JPH06507161A - Use of lipids for the manufacture of enteral pharmaceutical preparations for the treatment of lipid malabsorption - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] The present invention relates to the use of leftover lipids in the manufacture of enteral pharmaceutical formulations for the treatment of lipid malabsorption. comprising novel uses of types of lipids.

The lipids of interest are those belonging to the type MLM and/or SLS.

L (which represents a long-chain acyl group) is an acyl group having 14 to 24 carbon atoms; is a group such as valmitoyl (CHs (CHt) 14CO-), M (which represents a medium chain acyl group) has 6 to 13 carbon atoms An acyl group, such as belargonyl (CHs (CHt) tco-) , and S (which represents a short-chain acyl group) has 2 to 5 carbon atoms. It is an acyl group, for example, valeroyl (CHs (CH3CO-)).

Type M lipids are It is understood that it can be expressed as

For example, in WO-090104009, enteral emulsions of lipids of the type mentioned above are described. Specific examples of nutrition are described, and their use for nutritional purposes as well. The use of these is described. Also, patients for whom enteral emulsions of the aforementioned type are critical. It is stated that it can be used as a nutritional supplement for humans.

From PCT/DT90100343 (not yet published) Pase can be used as a drug that has biological effects on the intestinal mucosa.

It has now surprisingly been found that the above-mentioned types of lipids , patients with lipid malabsorption, e.g. pancreatic insufficiency, secondary biliary cirrhosis or cystic Can be used to treat patients suffering from fibrosis, i.e. these lipids It has been found that it can be used in patients suffering from lipid malabsorption. in patients with lipid malabsorption. One category, although less likely, is related to pancreatic lipase secretion. The lipase is responsible for the major portion of triglyceride hydrolysis in the intestine.

Surprisingly, therefore, according to the invention, oils of type MLM and/or SLS Despite the fact that pancreatic lipase activity is reduced or completely absent, intestinal It has been found that it can be absorbed within. MLM type assembled lipids Easily hydrolyzed by visceral lipase (see Example 1) and patients suffering from pancreatic insufficiency MLM type assembled lipids with very low activity of pancreatic lipase as in means that it will be hydrolyzed and the 2-monoglyceride formed will be absorbed. As is clear from Example 2, when MLM is given to pigs with pancreatic insufficiency, , a large amount of fat was absorbed, similar to when soybean oil was given to pigs with pancreatic insufficiency. pancreatic insufficiency A study by Kent (see Example 3) showed that total lipid absorption was When given as an assembled MLM, the randomized MLM or the corresponding fat The quality is greater than as a physical mixture. In addition, it contains the essential fatty acid linoleic acid. The amount is higher in the MLM group, meaning that the total absorption of linoleic acid is higher . This indicates that: more easily absorbed energy is In addition to providing membrane lipids and intracellular inclusions (e.g. provides essential fatty acids for cellular function, including the formation of phytosanoids.

Therefore, the type? The use according to the invention of lipids of ILM and/or SLS For the production of pharmaceutical preparations for the treatment of malabsorption. Fats relevant to the use according to the invention quality as part of a dressing or oil added to food or as an emulsion. It can be incorporated as part of a package.

Typically, lipids are administered in amounts of 0.5 to 4.5 g/kg body weight per day. Should. The use according to the invention can be used to treat lipid malabsorption in both humans and animals. related.

Stated another way, the use according to the invention of lipids of type MLM and/or SLS is for patients suffering from lipid malabsorption.

According to a preferred embodiment of the use according to the invention, the lipids are 20% of the lipids of type MLM. Including super. This type of fat is easily absorbed in the intestines.

In a preferred embodiment of the use according to the invention, the lipid is 10% of the lipid of type SLS. Contains super. This type of fat is easily absorbed in the intestines.

In a preferred embodiment of the use according to the invention, the preparation is formulated as an enteral preparation. Ru.

So, to summarize, type? ILM or SLS lipids are described and nutritional supplements Their use as lipids and the use of lipids for the treatment of lipid malabsorption have also been described. However, there is no mention of lipids of type MLM or SLS; especially international Publication date - 8,902,275 Ewing Grant' Deconess Hospice Tal Copf, international release date - to New England Dell on 9.012,080 - Cornes Hospital Corp), International Publication Date - A-8,601,715 (Se Center for Nutritional Research Caritaple Trust), Ca n, J, Physiol, Pharmasacol, +68 volume, 1990.519~ Page 523, CA, B, P, C, Clough et al.: “Triglylyse in the absence of lipase” "Absorption of Cerides" and The American Journalof C11 nical Nutrition, Volume 36, November, 1982.950-962 Page, American 5ociety for C11nical Nutr ition, USHA, C, Bach, etc.: "Medium chain triglycerides: latest" is specified Various lipids with a composition as follows and their use for the treatment of lipid malabsorption However, the lipids used according to the present invention are is not listed.

Lipids for enteral feeding of type LLL may be more difficult for patients suffering from lipid malabsorption. can be absorbed with Lipids for enteral nutrition of type MMM are does not contain L and therefore can be absorbed into the mucosa in the absence of pancreatic lipase. It contributes to the formation of essential fatty acids and the synthesis of cell membranes in the body, but it also contributes to the formation of essential fatty acids and the synthesis of cell membranes in the body. M contributes to the protection of the energy requirement, because M contributes to the protection of the energy requirement and L contributes to the formation of essential fatty acids and the synthesis of cell membranes in the body. Absorption of MMM has a smaller molecular weight and more compactness compared to long-chain triglycerides. structure and facilitated diffusion across the unstirred aqueous layer in the intestine. . Thio-1B, P, C, Schiefer, E, A, Persson, H, G, Lipase Absorption of triglycerides in the absence of Canj, Physiol, Pharm acol, 68.519-523.1990.

However, according to the present invention, lipases of the type indicated above can be used in individuals suffering from pancreatic insufficiency. was found to be able to be absorbed in the body, thus providing essential fatty acids. .

Example 1 No. 7 experiment of MLM type using pancreatic cisternase: Hydrolysis of triglycerides in 10% emulsion was determined by pu-stat titration. p) Measured with pancreatic lipase at 19 and 37°C. Lipid emulsion (50 d) with 5 ml of lipid, 41W1 of gum arabic (10% W/W) and 4d Ultra Tur emulsified for 3 x 5 minutes. Particle size distribution was determined under a microscope before and after titration. It was measured. For the incubation mixture, add 2.5d(7) lipid emulsion. , 2.0 m (7) buffer (0,005 M Tris, 0.04 M NaCl) and and 0.5 d of taurocholate solution (8% w/w) and 37° After equilibration with C, the mixture was titrated with 0.05N NaOH to an end point of pH 9. 2. After adding 0 m enzyme solution (25 μg) and stabilizing for 2 min, the rate of base addition was The pH was measured at pH 9.

result: Titrations were performed under conditions with excess lipid substrate and all titration curves were linear. It turned out that.

As is clear from Table 1, the introduction of CIl and/or C3° into the 1st and 3rd positions Significantly increases hydrolysis by pancreatic lipase.

１：　　　　　　　゛ a) Hydrolysis rate can be calculated from the following formula: μm base/mixture x normality of base Enzyme Sui Measurements were performed twice Values were corrected for decreased enzyme activity using time b) Long chain triglyceride control Increased hydrolysis rate compared to C) arachidonic acid rich in oil d) r-lylunic acid e) Fish oil rich in docosahexaenoic acid ``) Example 2 rich in fish oil in eicosapentaenoic acid W1 armpit Cs/Co in pancreatic insufficiency in pigs by catheterizing the pancreatic duct. −Large The absorption of soybean oil-C*/CIo (MLM) was investigated. Dividing the research into three studies In period 1, the pig had pancreatic insufficiency and was unable to eat food. - soybean Oil-Cs/Coo was received. All three periods lasted 7 days; the last 3 days The furuncle was collected and the fat content was determined. As is clear from Figure 1, MLM acquisition Excretion of fecal fat after feeding was almost the same in pigs with healthy pancreas as after feeding soybean oil. there were. This suggests that the assembled lipids are more effective than soybean oil in the pancreatic insufficiency pig model. meaning that it is more easily absorbed.

Example 3 A. Absorption of c c, -”-c c, into rat lymph experiment: Eighteen Wistar rats were treated with Cs/Co. - Soybean oil - Cs/Co.

(MLM), randomized MLM, or a physical mixture of soybean oil and MCT oil. They were divided into three groups, each receiving one. The fatty acid compositions of the three types of lipids were approximately the same. La The cat was anesthetized with Mbemer and all pancreatic secretions and bile were removed. A catheter was inserted into the biliary/pancreatic duct. by introducing a catheter into the chest tube. Collected lymph. Intragastric injection of lipids (in taurocholate emulsion) in rats 0.5 g (5 mM choline was added to this emulsion) and then Lymph collection was started immediately thereafter. lymph for 0.5 hours for the first 4 hours and then at 1 hour intervals for the next 4 hours.

result: Figure 2 shows total lymphatic drainage. The absorption peak was observed 5 hours after administration, which was slower than when pancreatic lipase and bile are present.

After the peak, absorption of MLH continues at higher levels than the other two lipids.

This leads to higher total absorption of MLM.

The content of the essential fatty acid linoleic acid in the lymph fraction is shown in FIG. The content of linoleic acid is , significantly higher in the MLM group than in the two other groups. follow Thus, the total absorption of linoleic acid is higher in the MLM group.

FIG. 1 FIG. 2 FIG.3 international search report +1-amb-w, 1&PC'r/DK 92100150In-w-maam +s-Icmaa114P Tenia/DK92100150 International Investigation Report

Claims (4)

[Claims] 1. Type MLM and/or for the production of enteral pharmaceutical preparations for the treatment of lipid malabsorption or the use of SLS lipids. 2. Type MLM and/or SLS lipids for patients suffering from lipid malabsorption. use. 3. Claim 1 or 2, wherein the lipid contains more than 20% of lipids of type MLM; Use as described in Section 2. 4. Claim 1 or 2, wherein the lipid contains more than 10% of lipids of type SLS; Use as described in Section 2.