Use Of Resiniferatoxin (Rtx) For Producing An Agent For Treating Joint Pains And Method For Applying Said Agent

Abstract

The use of resiniferatoxin (RTX) relates to a formulation, which does not contain any local anesthetic and preferably also no other pharmacologically active substances, for the preparation of an agent for the treatment of different pain conditions.

1 - 27 . (canceled) 
     
     
         28 . Use of resiniferatoxin (RTX) in a formulation for the preparation of an agent for the treatment of
 arthrosis   arthritis, especially rheumatoid arthritis and infectious arthritis   chondrocalcinosis   damage to ligaments   damage to the meniscus   cartilage damage   synovitis   arthrofibrosis   Sudeck's disease   necrosis of parts of the joints   neuropathic joint pain   Treatment of bone pain after bone surgery by administration on   the bone, for example after   iliac crest osteotomy   Hallux-Valgus correction   treatment of bone pain by injection into the bone
 for example, in the case of necrosis of the head of the femur into the latter into the body of a vertebra in the case of osteochondrosis; 
   treatment of joint stiffness, especially
 arthrofibrosis 
 frozen shoulder 
   treatment of muscle pain by intramuscular injection, for example, in the case of
 a muscle fiber tear 
 muscular soreness 
 spastic diseases 
   injection into the painful meniscus in the case of degeneration of or a tear in the meniscus;
 treatment of back pain by injection into the intervertebral disk in the case of degeneration of or a tear in the intervertebral disk; 
   injection about a painful nerve, for example in the case of
 trigeminus neuralgia 
 neurinoma 
 Morton neurinoma 
 phantom pain 
 scar neurinoma 
   treatment of intradental or peridental toothache in the case of
 dental caries 
 all forms of toothache 
 before, during or after tooth extraction 
 before, during or after a tooth implanting 
 applied in the case of parodontitis 
 applied in the case of an exposed neck of a tooth 
   injection into the pleural cavity in the case of pleuritic complaints   instillation into the intestines in the case of intestinal complaints, especially in the case of ulcerous colitis, Crohn's disease, anal fissures or hemorrhoids   joint pain   bone pain after an osteotomy   frozen shoulder   tendonitis   myalgia   pain in the case of soft tissue tumors   bone pain or   joint and adjacent bone pain,   wherein   a) the agent does not contain a local anesthetic,   b) the agent contains a permeation promoter   c) the agent additionally contains a calcium salt and the concentration of calcium ions is greater than 2 mmolar.   
     
     
         29 . The use of  claim 28 , wherein the agent is dissolved in a buffer solution with a pH higher than 7.6. 
     
     
         30 . The use of  claim 28 , wherein the permeation promoter is selected from the following group of substances: dimethyl sulfoxide, ethoxyethylene diglycol, ethanol, phosphatidyl cholines, propylene glycol dipelargonates (DPPG) or glycosylated ethoxylated glycerides. 
     
     
         31 . The use of  claim 29 , wherein the agent is dissolved in a buffer solution with a pH higher than 8.5. 
     
     
         32 . The use of  claim 28 , wherein the agent is dissolved in a buffer solution with a pH lower than 7.2. 
     
     
         33 . The use of  claim 32 , wherein the agent is dissolved in a buffer solution with a pH lower than 6.5. 
     
     
         34 . The use of  claim 28 , wherein the calcium ion concentration is greater than 4 mmolar. 
     
     
         35 . The use of  claim 28 , wherein the agent does not contain any other pharmacologically active substances. 
     
     
         36 . The use of resiniferatoxin (RTX) for producing an agent for the local treatment of
 postoperative pain   arthritis   for local wound pain after surgery in the form of a flushing solution for intraoperative use in the case of an open or arthroscopic or endoscopic operation, including liposuction,
 joint pain 
 bone pain after osteotomy 
 frozen shoulder 
   for local wound pain after surgery in the form of a flushing solution for intraoperative application in the case of an open or arthroscopic or endoscopic operation, including liposuction   local treatment of joint pain by intra-articular injection in the case of
 arthrosis 
 rheumatoid arthritis 
 infectious arthritis 
 chondrocalcinosis 
 damage to ligaments 
 meniscus lesion 
 damage to cartilage 
 synovitis 
 arthrofibrosis 
 Sudeck's disease 
 necrosis of portions of a joint 
 neuropathic joint pain 
   local treatment of joint pain after bone surgery by application on the bone, for example, after
 iliac crest osteotomy 
 Hallux-Valgus correction 
   treatment of bone pain by injection into the bone,
 for example, in the case of necrosis of the head of the femur into the latter 
 into the body of a vertebra in the case of osteochondrosis; 
   local treatment of joint stiffness, preferably arthrofibrosis or a frozen shoulder;   local treatment of muscle pain, by intramuscular injection, preferably in the case of a muscle tear, muscular soreness or spastic diseases;   local injection into the painful meniscus in the case of degeneration of or a tear in the meniscus;   treatment of back pain by injection into the intervertebral disk in the case of the degeneration of or a tear in the intervertebral disk;   injection about a painful nerve, especially in the case of trigeminus neuralgia, neurinoma, Morton neurinoma, phantom pain or scar neurinoma;   treatment of toothaches by local intradental or peridental administration, in the case of
 dental caries, 
 all forms of toothache, 
 before, during or after tooth extraction, 
 before, during or after a tooth implanting, 
 applied topically in the case of parodontitis, 
 applied topically in the case of an exposed neck of a tooth; 
   injection into the pleural cavity in the case of pleuritic complaints   instillation into the intestines in the case of intestinal disorders, especially of colitis ulcerosa, Crohn's disease and anal fissures,   wherein   a) the agent contains a permeation promoter   b) the agent additionally contains a calcium salt and the concentration of the calcium ions is greater than 2 mmolar.   
     
     
         37 . The use of  claim 36 , wherein the agent does not contain a local anesthetic. 
     
     
         38 . The use of  claim 36 , wherein the concentration of the RTX is between 100 nmolar and 1 μmolar. 
     
     
         39 . The use of  claim 38 , wherein the concentration of RTX is between 500 nmolar and 1 μmolar. 
     
     
         40 . The use of  claim 36 , wherein the agent does not contain alcohol and especially not ethanol. 
     
     
         41 . The use of  claim 36 , wherein the agent additionally contains an x-ray contrasting agent, preferably a gadolinium-containing, iodine-containing or barium-containing substance. 
     
     
         42 . The use of  claim 36 , wherein the agent additionally contains glycerin, preferably in a concentration of 10 to 95% by weight. 
     
     
         43 . The use of  claim 36 , wherein the agent additionally contains a steroid. 
     
     
         44 . The use of  claim 36 , wherein the agent additionally contains a vasoconstrictor, preferably adrenaline, noradrenaline, phenylephrine or ornipressin 
     
     
         45 . The use of  claim 36 , wherein the agent is dissolved in a solvent, which is compatible with the body, preferably in glycerin, lophendylate or propylene glycol. 
     
     
         46 . The use of  claim 36 , wherein the agent is used for denervation or neurolysis in degenerative the disease joints. 
     
     
         47 . The use of  claim 36 , wherein the agent is dissolved in a carrier liquid, a pharmaceutically acceptable vehicle, especially from the group of sodium chloride injection solution, Ringier's injection solution, isotonic dextrose, sterile water, dextrose solution, lactated Ringer's injection solution, distilled water or mixtures thereof, for a local injection. 
     
     
         48 . The use of  claim 36 , wherein the agent additionally contains a substance, which makes possible a delayed and prolonged release of the RTX, preferably glucosaminoglycans or hyaluronic acid. 
     
     
         49 . The use of  claim 47 , wherein the concentration of the salts and ions, dissolved in the solution medium, is higher than the physiologically normal concentration, for example, in Ringer's lactate solution. 
     
     
         50 . Method for the treatment of pain, wherein the resiniferatoxin (RTX) is dissolved in a suitable solvent, which is compatible with the body, and that preferably a liquid volume of 0.1 to 150 mL of the solution
 a) is injected locally into the pain-affected tissue structure of the patient or   b) applied dropwise locally into the surgical wound or   c) is injected locally into the intracapsular region or   d) is injected locally into the bursa of a joint affected by pain, wherein   the resiniferatoxin (RTX) is used in such a concentration that neurolysis occurs.   
     
     
         51 . The method of  claim 50 , wherein the nociceptive nerve fibers are made insensitive to pain by the resiniferatoxin (RTX) for a period of at least 14 days and preferably of at least 8 weeks. 
     
     
         52 . The method of  claim 50 , wherein the concentration of RTX is between approximately 10 nmolar (nM) and 100 μmolar (μM). 
     
     
         53 . The method of  claim 50 , wherein it is used for the following indications:
 for local wound pain after surgery in the form of a flushing solution for intraoperative application in the case of an open or arthroscopic or endoscopic operation, including liposuction   local treatment of joint pain by intra-articular injection in the case of
 arthrosis 
 rheumatoid arthritis 
 infectious arthritis 
 chondrocalcinosis 
 damage to ligaments 
 meniscus lesion 
 damage to cartilage 
 synovitis 
 arthrofibrosis 
 Sudeck's disease 
 necrosis of portions of a joint 
 neuropathic joint pain 
   local treatment of bone pain after bone surgery by application on the bone, for example, after
 iliac crest osteotomy or 
 Hallux-Valgus correction 
   treatment of bone pain by injection into the bone, for example, in the case of necrosis of the head of the femur into the latter, into the body of a vertebra in the case of osteochondrosis;   local treatment of joint stiffness, preferably arthrofibrosis or a frozen shoulder;   local treatment of muscle pain, by intramuscular injection, preferably in the case of a muscle tear, muscular soreness or spastic diseases;   local injection into the painful meniscus in the case of degeneration of or a tear in the meniscus;   treatment of back pain by injection into the intervertebral disk in the case of the degeneration of or a tear in the intervertebral disk;   injection about a painful nerve, especially in the case of trigeminus neuralgia, neurinoma, Morton neurinoma, phantom pain or scar neurinoma;   treatment of toothaches by local intradental or peridental administration, in the case of:
 dental caries, 
 all forms of toothache, 
 before, during or after tooth extraction, 
 before, during or after a tooth implanting, 
 applied topically in the case of parodontitis, 
 applied topically in the case of an exposed neck of a tooth; 
   injection into the pleural cavity in the case of pleuritic complaints   instillation into the intestines in the case of intestinal disorders, especially of colitis ulcerosa, Crohn's disease and anal fissures.   
     
     
         54 . The method of one of the  claim 50 , wherein the agent is injected into a synovial cavity, which is not lined with urothel.