WO2000030633A1 - Method of treating chronic obstructive pulmonary disease - Google Patents
Method of treating chronic obstructive pulmonary disease Download PDFInfo
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- WO2000030633A1 WO2000030633A1 PCT/US1999/027897 US9927897W WO0030633A1 WO 2000030633 A1 WO2000030633 A1 WO 2000030633A1 US 9927897 W US9927897 W US 9927897W WO 0030633 A1 WO0030633 A1 WO 0030633A1
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- Prior art keywords
- patient
- treatment
- need
- asthmatic
- drug
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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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
- A61P11/08—Bronchodilators
Definitions
- the present invention relates to a method of medical treatment. More particularly, the present invention concerns the use of certain ⁇ -substituted (1 , -benzoquinon-2-yl) - alkanoic acids for the treatment of chronic obstructive pulmonary disease.
- COPD chronic obstructive pulmonary disease
- therapeutic methods for the treatment of COPD included the administration, typically by means of metered dose inhaler (MDI) , of a sympathomimetic broncho- dilator such as ephedrine, epinephrine, or isoproterenol .
- MDI metered dose inhaler
- a sympathomimetic broncho- dilator such as ephedrine, epinephrine, or isoproterenol .
- ⁇ 2 -specific bronchodilators such as metaproterenol, albuterol, terbutaline, and bitolterol, generally administered as aerosols.
- Oral sustained-release formulations of theophylline are generally given for chronic maintenance therapy. Although the benefits of theophylline treatment in patients with COPD are generally difficult to prove, this form of treatment remains popular.
- Anticholinergics such as atropine sulfate and ipratroprium, a quaternary ammonium derivative of atropine, have been used for the inhalation treatment of COPD, although the former is not approved for use. Because of its quaternary ammonium salt nature, ipratroprium is minimally absorbed into the blood stream and has fewer side effects than atropine.
- United States Patent 5,534,548 to Killian discloses the use of a class of substituted ( ⁇ -l, 4-benzoquinon-2-yl) - alkanoic acids for the treatment or prevention of eclampsia or preeclampsia in pregnant women.
- a method of treating chronic obstructive pulmonary disease comprising the administration to a patient in need of such treatment a therapeutically effective amount of a compound, or pharmaceutically acceptable salt thereof, having the structure:
- R 1 is selected from the group consisting of unsubstituted phenyl; and phenyl substituted with one or more groups independently selected from halo, hydroxy, alkyl of one to three carbon atoms, and alkoxy of one to three carbon atoms.
- FIGURE 1 is a Venn diagram of various pulmonary disease conditions illustrating the scope of the definition of chronic obstructive pulmonary disease for the purpose of the present invention.
- FIGURE 2 is a graphical representation of forced expiratory volume in one second (FEV of patients taking part in the study.
- FIGURES 3 and 4 are graphical representations, respectively, of the P. M. and A.M. peak expiratory flow rates for patients taking part in the study.
- FIGURE 5 is a graphical representation of the percent changes from baseline in maximal voluntary ventilation of expiration in twelve seconds (MW 12 ) of patients taking part in the study.
- FIGURE 6 is a graphical representation of the distance covered by patients in the six-minute walk exercise test.
- FIGURE 7 is a graphical representation of the change from baseline in the COPD wheezing symptom of patients taking part in the study.
- FIGURE 8 is a graphical representation of the changes from baseline in COPD chest tightness symptom of patients taking part in the study.
- FIGURE 9 is a graphical representation of the changes from baseline of COPD cough symptom of patients taking part in the study.
- FIGURE 10 is a graphical representation of the changes from baseline in COPD dyspnea symptom of patients taking part in the study.
- FIGURE 11 is a graphical representation of the responses of patients to the Quality of Life Questionnaire with regard to mastery.
- FIGURE 12 is a graphical representation of the responses of patients to the Quality of Life Questionnaire with regard to fatigue.
- FIGURE 13 is a graphical representation of the responses of patients to the Chronic Respiratory Questionnaire with regard to dyspnea.
- FIGURE 14 is a graphical representation of the responses of patients to the Chronic Respiratory Questionnaire with regard to emotional function.
- FIGURE 15 is a histogram presenting change from baseline in daily symptom assessment of patients taking part in the study.
- FIGURE 16 is a histogram presenting change from baseline in nocturnal symptom assessment of patients taking part in the study.
- FIGURE 17 is a graphical representation of changes from baseline in the ease of bringing up sputum for patients taking part in the study.
- FIGURE 18 is a graphical representation of changes from baseline in the need for patients taking part in the study for PRN bronchodilator .
- FIGURE 19 is a graphical representation of the cough discomfort and tightness/congestion of patients taking part in the study.
- FIGURE 20 is a graphical representation of the frequency of cough episodes of patients taking part in the study.
- FIGURE 21 is a graphical representation of the cough severity of patients taking part in the study.
- treatment means the alleviation of the symptoms of chronic obstructive pulmonary disease and/or preservation of lung function and/or the general improvement in the patient's perceived quality of life as regards the disease conditions and symptoms.
- airway obstruction refers to an increased resistance to airflow exhibited by characteristic spirometric findings .
- chronic bronchitis refers to the condition associated with prolonged exposure to nonspecific bronchial irritants and is accompanied by mucus hypersecretion and structural changes in the bronchi .
- chronic obstructive bronchitis means the disease condition frequently associated with the symptoms of chronic bronchitis in which disease of the small airways has progressed to the point that there is clinically significant airway obstruction.
- pulmonary emphysema refers to enlargement of the airspaces distal to the terminal nonrespiratory bronchioles, accompanied by destructive changes of the alveolar walls.
- chronic obstructive emphysema refers to the condition when there has been sufficient loss of lung recoil to allow marked airway collapse upon expiration, leading to the physiologic pattern of airway obstruction.
- chronic asthmatic bronchitis refers to an underlying asthmatic condition in patients in whom asthma has become so persistent that clinically significant chronic airflow obstruction is present despite antiasthmatic therapy.
- chronic obstructive pulmonary disease is defined as a generally progressive disease state, due to chronic obstructive bronchitis or chronic obstructive emphysema, which may be accompanied by airway hyperreactivity and may be partially reversible.
- a Venn diagram shows various sets of patient populations, with the graphical representations of the subsets in the diagram not intended to represent actual patient populations.
- patient populations with chronic bronchitis, emphysema, and asthma are represented as falling within one of the three indicated overlapping circles.
- Patients suffering airflow obstruction fall within the rectangular box.
- Patients having chronic obstructive pulmonary disease (COPD) are those falling within the shaded subset classifications.
- COPD chronic obstructive pulmonary disease
- FEV 1 means the forced expiratory volume over one second as measured by standard spirometric techniques.
- FVC means the forced vital capacity and "MW 12 " means maximal voluntary ventilation in twelve seconds, both as also measured by spirometry.
- the compounds contemplated as falling within the scope of the method of the present invention are selected from those defined by the generic formula I given above in the Summary of the Invention, or a pharmaceutically acceptable salt or prod- rug thereof .
- the preferred compound of the method of the present invention is ( ⁇ ) -7- (3 , 5 , 6-trimethyl-l, 4-benzoquinon-2- yl) -7-phenylheptanoic acid (known generically as seratrodast) , or a pharmaceutically acceptable salt thereof or pro-drug and includes individual enantiomers and mixtures thereof, including the racemic mixture. Both compounds were shown to be systemically available following oral administration, and pre- clinical pharmacology studies show that both enantiomers are pharmacologically active.
- (+) -1-phenylethylamine, or the like followed by selective recrystallizations and regeneration of the free acid form of the compounds from their separated diastereomeric salts.
- the compounds can be separated on chiral chromatographic columns or by reverse phase HPLC using methods also well known in the art.
- the carboxylic acid function of compounds of the present invention is converted to a pharmaceutically acceptable salt by dissolution in an appropriate solvent and subsequent neutralization with the selected base.
- pharmaceutically acceptable salt refers to those salts which are within the scope of sound medical judgment, suitable for use in contact with the tissues of humans without undue toxicity, irritation, allergic response and the like, and are commensurate with a reasonable benefit/risk ratio.
- salts are well known in the pharmaceutical formulation art.
- S. M. Berge, et al describe pharmaceutically acceptable salts in detail in J ⁇ Pharmaceutical Sciences, 66: 1-19 (1977), the contents of which are incorporated herein by reference.
- the salts can be prepared in si tu during the final isolation and purification of the compounds of the invention, or separately by reacting the free acid function with a suitable inorganic or organic base .
- Representative pharmaceutically acceptable salts of the compounds utilized in the method of this invention include alkali or alkaline earth metal salts such as aluminum, calcium, sodium, lithium, potassium, magnesium and zinc salts and the like. Further pharmaceutically acceptable salts include, when appropriate, nontoxic ammonium, quaternary ammonium, and amine cations formed with the carboxyl function of the compounds contemplated for use in the method of the invention.
- pro-drug refers to compounds that are rapidly transformed in vivo to yield the parent compounds of Formula (I) , as for example, by hydrolysis in blood.
- T. Higuchi and V. Stella provide a thorough discussion of the pro-drug concept in "Pro-drugs as Novel Delivery Systems," Vol. 14 of the A.C.S. Symposium Series, American Chemical Society (1975) .
- esters for example, useful as pro-drugs for compounds containing carboxyl groups may be found on pages 14-21 of Bioreversible Carriers in Drug Design : Theory and Applica tion, edited by E.B. Roche, Pergamon Press (1987) .
- pro-drug ester group refers to any of several ester-forming groups that are hydrolyzed under physiological conditions.
- Examples of pro-drug ester groups include pivaloyloxymethyl, acetoxymethyl , phthalidyl, indanyl and methoxymethyl, as well as other such groups known in the art.
- compositions for use in the method of the present invention comprise a therapeutically effective amount of a compound of the present invention formulated together with one or more pharmaceutically acceptable carriers.
- pharmaceutically acceptable carrier means a non-toxic, inert solid, semi-solid or liquid filler, diluent, encapsulating material or formulation auxiliary of any type.
- materials which can serve as pharmaceutically acceptable carriers are sugars such as lactose, glucose and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil, glycols such as propylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol, and phosphate buffer solutions, as well as other non-toxic compatible lubricants such as sodium lauryl sulfate and magnesium stearate.
- sugars such as lactose, glucose and
- Coloring agents, releasing agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the composition, according to the judgment of the formulator.
- the pharmaceutical compositions of this invention can be administered to humans orally, parenterally, subcutaneously, or as an inhalation spray.
- Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups and elixirs.
- the liquid dosage forms may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof.
- inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzy
- the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents .
- adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents .
- injectable preparations for example, sterile injectable aqueous or oleaginous suspensions may be formulated according to the known art using suitable dispersing or wetting agents and suspending agents.
- the sterile injectable preparation may also be a sterile injectable solution, suspension or emulsion in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1, 3-butanediol .
- acceptable vehicles and solvents that may be employed are water, Ringer's solution, U.S. P.
- injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use.
- the rate of absorption of the drug then depends upon its rate of dissolution which, in turn, may depend upon crystal size and crystalline form.
- delayed absorption of a parenterally administered drug form is accomplished by dissolving or suspending the drug in an oil vehicle.
- injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polylactide-polyglycolide . Depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Examples of other biodegradable polymers include poly (orthoesters) and poly (anhydrides) Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions which are compatible with body tissues.
- Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules.
- the active compound is mixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and/or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid, b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia, c) humectants such as glycerol, d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, e) solution retarding agents such as paraffin, f) absorption accelerators such as quaternary ammonium compounds, g) wetting agents such as, for example, cetyl alcohol and gly
- the dosage form may also comprise buffering agents.
- Solid compositions of a similar type may also be employed as fillers in soft and hard- filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like.
- the solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient (s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner.
- coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient (s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner.
- embedding compositions which can be used include polymeric substances and waxes.
- compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like.
- the active compounds can also be in micro-encapsulated form with one or more excipients as noted above.
- the solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings, release controlling coatings and other coatings well known in the pharmaceutical formulating art.
- the active compound may be admixed with at least one inert diluent such as sucrose, lactose or starch.
- Such dosage forms may also comprise, as is normal practice, additional substances other than inert diluents, e.g., tableting lubricants and other tableting aids such a magnesium stearate and microcrystalline cellulose.
- the dosage forms may also comprise buffering agents. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient (s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner.
- buffering agents include polymeric substances and waxes .
- Powders and sprays can contain, in addition to the active compound of this invention, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates and polyamide powder, or mixtures of these substances.
- Sprays can additionally contain customary propellants such as chlorofluoro-hydrocarbons .
- Therapeutic Administration According to the method of treatment of the present invention, conditions subsumed under the above definition of chronic obstructive pulmonary disease (COPD) are treated in a patient in need of such treatment by administering to the patient a therapeutically effective amount of a compound of the invention, in such amounts and for such time as is necessary to achieve the desired result .
- COPD chronic obstructive pulmonary disease
- a “therapeutically effective amount” of a compound of the invention is meant a sufficient amount of the compound to effectively ameliorate the course of the disease and/or alleviate one or more symptoms of COPD, or improve the quality of life in a patient at a reasonable benefit/risk ratio applicable to any medical treatment . It will be understood, however, that the total daily usage of the compounds and compositions of the present invention will be decided by the attending physician within the scope of sound medical judgment.
- the specific therapeutically effective dose level for any particular patient will depend upon a variety of factors including the severity of the disorder; the activity of the compound employed; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the compound employed; the duration of the treatment; drugs used in combination or coincidental with the specific compound employed; and like factors well known in the medical arts. Since some of these parameters vary from patient to patient, it is a well-known technique utilized by medical practitioners to determine the proper dose for a particular patient by "dose titrating" the patient; that is, by using the technique of starting with a dose lower than that required to obtain the desired effect, and gradually increasing the dose over time until the desired therapeutic benefit is obtained.
- the total daily dose of the compounds of this invention administered to a human or other mammal in single or in divided doses can be in amounts ranging between about 0.5 mg/kg to about 20 mg/kg of body weight.
- Single dose compositions may contain such amounts or sub-multiples thereof to make up the daily dose.
- treatment regimens according to the present invention comprise administration to a patient in need of such treatment from about 50 mg to about 1000 mg, or more typically from about 250 mg to about 800 mg of the compound (s) of this invention per day in single or multiple doses.
- the study consisted of a two-week placebo lead-in period, followed by a fourteen-week double-blind treatment period. At the end of the two-week placebo lead-in period, eligibility of patients for entry into the fourteen-week double-blind period of the study was determined based upon study screening admission criteria and a review of the patient's diary entries and dosing compliance during the two-week lead-in.
- Table 1 shows the distribution of patients among the groups receiving placebo and various doses of the test compound .
- MW 12 measurements also indicated a favorable trend in the seratrodast groups, with between a 3.2% to 8.0% improvement over placebo.
- the Guyatt's quality of life instrument measured four categories: mastery, fatigue, dyspnea, and emotional functioning on a 1- to 7-point scale. On this scale, 1 represented “worst” and 7 represented “best” in terms of the symptom or quality being measured. Seratrodast-treated patients showed an improvement in all four categories when compared with placebo-treated patients, with the exception of the 160 mg group in the measurement of fatigue ( Figures 11- 14) .
- Patients also kept a diary during the study and recorded the following: daytime and nighttime symptoms; A.M. and P.M. PEFR (with the aid of a Wright peak flow meter) ;use of albuterol (beta agonist) , recording both the number of occasions of usage each day as well as the number of puffs administered per day.
- A.M. and P.M. PEFR with the aid of a Wright peak flow meter
- albuterol beta agonist
- cough- and sputum-related symptoms were measured using a Cough and Sputum Index. This questionnaire measured the following categories on a 1-5 or 7 point scale: cough frequency (1-5) ; cough severity (1-5) ; cough discomfort/tightness (1-5) ; need for the use of an aerosol bronchodilator (1-5) ; and ease in bringing up sputum on arising and throughout the day (1-7) .
Abstract
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Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE69924869T DE69924869T2 (en) | 1998-11-25 | 1999-11-24 | MEDICAMENT FOR THE TREATMENT OF CHRONIC OBSTRUCTIVE LUNG DISEASE |
AT99961803T ATE293443T1 (en) | 1998-11-25 | 1999-11-24 | MEDICINE FOR THE TREATMENT OF CHRONIC OBSTRUCTIVE LUNG DISEASE |
EP99961803A EP1135117B1 (en) | 1998-11-25 | 1999-11-24 | Medikament for treating chronic obstructive pulmonary disease |
AU18310/00A AU1831000A (en) | 1998-11-25 | 1999-11-24 | Method of treating chronic obstructive pulmonary disease |
JP2000583516A JP2002530329A (en) | 1998-11-25 | 1999-11-24 | Methods for treating chronic obstructive pulmonary disease |
DK99961803T DK1135117T3 (en) | 1998-11-25 | 1999-11-24 | Medication for the treatment of chronic obstructive pulmonary disease |
CA002352543A CA2352543A1 (en) | 1998-11-25 | 1999-11-24 | Method of treating chronic obstructive pulmonary disease |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US09/200,037 | 1998-11-25 | ||
US09/200,037 US6020380A (en) | 1998-11-25 | 1998-11-25 | Method of treating chronic obstructive pulmonary disease |
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WO2000030633A1 true WO2000030633A1 (en) | 2000-06-02 |
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Application Number | Title | Priority Date | Filing Date |
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PCT/US1999/027897 WO2000030633A1 (en) | 1998-11-25 | 1999-11-24 | Method of treating chronic obstructive pulmonary disease |
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US (1) | US6020380A (en) |
EP (1) | EP1135117B1 (en) |
JP (1) | JP2002530329A (en) |
AT (1) | ATE293443T1 (en) |
AU (1) | AU1831000A (en) |
CA (1) | CA2352543A1 (en) |
DE (1) | DE69924869T2 (en) |
DK (1) | DK1135117T3 (en) |
ES (1) | ES2241350T3 (en) |
PT (1) | PT1135117E (en) |
WO (1) | WO2000030633A1 (en) |
Families Citing this family (57)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5954766A (en) * | 1997-09-16 | 1999-09-21 | Zadno-Azizi; Gholam-Reza | Body fluid flow control device |
US6293951B1 (en) * | 1999-08-24 | 2001-09-25 | Spiration, Inc. | Lung reduction device, system, and method |
US6679264B1 (en) | 2000-03-04 | 2004-01-20 | Emphasys Medical, Inc. | Methods and devices for use in performing pulmonary procedures |
US20030070683A1 (en) | 2000-03-04 | 2003-04-17 | Deem Mark E. | Methods and devices for use in performing pulmonary procedures |
US20060020347A1 (en) * | 2004-03-08 | 2006-01-26 | Michael Barrett | Implanted bronchial isolation devices and methods |
US8474460B2 (en) * | 2000-03-04 | 2013-07-02 | Pulmonx Corporation | Implanted bronchial isolation devices and methods |
AU2001260611A1 (en) * | 2000-05-26 | 2001-12-03 | Takeda Chemical Industries Ltd. | Drugs acting on the bronchi |
US6623509B2 (en) | 2000-12-14 | 2003-09-23 | Core Medical, Inc. | Apparatus and methods for sealing vascular punctures |
US6846319B2 (en) * | 2000-12-14 | 2005-01-25 | Core Medical, Inc. | Devices for sealing openings through tissue and apparatus and methods for delivering them |
US6890343B2 (en) * | 2000-12-14 | 2005-05-10 | Ensure Medical, Inc. | Plug with detachable guidewire element and methods for use |
US6896692B2 (en) | 2000-12-14 | 2005-05-24 | Ensure Medical, Inc. | Plug with collet and apparatus and method for delivering such plugs |
US8083768B2 (en) | 2000-12-14 | 2011-12-27 | Ensure Medical, Inc. | Vascular plug having composite construction |
US20020112729A1 (en) * | 2001-02-21 | 2002-08-22 | Spiration, Inc. | Intra-bronchial obstructing device that controls biological interaction with the patient |
US7798147B2 (en) * | 2001-03-02 | 2010-09-21 | Pulmonx Corporation | Bronchial flow control devices with membrane seal |
US7011094B2 (en) * | 2001-03-02 | 2006-03-14 | Emphasys Medical, Inc. | Bronchial flow control devices and methods of use |
US20040074491A1 (en) * | 2001-03-02 | 2004-04-22 | Michael Hendricksen | Delivery methods and devices for implantable bronchial isolation devices |
US6743259B2 (en) | 2001-08-03 | 2004-06-01 | Core Medical, Inc. | Lung assist apparatus and methods for use |
US6645205B2 (en) | 2001-08-15 | 2003-11-11 | Core Medical, Inc. | Apparatus and methods for reducing lung volume |
US20030050648A1 (en) * | 2001-09-11 | 2003-03-13 | Spiration, Inc. | Removable lung reduction devices, systems, and methods |
AU2002347900B8 (en) * | 2001-10-11 | 2006-01-12 | Emphasys Medical, Inc. | Bronchial flow control devices and methods of use |
US6592594B2 (en) * | 2001-10-25 | 2003-07-15 | Spiration, Inc. | Bronchial obstruction device deployment system and method |
US20030154988A1 (en) * | 2002-02-21 | 2003-08-21 | Spiration, Inc. | Intra-bronchial device that provides a medicant intra-bronchially to the patient |
US20060235432A1 (en) * | 2002-02-21 | 2006-10-19 | Devore Lauri J | Intra-bronchial obstructing device that controls biological interaction with the patient |
US6929637B2 (en) * | 2002-02-21 | 2005-08-16 | Spiration, Inc. | Device and method for intra-bronchial provision of a therapeutic agent |
WO2003075796A2 (en) * | 2002-03-08 | 2003-09-18 | Emphasys Medical, Inc. | Methods and devices for inducing collapse in lung regions fed by collateral pathways |
US20030181922A1 (en) * | 2002-03-20 | 2003-09-25 | Spiration, Inc. | Removable anchored lung volume reduction devices and methods |
US20030216769A1 (en) | 2002-05-17 | 2003-11-20 | Dillard David H. | Removable anchored lung volume reduction devices and methods |
US20030195385A1 (en) * | 2002-04-16 | 2003-10-16 | Spiration, Inc. | Removable anchored lung volume reduction devices and methods |
EP1507491A1 (en) * | 2002-05-28 | 2005-02-23 | Emphasys Medical, Inc. | Implantable bronchial isolation devices and lung treatment methods |
US20040010209A1 (en) * | 2002-07-15 | 2004-01-15 | Spiration, Inc. | Device and method for measuring the diameter of an air passageway |
US20040059263A1 (en) * | 2002-09-24 | 2004-03-25 | Spiration, Inc. | Device and method for measuring the diameter of an air passageway |
EP1524942B1 (en) * | 2002-07-26 | 2008-09-10 | Emphasys Medical, Inc. | Bronchial flow control devices with membrane seal |
US7814912B2 (en) * | 2002-11-27 | 2010-10-19 | Pulmonx Corporation | Delivery methods and devices for implantable bronchial isolation devices |
WO2004049974A2 (en) * | 2002-11-27 | 2004-06-17 | Emphasys Medical, Inc. | Delivery method and device for implantable bronchial isolation devices |
US7100616B2 (en) * | 2003-04-08 | 2006-09-05 | Spiration, Inc. | Bronchoscopic lung volume reduction method |
US7200559B2 (en) * | 2003-05-29 | 2007-04-03 | Microsoft Corporation | Semantic object synchronous understanding implemented with speech application language tags |
US7533671B2 (en) * | 2003-08-08 | 2009-05-19 | Spiration, Inc. | Bronchoscopic repair of air leaks in a lung |
US8852229B2 (en) * | 2003-10-17 | 2014-10-07 | Cordis Corporation | Locator and closure device and method of use |
US7361183B2 (en) | 2003-10-17 | 2008-04-22 | Ensure Medical, Inc. | Locator and delivery device and method of use |
US20050178389A1 (en) * | 2004-01-27 | 2005-08-18 | Shaw David P. | Disease indications for selective endobronchial lung region isolation |
US8206684B2 (en) * | 2004-02-27 | 2012-06-26 | Pulmonx Corporation | Methods and devices for blocking flow through collateral pathways in the lung |
US20060030863A1 (en) * | 2004-07-21 | 2006-02-09 | Fields Antony J | Implanted bronchial isolation device delivery devices and methods |
WO2006009209A1 (en) * | 2004-07-22 | 2006-01-26 | Kaken Pharmaceutical Co., Ltd. | Preventive or therapeutic agent for chronic inflammatory lung disease |
US7771472B2 (en) * | 2004-11-19 | 2010-08-10 | Pulmonx Corporation | Bronchial flow control devices and methods of use |
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US8926654B2 (en) | 2005-05-04 | 2015-01-06 | Cordis Corporation | Locator and closure device and method of use |
US8088144B2 (en) * | 2005-05-04 | 2012-01-03 | Ensure Medical, Inc. | Locator and closure device and method of use |
US7691151B2 (en) | 2006-03-31 | 2010-04-06 | Spiration, Inc. | Articulable Anchor |
US7829986B2 (en) * | 2006-04-01 | 2010-11-09 | Stats Chippac Ltd. | Integrated circuit package system with net spacer |
WO2008027293A2 (en) * | 2006-08-25 | 2008-03-06 | Emphasys Medical, Inc. | Bronchial isolation devices for placement in short lumens |
WO2009007674A2 (en) * | 2007-07-11 | 2009-01-15 | Cardoz Ab | Combination for use in the treatment of atherosclerosis comprising a mast cell inhibitor and ramatroban or seratrodast |
EP2194933B1 (en) | 2007-10-12 | 2016-05-04 | Spiration, Inc. | Valve loader method, system, and apparatus |
US8043301B2 (en) * | 2007-10-12 | 2011-10-25 | Spiration, Inc. | Valve loader method, system, and apparatus |
US8795241B2 (en) | 2011-05-13 | 2014-08-05 | Spiration, Inc. | Deployment catheter |
US9994901B2 (en) * | 2012-04-09 | 2018-06-12 | National Jewish Health, A Non-Profit Organization | Pro-inflammatory mediators in diagnosis and treatment of chronic obstructive pulmonary disease |
US20150269348A1 (en) * | 2014-03-24 | 2015-09-24 | AsthmaMD, Inc. | Systems and methods for health management |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5304658A (en) * | 1984-08-01 | 1994-04-19 | Takeda Chemical Industries, Ltd. | Quinone derivatives, their production and use |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MX9203040A (en) * | 1984-08-01 | 1992-07-31 | Takeda Chemical Industries Ltd | DERIVATIVES OF QUINONA AND PHARMACEUTICAL COMPOSITION THAT CONTAINS THEM. |
WO1986000887A1 (en) * | 1984-08-01 | 1986-02-13 | Takeda Chemical Industries, Ltd. | Quinone derivatives, process for their preparation, and medicinal composition containing the same |
WO1987001698A2 (en) * | 1985-09-20 | 1987-03-26 | The Upjohn Company | 1,4-naphthalenediol and 1,4-hydroquinone derivatives |
US4939169A (en) * | 1985-09-20 | 1990-07-03 | The Upjohn Company | 1,4-naphthalenediol and 1,4-hydroquinone derivatives |
US4808627A (en) * | 1987-12-16 | 1989-02-28 | E. R. Squibb & Sons, Inc. | Method of preventing or treating toxemia in pregnancy using a thromboxane A2 receptor antagonist |
US5021448A (en) * | 1990-02-22 | 1991-06-04 | Ciba-Geigy Corporation | Method of reducing serum uric acid and/or increasing renal uric acid clearance with thromboxane synthetase inhibitor inhibitor and/or thromboxane receptor antagonist |
US5096916A (en) * | 1990-05-07 | 1992-03-17 | Aegis Technology, Inc. | Treatment of chronic obstructive pulmonary disease (copd) by inhalation of an imidazoline |
US5534548A (en) * | 1994-05-03 | 1996-07-09 | Tap Pharmaceuticals, Inc. | Method of treating preeclampsia |
-
1998
- 1998-11-25 US US09/200,037 patent/US6020380A/en not_active Expired - Fee Related
-
1999
- 1999-11-24 WO PCT/US1999/027897 patent/WO2000030633A1/en active IP Right Grant
- 1999-11-24 JP JP2000583516A patent/JP2002530329A/en active Pending
- 1999-11-24 AT AT99961803T patent/ATE293443T1/en not_active IP Right Cessation
- 1999-11-24 AU AU18310/00A patent/AU1831000A/en not_active Abandoned
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- 1999-11-24 PT PT99961803T patent/PT1135117E/en unknown
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Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5304658A (en) * | 1984-08-01 | 1994-04-19 | Takeda Chemical Industries, Ltd. | Quinone derivatives, their production and use |
Non-Patent Citations (2)
Title |
---|
AIZAWA H ET AL: "Effects of thromboxane A2 antagonist on airway hyperresponsiveness, exhaled nitric oxide, and induced sputum eosinophils in asthmatics.", PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, (1998 SEP) 59 (3) 185-90., XP000881579 * |
SAMARA E ET AL: "Population analysis of the pharmacokinetics and pharmacodynamics of seratrodast in patients with mild to moderate asthma.", CLINICAL PHARMACOLOGY AND THERAPEUTICS, (1997 OCT) 62 (4) 426-35., XP000881569 * |
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AU1831000A (en) | 2000-06-13 |
JP2002530329A (en) | 2002-09-17 |
EP1135117A1 (en) | 2001-09-26 |
CA2352543A1 (en) | 2000-06-02 |
EP1135117B1 (en) | 2005-04-20 |
ATE293443T1 (en) | 2005-05-15 |
ES2241350T3 (en) | 2005-10-16 |
DE69924869T2 (en) | 2006-03-09 |
US6020380A (en) | 2000-02-01 |
PT1135117E (en) | 2005-08-31 |
DK1135117T3 (en) | 2005-08-15 |
DE69924869D1 (en) | 2005-05-25 |
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