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WO2019203813A1 - Compositions containing tetrahydrocurcuminoids for improvement of oral health and hygiene - Google Patents

Compositions containing tetrahydrocurcuminoids for improvement of oral health and hygiene Download PDF

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Publication number
WO2019203813A1
WO2019203813A1 PCT/US2018/028077 US2018028077W WO2019203813A1 WO 2019203813 A1 WO2019203813 A1 WO 2019203813A1 US 2018028077 W US2018028077 W US 2018028077W WO 2019203813 A1 WO2019203813 A1 WO 2019203813A1
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WO
WIPO (PCT)
Prior art keywords
tablets
candies
gingivitis
lotions
ointments
Prior art date
Application number
PCT/US2018/028077
Other languages
French (fr)
Inventor
Muhammed Majeed
Kalyanam Nagabhushanam
Shaheen Majeed
Original Assignee
Muhammed Majeed
Kalyanam Nagabhushanam
Shaheen Majeed
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 Muhammed Majeed, Kalyanam Nagabhushanam, Shaheen Majeed filed Critical Muhammed Majeed
Priority to PCT/US2018/028077 priority Critical patent/WO2019203813A1/en
Publication of WO2019203813A1 publication Critical patent/WO2019203813A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/12Ketones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/906Zingiberaceae (Ginger family)
    • A61K36/9066Curcuma, e.g. common turmeric, East Indian arrowroot or mango ginger
    • 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
    • A61K47/02Inorganic compounds
    • 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
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12Carboxylic acids; Salts or anhydrides thereof
    • 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
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/20Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
    • 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
    • A61K47/26Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • 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
    • A61K47/32Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • 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
    • A61K47/36Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/38Cellulose; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783Angiosperms [Magnoliophyta]
    • A61K8/9794Liliopsida [monocotyledons]
    • 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
    • A61K9/0056Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • 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
    • 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
    • A61K9/0063Periodont
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/2027Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/205Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841Filling excipients; Inactive ingredients
    • A61K9/485Inorganic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841Filling excipients; Inactive ingredients
    • A61K9/4858Organic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841Filling excipients; Inactive ingredients
    • A61K9/4866Organic macromolecular compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses

Definitions

  • the present invention relates to a novel composition containing tetrahydroeurcuminoids for die improvement of oral health and hygiene. More specifically, the invention relates to a novel tetrahydrocurcuminoid composition and its application in therapeutic management of canker sore mid gingivitis.
  • the health and hygiene of the teeth, the mouth, and mucosal tracts of the oral cavity is important to a person's overall health-
  • the common type of oral disease include dental cavities, caries, bad breath and gum diseases, including canker sore, gingivitis, and periodontitis.
  • RAS Recurrent aphthous stomatitis
  • canker sores is one of the most common, painful oral ailments, characterized by multiple, small, round, or ovoid ulcers with circumscribed margins, erythematous haloes, and yellow or grey floors that presents itself in childhood or adolescence.
  • Scully C Porter S. Oral mucosal disease: recurrent aphthous stomatitis, Br J Oral Maxillofac Surg. 2008 Apr;46(3): 198-206; Preeti L, et al., Recurrent aphthous stomatitis, J Oral Maxillofac
  • Gingivitis affects an estimated 80% of the population and is the world's most predominant inflammatory periodontal disease. The disease is initiated with a pathogenic biofilm, or plaque, around the teeth followed by a host immune-inflammatory response that advances the disease.
  • the principle objective of the invention is to disclose a composition containing tetrahydrocurcuminoids and for the improvement of oral health and hygiene.
  • the present invention discloses a composition containing tetrahydrocurcuminoids for the improvement of oral health and hygiene. Specifically the invention discloses a novel composition of tetrahydrocurcuminoids for the therapeutic management of canker sore and gingivitis.
  • Fig,la shows graphical representation of median VAS seme at three time points; p value ⁇ 0.001 using Friedman ANNOV A,
  • Fig, lb shows graphical representation of median throat relief score at three points
  • Fig. lc shows graphical representation of distribution of patients as per throat numbness at different time points
  • Fig. 2a and 2b shows Line plots mean values of different LOE & SILNESS Index parameters ami total points at three times in Gingivitis group
  • the invention relates to a novel composition containing tetrahydrocurcuminoids for the improvement of oral health and hygiene.
  • the composition contains tetrahydrocurcumin, teirahydrodemethoxycurcumin, tetrahydrobis-demethoxycurcumin, octahydrocurcuminoids and hexahydrocurcuminoids.
  • the composition is formulated with pharmaceutically, nutraceuticaily and cosmeceutically acceptable excipients, adjuvants, diluents or carriers and administered in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, creams, gels, lotions, ointments, mouth wash, tooth paste and eatables.
  • the tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, creams, gels, lotions, ointments, mouth wash, tooth paste and eatables are available separately or together in an oral health kit containing the said forms.
  • the present invention discloses a method for therapeutic management of canker sore in mammals, said method comprising steps of administering an effective concentration of a composition containing tetrahydrocurcuminoids to mammals in need of such therapy, to bring about reduction in symptoms associated with canker sore.
  • the symptoms of canker sore include, but not limited to. throat pain, ulcer, lesion, throat numbness, sore throat, bleeding, swelling at the site, reddening at the site, inflammation at the site, burning, swelling and paid in lymph node, difficulty in chewing and difficulty in swallowing.
  • the composition is formulated with pharmaceutically, nutraceutically and cosmeceutically acceptable excipients, adjuvants, diluents of carriers and administered in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, creams, gels, lotions, ointments, mouth wash, tooth paste and eatables hi a related embodiment, the tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, creams, gels, lotions, ointments, mouth wash, tooth paste and eatables, are available separately or together in an oral health kit containing the said forms.
  • the mammal is preferably human.
  • the present invention discloses a method for therapeutic management of gingivitis in mammals, said method comprising steps of administering an effective concentration of a composition containing tetrahydrocurcuminoids to mammals in need of such therapy, to bring about reduction in symptoms associated with gingivitis.
  • the symptoms of gingivitis include, but not limited to, taste acceptability, burning sensation, dryness, soreness, ulcer, staining of teeth and tongue, and allergy.
  • the composition is formulated with pharmaceutically, nutraceutically and cosmeceutically acceptable excipients, adjuvants, diluents or carriers and administered in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, creams, gels, lotions, ointments, mouth wash, tooth paste and eatables.
  • the tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, creams, gels, lotions, ointments, mouth wash, tooth paste and eatables are available separately or together in an oral health kit containing the said forms.
  • the mammal is preferably human. [Para0017] Specific illustrative examples enunciating the most preferred embodiments are included herein below.
  • the sample size of the study was 60, with 30 subjects assigned to each of die two study arms in a manner there would be 30 subjects with canker sore and throat pain and 30 subjects with gingivitis. However, 31 subjects were enrolled for Canker Sore and 29 were enrolled for
  • [ParaOQ32] AU enrolled subjects were instructed to self administer one chewable tablet (oral dosing) twice daily containing lOOmg of tetrahydrocurcuminoids for a period of 21 days.
  • Table 1 Distribution of patients with different no of lesions across study visits.
  • Example 3 Compositions / formulations containing tetrahydrocurcuminoids
  • Tables 4-9 provide illustrative examples of nutraceutical formulations containing tetrahydrocurcuminoids for the management of canker sore and gingivitis [Para0059] Table 4: Tetrahydrocurcuminoids Chewable Tablet
  • Table 10 and 11 provides illustrative examples for a mouth gel and mouth wash formulation containing tetrahydrocurcuminoids for the management of canker sore and gingivitis
  • the invention also provides an illustrative example of an oral health kit comprising of formulation containing tetrahydracurcuminoids which include, but not limited to, the following: 1. Chewable tablets, candies and guinmies

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  • Engineering & Computer Science (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
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  • Oil, Petroleum & Natural Gas (AREA)
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Abstract

Disclosed is a novel composition containing tetrahydrocurcuminoids for the improvement of oral health and hygiene. More specifically, disclosed is a novel composition of tetrahydrocurcuminoids and its application in the therapeutic management of canker sore and gingivitis.

Description

COMPOSITIONS CONTAINING TETRAHYDROCURCUMINOIDS FOR
IMPROVEMENT OF ORAL HEALTH AND HYGIENE
FIELD OF THE INVENTION
[ParaOOOl] The present invention relates to a novel composition containing tetrahydroeurcuminoids for die improvement of oral health and hygiene. More specifically, the invention relates to a novel tetrahydrocurcuminoid composition and its application in therapeutic management of canker sore mid gingivitis.
BACKGROUND OF THE INVENTION
[ParaOOOl] DESCRIPTION OF PRIOR ART
[ParaOO03] The health and hygiene of the teeth, the mouth, and mucosal tracts of the oral cavity is important to a person's overall health- The common type of oral disease include dental cavities, caries, bad breath and gum diseases, including canker sore, gingivitis, and periodontitis.
Canker sores and gingivitis are the most commonly occurring oral problems. Recurrent aphthous stomatitis (RAS) (aphthae; canker sores) is one of the most common, painful oral ailments, characterized by multiple, small, round, or ovoid ulcers with circumscribed margins, erythematous haloes, and yellow or grey floors that presents itself in childhood or adolescence. (Scully C, Porter S. Oral mucosal disease: recurrent aphthous stomatitis, Br J Oral Maxillofac Surg. 2008 Apr;46(3): 198-206; Preeti L, et al., Recurrent aphthous stomatitis, J Oral Maxillofac
Pathol,. 2011; 15:252-6). Gingivitis affects an estimated 80% of the population and is the world's most predominant inflammatory periodontal disease. The disease is initiated with a pathogenic biofilm, or plaque, around the teeth followed by a host immune-inflammatory response that advances the disease.
[Para004] As a main stay to maintain oral hygiene, mechanical plaque control measures are generally employed. But, these techniques are either time consuming or require motivation and skill to be performed well for effective relief against the symptoms. Hence, antimicrobial agents such as chlorhexidine, metronidazole etc are being used extensively as an adjunct to mechanical cleaning. However, these artificial drugs have unpleasant side-effects and hence a safe and effective natural/herbal source in providing relief against oral health problems is the current industrial requirement.
[ParaOOS] Turmeric, especially curcumin is an effective natural alternative for the management of oral health problems which is specifically documented in the following :
1. Clinical efficacy of turmeric use in gingivitis: A comprehensive review, Stoyell KA,
Mappus JL, Gandhi MA, Complement Ther Clin Pract. 2016 Nov; 25: 13-17).
2. Efficacy of curcumin in the treatment of chronic gingivitis: a pilot study. Muglikar, S.,
Patil, K.C., Shivswami, S., and Hegde, R., Oral Health and Preventive Dentistry. 2012;
I l(l):81-86)
3. Comparison of effectiveness of curcumin with triamcinolone acetonide in the gel form in treatment of minor recurrent aphthous stomatitis: A randomized clinical trial, Deshmukh
RA, Bagewadi AS, Iht J Pharm Investig. 2014 Jul;4(3): 138-41). 4. Oral care compositions, Brading et al., US patent no. 8916139
[Para006] Owing to the problems associated with curcumin when incorporated in oral care compositions like bioavailability, degradation, discoloration, there is a need to develop a stable natural alternative for management of oral health and hygiene, especially for canker sore and gingivitis because of their different pathological features. The invention solves the above problem by disclosing a composition containing tetrahydrocurcuminoids for the therapeutic management of canker sore and gingivitis.
[Para007] The principle objective of the invention is to disclose a composition containing tetrahydrocurcuminoids and for the improvement of oral health and hygiene.
[Para008] It is another objective of the invention to disclose a composition containing tetrahydrocurcuminoids for therapeutic management of canker sore and gingivitis.
SUMMARY OF THE INVENTION
[Para009] The present invention discloses a composition containing tetrahydrocurcuminoids for the improvement of oral health and hygiene. Specifically the invention discloses a novel composition of tetrahydrocurcuminoids for the therapeutic management of canker sore and gingivitis.
BRIEF DESCRIPTION OF THE FIGURES (Fig.la, lb, lc, 2a and 2b)
[ParaOOlO] Fig,la shows graphical representation of median VAS seme at three time points; p value < 0.001 using Friedman ANNOV A,
[Para0011] Fig, lb shows graphical representation of median throat relief score at three points [Para0012] Fig. lc shows graphical representation of distribution of patients as per throat numbness at different time points
[Para0013] Fig. 2a and 2b shows Line plots mean values of different LOE & SILNESS Index parameters ami total points at three times in Gingivitis group
DESCRIPTION OF MOST PREFEERED EMBODIMENTS
[ParaOOH] hi a most preferred embodiment, the invention relates to a novel composition containing tetrahydrocurcuminoids for the improvement of oral health and hygiene. In a related embodiment the composition contains tetrahydrocurcumin, teirahydrodemethoxycurcumin, tetrahydrobis-demethoxycurcumin, octahydrocurcuminoids and hexahydrocurcuminoids. In a related embodiment the composition is formulated with pharmaceutically, nutraceuticaily and cosmeceutically acceptable excipients, adjuvants, diluents or carriers and administered in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, creams, gels, lotions, ointments, mouth wash, tooth paste and eatables. In a related embodiment, the tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, creams, gels, lotions, ointments, mouth wash, tooth paste and eatables, are available separately or together in an oral health kit containing the said forms.
[ParaOOlS] In another preferred embodiment, the present invention discloses a method for therapeutic management of canker sore in mammals, said method comprising steps of administering an effective concentration of a composition containing tetrahydrocurcuminoids to mammals in need of such therapy, to bring about reduction in symptoms associated with canker sore. In another related embodiment, the symptoms of canker sore include, but not limited to. throat pain, ulcer, lesion, throat numbness, sore throat, bleeding, swelling at the site, reddening at the site, inflammation at the site, burning, swelling and paid in lymph node, difficulty in chewing and difficulty in swallowing. In a yet another related embodiment the composition is formulated with pharmaceutically, nutraceutically and cosmeceutically acceptable excipients, adjuvants, diluents of carriers and administered in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, creams, gels, lotions, ointments, mouth wash, tooth paste and eatables hi a related embodiment, the tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, creams, gels, lotions, ointments, mouth wash, tooth paste and eatables, are available separately or together in an oral health kit containing the said forms. In another embodiment, the mammal is preferably human.
[Para0016] In another preferred embodiment, the present invention discloses a method for therapeutic management of gingivitis in mammals, said method comprising steps of administering an effective concentration of a composition containing tetrahydrocurcuminoids to mammals in need of such therapy, to bring about reduction in symptoms associated with gingivitis. In another related embodiment, the symptoms of gingivitis include, but not limited to, taste acceptability, burning sensation, dryness, soreness, ulcer, staining of teeth and tongue, and allergy. In a yet another related embodiment the composition is formulated with pharmaceutically, nutraceutically and cosmeceutically acceptable excipients, adjuvants, diluents or carriers and administered in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, creams, gels, lotions, ointments, mouth wash, tooth paste and eatables. In a related embodiment, the tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, creams, gels, lotions, ointments, mouth wash, tooth paste and eatables, are available separately or together in an oral health kit containing the said forms. In another embodiment, the mammal is preferably human. [Para0017] Specific illustrative examples enunciating the most preferred embodiments are included herein below.
[ParaOOlS] EXAMPLES
[Para0019j Example 1: Experimental procedures
[Para0020] Product description
[Para0021] The study supplements were supplied in the form of chewable tablets with oral dosing twice daily containing lOOmg of tetrahydrocurcuminoids.
[Para0022] Ethics and informed consent
[Para0023] This trial was conducted in accordance with the clinical research guidelines established by the Drugs and Cosmetics Act, 1940 of India, Drugs and Cosmetics Rules, 1945 of
India, Ethical Guidelines for Biomedical Research on Human Participants, 2006 of Indian
Council of Medical Research (ICMR) in India, die principles enunciated in the Declaration of
Helsinki, Edinburgh (Anonymous, 2000) and the ICH - harmonized tripartite guideline regarding
Good Clinical Practice (GCP). The study was approved by the Institutional ethics committee, a written informed consent was obtained, and the study was registered at Clinical Trials Registry-
India (www,ctri.nic,in) (Identifier: CTRV2017/01/007670). There were no changes to the methods or planned endpoints after study initiation.
[Para0024j Participants
[Para0025] Subjects were included in the study if indicated“Yes” to all of the inclusion criteria and "No” to all of the exclusion criteria. [Para0026J Inclusion Criteria:
1. Male and/or female - Healthy, with no systemic disease (diabetes).
2. Age between 18 to 60 years.
3. Patients having mouth ulcers with throat pain or Patients with mild to moderate gingivitis.
4. Patients having erupted teeth.
5. Willing to come for regular follow-up visits.
6. Able to give written informed consent
[Para0027] Exclusion Criteria:
1. Smokers.
2. Presence of any systemic hematological problems.
3. Drug or alcohol abuse.
4. Under systemic or topical corticosteroid therapy.
5. Pregnant women or lactating mothers
6. History of HIV and other vital infections.
7. History of any antibiotic therapy in past 3 months.
8. History of oral prophylaxis within 6 months previous to the study
9. Patients with mouth breathing habit. 10. Patients using orthodontic and prosthodontics appliances
11. Are on analgesics or antiseptics.
12. Patients who have received any periodontal therapy in the past 6 months.
[Para0028] Trial Design
[Para0029] A Prospective, open label, two arm, clinical study to evaluate the efficacy and safety in the treatment of canker sore and gingivitis was conducted in India at two different sites: 1)
Noble Hospital Pvt Ltd., Pune, Maharashtra, India. 2) Sri Venkateshwara Hospital, Bangalore,
India. The sample size of the study was 60, with 30 subjects assigned to each of die two study arms in a manner there would be 30 subjects with canker sore and throat pain and 30 subjects with gingivitis. However, 31 subjects were enrolled for Canker Sore and 29 were enrolled for
Gingivitis after obtaining signed Informed Consent from these subjects. Subjects were non blinded as it was an open label study. Compliance with study supplement was reviewed at each visit. The subjects were allowed to take their regular diet The study consisted of a 21 day intervention period. Subjects visited the study site on screening (day -3 i,e. three days prior to baseline visit), baseline (day 0), visit day 14 and day 21.
[Para0030] Intervention
[Para0031] Male and female subjects between the age group of 18 to 60 years suffering with mouth ulcers along with throat pain were screened for the study. The screening procedures included medical history, medication and treatment history, physical examination, demographics and vital signs, pregnancy test in case of females, laboratory investigation (haematology), and efficacy assessments were conducted. Comorbtd conditions including any active, chronic, recurrent or latent infections.
[ParaOQ32] AU enrolled subjects were instructed to self administer one chewable tablet (oral dosing) twice daily containing lOOmg of tetrahydrocurcuminoids for a period of 21 days.
[Para0033] Efficacy Outcomes
[Para0034] For Canker sore with throat pain -
• Number of ulcers healed.
• Pain intensity Assessment by VAS (Visual Analogue Scale).
• Ulcer size reduction.
• Duration of complete healing of ulcers.
• Clinical Photographs of the Lesion.
• Throat Numbness Scale.
• Sore Throat Relief Scale.
[Para0035] For Gingivitis -
• Loe and Silness Gingival index.
• Subjective criteria for Gingivitis.
• Objective criteria for Gingivitis. • Clinical Photographs of gingival region.
[Para0036] Secondary Objective
[Para0037] To assess the safety of tetrahydrocurcuminoids in the treatment of Canker sore with throat pain and gingivitis.
[Para0038] Safety Outcomes:
• Any reports of adverse or serious adverse events.
• Abnormal vital signs & lab parameters.
[Para0039] Statistical Analysis of Efficacy Evaluation
[Para0040] The average scores were calculated separately on a per-subject basis at Baseline and
Day 21. For statistical purpose die Screening scores were considered as Baseline. The Day 21 means for each endpoint were modeled separately with analysis of covariance, using the respective baseline score as a covariate. All treatment comparisons were tested at the two-sided
5% significance level.
[Para0041] Example 2: Results
[Para0O42] This Study was conducted in India across two sites from November 2016 to March
2017. A total of 60 adult patients were enrolled and treated for 21 days with twice a day dosing every morning and evening. A total of 11 women and 49 men participated in die study. Total of
31 patients were enrolled in canker sore, out of which 1 patient dropped out and total 29 patients were enrolled in gingivitis arm. The female to male ratio completing the study was 10:49 with one female dropout. Patients enrolled were having no other physical abnormalities except either canker sore or gingivitis.
(Para0043) Efficacy outcome
[Para0044] Canker sore
[Para0045] The clinical parameter like systolic and diastolic BP, pulse rate, heart rate, respiratory rate and BMI were compared using repeated measure analysis of variance and was insignificant in between two time points. Physical examination revealed that general appearance, heart, lungs, abdomen, extremities and neurological functions were normal.
[Para0046] There was gradual decrease in numbers of lesion across the study period (Table 1). The duration taken for tetrahydrocurcuminoids to treat canker sore was an average of 21 days as almost all the symptoms were reduced at the final visit There was statistically significant reduction in number of cases with numbness after treatment (Fig. la). Further, comparison of throat relief score before and after treatment showed significant improvement (Fig. lb). Also,
VAS scores before and after treatment has shown significant reduction from median score of 3 to
0 (Fig. lc).
[Para0047] Table 1: Distribution of patients with different no of lesions across study visits.
Figure imgf000012_0001
Figure imgf000013_0002
[Para0048] There was a significant change in the symptoms of canker sore with throat pain like pain at site, burning at site, reddening, difficulty in chewing and swallowing post treatment.
Bleeding was insignificant due to treatment during the study period (Table 2).
[Para0049] Table 2: Comparison of signs and symptoms before and after treatment of canker sore patients
Figure imgf000013_0001
Figure imgf000014_0001
P-value < 0.001 except for bleeding (P > 0.05)
[ParaOOSO] Gingivitis
[ParaOOSl] The clinical parameter like systolic and diastolic BP, pulse rate, heart rate, respiratory rate and BMI were compared using analysis of covariance and was insignificant in between two time points. The general appearance, heart, lungs, abdomen, extremities and neurological functions were shown normal by physical examination.The duration taken by tetrahydrocurcuminoids to treat ginvivitis is in average of 14- 21 days.
[Para0052] Loe & Silness index was compared between two time points. Appearance differed significantly before and after treatment as indicated by P-value of 0.008 using Wilcoxon signed rank test Also, there was significant difference in the bleeding scores between baseline and visit
4 as revealed by P-value of 0.002. Further, inflammation was also significantly reduced at visit 4 compared to baseline (P < 0,001), Overall, the total points reduced from median of 2 at baseline to 0 at visit 4; and the reduction was statistically significant (P < 0.001) (fig 2).
[Para0053] The gingivitis Criteria compared between baseline and visit 4 didnt show any statistical significance due to a fairly constant reponse at visit 3 and vsit 4 (Table 3). [Para0054] Table 3: Comparison of gingivitis criteria before and after treatment
Figure imgf000015_0001
Figure imgf000016_0001
[ParaOQ55] Safety Results
[Para0056] There were insignificant changes in the parameters like systolic BP, diastolic BP, pulse rate, heart rate, respiratory rate and BMI between two times. There were no abnormal laboratory values reported during the study and no significant change in haematology. There was no change in vital parameters as compared to baseline. None of the patient experienced AEs during the study period in both canker sore and gingivitis atm. Thus, the tetrahydrocurcuminoids composition was acceptable in the study population and demonstrated as a completely safe preparation.
[Para0057] Example 3: Compositions / formulations containing tetrahydrocurcuminoids
[Para0058] Tables 4-9 provide illustrative examples of nutraceutical formulations containing tetrahydrocurcuminoids for the management of canker sore and gingivitis [Para0059] Table 4: Tetrahydrocurcuminoids Chewable Tablet
Figure imgf000017_0001
[Para0062] Table 7; Tetrahydrocurcuminoids Tablet
Figure imgf000018_0001
[Para0065] Table 10 and 11 provides illustrative examples for a mouth gel and mouth wash formulation containing tetrahydrocurcuminoids for the management of canker sore and gingivitis
[Para0066] Table 10: Tetrahydrocurcuminoids mouth gel
Figure imgf000019_0001
[Para0070] Oral Health Kit
The invention also provides an illustrative example of an oral health kit comprising of formulation containing tetrahydracurcuminoids which include, but not limited to, the following: 1. Chewable tablets, candies and guinmies
2. Tablets and capsules containing tetrahydrocurcuminoids
3. Creams, lotions, ointments, gels containing tetrahydrocurcuminoids
4. Mouth wash and toothpaste
[ParaQ071] The above formulations are just illustrative examples, any formulation containing the above active ingredient intended for the said purpose will be considered equivalent.
[Para0072] Other modifications and variations to the invention will be apparent to those skilled in die art from the foregoing disclosure and teachings. Thus, while only certain embodiments of the invention have been specifically described herein, it will be apparent that numerous modifications may be made thereto without departing from the spirit and scope of the invention.

Claims

We claim;
1. A composition containing tetrahydrocurcuntinoids for the improvement of oral health and hygiene.
2. The composition as in claim 1, wherein the composition is formuiated with pharmaceutically, nutraceutically and cosmeceutical!y acceptable excipients, adjuvants, diluents or carriers and administered in the form of tablets, capsules, syrups, gummies, powders* suspensions, emulsions, chewables, candies, creams, gels, lotions, ointments, mouth wash, tooth paste and eatables.
3. The formulation as in claim 2, wherein the tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, creams, gels, lotions, ointments, mouth wash tooth paste and eatables, are available separately or together in an oral health kit containing the said forms.
4. A method for therapeutic management of canker sore in mammals, said method comprising steps of administering an effective concentration of a composition containing tetrahydrocurcuminoids to mammals in need of such therapy, to bring about reduction in symptoms associated with canker sore.
5. The method as in claim 4, wherein the symptoms of canker sore include, but not limited to, throat pain, ulcer, lesion, throat numbness, sore throat, bleeding, swelling at the site, reddening at die site, inflammation at the site, burning , swelling and pain in lymph node, difficulty in chewing and difficulty in swallowing.
6. The method as in claim 4, wherein the composition is formulated with pharmaceutically, nutraceutically and cosmeceutically acceptable excipients, adjuvants, diluents or carriers and administered in the form of tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, creams, gels, lotions, ointments, mouth wash, tooth paste and eatables.
7. The formulation as in claim 6, wherein the tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, creams, gels, lotions, ointments, mouth wash tooth paste and eatables, are available separately or together in an oral health kit containing the said forms.
8. The method as in claim 4, wherein the mammal is preferably human.
9. A method for therapeutic management of gingivitis in mammals, said method comprising steps of administering an effective concentration of a composition containing tetrabydrocorcuminoids to mammals in need of such therapy, to bring about reduction in symptoms associated with gingivitis.
10. The method as in claim 9, wherein the symptoms of gingivitis include, but not limited to, taste acceptability, burning sensation, dryness, soreness, ulcer, staining of teeth and tongue, and allergy.
11. The method as in claim 9, wherein the composition is formulated with pharmaceutically, nutracenticaliy and cosmeceutically acceptable excipients, adjuvants, diluents or carriers and administered in the form of tablets, capsules, syrups, gtunmies, powders, suspensions, emulsions, chewables, candies, creams, gels, lotions, ointments, mouth wash, tooth paste and eatables.
12. The formulation as in claim 11 , wherein the tablets, capsules, syrups, gummies, powders, suspensions, emulsions, chewables, candies, creams, gels, lotions, ointments, mouth wash, tooth paste and eatables, are available separately or together in a oral health kit containing the said forms.
13. The method as in claim 9, wherein the mammal is preferably human.
PCT/US2018/028077 2018-04-18 2018-04-18 Compositions containing tetrahydrocurcuminoids for improvement of oral health and hygiene WO2019203813A1 (en)

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Citations (5)

* Cited by examiner, † Cited by third party
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US20100034757A1 (en) * 2006-11-24 2010-02-11 Mitsukiyo Fujii Extract powder of indigo plant, and its preparation and uses
US8182843B2 (en) * 2006-06-30 2012-05-22 Piramal Life Sciences Limited Herbal compositions for the treatment of diseases of the oral cavity
US20140275271A1 (en) * 2011-10-17 2014-09-18 The Research Foundation For The State University Of New York Novel modified curcumins and their uses
US8916139B2 (en) * 2010-04-09 2014-12-23 Conopco, Inc. Oral care compositions
US20170319642A1 (en) * 2014-10-27 2017-11-09 Fbm Indústria Farmacêutica Ltda. Soluble, stable, anti-inflammatory, proliferative, protective and mucoadhesive pharmaceutical compositions; use thereof for treating mucositis conditions and method for producing same; base pharmaceutical composition for preparing the pharmaceutical compositions and method for producing same

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8182843B2 (en) * 2006-06-30 2012-05-22 Piramal Life Sciences Limited Herbal compositions for the treatment of diseases of the oral cavity
US20100034757A1 (en) * 2006-11-24 2010-02-11 Mitsukiyo Fujii Extract powder of indigo plant, and its preparation and uses
US8916139B2 (en) * 2010-04-09 2014-12-23 Conopco, Inc. Oral care compositions
US20140275271A1 (en) * 2011-10-17 2014-09-18 The Research Foundation For The State University Of New York Novel modified curcumins and their uses
US20170319642A1 (en) * 2014-10-27 2017-11-09 Fbm Indústria Farmacêutica Ltda. Soluble, stable, anti-inflammatory, proliferative, protective and mucoadhesive pharmaceutical compositions; use thereof for treating mucositis conditions and method for producing same; base pharmaceutical composition for preparing the pharmaceutical compositions and method for producing same

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