WO1993017674A1 - Topical use of local anaesthetic agents for rheumatoid arthritis as well as a pharmaceutical preparation and a method for the treatment thereof - Google Patents

Topical use of local anaesthetic agents for rheumatoid arthritis as well as a pharmaceutical preparation and a method for the treatment thereof Download PDF

Info

Publication number
WO1993017674A1
WO1993017674A1 PCT/SE1993/000208 SE9300208W WO9317674A1 WO 1993017674 A1 WO1993017674 A1 WO 1993017674A1 SE 9300208 W SE9300208 W SE 9300208W WO 9317674 A1 WO9317674 A1 WO 9317674A1
Authority
WO
WIPO (PCT)
Prior art keywords
local anaesthetic
rheumatoid arthritis
treatment
lidocaine
local
Prior art date
Application number
PCT/SE1993/000208
Other languages
French (fr)
Inventor
Hans Christer Arvid Evers
Original Assignee
Aktiebolaget Astra
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 Aktiebolaget Astra filed Critical Aktiebolaget Astra
Priority to AU37717/93A priority Critical patent/AU3771793A/en
Publication of WO1993017674A1 publication Critical patent/WO1993017674A1/en

Links

Classifications

    • 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
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • 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
    • A61K31/21—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
    • 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
    • A61K47/02—Inorganic compounds
    • 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
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • 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
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles

Definitions

  • the present invention is related to the use of a formulation intended for topical application, and 10 containing one or more local anaesthetic agents, or pharmaceutically acceptable salts thereof, for the treatment of rheumatoid arthritis and related inflammatory conditions.
  • Rheumatoid arthritis is a disease with a largely unknown etiology. In most cases it is a chronic disease often leading to pain and disability, especially in later stages of the disease. Rheumatoid arthritis (RA ) is
  • Injections into the joints is a painful clinical procedure, and in the case of RA affecting several sites, e.g. in the hands, many injections are often necessary.
  • a local ana ⁇ esthetic is frequently added to the steroid to decrease or eliminate the pain caused by the local irritating effect of the steroid containing solution.
  • the effect of the local anaesthetic added to the solution is entirely aimed at blocking the pain on injection.
  • Local ana ⁇ esthetics have been found to influence the mediation of an inflammatory tissue response, as described in many publications.
  • a topically applied local anaesthetic might have a beneficial effect also in cases of RA by reducing the inflammatory process in the joints situated at a distance from the medicated skin areas on the hands of patients with RA.
  • a local anaesthetic formulation (Emla cream) was applied to the joints and adjacent skin areas.
  • the topical anaesthetic was applied under occlusive dressings and left in contact with the skin for 2 hours. This treatment was repeated twice a day, for 2 days. After this treatment the pain had completely receded and the mobility in the treated hand was restored to normal.
  • the duration of the amelioration after this treatment was more than one week, indicating that the duration of the positive effect had no direct relation to the local anaesthetic effect, as such an effect has only a duration of about 5 hours, if investigated with the pin-prick technique, Juhlin L. & Evers H.
  • EMLA A New Topical Anaesthetic, Adv Dermatol 5: 75-92 (1990).
  • the positive effect induced by the local anaesthetic in this patient is thus probably related to a temporary break in the viscious-circle type reaction otherwise induced by the inflammatory disease (RA) .
  • RA inflammatory disease
  • the topical local anaesthetic formulation used according to the invention is characterized by its ability to penetrate intact skin due to its pharmaceutical properties, or may be transported into the skin and underlying tissues by the use of iontophoresis, or by the addition of a penetration enhancing formulation (e.g. DMSO, DMA or Azone ⁇ ).
  • a penetration enhancing formulation e.g. DMSO, DMA or Azone ⁇ .
  • a local anaesthetic agent in the form of its base or a pharmaceutically acceptable salt therof, or a eutectic mixture of local anaesthetics of the aminoamide type (e.g. lidocaine, prilocaine, bupivacaine, ropivacaine etc.).
  • the local anaesthetic(s) is(are) incorporated into a jelly, an emulsion, a cream, an ointment, spray solution or a film-forming formulation.
  • the local anaesthetic(s) into a pharmaceutical composition with sustained release of the active compound(s).
  • an even concentration of the active compound(s) during an extended period of time may be achieved without the need for a frequent change of dressings.
  • a further way to apply the local anaesthetic preparation is to use sterile, or non-sterile dressings soaked with the local anaesthetic preparation.
  • the local anaesthetic composition contains between 0.25% - 20% by weight of the local anaesthetic(s) , preferably 5% - 10%.
  • Lidocaine hydrochloride onohydrate 10.8 kg Hydroxypropyl methylcellulose 4000 cps 24,5 kg Sodium hydroxide 2M to pH 6.3-6.7
  • Lidocaine hydrochloride monohydrate and hydroxypropyl methylcellulose are dissolved in water_for injection.
  • the pH is adjusted to 6.3-6.7 with sodium hydroxide and the volume to 1000 1 with water.
  • Lidocaine hydrochloride monohydrate and hydroxypropyl methylcellulose are dissolved in water for injection.
  • the pH is adjusted to 6.2-6.6 with sodium hydroxide and the volume to 400 1 with water.
  • the resulting solution is autoclaved.
  • Lidocaine is dissolved in the water.
  • Sodium hydroxide is added to pH 6.5-6.7.
  • the resulting solution is autoclaved.
  • the emulsion is prepared by dissolving lidocaine in the oil (Miglyol 812) , whereafter it is melted together with the emulsifier (Arlatone ® 289). A minor amount of water is then added to the hot mixture. The resulting mixture is cooled whereafter the thickening agent (Carbopol ) mixed with the rest of the water is added as gel. The resulting mixture is homogenized to such an extent that the substantial part of the oil droplets have a diameter of ⁇ 3 ⁇ .
  • Miglyol 812 is a hardened coco-fat with mean chain length.
  • Arlatone 289 is a polyoxy-ethylene fatty acid ester and Carbopol 934 is a vinyl polymer with active carboxyl groups.
  • An emulsion cream is prepared as described in example 3,
  • An emulsion cream is prepared as described in example 3.
  • the two local anaesthetically active compounds in crystalline form are weighed together and heated to 30°C, whereby the two compounds melt and form a homogenous oil.
  • the mixture of crystals have a melting point of 22°C.
  • the mixture is then applied onto a carrier of paper in an amount of 1.5 mg/cm .
  • the carrier in suitable size is applied on the affected joints.
  • the best mode of carrying out the invention known at present is to use the preparation according to Example 7.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Emergency Medicine (AREA)
  • Dermatology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Use of one or more local anaesthetic agents, especially lidocaine and prilocaine, for the manufacture of a topical pharmaceutical preparation with curing effect on rheumatoid arthritis.

Description

Topical use of local anaesthetic agents for rheumatoid arthritis as well as a pharmaceutical preparation and a method for the treatment thereof
Field of the invention.
The present invention is related to the use of a formulation intended for topical application, and 10 containing one or more local anaesthetic agents, or pharmaceutically acceptable salts thereof, for the treatment of rheumatoid arthritis and related inflammatory conditions.
15 Background of the invention.
Rheumatoid arthritis is a disease with a largely unknown etiology. In most cases it is a chronic disease often leading to pain and disability, especially in later stages of the disease. Rheumatoid arthritis ( RA ) is
20 considered to be an inflammatory condition with symmetrical engagement of the joints and tendon sheets. Widenfalk B. has found several indications suggesting RA to be mediated to a partial extent via the nervous system.
25 Widenfalk B.f "A spinal transcommisural connection for symmetrical reflex response, Scand. J, Plast Reconstr. Hand. Surg. 24: pp. 207-212, (1990), and "Sympathetic , innervation, of normal and rheumatoid synergical tissue, Scand. J, Plast Reconstr. Hand. Surg. 25: pp. 31-31,
30 (1991), Widenfalk B. et al "Origin of Sympathetic and sensory innervation of the Elbow Joint in the Rat: A Re¬
* • trograde Axonal Tracing study with Wheat Germ Agglutinin conjugated Horse-Radish Peroxidase., The J. of Comparative Neurology 271: pp. 313-318 (1988) and
35 Widenfalk B., Wiberg M. "Origin of sympathetic and sensory innervation of the knee joint, Anat. Embryol. 180: pp. 317-323, (1989). An indication that RA is me¬ diated this way is the finding that a patient who suffers from the disease, and also sustains a cerebrovascular lesion with half-sided paresis does not show any inflammatory process in the paretic part of the body where the nerve transmission is damaged. Injection of anti-inflammatory agents, e.g. steroids into the joints of patients with RA have proven their therapeutic value by the treatment of the disease, and is considered to be the treatment of choice for such conditions. Injections into the joints is a painful clinical procedure, and in the case of RA affecting several sites, e.g. in the hands, many injections are often necessary. In order to minimize the pain by these procedures, a local ana¬ esthetic is frequently added to the steroid to decrease or eliminate the pain caused by the local irritating effect of the steroid containing solution. The effect of the local anaesthetic added to the solution is entirely aimed at blocking the pain on injection. Local ana¬ esthetics have been found to influence the mediation of an inflammatory tissue response, as described in many publications.
The mechanism of action for the anti-inflammatory effects of local anaesthetics is largely unknown, but has been defined as the result of a combination of a blocking of neural impulse transmission and an effect upon the local inflammatory mediators. A significant protective effect of local anaesthetics, applied prior to a standardized experimental trauma was investigated by Ohlsen L. et al, "Local anaesthetics modifying the dermal response of irridiation. "Acta Oncologica 26 (1987), Fasc. 6, pp. 467-476.
In an experimental study in rabbits the authors found that the pronounced inflammatory response in the dermal tissues of the animals, induced by high-energy irridiation, could be significantly modified, or even completely inhibited, by the topical application of a local anaesthetic ( Emla cream ) , applied to the skin of the experimental animals before or after the tissue- damaging irradiation. The results from this study indicate that it is possible after topical administration to ensure adequate tissue concentrations of the local anaesthetic for reducing the inflammatory response also in the deeper layers under the topically applied formulation.
Outline of the invention.
It was therefore of interest to investigate if a topically applied local anaesthetic might have a beneficial effect also in cases of RA by reducing the inflammatory process in the joints situated at a distance from the medicated skin areas on the hands of patients with RA. In a patient with prodromal symptoms of RA, including pain and a reduced mobility in both hands, a local anaesthetic formulation (Emla cream) was applied to the joints and adjacent skin areas. The topical anaesthetic was applied under occlusive dressings and left in contact with the skin for 2 hours. This treatment was repeated twice a day, for 2 days. After this treatment the pain had completely receded and the mobility in the treated hand was restored to normal. The duration of the amelioration after this treatment was more than one week, indicating that the duration of the positive effect had no direct relation to the local anaesthetic effect, as such an effect has only a duration of about 5 hours, if investigated with the pin-prick technique, Juhlin L. & Evers H.
EMLA: A New Topical Anaesthetic, Adv Dermatol 5: 75-92 (1990). The positive effect induced by the local anaesthetic in this patient is thus probably related to a temporary break in the viscious-circle type reaction otherwise induced by the inflammatory disease (RA) .
In order to further substantiate the beneficial effects in connection with the topical treatment of patients with RA with application of local anaesthetic compositions, five patients with diagnosed rheumatoid athritis in their hands were treated. Experimental data.
Five patients with diagnosed active rheumatoid arthritis were treated locally with topical treatment of EMLA for two weeks. All five patients noted a positive effect of the treatment with reduced pain and loss of swelling of the affected joints. Improvement of joint motion was also noted objectively and subjectively. In all patients the effect lasted more than two weeks of treatment but only in one patient the swelling was completely gone also six months after treatment.
Pharmaceutical preparations preferred according to the invention.
The topical local anaesthetic formulation used according to the invention is characterized by its ability to penetrate intact skin due to its pharmaceutical properties, or may be transported into the skin and underlying tissues by the use of iontophoresis, or by the addition of a penetration enhancing formulation (e.g. DMSO, DMA or Azone β).
It should contain at least one local anaesthetic agent in the form of its base or a pharmaceutically acceptable salt therof, or a eutectic mixture of local anaesthetics of the aminoamide type (e.g. lidocaine, prilocaine, bupivacaine, ropivacaine etc.).
The local anaesthetic(s) is(are) incorporated into a jelly, an emulsion, a cream, an ointment, spray solution or a film-forming formulation.
It is also possible to incorporate the local anaesthetic(s) into a pharmaceutical composition with sustained release of the active compound(s). Hereby an even concentration of the active compound(s) during an extended period of time may be achieved without the need for a frequent change of dressings.
A further way to apply the local anaesthetic preparation is to use sterile, or non-sterile dressings soaked with the local anaesthetic preparation.
The local anaesthetic composition contains between 0.25% - 20% by weight of the local anaesthetic(s) , preferably 5% - 10%.
Pharmaceutical preparations
Example 1
Jelly 1 %
Lidocaine hydrochloride onohydrate 10.8 kg Hydroxypropyl methylcellulose 4000 cps 24,5 kg Sodium hydroxide 2M to pH 6.3-6.7
Water for injection qs ad 1000 1
Lidocaine hydrochloride monohydrate and hydroxypropyl methylcellulose are dissolved in water_for injection. The pH is adjusted to 6.3-6.7 with sodium hydroxide and the volume to 1000 1 with water.
Example 2
Jelly 2 %
Lidocaine hydrochloride monohydrate 8.65 kg
Hydroxypropyl methylcellulose 4000 cps 9.8 kg Sodium hydroxide 2M to pH 6.2-6.6 Water for injection qs ad 400 1
Lidocaine hydrochloride monohydrate and hydroxypropyl methylcellulose are dissolved in water for injection. The pH is adjusted to 6.2-6.6 with sodium hydroxide and the volume to 400 1 with water. The resulting solution is autoclaved.
Example 3
Solution 40 mg/ml
Lidocaine hydrochloride monohydrate 4.28 kg
Sodium hydroxide 2M to pH 6.5-6.7 « 0.46 kg Purified water qs ad 95.56 kg
Lidocaine is dissolved in the water. Sodium hydroxide is added to pH 6.5-6.7. The resulting solution is autoclaved.
Example 4
Emulsion cream
Lidocaine 10 g
Miglyol® 812 27.6 "
Arlatone® 289 9.0 "
Carbopol® 934 1.0 "
Water ad 100 "
The emulsion is prepared by dissolving lidocaine in the oil (Miglyol 812) , whereafter it is melted together with the emulsifier (Arlatone ® 289). A minor amount of water is then added to the hot mixture. The resulting mixture is cooled whereafter the thickening agent (Carbopol ) mixed with the rest of the water is added as gel. The resulting mixture is homogenized to such an extent that the substantial part of the oil droplets have a diameter of <3μ. Miglyol 812 is a hardened coco-fat with mean chain length. Arlatone 289 is a polyoxy-ethylene fatty acid ester and Carbopol 934 is a vinyl polymer with active carboxyl groups.
Example 5
Figure imgf000009_0001
An emulsion cream is prepared as described in example 3,
Exam le 6
Figure imgf000009_0002
An emulsion cream is prepared as described in example 3.
Example 7
Prilocaine, base 52 g
Lidocaine 48 g
The two local anaesthetically active compounds in crystalline form are weighed together and heated to 30°C, whereby the two compounds melt and form a homogenous oil. The mixture of crystals have a melting point of 22°C. The mixture is then applied onto a carrier of paper in an amount of 1.5 mg/cm . At use the carrier in suitable size is applied on the affected joints. The best mode of carrying out the invention known at present is to use the preparation according to Example 7.
Conclusions
According to the present invention it has thus surprisingly been found that patients with rheumatoid arthritis have been successfully treated, with regard to pain and manual disability, with the exclusive use of topical application of a composition containing local anaesthetics. The follow-up period of these patients has been up to six months, after termination of the local application of the local anaesthetic.

Claims

Claims
1. Use of one or more local anaesthetic agents or pharma¬ ceutically acceptable salts therof in the manufacture of a topical pharmaceutical preparation without pre¬ servatives with curing effect on rheumatoid arthritis.
2. Use according to claim 1, wherein the preparation is used for its healing effect on rheumatoid arthritis on the hands.
3. Use according to claim 1, wherein the local anaesthetic is an eutectic mixture of lidocaine and prilocaine.
4. Use according to claim 1, wherein the local anaesthetic agent is lidocaine.
5. Use according to claim 3, wherein lidocaine and prilocaine are in the form of their bases.
6. Use according to claim 4, wherein lidocaine is in the form of its hydrochloride.
7. A method for the treatment of rheumatoid arthritis comprising topical administering to a patient suffering therefrom an amount of one or more local anaesthetic agents or pharmaceutically acceptable salts thereof sufficient for the treatment of said disease.
8. A pharmaceutical preparation for the use in the topical treatment of rheumatoid arthritis wherein the active ingredient is one or more local anaesthetic agents or pharmaceutically acceptable salts thereof.
PCT/SE1993/000208 1992-03-12 1993-03-10 Topical use of local anaesthetic agents for rheumatoid arthritis as well as a pharmaceutical preparation and a method for the treatment thereof WO1993017674A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU37717/93A AU3771793A (en) 1992-03-12 1993-03-10 Topical use of local anaesthetic agents for rheumatoid arthritis as well as a pharmaceutical preparation and a method for the treatment thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE9200762.4 1992-03-12
SE9200762A SE9200762D0 (en) 1992-03-12 1992-03-12 NEW TOPICAL USE

Publications (1)

Publication Number Publication Date
WO1993017674A1 true WO1993017674A1 (en) 1993-09-16

Family

ID=20385599

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/SE1993/000208 WO1993017674A1 (en) 1992-03-12 1993-03-10 Topical use of local anaesthetic agents for rheumatoid arthritis as well as a pharmaceutical preparation and a method for the treatment thereof

Country Status (5)

Country Link
IS (1) IS3984A (en)
SE (1) SE9200762D0 (en)
SI (1) SI9300115A (en)
WO (1) WO1993017674A1 (en)
ZA (1) ZA931079B (en)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0758548A1 (en) * 1995-07-17 1997-02-19 Rainer K. Dr. Liedtke Local anesthetics for topical treatment of back pain and muscle bracing
EP1073401A1 (en) * 1998-04-28 2001-02-07 James Castillo Topical anesthetic formulation
WO2001028550A1 (en) * 1999-10-15 2001-04-26 Mayo Foundation For Medical Education And Research Topical anesthetics useful for treating cancer, autoimmune diseases and ischemia
WO2011074015A2 (en) 2009-12-17 2011-06-23 Themis Medicare Limited Novel composition of pharmaceutical product to treat sexual dysfunction
US8119694B2 (en) 2008-08-15 2012-02-21 Arcion Therapeutics, Inc. High concentration local anesthetic formulations
EP3775116A4 (en) * 2018-04-05 2022-03-23 Bausch Health Ireland Limited Polymeric emulsion delivery systems
EP3957328A4 (en) * 2019-04-15 2023-03-22 Huzhou Innovation Pharmaceutical Co., Ltd. Lipid pharmaceutical preparation and application thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4628052A (en) * 1985-05-28 1986-12-09 Peat Raymond F Pharmaceutical compositions containing dehydroepiandrosterone and other anesthetic steroids in the treatment of arthritis and other joint disabilities
WO1989011853A1 (en) * 1988-06-01 1989-12-14 Aktiebolaget Astra Use of local anaesthetic agents in the manufacture of preparations with wound healing effect

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4628052A (en) * 1985-05-28 1986-12-09 Peat Raymond F Pharmaceutical compositions containing dehydroepiandrosterone and other anesthetic steroids in the treatment of arthritis and other joint disabilities
WO1989011853A1 (en) * 1988-06-01 1989-12-14 Aktiebolaget Astra Use of local anaesthetic agents in the manufacture of preparations with wound healing effect

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0758548A1 (en) * 1995-07-17 1997-02-19 Rainer K. Dr. Liedtke Local anesthetics for topical treatment of back pain and muscle bracing
EP1073401A1 (en) * 1998-04-28 2001-02-07 James Castillo Topical anesthetic formulation
EP1073401A4 (en) * 1998-04-28 2006-09-13 James Castillo Topical anesthetic formulation
WO2001028550A1 (en) * 1999-10-15 2001-04-26 Mayo Foundation For Medical Education And Research Topical anesthetics useful for treating cancer, autoimmune diseases and ischemia
US6391888B1 (en) 1999-10-15 2002-05-21 Mayo Foundation For Medical Education And Research Topical anesthetics useful for treating cancer
US8119694B2 (en) 2008-08-15 2012-02-21 Arcion Therapeutics, Inc. High concentration local anesthetic formulations
US9370500B2 (en) 2008-08-15 2016-06-21 Centrexion Therapeutics Corporation High concentration local anesthetic formulations
US10758502B2 (en) 2008-08-15 2020-09-01 Centrexion Therapeutics Corporation High concentration local anesthetic formulations
US11517546B2 (en) 2008-08-15 2022-12-06 Centrexion Therapeutics Corporation High concentration local anesthetic formulations
WO2011074015A2 (en) 2009-12-17 2011-06-23 Themis Medicare Limited Novel composition of pharmaceutical product to treat sexual dysfunction
EP3775116A4 (en) * 2018-04-05 2022-03-23 Bausch Health Ireland Limited Polymeric emulsion delivery systems
US11364198B2 (en) 2018-04-05 2022-06-21 Bausch Health Ireland Limited Polymeric emulsion delivery systems
EP3957328A4 (en) * 2019-04-15 2023-03-22 Huzhou Innovation Pharmaceutical Co., Ltd. Lipid pharmaceutical preparation and application thereof

Also Published As

Publication number Publication date
IS3984A (en) 1993-09-13
ZA931079B (en) 1993-11-08
SE9200762D0 (en) 1992-03-12
SI9300115A (en) 1993-09-30

Similar Documents

Publication Publication Date Title
CA2528360C (en) Anesthetic composition for topical administration comprising lidocaine, prilocaine and tetracaine
US8691283B2 (en) Standardized bee venom preparation
AU2019203449B2 (en) Topical diclofenac sodium compositions
AU3417595A (en) Topical anti-inflammatory composition and method
WO2002022128A1 (en) A method of local anesthesia and analgesia
JPH0780761B2 (en) Composition for treating painful disease or allergic disease and therapeutic method
KR20200119351A (en) Aqueous based capsaicinoid formulations and methods of manufacture and use
WO1993017674A1 (en) Topical use of local anaesthetic agents for rheumatoid arthritis as well as a pharmaceutical preparation and a method for the treatment thereof
CN111840553A (en) Lipid pharmaceutical preparation and application thereof
KR20050085736A (en) Ester combination local anesthetic
CA1169774A (en) Medication having penetration through cutaneous surfaces into articular and muscular areas
US6011022A (en) Topical application of muscarinic analgesic drugs such as neostigmine
EP1318801B1 (en) Topical analgesic compositions containing aliphatic polyamines and methods of using same
JP2002322071A (en) Vespid venom therapy not using vespid sting
WO2018147790A1 (en) Anaesthetic composition comprising ropivacaine, prilocaine and lidocaine
JP2001526217A (en) Novel use of local anesthetics for vascular headache
US11642328B2 (en) Creatine, its derivatives, compositions and methods of use thereof
KR100347883B1 (en) New pharmaceutical composition of gel preparation containing local anaesthetic agents
WO1989011853A1 (en) Use of local anaesthetic agents in the manufacture of preparations with wound healing effect
EP2298280A2 (en) Gel comprising a combination of flurbiprofen and muscle relaxant
JP2506216B2 (en) Anti-inflammatory analgesic external preparation
WO2006121209A1 (en) Therapeutic agent for eczema and dermatitis
EP1406604A2 (en) Topical application of muscarinic analgesic drugs such as neostigmine
JP2001163782A (en) Agent for external use for treating dermatosis
JPH013123A (en) Skin inflammation treatment agent

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AT AU BB BG BR CA CH CZ DE DK ES FI GB HU JP KP KR LK LU MG MN MW NL NO NZ PL PT RO RU SD SE SK UA VN

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WR Later publication of a revised version of an international search report
REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: CA