JP2000302677A - Medicine and food/feed composition having improving action on carnitine self production ability - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain both a medicine and the subject composition having improving action on carnitine self production ability and excellent safety by making the medicine and the subject composition include at least γ-linolenic acid as an active ingredient. SOLUTION: The medicine and the food/feed composition comprise γ-linolenic acid alone or γ-linolenic acid and a fat-soluble antioxidant (preferably vitamin E, coenzyme Q, ascorbyl palmitate, or the like, especially preferably vitamin E) as active ingredients. The amount of the fat-soluble antioxidant is <=50 wt.%, preferably 1-50 wt.% based on the γ-linolenic acid. The medicine can be administered as a capsule, for example, packed into a gelatin capsule. The capsule contains 50 mg of γ-linolenic acid and the daily dose is preferably 1-10 capsules for a patient requiring administration (preferably dialysis patient). The food/feed composition is useful for improving endurance and moving ability during exercise.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a medicament having a carnitine self-producing ability improving effect useful in the medical field.
In addition, the present invention relates to a food / feed composition having an effect of improving carnitine self-producing ability, which is useful in the food field (food for sports and diet), the feed field (livestock, sports animals, pet food, and the like).

[0002]

2. Description of the Related Art It is known that various complications occur in dialysis patients due to the elimination of renal function and dialysis, which play an important role in maintaining homeostasis.

[0003] With respect to such complications of dialysis patients, the present applicant already has a composition for treating pruritus cutaneous and hyperparathyroidism in dialysis patients containing γ-linolenic acid and the like. (Japanese Unexamined Patent Publication No. Hei 7-233302), an external preparation for treating bone disease of an artificial dialysis patient (Japanese Unexamined Patent Publication No. Hei 9-23062).
No. 295936), and a pharmaceutical and food / feed composition having a blood fluidity improving effect (JP-A-10-1475).
No. 23) has already been proposed.

According to these inventions, administration of a composition containing γ-linolenic acid or the like to dialysis patients (hereinafter referred to as dialysis patients) reduces itching, parathyroid hormone secretion, It has become possible to contribute to pain reduction of bone diseases caused by bone dystrophy and dialysis amyloidosis. In addition, by improving the flowability of red blood cells and white blood cells, blood flow is improved, and in particular, by stabilizing white blood cells, the release of inflammatory substances from white blood cells is suppressed as much as possible, and arteriosclerosis and It has been found that it is expected to prevent and improve various inflammatory diseases.

[0005] It is known that carnitine self-producing ability is greatly reduced in dialysis patients, resulting in chronic carnitine deficiency.

[0006] The cause is that carnitine is mainly synthesized in the liver and kidney, but in dialysis patients, the self-producing ability is reduced due to the elimination of renal function, and the source of carnitine from food is mainly Although there are meats and dairy products, it is conceivable that dialysis patients generally refrain from ingesting these foods and that they are removed by dialysis because they are water-soluble low molecular amines as shown in the following structural formula.

[0007]

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[0008] Carnitine is indispensable as a carrier for transporting fatty acids into mitochondria in the fatty acid oxidation system, and it is said that 90% of the human body is distributed in muscles such as skeletal muscle and cardiac muscle. Free fatty acids taken into muscle become acyl-CoA, then combine with carnitine to form acylcarnitine, undergo β-oxidation in mitochondria, enter the TCA cycle, and serve as an important energy source for ATP production.

It is said that 95% of the energy obtained from fatty acid oxidation is obtained from long-chain fatty acids requiring carnitine such as stearic acid, palmitic acid, oleic acid, linoleic acid, and arachidonic acid.

[0010] Therefore, in dialysis patients with chronic carnitine deficiency, QOL such as continuous muscle cramps, lack of energy and vitality that hinders daily activities, skeletal muscle weakness or muscle pain and difficulty walking can be inhibited. Cause muscle damage. In particular, organs that require a large amount of energy, such as the heart, may cause harmful effects such as cardiac disorders such as arrhythmia, or may cause sudden cardiac arrest when the energy supply becomes insufficient.

Conventionally, as a source of carnitine, artificially synthesized carnitine and carnitine extracted from meat and dairy products are known, and these are supplied as needed. It is not intended to improve the carnitine production ability in the body.

[0012]

SUMMARY OF THE INVENTION The inventors of the present invention have conducted intensive studies on the usefulness of γ-linolenic acid, and as a result, when γ-linolenic acid and vitamin E were administered to a dialysis patient, a low value was obtained. The present inventor has found that the carnitine concentration in the blood has increased and that the self-producing ability of carnitine in dialysis patients has been improved, and the present invention has been completed.

[0013] That is, an object of the present invention is to provide a highly safe drug and a food / feed composition having an effect of improving the self-producing ability of carnitine.

[0014] It has never been reported that γ-linolenic acid was administered to a dialysis patient to improve the self-producing ability of carnitine, and this was the first report made by the present inventors. In addition, there has been no report that the self-producing ability of carnitine was enhanced by administering a specific component.

[0015]

According to the present invention, there is provided a medicament having an effect of improving carnitine self-producing ability comprising γ-linolenic acid alone or γ-linolenic acid and a fat-soluble antioxidant as active ingredients. To provide.

According to a fourth aspect of the present invention, there is provided a food or feed having an effect of improving the self-producing ability of carnitine, which comprises γ-linolenic acid alone or γ-linolenic acid and a fat-soluble antioxidant. It provides a composition.

[0017]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below. The γ-linolenic acid used in the present invention is an endogenous substance known as an n-6 essential fatty acid, and is converted from linoleic acid by the enzyme δ6-desaturase. This step is the rate-limiting step of n-6 fatty acid metabolism, but its enzyme activity is weak and further weakened by various factors such as diabetes, alcohol intake, aging, zinc deficiency, and γ- It is said that the conversion to linolenic acid is hindered. Metabolism of γ-linolenic acid to dihomo-γ-linolenic acid occurs rapidly.
Therefore, γ-linolenic acid used in the present invention has a broad meaning including γ-linolenic acid, dihomo-γ-linolenic acid and derivatives thereof in a narrow sense. In this specification, unless otherwise specified, γ-linolenic acid in a broad sense refers to γ-linolenic acid in a broad sense.

The medicament having an effect of improving carnitine self-producing ability or the food / feed composition having an effect of improving carnitine self-producing ability according to the present invention is not only γ-linolenic acid alone but also fat-soluble in γ-linolenic acid. A food or feed having a carnitine self-producing ability improving action according to claim 4 or a supplement containing an antioxidant as the active ingredient (the medicine having the carnitine self-producing ability improving action according to claim 1). Composition). In addition, the carnitine self-producing ability improving action described herein includes, for example, an action of improving the carnitine self-producing ability (approaching a normal value) as in a dialysis patient and a carnitine self-producing ability in a healthy range. It refers to a concept that includes both the action of further improving the productivity.

It is needless to say that the "medicine" in the present invention described in claim 1 is used for diagnosis, treatment, treatment or prevention of human diseases. Specifically, in the present invention described in claim 1, "medicine"
“Pharmaceuticals” refers to “medicines” in the Pharmaceutical Affairs Law.

[0020] The above-mentioned γ-linolenic acid is used in mucol (Muc).
or) Genus, Mortierella
Genus, Risopus genus, etc., or plants such as evening primrose, borage etc., and oils and fats contained in algae such as spirulina, etc., which may be used as they are or extracts therefrom. Alternatively, a further purified product may be used. Further, γ-linolenic acid can be obtained by chemical synthesis, and a commercially available product may be used.

Note that γ-linolenic acid is a biological component originally contained in mother's milk, and has a health promoting effect from a nutritional point of view. Is a component widely used in the field of animal feed, and there is no particular problem in safety. Also, dihomo-γ-linolenic acid may be derived from microorganisms or chemically synthesized, but the origin is not particularly limited.

Γ-linolenic acid or dihomo-γ in a narrow sense
-Derivatives of linolenic acid include those obtained by reacting these with various alcohols, for example, ethyl esters, glycerol esters, phospholipids, etc., or inorganic or organic bases in an equimolar ratio. Such as sodium salt and potassium salt.

It is well known that newborn babies actively use fatty acids as a calorie source. In this case, exogenous carnitine derived from breast milk is mainly used. However, although carnitine levels in breast milk are lower than carnitine levels in most formulas, it is said that blood carnitine levels in breast-fed infants are higher than blood carnitine levels in formula-fed infants (Sc
imidt-Sommerfeld, E .; Others: Car
nitine and development of
newborn adipode tissue. P
editor. Res. , 12: 660,197.
8. ). Regarding this cause, the present inventors believe that gamma-linolenic acid ingested through breast milk contributes to the improvement of carnitine self-producing ability in newborns, which enables active fatty acid utilization in newborns. .

In the medicament having the effect of improving carnitine self-producing ability or the food / feed composition having the action of improving carnitine self-producing ability of the present invention, γ-linolenic acid as described above may be used alone. What added a fat-soluble antioxidant to linolenic acid can also be used. Examples of fat-soluble antioxidants include vitamin E, coenzyme Q, ascorbyl palmitate, ascorbyl stearate, β-carotene, lycopene and the like. Among these, vitamins considered to contribute to the stability of cell membranes It is preferable to use E.

In this case, the fat-soluble antioxidant is usually 50% by weight or less, preferably 1% by weight, based on γ-linolenic acid.
It is used in a proportion of ５０50% by weight, more preferably in a proportion of 2 to 30% by weight.

The pharmaceutical or food / feed composition having an effect of improving the carnitine self-producing ability according to the present invention is basically composed of the above-mentioned components. If necessary, α-linolenic acid, eicosapentaenoic acid and docosahexaene may be used. N-3 unsaturated fatty acids such as acids, n-5 unsaturated fatty acids such as myristoleic acid, n-7 unsaturated fatty acids such as palmitooleic acid, n such as oleic acid and erucic acid Saturated fatty acids such as -9 unsaturated fatty acids, lauric acid, and myristic acid may be added at an arbitrary ratio.

In the case of a food composition, it goes without saying that it is necessary to use additives permitted under the Food Sanitation Law.

Although the dosage form of the medicament of the present invention having an effect of improving carnitine self-producing ability is not particularly limited, γ-
Linolenic acid, one or two or more selected from dihomo-γ-linolenic acid and derivatives thereof, or an extract obtained from fats and oils of the above-mentioned filamentous fungi and plants, generally a harmless kind or a pharmaceutically acceptable or Mixed with two or more vehicles, carriers, excipients, integrators, preservatives, stabilizers, flavors, and internal preparations such as tablets, granules, capsules and solutions; sterile solutions and suspensions Injections, etc .; infusions can be used. These can be manufactured using a conventionally known technique.

For example, γ-linolenic acid, dihomo-
One or more selected from γ-linolenic acid and derivatives thereof, a binder such as corn starch and gelatin, an excipient such as microcrystalline cellulose, a bulking agent such as potato starch and sodium alginate, lactose, Tablets, granules and the like can be prepared by dispensing a sweetener such as sucrose. Capsules can be prepared by filling a mixture of γ-linolenic acid and other fats and oils into a soft gelatin capsule, a hard gelatin capsule, or the like according to a conventional method. Furthermore, a cyclodextrin clathrate of cyclodextrin and γ-linolenic acid can be prepared by a conventional method.

In the case of a food / feed composition,
The above components may be simply mixed, but such a composition may be formulated and consumed in the same manner as described above, or these may be mixed with food or feed. In particular, in the case of a food composition, it can be mixed with general foods, for example, various foods such as wafers, jellies, dressings, and margarine. There are no particular restrictions on the types of foods that can be mixed.

With respect to the amount of administration (dose), the amount of γ-linolenic acid, dihomo-γ-linolenic acid and derivatives thereof in a narrow sense depends on the age, medical history, type of disease, symptoms, etc. of the patient / ingestor. What is necessary is just to set suitably. Usually, γ-linolenic acid is used in the range of 5 to 5,000 mg / day, preferably in the range of 10 to 2,000 mg / day, and more preferably in the range of 30 to 1,000 mg / day.
If the dose is too small, it will not be possible to obtain a sufficient effect of improving carnitine self-producing ability. The administration is generally performed every day, but may be performed every other day, and may be appropriately set according to the age, medical history, type of disease, symptom, etc. of the patient / ingestor.

Specifically, for example, the product is administered in the form of a capsule filled in a gelatin capsule, and the capsule contains 50 mg of γ-linolenic acid, which reduces the self-producing ability of carnitine and hinders the use of fatty acids. Is administered at a dose of about 1 to 10 capsules per day.

The medicament having an effect of improving carnitine self-producing ability according to the present invention is excellent in safety and useful as an agent for improving human carnitine self-producing ability, particularly as a carnitine self-producing ability improving agent for dialysis patients. is there. In addition, dialysis patients and diabetic patients with diabetic nephropathy, as well as those in these reserve groups, have been able to replace the energy that accompanies dietary sugar intake with the replacement of fatty acids by improving carnitine self-producing ability. It is possible to supplement with the energy obtained by promoting oxidation, which is useful for preventing the progress of diabetes.

The food / feed composition having an effect of improving carnitine self-producing ability according to claim 4 is excellent in safety and is accumulated in muscles by energy supplementation obtained by promoting fatty acid oxidation. Energy consumption from reduced glycogen and the suppression of glycogen depletion as much as possible, which is useful for improving endurance and athletic performance during exercise of humans and animals, and promoting the burning of fatty acids. Useful for preventing obesity.

[0035]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in more detail with reference to embodiments. Production Example 1 (Production of Capsules) 235 parts by weight of fats and oils containing about 22% by weight of γ-linolenic acid and 65 parts by weight of vitamin E (mix-tocophenol) are mixed and stirred by a usual method, and gelatin capsules ( The capsule was filled into a capsule (Fuji Capsule Co., Ltd., football type No. 5), and capsules containing 50 mg of γ-linolenic acid in one capsule were produced.

The oils and fats containing γ-linolenic acid were those extracted by the method described in JP-A-63-283589. That is, Mucor circinelloides
s) Extraction from cultured cells of HUT (FERM P-9359) by n-hexane extraction method gave γ
-An oil or fat containing linolenic acid was obtained.

Example 1 (Clinical Test) The capsule obtained in Production Example 1 was applied to 5 dialysis patients
Take 6 capsules per day (i.e., at a dose of 300 mg per day as gamma-linolenic acid) for 10-19 weeks. Blood was collected before and after dialysis before and after the administration, and the total carnitine concentration (μmol / L) in the serum was measured. The results are summarized in Table 1.

The measurement of carnitine is described in Manuel
Paz et al. (CLIN. CHEM. 31/5, 75)
4-75. 1985). This measurement method is used as a general-purpose method for carnitine.

[0039]

[Table 1]

As is clear from Table 1, the total carnitine concentration in the blood increased in all cases due to the administration of γ-linolenic acid. In E, the self-producing ability of carnitine is further improved. This clearly shows that taking the composition according to the present invention has improved the self-producing ability of carnitine essential for fatty acid combustion.

In the present clinical case, no special treatment was performed before and after the start of administration, and the type and amount of medication were not changed during the administration period. No abnormalities were found in the laboratory test values that are regularly performed, and there was no problem in safety.

The present inventors have already conducted an acute toxicity test (single-dose toxicity test) on γ-linolenic acid-containing fats and oils using SD rats, and there is no particular problem in safety. (Japanese Patent Laid-Open No. 10-1475)
No. 23).

[0043]

EFFECTS OF THE INVENTION The medicament of the present invention having the effect of improving carnitine self-producing ability according to the present invention and the food and the food having the effect of improving carnitine self-producing ability of the present invention according to claim
The feed composition is excellent in safety and has no adverse effects such as side effects even after long-term administration.

The medicament having an effect of improving carnitine self-producing ability according to the first aspect of the present invention can improve the self-producing ability of carnitine which is indispensable for the burning of fatty acids. Prevent and improve muscular disorders that occur. Therefore, Claim 1
The described medicament for improving carnitine self-producing ability of the present invention is useful as a human carnitine self-producing ability improving agent, particularly as a carnitine self-producing ability improving agent for dialysis patients with chronic carnitine deficiency.

That is, muscular disorders that inhibit the QOL of dialysis patients, such as continuous muscle spasms, lack of energy and energy, skeletal muscle weakness or muscle pain and difficulty walking, and especially cardiac disorders such as arrhythmia and sudden It is useful as a prophylactic to prevent cardiac arrest. In addition, the lack of energy associated with the restriction of sugar intake from meals in dialysis patients and diabetic patients with diabetic nephropathy, and those in these reserve groups, can be obtained by improving carnitine self-producing ability and promoting oxidation of fatty acids. It is possible to supplement with the energy given, which can contribute to the prevention of the development of diabetes.

Further, the food / feed composition having an effect of improving carnitine self-producing ability according to claim 4 is excellent in safety, and is stored in muscle by energy supplementation obtained by accelerating fatty acid decomposition. To reduce energy consumption from glycogen and reduce glycogen depletion as much as possible, such as athletes,
It is also useful for improving the endurance and athletic ability of racing animals such as racehorses and race dogs.It also promotes the burning of fatty acids to give vitality to livestock and pets that have fallen short of energy and lack of vitality. It is useful for preventing obesity in people who tend to be short and pets kept at home.

Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat II (Reference) A61K 45/08 A61K 45/08 (72) Inventor Kenichi Yahiro 2-35-5 Arai, Nakano-ku, Tokyo F-term (reference) 2B150 AA01 AA06 AB03 AB20 DA58 DE13 DE15 4B018 LE02 MD13 MD23 MD26 ME01 ME02 ME14 4C084 AA27 MA05 NA14 ZC211 ZC212 4C086 AA01 AA02 BA09 MA01 MA02 MA04 MA05 NA14 ZC21 4C206 AA01 AA02 DA05 MA01 MA02 MA04 MA05

Claims (4)

[Claims] 1. A medicament having an effect of improving carnitine self-producing ability comprising γ-linolenic acid alone or γ-linolenic acid and a fat-soluble antioxidant as active ingredients. 2. A carnitine self-producing ability improving agent comprising γ-linolenic acid alone or γ-linolenic acid according to claim 1 and a fat-soluble antioxidant as active ingredients. 3. An agent for improving carnitine self-producing ability of an artificial dialysis patient, comprising the γ-linolenic acid alone or γ-linolenic acid and a fat-soluble antioxidant as active ingredients according to claim 1. 4. A food / feed composition having an effect of improving the self-producing ability of carnitine, which comprises γ-linolenic acid alone or γ-linolenic acid and a fat-soluble antioxidant.