MXPA99004609A - Aminohydrofluorides and their use as oral hygiene preparations - Google Patents
Aminohydrofluorides and their use as oral hygiene preparationsInfo
- Publication number
- MXPA99004609A MXPA99004609A MXPA/A/1999/004609A MX9904609A MXPA99004609A MX PA99004609 A MXPA99004609 A MX PA99004609A MX 9904609 A MX9904609 A MX 9904609A MX PA99004609 A MXPA99004609 A MX PA99004609A
- Authority
- MX
- Mexico
- Prior art keywords
- amine
- mixture
- fluorhydrates
- oil
- formula
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 239000000203 mixture Substances 0.000 claims abstract description 103
- 125000001183 hydrocarbyl group Chemical group 0.000 claims abstract description 16
- 125000004432 carbon atoms Chemical group C* 0.000 claims abstract description 11
- 150000001412 amines Chemical class 0.000 claims description 68
- 239000000243 solution Substances 0.000 claims description 48
- -1 amine hydrofluoride Chemical class 0.000 claims description 41
- KRHYYFGTRYWZRS-UHFFFAOYSA-N HF Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 claims description 23
- 239000000606 toothpaste Substances 0.000 claims description 19
- 229940034610 Toothpaste Drugs 0.000 claims description 14
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 13
- 239000000194 fatty acid Substances 0.000 claims description 13
- 150000004665 fatty acids Chemical class 0.000 claims description 13
- 239000003921 oil Substances 0.000 claims description 13
- 235000019198 oils Nutrition 0.000 claims description 13
- 239000003925 fat Substances 0.000 claims description 11
- 150000001875 compounds Chemical class 0.000 claims description 10
- 235000012424 soybean oil Nutrition 0.000 claims description 10
- 239000003549 soybean oil Substances 0.000 claims description 10
- 235000011293 Brassica napus Nutrition 0.000 claims description 9
- 235000000540 Brassica rapa subsp rapa Nutrition 0.000 claims description 9
- 229910000040 hydrogen fluoride Inorganic materials 0.000 claims description 9
- 239000007910 chewable tablet Substances 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 7
- 239000008158 vegetable oil Substances 0.000 claims description 7
- 241000283690 Bos taurus Species 0.000 claims description 6
- YUOWTJMRMWQJDA-UHFFFAOYSA-J Tin(IV) fluoride Chemical compound [F-].[F-].[F-].[F-].[Sn+4] YUOWTJMRMWQJDA-UHFFFAOYSA-J 0.000 claims description 6
- 239000010775 animal oil Substances 0.000 claims description 6
- 239000012487 rinsing solution Substances 0.000 claims description 6
- 239000003760 tallow Substances 0.000 claims description 6
- 230000000699 topical Effects 0.000 claims description 6
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000001117 oleyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C([H])=C([H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 229940068682 Chewable Tablet Drugs 0.000 claims description 2
- 208000007565 Gingivitis Diseases 0.000 claims description 2
- 208000003265 Stomatitis Diseases 0.000 claims description 2
- 125000001204 arachidyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 235000015278 beef Nutrition 0.000 claims description 2
- 201000001245 periodontitis Diseases 0.000 claims description 2
- 240000008100 Brassica rapa Species 0.000 claims 4
- 239000003242 anti bacterial agent Substances 0.000 claims 1
- 125000005644 linolenyl group Chemical group 0.000 claims 1
- 125000005645 linoleyl group Chemical group 0.000 claims 1
- 230000000069 prophylaxis Effects 0.000 claims 1
- 229960001245 olaflur Drugs 0.000 abstract description 19
- ZVVSSOQAYNYNPP-UHFFFAOYSA-N Olaflur Chemical compound F.F.CCCCCCCCCCCCCCCCCCN(CCO)CCCN(CCO)CCO ZVVSSOQAYNYNPP-UHFFFAOYSA-N 0.000 abstract description 11
- 230000000844 anti-bacterial Effects 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 2
- 230000000675 anti-caries Effects 0.000 abstract 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 239000002585 base Substances 0.000 description 17
- 230000000875 corresponding Effects 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 238000005259 measurement Methods 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000010790 dilution Methods 0.000 description 11
- QGLWBTPVKHMVHM-KTKRTIGZSA-N (Z)-octadec-9-en-1-amine Chemical compound CCCCCCCC\C=C/CCCCCCCCN QGLWBTPVKHMVHM-KTKRTIGZSA-N 0.000 description 10
- 235000019197 fats Nutrition 0.000 description 10
- CVHZOJJKTDOEJC-UHFFFAOYSA-N Saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 9
- 229940081974 Saccharin Drugs 0.000 description 9
- 235000019204 saccharin Nutrition 0.000 description 9
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 8
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 8
- 238000005755 formation reaction Methods 0.000 description 8
- 239000000499 gel Substances 0.000 description 8
- 239000000600 sorbitol Substances 0.000 description 8
- 235000010356 sorbitol Nutrition 0.000 description 8
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 8
- 150000002191 fatty alcohols Chemical class 0.000 description 7
- PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical compound [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 7
- CWSZBVAUYPTXTG-UHFFFAOYSA-N 5-[6-[[3,4-dihydroxy-6-(hydroxymethyl)-5-methoxyoxan-2-yl]oxymethyl]-3,4-dihydroxy-5-[4-hydroxy-3-(2-hydroxyethoxy)-6-(hydroxymethyl)-5-methoxyoxan-2-yl]oxyoxan-2-yl]oxy-6-(hydroxymethyl)-2-methyloxane-3,4-diol Chemical compound O1C(CO)C(OC)C(O)C(O)C1OCC1C(OC2C(C(O)C(OC)C(CO)O2)OCCO)C(O)C(O)C(OC2C(OC(C)C(O)C2O)CO)O1 CWSZBVAUYPTXTG-UHFFFAOYSA-N 0.000 description 6
- 210000003298 Dental Enamel Anatomy 0.000 description 6
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 6
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 6
- 235000016247 Mentha requienii Nutrition 0.000 description 6
- 235000002899 Mentha suaveolens Nutrition 0.000 description 6
- 239000000654 additive Substances 0.000 description 6
- 230000001580 bacterial Effects 0.000 description 6
- 235000006682 bigleaf mint Nutrition 0.000 description 6
- 239000012482 calibration solution Substances 0.000 description 6
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 6
- 235000006679 mint Nutrition 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- WHJKCPTVEYZNOG-UHFFFAOYSA-N 6-(hydroxymethyl)-5-methoxy-2-[4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane-3,4-diol Chemical compound COCC1OC(OC)C(OC)C(OC)C1OC1C(O)C(O)C(OC)C(CO)O1 WHJKCPTVEYZNOG-UHFFFAOYSA-N 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 5
- 240000002791 Brassica napus Species 0.000 description 5
- ANOBYBYXJXCGBS-UHFFFAOYSA-L Tin(II) fluoride Chemical compound F[Sn]F ANOBYBYXJXCGBS-UHFFFAOYSA-L 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- 239000001683 mentha spicata herb oil Substances 0.000 description 5
- 244000005700 microbiome Species 0.000 description 5
- 235000019721 spearmint oil Nutrition 0.000 description 5
- REYJJPSVUYRZGE-UHFFFAOYSA-N stearylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 230000002194 synthesizing Effects 0.000 description 5
- 235000019871 vegetable fat Nutrition 0.000 description 5
- 210000000214 Mouth Anatomy 0.000 description 4
- MWOOGOJBHIARFG-UHFFFAOYSA-N Vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 4
- HEBKCHPVOIAQTA-SCDXWVJYSA-N Xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 4
- 229960002675 Xylitol Drugs 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M buffer Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 238000009826 distribution Methods 0.000 description 4
- 239000000686 essence Substances 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- IAYPIBMASNFSPL-UHFFFAOYSA-N oxane Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000011775 sodium fluoride Substances 0.000 description 4
- 235000013024 sodium fluoride Nutrition 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000004408 titanium dioxide Substances 0.000 description 4
- 235000015112 vegetable and seed oil Nutrition 0.000 description 4
- 239000000080 wetting agent Substances 0.000 description 4
- 239000000811 xylitol Substances 0.000 description 4
- 235000010447 xylitol Nutrition 0.000 description 4
- 235000019737 Animal fat Nutrition 0.000 description 3
- ZBCBWPMODOFKDW-UHFFFAOYSA-N Diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 3
- 239000004698 Polyethylene (PE) Substances 0.000 description 3
- 229940076185 Staphylococcus aureus Drugs 0.000 description 3
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- 239000007983 Tris buffer Substances 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
- 238000004166 bioassay Methods 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000010531 catalytic reduction reaction Methods 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
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- 239000010642 eucalyptus oil Substances 0.000 description 3
- 150000004676 glycans Polymers 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 230000002209 hydrophobic Effects 0.000 description 3
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
- URWNNKHKJWTYMW-UHFFFAOYSA-M octadecan-1-amine;fluoride Chemical compound [F-].CCCCCCCCCCCCCCCCCCN URWNNKHKJWTYMW-UHFFFAOYSA-M 0.000 description 3
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- LNAZSHAWQACDHT-XIYTZBAFSA-N (2R,3R,4S,5R,6S)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2S,3R,4S,5R,6R)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2R,3R,4S,5R,6R)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 2
- WBZFUFAFFUEMEI-UHFFFAOYSA-N Acesulfame potassium Chemical compound [K+].CC1=CC(=O)NS(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-N 0.000 description 2
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- FBPFZTCFMRRESA-KAZBKCHUSA-N D-Mannitol Natural products OC[C@@H](O)[C@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KAZBKCHUSA-N 0.000 description 2
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- VDZOOKBUILJEDG-UHFFFAOYSA-M Tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 description 2
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- NDLNTMNRNCENRZ-UHFFFAOYSA-N 2-[2-hydroxyethyl(octadecyl)amino]ethanol Chemical group CCCCCCCCCCCCCCCCCCN(CCO)CCO NDLNTMNRNCENRZ-UHFFFAOYSA-N 0.000 description 1
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- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- PBEMAPHCPDXBQA-UHFFFAOYSA-N 3,5-diaminopentan-1-ol Chemical compound NCCC(N)CCO PBEMAPHCPDXBQA-UHFFFAOYSA-N 0.000 description 1
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- PZZYQPZGQPZBDN-UHFFFAOYSA-N Aluminium silicate Chemical class O=[Al]O[Si](=O)O[Al]=O PZZYQPZGQPZBDN-UHFFFAOYSA-N 0.000 description 1
- 241000228245 Aspergillus niger Species 0.000 description 1
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- 235000012137 Atriplex confertifolia Nutrition 0.000 description 1
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- WUKWITHWXAAZEY-UHFFFAOYSA-L Calcium fluoride Chemical compound [F-].[F-].[Ca+2] WUKWITHWXAAZEY-UHFFFAOYSA-L 0.000 description 1
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- 235000003255 Carthamus tinctorius Nutrition 0.000 description 1
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Abstract
Aminohydrofluorides with the general formula (I):R-N(CH 2CH 2OH) 2 . HF in which R is a straight-chain hydrocarbon residue with 10 to 20 carbon atoms, have an anti-bacterial and caries-prophylactic effect. They can be prepared in a higher purity than other known aminohydrofluorides like, for example, olaflur. Aminohydrofluorides of the formula (I), or mixtures of two or more of these, can be formulated as oral hygiene preparations.
Description
AMINE FLUORHYDRATES AND ITS USE AS PREPARATIONS FOR ORAL HYGIENE
FIELD OF THE INVENTION
The present invention relates to amine fluorhydrates and mixtures of these amine fluorhydrates, and to a process for the preparation of these amine hydrofluorides and their use in oral hygiene compositions.
BACKGROUND OF THE INVENTION
It is known that oral hygiene compositions, by their cleansing action, make a contribution to the hygiene of the oral cavity and thus to the preservation of the health of the teeth and gums. The cleansing action of these oral hygiene compositions is complemented by the mixture of active compounds which prevent or control the pathological symptoms in the oral cavity, in particular also, the formation of bacterial films on the teeth (plaque). These films
REF .: 30371 consist of polysaccharides, mainly dextrans. In addition to low molecular weight sugars, these polysaccharides form a source of nutrition for bacterial plaque (mainly streptococci and lactobacillaceae). Bacterial plaque gradually breaks polysaccharides to form acid degradation products (eg, pyruvic acid, lactic acid, etc.). The pH decreases resulting from this bridges around the degradation of the enamel of the teeth known as caries. Therefore, steps have already been taken against the formation of pathological symptoms in the oral cavity by using various compositions for oral hygiene comprising antibacterially active substances (for example, toothpastes, rinsing solutions or dental gels). The active compounds already known from the prior art are N-octadeca-9-enylamine hydrofluoride (name without international property "dectaflur") and in particular N '-octadecyl-N' hydrate, N, N-tris ( 2-hydroxyethyl) -1,3-propanediamine (name without international property "olaflur"). In the oral use of the hygienic composition, these active compounds form a thin hydrophobic film on the dental enamel, the initiator groups of amine fluorohydrate are in contact with the dental enamel. Thus, on the one hand dental enamel becomes more resistant to acid attacks on an estimate of CaF2 covering the formed layer, and on the other hand the long chain hydrocarbon residues form a hydrophobic layer which prevents the formation of deposits or residues and the attack of the products of acid degradation on the enamel of the teeth. The synthesis of olaflur starts from bovine fat, a fat that has a high content of stearic acid. The ester groups are hydrolyzed, the free fatty acids are converted to the corresponding amides using ammonium and these are dehydrated to the nitriles. The catalytic reduction of these produces a mixture of primary fatty amines with the octadecylamine of the main constituent. Reaction with acrylonitrile and catalytic re-reduction produces N-octadecyl-1,3-propanediamine, which is hydroxylethylated using ethylene oxide. The amounts of by-products are formed here, as the amino groups are in some cases low- or over-substituted. The introduced hydroxyethyl groups can also be etherified by means of additional ethylene oxide. Subsequent double hydrofluorination produces the final product olaflur in technical purity, in which N'-octadecyl-N '-N, -tris (2-hydroxyethyl) -1,3-propanediamine hydrofluoride occurs as the main component. The purification of by-products is eliminated for cost reasons. The presence of these by-products up to now has not been considered to be convenient, since in relation to the formation of the film on the enamel they are of secondary importance. However, it has been taken into account that in the course of the overall density of official procedures for active pharmaceutical compounds, in the future, sales authorizations for contaminated active compounds will make it difficult to obtain them.
DESCRIPTION OF THE INVENTION
The present invention is based on the object of providing active compounds which have an activity comparable to olaflur, but contain less by-products and are simpler to prepare. The described object is achieved according to the invention by amine fluorhydrates of the general formula (I):
R-N (CH2CH2OH) 2 * HF (I) wherein R is a straight-chain hydrocarbon residue having 10 to 20 carbon atoms. Primarily it has been found that these amine hydrofluoride and mixtures of two or more thereof have an antibacterial activity which is very similar to that of N '-octadecyl-N' -N, N-tris (2-hydroxyethyl) dihydrofluoride -1,3-propanediamine of olaflur already known. The antibacterial action manifests itself in the inhibition of the growth of a multiplicity of microorganisms, for example of Aspergillus niger, Candida albicans, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus feacalis and Enterobacter cloacae. with the invention, in particular they inhibit the degradation of sugar in the bacterial plaque that produces acid and, due to the formation of a hydrophobic film, they increase the acid resistance of the substance for hard teeth and thus have prophylactic action against caries. they favor the remineralization of the initial caries lesions The amine fluorhydrates according to the invention contain straight chain (ie, unbranched) hydrocarbon residues, they may have hydrocarbon residues with a chain length of even numbers and odd, the waste that has cade length Numbered numbered with even numbers are preferred with respect to physiological acceptability. The residues preferably can be fully saturated or mono-, di- or polyunsaturated. Examples of saturated hydrocarbon residues having a chain length with even numbers are decyl, dodecyl (lauryl), tetradecyl (myristyl), hexadecyl, (cetyl, palmityl), octadecyl (stearyl) and eicosanyl. Examples of unsaturated residues having a chain length with even numbers are 9-cis-octadecenyl (oleyl), 9-trans-octadecenyl (elaidyl), cis, cis-9, 12-octadecadienyl (linolyl), cis, cis, cis-9, 12, 15-octadecatrienyl
(linolenyl) or 9-cis-eicosaenyl (gadolyl). Lauryl, myristyl, cetyl, oleyl and stearyl residues are preferred. The amine fluorhydrates are prepared according to the invention by reacting an amine of the general formula (II):
R-N (CH2CH2OH) 2 di. '
wherein R is a hydrocarbon residue having from 10 to 20 carbon atoms, with hydrogen fluoride. The reaction can be carried out in all solvents which have a suitable solubility for the free amine of formula (II) and are not attacked by hydrogen fluoride. Examples of suitable solvents are alcohols of 1 to 4 carbon atoms and dimethyl sulfoxide: ethanol is particularly preferred. The addition of hydrogen fluoride is preferred as an aqueous solution, i.e. as hydrofluoric acid. The hydrogen fluoride is preferably added in an amount from 1 to 5, particularly preferably from 1.0 to 1.1, equivalents, based on the amine. The temperature of the reaction is not critical and can be generally between -10 and +100 ° C, therefore the upper limit can be given by the boiling point of the solvent, or the lower limit by the melting point of the solvent. The preferred temperature of the reaction is between 25 ° C and 40 ° C. After the addition of the hydrogen fluoride is complete, the reaction mixture can be evaporated and dried, whereby the amine hydrofluoride according to the invention is obtained. A possible loss of minor hydrogen fluoride during evaporation and drying can be compensated for by the subsequent addition of a corresponding amount of hydrofluoric acid in the preparation of the formulations according to the invention.
The amine of the formula (II) can be prepared in a manner which is known or known per se by hydroxyethylation of a primary amine R-NH 2, in which R has the above meaning, with ethylene oxide (oxirane), Ethoxylation is carried out virtually in quantitative form only at the nitrogen atom. The primary amine R-NH2 can be obtained in a known manner from a fatty acid of the formula R-COOH, in which R has the above meaning, by means of the formation / dehydration / catalytic reduction steps of amine, it can also be used in the synthesis of the already known olaflur. Fatty acids or mixtures of suitable fatty acids of the formula R-COOH and suitable amines or mixtures of amines of the formula R-NH 2 are known and in some cases commercially obtainable. According to a further variant, the amine of the formula (II) can be prepared by alkylation of diethanolamine in a nucleophilic Sn2 substitution:
R-X + HN (CH2CH2OH) 2 - > R-N (CH2CH2OH) 2 HX
wherein R-X is the alkylating agent, R has the same meaning as in the formula (II) and X is, for example, chlorine, bromine or iodine.
The amine of the formula (II) is first obtained here as an ammonium salt. This ammonium salt is deprotonated using a base, for example aqueous NaOH and then reacted according to the invention with hydrogen fluoride. The alkylating agent R-X can be obtained from the corresponding commercially available fatty alcohol by introducing a separation group:
R-OH + HX - > R-X + H20
wherein R-OH is the fatty alcohol, and HX is, for example, hydrogen chloride, hydrogen bromide or hydrogen iodide. A separation of possible homologs and / or double-bond isomers can be carried out in the fatty alcohol stage, for example, by fractional distillation and / or recrystallization, so that a pure fatty alcohol is obtained (for the necessary physical data, please quote). , for example Ropp, Chemielexikon [Chemical Encyclopedia], 9th Edition, Vol. 2, page 1337). The amine fluorhydrates according to the invention are preferably essentially free of di- or polyamine fluorhydrates, such as are typical of the known olaflur. They are free, in particular if the route of preparation by the alkylation of highly pure diethanolamine is selected, of products in which the amino groups are on or subhydroxylated (ie, because the amines are quaternary or secondary after hydroxyethylation) or the hydroxyethyl groups are etherified. The amine fluorhydrates according to the invention have a degree of hydroxyethylation of exactly two, if the route is selected by the alkylation of diethanolamine. According to the invention, the object is also achieved by a mixture of amine hydrofluoride comprising two or more compounds of the formula (I). Mixtures of amine fluorhydrates according to the invention can be mixtures in any desired ratio of two or more amine hydrhydrates which can be prepared according to one of the above processes. Mixtures of amine fluorhydrates are preferred which have been obtained from a fatty acid mixture of an animal or vegetable oil or fat and whose hydrocarbon residues R have a frequency distribution dependent on the chain length which reflects the frequency distribution of the corresponding fatty acid homologs in this fatty acid mixture. Such mixtures can be obtained by fluorhydration of mixtures of amines of the formula (II). Mixtures of amines are prepared here, starting from an animal or vegetable fat or oil, using the steps of synthesis hydrolysis / amine formation / dehydration / catalytic reduction / hydroxy-ethylation in analogy to the corresponding synthesis steps for the known olaflur . Examples of the vegetable oils or fat suitable for these mixtures of amines of the formula (II) are almond oil, pear avocado oil, corn germ oil, cottonseed oil, rape seed oil, flaxseed oil, olive oil, peanut oil, pumpkin seed oil, rice bran oil, oil safflower, sesame oil, soybean oil, sunflower oil, wheat germ oil, babassu oil, coconut oil, palm kernel oil, turnip oil and palm oil. Examples of animal oils or fats are bovine fat, chicken fat, goat fat, pork fat and juice, sheep fat, various fish oils and whale oil. A preferred animal fat is beef tallow: preferred vegetable oils are soybean oil, turnip oil or soybean oil / turnip mixture. A detailed table with the compositions of the fatty acid mixtures resulting from this animal or vegetable oils or fats is found, for example, in Ullmann's Encyclopaedia of Industrial Chemistry 5a. Edition, Vol. A10, page 176 et seq. The amounts of saturated fatty acids can be increased, if desired, by catalytic hydrogenation. Mixtures of amines of the formula (II) which have been obtained from vegetable or animal oil or fat, are commercially available. Examples are the products Ethomeen S / 12 (obtained from the mixture of the fatty acid from soybean oil), Ethomeen T / 12 and Ethomeen HT / 12 (both obtained from the mixture of fatty acid from bovine tallow, the last one is hydrogenated) sold by AKZO NOBEL. The main component is S / 12 and T / 12 is N-oleyldiethanolamine. The applicant should also be able to order a mixture of amines of the formula (II), whose main component is N-stearyldiethanolamine, from WITCO. This mixture is obtained from the bovine tallow fatty acid mixture, the oily residues that are hydrogenated give stearyl residues. A mixture of amine fluorhydrates according to the invention can also be obtained if a mixture of amine fluorhydrates which has been obtained from the fatty acid mixture of a vegetable or animal oil or gars, is mixed with one or more fluorhydrates of pure amine. Two or more mixtures of amine fluorhydrates that have been obtained from different fats or oils in each case can also be mixed. A fat as known in the art can also be reduced to a mixture of fatty alcohols, and this mixture of fatty alcohol can be processed, as described above for the synthesis of amine fluorhydrates in the pure form from fatty alcohols pure, to give a corresponding mixture of amine fluorhydrates. The invention also relates to compositions for oral hygiene comprising at least one of the amine fluorhydrates according to the invention in an effective amount. They can be prepared in analogy to conventional oral hygiene compositions and using the usual auxiliaries and additives. Preferably, the oral hygiene compositions according to the invention may also contain a mixture of amine fluorhydrates from an animal or vegetable fat or oil, in particular bovine tallow, soybean oil, turnip oil or oil blends. of soybean / turnip oil. In addition, an amine fluorhydrate or a mixture of amine fluorhydrates, oral hygiene compositions according to the invention can also preferably contain tin (II) fluoride. These oral hygiene compositions containing tin fluoride are active against gingivitis, periodontitis and stomatitis, similar to being prophylactically active in caries due to the content of amine fluorhydrates. In such oral hygiene compositions, the amine hydrofluoride (s) according to the invention lead to approximately a pharmaceutical stabilization of Sn (II) against precipitation to give the insoluble tin (IV) oxide. The lower limit for the weight content of amine hydrofluoride (s) in the oral hygienic composition, is determined by the still significant prophylactic action or prophylactic action against caries. The upper limit of the weight of the amine hydrofluoride (s) is not critical, however, it should not be so high with respect to the possible toxic side effects. In the case of an oral hygienic composition in the form of toothpastes, it is possible for amine fluorhydrates according to the invention, which are preferably contained in amounts from 0.02 to 5% by weight, particularly preferably from 2 to 3. % in weigh.
The additives and auxiliaries for toothpastes according to the invention are polishing or cleaning agents, binding agents, plasticizers, wetting agents and also flavoring and aromatic substances. Examples of polishing agents are alkaline earth metal phosphate (for example, dicalcium phosphate dihydrate, dicalcium phosphate anhydride, tricalcium phosphate), insoluble alkali metal metaphosphates, colloidal or finely ground silicas, aluminum hydroxide hydrates, silicates of aluminum, magnesium and aluminum silicates, and alkaline earth metal carbonates. Suitable plastics, for example, polyethylene, can also be used. These polishing agents are usually used in amounts of 20 to 60% by weight. The binding agents are gelling agents of natural or synthetic origin. Examples of these are water-insoluble alginates, carrageenan, guar gum, tragacanth, water-soluble cellulose esters (for example methylcellulose, hydroxyalkylcelluloses, carboxymethylcellulose), water-soluble salts of polyacrylic acids (cabopols), aerosils and bentonites. In general, the content of the binding agents is 0.5 to 10% by weight. Examples of plasticizers and wetting agents are polyhydric alcohols such as glycerol, propylene glycol, sorbitol, mannitol, glucose syrup, polyethylene glycols, polypropylene glycols and polyvinyl pyrrolidone. They are usually used in amounts of 10 to 40% by weight. Examples of flavorings are saccharin, quaternary ammonium saccharinates, cyclamates, coumarin and vanillin. The aromatic substances are usually ethereal oils, for example peppermint oil, spearmint oil, anise seed oil, menthol, anethole, lemon oil, etc., or other essences such as apple, eucalyptus or spearmint oil. The rinse solutions according to the invention are alcoholic solutions or mixtures of aqueous / alcoholic, preferably aqueous, with one or more of the amine fluorhydrates according to the invention. It is possible for the amine hydrofluoride (s) according to the invention to be present in amounts from 0.02 to 2% by weight, preferably from 0.2 to 0.3% by weight. The additives and auxiliaries for rinsing solutions are, for example, the aromatic and flavoring substances mentioned above, but also emulsifiers, wetting agents, sorbitol, xylitol and various drug extracts. As the carrier material, the dental gels according to the invention contain a thickened or expanded mixture of natural or synthetic hydrocolloids. Examples of these are methylcellulose, hydroxyalkylcelluloses, carboxymethylcellulose, swellable or expandable and water soluble salts of polyacrylic acids, alginates, carrageenates and guar gum. The aforementioned flavors and aromatics and wetting agents and possibly also pigments can be mixed in small amounts in the respective gel base. It is possible for one or more of the amine fluorhydrates according to the invention to be contained in amounts from 0.02 to 10% by weight, preferably from 4.9 to 5.0% by weight. To disguise the taste and / or as a source of additional fluoride, it is also possible to add sodium fluoride, in amounts up to 5% by weight Additional examples of oral hygiene compositions according to the invention, are topical application solutions and chewable tablets The content of amine fluorhydrates in topically applied solutions may alternatively be higher than in rinse solutions In topically applied solutions it may typically be from 5 to 25% by weight, preferably from 15 to 25% by weight. The same substances can be used as additives in solutions for topical application as in rinse solutions In the case of chewable tablets, the contents of amine fluorhydrate of typically 0.3 to 12% by weight, preferably from 2 to 7% by weight, may be present. The additives for the chewable tablets are binding agents and sucrose, glucose, lactose or preferably non-cariogenic sugar types such as xylitol, mannitol or sorbitol. They can be improved in flavor by the addition of aromatic substances. For the production of chewable tablets according to the invention, processes and compression for the formation of tablets known from conventional production of chewable tablets can be employed. In compositions for oral hygiene according to the invention, tin fluoride (II) can also be added in amounts of, as a rule, 0.001 to 2% by weight, as a solid or as, for example, an aqueous solution . The same additives and auxiliaries can be used as in the oral hygienic compositions free of tin fluoride. Since the tin (II) fluoride solutions are stabilized by the addition of the amine fluorhydrates according to the invention, such solutions remain clear for a long period and no turbidity occurs. The combinations of the amine fluorhydrates according to the invention and tin (II) fluoride are, therefore, particularly suitable for use in compositions for oral hygiene in the form of rinsing solutions. Rinse solutions containing effective amounts of one or more amine fluorohydrates and tin fluoride (II), are a preferred embodiment of the oral hygiene compositions according to the invention. The present invention is now illustrated in additional form by the following examples. All quantitative data in percent, ppm and parts, refers, if not mentioned otherwise, to pesos.
Example 1: Preparation of amine fluorhydrates
A quantity by weight of a mixture of amines of the formula (II) (Ethomeen T / 12 of AKZO NOBEL, typical distribution of the chain length of R: 1% C12, 4% C_., 31% Cie, 64% Cía ) was placed in a suitable reaction vessel or flask which has stirrer, homogenizer, temperature control with temperature indicator, vacuum equipment and a dosing device resistant to HF, this amount is selected in such a way that the filling of the container or flask was by far 10 to 20% by volume. The mixture was dissolved in two portions of ethanol at room temperature. 1015 equivalents of hydrogen fluoride was added from the dosing device in the form of 40% strength aqueous hydrofluoric acid. Care was taken here that the temperature of the mixture did not exceed 40 ° C. The dosing device was then rinsed with the same volume of distilled water. The mixture was evaporated to dryness by careful evacuation (foaming) and a maximum mixing temperature of 65 ° C. The mixture of amine fluorhydrates prepared herein is referred to as "oleyl amine fluoride" below.
Example 2: Preparation of amine fluorhydrates
The procedure was as in Example 1, except that the starting mixture was another mixture of amines of the formula (II) (Ethomeen HT / 12 from AKZO NOBEL, typical distribution of the chain length of R: 1% C_ .2, 4% C ?, 31% C? 6, 64% C? 8 essentially saturated by hydrogenation) instead of Ethomeen T / 12.
For the mixture of amine fluorhydrates prepared herein, the term "stearyl amine fluoride" is used in the following.
Example 3: Toothpaste
The reaction vessel used was a mixer with a homogenizer. 62 g of stearyl amine fluoride of Example 2 (corresponding to 2.48% of the finished toothpaste) were added to the blender and dissolved in 1097 kg of water at 55 ° C.
600 g of 70% sorbitol, 35.5 g of mint essence, 625 g of silica gel, 50 g of hydroxyethylcellulose (Tylosen
H 10,000 P, Hoechst), 25 g of titanium dioxide and 3.75 g of saccharin. The mixture was stirred at 100 rpm and level 1 of the homogenizer for 50 minutes at 35 ° C and a pressure of
0. 5 bars, then for an additional 15 minutes at room temperature and a pressure of 0.1 bar.
Example 4: Toothpaste
The reaction vessel used was a mixer having a homogenizer. 61.63 g of oleyl amine fluoride of Example 1 (corresponding to 2465% of the finished toothpaste) were added to the mixer and dissolved in 0.5 kg of water at room temperature. Then, 1.22 g of 42.21% resistant hydrofluoric acid, 600 g of 70% sorbitol, 37.5 g of mint essence, 596 g of water, 625 g of silica gel, 50 g of hydroxyethylcellulose (Tylose H 10,000 P, Hoechst), 25 g of titanium dioxide and 3.75 g of saccharin. The mixture was stirred at 100 rpm and level 1 of the homogenizer for 60 minutes at 35 ° C and a pressure of 0.5 bar, then for an additional 15 minutes at room temperature and a pressure of 0.1 bar.
Example 5: Toothpaste
The reaction vessel used was a mixer with a homogenizer. 69.5 g of stearyl amine fluoride of Example 2 (corresponding to 2.78% of the finished toothpaste) were added to the blender and dissolved in 1014 kg of water at 55 ° C. Then 750 g of 70% sorbitol, 30 g of eucalyptus oil, 325 g of polyethylene, 175 g of silica gel, 10 g of saccharin, 47.5 g of hydroxyethylcellulose (Tylose H 10,000 P, Hoechst), 25 g were added. of titanium dioxide and a solution of 3.75 g of NaOH in 50 g of water. The mixture was stirred at 100 rpm and level 1 of the homogenizer for 60 minutes at 32 ° C and a pressure of 0.6 bar, then for an additional 15 minutes at room temperature and a pressure of 0.1 bar.
Example 6: Toothpaste
The reaction vessel used was a mixer with a homogenizer. 69.0 g of oleyl amine fluoride of Example 1 (corresponding to 2761% of the finished toothpaste) were added to the mixer and dissolved in 0.5 kg of water at room temperature. Then 1.36 g of resistant or potent hydrofluoric acid was added to 42.21%, 750 g of 70% sorbitol, 30 g of eucalyptus oil, 513 g of water, 325 g of polyethylene, 175 g of silica gel, 10 g of saccharin, 47.5 g of hydroxyethylcellulose (Tylose H 10,000 P, Hoechst) and 25 g of titanium dioxide and a solution of 3.75 g of NaOH and 50 g of water. The mixture was stirred at 100 rpm at level 1 of the homogenizer for 65 minutes at 38 ° C and a pressure of 0.6 bar, then for an additional 15 minutes at 25 ° C and a pressure of 0.1 bar.
Example 7: Rinse solution
The preparation was carried out under a nitrogen gas shield, 2.48 g of stearyl amine fluoride of Example 2, (corresponding to 0.248% of the finished rinse solution) were dissolved in 918 g of water at 50 ° C in a flask or flask. reaction. Then 2 g of PEG-40-hydrogenated castor oil (Cremophor RH 410, BASF), 50 g of ethanol, 1 g of mint / spearmint oil, 25 g of xylitol, 250 mg of Acesulfam K, were added and dissolved. 0.5 g of 0.4% strong or strong pigment solution of Ariavit Blue 3.85 Cl 42051.
Example 8: Rinsing solution
Additional 0.575 g of tin (II) fluoride was added to a rinse solution prepared according to the formula of Example 7 and dissolved.
Example 9: Rinse solution
The preparation was carried out under nitrogen protective gas. 25 g of xylitol and 0.5 g of 0.4% strong or strong pigment solution of Ariavit Blue 3.85 Cl 42051 were dissolved in 918 g of water in a flask or reaction vessel. Then 2.47 g of oleyl amine fluoride from Example 1 (corresponding to 0.247% of the finished rinse solution), 2 g of PEG-40 hydrogenated castor oil (Cremophor RH 410, BASF), 50 g of ethanol were added and dissolved. , 1 g of mint / spearmint oil, 250 mg of Acesulfam K and 0.048 g of 42.2% resistant hydrofluoric acid.
Example 10: Rinse solution
0.556 g of tin (II) fluoride was further added to a rinse solution prepared according to the procedure of Example 9 and dissolved.
Example 11: Dental gel
The container or reaction vessel used was a mixer with a homogenizer. 124 g of stearylamine fluoride from Example 2 (corresponding to 4.96% of the finished dental gel) were added to the blender and dissolved in 1969 kg of water at 90 ° C. Then 45 g of mint / apple essence, 55.5 g of sodium fluoride, 10 g of saccharin, 250 g of propylene glycol and 46 g of hydroxyethylcellulose (Tylose H 10,000 P, Hoechst) were added. The mixture was stirred at 100 rpm and level 1 of the homogenizer for 40 minutes - at 30 ° C and a pressure of 0.4 bar, then for an additional 25 minutes at room temperature and a pressure of 0.1 bar.
Example 12: Dental gel
The container or reaction vessel used was a mixer with a homogenizer. 123 g of oleylamine fluoride from Example 1 (corresponding to 4.93% of the finished dental gel) were added to the mixer and dissolved in 1,000 kg of water. Then 2.4 g of 42.21% strong hydrofluoric acid, 45 g of mint / apple essence, 55.5 g of sodium fluoride, 10 g of saccharin, 250 g of propylene glycol and 46 g of hydroxyethylcellulose (Tylose H 10,000 P, Hoechst) were added. ). The dilution was carried out with an additional 968 g of water. The mixture was stirred at 100 rpm and level 1 of the homogenizer for 50 minutes at 30 ° C and a pressure of 0.4 bar, then for an additional 75 minutes at 25 ° C and a pressure of 0.1 bar.
Example 13: Chewable tablet
parts of oleylamine fluoride were suspended in about 20 parts of water and subsequently granulated by spray drying
(granules of the active compound). A mixture of 0.6 parts of saccharin, 3 parts of plasdone (cross-linked polyvinylpyrrolidone), 7.5 parts of Avicel (natural cellulose), 5 parts of talc, 48 parts of rice starch, 0.9 parts of peppermint oil and 220 parts of sorbitol, were also granulated by spray drying (auxiliary granules). The granules of the active compound were mixed with the auxiliary granules in a gravity mixer and compressed to give a batch of chewable tablets in a commercially available eccentric pressure. The average weight per tablet was 300 mg.
Example 14: Solution for topical application
19.85 parts of oleylamine fluoride corresponding to 19.85% of the solutions for topical application finished, 0.15 parts of saccharin, 2.5 parts of essence mixture (consisting of a part of 30 parts of anise seed oil, 7.5 parts of menthol, 1.0 parts of vanillin, 6.0 parts of spearmint oil and 55.5 parts of peppermint oil) and 77.5 parts of water.
A solution for topical application ready for use was obtained.
Example 15: Measurement of the total fluoride content of the amine fluorohydrate mixtures.
A heavy amount of oleylamine fluoride from Example 1 was dissolved in water and the fluoride content was determined by alkalimetric trituration with 0.1 N aqueous tetrabutylammonium hydroxide solution (assumption of equimolar amounts and fluoride and ammonium groups). The measurements showed a fluoride content of 4.28%. Similarly, a fluoride content of 5.04% was found for the stearylamine fluoride of Example 2.
Example 16: Measurements of the total fluoride content of toothpastes and dental gels.
The measurement was made using a fluoride electrode and a METRHOM 610 measuring apparatus. The calibration of the electrode was carried out with a calibration solution of 45.24 ppm of fluoride, which was elaborated as follows: a) 20 ml of the normal or standard solution of fluoride in water (containing 200 mg of NaF / liter of solution) , b) 20 ml of TISAB buffer, pH 5.5 to 5.5.
The TISAB buffer was prepared here as follows:
Solution I: 5 g of Komplexon IV, 57 g of glacial acetic acid and 58 g of sodium chloride in 500 g of water; Solution II: 32 g of NaOH in 350 g of water.
Solutions I and II were mixed and diluted to
1,000 ml with water.
The sample measurement solution was prepared by adjusting an accurately weighed amount of the sample from about 1 g to 20 g with water and mixed with 20 g of TISAB buffer. The measurement solution was measured under the same conditions as the calibration solution. The calculation of the fluoride content of the sample was made by means of the general formula: ppm F ~ = 45.24 measurement of the solution sample 40 measured from the calibration solution weight of the sample g
The total contents shown in Table 1 were found.
Table 1
Example 17: Measurement of the total fluoride content of the rinse solutions.
The measurement was made using a fluoride electrode and a METRHOM 610 measuring apparatus. The calibration of the electrode was carried out with a calibration solution of 125 ppm of fluoride, which was elaborated as follows:
a) 20 ml of standard or standard fluoride solution (250 ppm fluoride), in fluoride-free rinse solution b) 20 ml of TISAB buffer solution (compare Example 16).
The sample measurement solution was prepared by mixing 20 ml of the sample of the rinsing solution and mixing 20 ml of TISAB buffer. The measurement solution was measured under the same conditions as the calibration solution. The calculation of the fluoride content of the sample was made by means of the general formula:
ppm F "= 250 x measurement of the solution sample measured from the calibration solution
The total contents shown in Table 2 were found.
Table 2
Example 18: Determination of the microbial activity of the amine fluorhydrates against Staphylococcus aureus (ATCC 6538) and Streptococcus faecalis (ATCC 10541) in the assay for the determination of the minimum inhibitory concentration (MIC assay).
These two microorganisms were selected because they are of importance as representative cocci of the cocci of the oral cavity. They were adjusted to 100,000 bacterial cells / μl, and three base solutions were prepared from one part by weight of each of the media containing bacteria consisting of a so-called shaker culture based on the Caso broth, and one part by weight of each one of the three physiological saline solutions which contained the oleylamine fluoride of Example 1 (for the Base Solution A) or stearylamine fluoride of Example 2 (for the base solution B) and the olaflur already known (for the base solution C) . The concentration of the amine fluorhydrates in the saline physiological solutions was such that it resulted in each of the finished base solutions, a fluoride concentration of 3,000 ppm F ~ / 100 g of the base solution. A series of geometric dilution was formed from each of the base mixtures by dilution with physiological saline solution (dilution factor 2 in each case). It was investigated in which dilution a significant inhibition of the microorganism was not observed. Table 3 shows the higher dilution stages compared to base mixtures in which the bacteria was still destroyed in a current experiment.
Table 3
Taking into account the biological variability in the vitality of the bacteria, the three active substances are observed as approximately equal active.
Example 19: Determination of the microbiological activity of the toothpaste formulations against Staphylococcus aureus (ATCC 6538) and Streptococcus feacalis (ATCC.10541) in the MIC assay.
They were adjusted to 100,000 bacterial cells / μl, and three base solutions were prepared from one part by weight of each of the media containing bacteria consisting of a shaker culture based on the Caso broth, and one part by weight of a toothpaste (base mixture A: toothpaste of Example 3, base mixture B: toothpaste of Example 4, base mixture C: commercial toothpaste containing olaflu already known). The fluoride content by weight was the same in all the base mixtures. A series of geometric dilution of each of the base mixtures was formed by dilution with physiological saline solution (dilution factor 2 in each case). It was investigated in which dilution a significant inhibition of the microorganism was not observed. Table 4 shows the higher dilution steps compared to base mixtures in which the bacteria was still destroyed in a current experiment.
Table 4
Taking into account the biological variability in the vitality of the microorganism, the two toothpastes based on oleylamine fluoride or olaflur showed comparable efficacy.
It is noted that, with regard to this date, the best method known by the Applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.
Having described the invention as above, the content of the following is claimed as property.
Claims (19)
1. Amine Fluorhydrate of the general formula (I) R-N (CH2CH20H). HF (I) characterized in that R is a straight chain hydrocarbon residue having from 10 to 20 carbon atoms.
2. Amine Fluorhydrate according to claim 1, characterized in that the hydrocarbon residue R has an even number of carbon atoms.
3. Amine fluorohydrate according to claim 1, characterized in that the hydrocarbon residue R is a residue of lauryl, myristyl, cetyl, oleyl, linoleyl, linolenyl, stearyl, eicosanyl or eicosaenyl.
Amine Fluorohydrate of the general formula (I! R-N (CH2CH2OH) 2 • HF (I) characterized in that R is a straight-chain hydrocarbon residue having from 10 to 20 carbon atoms, as an antibacterial agent.
5. A mixture of amine hydrofluoride containing two or more compounds of the general formula (I): R-N (CH2CH2OH) 2 • HF (I) characterized in that R is a straight chain hydrocarbon residue having from 10 to 20 carbon atoms.
6. A mixture according to claim 5, obtained from the mixture of the fatty acid of a vegetable or animal oil or fat.
7. The mixture according to claim 5 or 6. Obtained from beef tallow, soybean oil, turnip oil or a mixture of soybean oil / turnip oil.
8. A process for the preparation of an amine hydrofluoride of the general formula (I): R-N (CH2CH2OH) 2 • HF (I) wherein R is a straight-chain hydrocarbon residue having from 10 to 20 carbon atoms, characterized in that an amine of the general formula (II): R-N (CH2CH2OH) 2 (II) in which R has the above meaning, it is reacted with hydrogen fluoride.
9. An oral hygienic composition, characterized in that it comprises at least one amine hydrofluoride of the general formula: R-N (CH2CH20H) 2 • HF (I) wherein R is a straight-chain hydrocarbon residue having from 10 to 20 carbon atoms, in an effective amount.
10. The oral hygienic composition according to claim 9, characterized in that it comprises a mixture of amine fluorhydrates of the formula (I) obtained from bovine tallow, soybean oil, turnip oil or a mixture of soybean oil / soybean oil. turnip.
11. The oral hygiene composition according to claim 9 or 10, characterized in that it is present in the form of a toothpaste and comprises one or more amine fluorhydrates of the formula (I) in an amount from 0.02 to 5, preferably 2 to 3, percent by weight.
12. The oral hygienic composition according to claim 9 or 10, characterized in that it is present in the form of a rinsing solution and comprises one or more amine fluorhydrates of the formula (I) in an amount from 0.02 to 2, preferably from 0.2 to 0.3, percent by weight.
13. The oral hygienic composition according to claim 9 or 10, characterized in that it is present in the form of a dental gel and comprises one or more amine fluorhydrates of the formula (I) in an amount from 0.02 to 10, preferably from 4.9 to 5.0, percent by weight.
14. The oral hygienic composition according to claim 9 or 10, characterized in that it is present in the form of a solution for topical application and comprises one or more amine fluorhydrates of the formula (I) in an amount from 5 to 25, preferably from 15 to 25, percent by weight.
15. The oral hygienic composition according to claim 9 or 10, characterized in that it is present in the form of a chewable tablet and comprises one or more amine fluorhydrates of the formula (I) in an amount from 0.3 to 12, preferably from 2 to 7, percent by weight.
16. The oral hygiene composition according to one of claims 9 or 15, characterized in that it comprises tin fluoride (II) in an amount of up to 2%.
17. The use of an amine hydrofluoride of the general formula (I): R-N (CH2CH20H) 2. HF (I! wherein R is a straight chain hydrocarbon residue having from 10 to 20 carbon atoms, for the preparation of an oral hygienic composition.
18. The use of an amine hydrofluoride according to claim 17, for the preparation of an oral hygienic composition having the prophylactic action against caries.
19. The use of an amine hydrofluoride according to claim 17 in combination with tin fluoride (II), for the preparation of an oral hygienic composition having action against gingivitis, periodontitis and stomatitis.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH2843/96 | 1996-11-18 |
Publications (1)
Publication Number | Publication Date |
---|---|
MXPA99004609A true MXPA99004609A (en) | 2000-05-01 |
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