Food or edible material: processes – compositions – and products – Products per se – or processes of preparing or treating... – Basic ingredient lacteal derived other than butter...
Reexamination Certificate
2001-08-07
2002-10-29
Criares, Theodore J. (Department: 1617)
Food or edible material: processes, compositions, and products
Products per se, or processes of preparing or treating...
Basic ingredient lacteal derived other than butter...
C514S642000, C424S489000
Reexamination Certificate
active
06472011
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to an L-carnitine agent and a method for producing thereof, wherein the starting material is milk or modified milk products of mammals. The L-carnitine agent of the present invention is characterized by features including simple handling, use of milk or modified milk products of mammals as a starting material, the absence of toxic D-carnitine, and thus superior safety.
2. Description of the Related Art
L-carnitine is a water-soluble compound which easily forms fatty-acids and ester via alcohol residue in the molecules, and is also referred to as Vitamin BT. Major function of L-carnitine in the body is the oxidation of fatty acids in mitochondria. Upon acting as a shuttle, L-carnitine transports fatty acids into and out of mitochondria via mitochondrial membrane. Thus, L-carnitine is an indispensable component for energy production in the body.
L-carnitine is biologically synthesized from lysine and methionine in the body. However, only 25% of the total metabolic turnover of L-carnitine is endogenously synthesized in the body. Therefore, the remaining 75% metabolic turnover is derived from food. Although the amount of endogenous L-carnitine is normally reported to be sufficient for older children or adults, it is observed that hypercatabolism of fat is enhanced at time of fasting even for healthy children, consequently increasing acyl CoA, and resulting in the increase of esterified L-carnitine. For pediatric patients with organic acidemia, for example, propionicacidemia or methylmalonicacidemia, the level of acyl-L-carnitine such as propionyl-L-carnitine is increased. Unlike free L-carnitine, acyl-L-carnitine is readily excreted into urine, thereby resulting in L-carnitine deficiency. Moreover, even with total carnitine concentration in blood within the normal range, the relative amount of free L-carnitine decreases due to the increase of acyl-L-carnitine. The administration of L-carnitine to such pediatric patients results in enhancement of the conversion of acyl CoA, such as propionyl CoA, deposited in blood into acyl-L-carnitine. Hence the recovery of mitochbndrial function is observed due to the excretion of toxic propionyl group and the increase in free CoA. Thus the administration of L-carnitine has therapeutic efficacy.
As L-carnitine is involved in metabolism of fatty acid in mitochondria and is regarded as an indispensable component of energy production, diverse research has been conducted. When L-carnitine is used as an additive for food or a beverage such as sports drink, it is disclosed that the efficient energy transduction of the fat stored in the body consequently results in the prevention of obesity or in stamina enhancement while engaging in sports activities.
Alternatively, in neonates, most of the desired amount of L-carnitine must be supplemented through mother's milk or artificial nourishment due to immature endogenous L-carnitine synthesis. However, therapeutic milk for the pediatric patients with metabolic disorders. which includes an amino acid mixture powder as the main ingredient, contains an extremely low level of L-carnitine. It is reported that when patients are nursed with such therapeutic milk, negative effect on normal development is observed.
Natural carnitine is levarotatory L-carnitine; and dextrarotatory D-carnitine is not present in natural substances. D-carnitine is regarded to be toxic because of its antagonistic inhibition against L-carnitine. Actually the adverse action due to the administration of racemate of carnitine, a mixture of L-carnitine and D-carnitine, for a longer period is also observed.
Carnitine can be produced synthetically. However, because carnitine obtained by chemical synthesis is racemic, purification processes of carnitine including optical resolution are required upon completion of the synthetic reaction, in order to remove toxic D-carnitine and to recover L-carnitine only. The synthetic method is disadvantageous in the view of the rather complicated manufacturing process, resulting in costly products and the possible risk of contamination with toxic D-carnitine due to insufficient purification.
Other biochemical methods have been developed for producing L-carnitine by means of using chemically synthesized dehydrocarnitine or apocarnitine as source materials with enzymes derived from microorganisms. However, these methods also indicate various disadvantages such as difficulty in purification methods of L-carnitine from the reactants, costly source materials, and no assurance of the safety of source materials. In addition, another attempt has been made to produce L-carnitine using fermentation by microorganisms, but it is not considered to be practical because of its low yield of L-carnitine.
Alternatively, some foods are known to be sources of L-carnitine. For example, milk such as cow's milk has been conventionally indicated to be a source for natural L-carnitine, but the content of L-carnitine in cow's milk is at about 20 &mgr;mol/100 g and regarded as considerably low. On the other hand, meat and fish contain relatively higher levels of L-carnitine. For example, beef, which is a source of higher level of L-carnitine, contains L-cartinine at about 800 mol/100 g. However there are disadvantages of a peculiar flavor or odor and difficulties in handling with respect to color or physical properties. Thus, it is significant that without modification, all of these methods have limited utilities and are considered impractical.
As for methods of producing L-carnitine from milk or modified milk products of mammals as the starting material disclosed in Japanese Patent Publication Sho62-63553 Public Bulletin is the method comprising the process of: using a byproduct (permeate) separated in the process of ultrafiltration of milk or modified milk products for starting material; desalting by means of electrodialysis; conducting column chromatography to absorb L-carnitine while passing through a column packed with strong acidic cationic ion-exchange resin; washing the column; and eluting to isolate L-carnitine. In this disclosure, it is described that lactose is preferably crystallized to precipitate for its removal before the desalting treatment. Further, as L-carnitine isolated by column chromatography is remarkably hygroscopic in powder form, it is preferable to disperse the concentrate onto lactose and use it as a triturated powder for practical use. Although the L-carnitine agent can be produced in this method, the efficiency of the entire process is not always regarded as desirable since the same lactose once removed in the processes is used again for trituration.
Furthermore, when the L-carnitine content in the resulting carnitine agent produced is 0.1 mmol/100 g or less, it is not considered to be practical because the daily dose for administration of the L-carnitine agent to introduce sufficient physiological effects becomes too high. On the other hand, when the L-carnitine content exceeds 100 mmol/100 g, more complicated manufacturing processes are required and the yield of L-carnitine decreases; this is economically inefficient. Additionally when the lactose content is 20 g/100 g or less, the function of lactose as filler is not sufficient, while a lactose content of 95 g/100 g or more makes it difficult to recover sufficient L-carnitine content. In addition, when ash content is 5 g/100 g or more, the agent tends to be hygroscopic with less fluidity.
As set forth, L-carnitine has an indispensable function in the body and also is useful material for pharmaceutical agents or food and drink. Therefore, it is advantageous to develop the method of producing the L-carnitine agent in a simple and effective manner, wherein the L-carnitine agent is: simple to handle; at higher concentrations and uniform in quality; economical; superior in safety; not only a highly concentrated form of L-carnitine but also containing a suitable filler; and useful as an additive for food or pharmaceutical agents without any modification.
SUMMARY
Idota Tadashi
Ozaki Kiyoko
Shimatani Masaharu
Yakabe Takafumi
Criares Theodore J.
Kim Jennifer
Knobbe Martens Olson & Bear LLP
Snow Brand Milk Products Co. Ltd.
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