TW200401645A - Enteric fat absorption inhibitors containing plant extract and foods containing the same - Google Patents

Abstract

Enteric fat absorption inhibitors, which contain a plant-origin and safe extract obtained by extracting sage and/or rosemary. These enteric fat absorption inhibitors can regulate the action of pancreatic lipase and thus inhibit the absorption of fat into the body even in a small dose. Therefore, obesity, hyperlipemia, etc. can be efficaciously treated or prevented by adding these enteric fat absorption inhibitors to various foods which can be easily taken in our everyday life.

Description

200401645 (1) Description of the invention: [Technical field to which the invention belongs 3 Field of the invention The present invention relates to a fat absorption inhibitor effective for the treatment or prevention of obesity and hyperlipidemia 5, which does not require the subject's gastric juice secretion to be inhibited in advance. The duodenum in the effective part exerts an inhibitory effect on pancreatic fat and an inhibitory effect on fat absorption. I: Prior art 3 Background of the invention 10 Obesity is considered to be caused by abnormal living habits such as insufficient exercise or overeating, and genetic factors are caused by a reduction in basal metabolism; in addition, in recent years, it has also begun to understand the secretion of fat cells Leptine's appetite control is closely related to obesity. Because obesity can be a major cause of lifestyle disorders such as branuria or cardiovascular disease (arteriosclerosis, stroke), it needs to be treated early. Explanation $ > 〇 萦 f 朿 can be described as L suppresses appetite, 2. inhibits the absorption of nutrients (especially lipid threat), 3. increases the generation of heat energy, 4 changes the metabolism of lipids or proteins, and 5. regulates The central body weight system and the like are being extensively studied. Among them, the obesity treatment drugs classified in [2] and 2 are only clinically applicable, but because there are many side effects and safety has not been established, there are few drugs that can be used for a long time in the world. In Japan, currently only the food-cooking coffee of age 1 is recognized. In contrast, those who have developed the function of the front 2 in addition to the therapeutic drug have been developed. 'For example, the food contains ingredients with the functions of the 2 above, The most 20 200401645 has recently attracted much attention with the increase in obese people or increased awareness of weight loss. It is different from the relationship that a therapeutic drug can be used without a prescription, and side effects are required as much as possible, but because it is easy to get started, it has the advantage of being ingestable in daily life. Those who have the above-mentioned two functions can include health foods such as those from crab / V and chitosan and chitosan, or fish cartilage < chondroitin sulfate. All of them have pancreatic lipopaid inhibitory activity, so the fat that is ingested is not decomposed by enzymes and water, and as a result, fat absorbed from the intestine can be suppressed. Problems to be Solved by the Invention Since these ingredients have a weak ability to inhibit fat absorption, they have the disadvantage that they must be taken in large amounts in daily life. SUMMARY OF THE INVENTION 3 Method for solving the problem The present inventors have repeatedly studied the results of fat-suppressing inhibitors of fats that are plant-safe and can inhibit fat pancreatic lipase from a small amount of intake. It was found that the extract taken from the leaves of sage or rosemary showed excellent pancreatic lipase inhibitory effect in vitro. Based on this knowledge, the results of the fat absorption inhibitory effect of the aforementioned extracts were tested in vivo in mice administered with olive oil. Although oral administration showed almost no fat absorption inhibitory effect, it was directly administered to mice. After duodenum, or the use of gastric secretion inhibitors to inhibit the gastric secretion of mice in advance, it is clear that there is a fat absorption inhibition effect. However, direct administration to the duodenum in daily life is not easy to implement. On the other hand, the use of gastric secretion inhibitors or antacids and acid neutralization

6 200401645, etc., it also affects nutrients other than fat digestion, and may cause side effects, so it is not suitable for daily use in daily diet. On the other hand, the present inventors have confirmed that by subjecting a fat absorption inhibitor provided with an extract of sage or rosemary to an enteric treatment, the subject's 5 gastric juices will not change and the extract will be changed. Reach the duodenum. Thus, the present invention provides an enteric fat absorption inhibitor containing an extract of sage and / or rosemary. The enteric fat absorption inhibitor 'of the present invention may be in the form of a tablet, granule, powder or capsule. Furthermore, the present invention also provides a food containing the aforementioned enteric fat absorption inhibitor. tApplication mode j Embodiment of the invention Extract The enteric fat absorption inhibitor of the present invention contains an extract of sage and / or rosemary. The sage extract used in the present invention is obtained by extracting fresh or dried leaves of sage, namely Persaceae plant rosemary (Salv 丨 a officinalis), with water or an appropriate organic solvent, or a combination solution thereof. After concentrating. Sage is widely known as a spice for meat dishes, and is used in European folk 20 to stop diarrhea, treat gastritis, enteritis and so on. In addition, it is now formulated in EnterosanolR, so it is considered to be very safe for the digestive organs. The extraction solvent used for the extraction can be mentioned lower alcohols such as ethanol, methanol, et al., And other special mixtures with water. Among them, since 7 200401645 is for human ingestion, it is preferable to use ethanol alone or a mixture with water (so-called water-containing ethanol). In particular, it is most effective to use an ethanol / water mixture having an ethanol to water ratio of 30% or more, or 100% ethanol. Therefore, in the examples described later, although 100% methanol is used when extracting from leaf extract 5 of sage and / or rosemary, it is a matter of course that 30% or more of ethanol / water mixture or 100% ethanol can be used instead. In fact, in vitro and in vivo tests using extracts of ethanol / water mixtures containing 30% or more of ethanol above 300% and the effective components isolated from them have been confirmed to be compatible with The 1000/0 methanol extract also exhibited excellent fat absorption inhibitory effect and pancreatic lipase inhibitory activity. When sage is subjected to immersion extraction at normal temperature (15 ~ 30 ° c), the volatile oil (Thyjone) or essential oil (α penene), eucalyptus brain ( m-cine〇ie), Borneol (Borne〇1)), are mixed in a large amount in the extract, and will stimulate the intestinal mucosa and have adverse effects on the living body. Therefore, it is better to heat the extract at 70 ~ 100 ° C. The amount of solvent or extraction time is because the plant body is a leaf. For lgm plants, a solvent of 5 to 20 nil is added, and it is preferable to extract at the above temperature for 1 to 3 hours. Furthermore, the extraction method can also use supercritical carbon dioxide extraction, and compared with the aforementioned solvent extraction of 20, it can produce extracts with a large amount of effective ingredients and high safety. The extraction method may be a method described in a literature (for example, Bauman D. et al., Acta. Alimentaria: Vol. 28, No. 1, pp. 15-28, 1999). Specifically, the leaves of the sage are first put into an extraction tank, under a pressure of 10 to 25 MPa (preferably 25 MPa) and a temperature of 40 to 100. [: (Preferably 100 ^), extraction is performed for 20 to _ minutes (preferably 20 to ⑼ minutes). Under these conditions, the essential oils that contain harmful components of Platycladus orientalis are almost extracted by spears and their residues at a pressure of 35 MPa or higher (47.5 MPa is preferred), and the temperature is 40 ~ loot (⑽t is preferred) Under the conditions of extraction of trowel bell (20 to 60 minutes as 隹), containing the active ingredient terpene diterpene (Diterpene) fractions, a high content of extracts can be obtained. At this time, in order to improve the extraction rate, the village needs to fill the g_ (E_iner) as needed. In the present invention, an extract obtained from Rosemary, which is a Perillaceae plant (Rosmarinus officinalis Linne (Labiatae)), can also be used. Rosemary is used as a cooking spice in the same way as sage, but it is also used as a wind repellent or stomach-enhancing agent because it contains Rosemary Hine, an essential oil. It is also used for traditional applications such as preservatives or antioxidants. Extraction can be performed in the same manner as described above with respect to sage. That is, 5 to 20 ml of the solvent is added to fresh or dried leaves of lgm rosemary, and extraction at the above temperature is preferably 1 to 3 hours. «Sage or rosemary extract used in this month includes water or solvent extract and supercritical carbon dioxide extract obtained according to the above steps, and the aforementioned extract is dried under reduced pressure known in the art or Spray drying and other methods are used to extract the solid content of the solvent, and the product obtained by separation and purification. The present invention relates to good separation and purification steps and conditions, which are described in detail in the first and third embodiments described below, such as combined silica gel tube chromatography, reverse phase ODS column chromatography, and fractionation.] 9? 1 ^, etc., under appropriate conditions, 200401645, although it is possible to use eluant (such as water, or hexane, acetic acid acetate, aerosol, ethanol, n-butanol and other organic solvents, or mixtures thereof) ), But not limited to these substances. The fractions obtained by separating and purifying the sage or rosemary extracts include several types of dimers and triterpenes. Among them, the diterpenoid orallynic acid represented by the fly type is the most effective ingredient for the purpose of inhibiting the lipid absorption of the present invention, and will be described below. [Chemical 2]

10 If sage is, for example, sage, it will be described in detail in the first and third embodiments described later that methanol extract can be prepared from sage and separated by silica gel chromatography. The obtained ethyl acetate fractions were prepared by separating and purifying hplc by ODS column chromatography. (Fat Absorption Inhibitor) 15 The present invention is an extract of sage or rosemary which has a function of inhibiting pancreatic lipase and exhibits fat absorption inhibiting effect, especially a fat absorption inhibitor with an extract containing sage acid And are enteric-coated capsules, granules, or lozenges (also including sustained-acting tablets (Repetab)). In addition to using the aforementioned extract 20 in the contents of the capsules, the traditional method of making soft capsules can also be used to make the capsules. Such a manufacturing method may be a method of manufacturing a capsule preparation using a capsule film sheet and sealing the contents with a rotary filler, or a method of manufacturing a seamless capsule by a dripping method. In addition, the granules are suitable for various conventional wet and dry granulation methods, and can be molded together with appropriate binders and excipients. Lozenges are granules containing 5 sage extracts prepared as described above, or the sage extract itself, with appropriate binders, excipients, decomposing agents, and lubricants as required. , Using the traditional method of ingot manufacturing. In order to make the fat absorption inhibitor of the present invention enteric, the surface of the fat absorption inhibitor is coated with an enteric coating agent. Alternatively, when the fat absorption inhibitor is a capsule or a tablet, an enteric agent may be added to the composition of the lipid absorption inhibitor, or an enteric agent may be used in a film material such as gelatin or starch. The capsule was filled with a fat absorption inhibitor composition. Examples of the enteric coating agent include methacrylic acid copolymer, hydroxypropyl methyl 15 cellulose phthalate, hydroxypropyl methyl cellulose acetate succinate, carboxymethyl cellulose, and cellulose acetate phthalate Such as cellulose, shellac and so on. But it is not limited to these. Such an insoluble coating agent can be coated on the surface of a fat absorption inhibitor according to a conventional method. On the other hand, examples of the aforementioned enteric agents include gums, alginic acid, cellulose 20 (e.g., carboxymethyl cellulose, cellulose acetate phthalate, etc.), methacrylic acid copolymers, and the like. The intake of the fat absorption inhibitor of the present invention is preferably taken before or during a meal. For the extract contained in the fat absorption inhibitor of the present invention, for example, when using water and / or solvent extracts of sage or rosemary, it is usually 10 times to 500 mg for adults once, and 20 to 200. mg ,! Take 3 times a day with meals. The extract in the present invention may be separated and purified by using the aforementioned water and / or solvent extract. The intake amount at this time is usually 丨 ~ 100rng for adults, and it is better to take 5 ~ 20mg, 3 times a day with meals. 5 Of course, the aforementioned intake should be appropriately increased or decreased depending on age or intake of fat components. The amount of the fat absorption inhibitor of the present invention may be used in an amount of about 1/20 to 1/40 when compared with the conventional natural shellfish such as chitin and chitin. (Foods containing enteric fat absorption inhibitors) 10. The enteric fat absorption inhibitors of the present invention can be added to ordinary foods in daily life, and particularly mixed with foods containing fat components such as processed meat or oils Medium is better. Therefore, the present invention also provides such a food containing an intestinal < gluten fat absorption inhibitor. Since the food of the present invention can be ingested daily, its effect of suppressing fat absorption is 15%, so it can be used as a useful health food. In such food and drink, the amount of the aforementioned extracts may be added within a range that does not impair the original taste of the food, depending on the type of target food. For general foods, it may be added in a range of 0.1 to 10% by weight. . [Embodiment] 20 Next, the present invention is described by way of examples, but the present invention is not limited to these embodiments. ▲ Dried sage from Albania. The leaf ⑽g) After fine cutting, add random methanol and extract at 70 ° C for 30 minutes. After filtration, the residue was further added with methanol, and then extracted after 200401645 for 3 hours. The filtrate obtained from the two extractions was collected, concentrated under reduced pressure, and dried to obtain a methanol extract with a yield of 30..4%. A part (9 ig) of the obtained methanol extract was dispersed in water, and ethyl acetate (1.8 L) was used for 3 partition operations. The obtained ethyl acetate fraction was concentrated under reduced pressure, and dried to obtain ethyl acetate (48.4 g, yield: 15.8%). Next, n-butanol (L8L) was added to the separated aqueous layer, and the same operation as in the case of obtaining the ethyl acetate layer was carried out to obtain a n-butanol fraction (10.3 g, yield: 3.4%). The remaining aqueous layer was concentrated under reduced pressure and freeze-dried to obtain a water 10 fraction (33.4 g, yield: 1 ·· 0%). Pancreas lipase inhibition test of sage sage methanol extract and various solvent fractions The lipase inhibition test was performed using porcine pancreatic lipase (Sigma) and a lipase kit (Dai Nihon Pharmaceutical). First, the rat 15 sage grass methanol extract and various solvent fractions (hereinafter collectively referred to as extracts) obtained in the first example were prepared by diluting each of them into a dilution series of 20 times the final concentration. For each extract, add a coloring solution (390 // L), the aforementioned dilution series (25 a L each) to the test tube, and prepare 40 # g / mL of lipase with the dilution solution attached to the kit. (25 // L) and esterase inhibitor (10 / z L), and the reaction was performed at 30 ° C for 30 minutes. After the reaction stop solution (1 mL) was added, the absorbance at 405 nm was measured, and the enzyme inhibition rate was calculated according to the following formula. [Number 1] Inhibition rate (%) = ι- sample ^ '^' sample blank) — χ 1 〇200200401645 In the above formula, ^ 〇.D. SamPle is the absorbance of various concentrations of extracts after enzyme treatment. ODsample blank is the absorbance of extracts with various concentrations without enzymes; ODeontrol is the absorbance of extracts without enzymes and treated with enzymes; 〇.D._trc > l blank is the absorbance without extracts and enzymes 5 Absorbance. The 50% pancreatic lipase activity inhibitory concentration (IG5G) of the extract was plotted on the horizontal axis of the graph as the extract concentration 'and plotted on the vertical axis to determine the inhibitory rate. The experimental results are shown in Figure 1. Based on the results of Fig. 1, it was found that the sage methanol extract had a lipase inhibitory activity (IG50: 94 // g / mL). In addition, it is estimated that the active ingredient of the fat beer inhibitory activity of the sage alcohol extract is mainly contained in the ethyl acetate fraction (IG5G ·· 64 / zg / tnL) separated from it. Example 3f: After the rat is extracted with alcohol, the main ingredient is separated. In the second example, the ethyl acetate 15 fractions showing lipase inhibitory activity were separated and purified. The aforementioned ethyl acetate fraction (20.lg) was carried out according to a silica gel column chromatography (600 g), and was burned: ethyl acetate:]) 4 (3: 1)-· > (1: 1) ~ Gas simulation: methanol (10: 1) -methanol was eluted in order to obtain fraction 1 (4.22 g), fraction 2 (4.25 g), fraction 3 (3.3 g) and fraction 4 (7.86 g). Regarding these 20 aliquots, the pancreatic lipase inhibitory rate measured at 100 # g / mL by the method of the second example was 43.4, 96.0, 92.6, and 67.7%, respectively. Fractions 2 and 3 with high pancreatic lipase inhibitory rate were respectively subjected to reversed-phase OD tube chromatography [220g, water: methanol (4: 6) — (3 :: 8)-> (1: 9 ) ~ Chloroform: methanol: water (6: 4: U] and purification in the order of HPLC [〇DS, solvent 75% methyl 14 200401645 alcohol]. The separated components were analyzed by towel and 13C NMR analysis, quality Spectral method 'Infrared spectrophotometry and ultraviolet-visible spectrophotometry were confirmed to be Carnosol (represented by ⑴ in the following formula, 5 yield from plants: 0 · 24 ° / 〇), rat Oxalic acid (the one represented by the following formula (2), the yield from the plant body: 0.29%), 7-methoxy rosemarnol (7-methoxy rosemarnol) (the one represented by the following formula (3), from Yield of the plant body: 0.08%), Royleanonic acid (represented by the following formula (4), yield from the plant body: 0.011%), rosemaryol (Rosemarnol) (in the following formula (5) Table 10 shows the yield from the plant body: 0.006%), and isorosemarnol (Isorosemarnol) (the one represented by the following formula (6), the yield from the plant body: 0.027 < 3 / 〇) and oleanolic acid (〇len n〇lic acid) (represented by ⑺ in the following formula, yield from plants: 0.47%).

The fourth step is to extract the lipase of the young components of the celestial medicinal extract and inhibit the separated components obtained in the third example. The lipase inhibitory activity was checked by the method of the second example. The results are shown in FIG. 2 . 15 200401645 As shown in Figure 2, the double-cell sapanol (1) shows the strongest lipase inhibitory activity (IG50: 4 // g / inL); sagebate (2), 7-methoxy Rosemary alcohol (3) and Royleanonic acid (4) are also believed to have inhibitory activities (IG%: 14, 33 and 50 // g / mL). In addition, it is also known that the oleanolate of triterpene also has a weak inhibitory effect on lipids. Furthermore, rosemary alcohol (5) and iso rosemyl alcohol (6) may be excessively decomposed due to oxidation, and lipase inhibitory activity cannot be measured. Poor-g Example Extracts of Stylosanthes serrata and ―Epilipids and Inhibition of Each Isolated Component

The sage methanol extract obtained in the first example and the ingredients obtained in the third example (herein, it is about sage alcohol (1), sage acid (2), 7-formamyl rosemary alcohol (3 ) And oleanolic acid (7) four kinds of fat absorption inhibitory effects, each administered orally to olive oil-loaded mice or duodenum, respectively, to measure and evaluate changes in triglyceride concentration in blood . 15 20 (orally administered) methanol extract or separate components, and 5% acacia gum suspended in water to prepare a suspension. A male Y-series immortal mouse on a fasting period of 20 to 24 hours was orally administered at a ratio of about 1 kg of body weight to Sml of the aqueous suspension. For example, after 5 minutes, the ratio of mkg body weight to olive oil 5nd is administered orally. 蚪: A is collected from the eye socket vein and the triglyceride concentration in the blood is measured.

The use of white juice for the day before bowel administration) is different from the aforementioned oral administration experiment = to check the inhibition of fat absorption when directly administered in the duodenum. Small: Open abdomen under B-scale anesthesia and directly administer to the duodenum at a weight ratio of about 1 kg to the front. After the incision is sutured, 30 knives and 4 miles are injected into the intestine of the night ten coffee.

k 16 200401645 Administration. The triglyceride concentration in blood was measured after 2 hours. Regarding the sage alcohol extract (administration amount: 250 or 500 rag / kg), the results of the experimental system of oral administration and intraduodenal administration were summarized as shown in Table 1 and 4 kinds obtained in Example 3 Ingredients (here are four results about sage alcohol (1), 5 sage acid (2), 7-methoxy rosemary alcohol (3) and oleanolic acid (7)), respectively This is shown in Tables 2 and 3.

17 200401645 [Table 1] In Tables 1 to 3, the methanol extract of sage and the separated components are administered to suppress the rise of triglyceride in the blood of olive oil-loaded mice, and triglyceride in blood (mg / dL) Intraduodenal administration of untreated group 150 ± 17 ** 117123 Olive oil administration group 409 ± 75 204 ± 25 Sage methanol extract (250mg / kg) + Olive oil administration group 383 ± 25 134 soil 15 sage methanol extract (500mg / kg) + olive oil administration group 395 persons 35 118 ± 15 [Table 2] triglyceride in blood (mg / dL) duodenum when administered orally Untreated group 181 soil 18 ** 128 ± 17 olive oil administration group 587 ± 43 193 soil 25 sage alcohol (100 mg / kg) + olive oil administration group 473 ± 58 169 ± 23 rats Salicol (200mg / kg) + olive oil administration group 514 ± 36 175 ± 23 sage acid (50mg / kg) + olive oil administration group 292 ± 41 143 ± 14 salicylic acid (100mg / kg ) + Olive oil administration group 265 ± 30 ** 97 ± 21 ** Salicylic acid (200mg / kg) + Olive oil administration group 234 ± 25 ** 20 ± 3 **

18 200401645 [Table 3] Triglycerides in blood (mg / dL) -__ Intraduodenal administration when administered orally 1 Disposal group 1844 ± 28 131 ± Π Syringa oil administration group 488 + 77 177117 7- Methoxy rosemary alcohol (200mg / kg) + olive oil administration group 438 ± 51 245 ± 38 oleanolic acid (200mg / kg) + olive oil administration group 528 + 76 178 ± 27 each value Expressed as the average and standard error of 7 animals. ** is the deviation value from the oil and oil group: expressed as P < 〇. 5 From the results in Table 1, it is known that, when oral administration of sage alcohol extract, the blood triglyceride vinegar rise inhibitory effect cannot be determined at all, but it appears as a medium triglyceride vinegar rise inhibitory effect. This means that the sage methanol extract has lost its pancreatic lipase activity in the stomach. From the results in Table 2, it was found that the fourth example showed the strongest sage alcohol, the sage alcohol, which was the most potent thief, and neither the oral administration nor the duodenal administration showed the inhibitory effect of triglyceride vinegar. (I.e., fat absorption inhibition), and salicylic acid (2), when administered orally, showed a triglyceride effect and inhibitory effect depending on the amount used '; however, this effect appeared to be enhanced when administered duodenal ^. Therefore, from Table 3, it can be seen that 7-methoxy rosemary alcohol or 15 g_ (7), no effect of inhibition of triglyceride rise was observed when administered by ° and intraduodenal administration. From the above results, it can be seen that the lipase inhibitory action 'of the sage methanol extract confirmed in the second example is strongly related to the fat absorption inhibitory action of sage oxalate, which is inactivated in the stomach. . 19 200401645 Nocturnal secretion inhibitor of olive oil g 苻 small tail to enzymes ^^ triglyceride rise inhibition effect from the results of the fifth example 'relating to the lipase inhibition effect of the lipase-inhibitory component In the formulas of the three embodiments, those represented by (2); the following 5 is simplified to (2)) The fat absorption inhibition effect is inactivated in the stomach, and the effect of gastric juice on the fat absorption inhibition effect is investigated in detail. Proceed as follows. (l) For male mice of ddY series who were on a fast for 24 hours, 5% acacia gum liquid knife and the inhibitor Cimeudine (50 mg / kg) were suspended in water. , Administered orally at a ratio of about 1 kg of body weight to 5 m. After two (U) 30 minutes, an aqueous suspension of 5% acacia gum and sage oxalic acid ((2), 100 mg / kg) l floating in water was orally administered at a ratio of approximately kg body weight to 5 ^ 丨Vote for. (m) After another 30 minutes, oral administration was performed at a ratio of 1 kg of body weight to 5 ml of olive oil. (lv) Two hours after (m), blood was collected from the orbital vein to measure blood triglyceride. The results are shown in Fig. 3. Figure 3 shows: 0 Lu Zhu (ColUmn) i is the unprocessed group "· system that only implements the method", and Guan Zhu 2 is the group that does not perform the method (out) ~ (w). "20 systems", & column 3 is sage oxalic acid (2), 100 mg / kg "+ olive oil administration group" other than method (1), that is, the system of ㈣ ~ ㈣ ", read 4 is cimetidine + photo-oil oil administration group (other than method ，, (0 and (111) implemented system), and 20 200401645 column 5 is cimetidine + sage acid "(2), 100mg / kg "+ olive oil administration group" ⑴ ~ (iv) all methods ". Each column is represented by the average value and standard error of 7 mice. In the third figure, ** and the olive oil administration group (Column 2) Deviation 5 value: ρ <0.05; and ** indicates the deviation value: p < 0.01. After the gastric secretion was inhibited with cimetidine, mice that were administered sagenic acid (2) (tube The concentration of triglyceride in the blood of column 5) is lower than that of mice without the addition of gastric secretion inhibitor, and only salicylic acid (2) was administered (column 3). This shows that it has a fat absorption inhibitory effect Salicylic acid (2), its activity The stomach fluid was used as 10 and disappeared. For the sake of confirmation, the sage methanol extract obtained in the first example was subjected to the same evaluation. The results are shown in Fig. 4. Fig. 4 shows that the column 1 is untreated. Group "System implementing method (iv) only", 15 column 2 is olive oil administration group "that is, system implementing method (iii) to (iv) only", column 3 is sage methanol extract (500mg / kg) + olive oil administration group "other than method (i), that is, the system of (ii) ~ (iv)", column 4 is cimetidine + olive oil administration group (other than method (ii), and 20 (iii) the system implemented), and column 5 is ximedidine + sage methanol extract (500mg / kg) + olive oil administration group "⑴ ~ (iv) all methods". Each column is based on The mean value and standard error of 7 mice are shown. In addition, in Fig. 4, ** indicates the deviation from the olive oil administration group (column 2). 21 200401645 Value · p < 0 · 〇1 〇 Comparison of columns 3 and 5 in Fig. 4 shows that sage extract of sage containing mouse salicylic acid (2) has an enhanced fat absorption inhibition effect because of the inhibition of gastric juice secretion in advance by cimetidine. 5 第 7 实 _ Example: Making a sagebrush supercritical two-gasified carbon extract. The dried leaves of sage are placed in an extraction tank, and the critical carbon dioxide at 100 ° C is supplied at a pressure of 25 MPa for 60 minutes. Then, the residue is at a pressure of 47.5 MPa At 60 ° C, extraction was performed for 60 minutes to obtain a sage supercritical carbon dioxide extract (7g). 10 The 8th example of the fat absorption inhibition effect of the sage supercritical two-gas decomposer Inhibition of fat absorption by the critical carbon dioxide extract of sage obtained in Example 7 was investigated in the same manner as in Example 5. The results are shown in Table 4. 15 [Table 4] Table 4 Sage supercritical carbon dioxide extract is administered to olive oil | Mice bearing blood cause triglyceride in blood _ rise inhibition Triglyceride in blood (mg / dL) Orally When administered, the duodenum was administered untreated group 144.5 to 88 131.2 ± 10.9 olive oil administration group 619.8 to 74.1 176.9 ± 17.2 rat tail single supercritical carbon dioxide — extract (50mg / kg) + olive oil administration group 403.8 ± 73.4 ** 140.9 ± 20.1 rat tail supercritical di-emulsified carbon extract (100mg / kg) + olive oil administration group 230.2 ± 38.0 ** 125.5 soil 10.4 Each value is the average and standard error of 7 animals. ** Indicates the deviation from the olive 22 200401645 oil injection group: p < 0.01. From this result, it is known that the sage supercritical carbon dioxide extract has a very strong fat absorption inhibition drama. First formulation example (manufactured by 5 of enteric capsule preparations containing sage extract) The sage extract containing alcohol (powder) was prepared with the composition and weight ratio shown in Table 5 below according to the following steps. ) 'S enteric capsule preparation. The sage methanol extract (powder) is a dry solid obtained in the first example and is pulverized by a grinder or agitator. 10 [Table 5] The weight ratio of capsule composition to the entire capsule (%) Capsule content Sage methanol extract 32% Powder hardened oil 8% Capsule inner film hardened oil 20% Mingsheng 28% Outside the capsule Film glycerin 8% pectin 4% Total! 00? / 〇 First, at 40 t: the sage alcohol extract was suspended in hardened fat (palm hardened fat) to prepare a capsule content. In addition, gelatin, glycerin, and pectin are mixed to prepare a capsule coating film. Then, in the capsule 15 manufacturing machine, the contents of the capsule are ejected from the innermost nozzle of the concentric triple nozzle, the hardened oil of the capsule endothelial membrane-forming substance is ejected from the middle nozzle, and the capsule outer membrane liquid is ejected from the outermost nozzle at the same time. The triple-structured seamless capsule is continuously produced in the liquid oil cooled down. The particle diameter of the obtained seamless capsule can be freely adjusted to 1 mm to 8 mm. 23 200401645 Whether the seamless capsule obtained was enteric was tested according to the collapse test method described by the Japan Pharmacy. As a result, the seamless capsule did not collapse within 2 hours in the first solution (pH 1.2), followed by Since the second liquid (pH 6.8) did not collapse within 60 minutes, it was confirmed that it was enteric. 5 Second Formulation Example (manufacturing of enteric capsule preparations containing rosemary alcohol extract) In addition to using rosemary instead of sage, the methanol extract of rosemary was prepared according to the procedure of the first embodiment. The obtained dried solid of the methanol extract was pulverized with a grinder or agitator to replace the rat 10 sage extract alcohol powder in Table 5 above and used the same amount, according to the same steps as in the first production example To produce an enteric capsule preparation containing rosemary methanol extract (powder). The obtained capsule was the same as in the first preparation example, and it was confirmed that the capsule had enteric solubility by a collapse test of the Japanese Pharmacy. Effect of the Invention 15 According to the present invention, the preparation containing a plant-derived (sage and rosemary) extract is suitable for enteric technology, and therefore effective pancreatic lipase inhibitory activity can be exhibited in a small amount. Since the enteric fat absorption inhibitor of the present invention is taken before meals or between meals, the ingested fat is less susceptible to hydrolysis by the enzymes of pancreatic lipase, and as a result, the amount of fat absorbed by the intestine can be reduced. Therefore, although foods rich in fat can be consumed, it can also inhibit the absorption of fat into the body, which is useful for prevention or treatment of lifestyle diseases such as obesity, arteriosclerosis, myocardial infarction, cerebral infarction, and diabetes. [Brief Description of the Drawings] 24 200401645 [Figure 1] is a graph showing the test performed in the second embodiment of the present invention, regarding the 50% pancreatic lipase activity inhibitory concentration (IC50) of sage alcohol extract. [Fig. 2] Fig. 5 is a diagram showing a test performed in the fourth embodiment of the present invention. [5] Fig. 5 is a diagram showing the inhibition of pancreatic lipase activity of each isolated component from the methanol extract of sage. [Figure 3] Shows the test carried out in the sixth embodiment of the present invention. For olive oil-loaded mice administered with gastric secretion inhibitors first, the administration of sarsolic acid (2) caused triglyceride in blood. Graph of rise suppression. 10 [Figure 4] Shows the test performed in the sixth embodiment of the present invention. For olive oil-loaded mice administered with gastric secretion inhibitor first, the sage alcohol extract obtained in the first embodiment was administered. Inhibition effect of triglyceride in blood caused by rise.

Claims (1)

200401645 Scope of patent application: 1. An enteric fat absorption inhibitor containing sage and / or rosemary extract. 2. The enteric fat absorption inhibitor according to item 1 of the scope of the patent application, which is in the form of tablets, granules or capsules 3. The enteric fat absorption inhibitor as described in the first or second scope of the patent application Agent, wherein the extract contains sage acid [Chemical Formula 1] 10 4. —A food containing an enteric fat absorption inhibitor containing sage and / or rosemary extract. 5. The food of the enteric fat absorption inhibitor according to item 4 of the patent application, wherein the enteric fat absorption inhibitor is in the form of a tablet, granule or capsule. 15 6. The food of the enteric fat absorption inhibitor according to item 4 or 5 of the scope of application for a patent, wherein the extract contains sage oxalic acid represented by the following formula [Chemical 1] 26