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WO1996014071A1 - Combinaison de composes pharmacologiques utilisee comme medicament destine a supprimer la dependence d'individus aux opiaces - Google Patents

Combinaison de composes pharmacologiques utilisee comme medicament destine a supprimer la dependence d'individus aux opiaces Download PDF

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Publication number
WO1996014071A1
WO1996014071A1 PCT/ES1994/000108 ES9400108W WO9614071A1 WO 1996014071 A1 WO1996014071 A1 WO 1996014071A1 ES 9400108 W ES9400108 W ES 9400108W WO 9614071 A1 WO9614071 A1 WO 9614071A1
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WO
WIPO (PCT)
Prior art keywords
combination
drugs
dose
milligrams
dependence
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Application number
PCT/ES1994/000108
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English (en)
Spanish (es)
Inventor
Juan José Legarda Ibañez
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to US08/666,533 priority Critical patent/US6103734A/en
Priority to HU9601835A priority patent/HUT75938A/hu
Priority to BR9408488A priority patent/BR9408488A/pt
Priority to CA002180117A priority patent/CA2180117A1/fr
Priority to FI962728A priority patent/FI962728L/fi
Priority to JP8515069A priority patent/JPH09507865A/ja
Application filed by Individual filed Critical Individual
Priority to PCT/ES1994/000108 priority patent/WO1996014071A1/fr
Priority claimed from BR9408488A external-priority patent/BR9408488A/pt
Publication of WO1996014071A1 publication Critical patent/WO1996014071A1/fr
Priority to NO962740A priority patent/NO962740L/no
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/485—Morphinan derivatives, e.g. morphine, codeine

Definitions

  • the present description deals with an invention based on the combination of certain chemical compounds or drugs through which the detoxification of drug addicts is carried out to opioid substances in a period of less than 24 hours.
  • abstinence is treated in various documents such as the article "Substance abuse disorders: a psychiatric priority" in Am. J. Psychiatry 148, concentrated on pages 1291 to 1300 written by the Group for the advancement of the Psychiatry Committee for Alcoholism and Addictions in 1991.
  • Detoxification methods may include drug substitution, using an opioid agonist such as methadone as indicated in the article by M. Gossop et al 1989 "Opiate withdrawal responses to 10-day and 21-day methadone withdrawal programs "(10 and 21 day methadone withdrawal programs) from British Journal Psychiatry 154, or through the use of partial opioid agonists such as Buprenorphine as indicated in” Human pharmacology and abuse potential of the analgesic buprenorphine "(Human Pharmacology and potential abuse of analgesic buprenorphine) by Jasinski et al in Arch. Gen. Psychiatry 35 in 1978.
  • an opioid agonist such as methadone as indicated in the article by M. Gossop et al 1989 "Opiate withdrawal responses to 10-day and 21-day methadone withdrawal programs "(10 and 21 day methadone withdrawal programs) from British Journal Psychiatry 154
  • partial opioid agonists such as Buprenorphine as indicated
  • adrenergic agonists such as clonidine or guanfacine as indicated in the articles "clonidine in opiate withdrawal” ( Clonidine in opioid withdrawal) from Ms Gold and others of 1978 in Lancet i, and in "Preliminary results of guanfacine treatment of acute opiate withdrawal” by Schubert et al in American Journal Psychiatry 141.
  • Psychiatry 148 as "Techniq ⁇ e for greatly shortening the transition from methadone to naltrexone maintenance of patients addicts to opiates" (Technique to minimize the transition in the maintenance of methadone to naltrexone in patients with opioid addiction). More recently, a new treatment route has been used with twenty individuals addicted to heroin. The procedure was non-invasive, that is, all medication was given orally and began twelve hours after the last heroin use as extracted from the article by N. Loimer and others of 1993 "ultrashort non invasive opiate detoxification” (Detoxification ultra short opioid non-invasive) published in Am. J. Psychiatry 150.
  • This procedure consisted of using the same sedative as in the previous experience, midazolam, but at even higher doses than in the previous case.
  • This procedure also included an alpha-adrenergic agonist, a clonidine that enhances sedation and decreases the symptoms of opioid withdrawal syndrome and an antiemetic, ondansetron.
  • an opioid antagonists naloxone and naltrexone, were used in very high doses, 4 and 50 milligrams respectively in a single dose.
  • the present invention represents a combination of drugs that allows an ultra-rapid pattern for the detoxification of drug illuminators addicted to heroin and / or methadone or other opiates.
  • the use of certain compounds will be carried out according to guidelines that, in the first place, can begin, unlike other guidelines, immediately after the patient has made his last opioid consumption, therefore, it is not necessary to wait as he puts in practice according to other treaties, just as it is not necessary to substitute an opioid for another before starting the application of the detoxification products provided for in the present invention, an additional novelty is the incorporation of one of the anesthetic sleep inductors used, the Propofol, a product that has never been used by other specialists in this field and both this and any other, for example midazolam, can be supplied in the recommended therapeutic doses without the need to dangerously increase its dosage.
  • patient monitoring must necessarily include blood pressure, cardiac activity and oxygen saturation in arterial blood. This last parameter has not been previously used by Other specialists in this field. Additionally, it should be mentioned that the products of the invention are used by invasive procedures. Likewise, sedation and / or anesthesia is maintained with monitoring for a minimum period of three hours. In addition, there are minimum requirements necessary to perform this type of intervention, a secretion aspirator and an apparatus for assisted breathing. The application of the drugs, therefore, must be carried out in the vicinity of an intensive care unit or in it, or in a hospital cabin that meets the necessary requirements.
  • the optional intake, one day before admission, of a laxative is required in order to perform as well as possible intestinal cleansing, the patient fasting at least eight hours before the intervention.
  • a complete medical and psychological examination will be carried out, discarding any type of pathology that contraindicates the treatment and the necessary analytical determinations such as blood count, biochemistry, pregnancy test will be performed in the case in which the patient is a woman in fertile age, and other complementary examinations directed according to the semiology found in the physical examination, such as chest x-ray, computerized axial tomography, electrocardiogram and electroencephalogram.
  • alpha adrenergic agents such as guanfacine or clomdine
  • guanfacine or clomdine will be administered at the time of admission, ensuring tension Blood pressure is not less than 90-60 mmHg or the heart rate is less than 55 systoles per minute, once the patient's examination is finished, the intervention can begin.
  • a peripheral venous route will be taken and, in the absence thereof, a central route, antiemetics such as ondansetron, and gastric protectors such as H2 antihistamines are administered, among which ranitidine and / or pump inhibitors can be found.
  • protons such as omeprazole and the patient is sedated or anesthetized with anesthetic agents such as propofol or propofol and a benzodiazepine such as midazolan and which will be kept in constant infusion at a dose adjusted to the patient's response and not higher than recommended by the pharmaceutical laboratory.
  • the opioid antagonist, naloxone and / or naltrexone is then given.
  • the administration of opioid antagonist will be repeated as appropriate and at doses that depend on the amount of heroin to which the patient is accustomed.
  • Each dose of naltrexone should never exceed 40 milligrams, nor will the total dose exceed 50 milligrams.
  • a naloxone test consisting of the intravenous administration of 0.8 milligrams of said substance is performed. If this test is negative, that is, no signs of withdrawal appear, the anesthetic administration is suspended, the patient is awakened, and the administration of an analgesic such as ketorolac, an H2 antihistamine such as ranitidine, a benzodiazepine such as ketazolam and an adrenergic agonist such as guanfacine.
  • an analgesic such as ketorolac, an H2 antihistamine such as ranitidine, a benzodiazepine such as ketazolam and an adrenergic agonist such as guanfacine.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Emergency Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Combinaison de composés pharmacologiques utilisée comme médicament destiné à la suppression de la dépendence d'individus aux opiacés, cette combinaison comprenant un laxatif ou irrigateur, des doses répétées d'agents alpha-adrénergiques, des antiémétiques, des protecteurs gastriques, éventuellement des inhibiteurs de la pompe à protons, un anxiolytique, une dose d'un agent induisant le sommeil anesthésique, et des doses déterminées d'un antagoniste opiacé, tel que la naxalone ou la naltrexone.
PCT/ES1994/000108 1994-11-04 1994-11-04 Combinaison de composes pharmacologiques utilisee comme medicament destine a supprimer la dependence d'individus aux opiaces Ceased WO1996014071A1 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
HU9601835A HUT75938A (hu) 1994-11-04 1994-11-04 Egyének opiátfüggőségének elnyomására szolgáló kombinációs gyógyszerkészítmények
BR9408488A BR9408488A (pt) 1994-11-04 1994-11-04 Combinação de drogas como um medicamento para suprimir a dependência de opiatos de indivíduos
CA002180117A CA2180117A1 (fr) 1994-11-04 1994-11-04 Combinaison de composes pharmacologiques utilisee comme medicament destine a supprimer la dependence d'individus aux opiaces
FI962728A FI962728L (fi) 1994-11-04 1994-11-04 Lääkeyhdistelmä yksilöiden riippuvuutta opiaateista ehkäisevänä lääkkeenä
JP8515069A JPH09507865A (ja) 1994-11-04 1994-11-04 麻薬への個人の依存を抑制する薬剤としての薬物の組み合わせ
US08/666,533 US6103734A (en) 1994-11-04 1994-11-04 Drug combination as a medicament to suppress the dependence of individuals to opiates
PCT/ES1994/000108 WO1996014071A1 (fr) 1994-11-04 1994-11-04 Combinaison de composes pharmacologiques utilisee comme medicament destine a supprimer la dependence d'individus aux opiaces
NO962740A NO962740L (no) 1994-11-04 1996-06-28 Medisinkobinasjon ment som medikament til undertrykkelse av individers opiatavhengighet

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
BR9408488A BR9408488A (pt) 1994-11-04 1994-11-04 Combinação de drogas como um medicamento para suprimir a dependência de opiatos de indivíduos
PCT/ES1994/000108 WO1996014071A1 (fr) 1994-11-04 1994-11-04 Combinaison de composes pharmacologiques utilisee comme medicament destine a supprimer la dependence d'individus aux opiaces

Publications (1)

Publication Number Publication Date
WO1996014071A1 true WO1996014071A1 (fr) 1996-05-17

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/ES1994/000108 Ceased WO1996014071A1 (fr) 1994-11-04 1994-11-04 Combinaison de composes pharmacologiques utilisee comme medicament destine a supprimer la dependence d'individus aux opiaces

Country Status (1)

Country Link
WO (1) WO1996014071A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998047481A1 (fr) * 1997-04-18 1998-10-29 Janssen Pharmaceutica N.V. Utilisation d'antagonistes du 5ht3 pour faciliter un lavage intestinal
WO2001068080A3 (fr) * 2000-03-15 2002-07-04 Wolfgang Sadee Antagonistes neutres et utilisation de ces derniers dans le traitement de l'abus des drogues
WO2001064201A3 (fr) * 2000-02-28 2002-07-18 Britannia Pharmaceuticals Ltd Substances diminuant la reapparition de l'usage de drogues

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
C. BREWER: "Opioid withdrawal and naltrexone induction in 48-72 hours with minimal drop-out, using a modification of the naltrexone-clonidine technique.", BR. J. PSICHIATRY, vol. 153, 1988, pages 340 - 343 *
E. VINING: "Clinical utility of rapid clonidine-naltrexone detoxificarion for opioid abusers", BR. J. ADDICT., vol. 83, no. 5, 1988, pages 567 - 575 *
J. FLOREZ: "Farmacología Humana", 1992, EDICIONES CIENTIFICAS Y TECNICAS, S.A., BARCELONA *
J.J. LEGARDA: "A 24-h inpatient detoxification treatment for heroin addicts: a preliminary investigation.", DRUG AND ALCOHOL DEPENDENCE, vol. 35, no. 2, May 1994 (1994-05-01), pages 91 - 93 *
N. LOIMER: "Ultrashort nonivasive opiate detoxification", AM J PSICHIATRY, vol. 150, no. 5, 1993, pages 839 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998047481A1 (fr) * 1997-04-18 1998-10-29 Janssen Pharmaceutica N.V. Utilisation d'antagonistes du 5ht3 pour faciliter un lavage intestinal
US6235745B1 (en) 1997-04-18 2001-05-22 Janssen Pharmaceutica N.V. Use of 5HT3, antagonists for promoting intestinal lavage
US6555546B2 (en) 1997-04-18 2003-04-29 Janssen Pharmaceutics, N.V. Use of 5HT3 antagonists for promoting intestinal lavage
WO2001064201A3 (fr) * 2000-02-28 2002-07-18 Britannia Pharmaceuticals Ltd Substances diminuant la reapparition de l'usage de drogues
WO2001068080A3 (fr) * 2000-03-15 2002-07-04 Wolfgang Sadee Antagonistes neutres et utilisation de ces derniers dans le traitement de l'abus des drogues
US6713488B2 (en) 2000-03-15 2004-03-30 Sadee Wolfgang Neutral antagonists and use thereof in treating drug abuse

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