Patent Grant
8007841
C10-C11-E2,E4-alkadienamide mixtures, obtainable synthetically or from a dried, ground Piper species, Piper longum Linn or Piper peepuloides, having beneficial flavor and sensory attributes in the oral cavity and on skin.
The presence of C10 and C12 diene and triene amide derivatives in a wide variety of botanicals is known and the use thereof to impart flavor and/or a tingling and/or warming sensations in the oral cavity and on skin when used in foodstuffs, chewing gum, oral care products, hair care products, colognes, topical cosmetic products or medicinal products. Such C10 and C12 diene and triene amide derivatives are also disclosed as exhibiting biological activity, most notably anti-bacterial, anti-fungal and insecticidal activity. The most significant compounds which are members of the genus: “C10 and C12 diene and triene amide derivatives” are those disclosed as follows:
Spilanthol or affinin having the structure:
the use of which in oral care, skin care and medicinal products is disclosed in Nakanatsu et al, Published European Patent Application EP 1,121,927 A2.
Pellitorine (N-isobutyl-2,4-decadienamide) has the structure:
lyeremide A (N-pyrrolidyl-2,4-decadienamide) has the structure:
lyeremide B (N-piperidyl-2,4-decadienamide) has the structure:
Piperine (N-piperidyl-5(3,4-methylenedioxyphenyl)-2,4-pentadienamide) and N-isobutyl-2,4-dodecadienamide are disclosed as constituents of Piper guineense stem by Adesina et al. in “GC/MS Investigations of the minor constituents of Piper guineense stem”, Pharmazie 57 (2002)9, pages 622-627. It is indicated in the introduction of the Adesina paper: “Piper guineense Schum and Thonn, Piperaceae . . . leaves and fruits . . . have been used as condiments, flavorants and generally as spices in foods. The sharp peppery taste of the fruit has contributed to its acceptability and use in some food and drug preparations.”
Piperine, N-piperidyl-5(3,4-methylenedioxyphenyl)-2,4-pentadienamide, is also disclosed in U.S. Pat. No. 6,365,601 as being extractable from the fruits of Piper species, including Piper longum, where it is present in a concentration of 4.5%. The corresponding 2,4-heptadienamide is also indicated to be extractable from Piper longum fruit by Das et al., “One New and Two Rare Alkamides from Two Samples of the Fruits of Piper longum”, Natural Product Sciences, 4(1):23-25(1998).
However, nothing set forth in the prior art discloses mixtures of four or more C10-C11-E2,E4-alkadienamide, particularly in high concentration, e.g., between 3% and 100%, which mixtures are useful for their beneficial flavor and sensory attributes in the oral cavity and on skin. Furthermore, nothing in the prior art discloses such. C10-C11-E2,E4-alkadienamide mixtures as extractable from the ground, dried fruit of the Piper species, Piper longum Linn or Piper peepuloides.
The invention is directed to mixtures of at least four C10-C11-E2,E4-alkadienamides, each of which alkadienamide is defined according to the structure:
wherein R represents C1-C2 n-alkyl; R1 is 2-methyl-1-propyl and R2 is hydrogen, or R1 and R2 taken together is a moiety having the formula —(CH2)n—, wherein n is 4 or 5.
The mixtures of the invention are useful for augmenting, enhancing or imparting an aroma, taste, chemesthetic effect and/or antibacterial effect in or to a consumable material and/or the oral cavity and/or the human epidermis. The term, ‘chemesthetic effect’ is herein intended to mean the sensations, tingling, warming and salivation in the oral cavity, including lips and tingling and warming on the human epidermis. Thus, the mixtures of the invention are useful in such materials as perfume compositions, perfumed articles, including cosmetics, soaps, detergents and fine fragrance compositions, foodstuffs, chewing gums, non-alcoholic beverages, alcoholic beverages, oral care products such as mouth washes, toothpastes, cough drops, cough syrups and throat lozenges, and skin care products including skin creams and lotions and hair care products including anti-dandruff compositions and shampoos.
The mixtures of the invention are hereinafter referred to as “C10-C11-E2,E4-alkadienamide mixtures”.
The C10-C11-E2,E4-alkadienamide mixtures of the invention may be obtained by means of (a) extraction of one of the Piper species, Piper longum Linn or Piper peepuloides, (b) natural product-forming synthesis or (c) synthetic-product forming synthesis. The invention is thus also directed to such C10-C11-E2,E4-alkadienamide mixture-forming processes.
Furthermore, the invention is directed to a process for augmenting, enhancing or imparting an aroma, taste, chemesthetic effect and/or antibacterial effect in or to a consumable material and/or the oral cavity and/or the human epidermis comprising the step of admixing with said consumable material and/or introducing into the oral cavity and/or applying to said human epidermis an aroma, taste, chemesthetic effect and/or antibacterial effect-effecting concentration and quantity of one or more of such C10-C11-E2,E4-alkadienamide mixtures.
The C10-C11-E2,E4-alkadienamide mixtures of the invention preferably are utilized in the practice of the invention in concentrations of from about 3% to about 100% by weight of the product in which the mixtures are employed. In addition, the C10-C11-E2,E4-alkadienamide mixtures of the invention preferably include the components:
i. N-isobutyl-E2,E4-decadienamide;
ii. N-isobutyl-E2,E4-undecadienamide;
iii. N-pyrollidyl-E2,E4-decadienamide; and
iv. N-piperidyl-E2,E4-decadienamide
having the structures:
respectively.
When the C10-C11-E2,E4-alkadienamide mixtures of the invention are obtained by means of extraction of one of the Piper species, Piper longum Linn or Piper peepuloides, the process employed comprises the steps of:
Preferred variations of the above described process are as follows:
In addition, the above mentioned process may also comprise the additional step of admixing the resulting extract, when the distillation step is not employed, or distillate with a food-grade diluent.
When the C10-C11-E2,E4-alkadienamide mixture components of the invention are obtained by means of natural product-forming synthesis, the process employed comprises the steps of:
The resulting individual amides are then admixed with one another thereby forming the mixture of C10-C11-E2,E4-alkadienamide components of the invention.
In the above described process, when the amine initially formed is isobutyl amine, it is preferably produced by reacting natural valine with a natural aromatic ketone or aromatic aldehyde to form an imine carboxylic acid; isomerizing and decarboxylating the resulting imine carboxylic acid to form a decarboxylated imine; hydrolyzing the resulting decarboxylated imine at a pH of from about 1.5 to about 3.5 thereby forming the natural isobutyl amine salt.
Preferably, the esterification in step vi. above of the E2,E4-dienoic acid is carried out with natural ethanol.
Thus, for example, in accordance with the above described generic process, the specific process for the production of natural N-isobutyl-E2,E4-decadienamide having the structure:
comprising the steps of:
and
When the C10-C11-E2,E4-alkadienamide mixture components of the invention are obtained by means of synthetic product-forming synthesis, the process employed comprises the steps of dissolving an E2,E4-dienoic acid selected from the group consisting of E2,E4-decadienoic acid and E2,E4-undecadienoic acid in a compatible solvent thereby forming a E2,E4-dienoic acid solution; admixing the resulting E2,E4-dienoic acid solution with from about 1 to about 2 equivalents of an acid-activating reagent selected from the group consisting of a lower alkyl haloformate, an N,N′-dialiphatic or cycloaliphatic azodicarbodiimide and a dihalo-oxalate at a temperature in the range of from about 0° C. to about 20° C. thereby forming an intermediate; cooling the resulting intermediate-containing solution to a temperature in the range of from about −10° C. to about +10° C. and, when using as a reactant the lower alkyl haloformate or the dihalooxalate, admixing therewith a tri-loweralkyl amine while maintaining the temperature of the mixture below +10° C.; then aging the resulting intermediate-containing product at ambient conditions for a period of from about 0.5 to about 3 hours, according to the reaction:
filtering the resulting product; separating the resulting filtrate and cooling the resulting filtrate to a temperature in the range of from about −5° C. to +5° C.; admixing the resulting cooled filtrate with from about 1 to about 4 equivalents of an amine selected from the group consisting of isobutyl amine, piperidine and pyrrolidine at ambient conditions thereby effecting an amidation reaction, and thereby forming an amide defined according to the structure:
and recovering the resulting amide.
The resulting individual amides are then admixed with one another thereby forming the mixture of C10-C11-E2,E4-alkadienamide components of the invention.
When using as an acid activating agent ethyl chloroformate, the reaction proceeds as follows:
The thus-formed mixtures of C10-C11-E2,E4-alkadienamide components of the invention may each be admixed with a substantial quantity and concentration of a tingling sensate, for example, one or more of such sensates selected from the group consisting of substantially pure spilanthol having the structure:
Acmella ciliata, Acmella (Spilanthes) oppositifolia, Anacyclus pyrethrum D. C., Spilanthes acmella L. var. oleraceae (Jambu) and Heliopsis longipes S. F. Blake (Chilcuan) and the resulting mixtures may then be used for augmenting, enhancing or imparting an aroma, taste, chemesthetic effect and/or antibacterial effect in or to a consumable material and/or the oral cavity and/or the human epidermis by means of a process comprising the step of admixing with said consumable material and or introducing into the oral cavity and/or applying to said human epidermis an aroma, taste, chemesthetic effect and/or antibacterial effect-effecting concentration and quantity of the resulting mixture.
The following Table I sets forth examples of processes and compositions where the mixtures of C10-C11-E2,E4-alkadienamide components of the invention are utilized. Each of the useful ingredients set forth in the cited U.S. Patent and patent application references, including the examples thereof is usable in the practice of the invention, and hereby incorporated by reference.
As used herein olfactory effective amount is understood to mean the amount of compound in flavor compositions, oral care compositions, nasal care compositions, skin care compositions, hair and scalp care compositions, cosmetic compositions and other consumable materials as defined supra, the individual component will contribute to its particular olfactory characteristics, but the flavor, taste and aroma effect on the overall composition will be the sum of the effects of each of the flavor ingredients. As used herein taste effects include bitterness and tingling effects. Thus the compounds of the invention can be used to alter the taste characteristics of the flavor composition by modifying the taste reaction contributed by another ingredient in the composition. The amount will vary depending on many factors including other ingredients, their relative amounts and the effect that is desired.
The level of use of the mixtures of C10-C11-E2,E4-alkadienamide components of the invention in products is greater than 10 parts per billion, generally provided at a level of from about 50 parts per billion to about 200 parts per million in the finished product, more preferably from about 100 parts per billion to about 100 parts per million by weight.
The usage level of the mixtures of C10-C11-E2,E4-alkadienamide components of the invention varies depending on the product in which the mixtures of C10-C11-E2,E4-alkadienamide components of the invention are employed. For example, alcoholic beverages the usage level is from about 0.5 to about 25 parts per million, preferably from about 2 to about 10 and most preferably from about 5 to about 10 parts per million by weight. Non-alcoholic beverages are flavored at levels of from about 25 parts per billion to about 2 parts per million, preferably from about 100 parts per billion to about 0.5 parts per million and in highly preferred situations of from about 150 to about 400 parts per billion. Snack foods can be advantageously flavored using the mixtures of C10-C11-E2,E4-alkadienamide components of the invention at levels of from about 5 to about 250 parts per million, preferably from about 25 to about 200 and most preferably from about 35 to about 75 parts per million by weight.
The term “foodstuff” as used herein includes both solid and liquid ingestible materials for man or animals, which materials usually do, but need not, have nutritional value. Thus, foodstuffs include meats, gravies, soups, convenience foods, malt, alcoholic and other beverages, milk and dairy products, seafood, including fish, crustaceans, mollusks and the like, candies, vegetables, cereals, soft drinks, snacks, dog and cat foods, other veterinary products and the like.
When the mixtures of C10-C11-E2,E4-alkadienamide components of the invention are used in a flavoring composition, they can be combined with conventional flavoring materials or adjuvants. Such co-ingredients or flavor adjuvants are well known in the art for such use and have been extensively described in the literature. Requirements of such adjuvant materials are: (1) that they be non-reactive with the components of the mixtures of C10-C11-E2,E4-alkadienamides of the invention (2) that they be organoleptically compatible with the components of the mixtures of C10-C11-E2,E4-alkadienamides of the invention whereby the flavor of the ultimate consumable material to which the components of the mixtures of C10-C11-E2,E4-alkadienamides of the invention are added is not detrimentally affected by the use of the adjuvant; and (3) that they be ingestible acceptable and thus nontoxic or otherwise non-deleterious. Apart from these requirements, conventional materials can be used and broadly include other flavor materials, vehicles, stabilizers, thickeners, surface active agents, conditioners and flavor intensifiers.
Such conventional flavoring materials include saturated fatty acids, unsaturated fatty acids and amino acids; alcohols including primary and secondary alcohols, esters, carbonyl compounds including ketones, lactones; other cyclic organic materials including benzene derivatives, acyclic compounds, heterocyclics such as furans, pyridines, pyrazines and the like; sulfur-containing compounds including thiols, sulfides, disulfides and the like; proteins; lipids, carbohydrates; so-called flavor potentiators such as monosodium glutamate; magnesium glutamate, calcium glutamate, guanylates and inosinates; natural flavoring materials such as hydrolyzates, cocoa, vanilla and caramel; essential oils and extracts such as anise oil, clove oil and the like and artificial flavoring materials such as vanillyl butyl ether, ethyl vanillin and the like.
Specific preferred flavor adjuvants include but are not limited to the following: anise oil; ethyl-2-methyl butyrate; vanillin; cis-3-heptenol; cis-3-hexenol; trans-2-heptenal; butyl valerate; 2,3-diethyl pyrazine; methyl cyclo-pentenolone; benzaldehyde; valerian oil; 3,4-dimeth-oxyphenol; amyl acetate; amyl cinnamate; γ-butyryl lactone; furfural; trimethyl pyrazine; phenyl acetic acid; isovaleraldehyde; ethyl maltol; ethyl vanillin; ethyl valerate; ethyl butyrate; cocoa extract; coffee extract; peppermint oil; spearmint oil; clove oil; anethol; cardamom oil; wintergreen oil; cinnamic aldehyde; ethyl-2-methyl valerate; γ-hexenyl lactone; 2,4-decadienal; 2,4-heptadienal; methyl thiazole alcohol (4-methyl-5-β-hydroxyethyl thiazole); 2-methyl butanethiol; 4-mercapto-2-butanone; 3-mercapto-2-pentanone; 1-mercapto-2-propane; benzaldehyde; furfural; furfuryl alcohol; 2-mercapto propionic acid; alkyl pyrazine; methyl pyrazine; 2-ethyl-3-methyl pyrazine; tetramethyl pyrazine; polysulfides; dipropyl disulfide; methyl benzyl disulfide; alkyl thiophene; 2,3-dimethyl thiophene; 5-methyl furfural; acetyl furan; 2,4-decadienal; guaiacol; phenyl acetaldehyde; β-decalactone; d-limonene; acetoin; amyl acetate; maltol; ethyl butyrate; levulinic acid; piperonal; ethyl acetate; n-octanal; n-pentanal; n-hexanal; diacetyl; monosodium glutamate; monopotassium glutamate; sulfur-containing amino acids, e.g., cysteine; hydrolyzed vegetable protein; 2-methylfuran-3-thiol; 2-methyldihydrofuran-3-thiol; 2,5-dimethylfuran-3-thiol; hydrolyzed fish protein; tetramethyl pyrazine; propylpropenyl disulfide; propylpropenyl trisulfide; diallyl disulfide; diallyl trisulfide; dipropenyl disulfide; dipropenyl trisulfide; 4-methyl-2-[(methylthio)-ethyl]-1,3-dithiolane; 4,5-dimethyl-2-(methylthiomethyl)-1,3-dithiolane; and 4-methyl-2-(methylthiomethyl)-1,3-dithiolane.
The components of the mixtures of C10-C11-E2,E4-alkadienamides of the invention or compositions incorporating them, as mentioned above, can be combined with one or more vehicles or carriers for adding them to the particular product. Vehicles can be water-soluble or oil-soluble edible or otherwise suitable materials such as triacetin, vegetable oil, triethyl citrate, ethyl alcohol, propylene glycol, water and the like. Carriers include materials such as gum arabic, carrageenan, xanthan gum, guar gum and the like.
Components of the mixtures of C10-C11-E2,E4-alkadienamides of the invention prepared according to the invention can be incorporated with the carriers by conventional means such as spray-drying, extrusion, drum-drying and the like. Such carriers can also include materials for coacervating the components of the mixtures of C10-C11-E2,E4-alkadienamides of the invention to provide encapsulated products, as set forth supra. When the carrier is an emulsion, the flavoring composition can also contain emulsifiers such as mono- and diglycerides or fatty acids and the like. With these carriers or vehicles, the desired physical form of the compositions can be prepared.
The quantity of the components of the mixtures of C10-C11-E2,E4-alkadienamides of the invention utilized should be sufficient to impart the desired flavor characteristic to the product, but on the other hand, the use of an excessive amount of the components of the mixtures of C10-C11-E2,E4-alkadienamides of the invention is not only wasteful and uneconomical, but in some instances, too large a quantity may unbalance the flavor or other organoleptic properties of the product consumed. The quantity used will vary depending upon the ultimate foodstuff; the amount and type of flavor initially present in the foodstuff; the further process or treatment steps to which the foodstuff will be subjected; regional and other preference factors; the type of storage, if any, to which the product will be subjected; and the preconsumption treatment such as baking, frying and so on, given to the product by the ultimate consumer. Accordingly, the terminology “effective amount” and “sufficient amount” is understood in the context of the present invention to be quantitatively adequate to alter the flavor of the foodstuff.
Referring to
Referring to
Referring to
Referring to
The following Table II sets forth the specific substance being compared identified by a specific reference numeral:
Piper peepuloides (contains 5% mixture of C10-C11-E2,E4-
Piper longum Linn (contains 35% mixture of C10-C11-E2,E4-
Referring to
The following Table III sets forth the specific substance being compared identified by a specific reference numeral:
Piper longum Linn (contains 35% mixture of C10-C11-E2,E4-
Piper longum Linn (contains 25% mixture of C10-C11-E2,E4-
Piper longum Linn (contains 7% mixture of C10-C11-E2,E4-
Piper peepuloides (contains 5% mixture of C10-C11-E2,E4-
The following examples are provided as specific embodiments of the present invention. Other modifications of this invention will be readily apparent to those skilled in the art, without departing from the scope of this invention. As used herein, both the specification and the following examples all percentages are weight percent unless noted to the contrary.
The following reaction sequence was used to prepare the specific compounds described by the NMR data set forth below:
2,4-Dienoic acid was dissolved in dichloromethane to which ethylchloroformate was added in 1.0 to 2.0 equivalents at temperature ranging from 0° C. to room temperature, most preferably from 10° C. to 20° C. The resulting solution was cooled to −10° C. to +10° C., and triethylamine was added in 1.0 to 2.0 equivalents such that the temperature range is below 10° C. and the mixture aged for 1 hour at room temperature. The mixture was filtered, and the filtrate cooled to 0° C.
The amine was added in 1.0 to 4.0 equivalents and the reaction was aged for about 1-3 hours at room temperature. The reaction was quenched with 10% aqueous hydrochloric acid, washed with 10% sodium hydroxide followed by sodium chloride solution, and the solvent was removed.
The crude product was purified by distillation or recrystallization depending on the physical properties. The reaction occurred in 40-60% mole yields based on the acids.
The amides were synthesized according to the general scheme above with the following specific examples. Equivalents set out are mole equivalents based on starting acid, yields are purified chemical yields based on starting acid.
E2,E4-decadienoic acid 1 eq, ethyl chloroformate 1.5 eq, triethylamine 1.5 eq, isobutylamine 3.0 eq, quench as per general procedure, yield=45%.
E2,E4-undecadienoic acid 1 eq, ethyl chloroformate 1.5 eq, triethylamine 1.5 eq, isobutylamine 3.0 eq, quench as per general procedure, yield=40%.
E2,E4-decadienoic acid 1 eq, ethyl chloroformate 1.1 eq, triethylamine 1.2 eq, piperidine 1.25 eq, quench as per general procedure, yield=40%.
E2,E4-decadienoic acid 1 eq, ethyl chloroformate 1.1 eq, triethylamine 1.2 eq, pyrrolidine 1.5 eq, quench as per general procedure, yield=58%.
The following fragrance was prepared for use with the shampoo of Example II:
At the rate of 0.8%, the fragrance was prepared according to Example IIA and admixed with the following aqueous shampoo base:
To the shampoo of Example IIB, zinc pyrithione was added at the rate of 1%, and the following mixture, the components of which were prepared according to Example I, were added at the rate of 0.3%:
A substantial tingling effect was exerted during use and 5 minutes post use of the shampoo, having a value of 9 on a scale of 1-9.
The following punch flavor was prepared:
20 Grams of the flavor composition of Example IIIA was emulsified in a solution containing 300 grams of gum acacia and 700 grams of water. The emulsion was spray-dried with a Bowen Lab Model Drier utilizing 250 cubic feet per minute of air with an inlet temperature of 500° F. and an outlet temperature of 200° F. and a wheel speed of 50,000 r, p, m.
A mixture of 300 grams of the liquid flavor of Example IIIA and 1 kg. of Cab-O-Sil M-5 (Cabot Corporation of Boston, Mass.) silica was prepared by dispersing the silica in the liquid flavor with vigorous stirring. The powder flavor prepared according to part (i) was then blended into the resulting viscous liquid with stirring at 25° C. for a period of about 30 minutes resulting in a sustained release flavor paste.
Into a Hobart mixer, 98.15 parts by weight of sorbitol was admixed with 0.05 parts by weight of FD&C yellow #6 lake (Warner Jenkinson).
To the resulting mixture, with stirring the following substances were added:
0.8 parts by weight of magnesium stearate was then added to the resulting mixture and the resulting mixture was tabletted, providing orange-punch-flavored tablets with a pleasant ‘tingle’ effect.
This application is a divisional of U.S. Ser. No. 10/678,558, filed on Oct. 3, 2003, the contents hereby incorporated by reference as if set forth in its entirety.
| Number | Name | Date | Kind |
|---|---|---|---|
| 6264926 | Farooqi et al. | Jul 2001 | B1 |
| 6451354 | Hebert et al. | Sep 2002 | B1 |
| Number | Date | Country |
|---|---|---|
| 2157226 | Oct 2000 | RU |
| Number | Date | Country | |
|---|---|---|---|
| 20080008811 A1 | Jan 2008 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | 10678558 | Oct 2003 | US |
| Child | 11857672 | US |
