EP1175206A1 - Compositions pharmaceutiques contenant de l'apocodeine et/ou ses derives - Google Patents

Compositions pharmaceutiques contenant de l'apocodeine et/ou ses derives

Info

Publication number
EP1175206A1
EP1175206A1 EP00925551A EP00925551A EP1175206A1 EP 1175206 A1 EP1175206 A1 EP 1175206A1 EP 00925551 A EP00925551 A EP 00925551A EP 00925551 A EP00925551 A EP 00925551A EP 1175206 A1 EP1175206 A1 EP 1175206A1
Authority
EP
European Patent Office
Prior art keywords
apc
derivatives
male
adhesive
active principle
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.)
Withdrawn
Application number
EP00925551A
Other languages
German (de)
English (en)
Inventor
Mario Baraldi
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.)
Unihart Corp
Original Assignee
Unihart Corp
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 Unihart Corp filed Critical Unihart Corp
Publication of EP1175206A1 publication Critical patent/EP1175206A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
    • 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
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • 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
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • 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
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
    • A61K9/7061—Polyacrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence

Definitions

  • the present invention which relates to the use of apocodeine (APC) and/or its derivatives for the preparation of various medicinal forms (patches, tablets, sprays), overcomes the current limitations of the treatment in use for treating the pathologies under consideration, since, in the forms and doses proposed, APC is effective, is free of side effects and requires only simple and cost-effective technology for its preparation.
  • APC apocodeine
  • compositions for the treatment of male impotence and for the stimulation of male and female libido.
  • APC apocodeine
  • the molecule APC and its derivatives are stable with respect to air and light.
  • APC is a powerful drug which can be administered transdermally.
  • the active principle (APC) is rapidly absorbed, becomes effective rapidly (latency time 8 ' -18 ' ) and is equally rapidly eliminated (half-life 30').
  • TDDS transdermal drug delivery system
  • a subject of the present invention is thus a pharmaceutical composition comprising, in pharmaceutically acceptable and effective doses, APC and/or its derivatives.
  • a further subject of the invention is a transdermal patch comprising, as active principle, APC and/or its derivatives, this patch having a type I, type II or type III structure, and its shape and size being suitably sized in relation to the site of application and the desired dosage.
  • a further subject of the invention is the use of APC and/or its derivatives, for the preparation of a transdermal patch for the treatment of male impotence and for the stimulation of male and female libido.
  • TYPE I is a device comprising an impermeable support film on which is a matrix or reservoir in which the active substance is dissolved and/or dispersed.
  • the matrix on the side opposite the support, is coated with a membrane which is permeable to the active substance and regulates its cross-flow.
  • a contact adhesive is layered on the free side of the permeable membrane (adhesive layer) , protected by a release strip.
  • the device is used as follows: the release strip is pulled off and the device is positioned over the desired part of the patient's body and applied with light pressure.
  • TYPE II This device comprises an impermeable support film on which is a matrix or reservoir in which the active substance is dissolved or dispersed. It lacks the membrane which is permeable to the active substance, which modulates the cross-flow, as a result of which the matrix is free on one side and comes into direct contact with the epidermis.
  • the adhesive is located around the edge of the device, as a kind of adhesive ring. The assembly is protected on the free side by a single removable release strip, as in type I.
  • the device is used as follows: the release strip is pulled off and the device is positioned over the desired part of the patient's body and applied with light pressure.
  • TYPE III This is also known as a "drug in an adhesive matrix" assembly.
  • the pharmacological dose is housed directly, in dissolved or dispersed form, in the adhesive, which thus also acts as a reservoir matrix and is layered on an impermeable support film.
  • the adhesive matrix is protected on one side by the support (backing) , and on the other side by the release strip.
  • the device is used as follows: the release strip is pulled off and the device is positioned over the desired part of the patient's body and applied with light pressure.
  • the preferred patch is the type III patch, and more preferably the type III patch with acrylic adhesives, in rectangular shape when it is desired to achieve constantly high doses for long periods, or in anatomical shape when a targeted rapid result is desired (e.g. treatment of sexual impotency) .
  • Fig. 1 is a graph of the accumulation of APC over time.
  • Fig. 2 is a graph of the flow of APC over time
  • Fig. 3 is the approximate curve representing the levels in human plasma at the times indicated, relative to the APC active principles.
  • the active principle APC or a derivative thereof is incorporated simultaneously with the other components (stabilizer, permeation activators, etc.) into the hot adhesive solution and is homogenized by stirring until the liquid adhesive matrix or reservoir is formed;
  • the blade of a knife is mounted across the entire width of the conveyor belt of the laminating machine on which the release strip is solidly positioned;
  • the "thready" adhesive matrix is poured in front of the blade which, as the conveyor belt advances, distributes a uniform layer (lamination) of adhesive matrix over the release strip;
  • the thickness of the layer is determined mainly by the distance between the edge of the knife blade and the release strip passing underneath it;
  • the process described allows the removal of the solvent, thus avoiding its occlusion by the rapid formation of a surface crust.
  • the support film (backing) is affixed.
  • Adhesive matrix formulation
  • antioxidant sodium metadisulphite, EDTA disodium salt
  • solubilizing agent a glycol
  • acrylic resin to improve the cohesive force • acrylic resin to improve the cohesive force: cationic copolymers based on dimethylaminoethyl methacrylate and methacrylic esters
  • surfactant SDS (sodium dodecyl sulphate);
  • pressure-contact adhesive mixture of two adhesives, A and B, in which A is an acrylic contact adhesive of average molecular weight which is not self-bonding, with a high interlacing index, a dermal irritation index of 0.20, classified as "minimally irritant” and containing 100% ethyl acetate as solvent; and B is an acrylic adhesive of high molecular weight, which is self-bonding, with a moderate interlacing index, a dermal irritation index of 0, classified as "non- irritant” and containing a mixture of ethyl acetate, isopropanol, hexane and toluene as solvent.
  • Release strip The release strip is a polyester film laminated with silicone on one side (the side facing the adhesive matrix) . The thickness is approximately 125 ⁇ m.
  • the backing is a laminated, clear, occlusive polyester film with a heat-welding layer.
  • the total thickness is approximately 51 um.
  • APC APC or its derivatives
  • APC/C batch with addition of permeation inducers, 0.5% active principle in the matrix (all of the drug is dissolved) : 1 ) APC/C 0 . 50%
  • the skin permeability of APC is sufficient per se and can be increased or decreased by means of various permeation activators such as fatty acids or alcohols. All of the in-vitro permeation studies were carried out on models using guinea-pig skin, which we know has comparable permeability to that of human skin and which gives more reproducible results than the latter.
  • the chemical stability of APC in the formulation of the patch is achieved by adding an antioxidant (sodium metabisulphite) and is demonstrated by means of a 15-day accelerated stability test at 40°C and 75% RH (relative humidity) .
  • the surfactant (SDS) is added to dissolve most of the APC, since only the dissolved APC is available for release and permeation.
  • the patches also demonstrated good physico- chemical properties, which can be optimized by those skilled in the art for the purposes of adhesion at the site of application and tolerability by the individual undergoing the treatment, without modifying the rate of permeation of the active principle.
  • compositions comprising apocodeine and/or its derivatives for the treatment of male impotence and for the stimulation of male and female libido.
  • APC is a powerful drug which can be administered orally.
  • the active principle is rapidly absorbed, becomes effective rapidly (latency time 8'-18') and is equally rapidly eliminated (half-life 30').
  • APC active principle
  • composition active principle APC 150 mg
  • Excipients corn starch 8 mg tribasic citrate 43 mg magnesium stearate 2 mg total 200 mg
  • B the dose/effect ratio for induction of the penile erection (PE) activity by means of oral apocodeine (APC) in rats.
  • the rats received apocodeine solution or saline solution.
  • the animals were counted in accordance with a double-blind experimental plan.
  • the penile erections were recorded continuously.
  • PEI penile erections
  • the number of animals is given in parentheses
  • the effective dose is between 10 and 40 mg/kg, the optimum being 20 mg/kg.
  • compositions comprising apocodeine and/or its derivatives for the treatment of male impotence and for the stimulation of male and female libido.
  • APC is a powerful drug which can be administered orally in the form of a spray.
  • the active principle is rapidly absorbed, becomes effective rapidly (latency time 8 '-18') and is equally rapidly eliminated (half-life 30').
  • APC single-dose spray Description single-dose bottle with distribution cap (deliverable volume 1 ml) .
  • A. P. APC and/or its derivatives 15% Menthol 0.84%
  • the suspension is prepared at the time of use and is distributed under aseptic conditions into the containers of the distributing machine which automatically closes the bottles by clamping the metering tap onto the neck of the container.

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Physiology (AREA)
  • Endocrinology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Reproductive Health (AREA)
  • Dermatology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Nutrition Science (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Gynecology & Obstetrics (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne trois compositions pharmaceutiques: timbres transdermiques à libération prolongée; pastilles à mâcher/sublinguales; aérosols à base d'apocodéine (APC) ou ses dérivés, pour le traitement de l'impuissance masculine et pour la stimulation de la libido chez les hommes et chez les femmes.
EP00925551A 1999-05-13 2000-05-12 Compositions pharmaceutiques contenant de l'apocodeine et/ou ses derives Withdrawn EP1175206A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
IE990389 1999-05-13
IE990389 1999-05-13
PCT/IE2000/000065 WO2000069416A1 (fr) 1999-05-13 2000-05-12 Compositions pharmaceutiques contenant de l'apocodeine et/ou ses derives

Publications (1)

Publication Number Publication Date
EP1175206A1 true EP1175206A1 (fr) 2002-01-30

Family

ID=11042062

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00925551A Withdrawn EP1175206A1 (fr) 1999-05-13 2000-05-12 Compositions pharmaceutiques contenant de l'apocodeine et/ou ses derives

Country Status (7)

Country Link
EP (1) EP1175206A1 (fr)
JP (1) JP2002544221A (fr)
AU (1) AU4427000A (fr)
CA (1) CA2371551A1 (fr)
MX (1) MXPA01011480A (fr)
NO (1) NO20015519L (fr)
WO (1) WO2000069416A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2405419A1 (fr) * 2000-04-07 2001-10-18 Tap Pharmaceutical Products Inc. Derives d'apomorphine et leurs procedes d'utilisation
SE0002934D0 (sv) * 2000-08-17 2000-08-17 Axon Biochemicals Bv New aporphine esters and in their use in therapy

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4806341A (en) * 1985-02-25 1989-02-21 Rutgers, The State University Of New Jersey Transdermal absorption dosage unit for narcotic analgesics and antagonists and process for administration
FI873429A (fi) * 1986-08-18 1988-02-19 Houston Biotechnology Oftalmologiska kompositioner foer behandling av nervdegenerationer.
DE69709646T2 (de) * 1996-03-12 2002-08-14 Alza Corp., Palo Alto Zusammensetzung und dosisform mit einem opioid-antagonisten

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0069416A1 *

Also Published As

Publication number Publication date
JP2002544221A (ja) 2002-12-24
WO2000069416A1 (fr) 2000-11-23
AU4427000A (en) 2000-12-05
NO20015519D0 (no) 2001-11-12
CA2371551A1 (fr) 2000-11-23
MXPA01011480A (es) 2002-06-04
NO20015519L (no) 2002-01-11

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