JP4353746B2 - Bile acid adsorbent - Google Patents

Description

In particular , the present invention relates to a bile acid adsorbent produced from fish clause.

  In recent years, ischemic heart disease, which is considered to be caused by hyperlipidemia due to an increase in blood cholesterol level, is expected to increase in the future due to an increase in lipid intake and caloric intake. On the other hand, research on substances expected to improve hyperlipidemia and elucidation of metabolic pathways are progressing from the viewpoint of preventive medicine, and soy protein, dietary fiber, taurine, lecithin, polyunsaturated fatty acids, etc. are attracting attention. Collecting.

  In addition, such attention has been reported to have similar effects on fish meat, and it has some effects on fish buns that are traditional Japanese fermented foods and contain abundant proteins, such as bonito. Guessed.

Therefore, conventionally, this kind of cholesterol-lowering agent as a proteolytic substance is obtained by adding water and an enzyme such as thermolysin to a fish slice, especially bonito sliced or powdered, and adding this slice or powder. It contains a hydrolyzed fermented product of the fish section. Then, by taking a cholesterol-lowering agent containing this degradation product, the blood cholesterol concentration and the blood triglyceride concentration are lowered (see, for example, Patent Document 1).
JP 2000-264845 A (page 2-3)

As described above, the cholesterol-lowering agent contains a lot of protein for fish buns, especially bonito, and has a physiological activity useful during a manufacturing process such as a long heating process or a fermentation process in the roasting process. Material may have been generated. However, this cholesterol-lowering agent is only known to have an effect of lowering blood cholesterol concentration and blood triglyceride concentration, and whether or not the cholesterol-lowering agent using fishfish as a raw material has the ability to adsorb bile acids. Has the problem of unknown.

This invention is made | formed in view of such a point, and it aims at providing the bile acid adsorption agent which has a bile acid adsorption capability.

The bile acid adsorbent according to claim 1 is produced by a filter residue obtained by filtering a solution containing a fish clause that has been enzymatically decomposed with an endo-exo protease derived from microorganisms, and has a bile acid adsorption ability.

And the bile acid adsorption agent produced | generated by carrying out the enzyme decomposition | disassembly of the fish section with the protease derived from microorganisms has a bile acid adsorption capability while reducing the blood cholesterol concentration and the blood triglyceride concentration.

In addition, by producing a bile acid adsorbent with the filter cake obtained by filtering a solution containing fish clauses that have been enzymatically degraded by proteases derived from microorganisms, the bile acid adsorbent has a bile acid adsorption capacity and blood cholesterol concentration. And the reduction of blood triglyceride concentration is improved.

Bile acid sequestrants of claim 2, in bile acid adsorbent according to claim 1, wherein, those produced by drying the濾渣.

By the濾渣solution of the enzyme degraded smoked fish with protease derived from a microorganism is dried to produce a bile acid adsorbent, since this bile acid adsorbent is solid, the bile acid sequestrants Is easy to handle.

Bile acid sequestrants of claim 3, wherein, in the bile acid adsorbent according to claim 1, in which contains lipid and smoked fish.

And since it has a stronger bile acid adsorption ability by the synergistic effect with the lipid contained in the fish section, the blood cholesterol level can be further reduced.

According to bile acid adsorbent according to claim 1, bile acid adsorbent produced by enzymatic degradation of smoked fish with protease derived from microorganisms, lowering the blood cholesterol level and blood triglyceride levels And has the ability to adsorb bile acids.

In addition, by producing a bile acid adsorbent with the filter cake obtained by filtering a solution containing fish clauses that have been enzymatically degraded by proteases derived from microorganisms, the bile acid adsorbent has a bile acid adsorption capacity and blood cholesterol concentration. Moreover, the fall of the blood triglyceride level can be improved.

According to bile acid adsorbent according to claim 2, by the濾渣solution of the enzyme degraded smoked fish with protease derived from a microorganism is dried to produce a bile acid adsorbent, the bile acid sequestrants Since it can be solid, the bile acid adsorbent can be easily handled.

According to bile acid adsorbent according to claim 3, by the synergistic effect with the lipid, because having a stronger bile acid adsorption capacity can be more reduced blood cholesterol levels.

Next, the Kazumi facilities in the form of bile acid sequestrants of the present invention with reference to FIGS. 1 and 4.

  As shown in FIG. 2, the method for producing fish buns is first thawed with bonito, mackerel, tuna, sardine, horse mackerel, etc., which are frozen and low in fat, as a raw material fish for bunching overnight (step 1). Here, the fish salmon is a fish that is dried and solidified after steaming and steaming the fish.

  Then, the node raw fish thawed in step 1 is cut (step 2). At this time, if the fish body is large, the head and internal organs are removed to drop three pieces, or the three pieces taken down are cut off (step 3). In addition, a small raw material fish can also be used as it is without cutting.

  Then, for example, the raw fish for cutting cut in step 2 is put in water set to 55 ° C. or higher and 95 ° C. or lower and heated for 30 minutes or longer and 2 hours or less to be steamed (step 4).

  Thereafter, the raw fish for node cooking steamed in step 4 is pulled out of hot water and drained to remove the bone (step 5).

  Then, the node raw fish drained in step 5 is dried (step 6). At this time, the raw fish for saving after draining is smoked with smoke for about half a day.

  Next, the smoked raw material fish is smoked in step 6 and the night fire is stopped and steamed (step 7). At this time, the moisture in the raw material fish is diffused and made uniform.

  Here, in order to reduce the moisture of the steamed knot raw material fish to near the limit, step 6 and step 7 are repeated nine times for the knot raw material fish for a total of about ten times (step 8). . This rough bonito is mainly brewed with dashi collecting flowers.

  Then, the surface of the rough knot, which has been roasted in step 6 and fumigated in step 7, is removed 10 times in total to remove tars attached to the surface of the rough knot and to form a bare knot. (Step 9).

  After that, this bare joint is placed in a mold storage cabinet having a temperature of 20 ° C. or more and 40 ° C. or less and a humidity of 70% or more and 90% or less and left for about two weeks, and then the bare joint is spontaneously attached to the bare joint (Step 10) and sun-dry the bare knots after the mold attachment (step 11), and repeat these mold attachments and sun-dryings at least two times within 4 times to obtain fish nodes as dead nodes (step 12). . This further reduces the moisture and fat in this bare joint.

Next, the manufacturing method of the bonito enzyme decomposition product as a bile acid adsorption agent is demonstrated.

  First, as shown in FIG. 1, various fish are boiled, the rough knot obtained in step 8 or the fish knot obtained in step 12 is cut into powder.

  Thereafter, the powder is converted into an atmosphere having a temperature of 10 ° C. or more and 60 ° C. or less and a pH of 3 or more and 11 or less by a protease derived from microorganisms, more specifically, two types of endo-exo proteases. In this case, the enzyme is decomposed for about 1 hour to 20 hours.

  Then, the solution containing the enzymatically decomposed fish knot decomposition product is filtered and separated into an aqueous solution fraction as a filtrate and an insoluble fraction as a filter residue.

In addition, the water-soluble fraction produced | generated by this filtration is used as a bonito enzymatic decomposition extract. Moreover, the insoluble fraction produced | generated by this filtration is made into a bile acid adsorption agent after drying.

Next, examples of the bonito enzyme degradation product as the bile acid adsorbent will be described in detail.

First, every year, elevated blood cholesterol levels, which is a cause of ischemic heart disease increases for the purpose of searching for a substance inhibiting, on rich in proteins, long-term in the roasting dry process heating step and fermentation step In the manufacturing process such as the above, there is a possibility that a useful physiologically active substance has been generated.

  Specifically, water-soluble and insoluble fractions were orally administered to 6-month-old Wister female rats recovered after ovary extraction, and these water-soluble and insoluble fractions were administered to rats. The effect was investigated.

  More specifically, 20% of casein as a protein source was given to 7 rats serving as a control group (Group C). In addition, bonito powder was given in place of casein as a feed for seven rats, which was the first test meal group (DB group).

  Here, the nutritious composition of bonito has a very high protein content of 77.1%, while the fat content is 2.9%, so bonito is a high protein / low fat food. In addition, the constituent amino acids of the protein contained in bonito are leucine, glutamic acid, arginine, lysine, histidine and the like.

  Furthermore, as a feed to 7 rats to be a second test diet group (DBES group), a product obtained by adding dextrin and lyophilizing when the water-soluble fraction was dried was given as a protein source. In addition, as a feed to 7 rats, which was the third test diet group (DBEI group), a dried insoluble fraction was given as a protein source.

  At this time, the feed given to each of the C group, the DB group, the DBES group, and the DBEI group is blended while converting the protein content so that the protein content and the dextrin content are adjusted to be the same.

  Then, for 3 weeks, that is, for 21 days, the rats of group C, DB group, DBES group, and DBEI group were given food and water according to each group by natural intake.

  Thereafter, from 3 days before the end of the test period, the feces of rats of each group were collected, and the bile acid content contained in the feces of these rats was measured.

  Furthermore, the blood of each group of rats was collected on the last day of the test period, and blood lipid concentration, specifically blood cholesterol concentration and blood triglyceride (TG) concentration of these rats were measured.

  As a result, there was no difference between the C group, the DBES group, and the DBEI group regarding feed efficiency, rat feed intake, and weight gain, but there was a tendency that the feed intake increased only in the DB group.

  In addition, as shown in FIG. 4 and Table 2, the blood cholesterol concentration decreased by 24.9% in the DB group, 14.1% in the DBES group, and 33.7% in the DBEI group as compared to the C group. At the same time, the blood triglyceride concentration decreased by 27.8% in the DB group, 15.8% in the DBES group, and 36.7% in the DBEI group compared to the C group.

  Therefore, each of the blood cholesterol concentration and the blood triglyceride concentration tended to decrease significantly in the DB group and the DBEI group as compared to the C group, and also decreased in the DBES group.

  Further, as shown in FIG. 3 and Table 2, the amount of bile acid excretion increased by 370.9% in the DB group, 73.5% in the DBES group, and 471.4% in the DBEI group as compared with the C group. Therefore, bile acid excretion was negatively correlated with results regarding blood lipid levels. Specifically, the amount of bile acid excretion tended to increase in each of the DB group, the DBES group, and the DBEI group as compared to the C group. As a result, it was found that the water-soluble fraction and the insoluble fraction used as feed in the DBES group and the DBEI group have the ability to adsorb bile acids.

  As described above, in one embodiment, the physiological action of the bonito enzyme degradation product produced by enzymatic degradation of bonito with two kinds of endo-exo proteases is to increase cholesterol excretion while increasing the amount of bile acid excretion. It is presumed that the catabolism is promoted and the blood cholesterol concentration and blood triglyceride concentration are reduced.

  In addition, bonito mash powder and bonito enzyme degradation products were confirmed to inhibit blood cholesterol levels and blood triglyceride levels in rats, and also to have an ability to adsorb bile acids by increasing bile acid excretion. It was confirmed that it had.

  In particular, the effects of suppressing the increase in blood cholesterol concentration and blood triglyceride concentration and the ability to adsorb bile acids were the strongest in the rats administered with the insoluble fraction of the kana enzyme digest. At this time, since the amount of bile acid excretion in the rat was increased, the catabolism of cholesterol was promoted, the blood cholesterol concentration was likely to be lowered, and the effect of improving constipation can be expected.

  Here, during the experiment, rat feces were collected, and the amount of bile acid contained in the feces was measured. As a result, a large amount was excreted in any of the DB, DBES, and DBEI groups compared to the C group. . Bile acid is a substance produced from cholesterol, and it can be predicted that bonito and bonito enzyme degradation products increased the amount of bile acid excretion, resulting in a decrease in blood cholesterol concentration.

Therefore, in recent years, there has been an increase in ischemic heart disease, which is thought to be caused by an increase in blood lipid levels due to the westernization of eating habits and an increase in fat intake. Alternatively, taking an insoluble fraction can be expected to help improve or prevent symptoms. At this time, the insoluble fraction of the bonito enzyme-decomposed product must be disposed of as a residue when making the bonito enzyme-degrading extract. However, since this residue can be used, it can be used for effective utilization of resources. Can be connected.

  Furthermore, since the insoluble fraction of the bonito enzyme degradation product is dried when administered to the rat, the insoluble fraction becomes a solid content. Therefore, administration and handling of the insoluble fraction to the rat can be facilitated.

Next, the synergistic effect of the protein in the bile acid adsorbent , which is the bonito enzyme degradation product , and the lipid contained in a small amount (for example, about 18%) in the bile acid adsorbent was tested.

First, the nutrient composition of the bile acid adsorbent , which is a bonito enzyme degradation product containing protein and lipid, was examined.

At this time, since the fat content in the bile acid adsorbent is derived from the raw material, the fat content of the final product varies depending on the raw material. Furthermore, the protein in the bile acid adsorbent is likely to be a resistant protein, which is an indigestible protein that is not easily affected by the action of protease, that is, a digestive enzyme.

Specifically, a 6-month-old Wister female rat recovered after removal of the ovaries was replaced with a control group (group C) that gave casein as a protein source, and 40% of the protein source was replaced with a bile acid adsorbent. First test meal group (DBEI group) giving a fresh feed, and a second test meal group (DBEI-P group) giving a feed in which 40% of the protein source is replaced with a protein lipid complex enzymatically degraded with pepsin And a third test meal group (DBEI-D group) in which 40% of the protein source was replaced with a defatted protein-lipid complex.

  And after raising each of these C groups, DBEI group, DBEI-P group, and DBEI-D group for 4 weeks (28 days), the feed efficiency of each rat of these groups, blood lipid (cholesterol, apoprotein, Triglyceride) concentration and liver lipid (cholesterol, triglyceride) concentration were measured and compared.

  Here, as shown in Table 4, the basis of the feed composition was based on AIN93M, and the protein content and fat content were adjusted to be equal in all groups.

  As a result, as shown in FIG. 5, the blood cholesterol level significantly decreased in the DBEI group and the DBEI-P group as compared to the C group. In particular, in this DBEI group, LDL cholesterol, which causes arterial effects, was reduced as bad cholesterol. In the DBEI-D group, the decrease in blood cholesterol concentration was halved compared to the DBEI group.

As a result, the action of lowering blood cholesterol level is considered to be due to the synergistic effect of the protein and lipid contained in the bile acid adsorbent . Here, as shown in FIG. 6, the bile acid adsorption test showed a synergistic effect on the amount of bile acid adsorption due to the complex state of protein and lipid. Thus, inhibition of intestinal circulation due to excretion by adsorbing a lot of bile acids bile acid adsorbent, is considered to have led to decrease in the blood cholesterol levels.

In addition, since bile acids are made from cholesterol, it is considered that ingesting a bile acid adsorbent that excretes a large amount of bile acids lowers the cholesterol concentration in the body. Thus, conjugates of proteins and lipids, than proteins bonito enzymatic decomposition product in having a higher bile acid adsorption capacity was found to have a strong blood cholesterol levels-lowering effect.

  Subsequently, when the blood apoprotein concentration in each of the C group, the DBEI group, the DBEI-P group, and the DBEI-D group was measured, the concentration of Apo-E in the DBEI group and the DBEI-P group as shown in FIG. It has been found that there is a tendency to decrease.

  In addition, when the blood triglyceride concentrations of these C group, DBEI group, DBEI-P group and DBEI-D group were measured, as shown in FIG. 8, in the DBEI group, DBEI-P group and DBEI-D group, respectively. The blood triglyceride level was significantly reduced.

Furthermore, when the cholesterol concentration in the liver of each of the C group, the DBEI group, the DBEI-P group, and the DBEI-D group was measured, as shown in FIG. 9, the DBEI group, the DBEI-P group, and the DBEI-D group, respectively. Free cholesterol increased, and the amount of cholesterol pooled in the liver increased. This is considered to be caused by an increase in the amount of bile acid excretion caused by the intake of the bile acid adsorbent .

Further, feces were collected for 3 days before the end of each experiment of the C group, DBEI group, DBEI-P group, and DBEI-D group. As a result, as shown in FIGS. 10 and 11, the fecal excretion amount and the bile acid excretion amount in the feces of the DBEI group, the DBEI-P group, and the DBEI-D group are increased as compared to the C group. Moreover, the effect with respect to constipation by a bile acid adsorption agent can also be expected.

Further, as a result of examining the composition of bile acids by gas chromatographic measurement, the fatty acids contained in the bile acid adsorbent were 45% saturated fatty acids, 20% polyunsaturated fatty acids, as shown in Table 5, and Contains 22% monounsaturated fatty acids. Therefore, it was found that a large amount of unsaturated fatty acid having an effect of lowering blood cholesterol level was contained alone.

Here, by combining the protein and lipid in the enzymatic decomposition product of bonito, the lower blood cholesterol level is higher than the action of lowering the blood cholesterol level of some fish proteins and some unsaturated fatty acids. It was found to have an effect. Furthermore, a bile acid adsorbent that is a protein-lipid complex containing protein and lipid can be easily obtained from the bonito enzyme degradation product by producing the bonito enzyme degradation product.

From these results, a decrease in blood cholesterol level can be expected by replacing a part of the protein with a bonito enzyme degradation product. In addition, the insoluble fraction of the obtained enzyme degradation product is highly likely to be an indigestible protein that is not easily degraded by digestive enzymes. Furthermore, the bile acid adsorbent that is a complex of the hardly soluble protein and lipid has a strong bile acid binding ability.

  In each of the above-described embodiments, the bonito enzyme digestion product produced mainly from bonito using bonito as a raw material has been described. Can be used.

It is process drawing which shows until it manufactures the bile acid adsorption agent of one embodiment of this invention from a fish section. It is process drawing which shows until it manufactures a fish clause same as the above. It is a graph which shows the bile acid excretion amount and feces excretion amount in the feces of the rat which administered the bile acid adsorbent which is a proteolytic substance same as the above. It is a graph which shows the blood lipid level of the rat which administered the bile acid adsorption agent which is a proteolytic substance same as the above. (Example 1) It is a graph which shows the blood cholesterol level of the rat which administered the bile acid adsorption agent which is a protein lipid complex containing a proteolytic substance same as the above. (Example 2) It is a graph which shows the bile acid adsorption amount per 1g of bile acid adsorption agent which is a protein lipid complex same as the above. (Example 2) It is a graph which shows the apoprotein density | concentration in the blood of the rat which administered the bile acid adsorption agent which is a protein lipid complex same as the above. (Example 2) It is a graph which shows the blood triglyceride density | concentration of the rat which administered the bile acid adsorption agent which is a protein lipid complex same as the above. (Example 2) It is a graph which shows the cholesterol concentration in the liver of the rat which administered the bile acid adsorption agent which is a protein lipid complex same as the above. (Example 2) It is a graph which shows the excretion amount of the feces of the rat which administered the bile acid adsorption agent which is a protein lipid complex same as the above. (Example 2) It is a graph which shows the bile acid excretion amount in the feces of the rat which administered the bile acid adsorption agent which is a protein lipid complex same as the above. (Example 2)

Claims (3)

Produced by a filter residue obtained by filtering a solution containing fish clauses enzymatically degraded with endo-exo protease derived from microorganisms,
Bile acid adsorbent is characterized by having a bile acid adsorption capacity. The bile acid adsorbent according to claim 1, wherein the adsorbent is produced by drying a residue. Bile acid adsorbent according to claim 1, wherein the characterized in that it contains lipids and smoked fish.

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