WO1996013226A1 - Methode de traitement de la periodontite et composition pharmaceutique utilisee dans le cadre de cette methode - Google Patents

Methode de traitement de la periodontite et composition pharmaceutique utilisee dans le cadre de cette methode Download PDF

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Publication number
WO1996013226A1
WO1996013226A1 PCT/US1995/013989 US9513989W WO9613226A1 WO 1996013226 A1 WO1996013226 A1 WO 1996013226A1 US 9513989 W US9513989 W US 9513989W WO 9613226 A1 WO9613226 A1 WO 9613226A1
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WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
growth factor
nsaid
dental tissue
pharmaceutically acceptable
Prior art date
Application number
PCT/US1995/013989
Other languages
English (en)
Inventor
A. K. Gunnar Aberg
Original Assignee
Sepracor Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sepracor Inc. filed Critical Sepracor Inc.
Priority to AU41375/96A priority Critical patent/AU4137596A/en
Publication of WO1996013226A1 publication Critical patent/WO1996013226A1/fr

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18Growth factors; Growth regulators
    • A61K38/1841Transforming growth factor [TGF]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18Growth factors; Growth regulators
    • A61K38/1858Platelet-derived growth factor [PDGF]
    • A61K38/1866Vascular endothelial growth factor [VEGF]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22Hormones
    • A61K38/30Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
    • 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
    • A61K31/167Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/60Salicylic acid; Derivatives thereof

Definitions

  • the present invention relates generally to the treatment of periodontal disease and more particularly to a novel method for treating periodontal disease and to a pharmaceutical composition useful in said method.
  • Periodontal disease which includes any abnormality, whether inflammatory or degenerative, of tissue around a tooth, is very common worldwide.
  • the World Health Organization estimated some years ago that, even if there were no new periodontal disease, it would still take 45 years to treat those people already afflicted therewith.
  • the Journal of Public Health Dentistry concluded in 1985 that "more than two out of three patients were affected by periodontal disease.” Moos, W.F., Medical Marketing & Media, 52-54 (1985).
  • Periodontal disease Two common types of periodontal disease are chronic gingivitis (i.e., an inflammation of the gingiva or gums) and chronic destructive periodontitis (i.e., a disease of the connective tissue which attaches a tooth to the alveolar bone, which disease results in alveolar bone resorption, increasing mobility of the tooth and, ultimately, tooth loss).
  • chronic gingivitis hereinafter simply “gingivitis”
  • chronic destructive periodontitis hereinafter simply “periodontitis” actually represent varying stages of periodontal disease, with gingivitis, if uncontrolled, progressing into periodontitis.
  • periodontal disease is caused, at least initially, by the accumulation of bacterial plaque on the teeth and under the gingiva of a patient, said accumulation of plaque triggering an inflammatory and immunological response in the patient.
  • Preventive techniques have relied heavily on establishing and maintaining good oral hygiene including mechanically and/or chemically preventing the accumulation of bacterial plaque on the teeth and under the gingiva.
  • Therapies directed at treating existing advanced periodontal disease have primarily been directed at expensive and ongoing medical procedures, such as periodontal surgery, which in many cases must be carried out often over an indefinite period of time and which have not been clearly shown to be effective in arresting alveolar bone loss and preserving teeth. Because of the initial inflammatory aspect of periodontal disease, a number of researchers have recently investigated the use of certain anti- inflammatory agents as possible therapies for treating gingivitis.
  • the method comprises applying to buccal membranes a therapeutically effective quantity of an enantiomer, generally an S enantiomer, of a nonsteroidal anti-inflammatory drug, such as (S)- flurbiprofen or (S)-ketoprofen.
  • an enantiomer generally an S enantiomer
  • a nonsteroidal anti-inflammatory drug such as (S)- flurbiprofen or (S)-ketoprofen.
  • the composition is a formulation which is a toothpaste or which is a mouthwash.
  • a method for regenerating mammalian dental tissue such as that afflicted with periodontitis (e.g., gum tissue, periodontal ligature, etc.) comprising the step of administering to the mammalian dental tissue a therapeutically effective amount of a pharmaceutical composition comprising a growth factor and an NSAID.
  • a pharmaceutical composition comprising a growth factor and an NSAID.
  • the growth factor of the present pharmaceutical composition is a polypeptide (i.e., proteinaceous) growth factor.
  • polypeptide growth factor refers to a class of natural biological mediators that regulate the proliferation, differentiation, motility and matrix synthesis of nearly all cell types. It is also believed that such factors play important roles in soft and hard tissue repair.
  • polypeptide growth factors include, but are not limited to, platelet-derived growth factor (PDGF), insulin-like growth factor-1 (IGF-1 ), transforming growth factor alpha (TGF- ⁇ ), cartilage-derived growth factor (CDGF) and growth hormones (such as human growth hormone).
  • polypeptide growth factors of the present invention may be naturally occurring polypeptide growth factors, polypeptide growth factors obtained by recombinant means expressed in either eukaryotic or prokaryotic systems, biologically active mutant forms of naturally occurring polypeptide growth factors, biologically active fragments or subunits of naturally occurring polypeptide growth factors, or biologically active mutants of biologically active fragments or subunits of naturally occurring polypeptide growth factors.
  • NSAID as used in the present specification and claims, is defined to mean a non-steroidal, anti-inflammatory drug and is to be contrasted with steroidal, anti-inflammatory drugs.
  • NSAID's include, but are not limited to acetaminophen, ketorolac, aspirin and the class of aryl propionic acids, such as ketoprofen, etodolac, flurbiprofen, carprofen, ibuprofen, naproxen, indoprofen, pierprofen, pranoprofen, microprofen, thiaoxa and aminoprofen.
  • the NSAID is preferably in the form of a substantially pure, pharmacologically active enantiomer.
  • the pharmacologically active enantiomer is the S(+) enantiomer.
  • a method of regenerating mammalian dental tissue afflicted with periodontitis and, over a subsequent period of time, preventing the resorption of the regenerated mammalian dental tissue comprising the steps of (a) administering to the afflicted mammalian dental tissue a therapeutically effective amount of a pharmaceutical composition comprising an NSAID and a growth factor, for example, a polypeptide growth factor; and (b) then, administering to the regenerated mammalian dental tissue a therapeutically effective amount of an NSAID to prevent the resorption of the regenerated mammalian dental tissue over said subsequent period of time.
  • the present invention is also directed to a pharmaceutical composition useful in regenerating mammalian dental tissue, such as that afflicted with periodontitis, the pharmaceutical composition comprising an NSAID and a growth factor, for example, a polypeptide growth factor.
  • the aforementioned pharmaceutical composition is also useful in reducing inflamed mammalian dental tissue, such as that afflicted with gingivitis.
  • the present invention is directed at a new method of treating periodontitis and at a new pharmaceutical composition useful in said method (it being understood that the present method and pharmaceutical composition could also be used to treat gingivitis).
  • the method of the present invention comprises the following steps: First, a pharmaceutical composition comprising a polypeptide growth factor and an NSAID is administered to a mammal suffering from periodontitis, the pharmaceutical composition being administered in a therapeutically effective amount to cause the regeneration and repair of afflicted dental tissue in the mammal. Then, an NSAID is administered to the afflicted mammal, the NSAID being administered in a therapeutically effective amount to prevent the repaired and regenerated dental tissue from thereafter being lost, for example, by alveolar bone resorption.
  • the aforementioned first step will be performed by a dentist or similar dental care provider by directly applying to the affected dental tissue a composition of the polypeptide growth factor and the NSAID in a pharmaceutically acceptable carrier for topical administration.
  • pharmaceutically acceptable carriers are ointments, creams, gels, matrices and liquids of the type described in U.S. Patent No. 5,149,691.
  • combinations of the aforementioned polypeptide growth factors such as PDGF+IGF-1 or PDGF+TGF ⁇ , may be used instead of a single polypeptide growth factor to achieve greater healing of the injured tissue.
  • combinations of NSAID's may be used instead of a single NSAID.
  • the NSAID is chiral, it is preferable to include only the pharmacologically active enantiomer, which is typically the S(+) enantiomer.
  • Flavoring or buffering agents may additionally be included in the above-described pharmaceutical composition to counter the unpleasant effects associated with the topical administration of NSAID's.
  • the range of concentration for the polypeptide growth factor in the subject pharmaceutical composition can be approximately 10 mg/ml to 1 g/ml, and the range of concentration for the NSAID in the subject pharmaceutical composition can be approximately 50 mg/ml to 50 g/ml.
  • the aforementioned second step of preserving the repaired and regenerated dental tissue will be performed by the patient by directly applying to the affected dental tissue a composition of an NSAID in a pharmaceutically acceptable formulation.
  • pharmaceutically acceptable formulations are toothpastes and mouthwashes of the type described in U.S. Patent No. 5,190,981 , as well as gels of the type typically applied using a dental impression-type tray.
  • suitable compositions comprising an NSAID in a toothpaste or mouthwash formulation are also described in U.S. Patent No. 5,190,981.
  • Such compositions preferably also include a cavity preventive agent, as well as a flavoring or buffering agent.
  • the NSAID-containing toothpaste or mouthwash will be administered by the patient twice daily over an indefinite period of time, i.e., the lifetime of the patient. Long-term use of the NSAID-containing toothpaste or mouthwash is presently deemed to be advisable to prevent the subsequent resorption of the newly regenerated dental tissue.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Vascular Medicine (AREA)
  • Diabetes (AREA)
  • Molecular Biology (AREA)
  • Endocrinology (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne une méthode de traitement de la périodontite et une composition pharmaceutique utilisée dans le cadre de cette méthode. Selon le mode de réalisation préféré, la méthode consiste à administrer à un mammifère atteint d'une périodontite une dose efficace sur le plan thérapeutique d'une composition pharmaceutique comprenant un facteur de croissance de polypeptide ainsi qu'un anti-inflammatoire non stéroïdien pour régénérer le tissu dentaire du mammifère malade et, par la suite, à lui administrer une dose efficace sur le plan thérapeutique d'un anti-inflammatoire non stéroïdien pour empêcher la résorption du tissu dentaire nouvellement régénéré.
PCT/US1995/013989 1994-10-31 1995-10-30 Methode de traitement de la periodontite et composition pharmaceutique utilisee dans le cadre de cette methode WO1996013226A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU41375/96A AU4137596A (en) 1994-10-31 1995-10-30 Method for the treatment of periodontal disease and a pharmaceutical composition useful in said method

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US33253294A 1994-10-31 1994-10-31
US08/332,532 1994-10-31

Publications (1)

Publication Number Publication Date
WO1996013226A1 true WO1996013226A1 (fr) 1996-05-09

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1995/013989 WO1996013226A1 (fr) 1994-10-31 1995-10-30 Methode de traitement de la periodontite et composition pharmaceutique utilisee dans le cadre de cette methode

Country Status (2)

Country Link
AU (1) AU4137596A (fr)
WO (1) WO1996013226A1 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0821970A1 (fr) * 1996-08-02 1998-02-04 Edward Henri Charles Verhaeren Véhicule pour moduler la perméabilité de la jonction étanche
EP2322226A3 (fr) * 1999-07-21 2011-08-17 Omeros Corporation Solutions et procédés pour l'inhibition de la douleur, la inflammation et la degradation du cartilage
US8870954B2 (en) 2008-09-09 2014-10-28 Biomimetic Therapeutics, Llc Platelet-derived growth factor compositions and methods for the treatment of tendon and ligament injuries
US9161967B2 (en) 2006-06-30 2015-10-20 Biomimetic Therapeutics, Llc Compositions and methods for treating the vertebral column
US9545377B2 (en) 2004-10-14 2017-01-17 Biomimetic Therapeutics, Llc Platelet-derived growth factor compositions and methods of use thereof
US9642891B2 (en) 2006-06-30 2017-05-09 Biomimetic Therapeutics, Llc Compositions and methods for treating rotator cuff injuries
US10258566B2 (en) 2004-10-14 2019-04-16 Biomimetic Therapeutics, Llc Compositions and methods for treating bone
US11235030B2 (en) 2010-02-22 2022-02-01 Biomimetic Therapeutics, Llc Platelet-derived growth factor compositions and methods for the treatment of tendinopathies

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4919939A (en) * 1986-04-29 1990-04-24 Pharmetrix Corporation Periodontal disease treatment system
US5324519A (en) * 1989-07-24 1994-06-28 Atrix Laboratories, Inc. Biodegradable polymer composition
US5447725A (en) * 1993-06-11 1995-09-05 The Procter & Gamble Company Methods for aiding periodontal tissue regeneration

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4919939A (en) * 1986-04-29 1990-04-24 Pharmetrix Corporation Periodontal disease treatment system
US5324519A (en) * 1989-07-24 1994-06-28 Atrix Laboratories, Inc. Biodegradable polymer composition
US5447725A (en) * 1993-06-11 1995-09-05 The Procter & Gamble Company Methods for aiding periodontal tissue regeneration

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0821970A1 (fr) * 1996-08-02 1998-02-04 Edward Henri Charles Verhaeren Véhicule pour moduler la perméabilité de la jonction étanche
WO1998005359A1 (fr) * 1996-08-02 1998-02-12 Ghyssaert, Joris, Rosa, Michael Composition de transport destinee a influencer la permeabilite des jonctions serrees
EP2322226A3 (fr) * 1999-07-21 2011-08-17 Omeros Corporation Solutions et procédés pour l'inhibition de la douleur, la inflammation et la degradation du cartilage
US11571497B2 (en) 2004-10-14 2023-02-07 Biomimetic Therapeutics, Llc Platelet-derived growth factor compositions and methods of use thereof
US11364325B2 (en) 2004-10-14 2022-06-21 Biomimetic Therapeutics, Llc Platelet-derived growth factor compositions and methods of use thereof
US9545377B2 (en) 2004-10-14 2017-01-17 Biomimetic Therapeutics, Llc Platelet-derived growth factor compositions and methods of use thereof
US11318230B2 (en) 2004-10-14 2022-05-03 Biomimetic Therapeutics, Llc Platelet-derived growth factor compositions and methods of use thereof
US10258566B2 (en) 2004-10-14 2019-04-16 Biomimetic Therapeutics, Llc Compositions and methods for treating bone
US11058801B2 (en) 2006-06-30 2021-07-13 Biomimetic Therapeutics, Llc Compositions and methods for treating the vertebral column
US10456450B2 (en) 2006-06-30 2019-10-29 Biomimetic Therapeutics, Llc Compositions and methods for treating rotator cuff injuries
US9642891B2 (en) 2006-06-30 2017-05-09 Biomimetic Therapeutics, Llc Compositions and methods for treating rotator cuff injuries
US9161967B2 (en) 2006-06-30 2015-10-20 Biomimetic Therapeutics, Llc Compositions and methods for treating the vertebral column
US11135341B2 (en) 2008-09-09 2021-10-05 Biomimetic Therapeutics, Llc Platelet-derived growth factor composition and methods for the treatment of tendon and ligament injuries
US8870954B2 (en) 2008-09-09 2014-10-28 Biomimetic Therapeutics, Llc Platelet-derived growth factor compositions and methods for the treatment of tendon and ligament injuries
US11235030B2 (en) 2010-02-22 2022-02-01 Biomimetic Therapeutics, Llc Platelet-derived growth factor compositions and methods for the treatment of tendinopathies

Also Published As

Publication number Publication date
AU4137596A (en) 1996-05-23

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