WO1998017231A2 - Traitement et administration d'hydroxychloroquine - Google Patents
Traitement et administration d'hydroxychloroquine Download PDFInfo
- Publication number
- WO1998017231A2 WO1998017231A2 PCT/US1997/019170 US9719170W WO9817231A2 WO 1998017231 A2 WO1998017231 A2 WO 1998017231A2 US 9719170 W US9719170 W US 9719170W WO 9817231 A2 WO9817231 A2 WO 9817231A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- see
- hcq
- asthma
- treatment
- hydroxychloroquine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
Classifications
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4706—4-Aminoquinolines; 8-Aminoquinolines, e.g. chloroquine, primaquine
Definitions
- Hydroxychloroquine (HCQ) and other members of this anti-malarial class of drugs have been administered per ora and been found useful as therapeutic systemic anti-inflammatory agents for a variety of serious inflammatory and auto-immune diseases such as rheumatoid arthritis and lupus erythematosus for much of the last half century.
- HCQ has a remarkably wide range of actions including antagonist activity to histamine and antigen-induced bronchospasm and reduction of antibody responses, particularly those involving production of allergic antibody.
- Other actions relevant to the anti-asthmatic anti-allergic actions contained in this application include alterations in cell-mediated immunity, alterations in mediator effects and pathways, including evidence for inhibition of the arachidonic pathway cascade which results in the production of potent spasmogenic and inflammatory mediators such as leukotrienes, some novel and potentially important antiviral actions as well as other significant miscellaneous anti-inflammatory effects.
- HCQ is thought to inhibit T-cell participation in the immune response both through the inhibition of APC antigen presentation (see references above) coupled with direct alteration of surface markers on lymphocytes [and platelets], (Fox R, Kang H. Mechanism of action of antimalarial drugs: inhibition of antigen processing and presentation. Lupus 1993;2(1):S9-12.) (Nordhagen R, Flaathen S. Chloroquine removal of HLA antigens from platelets for the platelet immunofluorescence test. Vox Sang 1985;48: 156-59.) (Nagarkatti P, Nagarkatti M, Jain V. In vivo and in vitro action of chloroquine on surface markers of human peripheral lymphocytes.
- HCQ inhibits both leukotriene and histamine release from human lung. See, Kench JG, Seale JP, Temple DM, et al. The Effects of Non-steroidal Inhibitors of Phospholipase A2 on Leukotriene and Histamine Release from Human and Guinea Pig Lung. Prostaglandins 1985;30(2): 199-207. This finding is not unexpected, given the fact that the anti-malarials have found common usage as phospholipase A2 inhibitors in a wide variety of tissues, (Matsuzawa Y, Hostetler KY.
- cytokines such as IL-1, IL-6 and tumor necrosis factor
- alveolar macrophages such as IL-1, IL-6 and tumor necrosis factor
- IL-6 tumor necrosis factor
- Histamine activates bronchial epithilial cells to release inflammatory cytokines in vitro.
- Nit Arch Allergy Immunol 1995;108(3):260-67. See, Zitnik R, Whiting N, Elias J.
- HCQ is also known to inhibit platelet aggregation, (Winocour P, Kinlough-Rathbone R, Mustard J. The effect of the phospholipase inhibitor mepacrine on platelet aggregation, the platelet release reaction and fibrinogen binding to the platelet surface. Thrombos. Haemostas 1981;45(3):257-62.) and is commonly used as prophylaxis against thromboembolism after total hip replacement at some centers. See, Loudon J. Hydroxychloroquine and postoperative thromboembolism after total hip replacement. American Journal of Medicine 1988;85(4A):57-61.
- Hydroxychloroquine is currently available only by oral dosing. It is used as primary therapy as a disease-modifying agent anti- rheumatic agent for such diseases as rheumatoid arthritis and lupus erythematosus where it has achieved recognition for a low side effect profile and cost. See, Ostensen M. Treatment with immunosuppressive and disease modifying drugs during pregnancy and lactation. Am J Reprod Immunol 1992;28: 148-52. See, Parke A. Antimalarial drugs, pregnancy and lactation. Lupus 1993;2:S21-3. In comparison with currently available alternative therapies, its safety profile recommends its use in women exposed to pregnancy during treatment and in some more severe cases even during gestation.
- HCQ hypergammaglobulinemia of Waldenstrom associated with systemic lupus erythematosus (Soukasian S, Foster C, Raizman M. Treatment strategies for scleritis and uveitis associated with inflammatory bowel disease. Am J Opthalmol 1994; 118:601-11.) (Mathur A, Kremer J. Immunopathology, rheumatic features, and the therapy of sarcoidosis.
- This invention represents and is directed to the treatment of various disease states and/or an improved delivery of HCQ.
- the invention overcomes certain well-known problems and deficiencies in current therapies and treatment regimes.
- HCQ HCQ
- Perennial bronchial asthma is a common disease pathologically marked by hyper-reactive airways, inflammation and edema of the bronchial epithelium and mucus secretory abnormalities.
- the clinical spectrum of asthma is quite broad— ranging from patients who have only very mild evanescent attacks to patients who have severe umemitting and often disabling asthma only poorly responsive to treatment with intense multi-drug therapy.
- cromolyn sodium, nedocromil sodium and corticosteroids have specific anti-inflammatory actions.
- cromolyn and nedocromil have the capability to prevent late-phase reactions, their actions appear to be relatively mild and they are useful only in mild cases of asthma or as prophylaxis for challenge-induced bronchospasm (e.g., exercise). See, Cockcroft DW. Therapy for airway inflammation in asthma. Journal of Allergy and Clinical Immunology 1991 ;87(5):914-919.
- corticosteroid family of drugs has unique actions in the treatment of asthma: active reduction of bronchial edema and mucus secretion, with demonstrable reduction of bronchial hyperactivity.
- active reduction of bronchial edema and mucus secretion with demonstrable reduction of bronchial hyperactivity.
- corticosteroids appear to synergize with spasmolytic agents in promoting relaxation of bronchial smooth muscle spasm.
- IVIG intravenous immune globulin
- plasmapheresis are an economically unfeasible alternative.
- HCQ Observations concerning HCQ have also included pre- and post- treatment IgE levels, summarized in Table VI.
- IgE levels In general treatment with HCQ led to substantial reduction in serum IgE levels, amounting to approximately a 40% decrease.
- Significant declines in IgE were virtually completely confined to that segment of the patients who entered treatment with elevated IgE levels.
- HCQ appears to act as an immuno- modulator for circulating IgE rather than simply as an immuno-suppressive.
- sensitivity to house dust mite allergen is a predictor of the subsequent development of asthma in children. See, Sporik R, Holgate S, Platts-Mills T, et al. Exposure to house-dust mite allergen (Der p I) and the development of asthma in childhood. NEJM 1990;323(8):502-07.
- a topically administered agent which reduces IgE production such as HCQ, may be useful to help reduce the stimulus to bronchial inflammation caused by allergic reactions to these and other inhalants.
- Involuntary sytems i.e., nocturnal asthma
- the steroid-sparing is similar to alternate experimental modalities.
- Prior trials of new drugs have failed to induce similar effect. These improvements are evidenced despite decreased usage of conventional prescriptions.
- HCQ Compared to alternative systemic agents, use of HCQ, as shown herein, provides unmatched safety, side effect, and cost profile; anti-asthmatic effects are matched only by CsA; and IgE immunomodulating effects are matched only by Au.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
La présente invention concerne le traitement par l'hydroxychloroquine de différents états pathologiques.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2863896P | 1996-10-18 | 1996-10-18 | |
| US60/028,638 | 1996-10-18 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1998017231A2 true WO1998017231A2 (fr) | 1998-04-30 |
| WO1998017231A3 WO1998017231A3 (fr) | 1998-10-08 |
Family
ID=21844595
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1997/019170 Ceased WO1998017231A2 (fr) | 1996-10-18 | 1997-10-17 | Traitement et administration d'hydroxychloroquine |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO1998017231A2 (fr) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7183112B2 (en) | 1999-04-30 | 2007-02-27 | Apt Pharmaceuticals, Llc | Uses for anti-malarial therapeutic agents |
| EP3317274A4 (fr) * | 2015-06-30 | 2019-05-08 | Eiger Group International, Inc. | Utilisation de composés de chloroquine et de clémizole pour le traitement d'états pathologiques inflammatoires et cancéreux |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4181725A (en) * | 1977-05-02 | 1980-01-01 | The Regents Of The University Of Michigan | Method for alleviating psoriasis |
-
1997
- 1997-10-17 WO PCT/US1997/019170 patent/WO1998017231A2/fr not_active Ceased
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7183112B2 (en) | 1999-04-30 | 2007-02-27 | Apt Pharmaceuticals, Llc | Uses for anti-malarial therapeutic agents |
| EP3317274A4 (fr) * | 2015-06-30 | 2019-05-08 | Eiger Group International, Inc. | Utilisation de composés de chloroquine et de clémizole pour le traitement d'états pathologiques inflammatoires et cancéreux |
| US10688083B2 (en) | 2015-06-30 | 2020-06-23 | Eiger Group International, Inc. | Use of chloroquine and clemizole compounds for treatment of inflammatory and cancerous conditions |
| AU2016288699B2 (en) * | 2015-06-30 | 2020-11-26 | Eiger Group International, Inc. | Use of chloroquine and clemizole compounds for treatment of inflammatory and cancerous conditions |
| US12090141B2 (en) | 2015-06-30 | 2024-09-17 | Eiger Group International, Inc. | Use of clemizole compounds for treatment of inflammatory conditions |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1998017231A3 (fr) | 1998-10-08 |
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