La liberación de eugenol ocurre, como se mencionó anteriormente, por la hidrólisis que experimenta el eugenolato de zinc al entrar en contacto con un medio. J Dent. Apr;16(2) Eugenol release and the cytotoxicity of different zinc oxide-eugenol combination. Meryon SD, Johnson SG, Smith AJ. Oral Surg Oral Med Oral Pathol. Jun;73(6) Biologic properties of eugenol and zinc oxide-eugenol. A clinically oriented review. Markowitz K(1).
|Published (Last):||15 November 2014|
|PDF File Size:||19.63 Mb|
|ePub File Size:||18.95 Mb|
|Price:||Free* [*Free Regsitration Required]|
Biologic properties of eugenol and zinc oxide-eugenol. A clinically oriented review.
Background of the Invention This invention relates to a chelated mineral composition containing 1,2-disubstituted aromatic ligands. More particularly, this invention relates to mineral chelates containing 1, 2-disubstituted aromatic ligands and particularly 2-alkoxyphenol ligands, such as vanillin, and metals selected from the group consisting of Mg, Ca, Cr, Mn, Fe, Co, Cu, Zn, Se and Mo wherein the ligand to metal ratio is 1: When a metal combines with an electron donor, a complex or coordination compound is formed.
When the electron donor, also referred to as a ligand or chelating agent, eeugenolato two or more donor groups tied together in some way, the resulting complex is a chelate. The essential and characteristic feature found in all chelates is formation of a ring between the ligand and the metal atom. For ring formation to occur, the electron donor molecule must contain two or more groups that can each combine with the metal atom with formation of at least one coordinate covalent bond.
Also, groups or atoms such as oxygen, nitrogen, hydroxyl, and amino must be present that can coordinate with the metal atom through their lone electron pair. Further, these donor groups must be separated from each other by chains of suitable length to permit formation of rings with five or six member rings being most stable.
Amino acids comprise a group of ligands that have been used to chelate minerals. Such a five-member ring is defined by the metal atom, the carboxyl oxygen, the carbonyl carbon, the a-carbon, and the a-amino nitrogen and is generally represented by Formula I. However, the actual structure will depend upon the ligand to metal eugeonlato ratio.
The ligand to metal mole ratio is at least 1: Most typically, an amino acid chelate may be represented at a ligand to metal ratio of 2: However, R could represent any of the side chains of the other twenty or so naturally occurring amino acids derived from proteins. In other words, the chelate ring is defined by the same atoms in each instance. It is officially defined as the product resulting from the reaction of a metal ion from a re metal salt with amino acids with a mole df of one mole of metal to one to three preferably two moles of amino acids to form coordinate covalent bonds.
The average weight of the hydrolyzed amino acids must be approximately and the resulting molecular weight of the chelate must not exceed The products are identified by the specific metal forming the chelate, i.
Amino acid chelates can also be formed using peptide ligands instead of single amino acids. These will usually be in the form of dipeptides or tripeptides because larger ligands would have a molecular weight which would be too great for direct assimilation of the chelate formed.
Generally, peptide ligands wugenolato be derived by the hydrolysis of protein. However, peptides prepared by conventional synthetic techniques or genetic engineering can also be used.
When a ligand is a di- or tripeptide, a radical of the formula [C 0 CHRNH] e H will replace one of the hydrogens attached to the nitrogen atom in.
Eugenol release and the cytotoxicity of different zinc oxide-eugenol combination.
R, as defined in Formula I, can be H, or the side chain of any other naturally occurring amino acid and e fugenolato be an integer of 1 or 2. When e is 1 the ligand will be a dipeptide and when e ekgenolato 2 the ligand will be a tripeptide. The structure, chemistry, and bioavailability of amino acid chelates is well documented in the literature, e. Thomas Publishers, Springfield, Illinois; Ashmead et al.
Patents 4,; 4,; 4,. Flavored effervescent mixtures of vitamins and amino acid chelates for administration to humans in the form of a beverage are disclosed in U.
Metodos para determinar la biocompatibilidad en materiales dentales.
In the field of mineral nutrition, amino acid chelates have increasingly been recognized as providing certain advantages over inorganic mineral salts. One advantage is attributed to the fact that these chelates are readily absorbed in the gut and mucosal cells by means of active transport as though they were small peptides. In other words, the minerals are absorbed along with the amino acids as a single unit utilizing the amino acids as carrier molecules.
Since this method of absorption does not involve the absorption sites for free metal ions, the problems of competition of ions for active sites and suppression of one nutritive mineral element by uegenolato are avoided.
Other advantages of amino acid chelates include stimulation of gonadotropic hormones, U. Despite these advantages, use of amino acid chelates for human consumption has the drawback of a metallic aftertaste that some people find disagreeable. Thus, amino acid chelates have had to be taken in capsules and other forms that avoid the aftertaste.
Use of amino acid chelates in nutritional beverages has also been limited by this aftertaste. In view of the foregoing, it will be appreciated that zihc chelates that do not contain amino acids or an unpleasant aftertaste, yet provide the advantage of increased absorption of minerals compared to inorganic minerals, would be a significant advancement in the art.
Objects and Summary of the Invention It is an object of the present invention to provide mineral chelates wherein the mineral is in a bioavailable form but without the associated unpleasant taste attributed to the use of amino acids. It is another object of the invention to provide mineral chelates that have a pleasant or neutral eugenolaho. It is also an object of the invention to provide mineral chelates wherein the ligand is generally recognized by regulatory agencies as an acceptable food additive or supplement.
It is a further object of the invention to provide mineral chelates that are relatively non-polar so that they easily cross cellular membranes.
WOA1 – 1,2-disubstituted aromatic chelates – Google Patents
The 1, 2-disubstituted aromatic moiety is represented by Formula II:. The metal ion “M” utilized in the chelate formation is selected from the group consisting of Mg, Ca, Cr, Mn, Fe, Co, Cu, and Zn and is present in a form suitable for reaction. M is preferably present as a soluble metal salt, such as a chloride, sulfate, nitrate or acetate.
Detailed Description of the Invention Before the present 1,2-disubstituted aromatic mineral chelate compositions and methods of making them are disclosed and zknc, it is to be understood that this invention is not limited to the particular process steps and materials disclosed herein as such process steps and materials may vary somewhat.
It is also to be understood that the terminology used herein is used for the purpose of describing particular embodiments only and is not intended to be limiting since the scope of the present invention will be limited only by the appended claims and their dee.
There are many eugenooato, 2-disubstituted aromatic compounds found in nature which possess the formula: There is a proviso that none of eugenolayo R 3 through R 6 substituents can be more polar than the 1,2 ring substituents so as to tend to withdraw electrons from these substituents which would inhibit or prevent their chelate forming characteristics. Prominent among the 1,2-disubstituted aromatic compounds, and preferred in the present invention are the 2-alkoxyphenols, i.
Particularly preferred are vanillin and guaiacol. To be technically correct, vanillin is a benzaldehyde derivative and the numbering of the carbon atoms on the aromatic ring begins with the aldehyde carbon and thus has the name eubenolato methoxybenzaldehyde.
However, for purposes of the present invention, the numbering on the aromatic ring begins eugneolato the carbon containing the XM’ group as the 1 carbon and the adjacent carbon containing the XR group is the 2 carbon. Therefor the subscript on substituents R 3 through R 6 is representative of the carbon atom position on the aromatic ring to which they are attached.
These compounds have the necessary atoms and groups to function as electron donors for formation of covalent bonds with metals that are needed to form stable eguenolato. Further, 2-alkoxyphenols contain resonance electrons in the benzene ring that can contribute to the stabilization of mineral chelates containing such ligands. Due to their relatively non- polar structure, particularly when R 4 and R 5 are H or unsubstituted R groups, there may be enhanced transport across cellular membranes. As noted above, the thio and amine analogs of the phenol or the alkoxy group, which can contribute or donate electrons in the formation of chelates, can eugenolafo used in the place of the phenol or alkoxy groups.
By alkoxy is meant so-called lower alkyl groups usually containing from one to ten carbon atoms and preferably from one to five carbon atoms. Methoxy ziinc the preferred alkoxy group. The invention will be primarily described in terms of 2-alkoxyphenols as the ligand source. However, by analogy, any of the 1, 2-disubstituted aromatic ligands could also be utilized.
Mineral zijc chelates are synthesized by reacting a 2-alkoxyphenol with a hydroxide of a monovalent cation, such as an alkali metal hydroxide or ammonium hydroxide, to form a monovalent cation salt of the 2-alkoxyphenol. In this reaction, the eugrnolato of a monovalent cation removes a hydrogen ion from the 1-hydroxyl group of the 2-alkoxyphenol to form the monovalent cation salt eugdnolato this position.
This reaction renders the 2- alkoxyphenol molecule readily soluble in aqueous solution and also ionizes the 2-alkoxyphenol for forming a chelate.
A soluble metal salt, such eygenolato a chloride, sulfate, nitrate or acetate, wherein the metal is selected from the group consisting of Mg, Ca. The eygenolato and the monovalent cation exchange places, and the 1-hydroxyl oxygen of the alkoxyphenol donates two electrons to form a covalent bond between this oxygen atom and the metal. Further, the oxygen atom of the 2-alkoxy group also donates two electrons to form a second covalent bond with the metal.
The resulting chelate contains a five-member ring defined by the metal atom, the 2-alkoxy oxygen, the 2-carbon, the 1-carbon, and the 1-hydroxyl oxygen. This reaction scheme is expressed for a ligand to metal mole ratio of 2: The reaction of the monovalent cation salt of the 2- alkoxyphenol with the metal salt is expressed for a ligand to metal mole ratio of 3: A 1, 2-disubstituted aromatic mineral chelate according to the present invention may be represented by Formula III: As previously df, a preferred alkoxyphenol is vanillin 3-methoxyhydroxyl-benzaldehyde.
Vanillin is a known and accepted food ingredient that is generally regarded as safe. It has both a pleasing odor and taste, and is relatively easy to obtain in pure form. Mineral vanillin chelates can be synthesized by reacting vanillin with a hydroxide of a monovalent cation, such as an alkali metal hydroxide or ammonium hydroxide, eugenilato form a vanillin salt, and then adding a soluble metal salt such as a chloride, sulfate, nitrate or acetate to result in formation of the vanillin chelate.
An example of such reactions is expressed according to the znc schemes, using NaOH as a preferred alkali metal hydroxide and a metal chloride to prepare a vanillin metal chelate with a ligand to metal mole ratio of 2: A vanillin chelate may be represented at a ligand to metal ratio of 2: The five-member chelate eugrnolato may be further stabilized eugnolato the 7r-electrons of the benzene ring.
The vanillin chelate is less polar than vanillin per se, and precipitates out of solution at concentrations where vanillin is soluble. In addition to solubility in aqueous solution, vanillin chelates have other properties that differ from the parent compounds, such as taste, melting point, infrared spectroscopy, and elemental analysis, further indicating the formation of metal chelates.
The aldehyde functional group of the vanillin molecule is not believed to be involved in the reaction. The following examples are illustrative of numerous 2-alkoxyphenol chelates falling within the scope of the invention and means of their preparation.
The data presented show the best mode presently known of practicing the invention using vanillin and guaiacol as ligands through which the covalent bonds are formed with the metal. A yellowish white precipitate was formed.
This precipitate is a chelate according to reaction 4, containing a ligand to metal ratio of 2: The precipitate was collected by vacuum filtration, washed with 20 ml of distilled water, and dried. A white precipitate, which is a chelate according to reaction 4, was formed containing a ligand to metal ratio of 2: A greenish precipitate, which is a chelate according to reaction 4, was formed containing a ligand to metal ratio of 2: A brownish precipitate was formed, which then turned yellow- green.
A reddish- brown precipitate, which is a chelate according to reaction 4, was formed, containing a ligand to metal ratio of 2: A bright white precipitate, which is a chelate according to reaction 4, was formed, containing a ligand to metal ratio of 2: A bright yellow precipitate, which is a chelate according to reaction 4, was formed, containing a ligand to metal ratio of 2: A gray-green precipitate, which is a chelate according to reaction 2′, was formed containing a ligand to metal ratio of 3: A bright yellow precipitate, which is a chelate according to reaction 2, was formed, containing a ligand to metal ratio of 2: The precipitate was collected by vacuum filtration, washed with distilled water, and dried.
A yellow-green precipitate, which is a chelate according to reaction 2, was formed, containing a ligand to metal ratio of 2: To test the mechanism of chelate formation described above, vanillic acid 4-hydroxy methoxybenzoic acid was substituted for vanillin in the reaction schemes described above for synthesis of vanillin chelates.
To a solution containing 0.