WO2004054518A1 - Temporary, pharmacologically-inactive dental coating for the in situ protection of dental therapeutic agents from saliva and abrasion from chewing - Google Patents
Temporary, pharmacologically-inactive dental coating for the in situ protection of dental therapeutic agents from saliva and abrasion from chewing Download PDFInfo
- Publication number
- WO2004054518A1 WO2004054518A1 PCT/CA2003/001943 CA0301943W WO2004054518A1 WO 2004054518 A1 WO2004054518 A1 WO 2004054518A1 CA 0301943 W CA0301943 W CA 0301943W WO 2004054518 A1 WO2004054518 A1 WO 2004054518A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- pharmacologically
- formulation
- coating
- polymethylmethacrylate
- plasticizer
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K6/00—Preparations for dentistry
- A61K6/60—Preparations for dentistry comprising organic or organo-metallic additives
- A61K6/69—Medicaments
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K6/00—Preparations for dentistry
- A61K6/20—Protective coatings for natural or artificial teeth, e.g. sealings, dye coatings or varnish
Definitions
- the invention relates to a composition of a pharmacologically-inactive coating that acts as a temporary mechanical barrier to protect an underlying layer containing pharmacologically-active agents, such as dental therapeutic agents, residing on a tooth surface, against erosion from salivary washings and abrasion from eating foods, and methods of use thereof.
- pharmacologically-inactive coating that acts as a temporary mechanical barrier to protect an underlying layer containing pharmacologically-active agents, such as dental therapeutic agents, residing on a tooth surface, against erosion from salivary washings and abrasion from eating foods, and methods of use thereof.
- Dental caries is a chronic, asymptomatic, transmittable bacterial infection on the surface of the teeth, which affects about 20% of the population. It is the most prevalent chronic disease in adults affecting about one in three adults over the age of 50, and is also the most common pediatric disease.
- the dental research literature and common dental practice support the use of two common dental therapeutic compounds to combat dental caries, namely: the antimicrobial compound chlorhexidine, and the remineralizing compound fluoride. Both compounds may be administered separately in varnish modalities of varying concentrations by the dental professional to the teeth of patients in the dental office. Varnishes containing these therapeutic agents have the benefit" of delivering the agent to the site of caries at relatively high concentrations compared to oral rinses or gels, of delivering these agents for reportedly long periods of time in the oral cavity, and ensuring patient compliance.
- chlorhexidine varnishes are an accepted standard of preventive dental care.
- chlorhexidine-containing varnishes include those sold under the trademarks PREVORA (10% (w/v) chlorhexidine) by CHX Technologies,
- Banting, et al. reported significant reductions of caries in a controlled clinical study of high-risk adult patients using a two-stage chlorhexidine varnish (see, D.
- EUDRAGIT brand polymers have also been used as excipients in sustained release dosage forms and to form transdermal drug delivery systems.
- composition and Method of Use describes an oral composition for plaque prevention and tooth hypersensitivity consisting of an antibacterial agent embedded in a carrier such as an acrylic polymer, and preferably an EUDRAGIT acrylic, and the use of this composition to prevent caries.
- Diarra, et al. describe a 200 mg tablet consisting of a granular matrix of hydroxyapatite, ethyl cellulose and EUDRAGIT polymers, along with an active drug substance, which is then fixed on to the tooth for sustained release of the pharmacologically active substance; see, M. Diarra, et al. , "Elaboration and Evaluation of an Intraoral Controlled Release Delivery System," Biomaterials, Vol. 19, pp. 1523- 1527 (1998).
- Patel, et al. describe a rigid polymeric device consisting of polyethyl methacrylate and tetrahydrofurfuryl plus chlorhexidine for the reduction of fungus in the oral cavity; the device was tested in vitro for its reduction of Candida albicans. See M. Patel, et al. , "A polymeric system for the intra-oral delivery of an anti-fungal agent," Biomaterials, Vol. 22, pp. 2319-2324 (2001).
- PMMA has been used widely in the oral cavity as evident from its approval for use in the U.S. Code of Federal Regulations (CFR) Chapter 21, and in particular Section 872.3820 for root canal filling resins, Section 872.3770 for crown and bridge resins, Section 872.3760 for denture relining, repairing and rebasing resin, Section 872.3750 for bracket adhesive resin and tooth conditioner, and Section 827.3765 for pit and fissure sealant and conditioner. In all these uses, however, PMMA is applied on permanent basis and/or as part of an oral device of rigid structure.
- CFR Code of Federal Regulations
- Triethyl citrate is also an approved plasticizer in the U.S. Code of Federal Regulations Chapter 21, Section 181.27.
- a formulation for a pharmacologically-inactive, inert polymer coating comprising a PMMA-type polymer and a plasticizer is provided as a liquid that can be applied as a film to the surface of a tooth in the oral cavity of a dental patient.
- the inert polymer coating when placed on top of a temporary coating of a pharmacologically-active substance applied to a surface of the tooth, functions as a temporary mechanical barrier to delay erosion of the active substance due to salivary washing and abrasion from the eating of food, and thereby enhances retention of the pharmacologically-active agents that have been applied as a coating to tooth surfaces.
- pharmacologically-active agents include, without limitation, the antimicrobial compound chlorhexidine, and the remineralizing compound fluoride, both of which are known to be effective in the treatment and prevention of dental caries.
- Clorhexidine for example, has a bitter taste, and the provision of an inert mechanical barrier layer helps to improve the acceptance of these therapeutic agents by the patient and, hence, the patient's compliance to treatment. Thus, higher concentrations of therapeutic agents can be administered to the patient over a longer period of time.
- the formulation is intended for as an oral composition, it should have acceptable taste, clarity, color, durability and application characteristics for the dental professional, as well as biocompatibility to permit its use on patients ' teeth as a separate temporary protective coating for dental therapeutic compounds.
- an aqueous dispersion of a polymethylmethacrylate copolymer includes a sufficient amount of a plasticizer to form a film in situ when applied to a tooth surface that has appropriate flexibility and that dries quickly in the oral cavity.
- a plasticizer to form a film in situ when applied to a tooth surface that has appropriate flexibility and that dries quickly in the oral cavity.
- Polymethylmethacrylate copolymers suitable for the practice of the invention, are commercially available, such as the copolymers of methacrylic acid and methacrylate marketed by Rohm GmbH, Darmstadt, Germany as the EUDRAGIT brand family of polymethylmethacrylates.
- the polymethylmethacrylate is an ammonio methacrylate copolymer type B USP/NF, such as EUDRAGIT RS 30 D brand polymethylmethacrylate.
- EUDRAGIT RS 30 D conforms to the specifications of an ammonio methacrylate copolymer, Type B in the U.S. Pharmacopeia and the U.S. National Formulary.
- EUDRAGIT RS 30D which is an aqueous dispersion of acrylic polymer, has been used according to the manufacturer's directions of use and industry standards, as an approved pharmaceutical and cosmetic excipient in oral and dermal applications for drug delivery in solid dosage forms in the gastrointestinal tract or on the skin for many years.
- Suitable plasticizers for the PMMA include pharmaceutical grade triethyl citrate, dibutyl sebacate, dibutyl phthalate, and diethyl phthalate, and the like. Triethyl citrate, however, is particularly preferred. Preferred concentrations of plasticizer range from between 1 % w/w and 20% w/w. In the formulation process, the plasticizer is preferably added to the aqueous dispersion of PMMA over a period of between 10 and 30 minutes.
- the liquid formulation of the present invention preferably, has a viscosity of between 5 cP and 30 cP, and is preferably between 5 cP and 20 cP, and a specific gravity of 1.054 g/ml plus or minus 0.050 g/ml.
- the formulation comprises a liquid dispersion (w/w) of:
- the formulation comprises (w/w):
- a formulation in accordance with the present invention is applied to the surfaces of teeth to form a pharmacologically inert barrier coating over prior coating(s) containing pharmacologically-active substances.
- the pharmacologically-active substance(s) comprise one or more active agents of the type known to reduce caries when applied to the tooth, illustratively, chlorhexidine and/or fluoride.
- the liquid formulation which is clear, tasteless, and odorless, can be applied by a dental professional with a brush or cotton balls, or by any other means, so as to form, when dried, a film in situ on the tooth surface.
- the formulation dries within seconds, preferably after using an air syringe.
- the inert barrier coating formed by the composition of the invention remains intact on the surface of the teeth for as long as the patient avoids chewing hard foods, such as meat, raw fruit, or crusty rolls.
- the coating is not affected by chewing soft foods such as soup and cheese.
- the coating affected by heat, such as by drinking hot beverages.
- a method of preventing or reducing the incidence of caries in teeth includes the steps of applying a liquid coating of pharmacologically-active substances of the type used to reduce caries to a tooth surface; followed by applying a pharmacologically inert barrier coating, in accordance with the present invention, on top of the coating containing the pharmacologically-active substance.
- the inert barrier coating serves as a temporary mechanical barrier to delay erosion of the therapeutic coating caused by the washings of saliva and abrasion caused by eating food.
- the coatings are dried by the dental professional.
- the components used in the practice of the method aspect of the invention can be provided as a two component kit, the ingredients of which are capable of reducing caries in the oral cavity.
- This embodiment would provide a separate compositions, the first composition including a therapeutic agent, such as chlorhexidine and/or fluoride and the second composition in accordance with the present invention comprising, for example, a PMMA in an aqueous dispersion with sufficient triethyl citrate to ensure flexibility and rapid drying in the oral cavity.
- a pharmacologically inert, bio-acceptable, liquid formulation of a water-suspended PMMA and plasticizer is formulated as follows: 28% EUDRAGIT RS 30 D polymethylmethacrylate;
- a dental professional applies this formulation to the surface of teeth in a dental patient with a brush following the application of a coating of a pharmacologically-active substance, specifically chlorhexidine and/or fluoride in accordance with methods that are known and practiced in the art.
- the first coating is dried, such as with an air syringe, or is permitted to dry prior to application of the pharmacologically-inert barrier coating.
- the pharmacologically-active layer was a chlorhexidine (10% w/v) solution sold under the trademark PREVORA by CHX
- the liquid formulation was evaluated in vivo for durability and patient acceptability on six different occasions separated by 48 hours or more, by one volunteer human subject.
- the formulation once colored with red food dye for ease of observation, was self-applied by this volunteer to the buccal (outer) surfaces of the upper central incisor teeth plus the upper two canine teeth.
- the volunteer visibly observed the durability of the coating over the course of both day and night, and during meals. Recorded observations showed that the patient found this coating to be acceptable to taste and feel by the tongue as well as durable for a period of more than 12 hours or the period when the volunteer did not eat.
- the coating was abraded from the tooth surface by chewing hard foods, but not by chewing soft foods.
- a pharmacologically-active liquid coating of chlorhexidine (10% w/v) was applied by a dental professional to the buccal (other) upper right central incisor teeth and the upper canine tooth of six volunteer subjects. The chlorhexidine coating was then air dried. Immediately thereafter, an aqueous dispersion of the formulation set forth in this section was applied over top the first coating of chlorhexidine and was also air dried.
- the buccal surfaces of these teeth were tested for chlorhexidine residue by way of dry blotter paper discs placed on the teeth surfaces for one minute.
- the presence or absence of chlorhexidine on these paper discs was then tested by way of standard microbiology procedures involving zones of inhibition, using a strain of Streptococcus mutans bacteria in agar.
- the test was conducted over a 24 hour period and involved discs retrieved from the tooth surface at 1 hour, 2 hours, 4 hours and 24 hours after application of the inert coating herein described. In 3 of 6 patients for a period of up to 2 hours after application of the liquid coating, the discs inhibited bacterial growth and hence contained chlorhexidine.
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- Health & Medical Sciences (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Cosmetics (AREA)
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA2510152A CA2510152C (en) | 2002-12-16 | 2003-12-16 | Temporary, pharmacologically-inactive dental coating for the in situ protection of dental therapeutic agents from saliva and abrasion from chewing |
US10/539,923 US20060134012A1 (en) | 2002-12-16 | 2003-12-16 | Temporary pharmacologically-inactive dental coating for the in situ protection of dental therapeutic agents from saliva and abrasion from chewing |
EP03785413A EP1572107A1 (en) | 2002-12-16 | 2003-12-16 | Temporary, pharmacologically-inactive dental coating for the "in situ" protection of dental therapeutic agents from saliva and abrasion from chewing |
AU2003294520A AU2003294520A1 (en) | 2002-12-16 | 2003-12-16 | Temporary, pharmacologically-inactive dental coating for the in situ protection of dental therapeutic agents from saliva and abrasion from chewing |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US43393302P | 2002-12-16 | 2002-12-16 | |
US60/433,933 | 2002-12-16 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2004054518A1 true WO2004054518A1 (en) | 2004-07-01 |
Family
ID=32595249
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/CA2003/001943 WO2004054518A1 (en) | 2002-12-16 | 2003-12-16 | Temporary, pharmacologically-inactive dental coating for the in situ protection of dental therapeutic agents from saliva and abrasion from chewing |
Country Status (5)
Country | Link |
---|---|
US (1) | US20060134012A1 (en) |
EP (1) | EP1572107A1 (en) |
AU (1) | AU2003294520A1 (en) |
CA (1) | CA2510152C (en) |
WO (1) | WO2004054518A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2404588A (en) * | 2003-08-02 | 2005-02-09 | Boots Co Plc | Methods for providing a protective polymer layer over a substance in contact with the skin |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20130288194A1 (en) * | 2012-04-25 | 2013-10-31 | Therametric Technologies, Inc. | Fluoride varnish |
US9107838B2 (en) | 2012-04-25 | 2015-08-18 | Therametrics Technologies, Inc. | Fluoride varnish |
ES2707880T3 (en) * | 2012-09-07 | 2019-04-05 | Ivoclar Vivadent Ag | Varnish containing fluoride for application to the dental surface |
WO2019172884A1 (en) * | 2018-03-06 | 2019-09-12 | Otero Lindsey E | Heat moldable material |
CA3109267A1 (en) * | 2018-08-10 | 2020-03-12 | Chx Technologies, Inc., A Corporation Created And Existing Under The Laws Of Canada | Method of preventing both caries and periodontal disease simultaneously in one procedure |
WO2020161771A1 (en) * | 2019-02-04 | 2020-08-13 | マルホ株式会社 | Skin composition |
WO2021042325A1 (en) * | 2019-09-05 | 2021-03-11 | 台北科技大学 | Composition of temporary dental material |
Citations (7)
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US4883534A (en) * | 1983-05-11 | 1989-11-28 | University Of Toronto Innovations Foundations | Benzoin antimicrobial dental varnishes |
DE4125048A1 (en) * | 1991-07-29 | 1993-02-04 | Peggy Albrecht | Retard pharmaceutical prepn. for periodontitis treatment - contains anti-periodontitis drug esp. metronidazole, in cationic (meth)acrylic] polymer matrix pref. used as film strip |
US5330746A (en) * | 1988-05-03 | 1994-07-19 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Dental varnish composition, and method of use |
EP1112750A1 (en) * | 1999-07-12 | 2001-07-04 | Suntory Limited | Drug composition for topical administration |
US20010024657A1 (en) * | 1997-07-24 | 2001-09-27 | Lerner E. Itzhak | Pharmaceutical oral patch for controlled release of pharmaceutical agents in the oral cavity |
WO2001082897A2 (en) * | 2000-05-02 | 2001-11-08 | Enzrel, Inc. | Liposome drug delivery |
WO2002009675A1 (en) * | 2000-08-02 | 2002-02-07 | Pfizer Limited | Particulate composition of eletriptan showing a sigmoidal pattern of controlled release |
Family Cites Families (5)
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US4064285A (en) * | 1975-12-22 | 1977-12-20 | Xerox Corporation | Electrophotographic decalcomanias |
US4496322A (en) * | 1983-05-11 | 1985-01-29 | University Of Toronto Innovations Foundation | Benzoin antimicrobial dental varnishes |
US5160737A (en) * | 1988-05-03 | 1992-11-03 | Perio Products Ltd. | Liquid polymer composition, and method of use |
US5438076A (en) * | 1988-05-03 | 1995-08-01 | Perio Products, Ltd. | Liquid polymer composition, and method of use |
US5286497A (en) * | 1991-05-20 | 1994-02-15 | Carderm Capital L.P. | Diltiazem formulation |
-
2003
- 2003-12-16 CA CA2510152A patent/CA2510152C/en not_active Expired - Fee Related
- 2003-12-16 AU AU2003294520A patent/AU2003294520A1/en not_active Abandoned
- 2003-12-16 EP EP03785413A patent/EP1572107A1/en not_active Withdrawn
- 2003-12-16 US US10/539,923 patent/US20060134012A1/en not_active Abandoned
- 2003-12-16 WO PCT/CA2003/001943 patent/WO2004054518A1/en not_active Application Discontinuation
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
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US4883534A (en) * | 1983-05-11 | 1989-11-28 | University Of Toronto Innovations Foundations | Benzoin antimicrobial dental varnishes |
US5330746A (en) * | 1988-05-03 | 1994-07-19 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Dental varnish composition, and method of use |
DE4125048A1 (en) * | 1991-07-29 | 1993-02-04 | Peggy Albrecht | Retard pharmaceutical prepn. for periodontitis treatment - contains anti-periodontitis drug esp. metronidazole, in cationic (meth)acrylic] polymer matrix pref. used as film strip |
US20010024657A1 (en) * | 1997-07-24 | 2001-09-27 | Lerner E. Itzhak | Pharmaceutical oral patch for controlled release of pharmaceutical agents in the oral cavity |
EP1112750A1 (en) * | 1999-07-12 | 2001-07-04 | Suntory Limited | Drug composition for topical administration |
WO2001082897A2 (en) * | 2000-05-02 | 2001-11-08 | Enzrel, Inc. | Liposome drug delivery |
WO2002009675A1 (en) * | 2000-08-02 | 2002-02-07 | Pfizer Limited | Particulate composition of eletriptan showing a sigmoidal pattern of controlled release |
Non-Patent Citations (2)
Title |
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AMIGHI K ET AL: "INFLUENCE OF PLASTICIZER CONCENTRATION AND STORAGE CONDITIONS ON THE DRUG RELEASE RATE FROM EUDRAGIT RS30D FILM-COATED SUSTAINED-RELEASE THEOPHYLLINE PELLETS", EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, ELSEVIER SCIENCE PUBLISHERS B.V., AMSTERDAM, NL, vol. 42, no. 1, 1996, pages 29 - 35, XP000555020, ISSN: 0939-6411 * |
LIN S-Y ET AL: "Organic esters of plasticizers affecting the water absorption, adhesive property, glass transition temperature and plasticizer permanence of Eudragit acrylic films", JOURNAL OF CONTROLLED RELEASE, ELSEVIER SCIENCE PUBLISHERS B.V. AMSTERDAM, NL, vol. 68, no. 3, 3 September 2000 (2000-09-03), pages 343 - 350, XP004208505, ISSN: 0168-3659 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2404588A (en) * | 2003-08-02 | 2005-02-09 | Boots Co Plc | Methods for providing a protective polymer layer over a substance in contact with the skin |
GB2404588B (en) * | 2003-08-02 | 2007-05-02 | Boots Co Plc | Products for providing a protective layer over a sunscreen composition in contact with the skin |
Also Published As
Publication number | Publication date |
---|---|
EP1572107A1 (en) | 2005-09-14 |
CA2510152C (en) | 2013-04-02 |
CA2510152A1 (en) | 2004-07-01 |
US20060134012A1 (en) | 2006-06-22 |
AU2003294520A1 (en) | 2004-07-09 |
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