JPH0667833B2 - Enteral nutrition - Google Patents

Description

Description: FIELD OF THE INVENTION The present invention relates to preoperative and postoperative oral administration in patients with heart disease such as angina, arrhythmia heart failure and ischemic heart disease, liver disease and renal disease. The present invention relates to an enteral nutrient used for enhancing the therapeutic effect on each of these diseases by administering it enterally when it is difficult to take. Further, the enteral nutritional agent according to the present invention, before and after surgery, of hyperlipidemia or hepatic disorder often seen when a high-calorie one is fed for the purpose of enhancing physical strength or early recovery of physical strength of patients. It is also used for prevention and treatment.

Conventional technology Enteral nutrition is usually aimed at early recovery of physical strength to withstand surgical invasion or post-operative catabolic transition to anabolic phase in patients who have difficulty in oral intake before and after surgery. It is often administered in high calorie with high fat content, but it often causes hyperlipidemia or liver damage.

Therefore, there is a demand for the supply of an enteral nutritional agent that does not cause hyperlipidemia or liver damage even when a high-calorie food having a high fat content is administered.

Problems to be Solved by the Invention The present invention has been made in view of the above situation,
Even when administered in high calorie with high fat content, the above-mentioned symptoms do not occur, and pre-operative and post-operative oral intake is difficult,
It is an object of the present invention to provide an enteral nutritional agent having an action of enhancing the therapeutic effect on a patient with heart disease, liver disease and renal disease when administered to these patients.

The present inventors have found that the pharmacological effect of L-carnitine on heart diseases such as angina, arrhythmic heart failure, ischemic heart disease and the like, as well as renal diseases, especially uremic diseases undergoing regular hemodialysis therapy, Focusing on the physiological action described later, succeeded in achieving the above-mentioned object by including L-carnitine in the enteral nutritional supplement as one of its active ingredients.

Incidentally, in recent years, it has been proposed to add carnitine or a salt thereof in the parenteral nutritional supplement for the purpose of enhancing the therapeutic effect of triglycerides necessary for patients with shock or trauma especially (JP-A-54). -154512).

However, no report has been made yet on adding L-carnitine or a salt thereof to an enteral nutritional agent, that is, a nutritional agent to be directly administered into the intestinal tract for the purpose of the above.

Structure of the Invention The feature of the present invention is that L-carnitine or a salt thereof is 0.1 to 1.0.
An enteral nutritional preparation containing 1% to 40% by weight of triglycerides and 1% to 60% by weight of a nitrogen source selected from the group consisting of amino acids, peptides and proteins as an active ingredient.

L-carnitine (hereinafter referred to as carnitine) used as one of the active ingredients here is a substance synthesized from the amino acids lysine and methionine in vivo, and in mammals, it is first converted into protein lysine in the kidney. Three methyl groups are combined to form trimethyllysine,
It is then liberated and transported to the liver in the form of γ-butyrobetaine, where it is hydroxylated to carnitine. Therefore, although carnitine is not considered to be an essential nutritional component such as vitamin, carnitine can be produced from outside the body in a state where the synthesis of carnitine in vivo is not smoothly performed, such as during liver disease or renal disease. Carnitine supplementation is considered necessary.

In addition, carnitine is involved in the passage of fatty acids in the mitochondrial inner membrane in vivo, and carnitine acetyl transformase I and II, and further in the enzyme system of carnitine-acetylcarnitine translocase, fatty acid It is loaded inside the membrane and consequently promotes β-oxidation of fatty acids. In other words, carnitine serves to improve the effective utilization of triglyceride as an energy source.

On the other hand, carnitine administered from the outside promotes the synthesis of acylcarnitine in the hepatocyte matrix and excretes it out of the membrane, but since acylcarnitine acts as a cytotoxin in the matrix, Carnitine is considered to also have a detoxifying action, and for example, the effect of preventing carcinine from intoxication death due to hyperammonemia by administration of carnitine has been reported based on animal experiments.

Next, the results of testing the pharmacological effect of carnitine on liver damage are shown.

Test method: Carbon tetrachloride was administered to each group of 10 SD male rats (body weight: about 130 g) to cause drug liver damage, and the preventive effect of carnitine against this was examined by the following.

First, L-carnitine hydrochloride neutralized with 0.1 N sodium hydroxide was intraperitoneally injected at a rate of 1 nmol / kg body weight, and 30 minutes later, 0.5 ml / kg body weight of carbon tetrachloride was intraperitoneally injected. Injected. After overnight fasting, serum lipid metabolism and GOT and GPT activities were measured. As a control, the same amount of physiological saline instead of carnitine was also measured.

The results are shown in Table 1.

As shown in Table 1, serum triglyceride, β-lipoprotein and free fatty acid were decreased in the carnitine-injected group and GOT activity was also decreased as compared with the control group, and carnitine was treated against drug liver damage. Preventive effect is recognized.

Means for Solving the Problems The present invention utilizes the above-mentioned pharmacological action of carnitine for an enteral nutritional agent, particularly a high-calorie enteral nutritional agent having a high fat content.

The content of carnitine or a salt thereof in the enteral nutritional supplement according to the present invention is 0.1 to 1.0% by weight in the nutritional supplement, preferably
The content is 0.3 to 0.5% by weight, and the above-mentioned pharmacological effects of carnitine can be expected depending on this content.

In addition, the content of triglycerides in enteral nutrition is 1 to
The content is 40% by weight, preferably 5 to 20% by weight, and the triglyceride is efficiently energized with this content.

As the triglycerides used here, corn oil, safflower oil, soybean oil, which have been conventionally applied to enteral nutrition,
Examples include sunflower oil, milk fat and medium chain fatty acid triglyceride (MCT).

The enteral nutritional product according to the present invention further contains, as an essential active ingredient, at least one nitrogen source selected from the group consisting of amino acids, peptides and proteins. As such a nitrogen source, animal and plant proteins, low molecular weight peptides and amino acid mixtures are used, and it is particularly preferable to use milk protein as the protein from the viewpoint of its amino acid composition balance and flavor. In addition, when there is a problem in the balance of the amino acid composition in using the protein, it is preferable to supplement the lacking amino acid.

These nitrogen sources are contained in the enteral nutritional supplement in an amount of 1 to 60% by weight, preferably 10 to 30% by weight.

In the present invention, in addition to the above-mentioned essential components, sugars, minerals, vitamins, and if necessary, an emulsifier, a stabilizer and the like can be added.

The sugar used here is a monosaccharide such as glucose,
Examples of the sugar include disaccharides such as sucrose and maltose, and polysaccharides such as dextrin. These may be used alone or in combination, and lactose or galactose may be used in mixture with glucose or the like.

Examples of minerals include sodium, potassium, magnesium, calcium, phosphorus, iron, zinc, copper, chlorine, and manganese, iodine, cobalt, selenium, and the like. Examples of vitamins include vitamins A, D, and E. K, B ₁ ,
Examples include B ₂ , B ₆ , B ₁₂ , C, nicotinamide, folic acid, vantothenic acid, and biotin.

The enteral nutrient according to the present invention has carnitine, triglycerides and the nitrogen source as essential components, and the above-mentioned sugars, minerals, vitamins, and if necessary, an emulsifier and a stabilizer are mixed in appropriate amounts. By doing
It can be prepared.

The composition and effect of the enteral nutritional supplement according to the present invention will be specifically described below with reference to examples.

Example 1 Enteral nutritional composition: The following composition was uniformly mixed and prepared.

(A) Composition Content / 100g Milk protein 19.56g Methionine 0.19g Cystine 0.19g Tryptophan 0.06g Corn oil 12.8g Lecithin 2.2g L-carnitine hydrochloride 0.3g Dextrin 40.7g Glucose 9.6g Lactose 6.0g Galactose 5.4g Vitamin A 1000I.U.〃 D 100I.U.〃 E 2.28mg 〃 B ₁ 0.5mg 〃 B ₂ 0.8mg 〃 B ₆ 1.0mg 〃 B ₁₂ 0.68mg 〃 C 10.2mg Nicotinic acid 4.5mg Bantothenic acid 3.4mg Folic acid 90μg Sodium 254mg Potassium 530mg Calcium 444mg Magnesium 40mg Phosphorus 371mg Chlorine 373mg Iron 5mg Zinc 4.5mg Copper 0.6mg (b) Composition content / 100g Low molecular weight peptide 17.5g Methionine 0.2g cystine 0.2g Tryptophan 0.1g Medium chain fatty acid triglyceride 11.0g Safflower oil 4.0g Lecithin 2.5g L-carnitine hydrochloride 0.5g Dextrin 61.5g Vitamin A 600I.U.〃 D 30I.U.〃 E 3I.U.〃 B ₁ 0.3mg 〃 B ₂ 0.42mg 〃 B ₆ 0.54mg 〃 B ₁₂ 0.9mg 〃 15 mg Nicotinic acid 5.1 mg Bantothenic acid 2.1 mg Folic acid 0.06 mg Biotin 30 μg Vitamin K 0.042 mg Sodium 330 mg Potassium 563 mg Calcium 180 mg Magnesium 105 mg Phosphorus 180 mg Chlorine 510 mg Iron 3 mg Zinc 4.5 mg Copper 0.6 mg Iodine 45 μg Cobalt 0.05 mg Selenium 0.04 mg Manganese 1.2 mg ( C) Composition Content / 100g Amino acid mixture 19.7g Aspartic acid 7.2% Threonine 4.3〃 Serine 6.0〃 Glutamic acid 21.6〃 Glycine 1.8〃 Alanine 2.9〃 Cystine 0.4〃 Valine 6.1〃 Methionine 2.6〃 Isoleucine 4.9〃 Leucine 9.0〃 Leucine 9.0〃 Enylalanine 4.6〃 Lysine 8.0〃 Histidine 2.8〃 Tryptophan 1.0〃 Arginine 3.4〃 Proline 8.1〃 Corn oil 15g L-Carnitine hydrochloride 0.3g Dextrin 62.5g Vitamin A 600I.U.〃 D 30I.U.〃 E 3I.U. 〃 B ₁ 0.3 mg 〃 B ₂ 0.42 mg 〃 B ₆ 0.54 mg 〃 B ₁₂ 0.9 mg 〃 C 15 m g Nicotinic acid 5.1 mg Bantothenic acid 2.1 mg Folic acid 0.06 mg Biotin 30 μg Vitamin K 0.042 mg Sodium 330 mg Potassium 563 mg Calcium 180 mg Magnesium 105 mg Phosphorus 180 mg Chlorine 510 mg Iron 5 mg Zinc 4.5 mg Copper 0.6 mg Manganese 1.2 mg Iodine 45 μg Example 2 Enteral nutritional supplement Preparation of milk protein 19.7% by weight, L-cystine 0.3% by weight, corn oil 1
An enteral nutrient was prepared by uniformly mixing 5% by weight, 54.5% by weight of dextrin, 6% by weight of minerals, 2% by weight of vitamins and 0.3% by weight of L-carnitine hydrochloride.

Pharmacological effect of enteral nutritional supplement: Enteral nutritional supplement obtained as described above was enterally administered to each group of 10 SD male rats (body weight: about 130 g) in an amount of about 297 g for 3 weeks. , Serum lipid-related components and GOT and GPT
Was measured.

As a control, the same administration was performed for the above composition containing 0.3% by weight of dextrin instead of L-carnitine hydrochloride.

The results are shown in Tables 2 and 3.

The values in parentheses in Tables 2 and 3 are 100% for the control group.
Shows the ratio.

In Table 3, GOT indicates glutamate oxaloacetate transaminase, and GPT indicates glutamate pyruvate transaminase.

As can be seen from Tables 2 and 3, in the test group in which the enteral nutrient containing carnitine was enterally administered, the lipid metabolites such as triglyceride in the serum were decreased in comparison with the control group, and GOT and GPT were also decreased. The activity is also decreased, and the effect of the enteral nutritional supplement of the present invention for improving lipid metabolism and liver dysfunction is recognized.

Example 3 The same as described in Example 2 except that 12% by weight of medium-chain fatty acid triglyceride and 3% by weight of safflower oil were used in place of the corn oil of the enteral feeding agent in Example 2. The test was carried out according to the procedure described above, and lipid-related components in serum and GOT and GPT were measured for each rat group. The same measurement as in Example 2 was used as a control, and the same measurement was performed.

The results are shown in Tables 4 and 5.

The numerical values in parentheses in Tables 4 and 5 indicate the ratios when the control group is 100%.

As seen in Tables 4 and 5, even when the type of triglyceride is changed in the present invention, the pharmacological effect of the enteral nutrient is recognized.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (56) Reference JP-A-57-48907 (JP, A) JP-A-54-113409 (JP, A) Eiichi Hiraoka "High Calorie Infusion in the Pharmaceutical Field" (1980) Pharmaceuticals Journal, P. 8-21 Hiroshi Kumagai “Clinical Pharmacology, Volume 8” (1966) Nakayama Shoten, p. 95-103

Claims (1)

[Claims] 1. L-carnitine or a salt thereof 0.1 to 1.0% by weight, triglycerides 1 to 40% by weight, and at least one nitrogen source 1 to 60% by weight selected from the group consisting of amino acids, peptides and proteins. An enteral nutritional product containing as an active ingredient.