Noninvasive dermal anesthetics

• US 5,919,479 A
• Filed: 03/18/1997
• Issued: 07/06/1999
• Est. Priority Date: 07/28/1995
• Status: Expired due to Term

• Current Assignee: Nuvo Research AG (Searchlight Pharma, Inc.)
• Original Assignee: Zars, Inc.
• Inventors: Zhang, Hao, Zhang, Jie
• Primary Examiner(s): BROUILLETTE, D GABRIELLE
• Application Number:
  US08/819,880
• Time in Patent Office: 840 Days
• Field of Search: 424/448, 424/449, 514/937, 514/944, 514/938, 514/817
• US Class Current: 424/449
• CPC Class Codes: A61F 2007/0261 medicated
• CPC Class Codes: A61F 2013/00187 insulating; warmth or cold applying
• CPC Class Codes: A61F 2013/00204 insulating
• CPC Class Codes: A61F 2013/00906 for transcutaneous or transdermal drugs application
• CPC Class Codes: A61F 2013/0091 with disinfecting or anaesthetics means, e.g. anti-mycrobic
• CPC Class Codes: A61F 7/034 Flameless
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 31/245 Amino benzoic acid types, e.g. procaine, novocaine salicylic acid esters A61K31/60
• CPC Class Codes: A61K 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: A61M 37/00 Other apparatus for introducing media into the body for reproduction or fertilisation A61B17/425; apparatus for iontophoresis or cataphoresis A61N1/30; Percutany, i.e. introducing medicines into the body by diffusion through the skin salt baths A61H33/04
• CPC Class Codes: A61P 23/00 Anaesthetics
• CPC Class Codes: A61P 23/02 Local anaesthetics

Abstract

An apparatus, product formulation, and method for improved dermal permeation of pharmaceuticals wherein the apparatus includes a thin drug formulation reservoir and a heat-generating chamber separated by a first non-permeable wall, wherein the reservoir and chamber are formed in or supported by a housing. The drug formulation reservoir houses or is capable of housing a predetermined amount of a formulation containing pharmaceutically-active agent(s). The heat-generating/temperature-regulating chamber includes a medium for generating controlled heat, preferably a chemical composition made of carbon, iron, water and/or salt which is activated upon contact with air (oxygen). The function of the heat-generating/temperature-regulating element is to heat the user'"'"'s skin, rapidly bring the skin temperature to a desired and elevated narrow range and keep it in this range for sufficient time to obtain more rapid, enhanced and less variable dermal absorption of selected pharmaceutically-active agents and to obtain improved clinical effects. Structure for controlling the generation of heat is also disclosed. The apparatus may optionally include a spacing or standoff structure which spans the drug formulation reservoir between the non-permeable wall and the user'"'"'s skin surface for maintaining a predetermined thickness of the drug formulation on the user'"'"'s skin surface. Also, a novel product formulation which can be used with the apparatus which uses high percentage of eutectic mixture of local anesthetics to reduce the overall degradation rate of the local anesthetic compound(s) in formulations which are subject to hydrolysis.

Claims

1. A formulation with reduced degradation rate of anesthetic(s) and improved noninvasive dermal anesthesia comprising:

an emulsion with an oil phase and an aqueous phase; and

said oil phase being a eutectic mixture of tetracaine and lidocaine, wherein the weight percentage of said eutectic mixture in said formulation is about 12% or greater.

2. The formulation of claim 1, wherein said emulsion is thickened such that it is substantially non-flowable and cohesive at ambient temperature.

3. The formulation of claim 1, further including pH regulating agent(s), coloring agent(s), permeation enhancing agent(s), or a combination thereof.

4. The formulation of claim 1, wherein the ratio of tetracaine to lidocaine is between 1:

0.5 and 1;

1.5.

5. The formulation of claim 1, wherein said tetracaine and lidocaine in said eutectic mixture is formulated in a substantially one to one weight ratio.

6. The formulation of claim 1, wherein the weight percentage of said eutectic mixture in said formulation is greater than about 18%.

7. The formulation of claim 1, further including at least one compound that is an emulsifying agent, a gelling agent, or a thickening agent.

8. The formulation of claim 7, wherein said emulsion is gelled.

9. The formulation of claim 8, wherein said gelled emulsion rapidly melts or significantly softens when heated to greater than about 30°

C.

10. The formulation of claim 8, wherein said gelled emulsion does not melt or significantly soften when heated to about 30°

C.

11. A formulation with reduced degradation rate of anesthetic(s) and improved noninvasive dermal anesthesia comprising:

a gelled-emulsion with an oil phase and an aqueous phase which melts or significantly softens when heated to about 30°

C.;

said oil phase being a eutectic mixture of tetracaine and lidocaine;

the weight percentage of said eutectic mixture in said emulsion being about 12% or greater;

said formulation having at least one compound that is an emulsifying agent, a gelling agent, or a thickening agent; and

said gelled-emulsion optionally including pH regulating agent(s), coloring agent(s), permeation enhancing agent(s), or a combination thereof.

12. A formulation with reduced degradation rate of anesthetic(s) and improved noninvasive dermal anesthesia comprising:

a gelled-emulsion with an oil phase and an aqueous phase which does not melt or significantly softens when heated to about 30°

C.;

said oil phase being a eutectic mixture of tetracaine and lidocaine;

the weight percentage of said eutectic mixture in said emulsion being about 12% or greater;

said formulation having at least one compound that is an emulsifying agent, a gelling agent, or a thickening agent; and

said gelled-emulsion optionally including pH regulating agent(s), coloring agent(s), permeation enhancing agent(s), or a combination thereof.