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(12) Patent Application Publication (10) Pub. No.: US 2005/0255169 A1 Pilger Et Al

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(12) Patent Application Publication (10) Pub. No.: US 2005/0255169 A1 Pilger Et Al US 2005O255169A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2005/0255169 A1 Pilger et al. (43) Pub. Date: Nov. 17, 2005 (54) ADJUVANT CONTAINING XENON Aug. 10, 2002 (DE)..................................... 102 36 761.2 Aug. 10, 2002 (DE)..................................... 102 36 760.4 (75) Inventors: Carsten Pilger, Rheurdt (DE); Peter Neu, Duisburg (DE); Matthias Publication Classification Reyle-Hahn, Berlin (DE) (51) Int. Cl." ......................... A61K 33/00; A61K 31/46; Correspondence Address: A61K 31/24 CONNOLLY BOVE LODGE & HUTZ, LLP (52) U.S. Cl. ........................... 424/600; 514/304; 514/537 PO BOX 22O7 WILMINGTON, DE 19899 (US) (57) ABSTRACT (73) Assignee: MESSER GRIESHEIM The invention relates to Xenon or Xenon-containing gases which is/are used for producing an adjuvant that is admin (21) Appl. No.: 10/518,067 istered together with another medicament, Such as an anti Viral, antibacterial, antimycotic, neuroprotective, or antican (22) PCT Fed: Jul. 4, 2003 cerogenic agent, parasympathomimetic, parasympatholytic, Spasmolytic, Symnpathomimetic, Sym (86) PCT No.: PCT/EP03/07186 patholytic, preceptor blocker, tranquilizer, neuroleptic, anti (30) Foreign Application Priority Data depressant, analgesic, antipyretic, anticephalalgic, anti-Par kinson's drug, analeptic, antiepileptic, antiemetic, emetic, a Jul. 5, 2002 (DE)..................................... 10230544.7 Substance influencing coagulation, an amino acid, a Vitamin, Aug. 10, 2002 (DE)..................................... 102 36 762O or a hormone. US 2005/0255169 A1 Nov. 17, 2005 ADJUVANT CONTAINING XENON ally. The adjuvant or inhalable medicament comprises gas eous Xenon in pharmacologically or therapeutically effective 0001. The invention relates to a medicament comprising amount, in particular in an amount, concentration or dosage XCO. which has a Subsedative effect, Sedative effect, Subanalgesic 0002 WO 02/22141 A2 describes the use of xenon or activity, analgesic activity, Subhypnotic activity, hypnotic Xenon-containing gases as medicaments, in particular car activity, Subanesthetic activity or anesthetic activity. diovascular agents. 0014 Subanesthetic amounts of xenon mean the 0003) DE 19933704 A1 describes the use of a liquid amounts, concentrations or dosages of Xenon which are preparation which comprises a lipophilic gas Such as Xenon insufficient for general anesthesia. Subsedative amounts of for neuroprotection and neuroregeneration. Xenon mean the amounts, concentrations or dosages of xenon which are insufficient for sedation. Subhypnotic 0004. Many pharmacological active ingredients reach the amounts of Xenon mean the amounts, concentrations or target site (site of action) in a patient's body via the dosages of Xenon which are insufficient for inducing and bloodstream. If the blood flow in a part of the body is maintaining Sleep. Subanalgesic or analegesically active restricted, the active ingredients cannot reach the Site of action in Sufficient quantity. Bloodlessness of individual amounts of Xenon mean the amounts, concentrations or parts of organs as a result of insufficient blood Supply is dosages of Xenon which are insufficient for an analgesic referred to as ischemia. Ischemia arises for example in effect. connection with thrombosis or embolism. Particularly seri 0015 The combination medicament is usually employed ous impairments of blood flow in the brain occur in con for humans or mammals. nection with Stroke. 0016. The medicaments which are combined with the 0005 For many medicaments an inadequate concentra adjuvant include besides the medicaments with pharmaco tion of active ingredient in the brain also derives from the logically active Substances (active ingredients) also diag blood-brain barrier. Medicaments are administered in higher nostic aids, X-ray contrast agents, radioactive isotopes. dose for this reason. 0017. The adjuvant is used for example in combination 0006 Means assisting the effect of a medicament are with an antiviral, antibacterial, antimycotic, neuroprotective, referred to in medicine as adjuvant. anticarcinogenic, Sedative, analgesically or anesthetically acting Substance, in particular with opioids (e.g. Sufentanil, 0007. The invention is based on the object of improving remifentanil), anesthetics, volatile anesthetics (e.g. meth the medicament Supply or active ingredient Supply to parts oxyflurane, halothane, enflurane, isoflurane, Sevoflurane and of the body, in particular of the brain. desflurane), C2-adrenoceptor agonists (e.g. clonidine, 0008. The invention relates to an adjuvant having the dexmedetomidine) or catecholamines. The active ingredi features described in claim 1. ents of the assisted medicaments are usually organic Sub 0009 Xenon or xenon-containing gases (gas mixtures) StanceS. are used as adjuvant or as component of an adjuvant. 0018. The adjuvant is advantageously combined with 0.010 The adjuvant assists in particular medicaments parasympathomimetics, parasympatholytics, Spasmolytics, whose active ingredient or active ingredients are transported Sympathomimetics, Sympatholytics, 3-receptor blockers, via the bloodstream. Medicaments with one or more active tranquilizers, neuroleptics, antidepressants, Sedatives (sedat ingredients which are transported via the bloodstream are ing agents), analgesics, antipyretics, migraine remedies, referred to herein as hemogenous medicaments. Medica antiparkinson agents, analeptics, antiepileptics, antiemetics, ments assisted by the adjuvant are preferably medicaments emetics, Substances influencing blood clotting, amino acids, intended to act in the brain (cerebral medicaments), espe Vitamins or hormones. cially hemogenous cerebral medicaments. 0019. The adjuvant is further employed with medica 0.011 The adjuvant is preferably administered by inhala ments for NOS inhibition, with medicaments for treating tion. The adjuvant is therefore preferably employed as migraine, with medicaments for treating Septic shock, mul inhalable medicament. tiple Sclerosis, inflammations or inflammatory pain. 0012. Adjuvant and supported medicament which are 0020. The adjuvant is used for example with medica employed together are regarded as combination product or ments for the treatment and/or prophylaxis of Stroke, rep combination medicament, the adjuvant and Supported medi erfusion damage, brain trauma, of impairments of the blood cament being administered together in one medicament (the flow in the brain, of impairment of cerebral perfusion, of adjuvant is present in the medicament) or as separate medi cognitive disorders or of post-ischemia Syndrome. CamentS. 0021. The adjuvant is further employed with a medica 0013 The combination medicament composed of a ment for neuroprotection, a medicament for the prophylaxis Xenon-containing medicament, the adjuvant and a further and/or therapy of impairments of cognitive performance, a medicament (the medicament assisted by the adjuvant) serve medicament for improving the oxygen Supply in the brain or for Simultaneous, Separate or Sequential use of the medica a medicament for promoting blood flow in the brain. ments (of the components of the combination medicament). 0022. The combination medicaments include in particu The combination medicament preferably consists of an lar the adjuvant and a medicament for the therapy of inhalable medicament which comprises xenon (e.g. Xenon or disorders associated with a loSS of cognitive and memory a xenon-containing gas), and of a hemogenous medicament, functions, e.g. in the course of pathological aging process e.g. a medicament which is administered orally or parenter Such as, for example, Parkinson's disease, Alzheimer's US 2005/0255169 A1 Nov. 17, 2005 disease, the organic brain Syndrome, AIDS dementia, 0029 Salicylic acid derivatives are acetylsalicylic acid, depressive pseudodementias, dementing Syndromes, deliria benorilate, diflunisal, ethenZamide gentisate Sodium, Salac as acute organic brain Syndromes, intoxications, withdrawal etamide, Salicylamide, Salicylic acid or Salsalate. Pyrazolone Syndromes or cytopathic influences. derivatives are metamizole (noramidopyrine), moraZone, phenaZone or propyphenaZone. An aminophenol derivative 0023 The adjuvant is advantageously employed in com is paracetamol. Further analgesics are quinine, flunixine, bination with medicaments for chronic neurodegenerative disorderS Such as Huntington's disease, amyotropically lat flupirtine or benzyl phenylglycolate (mandelic acid benzyl eral Sclerosis, Parkinson's disease, AIDS dementia, Alzhe ester, benzyl mandelate). imer's disease or acute neurodegenerative disorderS Such as 0030 The adjuvant is further employed in combination ischemias of the brain and neurotraumata. with a local anesthetic agent (local anesthetic). Local anes thetic agents are, for example, articaine, benzoVaine, bupi 0024. The adjuvant is advantageously used in combina vacaine, butanilicaine, butoxycaine, cinchocaine, cocaine, tion with Sedative Substances, in particular with centrally etidocaine, fomocaine, lidocaine, mepivacaine, OXetacaine, Sedative Substances. The Sedative Substances are usually Oxybuprocaine, pramocaine, prilocaine, procaine, organic active ingredients having a Sedative effect. The proxymetacaine, ropivacaine, tolycaine or tetracaine. The Sedative Substances are usually contained in a medicament (sedative medicament, Sedating agent or sedative) which is assisted medicament may also be a mixture of two or more administered with the adjuvant, in particular as combination
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