WO2011028542A2 - Méthodes de traitement de la douleur associée à un syndrome de douleur régional complexe - Google Patents

Méthodes de traitement de la douleur associée à un syndrome de douleur régional complexe Download PDF

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Publication number
WO2011028542A2
WO2011028542A2 PCT/US2010/046523 US2010046523W WO2011028542A2 WO 2011028542 A2 WO2011028542 A2 WO 2011028542A2 US 2010046523 W US2010046523 W US 2010046523W WO 2011028542 A2 WO2011028542 A2 WO 2011028542A2
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WO
WIPO (PCT)
Prior art keywords
local anesthetic
heating
skin surface
complex regional
skin
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Application number
PCT/US2010/046523
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English (en)
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WO2011028542A3 (fr
Inventor
Jie Zhang
Andrew Crockett
Larry Rigby
Original Assignee
Zars Pharma, Inc.
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Publication of WO2011028542A2 publication Critical patent/WO2011028542A2/fr
Publication of WO2011028542A3 publication Critical patent/WO2011028542A3/fr

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Classifications

    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
    • A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
    • 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
    • A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
    • A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
    • A61K31/245—Amino benzoic acid types, e.g. procaine, novocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • CRPS Complex Regional Pain Syndrome
  • RSD Pain associated with complex regional pain syndrome is suffered by many people and is frequently treated with opioid and non-opioid analgesics. Unfortunately, these treatment options suffer from various drawbacks and undesirable side-effects. These undesirable side-effects are frequently due to their systemic delivery.
  • FIG. 1 is a schematic representation of an exemplary analgesic system in the form of a patch which can be used for treating pain associated with Complex regional pain syndrome.
  • Skin is defined to include human skin (intact, diseased, ulcerous, or broken), and mucosal surfaces that are usually at least partially exposed to air such as lips, genital and anal mucosa, and nasal and oral mucosa.
  • local anesthetics in appropriate formulations can be used to provide skin “anesthesia,” which by medical definition means preventing a pain before it happens, such as preventing a pain caused by needle stick.
  • the present disclosure is related to methods of using a local anesthetic formulation to provide "analgesia,” which by medical definition means to reduce or eliminate an existing pain, e.g., pain associated with complex regional pain syndrome.
  • controlled heating and "controlled heat” are defined as heat application that is capable of heating a skin surface to pre-determined narrow temperature range for a predetermined duration.
  • a controlled heating device that can be used in accordance with systems and methods of the present disclosure can be configured to generate heat promptly when activated. Controlled heating can be achieved through special design of the heating component. For example, controlled heating can be achieved through the use of a properly configured heating element(s) including an exothermic chemical composition.
  • the heating component can provide heat at a temperature greater than body temperature, but less than a temperature that would cause irreversible skin damage, e.g., burn the skin.
  • An exemplary temperature range that can be implemented for use is from about 35°C to about 47°C.
  • another temperature range can be from about 36°C to 42°C.
  • Other desired temperature ranges include from about 38°C to 42°C, or from 36°C to 40°C.
  • Complex regional pain syndrome which is used interchangeably with the term “reflex sympathetic dystrophy” in the current invention, has the same definition as that commonly used in modern medicine, namely a chronic pain condition, the primary symptom of which is continuous, intense pain, typically in the arms, legs, hands or feet, that is out of proportion to the severity of the injury and which gets worse rather than better over time. Accordingly, "pain associated with complex regional pain syndrome” is pain that is present in a subject as a result of complex regional pain syndromw.
  • the term "about” is used to provide flexibility to a numerical range endpoint by providing that a given value may be "a little above” or “a little below” the endpoint.
  • the degree of flexibility of this term can be dictated by the particular variable and would be within the knowledge of those skilled in the art to determine based on experience and the associated description herein.
  • a method for treating the pain associated with complex regional pain syndrome includes the application of an analgesic system to a skin surface of a subject experiencing the pain and maintaining the analgesic system on the skin surface for a period of time of at least 30 minutes.
  • the application site is typically a skin area proximate the pain.
  • the analgesic system applied to the skin surface can include a heating component and a local anesthetic formulation including at least one local anesthetic.
  • the heating component can be capable of heating the skin surface to a temperature of 36 °C to 42 °C for a sustained period of time within this narrow temperature range.
  • the methods of the present disclosure can harness the benefits of both increased delivery of the local anesthetic and the therapeutic effect of heating. Furthermore, in some embodiments, the use of heat can actually improve the penetration and benefit of the local anesthetic(s) compared to the use of the same formulation without application of heat. Stated another way, the methods of the present application can provide enhanced transdermal delivery of the local anesthetic through the use of controlled heating, and the added benefit provided by the heat itself. As the skin is heated, the permeability of the skin to the local anesthetics drugs can increase. Additionally, the heating of the skin itself is also believed to reduce the existing pain. Accordingly, the combination of the transdermal delivery of the local anesthetic from the local anesthetic formulation with the heat from the heating component can cause a more efficient, i.e. faster and more effective, reduction in pain than either the drug or the heat alone.
  • the analgesic systems used in the methods of the present disclosure can comprise two major components: a controlled heating component and a local anesthetic formulation.
  • the local anesthetic formulation can be incorporated in a patch and can include an amount of the local anesthetic to provide, with the help of the heating component, sufficient transdermal delivery of the local anesthetic for reducing or eliminating existing pain.
  • a sufficient transdermal delivery of the local anesthetic is defined as a rate of delivery that is high enough to reduce the pain intensity (as measured by patient report of pain intensity) in an average patient by at least 20%, and often at least 30% or even 50%. With some patients and some conditions, complete pain relief can be achieved.
  • the heating device can be configured for application over the patch and the human skin site.
  • the heating device can be configured to heat a skin site to which it is applied to a temperature that provides a therapeutic effect, such as from about 36 °C to about 42 °C.
  • the heating device can further be capable of maintaining the skin within the above temperature range for a period of time of at least 30 minutes, or in other embodiments, at least 1 hour.
  • the analgesic systems of the present disclosure can include a local anesthetic formulation and a heating component.
  • the local anesthetic formulation can be designed to transdermally deliver at least one local anesthetic.
  • the local anesthetic can generally be any local anesthetic known in the art.
  • the local anesthetic can be selected from the group consisting of tetracaine, lidocaine, prilocaine, ropivacaine, bupivacaine, benzocaine, and combinations thereof.
  • the local anesthetic formulation can include lidocaine base.
  • the local anesthetic formulation can include tetracaine base.
  • the local anesthetic formulation can include a eutectic mixture of lidocaine base and tetracaine base.
  • the local anesthetic formulation can comprise at least 30 wt% (alone or in combination) of total local anesthetic, e.g., at least 30 wt% of a 1 :1 (by weight) of a eutectic mixture of lidocaine and tetracaine (in combination), or at least 30 wt% of lidocaine or other local anesthetic base (alone).
  • lower concentrations of local anesthetics can be used, e.g., at least 15 wt% local anesthetic, at least 20 wt% local anesthetic, or at least 25 wt% local anesthetic
  • the local anesthetic formulation may also include other ingredients and excipients such as polymers, emulsifiers, chemical permeation enhancers, water or other solvents, and preservatives.
  • the local anesthetic formulation can include a solidification polymer such as polyvinyl alcohol.
  • the local anesthetic formulation can include an adhesive polymer which is capable of adhering to skin.
  • the local anesthetic formulation portion of the analgesic system can have a skin contact region where the local anesthetic formulation contacts the skin surface.
  • the size of the skin contact area can vary depending on the targeted region of the subject's body and the nature of the pain being treated.
  • the skin contact region can have an area of 2 cm 2 to 200 cm 2 , 7 cm 2 to 150 cm 2 , or 8 cm 2 to 15 cm 2 . In various other embodiments, other size ranges may be appropriate.
  • the skin contact region can have an area of 3 cm 2 to 150 cm 2 , 5 cm 2 to 130 cm 2 , 6 cm 2 to 100 cm 2 , 7 cm 2 to 80 cm 2 , 8 cm 2 to 40 cm 2 , or 8 to about 1 3 cm 2 , etc.
  • a layer of adhesive can be coated onto the analgesic outside the contact area, and/or between the skin and the local anesthetic formulation for affixing the system on the skin.
  • the heating components of the analgesic systems used in the method of the present application can be configured to raise the temperature of a skin surface to which the analgesic system is applied to a therapeutically effective temperature (for providing heat to the site and/or for providing enhanced drug delivery), e.g., about 36 °C to about 42 °C.
  • the heating component can further be configured to maintain the temperature of the skin surface in the above range for a period of time of at least 30 minutes.
  • the heating component can be configured to maintain the skin surface in the above described temperature range for a period of at least 60 minutes.
  • the heating component can be configured to maintain the skin surface in the above described temperature range for a period of at least 2 hours, 4 hours, 6 hours, 8 hours, or 12 hours.
  • the analgesic systems used in the methods of the present disclosure can be configured to relieve the pain associated with complex regional pain syndrome.
  • the pain can be relieved for a period of time beyond the period of time in which the heating component heats and/or which the analgesic system is maintained on the skin surface.
  • the methods of the present disclosure can provide relief of existing pain for a period of time of at least 4 hours.
  • the relief of pain can be for a period of time of at least 6 hours.
  • the relief of pain can be for a period of time of at least 12 hours.
  • the system can be used on a chronic basis (at least once a day for at least 75% of the days in a period of time lasting at least two weeks). In further embodiments, the system can be used more than once a day and for more than 2 weeks.
  • the heating components of the analgesic systems used in the methods of the present disclosure can generate heat through a number of mechanisms or means. In one embodiment, the heating component can generate the heat through chemical-based exothermic reactions. Other heating mechanisms can also be used, such as heating by phase transition of supersaturated solutions (such as phase transition of sodium acetate solutions), radiation (microwave or infrared, for example), electricity-resistor, combinations thereof, and/or other heating sources. In one embodiment, the heating component can be an electric heating device.
  • Such electric heating device can be powered by a variety of sources, for example, battery and/or alternating electric current.
  • Electric devices can be configured to provide a predetermined heating profile so that the heating profile is met automatically after engaging or turning on the electric device, e.g., use of timers, programmed electricity supply, finite batter power, etc.
  • the heating profile can be met merely by providing heat at an appropriate temperature with an instruction to the user to remove the heating device after a specific period of time.
  • the heating component can generate heat by an exothermic oxidative chemical reaction.
  • the chemical-based exothermic oxidation reaction can generate heat through the contact of the oxidative material, e.g. iron, with ambient air.
  • U.S. Patent No. 6,756,053 which is incorporated herein by reference in its entirety, describes examples of exothermic heating components and devices.
  • the amount of exothermic chemical composition in the heating component can vary from depending on the desired duration of heating and the size of the heating component. It can be beneficial to limit the amount of the exothermic chemical composition in the heating component, as a large amount of exothermic chemical composition can cause the heating component to be excessively large or cumbersome and impractical for use.
  • the heating device can include up to 2 grams of an exothermic chemical composition and can be configured to heat an area of skin greater than about 8 cm 2 .
  • composition can further include activated carbon, salt (such as sodium chloride), and water.
  • salt such as sodium chloride
  • water can also be included in the heating component.
  • the exothermic chemical composition of the heating component can be manufactured in a manner so as to only have access to ambient oxygen through the holes in a cover that is made of air-impermeable material.
  • the flow rate of oxygen from ambient air into the exothermic chemical composition which in turn is a factor which can affect the amount and rate of heat generated by the heating component and the temperature of the skin surface on which the analgesic system is applied.
  • Other factors which can influence the temperature and heat generation of the heating component can be the size of the heating component, the amount of the exothermic chemical composition in the heating component, the number and configuration of holes in the heating component's air impermeable cover material, etc.
  • FIG. 1 is a schematic profile of one embodiment of an analgesic system which could be used in accordance with the methods of the present application.
  • the analgesic system includes a heating component 34 and a local anesthetic formulation 30.
  • the heating component includes an air- impermeable top cover film 20 having a plurality of holes 36 therein. When exposed to ambient air, the holes allow for the passage of the ambient air through the air-impermeable top cover film to the exothermic chemical composition 22.
  • the layer of exothermic chemical composition is disposed between the air-impermeable top cover film and an adhesive film layer 24.
  • the adhesive film layer extends beyond the circumference of the exothermic chemical composition layer and the local anesthetic formulation layer and can function, at least in part, to adhere to the analgesic system to a skin surface.
  • a heat sealable film layer 26 is below to the adhesive film layer and acts to impede the transfer of substances, particularly moisture, between the local anesthetic formulation layer and the exothermic chemical composition layer.
  • a sodium-borate coated non-woven film layer 28 acts aids in gelling the local anesthetic formulation during manufacturing.
  • the entire analgesic system is adhered in an air and moisture impermeable packing tray 32 which holds the local anesthetic formulation during storage.
  • Example 1 System for treating pain associated with complex regional pain syndrome
  • the analgesic system described herein has two components: a drug
  • drug formulation composition in a patch drug formulation composition in a patch
  • heating component drug formulation composition in a heating component
  • Table 1 lists exemplary ingredients in the drug formulation.
  • Table 2 lists exemplary ingredients in the drug formulation.
  • the drug formulation of the system has a skin contact area of about 10 cm 2 .
  • FIG.1 The physical configurations of the drug component and the heating component, and their integration, are schematically shown in FIG.1 .
  • the heat generating medium is enclosed in a closed space as shown in FIG. 1 , and has access to the external environment only through the 6 holes on the air- impermeable cover.
  • the diameter of each of the holes is about 1/16 of an inch.
  • This heat generating medium can provide controlled heat at from 36 to 42 °C for a sustained period of time.
  • Example 2 System for treating pain associated with complex regional pain syndrome
  • Example 1 Four small analgesic systems described in Example 1 are prepared, except that the size of the patches are varied to have a skin contact area of 2 cm 2 , 3 cm 2 , 6 cm 2 , and 8 cm 2 , respectively.
  • the weight percentages are the same for both the drug formulation (Table 1 ) and the heat generating medium (Table 2), but since the patches are smaller in size, the total amount of each ingredient is proportionally reduced.
  • the number of holes or the size of the holes is also modified so that the total hole area (number of holes times the surface area of each hole) is adjusted proportionally in order to achieve a similar heating profile for the patch size, e.g., 1 -6 holes of similar or slightly different size.
  • Example 3 System for treating pain associated with complex regional pain syndrome
  • Example 2 Four large analgesic systems described in Example 1 are prepared, except that the size of the patches are varied to have a skin contact area of 40 cm 2 , 60 cm 2 , 120 cm 2 , 180 cm 2 , respectively.
  • the weight percentages are the same for both the drug formulation (Table 1 ) and the heat generating medium (Table 2), but since the patches are much larger in size, the total amount of each ingredient is proportionally increased.
  • the number of holes or the size of the holes is also adjusted proportionally in order to achieve a similar heating profile for the patch size.
  • the number of holes or the size of the holes is also modified so that the total hole area (number of holes times the surface area of each hole) is adjusted proportionally in order to achieve a similar heating profile for the patch size, e.g., 12-100 holes of similar or slightly different size.
  • Example 4 System for treating pain associated with complex regional pain syndrome
  • An analgesic systems described in Example 1 is prepared, except that 40 wt% lidocaine base is used rather than 40 wt% of eutectic mixture of lidocaine and tetracaine base.
  • the patch size is modified to be 120 cm 2 .
  • the weight percentages are the same for both the drug formulation (Table 1 ) and the heat generating medium (Table 2), but since the patch is larger in size, the total amount of each ingredient is proportionally increased.
  • the number of holes or the size of the holes is also modified so that the total hole area (number of holes times the surface area of each hole) is adjusted proportionally in order to achieve a similar heating profile for the patch size, e.g., 40-80 holes of similar or slightly different size.
  • Example 5 System for treating pain associated with complex regional pain syndrome
  • Example 6 An analgesic systems described in Example 1 is prepared, except that 40 wt% ropivacaine base is used rather than 40 wt% of eutectic mixture of lidocaine and tetracaine base.
  • the patch size is modified to be 120 cm 2 .
  • the weight percentages are the same for both the drug formulation (Table 1 ) and the heat generating medium (Table 2), but since the patch is larger in size, the total amount of each ingredient is proportionally increased.
  • the number of holes or the size of the holes is modified so that the total hole area (number of holes times the surface area of each hole) is adjusted proportionally in order to achieve a similar heating profile for the patch size, e.g., 40-80 holes of similar or slightly different size.
  • Example 1 An analgesic systems described in Example 1 is prepared, except that the heat generating medium is from an electric heating device, and the patch size is modified to 120 cm 2 .
  • the weight percentage is the same for the drug formulation (Table 1 ), but since the patch is larger in size, the total amount of each ingredient is proportionally increased.
  • Example 7 Treating pain associated with complex regional pain syndrome
  • a patient is suffering from severe pain associated with complex regional pain syndrome in his neck.
  • An analgesic system similar to that described in Example 1 is applied to the neck twice daily (every 12 hours) for two hours each time, which reduces the pain and enables her to discontinue the oral pain medications.
  • Example 8 Treating pain associated with complex regional pain syndrome
  • a patient experiencing pain associated with complex regional pain syndrome in his arm is treated with an analgesic system similar to that in
  • Example 1 The analgesic system is applied to the skin site under which the pain exists and removed after one hour. Pain relief is obtained within 30 minutes following the commencement of the application and lasted 10-12 hours.
  • Example 7 Same as that described in Example 7, except that the analgesic system is similar to that described in Example 2 with a skin contact area of 6 cm 2 .
  • Example 10 Treating pain associated with complex regional pain syndrome
  • Example 8 Same as that described in Example 8, except that the analgesic system similar to that described in Example 3 with a skin contact area of 40 cm 2

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Emergency Medicine (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Cette invention concerne des méthodes de traitement de la douleur associée à un syndrome de douleur régional complexe. Plus spécifiquement, une méthode de traitement de la douleur associée à un syndrome de douleur régional complexe selon l'invention comprend l'application d'un système analgésique à une surface de la peau d'un sujet éprouvant ladite douleur et le maintien dudit système analgésique sur la surface de la peau pendant une période de temps d'au moins 30 minutes. Le système analgésique appliqué à la surface de la peau peut comprendre un composant chauffant et une formulation anesthésique locale qui contient au moins un anesthésique local. Le composant chauffant doit pouvoir chauffer la surface de la peau jusqu'à une température de 36 à 42°C.
PCT/US2010/046523 2009-08-24 2010-08-24 Méthodes de traitement de la douleur associée à un syndrome de douleur régional complexe WO2011028542A2 (fr)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9186334B2 (en) 2009-05-04 2015-11-17 Nuvo Research Inc. Heat assisted lidocaine and tetracaine for transdermal analgesia
US9186273B2 (en) 2009-05-04 2015-11-17 Nuvo Research Inc. Methods of treating pains associated with neuroma, nerve entrapment, and other conditions

Citations (3)

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Publication number Priority date Publication date Assignee Title
US20010037104A1 (en) * 1998-09-29 2001-11-01 Jie Zhang Methods and apparatus for using controlled heat to regulate transdermal and controlled release delivery of fentanyl, other analgesics, and other medical substances
US20030012830A1 (en) * 2001-07-06 2003-01-16 Robert Small Topical compositions and methods for treating pain
US20060078600A1 (en) * 2003-02-07 2006-04-13 Lts Lohmann Therapie-Systeme Ag Transdermal therapeutic system suitable for heat application for promoting the permeation of active substances, and the use thereof

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Publication number Priority date Publication date Assignee Title
US20010037104A1 (en) * 1998-09-29 2001-11-01 Jie Zhang Methods and apparatus for using controlled heat to regulate transdermal and controlled release delivery of fentanyl, other analgesics, and other medical substances
US20030012830A1 (en) * 2001-07-06 2003-01-16 Robert Small Topical compositions and methods for treating pain
US20060078600A1 (en) * 2003-02-07 2006-04-13 Lts Lohmann Therapie-Systeme Ag Transdermal therapeutic system suitable for heat application for promoting the permeation of active substances, and the use thereof

Non-Patent Citations (1)

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Title
DENNIS, J. ET AL.: 'Lidocaine/Tetracaine Patch' HOSPITAL PHARMACY vol. 41, no. 3, 2006, pages 265 - 273 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9186334B2 (en) 2009-05-04 2015-11-17 Nuvo Research Inc. Heat assisted lidocaine and tetracaine for transdermal analgesia
US9186273B2 (en) 2009-05-04 2015-11-17 Nuvo Research Inc. Methods of treating pains associated with neuroma, nerve entrapment, and other conditions

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