WO2001047451A1 - Dispositif et methode d'administration de composes a un organisme vivant - Google Patents
Dispositif et methode d'administration de composes a un organisme vivant Download PDFInfo
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- WO2001047451A1 WO2001047451A1 PCT/US2000/035641 US0035641W WO0147451A1 WO 2001047451 A1 WO2001047451 A1 WO 2001047451A1 US 0035641 W US0035641 W US 0035641W WO 0147451 A1 WO0147451 A1 WO 0147451A1
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- hormone
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- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/10—Balloon catheters
- A61M2025/1043—Balloon catheters with special features or adapted for special applications
- A61M2025/1072—Balloon catheters with special features or adapted for special applications having balloons with two or more compartments
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/10—Balloon catheters
Definitions
- the invention relates to local-delivery devices and methods for treating and preventing vascular diseases in a living organism. More particularly, the invention relates to local-delivery devices coated with a composition comprising a sex hormone, anti- hormone, sex-hormone agonist, steroid-hormone inhibitor/antagonist (partial or full), selective estrogen receptor modulator (SERM), or a combination thereof.
- the local- delivery device e.g. a stent, catheter or balloon-injection catheter, is inserted into an affected area of a living organism to treat or prevent the vascular disease.
- Vascular diseases include diseases that affect areas of a living organism relating to or containing blood vessels.
- stenosis is a narrowing or constricting of arterial lumen in a living organism (e.g., a human) usually due to atherosclerosis/coronary heart disease (CHD).
- Restenosis is a recurrence of stenosis after a percuteneous intervention such as angioplasty and stenting.
- the underlying mechanisms of restenosis comprise a combination of effects from vessel recoil, negative vascular remodeling, thrombus formation and neointimal hyperplasia. It has been shown that restenosis after balloon angioplasty is mainly due to vessel remodeling and neointimal hyperplasia.
- Treatment for stenosis and restenosis varies. Stenosis caused by CHD often forces individuals to restrict and limit their activity levels in order to avoid complications, stroke, heart attack, sudden death and loss of limb or function of a limb stemming from the stenosis.
- the reconstruction of blood vessels, arteries and veins may also be needed to treat individuals suffering from stenosis and restenosis.
- Coronary bypass can also be utilized to revascularize the heart and restore normal blood flow.
- balloon angioplasty may be conducted to increase the orifice size of affected areas. Overall, these treatments address the problems associated with stenosis, but they also create a high rate of restenosis that can result in recurrence of cardiac symptoms and mortality.
- Atherosclerosis affects medium and large arteries and is characterized by a patchy, intramural thickening that encroaches on the arterial lumen and, in most severe form, causes obstruction.
- the atherosclerotic plaque consists of an accumulation of intracellular and extracellular lipids, smooth muscle cells and connective tissue.
- the earliest lesion of atherosclerosis is the fatty streak that evolves into a fibrous plaque coating the artery.
- Atherosclerotic vessels have reduced systolic expansion and abnormal wave propagation.
- Atherosclerosis Treatment of atherosclerosis is usually directed at its complications, for example, arrhythmia, heart failure, kidney failure, stroke, and peripheral arterial occlusion.
- New and improved methods and devices are being sought for treatment and prevention of vascular diseases such as stenosis, restenosis and atherosclerosis.
- the present invention provides a method of treating or preventing vascular disease in a living organism.
- the method includes applying an effective amount of a composition comprising a sex hormone, anti-hormone, sex-hormone agonist, steroid-hormone inhibitor/antagonist (partial or full), selective estrogen receptor modulator (SERM), or a combination thereof, to a local-delivery device.
- a composition comprising a sex hormone, anti-hormone, sex-hormone agonist, steroid-hormone inhibitor/antagonist (partial or full), selective estrogen receptor modulator (SERM), or a combination thereof.
- SERM selective estrogen receptor modulator
- the method also includes inserting the local-delivery device into an affected area of a living organism and allowing at least a portion of the sex hormone, anti-hormone, sex-hormone agonist, steroid-hormone inhibitor/antagonist (partial or full), selective estrogen receptor modulator (SERM), or combination thereof, to gradually release or inject into the affected area of the living organism.
- SERM selective estrogen receptor modulator
- the invention also provides a local-delivery system effective for treating and preventing vascular disease in a living organism.
- the system includes a local-delivery device and a composition at least partially applied thereto.
- the composition comprises a sex hormone, anti-hormone, sex-hormone agonist, steroid-hormone inhibitor/antagonist (partial or full), selective estrogen receptor modulator (SERM), or a combination thereof.
- SERM selective estrogen receptor modulator
- Figure 1 is a perspective view of a stent embodying the invention.
- Figure 2 is a cross-sectional view taken along line 2—2 in Figure 1.
- Figure 3 is a perspective view of a balloon-injection catheter embodying the invention.
- Figure 4 is cross-sectional view taken along line 4—4 of Figure 3.
- Figure 5 is a cross-sectional view taken along line 5—5 in Figure 5, wherein the catheter is inserted into an affected area of a living organism.
- Figure 6 is a cross-sectional view taken along line 6—6 of Figure 1.
- the present invention provides apparatuses and methods for delivering a composition to a localized area of a living organism. More particularly, the invention provides apparatuses and methods for locally delivering a sex hormone (e.g. estrogen), an anti-hormone, a sex-hormone agonist, a steroid-hormone inhibitor/antagonist (partial or full) or a selective estrogen receptor modulator (SERM), or a combination thereof, to a portion of a living organism inflicted by or susceptible to a vascular disease such as stenosis or restenosis.
- a sex hormone e.g. estrogen
- an anti-hormone e.g. estrogen
- a sex-hormone agonist e.g. sex-hormone agonist
- a steroid-hormone inhibitor/antagonist e.g., partial or full
- SERM selective estrogen receptor modulator
- Estrogen is known to favorably alter the atherogenic lipid profile and may also have a direct action on blood vessel walls. Estrogen can have both rapid and long-term effects on the vasculature including the local production of coagulation and fibrinolytic factors, antioxidants and the production of other vasoactive molecules, such as nitric oxide and prostaglandins, all of which are known to influence the development of vascular disease. Experimental work suggests that estrogen can also act on the endothelium and smooth muscle cells either directly or via estrogen receptors in both men and women. This appears to have an inhibitory effect on many steps in the atherosclerotic process.
- Estrogen appears to inhibit the response to balloon injury to the vascular wall.
- Estrogen can repair and accelerate endothehal cell growth in- vitro and in-vivo. Early restoration of endothehal cell integrity may contribute to the attenuation of the response to injury by increasing the availability of nitric oxide. This in turn can directly inhibit the proliferation of smooth muscle cells.
- estrogen has been shown to inhibit the proliferation and migration of smooth muscle cells in response to balloon injury. Estrogen has also proved to inhibit adventitial fibroblast migration which may in turn have an effect on negative remodeling.
- Sex hormones and sex-hormone agonists may be helpful in preventing and treating certain vascular diseases.
- suitable sex hormones include, but are in no way limited to, estrogens, progesterones, testosterones, dehydroepiandrostrones (DHEAs) and dehydroepiandrosteronesulfates (DHEAs).
- DHEAs dehydroepiandrostrones
- DHEAs dehydroepiandrosteronesulfates
- estrogen has proven to be the most effective in preventing and treating vascular diseases.
- Naturally occurring/plant estrogens or phytoestrogens including isoflavones such as genistein, daidzein and resveratrol are also useful in the treatment of vascular disease.
- Suitable sex- hormone agonists include, but are in no way limited to, estradiol, estrone, ethinyl estradiol and conjugated equine estrogens.
- anti-hormones and steroid-hormone inhibitors/antagonist may be effective in preventing vascular diseases.
- Anti-hormones inhibit or prevent the usual effects of certain other hormones, thereby increasing the relative effectiveness of hormones that are not being inhibited or prevented by these anti-hormones.
- Anti- hormones effective in preventing vascular diseases include, but are not limited to, anti- estrogens (e.g. Faslodex), anti-androgens (e.g. cyproterone acetate) and anti-testosterone (e.g. anti-testosterone wild-type Fab fragment and mutant Fab fragments).
- Examples of steroid-hormone inhibitors/antagonist include, but are not limited to, aminogluthemide, anastrazole and letrozole.
- Selective estrogen receptor modulators including but not limited to raloxifene, tamoxifen and idoxifene, may also be effective in treating or preventing vascular diseases such as stenosis and restenosis.
- these compounds are generally found in a powdered form.
- the powder In order to apply the compound to a local-delivery device or to locally inject the compound into an affected area, the powder is generally mixed with a solution of saline or ethanol. This facilitates coating the local-delivery devices or injecting the composition as described below.
- the composition can also be mixed into another solution, gel or substance to control the rate of release from the stent and into the tissue.
- compositions in the exact area of disease or potential disease avoids the negative systemic effects these compounds can produce when administered generally.
- oral use of conjugated equine estrogen in combination with a progestin may have effects on the coagulation pathways that attenuate the benefits that may potentially occur to a vascular wall.
- hyperplastic effects of estrogen on the uterus and breast tissue may exist when estrogen is administered systemically.
- general administration may result in potential feminizing effects in males.
- the local delivery of estrogen and the other compositions described above to atherosclerotic plaque is a promising alternative to the systemic use of this hormone.
- the basic anti-atherogenic properties of these compositions and their potential to inhibit neointimal proliferation while simultaneously attenuating endothehal repair make them ideal for local administration in the coronary artery to inhibit restenosis.
- Localized delivery of other compositions comprising sex hormones, anti-hormones, sex-hormone agonists, steroid-hormone inhibitors/antagonist (partial or full) or selective estrogen receptor modulators (SERMS), or combinations thereof, to the vasculature may prevent and treat vascular diseases such as stenosis, restenosis and atherosclerosis.
- SERMS selective estrogen receptor modulators
- the local-delivery systems generally comprise a local-delivery device and at least one of the effective compositions described above.
- the compositions can be delivered locally to tissue, tubular organs, blood vessels, the coronary or peripheral of organs as well as to muscles (myocardium, skeletal or smooth muscles).
- the compositions can also be injected directly into the vessel, vessel wall or muscle.
- the local-delivery system is a stent that delivers the above-described compositions to the localized portion of the body of a living organism.
- Figure 1 illustrates a stent 10, which is a hollow member that lies within the lumen of a tubular structure and provides support and assures patency of an intact but contracted lumen. Stents may be made from stainless steel or any other suitable material. Effective compositions as described above coat or are applied to the stent.
- Figure 2 shows a portion of the stent 10 coated with a composition 12 in cross-section.
- the stent Because the stent remains in the artery after the angioplasty procedure is performed, it enables the composition 12 to slowly diffuse from the outside of its surface 10 into the adjacent atherosclerotic plaque to which it can affect. The rate of this diffusion varies according to the molecular weight of the compound being administered. Also, the structure of the stent and the type of coating applied thereto also affect the rate of diffusion.
- an effective composition is applied to an injection catheter, and more particularly to a balloon-injection catheter 14.
- a balloon-injection catheter 14 is similar to a balloon angioplasty, except for the added feature of a chamber 16 including injection ports 18 for injecting the compositions described above.
- Figure 5 illustrates a balloon-injection catheter 14 in cross-section after being injected into an affected area 20 of a living organism.
- the hormone can be injected directly into the plaque, vessel wall or tissue 22 via these injection ports 18. If an injection catheter injects the compound into the plaque 22, the composition releases immediately after injection. Accordingly, there is no residual release of the composition once the injection catheter is removed.
- Angiographic, angioplasty, delivery and infusion catheters may also be used to deliver these compounds to affected areas.
- the above-described compositions can be locally delivered to a variety of body structures including grafts, saphenos vein grafts, arterial grafts, synthetic grafts, implants, prostheses or endoprostheses, homo or zeno grafts, cardiac muscle, skeletal or smooth muscle body structure. Applving the Effective Compositions to the Local-Delivery Devices
- compositions to a stent or other local-delivery device can be achieved in a number of different ways.
- the compound can be mechanically or electromechanically bonded to the delivery device, e.g. by a covalent bonding process.
- the compounds are directly embedded into a metal or other suitable substance from which the local-delivery system is comprised.
- the effective composition can also be applied using a chemical coating/bonding process, whereby layers of a suitable pharmaceutical agent, vehicle, or carrier entrap the compound.
- a biological or pharmacological coating already present on the local-delivery device acts as a platform for coating the compounds described above.
- platforms include, but are not limited to, silicon carbide, carbon, diamond or diamond-like coating, e.g. polytetrafluoroethylene, hylauronic acid or polyactone.
- suitable synthetic pharmaceutical agents include, but are not limited to, polyurethane, segmented polyurethane, poly-L-lactic acid, cellulose ester, polyethylene glycol as well as polyphosphate esters.
- Naturally occurring vehicles or carriers include collagens, laminens, heparins, fibrins, and other naturally occurring substances that absorb to cellulose.
- Using a chemical coating of the stent or other device is particularly advantageous in that it allows the compound or sex hormone to slowly release from the carrier, vehicle, or agent. This extends the time that the affected portion of the body sustains the efficacious effects of the compounds.
- the manner in which these carriers or vehicles interact with the device material as well as the inherent structure of these carriers and vehicles provide a diffusion barrier, thereby controlling the release of the entrapped compounds or sex hormones.
- Estrogen and the other effective compositions described above can also be coated onto or delivered with other drugs or compounds in order to administer synergistic treatment.
- Suitable drugs and compounds include antibodies, oligonucleotides (e.g. antisense oligonucleotides), antiproliferatives, anticancer or antimicrotubular agents (e.g. rapamycin, paclitaxel), antiproliferative agents, growth factors, genes, antisense or antithrombotic agents or any other chemical or biological compound that will act synergistically to increase the effectiveness of the primary hormone or compound.
- stent coatings can absorb and release these materials, thus providing an inert depot for controlled drug administration. Loading of the drug can occur for example via diffusion of the drug solution into the coating by hydration/swelling of the polymer matrix.
- Example 1 powdered estrogen is mixed with a carrier such as ethanol to form a solution or gel.
- the estrogen gel is then applied to a stainless steel stent using chemical coating methods that are well-known in the art.
- the coated stent is inserted into an arterial lumen of a human being suffering from atherosclerosis.
- the coated stent is inserted into an artery plagued by patchy, intramural plaque.
- the estrogen in the coating slowly diffuses into and penetrates the plaque, thereby providing treatment for this vascular disease.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Physics & Mathematics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Transplantation (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Optics & Photonics (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Urology & Nephrology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biophysics (AREA)
- Pulmonology (AREA)
- Anesthesiology (AREA)
- Hematology (AREA)
- Surgery (AREA)
- Materials For Medical Uses (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU26094/01A AU2609401A (en) | 1999-12-29 | 2000-12-29 | Apparatus and method for delivering compounds to a living organism |
EP00989608A EP1278493A4 (fr) | 1999-12-29 | 2000-12-29 | Dispositif et methode d'administration de composes a un organisme vivant |
US09/943,648 US6471979B2 (en) | 1999-12-29 | 2001-08-30 | Apparatus and method for delivering compounds to a living organism |
US10/260,954 US20030039677A1 (en) | 1999-12-29 | 2002-09-30 | Apparatus and method for delivering compounds to a living organism |
US10/661,820 US20040127475A1 (en) | 1999-12-29 | 2003-09-12 | Apparatus and method for delivering compounds to a living organism |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US17345199P | 1999-12-29 | 1999-12-29 | |
US60/173,451 | 1999-12-29 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/943,648 Continuation-In-Part US6471979B2 (en) | 1999-12-29 | 2001-08-30 | Apparatus and method for delivering compounds to a living organism |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2001047451A1 true WO2001047451A1 (fr) | 2001-07-05 |
Family
ID=22632100
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2000/035641 WO2001047451A1 (fr) | 1999-12-29 | 2000-12-29 | Dispositif et methode d'administration de composes a un organisme vivant |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP1278493A4 (fr) |
AU (1) | AU2609401A (fr) |
WO (1) | WO2001047451A1 (fr) |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003020329A1 (fr) * | 2001-08-30 | 2003-03-13 | Estrogen Vascular Technology, Lcc | Endoprothese recouverte d'hormones permettant de prevenir la stenose ou l'arteriosclerose |
WO2004024206A1 (fr) * | 2002-09-12 | 2004-03-25 | Estrogen Vascular Technology, Llc | Dispositif et procede servant a introduire des composes dans un organisme vivant |
DE10311729A1 (de) * | 2003-03-18 | 2004-09-30 | Schultheiss, Heinz-Peter, Prof. Dr. | Endovaskuläres Implantat mit einer mindestens abschnittsweisen aktiven Beschichtung aus Ratjadon und/oder einem Ratjadon-Derivat |
EP1594510A2 (fr) * | 2003-01-21 | 2005-11-16 | Dimera Inc. | Procede et kit pour reduire les symptomes des troubles du systeme vasculaire peripherique |
FR2880796A1 (fr) * | 2005-01-18 | 2006-07-21 | Novatech Sa Sa | Endoprothese pour canal anotomique |
US7273655B2 (en) | 1999-04-09 | 2007-09-25 | Shojiro Miyake | Slidably movable member and method of producing same |
US7771821B2 (en) | 2003-08-21 | 2010-08-10 | Nissan Motor Co., Ltd. | Low-friction sliding member and low-friction sliding mechanism using same |
US8096205B2 (en) | 2003-07-31 | 2012-01-17 | Nissan Motor Co., Ltd. | Gear |
US8152377B2 (en) | 2002-11-06 | 2012-04-10 | Nissan Motor Co., Ltd. | Low-friction sliding mechanism |
DE10107795B4 (de) * | 2001-02-13 | 2014-05-15 | Berlex Ag | Gefäßstütze mit einem Grundkörper, Verfahren zur Herstellung der Gefäßstütze, Vorrichtung zur Beschichtung der Gefäßstütze |
Citations (3)
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US5242397A (en) * | 1989-06-20 | 1993-09-07 | Cedars-Sinai Medical Center | Catheter device and method of use for intramural delivery of protein kinase C and tyrosine protein kinase inhibitors to prevent restenosis after balloon angioplasty |
US5866561A (en) * | 1997-08-21 | 1999-02-02 | Scimed Life Systems, Inc. | Local delivery of estrogen for angiogenesis |
US5962475A (en) * | 1996-10-25 | 1999-10-05 | Eli Lilly And Company | Substituted benzo(B)thiophene compounds having activity as selective estrogen receptor modulators |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
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ATE339975T1 (de) * | 1993-07-19 | 2006-10-15 | Angiotech Pharm Inc | Anti-angiogener stent und verfahren zu dessen herstellung |
AU716005B2 (en) * | 1995-06-07 | 2000-02-17 | Cook Medical Technologies Llc | Implantable medical device |
DE69935716T2 (de) * | 1998-05-05 | 2007-08-16 | Boston Scientific Ltd., St. Michael | Stent mit glatten enden |
-
2000
- 2000-12-29 EP EP00989608A patent/EP1278493A4/fr not_active Withdrawn
- 2000-12-29 AU AU26094/01A patent/AU2609401A/en not_active Abandoned
- 2000-12-29 WO PCT/US2000/035641 patent/WO2001047451A1/fr not_active Application Discontinuation
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5242397A (en) * | 1989-06-20 | 1993-09-07 | Cedars-Sinai Medical Center | Catheter device and method of use for intramural delivery of protein kinase C and tyrosine protein kinase inhibitors to prevent restenosis after balloon angioplasty |
US5962475A (en) * | 1996-10-25 | 1999-10-05 | Eli Lilly And Company | Substituted benzo(B)thiophene compounds having activity as selective estrogen receptor modulators |
US5866561A (en) * | 1997-08-21 | 1999-02-02 | Scimed Life Systems, Inc. | Local delivery of estrogen for angiogenesis |
Non-Patent Citations (1)
Title |
---|
See also references of EP1278493A4 * |
Cited By (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7273655B2 (en) | 1999-04-09 | 2007-09-25 | Shojiro Miyake | Slidably movable member and method of producing same |
DE10107795B4 (de) * | 2001-02-13 | 2014-05-15 | Berlex Ag | Gefäßstütze mit einem Grundkörper, Verfahren zur Herstellung der Gefäßstütze, Vorrichtung zur Beschichtung der Gefäßstütze |
WO2003020329A1 (fr) * | 2001-08-30 | 2003-03-13 | Estrogen Vascular Technology, Lcc | Endoprothese recouverte d'hormones permettant de prevenir la stenose ou l'arteriosclerose |
WO2004024206A1 (fr) * | 2002-09-12 | 2004-03-25 | Estrogen Vascular Technology, Llc | Dispositif et procede servant a introduire des composes dans un organisme vivant |
US8152377B2 (en) | 2002-11-06 | 2012-04-10 | Nissan Motor Co., Ltd. | Low-friction sliding mechanism |
EP1594510A4 (fr) * | 2003-01-21 | 2008-07-23 | Dimera Inc | Procede et kit pour reduire les symptomes des troubles du systeme vasculaire peripherique |
US7572780B2 (en) | 2003-01-21 | 2009-08-11 | Dimera, Incorporated | Method and kit for reducing the symptoms of peripheral vascular disease |
EP1594510A2 (fr) * | 2003-01-21 | 2005-11-16 | Dimera Inc. | Procede et kit pour reduire les symptomes des troubles du systeme vasculaire peripherique |
US8182833B2 (en) | 2003-01-21 | 2012-05-22 | Dimera Incorporated | Method and kit for reducing the symptoms of peripheral vascular disease with topical progesterone |
US8420111B2 (en) | 2003-01-21 | 2013-04-16 | Dimera Incorporated | Method and kit for reducing the symptoms of peripheral vascular disease |
DE10311729A1 (de) * | 2003-03-18 | 2004-09-30 | Schultheiss, Heinz-Peter, Prof. Dr. | Endovaskuläres Implantat mit einer mindestens abschnittsweisen aktiven Beschichtung aus Ratjadon und/oder einem Ratjadon-Derivat |
US8096205B2 (en) | 2003-07-31 | 2012-01-17 | Nissan Motor Co., Ltd. | Gear |
US7771821B2 (en) | 2003-08-21 | 2010-08-10 | Nissan Motor Co., Ltd. | Low-friction sliding member and low-friction sliding mechanism using same |
FR2880796A1 (fr) * | 2005-01-18 | 2006-07-21 | Novatech Sa Sa | Endoprothese pour canal anotomique |
US7520903B2 (en) | 2005-01-18 | 2009-04-21 | Novatech Sa | Endoprosthesis with projections for delivering active agents |
Also Published As
Publication number | Publication date |
---|---|
EP1278493A4 (fr) | 2006-09-27 |
AU2609401A (en) | 2001-07-09 |
EP1278493A1 (fr) | 2003-01-29 |
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