EP4106869A1 - Collagen hydrolysate as active substance against periodontitis or gingivitis - Google Patents
Collagen hydrolysate as active substance against periodontitis or gingivitisInfo
- Publication number
- EP4106869A1 EP4106869A1 EP20839280.3A EP20839280A EP4106869A1 EP 4106869 A1 EP4106869 A1 EP 4106869A1 EP 20839280 A EP20839280 A EP 20839280A EP 4106869 A1 EP4106869 A1 EP 4106869A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- collagen hydrolyzate
- use according
- collagen
- hydrolyzate
- approx
- 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.)
- Pending
Links
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/01—Hydrolysed proteins; Derivatives thereof
- A61K38/012—Hydrolysed proteins; Derivatives thereof from animals
- A61K38/014—Hydrolysed proteins; Derivatives thereof from animals from connective tissue peptides, e.g. gelatin, collagen
-
- 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
- Collagen hydrolyzate as an active ingredient against periodontitis or gingivitis
- the present invention relates to collagen hydrolyzate for use as an active ingredient in the treatment and / or prevention of periodontitis or gingivitis.
- Periodontitis is an inflammation of the so-called tooth supporting apparatus, i.e. the entire tissue that holds the tooth in the jawbone is affected by this disease. Colloquially, but not medically correct, this disease is often referred to as periodontal disease.
- gingivitis is only an inflammation of the gums (gingiva) or the gum margin. Often, however, gingivitis is a preliminary stage of periodontitis and can develop into such, especially if it is not treated. Therefore, in the context of the present description, whenever a treatment or prevention of periodontitis is mentioned, it always includes treatment or prevention of gingivitis, unless the context indicates otherwise.
- Periodontitis can be acute, but very often it takes a chronic course. Since it is usually painless in the early stages, it is often recognized too late, often in patients between the ages of 40 and 50. Typical symptoms are redness, swelling, bleeding gums and receding gums. The latter leads to an increased sensitivity to pain in the exposed tooth necks. At a more advanced stage, periodontitis can lead to loosening of the teeth and ultimately to tooth loss. In addition to the negative and sometimes serious effects on the teeth holding apparatus or teeth, periodontitis can also have systemic effects. On the one hand, the inflamed tooth-supporting apparatus facilitates the penetration of pathogens into the bloodstream, and on the other hand, the inflammation-promoting messenger substances are poured out from the affected tissue. As a result, chronic periodontitis leads to a sometimes significantly increased risk of cardiovascular diseases, respiratory diseases, heart attacks and strokes.
- a causal treatment of periodontitis is not yet known.
- the course of the disease can, however, be contained, in particular by regular mechanical removal of supragingival and subgingival dental plaque, with surgical opening of the gums being necessary in the advanced stage. In some cases it is also advisable to administer antibiotics. Overall, this treatment of periodontal disease is lengthy and complex.
- the invention is based on the object of proposing an active substance for the treatment and / or prevention of periodontitis or gingivitis.
- collagen hydrolyzate is proposed as a corresponding active ingredient.
- the effectiveness of collagen hydrolyzate in the treatment of periodontal disease was clearly demonstrated on the basis of a double-blind, placebo-controlled clinical study, the results of which are presented in detail below.
- collagen hydrolyzate physiological effects have been known for a long time, especially in connection with osteoporosis or joint complaints. Positive effects of collagen hydrolyzate on the health of the skin have already been described, for example in the international patent application WO 2012/065782 A2. Nevertheless, the high effectiveness of collagen hydrolyzate in the treatment of periodontal disease is surprising.
- Collagen hydrolyzate is a degradation product of animal raw materials, which are also used as food, and is completely harmless to health and has no known harmful side effects. It does not require any legal approval as a medicinal product, but can, in particular, be placed on the market and used in the form of a dietary supplement.
- collagen hydrolyzate as a food supplement, as an over-the-counter drug (OTC) or as a prescription drug (in particular in combination with other active ingredients) is encompassed.
- OTC over-the-counter drug
- the collagen hydrolyzate is a therapeutic agent.
- the collagen hydrolyzate is conveniently administered orally. It is known that the peptides of the collagen hydrolyzate are at least to a certain extent absorbed in the intestine, even with relatively high molecular weights of up to 10,000 Da.
- the specific form of administration of the collagen hydrolyzate can be that of a powder, a solution, a tablet or a capsule.
- compositions are chewing gum, in particular based on compressed tablets, lozenges or similar products that remain in the mouth for a longer period of time, as well as drinkable mouthwashes.
- this type of administration also enables an intensive local action of the collagen hydrolyzate on the gums.
- the daily dose of the administered collagen hydrolyzate is favorably from approx. 1 to approx. 20 g, preferably from approx. 2 to approx. 15 g, more preferably from approx. 3 to approx. 10 g.
- An effectiveness could be shown in the clinical study with a daily dose of 5 g collagen hydrolyzate.
- a preferred embodiment of the invention relates to the treatment of periodontitis or gingivitis, ie the administration of the collagen hydrolyzate to a patient with a corresponding disease, in particular with chronic periodontitis.
- the administration particularly in the case of an advanced disease, is advantageously carried out in combination with another therapy for periodontal disease.
- This additional therapy includes, in particular, the mechanical removal of supragingival and subgingival plaque (biofilm and tartar). Even if the administration of collagen hydrolyzate according to the invention does not replace the removal of the plaque, it can positively influence the course of the disease and significantly reduce the symptoms and complaints of periodontitis. Under certain circumstances, a severe course of the disease, which ultimately also requires surgical measures, can be prevented by the administration of collagen hydrolyzate.
- Another embodiment of the invention relates to the prevention of periodontitis or gingivitis.
- it is particularly advantageous to administer collagen hydrolyzate to a patient who has one or more risk factors for these diseases.
- the risk factors for periodontitis include, in particular, a weakened immune system, tobacco smoke, hormonal changes (e.g. menopause) and certain genetic diseases (e.g. Down syndrome).
- Existing gingivitis can generally be viewed as a risk factor for periodontitis, so that treatment of gingivitis by administering collagen hydrolyzate is also a prevention of periodontitis.
- the collagen hydrolyzate as the active ingredient according to the invention typically has an average molecular weight of 500 to 15,000 Da, preferably 1,000 to 8,000 Da, more preferably 1,500 to 5,000 Da, most preferably 1,800 to 2,200 Da. This information always means the weight average molecular weight, which can be determined in particular by gel permeation chromatography.
- the collagen hydrolyzate is preferably produced by enzymatic hydrolysis of a collagen-containing starting material. Be for this hydrolysis in particular endopeptidases or exopeptidases of microbial or plant origin are used. By suitable selection of the peptidases and the hydrolysis conditions, collagen hydrolysates can be produced in the particular molecular weight range desired.
- the collagen-containing starting material is usually selected from the skin or bones of vertebrates, preferably from mammals or birds, and in particular from the skin of cattle or pigs (beef split or pig skin) or of sheep.
- the collagen-containing starting material can be selected from the skin, bones and / or scales of fish, in particular cold or warm water fish.
- the collagen hydrolyzate can either be produced in a one-step process from these starting materials or via the intermediate gelatin, in which case both type A and type B gelatin can be used.
- the collagen hydrolyzate is preferably produced by the successive action of at least two endoproteases with a different specificity, in particular of at least two different metalloproteases and / or serine proteases, ie of proteases which have the amino acid sequence of the collagen molecules before or after certain ami nosacids split.
- the metalloproteases and / or serine proteases are advantageously enzymes from the microorganisms Bacillus subtilis, Bacillus licheniformis, Bacillus amyloliquefaciens, Aspergillus oryzae and Aspergillus melleus.
- the collagen hydrolyzate can be produced in the context of the invention by recombinant gene expression.
- natural collagen sequences especially from cattle or pigs, and expressing them in genetically modified cells (e.g. yeast, bacteria or plant cells, especially tobacco)
- genetically modified cells e.g. yeast, bacteria or plant cells, especially tobacco
- products can be produced which are essentially identical to the hydrolysis products of the corresponding collagen-containing raw materials. It is possible, please include to keep a narrower or precisely predetermined molecular weight distribution.
- the present invention also relates to a therapeutic method for the treatment and / or prevention of periodontal disease or gingivitis, comprising the administration of collagen hydrolyzate to a patient. Advantages and preferred embodiments of this method have already been described in connection with the collagen hydrolyzate according to the invention.
- the double-blind, placebo-controlled clinical study was carried out at the Department of Periodontology at the University Hospital Würzburg with 43 patients who were receiving regular treatment there for existing periodontitis (removal of subgingival plaque two to four times a year). All study participants had at least three teeth with a gingival index of 1 or 2 (see below) and a probing depth of the gingival pockets of at least 3 mm. The participants were between 35 and 70 years old and had a BMI between 24 and 30. The participants were randomly divided into a treatment group with 23 patients and a placebo group with 20 patients, whereby neither the participants nor the treating staff were informed about the classification of the individual participants.
- the participants in the treatment group received a daily dose of 5 g collagen hydrolyzate for the entire study period of 90 ⁇ 14 days.
- VERISOL B 2,000 Da is used, which is sold by the applicant GELITA AG under the name VERISOL B.
- the production of VERISOL B essentially corresponds to the production process described in WO 2012/065782 A2.
- the participants in the placebo group received a corresponding daily dose of a placebo, which was indistinguishable from the collagen hydrolyzate in terms of packaging, texture and taste.
- PCR plaque control record
- Table 2 Plaque Control Record (PCR) The results show that the PCR decreased in all patients during the study period, but significantly more so in the participants in the treatment group than in the participants in the placebo group.
- the gingival index (Gl) results from the visual assessment of the acute inflammation of the gums on the buccal side according to the following scheme:
- Grade 1 color change of a gum area, but not the entire gumline or the gingival papilla
- Grade 2 color change that includes the entire gumline or the gingival papilla
- Grade 3 as in Grade 2, but pronounced reddening
- the gingival index Gl is the mean value of the indexes for all teeth.
- the test results for the gingival index are shown in Table 3 below.
- the PISA score indicates the extent of the periodontal inflamed surface area in mm 2 .
- the PISA score can be calculated from the parameters described above; the results are shown in Table 4 below.
- the gums are made up of gingival fibroblasts (gum cells) and the extracellular matrix formed by these cells, which contains various types of collagen and proteoglycans.
- gingival fibroblasts tissue cells
- the extracellular matrix formed by these cells which contains various types of collagen and proteoglycans.
- Stimulation of the synthesis of matrix proteins by the fibroblasts can thus counteract periodontitis or gingivitis.
- the human gingival fibroblasts were isolated from surgically removed gums by enzymatic digestion and cultivated in HAMs F12 medium, which was supplemented with 10% fetal calf serum, 20 U / ml penicillin-streptomycin and 50 pg / ml partricin. After a confluence of 80% had been reached, the culture medium was exchanged for fresh medium which had been supplemented with 0.5 mg / ml collagen hydrolyzate.
- the cell tests were carried out with three different collagen hydrolyzates: (1) a bovine collagen hydrolyzate with an average molecular weight of approx. 2,000 Da, which was also used in the above clinical study, (2) a porcine collagen hydrolyzate with an average molecular weight of approx. 3,000 Da and (3) a bovine collagen hydrolyzate with an average molecular weight of approx. 6,000 Da.
- the cells were harvested and lysed, and then the entire RNA was extracted and precipitated.
- Figure 1 Stimulation of the synthesis of matrix proteins by a bovine
- FIG. 2 Stimulation of the synthesis of matrix proteins by a porcine collagen hydrolyzate with approx. 3,000 Da; and
- Figure 3 Stimulation of the synthesis of matrix proteins by a bovine
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102020104279.5A DE102020104279A1 (en) | 2020-02-18 | 2020-02-18 | Collagen hydrolyzate as an active ingredient against periodontitis or gingivitis |
PCT/EP2020/086865 WO2021164925A1 (en) | 2020-02-18 | 2020-12-17 | Collagen hydrolysate as active substance against periodontitis or gingivitis |
Publications (1)
Publication Number | Publication Date |
---|---|
EP4106869A1 true EP4106869A1 (en) | 2022-12-28 |
Family
ID=74181122
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP20839280.3A Pending EP4106869A1 (en) | 2020-02-18 | 2020-12-17 | Collagen hydrolysate as active substance against periodontitis or gingivitis |
Country Status (11)
Country | Link |
---|---|
US (1) | US20220387545A1 (en) |
EP (1) | EP4106869A1 (en) |
JP (1) | JP2023515440A (en) |
KR (1) | KR20220143012A (en) |
CN (1) | CN115279457A (en) |
AU (1) | AU2020430016A1 (en) |
BR (1) | BR112022014640A2 (en) |
CA (1) | CA3168164A1 (en) |
DE (1) | DE102020104279A1 (en) |
MX (1) | MX2022009473A (en) |
WO (1) | WO2021164925A1 (en) |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2792202B1 (en) | 1999-04-19 | 2003-06-13 | Pharmascience Lab | LUPINE PEPTIDE EXTRACT AND PHARMACEUTICAL OR COSMETIC OR NUTRACEUTICAL COMPOSITION COMPRISING SUCH EXTRACT |
ITRM20010380A1 (en) | 2001-07-02 | 2003-01-02 | Bioprogress Spa | COMPOSITION INCLUDING PARTIALLY HYDROLYZED FISH JELLY AND THEIR USE. |
JP5732192B2 (en) * | 2009-10-14 | 2015-06-10 | 日本ゼトック株式会社 | Oral composition |
DE102010060564A1 (en) | 2010-11-15 | 2012-05-16 | Gelita Ag | Use of collagen hydrolyzate to improve the health of human skin, hair and / or nails |
US9347081B2 (en) * | 2011-04-19 | 2016-05-24 | Bioiberica, S.A. | Cartilage product |
DE102011055800A1 (en) * | 2011-11-29 | 2013-05-29 | Gelita Ag | Use of collagen hydrolyzate for treating and/or preventing cellulite, and as food supplement |
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2020
- 2020-02-18 DE DE102020104279.5A patent/DE102020104279A1/en not_active Withdrawn
- 2020-12-17 EP EP20839280.3A patent/EP4106869A1/en active Pending
- 2020-12-17 WO PCT/EP2020/086865 patent/WO2021164925A1/en unknown
- 2020-12-17 MX MX2022009473A patent/MX2022009473A/en unknown
- 2020-12-17 JP JP2022549539A patent/JP2023515440A/en active Pending
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- 2020-12-17 KR KR1020227026421A patent/KR20220143012A/en unknown
- 2020-12-17 CA CA3168164A patent/CA3168164A1/en active Pending
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- 2020-12-17 BR BR112022014640A patent/BR112022014640A2/en not_active Application Discontinuation
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2022
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DE102020104279A1 (en) | 2021-08-19 |
KR20220143012A (en) | 2022-10-24 |
WO2021164925A1 (en) | 2021-08-26 |
US20220387545A1 (en) | 2022-12-08 |
CA3168164A1 (en) | 2021-08-26 |
AU2020430016A1 (en) | 2022-08-25 |
MX2022009473A (en) | 2022-08-22 |
CN115279457A (en) | 2022-11-01 |
BR112022014640A2 (en) | 2022-09-13 |
JP2023515440A (en) | 2023-04-13 |
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