Patent Application
20130165514
The present invention relates to an orally administered composition and a dietary composition, having a serum lipid improving effect. More particularly, the present invention relates to an orally administered composition and a dietary composition, comprising a small amount of high-purity docosahexaenoic acid ethyl ester, and used as a pharmaceutical or supplement.
N-3 polyunsaturated fatty acids, such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), characteristically comprised in marine products, have various types of bioactivity, such as an action for improvement in lipid metabolism, and an anti-atherogenic action. Thus, the n-3 polyunsaturated fatty acids are used as a pharmaceutical or supplement.
For example, Japanese Laid-Open Publication No. 2000-95683 (Patent Document 1) describes a skin external preparation comprising a docosahexaenoic acid ester derivative. It describes that the purity of the ester derivative of EPA or DHA is preferably high so as the dose can be small (paragraph 0006).
However, Patent Document 1 relates to a skin external preparation, and not to an orally administered composition or a dietary composition. Furthermore, Patent Document 1 does not disclose any serum lipid improving effect at all.
Japanese Laid-Open Publication No. 2000-44470 (Patent Document 2) describes a hyperlipidemia drug comprising a docosahexaenoic acid ester derivative. It describes that the purity of the docosahexaenoic acid ester derivative is preferably high so as the dose can be small (paragraph 0008),
However, Patent Document 2 does not concern the absorption of ester derivatives of eicosapentaenoic acid or docosahexaenoic acid of low purity; and it does not disclose a serum lipid improving effect.
Patent Document 1; Japanese Laid-Open Publication No. 2000-95683
Patent Document 2: Japanese Laid-Open Publication No. 2000-44470
The present invention is provided for solving the above-mentioned defects, and the purpose of the present invention is to provide an orally administered composition and a dietary composition, having a serum lipid improving effect.
The dietary composition according to the present invention has the following features.
The orally administered composition according to the present invention has the following features.
The orally administered composition according to the Present.. invention described above is preferably a pharmaceutical composition.
When the purity of DHA is low, fatty acids other than DHA will undergo enzymatic degradation, and thereby DHA will be less likely to influence the action of the enzyme. However, the dietary composition or orally administered composition according to the present invention comprises 2.0% by weight or less of a DHA ethyl ester composition that comprises 75% by weight or more of DHA ethyl ester. Thus, high-purity DNA has more opportunities to be influenced by the action of enzyme, which increases the absorption rate of DHA. The dietary composition or orally administered composition according to the present invention has a serum lipid improving effect, an anti-inflammatory effect and a serum triglyceride reducing effect.
Hereinafter, embodiments of the present invention will be described.
The orally administered composition and dietary composition according to the present invention comprises 2.0% by weight or less of a DHA ethyl ester composition comprising high-purity (i.e., comprising 75% by weight or more of) DNA ethyl ester. The orally administered composition according to the present invention is preferably a pharmaceutical composition.
In the DHA ethyl ester composition, the content of the DHA ethyl ester is preferably 80% by weight or more, and more preferably 90% by weight or more.
In addition, the orally administered composition and dietary composition according to the present invention preferably comprise 1.2% by weight or less of the DHA ethyl ester composition comprising high-purity DHA ethyl ester.
A dietary composition comprising a large amount of a DHA ethyl ester composition comprising low purity (i.e., comprising 30% by weight or less) of DHA ethyl ester has a low serum lipid improving effect. The reason for this is assumed that a DHA ethyl ester composition comprising a low purity DHA ethyl ester has a large amount of fatty acid ethyl ester, other than DHA, compared to a DHA ethyl ester composition comprising high-purity DHA ethyl ester, and that is why lipase is not able to react to the DHA ethyl ester (hereinafter, referred to as DHA-EE). Accordingly, in consideration of the absorption efficiency on the premise of the expression of functionality, it is more desirable to ingest a smaller amount of high-purity DHA-EE than to ingest a large amount of low purity DHA-EE.
With regard to the orally administered composition and dietary composition according to the present invention, the effective ingredient, DHA-EE, will be effectively absorbed when the composition comprises a small amount of high-purity DHA-EE, thus avoiding problems with side effects due to other ingredients comprised, and thus allowing the form of the formulation (e.g., soft capsule) per dosage to be small, which makes it easy to administer.
The orally administered composition and dietary Composition according to the present invention are formulated in the form of tablets, capsules, granules, powders or a liquid formulation.
For an orally administered carrier, an ordinarily used agent can be used such as emulsifier, excipient, binder, lubricant, colorant or disintegrator. For example, the excipient includes lactose, sucrose, starch, talc, magnesium stearate, crystalline cellulose, methyl cellulose, carboxy methyl cellulose, glycerin, sodium alginate, gum arabic and the like. The binder includes polyvinyl alcohol, polyvinyl ether, ethyl cellulose, gum arabic, shellac, saccharose and the like. In addition, publicly known colorants and disintegrators can be used. The tablets may be coated using any publicly known method. Furthermore, the liquid formulation may be an aqueous or oily suspension, emulsifier, solution, syrup, elixir and the like. The liquid formulation is formulated using an ordinarily used method.
The particularly preferable administration form of the orally administered composition and dietary composition according to the present invention is capsules and granules.
The orally administered composition and dietary composition according to the present invention is administered, either solely or together with a publicly known agent, to mammals such as humans, cows, horses, dogs, cats, mice, rats and the like. The human dose of the dietary composition according to the present invention is, without any particular limitation, preferably 0.1 to 10 g/day, and more preferably 0.5 to 5 g/day as DHA.
Hereinafter, the present invention will be described in more detail with reference to Examples or the like; however, the present invention will not be limited to those Examples.
With regard to the influence by high-purity and low-purity DHA--EE with different DHA contents on lipid metabolism, rats were used as an experimental animal to examine influence of PEA content on serum, hepatic lipid contents, the liver and the brain.
The compositions of the feed (adjusted with AIN93G as original) are as follows:
The fatty acid composition (% by weight) in the DHA-75EE (high-purity DHA-EE) and the fatty acid composition (% by weight) in the DHA-25EE (low-purity DHA-EE) are shown on Table 1.
As shown in Table 1, the amounts of DHA administered were adjusted to be the same in the experiment. This was because the amounts of DHA would not be the same as the high-purity DHA ethyl ester product unless a large amount (about three times) of the low concentration DHA ethyl ester product would be administered.
The fatty acid compositions (% by weight) in the DHA-7SEE feed and DHA-25EE feed are as shown in Table 2.
Results are shown in
In
Results are shown in
In
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Results are shown in
According to the following method, the amount of respective fatty acids in the livers and brains as well as the amount of DHA-EE excreted with feces were measured.
The livers and brains are homogenized. Next, total lipid is extracted according to the Bligh & Dyer method. Next, as the internal standard, heptadecanoic acid methyl ester ‘17:0) is added. Next, methyl esterification (60° C., 10 minutes) is performed using 0.5M sodium methoxide. Thereafter, a methyl ester layer is extracted using a silica column, and the measurement is conducted using GCMS (QP2010, Shimadzu Corporation).
Conditions for the GCMS are as follows.
For each group, each day's total feces are powderized using a mill (for seven days). Next, total lipid is extracted in accordance with the Bligh & Dyer method. Next, as the internal standard, heptadecanoic acid methyl ester ‘17:0) is added. Next, an ethyl ester layer is extracted using a silica column, and the measurement is conducted using GCMS (QP2010, Shimadzu Corporation).
Conditions for GCMS are the same as described above.
In
The DHA content in the total hepatic lipid was as follows: 2.24 mg/gLiver for DHA75EE; 1.91 mg/gLiver for DHA25EE; and 0.81 mg/gLiver for soybean oil.
As apparent from
In
As apparent from
The amount of DHA ester, which was excreted without being absorbed and without being influenced by actions of enzyme, was measured.
For DHA-25EE, 0.630 mg/day group was excreted. For DHA-75EE, 0.441 mg/day group was excreted. While the same amount of DHA was ingested, more DHA was excreted from the low concentration product.
As apparent from
From the foregoing, the following matters are Understood.
With regard to the serum lipid composition, there was a tendency of reduced total lipid amount in the DHA-EE intake group compared to the control group, and significant reduction in the total cholesterol was observed in the DHA-EE intake group.
No difference was observed in the serum lipid composition between the DHA-25EE group and DHA-75EE group.
With regard to the hepatic lipid composition, reduction in the total lipid and TG amount was observed in the DHA-EE group compared to the control group, and in particular, strong reduction in the TG amount was confirmed in the DHA-25EE group.
With regard to the DHA amount in the total lipid, significant increase was observed in the DHA-75EE group compared to the DHA-25EE group.
With regard to the total brain lipid DHA, there was a tendency of increase in the DHA-EE feed group compared to the control group, but there was no difference between the DHA-25EE group and the DHA-75EE group.
With regard to the DHA-EE amount excreted with feces, significant increase was observed in the DHA-25EE group compared to the DHA-75EE group. It is assumed that since the amount of fatty acid EE in the feed for the DHA-25EE group was greater than that of the DHA-75EE group, DHA-EE was not influenced by the action of lipase and was thus excreted with feces.
From the present invention, in consideration of the absorption efficiency on the premise of the expression of functionality, it is considered to be more desirable to intake a small amount of high purity DHA-EE than to intake a large amount of low purity DHA-EE.
As described above, the present invention is exemplified by the use of its preferred Embodiments. However, it is understood that the scope of the present invention should be interpreted solely based on the claims. Furthermore, it is understood that any patent, any patent application and any references cited in the present specification should be incorporated by reference in the present specification in the same manner as the contents are specifically described therein.
According to the present invention, an orally administered composition and a dietary composition can be provided which are used as a pharmaceutical or supplement that comprises a small amount of high purity docosahexaenoic acid ethyl ester.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2010-195157 | Aug 2010 | JP | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/JP2011/000930 | 2/18/2011 | WO | 00 | 3/7/2013 |
