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WO1998030171A1 - Implant antagoniste des opiaces et procede de preparation correspondant - Google Patents

Implant antagoniste des opiaces et procede de preparation correspondant Download PDF

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Publication number
WO1998030171A1
WO1998030171A1 PCT/US1998/000510 US9800510W WO9830171A1 WO 1998030171 A1 WO1998030171 A1 WO 1998030171A1 US 9800510 W US9800510 W US 9800510W WO 9830171 A1 WO9830171 A1 WO 9830171A1
Authority
WO
WIPO (PCT)
Prior art keywords
implant
opiate antagonist
naltrexone
opiate
approximately
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.)
Ceased
Application number
PCT/US1998/000510
Other languages
English (en)
Inventor
Lance L. Gooberman
George J. Malmberg
Alan R. Tripp
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
Application filed by Individual filed Critical Individual
Priority to CA002278137A priority Critical patent/CA2278137A1/fr
Priority to AU59130/98A priority patent/AU5913098A/en
Publication of WO1998030171A1 publication Critical patent/WO1998030171A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

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
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
    • 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
    • A61K31/439—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 the ring forming part of a bridged ring system, e.g. quinuclidine
    • 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
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • 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

Definitions

  • Heroin addiction is a growing health care problem in the United States.
  • the United States Department of Health and Human Services ' Substance Abuse Branch issued a report in December of 1994 stating that the number of emergency department visits directly related to heroin use rose from 48,000 in 1992 to 63,000 in 1993, a 31% increase.
  • the rate of heroin-related episodes per 100,000 people rose 81%, from 15 to 28 per 100,000, between 1990 and 1993.
  • U.S. Patent No. 5,486,362 has disclosed a subcutaneous implantable drug delivery system said to useful for treating nicotine-addicted individuals which consists of a physical constraint modulation system ("PCMS") containing a drug substitute such as lobeline, a substituted piperidine compound obtained from dried leaves of the Indian tobacco herb Lobelia inflata .
  • PCMS physical constraint modulation system
  • lobeline a substituted piperidine compound obtained from dried leaves of the Indian tobacco herb Lobelia inflata .
  • Lobeline is said to produce physiological effects similar to nicotine and thus is an effective nicotine substitute which assists individuals in lessening addiction to nicotine, albeit with some undesirable side effects.
  • Other drug substitutes said to be deliverable include the opiate antagonist naltrexone.
  • inventive implants which are comprised of compressed antagonist compounds and a pharmaceutically acceptable carrier or filler, advantageously avoids the use of conventional complex copolymer delivery systems, polymer matrices, encapsulating agents and other expensive and complex time-release agents, which have been found to produce unacceptable complications in humans in earlier studies.
  • inventive implants are easily manufactured with active ingredient antagonist in concentrated form for direct subcutaneous implantation in humans to treat addiction and to prevent various re-addiction.
  • the respective amounts of antagonist and binder may vary from about 0.01% antagonist/99.9% binder to 99.9% antagonist/0.01% binder, with the preferred antagonist range being from about 45% wt to about 95% wt with the remainder carrier or filler material binder.
  • EXAMPLE I PREPARATION A quantity of naltrexone hydrochloric acid is mixed with purified water in the ratio of 1 gram of naltrexone HCL for every 3 ml of water in order to obtain a slurry. A 10% sodium hydroxide solution is then added to and mixed with the slurry in a ratio of 1.06 ml for every gram of naltrexone HCL in the slurry.
  • the naltrexone and magnesium stearate mixture is uniformly compressed into pellets of equal density. This is preferably accomplished by using a hand operated pellet press such as the Parr Pellet Press, Model # Parr. To obtain a pellet of one preferred size, approximately 1.079 grams of the naltrexone/magnesium stearate 15:1 mix is weighed out and then pressed using a 1/2" die and punch. The pellet press used preferably applies approximately 1000 psi of pressure on the punch which causes a firm pellet having a homogenous density to be formed.
  • the resulting implantable pellet is preferably cylindrical in shape, has a diameter of approximately 13 mm, has a length of 8 mm, weighs approximately 1.04 grams, has a naltrexone content of approximately 1.006 grams and has a hardness in the range of about 12.5 to about 14.0 kiloponds.
  • a pellet having such properties is expected to deliver therapeutically effective amounts of naltrexone in a patient in which the pellet has been subcutaneously implanted for approximately one month or longer to effectively inhibit the effects of a number of addictive drugs including heroin, cocaine, alcohol, and nicotine .
  • Such time will depend on the size of the pellet inserted in addition to the type and the percentage of the opiate antagonist contained therein.
  • a pellet comprising approximately 95% naltrexone, which is approximately 8 mm long and has a diameter of approximately 13 mm, will supply therapeutic amounts of the opiate antagonist for up to one month or longer.
  • the delivery of sufficient levels of the opiate antagonist in the patient eliminates the mood-altering effects of any opiate that the patient takes, and will help to maintain sobriety while the patient seeks counseling.
  • the implant is also useful in eliminating the mood-altering effects of cocaine, alcohol, and nicotine.
  • larger pellets may be manufactured and implanted.
  • the first group received naltrexone maintenance therapy by oral administration of 50 mgs of naltrexone per day.
  • the second group (DNM) received naltrexone maintenance through a depot naltrexone preparation containing 1000 mgs of naltrexone per month, via a pellet implant used in Table I.

Landscapes

  • 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)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Dermatology (AREA)
  • Emergency Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention se rapporte à un implant antagoniste des opiacés qui est un mélange d'un antagoniste d'opiacés, soit sous forme basique ou sous forme acide, et d'un excipient pharmaceutiquement acceptable. Ledit mélange est uniformément comprimé en une pastille susceptible d'être implantée par voie sous-cutanée, qui sert à libérer des concentrations de l'antagoniste d'opiacés, pendant des périodes désirées, après qu'on l'ait implantée chez un patient dans le but d'inhiber efficacement les effets de certaines drogues engendrant une dépendance.
PCT/US1998/000510 1997-01-13 1998-01-13 Implant antagoniste des opiaces et procede de preparation correspondant Ceased WO1998030171A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CA002278137A CA2278137A1 (fr) 1997-01-13 1998-01-13 Implant antagoniste des opiaces et procede de preparation correspondant
AU59130/98A AU5913098A (en) 1997-01-13 1998-01-13 Opiate antagonist implant and process of preparation therefor

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US2860597P 1997-01-13 1997-01-13
US60/028,605 1997-01-13
US82900397A 1997-03-31 1997-03-31
US08/829,003 1997-03-31

Publications (1)

Publication Number Publication Date
WO1998030171A1 true WO1998030171A1 (fr) 1998-07-16

Family

ID=26703898

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1998/000510 Ceased WO1998030171A1 (fr) 1997-01-13 1998-01-13 Implant antagoniste des opiaces et procede de preparation correspondant

Country Status (3)

Country Link
AU (1) AU5913098A (fr)
CA (1) CA2278137A1 (fr)
WO (1) WO1998030171A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20210059943A1 (en) * 2019-09-04 2021-03-04 Buffalo Pacific LLC Systems and methods addressing multiple aspects to provide a comprehensive recovery program for addictions, chronic conditions and diseases
US11197819B1 (en) 2021-04-09 2021-12-14 Drug Delivery Company, Llc Extended release bioabsorbable subcutaneous medicinal dosage delivery implant system
WO2022120444A1 (fr) * 2020-12-11 2022-06-16 Luiz Peracchi Edson Implant sous-cutané réabsorbable de longue durée à libération prolongée de substance pharmacologiquement active pré-concentrée en polymère pour le traitement de la dépendance à la nicotine et procédé
US20230097377A1 (en) * 2021-09-17 2023-03-30 Biocorrx, Inc. Biodegradable Implant Including Naltrexone
WO2023164438A1 (fr) * 2022-02-22 2023-08-31 Delpor, Inc. Dispositifs implantables pour l'administration prolongée d'un antagoniste opioïde et procédés de traitement de troubles inflammatoires, neuroinflammatoires et métaboliques

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4351337A (en) * 1973-05-17 1982-09-28 Arthur D. Little, Inc. Biodegradable, implantable drug delivery device, and process for preparing and using the same
US4935428A (en) * 1987-12-03 1990-06-19 Reckitt & Colman Products Limited Treating opiate dependence

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4351337A (en) * 1973-05-17 1982-09-28 Arthur D. Little, Inc. Biodegradable, implantable drug delivery device, and process for preparing and using the same
US4935428A (en) * 1987-12-03 1990-06-19 Reckitt & Colman Products Limited Treating opiate dependence

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20210059943A1 (en) * 2019-09-04 2021-03-04 Buffalo Pacific LLC Systems and methods addressing multiple aspects to provide a comprehensive recovery program for addictions, chronic conditions and diseases
US20240016740A1 (en) * 2019-09-04 2024-01-18 David Lee Allen Medical treatment delivery system employing subcutaneous implants for sustained medication release
WO2022120444A1 (fr) * 2020-12-11 2022-06-16 Luiz Peracchi Edson Implant sous-cutané réabsorbable de longue durée à libération prolongée de substance pharmacologiquement active pré-concentrée en polymère pour le traitement de la dépendance à la nicotine et procédé
US11197819B1 (en) 2021-04-09 2021-12-14 Drug Delivery Company, Llc Extended release bioabsorbable subcutaneous medicinal dosage delivery implant system
US20230097377A1 (en) * 2021-09-17 2023-03-30 Biocorrx, Inc. Biodegradable Implant Including Naltrexone
WO2023164438A1 (fr) * 2022-02-22 2023-08-31 Delpor, Inc. Dispositifs implantables pour l'administration prolongée d'un antagoniste opioïde et procédés de traitement de troubles inflammatoires, neuroinflammatoires et métaboliques

Also Published As

Publication number Publication date
CA2278137A1 (fr) 1998-07-16
AU5913098A (en) 1998-08-03

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