Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Web – sheet or filament bases; compositions of bandages; or...
Patent
1996-10-09
1998-01-06
Phelan, D. Gabrielle
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Web, sheet or filament bases; compositions of bandages; or...
424449, A61F 1302
Patent
active
057051860
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP95/00031, filed Jan. 5, 1995.
The present invention relates to the systemic transdermal administration of morphine-6-glucuronide. ##STR1##
BACKGROUND OF THE INVENTION
Morphine-6-glucuronide (glucuronic acid-6-(7,8-didehydro-4,5 epoxy-17-methylmorphinan-3,6 diolyl) ester) is described in literature as active metabolite of morphine, being more effective than the morphine (1980)). The synthesis of morphine-6-glucuronide and of the pharmaceutically usable acid addition salts are described in WO-9305057 and WO-9303051.
Morphine is the drug of choice for the treatment of chronic pain, e.g., in patients suffering from a tumor. The administration of the relatively high daily doses involves some difficulties. Although morphine-6-glucuronide has a higher effectiveness its medical application is still in the beginning. Thus, it is the object of the present invention to find a possibility of applying morphine-6-glucuronide in a simple manner and in the required dosage.
DESCRIPTION OF THE INVENTION
Most surprisingly, this object is achieved by administering morphine-6-glucuronide or its salts transdermally. This solution is surprising all the more since--contrary to all expectations--morphine-6-glucuronide diffuses through the skin more easily than the smaller-sized morphine.
This result could not be expected since a glucuronated compound, as compared with the parent compound, has an increased hydrophilia and polarity, involving the fact that the skin is less passable.
Since morphine-6-glucuronide is an active metabolite of morphine it must be assessed like this with respect to toxicology. This is an advantage of morphine-6-glucuronide as compared with other opioids, such as fentanyl and its derivatives.
The term "pharmaceutical composition for the transdermal administration" is meant to comprise any conventional liquid, semiliquid, or solid preparation, e.g., solutions, ointments, pastes, gels, tinctures, and the like, or polymer-containing matrices.
A transdermal therapeutic system (TTS) is meant to be understood according to Zaffaroni as "a drug-containing device or administration form continuously releasing one or several drugs at a predetermined rate over a predetermined period of time to a fixed place of application" (quoted according to: Hellmann, Klaus: Therapeutische Systeme--Konzept und Realisation programmierter Arzneiverabreichung, 4th edition, Ferdinand Enke Verlag, Stuttgart 1984, p. 26). In the present case the place of application is on the skin.
The structure of transdermal systems is known to those skilled in the art. DE 33 15 272, DE 38 43 239, and U.S. Pat. No. 3,598,122 are examples of patent describing the basic structure.
When a transdermal therapeutic system is applied on the skin of a patient, the drug is to be released to take a topic or systemic effect in the patient. Administration forms of this kind have been used therapeutically for some time. The particularly preferred transdermal system in the form of a patch consists of a backing layer which is impermeable to the active substance, a pressure sensitive adhesive reservoir layer, and optionally of a removable protective layer.
In this connection, the backing layer which is impermeable to the active substance may consist of a flexible or inflexible material. Substances suitable for its production are polymeric sheets or foils, such as an aluminum foil, which are used alone or coated with a polymeric substrate. Textile fabrics may also be used, provided that the components of the reservoir, owing to their physical property, cannot penetrate through them. According to a preferred embodiment, the backing layer is a composite of an aluminized foil.
The reservoir layer comprises a polymer matrix and the active substance, the polymer matrix having the property of ensuring the cohesion of the system. It consists of a base polymer and, optionally, of the usual additives. The choice of the base polymer depends on the chemical and physical properties of the active substance. Examples of such polymers include r
REFERENCES:
patent: 3598122 (1971-08-01), Zaffaroni
Oguri, J. Pharmal. Soc. Japan (Yakugaku Zasshi), 100 (2), pp. 117-125 (1980).
Heilmann, Therapeutische Systeme-Konzept und Realisation programmierter Arzneiverabreichung, 4th Edtion, Ferdinand Enke Verlag. Stuttgard, 1984 (page 26).
Franz, The Journal of Investigative Dermatology, vol. 64, pp. 190-195 (1975).
Hille Thomas
Otto Karlheinz
LTS Lohmann Therapie-Systeme GmbH
Phelan D. Gabrielle
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