WO2018227044A1 - Formulations de gel analgésique topique et procédés d'utilisation de ces derniers - Google Patents

Formulations de gel analgésique topique et procédés d'utilisation de ces derniers Download PDF

Info

Publication number
WO2018227044A1
WO2018227044A1 PCT/US2018/036600 US2018036600W WO2018227044A1 WO 2018227044 A1 WO2018227044 A1 WO 2018227044A1 US 2018036600 W US2018036600 W US 2018036600W WO 2018227044 A1 WO2018227044 A1 WO 2018227044A1
Authority
WO
WIPO (PCT)
Prior art keywords
formulation
analgesic
weight
ibuprofen
skin
Prior art date
Application number
PCT/US2018/036600
Other languages
English (en)
Inventor
Wiley William Hitchcock
Original Assignee
Wiley William Hitchcock
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 Wiley William Hitchcock filed Critical Wiley William Hitchcock
Publication of WO2018227044A1 publication Critical patent/WO2018227044A1/fr

Links

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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 

Definitions

  • This disclosure relates topical analgesic formulations suitable for transdermal use, and to methods of making these formulations.
  • a topical, transdermal pain and swelling treatment that can be applied directly to injured or sore body parts and deliver appropriate dosing levels of drugs equivalent to those taken orally.
  • total-body dosing for localized pain is no longer necessary due to the effective transdermal drug delivery mechanism of the inventive formulation.
  • topical formulations described herein allow for the use of ibuprofen by people with cardiac problems or those with sensitive stomachs, for whom ibuprofen is currently off limits.
  • Other analgesic compounds in addition to or instead of ibuprofen can also be used.
  • a topical analgesic gel formulation comprises an effective amount of an analgesic agent, at least one skin-penetration enhancer, at least one non-aqueous solvent, at least one keratolytic agent, and water.
  • a method of treating pain in a mammal comprises the step of applying an effective amount of an analgesic gel topically to mammalian tissue, wherein the analgesic gel comprises an effective amount of an analgesic agent, at least one skin-penetration enhancer, at least one non-aqueous solvent, at least one keratolytic agent, and water.
  • analgesic agent refers to a quantity of one or more pharmaceutically active ingredients, as set forth below, capable of producing the desired level of pain relief.
  • the desired level of pain relief will be such that the individual using the inventive composition will no longer be bothered by the pain he or she felt prior to the administration of the inventive composition.
  • compositions of the invention are intended for topical, noninvasive, application to the skin, particularly to the region where the analgesic agent is intended to exert its
  • pharmacological activity usually to a region of inflammation, injury or pain to the muscles or joints, or other form of cutaneous disorders or disruptions characterized by skin inflammation and/or hyperproliferative activity in the epidermis.
  • a topical analgesic gel formulation comprises an effective amount of an analgesic agent, at least one skin-penetration enhancer, at least one non-aqueous solvent, at least one keratolytic agent, and water.
  • the water is de-ionized water.
  • the analgesic agent is a nonsteroidal anti-inflammatory drug.
  • non-steroidal anti-inflammatory drugs examples include heteroaryl acetic acids, such as, for example, tolmetin, diclofenac, ketorolac; arylpropionic acids, such as, for example, ibuprofen, naproxen, flurbiprofen, ketoprofen, fenoprofen, oxaprozin; anthranilic acids (fenamates), such as, for example, mefenamic acid, meclofenamic acid, fhilenamic acid; enolic acids, such as, for example, oxicams (e.g., piroxicam, tenoxicam), pyrazolidinediones (e.g., phenylbutazone, oxyphenthatrazone); alkanones, such as, for example, nabumetone.
  • heteroaryl acetic acids such as, for example, tolmetin, diclofenac, ketorolac
  • arylpropionic acids
  • any approved NSAIDs such as those listed in the current edition of The Merck Index or the FDA Orange Book, can be used.
  • the aforementioned non-steroidal anti-inflammatory analgesics can be used alone or in combinations of two or more.
  • any of the aforementioned NSAIDs can also be administered as pharmacologically acceptable neutral salts.
  • the formulations may be made substantially neutral by addition of a pH modifying agent (base) in an amount to provide a pH in the range of from 6.0 to 8.0, preferably from 6.5 to 7.5, especially preferably from 6.8 to 7.4, such as 7.0.
  • any of the well-known and pharmacologically safe inorganic or organic basic compounds can be used for this purpose and examples include inorganic salts, such as the sodium or other alkali or alkaline earth metal salts such as hydroxides, e.g., sodium hydroxide or potassium hydroxide; ammonium salt; or organic salt, especially amine salt, such as, for example, diethylamine; diethanolamine, triethanolamine, diisopropanolamine, N-methylglucamine, ethanolamine, isopropylamine, tetrahydroxypropyl ethylene diamine methylamine, ethylamine, propylamine, and the like.
  • inorganic salts such as the sodium or other alkali or alkaline earth metal salts such as hydroxides, e.g., sodium hydroxide or potassium hydroxide; ammonium salt; or organic salt, especially amine salt, such as, for example, diethylamine; diethanolamine, triethanolamine, diisopropanol
  • the NSAID and other ingredients can be selected to achieve the desired drug delivery profile and the amount of penetration desired.
  • the optimum pH can be determined and will depend on, for example, the nature of the NSAID, the base, and degree of flux required.
  • the analgesic agent may be ibuprofen, naproxen, flurbiprofen, ketoprofen, or fenoprofen, or pharmaceutically acceptable salts thereof.
  • the analgesic agent may be ibuprofen or a pharmaceutically acceptable salt thereof. Any physiologically compatible base capable of forming a neutral salt with ibuprofen can be used.
  • the ibuprofen or its pharmaceutically acceptable salt may be present in an amount ranging from 1 to 5 % by weight. In another embodiment, the ibuprofen or its pharmaceutically acceptable salt may be present in an amount ranging from 1 to 2% by weight. In one embodiment, the effective amount of ibuprofen or its pharmaceutically acceptable salt may range from 5 to 10 mg.
  • the inventive compositions may be formulated as gels.
  • lotions, creams, mousses, aerosols, ointments, lubricants, etc. can be used so long as when applied to the affected area of the skin the formulation will stay in place, i.e., without run-off, for sufficient time, to permit an individual to spread and retain the composition over and on the affected area.
  • poultice bases used for a poultice according to the invention, and any commonly used one can be selected.
  • components to be contained in such poultice bases there may be mentioned thickening agents, synthetic water- soluble polymers (sodium polyacrylate, polyacrylic acid, polyvinyl alcohol,
  • polyvinylpyrrolidone polyethylene oxide, polyvinyl methacrylate, etc.
  • natural substances gum arabic, starch, gelatin, methyl cellulose, hydroxypropyl cellulose, alginic acid, sodium alginate, ammonium alginate, carboxymethylcellulose sodium, etc.
  • humectants urea, glycerin, propylene glycol, butylene glycol, sorbitol, etc.
  • fillers kaolin, zinc oxide, talc, titanium, bentonite, epoxy resins
  • organic acids citric acid, tartaric acid, maleic acid, maleic anhydride, succimc acid, etc.
  • solubilizers propylene carbonate, crotamiton, diisopropyl adipate, etc.
  • tackifiers Rosins, ester gums, polybutene, polyacrylic esters, etc.
  • rash-preventing agents diphenhydranune hydrochloride
  • a poultice according to the invention can be obtained by mixing the aforementioned analgesic agent with a poultice base composed of a mixture of various components selected from the above.
  • plaster bases used for a plaster according to the invention there are no particular restrictions on plaster bases used for a plaster according to the invention, and any commonly used one can be selected.
  • components to be contained in such plaster bases there may be mentioned polymer bases, acrylic-based
  • compositions which are copolymers with vinyl monomers (methacrylic esters, acrylonitrile, vinyl acetate, vinyl propionate, etc.), silicone resins, polyisoprene rubber, polyisobutylene rubber, natural rubber, acrylic rubber, styrene-butadiene-styrene block copolymer, styrene-isoprene- styrene block copolymer; etc., fats/oils or higher fatty acids (almond oil, olive oil, camellia oil, apricot oil, peanut oil, olein oil, liquid paraffin, polybutene, etc.), tackifiers (rosins, rosin- modified maleic acid, hydrogenated rosin esters, etc.), fatty acid metal salts (zinc undecylenate, zinc stearate, calcium stearate, aluminum stearate, magnesium stearate, sodium stearate, zinc palmitate, zinc myristate, magnesium my
  • ointment bases used for an ointment according to the invention there are no particular restrictions on ointment bases used for an ointment according to the invention, and any commonly used one, can be selected.
  • components to be contained in such ointment bases there may be mentioned higher fatty acids or their esters (adipic acid, myristic acid, palmitic acid, stearic acid, oleic acid, adipic esters, myristic esters, palmitic esters, diethyl sebacate, hexyl laurate, cetyl isooctanate, etc.), waxes (spermaceti, beeswax, ceresin, etc.), surfactants (polyoxyethylene alkyl ether phosphates, etc.), higher alcohols (cetanol, stearyl alcohol, cetostearyl alcohol, etc.), silicone oils (dimethylpolysiloxane, methylphenylpolysiloxane,
  • cream bases used for a cream according to the invention there are no particular restrictions on cream bases used for a cream according to the invention, and any commonly used one may be selected.
  • higher fatty acid esters myristic esters, palmitic esters, diethyl sebacate, hexyl laurate, cetyl isooctanate, etc.
  • lower alcohols ethanol, isopropyl alcohol, etc.
  • carbohydratres liquid paraffin, squalane, etc.
  • polyhydric alcohols propylene glycol, 1,3-butylene glycol, etc.
  • higher alcohols (2-hexyldecanol, cetanol, 2- octyldodecanol, etc.
  • emulsifiers polyoxyethylene alltyl ethers, fatty acid esters, polyethylene glycol fatty acid esters, etc.
  • preservatives paraoxybenzoic acid esters, etc.
  • absorption enhancers propylene carbonate
  • a cream according to the invention can be obtained by mixing the aforementioned analgesic agent with a cream base comprising a mixture of various components selected from the above.
  • a gel cream (a dosage form having properties intermediate between a cream and a gel) according to the invention can be obtained by adding a gelling agent (carboxyvinyl polymer, hydroxyethyl cellulose, hydroxypropyl cellulose, ethyl cellulose, carboxymethyl cellulose, etc.) to the aforementioned cream, and further adjusting the pH to 4-8 (preferably 5-6.5) by addition of a neutralizing agent (diisopropylalcohol amines, triethanolamine, sodium hydroxide, etc.).
  • a gelling agent carboxyvinyl polymer, hydroxyethyl cellulose, hydroxypropyl cellulose, ethyl cellulose, carboxymethyl cellulose, etc.
  • a neutralizing agent diisopropylalcohol amines, triethanolamine, sodium hydroxide, etc.
  • liniment bases used for a liniment according to the invention there are no particular restrictions on liniment bases used for a liniment according to the invention, and any commonly used one may be selected.
  • liniment bases there may be mentioned mixtures composed of 10-70 parts by weight of an alcohol (a)
  • polyethylene glycol, propylene glycol, butylene glycol, etc. or the like
  • up to 55 parts by weight of water up to 60 parts by weight of a fatty acid ester (an ester of adipic acid, sebacic acid, myristic acid, etc.) and up to 10 parts by weight of a surfactant (poly oxy ethylene alkyl ether).
  • a surfactant poly oxy ethylene alkyl ether
  • neutralizing agents for pH adjustment
  • tackifiers methyl cellulose, carboxyvinyl polymer, hydroxypropyl cellulose, etc.
  • rash-preventing agents for example, salicylic acid, methyl salicylate, glycol salicylate, 1 -menthol, camphor;
  • peppermint oil may also be added in the liniment of the invention.
  • the vehicle for the forms of the compositions of the invention can include glycols, e.g., propylene glycol, butylene glycol, hexylene glycol, etc. (except in the case of some embodiments as described herein), lower alcohols, e.g., ethanol, isopropanol, and, usually, water.
  • a thickening or gelling agent can optionally be included to facilitate application of the formulation to the skin.
  • a thickening agent such as hydroxypropyl cellulose
  • any other pharmaceutically acceptable thickening/gelling agent may be used.
  • other thickening agents include cellulosic ethers, polymeric thickening agents, e.g., acrylic acid polymers, Carbopol RTM, thickeners, etc., xanthan gum, guar gum, and the like, as well as inorganic thickeners/gelling agents.
  • the amount of-the thickening agent can be selected to provide the desired product consistency or viscosity to allow for easy application to the skin but which will not be too watery or loose so that it will stay where applied.
  • amounts of thickening agent up to about 5% w/w, such as, for example, from 0.1 to about 2% w/w, of the composition will provide the desired effect.
  • the formulations can optionally include one or more moisturizers for hydrating the skin and emollients for softening and smoothing the skin.
  • Glycerin is an example of such a suitable moisturizing additive.
  • the additive When present, the additive will usually be incorporated in an amount of up to about 5 percent by weight of the composition, for example, from about 0.1 to 5% w/w.
  • the transdermal formulation for external application of the invention can contain, in addition to the aforementioned anti-inflammatory analgesic, a base selected depending on the dosage form of the formulation.
  • dosage forms of the transdermal formulation for external application of the invention there may be mentioned patches (poultices, plasters and the like), gels, creams, ointments and liniments.
  • the transdermal formulation for external application of the invention can also contain an antioxidant and/or an ultraviolet absorbent.
  • Preferred antioxidants include tocopherol and its ester derivatives, ascorbic acid, ascorbyl stearate, nordihydroguaiaretic acid and the like.
  • Preferred ultraviolet absorbents include p-aminobenzoic acid derivatives, anthranilic acid derivatives, salicylic acid derivatives, coumarin derivatives, amino acid-based compounds, imidazoline derivatives, pyrimidine derivatives, dioxane derivatives and the like.
  • the respective contents of such an antioxidant and such an ultraviolet absorbent are not particularly restricted, but are preferably 0-10% by weight and more preferably 0-5% by weight based on the total formulation.
  • one or more skin-penetration enhancers can be used.
  • the skin- penetration enhancer is preferably non-toxic, non-irritating, and non-allergenic.
  • a variety of skin-penetration enhancers can be used with the inventive formulation, including, but not limited to DMSO (dimethyl sulfoxide), Azone (l-dodecylazacycloheptan-2-one or laurocapran), chitosan, pyrrolidones (e.g. N-methyl-2-pyrrolidone), fatty acids (e.g. oleic acid, lauric acid, myristic acid, and capric acid), terpenes and terpenoids, oxazolidinones (e.g. 4-decyloxazolidin- 2-one), and urea.
  • DMSO dimethyl sulfoxide
  • Azone l-dodecylazacycloheptan-2-one or laurocapran
  • the skin-penetration enhancer comprises chitosan, DMSO, or combinations thereof.
  • the chitosan may be present in an amount ranging from 0.1 % to 10 % by weight.
  • the DMSO may be present in an amount of 0.1 % to 10 % by weight.
  • the analgesic gel formulation comprises non-aqueous solvent.
  • Preferred non-aqueous solvents include saturated and unsaturated C1-C5 alcohols and
  • the non-aqueous solvent comprises ethanol.
  • the non-aqueous solvent further comprises glycerol.
  • the glycerol may be present in an amount ranging from 0.1 % to 10 % by weight. In one
  • the ethanol is present in an amount ranging from 35 % to 90 % by weight.
  • the non-aqueous solvent may be present in an amount ranging from 35 % to 90 % by weight.
  • the analgesic gel formulation comprises one or more keratolytic agents. Keratolytic agents can soften the area of the skin to which they are applied. In some embodiments, the keratolytic agent comprises lactic acid, methyl salicylate, or combinations thereof. In one embodiment, the lactic acid is present in an amount ranging from 0.1 to 10 % by weight.
  • the concentration of keratolytic agent may be proportional to the concentration of the skin-penetration enhancer in the formulation. In certain embodiments, the concentration of keratolytic agent may be essentially equivalent to the concentration of the skin- penetration enhancer in the formulation. For example, in some embodiments, the concentration of lactic acid may be essentially equivalent to the concentration of chitosan powder in the formulation.
  • the ratio of the skin-penetration enhancer to the non-aqueous solvent is about 0.055 to 1. In one embodiment, the ratio of DMSO to ethanol is 0.055 to 1.
  • the method comprises applying an effective amount of an analgesic gel topically to mammalian tissue.
  • the analgesic gel formulation comprises an effective amount of an analgesic agent, at least one skin-penetration enhancer, at least one non-aqueous solvent, at least one keratolytic agent, and water.
  • the water is de-ionized water.
  • compositions described herein are typically applied to skin tissue, any tissue can be effectively treated with the inventive compositions provided that the tissue can be exposed to the inventive compositions for a time sufficient to deliver an effective therapeutic dose, and provided that no discomfort ensues from applying the composition to the tissue.
  • the tissue comprises human skin, mucous membranes, buccal tissue, or combinations thereof.
  • the analgesic agent comprises ibuprofen.
  • the effective amount of the analgesic gel has an average applied dosage of 5 to 10 mg of ibuprofen.
  • Example 1 describes a typical inventive analgesic gel formulation.
  • two solutions are prepared according to the methods set forth below. Although specific amounts of reagents are used herein, the absolute amounts can be increased or decreased as necessary to produce the desired amount of analgesic gel.
  • Ibuprofen powder (20 g), methyl salicylate (20 g), dimethyl sulfoxide (25 g), and absolute ethanol (455 mL) were added sequentially in to a 1 L glass bottle. The bottle was capped, and the contents vigorously shaken to produce a solution.
  • Solution 1 (480 g of 3% chitosan gel) was added to solution 2. The mixture was shaken and mixed until the solution appearance changed from cloudy to totally clear, without any visible cloudy sections. A clear, gel with bubbles dispersed throughout resulted.
  • any reference to methods, compositions, or articles is understood as a reference to each of those methods, compositions, or articles disjunctively (e.g., "Illustrative embodiment 1-4 is understood as illustrative embodiment 1, 2, 3, or 4.”).
  • Illustrative embodiment 1 is a topical analgesic gel formulation, comprising an effective amount of an analgesic agent, at least one skin-penetration enhancer, at least one nonaqueous solvent, at least one keratolytic agent, and water.
  • Illustrative embodiment 2 is the formulation of any preceding or subsequent illustrative embodiment, wherein the analgesic agent is ibuprofen.
  • Illustrative embodiment 3 is the formulation of any preceding or subsequent illustrative embodiment, wherein the ibuprofen is present in an amount ranging from 1 to 5 % by weight.
  • Illustrative embodiment 4 is the formulation of any preceding or subsequent illustrative embodiment, wherein the ibuprofen is present in an amount ranging from 1 to 2% by weight.
  • Illustrative embodiment 5 is the formulation of any preceding or subsequent illustrative embodiment, wherein the effective amount of ibuprofen ranges from 5 to 10 mg.
  • Illustrative embodiment 6 is the formulation of any preceding or subsequent illustrative embodiment, wherein the skin-penetration enhancer comprises chitosan, DMSO, or combinations thereof.
  • Illustrative embodiment 7 is the formulation of any preceding or subsequent illustrative embodiment, wherein the chitosan is present in an amount ranging from 0.1% to 10 % by weight.
  • Illustrative embodiment 8 is the formulation of any preceding or subsequent illustrative embodiment, wherein the DMSO is present in an amount of 0.1 % to 10 % by weight.
  • Illustrative embodiment 9 is the formulation of any preceding or subsequent illustrative embodiment, wherein the non-aqueous solvent comprises ethanol.
  • Illustrative embodiment 10 is the formulation of any preceding or subsequent illustrative embodiment, wherein the non-aqueous solvent further comprises glycerol.
  • Illustrative embodiment 11 is the formulation of any preceding or subsequent illustrative embodiment, wherein the glycerol is present in an amount ranging from 0.1 % to 10 % by weight.
  • Illustrative embodiment 12 is the formulation of any preceding or subsequent illustrative embodiment, wherein the ethanol is present in an amount ranging from 35 % to 90 % by weight.
  • Illustrative embodiment 13 is the formulation of any preceding or subsequent illustrative embodiment, wherein the keratolytic agent comprises lactic acid, methyl salicylate, or combinations thereof.
  • Illustrative embodiment 14 is the formulation of any preceding or subsequent illustrative embodiment, wherein the lactic acid is present in an amount ranging from 0.1 % to 10 % by weight.
  • Illustrative embodiment 15 is the formulation of any preceding or subsequent illustrative embodiment, wherein the ratio of the skin-penetration enhancer to the non-aqueous solvent is about 0.055 to 1.
  • Illustrative embodiment 16 is the formulation of any preceding or subsequent illustrative embodiment, wherein the ratio DMSO to ethanol is about 0.055 to 1.
  • Illustrative embodiment 17 is the formulation of any preceding or subsequent illustrative embodiment, wherein the water is de-ionized water.
  • Illustrative embodiment 18 is a method of treating pain in a mammal, comprising applying an effective amount of an analgesic gel topically to mammalian tissue, wherein the analgesic gel comprises: an effective amount of an analgesic agent; at least one skin-penetration enhancer; at least one non-aqueous solvent; at least one keratolytic agent; and water.
  • Illustrative embodiment 19 is the method of any preceding or subsequent illustrative embodiment, wherein the tissue comprises human skin, mucous membranes, buccal tissue, or combinations thereof.
  • Illustrative embodiment 20 is the method of any preceding or subsequent illustrative embodiment, wherein the analgesic agent is ibuprofen.
  • Illustrative embodiment 21 is the method of any preceding or subsequent illustrative embodiment, wherein the effective amount of the analgesic gel has an average applied dosage of 5 to 10 mg of ibuprofen.

Abstract

L'invention concerne des formulations analgésiques topiques et des procédés d'utilisation de formulations analgésiques topiques.
PCT/US2018/036600 2017-06-09 2018-06-08 Formulations de gel analgésique topique et procédés d'utilisation de ces derniers WO2018227044A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201762517237P 2017-06-09 2017-06-09
US62/517,237 2017-06-09

Publications (1)

Publication Number Publication Date
WO2018227044A1 true WO2018227044A1 (fr) 2018-12-13

Family

ID=64567343

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2018/036600 WO2018227044A1 (fr) 2017-06-09 2018-06-08 Formulations de gel analgésique topique et procédés d'utilisation de ces derniers

Country Status (1)

Country Link
WO (1) WO2018227044A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021236782A1 (fr) * 2020-05-19 2021-11-25 Mig Usa, Llc Compositions topiques et méthodes de traitement de la douleur

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6143278A (en) * 1998-02-23 2000-11-07 Elkhoury; George F. Topical application of opioid analgesic drugs such as morphine
US6399093B1 (en) * 1999-05-19 2002-06-04 Advanced Medical Instruments Method and composition to treat musculoskeletal disorders
US8217078B1 (en) * 2009-03-31 2012-07-10 Nuvo Research Inc. Treatment of pain with topical diclofenac
US20120232152A1 (en) * 2009-11-27 2012-09-13 Nuvo Research Inc. Topical ibuprofen formulations

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6143278A (en) * 1998-02-23 2000-11-07 Elkhoury; George F. Topical application of opioid analgesic drugs such as morphine
US6399093B1 (en) * 1999-05-19 2002-06-04 Advanced Medical Instruments Method and composition to treat musculoskeletal disorders
US8217078B1 (en) * 2009-03-31 2012-07-10 Nuvo Research Inc. Treatment of pain with topical diclofenac
US20120232152A1 (en) * 2009-11-27 2012-09-13 Nuvo Research Inc. Topical ibuprofen formulations

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021236782A1 (fr) * 2020-05-19 2021-11-25 Mig Usa, Llc Compositions topiques et méthodes de traitement de la douleur

Similar Documents

Publication Publication Date Title
US10117829B2 (en) Diclofenac formulations
US8470886B2 (en) Topical ibuprofen formulations
AU2019203449B2 (en) Topical diclofenac sodium compositions
JP2001513543A (ja) 皮膚への局所適用のための非ステロイド性抗炎症薬製剤
JP4549006B2 (ja) ゲル軟膏
WO1997028793A1 (fr) Preparation a usage externe comprenant du tranilast et processus de production de cette preparation
KR20110017451A (ko) 소염 진통 외용제
JP2009149692A (ja) ゲル軟膏
JP6765299B2 (ja) 水性製剤
WO2018227044A1 (fr) Formulations de gel analgésique topique et procédés d'utilisation de ces derniers
JP4256125B2 (ja) 外用組成物
US9687549B2 (en) Topical pharmaceutical gel composition of diclofenac sodium
JP7092498B2 (ja) 尿かぶれ改善剤
TW201002313A (en) Antipruritic and analgesic medicine containing oxybuprocaine for external use
US20160263065A1 (en) Topical pharmaceutical gel composition of diclofenac sodium
JP2021195323A (ja) 外用組成物

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 18813609

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 18813609

Country of ref document: EP

Kind code of ref document: A1