WO1994020111A1 - Methods for preventing progressive tissue necrosis, reperfusion injury, bacterial translocation and adult respiratory distress syndrome - Google Patents
Methods for preventing progressive tissue necrosis, reperfusion injury, bacterial translocation and adult respiratory distress syndrome Download PDFInfo
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- WO1994020111A1 WO1994020111A1 PCT/US1994/002558 US9402558W WO9420111A1 WO 1994020111 A1 WO1994020111 A1 WO 1994020111A1 US 9402558 W US9402558 W US 9402558W WO 9420111 A1 WO9420111 A1 WO 9420111A1
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- Prior art keywords
- dhea
- injury
- compound
- alkenyl
- alkyl
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
- A61K31/569—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone substituted in position 17 alpha, e.g. ethisterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/566—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol having an oxo group in position 17, e.g. estrone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Definitions
- the present invention is related to a method for preventing or reducing the effects of ischemia.
- the ischemia may be associated with injury, such as occurs as a result of infarctions, thermal injury (burns), surgical trauma, accidental trauma and the like.
- the ischemia may also precede reperfusion injury.
- the invention is also related to methods for preventing or reducing bacterial translocation and adult respiratory distress syndrome. In accordance with the present invention, these conditions are prevented by administering dehydroepiandrosterone (DHEA) or DHEA derivatives.
- DHEA dehydroepiandrosterone
- ischemia Interference with the supply of oxygenated blood to tissues is defined as ischemia.
- the effects of ischemia are known to be progressive, such that over time cellular vitality continues to deteriorate and tissues become necrotic.
- Ischemia is probably the most important cause of coagulative necrosis in human disease.
- reperfusion injury To place reperfusion injury into a clinical perspective, there are three different degrees of cell injury, depending on the duration of ischemia:
- the reversibility of cell injury as a consequence of ischemia is determined not only by the type and duration of the injury, but also by the cell target. Neurons exhibit very high sensitivity to ischemia, whereas myocardial, pulmonary, hepatic and renal tissues are intermediate in sensitivity. Fibroblasts, epidermis and skeletal muscle have the lowest susceptibility to ischemic injury, requiring several hours without blood supply to develop irreversible damage.
- Figure 3D shows the progressive ischemic conse- quences of thermal injury to the ear when vehicle alone is administered.
- Figure 4 shows the effect of treatment with DHEA on progressive ischemia when administered from 0-6 hours post-thermal injury.
- the present invention is directed to a method for preventing or reducing reperfusion injury following ischemia, and cellular damage associated with ischemic episodes, such as infarction or traumatic injury.
- An example of an infarction is a myocardial infarction.
- Examples of traumatic injury include thermal injury, surgery, chemical burns, blunt trauma or lacerations and the like.
- the present invention is also directed to a method for preventing or reducing adult respiratory distress syndrome (ARDS) .
- ARDS is prevented or reduced in a patient by administering DHEA or DHEA derivatives as described above.
- the DHEA or DHEA derivative is administered prior to clinical symptoms of ARDS, primarily to individuals at risk for ARDS.
- DHEA and suitable DHEA derivatives are represented by the following Formula I:
- X is the same or different, and is halogen, C 1-4 alkyl, C 1-4 alkenyl, C 1-4 alkoxy, carboxy, nitro, sulfate, sulfonyl, C 1-6 carboxylesters or C ⁇ sulfate esters; and n is O, 1, 2 or 3.
- Suitable halogens include Br, CI, F and I.
- suitable substituents for R 4 , R 5 or R 6 are OH and Br.
- Other suitable substituents can be readily identified by (a) administering the DHEA derivative in the burn model described herein and noting its anti-ischemic effect, and (b) determining the amount of sulfated derivative.
- zones comprise the zone of complete capillary occlusion, the zone of partial occlusion (stasis), and the zone of capillary hyperemia (13).
- the zone of complete capillary occlusion is restricted to the distal margin of the mouse ear.
- the zone of partial occlusion or stasis is Located more proximally to this outermost, and immediately sensitive area, is the zone of partial occlusion or stasis. It is this major area of ear tissue which becomes progressively ischemic over the 24-72 hour period following thermal injury, and which ultimately undergoes necrosis.
- the most proximal area of the affected ear is the zone of hyperemia. This area is fairly resistant to Progressive- sive post-burn ischemia.
- the DHEA or DHEA derivative of Formula I be administered within two hours of the patient's sustaining the reperfusion, infarction or traumatic injury.
- the DHEA or DHEA derivative of Formula I is administered to patients in ester or other pharmaceutically acceptable form and within binders, elixirs or other pharmaceutically acceptable mixtures, or with other pharmaceutically acceptable carriers.
- Pharmaceutical compositions containing a compound of the present invention as the active ingredient in intimate admixture with a pharmaceutical carrier can be prepared according to conventional pharmaceutical compounding techniques.
- the carrier may take a wide variety of forms depending on the form of preparation desired for administration, e.g., intravenous, oral or parenteral.
- unprotected compounds i.e., those which can be sulfated by human sulfotransferases or sulfatases
- unprotected compounds be administered daily, whereas protected compounds can be administered either daily or every other day.
- the patient is treated with the DHEA or DHEA derivative of Formula I for 3-30 days, preferably 7-14 days, following the infarction or traumatic injury.
- DHEA or DHEA derivative of Formula I be administered soon after reperfusion injury, infarction or traumatic injury in order to prevent or reduce any cellular damage. If the administration of these compounds occurs too late, blood vessels will become occluded (initially with neutrophils adhering to endothelial cells), at which point the administration of these compounds will be unable to prevent or reduce the ischemia.
- the time frame within which the administration should begin may be dependent on the type of reperfusion injury, infarction or traumatic injury, and can be readily determined by appropriate animal models. However, it is preferred that administration of the DHEA or DHEA derivatives commence within four hours, and most preferably within two hours of the ischemia, infarction or traumatic injury.
- the administration of the DHEA or DHEA derivatives to prevent or reduce bacterial translocation should begin within 24 hours of the injury or stress-causing event. It is preferred that administration of these compounds to prevent or reduce bacterial translocation begin within four hours, and most preferably within two hours.
- the administration of the DHEA or DHEA derivatives to prevent or reduce ARDS should begin before the onset of clinical symptoms. Generally, the compounds will be administered to patients at risk of ARDS.
- the present invention is described by reference to the following Examples, which are offered by way of illustration and are not intended to limit the inven ⁇ tion in any manner. Standard techniques well known in the art or the techniques specifically described below were utilized.
- mice approximately 9 weeks old, were given an identifying mark, and then divided into control and treated subgroups. The thickness of the ear to be immersed in hot water was recorded, and then the entire ear of the anesthetized mouse was dipped into 52°C water for exactly 24 seconds. Each mouse was returned to its cage after an injection of either the propylene glycol vehicle (control) or 100 ⁇ g of DHEA agent dissolved in propylene glycol. Ear swelling changes were monitored on individual mice at pre-burn, and at 1, 3, 6, 9, 12, 18, 24 and 48 hours after thermal injury.
- 16 ⁇ - hydroxy-DHEA was less protective, i.e., reduced the extent of, but did not totally prevent progressive ischemia, and 16 ⁇ -chloro-DHEA was slightly protective against progressive ischemia.
- mice were anesthe ⁇ tized, administered a burn and then, while under anesthesia, four mice were given vehicle alone, four mice were given 100 ⁇ g DHEA, and the remaining mice were divided into additional groups of four. All of the mice in a single group would receive 100 ⁇ g DHEA either one, two, four or six hours after thermal injury. Tissue loss by each mouse was evaluated 72 hours after thermal injury, and the results of the scoring are presented in Figure 4.
- Androstenedione also a secondary metabolite of DHEA, can be metabolized only to downstream products, (e.g., testosterone and estrogens), with no known conversion to DHEA. Because androstenedione cannot protect against progressive dermal ischemia in this model, its lack of effect supports the conclusion that the active steroid is DHEA, not a downstream androgen or estrogen. Further, it was found that sulfated DHEA, which occurs naturally in the human body, was unable to protect against progressive ischemia. DHEA possesses the published ability to overcome some of the biological effects caused by glucocorti- coids.
- the testis with cremaster muscle intact is then dissected away from the scrotum.
- An opening of 1 cm is made on the ventral surface of the cremaster, and the testis and spermatic cord are removed.
- the neurovascular pedicle consisting of the pubic-epigastric arteries, vein, and genitofemoral nerve, is then completely isolated by dissecting to the origin of the vessels from the external iliac artery and vein.
- the front wall of the cremaster muscle sac is opened and the island cremaster muscle flap is prepared for intravital videomicroscopy.
- the rat is secured on a specially designed tissue bath, and the cremaster muscle flap is spread over the coverglass in the opening at the bottom of the bath and fixed with 5-0 silk sutures.
- the muscle is then transilluminated from below, using a fiberoptic tungsten lamp.
- the muscle is kept moist and covered with impermeable plastic film.
- the tissue bath designed specifically for temperature control, is filled with 0.9% saline and the temperature maintained at between 35°C-36°C.
- the microscope is equipped with a color video camera. The video image of the microcirculation is displayed on a 19" monitor, where the final magnification is x 1800.
- Measurement of microvascular activity is recorded after isolation of the muscle to establish the pre-ischemia baseline. After proper positioning of clamps to completely shut down blood flow to the muscle flap, the duration of the ischemic period is six hours.
- Zone 1, 2 and 3 is measured by counting the number of flowing capillaries in proximity to the preselected postcapillary venule.
- Nine visual fields of capillaries are counted at each postcapillary venule site, for a total of 27 fields per cremaster muscle flap. Results are shown in Figures 5A, 5B and 5C for Zones 1, 2 and 3, respectively.
- Red Blood Cell Velocities in Al (First Order) and A2 (Second Order) Arterioles Red Blood Cell Velocities in Al (First Order) and A2 (Second Order) Arterioles.
- Red blood cell velo ⁇ cities are recorded in the main arterioles of the cremaster flap using a custom-made optical Doppler velocimeter. Results are shown in Figures 7A and 7B, for velocity of venous and arterial blood, respectively.
Abstract
Description
Claims
Priority Applications (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AT94911522T ATE283052T1 (en) | 1993-03-09 | 1994-03-08 | USE OF DHEA OR ITS DERIVATIVES FOR THE PRODUCTION OF A MEDICATION FOR PREVENTING PROGRESSIVE TISSUE NECROSIS, REPERFUSION INJURY, BACTERIAL TRANSLOCATION AND RESPIRATORY DISORDER SYNDROME IN ADULTS |
SK1031-95A SK103195A3 (en) | 1993-03-09 | 1994-03-08 | Use of dehydroepiandrosterone derivative for pharmaceutical compositions production and pharmaceutical composition containing dehydroepiandrosterone derivative |
KR1019950703800A KR960700728A (en) | 1993-03-09 | 1994-03-08 | Methods for Preventing Progressive Tissue Necrosis, Reperfusion Injury, Bacterial Translocation and Adult Respiratory Distress Syndrome |
AU64007/94A AU677308B2 (en) | 1993-03-09 | 1994-03-08 | Methods for preventing progressive tissue necrosis, reperfusion injury, bacterial translocation and adult respiratory distress syndrome |
US08/284,688 US5532230A (en) | 1993-03-09 | 1994-03-08 | Methods for preventing progressive tissue necrosis, reperfusion injury, bacterial translocation and adult respiratory distress syndrome |
DE69434149T DE69434149T2 (en) | 1993-03-09 | 1994-03-08 | USE OF DHEA OR ITS DERIVATIVES FOR THE MANUFACTURE OF A MEDICAMENT FOR PREVENTING PROGRESSIVE TISSUE NEKROSIS, REPERFUSION INJURY, BACTERIAL TRANSLATION, AND ATOMIC SYNDROME IN ADULTS |
EP94911522A EP0688220B1 (en) | 1993-03-09 | 1994-03-08 | Use of dhea and derivatives thereof for the manufacture of a medicament for preventing progressive tissue necrosis, reperfusion injury, bacterial translocation and adult respiratory distress syndrome |
NO952800A NO952800L (en) | 1993-03-09 | 1995-07-14 | Procedures for preventing progressive tissue necrosis, reperfusion injury, bacterial translocation, and acute lung failure syndrome in adults |
FI953814A FI953814A (en) | 1993-03-09 | 1995-08-11 | Methods to prevent progressive tissue necrosis, bacterial translocation, reperfusion injury, and respiratory failure |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US2942293A | 1993-03-09 | 1993-03-09 | |
US08/029,422 | 1993-03-09 |
Publications (1)
Publication Number | Publication Date |
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WO1994020111A1 true WO1994020111A1 (en) | 1994-09-15 |
Family
ID=21848945
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1994/002558 WO1994020111A1 (en) | 1993-03-09 | 1994-03-08 | Methods for preventing progressive tissue necrosis, reperfusion injury, bacterial translocation and adult respiratory distress syndrome |
Country Status (15)
Country | Link |
---|---|
US (3) | US5532230A (en) |
EP (1) | EP0688220B1 (en) |
JP (1) | JP2858046B2 (en) |
KR (1) | KR960700728A (en) |
AT (1) | ATE283052T1 (en) |
AU (3) | AU677308B2 (en) |
CA (1) | CA2153895A1 (en) |
CZ (1) | CZ193495A3 (en) |
DE (1) | DE69434149T2 (en) |
ES (1) | ES2229215T3 (en) |
FI (1) | FI953814A (en) |
HU (1) | HUT72968A (en) |
NO (1) | NO952800L (en) |
SK (1) | SK103195A3 (en) |
WO (1) | WO1994020111A1 (en) |
Cited By (9)
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WO1996040152A1 (en) * | 1995-06-07 | 1996-12-19 | Paradigm Biosciences, Inc. | Dehydroepiandrosterone derivatives for preventing progressive tissue necrosis reperfusion injury, bacterial translocation and adult respiratory distress syndrome |
US5736537A (en) * | 1995-09-12 | 1998-04-07 | Estee Lauder, Inc. | Dehydroep:androsterone sailcylate useful against skin atrophy |
EP0934745A1 (en) * | 1998-02-04 | 1999-08-11 | CHARLOTTE-MECKLENBURG HOSPITAL doing business as Carolinas Medical Center | Use of androsterone derivatives for inhibiting DNA binding of ap-1 and airway smooth muscle proliferation |
EP1011607A2 (en) * | 1997-06-05 | 2000-06-28 | University Of Utah Research Foundation | Methods for preventing progressive tissue necrosis, reperfusion injury, bacterial translocation and adult respiratory distress syndrome |
SG79237A1 (en) * | 1995-02-24 | 2001-03-20 | Univ East Carolina | Composition & use for reducing adenosine levels & treating diseases & conditions associated with it with a dehydroepiandrosterone & optionally a ubiquinone |
GB2363984A (en) * | 2000-06-29 | 2002-01-16 | Hunter Fleming Ltd | Protection against neuronal damage using 3-hydroxy-7 -hydroxy steroids and 3-oxo-7 -hydroxy steroids |
EP1539183A1 (en) * | 2002-08-28 | 2005-06-15 | Hollis-Eden Pharmaceuticals Inc. | Therapeutic treatment methods |
US7524835B2 (en) | 1999-03-23 | 2009-04-28 | Hollis-Eden Pharmaceuticals, Inc. | Tetrol steroids and esters |
US7718639B2 (en) | 2000-06-29 | 2010-05-18 | Hunter-Fleming Limited | 7-hydroxyepiandrosterone having neuroprotective activity |
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US5641766A (en) * | 1990-08-29 | 1997-06-24 | Humanetics Corporation | UP-regulation of immune system with Δ 5-Androstenes |
US5922701A (en) * | 1992-05-01 | 1999-07-13 | University Of Utah Research Foundation | Method for enhancing or accelerating re-epithelialization or re-endothelialization of a tissue |
US5929060A (en) * | 1992-05-01 | 1999-07-27 | University Of Utah Research Foundation | Method for enhancing or accelerating re-epithelialization or re-endothelialization of a tissue |
US20020091155A1 (en) * | 1995-06-22 | 2002-07-11 | Btg Pharmaceutical Corp. | Method for ameliorating muscle weakness/wasting in a patient infected with human immunodeficiency virus-type 1 |
US5587369A (en) * | 1993-03-09 | 1996-12-24 | University Of Utah Research Foundation | Methods for preventing progressive tissue necrosis, reperfusion injury, bacterial translocation and adult respiratory distress syndrome |
US20020032160A1 (en) * | 1995-02-24 | 2002-03-14 | Nyce Jonathan W. | Compositions & formulations with an epiandrosterone or a ubiquinone & kits & their use for treatment of asthma symptoms & for reducing adenosine/adenosine receptor levels |
US5859000A (en) * | 1995-06-07 | 1999-01-12 | University Of Utah Research Foundation | Method for reducing mast cell mediated allergic reactions |
US6576659B1 (en) * | 1996-12-05 | 2003-06-10 | Bio-Technology General Corp. | Use of oxandrolone in the treatment of burns an other wounds |
AU8779898A (en) * | 1997-08-11 | 1999-03-01 | Weider Nutrition International, Inc. | Compositions and treatments to reduce side effects of administration of androgenic testosterone precursors |
US5958946A (en) * | 1998-01-20 | 1999-09-28 | Styczynski; Peter | Modulation of hair growth |
US6230713B1 (en) * | 1998-01-29 | 2001-05-15 | Margaret R. Dalesandro | Determining a treatment plan for patients undergoing thrombotic event by monitoring P-selectin |
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US20060079492A1 (en) * | 1999-10-25 | 2006-04-13 | Ahlem Clarence N | Compositions and treatment methods |
US20080015174A1 (en) * | 1998-11-24 | 2008-01-17 | Reading Christopher L | Metabolic Disease Treatments |
US20030060425A1 (en) * | 1998-11-24 | 2003-03-27 | Ahlem Clarence N. | Immune modulation method using steroid compounds |
CA2386095A1 (en) | 1999-09-30 | 2001-04-05 | Hollis-Eden Pharmaceuticals, Inc. | Therapeutic treatment of androgen receptor driven conditions |
EP2135611A1 (en) | 2001-03-01 | 2009-12-23 | Hollis-Eden Pharmaceuticals Inc. | Pregn-5-en-20-yne-3,7,17-triol derivatives for use in therapy |
WO2002085296A2 (en) * | 2001-04-24 | 2002-10-31 | Epigenesis Pharmaceuticals, Inc. | Composition, formulations and kit for treatment of respiratory and lung disease with non-glucocorticoid steroids and/or ubiquinone and a bronchodilating agent |
WO2002085297A2 (en) * | 2001-04-24 | 2002-10-31 | East Carolina University | Compositions & formulations with a non-glucocorticoid steroid &/or a ubiquinone & kit for treatment of respiratory & lung disease |
GB2378898A (en) * | 2001-08-14 | 2003-02-26 | Hunter Fleming Ltd | Prophylactic and therapeutic use of hydroxysteroids |
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US7405207B2 (en) * | 2002-06-17 | 2008-07-29 | Epigenesis Pharmaceuticals, Inc. | Nebulizer formulations of dehydroepiandrosterone and methods of treating asthma or chronic obstructive pulmonary disease using compositions thereof |
US20040121991A1 (en) * | 2002-12-20 | 2004-06-24 | Araneo Barbara A. | Dehydroepiandrosterone (DHEA) congeners for prevention and/or treatment of ulcers |
WO2004089304A2 (en) * | 2003-04-01 | 2004-10-21 | Hollis-Eden Pharmaceuticals, Inc. | Antiandrogens with marginal agonist activity and methods of use |
US20090274676A1 (en) * | 2003-07-31 | 2009-11-05 | Robinson Cynthia B | Combination of dehydroepiandrosterone or dehydroepiandrosterone-sulfate with a pde-4 inhibitor for treatment of asthma or chronic obstructive pulmonary disease |
US20090263381A1 (en) * | 2003-07-31 | 2009-10-22 | Robinson Cynthia B | Combination of dehydroepiandrosterone or dehydroepiandrosterone-sulfate with an anti-ige antibody for treatment of asthma or chronic obstructive pulmonary disease |
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US20050113318A1 (en) * | 2003-07-31 | 2005-05-26 | Robinson Cynthia B. | Combination of dehydroepiandrosterone or dehydroepiandrosterone-sulfate with a beta-agonist bronchodilator for treatment of asthma or chronic obstructive pulmonary disease |
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US20050026890A1 (en) * | 2003-07-31 | 2005-02-03 | Robinson Cynthia B. | Combination of dehydroepiandrosterone or dehydroepiandrosterone-sulfate with an antihistamine for treatment of asthma or chronic obstructive pulmonary disease |
US20050026884A1 (en) * | 2003-07-31 | 2005-02-03 | Robinson Cynthia B. | Combination of dehydroepiandrosterone or dehydroepiandrosterone-sulfate with a beta-agonist bronchodilator for treatment of asthma or chronic obstructive pulmonary disease |
US20050026879A1 (en) * | 2003-07-31 | 2005-02-03 | Robinson Cynthia B. | Combination of dehydroepiandrosterone or dehydroepiandrosterone-sulfate with a tyrosine kinase inhibitor, delta opioid receptor antagonist, neurokinin receptor antagonist, or VCAM inhibitor for treatment of asthma or chronic obstructive pulmonary disease |
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1994
- 1994-03-08 US US08/284,688 patent/US5532230A/en not_active Expired - Fee Related
- 1994-03-08 ES ES94911522T patent/ES2229215T3/en not_active Expired - Lifetime
- 1994-03-08 AU AU64007/94A patent/AU677308B2/en not_active Ceased
- 1994-03-08 WO PCT/US1994/002558 patent/WO1994020111A1/en active IP Right Grant
- 1994-03-08 CA CA002153895A patent/CA2153895A1/en not_active Abandoned
- 1994-03-08 DE DE69434149T patent/DE69434149T2/en not_active Expired - Fee Related
- 1994-03-08 CZ CZ951934A patent/CZ193495A3/en unknown
- 1994-03-08 AT AT94911522T patent/ATE283052T1/en not_active IP Right Cessation
- 1994-03-08 SK SK1031-95A patent/SK103195A3/en unknown
- 1994-03-08 EP EP94911522A patent/EP0688220B1/en not_active Expired - Lifetime
- 1994-03-08 HU HU9502126A patent/HUT72968A/en unknown
- 1994-03-08 JP JP6520289A patent/JP2858046B2/en not_active Expired - Fee Related
- 1994-03-08 KR KR1019950703800A patent/KR960700728A/en not_active Application Discontinuation
-
1995
- 1995-05-19 US US08/446,568 patent/US5583126A/en not_active Expired - Fee Related
- 1995-05-19 US US08/446,569 patent/US5489581A/en not_active Expired - Fee Related
- 1995-07-14 NO NO952800A patent/NO952800L/en unknown
- 1995-08-11 FI FI953814A patent/FI953814A/en unknown
-
1997
- 1997-05-08 AU AU20132/97A patent/AU691776B2/en not_active Ceased
- 1997-05-08 AU AU20131/97A patent/AU687704B2/en not_active Ceased
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SG79237A1 (en) * | 1995-02-24 | 2001-03-20 | Univ East Carolina | Composition & use for reducing adenosine levels & treating diseases & conditions associated with it with a dehydroepiandrosterone & optionally a ubiquinone |
WO1996040152A1 (en) * | 1995-06-07 | 1996-12-19 | Paradigm Biosciences, Inc. | Dehydroepiandrosterone derivatives for preventing progressive tissue necrosis reperfusion injury, bacterial translocation and adult respiratory distress syndrome |
US6284750B1 (en) | 1995-09-12 | 2001-09-04 | Estee Lauder Inc. | α-hydroxyacid esters of DHEA useful against skin disorders |
US6025347A (en) * | 1995-09-12 | 2000-02-15 | Estee Lauder Inc. | Steroid esters useful against skin disorders |
US5736537A (en) * | 1995-09-12 | 1998-04-07 | Estee Lauder, Inc. | Dehydroep:androsterone sailcylate useful against skin atrophy |
EP1011607A2 (en) * | 1997-06-05 | 2000-06-28 | University Of Utah Research Foundation | Methods for preventing progressive tissue necrosis, reperfusion injury, bacterial translocation and adult respiratory distress syndrome |
EP1011607A4 (en) * | 1997-06-05 | 2005-01-12 | Univ Utah Res Found | Methods for preventing progressive tissue necrosis, reperfusion injury, bacterial translocation and adult respiratory distress syndrome |
EP0934745A1 (en) * | 1998-02-04 | 1999-08-11 | CHARLOTTE-MECKLENBURG HOSPITAL doing business as Carolinas Medical Center | Use of androsterone derivatives for inhibiting DNA binding of ap-1 and airway smooth muscle proliferation |
US7524835B2 (en) | 1999-03-23 | 2009-04-28 | Hollis-Eden Pharmaceuticals, Inc. | Tetrol steroids and esters |
GB2363984A (en) * | 2000-06-29 | 2002-01-16 | Hunter Fleming Ltd | Protection against neuronal damage using 3-hydroxy-7 -hydroxy steroids and 3-oxo-7 -hydroxy steroids |
US7718639B2 (en) | 2000-06-29 | 2010-05-18 | Hunter-Fleming Limited | 7-hydroxyepiandrosterone having neuroprotective activity |
EP1539183A1 (en) * | 2002-08-28 | 2005-06-15 | Hollis-Eden Pharmaceuticals Inc. | Therapeutic treatment methods |
EP1539183A4 (en) * | 2002-08-28 | 2007-04-25 | Hollis Eden Pharmaceuticals | Therapeutic treatment methods |
AU2003278744B2 (en) * | 2002-08-28 | 2010-07-29 | Harbor Biosciences, Inc. | Therapeutic treatment methods |
US7935839B2 (en) | 2002-08-28 | 2011-05-03 | Harbor Biosciences, Inc. | Sepsis treatment methods |
Also Published As
Publication number | Publication date |
---|---|
AU687704B2 (en) | 1998-02-26 |
US5489581A (en) | 1996-02-06 |
JP2858046B2 (en) | 1999-02-17 |
ES2229215T3 (en) | 2005-04-16 |
CA2153895A1 (en) | 1994-09-15 |
EP0688220B1 (en) | 2004-11-24 |
AU677308B2 (en) | 1997-04-17 |
KR960700728A (en) | 1996-02-24 |
CZ193495A3 (en) | 1996-04-17 |
DE69434149T2 (en) | 2006-07-20 |
US5583126A (en) | 1996-12-10 |
JPH08507531A (en) | 1996-08-13 |
NO952800L (en) | 1995-09-14 |
SK103195A3 (en) | 1996-12-04 |
HU9502126D0 (en) | 1995-09-28 |
FI953814A0 (en) | 1995-08-11 |
AU691776B2 (en) | 1998-05-21 |
EP0688220A1 (en) | 1995-12-27 |
NO952800D0 (en) | 1995-07-14 |
DE69434149D1 (en) | 2004-12-30 |
US5532230A (en) | 1996-07-02 |
EP0688220A4 (en) | 1998-04-01 |
AU6400794A (en) | 1994-09-26 |
HUT72968A (en) | 1996-06-28 |
AU2013297A (en) | 1997-07-10 |
FI953814A (en) | 1995-11-07 |
ATE283052T1 (en) | 2004-12-15 |
AU2013197A (en) | 1997-07-10 |
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