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EP0863759A1 - Utilisation d'une combinaison de pentoxifylline et d'interferons de type i pour le traitement de la sclerose en plaques - Google Patents

Utilisation d'une combinaison de pentoxifylline et d'interferons de type i pour le traitement de la sclerose en plaques

Info

Publication number
EP0863759A1
EP0863759A1 EP96938998A EP96938998A EP0863759A1 EP 0863759 A1 EP0863759 A1 EP 0863759A1 EP 96938998 A EP96938998 A EP 96938998A EP 96938998 A EP96938998 A EP 96938998A EP 0863759 A1 EP0863759 A1 EP 0863759A1
Authority
EP
European Patent Office
Prior art keywords
interferon
pentoxifylline
type
combination
million
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.)
Withdrawn
Application number
EP96938998A
Other languages
German (de)
English (en)
Inventor
Peter Rieckmann
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Dr Rentschler Arzneimittel GmbH and Co KG
Original Assignee
Dr Rentschler Arzneimittel GmbH and Co KG
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Dr Rentschler Arzneimittel GmbH and Co KG filed Critical Dr Rentschler Arzneimittel GmbH and Co KG
Publication of EP0863759A1 publication Critical patent/EP0863759A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/21—Interferons [IFN]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system

Definitions

  • the invention relates to the combination of pentoxifylline and type I interferons for the treatment of relapsing multiple sclerosis, including relapsing and secondary progressive MS.
  • the invention relates to a combined use of ⁇ -interferon by subcutaneous injections together with pentoxifylline in the form of orally administrable medicinal products in relapsing multiple sclerosis.
  • the invention is characterized in the form of the combined use and of combination preparations in the claims.
  • German patent specification No. 43 43 034 there is also the possibility of applying a combination of the pentoxifylline together with corticosteroids for acute therapy of multiple sclerosis episodes due to the synergistic effect of this combination of both substances when administered together.
  • the preferred corticosteroids for this type of therapy are acute multiples Sclerosis especially the prednisone, prednisolone, Predn ⁇ solon-21-acetate, prednylidene and the methyl prednisone, especially the methyl prednisolone, into consideration.
  • MS Multiple sclerosis
  • the well-known clinical picture of MS includes the dissemminated foci of de-marking in the patient's central nervous system (CNS). This inflammation-related demyhnization occurs in batches in the CNS and leads to the so-called episodes with neurological failures that characterize the symptoms of the disease. In addition, about 1/3 of the patients experience a definable, new disease stage of constant progression. It can be assumed that pathomechanisms other than the progressive demyehnisation also play an additional role at this late stage.
  • the disease could only be treated symptomatically if flare-ups occurred by the administration of corticosteroids (eg lg / day methylprednisolone iv over a period of three days), which leads to a reduction in the duration of the relapse .
  • corticosteroids eg lg / day methylprednisolone iv over a period of three days
  • preventive continuous therapy with these hormones cannot be carried out without further ado.
  • there are also other serious concerns about treating patients who additionally suffer from other diseases which are influenced by corticosteroids for example type 1 diabetes mellitus, with these adrenal cortex hormones or their descendants.
  • Such drug therapy is extremely difficult and risky.
  • various other groups of drugs have also been tested for their effectiveness against MS.
  • the object of the invention is therefore to create a therapy for MS or a use of drugs for the treatment of MS, which overcomes the disadvantages set out at the beginning.
  • the object on which the invention is based is achieved in a completely surprising manner by the combination therapy of type I interferons, for example ⁇ -interferon and / or ⁇ -interferon, by subcutaneous route in connection with orally administered pentoxifylline in the relapsing form of MS.
  • interferon type I and pentoxifilline has the administration of IO 4 to IO 8 , in particular 1 to 16 million units of a ⁇ -interferon or ⁇ -interferon subcutaneously with simultaneous oral administration of 1 to 5 times a day 100 to 1600 mg or 2000 mg pentoxifylline to the subject, the pentoxifylline may optionally be in the form of a sustained release preparation.
  • the doses of interferon and pentoxifylline to be used in each case are based on the general condition and the weight of the patients to be treated.
  • the dose of interferons is generally between 1.5 ⁇ 10 5 to 30 ⁇ IO 5 IU with subcutaneous administration, preferably with 3 x 10 5 to 20 x 10 5 , more preferably 1.5 x IO 5 IU with subcutaneous or intramuscular administration, each per kilogram of body weight.
  • Dosages of 0.3 x 10 5 , 1 x 10 5 , 2 x IO 5 , 2.5 can also be used x IO 5 , 3.0 x 10 5 up to 3.5 or 4.0 x IO 5 IU can be administered subcutaneously or intramuscularly in solution. Expressed in million units, an application of 8 million units is preferred, but it is also possible to administer 2, 4, 6, 10, 12, 14, 15 or 16 or 18 or 20 million units per patient.
  • Interferons of natural or genetic engineering origin can be used therapeutically.
  • concentration of this active ingredient is IO 4 ie to 10 8 iE per ampoule or vial and per application.
  • the dosage form can be an ampoule, the drug being dissolved in liquid form, or a lyophilisate, ie a freeze-dried, water-soluble powder for injection purposes.
  • Suitable adjuvants for setting a physiological pH of the injection solution or the lyophilisate are buffer systems such as glycine / sodium hydroxide, sodium dihydrogen phosphate / dinate hydrogen phosphate or the corresponding potassium salts, tris (hydroxymethyl) aminomethane / HCl or sodium / essic acid.
  • the solvent used here is water for injections or distilled water. according to the valid pharmacopoeia regulations.
  • scaffolds such as mannitol, dextran, sucrose. Human albumin, lactose and polyvinyl pyrrolidone required.
  • the corresponding injection solutions or the lyophilisate are filled aseptically into the corresponding injection glasses or ampoules.
  • the individual dosage of pentoxifylline is at least 400 mg each per oral administration, but can also be 300, 500, 600, 800, 1000, 1200 or even 1500 to 1600 or 2000 mg.
  • the daily dose can be between 300 or 400 mg and 4500 mg, a daily dose of 1200 mg per patient is very particularly preferred. But it can daily doses of 500, 600, 1000, 1200, 1500, 2000, 2500, 3000, 3500 and 4000 or 4500 mg per patient can also be administered.
  • the range between 500 mg daily and 2500 mg daily is preferred.
  • the dosages used for single administration are at least 3 mg up to 300 mg each per kilogram. The range from 3 mg per kilogram to 18 mg per kilogram is particularly preferred, a single dose of 6 mg per kilogram being particularly preferred.
  • the respective total daily doses are understood accordingly for the administration at least once a day, preferably 2 to a maximum of 5 times a day.
  • Tablets, coated tablets, capsules or granules are suitable as dosage forms for the retarded or non-retarded pentoxifylline.
  • the dosage per dosage form is 200 to 1000 mg or up to 2000 mg pentoxifylline.
  • the auxiliaries below are particularly suitable for the retardation.
  • These substances are used in combination with the usual galenic binders, fillers, lubricants and release agents such as lactose, starch types, microcrystalline cellulose, dicalcium phosphate, calcium calcium phosphate, colloidal silicon dioxide, talc, magnesium stearate, polyvinylpyrrolidone or methyl cellulose
  • Capsule preparations are soft or hard gelatin capsule preparations.
  • the usual carrier, retarding, sliding and thinning substances or encapsulating materials such as gelatin can be used as auxiliary substances for the production of capsules.
  • the oblong forms are preferred because of easier administration
  • a combination medicinal product is also provided which is characterized in that the pack contains ampules with injection solutions or lyphylisate containing an interferon and possibly retarded pentoxifylline in the form of tablets, dragees, capsules or granules, separately from one another, wherein the respective dose units of both active substances are present in the amounts indicated above.
  • a 25-year-old patient was diagnosed with multiple sclerosis three years ago. Initially, relapses occurred every six months, which improved quickly after cortisone administration. First a left leg paresis, then gangataxy, as well as intermittent urinary and fecal incontinence and temporary double images were diagnosed. For a year now only partially remitting relapses under cortisone treatment and increasing atactic gait disorder. During a stable phase, start therapy with ß-interferon (8 million units Betaseron ® ) subcutaneously with simultaneous administration of 3 x 400 mg pentoxifylline retard.
  • the 26-year-old patent had suffered from relapsing MS for four years. As initial symptoms, emotional disorders in both legs and on the left arm, which occurred several times in succession, were diagnosed. A year ago, spastic paraparesis began with a marked exacerbation of the symptoms after a subcapital upper arm fracture on the left, which was treated with surgery. Eight weeks after the accident was interferon treatment SS in combination with pentoxifylline after again been incurred stability started (Betaseron ®, 8 million units every other day subcutaneously, Pent ⁇ oxifyllin 4 x 400 mg retard oral). On the first day of treatment, the patient noticed a general feeling of weakness four hours after the ß-interferon injection. no tiredness, headache and blurred vision.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Zoology (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne la thérapie combinée de la sclérose en plaques progressive secondaire évoluant par poussées successives, par administration sous-cutanée ou intramusculaire d'interférons de type I et administration par voie orale de pentoxifylline, éventuellement sous forme retard.
EP96938998A 1995-11-30 1996-11-08 Utilisation d'une combinaison de pentoxifylline et d'interferons de type i pour le traitement de la sclerose en plaques Withdrawn EP0863759A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19544768 1995-11-30
DE19544768A DE19544768C1 (de) 1995-11-30 1995-11-30 Verwendung einer Kombination aus Pentoxifyllin mit Typ-I-Interferonen zur Behandlung der Multiplen Sklerose
PCT/EP1996/004906 WO1997019686A1 (fr) 1995-11-30 1996-11-08 Utilisation d'une combinaison de pentoxifylline et d'interferons de type i pour le traitement de la sclerose en plaques

Publications (1)

Publication Number Publication Date
EP0863759A1 true EP0863759A1 (fr) 1998-09-16

Family

ID=7778885

Family Applications (1)

Application Number Title Priority Date Filing Date
EP96938998A Withdrawn EP0863759A1 (fr) 1995-11-30 1996-11-08 Utilisation d'une combinaison de pentoxifylline et d'interferons de type i pour le traitement de la sclerose en plaques

Country Status (7)

Country Link
EP (1) EP0863759A1 (fr)
JP (1) JP2000501085A (fr)
CA (1) CA2238770A1 (fr)
DE (1) DE19544768C1 (fr)
HU (1) HUP9903698A2 (fr)
NO (1) NO982463D0 (fr)
WO (1) WO1997019686A1 (fr)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AUPP823999A0 (en) * 1999-01-20 1999-02-11 University Of Queensland, The A treatment
US20070105878A1 (en) * 2005-10-03 2007-05-10 Andrew Reaume Purine formulations and methods for managing disorders
EP2265334A2 (fr) 2008-02-29 2010-12-29 Concert Pharmaceuticals, Inc. Dérivés de xanthine substitués
US20110053961A1 (en) 2009-02-27 2011-03-03 Concert Pharmaceuticals, Inc. Substituted xanthine derivatives
EP2473052A4 (fr) 2009-09-02 2013-03-20 Concert Pharmaceuticals Inc Dérivés de xanthine substitués
US20130324564A1 (en) 2010-09-01 2013-12-05 Concert Pharmaceuticals, Inc. Polymorphs of (s)-1-(4,4,6,6,6-pentadeutero-5-hydroxyhexyl)-3-7-dimethyl-1h-purine-2,6(3h,7h)-dione
WO2013013052A1 (fr) 2011-07-19 2013-01-24 Concert Pharmaceuticals, Inc. Dérivés de xanthine substitués
CN104364255A (zh) 2012-04-13 2015-02-18 康塞特医药品有限公司 取代的黄嘌呤衍生物
WO2013159006A1 (fr) 2012-04-20 2013-10-24 Concert Pharmaceuticals, Inc. Polymorphes de (s)-1-(4,4,6,6,6-pentadeutéro-5-hydroxyhexyl)-3,7-diméthyl-1h-purine-2,6(3h,7h)-dione
CA2981791A1 (fr) 2014-04-18 2015-10-22 Concert Pharmaceuticals, Inc. Methodes de traitement de l'hyperglycemie

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU538186B2 (en) * 1980-03-07 1984-08-02 Scotia Holdings Plc Prostaglandin precursors
US5668117A (en) * 1991-02-22 1997-09-16 Shapiro; Howard K. Methods of treating neurological diseases and etiologically related symptomology using carbonyl trapping agents in combination with previously known medicaments
US5763446A (en) * 1992-03-26 1998-06-09 University Of Southern California Use of pentoxifylline and other tumor necrosis factor blockers for the treatment of aids-associated optic neuropathy and other central nervous system diseases
GB9218810D0 (en) * 1992-09-04 1992-10-21 Univ Birmingham Antiviral pyrimidine nucleosides
DE4343034C1 (de) * 1993-12-16 1995-06-08 Rentschler Arzneimittel Verwendung von Pentoxifyllin zur Behandlung von Multipler Sklerose

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9719686A1 *

Also Published As

Publication number Publication date
JP2000501085A (ja) 2000-02-02
WO1997019686A1 (fr) 1997-06-05
HUP9903698A2 (hu) 2000-03-28
NO982463L (no) 1998-05-29
NO982463D0 (no) 1998-05-29
DE19544768C1 (de) 1997-07-10
CA2238770A1 (fr) 1997-06-05

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