In ons centrum voor de behandeling van neuropathische pijnen kiezen we vaak voor de multimodale aanpak. Dat wil zeggen, verschillende soorten pijnstillers en dan van elk een relatief kleine dosering. Zo kan je synergie bewerkstelligen. Dat wil zeggen dat het geheel meer is dan de som der delen. 1 plus 1 is 3. Daarvoor moet je middelen kiezen uit verschillende groepen. Ook bij de iontoforese kan dit principe gevolgd worden. Het was een van de discussie-onderwerpen op een congres in Utrecht op dit gebied in 2009. In verband met dit thema deed ons centrum een zogenaamde patent search. Boeiend was dat we een patent (oktrooi) vonden dat precies dit principe ook huldigde. We citeren passages uit het patent:
Treatment of pain in humans is a topic of increasing research emphasis. One promising approach is by use of topical cocktails of ingredients for blocking pain from many origins. Rather than offering mere additive results, the multi-component cocktail of ingredients promises an unexpectedly high level of efficacy. Another developing approach is the use of improved delivery systems, which often can be used for the administration of treatments for diseases and conditions not solely limited to pain. Such delivery systems employ, gels creams, ointments, patches, bioadhesives, and iontophoresis that can deliver a variety of pharmaceuticals, alone or in combined administration. These approaches are exemplified in the following patents.
U.S. Pat. No. 5,900,249 to Smith discloses treatment of specific types and causes of pain by administration of a multi-component topical composition. For example, one component offers anesthetic pain relief that masks pain but does not correct the underlying cause. Another component reduces the sensation of pain by alleviating the physiological and neurotransmitter etiology of the pain. Each of the various active components functions differently in order to treat pain comprehensively, regardless of causes.
Multiple components include, first, a vasodilating agent such as nifedipine; second, an antiinflammatory agent to reduce pain mediated by prostaglandins; third, a membrane stabilizing agent such as carbamazepine; and fourth, seratogenic [bedoeld werd natuurlijk serotonergic] and nonadrenergic reuptake inhibitor. These may be supplemented with a topical anesthetic and an anti-inflammatory steroid. These medications are delivered in a gel, ointment, or cream.
An improved polypharmaceutical preparation can be formulated by the suitable selection and combination of an array of drugs. The preferred candidates include ketamine, which topically blocks the NMDA Ca ++ channels. Gabapentin also is a glutamate antagonist. Carbamazepine is an AMPA (Na + channel) receptor blocker, as is gabapentin. The 10-11 epoxide is the active molecule that modulates C fiber afferents at the Langerhans complex. Carbamazepine blocks peripheral sympathetic nerve receptors via the voltage-dependent sodium channels, in the same manner as it blocks these receptors in the dorsal root ganglion (DRG). Clonidine is an alpha 2 blocker that similarly blocks the alpha 2 receptor. Phenoxybenzamine is an alpha 1 agonist. It has much more power to block dorsal ganglionic afferents that synapse with the interneurons of the wide range neurons of areas V to IX of the dorsal horn, before ascending up Lissauer’s spinothalamic tract, carrying afferent painful stimuli to the thalamus. Nifedipine is useful for non-NMDA, voltage-sensitive calcium-channel blockade, which down regulates nitric oxide (NO) synthesis.
Pluronic lecithin organogel (PLO), topical vehicle allows the above pharmaceuticals to penetrate to the dermis and modulate up regulated activity in all these pathways that cause acute and chronic pain, modulation at the periphery.
En verder qua polyfarmacie het volgende nog uit dat patent:
According to another aspect of the invention, a polypharmaceutical composition for treating chronic pain by producing a blockade of the initiation and propagation of the pain stimulus in the Langerhans and other neuroendocrine vascular structures of the superficial and deep dermis is composed of, in combination, at least two pharmaceutical agents selected from the group consisting of an NMDA receptor blocker, a GABA receptor blocker, an AMPA receptor blocker, a nitric oxide synthase receptor blocker, a calcium channel blocker, an ACDP receptor blocker, a prostaglandin blocker, a leukotriene blocker, a substance P blocker, a bradykinin blocker, a neurotenin blocker, a peptide blocker, a TNF alpha blocker, a sympathetic alpha 1 receptor blocker, a sympathetic alpha 2 receptor blocker, and a non-NMDA calcium-channel blocker.
According to still another aspect of the invention, a method of treating pain by producing a blockade of the initiation and propagation of the pain stimulus in the Langerhans and other neuroendocrine vascular structures of the superficial and deep dermis, is performed through an administration step by topically administering to a person in need of such treatment an effective dosage of a combination of at least two pharmaceutical agents selected from the group consisting of an NMDA receptor blocker, a GABA receptor blocker, an AMPA receptor blocker, a nitric oxide synthase receptor blocker, a calcium channel blocker, an ACDP receptor blocker, a prostaglandin blocker, a leukotriene blocker, a substance P blocker, a bradykinin blocker, a neurotenin blocker, a peptide blocker, a TNF alpha blocker, a sympathetic alpha 1 receptor blocker, a sympathetic alpha 2 receptor blocker, and a non-NMDA calcium-channel blocker.
According to a further aspect of the invention, a method of treating pain in a human or animal subject by administering a combination of preselected effective pharmaceutical agents in an suitable dosage to treat a subject in need thereof, is carried out by, first, performing a point locating step by locating a predetermined neurodermal point associated with the pain.
Second, the preselected pharmaceutical agents for treating pain are provided in a gel patch suited for delivery by electrically driving charged ions of the pharmaceutical agents from the path and into the subject.
Third, an application step is performed by applying the provided gel patch to the predetermined neurodermal point on the subject.
Fourth, a delivery step is performed by delivering the selected pharmaceutical agents from the patch to the subject by electrically driving charged ions of the pharmaceutical agents into the subject.
Auteurs: Prof.dr. Jan M. Keppel Hesselink, MD en DJ Kopsky, MD, versie juli 2009