Concentrated methotrexate solutions

Abstract

Concentrated methotrexate solutions are described which are suitable for the use of an active substance in the production of a parenterally administered medicament for the treatment of inflammatory autoimmune diseases. The methotrexate is added to a pharmaceutically acceptable solvent at a concentration of more than 25 mg/ml. The invention also relates to a ready-made syringe and a carpule containing such a pharmaceutical solution formulation, as well as a pen injector comprising such a carpule and/or a ready-made syringe.

1 . Use of methotrexate for the production of a subcutaneous administered medicament for the treatment of inflammatory autoimmune diseases, wherein the methotrexate is present in a pharmaceutically acceptable solvent at a concentration of more than 30 mg/ml. 
     
     
         2 . Use according to  claim 1 , wherein the methotrexate is present at a concentration of more than 30 mg/ml to 100 mg/ml. 
     
     
         3 . Use according to  claim 2 , wherein the methotrexate is present at a concentration of about 50 mg/ml. 
     
     
         4 . Use according to  claim 1 , wherein the pharmaceutically acceptable solvent is selected from water, water for injection purposes, water comprising isotonization additives and sodium chloride solution, in particular isotonic sodium chloride solution. 
     
     
         5 . Use according to  claim 1 , wherein the inflammatory autoimmune disease is selected from rheumatoid arthritis, juvenile arthritides, vasculitides, collagenoses, Crohn's disease, colitis ulcerosa, bronchial asthma, Alzheimer's disease, multiple sclerosis, Bechterew's disease, joint arthroses, or psoriasis. 
     
     
         6 . Use according to  claim 5 , wherein the inflammatory autoimmune disease is rheumatoid arthritis, in particular juvenile rheumatoid arthritis. 
     
     
         7 . Use according to  claim 1 , wherein the medicament is present in a form suitable for patient self-administration. 
     
     
         8 . Use according to  claim 1 , wherein the medicament is contained in an injection device for a single application. 
     
     
         9 . Use according to  claim 8 , wherein the injection device contains a dosage of 5 to 40 mg, in particular 5.0, 7.5, 10.0, 12.5, 15.0, 17.5, 20.0, 22.5, 25.0, 27.5, 30.0, 32.5, 35.0, 37.5 or 40.0 mg, of methotrexate. 
     
     
         10 . Use according to  claim 8 , wherein the injection device is a ready-made syringe. 
     
     
         11 . Use according to  claim 1 , wherein the medicament is contained in a storage container. 
     
     
         12 . Use according to  claim 11 , wherein the medicament furthermore comprises a preservative. 
     
     
         13 . Use according to  claim 11 , wherein the storage container contains a total dosage amount of 5 to 5,000 mg. 
     
     
         14 . Use according  claim 11 , wherein the storage container is an injection bottle, a vial, a bag, a glass ampoule, or a carpule. 
     
     
         15 . Use according to  claim 14 , wherein the storage container is a carpule and wherein said carpule is suitable for administering the medicament by means of an injection device, in particular a pen injector. 
     
     
         16 . Use according to  claim 15 , wherein the carpule and the pen injector are provided such that multiple applications of single dosages can be administered. 
     
     
         17 . Use according to  claim 16 , wherein the single dosages per application can be adjusted to 5 to 40 mg each, in particular 5.0, 7.5, 10.0, 12.5, 15.0, 17.5, 20.0, 22.5, 25.0, 27.5, 30.0, 32.5, 35.0, 37.5 or 40.0 mg each, of methotrexate. 
     
     
         18 . Ready-made syringe, comprising a pharmaceutical solution formulation of methotrexate with a concentration of more than 30 mg/ml in a pharmaceutically acceptable solvent for subcutaneous administration. 
     
     
         19 . Ready-made syringe according to  claim 19 , wherein the methotrexate is present at a concentration of more than 30 mg/ml to 100 mg/ml. 
     
     
         20 . Ready-made syringe according to  claim 19 , wherein the methotrexate is present at a concentration of about 50 mg/ml. 
     
     
         21 . Ready-made syringe according to  claim 18 , comprising a dosage of 5 to 40 mg, in particular 5.0, 7.5, 10.0, 12.5, 15.0, 17.5, 20.0, 22.5, 25.0, 27.5, 30.0, 32.5, 35.0, 37.5 or 40.0 mg, of methotrexate. 
     
     
         22 . Ready-made syringe according to  claim 18 , wherein the pharmaceutically acceptable solvent is selected from water, water for injection purposes, water comprising isotonization additives and sodium chloride solution, in particular isotonic sodium chloride solution. 
     
     
         23 . Ready-made syringe according to  claim 18 , wherein the ready-made syringe is constructed such that it allows patient self-administration by a patient with limited fine motor skills. 
     
     
         24 . Carpule, comprising a pharmaceutical solution formulation of methotrexate with a concentration of more 30 mg/ml in a pharmaceutically acceptable solvent for subcutaneous administration. 
     
     
         25 . Carpule according to  claim 24 , wherein the methotrexate is present at a concentration of more than 30 mg/ml to 100 mg/ml. 
     
     
         26 . Carpule according to  claim 25 , wherein the methotrexate is present at a concentration of about 50 mg/ml. 
     
     
         27 . Carpule according to  claim 24 , wherein the pharmaceutical solution formulation furthermore comprises a preservative. 
     
     
         28 . Carpule according to  claim 24 , wherein said carpule contains a total dosage amount of 5 to 5,000 mg, in particular 7.5 to 300 mg, of methotrexate. 
     
     
         29 . Carpule according to  claim 24 , wherein the pharmaceutically acceptable solvent is selected from water, water for injection purposes, water comprising isotonization additives and sodium chloride solution, in particular isotonic sodium chloride solution. 
     
     
         30 . Pen injector comprising a carpule according to  claim 24 . 
     
     
         31 . Pen injector according to  claim 30 , wherein the carpule and the pen injector are provided such that multiple applications of single dosages can be administered. 
     
     
         32 . Pen injector according to  claim 31 , wherein the single dosages per application can be adjusted to 5 to 40 mg each, in particular 5.0, 7.5, 10.0, 12.5, 15.0, 17.5, 20.0, 22.5, 25.0, 27.5, 30.0, 32.5, 35.0, 37.5 or 40.0 mg each, of methotrexate.