Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0085—Brain, e.g. brain implants; Spinal cord
• • 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
  • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
  • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
  • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
  • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom

Definitions

• Morphine is the opioid drug of choice for management of chronic pain This preference for morphine is due at least m part to its low cost, the ability of the drug to provide relief from pam of a vanety of origins, and the vast experience with this drug Despite the apparent advantages of morphine, many experts in pain management believe that morphine and other narcotics are under- prescribed for chronic pain patients
• the invention has the additional advantage that it avoids the need for placement of external needles and/or external catheters m the subject, which provides sites subject to infection
• use of an implanted device mcreases patient compliance with a presc ⁇ bed therapeutic regimen, and substantially decreases or completely avoids the ⁇ sk of abuse or overdose of the drug
• M6G mesenchymal growth factor-6-glucuron ⁇ de
• “temporal” drug delivery is meant to encompass delivery of drug at an mcreasmg, decreasmg, substantially constant, or pulsatile, rate or range of rates (e g , amount of drug per unit time, or volume of drug formulation for a unit time), and further encompasses delivery that is continuous or substantially continuous, or chronic
• substantially continuous as used in, for example, the context of “substantially continuous delivery”, is meant to refer to delivery of a substance (e g , a drug) in a manner that is substantially uninterrupted for a pre-selected pe ⁇ od of drug delivery (other than a pe ⁇ od associated with, for example, a bolus injection)
• substantially continuous drug delivery can also encompass delivery of drug at a substantially constant, pre-selected rate or range of rates (e g , amount of drug per unit time, or volume of drug formulation for a unit time) that is substantially uninterrupted for a pre-selected period of drug delivery
• low volume rate as used herein with reference to mtracerebrospinal delivery of M6G is generally meant a volume rate of from about 10 nl/day to about 2 ml/day, generally from about 40 nl/day to about 1 ml/day, usually about 0 2 ⁇ l/day to about 0 5 ml/day, typically from about 1 0
• mtracerebrospmal delivery includes those associated with cytotoxicity of the drug or other drug formulation component, nausea, vomiting, confusion, respiratory depression, constipation, whilry retention, etc )
• the methods and devices of the invention can also serve to mitigate side effects associated with delivery of any drug formulation (e g , side effects associated with disturbance of the tissues at the site of implantation, with disturbance at the site of drug delivery, fluctuations in CSF volume due to the volume of drug formulation delivered or leakage of CSF (e g , spinal headaches) etc )
• the mitigation or avoidance of the latter types of side effects can be attributed at least m part to the small dimensions of the drug delivery catheter and to the low mass dose and/or low volume delivery rate used to accomplish drug delivery to the CNS
• smce the invention can be carried out with low volumes of drug and small diameter catheters, the ⁇ sk of mcidence of spinal headaches is diminished
• the actual dose of M6G delivered will vary with a va
• the catheter used m the drug delivery system suitable for use m the invention is generally an elongate, substantially hollow structure having a proximal end associated with the drug delivery device of the drug delivery device, and a distal end for delivery of M6G to a desired delivery site
• the proximal end of the catheter is associated with or attached to the drug delivery device so that drug in the drug reservoir of the delivery device can flow from the drug delivery device, mto and through the catheter, and out the distal catheter end adjacent the mtracerebrospmal delivery site
• the drug delivery catheter compnses a lumen having a diameter that can be equal to, or can be greater or less than, the diameter of the drug delivery device onfice that serves as a drug reservoir outlet, with the proviso that the catheter is attached in a manner that avoids leakage of drug out of the drug delivery system
• the drug delivery device dispenses drug by convection (as in, e g , osmotic drug delivery systems), the orifice size as well as the
• the catheter may be produced from any of a vanety of suitable, substantially impermeable materials
• catheter body materials include, but are not necessanly limited to, polymers, metals, glasses, polyolefins (high density polyethylene (HDPE), low density polyethylene (LDPE), linear low density polyethylene (LLDPE), polypropylene (PP), and the like), nylons, polyethylene terephtholate, silicones, urethanes, liquid crystal polymers, PEBAXTM, HYTRELTM, TEFLONTM, perflouroethylene (PFE) perflouroalkoxy resms (PFA), poly(methyl methacrylate) (PMMA), multilammates of polymer, metals, and/or glass, nickel titanium alloy (e g , NlllNOLTM), and the like
• the catheter can comprise additional matenals or agents (e g , coatings on the external or internal catheter body surface(s)) to facilitate placement of the catheter and/or to
• M6G for delivery accordmg to the invention can be provided m any of a vanety of formulations compatible with mtracerebrospmal delivery
• concentration of M6G m the formulation can vary from about 0 1 wt % to about 50 or 75 wt %
• the drug can be provided in any form suitable for mtracerebrospmal administration, e g , solid, semi-solid, gel, liquid, suspension, emulsion, osmotic dosage formulation, diffusion dosage formulation, erodible formulation, etc
• admmistration usmg an external or implanted pump, particularly an implanted pump, more particularly an osmotic dosage form suitable for use with an osmotic pump
• Pharmaceutical grade organic or inorganic earners and/or diluents suitable for mtracerebrospinal delivery can be mcluded in the formulations of the invention
• physiologically acceptable earners are well known in the art
• the formulations for delivery according to the invention can compnse additional active ingredients
• the formulation can comprise an opioid antagonist (e g , to further decrease the possibility of addiction or dependence, see, e g , an exemplary osmotic dosage formulation compnsmg an opioid agonist and an opioid antagonist is desc ⁇ bed m U S Pat No 5,866,164

Landscapes

• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• General Health & Medical Sciences (AREA)
• Epidemiology (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Psychology (AREA)
• Biomedical Technology (AREA)
• Engineering & Computer Science (AREA)
• Orthopedic Medicine & Surgery (AREA)
• Neurosurgery (AREA)
• Neurology (AREA)
• Molecular Biology (AREA)
• Medicinal Preparation (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Priority Applications (1)

Applications Claiming Priority (2)

Publications (1)

Family

ID=22626732

Family Applications (1)

Country Status (2)

Cited By (23)

• 2000
  • 2000-12-12 AU AU20927/01A patent/AU2092701A/en not_active Abandoned
  • 2000-12-12 WO PCT/US2000/033735 patent/WO2001043528A2/fr not_active Ceased

Also Published As

Similar Documents

Legal Events