CA2333076A1 - Topical application of muscarinic analgesic drugs such as neostigmine - Google Patents

Topical application of muscarinic analgesic drugs such as neostigmine Download PDF

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Publication number
CA2333076A1
CA2333076A1 CA002333076A CA2333076A CA2333076A1 CA 2333076 A1 CA2333076 A1 CA 2333076A1 CA 002333076 A CA002333076 A CA 002333076A CA 2333076 A CA2333076 A CA 2333076A CA 2333076 A1 CA2333076 A1 CA 2333076A1
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CA
Canada
Prior art keywords
skin
analgesic agent
mucosal
inflamed
penetration enhancer
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.)
Granted
Application number
CA002333076A
Other languages
French (fr)
Other versions
CA2333076C (en
Inventor
George F. El Khoury
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Individual
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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
Publication of CA2333076A1 publication Critical patent/CA2333076A1/en
Application granted granted Critical
Publication of CA2333076C publication Critical patent/CA2333076C/en
Anticipated expiration legal-status Critical
Expired - Fee Related 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
    • A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/27—Esters, e.g. nitroglycerine, selenocyanates of carbamic or thiocarbamic acids, meprobamate, carbachol, neostigmine
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids

Abstract

The invention is directed to methods and pharmaceutical compositions for the topical administration of analgesic drugs which affects peripheral muscarinic receptors such as neostigmine. In particular, the invention relates to topical administration of an analgesic agent, e.g., neostigmine, optionally in admixture with a skin- or mucosal-specific penetration enhancer, to produce a localized analgesic effect in inflamed or non-inflamed skin or mucosal tissue, and without a transdermal or transmucosal migration of the agent, e.g., into the central nervous system.

Claims (25)

1. A method of inducing analgesia in inflamed or non-inflamed skin or mucosal tissue, comprising topically administering to a patient in need of such treatment a topically effective amount of an analgesic agent which affects peripheral muscarinic receptors, which amount is systemically ineffective for induction of analgesia, optionally admixed with a skin- or mucosal-specific penetration enhancer and a pharmaceutically acceptable excipient for topical administration, whereby effective analgesia in the inflamed or non-inflamed skin or mucosal tissue is induced in the substantial absence of transdermal or transmucosal delivery of the analgesic agent to the central nervous system.
2. A method of claim 1, wherein the skin- or mucosal-specific penetration enhancer is present and is lecithin.
3. A method of claim 1, wherein the analgesic agent is administered in an amount analgesically equivalent to 100 mg of neostigmine per 6 in2 of skin.
4. A method of claim 1, wherein the analgesic agent is neostigmine.
5. A method of claim 1, wherein the excipient is a liquid and the admixture is administered by spraying the liquid onto the skin or mucosal tissue.
6. A method of claim 1, wherein the excipient is a gel or cream and the admixture is administered by spreading the gel or cream on the skin or mucosal tissue.
7. A method of claim 6, wherein the amount administered is analgesically equivalent to 100 mg of neostigmine.
8. A pharmaceutical composition comprising an admixture of an analgesic agent which affects peripheral muscarinic receptors, a skin- or mucosal-specific penetration enhancer and a pharmaceutically acceptable excipient for topical administration to inflamed or non-inflamed skin or mucosal tissue, wherein a unit dosage amount of the admixture contains a systemically ineffective amount of the analgesic agent, and the amount of penetration enhancer is effective to enhance penetration of the analgesic agent into the skin or mucosal tissue, and the penetration enhancer and excipient do not enhance transdermal or transmucosal transmission of the analgesic agent to the central nervous system, with the proviso that, when the admixture is a liquid, it further comprises a component that is pharmaceutically unacceptable for parenteral administration.
9. A pharmaceutical composition of claim 8, wherein a unit dosage amount of the analgesic agent is analgesically equivalent to 100 mg of neostigmine per 6 in2 of skin.
10. A pharmaceutical composition of claim 8, wherein the analgesic agent is neostigmine.
11. A pharmaceutical composition of claim 8, wherein the excipient is a liquid and the admixture is administered by spraying the liquid onto the skin or mucosal tissue.
12. A pharmaceutical composition of claim 8, wherein the excipient is a gel or cream and the admixture is administered by spreading the gel or cream on the skin or mucosal tissue.
13. A pharmaceutical composition of claim 8, in a unit dosage form analgesically equivalent to 50 - 100 mg of neostigmine.
14. A pharmaceutical composition comprising an admixture of an analgesic agent which affects peripheral muscarinic receptors, optionally a skin- or mucosal-penetration enhancer and a pharmaceutically acceptable excipient for topical administration, wherein the enhancer and the excipient do not substantially enhance transdermal or transmucosal transmission of the analgesic agent to the central nervous system, in a unit dosage form analgesically equivalent to 50 - 100 mg of neostigmine.
15. A container adapted for spraying a measured amount of a liquid onto skin, and containing a pharmaceutical composition comprising an admixture of an analgesic agent which affects peripheral muscarinic receptors, optionally a skin- or mucosal-penetration enhancer and a pharmaceutically acceptable excipient for topical administration.
16. A method of inducing analgesia in inflamed or non-inflamed skin or mucosal tissue, comprising topically administering to a patient in need of such treatment a topically analgesically effective amount of an analgesic agent which affects peripheral muscarinic receptors, optionally admixed with a skin- or mucosal-penetration enhancer and a pharmaceutically acceptable excipient for topical administration, wherein the amount of analgesic agent is sufficient to directly activate peripheral muscarinic receptors in the inflamed or non-inflamed skin or mucosal tissue, but not sufficient to activate central nervous system muscarinic receptors.
17. A method of claim 16, whereby effective analgesia in the inflamed or non-inflamed skin or mucosal tissue is induced in the substantial absence of transdermal or transmucosal delivery of the analgesic agent.
18. A method of claim 16, wherein the analgesic agent is administered in an amount analgesically equivalent to 100 mg of neostigmine per 6 in2 of skin.
19. A pharmaceutical composition of claim 8, wherein the skin- or mucosal-specific penetration enhancer is present and is lecithin.
20. A pharmaceutical composition of claim 14, wherein the skin- or mucosal-specific penetration enhancer is present and is lecithin.
21. A container of claim 15, wherein the skin- or mucosal-specific penetration enhancer is present and is lecithin.
22. A method of claim 16, wherein the skin- or mucosal-specific penetration enhancer is present and is lecithin.
23. A pharmaceutical composition of claim 8, further comprising an effective amount of dextromethorphan.
24. A method of claim 1, further comprising administering an effective amount of dextromethorphan.
25. A method of claim 16, further comprising administering an effective amount of dextromethorphan.
CA002333076A 1998-05-21 1999-05-21 Topical application of muscarinic analgesic drugs such as neostigmine Expired - Fee Related CA2333076C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US09/083,431 US6011022A (en) 1998-03-03 1998-05-21 Topical application of muscarinic analgesic drugs such as neostigmine
US09/083,431 1998-05-21
PCT/US1999/011189 WO1999059577A1 (en) 1998-05-21 1999-05-21 Topical application of muscarinic analgesic drugs such as neostigmine

Publications (2)

Publication Number Publication Date
CA2333076A1 true CA2333076A1 (en) 1999-11-25
CA2333076C CA2333076C (en) 2009-12-08

Family

ID=22178285

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002333076A Expired - Fee Related CA2333076C (en) 1998-05-21 1999-05-21 Topical application of muscarinic analgesic drugs such as neostigmine

Country Status (6)

Country Link
US (1) US6011022A (en)
EP (1) EP1083892A1 (en)
AU (1) AU767544B2 (en)
CA (1) CA2333076C (en)
TW (1) TWI265027B (en)
WO (1) WO1999059577A1 (en)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6787149B1 (en) * 1996-12-12 2004-09-07 El Khoury And Stein Ltd. Topical application of opioid analgesic drugs such as morphine
US5994330A (en) * 1998-11-09 1999-11-30 El Khoury; Georges F. Topical application of muscarinic agents such as neostigmine for treatment of acne and other inflammatory conditions
GB9918760D0 (en) * 1999-08-09 1999-10-13 Darwin Discovery Ltd Topical treatment
EP1406604A2 (en) * 1999-11-16 2004-04-14 George F. El Khoury Topical application of muscarinic analgesic drugs such as neostigmine
WO2004089357A2 (en) * 2003-04-02 2004-10-21 Regents Of The University Of Minnesota Anti-fungal formulation of triterpene and essential oil
US7662177B2 (en) * 2006-04-12 2010-02-16 Bacoustics, Llc Apparatus and methods for pain relief using ultrasound waves in combination with cryogenic energy
US10493049B2 (en) 2016-02-10 2019-12-03 Niracle LLC Applicator-based transdermal drug delivery system for administration of drugs in combination with topical formulations
CN114010575A (en) * 2021-10-22 2022-02-08 江苏谛奇医药科技有限公司 Novel formulations of neostigmine and derivatives thereof
CN117545474A (en) 2021-11-08 2024-02-09 李维庸 Transdermal drug delivery system for delivering a drug to a patient

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3275510A (en) * 1966-09-27 Topical antitussive preparations
US4328222A (en) * 1978-11-21 1982-05-04 Hoffmann-La Roche Inc. Pharmaceutical compositions for parenteral or local administration
US4416886A (en) * 1981-07-29 1983-11-22 Dermall Limited Method of treating pruritis and composition therefor
US4493848A (en) * 1983-07-14 1985-01-15 The Procter & Gamble Company Compositions and methods useful for producing analgesia
US4626539A (en) * 1984-08-10 1986-12-02 E. I. Dupont De Nemours And Company Trandermal delivery of opioids
US4783450A (en) * 1987-04-13 1988-11-08 Warner-Lambert Company Use of commercial lecithin as skin penetration enhancer
US4897260A (en) * 1987-05-22 1990-01-30 The Rockefeller University Compositions that affect suppression of cutaneous delayed hypersensitivity and products including same
DE3874229T2 (en) * 1987-06-16 1993-03-25 British Tech Group USE OF DIOXOPIPERIDINE DERIVATIVES FOR PRODUCING A TOPICAL PREPARATION AS AN ANALGETIC.
US5719197A (en) * 1988-03-04 1998-02-17 Noven Pharmaceuticals, Inc. Compositions and methods for topical administration of pharmaceutically active agents
US5446070A (en) * 1991-02-27 1995-08-29 Nover Pharmaceuticals, Inc. Compositions and methods for topical administration of pharmaceutically active agents
US5725871A (en) * 1989-08-18 1998-03-10 Danbiosyst Uk Limited Drug delivery compositions comprising lysophosphoglycerolipid
US5069909A (en) * 1990-06-20 1991-12-03 Cygnus Therapeutic Systems Transdermal administration of buprenorphine
WO1992013540A1 (en) * 1991-02-06 1992-08-20 Guy Parent Antalgic ointment
US5589480A (en) * 1994-08-17 1996-12-31 Elkhoury; George F. Topical application of opioid analgesic drugs such as morphine
US5654337A (en) * 1995-03-24 1997-08-05 II William Scott Snyder Topical formulation for local delivery of a pharmaceutically active agent
US5584480A (en) * 1995-07-25 1996-12-17 Grimsrud; Chris A. Portable sports target frame

Also Published As

Publication number Publication date
WO1999059577A1 (en) 1999-11-25
AU4309599A (en) 1999-12-06
CA2333076C (en) 2009-12-08
TWI265027B (en) 2006-11-01
EP1083892A1 (en) 2001-03-21
US6011022A (en) 2000-01-04
AU767544B2 (en) 2003-11-13

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Effective date: 20180522