WO2008029846A1 - Lipase inhibitor - Google Patents

Abstract

It is intended to provide a fat-soluble lipase inhibitor which contributes to the prevention and treatment of obesity due to the over fat intake and diseases caused by obesity and can be added to any fats and oils. A fat-soluble, widely usable and highly safe lipase inhibitor can be obtained by using as the active ingredient an acyl glycerol having an unsaturated fatty acid, which has an unsaturated bond at the position of an integer Δ that is less than n/2, as the constituting fatty acid, wherein n stands for the number of carbon atoms in the fatty acid and Δ stand for a carbon atom position counted from the carboxyl end.

Description

 Specification

 Lipase inhibitor

 Technical field

 [0001] The present invention relates to a lipase inhibitor and a food containing the same. More specifically, it is safe to digest and absorb lipids in the body, and effectively inhibits the presumptive lipase, which is the key to obesity and hyperlipidemia, and contributes to the prevention and prevention of these diseases. The present invention relates to highly oil-soluble lyase inhibitors. Background art

 [0002] In recent years, the relationship between obesity due to excessive intake of fat from the diet and lifestyle-related diseases such as diabetes, hyperlipidemia, and cardiovascular disease has been taken up and has become a problem. Methods to improve this include: 1. Decrease in fat content in foods, 2. Reduce calorie of fat itself, 3. Replacement with fat substitute, 4. Promote metabolism, 5. Lipase inhibitor, etc. Proposed. With regard to the lipase inhibitor in 5., an attempt has been made to develop a drug that suppresses and prevents obesity by inhibiting the degradation of fat by viable lipase. For example, in Patent Document 1, Red Scenic Sky, Iwabenkei, Savonsou, Bold, Pastia Force, Tormentilla, El Campuri, Tucon Isomatsu, Chuchuashi, Kyak-Luck, Cinnamon, Yam, Sendangsa, Mugigi, Strawberry, Morge, Rose, 柿, Se A lipase inhibitor containing at least one species selected from the group of plants consisting of Hypericum perforatum, Tochu and white tea has been proposed.

 [0003] Further, in Patent Document 2, at least one material strength selected from the group consisting of yucca, ginseng, jasmine tea, yamako, yellow cocoon tea, rooibos tea, soybean germ, ginger and tochu tea, A lipase inhibitor containing an extract as an active ingredient has been proposed. However, the extract is almost water-soluble and cannot be mixed with fats and oils, it can only be taken at the time of eating, is complicated, and the effect of the extract is insufficient. Most of them are in the hall!

[0004] On the other hand, as an oil-soluble substance that can be dissolved in fats and oils, Patent Document 3 proposes to use tetrahydrolipstatin as a gastrointestinal lipase inhibitor. This inhibitor is said to inactivate by covalent bonding directly with the lipase itself, and its effect is quite significant. Although it is more powerful, some have diarrhea symptoms, food safety concerns remain, and oil-soluble lipase inhibitors that are more mildly effective are desired.

[0005] Under these circumstances, Patent Literature 4 recently proposed LUU-type triacylglycerol as a lipase inhibitor that exhibits a mild effect! /, And has a melting point of 30 ° C. There is more

When added to liquid oil, crystals may appear. For applications such as frying oil and dressing, a lipase inhibitor with a lower melting point is desired.

[0006] Patent Document 1: Japanese Patent Application Laid-Open No. 2002-179586

 Patent Document 2: Japanese Patent Laid-Open No. 2002-275077

 Patent Document 3: U.S. Pat.No. 4598089

 Patent Document 4: JP-A-2006-151875

 Disclosure of the invention

 Problems to be solved by the invention

[0007] An object of the present invention is to contribute to prevention and treatment of obesity caused by excessive intake of fat and diseases caused by obesity, and a low melting point oil-soluble river which can be added to any oil and fat. It is to provide a zeta inhibitor. Means for solving the problem

[0008] As a result of intensive studies to solve the above problems, the present inventors have found that an acetylene glycerol containing an unsaturated fatty acid having an unsaturated bond at an integer Δ position of less than n / 2 in the glyceride. We discovered that it inhibits the activity of lipase, and found that the degradation rate of the whole fats and oils was reduced by containing a small amount of this acylglycerin in other fats and oils, thereby completing the present invention. That is, the present invention

 (1) A lipase inhibitor comprising, as an active ingredient, acyl glycerol, an unsaturated fatty acid having an unsaturated bond at an integer Δ position less than n / 2 as a constituent fatty acid. (Where n is the number of carbon atoms in the fatty acid, and Δ is the position of the carbon atom counted from the end of the carboxyl group.)

(2) The lipase inhibitor according to (1), wherein the fatty acid is a monounsaturated fatty acid.

 (3) A lipid absorption inhibitor comprising asyl glycerol as an active ingredient according to (1) or (2).

(4) An anti-obesity agent comprising the acyl glycerol described in (1) or (2) as an active ingredient.

(5) A liver lipid reducing agent comprising the acyl glycerol as described in (1) or (2) as an active ingredient. ½) A hyperlipidemia ameliorating agent comprising the acyl glycerol described in (1) or (2) as an active ingredient.

 (7) A food containing the agent according to any one of (1) to (6).

 (8) A medicament comprising the agent according to any one of (1) to (6).

 It is.

 The invention's effect

 [0009] In the present invention, acyl glycerol, which comprises an unsaturated fatty acid having an unsaturated bond at the Δ position of an integer less than n / 2 as a constituent fatty acid, strongly inhibits lipase activity and has a low melting point. It is oil-soluble and can be added to all types of fats and oils. It is effective in preventing and treating obesity caused by excessive intake of fat and diseases caused by obesity.

 BEST MODE FOR CARRYING OUT THE INVENTION

[0010] Acylglycerol, which is an oil-soluble substance that delays hydrolysis by lipase in the present invention, contains an unsaturated fatty acid residue having an unsaturated bond at the Δ position of an integer less than n / 2 in the glyceride. It is acyl glycerol containing more than residues. “N” indicates the number of carbon atoms constituting the fatty acid, “Δ” indicates the position of the carbon atom counted from the end of the carboxyl group of the fatty acid, and Δ is an integer less than n / 2. For example, in the case of a fatty acid having 18 carbon atoms (n), it means that there is an unsaturated bond between carbon atoms at any of the 2nd to 8th carbon atoms from the end of the carboxyl group. At this time, the first carbon atom is the carbon atom of the carboxyl group, and since it does not participate in the unsaturated bond between carbon atoms, it is excluded from the target power.

[0011] Examples of unsaturated fatty acids having an unsaturated bond at an integer Δ position of less than n / 2 include cis-4-decenoic acid having 10 carbon atoms (obucsylic acid: η10 Δ 4), cis-4-dodecenoic acid having 12 carbon atoms (lindelic acid: η12 Δ 4), cis-4-tetradecenoic acid having 14 carbon atoms (zudic acid: η14 Δ 4), cis-5-tetradecenoic acid (Phyzeteric acid: η14 Δ5), cis-6-hexadecenoic acid with 16 carbon atoms (η16 Δ6), cis-6-octadecenoic acid with 18 carbon atoms (petroseric acid: η18 Δ6), etc. Is done. In addition, sorbic acid, decadienoic acid, hiragoic acid, γ-linolenic acid, eicosatrienoic acid, docosatrienoic acid, hexadecatetraenoic acid, arachidonic acid, eicosapentaenoic acid, and the like can also be used. Of these, petroceric acid is most preferable from the viewpoint of the supply amount that monounsaturated fatty acid is functionally preferred. Also these fatty acids The melting point of acylglycol containing fatty acids and fatty acids is generally less than 30 ° C, except when other long-chain saturated fatty acids coexist, and is highly versatile and easy to use.

[0012] The acyl glycerol containing these fatty acids may exist in any of mono-, di-, and tri-forms, but considering the point that crystallization is minimized and the lipase is easily recognized as a substrate. The triacylglycerol form is preferred. The unsaturated fatty acid having an unsaturated bond at an integer Δ position less than n / 2 needs to be contained in one or more residues in the glyceride, and preferably in two or more residues.

[0013] The acyl glycerol containing an unsaturated fatty acid having an unsaturated bond at the Δ position of an integer less than n / 2, which is an active ingredient of the lipase inhibitor of the present invention, is various animals, plants, fishes. Oils and fats derived from vegetable oils such as kumoji seed oil, tuna oil, parsley seed oil, sardine seed oil, nakamado oil, red arabic seed oil, purple seed oil, evening primrose oil, borage oil, sardine oil, Animal fats such as shark liver oil and herring oil can be used as raw materials. These acyl glycerols can be fractionated, distilled or concentrated as necessary, and can be transesterified with other animal and plant oils by known methods.

[0014] The acyl glycerol containing an unsaturated fatty acid having an unsaturated bond at an integer Δ position of less than n / 2 may be used as it is as a lipase inhibitor, and optionally, to other base fats and oils. You may blend and use. These oils can be used in place of conventional processing oils. In addition, there is no limitation if the base fat is edible animal or vegetable fat.

 The lipase inhibitor of the present invention preferably has a mild inhibitory effect on the relaxation and delay of hydrolysis of the ingested oil and fat. Specifically, about 10 to 30% of the ingested oil and fat is preferable. Ideally, it should be in a state where about 20% is hardly decomposed.

[0016] In order to achieve this, the lipase inhibitor of the present invention is an acyl oil containing an unsaturated fatty acid having an unsaturated bond at an Δ position of an integer less than n / 2, and ingested oil and fat. By using more than 1% by weight, preferably more than 3% by weight, it is possible to reduce or delay the hydrolysis by lipase. If the amount of acylglyceride containing unsaturated fatty acid having an unsaturated bond at the Δ position of an integer less than n / 2 is less than the ingested fat and oil, the lipase inhibitory effect is weakened. Also, an unsaturated bond is formed at the position of an integer Δ less than n / 2. As for the acyl glycerol containing the unsaturated fatty acid having a combination, there is almost no effect due to the large amount used. However, since it is difficult to replace fats and oils in all foods, it is usually used at 30% by weight or less, preferably 15% by weight or less of the fats and oils to be ingested.

[0017] The lipase inhibitor of the present invention can be used as a lipid absorption inhibitor, an anti-obesity agent, a liver lipid reducing agent, and a hyperlipidemia improving agent. These can be used widely in foods that usually contain fats and oils. For example, emulsified foods such as cream, margarine, mayonnaise, dressing, dairy products, processed foods such as confectionery represented by chocolate, bread, ham, sausage, marine processed foods such as power, maboko, chikuwa, etc. It can be added without sacrificing flavor and texture.

 [0018] Alternatively, the lipase inhibitor, lipid absorption inhibitor, anti-obesity agent, hepatic lipid reducing agent, and hyperlipidemia ameliorating agent of the present invention can also be used as pharmaceuticals. The administration method of the medicine containing these may be either oral administration or parenteral administration. In administration, the active ingredient can be mixed with a solid or liquid pharmaceutical carrier suitable for administration methods such as oral administration and rectal administration, and administered in the form of a preparation.

 Example

 [0019] Ability to describe the present invention in more detail below with reference to examples of the present invention The spirit of the present invention is not limited to the following examples. In the examples, “%” and “part” mean weight standards.

 [0020] Example 1

Commercial reagent triperothelin (18 carbon atoms, Δ 6; NU-CHEK-PREP, Inc., purity 9 9% or more, melting point 22 ° C) and commercial reagent triolein (carbon atoms 18, Δ 9 , Manufactured by EXTRASYMTH ESE SA, purity 99% or more) and mixed at the ratio of 100/0, 95/5, 90/10, 80/20, 60/40, 0/100 respectively The lipase activity was measured. 80 mg of each fat and oil was sampled, phosphatidylcholine (manufactured by Sigma) 80 mg, sodium taurocholate (manufactured by Wako Pure Chemical Industries, Ltd.) 5 mg, 0.1 M TES buffer 9 ml (pH 7) containing 0.1 M NaCl, A substrate emulsified with a sonic oscillator for 1 minute was used. Collect substrate 3001, add 15 1 (15U) of porcine spleen lipase (manufactured by Sigma), react at 37 ° C for 1 hour, and then extract 3 ml of extraction solvent (black mouth form / heptane / methanol = 49 parts / 49 parts / 2 parts mixed) After stirring well, centrifuge for 5 minutes at 2500 rpm, remove the upper layer, and dissolve copper reagent (2.98 g of triethanolamine, 2.42 g of copper nitrate, 0.48 g of NaOH in 200 ml of water) in the lower layer. Lml of 66g NaCl) was added, stirred for 10 minutes, centrifuged at 2,500rpm for 10 minutes, 1.5ml of the upper layer was collected, and coloring reagent (0.2g of bathocuproin, butylhydroxylazole O.lg) was added. 1.5 ml was added and the free fatty acid was quantified by absorbance at OD480.

 〇 Table 1 Lipase activity Oil / fat mixture ratio (wt%) 脬 Lipase activity 卜 ■ ”of tripetroceric acid and oleic acid mixed system

 (Ai mol / ml) (relative%)

 Ί 00 0 0.40 Ί 00.0

 95 5 0.32 80.0

90 1 0 0.25 62.5

80 20 0.21 52.5

60 40 0.1 8 45.0

 0 1 00 0.1 1 27.5

 [0022] As shown in Table 1, compared with triolein, tripetroserine has lipase activity.

 More than 70% was found to be inhibited. The inhibition proceeded in a dose-dependent manner.

[0023] ○ Test example (digestion and absorption test in rats)

The control soybean oil group (Comparative Zone 1) and the fats and oils extracted from parsley seeds (petrocellinic acid content 75% of acylglycol) were large so that the petroleum oil containing petrothelic acid was 10% in the mixed oil. Absorption and absorption test in rats using 3 groups of fat and oil group (test group) substituted with bean oil and group (comparative group 2) where the same amount of parsley seed oil was replaced with hyoleic castor oil Went. Rats were purchased from 5-week-old SD male rats, preliminarily raised for 1 week, divided into groups, and the diet composition was 10 for each group of 5 animals in the mixed diet shown in Table 2 with some modifications to the AIN-93G composition. The animals were reared for 6 days and dissected after 6 hours of fasting. Body weight change, feed efficiency, blood fat content, wrinkle Peripheral fat mass, renal circumference

[0024] 〇 Table 2 Diet composition (wt%) Comparative plot 1 Test plot Comparative plot 2

 Soybean oil 30 26.8 26.8

 Parsley seed oil ― 3.2 ―

 High-grade Latex Castor Oil ― ― 3.2

 Casein 20 20 20

 Sucros6 10 10 10

 β-corn starch 16.75 16.75 16.75

 a -corn starch Ί3.2 Ί3.2 Ί3.2

 Les Cystine 0.3 0.3 0.3

 cellulose powder 5.0 5.0 5.0

 Min.mix (AIN-93G) 3.5 3.5 3.5

 Vitamin mix (AIN-93G) Ί.Ο Ί.0 Ί.0

 Choline bitartrate 0.25 0.25 0.25

 Total weight 100.0 100.0 100.0

 [0025] As a result of the 10-day digestion and absorption test in rats, the body weight and feed efficiency were almost the same in the test group to which the petroceric acid-containing acylglycol was added as compared to the comparative group 1, but the neutrality in the blood The amount of fat decreased by more than 50%, and the amount of internal fat and liver lipid also decreased by more than 10%. Compared to this, it was found that these effects were low in Comparative Zone 2 where the oil was replaced with high-rate castor oil. These results are summarized in Table 3.

[0026] 〇 Table 3 Rearing results Comparison group 1 δ-type experiment 11 Comparison group 2 Initial weight (g) 211 210 211 Final weight (g) 307 291 305 Feed efficiency (%) 0.471 0.442 0.468 Visceral fat (g) 19.8 16.6 19.2 Liver weight (g) 15.9 12.7 15.5 Liver lipid level (mg / g Liver) 29.2 23.0 27.9 Serum TG level (mg / dl) 286 120 253 Industrial applicability

 According to the present invention, lipase inhibition is effective for the prevention and treatment of obesity due to excessive intake of fat and obesity due to obesity due to the lipase activity that is slowly inhibited and oil-soluble and can be added to any edible oil. It became possible to obtain an agent and an oil and fat composition containing the agent.

Claims

The scope of the claims  [1] A lipase inhibitor comprising, as an active ingredient, acyl glycerol, an unsaturated fatty acid having an unsaturated bond at an integer Δ position less than n / 2 as a constituent fatty acid. (Where n is the number of carbon atoms in the fatty acid, and Δ is the position of the carbon atom counted from the end of the carboxyl group.) [2] The lipase inhibitor according to [1], wherein the fatty acid is a monounsaturated fatty acid. [3] A lipid absorption inhibitor comprising the acyl glycerol according to claim 1 or 2 as an active ingredient.  [4] An anti-obesity agent containing the acyl glycerol according to claim 1 or 2 as an active ingredient.  [5] A liver lipid-reducing agent comprising the acyl glycerol according to claim 1 or 2 as an active ingredient.  [6] A hyperlipidemia ameliorating agent comprising the acyl glycerol according to claim 1 or 2 as an active ingredient.  [7] A food containing the agent according to any one of claims 1 to 6. [8] A medicament comprising the agent according to any one of claims 1 to 6.