DOCSLIB.ORG

WO 2018/002637 Al 04 January 2018 (04.01.2018) W !P O PCT

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
WO 2018/002637 Al 04 January 2018 (04.01.2018) W !P O PCT (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2018/002637 Al 04 January 2018 (04.01.2018) W !P O PCT (51) International Patent Classification: A61K 9/00 (2006.01) A61K 47/44 (2017.01) A61K 9/08 (2006.01) (21) International Application Number: PCT/GB2017/051914 (22) International Filing Date: 29 June 2017 (29.06.2017) (25) Filing Language: English (26) Publication Language: English (30) Priority Data: 161 1547.9 0 1 July 2016 (01 .07.2016) GB (71) Applicant: GW RESEARCH LIMITED [GB/GB]; Sov ereign House, Vision Park, Chivers Way, Histon, Cam bridge Cambridgeshire CB24 9BZ (GB). (72) Inventor: SHAH, Harshit; Sovereign House, Vision Park, Chivers Way, Histon, Cambridge Cambridgeshire CB24 9BZ (GB). (74) Agent: HGF LIMITED; 4th Floor, Merchant Exchange, 17-19 Whitworth Street West, Manchester Greater Man chester M l 5WG (GB). (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Declarations under Rule 4.17: — of inventorship (Rule 4.1 7(iv)) Published: — with international search report (Art. 2 (3)) o o 00 (54) Title: ORAL CANNABINOID FORMULATIONS © (57) Abstract: The present invention relates to a cannabinoid containing oral solution. Preferably the oral solution comprises a cannabi- noid, a lipid solvent, a sweetener and ethanol, characterised in that the sweetener is an ultrahigh potency sweetener. ORAL CANNABINOID FORMULATIONS [0001] The present invention relates to a cannabinoid containing oral solution. BACKGROUND TO THE INVENTION [0002] The use of cannabinoids in medicine has necessitated finding more effective ways of drug delivery. This is in part due to factors such as, poor aqueous solubility, limited bioavailability, and cannabinoid instability, but the use of cannabinoids at relatively high doses (in daily amounts of up to 2000mg) and / or in challenging patient groups, e.g. young children, and / or for particular indications, can create additional challenges. [0003] There are currently three commercially available cannabinoid formulations on the market. [0004] Dronabinol (Marinol®) is a synthetic tetrahydrocannabinol (THC) which is delivered orally, in sesame oil as capsules. [0005] Nabilone (Cesamet®) is a synthetic cannabinoid and an analog of THC and is delivered orally in capsules with povidone and corn starch. [0006] Nabiximols (Sativex®) is a natural extract of cannabinoids containing defined amounts of THC and Cannabidiol (CBD) and is delivered as a liquid, by way of an oromucosal spray. [0007] The applicant also provides an oral solution containing CBD (Epidiolex®) on a named patient basis. The CBD is formulated in sesame seed oil and further comprises the sweetener sucralose (600x the sweetness intensity of sucrose), strawberry flavouring and up to 10% v/v ethanol. [0008] Whilst there is no clear FDA guidance for maximum allowable ethanol concentration in prescription medicines, an article (Ethanol in Liquid Preparations Intended for Children, Paediatrics: Official Journal of The American Academy of Paediatrics, 1984: 73:405), recommends that a Blood Alcohol Concentration (BAC) of 0.25 g/L (250 mg/L) should not be exceeded following a single dose of alcohol containing medications. [0009] WO 2015/184127 (Insys) discloses a number of different oral formulations including: an alcohol free formulation in which the cannabinoid is formulated in a mix of polyethylene glycol and propylene glycol, optionally with water, a formulation containing alcohol and a formulation containing lipids. In each of the formulations disclosed, the cannabinoid is a synthetically produced (as opposed to a naturally extracted) cannabidiol. [0010] The specification teaches the inclusion of a number of pharmaceutically acceptable excipients such as, anti-oxidants, sweeteners, enhancers, preservatives, flavouring agents and pH modifiers. [001 1] According to European Medicine Agency draft guideline (EMA/CHMP/507988/2013), for 2 to 6 years old children, a theoretical limit for Blood Alcohol Concentration (BAC) following single administration of a formulation containing alcohol is not more than 0.01 g/L (10mg/L) and ethanol intake should be not more than 6 mg/kg/day. [0012] For paediatric products aimed at younger children, it is desirable to have low or no ethanol formulations, preferably dispensed as syrup, as younger children find it difficult to swallow capsules. They also favour sweet, flavoured products, particularly where the taste of cannabinoid requires masking. [0013] A problem with the use of pharmaceutically acceptable sweeteners, and flavouring agents is that they are generally polar in nature, and thus unlike the cannabinoids which are highly lipophilic, they require a polar solvent to dissolve them. [0014] An object of the present invention was to develop a lipid based oral formulation which contained less than 0% (v/v) ethanol, which was palatable, and could be delivered to young children as syrup, in relatively small volumes, typically less than 10 ml. BRIEF SUMMARY OF THE DISCLOSURE [0015] In accordance with a first aspect of the present invention there is provided a cannabinoid containing oral solution comprising: a cannabinoid, a lipid solvent, a sweetener and ethanol, characterised in that the sweetener is an ultrahigh potency sweetener. [0016] An ultrahigh potency sweetener is defined herein as a sweetener with a sweetness intensity compared to sucrose of greater than 750. [0017] Preferably the ultrahigh potency sweetener has a sweetness intensity compared to sucrose of greater than 1000, more preferably greater than 5000. [0018] In one embodiment of the invention the ultrahigh potency sweetener is (N-[N-(3,3- dimethylbutyl)-L-a-aspartyl]-L-phenylalanine 1-methyl ester) (Neotame). [0019] In a further embodiment the ultrahigh potency sweetener is N-[N-3-(3-hydroxy-4- methoxyphenyl)propyl-a-L-aspartyl]-L-phenylalanine 1-methyl ester) (Advantame). [0020] Preferably the cannabinoid containing oral solution further comprises a flavourant. [0021] Preferably the cannabinoid is selected from: cannabichromene (CBC), cannabichromenic acid (CBCV), cannabidiol (CBD), cannabidiolic acid (CBDA), cannabidivarin (CBDV), cannabigerol (CBG), cannabigerol propyl variant (CBGV), cannabicyclol (CBL), cannabinol (CBN), cannabinol propyl variant (CBNV), cannabitriol (CBO), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), tetrahydrocannabivarin (THCV) and tetrahydrocannabivarinic acid (THCVA). More preferably the cannabinoid is CBD. [0022] It is preferred that the cannabinoid containing oral solution has a cannabinoid present in an amount of from 5 to 40% (w/v), ethanol present in an amount of less than 2% (w/v), ultrahigh potency sweetener present in less than 0.05% (w/v) flavourant, more preferably still less than 0.01% (w/v) flavourant present in an amount of less 0.2% (w/v) and lipid solvent present q.s. to 100%. [0023] More preferably the cannabinoid is CBD, the ultrahigh potency sweetener is Neotame, the flavourant is strawberry flavour and the lipid solvent is sesame oil. [0024] Preferably the cannabinoid containing oral solution is stable in climatic zones I and II for up to 24 months at 25°C or is stable in climatic zones III and IV for up to 18 months at 30°C. [0025] Surprisingly, the formulations of the invention were stable without the need for the incorporation of stability enhancers such as anti-oxidants or complexing agents. [0026] Preferably the cannabinoid containing oral solution is absent of a stabilizing agent. [0027] More preferably the stabilizing agent which the cannabinoid containing oral solution is absent of is an antioxidant or a chelating agent. [0028] The formulation may be packaged for use in a bottle, oral or enteral syringe, metered dose device or other container used to store or administer liquid oral medications. [0029] In accordance with a second aspect of the present invention there is provided a method of treating a subject comprising administering a cannabinoid containing oral solution. [0030] Preferably the subject is a human. [0031] Preferably the cannabinoid containing oral solution is for use in the treatment of epilepsy and syndromes associated therewith, Dravet Syndrome, Lennox Gastaut Syndrome, myocolonic seizures, juvenile mycolonic epilepsy, refractory epilepsy, schizophrenia, juvenile spasms, West syndrome, infantile spasms, refractory infantile spasms, tuberous sclerosis complex, brain tumors, neuropathic pain, cannabis
Load more

Recommended publications
  • Advantame Chemical and Technical Assessment Prepared by Ivan Stankovic, Ph.D
    Advantame Chemical and Technical Assessment Prepared by Ivan Stankovic, Ph.D. and reviewed by Daniel E Folmer, Ph.D. 1. Summary Advantame was not previously evaluated by JECFA and it has been recommended for priority evaluation at the 44th Session of the Codex Committee on Food Additives (CCFA) (FAO/WHO, 2012). This Chemical and Technical Assessment document is based on data and information submitted by Ajinomoto Co., Inc., in the dossier dated December, 2012 (Ajinomoto, 2012). Advantame (ANS9801 - laboratory code name) is an N-substituted (aspartic acid portion) derivative of aspartame that is intended for use as a non-nutritive sweetener. Advantame has been demonstrated to be approximately 100 times sweeter than aspartame and approximately 37000 times sweeter than sucrose. Advantame is manufactured via a chemical synthesis. Approval for the use of advantame as a Schedule 2 food additive [permitted to Good Manufacturing Practices (GMP) in processed foods] in Australia/New Zealand has been recently issued by Food Standards Australia New Zealand (FSANZ) (FSANZ, 2011). INS No. 969 has been assigned to advantame at the 45th Session of the CCFA in 2013 (FAO/WHO, 2013) New tentative specifications were prepared at the 77th JECFA (2013) and published in FAO JECFA Monographs 14 (2013) requesting information on: • Suitability of the head space GC method (using appropriate dissolution solvent) for determination of residual solvents published in the “Combined Compendium of Food Additives Specifications, Vol. 4” and data, in a minimum of 5 batches, using the method, • An alternative/improved HPLC method for the assay of advantame and advantame-acid using a standard curve, • Additional data and analytical methods for determination of palladium and platinum, • Information on the purity and availability of the commercial reference standards used in the assay of advantame and advantame-acid 2.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2016/0304439 A1 Divi Et Al
    US 20160304439A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2016/0304439 A1 Divi et al. (43) Pub. Date: Oct. 20, 2016 (54) PROCESS FOR THE PREPARATION OF Publication Classification ADVANTAME (51) Int. Cl. (71) Applicant: Divi's Laboratories Limited, Ameerpet CD7C 2.3L/2 (2006.01) (IN) CD7C 45/45 (2006.01) (52) U.S. Cl. (72) Inventors: Murali Krishna Prasad Divi, CPC ............. C07C 231/12 (2013.01); C07C 45/45 Ameerpet (IN); Mysore Aswatha (2013.01) Narayana Rao, Ameerpet (IN); Shaik Nowshuddin, Ameerpet (IN) (57) ABSTRACT (21) Appl. No.: 14/848,533 A novel process for the preparation of N—N-3-(3-hydroxy (22) Filed: Sep. 9, 2015 4-methoxyphenyl)-propyl-L-C.-aspartyl-L-phenylalanine 1-methyl ester is described. It comprises, reacting isovanillin (30) Foreign Application Priority Data or its derivative with vinyl acetate followed by reductive condensation with L-C.-aspartyl-L-phenylalanine-1- Apr. 20, 2015 (IN) ........................... 2019/CHFA2015 methyl ester. US 2016/0304439 A1 Oct. 20, 2016 PROCESS FOR THE PREPARATION OF ADVANTAME MeO O FIELD OF INVENTION NH HO NH 0001. The present invention relates to an improved pro OH cess for the preparation of N—N-3-(3-hydroxy-4- Advantame COOMe methoxyphenyl)propyl-L-C.-aspartyl-L-phenylalanine-1- O methyl ester, known as Advantame, a non-caloric Sweetener. BACKGROUND OF THE INVENTION 0002 Advantame is a novel sweetener developed by 0003. The U.S. Pat. No. 6,794,531 B2, assigned to Aji Ajinomoto Co. It is a derivative of Aspartame, chemically nomoto Co., describes a process for the preparation of N—N-3-(3-hydroxy-4-methoxyphenyl)propyl-L-C.-as Advantame (Scheme 1), involving condensation of 3-(3- partyl-L-phenylalanine-1-methyl ester, having the follow hydroxy-4-methoxyphenyl)-propionaldehyde (III) with ing structure: Aspartame.
    [Show full text]
  • JOINT FAO/WHO EXPERT COMMITTEE on FOOD ADDITIVES Seventy-Seventh Meeting Rome, 4–13 June 2013
    JECFA/77/SC JOINT FAO/WHO EXPERT COMMITTEE ON FOOD ADDITIVES Seventy-seventh meeting Rome, 4–13 June 2013 SUMMARY AND CONCLUSIONS Issued 19 June 2013 A meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA) was held in Rome, Italy, from 4 to 13 June 2013. The purpose of the meeting was to evaluate certain food additives and contaminants. Mrs I. Meyland, Denmark, served as Chairperson, and Dr D. Benford, Food Standards Agency, United Kingdom, served as Vice-Chairperson. Mr S.J. Crossley, Food Safety, Food and Agriculture Organization of the United Nations, and Dr A. Tritscher, Department of Food Safety and Zoonoses, World Health Organization, served as Joint Secretaries. The present meeting was the seventy-seventh in a series of similar meetings. The tasks before the Committee were (a) to elaborate principles governing the evaluation of food additives, (b) to evaluate certain food additives and contaminants and (c) to review and prepare specifications for selected food additives. The report of the meeting will be published in the WHO Technical Report Series. Its presentation will be similar to that of previous reports—namely, general considerations, comments on specific substances and recommendations for future work. An annex will include detailed tables (similar to the tables in this report) summarizing the main conclusions of the Committee in terms of acceptable or tolerable daily intakes and other toxicological and safety recommendations. Information on the specifications for the identity and purity of certain food additives examined by the Committee will also be included. The participants in the meeting are listed in Annex 1.
    [Show full text]
  • Risk Assessment Report Advantame (Food Additives)
    [Tentative translation] Risk Assessment Report Advantame (Food Additives) Food Safety Commission of Japan (FSCJ) July 2013 1 [Tentative translation] Contents Page Chronology of Discussions ................................................................................................. 3 List of members of the Food Safety Commission of Japan (FSCJ) ................................. 3 List of members of the Expert Committee on Food Additives, the Food Safety Commission of Japan (FSCJ)............................................................................................. 4 Executive summary............................................................................................................. 5 I. Outline of the items under assessment ........................................................................... 6 1. Use ................................................................................................................................ 6 2. Names of the principal components ........................................................................... 6 3. Molecular and structural formulae ........................................................................... 6 4. Molecular weights ....................................................................................................... 6 5. Characteristics ............................................................................................................ 6 6. Stability .......................................................................................................................
    [Show full text]
  • Optimizing Flavors and Sweeteners
    [Sweeteners] Vol. 22 No. 11 November 2012 Optimizing Flavors and Sweeteners By Cindy Hazen, Contributing Editor Whether we’re talking economic or environmental issues, there’s a common theme: We should do more with less. The food industry can relate. We’ve all heard consumers say they want a longer shelf life but no preservatives; natural, organic and artisan at low cost; full flavor and sodium reduction; and no added sugar without compromising sweetness. We can’t meet every consumer expectation in this space, but we can give you some tips to help you get the most out of your sweetener system. First things first Sweeteners don’t look alike, taste alike or behave alike. Yet, there’s a tendency to compare. Sugar, or sucrose, is the standard, because it’s familiar to us and, importantly, it’s sweet from start to finish. “Sweetness is measured in how quick and how long sweet lasts in your mouth,” explains Laura Ennis, senior beverage innovation technologist, David Michael & Co., Philadelphia. This can be measured by a temporal sweetness profile. “Different sweeteners are rated on their intensity over time, and these results can be plotted onto a graph. For example, crystalline fructose peaks very early and fades rather quickly, whereas sucrose peaks later and lasts longer, hence the reason that most chewing gums are accentuated with artificial sweeteners to keep the sweet profile lasting longer. Non-nutritive sweeteners tend to take the longest to peak and, therefore, lack this upfront sweetness.” Perception of sweetness occurs when a sweet molecule comes in contact with a sweet receptor in the taste bud.
    [Show full text]
  • Rules and Regulations Federal Register Vol
    Vol. 79 Wednesday, No. 98 May 21, 2014 Pages 29069–29322 OFFICE OF THE FEDERAL REGISTER VerDate Mar 15 2010 20:03 May 20, 2014 Jkt 232001 PO 00000 Frm 00001 Fmt 4710 Sfmt 4710 E:\FR\FM\21MYWS.LOC 21MYWS tkelley on DSK3SPTVN1PROD with WS.LOC II Federal Register / Vol. 79, No. 98 / Wednesday, May 21, 2014 The FEDERAL REGISTER (ISSN 0097–6326) is published daily, SUBSCRIPTIONS AND COPIES Monday through Friday, except official holidays, by the Office PUBLIC of the Federal Register, National Archives and Records Administration, Washington, DC 20408, under the Federal Register Subscriptions: Act (44 U.S.C. Ch. 15) and the regulations of the Administrative Paper or fiche 202–512–1800 Committee of the Federal Register (1 CFR Ch. I). The Assistance with public subscriptions 202–512–1806 Superintendent of Documents, U.S. Government Printing Office, Washington, DC 20402 is the exclusive distributor of the official General online information 202–512–1530; 1–888–293–6498 edition. Periodicals postage is paid at Washington, DC. Single copies/back copies: The FEDERAL REGISTER provides a uniform system for making Paper or fiche 202–512–1800 available to the public regulations and legal notices issued by Assistance with public single copies 1–866–512–1800 Federal agencies. These include Presidential proclamations and (Toll-Free) Executive Orders, Federal agency documents having general FEDERAL AGENCIES applicability and legal effect, documents required to be published Subscriptions: by act of Congress, and other Federal agency documents of public interest. Assistance with Federal agency subscriptions: Documents are on file for public inspection in the Office of the Email [email protected] Federal Register the day before they are published, unless the Phone 202–741–6000 issuing agency requests earlier filing.
    [Show full text]
  • Senior Health Line
    Senior Health Line March 2020 Artificial Sweeteners Artificial sweeteners may seem like they are as add calories and carbohydrates to your diet. beneficial for a weight loss diet or for There are reduced calorie sweeteners that are controlling diabetes, but are they? Artificial also known as sugar alcohols, these are known sweeteners or sugar substitutes are low calorie as isomalt, mannitol, sorbitol, xylitol and or calorie free nonnutritive sweeteners. They maltitol. These sweeteners contain about half provide sweetness without the calories of the calories of sugars and they will raise your sugar or other things like honey. Sugar blood glucose levels. They may also cause substitutes are many times sweeter than sugar gastrointestinal upset and diarrhea. and only a small amount is needed to give the The Food and Drug Administration sweet taste to foods. This is why there is less approved the use of five artificial sweeteners calories in foods sweetened by artificial for human use in the United States. These are: sweeteners. -Acesulfame potassium: This is a white Artificial sweeteners are usually considered crystalline sweetener that the human intestinal a “free food” in a diabetic exchange diet. This tract cannot break down and is eliminated from means it has 20 calories or less and less than the body through the urine. It can be used for 5 grams of carbohydrates in a serving. cooking and baking. Sugars come in many forms and are -Saccharin: While this is approved for use, naturally occurring carbohydrates. They can be it is not recommended for use during white cane or beet sugar, brown sugar or pregnancy or breastfeeding.
    [Show full text]
  • (GRN) No. 669, Cow's Milk-Derived Lactoferrin
    GRAS Notice (GRN) No. 669 https://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/NoticeInventory/default.htm FDA COMPLIANCE All FSI polypropylene filtration media product lines are manufactured using FDA compliant materials under the Federal Food, Drug, and Cosmetic Act under regulations: 21 C.F.R. 177.1520 (c) 1.1 21 C.F.R. 177.2800 21 C.F.R. 178.3400 Provided that the end user is complying with FDA's good manufacturing practices under Title 21 C.F.R. 174.5. (b)(6) 5130113 Quality Assi/ance Manager date Part 7: Appendix I 000135 Al: 6 KMS HFKD -131 FOOD D DAIRY UF ELEMENTS Ultrafiltration 4", 6" and 8" Spiral Element Series PRODUCT Membrane Chemistry: Proprietary semi-permeable polyethersulfone (PES) Membrane Type: HFK™-131 with observed separation range of 10,000 Daltons DESCRIPTION Construction: Sanitary spiral wound element with net outer wrap Regulatory Status: Conform to USDA 3-A standards and FDA regulations (CFR Title 21) Options: Diameter: 3.8", 4.3", 6.3", 6.4", 8.0", or 8.3" Length: 33", 35.5", or 38" Feed Spacer: N(31 mil), V (46 mil), H (62 mil), or F (80 mil), D (100 mil) Outer wrap: Controlled (e.g. NYV) or trimmable (e.g. NYT) SPECIFICATIONS Model Active Membrane Area NYVIT Spacer (31 mil) VYVIT Spacer (46 mil) HYVIT Spacer (62 mil) FYVIT Spacer (80 mil) DYVIT Spacer (100 mil) ft2 (m2) ft2 (m2) ft2 (ml) ftl (ml) ftl (ml) 3838 HFK-131 72 (6.7) 58 (5.4) 45 (4.2) 4333 HFK-131 93 (8.6) 73 (6.8) 55 (5.1) 44 (4.1 ) 4336 HFK-131 95 (8.8) 79 (7.3) 59 (5.5) 4338 HFK-131 102 (9.5) 81 (7.5) 6338 HFK-131 228 (21.2) 180 (16.7) 142 (13.2) 119 (1 1.1) 102 (9.5) 6438 HFK-131 228 (21.2) 180 (16.7) 142 (13.2) 119 (11.1) 8038 HFK-131 358 (33.2) 276 (25.6) 215 (20.0) 8338 HFK-131 308 (28.6) 241 (22.4) 194 (18.0) Not all combinations are available.
    [Show full text]
  • Key Facts on Sugar Substitutes Traci Armstrong Florian, MS, RD; Heidi L
    az1691 January 2016 Key Facts on Sugar Substitutes Traci Armstrong Florian, MS, RD; Heidi L. Keeling, BS; Scottie Misner, PhD, RD; Evelyn Whitmer, MEd Introduction Approved Sweeteners Artificial sweeteners can help consumers cut down on Aspartame (NutraSweet®, Equal®, Sugar Twin®) calories and control weight, help to manage chronic conditions Aspartame was first approved in 19811. It is 200 times such as diabetes, and potentially prevent cavities. The most sweeter than sugar, with a caloric value similar to sugar (4 commonly used sweeteners approved by the Food and Drug kcal/gram). However, since small amounts are used in foods Administration (FDA) for use in foods and beverages in the it is considered essentially free of calories. In the mid-1990’s, a United States include: aspartame, saccharin, advantame, researcher raised concerns that a rise in brain cancer incidence acesulfame-K, neotame, luo han guo fruit extracts, stevia, and was linked to aspartame use3. However, after intense testing sucralose1. The agency regulates artificial sweeteners, which both in animals and humans, there has been no link to must be approved as safe before they can be marketed. The aspartame and cancer. There has also been no evidence to FDA evaluates a sweetener’s composition and properties, how support any other side effects connected to the sweetener. much is likely to be consumed, and various types of safety One safety exception is for people who have phenylketonuria studies. For each of the sweeteners, the typical amount used (PKU), a rare genetic condition in which the body cannot by an individual is well within levels that can be consumed 2 metabolize the amino acid phenylalanine (a component of safely .
    [Show full text]
  • And No-Calorie Sweeteners: Safety, Nutritional Aspects and Benefits in Food and Beverages
    nutrients Review Ibero–American Consensus on Low- and No-Calorie Sweeteners: Safety, Nutritional Aspects and Benefits in Food and Beverages Lluis Serra-Majem 1,2,3,4,* ID , António Raposo 5 ID , Javier Aranceta-Bartrina 2,4,6,7, Gregorio Varela-Moreiras 2,8,9, Caomhan Logue 10, Hugo Laviada 11, Susana Socolovsky 12, Carmen Pérez-Rodrigo 2,6,7 ID , Jorge Antonio Aldrete-Velasco 13, Eduardo Meneses Sierra 13,14, Rebeca López-García 15, Adriana Ortiz-Andrellucchi 1,4, Carmen Gómez-Candela 16,17, Rodrigo Abreu 18, Erick Alexanderson 19,20,21, Rolando Joel Álvarez-Álvarez 21, Ana Luisa Álvarez Falcón 1,22, Arturo Anadón 23, France Bellisle 24, Ina Alejandra Beristain-Navarrete 25, Raquel Blasco Redondo 26, Tommaso Bochicchio 27,28, José Camolas 29, Fernando G. Cardini 30,Márcio Carocho 31 ID , Maria do Céu Costa 32 ID , Adam Drewnowski 33, Samuel Durán 34 ID ,Víctor Faundes 35 ID , Roxana Fernández-Condori 36, Pedro P. García-Luna 37, Juan Carlos Garnica 38, Marcela González-Gross 4,39, Carlo La Vecchia 40 ID , Rosaura Leis 4,41,42, Ana María López-Sobaler 43 ID , Miguel Agustín Madero 38, Ascensión Marcos 44,45, Luis Alfonso Mariscal Ramírez 46, Danika M. Martyn 47, Lorenza Mistura 48 ID , Rafael Moreno Rojas 49 ID , José Manuel Moreno Villares 50, José Antonio Niño-Cruz 46,51, María Beatriz P. P. Oliveira 52 ID , Nieves Palacios Gil-Antuñano 53, Lucía Pérez-Castells 54, Lourdes Ribas-Barba 3,4, Rodolfo Rincón Pedrero 55, Pilar Riobó 56,57, Juan Rivera Medina 58,59 ID , Catarina Tinoco de Faria 1, Roxana Valdés-Ramos 60 ID , Elsa Vasco 61 ID , Sandra N.
    [Show full text]
  • FCC 10, Second Supplement the Following Index Is for Convenience and Informational Use Only and Shall Not Be Used for Interpretive Purposes
    Index to FCC 10, Second Supplement The following Index is for convenience and informational use only and shall not be used for interpretive purposes. In addition to effective articles, this Index may also include items recently omitted from the FCC in the indicated Book or Supplement. The monographs and general tests and assay listed in this Index may reference other general test and assay specifications. The articles listed in this Index are not intended to be autonomous standards and should only be interpreted in the context of the entire FCC publication. For the most current version of the FCC please see the FCC Online. Second Supplement, FCC 10 Index / Allura Red AC / I-1 Index Titles of monographs are shown in the boldface type. A 2-Acetylpyrrole, 21 Alcohol, 90%, 1625 2-Acetyl Thiazole, 18 Alcohol, Absolute, 1624 Abbreviations, 7, 3779, 3827 Acetyl Valeryl, 608 Alcohol, Aldehyde-Free, 1625 Absolute Alcohol (Reagent), 5, 3777, Acetyl Value, 1510 Alcohol C-6, 626 3825 Achilleic Acid, 25 Alcohol C-8, 933 Acacia, 602 Acid (Reagent), 5, 3777, 3825 Alcohol C-9, 922 ªAccuracyº, Defined, 1641 Acid-Hydrolyzed Milk Protein, 22 Alcohol C-10, 390 Acesulfame K, 9 Acid-Hydrolyzed Proteins, 22 Alcohol C-11, 1328 Acesulfame Potassium, 9 Acid Calcium Phosphate, 240 Alcohol C-12, 738 Acetal, 10 Acid Hydrolysates of Proteins, 22 Alcohol C-16, 614 Acetaldehyde, 11 Acidic Sodium Aluminum Phosphate, Alcohol Content of Ethyl Oxyhydrate Acetaldehyde Diethyl Acetal, 10 1148 Flavor Chemicals (Other than Acetaldehyde Test Paper, 1636 Acidified Sodium Chlorite
    [Show full text]
  • Sugar Substitutes Your Health
    Despite the popularity of low-calorie, sugar-free foods and beverages, some people have concerns or questions about the safety of the sugar substitutes that make these products possible. Misinformation about sugar substitutes abounds, especially on the Internet, and people may have difficulty distinguishing trustworthy sources of information on this topic from less reliable ones. This revised and updated report by the American Council on Science and Health summarizes the scientific facts about the safety of sugar substitutes. This consumer-friendly publication is based on the manuscript “Low-Calorie Sweeteners and Other Sugar Substitutes: A Review of the Safety Issues,” published in the journal Comprehensive Reviews in Food Science and Food Safety, by Dr. Manfred Kroger of Pennsylvania State University and Kathleen Meister and Dr. Ruth Kava of the American Council SUGAR on Science and Health. This second edition was updated and revised by ACSH’s Dr. Ruth Kava, and Ariel Savransky, M.S. SUBSTITUTES The American Council on Science and Health is a consumer education consortium concerned with issues related to food, nutrition, chemicals, pharmaceuticals, lifestyle, the environment and health. It was founded in 1978 by a group of scientists concerned that many important public policies related to health and the environment did not have a sound scientific basis. These scientists created the organization to add reason and balance to debates about public health issues and bring common sense views to the public. & YOUR HEALTH American Council on Science and Health 1995 Broadway, Suite 202 New York, New York 10023-5882 Tel. (212) 362-7044 Fax (212) 362-4919 URL: http://www.acsh.org Email: [email protected] SUGAR SUBSTITUTES & YOUR HEALTH First Edition by Kathleen Meister, M.S.
    [Show full text]