AU2009356961B2

AU2009356961B2 - Effervescent L-carnitine-based composition

Info

Publication number: AU2009356961B2
Application number: AU2009356961A
Authority: AU
Inventors: Cathrine Neuendorf; Norman Ohl
Original assignee: JUBILENT GLOBAL Ltd
Current assignee: JUBILENT GLOBAL Ltd
Priority date: 2009-12-14
Filing date: 2009-12-14
Publication date: 2016-05-19
Anticipated expiration: 2029-12-14
Also published as: AU2009356961A1; WO2011072320A1

Abstract

This invention relates to an effervescent composition containing L-carnitine (levocarnitine) and to a method of manufacturing said composition. In one aspect, the invention concerns an effervescent composition which effectively masks the off-notes and poor taste normally associated with L-carnitine as well as reducing 'fishy' odours and flatulence normally resulting from L-carnitine ingestion and metabolism.

Description

WO 2011/072320 PCT/AU2009/001619 1 EFFERVESCENT L-CARNITINE-BASED COMPOSITION TECHNICAL FIELD This invention relates to an effervescent composition containing L-carnitine (levocamitine) and to a method of manufacturing said composition. In one aspect, the 5 invention concerns an effervescent composition which effectively masks the off-notes and poor taste normally associated with L-carnitine as well as reducing 'fishy' odours and flatulence normally resulting from L-carnitine ingestion and metabolism. BACKGROUND ART Carnitine is a quaternary ammonium compound having the following chemical 10 structure: OH O The biologically active form is the isomer L-carnitine, which is essential for energy production and fat metabolism in birds, fish and mammals. In such animals, L carnitine plays a role in the transportation of long-chain fatty acids across the inner 15 mitochondrial membrane during the breakdown of fats and lipids, resulting in the generation of metabolic energy in the form of ATP. In view of its biological activity, it is no surprise that L-carnitine is widely sold and used as an orally taken dietary supplement for treating various physiological conditions, and in particular for reducing body fat, enhancing lean muscle mass, fighting 20 fatigue and increasing stamina. However, since L-carnitine is a highly hygroscopic compound, the preparation of oral formulations containing L-carnitine and the storage of such formulations has been problematic. Another problem with known L-carnitine based oral formulations is that L carnitine has an unpleasant odor and unpleasant taste, which are both difficult to mask. 25 Further problems arising with use of L-carnitine as a dietary supplement relate to a known metabolite, trimethylamine. Trimethylamine has a 'fishy' odour and as a result of WO 2011/072320 PCT/AU2009/001619 2 the metabolism of the L-carnitine, some individuals taking L-carnitine may develop a 'fishy' odor in their breath and sweat. A build-up of 'fishy' gas in the bowel can also result, leading to flatulence. DETAILED DESCRIPTION OF THE INVENTION 5 It is an object of the present invention to minimise or overcome one or more of the problems described above, or to provide the public with a useful or commercial choice. The inventors have discovered that L-carnitine, when taken orally in an effervescent form/composition (which preferably creates an acidic environment when in solution), can reduce the physiological problems normally observed with L-carnitine 10 ingestion and metabolism, namely 'fishy' odour and flatulence. The inventors have also discovered that the effervescent form/composition, particularly when further containing a sweetening agent and/or flavouring agent, can effectively mask the off-notes and poor taste normally associated with L-carnitine. The inventors have further discovered that the effervescent form/composition is 15 less problematic to prepare and store than other types of L-carnitine compositions as it tends to be less hygroscopic. Broadly, the invention concerns an effervescent L-carnitine based composition for treating a physiological condition yet minimising a physiological problem normally resulting from L-carnitine metabolism, said composition comprising: 20 an effective amount of L-carnitine for treating said physiological condition; and effervescent agents. According to a first aspect of the present invention, there is provided an effervescent L-carnitine based composition for treating a physiological condition yet minimising a physiological problem normally resulting from L-carnitine metabolism, said 25 composition comprising: an effective amount of L-carnitine for treating said physiological condition; and WO 2011/072320 PCT/AU2009/001619 3 effervescent agents for creating an acidic environment when the composition is in solution. Any suitable amount and form of L-carnitine may be used in the composition, provided that it is ingestable and can provide the desired physiological effect. For 5 instance, the L-carnitine may be in the form of a free base or salt. Preferably, approximately 40-60% w/w L-carnitine is used, and more preferably about 52% w/w. Any suitable types and amounts of effervescent agents may be used in the composition. Typically, this will be a combination of at least one type of acid and base. The acid may be one or more of the following: citric, malic, tartaric, adipic, and fumaric 10 acid. Preferably, the composition comprises approximately 15-40 % w/w anhydrous citric acid, and more preferably about 29% w/w. The base may be one or more of the following: sodium bicarbonate, potassium bicarbonate, sodium carbonate and potassium carbonate. Preferably, the composition comprises approximately 10-30% w/w sodium bicarbonate, and more preferably about 19% w/w. 15 Preferably, the acid environment has a pH of approximately 4 to 5, and more preferably, a pH of about 4.7 (in 100 mL water) or 4.8 (200 mL water). The composition can further comprise a sweetening agent and/or flavouring agent for further masking the off-notes and poor taste normally associated with L-carnitine. Any suitable type and amount of sweetening agent and/or flavouring agent may be used. 20 The sweetening agent may be a natural or artificial sweetener, or a mixture of both. Preferably, the sweetening agent is a non-calorific natural sweetener such as stevia or sucralose. Preferably, the composition comprises approximately 0.2-0.8% w/w sucralose, and more preferably about 0.4% w/w. The composition may be of any suitable form, including in the form of an 25 effervescent powder, granule or tablet. The composition may be packaged in the form of a capsule. The capsule can be any suitable capsule known in the art, including hard or soft gelatine prepared from beef and/or pork gelatin. Alternatively, the capsule, whether hard or soft, can be prepared from plant-based gelling substances so as to be suitable for persons on a vegetarian diet. Plant-based gelling substances suitable for the preparation 30 of vegetarian capsules include carrageenans or modified forms of starch and cellulose.

WO 2011/072320 PCT/AU2009/001619 4 Depending on the form of the composition, the composition may further comprise one or more of the following: a binding agent, buffering agent, disintegrating agent, lubricant, glidant and flow regulating agent. The composition may further comprise other types of ingredients such as, for 5 example, a colouring agent. The colouring agent may be any suitable natural and/or artificial colouring agent. Preferably, the composition comprises approximately 0.01 0.3% w/w carminic acid (cochineal), and more preferably about 0.1% w/w. According to a preferred embodiment, the effervescent L-carnitine based composition comprises: 10 approximately 52.08% w/w L-carnitine; approximately 28.65% w/w anhydrous citric acid; approximately 18.78% w/w sodium bicarbonate; approximately 00.39% w/w sucralose; and approximately 00.10% w/w cochineal. 15 According to a second aspect of the present invention, there is provided a method of treating a physiological condition of an individual with an effervescent L-carnitine based composition yet minimising a physiological problem normally resulting from L carnitine metabolism by the individual, said method comprising the step of orally administering to the individual an effervescent L-carnitine based composition comprising: 20 a physiologically effective amount of L-carnitine for treating said physiological condition; and effervescent agents, preferably for creating an acidic environment when the composition is in solution. According to a third aspect of the present invention, there is provided the use of a 25 physiologically effective amount of L-carnitine in combination with effervescent agents, for creating an acidic environment when the L-carnitine is in solution, in the preparation of a medicament (composition) for treating a physiological condition of an individual yet WO 2011/072320 PCT/AU2009/001619 5 minimising a physiological problem normally resulting from L-carnitine metabolism by the individual. The composition may be used to treat any suitable type of physiological condition. For instance, the composition may be used to reduce body fat, enhance lean muscle mass, 5 fight fatigue and increase stamina. The physiological problem normally observed with L-carnitine ingestion and metabolism may be the 'fishy' odour of the individual's sweat or breath or flatulence. Any suitable administration regime may be used for the individual. Preferably, the composition is dissolved in water and ingested twice daily. Preferably, approximately 10 3-4 g of the composition of the preferred embodiment described above is dissolved in 100-200 mL water and ingested twice daily (morning and afternoon). According to a fourth aspect of the present invention, there is provided a method of preparing an effervescent L-carnitine based composition for treating a physiological condition yet minimising a physiological problem normally resulting from L-carnitine 15 metabolism, said method comprising the step of: blending an effective amount of L-carnitine for treating said physiological condition with effervescent agents, preferably for creating an acidic environment when the L-carnitine is in solution. Preferably, the method further comprises the step of blending at least one 20 sweetening agent with the effervescent agents prior to blending with L-carnitine. Preferably, the effervescent agents are dried prior to addition to the sweetening agent or L-carnitine. In a particularly preferred embodiment, the blending is undertaken in a low relative humidity (RH) environment, preferably at less than about 20% RH. Preferably, the method further comprises the step of blending in a colouring agent. 25 In order that the invention may be more readily understood and put into practice, one or more preferred embodiments thereof will now be described, by way of example only.

WO 2011/072320 PCT/AU2009/001619 6 BEST MODE FOR CARRYING OUT THE INVENTION As mentioned above, the inventors have discovered that L-carnitine, when taken orally in an effervescent form/composition, which preferably creates an acidic environment when in solution, can reduce the physiological problems normally observed 5 with L-carnitine ingestion and metabolism. The inventors have also discovered that the effervescent form/composition, particularly when further containing a sweetening agent and/or flavouring agent, can effectively mask the off-notes and poor taste normally associated with L-carnitine. The inventors have further discovered that the effervescent form/composition is less problematic to prepare and store than other types of L-carnitine 10 compositions as it tends to be less hygroscopic. In a particularly preferred embodiment of the invention (shown in TABLE 1), the composition comprises L-carnitine in combination with the effervescent agents anhydrous citric acid and sodium bicarbonate, the sweetening agent sucralose, and the colouring agent carminic acid to colour the composition pink. The composition is preferably in 15 powder form. The masking of the poor taste and off-notes of L-carnitine is believed to be provided by the citric acid and sodium bicarbonate combination, further enhanced by the sweetening agent sucralose. The stoichiometry of this combination, when dissolved in water, creates a pleasant tasting and non-odourous solution that can be easily consumed. 20 In addition, the effervescent agents produce an acidic environment when the composition is in solution, such as in water. Not wishing to be bound by theory, the inventors believe that the effervescent agents produce a low pH environment in the portal circulation of the individual to whom the composition is administered. As a result of this low pH environment, there are reduced amounts of amines such as ammonia in the portal 25 circulation, as the ammonia is converted to ammonium ions in the low pH environment, which are readily excreted without the odor associated with free amines. The individual therefore does not suffer from a build-up of 'fishy' gas in the bowel nor 'fishy' odor in their breath and sweat. In an acidic environment free H+ are readily available to create NH 3 * + H* -> 30 NH 4 * and in a more neutral or alkaline environment in the digestive process there may be WO 2011/072320 PCT/AU2009/001619 7 insufficient free hydrogen donors available to drive the conversion of free ammonia in the lower gastrointestinal tract to the ammonium group which can be readily excreted. One theory to explain the reported removal of the 'fishy' flatulence would be the excessive excretion of free NH 3 + via the systemic circulation. 5 Normally, 3.84 g of the composition (ie. single sachet) as described in TABLE 1 was dissolved in 100-200 mL water and taken orally by an individual twice daily (morning and afternoon). When combined with tap water having a pH of 7.5, L-camitine in 100 mL of tap water yielded a pH of 4.7, whereas L-carnitine in 200 mL of tap water yielded a pH of 4.8. 10 Individuals who had been taking commercially available L-carnitine dietary supplements, such as the MusahiTM carnitine supplement, and then the composition as herein exemplified noted the differences in taste, smell and 'fishy' flatulence. In particular, individuals generally noted that the composition as herein exemplified was pleasant tasting and smelling, and removed the 'fishy' flatulence that resulted from taking 15 commercially available supplements. A general procedure for the preparation of the L-camitine based composition preferably entails the following steps: (i) dispensing all ingredients of the composition in a low RH environment; (ii) drying the effervescent agents to remove any excess moisture; 20 (iii) blending the sweetening agent and the effervescent agents; (iv) adding L-carnitine to the blend of step (iii) and (v) blending to achieve homogeneity of the composition. To minimise the absorption of atmospheric moisture, it is preferable for the resultant blend to be formed into the appropriate form (powder, granulate or tablet) and 25 packed relatively soon after preparation. It is particularly preferred for the packing to be undertaken within 5-8 hours of blending the composition. A detailed description of the preparation of the preferred L-carnitine based composition follows.

WO 2011/072320 PCT/AU2009/001619 8 Step 1 L-carnitine USP (260.40 kg) was dispensed in a controlled RH (no more than 30%) and temperature (no more than 25 *C) atmosphere. Step 2 5 Two batches of sodium bicarbonate BP (each of 46.95 kg) and citric acid BP (143.25 kg) were separately dried in an oven at 50 "C until the moisture content of each compound was no more than 0.3%. The compounds were then transferred to a controlled RH (no more than 30%) and temperature (no more than 25 *C) atmosphere. Step 3 10 One batch of sodium bicarbonate from Step 2 was sieved through a stainless steel mesh #22 with cochineal C175470 (0.25 kg) and sucralose USP (0.975 kg). The sieved materials were mixed for five minutes on a drum roller. Step 4 The second batch of sodium bicarbonate from Step 2 was sieved through a stainless steel 15 mesh #22 with cochineal C175470 (0.25 kg) and sucralose USP (0.975 kg). The sieved materials were mixed for five minutes on a drum roller. Step 5 The L-camitine from Step 1 was sieved through a stainless steel mesh #12. Step 6 20 The citric acid from Step 2 was sieved through a stainless steel mesh #12. Step 7 The mixes resulting from Step 3 and Step 4 and the L-carnitine from Step 5 were combined and mixed for 5 minutes using a bin mixer.

WO 2011/072320 PCT/AU2009/001619 9 Step 8 The citric acid from Step 6 was combined with the mix from Step 7 and mixed for ten minutes using a bin mixer. Five samples were removed and tested to ensure that the moisture content was not more than 0.5%. The blend was then mixed for a further five 5 minutes using a bin mixer. A further five samples were removed and tested to ensure that the moisture content was not more than 0.5%. Step 9 The blended product was then stored at 14-19% RH in readiness for packing. Step 10 10 Packing was undertaken in a controlled atmosphere of 15% RH and 20 *C into sachets containing 3.84 g of the effervescent composition. Each 3.84 g sachet comprised the following composition: TABLE 1 Ingredient status % g L-carnitine active 52.08 2.000 anhydrous citric acid effervescent agent 28.65 1.100 sodium bicarbonate effervescent agent 18.78 0.721 sucralose non-calorie natural source sweetening agent 00.39 0.015 cochineal natural red colour agent 00.10 0.004 It is clear from the foregoing that the invention provides novel compositions 15 comprising L-carnitine which overcome or at least ameliorate some of the problems associated with known L-carnitine based supplements. The foregoing embodiments are illustrative only of the principles of the invention, and various modifications and changes will readily occur to those skilled in the art. The WO 2011/072320 PCT/AU2009/001619 10 invention is capable of being practiced and carried out in various ways and in other embodiments. It is also to be understood that the terminology employed herein is for the purpose of description and should not be regarded as limiting. The term "comprise" and variants of the term such as "comprises" or 5 "comprising" are used herein to denote the inclusion of a stated integer or stated integers but not to exclude any other integer or any other integers, unless in the context or usage an exclusive interpretation of the term is required.

Claims

1. An effervescent L-carnitine based composition for treating a physiological condition yet minimising a physiological problem normally resulting from L-carnitine metabolism, said composition comprising: approximately 40-60% w/w of L-carnitine for treating said physiological condition; and effervescent agents for creating an acidic environment when the composition is in solution.

2. The composition of claim 1, wherein the effervescent agents comprise a combination of at least one type of acid and base selected from the group consisting of citric acid, malic acid, tartaric acid, adipic adic, fuiaric acid, sodium bicarbonate, potassium bicarbonate, sodium carbonate and potassium carbonate.

3. The composition of claim 2, wherein the effervescent agents comprise approximately

15-40% w/w anhydrous citric acid and approximately 10-30% w/w sodium bicarbonate. 4. The composition of claim I further comprising a sweetening agent and/or flavouring agent for further masking the off-notes and poor taste normally associated with L-carnitine. 5. The composition of claim 4, wherein the composition comprises approximately 0.2 0.8% w/w sucralose as the sweetening agent. 6. The composition of claim 1, wherein the composition is in the form of an effervescent powder, granule, tablet or capsule. 7. The composition of claim 6, wherein the composition is in the form of an effervescent powder, and when dissolved in tap water the acidic environment has a pH of about 4.7 or 4.8. 8. An L-camitine based composition comprising: approximately 52.08% w/w L-carnitine; approximately 28.65% w/w anhydrous citric acid; approximately 18.78% w/w sodium bicarbonate; approximately 00.39% w/w sucralose; and approximately 00.10% w/w cochineal. - 12 9. A method of treating a physiological condition of an individual with an effervescent L camitine based composition yet minimising a physiological problem normally resulting from L carnitine metabolism by the individual, said method comprising the step of orally administering to the individual an effervescent L-carnitine based composition comprising: approximately 40-60% w/w of L-carnitine for treating said physiological condition; and effervescent agents for creating an acidic environment when the composition is in solution. 10. The method of claim 9, wherein the effervescent agents comprise a combination of at least one type of acid and base selected from the group consisting of citric acid, malic acid, tartaric acid, adipic adic, fumaric acid, sodium bicarbonate, potassium bicarbonate, sodium carbonate and potassium carbonate. 11. The method of claim 10, wherein the effervescent agents comprise approximately 15 40 % w/w anhydrous citric acid and approximately 10-30% w/w sodium bicarbonate. 12. The method of claim 9, wherein the composition further comprises a sweetening agent and/or flavouring agent for further masking the off-notes and poor taste normally associated with L-carnitine. 13. The method of claim 12, wherein the composition comprises approximately 0.2-0.8% w/w sucralose as the sweetening agent. 14. The method of claim 9, wherein the composition is in the form of an effervescent powder, granule, tablet or capsule. 15. The method of claim 14, wherein the composition is in the form of an effervescent powder, and when dissolved in tap water the acidic environment has a pH of about 4.7 or 4.8.

16. The method of claim 9, wherein the composition comprises: approximately 52.08% w/w L-carnitine; approximately 28.65% w/w anhydrous citric acid; approximately 18.78% w/w sodium bicarbonate; approximately 00.39% w/w sucralose; and approximately 00.10% w/w cochineal. -13 17. The method of claim 9, wherein the composition is dissolved in water and ingested twice daily. 18, The method of claim 16, wherein approximately 3-4 g of the composition is dissolved in

100-200 mL water and ingested twice daily. 19, The method of claim 9, wherein the composition is used to reduce body fat, enhance lean muscle mass, fight fatigue or increase stamina, 20. The method of claim 9. wherein the physiological problem normally observed with L carnitine ingestion and metabolism is 'fishy' odour of the individual's sweat or breath or flatulence, 21. The use of approximately 40-60% w/w of L-carnitine in combination with effervescent agents, for creating an acidic environment when the L-carnitine is in solution, in the preparation of a medicament for treating a physiological condition of an individual yet minimising a physiological problem normally resulting from L-carnitine metabolism by the individual, 22. A method of preparing an effervescent L-carnitine based composition for treating a physiological condition yet minimising a physiological problem normally resulting from L carnitine metabolism, said method comprising the step of: blending approximately 40-60% w/w of L-carnitine for treating said physiological condition with effervescent agents for creating an acidic environment when the L-carnitine is in solution. 23. The method of claim 22, wherein the method further comprises the step of blending at least one sweetening agent with the effervescent agents prior to blending with L-carnitine. 24. The method of claim 22, wherein the effervescent agents are dried prior to addition to the sweetening agent or L-carnitine. 25. An effervescent L-carnitine based composition for treating a physiological condition yet minimising a physiological problem normally resulting from L-carnitine -metabolism, said composition comprising: approximately 40-60% w/w of L-camnitine for treating said physiological condition; and effervescent agents. - 14 26. A method of treating a physiological condition of an individual with an effervescent L carnitine based composition yet minimising a physiological problem normally resulting from L carnitine metabolism by the individual, said method comprising the step of orally administering to the individual an effervescent L-carnitine based composition comprising: approximately 40-60% w/w of L-carnitine for treating said physiological condition; and effervescent agents. 27. A method of preparing an effervescent L-carnitine based composition for treating a physiological condition yet minimising a physiological problem normally resulting from L carnitine metabolism, said method comprising the step of: blending approximately 40-60% w/w of L-carnitine for treating said physiological condition with effervescent agents.