JP2007314491A - Creatine-increasing agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new substance increasing creatine in a body. <P>SOLUTION: This creatine-increasing agent consists of astaxanthin and/or its ester. By the creatine-increasing agent, it is possible to increase the creatine in the body without lowering renal function, and therefore, the creatine-increasing agent has high safety, Since it can be used daily as a health food, etc., for a preventive purpose, it is very useful for improving the athletic ability of muscle power and other tissues. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a creatine increasing agent. More particularly, the present invention relates to a creatine increasing agent in muscle comprising astaxanthin and / or its ester.

  Creatine is found in large amounts, particularly in skeletal muscle and tissues characterized by high variable energy demand capabilities (eg, smooth muscle, heart muscle, or sperm). Creatine is generated in vivo from arginine and glycine, receives phosphate from ATP by creatine kinase, and exists as phosphocreatine. Phosphocreatine plays a role in storing high-energy phosphate bonds in cells that rapidly consume large amounts of energy, such as muscle. Phosphocreatine regenerates ATP upon muscle contraction under anaerobic conditions such as exercise, and at the same time returns to creatine or is excreted in urine as creatinine by a non-enzymatic reaction.

  Creatine in the body is also increased by the intake of creatine present in meat. For example, in Patent Document 1, creatine is administered together with β-alanine, which is a precursor of β-alanyl histidine dipeptide found in muscles where anaerobic glycolysis due to rapid contraction occurs for the purpose of enhancing anaerobic exercise capacity. is doing. Moreover, in patent document 2, in order to increase an energy level (for example, intracellular ATP density | concentration), creatine is administered with the pentose sugar which is an ATP precursor (patent document 2). Thus, in order to increase creatine, it is common to take creatine directly. For example, various supplements for athletes who require instantaneous power are commercially available. However, the amount of creatine that can be retained in the body is limited by muscle mass, so not all creatine is used even if it is ingested. Unused creatine is filtered by the kidney glomeruli but reabsorbed by the tubules and is not easily excreted. In addition, when creatine is ingested excessively, the concentration of creatinine, which is a decomposition product thereof, increases excessively in plasma, so that excessive intake of creatine places a burden on the kidney and heart. Therefore, creatine intake with supplements must be done with sufficient care and control.

  By the way, it is known that astaxanthin improves the duration of muscle function and can be used for the treatment of muscle disorders or rhabdomyolysis (Patent Document 3). It has also been reported that astaxanthin has a fatigue recovery effect (Patent Document 4). However, nothing is known about the relationship between astaxanthin and creatine.

On the other hand, regarding the relationship between astaxanthin and creatinine, astaxanthin caused a decrease in blood creatinine in mercury-induced nephropathy rats, which are model animals of drug disorders (Patent Document 5), and continuous astaxanthin in normal individuals. It has been reported that the renal clearance value of creatinine was improved by administration (Patent Document 6).
Special Table 2000-516464 JP-T-2002-518321 Special table 2001-514215 gazette JP 2006-16409 A JP 2002-226367 A JP 2006-8720 A

  An object of the present invention is to provide a novel substance capable of increasing creatine in the body.

  The present invention provides a creatine increasing agent comprising astaxanthin and / or an ester thereof.

  In one embodiment, the creatine is increased in muscle.

  ADVANTAGE OF THE INVENTION According to this invention, the new creatine increase agent which can increase the creatine in a body, without ingesting creatine directly is provided. The creatine-increasing agent of the present invention promotes the use of ATP in cells and can enhance the exercise capacity of muscles and other tissues.

  Astaxanthin and / or its ester contained in the creatine increasing agent of the present invention has the following formula:

(Wherein R ¹ and R ² are each independently a hydrogen atom or a fatty acid residue). The ester of astaxanthin is not particularly limited. Examples thereof include monoesters or diesters of unsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid. These can be used alone or in appropriate combination. Astaxanthin has a structure having an extra oxo group and hydroxy group at both ends of the skeleton of β-carotene, and thus has low molecular stability unlike β-carotene. On the other hand, the ester body (for example, krill extract) in which the hydroxyl groups at both ends are esterified with an unsaturated fatty acid or the like is more stable.

  Astaxanthin and / or its ester used in the present invention may be either chemically synthesized or derived from natural products. Examples of the latter natural products include red yeast containing astaxanthin and / or an ester thereof; shellfish shells such as tigliopath (red daphnia) and krill; and microalgae such as green algae. In the present invention, an extract containing astaxanthin and / or its ester produced by any method can be used as long as the characteristics of astaxanthin and / or its ester can be utilized. In general, extracts from these natural products are used, and the extract may be in the form of an extract or may be appropriately purified as necessary. In the present invention, such a crude extract or crushed powder containing astaxanthin and / or an ester thereof, or an appropriately purified or chemically synthesized product containing astaxanthin and / or its ester may be used alone or in appropriate combination. Can do. In view of chemical stability, an ester form is preferably used.

  The creatine increasing agent of the present invention increases creatine in vivo. Most of creatine is present in muscles, etc., and there is little in blood. It is known that creatinine, which is a metabolite, is present in blood, and its amount is proportional to the amount of creatine in muscle. Therefore, in general, creatine in a living body can be detected and quantified as creatinine in blood. As a method for detecting and quantifying creatinine, a method usually performed in a clinical test can be mentioned. Suitably, an enzymatic method (for example, creatinase-saloxidase-POD method) may be employed. In the creatinase-zar oxidase-POD method, creatinine is hydrolyzed to creatine by creatininase, creatine is hydrolyzed to sarcosine by creatinase, and hydrogen peroxide is then generated from sarcosine by sarcosine oxidase. Quantifies quinone dyes produced from various chromogens in the presence of coexistence.

  Creatine, which is present in a small amount in the blood, is filtered by the glomerulus, but is hardly absorbed in the urine because it is reabsorbed from the tubule. On the other hand, creatinine, which is a metabolite of creatine, is not reabsorbed by tubules after being filtered by glomeruli. Therefore, when renal function falls and filtration function falls, creatinine in blood will become high and creatinine in urine will become low. Accordingly, creatinine is a substance to be measured for renal clearance, which is one of the indicators of renal function that is usually employed in clinical tests. The creatine increasing agent of the present invention increases creatinine in the living body, that is, increases creatine in muscle and creatinine in blood, but does not adversely affect renal function.

  The administration route of the creatine increasing agent of the present invention may be either oral administration or parenteral administration. The dosage form is appropriately selected depending on the administration route. For example, injections, infusions, powders, granules, tablets, capsules, pills, enteric solvents, troches, liquids for internal use, suspensions, emulsions, syrups, liquids for external use, poultices, nasal drops, ear drops Agents, eye drops, inhalants, ointments, lotions, suppositories, enteral nutrients and the like. These can be used alone or in combination depending on the application. In these preparations, auxiliary agents usually used in the pharmaceutical preparation technical field such as excipients, binders, preservatives, oxidation stabilizers, disintegrants, lubricants, and corrigents are used as necessary. .

  The dose of the creatine-increasing agent of the present invention varies depending on the purpose of administration and the situation (sex, age, weight, etc.) of the administration subject. Usually, for adults, 0.1 mg to 2 g per day, preferably 4 mg to 500 mg per day in the case of oral administration, in terms of astaxanthin free body, while 0.01 mg to 1 g per day for parenteral administration, Preferably it can be administered at 0.1 mg to 500 mg.

  The creatine increasing agent of the present invention can be used not only as a pharmaceutical as described above, but also as a quasi-drug, cosmetic, functional food, nutritional supplement, food and drink, and the like. When used as a quasi-drug or cosmetic, it can be used together with various adjuvants commonly used in the technical field such as quasi-drug or cosmetic, if necessary. Or, when used as a functional food, nutritional supplement, or food and drink, it is usually used in foods such as sweeteners, spices, seasonings, preservatives, preservatives, bactericides, and antioxidants as necessary. You may use with the additive used. Further, it may be used in a desired shape such as solution, suspension, syrup, granule, cream, paste, jelly, etc., or as necessary. The ratio contained in these is not specifically limited, It can select suitably according to a use purpose, a usage form, and a usage-amount.

(Preparation Example 1: Preparation of astaxanthin capsule)
First, astaxanthin was prepared as follows. The Haematococcus pulvialis K0084 strain was cultured at 25 ° C. while aerated with a gas containing 3% CO ₂ under light irradiation conditions. Then, it was made cyst by applying nutritional stress (nitrogen source deficiency). The cysted cells were crushed by means usually used by those skilled in the art, and an oily fraction containing astaxanthin was extracted with ethanol. The extract was concentrated under reduced pressure to distill off ethanol, and an extract containing 8.0% of astaxanthin in terms of free form was prepared.

  Using the extract containing 8.0% of this astaxanthin, soft capsules containing the components shown in Table 1 below per capsule were prepared.

  Each obtained soft capsule contains 4.16 mg of astaxanthin as a free form.

(Example 1: Effect on blood creatinine concentration-1)
The astaxanthin capsules obtained in Preparation Example 1 were ingested by 38 subjects in their 20s to 70s, 2 capsules once a day for 4 weeks. Prior to breakfast on the day of ingestion and before breakfast on the day after the end of ingestion, blood was collected from each subject, and blood creatinine concentration and urea nitrogen were measured. The creatinine concentration was measured by the enzyme method described above (creatinase-zal oxidase-POD method). In the present Example, it carried out by the method (CRE-EN kainos: Kainos Co., Ltd.) using 3-hydroxy-2,4,6-triiodobenzoic acid and 4-aminoantipyrine as a chromogen. The blood urea nitrogen concentration was measured by the urease GLDH method. Specifically, urea is decomposed with urease into ammonia and carbon dioxide, and the produced ammonia is reacted with glutamate dehydrogenase in the presence of α-ketoglutarate and NADPH, thereby reducing NADPH as a decrease in absorbance. This was done by measuring the speed. The results of blood creatinine concentration measurement are shown in FIGS. FIG. 1 shows the change in blood creatinine concentration before and after ingestion of astaxanthin capsules for each subject, and FIG. 2 shows the mean value. In any figure, the unit of numerical values on the vertical axis is mg / dL.

  As can be seen from FIG. 1, the blood creatinine concentration increased in 34 of 38 subjects. Moreover, as can be seen from FIG. 2, the average value of the creatinine concentration of all the subjects was significantly increased (p <0.01). The standard value of creatinine concentration in blood is said to be about 0.8 to 1.2 mg / dL for men and about 0.6 to 1.0 mg / dL for women. In particular, in subjects whose creatinine concentration before ingestion of astaxanthin capsules was 0.7 mg / dL or less, all of them increased, and when the value before ingestion was taken as 100%, the average increased by 13.4%. In particular, it can be seen that the increase effect was high in subjects with low creatinine concentrations.

  Urea nitrogen (BUN), which is an index of renal function, had an average value before ingestion of 12.21 mg / dL and an average value after ingestion of 12.60 mg / dL, which did not increase significantly (p = 0.32). Thus, no decrease in renal function was observed. Therefore, it can be seen that the increase in creatinine concentration is not due to a decrease in renal function but due to an increase in creatine in the body.

(Example 2: Effect on blood creatinine concentration-2)
Astaxanthin capsules obtained in Preparation Example 1 were ingested by 18 subjects in their 20s to 70s, 5 capsules once a day for 4 weeks. In the same manner as in Example 1 above, blood was collected from each subject before breakfast on the day of ingestion and on the day after the end of ingestion, and blood creatinine concentration and urea nitrogen were measured. As a result, similar to the result of Example 1 above, the average value of the creatinine concentration of all subjects was significantly increased (p <0.01), there was no significant increase in urea nitrogen (BUN), and renal function There was no decline in Therefore, even when a large amount of astaxanthin is ingested, it can be seen that the increase in creatinine concentration is not due to a decrease in renal function but due to an increase in creatine in the body.

  ADVANTAGE OF THE INVENTION According to this invention, the new creatine increase agent which can increase the creatine in a body, without ingesting creatine directly is provided. The creatine-increasing agent of the present invention promotes the use of ATP in cells and can enhance the exercise capacity of muscles and other tissues. In addition, astaxanthin and / or its ester, which is an active ingredient of the creatine-increasing agent of the present invention, is also known to have muscle sustainability and fatigue recovery effects, so it is very useful for improving muscle performance. Conceivable.

  Astaxanthin and / or its ester, which is an active ingredient of the creatine-increasing agent of the present invention, has a long diet and very low toxicity. Therefore, it can be used prophylactically as a health food.

It is a graph which shows the change of the blood creatinine density | concentration before and behind astaxanthin capsule about each subject. It is a graph which shows the average value of the blood creatinine density | concentration of the test subject before and after an astaxanthin capsule ingestion.

Claims (2)

  A creatine increasing agent comprising astaxanthin and / or an ester thereof.   The creatine increasing agent according to claim 1, wherein the creatine is increased in muscle.

Images