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WO2001028590A2 - COMPOSITIONS PHARMACEUTIQUES RENFERMANT UN ESTER N-[N-(3,3-DIMETHYLBUTYL)-1-α-ASPARTYL]-L-PHENYLALANINE METHYL - Google Patents

COMPOSITIONS PHARMACEUTIQUES RENFERMANT UN ESTER N-[N-(3,3-DIMETHYLBUTYL)-1-α-ASPARTYL]-L-PHENYLALANINE METHYL Download PDF

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Publication number
WO2001028590A2
WO2001028590A2 PCT/US2000/028731 US0028731W WO0128590A2 WO 2001028590 A2 WO2001028590 A2 WO 2001028590A2 US 0028731 W US0028731 W US 0028731W WO 0128590 A2 WO0128590 A2 WO 0128590A2
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WO
WIPO (PCT)
Prior art keywords
neotame
ppm
medication
taste
amount
Prior art date
Application number
PCT/US2000/028731
Other languages
English (en)
Other versions
WO2001028590A3 (fr
Inventor
Subbarao V. Ponakala
Original Assignee
The Nutrasweet Company
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by The Nutrasweet Company filed Critical The Nutrasweet Company
Priority to AU10934/01A priority Critical patent/AU1093401A/en
Publication of WO2001028590A2 publication Critical patent/WO2001028590A2/fr
Publication of WO2001028590A3 publication Critical patent/WO2001028590A3/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/30—Artificial sweetening agents
    • A23L27/31—Artificial sweetening agents containing amino acids, nucleotides, peptides or derivatives
    • A23L27/32—Artificial sweetening agents containing amino acids, nucleotides, peptides or derivatives containing dipeptides or derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
    • A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
    • A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals

Definitions

  • the present invention relates to the use of N-[N-(3,3-dimethylbutyl)-L- ⁇ -aspartyl]-L- phenylalanine 1 -methyl ester (neotame) as a means of improving the taste or aroma of pharmaceutical products and related compositions.
  • the invention relates to the use of neotame in both over-the-counter type products and ethical compositions obtained as prescription medications.
  • Pharmaceutical products are useful in society for a variety of health benefits and are used by people in order to maintain an adequate and satisfactory standard of living.
  • the types of pharmaceutical products are diverse and include ethical compositions as well as numerous compositions which are available over the counter, such as non-presc ⁇ ption drugs.
  • the types of formulations are also very diverse, and include powders, tablets, pills, capsules, aerosols, syrups, liquid formulations, lozenges (drops), and chewable and non-chewable forms. Depending on the targeted end application, these forms are formulated with a wide variety of active and in-active ingredients.
  • Pharmaceutical products contain essential ingredients (i.e. active ingredients) which may impart undesirable tastes or aromas when administered. Therefore, without the aid of a taste masking agent the product may be deemed unacceptable by consumers.
  • a pleasing taste or aroma is necessary to help achieve the heath benefit of these products since diminishing undesirable taste qualities will result in a more thorough use and administration of the particular product.
  • Many compounds which function as medicinal substances have bitter and astringent characteristics which make the substance unpalatable, especially to younger children and older adults who may be less tolerable to the inherent taste properties of the substance.
  • many medicinal substances are targeted for the elderly and young children and thus the problem of achieving effective administration of the product is exacerbated. As a consequence there remains a need to increase the level of patient compliance of many pharmaceutical related products and compositions.
  • Taste-masking agents and flavoring ingredients are generally added to pharmaceutical products in order to mask the undesirable off- tastes contributed by either the active or inactive ingredients required for functionality.
  • Flavoring systems can also be used and include a variety of different agents, including mint oils such as peppermint and spearmint, as well as numerous flavor- modifying compounds recognized as flavoring ingredients in the food industry.
  • Fruit flavors are often used in products targeted for children in order to increase the level of palatability.
  • High- intensity sweeteners such aspartame, saccharine and acesulfame-K have also been used as taste- masking agents.
  • the flavor or taste-masking agent is generally incorporated as part of the pharmaceutical composition.
  • taste-masking substances cannot be used without first considering the other ingredients which make up the composition.
  • the taste-masking agent needs to be compatible with both the active and non- active ingredients that make up the particular product as well as be compatible and blend well with other flavor agents used.
  • U.S. Patent No. 5,084,278 discloses a polymeric mixture coating that masks the bitter taste of chewable acetaminophen tablets.
  • U.S. Patent No. 5,437,873 discloses a method for improving the taste of antacid tablets and calcium supplements. Aspartame is shown to be effective for improving the taste properties of chewable vitamins (JP Patent No. 60,198,571).
  • a taste improvement was achieved using a co-spray-dried form of a polyol as disclosed in WO Patent No. 9,741,835. Saccharin has been used to mask undesirable tastes in laxatives as described in U.S. Patent No. 5,498,425.
  • the N-alkylated aspartame derivative, neotame is a highly intense non-nutritive sweetening agent useful to impart sweetness of a wide variety of food products.
  • This compound disclosed in U.S. Patent No. 5,480,668, is approximately 8,000 times as sweet as sucrose and 40 times as sweet as aspartame on a weight basis.
  • neotame is able to mask undesirable tastes and aromas of pharmaceutical compositions and as a result make such products more pleasing and acceptable.
  • neotame is able to improve the taste and aroma of pharmaceutical products by modifying flavoring ingredients traditionally used.
  • Neotame's ability to improve the flavor characteristics of many different flavor systems used in pharmaceutical formulations is also unique among flavor enhancing ingredients in general and high-intensity sweeteners in particular. It therefore would be advantageous to utilize these properties of neotame in pharmaceutical products. Such use is not described or suggested by the prior art.
  • neotame neotame in an amount effective to mask the unpleasant taste or aroma of the pharmaceutical product, and therefore achieve an more palatable product.
  • pharmaceutical products comprising a blend of neotame with other taste- masking agents in a combined amount effective to produce a more desirable taste in the pharmaceutical product.
  • the invention includes the use of neotame to modify the taste characteristics of certain bulking agents and inert ingredients as it has also been discovered that neotame, when used at taste-masking levels reduces or eliminates the off-tastes of said bulking or inert agents which are traditionally used.
  • the invention also relates to the method of preparing compositions of pharmaceutical products containing neotame.
  • This invention is related to the improvement of the taste or aroma of pharmaceutical products by neotame. If neotame is used exclusively the amount will range from about 1 to about 2000 parts per million (ppm). More preferably, the amounts will range from about 5 to about 500 ppm. If neotame is used as part of a flavoring system comprising other flavoring agents or taste improvement agents the amount of neotame will range from about 0.01 to about 1000 ppm.
  • the types of pharmaceutical products that can be improved according to this invention are very diverse and represent a variety of different compositions that can be prepared from ingredients traditionally used in the formulation of pharmaceutical compositions.
  • the pharmaceutical product can exist in a variety of different forms. These include powders, tablets, pills, capsules, gels, lozenges (drops), aerosols, and liquid formulations such as syrups, emulsions, suspensions, and extractives. Tablets, pills, capsules, gels, or lozenges can be either the chewable type or coated.
  • Types of pharmaceutical products include, but not limited to antacids, laxatives, multi-vitamins, analgesics (for example, aspirin, acetaminophen, and ibuprofen compositions), cough medications (syrups, lozenges, etc.), cold and flu medications, and sinus and allergy-relief medications.
  • analgesics for example, aspirin, acetaminophen, and ibuprofen compositions
  • cough medications sleep medications
  • cold and flu medications cold and flu medications
  • sinus and allergy-relief medications sinus and allergy-relief medications.
  • One object of this invention is to provide a pharmaceutical composition which has a reduction or elimination of undesirable taste or aroma characteristics imparted by either the active or inert ingredients used in the formulation.
  • Use of high-intensity sweeteners in pharmaceutical products generally requires the use of a bulking agent or other inert ingredient to provide a desirable delivery form. These bulking agents are commonly used to achieve targeted functionality as well as provide a particular delivery form. Accordingly, there is a need to mask or diminish the taste characteristics of said ingredients such as bitterness or other unpleasant off-notes without the added addition of costly masking ingredients.
  • Such pharmaceutical compositions containing neotame would not only provide an improved taste or aroma but also allow for .a reduced total amount of flavoring agent required, thereby reducing costs of production.
  • Common bulking agents used in pharmaceutical compositions include, but are not limited to, starch and starch derivatives, cellulose and cellulose derivatives, mannitol, lactose, dextrose, sorbitol, and gelatin. Some bulking agents such as sugars, carbohydrates, and sugar alcohols can also provide added sweetness and work in combination with neotame to aid in the taste-masking effect. Use of bulking agents as inert ingredients in the pharmaceuticals industry is well known and the particular formulation considerations in using a particular bulking agent can be utilized by those skilled in the art.
  • Another aspect of the invention is the longer lasting perception of the flavor or aroma provided by the pharmaceutical composition containing neotame, thereby making the composition more appealing after administration.
  • neotame neotame
  • Another aspect of the invention is the longer lasting perception of the flavor or aroma provided by the pharmaceutical composition containing neotame, thereby making the composition more appealing after administration.
  • neotame used in these types of pharmaceutical products may take any form.
  • it may be a salt or complex such as described in U.S. Patent Application No. 09/146,963, U.S. Patent Application No. 09/146,964, U.S. Patent Application No. 09/148,134, U.S. Patent Application No. 09/146,965, U.S. Patent Application No. 09/154,568, and U.S. Provisional Patent Application No. 60/126,363, the disclosure of each of which is incorporated by reference herein.
  • Other exemplary forms of neotame that may be used in this invention include co-crystallized forms and cyclodextrin complexes, such as described in U.S. Patent Application No.
  • Neotame described herein may be blended with one or more other taste-masking agents or high-intensity sweeteners to mask the undesirable taste of some ingredients in such pharmaceutical products.
  • sweeteners may be conventional caloric sweeteners, sugar alcohols, or high-intensity sweeteners.
  • Suitable sugars include monosaccharides, disaccharides, and polysaccharides such as xylose, ribulose, glucose (dextrose), mannose, galactose, fructose (levulose), sucrose (sugar), maltose, invert sugar, partially hydrolyzed starch and corn syrup solids, and mixtures thereof.
  • Suitable sugar alcohols include sorbitol, xylitol, mannitol, lactitol, isomalt (a racemic mixture of ⁇ -D-glusopyranosyl-l,6-mannitol and ⁇ -D-glucopytanosyl-l,6-sorbitol manufactured under the tradename PalatinitTM), and mixtures thereof.
  • Other sugar related substances include maltodextrins, hydrogenated starch hydrolysates, hydrogenated hexoses, hydrogenated disaccharides, and the like, and mixtures thereof.
  • suitable high-intensity sweeteners include (A) water-soluble naturally-occurring intense sweeteners such as dihyroxychalcones, monellin, steviosides, glycyrrhizins,. dihydroflavenol, and L-aminodicarboxylic acid aminoalkenoic acid ester amides, such as those disclosed in U.S. Pat. No.
  • water-soluble artificial sweeteners including the soluble saccharin salts of 3,4-dihydro-6-methyl-l,2,3-oxathiazine-4- one-2,2-dioxide, the potassium salt of 3,4-dihydro-6-methyl-l,2,3-oxathiazine-4-one-2,2- dioxide (Acesulfame-K), the free acid form of saccharin, and the like, and mixtures thereof;
  • dipeptide based sweeteners including L-aspartic acid derivatives described in U.S. Pat. No.
  • chlorodeoxysugar derivatives and mixtures thereof and (E) protein based intense sweeteners such as thaumaoccous danielli (thaumatin I and II). Use of these sweeteners in the pharmaceutical composition would naturally reduce the level of neotame required for a particular application.
  • compositions typically contain a variety of different colorants and flavorings.
  • colorants that can be used in compositions containing neotame and therefore any colorant recognized as a traditional pharmaceutical colorant by those skilled in the art can be used.
  • flavoring ingredients which can be used in a pharmaceutical product sweetened with neotame.
  • Commonly used flavors include the mints such as spearmint and peppermint, menthol, ethyl vanillin, methyl salicylate, and various fruit flavors like cherry or orange, whether employed individually or in admixture.
  • the amounts of colorants and flavorings used are normally a matter of preference subject to type and desired end-strength.
  • the amount of neotame used to mask an unpleasant taste or aroma in the pharmaceutical composition will be dependent on the particular application and also subject to individual preference of degree of palatability improvement.
  • the desired concentration ranges of neotame may vary due to the targeted improvement level, pH, acidity, and processing conditions. The objective in determining the exact amount of neotame for a particular pharmaceutical product is guided by the degree of improvement desired.
  • One embodiment of this invention relates to chewable or coated vitamins formulated with neotame.
  • Vitamins are generally formulated with a mannitol base, various individual vitamins, fruit flavors such as grape or cherry, and a binder such as magnesium stearate.
  • the usage range level of neotame that provides acceptable sweetness in chewable or coated vitamins is about 1 to about 250 ppm, more preferably between 5 and 150 ppm, and most preferably between 10 and 100 ppm.
  • Antacids are generally formulated with a mannitol base, calcium carbonate, a flavor such as mint or menthol, and a binder such as magnesium stearate.
  • the usage range level of neotame that provides acceptable taste-masking in antacids is about 1 to about 2000 ppm, more preferably between 5 and 1000 ppm, and most preferably between 10 and 100 ppm.
  • Yet another embodiment of this invention includes the use of neotame to improve the taste of analgesics.
  • Analgesics are generally formulated with a mannitol base, active ingredient such as aspirin, ibuprofen, or acetaminophen, flavor agent, and a binder such as magnesium stearate.
  • the usage range level of neotame that provides acceptable taste improvement in analgesics is about 1 to about 230 ppm, more preferably between 5 and 130 ppm, and most preferably between 10 and 75 ppm.
  • Cough medicines are typically syrups or lozenges.
  • Cough lozenges are often formulated with hydrogenated starch hydrosylate, corn oil, eucalyptus oil, and a flavor such as menthol.
  • the usage range level of neotame that provides acceptable taste improvement in cough lozenges is about 5 to about 2000 ppm, more preferably between 10 and 1000 ppm, and most preferably between 15 and 300 ppm.
  • Still another embodiment of this invention relates to the used of neotame to improve the taste or aroma of cold and flu medications.
  • Cold and flu medications contain a variety of different ingredients and include many types of over-the-counter and prescription drug products.
  • the medications also come in many different forms.
  • the usage range level of neotame that provides an acceptable taste improvement in these products is about 1 to 1000 ppm, more preferably between 5 and 750 ppm, and most preferably between 10 and 500 ppm.
  • neotame in sinus and allergy- relief medications. These medications also include many types of over-the-counter and prescription products and come in many forms.
  • the usage level of neotame that provides an acceptable taste improvement is about 1 to 1000 ppm, more preferably between 5 and 750 ppm, and most preferably between 10 and 500 ppm.
  • neotame in laxatives.
  • These types of pharmaceuticals use a variety of different ingredients and flavoring systems.
  • a bulk fiber laxative is generally formulated of a mannitol base and psyllium seed husks.
  • the usage range level of neotame that provides acceptable sweetness in mint pharmaceuticals is about 1 to about 130 ppm, more preferably between 5 and 45 ppm, and most preferably between 10 and 25 ppm.
  • the amount of the blend may be adjusted to provide a sweetness equivalent to the sweetness provided by between about 0.1 ppm and about 2000 ppm of neotame based on the total amount of the pharmaceutical composition.
  • the neotame blend is present in an amount that will provide a sweetness equivalent to that provided by between about 5 ppm and about 1000 ppm of neotame. More preferably, the neotame sweetener blend is present in an amount witch will provide a sweetness equivalent to that provided by between about 10 ppm and about 100 ppm of neotame.
  • neotame or neotame sweetener blend may be incorporated into the pharmaceutical composition in a variety of ways.
  • neotame or the neotame sweetener blend may be applied as an ingredient in the coating, sprayed on the surface, or incorporated in the actual pharmaceutical composition as part of the ingredient formulation and processed.
  • the pharmaceutical products of this invention may be prepared using ingredients and techniques that are well known to those skilled in the art.
  • Table 1 provides a prophetic formulation of a cough lozenge that can prepared according to the present invention.
  • a cough lozenge can be prepared by first precooking liquid hydrogenated starch hydroyslate in a precooker to about 245 °F, pumped through a cooking unit and cooked to about 295 °F (final cool temperature will vary with the type of type of hydrogenated starch hydrolysate).
  • the cooked syrup is then drained into a vacuum chamber to decrease moisture content to 1.5% (finished product moisture will depend on the type of hydrogenated starch hydrolysate and the cook process used).
  • the cooked syrup is mixed with neotame and the remaining ingredients in an in-line mixer (temperature 265-290°F) and the product tempered on a tempering band, formed into a rope, die cut into desired form, and cooled to room temperature.
  • Table 2 provides a prophetic formulation of an antacid tablet that is prepared according to the present invention.
  • the ingredients are blended thoroughly in a mixer.
  • the resulting mix is then pressed to 4-6 kilopound hardness and packaged in airtight containers prior to sensory evaluation.
  • Formulation of antacid tablets containin neotame.
  • Table 3 provides a prophetic formulation of a bulk fiber laxative that can be prepared according to the present invention.
  • the neotame and a portion of the psyllium husks are blended together, known in the process as Product A.
  • the mannitol is dissolved in distilled water to produce a 10% weight/volume solution, known in the process as Product B.
  • the bowl of a fluidized bed spray agglomerator is the loaded with the rest of the psyllium husks and Product A.
  • the fluidized bed spray agglomerator is then secured, energized and agglomerated with the mannitol solution marked Product B.
  • the dried agglomerate is then screened and packaged in airtight containers.
  • Table 4 provides a prophetic formulation for chewable analgesic tablets that can be prepared according to the present invention.
  • the ingredients are blended in a mixer thoroughly.
  • the resulting mix is pressed to 4-6 kilopound hardness and packaged in airtight containers prior to sensory evaluation.
  • Formulation of chewable anal esic tablets containin neotame.
  • Table 5 provides a prophetic formulation for children's multi-vitamin chewable tablets that can be prepared according to the present invention.
  • the ingredients are blended thoroughly in a mixer and the resulting mix is then pressed to 4-6 kilopound hardness and packaged in airtight containers prior to sensory evaluation.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Medicinal Preparation (AREA)
  • Seasonings (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne des produits pharmaceutiques et des compositions associées renfermant du néotame. Ces compositions pharmaceutiques ont démontré avoir des caractéristiques de goût et d'arôme améliorées.
PCT/US2000/028731 1999-10-19 2000-10-18 COMPOSITIONS PHARMACEUTIQUES RENFERMANT UN ESTER N-[N-(3,3-DIMETHYLBUTYL)-1-α-ASPARTYL]-L-PHENYLALANINE METHYL WO2001028590A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU10934/01A AU1093401A (en) 1999-10-19 2000-10-18 Pharmaceutical compositions containing n-(n-(3,3-dimethylbutyl)-1-alpha-aspartyl)-l-phenylalanine methyl ester

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US16030599P 1999-10-19 1999-10-19
US60/160,305 1999-10-19

Publications (2)

Publication Number Publication Date
WO2001028590A2 true WO2001028590A2 (fr) 2001-04-26
WO2001028590A3 WO2001028590A3 (fr) 2008-01-03

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AU (1) AU1093401A (fr)
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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1514481A1 (fr) * 2003-09-11 2005-03-16 Christian Fenioux Utilisation de la néohespéridine dihydrochalcone dans des comprimés à croquer comprenant des vitamines et/ou minéraux
JP2012175930A (ja) * 2011-02-25 2012-09-13 Ogawa & Co Ltd 高甘味度甘味料の呈味改善剤
US11229612B2 (en) 2016-07-01 2022-01-25 GW Research Limited Parenteral formulations
US11291631B2 (en) 2016-07-01 2022-04-05 GW Research Limited Oral cannabinoid formulations
US11426362B2 (en) 2017-02-17 2022-08-30 GW Research Limited Oral cannabinoid formulations
US11806319B2 (en) 2018-01-03 2023-11-07 GW Research Limited Pharmaceutical composition comprising a cannabinoid

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10259194A (ja) * 1997-03-18 1998-09-29 Ajinomoto Co Inc 新規ジペプチド誘導体及び甘味剤
US6291004B1 (en) * 1997-09-11 2001-09-18 The Nutrasweet Company Basic salts of n-[n-(3,3-dimethylbutyl)-l-α-aspartyl]-l-phenylalanine 1-methyl ester
AR014129A1 (es) * 1997-12-17 2001-02-07 Nutrasweet Co Bebida que comprende fundamentalmente un ester n-[n-(3,3-dimetilbutil)-l- alfa-aspartil]-l-fenilamina 1 - metilico, bebida sin alcohol carbonatada,bebida de jugo, bebida envasada caliente y bebida deportiva de bajas calorias.
JPH11279081A (ja) * 1998-03-27 1999-10-12 Ajinomoto Co Inc 苦味物質含有組成物
JP3643921B2 (ja) * 1998-05-08 2005-04-27 味の素株式会社 新規甘味料組成物
CA2334385C (fr) * 1998-06-05 2005-11-15 Wm. Wrigley Jr. Company Procede pour moduler la liberation de derives n-substitues d'aspartame dans une gomme a macher et gomme ainsi produite
US20030008046A1 (en) * 1998-12-18 2003-01-09 Paula A. Gerlat Use of n-neohexyl-a-aspartyl-l-phenylalanine methyl ester as a flavor modifier
AU4038800A (en) * 1999-03-29 2000-10-16 Nutrasweet Company, The Nutraceuticals having

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1514481A1 (fr) * 2003-09-11 2005-03-16 Christian Fenioux Utilisation de la néohespéridine dihydrochalcone dans des comprimés à croquer comprenant des vitamines et/ou minéraux
FR2859603A1 (fr) * 2003-09-11 2005-03-18 Christian Fenioux Utilisation de la neohesperidine dihydrochalcone dans des compositions orales comprenant des vitamines et/ou des mineraux
JP2012175930A (ja) * 2011-02-25 2012-09-13 Ogawa & Co Ltd 高甘味度甘味料の呈味改善剤
US11229612B2 (en) 2016-07-01 2022-01-25 GW Research Limited Parenteral formulations
US11291631B2 (en) 2016-07-01 2022-04-05 GW Research Limited Oral cannabinoid formulations
US12064398B2 (en) 2016-07-01 2024-08-20 Jazz Pharmaceuticals Research Uk Limited Parenteral formulations
US12213985B2 (en) 2016-07-01 2025-02-04 Jazz Pharmaceuticals Research Uk Limited Oral cannabinoid formulations
US11426362B2 (en) 2017-02-17 2022-08-30 GW Research Limited Oral cannabinoid formulations
US11806319B2 (en) 2018-01-03 2023-11-07 GW Research Limited Pharmaceutical composition comprising a cannabinoid

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AU1093401A (en) 2001-04-30
WO2001028590A3 (fr) 2008-01-03

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