WO1988009169A1 - Unit-dose film composition for percutaneous anaesthesia and associated method - Google Patents
Unit-dose film composition for percutaneous anaesthesia and associated method Download PDFInfo
- Publication number
- WO1988009169A1 WO1988009169A1 PCT/GB1988/000416 GB8800416W WO8809169A1 WO 1988009169 A1 WO1988009169 A1 WO 1988009169A1 GB 8800416 W GB8800416 W GB 8800416W WO 8809169 A1 WO8809169 A1 WO 8809169A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- composition
- water
- amethocaine
- drying
- film
- Prior art date
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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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
Definitions
- the Anaesthetic may be amethocaine and may be dispersed in a solid matrix such as a hydrophitic synthetic plastics material film.
- Amethocaine (2-dimethyl aminoethyl p-butyl-amin- meritzoate) is used in topical preparations to provide surface anaesthesia.
- Topical percutaneous anaesthetic compositions containing amethocaine and in which the anaesthetic agent penetrates the stratum corneum are disclosed in U..K. Patent No. 2,163,956B. These compositions are presented as aqueous gels. When an effective amount of such compositions is applied to intact skin the anaesthetic agent penetrates the skin sufficiently to produce a deep anaesthesia sufficient to allow the painless removal donor skin for full-thickness grafts, penetration of the skin by needles (e.g. venepuncture) and other minor surgical procedures.
- needles e.g. venepuncture
- compositions suffer from a number of disadvantages in terms of convenience of application: (1) They cannot be presented in the form of a single defined application (unit-dose). It is known in the art that unit-dose compositions offer advantages in terms of patient safety. (2) The amount of the composition placed on the skin is variable, hence the area of the skin anaesthetised is also variable. (3) When large areas of skin are required to be anaesthetised e.g. in the taking of skin for subsequent grafting, the gel composition must be carefully spread in an even manner over the donor site in order to ensure adequate anaesthesia, the process being time-consuming and prone to human error. (4) In all cases the gel compositions must be covered with a separate suitable dressing.
- composition for topical application comprising a percutaneous anaesthetic component dispensed in a solid matrix.
- compositions for use as a unit-dose topical percutaneous anesthetic comprising a local anaesthetic dispersed in a hydrophilic plastic film.
- a method of preparing a mixture comprising amethocaine, an aqueous gelling agent and water such that a gel substantially free from entrapped air bubbles and capable of forming a smooth plastic film (following casting or extrusion of the gel and subsequent drying) is produced.
- a method of providing topical percultaneous anaesthesia with a unit-dose composition as claimed in any preceding claim comprising wetting a suitable defined area unit-dose of the anaesthetic containing matrix or the hydrophilic side of the laminate with water or other aqueous fluid such that the surface hydrophilic layer becomes gelatinous and applying the wet matrix or hydrophilic side of the laminate to intact skin for a minimum period of twenty minutes.
- a particularly suitable matrix is a hydrophilic plastic film.
- Preferred hydrophilic film-forming materials useful in the invention include (a) copolymers of acrylic acid and a polyallyl sucrose (b) reaction products of cellulose or glucose with acids or alkylene oxides (c) water-soluble vinyl polymers and copolymers, and (d) mixtures of any of the foregoing materials.
- Suitable sucrose and acrylic acid copolymers are disclosed and preparations thereof described in U.S. Patent No. 2,798,053.
- Typical sucrose copolymers or carbomers are obtained commercially as Carbopol 934, 940 and 941. Carbopol is a registered Trademark.
- Suitable cellulose derivatives are (i) sodium carboxymethylcellulose, the product of reaction between an alkali cellulose and monochloroacetic acid, sold under the tradename "CMC” (ii) cellulose and methyl chloride r sold under the tradename “Methocel” and (iii) hydroxyalkyl cellulose, the reaction product of an alkali cellulose and an alkylene oxide, as ethylene or propylene oxide , and sold under the tradenames"Natrosol” and "Klucel".
- a particularly preferred composition is prepared using hydroxypropyl-cellulose ("Klucel").
- Suitable water-soluble vinyl polymers and copolymers include polyvinyl alcohol, polyvinyl acetate and polyvinyl pyrrolidone.
- a further aspect of the present invention relates to amethocaine containing hydrophilic plastic compositions bonded on one surface to a hydrophobic (water-insoluble) plastic film to form a laminate, such bonding being achieved by direct application of cellulose-based adhesives known in the art, or other suitable means known in the art.
- the upper hydrophobic surface acts as an integral dressing protecting the hydrophilic layer, maintaining its moisture content and also protecting clothing.
- the hydrophobic side of the laminate may be impermeable or semi-permeable to the passage of air and water vapour.
- water-insoluble plastic materials which may be used for this purpose are polyethylene, polyvinyl chloride, copolymers or ethoxyethyl methacrylate and methoxyethyl methacryl . ate (known commercially as "Hydron") urethane polymers, polyesters such as polyethylene terephthalate or other such materials known in the art.
- the invention also comprises the method of providing topical percutaneous anaesthesia by soaking the hydrophilic film or the hydrophilic side of the laminate composition in water or other aqueous fluid such as saline for a sufficient time to form a gelatinous layer on the hydrophilic surface.
- the time required for this purpose is typically between 2 and 5 seconds.
- the wet gelatinous surface of the hydrophilic film or laminate is placed in contact with an area of intact skin, such contact being maintained for a minimum of 20 minutes. Thereafter the film or laminate composition is removed before the surgical procedure takes place.
- the general method for forming the hydrophilic amethocaine-containing film compositions require amethocaine (0.05% to 7% but preferably between 0.05 and 0.5%, the said percentages being by weight based on the total weight of the composition) to be dispersed in an aqueous gel formed with, for example, Klucel MF.
- aqueous gel formed with, for example, Klucel MF.
- Such a gel contains between 0.5% and 20%, but preferably 3% of
- the film—forming composition can be formulated as a solution.
- Such solutions may suitably contain from 10 to 40%, preferably about 20% by weight, of a film-forming polymer such as polyvinyl alcohol.
- the percutaneous anaesthetic component e.g. amethocaine
- concentrations ranging form 10 to 20%, preferably about 15% by weight.
- the gel or solution can then be air-dried at ambient temperature (following either
- plastic films 15 conventional casting onto a suitable non-stick surface or extrusion techniques known in the art for the formation of plastic films) to form a plastic film.
- Such films may be of various thicknesses between 0.01mm and 2mm, but preferably between 0.08mm and
- amethocaine content of the gels and the thicknesses of the dry films produced determine the amethocaine content of the film compositions.
- a 3 centimetres square film contains between 9 and 14 milligrams of amethocaine.
- Example 1 The following examples are given to illustrate the present invention.
- the following ingredients are mixed together by dispersing the gelling agent in approximately one third and total volume of water to be used and maintaining the mixture between 50 and 60 degrees centigrade until the gelling agent is thoroughly wetted, about 10 minutes. A further one third of the total volume of water at a temperature below 10 degrees centigrade is then added and the mixture gently stirred for a few seconds prior to addition of the final one third of the total volume of water containing the total weight of amethocaine. The final mixture is gently stirred until the gel is fully set. When mixed in this way the gel is substantially free from entrapped air bubbles whereupon a smooth hydrophilic film of even thickness is then formed in the manner already described. amethocaine 0.4%
- the hydrophilic film may be applied directly to the skin but preferably is applied in the lainate form with integral water-insoluble plastic dressing.
- the laminate may be prepared in a variety of suitable sizes for unit-dose application. Complete anaesthesia of the treated area occurs within 45 minutes of the initial application. The anaesthetic effect may persist for up to 8 hours in some individuals but is typically present for between 3 and 4 hours depending on individual variation.
- a 17.12% (w/w) solution of polyvinyl alcohol was prepared by mixing PVA into sterilised water, heated to 80°C on a steam bath. The solution was allowed to stand to fully de-aerate and thereafter placed in an autoclave oven for 15 minutes at 121°C.
- Solid amethocaine was passed through a 106 ⁇ m mesh screen and added, with stirring, to the PVA solution at ambient temperature, to bring the total solids content up to 20% (w/w) and this solution left to stand to fully de-aerate.
- the de-aerated 20% solution of PVA/Amethocaine was knife coated at a temperature of 80°C onto a roll of polyethylene terephthalate (sold under the trade mark "Melinex" ) .
- the gap of the spreading block was set to 20 thou. (500 ⁇ m). After coating, the coated film was dried in a heated drying tunnel to reduce the water content by about 80%.
- the final thickness of dried coating was about 0.06mm and the amethocaine concentration in the coating was about 14% w/w or 1. lmg cm
- the particle screening step was omitted and the amethocaine was heated to melting before being added with stirring to the PVA solution which had been heated to 60°C.
- the de-aeration time was found to be much less than that required for the amethocaine addition at ambient temperature.
- A Amethocain/PVA/"Melinex
- B PVA/"Melinex
Abstract
Anaesthetic such as amethocaine is disposed in a solid matrix such as a hydrophilic synthetic plastics material film. The film may be applied directly to the skin but is preferably applied in the laminate form with integral water insoluble plastics material dressing.
Description
UNIT-DOSE FILM COMPOSITION FOR PERCUTANEOUS ANAESTHESIA AND ASSOCIATED METHOD
This invention relates to anaesthetic-containing compositions. The Anaesthetic may be amethocaine and may be dispersed in a solid matrix such as a hydrophitic synthetic plastics material film.
Amethocaine (2-dimethyl aminoethyl p-butyl-amin- obenzoate) is used in topical preparations to provide surface anaesthesia. Topical percutaneous anaesthetic compositions containing amethocaine and in which the anaesthetic agent penetrates the stratum corneum are disclosed in U..K. Patent No. 2,163,956B. These compositions are presented as aqueous gels. When an effective amount of such compositions is applied to intact skin the anaesthetic agent penetrates the skin sufficiently to produce a deep anaesthesia sufficient to allow the painless removal donor skin for full-thickness grafts, penetration of the skin by needles (e.g. venepuncture) and other minor surgical procedures. Such compositions suffer from a number of disadvantages in terms of convenience of application: (1) They cannot be presented in the form of a single defined application (unit-dose). It is known in the art that unit-dose compositions offer advantages in terms of patient safety. (2) The amount of the composition
placed on the skin is variable, hence the area of the skin anaesthetised is also variable. (3) When large areas of skin are required to be anaesthetised e.g. in the taking of skin for subsequent grafting, the gel composition must be carefully spread in an even manner over the donor site in order to ensure adequate anaesthesia, the process being time-consuming and prone to human error. (4) In all cases the gel compositions must be covered with a separate suitable dressing.
According to one aspect of the present invention, there is provided a composition for topical application comprising a percutaneous anaesthetic component dispensed in a solid matrix.
According to another aspect of the present invention,there is provided a composition for use as a unit-dose topical percutaneous anesthetic and comprising a local anaesthetic dispersed in a hydrophilic plastic film.
According to a further aspect of the present invention , there is provided a method of preparing a mixture comprising amethocaine, an aqueous gelling agent and water such that a gel substantially free from entrapped air bubbles and capable of forming a smooth plastic film (following casting or extrusion of the gel and subsequent drying) is produced.
According to a still further aspect of the present invention, there is provided a method of providing topical percultaneous anaesthesia with a unit-dose composition as claimed in any preceding claim comprising wetting a suitable defined area unit-dose of the anaesthetic containing matrix or the hydrophilic side of the laminate with water or other aqueous fluid such that the surface hydrophilic layer becomes gelatinous and applying the wet matrix or hydrophilic side of the laminate to intact skin for a minimum period of twenty minutes.
A particularly suitable matrix is a hydrophilic plastic film. Preferred hydrophilic film-forming materials useful in the invention include (a) copolymers of acrylic acid and a polyallyl sucrose (b) reaction products of cellulose or glucose with acids or alkylene oxides (c) water-soluble vinyl polymers and copolymers, and (d) mixtures of any of the foregoing materials. Suitable sucrose and acrylic acid copolymers are disclosed and preparations thereof described in U.S. Patent No. 2,798,053. Typical sucrose copolymers or carbomers are obtained commercially as Carbopol 934, 940 and 941. Carbopol is a registered Trademark.
Suitable cellulose derivatives are (i) sodium carboxymethylcellulose, the product of reaction between
an alkali cellulose and monochloroacetic acid, sold under the tradename "CMC" (ii) cellulose and methyl chloride r sold under the tradename "Methocel" and (iii) hydroxyalkyl cellulose, the reaction product of an alkali cellulose and an alkylene oxide, as ethylene or propylene oxide , and sold under the tradenames"Natrosol" and "Klucel". A particularly preferred composition is prepared using hydroxypropyl-cellulose ("Klucel").
Suitable water-soluble vinyl polymers and copolymers include polyvinyl alcohol, polyvinyl acetate and polyvinyl pyrrolidone.
A further aspect of the present invention relates to amethocaine containing hydrophilic plastic compositions bonded on one surface to a hydrophobic (water-insoluble) plastic film to form a laminate, such bonding being achieved by direct application of cellulose-based adhesives known in the art, or other suitable means known in the art. The upper hydrophobic surface acts as an integral dressing protecting the hydrophilic layer, maintaining its moisture content and also protecting clothing. The hydrophobic side of the laminate may be impermeable or semi-permeable to the passage of air and water vapour. Examples of water-insoluble plastic materials which may be used for this purpose are polyethylene, polyvinyl chloride, copolymers or ethoxyethyl methacrylate and
methoxyethyl methacryl.ate (known commercially as "Hydron") urethane polymers, polyesters such as polyethylene terephthalate or other such materials known in the art.
The invention also comprises the method of providing topical percutaneous anaesthesia by soaking the hydrophilic film or the hydrophilic side of the laminate composition in water or other aqueous fluid such as saline for a sufficient time to form a gelatinous layer on the hydrophilic surface. The time required for this purpose is typically between 2 and 5 seconds. The wet gelatinous surface of the hydrophilic film or laminate is placed in contact with an area of intact skin, such contact being maintained for a minimum of 20 minutes. Thereafter the film or laminate composition is removed before the surgical procedure takes place. These compositions provide a profound anaesthetic effect. Each individual application of the compositions is identical . An even and uniform contact with the skin is achieved due to the conforming nature of the film and laminate compositions, thereby ensuring ease and rapidity of application by nursing staff or the patient themselves.
The general method for forming the hydrophilic amethocaine-containing film compositions require amethocaine (0.05% to 7% but preferably between 0.05 and
0.5%, the said percentages being by weight based on the total weight of the composition) to be dispersed in an aqueous gel formed with, for example, Klucel MF. Such a gel contains between 0.5% and 20%, but preferably 3% of
5. the aqueous gelling agent. Alternatively, the film—forming composition can be formulated as a solution. Such solutions may suitably contain from 10 to 40%, preferably about 20% by weight, of a film-forming polymer such as polyvinyl alcohol.
10 The percutaneous anaesthetic component, e.g. amethocaine, of such solutions may be present in concentrations ranging form 10 to 20%, preferably about 15% by weight. The gel or solution can then be air-dried at ambient temperature (following either
15 conventional casting onto a suitable non-stick surface or extrusion techniques known in the art for the formation of plastic films) to form a plastic film. Such films may be of various thicknesses between 0.01mm and 2mm, but preferably between 0.08mm and
20 0.15mm. The amethocaine content of the gels and the thicknesses of the dry films produced determine the amethocaine content of the film compositions. Typically, a 3 centimetres square film contains between 9 and 14 milligrams of amethocaine.
25
The following examples are given to illustrate the present invention.
Example 1.
The following ingredients are mixed together by dispersing the gelling agent in approximately one third and total volume of water to be used and maintaining the mixture between 50 and 60 degrees centigrade until the gelling agent is thoroughly wetted, about 10 minutes. A further one third of the total volume of water at a temperature below 10 degrees centigrade is then added and the mixture gently stirred for a few seconds prior to addition of the final one third of the total volume of water containing the total weight of amethocaine. The final mixture is gently stirred until the gel is fully set. When mixed in this way the gel is substantially free from entrapped air bubbles whereupon a smooth hydrophilic film of even thickness is then formed in the manner already described. amethocaine 0.4%
Klucel MF 3.0% water 96.6%
The hydrophilic film may be applied directly to the skin but preferably is applied in the lainate form with integral water-insoluble plastic dressing. The laminate may be prepared in a variety of suitable sizes for unit-dose application. Complete anaesthesia of the treated area occurs within 45 minutes of the initial application. The anaesthetic effect may persist for up to 8 hours in some individuals but is typically present
for between 3 and 4 hours depending on individual variation.
Example 2. Preparation of film
A 17.12% (w/w) solution of polyvinyl alcohol was prepared by mixing PVA into sterilised water, heated to 80°C on a steam bath. The solution was allowed to stand to fully de-aerate and thereafter placed in an autoclave oven for 15 minutes at 121°C.
Solid amethocaine was passed through a 106μm mesh screen and added, with stirring, to the PVA solution at ambient temperature, to bring the total solids content up to 20% (w/w) and this solution left to stand to fully de-aerate.
The de-aerated 20% solution of PVA/Amethocaine was knife coated at a temperature of 80°C onto a roll of polyethylene terephthalate (sold under the trade mark "Melinex" ) . The gap of the spreading block was set to 20 thou. (500μm). After coating, the coated film was dried in a heated drying tunnel to reduce the water content by about 80%.
The final thickness of dried coating was about 0.06mm and the amethocaine concentration in the coating was about 14% w/w or 1. lmg cm
In an alternative procedure for the preparation of the casting solution the particle screening step was omitted and the amethocaine was heated to melting before being added with stirring to the PVA solution which had been heated to 60°C. The de-aeration time was found to be much less than that required for the amethocaine addition at ambient temperature.
Testing 3x3cm patches of "Melinex", coated with PVA/Amethocaine, were thoroughly wetted with water, applied from a syringe, and applied to the skin of volunteers. The patches were left in situ for 30 minutes after which they were removed. Negative control patches, comprising 3x3cm patches of "Melinex" coated only with PVA were simultaneously, treated with water, applied for 30 minutes and removed.
Each volunteer was requested to press the point of an orthopaedic pin into the area of skin previously covered by a patch and to record, on a chart, the level of discomfort felt. The chart was graded from 0 (pain) to 10 (no sensation). The tests were repeated at periods of 45 minutes, 1 hour, 2 hours, 3 hours and 4 hours after application of the patch in order to determine the level of local anaesthesia.
The results are summarised below:-
Test Assessment Time Material 30 45 1 2 3
A 3 5 6 7 7 7
B 0 0 0 0 0 0
A = Amethocain/PVA/"Melinex" B = PVA/"Melinex"
It will be appreciated that the above embodiment has been described by way of example only and that many variations are possible without departing from the invention.
Claims
1. A composition for topical application comprising a percutaneous anaesthetic component dispensed in a solid matrix.
2. A composition as claimed in claim 1, in which the percutaneous anaesthetic component is amethocaine.
3. A composition as claimed in claim 1 or 2, in which the solid matrix comprises a hydrophilic synthetic plastics material film.
4. A composition as claimed in claim 2, or 3 when appendent to 2, prepared from a mixture comprising 0.05% to 7% of amethocaine by weight based on the total weight of the composition prior to drying.
5. A composition as claimed in any preceding claim prepared from a mixture comprising 0.5 to 20% of an aqueous gelling agent by weight based on the total weight of the composition prior to drying.
6. A composition as claimed in any preceding claim, prepared from a mixture comprising 73 to 99.45% water by weight based on the total weight of the composition prior to drying.
7. A composition for use as a unit-dose topical percutaneous anesthetic and comprising a local anaesthetic dispersed in a hydrophilic plastic film.
8. A composition as claimed in claim 7, in which the anaesthetic is amethocaine.
9. A composition as claimed in claim 7 or 8 prepared from a mixture containing 0.05% to 20% of amethocaine by weight based on the total weight of the composition prior to drying.
10. A composition as claimed in claim 7, 8 or 9, prepared from a mixture containing 0.5 to 7% of an aqueous gelling agent by weight based on the total weight of the composition prior to drying.
11. A composition as claimed in climed 5,6,7 or 8 prepared from a mixture containing 73 to 99.45% water by weight based on the total weight of the composition prior to drying.
12. A composition according to any previous claim in which the aqueous gelling agent is capable of forming and aqueous gel from which a hydrophilic plastic film may be produced following casting or extrusion of the gel and subsequent removal of water by drying. -I S¬
IS. A composition according to any previous claim in which the aqueous gelling agent is hydroxypropylcellulose or other cellulo.se derivative.
14. A composition according to any previous claim in which mixtures of aqueous gelling agents are used.
15. A unit-dose composition for topical application comprising amethocaine dispersed in a hydrophilic plastic film according to any previous claim which is bonded on one surface by use of a suitable adhesive material or otherwise attached to a water-insoluble plastic film which acts as an integral covering dressing.
16. A laminate film composition according to claim 16 in which the water-insoluble film is polyethylene.
17. A laminate film composition according to claim 16 in which the water-insoluble material is polyvinyl chloride.
18. A laminate film composition according to claim 16 in which the water-insoluble material is a copolymer of ethoxyethyl methacrylate and methoxyethyl methacrylate.
19. A method of preparing a mixture comprising amethocaine, an aqueous gelling agent and water such that a gel substantially free from entrapped air bubbles and capable of forming a smooth plastic film (following casting or extrusion of the gel and subsequent drying) is produced.
20. A method of providing topical percultaneous anaesthesia with a unit-dose composition as claimed in any preceding claim comprising wetting a suitable defined area unit-dose of the anaesthetic containing matrix or the hydrophilic side of the laminate with water or other aqueous fluid such that the surface hydrophilic layer becomes gelatinous and applying the wet matrix or hydrophilic side of the laminate to intact skin for a minimum period of twenty minutes.
21. A composition for topical application according to Example 1 or Example 2 of the specification.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8712518 | 1987-05-28 | ||
| GB878712518A GB8712518D0 (en) | 1987-05-28 | 1987-05-28 | Unit-dose film composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1988009169A1 true WO1988009169A1 (en) | 1988-12-01 |
Family
ID=10618022
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/GB1988/000416 WO1988009169A1 (en) | 1987-05-28 | 1988-05-26 | Unit-dose film composition for percutaneous anaesthesia and associated method |
Country Status (4)
| Country | Link |
|---|---|
| AU (1) | AU1794688A (en) |
| GB (2) | GB8712518D0 (en) |
| WO (1) | WO1988009169A1 (en) |
| ZA (1) | ZA883825B (en) |
Cited By (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0388306A2 (en) * | 1989-03-17 | 1990-09-19 | Hind Health Care, Inc. | Method for treating pain associated with herpes-zoster and post-herpetic neuralgia by topical application of local anesthetics |
| WO1992013533A1 (en) * | 1991-01-30 | 1992-08-20 | Smith & Nephew Plc | Pharmaceutical compositions containing amethocaine |
| WO1992016202A1 (en) * | 1991-03-21 | 1992-10-01 | Smith & Nephew Plc | Percutaneous anaesthesia |
| US5411738A (en) * | 1989-03-17 | 1995-05-02 | Hind Health Care, Inc. | Method for treating nerve injury pain associated with shingles (herpes-zoster and post-herpetic neuralgia) by topical application of lidocaine |
| WO1997002003A2 (en) * | 1995-07-06 | 1997-01-23 | Smith & Nephew Plc | Compositions |
| US5658583A (en) * | 1995-07-28 | 1997-08-19 | Zhang; Jie | Apparatus and methods for improved noninvasive dermal administration of pharmaceuticals |
| US5912271A (en) * | 1994-07-12 | 1999-06-15 | Astra Ab | Pharmaceutical preparation for pain management |
| US6245347B1 (en) | 1995-07-28 | 2001-06-12 | Zars, Inc. | Methods and apparatus for improved administration of pharmaceutically active compounds |
| US6261595B1 (en) | 2000-02-29 | 2001-07-17 | Zars, Inc. | Transdermal drug patch with attached pocket for controlled heating device |
| US6284266B1 (en) | 1995-07-28 | 2001-09-04 | Zars, Inc. | Methods and apparatus for improved administration of fentanyl and sufentanil |
| AU744913B2 (en) * | 1995-07-06 | 2002-03-07 | Smith & Nephew Plc | Water activable adhesive matrix containing amethocaine |
| US6453648B1 (en) | 1999-07-06 | 2002-09-24 | Zars, Inc. | Method for manufacturing a heat generating apparatus |
| US6955819B2 (en) | 1998-09-29 | 2005-10-18 | Zars, Inc. | Methods and apparatus for using controlled heat to regulate transdermal and controlled release delivery of fentanyl, other analgesics, and other medical substances |
| US9012477B2 (en) | 2009-01-06 | 2015-04-21 | Nuvo Research Inc. | Method of treating neuropathic pain |
| US9078833B2 (en) | 2002-08-30 | 2015-07-14 | Alza Corporation | Multilaminate backing construction |
| US9186273B2 (en) | 2009-05-04 | 2015-11-17 | Nuvo Research Inc. | Methods of treating pains associated with neuroma, nerve entrapment, and other conditions |
| US9186334B2 (en) | 2009-05-04 | 2015-11-17 | Nuvo Research Inc. | Heat assisted lidocaine and tetracaine for transdermal analgesia |
| US9693976B2 (en) | 2010-01-14 | 2017-07-04 | Crescita Therapeutics Inc. | Solid-forming local anesthetic formulations for pain control |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1108837A (en) * | 1965-11-30 | 1968-04-03 | Astra Pharma Prod | Improvements in material for causing local anaesthesia |
| US3978201A (en) * | 1972-11-27 | 1976-08-31 | Gennady Lvovich Khromov | Base for ophthalmological medicinal preparation on opthalmological medicinal film |
| EP0175609A2 (en) * | 1984-09-08 | 1986-03-26 | SMITH & NEPHEW plc | Transdermal anaesthetic composition for topical use and process for its application |
| EP0250187A2 (en) * | 1986-06-16 | 1987-12-23 | JOHNSON & JOHNSON CONSUMER PRODUCTS, INC. | Bioadhesive extruded film for intra-oral drug delivery and process |
| JPH06263513A (en) * | 1993-03-10 | 1994-09-20 | Eishu Sen | Preparation of cylindrical artificial marble |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA711727B (en) * | 1970-03-24 | 1971-12-29 | Itek Corp | Gelled burn-treating solutions |
| GB1384537A (en) * | 1971-05-20 | 1975-02-19 | Sterling Winthrop Group Ltd | Wound coverings |
| US3969498A (en) * | 1973-09-13 | 1976-07-13 | University Of The Pacific | Dressing and method for treating a wound |
| JPS5758615A (en) * | 1980-09-26 | 1982-04-08 | Nippon Soda Co Ltd | Film agnent and its preparation |
| GB2133284A (en) * | 1983-01-07 | 1984-07-25 | English Grains Limited | Resilient pharmaceutical unit for treating mouth ulcers |
-
1987
- 1987-05-28 GB GB878712518A patent/GB8712518D0/en active Pending
-
1988
- 1988-05-26 GB GB08812517A patent/GB2206044A/en not_active Withdrawn
- 1988-05-26 WO PCT/GB1988/000416 patent/WO1988009169A1/en unknown
- 1988-05-26 AU AU17946/88A patent/AU1794688A/en not_active Abandoned
- 1988-05-27 ZA ZA883825A patent/ZA883825B/en unknown
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1108837A (en) * | 1965-11-30 | 1968-04-03 | Astra Pharma Prod | Improvements in material for causing local anaesthesia |
| US3978201A (en) * | 1972-11-27 | 1976-08-31 | Gennady Lvovich Khromov | Base for ophthalmological medicinal preparation on opthalmological medicinal film |
| EP0175609A2 (en) * | 1984-09-08 | 1986-03-26 | SMITH & NEPHEW plc | Transdermal anaesthetic composition for topical use and process for its application |
| EP0250187A2 (en) * | 1986-06-16 | 1987-12-23 | JOHNSON & JOHNSON CONSUMER PRODUCTS, INC. | Bioadhesive extruded film for intra-oral drug delivery and process |
| JPH06263513A (en) * | 1993-03-10 | 1994-09-20 | Eishu Sen | Preparation of cylindrical artificial marble |
Non-Patent Citations (1)
| Title |
|---|
| Patent Abstracts of Japan, volume 11, no. 262 (C-442)(2709), 25 August 1987; & JP-A-6263513 (NIPPON SHINYAKU CO. LTD) 20 March 1987 * |
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| US5411738A (en) * | 1989-03-17 | 1995-05-02 | Hind Health Care, Inc. | Method for treating nerve injury pain associated with shingles (herpes-zoster and post-herpetic neuralgia) by topical application of lidocaine |
| EP0388306A3 (en) * | 1989-03-17 | 1991-03-06 | Hind Health Care, Inc. | Method for treating pain associated with herpes-zoster and post-herpetic neuralgia by topical application of local anesthetics |
| USRE37727E1 (en) | 1989-03-17 | 2002-06-04 | Hind Health Care | Method for treating nerve injury pain associated with shingles |
| US5601838A (en) * | 1989-03-17 | 1997-02-11 | Hind Health Care, Inc. | Method for treating pain associated with herpes-zoster and post-herpetic neuralgia |
| EP0388306A2 (en) * | 1989-03-17 | 1990-09-19 | Hind Health Care, Inc. | Method for treating pain associated with herpes-zoster and post-herpetic neuralgia by topical application of local anesthetics |
| US5589180A (en) * | 1989-03-17 | 1996-12-31 | Hind Health Care, Inc. | Method for treating nerve injury pain associated with shingles (herpes-zoster and post-herpetic neuralgia) by topical application of lidocaine |
| GB2258397A (en) * | 1991-01-30 | 1993-02-10 | Smith & Nephew | Pharmaceutical compositions containing amethocaine |
| GB2258397B (en) * | 1991-01-30 | 1994-11-09 | Smith & Nephew | Pharmaceutical compositions containing amethocaine |
| US5580901A (en) * | 1991-01-30 | 1996-12-03 | T. J. Smith & Newphew Limited | Pharmaceutical compositions of amethocaine free base |
| WO1992013533A1 (en) * | 1991-01-30 | 1992-08-20 | Smith & Nephew Plc | Pharmaceutical compositions containing amethocaine |
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| GB2269099B (en) * | 1991-03-21 | 1994-09-14 | Smith & Nephew | Percutaneous amethocaine delivery device |
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| GB2269099A (en) * | 1991-03-21 | 1994-02-02 | Smith & Nephew | Percutaneous anaesthesia |
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| US6245347B1 (en) | 1995-07-28 | 2001-06-12 | Zars, Inc. | Methods and apparatus for improved administration of pharmaceutically active compounds |
| US6306431B1 (en) | 1995-07-28 | 2001-10-23 | Zars, Inc. | Apparatus for heating to a desired temperature for improved administration of pharmaceutically active compounds |
| US6340472B1 (en) | 1995-07-28 | 2002-01-22 | Zars, Inc. | Method for reducing onset time of pharmaceutically active compounds |
| US5919479A (en) * | 1995-07-28 | 1999-07-06 | Zars, Inc. | Noninvasive dermal anesthetics |
| US5658583A (en) * | 1995-07-28 | 1997-08-19 | Zhang; Jie | Apparatus and methods for improved noninvasive dermal administration of pharmaceuticals |
| US6613350B1 (en) | 1995-07-28 | 2003-09-02 | Zars, Inc. | Electrical apparatus for heating to a desired temperature for improved administration of pharmaceutically active compounds |
| US6465006B1 (en) | 1995-07-28 | 2002-10-15 | Zars, Inc. | Method for facilitating absorption of pharmaceutically active compounds |
| US6546281B1 (en) | 1995-07-28 | 2003-04-08 | Zars, Inc. | Integrated apparatus for controlled heat aided dermal drug delivery |
| US6955819B2 (en) | 1998-09-29 | 2005-10-18 | Zars, Inc. | Methods and apparatus for using controlled heat to regulate transdermal and controlled release delivery of fentanyl, other analgesics, and other medical substances |
| US6453648B1 (en) | 1999-07-06 | 2002-09-24 | Zars, Inc. | Method for manufacturing a heat generating apparatus |
| US6488959B2 (en) | 2000-02-29 | 2002-12-03 | Zars, Inc. | Transdermal drug patch with attached pocket for controlled heating device |
| US6261595B1 (en) | 2000-02-29 | 2001-07-17 | Zars, Inc. | Transdermal drug patch with attached pocket for controlled heating device |
| US9522122B2 (en) | 2002-08-30 | 2016-12-20 | Alza Corporation | Multilaminate backing construction |
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| US9012477B2 (en) | 2009-01-06 | 2015-04-21 | Nuvo Research Inc. | Method of treating neuropathic pain |
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| US9186334B2 (en) | 2009-05-04 | 2015-11-17 | Nuvo Research Inc. | Heat assisted lidocaine and tetracaine for transdermal analgesia |
| US9693976B2 (en) | 2010-01-14 | 2017-07-04 | Crescita Therapeutics Inc. | Solid-forming local anesthetic formulations for pain control |
| US10350180B2 (en) | 2010-01-14 | 2019-07-16 | Crescita Therapeutics Inc. | Solid-forming local anesthetic formulations for pain control |
| US10603293B2 (en) | 2010-01-14 | 2020-03-31 | Crescita Therapeutics Inc. | Solid-forming local anesthetic formulations for pain control |
| US10751305B2 (en) | 2010-01-14 | 2020-08-25 | Crescita Therapeutics Inc. | Solid-forming topical formulations for pain control |
Also Published As
| Publication number | Publication date |
|---|---|
| AU1794688A (en) | 1988-12-21 |
| ZA883825B (en) | 1989-03-29 |
| GB8712518D0 (en) | 1987-07-01 |
| GB2206044A (en) | 1988-12-29 |
| GB8812517D0 (en) | 1988-06-29 |
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