• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    The present invention relates to a pharmaceutical composition comprising tocopherols and / or tocotrienols, ascorbic acid, polyphenols and pharmaceutically acceptable excipients and / or diluents, it further relates to the use of the pharmaceutical composition in the prevention or treatment of gingivitis or periodontitis in humans or animals, to a method of preparing the pharmaceutical composition and / or a kit comprising the pharmaceutical composition.
    公开号:BE1020183A3
    申请号:E2011/0484
    申请日:2011-08-05
    公开日:2013-06-04
    发明作者:Eric Jan Ostwald
    申请人:Eric Jan Ostwald；
    IPC主号:
    专利说明:

    PHARMACEUTICAL COMPOSITION FOR USE IN PREVENTION AND TREATMENT OF GINGIVITIS AND PARODONTITIS
    Field of the invention
    The present invention relates to a pharmaceutical composition comprising tocopherols and / or tocotrienols, ascorbic acid, polyphenols and pharmaceutically acceptable excipients and / or diluents. The invention further relates to a method for preparing such pharmaceutical compositions, to the use of such a pharmaceutical composition in the treatment or prevention of gingivitis or periodontitis in humans or animals, and to a kit comprising such a pharmaceutical composition.
    BACKGROUND OF THE INVENTION
    Any inflammatory response of tissue in an organism can be considered as a response to tissue damage caused by chemical physical or biological factors. The purpose of such a reaction is to eliminate the cause of these reactions and to create suitable conditions for repairing the damaged tissue.
    During inflammation of a tissue, so-called polymorphic nuclear leukocytes produce a significant amount of free oxygen radicals. These radicals disturb the balance between the oxidative and anti-oxidative processes. Because of this imbalance, fibroblasts are stimulated to make collagenases, which leads to the breakdown of collagen fibers in the inflamed area {Brenneisen et al., Hydrogen peroxide (H202) increases the steady-state mRNA levels of collagenease / MMP -1 in human dermal fibroblasts. Free Radie Biol Med 1997: 22: 515-524).
    Furthermore, many of the inflammatory cells die and enzymes are released such as catpsin and gelatinicine or elastases. These enzymes are capable of breaking down various proteins in connective tissue, causing even more damage.
    The living cells (and extra cellular space) have certain protective mechanisms against oxidative processes. The two most important protective mechanisms are enzymes that break down free oxygen radicals, for example catalase, and the presence of anti-oxidative micronutrients in the area of the damaged tissue.
    One of the most important anti-oxidative micronutrients is ascorbic acid (vitamin C). This compound is essential for the hydroxylation of proline and lysine and is therefore critical for the formation of collagen fibers. As has been shown in various studies, a low serum concentration of ascorbic acid gives a greater chance of developing periodontitis. (Nishida et al, Dietary vitamin C and the risk for periodontal disease. J. Peridontol. 2000: 71: 1215-1223; Amaliya et al., Java project on periodontal diseases: the relationship between vitamin C and the severity of peridontitis. J Clin Peridontol 2007: 34: 299-304). However, the use of other anti-oxidative micronutrients or combinations of micronutrients for the prevention or treatment of periodontitis has not previously been extensively studied.
    The individual use of polyphenols for use in the treatment of periodontitis has been described in the literature (Makimura et al., Inhibitory effect or tea catechins on collagenesis activity. J. Peridontol 1993: 64: 630-636). However, the results obtained were poor. A combination therapy of polyphenols with, for example, anti-oxidative micronutrients such as ascorbic acid has not been previously investigated.
    A clinical and experimental study has shown that cholecalciferol (vitamin D) can play an important role in the prevention of periodontitis {Krall et al, Calcium and vitamin D supplements reduce tooth loss in the elderly. Am. J. Med. 2001: 111: 452-456). The effect of cholecalciferol is probably not only based on the prevention of degradation of peridonal bone, but also on its anti-microbial function (Jagelaviciene et al., The relationship between general osteoporosis and the organism and periodontal diseases. Medicina Kaunas 2006: 42: 613-618).
    Although different approaches have been followed to find a way to prevent or treat gingivitis or periodontitis, the results obtained to date are relatively poor. So there is still a need for a product that can prevent or treat gingivitis or periodontitis.
    Detailed description of the invention
    As indicated above, a balanced pharmaceutical composition that can be used for the prevention or treatment of gingivitis or periodontitis has not been previously described, let alone that it has already been marketed. It is therefore an object of the present invention to provide a medicament that can be used for the prevention or treatment of gingivitis or periodontitis. The term pharmaceutical composition used in the present application means a composition suitable for human and animal use and capable of initiating a health-promoting reaction in or on the human or animal body. A nutritional supplement with the above-described properties would thus fall within the scope of the present invention.
    A first aspect of the present invention relates to a pharmaceutical composition comprising: - 2 to 25% by weight of tocopherols and / or tocotrienols; 15 to 40 wt% ascorbic acid; - 5 to 30% by weight of polyphenols; 15 to 30% by weight of pharmaceutically acceptable excipients and / or diluents
    As can be seen from the experimental part below, a surprisingly large reduction is achieved with the composition of the present invention in preventing bleeding of the gingiva. Reducing such bleeding is generally considered as an indication that the tissue is recovering from, for example, periodontitis. It will be appreciated that the composition of the present invention is capable of preventing or treating gingivitis or periodontitis.
    Although some of the components of the present invention have been previously used or tested for their efficacy in the prevention or treatment of gingivitis or periodontitis, they have never been used in combination before. In addition, the efficacy of the components individually is considerably lower than the efficacy of the composition of the present invention. In other words, there is a synergistic effect between the components of the claimed composition when it is used for the prevention or treatment of gingivitis or periodontitis.
    The ascorbic acid used in the composition of the present invention is believed to further improve the beneficial effect of tocopherols and / or tocotrienols. It helps with the regeneration of tocopherols and / or tocotrienols radicals and thereby improves the antioxidant effect of tocopherols and / or tocotrienols. (Nikt, Action of ascorbic acid as a scavenger or active and stable oxygen radicals, The American Journal of Clinical Nutrition, 1991; 54: 1119S-24S).
    Preferably, the tocopherols used are alpha, beta, gamma, or delta tocopherols, or a mixture thereof. The polyphenols that are used are preferably derived from a green tea extract.
    In addition to the aforementioned ingredients, the composition of the present invention may also preferably include cholecalciferol. The amount of cholecalciferol used in the composition is preferably 0.001% to 0.5% by weight. The presence of cholecalciferol in the composition of the invention is particularly relevant when the composition is used by humans. In general, the human diet does not include sufficient amounts of cholecalciferol. Serum cholecalciferol levels in humans are relatively low, particularly in winter. Generally, the animal diet includes more than enough cholecalciferol and additional addition thereof is usually not necessary.
    In a composition that is particularly suitable for use in animals, 5 to 10% by weight of curcuma longa extract is used. The Biocurcumax product is preferably used, although other curcuma longa extracts can also be used. The advantage of using Biocurcumax is that its bioavailability is very good. In addition to the curcuma longa, the composition which is particularly suitable for animals comprises 15 to 45% by weight, preferably 20-30% by weight of SAMe (S-adenosylmethionine). It is further preferred to also add to this composition 0.1 to 3% by weight of zinc and / or traces of selenium. The amount of selenium that is used is preferably 0.0001% by weight to 0.01% by weight.
    In a very preferred embodiment of the present composition for use in animals, although it can also be administered to humans, the composition comprises 2-5% by weight of tocopherols and / or tocotrienols, 10-20% by weight of ascorbic acid, 5-15% by weight % polyphenols, 20-30% by weight of exipients and / or diluents, 5-10% by weight of curcuma longa extract and 30-45% by weight (S-adenosylmethionine. Preferably, the composition also comprises 0.1-3% by weight of zinc or salts thereof and optionally traces of selenium If the composition described above is administered to humans, the composition optionally also comprises 0.1-1% by weight of cholecalciferol.
    In a preferred embodiment of the present invention for use in humans, the composition comprises 20-25% by weight of tocopherols and / or tocotrienols, 30-40% by weight of ascorbic acid, 20-30% by weight of polyphenols, 15-25% by weight of pharmaceutically acceptable excipients and / or diluents and optionally 0.1-1 wt% cholecalciferol.
    In a further preferred embodiment, the above-described human composition may also include S-adenosylmethionine. In such a composition, preferably 15-45% by weight, more preferably 20-30% by weight of S-adenosylmethionine is used.
    The composition of the invention may also include excipients and / or diluents to make a formulation that can be administered or easily applied and remains stable over a longer period of time. Exipients used in pharmaceutical composition according to the present invention are preferably microcrystalline cellulose, hydroxypropyl cellulose, magnesium stearate, or stearic acid. However, it is also possible to use other similar exipients, such as described in The Handbook of Pharmaceutical Excipients or Rowe et al., 2006.
    The composition is preferably formulated as a tablet, sugar-coated pill, capsule, pastille, liquid, drinkable suspension, or ointment. It is most preferred to formulate the composition as a tablet.
    Preferably, the human or animal patients are administered a total daily dosage of 10-200 mg / kg body weight of the composition, preferably 25-150 mg / kg body weight, most preferably 75-125 mg / kg body weight. This total daily dosage is preferably prepared via once or twice daily administration of the pharmaceutical composition according to the invention.
    A particularly preferred single dosage unit of the invention for humans comprises 400 mg to 2000 mg, preferably 500 mg to 1250 mg, most preferably about 1000 mg.
    Another unit dosage of the composition of the present invention, which may be particularly suitable for administration to animals, for example (dogs and cats), although it may also be administered to humans, comprises 200 to 1000 mg, preferably 300 to 600 mg, most preferably about 550 mg.
    It is particularly preferred to administer the composition of the present invention to humans or animals that have a history of gingivitis or periodontitis. A second aspect of the invention relates to a method for preparing a pharmaceutical composition as described above.
    A third aspect of the present invention of the present invention relates to a kit comprising the pharmaceutical composition described above. The kit preferably comprises a blister pack (blister pack) or a container, such as for example a bottle.
    The invention will now be further described with reference to the non-limiting examples.
    EXAMPLES
    Material and methods
    The pharmaceutical composition of the present invention was tested on 32 patients suffering from periodontitis. The patients were between 18 and 65 years old and had at least eight peridontal pockets of 4 mm or more, spread over at least four dentition elements. Exclusion criteria were diabetes mellitus, renal insufficiency, pregnancy, use of anticoagulants and regular use of immunosuppressive drugs.
    All patients received the same instructions for dental care and also received the same toothpaste. The patients administered themselves or the composition according to the invention or a placebo. The total daily dosage of the active ingredients of the pharmaceutical composition used was: - 200 mg of D, L alpha-tocopherol acetate; - 600 mg ascorbic acid; 10 micrograms of cholecalciferol; - 400 mg of green tea extract, 98%. Polyphenols.
    This total daily dose was divided into four single dose units, namely capsules. Two capsules were taken in the morning 7 BE 2011/0484 and two in the evening. The capsules with the pharmaceutical composition according to the invention could not be visually distinguished from the placebo capsules.
    Preventing bleeding of the gingiva as well as the amount and depth of the peridontal pockets was determined prior to the study by dentists. This was done again three months and six months after the composition was used. A clear improvement was defined as a decrease in the amount of gingival bleeding or as a reduction in the sum of the pocket depth by at least 40%. The so-called one-tailed t test was used for statistical analysis.
    Results
    After six months, the amount of gingiva bleeding in patients treated with the composition of the present invention decreased by 46% compared to 27% in the placebo group. In the group that received the composition according to the invention, 38% of the patients showed a significant decrease in the added pocket size. In the placebo group this decrease was only 12.5%. The results clearly demonstrate the beneficial effects of the composition of the present invention.
    权利要求:
    Claims (18)
    [1]
    A pharmaceutical composition comprising: - 2 to 25% by weight of tocopherols and / or tocotrienols; - 15 to 40% by weight of ascorbic acid; - 5 to 30 wt% polyphenols; and - 15 to 30% by weight of pharmaceutically acceptable excipients and / or diluents.
    [2]
    The pharmaceutical composition of claim 1, further comprising 0.01 and 0.5% by weight of cholecalciferol.
    [3]
    The pharmaceutical composition of claim 1, further comprising 5 to 10% by weight of curcuma longa extract.
    [4]
    Pharmaceutical composition according to any of claims 1-3, further comprising 15-45% by weight of S-adenosylmethionine, preferably 20-30% by weight of S-adenosylmethionine.
    [5]
    The pharmaceutical composition according to claim 3 or 4, further comprising 0.1 to 3% by weight of zinc or salts thereof and / or traces of selenium.
    [6]
    Pharmaceutical composition according to any of claims 1-5, wherein the polyphenols are obtained from a green tea extract.
    [7]
    A pharmaceutical composition according to any of claims 1-6, wherein the tocopherols are alpha, beta, gamma or delta tocopherol, or a mixture thereof.
    [8]
    A pharmaceutical composition according to any of claims 1-7, wherein the excipients used are selected from the group consisting of microcrystalline cellulose, hydroxypropyl cellulose, magnesium stearate, or stearic acid.
    [9]
    A pharmaceutical composition according to any of claims 1-8, wherein the composition is formulated as a tablet, a sugar-coated capsule, pastille, liquid or drinkable suspension or ointment.
    [10]
    A pharmaceutical composition according to any of claims 1-9, for use in the prevention and treatment of gingivitis or periodontitis in humans or animals.
    [11]
    A pharmaceutical composition according to claim 10, wherein the human or animal patients are administered a total daily dose of 10-200 mg / kg body weight of the composition, preferably 25-150 mg / kg body weight, most preferably 75-125 mg / kg.
    [12]
    A pharmaceutical composition according to claim 10 or 11, wherein the pharmaceutical composition is administered once or twice a day.
    [13]
    A pharmaceutical composition according to any of claims 10-12, wherein a unit dosage for humans comprises 400 mg to 2000 mg, preferably 500 to 1250 mg and most preferably about 1000 mg.
    [14]
    A pharmaceutical composition according to any of claims 10-12, wherein a unit dose for animals comprises 200 to 1000 mg, preferably 300 to 600 mg, most preferably about 550 mg.
    [15]
    The pharmaceutical composition according to any of claims 10-14, wherein the composition is administered to people who have a history of suffering from gingivitis or periodontitis.
    [16]
    A method for manufacturing a pharmaceutical composition according to any of claims 1-9.
    [17]
    A kit comprising a pharmaceutical composition according to any of claims 1-9.
    [18]
    The kit of claim 17, wherein the kit is a blister pack or a container.
    类似技术:
    公开号 | 公开日 | 专利标题
    US6716451B1|2004-04-06|Formulation and delivery method to enhance antioxidant potency of vitamin E
    US20180369228A1|2018-12-27|Combination of laquinimod and pridopidine for treating neurodegenerative disorders, in particular huntington's disease
    JPH11302142A|1999-11-02|Food composition for prevention and treatment of periodontal disease, oral composition and pharmaceutical composition
    KR20000075919A|2000-12-26|Method of suppressing tumor growth with combinations of isoprenoids and statins
    EP1640001A1|2006-03-29|Composition against cardiovascular diseases
    Kennedy et al.2007|Modulation of cognitive performance following single doses of 120 mg Ginkgo biloba extract administered to healthy young volunteers
    KR20120046795A|2012-05-10|Method of treatment of neurodegenerative or neuro-muscular degenerative diseases and therapeutic agent to treat the same
    BE1020183A3|2013-06-04|PHARMACEUTICAL COMPOSITION FOR USE IN THE TREATMENT AND PREVENTION OF GINGIVITIS AND PARODONTITIS.
    US20190091274A1|2019-03-28|Maca compositions and methods of use
    US20020120001A1|2002-08-29|Compositions containing tryptamines, cartenoids and tocotrienols and having synergistic antioxidant effect
    US10668121B2|2020-06-02|Dietary supplements for treating ADHD and related disorders
    US10391139B2|2019-08-27|Blood pressure reduction with dietary supplements
    WO2021205975A1|2021-10-14|Composition for suppressing cellular senescence, and method for suppressing cellular senescence
    RU2414231C1|2011-03-20|Antioxidant
    CN101449818A|2009-06-10|Medicine composition capable of delaying female aging and preparation method thereof
    RU2414828C2|2011-03-27|Composition for immune system activation
    JP2006232815A|2006-09-07|Medicine composition for increasing blood coq10 amount
    KR20020069539A|2002-09-05|Composition for healthy brain
    WO2021154773A1|2021-08-05|Method of improving resilience and recovery in healthy mammals
    Morita et al.2014|Association Between Oxidative Stress and Periodontal Diseases in Animal Model Studies
    EP2341923A2|2011-07-13|Pharmaceutical composition comprising coenzyme q10
    同族专利:
    公开号 | 公开日
    NL2005194C2|2012-02-07|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    EP1072254A1|1998-04-24|2001-01-31|Sunstar Inc.|Food compositions, compositions for oral cavity and medicinal compositions for preventing or treating periodontosis and method for preventing or treating periodontosis|
    JP2002029953A|2000-07-19|2002-01-29|Sunstar Inc|Food composition and composition for oral cavity for prophylaxis or treatment of periodontal disease|
    DE10257478A1|2002-12-09|2004-07-08|Dahlhaus, Ulrich, Dr.|Composition containing antioxidants and micronutrients, useful for treatment or prevention of paradontitis and associated disorders, also osteoporosis|
    JP2005112852A|2003-09-19|2005-04-28|Sunstar Inc|Internal medicinal composition for inhibiting gingival inflammation and periodontal membrane loss|
    US20060134014A1|2004-12-22|2006-06-22|Dale Scherl|Method to promote oral health in companion animals|
    JP5384777B2|2001-12-18|2014-01-08|有限会社大長企画|Strong muscle agent, anti-inflammatory agent|
    JP2005533864A|2002-07-26|2005-11-10|ディーエスエムアイピーアセッツビー．ブイ．|Composition comprising lactoferrin|
    AU2003256095A1|2002-07-31|2004-02-16|Bon-Gil Koo|Liquid composition for protecting oral cavities and teeth of pet animals and use thereof in plaything for pet animals|
    CN1615744A|2004-12-08|2005-05-18|肖新房|Health food for delaying senility|
    WO2006069662A1|2004-12-31|2006-07-06|Dsm Ip Assets B.V.|Pet food|
    WO2008025468A1|2006-08-31|2008-03-06|Dsm Ip Assets B.V.|Oral care effervescent composition|AU2014247122B2|2013-04-05|2018-12-06|Société des Produits Nestlé S.A.|Compositions for use in stimulating bone growth|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    NL2005194|2010-08-05|
    NL2005194A|NL2005194C2|2010-08-05|2010-08-05|Pharmaceutical composition for use in the prevention and treatment of gingivitis and parodontitis.|
    [返回顶部]