EP2349199A2 - Pharmaceutical composition for the treatment of periodontal diseases - Google Patents
Pharmaceutical composition for the treatment of periodontal diseasesInfo
- Publication number
- EP2349199A2 EP2349199A2 EP09737192A EP09737192A EP2349199A2 EP 2349199 A2 EP2349199 A2 EP 2349199A2 EP 09737192 A EP09737192 A EP 09737192A EP 09737192 A EP09737192 A EP 09737192A EP 2349199 A2 EP2349199 A2 EP 2349199A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- mass
- pharmaceutical composition
- treatment
- human
- periodontal
- Prior art date
- Legal status (The legal status 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 status listed.)
- Withdrawn
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0063—Periodont
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/55—Protease inhibitors
- A61K38/56—Protease inhibitors from plants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/55—Protease inhibitors
- A61K38/57—Protease inhibitors from animals; from humans
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
Definitions
- composition for the treatment of periodontal diseases is provided.
- the subject of the present invention is a pharmaceutical composition for the treatment of periodontal disease during both walk-in and hospitalized dentistry, as well as in dental surgery.
- Periodontitis does not only concern older persons, but also 20 and 30-year olds, and a number of forms are observed in children as well, and constitute the most common cause of tooth loss.
- Statistical analyses show that inflammatory changes of the gums constitute the most serious cause of tooth loss, and some 60% of the population of the European Union suffers from this problem. This is most often caused by improper oral hygiene and leads to plaque formation, which may be a cause of gingivitis.
- Periodontitis is aided by some genetic factors, smoking, cavities, over or under-bites, poorly set fillings, hormonal disruptions, the activity of certain drugs or heavy metal poisoning.
- teeth are supported by the gum, the periodontium or connective tissue between the tooth and the jaw, as well as the jaw bone.
- the periodontal apparatus is susceptible to inflammation, chiefly due to improper oral hygiene.
- Periodontal disease including gingivitis
- gingivitis leads to a disappearance of tissues around the teeth. In most cases, they disappear and leave the neck of the tooth exposed. The disease develops slowly, and symptoms may include bleeding during brushing or flossing, reddened gums, receding gums or plaque. When these problems are not observed sufficiently early, this leads to osteological changes in periodontium, which is evidenced by its increased mobility. The cause of changes in the gums and the bone surrounding the tooth is inflammation. Bacteria accrue in the periodontal space, which cause inflammation, whence the teeth begin to move and fall out. Inflammation is caused by bacteria which settle on the surface of the root of the tooth, which develop underneath the gum, and the inflammation progresses deeper.
- Cystatin S in saliva inhibits the development of P. gingivalis as well as the activity of cysteine endopeptidases secreted by periodontal bacteria as well as egg protein inhibitors which inhibit the growth of P. gingivalis in vitro in gingival crevice fluid.
- Bokenvoorde MFJ. Henskens Wim van 't Hot YMC, Amerongen AV N. (1996): Inhibition of the growth and cysteine proteinase activity of porphyromonas gingivalis by human salivary cystatin S and chicken cystatin. Biol. Chern. 377, 847-850).
- Three cystatins have been isolated from human saliva so far, which are produced in the salivary glands.
- a curettage is performed. This consists of scraping off the plaque. Bacteria and diseased tissues are thus removed, and the periodontium can heal and regenerate, thus form new tissue. If the disease has destroyed most of the periodontium, and the teeth are poorly held in the bone, they can be bridged, or stiffened. In this procedure, the teeth are connected to one another using various techniques. This may consist of a ligature, or special wires, or a bridging prosthesis, or splints of a composite material. Such a stiff structure of connected teeth stops them from swinging too much. When the wounds in the gums have healed and the periodontium has regenerated, these may be removed.
- the goal of surgical treatment is to remove disease-altered tissues as well as their regeneration or reformation.
- a periodontologist has in his arsenal several treatment methods including: root-to-crown, controlled tissue regeneration using implantable barrier membranes, bone grafts of human or animal bone or natural or synthetic bioglass.
- new tissue is formed which is a copy of the natural one, both in terms of structure and functionality.
- Of paramount importance is the reconstruction of adhesive function, of the periodontal attachments.
- a novel preparation, emdogain gives some hope. It contains enamel proteins, the so-called hydrophobic proteins, which stimulate the regeneration of tissues.
- cysteine peptidase inhibitors are used in the form of preparations purified from various sources, including egg proteins in a composition with vitamins K and D, and the fundamental goal is to rebuild a degraded periodontium and bony periodontal fragments, including the root degraded during periodontitis ( Takada Y., Atsushi Serizawa A., Hidetoshi Ishikawa H., Tomoe Y.,_ Seiichiro Aoe S. (2003) P USA 420102. Bone resorption suppressing agent. Reynolds EC, Bhogal PS., Slakeski N. (2003): Diagnostics and treatments of periodontal disease. P USA 66330 ).
- Polish patent No. 148352 reveals an agent for the treatment of advanced periodontitis in the form of a cellulose derivative at 3 - 7 % by mass, with a polyhydroxyl alcohol or a polymer thereof at 1 - 5% by mass, with an addition of 0.25 % by mass of Kunitz protease inhibitor and water to 100% by mass.
- This complex is a hydrophilic gel with thixotropic properties and a high flow threshold, due to which it may be considered a pseudoplastic substance, which makes it resistant to the activity of mechanical factors such as the activity of saliva, beverages and food.
- Polish patent No. 164585 reveals a therapeutic agent for use in dental surgery, composed of 10-50% gelatin by mass, 2 - 50 % glycerol by mass, or 1.2-propylene glycol, or polyoxyethylene glycol with a molar mass of 200-15000 as well as 1 - 25% by mass of polyvinylpyrolidone with a molar mass of 160000-360000, or polyvinyl alcohol and water to 100% by mass.
- This substance is dosed into wounds, where it becomes hydrolysed by systemic enzymes, and the hydrolysis products comprising amino acids are resorbed. As the bone becomes replenished, the therapeutic agent diminishes in volume, so it requires no replacement.
- gelatin a substance of animal origin, ensures resorption due to hydrolysis into amino-acids.
- Polyvinyl alcohol and polyvinylpyrolidone are also metabolised in the human.
- the release of therapeutically active substances into the tissues follows a zero-order kinetic process, which ensures a constant concentration of the drug in the tissue.
- Polish patent No. 311322 releases a dental gel containing 70-90% by mass of a carrier, composed of water physiological saline and a moisturizer, preferentially hydroxyethylcellulose, a plant extract containing tannins and 0.1-5% by mass of sweeteners and aromas.
- This gel also contains a composition comprising antibiotics such as dethreomycine, colistine, clindamycine in a mass percentage ratio of 1:0.23:5, a steroid anti-inflammatory substance, particularly hydrocortisone at 0.02-1% by mass as well as a plant extract, preferentially of Bergenia, at 1-5 % by mass.
- the dental gel according to the application in question is useful in the treatment of periodontitis.
- the present invention relaters to a pharmaceutical composition for the treatment of periodontitis containing at least gel-forming substances.
- the active substance of the composition is a cysteine protease inhibitor from egg proteins, urine, human and animal amniotic fluid, human and animal placentae, and from plants, which is suspended in 50 g of a polyhydroxyl alcohol, preferentially glycerol, and 50 g of a 0.05 M phosphate buffer solution , pH 6.0 to 7.5, which constitutes a base for the composition in an amount from 20 to 50% by mass, whereas the carrier comprises gelling substances at 7 to 20 % by mass as well as water to 100 % by mass.
- the gelling substances comprise methylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose sodium salt, gelatin, apple- citrus pectin, dextran or a mixture thereof.
- the composition contains additives in the form of polyhydroxyl alcohols such as glycerol, polyvinylpirolidone K-30 or K-90, polyoxyethylene glycol-200 or glycol propylene-1,2 at 5 to 25 % by mass.
- polyhydroxyl alcohols such as glycerol, polyvinylpirolidone K-30 or K-90, polyoxyethylene glycol-200 or glycol propylene-1,2 at 5 to 25 % by mass.
- a preservative is included in the composition, preferentially in the form of Nipagin.
- compositions in the example sets were used in tests of their ability to treat periodentosis.
- the observation showed that the activity of cysteine proteases was inhibited in the gingival crevices by specific inhibitors obtained from chicken eggs.
- the determinations were made on a 30-patient group at the Facial and Jaw clinic of the Medical Academy of Wroclaw. Gingival crevice fluid was collected from two distant crevices from a patient, and then cysteine peptidase activity was quantified, and then inhibited with cystein protease inhibitors. The inhibition exceeded 90%.
- these inhibitors are suitable for treatment of periodontal inflammations by using appropriate compositions thereof administered directly into periodontal crevices and in mouthwashes for periodontitis patients.
- compositions using cysteine peptidase inhibitors are easily obtained and inexpensive.
- the research also indicates the possibility of using other sources of inhibitors in novel drugs, provided that they are not toxic to the human.
- the research was performed in vitro in fluid collected from the periodontal crevices of patients with diagnosed periodontitis.
- the base which is also an active substance of the composition, composed of the cysteine peptidase inhibitor, polyhydroxyl alcohol and phosphate buffer solution of an appropriate pH may be maintained at 4°C for up to 12 months.
- compositions according to the invention are suitable for both prophylaxis as well as in curettage or surgical treatment as a supplemental treatment.
- the subject of the present invention is shown in example embodiments.
- BASE cysteine peptidase inhibitor, 1-50 activity units suspended in 50 g glycerol, and 50 g 0.05 M phosphate buffer solution pH 6.0 to 7.5 30.0
- Nipagin (Aseptins, Parabens) 0.1 Water 48.
- composition base is prepared by mixing the planned quantities of its components, meaning an appropriate number of units of the cysteine peptidase inhibitor with the polyhydroxyl alcohol and 0.05M phosphate buffer solution with a selected pH. in the range of 6.0 to 7.5.
- the base is apportioned into plastic or glass containers, and stored, preferentially at 4°C.
- the measured quantity of base is supplemented with the given quantities of the remaining components and mixed until homogeneity.
- the gel produced, with a viscosity of 337.53 mPa*s is apportioned into 20 or 50 ml containers.
- the example composition is meant for rinsing the jaw pocket.
- Example composition is produced as in Example 1, by first selecting the components, and then apportioning in the same way.
- the example composition is produced as in Example 1, by first selecting the components, and then apportioning in the same way.
- the example composition is produced as in Example 1, by first selecting the components, and then apportioning in the same way.
- the example composition is produced as in Example 1, by first selecting the components, and then apportioning in the same way.
- the example composition is produced as in Example 1, by first selecting the components, and then apportioning in the same way.
- Table 1 Inhibition of cysteine peptidases in the gingival crevice fluid by egg protein cystatins using a colorimetric method.
- Table 2 Inhibition of cysteine peptidases in gingival crevice fluid by egg protein cystatins (5 ⁇ g ). Inhibitor activity (180 imEU/mg protein) using spectrofluorometry.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- General Chemical & Material Sciences (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Zoology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Botany (AREA)
- Cosmetics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PL385972A PL219098B1 (en) | 2008-08-28 | 2008-08-28 | Pharmaceutical composition for therapy of parodonthium deseases |
PCT/PL2009/050024 WO2010024702A2 (en) | 2008-08-28 | 2009-08-28 | Pharmaceutical composition for the treatment of periodontal diseases |
Publications (1)
Publication Number | Publication Date |
---|---|
EP2349199A2 true EP2349199A2 (en) | 2011-08-03 |
Family
ID=41343718
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP09737192A Withdrawn EP2349199A2 (en) | 2008-08-28 | 2009-08-28 | Pharmaceutical composition for the treatment of periodontal diseases |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP2349199A2 (en) |
PL (1) | PL219098B1 (en) |
WO (1) | WO2010024702A2 (en) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012113037A1 (en) * | 2011-02-25 | 2012-08-30 | The University Of Melbourne | Method for inhibiting proteins |
RU2606040C2 (en) * | 2015-04-01 | 2017-01-10 | Ирина Николаевна Усманова | Method for treating chronic inflammation of paradentium tissues and mucous membrane with hyperkeratosis in young individuals |
RU2637413C1 (en) * | 2016-07-04 | 2017-12-04 | Ирина Николаевна Усманова | Method for treatment of oral mucosa chronic inflammation with hyperkeratosis elements in young persons |
PL239917B1 (en) * | 2018-11-28 | 2022-01-24 | Univ Medyczny Im Piastow Slaskich We Wroclawiu | Implantological composition containing cystatin and its composition in bone implantology |
WO2020167152A1 (en) * | 2019-02-15 | 2020-08-20 | RAPAK, Andrzej Marek | Inhibitors of cysteine peptidases isolated from natural raw materials and use of the inhibitors in medicine and veterinary medicine |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4592127B2 (en) * | 1999-03-30 | 2010-12-01 | 雪印乳業株式会社 | Bone resorption inhibitor |
PL190404B1 (en) * | 1999-08-02 | 2005-12-30 | Akad Medyczna | Pharmacological agent effectively acting against neoplasms, pathogenic micro-organisms and invasive diseases |
PL195665B1 (en) * | 2000-06-13 | 2007-10-31 | Przed Farmaceutyczne Jelfa Sa | Pharmacological agent for local application in treating parodontium diseases |
US8283135B2 (en) * | 2000-06-30 | 2012-10-09 | The Procter & Gamble Company | Oral care compositions containing combinations of anti-bacterial and host-response modulating agents |
-
2008
- 2008-08-28 PL PL385972A patent/PL219098B1/en unknown
-
2009
- 2009-08-28 WO PCT/PL2009/050024 patent/WO2010024702A2/en active Application Filing
- 2009-08-28 EP EP09737192A patent/EP2349199A2/en not_active Withdrawn
Non-Patent Citations (1)
Title |
---|
See references of WO2010024702A2 * |
Also Published As
Publication number | Publication date |
---|---|
PL385972A1 (en) | 2010-03-01 |
PL219098B1 (en) | 2015-03-31 |
WO2010024702A3 (en) | 2011-06-03 |
WO2010024702A2 (en) | 2010-03-04 |
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Legal Events
Date | Code | Title | Description |
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PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
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AK | Designated contracting states |
Kind code of ref document: A2 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK SM TR |
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AX | Request for extension of the european patent |
Extension state: AL BA RS |
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RIN1 | Information on inventor provided before grant (corrected) |
Inventor name: TRZISZKA, TADEUSZ Inventor name: BRYJAK, MAREK Inventor name: SEBZDA, TADEUSZ Inventor name: NIENARTOWICZ, JAN Inventor name: MALOLEPSZA-JARMOLOWSKA, KATARZYNA Inventor name: WNUKIEWICZ, BEATA Inventor name: WNUKIEWICZ, JAN Inventor name: SIEWINSKI, MACIEJ |
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RIN1 | Information on inventor provided before grant (corrected) |
Inventor name: TRZISZKA, TADEUSZ Inventor name: BRYJAK, MAREK Inventor name: SEBZDA, TADEUSZ Inventor name: NIENARTOWICZ, JAN Inventor name: MALOLEPSZA-JARMOLOWSKA, KATARZYNA Inventor name: WNUKIEWICZ, BEATA Inventor name: WNUKIEWICZ, JAN Inventor name: SIEWINSKI, MACIEJ |
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17P | Request for examination filed |
Effective date: 20111205 |
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RBV | Designated contracting states (corrected) |
Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK SM TR |
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DAX | Request for extension of the european patent (deleted) | ||
17Q | First examination report despatched |
Effective date: 20120522 |
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STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
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18D | Application deemed to be withdrawn |
Effective date: 20160301 |