass beads.
[0006] Embodiments hereof are directed to methods and apparatus for filling a fluid drug formulation within a lumenal space of a hollow wire having a plurality of side openings along a length thereof that forms a drug-eluting stent with a plurality of side drug delivery openings. In an embodiment hereof, a stent formed from a hollow wire having a plurality of side openings is placed within a first chamber of an apparatus. The apparatus includes a valve positioned between the first chamber and a second chamber that houses a wicking means that is in contact with a fluid drug formulation and the valve is closed such that the first chamber and second chamber are not in fluid communication. The valve is opened such that the first chamber and second chamber are in fluid communication. The first and second chambers reach solvent vapor saturation or near solvent vapor saturation. A portion of the stent is placed into contact with the wicking means within the second chamber such that at least one of the plurality of side openings is in contact with the wicking means. Contact between the wicking means and the selected portion of the stent is maintained until a lumenal space defined by the hollow wire is filled with the fluid drug formulation via capillary action through the at least one of the plurality of side openings in contact with the wicking means. The stent is retracted such that the portion of the stent is no longer in contact with the wicking means and is located within the first chamber. The valve is closed such that the first chamber and second chamber are not in fluid communication, and the solvent vapor pressure in the first chamber is reduced to evaporate a solvent of the fluid drug formulation.
[0014] FIGS. 4A-7 are schematic illustrations of the method of the flow chart of FIG. 3 performed in an apparatus having upper and lower chambers, wherein the stents come into contact with the fluid drug formulation via a wicking means.
[0032] FIGS. 23A-B illustrate an embodiment of a wicking means, which controls transfer of a fluid drug formulation to a stent during the capillary filling procedure described in FIGS. 4A-7.
[0033] FIG. 24 illustrates another embodiment of a wicking means, which controls transfer of a fluid drug formulation to a stent during the capillary filling procedure described in FIGS. 4A-7.
[0034] FIG. 25 illustrates another embodiment of a wicking means, which controls transfer of a fluid drug formulation to a stent during the capillary filling procedure described in FIGS. 4A-7.
[0035] FIG. 26 illustrates another embodiment of a wicking means, which controls transfer of a fluid drug formulation to a stent during the capillary filling procedure described in FIGS. 4A-7.
[0036] FIGS. 27A-27B illustrate another embodiment of a wicking means, which controls transfer of a fluid drug formulation to a stent during the capillary filling procedure described in FIGS. 4A-7.
[0037] FIG. 28 illustrates another embodiment of a wicking means, which controls transfer of a fluid drug formulation to a stent during the capillary filling procedure described in FIGS. 4A-7.
[0038] FIG. 29 illustrates another embodiment of a wicking means, which controls transfer of a fluid drug formulation to a stent during the capillary filling procedure described in FIGS. 4A-7.
[0039] FIG. 30 illustrates another embodiment of a wicking means, which controls transfer of a fluid drug formulation to a stent during the capillary filling procedure described in FIGS. 4A-7.
[0040] FIGS. 31A-31B illustrate another embodiment of a wicking means, which controls transfer of a fluid drug formulation to a stent during the capillary filling procedure described in FIGS. 4A-7.
[0041] FIGS. 32A-32B illustrate another embodiment of a wicking means, which controls transfer of a fluid drug formulation to a stent during the capillary filling procedure described in FIGS. 4A-7.
[0042] FIG. 33 illustrates another embodiment of a wicking means, which controls transfer of a fluid drug formulation to a stent during the capillary filling procedure described in FIGS. 4A-7.
[0043] FIG. 34 illustrates another embodiment of a wicking means, which minimizes the contact area between each stent and the fluid drug formulation in order to control transfer of a fluid drug formulation to a stent during the capillary filling procedure described in FIGS. 4A-7.
[0044] FIG. 35 illustrates another embodiment of a wicking means, which minimizes the contact area between each stent and the fluid drug formulation in order to control transfer of a fluid drug formulation to a stent during the capillary filling procedure described in FIGS. 4A-7.
[0045] FIGS. 36A-36C illustrate another embodiment of a wicking means, which minimizes the contact area between each stent and the fluid drug formulation in order to control transfer of a fluid drug formulation to a stent during the capillary filling procedure described in FIGS. 4A-7.
[0046] FIGS. 37A-37C illustrate another embodiment of a wicking means, which minimizes the contact area between each stent and the fluid drug formulation in order to control transfer of a fluid drug formulation to a stent during the capillary filling procedure described in FIGS. 4A-7.
[0047] FIGS. 38A-38B illustrate another embodiment of a wicking means, which minimizes the contact area between each stent and the fluid drug formulation in order to control transfer of a fluid drug formulation to a stent during the capillary filling procedure described in FIGS. 4A-7.
[0048] FIG. 39 is a schematic illustration of an apparatus having upper and lower chambers for performing the method of the flow chart of FIG. 3, wherein the stents come into direct contact with the fluid drug formulation without the assistance of a wicking means.
[0058] Embodiments hereof relate to the use of capillary action to fill lumen 103 of hollow wire 102. Capillary action as used herein relates to the ability of a liquid to flow in narrow spaces without the assistance of, and in opposition to, external forces like gravity. As will be explained in further detail herein, only a portion of stent 100 having at least one side hole 104 is required to be submerged or exposed to a fluid drug formulation, or submerged or exposed to a wicking means in contact with a fluid drug formulation. The fluid drug formulation will then wick or travel into lumen 103 of hollow wire 102 via submerged/exposed holes 104 and fill or load the entire length of lumen 103 via capillary action. Capillary action occurs because of inter-molecular attractive forces between the fluid drug formulation and hollow wire 102. When lumen 103 of hollow wire 102 is sufficiently small, then the combination of surface tension and adhesive forces formed between the fluid drug formulation and hollow wire 102 act to lift the fluid drug formulation and fill the hollow wire. Filling stents 100 via capillary action result in a filling method that streamlines the drug filling process because such a method may be utilized to batch fill a plurality of stents in a relatively short time period. In addition, filling stents 100 via capillary action reduces drug load variability and makes the drug fill process more controllable and predictable. Capillary action results in fluid drug formulation uniformly filling or deposited within lumen 103 of hollow wire 102, and after solvent/dispersion medium extraction which is described in more detail below, lumen 103 of hollow wire 102 has a uniform drug content along its length.
[0059] More particularly, FIG. 3 is a flow chart of a method for filling lumen 103 of a stent 100 with a fluid drug formulation 432 via capillary action. FIG. 3 will be described in conjunction with FIGS. 4A-7, which are schematic illustrations of an apparatus 420 which may be utilized to perform the method steps of FIG. 3. As will be described in more detail herein, FIGS. 4A-7 represent an embodiment hereof in which a wicking means controls the transfer of fluid drug formulation into lumen 103 while FIG. 39 represents an embodiment hereof in which the stents directly contact fluid drug formulation without a wicking means in order to fill lumen 103. For illustrative purposes only, stents 100 are represented as straight tubular structures in FIGS. 4A-7 although it will be understood by one of ordinary skill in the art that stents 100 are a hollow wire shaped into a desired stent pattern as previously described with reference to FIG. 1. Apparatus 420 includes a first or upper chamber 422 which houses a manifold or stent suspension means 428 and an open container or reservoir 431 filled with a liquid or fluid solvent 433, a second or lower chamber 424 which houses a wicking means 430 that is in contact with fluid drug formulation 432 that includes therapeutic substance or drug 112, and a valve 426 positioned between upper chamber 422 and lower chamber 424. Solvent 433 within reservoir 431 is the same solvent as used in fluid drug formulation 432. Valve 426 is operable to alternate between an open configuration in which the first chamber and second chamber are in fluid communication, and a closed configuration in which the first chamber and second chamber are not in fluid communication. A plurality of stents 100 are loaded onto stent suspension means 428, which holds or suspends them in place during the capillary filling procedure, as shown in step 301A of FIG. 3. Stent suspension means 428 may suspend stents 100 in a vertical orientation as shown in FIG. 4A, or alternatively may suspend stents 100 in a horizontal orientation as shown in FIG. 4B. Stent suspension means 428 is operable to move the plurality of stents 100 between upper and lower chambers 422, 424. The capillary filling procedures in accordance with embodiment hereof may be readily scalable as batch processes. When loaded onto stent suspension means 428, stents 100 are already formed, that is, hollow wire 102 has previously been shaped or formed into a desired waveform and formed into cylindrical stent 100 as described above with respect to FIG. 1. Alternatively, if desired, the capillary filling process may be performed on straight hollow wires prior to shaping or forming hollow wire 102 into the desired waveform and subsequent stent configuration. As will be explained in more detail herein, in an embodiment hereof, stent suspension means 428 holds stents 100 in place by slightly expanding the inner diameter of the stents, thereby increasing friction between the stents and stent suspension means 428 and minimizing undesired movement of the stents.
[0061] There are several ways to reduce the amount of time required to reach solvent vapor saturation of chambers 422, 424, thereby reducing overall processing time to increase throughput. In one embodiment, a large surface area is created to reduce the amount of time required to reach vapor saturation. In an embodiment, a large surface area may be created by atomizing droplets within upper and/or lower chamber 422, 424 with ultrasonic spray nozzles. In another embodiment, a large surface area may be created by providing wicking means 430 with a large surface area as shown in FIGS. 4A-7 in order to increase the surface area of the evaporating solvent. The amount of time required to reach vapor saturation may also be reduced by increasing the temperature of the solvent/dispersion medium. Since solvent vapor pressure is usually very dependent on temperature, heat source 435 (which may alternatively be located within second lower chamber 424) may be utilized to control the temperature of fluid drug formulation 432. The amount of time required to reach vapor saturation may also be reduced by via convection of gas across the solvent surface. For example, a fan 499 may be utilized in upper chamber 422 to create convection across reservoir 431 containing a supply of solvent 433. Reservoir 431 of solvent 433 thus supplies the vapor required to reach solvent vapor saturation. The above-described methods for reducing the amount of time required to reach solvent vapor saturation of chambers 422, 424 may be used individually or in any combination thereof.
[0062] Once both chambers 422, 424 are at or near solvent vapor saturation, capillary filling may be initiated by moving stents 100 into contact with or submersed into wicking means 430 as shown in step 301E of FIG. 3 and as shown in FIG. 6. Wicking means 430 is in contact with fluid drug formulation 432, to control transfer of the fluid drug formulation into lumen 103 of hollow wire 102 of stent 100. In one embodiment, wicking means 430 is an open-celled polyurethane sponge or foam although various alternative embodiments of the wicking means are discussed herein. Stents 100 are pushed into or onto wicking means 430, thereby deforming wicking means 430. As the wicking means deforms, wicking means 430 transfers fluid drug formulation 432 from lower chamber 424 into submersed holes 104 of stent 100. Lumen 103 of hollow wire 102 of stent 100 is filled by surface tension driving fluid drug formulation 432 through the stent lumen, until the entire length of lumen 103 is filled via capillary action forces, as shown in step 301F of FIG. 3. During the filling step, chambers 422, 424 are maintained at or near the vapor-liquid equilibrium of solvent 433 such that evaporation does not precipitate therapeutic substance or drug 112 as fluid drug formulation 432 fills lumen 103 of hollow wire 102 of stents 100.
[0063] FIGS. 6A-6C are schematic illustrations of a portion of a stent 100 submersed or in contact with wicking means 430 to demonstrate the capillary filling process. Notably, only a portion of each stent having at least one side hole or port 104 is required to be submersed into wicking means 430. As such, a minimal amount of the exterior surfaces of wires 102 of stents 100 are exposed to the fluid drug formulation and most of the exterior surface of the hollow wire of the stent is never exposed to the fluid drug formulation, therefore not requiring additional cleaning or removal of drug residue. FIG. 6A corresponds to FIG. 4A, in which stent suspension means 428 hold stents 100 in a vertical orientation. When held vertically, only a tip 107 of each stent 100 is submersed into wicking means 430 such that at least one side hole 104 is in contact with wicking means 430 and exposed to fluid drug formulation 432. For example, in an embodiment, approximately 0.3 mm of the length of each stent is exposed or driven into to the wicking means. FIG. 6B corresponds to FIG. 4B, in which stent suspension means 428 hold stents 100 in a horizontal orientation. When held horizontally, a longitudinal strip or segment 611 along an outer surface of each stent 100 is submersed into wicking means 430 such that at least one side hole 104 is in contact with wicking means 430 and exposed to fluid drug formulation 432. Regardless of how stents 100 are oriented, fluid drug formulation 432 passes through hole(s) 104 on hollow wire 102 that are in contact with wicking means 430 as shown in FIG. 6C, which illustrates only a portion of hollow wire 102 having a side hole 104 submersed into wicking means 430. Fluid drug formulation 432 forms a concave meniscus within lumen 103 of hollow wire 102. Adhesion forces pull fluid drug formulation 432 up until there is a sufficient mass of fluid drug formulation 432 present for gravitational forces to overcome the intermolecular forces between fluid drug formulation 432 and hollow wire 102, or the advancing fluid column completely fills the lumen. The height h of a column of fluid drug formulation 432 is determined by
[0066] After lumen 103 is completely filled, with reference to FIG. 7, stents 100 are retracted or pulled up such that stents 100 are no longer in contact with wicking means 430. As stents 100 are retracted out of wicking means 430, wicking means 430 removes excess fluid drug formulation 432 from the exterior surfaces of wires 102 of stents 100 such that stents 100 are free or substantially free of drug residue on their exterior surfaces, leaving fluid drug formulation 432 only within lumen 103 of hollow wire 102 of stent 100. The final step of the capillary action filling process includes extracting the solvent or dispersion medium of fluid drug formulation 432 from within the lumenal space, thereby precipitating the solute, i.e., therapeutic substance or drug 112, within lumen 103 and creating a drug-filled stent 100 with primarily only therapeutic substance or drug 112 and one or more excipients within stent 100 to be eluted into the body. More particularly, stents 100 are retracted into upper chamber 422, which is still at or near vapor-liquid equilibrium of solvent 433, as shown in step 301G of FIG. 3. Valve 426 is then closed such that the chambers 422, 424 are no longer in fluid communication as shown in step 301H of FIG. 3 and as shown in FIG. 7. Valve 426 is closed to isolate fluid drug formulation 432 from the upper chamber 422 so that evaporation does not occur from the fluid drug formulation and additional batches of stents may be filled with the same fluid drug formulation without concentration changes. Upper chamber 422 is then vented to reduce its solvent vapor pressure back to ambient pressure, as shown in step 301I of FIG. 3. As the solvent vapor pressure is reduced in the upper chamber, evaporation within lumen 103 of hollow wire 102 is initiated and the solvent of drug fluid formulation 432 is removed, thereby precipitating its constituents. After the solvent or dispersion medium is removed from lumen 103, therapeutic substance or drug 112 fills at least a portion of lumen 103. Stents 100 may then be removed from apparatus 420.
[0077] FIG. 16 illustrates another embodiment of a stent suspension means 1628 includes a header or carousel 1636, a portion of which is shown in the figure, and an elongated tubular component 1672 for holding a stent 100 in place during the capillary filling procedure described with reference to FIGS. 4A-7. Although only one tubular component 1672 is shown, it will be understood by one of ordinary skill in the art that a plurality of tubular components may be coupled to header or carousel 1636 for accommodating a plurality of stents 100. Header or carousel 1636 is a generally flat sheet-like component. A lumen or passageway 1674 of tubular component 1672 is slightly greater than the outer diameter of stent 100. A first open end 1671 of tubular component 1672 is coupled or attached to header or carousel 1636, and a second open end 1673 of tubular component 1672 is positioned adjacent or proximate to a wicking means 1630. Lumen 1674 of tubular component 1672 is in fluid communication with a vacuum source 1670. In operation, stent 100 is within the lumen of tubular component 1672, and vacuum source 1670 is controlled to lower or raise the stent towards or away from wicking means 1630 as desired. For example, after stent 100 is filled, suction may be applied from vacuum source 1670 in order to retract stent 100 away from wicking means 1630. In one embodiment, a cylindrical plug 1675 may be positioned within the inner diameter of stent 100 to minimize air passage through stent 100 when vacuum source 1670 is used to control the longitudinal position of the stent within tubular component 1672.
[0083] FIGS. 21-21A illustrate another embodiment of a stent suspension means 2128 that includes a header or carousel 2136, a portion of which is shown in the figure, and a mandrel 2150 for holding a stent 100 in place during the capillary filling procedure described with reference to FIGS. 4A-7. FIG. 21A is a top view of FIG. 21 with header or carousel 2136 removed. Although only one mandrel 2150 is shown, it will be understood by one of ordinary skill in the art that a plurality of mandrels may be coupled to header or carousel 2136 for accommodating a plurality of stents 100. Header or carousel 2136 is a generally flat sheet-like component and a first end portion 2162 of mandrel 2150 is coupled to header or carousel 2136. First end portion 2162 of mandrel 2150 has a smaller outer diameter than a second end portion 2163 of mandrel 2150. The outer diameter of second end portion 2163 of mandrel 2150 abuts against the inner diameter of stent 100 in an interference or friction fit. To position stent 100 over mandrel 2150, stent 100 is slid up mandrel 2150 until end 105 of stent 100 is past wider second end portion 2163 of mandrel 2150 and is positioned over narrower first end portion 2162 of mandrel 2150. A stationary cantilevered spring leaf or arm 2184 extends adjacent to first end portion 2162 of mandrel 2150 and contacts and abuts against end 105 of stent 100. When stent 100 is lowered into wicking component 430 within second chamber 424, the stent may experience an upward force due to the interaction of the stent with the wicking component 430 that may cause the stent to unintentionally slip up mandrel 2150. Spring arm 2184 counters any unintentional upward forces that result due to the interaction of the stent with the wicking component 430 by exerting a downward force onto stent 100 if spring arm 2184 is deflected from its neutral position shown in FIG. 21. Spring arm 2184 thus acts to press stent 100 into the wicking component for more uniform loading during the filling process when a plurality of stents are present.
[0084] FIGS. 22A-22C illustrate another embodiment of a stent suspension means 2228 that includes a header or carousel 2236, a portion of which is shown in the figure, and a mandrel 2250 for holding a stent 100 in place during the capillary filling procedure described with reference to FIGS. 4A-7. FIG. 22C is a sectional view taken along line C-C of FIG. 22B. Although only one mandrel 2250 is shown, it will be understood by one of ordinary skill in the art that a plurality of mandrels may be coupled to header or carousel 2236 for accommodating a plurality of stents 100. Header or carousel 2236 is a generally flat sheet-like component and a first end 2262 of mandrel 2250 is coupled to header or carousel 2236. In operation, stent 100 is placed over mandrel 2250 as shown in FIG. 22A. Once stent 100 is in position as desired, a spring-loaded, movable arm 2285 pushes stent 100 against mandrel 2250 as shown in FIGS. 22B and 22C to effectively sandwich or capture stent 100 between arm 2285 and the exterior surface of mandrel 2250. Arm 2285 rotates or moves via a spring 2286 and a pivot 2287.
Means for Wicking Fluid Drug Formulation
[0085] FIGS. 23-33 illustrate several embodiments of wicking means 430, which is in contact with fluid drug formulation 432 to control transfer of the fluid drug formulation 432 into lumen 103 of hollow wire 102 during the capillary filling procedure as described in FIGS. 4A-7. "Wicking means" as used herein refers to a medium or component that acts or functions to move or convey, or acts or functions to assist in the movement of, the fluid drug formulation 432 by capillary action from within second or lower chamber 424 into lumen 103 of hollow wire 102. In addition to controlling transfer of the fluid drug formulation, in some embodiments hereof, wicking means 430 also removes excess fluid drug formulation from the exterior surfaces of hollow wire 102 of stent 100 when stent 100 is retracted out of the wicking means. When wicking means 430 performs this excess removal function, an additional processing or cleaning step is not required to make stents 100 free or substantially free of drug residue on the exterior surfaces of hollow wire 102. Wicking means 430 preferably has several characteristics or properties, including that is does not degrade or add contaminants into fluid drug formulation 432, that it is inert in fluid drug formulation 432, that it does not cause a phase separation within fluid drug formulation 432, and that it is usable and/or stable for several days or weeks.
[0086] As previously mentioned, in one embodiment wicking means 430 is an open-celled polyurethane sponge. Several characteristics or properties may be varied to improve the sponge's effectiveness to further reduce fill weight variability, including the polymer material's chemical structure, the hydrophilicity of the sponge, the pore size of the sponge, the density of the sponge, the compression modulus of the sponge, and/or the shape or dimensions of the sponge. For example, hydrophilicity and pore size have a direct correlation with capillary action and therefore fluid affinity. Thus, optimization of these properties allows the sponge to better clean the exterior surfaces of hollow wire 102 of stent 100. In addition, the compression modulus of the sponge allows for a controlled amount of the stent to come into contact with the wicking means. An optimized amount of deformation permits the sponge to come into contact with side holes 104 of stent 100 while limiting the amount of exterior surface of hollow wire 102 of stent 100 that comes into contact with the fluid drug formulation.
[0087] As an alternative to a sponge wicking means, the wicking means may be an intermediate surface or component between the stents and the fluid drug formulation 432 that makes contact with fluid drug formulation 432 to control transfer of the fluid drug formulation 432 into lumen 103 of hollow wire 102 during the capillary filling procedure as described in FIGS. 4A-7. For illustrative purposes, stents 100 are represented as straight tubular structures in FIGS. 23-33 although it will be understood by one of ordinary skill in the art that stents 100 are a hollow wire shaped into a desired stent pattern as discussed with reference to FIG. 1. For example, FIG. 23 illustrates a portion of lower or second chamber 424 having a portion of a stent 100 lowered to contact a wicking means 2330. Wicking means 2330 is a deformable membrane or sheet that is held over a layer of fluid drug formulation 432 held within a container 2327 second chamber 424. In one embodiment, wicking means 2330 is a continuous filament polyester fiber sheet of material, or a purity wipe. The position or configuration of wicking means 2330 is controlled via two concentric tubes, a first or outer stationary tube 2388A and a second or inner movable tube 2388B. Tubes 2388A, 2388B may be cylindrical or rectangular in cross-section. Wicking means 2330 extends or drapes over a top of outer stationary tube 2388A and is held in place over outer stationary tube 2388A via an O-ring 2329 formed of an inert substance such as Teflon. In another embodiment, wicking means 2330 may be held in place over outer stationary tube 2388A via a clamp. In operation, wicking means 2330 is draped over outer stationary tube 2388A such that a center of the wicking means sages and contacts fluid drug formulation 432 held within container 2327 as shown in FIG. 23A.Wicking means 2330 thus becomes wetted with fluid drug formulation 432 in a first configuration such that when end 107 of stent 100 is placed into contact with wicking means 2330, fluid drug formulation 432 fills or is wicked up into lumen 103 of hollow wire 102 via capillary action. When filling is complete, stent 100 is raised in conjunction with inner movable tube 2388B. Inner movable tube 2388B is raised via an applied electromotive force via an EMF source, and pushes wicking means 2330 upwards into a second configuration in which the deformable sheet is not in contact with fluid drug formulation 432 held within container 2327 as shown in FIG. 23B. The deformable sheet or membrane of wicking means 2330 becomes taut and allows excess fluid drug formulation on exterior surfaces of hollow wire 102 of stent 100 to drain from the stent onto the wicking means. Once the excess fluid drug formulation 432 has drained, the electromotive force is removed and inner movable tube 2388B is lowered to the original position of FIG. 23A.
[0088] FIG. 24 is another embodiment of the wicking means as an intermediate surface or component that is in contact with fluid drug formulation 432 to control transfer of the fluid drug formulation 432 into lumen 103 of hollow wire 102 during the capillary filling procedure as described in FIGS. 4A-7. FIG. 24 illustrates a portion of lower or second chamber 424 having a portion of a stent 100 lowered to contact a wicking means 2430. Wicking means 2430 is mesh material positioned within a layer of fluid drug formulation 432 contained within second chamber 424. When end 107 of stent 100 is placed into contact with wicking means 2430, the mesh material deforms or buckles in order to connect and allow contact between stent 100 and the layer of fluid drug formulation 432. After stents 100 have been filled, stents 100 are retracted from contact with wicking means 2430. During retraction of stents 100, the mesh material of wicking means 2430 returns to its original shape and pulls or removes excess fluid drug formulation from the exterior surfaces of stents 100. Exemplary materials for the mesh material of wicking means 2430 include but are not limited to nylon, polyester, polypropylene, or rubber.
[0089] FIG. 25 is another embodiment of the wicking means as an intermediate surface or component that is in contact with fluid drug formulation 432 to control transfer of the fluid drug formulation 432 into lumen 103 of hollow wire 102 during the capillary filling procedure as described in FIGS. 4A-7. FIG. 25 illustrates a portion of second chamber 424 having a portion of a stent 100 lowered to contact a wicking means 2530. Wicking means 2530 is flocked or textured material positioned within a layer of fluid drug formulation 432 contained within second chamber 424. The flocked or textured sheet of material may be VELCRO, cotton, cellulose, polymer foam, porous polymer blocks, or polymer fibers, and/or artificial grass. When end 107 of stent 100 is placed into contact with wicking means 2530, the textured material deforms or buckles in order to connect and allow contact between stent 100 and the layer of fluid drug formulation 432. After stents 100 have been filled, stents 100 are retracted from contacting wicking means 2530. During retraction of stents 100, the textured material of wicking means 2530 returns to its original shape and pulls or removes excess fluid drug formulation from the exterior surfaces of hollow wires 102 of stents 100.
[0090] FIG. 26 is another embodiment of the wicking means as an intermediate surface or component that is in contact with fluid drug formulation 432 to control transfer of the fluid drug formulation 432 into lumen 103 of hollow wire 102 during the capillary filling procedure as described in FIGS. 4A-7. FIG. 26 illustrates a portion of second chamber 424 having a portion of a stent 100 lowered through a wicking means 2630. Wicking means 2630 is a layer of PEG (polyethylene glycol) gel or an immiscible liquid that, when poured into second chamber 424, will separate from and form a top layer on the fluid drug formulation 432. End 107 of stent 100 is placed through wicking means 2630 until the stents 100 are in contact with the layer of fluid drug formulation 432. After stents 100 have been filled, stents 100 are retracted through wicking means 2630. During retraction of stents 100, the cellulose, PEG gel, or immiscible liquid may pull or remove excess fluid drug formulation from the exterior surfaces of stents 100.
[0091] FIGS. 27A-27B illustrates another embodiment of the wicking means that includes an intermediate surface or component that is in contact with fluid drug formulation 432 to control transfer of the fluid drug formulation 432 into lumen 103 of hollow wire 102 during the capillary filling procedure as described in FIGS. 4A-7. FIGS. 27A-27B illustrate a portion of second chamber 424 having a portion of a stent 100 lowered to contact a wicking means 2730. Wicking means 2730 is a plurality of hypotubes or cylindrical microchannels within the layer of fluid drug formulation 432 contained within second chamber 424. The hypotubes are formed out of material that changes orientation when a magnetic or electric field is applied thereto. Stent 100 is placed into the hypotubes of wicking means 2730 until end 107 stent 100 contacts the layer of fluid drug formulation 432. The individual size of the hypotubes, as well as the height of the layer of hypotubes, may vary according to application. During the filling steps, the hypotubes of wicking means 2730 have a first or vertical orientation shown in FIG. 27A which allows fluid drug formulation 432 to pass through the hypotube lumens via capillary action. When fluid drug formulation 432 travels up the hypotubes of wicking means 2730, fluid drug formulation 432 comes into contact with end 107 of stent 100, thereby allowing the lumen 103 of hollow wire 102 of stent 100 to fill via capillary action. Only the open bottoms of the hypotubes are required to be submersed in the fluid drug formulation in order to fill the hypotubes via capillary action. After stents 100 have been filled, an electric or magnetic field is applied to move the hypotubes of wicking means 2730 to a second or horizontal orientation. In the horizontal orientation shown in FIG. 27B, fluid drug formulation 432 does not contact or interact with stent 100 so filling of the stent via capillary action is stopped. Changing the orientation of the hypotubes of wicking means 2730 changes the fluid transfer properties between stent 100 and fluid drug formulation 432. In their vertical orientation, hypotubes readily transfer fluid drug formulation 432 to stent 100 and in their horizontal orientation, capillary action is stopped and fluid affinity is modified to make it easier to clean the exterior surfaces of hollow wire 102 of stent 100.
[0092] FIG. 28 is another embodiment of the wicking means as an intermediate surface or component that is in contact with fluid drug formulation 432 to control transfer of the fluid drug formulation 432 into lumen 103 of hollow wire 102 during the capillary filling procedure as described in FIGS. 4A-7. FIG. 28 illustrates a portion of lower or second chamber 424 having a portion of a stent 100 lowered to contact a wicking means 2830. Wicking means 2830 is a cellulose column positioned within and extending past or beyond a layer of fluid drug formulation 432 contained within second chamber 424. End 107 of stent 100 is placed into contact with a side surface of wicking means 2830, which acts as a bridge or conduit between stent 100 and fluid drug formulation 432 to transfer the fluid drug formulation to stent 100. End 107 of stent 100 may alternatively be placed into contact with a top surface of wicking means 2830. The cellulose column minimizes the contact area between stents 100 and fluid drug formulation 432 to control surface energy properties during the filling procedure. As described in more detail here with respect to embodiments in which the stent directly contacts the fluid drug formulation, the surface energy properties of the fluid drug formulation must be controlled in order for the fluid drug formulation to have the greatest affinity for lumen 103 of hollow wire 102 rather than on the exterior surfaces of hollow wire 102 so that the maximum amount of exterior surfaces are kept clean, or substantially free of fluid drug formulation 432, during the filling process.
[0093] Similar to FIG. 28, FIG. 29 is another embodiment of the wicking means as an intermediate surface or component that is in contact with fluid drug formulation 432 to control transfer of the fluid drug formulation 432 into lumen 103 of hollow wire 102 during the capillary filling procedure as described in FIGS. 4A-7. FIG. 29 illustrates a portion of lower or second chamber 424 having a portion of a stent 100 lowered to contact a wicking means 2930. Wicking means 2930 is a fiber/filament or a plurality of woven or parallel fibers/filaments positioned within and extending past or beyond a layer of fluid drug formulation 432 contained within second chamber 424. End 107 of stent 100 is placed into contact with a top surface of wicking means 2930 such that wicking means 2930 is in direct contact with an opening or hole 104 formed within wire 102. Wicking means 2930 transfers fluid drug formulation 432 to stent 100 and minimizes the contact area between stents 100 and fluid drug formulation 432 to control surface energy properties during the filling procedure. In another embodiment, wicking means 2930 is a plug of cotton or similar fibrous material.
[0094] In FIGS. 28 and 29, the cellulose column or fiber(s) are positioned within and extending past or beyond a layer of fluid drug formulation 432 contained within second chamber 424. Alternatively, as shown in FIG. 30, a wicking means 3030 may extend from end 107 of stent 100 and be dipped or lowered into a layer of fluid drug formulation 432. FIG. 30 illustrates a portion of lower or second chamber 424 having a portion of a stent 100 lowered to contact wicking means 3030. Wicking means 3030 may be a cellulose extension, a fiber/filament, a plurality of woven or parallel fibers/filaments, or a plug of cotton. Wicking means 3030 is coupled to end 107 of stent 100, and stent 100 is lowered within second chamber 424 until a bottom surface of wicking means 3030 is in contact with fluid drug formulation 432. Wicking means 3030 transfers fluid drug formulation 432 to stent 100 and minimizes the contact area between stent 100 and fluid drug formulation 432 to control surface energy properties during the filling procedure.
[0095] FIGS. 31A-31B illustrate another embodiment of the wicking means in which an intermediate surface or component that is in contact with fluid drug formulation 432 to control transfer of the fluid drug formulation 432 into lumen 103 of hollow wire 102 during the capillary filling procedure as described in FIGS. 4A-7. FIGS. 31A-31B illustrate a portion of lower or second chamber 424 having a portion of a stent 100 lowered to contact a wicking means 3130A, 3130B, respectively. Wicking means 3130A is a sheet or generally flat solid/impervious substrate in contact with a heating element HE, while wicking means 3130B is a porous or open-celled substrate in contact with a heating element HE. To fill stent 100 via capillary action in FIG. 31A, fluid drug formulation 432 is placed on the top surface of impervious wicking means 3130A. Fluid drug formulation 432 spreads out over the top surface of wicking means 3130A, thereby extending to or reaching stent 100 which is also placed on or adjacent to the top surface of wicking means 3130A. To fill stent 100 via capillary action in FIG. 31B, stent 100 is brought into contact with the top surface of porous wicking means 3130B, which is in contact with fluid drug formulation 432 and conveys the fluid drug formulation to the stent. When filling is complete, wicking means 3130A, 3130B are heated via the heating element to alter the surface tension of the wicking means. When wicking means 3130A, 3130B are heated, the surface tension forces between fluid drug formulation 432 and stent 100 are weakened and the fluid drug formulation is prevented from adhering to the interface between wicking means 3130A, 3130B and stent 100. Changes of the temperature of wicking means 3130A, 3130B changes surface tension/affinity properties, and thereby controls transfer of the fluid drug formulation 432 into lumen 103 of hollow wire 102 during the capillary filling procedure.
[0096] FIGS. 32A-32B illustrate another embodiment of the wicking means in which an intermediate surface or component that is in contact with fluid drug formulation 432 to control transfer of the fluid drug formulation 432 into lumen 103 of hollow wire 102 during the capillary filling procedure as described in FIGS. 4A-7. FIGS. 32A-32B illustrate a portion of lower or second chamber 424 having a portion of a stent 100 lowered to contact a wicking means 3230A, 3230B, respectively. Wicking means 3230A is a sheet or generally flat solid/impervious substrate in contact with a voltage source (not shown), while wicking means 3230B is a porous or open-celled substrate in contact with a voltage (not shown). Wicking means 3230A, 3230B are formed from a polymer material that switches between hydrophilic and hydrophobic based upon applied voltage. To fill stent 100 via capillary action in FIG. 32A, fluid drug formulation 432 is placed on the top surface of impervious wicking means 3230A. Fluid drug formulation 432 spreads out over the top surface of wicking means 3230A, thereby extending to or reaching stent 100 which is also placed on or adjacent to the top surface of wicking means 3230A. To fill stent 100 via capillary action in FIG. 32B, stent 100 is brought into contact with the top surface of porous wicking means 3230B, which is in contact with fluid drug formulation 432 and conveys the fluid drug formulation to the stent. During the filling step, wicking means 3230A, 3230B is hydrophobic to allow fluid drug formulation 432 to fill stent 100 via capillary action. When filling is complete, a voltage or potential is applied to wicking means 3230A, 3230B via the voltage source to change the wicking means to hydrophilic. When the wicking means becomes hydrophilic, the surface tension forces between fluid drug formulation 432 and stent 100 is weakened and the fluid drug formulation is prevented from adhering to the interface between wicking means 3230A, 3230B and stent 100. Suitable polymers for wicking means 3230A, 3230B are described in "Electrically Controlled Hydrophobicity in a Surface Modified Nanoporous Carbon" by Kim et al. (2011) and "Electrowetting of Water and Aqueous Solutions on Poly(ethylene Terephthalate) Insulating Films" by Vallet et al. (1996), each of which is herein incorporated by reference in its entirety.
[0097] FIG. 33 is another embodiment of the wicking means as an intermediate surface or component that is in contact with fluid drug formulation 432 to control transfer of the fluid drug formulation 432 into lumen 103 of hollow wire 102 during the capillary filling procedure as described in FIGS. 4A-7. FIG. 33 illustrates a portion of lower or second chamber 424 having a portion of a stent 100 lowered to contact a wicking means 3330. Wicking means 3330 is a porous or open-celled substrate. In an embodiment, wicking means 3330 includes a top layer or polyurethane sheet that has been welded to a sheet of open celled polyethylene foam. A top surface or portion of wicking means 3330 is more hydrophilic than a center or middle portion of wicking means 3330. Wicking means 3330 is in contact with fluid drug formulation 432 and conveys the fluid drug formulation to the stent. To initiate filling, stent 100 is pressed into the less hydrophilic center of wicking means 3330. Since the center portion of wicking means 3330 is less hydrophilic, fluid drug formulation 432 is permitted to fill stent 100 via capillary action. When filling is complete, stent 100 is retracted out of wicking means 3330 and as the stent passes through the top portion, any excess fluid drug formulation 432 which is on an exterior surface of the hollow wire is attracted to the more hydrophilic top portion of wicking means 3330. Thus, during retraction of stents 100, the more hydrophilic top portion of wicking means 3370 may pull or remove excess fluid drug formulation from the exterior surfaces of hollow wires 102 of stents 100.
[0098] FIGS. 34-38B illustrate various wicking means embodiments in which the wicking means that minimize the contact area between stent 100 and fluid drug formulation 432 in order to assist in the movement of fluid drug formulation 432 into lumen 103 of hollow wire 102. More particularly, in the embodiments of FIGS. 34-38B, a portion of each stent 100 directly contacts fluid drug formulation 432 but a wicking means is utilized in order to minimize the contact area there between. For illustrative purposes, stents 100 are represented as straight tubular structures in FIGS. 34-38B although it will be understood by one of ordinary skill in the art that stents 100 are a hollow wire shaped into a desired stent pattern as described with reference to FIG. 1. When stents 100 contact fluid drug formulation 432 directly, the surface energy properties of the fluid drug formulation are preferably controlled in order to accurately and predictably fill lumen 103 of hollow wire 102. Without modification of the surface energy properties, the fluid drug formulation may travel up the lumen or central blood flow passageway 113 of stent 100 (see FIG. 1A) and stick to the inner surface or diameter of the stent. It is preferable for fluid drug formulation 432 to have the greatest affinity for lumen 103 of hollow wire 102 rather than on the exterior surfaces of hollow wire 102 so that the maximum amount of exterior surfaces are kept clean, or substantially free of fluid drug formulation 432, during the filling process. One way to decrease the surface tension of fluid drug formulation 432 is to utilize a wicking means that minimizes the contact area between stent 100 and fluid drug formulation 432.
[0099] More particularly, FIG. 34 is an embodiment hereof in which a wicking means 3430 is utilized to reduce the amount of fluid drug formulation 432 exposed to stent 100. FIG. 34 illustrates a portion of lower or second chamber 424 having a portion of a stent 100 lowered to contact (not shown) a wicking means 3430. Although only one stent 100 is shown, it will be understood by one of ordinary skill in the art that wicking means 3430 may accommodate a plurality of stents 100. Wicking means 3430 includes a wire loop 3490 coupled to a wire handle 3491. Stent 100 is placed into second chamber 424 until end 107 of stent 100 is just above but not in contact with the layer of fluid drug formulation 432. Wicking means 3430 is lifted out of fluid drug formulation 432 and brought into contact with end 107 of stent 100.
[0100] FIG. 35 is another embodiment for minimizing the contact area between stent 100 and fluid drug formulation 432. FIG. 35 illustrates a portion of lower or second chamber 424 having a portion of a stent 100 lowered to contact a wicking means 3530. Although only one stent 100 is shown, it will be understood by one of ordinary skill in the art that wicking means 3530 may accommodate a plurality of stents 100. Wicking means 3530 is a plurality of beads within the layer of fluid drug formulation 432 contained within second chamber 424. Stent 100 is placed into a layer of beads until end 107 of stent 100 contacts fluid drug formulation 432. The individual size of the beads, as well as the height of the layer of beads, may vary according to application. The beads minimize the contact area between stents 100 and fluid drug formulation 432 to control surface energy properties during the filling procedure. After stents 100 have been filled, stents 100 are retracted through the beads of wicking means 3530. During retraction of stents 100, the beads pull or remove excess fluid drug formulation from the exterior surfaces of hollow wires 102 of stents 100. In FIG. 35, the layer of fluid drug formulation is approximately the same height as the layer of beads. However, in another embodiment (not shown), the layer of beads has a greater height than the layer of fluid drug formulation such that a layer of "dry" beads extend over the "wet" beads that are submersed in the layer of fluid drug formulation. The layer of "dry" beads provides additional cleaning of the exterior surfaces of stents 100 when stents 100 are retracted out of the beads. In an embodiment, the beads of wicking means 3430 may be stirred or shifted during the filling and retracting steps of the process. For example, a magnetic stir stick (not shown) may be used to stir the beads and ensure that the stents are constantly supplied with fluid drug formulation during the filling step. In another example, a piezoelectric crystal (not shown) may be used to vibrate the beads within second chamber 424 to ensure that the stents are constantly supplied with fluid drug formulation during the filling step.
[0101] In one embodiment, the beads of wicking means 3530 may be glass beads. Other suitable materials for the beads of wicking means 3530 include ceramic, steel, aluminum, titanitum, or stainless steel. Optionally, the beads may be encased in a mesh bag or container (not shown) to ensure that the beads do not stick to stent 100. In another embodiment, the beads may be formed out of a magnetic material. If the magnetic beads stick to stent 100 when stent 100 is retracted out of the wicking means, a magnet (not shown) may be utilized to remove the magnetic beads from stent 100.
[0102] FIGS. 36A-37C illustrate another embodiment for minimizing the contact area between stent 100 and fluid drug formulation 432. FIG. 36A illustrates a portion of second chamber 424 having a portion of a stent 100 lowered to contact a wicking means 3630, while FIGS. 37B and 37C illustrate top and side views, respectively, of the wicking means 3630 removed from the chamber and devoid of fluid drug formulation for illustrative purposes. Wicking means 3630 is a generally flat solid plate 3692 having a plurality of reservoirs or grooves 3694 formed on a top surface thereof. Grooves 3694 are channels that are etched onto plate 3692 and function to receive fluid drug formulation. The size and shape of each groove depends upon the size and shape of a stent which is to be placed into contact with the fluid drug formulation within the groove. Although wicking means 3630 is shown with six grooves 3694 for accommodating six stents, it will be understood by one of ordinary skill in the art that wicking means 3630 may include a greater or lesser number of grooves to accommodate the desired number of stents. Plate 3692 is shown as rectangular, but may be any shape that fits within and on a bottom surface of chamber 424. In an embodiment, plate 3692 is glass. Plate 3692 is positioned on the bottom surface of chamber 424, and fluid drug formulation 432 is poured into grooves 3694. Stent 100 is lowered into second chamber 424 until end 107 of each stent 100 contacts fluid drug formulation 432 contained within a respective groove 3694. Since fluid drug formulation 432 is only held within grooves 3694 rather than as a layer on the bottom surface of the chamber, wicking means 3630 minimizes the contact area between stents 100 and fluid drug formulation 432 to control surface energy properties during the filling procedure.
[0103] Similar to the embodiment of FIGS. 36A-36C, FIGS. 37A-37C illustrate another embodiment for minimizing the contact area between stent 100 and fluid drug formulation 432. FIG. 37A illustrates a portion of second chamber 424 having a portion of a stent 100 lowered to contact a wicking means 3730, while FIGS. 37B and 37C illustrate top and side views, respectively, of the contact area minimize 3730 removed from the chamber and devoid of fluid drug formulation for illustrative purposes. Wicking means 3730 is a generally flat solid plate 3792 having a plurality of holes or fluid passageways 3794 formed there through. Although wicking means 3730 is shown with six holes 3794 for accommodating six stents, it will be understood by one of ordinary skill in the art that wicking means 3730 may include a greater or lesser number of holes to accommodate the desired number of stents. Plate 3792 is shown as rectangular, but may be any shape that fits within and on a bottom surface of chamber 424. In an embodiment, plate 3792 is stainless steel. Plate 3792 is positioned within chamber 424 on top of a layer of fluid drug formulation 432. Fluid drug formulation 432 seeps through and fills holes 3794 of plate 3792 as shown in FIG. 37A. The size and shape of each hole depends upon the size and shape of a stent which is to be placed into contact with the fluid drug formulation disposed within the hole. To initiate fill, plate 3792 is placed on top of a layer of fluid drug formulation 432 such that fluid drug formulation 432 seeps up into and fills holes 3794 of plate 3792. Stents 100 are then lowered into second chamber 424 until end 107 of each stent 100 contacts the fluid drug formulation 432 disposed within a respective hole 3794. Alternatively, to initiate fill, stents 100 may first be lowered into a position slightly above the layer of fluid drug formulation 432, and plate 3792 may subsequently be lowered into fluid drug formulation 432 with stents 100 passing through holes 3794 of plate 3792. After the plate is placed on top of the layer of fluid drug formulation 432, the fluid drug formulation 432 will seep up or rise into holes 3794 and contact ends 107 of stents 100. Since stents 100 only contact a relatively small amount of fluid drug formulation 432 held within holes 3794, wicking means 3730 minimizes the contact area between stents 100 and fluid drug formulation 432 to control surface energy properties during the filling procedure. After filling is complete, stents 100 and/or plate 3792 may be retracted such that stents 100 are no longer in contact with fluid drug formulation 432.
[0104] FIGS. 38A-38B illustrate another embodiment for minimizing the contact area between stent 100 and fluid drug formulation 432. FIG. 38A illustrates a portion of lower or second chamber 424 having a portion of a stent 100 lowered to contact (not shown) a wicking means 3830. Although only one stent 100 is shown, it will be understood by one of ordinary skill in the art that wicking means 3830 may accommodate a plurality of stents 100. Wicking means 3830 is a movable plate having an outer diameter or dimension smaller than an inner diameter or dimension of second chamber 424. Prior to and/or during the filling step, the movable plate of wicking means 3830 is positioned within the layer of fluid drug formulation 432, i.e., below the top surface of the layer, as shown in FIG. 38A. To initiate filling, stents 100 are lowered into second chamber 424 until end 107 of stent 100 contacts the layer of fluid drug formulation 432. When it is desired to slow or stop filling, the movable plate of wicking means 3830 is moved up towards stent 100. The movable plate of wicking means 3830 maybe moved via any suitable mechanical or magnetic means. As the movable plate of wicking means 3830 is being moved up, the amount of fluid drug formulation 432 exposed to stent 100 is continually decreased, thereby slowing filling of stent 100. When the movable plate is positioned adjacent to end 107 of stent 100, above the top surface of the layer of fluid drug formulation 432 as shown in FIG. 38B, stent 100 is no longer in contact with the layer of fluid drug formulation 432 and thus stent 100 stops filling.
[0105] Although wicking means embodiments described herein may be shown with only one stent 100, it will be understood by one of ordinary skill in the art that any wicking means described herein may accommodate a plurality of stents 100.
Embodiments in which Stents Directly Contact Fluid Drug Formulation without a Wicking Means
[0106] Although the capillary filling procedure described in FIGS. 4A-7 utilizes a wicking means 430 that is in contact with drug formulation 3932, in another embodiment hereof stent 100 may contact the fluid drug formulation directly without a wicking means. More particularly, FIG. 39 is a schematic illustration of an apparatus 3920 for filling lumen 103 of a stent 100 with a fluid drug formulation 3932 via capillary action without the use of a wicking means. Similar to apparatus 420, apparatus 3920 includes a first or upper chamber 3922 which houses a manifold or stent suspension means 3928 and a reservoir 3931 filled with a liquid or fluid solvent 3933, a second or lower chamber 3924 which houses a fluid drug formulation 3932 that includes therapeutic substance or drug 112, and a valve 3926 extending between upper chamber 3922 and lower chamber 3924. Solvent 3933 within reservoir 3931 is the same solvent as used in fluid drug formulation 3932. A plurality of stents 100 are loaded onto stent suspension means 3928, which holds them in place during the capillary filling procedure and may be any stent suspension means described herein. Prior to the initiation of capillary filling, valve 3926 is closed such that first or upper chamber 3922 and second or lower chamber 3924 are separated and not in fluid communication. A pressure source 3934 and a heat source 3935 are connected to the interior of the upper chamber 3922. Before placing stents 100 into upper chamber 3922, pressure source 3934 is used to purge any residual solvent vapor from the upper chamber. After the purge, stent suspension means 3928 holding stents 100 are placed into upper chamber 3922 and pressure source 3934 is stopped to allow solvent vapor from reservoir 3931 contained solvent 3933 to fill upper chamber 3922. When evaporation has stopped or sufficiently slowed, valve 3926 is opened and first or upper chamber 3922 and second or lower chamber 3924 are exposed to each other and in fluid communication. Both chambers 3922, 3924 are then required to reach or near solvent vapor saturation, or at or near the vapor-liquid equilibrium of solvent 3933, such that little to no net evaporation of the fluid drug formulation is present. In order to reduce the amount of time required for upper and lower chambers 3922, 3924 to reach solvent vapor saturation, upper chamber 3922 may include a fan 3999 to create convection across reservoir 3931 containing a supply of solvent 3933. In addition, any of the methods described above with respect to FIGS. 4A-7 for reducing the amount of time required to reach solvent vapor saturation may be utilized.
[0109] When stents 100 directly contact the fluid drug formulation without a wicking means, an additional cleaning step may be utilized after the stent is filled via capillary action in order to remove excess fluid drug formulation from the exterior surfaces of stents 100. If included, the additional cleaning step is preferably performed after the filling step but prior to the solvent evaporation step. Thus, stent 100 may remain in second chamber 3924 of apparatus 3900 during the cleaning step or may be retracted into the upper chamber 3922 of apparatus 3900 during the cleaning step as shown in FIG. 39. A cleaning element 3995 that removes excess fluid drug formulation from the exterior surfaces of hollow wire 102 of stent 100 may be included within first or second chamber 3922, 3924 of apparatus 3900. For example, in one embodiment, cleaning element 3995 is a dry sponge (independent from a sponge that may be utilized as a wicking means) that stents 100 may be dabbed or blotted on to remove excess fluid drug formulation from the exterior surfaces of stent 100. In another embodiment, cleaning element 3995 is a reservoir of dry glass beads (independent from any beads being utilized as a wicking means) that stents 100 may be inserted into to remove excess fluid drug formulation from the exterior surfaces of hollow wire 102 of stent 100. The dry glass beads may be vibrated, i.e., via a piezoelectric crystal, to assist in the cleaning step. In yet another embodiment, cleaning element 3995 is a squeegee that stents 100 may be inserted into to remove excess fluid drug formulation from the exterior surfaces of stent 100. In yet another embodiment, cleaning element 3995 generates movement in order to remove excess fluid drug formulation from the exterior surfaces of stents 100. For example, cleaning element 3995 may generate force by acceleration and/or deceleration to remove excess fluid drug formulation from the exterior surfaces of hollow wire 102 of stent 100. More particularly, stents 100 may be accelerated to spin off excess fluid drug formulation from the exterior surfaces of stents 100. Alternatively or in addition, cleaning element 3995 may be a piezoelectric crystal that generates movement/vibration to removes excess fluid drug formulation from the exterior surfaces of stent 100. A piezoelectric crystal may be incorporated onto the carousel/mandrel of the stent suspension means in the upper chamber of the apparatus.
[0111] Although the cleaning and/or masking embodiments described above have been discussed in conjunction with embodiments in which stents directly contacts a fluid drug formulation without a wicking means, such cleaning and/or masking embodiments described herein may be utilized with any embodiment described herein, including those which utilize a wicking means. In addition, although the cleaning embodiments described above occur between the filling and drying/evaporation steps of the process, additional and/or alternative cleaning steps may be applied after the drying/evaporation step of the process. For example, U.S. Patent Application Publication 2012/0070562 entitled "Apparatus and Methods for Filling a Drug Eluting Medical Device" to Avelar et al., herein incorporated by reference in its entirety, describes several stent cleaning methods that may be utilized herewith. Any combination of the aforementioned cleaning methods can be employed to clean the stent. The selection of cleaning method(s) may be governed by factors such as the drug formulation components and the degree of drug residue after the filling process via capillary action is complete.
zhong.yang@medtronic.com