CA2222676C - New pharmaceutical composition with anaesthetic effect - Google Patents

New pharmaceutical composition with anaesthetic effect Download PDF

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Publication number
CA2222676C
CA2222676C CA002222676A CA2222676A CA2222676C CA 2222676 C CA2222676 C CA 2222676C CA 002222676 A CA002222676 A CA 002222676A CA 2222676 A CA2222676 A CA 2222676A CA 2222676 C CA2222676 C CA 2222676C
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Prior art keywords
pharmaceutical composition
composition according
surfactant
weight
local anaesthetics
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CA002222676A
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French (fr)
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CA2222676A1 (en
Inventor
Arne Brodin
Lars Heijl
Adela Nyqvist-Mayer
Marie Scherlund
Raymond Fynes
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Maillefer Instruments Trading SARL
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Maillefer Instruments Trading SARL
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/06Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44Oils, 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/13Amines
    • A61K31/135Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/138Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/16Amides, e.g. hydroxamic acids
    • A61K31/165Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183Amino acids, e.g. glycine, EDTA or aspartame
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P23/00Anaesthetics
    • A61P23/02Local anaesthetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/02Drugs for disorders of the nervous system for peripheral neuropathies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0053Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays

Abstract

The invention is directed to a novel pharmaceutical composition comprising o ne or more local anaesthetics in oil form, one or more surfactants, water and optionally a taste masking agent. The novel compositi on is advantageously used as a local anaesthetic for pain relief within the oral cavity.

Description

WO 97/38675 PCT/SE97/00566 _ NEW PHARMACEUTICAL COMPOSITION WITH ANAESTHETIC EFFECT

The field of the invention The present invention is directed to a new pharmaceutical composition and its use in therapy, particularly as an anaesthetic for use on mucous membranes and particularly within the oral cavity.

io Background and prior art It is estimated that approximately 10-13 % of the population suffers from periodontal diseases with pathological periodontal pockets. In order to eliminate or control the disease and arrest further periodontal tissue destruction, periodontal pockets need repeated subgingival mechanical debridement/cleansing. The number of periodontal pockets in a patient may vary as can the pocket depth measurement. Approximately 40 % of all periodontal scaling procedures performed involve some kind of anaesthesia.

Accumulation of bacterial plaque on teeth and in the gingival sulcus elicits an inflammatory response in the marginal gingiva which may spread in an apical direction and result in loss of tooth support with the formation of periodontal pockets. The object of mechanical debridement of periodontal pockets is to control and arrest further destruction of tooth support by removal of plaque and calculus from within the pockets.

The majority of the scaling procedures are performed by hygienists. The main use of anaesthesia techniques used in conjunction with periodontal scaling is either a nerve block or infiltration. Infiltration anaesthesia is either carried out alone or in combination with topical anaesthesia, mainly jelly, ointment or spray. However, the problem with existing topical products are lack of efficacy due to inadequate depth of penetration, too short duration and difficulties in administration due to spread, taste etc.

WO 97/38675 PCT/SE97/00566 _ EP 244 118 discloses a controlled release drug delivery system for placement in the periodontal pocket, having a plurality of discrete microparticles consisting of a rate-controlling polymer matrix having a drug dispersed therein, said microparticles being in the range of 10-500 m. EP 241 178 also discloses a controlled release drug delivery system s for placement in the periodontal pocket, which composition comprises solid particles having an average size of 1-500 m. However, the drug delivery systems disclosed in both these prior art patents are deviced for administration of a medicament for a longer period of time.
Thus the drug delivery systems of EP 244 118 and EP 241 178 are not suitable for use in pain management in conjunction with minor surgical procedures, where a fast onset of ia action and relatively short duration is required.

Thus, the problem underlying the present invention is to provide a pharmaceutical composition which would provide effective pain relief in conjunction with periodontal scaling and root planing following local administration. In other words, the object of the Is invention is to provide a local anaesthetic that can be applied in a facile manner in the oral cavity, and more precisely within periodontal pockets. A further object of the invention is to provide a pharmaceutical composition having a short onset time and an adequate duration for the intended procedure, with no inconvenient anaesthesia.
Outline of the invention The problem identified above has now been solved by providing a new pharmaceutical composition which preferably is in form of an emulsion, more preferably in form of a microemulsion, comprising the following ingredients:

(i) one or more local anaesthetics in oil form in the final composition;

(ii) one or more surfactants, together present in an amount effective to produce a homogenous formulation; and (iii) water up to 100% by weight, based on the total weight of the composition.

According to one aspect of the present invention, there is provided a pharmaceutical composition comprising (i) one or more surfactants, together present in an amount effective to produce a homogenous formulation, wherein, if more than one surfactant is present in the composition, at least one of the surfactants has thermoreversible gelling properties, and if only one surfactant is present in the composition, the surfactant acts as a thickening agent with thermoreversible gelling properties, as a solubilizer and as an emulsifier; (ii) one or more local anaesthetics in oil form in the final composition; and (iii) water up to 100% by weight, based on the total weight of the composition;
wherein the pharmaceutical composition is in the form of an emulsion or microemulsion.

The local anaesthetic in the final composition is one or more local anaesthetics in oil form as such, or a eutectic mixture formed by two or more local anaesthetics.

3a The amount of the local anaesthetic in the oil phase depends on the pH-value of the formulation.

In a particularly preferred embodiment of the invention the local anaesthetic is a eutectic mixture of lidocaine base and prilocaine base.

In a further embodiment of the invention a eutectic mixture may also be formed by two or more substances, where at least one of these substances is a local anaesthetic.

The amount of the local anaesthetic or mixture of local anaesthetics is preferably in the range 0.5 - 20% by weight, more preferably in the range 2-7% by weight, based on the total weight of the composition.

The local anaesthetic(s) in the final composition are present in a non-solid form.
By the wording "surfactant" we mean any agent that acts as a solubilizer and/or as an emulsifier and/or as a thickening agent with thermoreversible gelling properties. The wording surfactant is also intended to include thickening agents without thermoreversible properties. If only one surfactant is used in the composition, it must be selected with care and in suitable amounts so that it acts both as a solubilizer and/or as an emulsifier, as well as a thickening agent with thermoreversible gelling properties. If more than one surfactant is present in the composition, at least one of the surfactants should have thermoreversible gelling properties. The total amount of the surfactant(s) should be present in an amount effective to produce a homogenous formulation.
The surfactants are preferably selected from non-ionic surfactants, more preferably from any non-ionic poloxamer known in the art.

Poloxamers are synthetic block copolymers of hydrophilic ethylene oxide chains and hydrophobic propylene oxide chains, having the general formula HO-[C2H4O]a-jC3H6O]5-[C2H4Oja-H, a and b representing the number of the hydrophilic and hydrophobic chains respectively.

By choosing the surfactant(s) having hydrophobic and hydrophilic domains in appropriate amounts, in combination with an appropriate amount of the local anaesthetic or mixture of local anaesthetics, it is possible to achieve a composition having suitable thermoreversible gelling properties, i.e. the system remains less viscous at room temperature, and upon application into a periodontal pocket the viscosity of the composition is increased. In other words, the pharmaceutical composition according to the present invention is less viscous at room temperature. Above this temperature the composition is more viscous, providing the advantage of remaining in the periodontal pockets for the time necessary to induce local anaesthesia. The change in viscosity is reversible with temperature.
5 PCT/SE97/00566 _ In a particularly preferred embodiment of the invention the surfactant is one or more of Lutrol F68~ , which also has the name poloxamer 188 and wherein a= 80 and b=27, and Lutrol F127 , which also has the name poloxamer 407 and wherein a=101 and b=56, the 5 definitions being in accordance with USP (1995) NF18, p. 2279. Lutrol F68 and Lutrol F127(D are commercially available from BASF.

In a further preferred embodiment of the invention the surfactant Arlatone 289 is used, which also has the name polyoxyethylene hydrogenated castor oil, as well as Adinol CT95 which is sodium N-methyl N-cocoyl taurate.

The total amount of surfactant(s) is preferably present in an amount of up to 50 % by weight, based on the total weight of the composition.

The pH-value of the pharmaceutical composition is adjusted with suitable acid or base in such a way that the final pH-value for the composition is:

(A) pH ?[pKa (local anaesthetic) - 1.0] if the composition comprises one local anaesthetic;
or (B) pH ?[pKa (local anaesthetic with the lowest pKa value) - 1.0] if the composition comprises two or more local anaesthetics.

Preferably the pH is over 7.5.

Since local anaesthetics by nature have an unpleasant bitter taste, one or more taste masking agents may optionally be added to the pharmaceutical composition. The choice of taste masking agents will be appreciated by a person skilled in the art, but as an example any fruit flavours may be mentioned.
By topical application within the periodontal pocket, local anaesthesia is achieved in a very localised area, without causing the often extensive soft tissues such as the tongue, cheek and lips, to get anaesthetized which is often the case with infiltration anaesthesia. Preferably the composition is applied into a periodontal pocket by means of a blunt needle, thereby facilitating the administration of the anaesthetic and giving an increased patient comfort.
The pharmaceutical composition of the present invention has a fast onset of action being from seconds and up to approximately 5-15 minutes. The onset time is most preferably io from seconds and up to approximately 5 minutes.

For the definition of emulsions, we refer to Pharmaceutics, The Science of Dosage Form Design, 1988, p. 109-110, by ME Aulton.

is The pharmaceutical composition according to the present invention is preferably a microemulsion. By microemulsion we mean a formulation that consists of water, oil and amphiphile(s) which constitute a single optically isotropic and thermodynamically stable liquid solution (I. Danielsson and B Lindnzan, Colloids Surf. 3:391, (1981)).
This provides a suitable amount of the local anaesthetic in the oil phase, which in turn 20 confers a fast onset of action. No separate oil needs to be added to the composition, since the oil is already present by the active component(s) as such. A further advantage is that a thermodynamically stable composition is achieved in a temperature range of 5-40 C.

The pharmaceutical composition according to the present invention may advantageously 25 also be used as a local anaesthetic on other surfaces and/or cavities than in the oral cavity.
The composition may thus also be used vaginally, genitally and rectally.

The local anaesthetic(s) used for preparing a pharmaceutical composition according to the =
present invention may be selected from any local anaesthetic. Preferably the local 30 anaesthetic as the starting material is in a non-ionized form.

WO 97/38675 PCT/SE97/00566 _ In the final composition a fraction of the local anaesthetic or mixture of local anaesthetics are present in oil form. The size of this fraction, local anaesthetics in oil form, depends on the pH of the composition.

The best mode of performing the invention known at present, is to use the composition according to Example 1.

Methods of preparation The pharmaceutical composition according to the present invention may be prepared by the following steps:

(i) the local anaesthetic(s) and the surfactant with the lowest molecular weight if more than is one surfactant is used, are melted together;

(ii) a part of the water is slowly added to the melt (i) during homogenization, forming an emulsion concentrate;

(iii) if more than one surfactant is used, the surfactant with the higher molecular weight is dispersed in water;

(iv) the emulsion concentrate of step (ii) and part of the surfactant solution of step (iii) are thoroughly mixed;
(v) the pH-value is adjusted by the addition of a suitable acid or base;

(vi) the weight is adjusted with water to the final weight of the composition.

The composition is preferably kept at 5 C until a homogenous composition is obtained.

WO 97/38675 PCT/SE97/00566 _ Detailed description of the invention The invention will now be described in more detail by the following examples, which are not to be construed as limiting the invention.

Example 1 [% bv weiehtl Lidocaine 2.50 Prilocaine 2.50 io Lutrol F68 5.50 Lutrol F127 15.50 purified water up to a total weight of 100 %.

The composition was prepared by following the procedure described above, and the pH-is value was adjusted by adding 2 M hydrochloric acid.

Exam.~~le 2 j% by weightj Lidocaine 2.50 Prilocaine 2.50 20 Lutrol F68 5.00 Lutrol F127 16.25 purified water up to a total weight of 100 %.

The composition was prepared by following the procedure described above, and the pH-25 value was adjusted by adding 2 M hydrochloric acid.

WO 97/38675 PCT/SE97/00566 _ Example 3 _ [% by weight]
Lidocaine 2.25 Prilocaine 2.25 Lutrol F68 3.5 Lutrol F127 14.0 purified water up to a total weight of 100 %.

The composition was prepared by following the procedure described above, and the pH-value was adjusted by adding 2 M hydrochloric acid.

Example 4 [% by weightl Lidocaine 2.25 Prilocaine 2.25 is Arlatone 289 1.90 Adinol CT95 0.07 Lutrol F127 14.00 purified water up to a total weight of 100 %.

The composition was prepared by following the procedure described above, and the pH-value was adjusted by adding 2 M hydrochloric acid.

WO 97/38675 PCT/SE97/00566 _ Example 5 [% by weigghtT
Lidocaine 2.25 Prilocaine 2.25 5 Arlatone 289 1.90 Adinol CT95 0.16 Lutrol F 127 14.00 purified water up to a total weight of 100 %.

io The composition was prepared by following the procedure described above, and the pH-value was adjusted by adding 2 M hydrochloric acid.

Example 6 [% by weilzhtl Lidocaine 2.25 Prilocaine 2.25 Arlatone 289 1.90 Adinol CT95 0.28 Lutrol F 127 14.00 purified water up to a total weight of 100 %.

The composition was prepared by following the procedure described above, and the pH-value was adjusted by adding 2 M hydrochloric acid.

Examnle 7 and 8 In Examples 7 and 8, a local anaesthetic of the formula (1) was used as the active ingredient.

O N
s This compound is disclosed in the Interaational Patent Publication No. WO
97/15548.
The following pharmaceutical compositions were prepared.
Exa=le 7 f 9b by we iahtl Compound (I) 2.5 Lutrol F127 17.0 Lutrol F68 5.5 Is purified water up to a total weight of 100 96.

The composition was prepared by following the procedure described above, and the pH-value was adjusted by adding 2 M hydrochloric acid.

Example 8 [% by weiehtl Compound (I) 2.5 Lutrol F127 20.0 Lutrol F68 5.5 purified water up to a total weight of 100 %.

The composition was prepared by following the procedure described above, and the pH-value was adjusted by adding 2 M hydrochloric acid.

Biolog,ical studies A pharmaceutical composition according to Example 1 was applied to a human periodontal io pocket with a blunt end needle. After an onset time of 30 - 45 seconds, a satisfactory anaesthetic effect had been achieved in order that periodontal scaling could be performed.
The scaling was initiated, and the time taken to scale the toth was noted. At the end of the scaling, the intensity of pain was measured by means of a visual analogue scale (VAS). The duration of the anaesthetic effect was 10-20 minutes.
i5

Claims (18)

CLAIMS:
1. A pharmaceutical composition comprising (i) one or more surfactants, together present in an amount effective to produce a homogenous formulation, wherein, if more than one surfactant is present in the composition, at least one of the surfactants has thermoreversible gelling properties, and if only one surfactant is present in the composition, the surfactant acts as a thickening agent with thermoreversible gelling properties, as a solubilizer and as an emulsifier;

(ii) one or more local anaesthetics in oil form in the final composition; and (iii) water up to 100% by weight, based on the total weight of the composition; wherein the pharmaceutical composition is in the form of an emulsion or a microemulsion.
2. A pharmaceutical composition according to claim 1, further comprising one or more taste masking agents.
3. A pharmaceutical composition according to claim 1 or 2, wherein the one or more local anaesthetics are present in an amount of 0.5 - 20% by weight based on the total weight of the composition.
4. A pharmaceutical composition according to claim 3, wherein the one or more local anaesthetics are present in an amount of 2-7% by weight based on the total weight of the composition.
5. A pharmaceutical composition according to any one of claims 1 to 4, wherein the one or more local anaesthetics is a eutectic mixture of local anaesthetics.
6. A pharmaceutical composition according to claim 5, wherein the one or more local anaesthetics is a eutectic mixture of lidocaine and prilocaine.
7. A pharmaceutical composition according to claim 1, wherein the one or more local anaesthetics is
8. A pharmaceutical composition according to any one of claims 1 to 7, wherein the total amount of the one or more surfactants is up to 50% by weight based on the total weight of the composition.
9. A pharmaceutical composition according to any one of claims 1 to 8, wherein the one or more surfactants comprise a non-ionic surfactant.
10. A pharmaceutical composition according to claim 9, wherein the non-ionic surfactant is a poloxamer.
11. A pharmaceutical composition according to any one of claims 1 to 10, wherein the one or more surfactants comprise Lutrol F68® and Lutrol F127®.
12. A pharmaceutical composition according to any one of claims 1 to 11 for locally anaesthetising mucosa of the oral cavity.
13. Use of components (i), (ii) and (iii), as defined in any one of claims 1 and 3 to 11 in manufacture of a pharmaceutical composition for locally anaesthetising mucosa of the oral cavity.
14. Use of a pharmaceutical composition according to any one of claims 1 to 11 for locally anaesthetising mucosa of the oral cavity.
15. A pharmaceutical composition according to any one of claims 1 to 11 for pain relief during periodontal scaling.
16. Use of components (i), (ii) and (iii), as defined in any one of claims 1 and 3 to 11, in manufacture of a medicament for pain relief during periodontal scaling.
17. A use of a pharmaceutical composition according to any one of claims 1 to 11 for pain relief during periodontal scaling, in a patient in need thereof.
18. A process for the manufacture of a pharmaceutical composition according to claim 1, whereby (i) the one or more local anaesthetics and the surfactant with the lowest molecular weight, if more than one surfactant is used, are melted together;

(ii) a part of the water is slowly added to the melt (i) during homogenization, forming an emulsion concentrate;

(iii) if more than one surfactant is used, the surfactant with the higher molecular weight is dispersed in water;

(iv) the emulsion concentrate of step (ii) and part of the surfactant solution of step (iii) are thoroughly mixed;

(v) the pH-value is adjusted by the addition of a suitable acid or base;

(vi) the weight is adjusted with water to the final weight of the composition.
CA002222676A 1996-04-12 1997-04-01 New pharmaceutical composition with anaesthetic effect Expired - Lifetime CA2222676C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
SE9601421A SE9601421D0 (en) 1996-04-12 1996-04-12 New composition
SE9601421-2 1996-04-12
PCT/SE1997/000566 WO1997038675A1 (en) 1996-04-12 1997-04-01 New pharmaceutical composition with anaesthetic effect

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Publication Number Publication Date
CA2222676A1 CA2222676A1 (en) 1997-10-23
CA2222676C true CA2222676C (en) 2008-01-22

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US (1) US6031007A (en)
EP (1) EP0833612B1 (en)
JP (2) JPH11501678A (en)
KR (1) KR100508601B1 (en)
CN (1) CN1149072C (en)
AR (1) AR006484A1 (en)
AT (1) ATE248584T1 (en)
AU (1) AU716540B2 (en)
BR (1) BR9702147A (en)
CA (1) CA2222676C (en)
CZ (1) CZ371197A3 (en)
DE (1) DE69724545T2 (en)
DK (1) DK0833612T3 (en)
EE (1) EE9700363A (en)
ES (1) ES2203799T3 (en)
HK (1) HK1010144A1 (en)
HU (1) HUP9903544A3 (en)
ID (1) ID16420A (en)
IL (1) IL122447A (en)
IS (1) IS4618A (en)
NO (1) NO318239B1 (en)
NZ (1) NZ329246A (en)
PL (1) PL324170A1 (en)
RU (1) RU2185153C2 (en)
SE (1) SE9601421D0 (en)
SK (1) SK169897A3 (en)
TR (1) TR199701584T1 (en)
TW (1) TW473386B (en)
WO (1) WO1997038675A1 (en)
ZA (1) ZA973022B (en)

Families Citing this family (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2764800B1 (en) * 1997-06-23 1999-09-10 Sanofi Sa SOLID PHARMACEUTICAL COMPOSITION CONTAINING BENZOFURAN DERIVATIVES
US7799337B2 (en) 1997-07-21 2010-09-21 Levin Bruce H Method for directed intranasal administration of a composition
KR100777647B1 (en) * 1998-08-19 2007-11-19 스키에파마 캐나다 인코포레이티드 Injectable Aqueous Dispersions of Propofol
US6528086B2 (en) * 1999-09-28 2003-03-04 Zars, Inc. Methods and apparatus for drug delivery involving phase changing formulations
US20020013331A1 (en) * 2000-06-26 2002-01-31 Williams Robert O. Methods and compositions for treating pain of the mucous membrane
KR100416646B1 (en) * 2000-08-14 2004-02-05 구주제약주식회사 Hydrogel Preparation of Lidocaine Microemulsion for the Treatment of Premature Ejaculation
GB0120701D0 (en) 2001-08-24 2001-10-17 Maelor Pharmaceuticals Ltd Pharmaceutical formulations
US20040087520A1 (en) * 2002-10-25 2004-05-06 Chowdhury Dipak K. Compositions and methods for delivery of therapeutic agents
TW200410717A (en) * 2002-12-31 2004-07-01 Ind Tech Res Inst Delivery system for control release of temperature sensitive bioactive material
US8802116B2 (en) 2003-02-27 2014-08-12 Novasel Australia Pty. Ltd. Poloxamer emulsion preparations
AU2003900887A0 (en) * 2003-02-27 2003-03-13 Novasel Australia Pty Ltd Poloxamer emulsion preparations
BR0301968A (en) * 2003-05-22 2005-06-28 Cristalia Prod Quimicos Farm Ternary and quaternary eutectic mixtures composed of local anesthetic substances, their use in the preparation of pharmaceutical compositions and their use in anesthesia and topical analgesia
JP4669960B2 (en) * 2003-06-03 2011-04-13 株式会社 メドレックス Oral or pharyngeal preparations containing local anesthetics
US20050123596A1 (en) * 2003-09-23 2005-06-09 Kohane Daniel S. pH-triggered microparticles
US7943179B2 (en) * 2003-09-23 2011-05-17 Massachusetts Institute Of Technology pH triggerable polymeric particles
US20070232695A1 (en) * 2004-01-28 2007-10-04 Collegium Pharmaceutical, Inc. Gelled Periodontal Anesthetic Preparation
US8741332B2 (en) 2004-06-07 2014-06-03 Nuvo Research Inc. Compositions and methods for dermally treating neuropathic pain
US8907153B2 (en) 2004-06-07 2014-12-09 Nuvo Research Inc. Adhesive peel-forming formulations for dermal delivery of drugs and methods of using the same
US8741333B2 (en) 2004-06-07 2014-06-03 Nuvo Research Inc. Compositions and methods for treating dermatitis or psoriasis
US20060079558A1 (en) * 2004-09-27 2006-04-13 Bridge Pharma. Inc. R-isomer of 2-{2[N-(2-indanyl)-N-phenylamino]ethyl}piperidine and other dermal anesthetics
US7718674B2 (en) * 2004-09-27 2010-05-18 Bridge Pharma, Inc. Methods of relieving neuropathic pain with the S-isomer of 2-{2[N-(2-indanyl)-N-phenylamino]ethyl}piperidine
CA2655809C (en) * 2006-07-21 2013-10-01 Bridge Pharma, Inc. Dermal anesthetic compounds
US20090123527A1 (en) * 2006-07-24 2009-05-14 Akorn, Inc. Method of inducing topical anesthesia and transdermal patch
US20080021068A1 (en) * 2006-07-24 2008-01-24 Akorn, Inc. Aqueous gel formulation and method for inducing topical anesthesia
US8473062B2 (en) 2008-05-01 2013-06-25 Autonomic Technologies, Inc. Method and device for the treatment of headache
US8412336B2 (en) 2008-12-29 2013-04-02 Autonomic Technologies, Inc. Integrated delivery and visualization tool for a neuromodulation system
US9012477B2 (en) 2009-01-06 2015-04-21 Nuvo Research Inc. Method of treating neuropathic pain
US9320908B2 (en) 2009-01-15 2016-04-26 Autonomic Technologies, Inc. Approval per use implanted neurostimulator
US8494641B2 (en) 2009-04-22 2013-07-23 Autonomic Technologies, Inc. Implantable neurostimulator with integral hermetic electronic enclosure, circuit substrate, monolithic feed-through, lead assembly and anchoring mechanism
EP2421496A4 (en) * 2009-04-22 2014-01-15 Agency Science Tech & Res Emulsions for transdermal delivery
WO2011074015A2 (en) 2009-12-17 2011-06-23 Themis Medicare Limited Novel composition of pharmaceutical product to treat sexual dysfunction
AU2011205730C1 (en) 2010-01-14 2014-10-09 Nuvo Research Inc. Solid-forming local anesthetic formulations for pain control
MY163215A (en) 2010-04-01 2017-08-30 Pharmanest Ab Thermogelling anaesthetic compositions
SG184072A1 (en) * 2010-04-01 2012-10-30 Pharmanest Ab Bioadhesive compositions of local anaesthetics
WO2011121034A2 (en) 2010-04-01 2011-10-06 Pharmanest Ab Water-free pharmaceutical compositions suitable for local anaesthetics
AU2010351562B2 (en) * 2010-04-21 2013-10-10 Teikoku Pharma Usa, Inc. Local anesthetic emulsion compositions and methods of making and using the same
GB201222455D0 (en) * 2012-12-13 2013-01-30 Perioc Ltd Novel pharmaceutical formulations and their use in the treatment of periodontaldisease
EP2968247A4 (en) * 2013-03-14 2017-04-26 Jsn I Llc Taste masking of anesthetics and analgesics
WO2017039559A1 (en) 2015-09-02 2017-03-09 T.C. Istanbul Medipol Universitesi Formulations of benzocaine loaded microemulsion based hydrogels for therapeutic purposes and their production method
WO2020182535A1 (en) 2019-03-08 2020-09-17 Bayer Oy Uterine sound tube with anaesthetic applicator
CN113244167B (en) * 2021-05-20 2022-11-29 河北科技大学 Lidocaine hydrochloride gel and preparation method thereof

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4188373A (en) * 1976-02-26 1980-02-12 Cooper Laboratories, Inc. Clear, water-miscible, liquid pharmaceutical vehicles and compositions which gel at body temperature for drug delivery to mucous membranes
US4478822A (en) * 1983-05-16 1984-10-23 Merck & Co., Inc. Drug delivery system utilizing thermosetting gels
US5288498A (en) * 1985-05-01 1994-02-22 University Of Utah Research Foundation Compositions of oral nondissolvable matrixes for transmucosal administration of medicaments
US5288497A (en) * 1985-05-01 1994-02-22 The University Of Utah Compositions of oral dissolvable medicaments
JPS62223112A (en) * 1986-03-25 1987-10-01 Rooto Seiyaku Kk Remedy for periodontosis
US4780320A (en) * 1986-04-29 1988-10-25 Pharmetrix Corp. Controlled release drug delivery system for the periodontal pocket
US5114719A (en) * 1987-04-29 1992-05-19 Sabel Bernhard A Extended drug delivery of small, water-soluble molecules
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
US5292516A (en) * 1990-05-01 1994-03-08 Mediventures, Inc. Body cavity drug delivery with thermoreversible gels containing polyoxyalkylene copolymers
CA2040460C (en) * 1990-05-01 1997-06-10 Tacey X. Viegas Drug delivery with thermoreversible gels
FR2704429B3 (en) * 1993-04-30 1995-07-13 Algovital Sarl Formulation combining an alkaline reaction and essential oil components to perform local anesthesia, externally, transcutaneously, without injection.
US5635540A (en) * 1994-12-09 1997-06-03 The University Of Virginia Patent Foundation Stabilized topical pharmaceutical preparations
US5612052A (en) * 1995-04-13 1997-03-18 Poly-Med, Inc. Hydrogel-forming, self-solvating absorbable polyester copolymers, and methods for use thereof

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