US 2019/0262453 Al  10  Aug. 29, 2019  [0108]  The amount of active ingredient, or an active salt or  derivative thereof, for use in treatment will vary not only  with the particular salt selected but also with the route of  administration, the nature of the condition being treated and  the age and condition of the patient and will ultimately be at  the discretion of the attendant physician or clinician. In  general, one skilled in the art understands how to extrapolate  in vivo data obtained in a model system, typically an animal  model, to another, such as a human. In some circumstances,  these extrapolations may merely be based on the weight of  the animal model in comparison to another, such as a  mammal, preferably a human, however, more often, these  extrapolations are not simply based on weights, but rather  incorporate a variety of factors. Representative factors  include the type, age, weight, sex, diet and medical condi› tion of the patient, the severity of the disease, the route of  administration, pharmacological considerations such as the  activity, efficacy, pharmacokinetic and toxicology profiles of  the particular compound employed, whether a drug delivery  system is utilized, on whether an acute or chronic disease  state is being treated or prophylaxis is conducted or on  whether further active compounds are administered in addi› tion to the compounds described herein and as part of a drug  combination. The dosage regimen for treating a disease  condition with the compounds and/or compositions is  selected in accordance with a variety factors as cited above.  Thus, the actual dosage regimen employed may vary widely  and therefore may deviate from a preferred dosage regimen  and one skilled in the art will recognize that dosage and  dosage regimen outside these typical ranges can be tested  and, where appropriate, may be used in the methods  described herein.  [0106]  The  compounds  described  herein,  optionally  together with a conventional adjuvant, carrier, or diluent,  may thus be placed into the form of pharmaceutical formu› lations and unit dosages thereof and in such form may be  employed as solids, such as tablets or filled capsules, or  [0105]  Pharmaceutical formulations include those suitable  for oral, rectal, nasal, topical (including buccal and sub› lingual), vaginal or parenteral (including intramuscular, sub› cutaneous and intravenous) administration or in a form  suitable for administration by inhalation, insuf!Iation or by a  transdermal patch. Transdermal patches dispense a drug at a  controlled rate by presenting the drug for absorption in an  efficient manner with minimal degradation of the drug.  Typically, transdermal patches comprise an impermeable  backing layer, a single pressure sensitive adhesive and a  removable protective layer with a release liner. One of  ordinary skill in the art will understand and appreciate the  techniques appropriate for manufacturing a desired effica› cious transdermal patch based upon the needs of the artisan.  [0107]  The dose when using the compounds and formu› lations described herein can vary within wide limits and as  is customary and is known to the physician, it is to be  tailored to the individual conditions in each individual case.  It depends, for example, on the nature and severity of the  illness to be treated, on the condition of the patient, on the  compound employed or on whether an acute or chronic  disease state is treated or prophylaxis is conducted or on  whether further active compounds are administered in addi› tion to the compounds. Representative doses include, but not  limited to, about 0.001 mg to about 5000 mg, about 0.001  mg to about 2500 mg, about 0.001 mg to about 1000 mg,  0.001 mg to about 500 mg, 0.001 mg to about 250 mg, about  0.001 mg to 100 mg, about 0.001 mg to about 50 mg and  about 0.001 mg to about 25 mg. Multiple doses may be  administered during the day, especially when relatively large  amounts are deemed to be needed, for example 2, 3 or 4  doses. Depending on the individual and as deemed appro› priate from the patient’s physician or caregiver it may be  necessary to deviate upward or downward from the doses  described herein.  [0104]  Additional types of inflammatory disorders that  may be treated as described herein include a variety of  disease states, including diseases such as hay fever, athero› sclerosis, arthritis (rheumatoid, bursitis, gouty arthritis,  osteoarthritis, polymyalgia rheumatic, etc.), asthma, auto› immune diseases, chronic inflammation, chronic prostatitis,  glomerulonephritis, nephritis, inflammatory bowel diseases,  pelvic inflammatory disease, reperfusion injury, transplant  rejection, vasculitis, myocarditis, colitis, appendicitis, peptic  ulcer, gastric ulcer, duodenal ulcer, peritonitis, pancreatitis,  ulcerative colitis, seudomembranous colitis, acute colitis,  ischemic colitis, diverticulitis, epiglottitis, achalasia, cho› langitis, cholecystitits, hepatitis, Crohn’s disease, enteritis,  Whipple’s disease, allergy, anaphylactic shock, immune  complex disease, organ ischemia, reperfusion injury, organ  necrosis, hay fever, sepsis, septicemia, endotoxic shock,  cachexia, hyperpyrexia, eosinophilic granuloma, granulo› matosis, sarcoidosis, septic abortion, epididymitis, vaginitis,  prostatitis, urethritis, bronchitis, emphysema, rhinitis, pneu› monitits,  pneumoultramicroscopic  silicovolcanoconiosis,  alvealitis, bronchiolitis, pharyngitis, pleurisy,  sinusitis,  influenza, respiratory syncytial virus infection, HIV infec› tion, hepatitis B virus infection, hepatitis C virus infection,  herpes virus infection disseminated bacteremia, Dengue  fever, candidiasis, malaria, filariasis, amebiasis, hydatid› cysts, bums, dermatitis, dermatomyositis, sunburn, urticaria,  Warts, Wheals, vasulitis, angiitis, endocarditis, arteritis, ath› erosclerosis, thrombophlebitis, pericarditis, myocarditis,  myocardial ischemia, periarteritis nodosa, rheumatic fever,  Alzheimer’s disease, coeliac disease, congestive heart fail› ure,  adult  respiratory  distress  syndrome,  meningitis,  encephalitis, multiple sclerosis, cerebral infarction, cerebral  embolism, Guillame-Barre syndrome, neuritis, neuralgia,  spinal cord injury, paralysis, uveitis, arthritides, arthralgias,  osteomyelitis, fasciitis, Paget’s disease, gout, periodontal  disease, rheumatoid arthritis, synovitis, myasthenia gravis,  thyroiditis, systemic lupus erythematosis, Goodpasture’s  syndrome, Behcet’s syndrome, allograft rejection, graft› versus-host disease, Type I diabetes, Type II diabetes, anky› losing spondylitis, Berger’s disease, Reiter’s syndrome,  Hodgkin’s disease, ileus, hypertension, irritable boWel syn› drome, myocardial infarction, sleeplessness, anxiety and  stent thrombosis.  liquids such as solutions, suspensions, emulsions, elixirs,  gels or capsules filled with the same, all for oral use, in the  form of suppositories for rectal administration; or in the  form of sterile injectable solutions for parenteral (including  subcutaneous) use. Such pharmaceutical compositions and  unit dosage forms thereof may comprise conventional ingre› dients in conventional proportions, with or without addi› tional active compounds or principles and such unit dosage  forms may contain any suitable effective amount of the  active ingredient commensurate with the intended daily  dosage range to be employed.  and so is called reactive arthritis. In reactive arthritis, the  joint is inflamed but not actually infected. 