SK111894A3 - Pharmaceutical agents for treatment of granulomatese and fibrously pulmonary illnesess - Google Patents
Pharmaceutical agents for treatment of granulomatese and fibrously pulmonary illnesess Download PDFInfo
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- SK111894A3 SK111894A3 SK1118-94A SK111894A SK111894A3 SK 111894 A3 SK111894 A3 SK 111894A3 SK 111894 A SK111894 A SK 111894A SK 111894 A3 SK111894 A3 SK 111894A3
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- treatment
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- pentoxifylline
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
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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
- 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
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- 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
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- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
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- General Health & Medical Sciences (AREA)
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- Animal Behavior & Ethology (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
Oblasť technikyTechnical field
Vynález sa týka použitia pentoxifylínu na liečbu granulomatóznych a fibrotizujúcich pľúcnych chorôb.The invention relates to the use of pentoxifylline for the treatment of granulomatous and fibrotic pulmonary diseases.
Doterajší stav technikyBACKGROUND OF THE INVENTION
Pľúcna granulomatóza predstavuje chorobné zmnoženie väzobného tkaniva v pľúcnej sieťovine, ktorá vzniká účinkom rôznych škodlivín na pľúca. Škodliviny, ktoré pôsobia na vznik granulomatózneho ochorenia pľúc sú mykobaktérie, imunokomplexy, protilátky ako aj rada iných substancií. Naopak u sarkoidózy je stimul nezmámy. Pri sarkoidóze ide o systémové granulomatózne ochorenie neznámej etiológie, ktoré zvyčajne vedie ku granulomatóznym zmenám v pľúcach a hilových lymfatických uzlinách. Fakultatívne môžu byť zahrnuté do procesu systémového ochorenia všetky orgány, predovšetkým CNS, pečeň, srdce, oči a kosti. Pulinonálne zmeny môžu prechádzať pri chronickej aktivite procesu na ireverzibilnú pľúcnu fibrózu s trvalým orgánovýcm poškodením.Pulmonary granulomatosis is a disease-related multiplication of connective tissue in the pulmonary meshwork, which results from various harmful effects on the lungs. The harmful substances that cause the development of granulomatous lung disease are mycobacteria, immunocomplexes, antibodies as well as many other substances. In contrast, in sarcoidosis, the stimulus is immense. Sarcoidosis is a systemic granulomatous disease of unknown etiology, which usually results in granulomatous changes in the lungs and hilic lymph nodes. Optionally, all organs, especially the CNS, liver, heart, eyes and bones, can be involved in the systemic disease process. Pulinonal changes may turn into irreversible pulmonary fibrosis with permanent organ damage in chronic process activity.
Prostriedkom voľby je pre terapiu uvedených pľúcnych chorôb podľa stavu techniky symptomatická, systémová kortikosteroidná terapia. Keďže ide o dlhodobú kortikosteroidná terapiu s dávkami nad Cushingov prah, môže dochádzať k obvyklým vedľajším účinkom vyvolaných kortikosteroidmi. V prípade fibrotizujúcich pľúcnych chorôb sa podľa etiológie doporučuje podľa stavu techniky kortikosteroidná terapia buď samotná, alebo v kombinácii s ďalšími iinunosupresívami a cytostatikami. Celkovo však možno konštatovať, že vyššie percento pľúcnych fibróz neodpovedá na žiadnu z uvedených terapeutických foriem, nakoľko je potrebná dlhodobá liečba s uvedenými substanciami a tomu zodpovedajúcimi drastickými vedľajšími účinkami. Pľúcna fibróza, vznikajúca v rámci systémovej sklerodermie, pravidelne neodpovedá na žiadnu doposiaľ známu terapiu, takže skleroderiniou progradovaná fibrotizácia pľúc vedie k úmrtiu.The means of choice is the symptomatic, systemic corticosteroid therapy for the treatment of said pulmonary diseases of the prior art. As it is a long-term corticosteroid therapy with doses above the Cushing threshold, the usual corticosteroid-induced side effects may occur. In the case of fibrotic lung diseases, corticosteroid therapy, either alone or in combination with other immunosuppressants and cytostatics, is recommended by the prior art according to the prior art. Overall, however, it can be stated that a higher percentage of pulmonary fibrosis does not respond to any of these therapeutic forms, as long-term treatment with these substances and corresponding drastic side effects is required. Pulmonary fibrosis, resulting from systemic scleroderma, does not respond regularly to any of the therapies known so far, so that scleroderma-mediated lung fibrosis leads to death.
Podstata vynálezuSUMMARY OF THE INVENTION
Zistilo sa, že pentoxifylín je vhodný na liečbu uvedených chorôb bez toho, aby dochádzalo k vedľajším účinkom, ktoré sú spojené s doteraz známymi liečebnými postupmi.It has been found that pentoxifylline is suitable for the treatment of these diseases without the side effects associated with the hitherto known treatments.
V rámci otvorenej terapeutickej štúdie sa zistilo, že u pacientov s bronchoskopicky dokázanou intratorakálnou sarkoidózou, títo odpovedajú v 80 % prípadov na zodpovedajúce liečenie pentoxifylínom 4 až 5 x 400 mg per os/deň po 3 až 6 mesiacoch. Ukazuje sa zmenšovanie rádiologických zmien v oblasti pľúc a hilových lymfatických uzlín, alebo zlepšenie až normalizácia funkčných parametrov pľúc. V asi 30 % prípadov dochádzalo po ukončení pentoxifylínovej terapie po 6 mesiacoch k obnovenej aktivite ochorenia, ktorá po obnovení pentoxifylínovej terapie sa opäť zastavila. Bohužiaľ, v 16 % prípadov sa zistilo, že nedochádza k žiadnej odpovedi na pentoxifylín a až kombináciou terapií, ktoré pozostávali z pentoxifylínu a kortikosteroidov, mohlo byť dosiahnuté rádiologické zlepšenie a zlepšenie funkcie pľúc s udržovanou remisiou.In an open-label therapeutic study, it was found that in patients with bronchoscopically proven intratoracal sarcoidosis, these respond in 80% of cases to corresponding pentoxifylline treatment of 4 to 5 x 400 mg per os / day after 3 to 6 months. It has been shown that the radiological changes in the lungs and hilic lymph nodes are diminishing, or the lung function parameters are improved or normalized. In about 30% of cases, after the end of the pentoxifylline therapy, the disease activity was restored after 6 months and stopped again after the pentoxifylline therapy was resumed. Unfortunately, in 16% of the cases it was found that there was no response to pentoxifylline and only a combination of therapies consisting of pentoxifylline and corticosteroids could achieve radiological improvement and improved lung function with sustained remission.
Použitá dávka pentoxifylínu prirodzene závisí na závažnosti ochorenia, stavu a hmotnosti liečených pacientov. Všeobecne však predstavuje 1.00 až 3.00 g/deň a výhodne 1.20 až 2.50 g/deň.The dose of pentoxifylline used naturally depends on the severity of the disease, the condition and the weight of the patients treated. However, it is generally from 1.00 to 3.00 g / day and preferably from 1.20 to 2.50 g / day.
Pentoxxfylín môže, ako už bolo uvedené, byť použitý v kombinácii s kortikosteroidini. Výhodnými kortikosteroidmi sú prednison, prednisolon, prednisolon-21-acetát, prednyliden a metylprednison. Koncentrácia použitých kortikosteroidov predstavuje v. počiatočnej fáze (asi 2 týždne) 0.3 až 1.2 mg, výhodne 0.5 až 1.0 mg/kg telesnej hmotnosti. Po počiatočnej fáze nasleduje pomalé znižovanie dávky na udržovaciu dávku 2.5 až 7.5 mg/den, výhodne 10 až 20 mg/deň.As already mentioned, pentoxxphylline can be used in combination with corticosteroidini. Preferred corticosteroids are prednisone, prednisolone, prednisolone-21-acetate, prednylidene and methylprednisone. The concentration of corticosteroids used is in. Initial phase (about 2 weeks) 0.3 to 1.2 mg, preferably 0.5 to 1.0 mg / kg body weight. The initial phase is followed by a slow dose reduction to a maintenance dose of 2.5 to 7.5 mg / day, preferably 10 to 20 mg / day.
Výhodná aplikácia prípravkov je per os, sú však tiež možné iné formy podávania.The preferred application of the formulations is per os, but other forms of administration are also possible.
Príklady uskutočnenia vynálezuDETAILED DESCRIPTION OF THE INVENTION
Príklad 1 • Pacient mužského pohlavia (51 rokov, 88 kg, W.L.), ktorý mal už 7 rokov známu progresívnu systémovú sklerodermiu (Raynaudov fenomén na akroch s nekrózou na prstoch ruky a nohy, poruchy prehltania v oblasti ezofágu, fibróza pľúc s vysoko gradovanou respiračnou parciálnou nedostatočnosťou), bol bez účinku liečený podľa rôznych imunosupresívnych terapeutických schém (vysoké dávky kortikosteroidov s cyklofosfamidom, plazmová separácia s cyklofosfamidovou nárazovou terapiou, kortikosteroidmi s cyklosporínom A). Po 3 mesačnej liečbe kombináciou pentoxifylínu (5 x 400 mg perorálne/deň) s kortikosteroidmi v klesajúcej dávke až na udržovaciu terapiu 10 mg metylprednisolonu perorálne/deň sa dostavil významný rádiologický nález regresie fibrotizujúcich zmien, normalizácia krvnéhu plynu za kľudu, vymiznutie porúch prehltania a uzdravenie nekróz v oblasti akrov. Doposiaľ je zachovaná remisia viac ako 1 rok pri pokračovaní uvedenej • terapie.Example 1 • A male patient (51 years, 88 kg, WL) who has been known for 7 years with progressive systemic scleroderma (Raynaud's phenomenon on acres with toes and toes, swallowing disorders in the esophagus, lung fibrosis with highly graded respiratory tract has been treated without effect according to various immunosuppressive therapeutic regimens (high doses of corticosteroids with cyclophosphamide, plasma separation with cyclophosphamide shock therapy, corticosteroids with cyclosporin A). After 3 months of treatment with the combination of pentoxifylline (5 x 400 mg orally / day) with corticosteroids at a decreasing dose up to maintenance therapy of 10 mg methylprednisolone orally / day, a significant radiological finding of fibrosis change regression, normalization of blood gas at rest and disappearance of disorders necrosis in acres. To date, remission has been maintained for more than 1 year while continuing the therapy.
' Príklad 2Example 2
Pacient mužského pohlavia (45 rokov, 61 kg, R.S.), ktorý má už 6 rokov diagnostikovanú progresívnu sklerodermiu (poruchy prehltania pri ezofágu, fibróza pľúc s respiračnou globálnou nedostatočnosťou), dlhodobá kyslíková terapia, neodpovedal na najrôznejšie imunosupresívne stratégie. Pri kombinácii pentoxifylínu (4 x 400 mg perorálne/deň) s kortikosteroidmi v klesajúcej dávke až na dávku 20 mg metylprednisolonu perorálne/deň nastalo po 6 mesiacoch terapie vynikajúce zlepšenie parametrov funkcie pľúc (respiračná parciálna nedostatočnosť).A male patient (45 years, 61 kg, R.S.), who has been diagnosed for 6 years with progressive scleroderma (esophageal swallowing disorders, lung fibrosis with respiratory global insufficiency), long-term oxygen therapy, did not respond to a variety of immunosuppressive strategies. Combination of pentoxifylline (4 x 400 mg orally / day) with corticosteroids at decreasing doses up to 20 mg methylprednisolone orally / day resulted in an excellent improvement in lung function parameters (respiratory partial insufficiency) after 6 months of therapy.
Príklady 3 až 7 pacientov (žena 28 rokov, C.W.; žena 45 rokov, D.H.; muž, 48 rokov, K.K.; muž 24 rokov, G.H.; muž 42 rokov, J.S.) vykazuje terapeutickú odpoveď, ktorá je dokumentovaná zmenšovaním rádiologickým zmien v oblasti plúc a hilových uzlín a/alebo zlepšením až normalizáciou parametra funkcie pľúc. Pancienti dostávali len * pentoxifylín v dávke 4 x 400 mg perorálne/deň.Examples of 3 to 7 patients (female 28 years, CW; female 45 years, DH; male, 48 years, KK; male 24 years, GH; male 42 years, JS) show a therapeutic response documented by decreasing lung radiological changes and helix nodes and / or by improving or normalizing the lung function parameter. Pancients received only pentoxifylline at a dose of 4 x 400 mg orally / day.
’ Príklad 8Example 8
Pacient (muž, 31 rokov, H.G.) nereagoval na pentoxifylín žiadnou odpoveďou zmeny aktivity choroby, takže terapia bola zmenená na kortikosteroidnú terapiu. Keď sa tiež pri nej po 6 týždňoch neobjavil žiaden účinok, bol liečený kombináciou pentoxifylínu s kortikosteroidmi (4 x 400 mg perorálne/deň a 60 mg metylprednysolonu perorálne/deň). Po dvoch týždňoch sa objavilo zlepšenie, dokumentovateľné rádiologický, na funkcii pľúc, teda dávka kortikosteroidov mohla byť znížená až na udržovaciu dávku 10 mg/deň. Remisia pretrváva ešte po 9 mesiacoch.The patient (male, 31 years, H.G.) did not respond to pentoxifylline by any response to disease activity change, so the therapy was changed to corticosteroid therapy. Also, when there was no effect after 6 weeks, he was treated with a combination of pentoxifylline with corticosteroids (4 x 400 mg oral / day and 60 mg methylprednysolone oral / day). After two weeks there was an improvement, documented radiologically, in lung function, thus the corticosteroid dose could be reduced to a maintenance dose of 10 mg / day. Remission persists after 9 months.
Príklady 9 až 10Examples 9 to 10
U 2 pacientov (žena, 28 rokov, G.W.; žena, 45 rokov, D.H.) 1 nastalo po ukončení pentoxifylínovej terapie po 6 mesiacoch obnovenie aktivity ochorenia, ktorá opätovne prestala pri znovuzavedení pentoxifylínovej terapie 4 x 400 mg/deň. Obe pacientky naviac dostávali 10 mg prednisonu/deň, ktorý sa podával perorálne.In 2 patients (female, 28 years, GW; female, 45 years, DH) 1, after the end of pentoxifylline therapy, the disease activity resumed after 6 months, which resumed upon reintroduction of pentoxifylline 4 x 400 mg / day. In addition, both patients received 10 mg of prednisone / day administered orally.
Claims (3)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE4332041A DE4332041C2 (en) | 1993-09-21 | 1993-09-21 | Use of pentoxifylline in certain lung diseases |
Publications (1)
Publication Number | Publication Date |
---|---|
SK111894A3 true SK111894A3 (en) | 1995-05-10 |
Family
ID=6498198
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SK1118-94A SK111894A3 (en) | 1993-09-21 | 1994-09-16 | Pharmaceutical agents for treatment of granulomatese and fibrously pulmonary illnesess |
Country Status (7)
Country | Link |
---|---|
EP (1) | EP0670163A1 (en) |
JP (1) | JPH07247215A (en) |
CZ (1) | CZ230094A3 (en) |
DE (1) | DE4332041C2 (en) |
HU (1) | HUT70054A (en) |
NO (1) | NO943288L (en) |
SK (1) | SK111894A3 (en) |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6294350B1 (en) * | 1997-06-05 | 2001-09-25 | Dalhousie University | Methods for treating fibroproliferative diseases |
FR2779063A1 (en) * | 1998-05-29 | 1999-12-03 | Assist Publ Hopitaux De Paris | PENTOXIFYLLIN COMPOSITIONS AND THEIR THERAPEUTIC USE |
AR029189A1 (en) * | 1999-11-02 | 2003-06-18 | Smithkline Beecham Corp | USE OF A PHOSPHODIESTERASE 4 INHIBITOR AND AN ANTI-INFLAMMATORY CORTICOESTEROID IN COMBINED FORM, SEPARATELY OR SEPARATELY SEQUENTIALLY FOR THE PREPARATION OF A MEDICINAL PRODUCT |
EP1297848A4 (en) * | 2000-06-16 | 2004-05-19 | Chugai Pharmaceutical Co Ltd | Preventives/remedies for granuloma |
WO2004067006A1 (en) * | 2003-01-27 | 2004-08-12 | Pharmacia Corporation | Combination of a pde iv inhibitor and a tnf-alpha antagonist |
CA2581816A1 (en) * | 2004-09-27 | 2006-04-06 | Sigmoid Biotechnologies Limited | Microcapsules comprising a methylxanthine and a corticosteroid |
CA2683409A1 (en) | 2007-04-04 | 2008-10-16 | Sigmoid Pharma Limited | A pharmaceutical composition of tacrolimus |
EP2432455B1 (en) | 2009-05-18 | 2014-11-12 | Sigmoid Pharma Limited | Composition comprising oil drops |
CA2770570A1 (en) | 2009-08-12 | 2011-02-17 | Sigmoid Pharma Limited | Immunomodulatory compositions comprising a polymer matrix and an oil phase |
GB201020032D0 (en) | 2010-11-25 | 2011-01-12 | Sigmoid Pharma Ltd | Composition |
GB201212010D0 (en) | 2012-07-05 | 2012-08-22 | Sigmoid Pharma Ltd | Formulations |
GB201304662D0 (en) | 2013-03-14 | 2013-05-01 | Sigmoid Pharma Ltd | Compositions |
KR101512223B1 (en) * | 2013-02-22 | 2015-04-24 | 가톨릭대학교 산학협력단 | anti-cancer adjuvant comprising pentoxifylline |
PL3215127T3 (en) | 2014-11-07 | 2021-05-17 | Sublimity Therapeutics Limited | Compositions comprising cyclosporin |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5192528A (en) * | 1985-05-22 | 1993-03-09 | Liposome Technology, Inc. | Corticosteroid inhalation treatment method |
-
1993
- 1993-09-21 DE DE4332041A patent/DE4332041C2/en not_active Expired - Fee Related
-
1994
- 1994-08-09 EP EP94112421A patent/EP0670163A1/en not_active Withdrawn
- 1994-09-06 NO NO943288A patent/NO943288L/en unknown
- 1994-09-16 SK SK1118-94A patent/SK111894A3/en unknown
- 1994-09-20 HU HU9402709A patent/HUT70054A/en unknown
- 1994-09-20 CZ CZ942300A patent/CZ230094A3/en unknown
- 1994-09-20 JP JP6224801A patent/JPH07247215A/en active Pending
Also Published As
Publication number | Publication date |
---|---|
DE4332041A1 (en) | 1995-03-23 |
CZ230094A3 (en) | 1995-04-12 |
JPH07247215A (en) | 1995-09-26 |
EP0670163A1 (en) | 1995-09-06 |
NO943288D0 (en) | 1994-09-06 |
NO943288L (en) | 1995-03-22 |
DE4332041C2 (en) | 1997-12-11 |
HUT70054A (en) | 1995-09-28 |
HU9402709D0 (en) | 1995-02-28 |
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