IL102313A - Method for inhibiting growth of helicobacter pylori - Google Patents
Method for inhibiting growth of helicobacter pyloriInfo
- Publication number
- IL102313A IL102313A IL10231392A IL10231392A IL102313A IL 102313 A IL102313 A IL 102313A IL 10231392 A IL10231392 A IL 10231392A IL 10231392 A IL10231392 A IL 10231392A IL 102313 A IL102313 A IL 102313A
- Authority
- IL
- Israel
- Prior art keywords
- helicobacter pylori
- pharmaceutical composition
- solution
- growth
- extract
- Prior art date
Links
- 241000590002 Helicobacter pylori Species 0.000 title claims description 29
- 229940037467 helicobacter pylori Drugs 0.000 title claims description 29
- 238000000034 method Methods 0.000 title claims description 20
- 230000002401 inhibitory effect Effects 0.000 title claims description 12
- 240000002657 Thymus vulgaris Species 0.000 claims description 19
- 235000007303 Thymus vulgaris Nutrition 0.000 claims description 19
- 230000000694 effects Effects 0.000 claims description 19
- 239000001585 thymus vulgaris Substances 0.000 claims description 19
- 239000000284 extract Substances 0.000 claims description 18
- 241000894006 Bacteria Species 0.000 claims description 15
- 241000196324 Embryophyta Species 0.000 claims description 15
- 108010046334 Urease Proteins 0.000 claims description 10
- 239000006286 aqueous extract Substances 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 238000000338 in vitro Methods 0.000 claims description 6
- 210000001541 thymus gland Anatomy 0.000 claims description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 244000290929 Coridothymus capitatus Species 0.000 claims description 3
- 235000000294 Coridothymus capitatus Nutrition 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 2
- 239000004615 ingredient Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 8
- 241000589989 Helicobacter Species 0.000 claims 1
- 150000002894 organic compounds Chemical class 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 description 22
- 239000003242 anti bacterial agent Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- 208000002064 Dental Plaque Diseases 0.000 description 5
- 208000007882 Gastritis Diseases 0.000 description 5
- 229940088710 antibiotic agent Drugs 0.000 description 5
- 230000001580 bacterial effect Effects 0.000 description 5
- 210000002784 stomach Anatomy 0.000 description 5
- 206010019375 Helicobacter infections Diseases 0.000 description 3
- 229960003022 amoxicillin Drugs 0.000 description 3
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 229910052797 bismuth Inorganic materials 0.000 description 3
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 3
- ZQUAVILLCXTKTF-UHFFFAOYSA-H bismuth;tripotassium;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound [K+].[K+].[K+].[Bi+3].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O ZQUAVILLCXTKTF-UHFFFAOYSA-H 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 210000004877 mucosa Anatomy 0.000 description 3
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- YZEUHQHUFTYLPH-UHFFFAOYSA-N 2-nitroimidazole Chemical compound [O-][N+](=O)C1=NC=CN1 YZEUHQHUFTYLPH-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 208000008469 Peptic Ulcer Diseases 0.000 description 2
- 241001184553 Thymus x citriodorus Species 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 229960004645 bismuth subcitrate Drugs 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 201000006549 dyspepsia Diseases 0.000 description 2
- 230000009036 growth inhibition Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 description 2
- NZWPVDFOIUKVSJ-YFKPBYRVSA-N (2s)-2,6-diamino-n-hydroxyhexanamide Chemical compound NCCCC[C@H](N)C(=O)NO NZWPVDFOIUKVSJ-YFKPBYRVSA-N 0.000 description 1
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
- 240000002234 Allium sativum Species 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 206010009657 Clostridium difficile colitis Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 240000007817 Olea europaea Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- RRUDCFGSUDOHDG-UHFFFAOYSA-N acetohydroxamic acid Chemical compound CC(O)=NO RRUDCFGSUDOHDG-UHFFFAOYSA-N 0.000 description 1
- 229960001171 acetohydroxamic acid Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001621 bismuth Chemical class 0.000 description 1
- 150000001622 bismuth compounds Chemical class 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 208000023652 chronic gastritis Diseases 0.000 description 1
- 231100000749 chronicity Toxicity 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 238000002828 disc diffusion antibiotic sensitivity testing Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 235000013345 egg yolk Nutrition 0.000 description 1
- 210000002969 egg yolk Anatomy 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000004611 garlic Nutrition 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000002962 histologic effect Effects 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 229940079905 intestinal adsorbents bismuth preparations Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- YKQOSKADJPQZHB-RGYSVOEGSA-N n-[(2s)-4-amino-1-[[(2s,3r)-1-[[(2s)-4-amino-1-oxo-1-[[(6r,9s,12r,15r,18s,21s)-6,9,18-tris(2-aminoethyl)-3-[(1r)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-hydr Chemical compound CCC(C)CCCC(=O)N[C@@H](CCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)C([C@@H](C)O)NC(=O)[C@@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O YKQOSKADJPQZHB-RGYSVOEGSA-N 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000003950 pathogenic mechanism Effects 0.000 description 1
- 230000001175 peptic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229960005404 sulfamethoxazole Drugs 0.000 description 1
- JLKIGFTWXXRPMT-UHFFFAOYSA-N sulphamethoxazole Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 JLKIGFTWXXRPMT-UHFFFAOYSA-N 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Botany (AREA)
- Mycology (AREA)
- Biotechnology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Communicable Diseases (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Alternative & Traditional Medicine (AREA)
- Obesity (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Medicines Containing Plant Substances (AREA)
- Food Preservation Except Freezing, Refrigeration, And Drying (AREA)
- Enzymes And Modification Thereof (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IL10231392A IL102313A (en) | 1992-06-25 | 1992-06-25 | Method for inhibiting growth of helicobacter pylori |
| JP5177413A JPH0687757A (ja) | 1992-06-25 | 1993-06-24 | ヘリコバクテルピロリバクテリアの増殖およびウレアーゼ活性の抑制方法 |
| DE69323246T DE69323246T2 (de) | 1992-06-25 | 1993-06-25 | Neue therapeutische Anwendungsform eines Thymianextraktes und in-vitro-Verfahren zur Inhibierung des Wachstums und der Ureaseaktivität von Helicobacter pylori |
| EP93401638A EP0577481B1 (de) | 1992-06-25 | 1993-06-25 | Neue therapeutische Anwendungsform eines Thymianextraktes und in-vitro-Verfahren zur Inhibierung des Wachstums und der Ureaseaktivität von Helicobacter pylori |
| US08/225,951 US5472695A (en) | 1992-06-25 | 1994-04-08 | Therapeutic application of a thyme extract and in - vitro methods for inhibiting the growth and urease activity of helicobacter pylori |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IL10231392A IL102313A (en) | 1992-06-25 | 1992-06-25 | Method for inhibiting growth of helicobacter pylori |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL102313A0 IL102313A0 (en) | 1993-01-14 |
| IL102313A true IL102313A (en) | 1996-12-05 |
Family
ID=11063763
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL10231392A IL102313A (en) | 1992-06-25 | 1992-06-25 | Method for inhibiting growth of helicobacter pylori |
Country Status (4)
| Country | Link |
|---|---|
| EP (1) | EP0577481B1 (de) |
| JP (1) | JPH0687757A (de) |
| DE (1) | DE69323246T2 (de) |
| IL (1) | IL102313A (de) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5560912A (en) * | 1994-06-27 | 1996-10-01 | Technion Research & Development Foundation Ltd. | Method for inhibiting growth of helicobacter pylori |
| CA2182917C (en) * | 1996-03-26 | 2001-05-08 | Alvin B. Segelman | Composition and method for treating and preventing helicobactor pylori-associated stomach gastritis, ulcers and cancer |
| EP1080727A1 (de) * | 1999-08-31 | 2001-03-07 | Anastasios Emmanouilidis | Verwendung eines Extraktes von Thymus vulgaris für die Herstellung eines Arzneimittels für die Behandlung von ulzerativer Kolitis und Morbus chron |
| US11179430B2 (en) | 2012-06-08 | 2021-11-23 | Finzelberg Gmbh & Co. Kg | Extracts from mother-of-thyme and the use i'hereof |
| PL245199B1 (pl) * | 2018-04-13 | 2024-06-03 | Osrodek Badawczo Produkcyjny Politechniki Lodzkiej Ichem Spolka Z Ograniczona Odpowiedzialnoscia | Kompozycja do zastosowania do wspomagania odporności organizmu w profilaktyce i leczeniu zakażeń Helicobacter pylori |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| LU85877A1 (fr) * | 1985-05-06 | 1986-12-05 | Bentchikou Abdelhamid | Compositions pharmaceutiques pour le traitement de colites et colopathies |
| CH675685A5 (de) * | 1988-06-24 | 1990-10-31 | Flachsmann Ag Emil | |
| DE68916430T2 (de) * | 1989-04-28 | 1994-10-13 | Deryabin Alexandr Mikhailovic | Arzneimittelzubereitung zur behandlung von mastitis bei tier und mensch. |
| DE4027227C2 (de) * | 1990-08-29 | 1997-04-24 | Krewel Meuselbach Gmbh | Verfahren zur Herstellung eines arzneibuchkonformen alkoholfreien Thymian-Fluid-Extraktes |
-
1992
- 1992-06-25 IL IL10231392A patent/IL102313A/en not_active IP Right Cessation
-
1993
- 1993-06-24 JP JP5177413A patent/JPH0687757A/ja active Pending
- 1993-06-25 EP EP93401638A patent/EP0577481B1/de not_active Expired - Lifetime
- 1993-06-25 DE DE69323246T patent/DE69323246T2/de not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP0577481B1 (de) | 1999-01-27 |
| DE69323246D1 (de) | 1999-03-11 |
| IL102313A0 (en) | 1993-01-14 |
| JPH0687757A (ja) | 1994-03-29 |
| DE69323246T2 (de) | 1999-09-02 |
| EP0577481A1 (de) | 1994-01-05 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| MM9K | Patent not in force due to non-payment of renewal fees |