JP6446265B2 - Solid composition - Google Patents

Description

  The present invention relates to a solid composition containing carnitine and a fat globule membrane component.

L-carnitine is a nutrient essential for permeation of long-chain fatty acids into the mitochondrial membrane, and is present in muscle cells at high concentrations. L-carnitine has many physiological functions such as visceral fat accumulation and long-term intake of high-fat diet, inhibiting and improving lipid metabolism abnormalities, enhancing skeletal muscle endurance, and reducing muscle fatigue. Have been reported (Non-Patent Documents 1 and 2).
In recent years, the obese population has continued to increase, and the number of patients with metabolic syndrome and locomotive syndrome has increased significantly, which has become a major social problem. Therefore, widespread use of carnitine having the physiological functions described above is expected. Has been.

In order to effectively obtain the physiological function of carnitine, it is desirable to form a solid composition that can be easily and easily ingested for a long period of time. However, since carnitine has a strong acidity, it is difficult to formulate it in a particularly high concentration.
So far, as a technique for suppressing acidity derived from carnitine, a beverage composition in which a pH adjuster is combined so that the pH of an aqueous solution of carnitine salt is 5 or more has been reported (Patent Document 1). The composition form has not been studied.

JP 2012-135322 A

“Journal of Japanese Society of Nutrition and Food”, 2006, Vol. 59, No. 2, p. 107-113 "The 26th Health Medical Science Grants", 2009, 2011, p. 102-109

When a large amount of carnitine is blended in the solid composition, the acidity derived from carnitine may remain not only at the time of ingestion but also after ingestion, and the flavor is not preferable.
Therefore, the present invention relates to providing a solid composition having a good flavor and low acidity while containing carnitine.

As a result of intensive studies to solve the above problems, the present inventors have found that the fat globule membrane component has an effect of suppressing the acidity of carnitine. Further, by combining carnitine with a fat globule membrane component within a certain range, the intense sourness derived from carnitine is reduced, and this sourness does not remain even after ingestion, and a solid composition with good flavor is obtained. I found out that I can do it.
The fat globule membrane component is a membrane component that covers milk fat globule secreted from the mammary gland.

That is, the present invention includes the following components (A) and (B):
(A) Carnitine or a salt thereof 6 to 35% by mass,
(B) Fat globule membrane component 10-50% by mass,
The solid-state composition containing this is provided.

  ADVANTAGE OF THE INVENTION According to this invention, the solid composition with few sourness derived from carnitine and favorable flavor can be provided.

The (A) carnitine used in the present invention may be D-form or L-form, and may be DL-carnitine in which both isomers are mixed. Of these, L-carnitine is preferable from the viewpoint of physiological effects.
Carnitine salts include, for example, mineral salts such as nitrates, hydrochlorides and sulfates; acetates, propionates, tartrate, fumarate, maleates, malates, citrates, methanesulfonic acids And organic acid salts such as salts, p-toluenesulfonic acid salts, and trifluoroacetic acid salts.
Further, as carnitine or a salt thereof, alkanoylcarnitine such as acetyl-L-carnitine or a salt thereof may be used.
(A) Carnitine or a salt thereof may be produced by a known method, or a commercially available product may be used.

  In the solid composition of the present invention, the content of (A) carnitine or a salt thereof is 6 to 35% by mass (hereinafter, simply referred to as “%”). 10% or more is preferable from the point that it is possible to take a small amount at once, and 30% or less is preferable and 20% or less is more preferable from the point of flavor. Further, the content of (A) carnitine or a salt thereof in the solid composition is preferably 10 to 30%, more preferably 10 to 20%. In addition, content of a component (A) is a carnitine conversion value.

The (B) fat globule membrane component used in the present invention is defined as a film covering milk fat globules and a mixture of components constituting the membrane. The fat globule membrane is generally composed of lipids in about half of the dry weight, and the lipids are known to include triglycerides, phospholipids, and glycosphingolipids (Miura Akira, FOOD STYLE 21, 2009). And Keenan TW, Applied Science Publishers, 1983, pp89-pp130). It is known that phospholipids include sphingophospholipids such as sphingomyelin and glycerophospholipids such as phosphatidylcholine and phosphatidylethanolamine.
In addition, it is known that a component other than lipid includes a glycoprotein called milk mucin (Mother, Biochim Biophys Acta, 1978).

  The (B) fat globule membrane component used in the present invention preferably has a lipid content of 10% or more, further 20% or more, and further 30% or more from the viewpoint of reducing the sourness derived from carnitine. Further, from the viewpoint of flavor and handling, it is preferably 100% or less, more preferably 90% or less, and further preferably 60% or less. Further, the lipid content in the fat globule membrane component is preferably 10 to 100%, more preferably 20 to 90%, and further preferably 30 to 60%.

  In addition, the (B) fat globule membrane component has a phospholipid content of 5% or more, further 8% or more, further 10% or more, and further 15% or more from the viewpoint of reducing acidity derived from carnitine. From the viewpoint of flavor and handling, it is preferably 100% or less, more preferably 85% or less, further 70% or less, and further preferably 60% or less. The content of phospholipid in the fat globule membrane component is preferably 5 to 100%, more preferably 8 to 90%, further 10 to 70%, and further preferably 15 to 60%.

In addition, (B) the fat globule membrane component preferably contains sphingomyelin as a phospholipid from the viewpoint of reducing the acidity derived from carnitine, and the content of sphingomyelin in the fat globule membrane component is 1% or more Further, it is preferably 2% or more, more preferably 3% or more, and from the viewpoint of flavor and handling, it is preferably 50% or less, more preferably 30% or less, further 25% or less, and further preferably 20% or less. The content of sphingomyelin in the fat globule membrane component is preferably 1 to 50%, more preferably 2 to 30%, further 3 to 25%, and further preferably 3 to 20%.
From the same point, the sphingomyelin content in the total phospholipid of the fat globule membrane component is preferably 3% or more, more preferably 5% or more, further 10% or more, and further preferably 15% or more, and more preferably 50%. Hereinafter, it is preferably 40% or less, further 35% or less, and further preferably 30% or less. The sphingomyelin content in the total phospholipid of the fat globule membrane component is preferably 3 to 50%, more preferably 5 to 40%, further 10 to 35%, and further preferably 15 to 30%.
In the present specification, the content of lipid, phospholipid and sphingomyelin in the fat globule membrane component, and the sphingomyelin content in the total phospholipid of the fat globule membrane component are the mass of the fat globule membrane component with respect to the dried product. A percentage.

Said (B) fat globule membrane | film | coat component can be obtained from well-known methods, such as a centrifugation method and an organic-solvent extraction method, from raw material milk. For example, the method for preparing a fat globule film component described in JP-A-3-47192 can be used. Also, the methods described in Japanese Patent No. 3103218 and Japanese Patent Application Laid-Open No. 2007-89535 can be used. Furthermore, you may use what improved purity by refine | purifying with methods, such as a dialysis, an ammonium sulfate fraction, gel filtration, isoelectric precipitation, ion-exchange chromatography, and a solvent fraction.
In addition, the form of the (B) fat globule membrane component is not particularly limited, and any of liquid, semi-solid (paste, etc.), solid (powder, solid, granule, etc.), etc., at room temperature (15-25 ° C.) These may be used alone or in combination of two or more.

(B) Examples of the raw milk for the fat globule membrane component include milk and goat milk. Of these, milk is preferred because of its rich food experience and low cost. In addition, raw milk includes milk such as raw milk, whole milk powder and processed milk, as well as dairy products. Examples of dairy products include buttermilk, butter oil, buttersarum, whey protein concentrate (WPC) and the like. It is done.
Buttermilk is obtained when producing butter granules from cream obtained by centrifuging milk and the like. Since the buttermilk contains a lot of fat globule membrane components, buttermilk is used as a fat globule membrane component. It may be used as it is. Similarly, since the fat globule film component is contained in the butter serum produced when producing the butter oil, the butter serum may be used as it is as the fat globule film component.

  (B) A commercial item can also be used for a fat globule membrane component. Examples of such commercially available products include Megre Japan Co., Ltd. “BSCP”, Snow Brand Milk Products Co., Ltd. “Milk Ceramide MC-5”, New Zealand Milk Products “Phospholipid Concentrate Series (500, 700)”, and the like.

In the solid composition of the present invention, the content of the (B) fat globule film component is 10 to 50%. (B) By containing 10% or more of the fat globule membrane component, the acidity derived from carnitine can be reduced. On the other hand, when (B) the fat globule membrane component is large, stickiness / adhesion in the mouth is likely to occur at the time of eating, and carnitine has the effect of suppressing the adhesion / attachment of the fat globule membrane component in the mouth. I found. Therefore, by including a predetermined amount of (A) carnitine or a salt thereof, even when (B) the fat globule membrane component is contained at a high concentration of 50% or less, there is less stickiness and adhesion in the mouth at the time of eating can do.
In the solid composition, the content of the (B) fat globule film component is preferably 20% or more from the viewpoint of reducing the sourness derived from carnitine, and the stickiness and adhesion in the mouth at the time of eating 40% or less is preferable from the point that there is little and the aftertaste is good. Moreover, 20-50% is preferable and, as for content of the (B) fat globule membrane | film | coat component in a solid composition, 20-40% is more preferable.

  Further, in the solid composition of the present invention, the content of phospholipid is preferably 1% or more from the viewpoint of reducing the sourness derived from carnitine. 30% or less is preferable from the viewpoint of less sticking and adhesion and good aftertaste. Further, the content of the phospholipid in the solid composition is preferably 1 to 30%.

In the solid composition of the present invention, the sphingomyelin content is preferably 0.3% or more, more preferably 0.5% or more, from the viewpoint of reducing the acidity derived from carnitine, It is preferably 5% or less, more preferably 4% or less from the viewpoint that there is little stickiness / attachment in the mouth at the time of eating and that the aftertaste is good. The sphingomyelin content in the solid composition is preferably 0.3 to 5%, more preferably 0.5 to 4%.
The contents of lipid, phospholipid, and sphingomyelin in the fat globule membrane component or in the solid composition can be measured by an acid decomposition method, a colorimetric method, or a thin layer chromatographic method.

  In the solid composition of the present invention, the mass ratio [(B) / (A)] of the component (A) and the component (B) in the solid composition reduces the acidity derived from carnitine. 0.3 or more is preferable, 0.5 or more is more preferable, and 1 or more is more preferable. Moreover, from the point of stickiness, 8 or less is preferable, 7 or less is more preferable, and 4 or less is still more preferable. The range of the mass ratio is preferably 0.3 to 8, more preferably 0.5 to 7, and still more preferably 1 to 4.

  Further, the solid composition of the present invention includes amino acids such as glutamine and minerals (for example, iron, zinc, chromium, selenium, manganese, molybdenum, copper, iodine, phosphorus, potassium, and the like within a range that does not impair the effects of the present invention. Sodium), vitamins (eg, vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, folic acid and their salts, or esters thereof), sweeteners (eg, simple sugars, oligosaccharides, sugars) Alcohols, synthetic sweeteners), acidulants (for example, succinic acid, adipic acid, glucono delta lactone, acetic acid, fumaric acid), flavoring agents, coloring agents, preservatives and the like may be appropriately blended.

The form of the solid composition of the present invention is not particularly limited as long as it is solid at room temperature (15 to 25 ° C.). For example, capsules, granules, powders, tablets, pills, troches, etc. Is mentioned. Of these, tablets are preferable and chewable tablets are more preferable because they can be taken in a small amount per time and can be taken easily. The solid state means a solid state such as powder, solid, granule and the like.
In order to prepare such a composition of dosage form, an acceptable carrier can be blended as necessary. For example, excipients (eg, lactose, starches, crystalline cellulose, sucrose, mannitol, light anhydrous silicic acid, calcium hydrogen phosphate, etc.), binders (eg, hydroxypropyl methylcellulose, hydroxypropylcellulose, gelatin, pregelatinized starch , Polyvinyl pyrrolidone, polyvinyl alcohol, pullulan, methylcellulose, hydrogenated oil, etc.), disintegrating agents (eg, carmellose, carmellose calcium, croscarmellose sodium, crospovidone, corn starch, low substituted hydroxypropylcellulose, etc.), lubricants (Eg, calcium stearate, magnesium stearate, sucrose fatty acid ester, sodium stearyl fumarate, talc, silicon dioxide, etc.), flavoring agents (eg, stevia etc.), extenders, field Active agents, dispersing agents, buffering agents, preservatives, include carriers such as diluents.

  The shape of the tablet may be a round tablet or various deformed tablets having a surface shape such as an oval, an oval, or a square. Further, the compression molding pressure at the time of tableting is preferably about 10 to 30 Mpa from the viewpoint of maintaining the hardness of the molded product, disintegrating property, and the like.

  In addition, the weight per piece of the solid composition of the present invention is 0.1 to 1.5 g, preferably 0.2 to 1.25 g, and more preferably 0.3 to 1 g in order to improve the feeling of administration and effectiveness. This is preferable.

The solid composition of the present invention is produced according to a conventional method without any particular limitation. For example, it can be produced by compression molding after preparing a mixture of (A) carnitine or a salt thereof, (B) a fat globule membrane component, and an additive added as necessary. For example, when manufacturing a tablet, even if the raw material powder is directly compressed and molded (direct powder compression method), it is granulated using a dry granulation method, a wet granulation method, etc. and then compressed (molded) Compression method). Especially, it is preferable to use a direct powder compression method to make a tablet from the point of simplicity of the process.
When a tablet is produced by direct compression and molding, a conventional tableting machine such as a rotary tableting machine or a single-shot tableting machine can be used.
In addition, when a tablet is formed after granulation by a granulation method, an extrusion granulation method using a cylindrical granulator, a spherical granulator, a pelleter, etc .; a crushing granulation method using a speed mill, a power mill, etc .; A granulated product is produced by dynamic granulation method, stirring granulation method, fluidized bed granulation method, etc., dried and sized, and then the obtained granulated product is compressed by the tableting machine to form tablets. it can.

[Analysis method]
(1) Protein analysis The amount of protein was determined as a nitrogen / protein conversion factor 6.38 using the Kjeldahl method.

(2) Analysis of lipid The amount of lipid was determined by an acid decomposition method. 1 g of a sample was weighed and decomposed with hydrochloric acid, and then diethyl ether and petroleum ether were added and mixed with stirring. The ether mixture layer was taken out and washed with water. After the solvent was distilled off and dried, the amount of lipid was determined by weighing the weight.

(3) Carbohydrate analysis The amount of carbohydrate was determined by excluding the amount of protein, the mass of lipid, the amount of ash, and the amount of water in the sample from the mass of the sample. The amount of ash was determined by a direct ashing method (a sample was ashed at 550 ° C. and weighed), and the amount of water was determined by a normal pressure heating drying method (105 ° C. for 4 hours and weighed).

(4) Analysis of phospholipid A 1 g sample was weighed and homogenized in 150 mL, 100 mL, and 20 mL of a 2: 1 (V / V) mixture of chloroform and methanol, and then 93 mL of 0.88% (W / V) aqueous potassium chloride solution. Was added and left at room temperature overnight. After dehydration filtration and solvent distillation, chloroform was added to make the total volume 50 mL. Of this, 2 mL was collected and the solvent was distilled off, followed by ashing by heat treatment at 550 ° C. for 16 hours. After the ash was dissolved in 5 mL of 6M hydrochloric acid aqueous solution, distilled water was added to make the total amount 50 mL. 3 mL was fractionated, 5 mL of molybdenum blue coloring reagent, 1 mL of 5% (W / V) ascorbic acid aqueous solution and distilled water were added to make the total amount 50 mL, and the absorbance at 710 nm was measured. The amount of phosphorus was determined from a calibration curve using potassium dihydrogen phosphate, and the value obtained by multiplying the amount of phosphorus by 25.4 was taken as the amount of phospholipid.

(5) Analysis of sphingomyelin 1 g of a sample was weighed and homogenized in 150 mL, 100 mL, and 20 mL of a 2: 1 (V / V) mixture of chloroform and methanol, and then 93 mL of 0.88% (W / V) aqueous potassium chloride solution. Was added and left at room temperature overnight. After dehydration filtration and solvent distillation, chloroform was added to make the total volume 50 mL. 10 mL of this was collected and added to a silica cartridge column. The column was washed with 20 mL of chloroform, phospholipid was eluted with 30 mL of methanol, the solvent was distilled off, and the residue was dissolved in 1.88 mL of chloroform. A silica gel thin layer plate was loaded with 20 μL, and tetrahydrofuran: acetone: methanol: water = 50: 20: 40: 8 (V / V) as a one-dimensional developing solvent chloroform: acetone: methanol: acetic acid: water as a two-dimensional developing solvent. = Two-dimensional development was performed using 50: 20: 10: 15: 5 (V / V). The developed thin-layer plate was sprayed with a ditomer reagent, the sphingomyelin spot was scraped off, and 2 mL of a 3% (V / V) nitric acid-containing perchloric acid solution was added, followed by heat treatment at 170 ° C. for 3 hours. After adding 5 mL of distilled water, 5 mL of molybdenum blue coloring reagent, 1 mL of 5% (W / V) ascorbic acid aqueous solution and distilled water were added to make the total amount 50 mL, and the absorbance at 710 nm was measured. The amount of phosphorus was determined from a calibration curve using potassium dihydrogen phosphate, and the value obtained by multiplying the amount of phosphorus by 25.4 was taken as the amount of sphingomyelin.

(6) Analysis of carnitine Carnitine can be analyzed in accordance with the analysis method described in “Analysis of L-carnitine in LC Technical Note 20 supplement / nutrition drink (GL Sciences Inc)”.
Specifically, it can be measured under the following conditions using HPLC.
<HPLC conditions>
Column: Inertsil ODS-3 (5 μm, 150 × 4.6 mm ID)
Eluent: A) CH3OH, B) 20 mM phosphate buffer with 5 mM ion-pairing agent A / B = 30/70, v / v
Flow rate: 1.0 mL / min, column temperature: 40 ° C.
Detection: UV 210nm,
Injection volume: 10 μL

[material]
L-carnitine tartrate: Lonza Japan Co., Ltd. Fat globule membrane component 1: BSCP, Megre Japan Co., Ltd. (moisture 5.1%)
Fat globule membrane component 2: Milk Ceramide MC-5, Snow Brand Milk Products Co., Ltd. (moisture 4.3%)
Aspartame: PAL SWEET DIET, Ajinomoto Healthy Supply Co., Ltd., 100% by mass purity
Maltitol: Amarty MR-100, Mitsubishi Corporation Foodtech Co., Ltd. Powdered cellulose: KC Flock W-400G, Nippon Paper Chemicals Co., Ltd. Sucrose fatty acid ester: Ryoto Sugar Ester B-370F, Mitsubishi Chemical Foods Corporation

The composition of fat globule membrane component 1 was carbohydrate: 10.7%, lipid: 23.8%, protein: 50.9% in terms of dry matter. Moreover, in fat globule membrane component 1, the phospholipid content was 16.6% and the sphingomyelin content was 3.62%.
The composition of fat globule membrane component 2 was 26.1% carbohydrate, 43.3% lipid, and 21.2% protein in terms of dry matter. In fat globule membrane component 2, the phospholipid content was 33.3% and the sphingomyelin content was 8.03%.

[Preparation of chewable tablets]
Examples 1-14 and Comparative Examples 1-9
The raw material having a large particle size was pulverized and passed through 50 mesh, and then each raw material component was mixed with the composition shown in Table 1 or Table 2. Next, using a single-type tableting machine (manufactured by RIKEN), the tablet was tableted at a tablet weight of 500 mg with a ring-shaped punch with a hole diameter of 9.5 mm to obtain a chewable tablet.

Sensory evaluation was performed on the product of the present invention and the comparative product obtained above. Evaluation was performed on all samples first by four professional panels according to the criteria shown below for the acidity derived from carnitine at the time of feeding, the acidity derived from carnitine remaining afterwards, and the oral adhesion, and the highest evaluation The example was “5”, and the example with the lowest evaluation was “1”. Next, the other samples were positioned relative to each other on a 5-step scale between “1” and “5”, and the average value of the four persons was used as a score (rounded off to the nearest 0.5). “Sour taste” is a flavor that is initially felt in the mouth when eating, and “aftertaste” is a flavor that remains in the mouth after eating. In addition, “adhesiveness in the mouth” is a feeling that stickiness occurs during eating and is easily attached to the mouth.
The results are shown in Tables 1 and 2.

〔acidity〕
Example 2 was evaluated as “5” and Comparative Example 7 as “1”. Specifically, the following items were evaluated.
5: Does not feel the sourness derived from carnitine 4: Feels almost no sourness derived from carnitine 3: Feels the acidity derived from carnitine 2: Feels the acidity derived from carnitine strongly 1: Feels the acidity derived from carnitine very strongly

〔aftertaste〕
Example 12 was evaluated as “5” and Comparative Example 7 as “1”. Specifically, the following items were evaluated.
5: No sour taste, very good aftertaste 4: No sour taste, good aftertaste 3: Little sourness, slightly good aftertaste 2: Feeling sour, bad aftertaste 1: Strongly felt sourness The aftertaste is very bad

(Oral adhesion)
Example 4 was evaluated as “5” and Comparative Example 9 as “1”. Specifically, the following items were evaluated.
5: Adhesion to teeth and tongue is very weak 4: Adhesion to teeth and tongue is weak 3: Adhesion to teeth and tongue is slightly strong 2: Adhesion to teeth and tongue is strong 1: Very strong adhesion to teeth and tongue

  As is clear from Tables 1 and 2, the product of the present invention had a good flavor with less sourness derived from carnitine from the time of ingestion to after the ingestion, as compared with the comparative product. Furthermore, the product of the present invention had less stickiness and adhesion in the mouth while eating.

Claims (5)

The following components (A) and (B):
(A) Carnitine or a salt thereof 6 to 35% by mass,
(B) 10-50% by mass of a fat globule film component containing 2-20% by mass of sphingomyelin ,
Containing a solid composition.   The solid composition according to claim 1, wherein the content of the phospholipid in the solid composition is 1% by mass or more.   The solid composition according to claim 1 or 2, wherein the sphingomyelin content in the solid composition is 0.3% by mass or more. Component (A) and the content mass ratio of component (B) [(B) / (A)] is solid composition of any one of claims 1 to 3 is 0.3 to 8.   It is a chewable tablet, The solid composition of any one of Claims 1-4.