JPH0549646B2 - - Google Patents

Description

[Detailed description of the invention]

[0001]

FIELD OF THE INVENTION The present invention relates to growth promoters for animals and humans.

【0002】

[Prior Art] In recent years, various experiments have been conducted regarding the physiological effects of d1-carnitine, but the main ones include enhancement of digestive motility, enhancement of secretion of digestive juices, and promotion of bone growth. It's been raised. However, d1-carnitine cannot be expected to have the above-mentioned effects or is ineffective in animals, and currently does not have sufficiently satisfactory effects in humans.

【0003】

[Problems to be Solved by the Invention] The purpose of the present invention is to provide a drug that has excellent improvement effects and growth promotion not only for patients suffering from poor weight gain, but also for healthy people and even animals. It is something.

[0004]

[Means for solving the problem] The above objectives are: 1.
- By a growth promoter containing at least one selected from carnitine (i.e., el-carnitine), acyl-1-carnitine (i.e., acyl-el-carnitine), and physiologically acceptable salts thereof as an active ingredient. achieved.

[0005] Carnitine, which is an active ingredient in the present invention, was developed in 1905 by Gulewitsch,
It is a compound discovered from meat extract by Krimberg and Kutscher. 1947, Fraenkel
and Rlewett discovered that an unknown substance contained in yeast or liver extract was essential for the growth of the brown rice beetle, and named it vitamin Br. Later, in 1952, Carter et al. isolated a crystal with the above-mentioned vitamin Br activity and confirmed that it was the same substance as carnitine. Carnitine is distributed in a wide range of organisms, from humans to microorganisms, and is known to be particularly present in large amounts in muscle and pancreatic juice. Furthermore, a series of studies by Frits et al. have been reported regarding its physiological and biochemical significance (Frits 1.B.et al.J.Lipid.Res.4 279
1963). Carnitine [(CH ₃ ) ₃ N ⁺ CH ₂ CH (OH)
_CH2COO- ^] promotes the uptake of Acyl-CoA, an active fatty acid, into the mitochondria during β-oxidation of fatty acids in the mitochondria present in living cells. In other words, carnitine converts Acyl-CoA into
Acyl-CoA is converted to Acy1-carnitine through the action of carnitine transferase, quickly passes through the barrier, and is converted into β-carnitine in the endomembrane system.
It is said to be involved in oxidation and help produce energy. Therefore, carnitine can be expected to have various pharmacological effects by utilizing its physiological effects, but there have been no reports of actual prevention or treatment of poor weight gain, etc. using the active ingredient of the present invention.

[0006] The present invention provides 1-carnitine, acyl-1
- Drugs containing carnitine and its physiologically acceptable salts as active ingredients can be administered to humans with poor weight gain, or to animals such as livestock that do not promote growth or require growth promotion. It was discovered and completed that the above-mentioned symptoms can be successfully prevented and treated by administering this drug.

[0007] The carnitine used as an active ingredient in the present invention can be in the form of a physiologically acceptable salt.

[0008] Next, the toxicity of 1-carnitine and acyl-1-carnitine used in the present invention will be explained using a table. Acute toxicity ( _LD50 )

[0009]

[Table 1] ■■■ Turtle shell [0010] ■■■

[0010]

[Table 2] ■■■ Turtle shell [0011] ■■■

[0011]

[Table 3] ■■■ Tortoise Shell [0012] ■■■ Also, its pharmacological effects will be detailed in Examples later, but by administering an appropriate amount of the above carnitine, weight gain became noticeable. We were able to demonstrate that this technology enables people to live comfortably in their daily lives. The reason for such a remarkable effect is currently not clear, but it is thought to be related to the fact that the administered carnitine or its salt has the effect of promoting an increase in free hydrochloric acid and an increase in gastric juice acidity.

[0012] In any case, the above-mentioned carnitine or its salts exhibit excellent effects in preventing and treating these symptoms in patients with poor weight gain, or in animals such as livestock that are lacking in growth or require growth promotion. It has extremely low toxicity as an indicator, and no side effects are observed when administered, making it extremely effective as a growth promoter.

[0013] The growth promoter of the present invention is usually formulated into a pharmaceutical composition depending on the administration method by using a pharmaceutical carrier together with the active ingredient compound. As carriers, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, lubricants, etc., which are commonly used to prepare drugs according to the usage form, can be used. Can be used. There are no particular restrictions on the method of administration, and various methods such as oral administration, intravenous administration, subcutaneous administration, and intraperitoneal administration can be employed, but oral administration is most preferred. Examples of dosage forms suitable for oral administration include tablets, pills, powders, liquids, granules, capsules, and drinks. Further, as a formulation suitable for intravenous administration, it is preferable to use an injection such as an aqueous solution or suspension.

[0014] The amount of the active ingredient in the pharmaceutical composition formulated into a dosage unit form is not particularly limited and can be appropriately selected within a wide range, but is usually preferably 1 to 70% by weight of the total composition. In addition, the dosage of each preparation depends on various conditions, such as the age, sex, weight, severity of the disease, etc. of the patient, and the method of administration.In the case of oral administration, for a normal adult, the active ingredient should be administered at each dose. 5mg～100mg
Preferably, a pharmaceutical composition containing the drug may be administered in a range of 10 mg to 50 mg, and the number of administrations may be increased or decreased depending on the patient's severity, with the aim of administering the drug 3 times a day.

【0015】

[Example] Next, Examples for formulating the drug of the present invention will be shown, but the composition is not necessarily limited to the following composition.

[Example 1] Additives consisting of 266 mg of crystalline cellulose, 266 mg of carboxymethyl cellulose, 50 mg of light anhydrous silicic acid, and 50 mg of macrogol 6000 were added with 1-carnitine and acyl-1-
Containing 20 to 500 mg of at least one selected from carnitine or salts thereof, granules, fine granules,
Manufacture powder.

[Example 2] 1-carnitine and acyl-1-
Capsules containing 50 to 500 mg of at least one selected from carnitine or a salt thereof are prepared.

[Example 3] 1-carnitine, acyl-1-
Tablets containing 20 to 500 mg of at least one selected from carnitine or their salts (uncoated tablets,
Manufactures film-coated tablets and sugar-coated tablets.

[Example 4] 1-carnitine, acyl-1-
An oral liquid preparation containing 100 to 500 mg/ml of at least one selected from carnitine or a salt thereof and adding a sufficient amount of sterile purified water is prepared in a 10 to 100 ml ampoule, glass bottle, or synthetic resin container.

[Example 5] 1- to physiological saline or Ringer's solution
5 to 250 at least one selected from carnitine, acyl-1-carnitine, or salts thereof
Injections containing 10 to 500 ml of mg/ml in ampoules, vials, or plastic containers for rinsing are produced.

[0016] Next, specific effects of the present invention will be explained in detail by giving experimental examples. 1 Animal experiment example The animals used were Wistar rats. weight 45
Male rat rat pups around the age of 1.5 g were test-reared for one week, and those with similar weight increases were divided into two groups, each group containing 5 rats. The target group was given the following various feeds, and 1-
In the carnitine and acyl-1-carnitine groups, 10 to 45 mg/Kg of these were further administered daily. The breeding period was 26 to 43 days, during which body weight was measured every other day. On the day of completion of rearing, autopsies were performed under ether anesthesia to determine serum protein content (Hitachi protein meter), A/G ratio (Yoshikawa and Saito method), liver weight, liver water content, liver fat content (Soxhlet fat extractor), Hepatic glycogen content (Somogyi's method), hepatic air content (Kjeldahl-Nessler method), liver nucleic acid image (Brachet's staining), etc. were measured and observed. The results are shown in Tables 4, 5 and 6. Feed: Basic solid food Oriental solid food Basic synthetic food Casein 15%, soybean oil 5%,
74% potato starch, 5% pine column salt, 1% panvitan

[0017]

[Table 4] ■■■ Turtle shell [0013] ■■■

[0018]

[Table 5] ■■■ Turtle shell [0014] ■■■

[0019]

[Table 6] ■■■ Tortoise shell [0015] ■■■ As is clear from the above Tables 4, 5 and 6, the products of the present invention showed a significant increase in weight compared to the control group, and had extremely significant growth effects. The difference was confirmed. 2. Clinical experiment example The subjects were subjects (7 males, 16 females) who complained of anorexia and poor weight gain, aged between 2 months and 10 years.
There were 11 infants, young children, and 12 school children. drug is 10
The daily dose was ~25 mg/Kg, which was divided into 2 to 3 doses and administered for 1 month.

[0020] Judgment was made based on the effect on appetite, observation by the mother or nurse, or the amount of leftover food. Regarding body weight, those whose weight increase (daily dose) for one month after administration is 10 g more than before administration are considered effective (+), and those whose weight increase is 50 g or more are considered excellent effects (+/
+). The results are shown in Table 7.

[0021]

[Table 7] ■■■ Turtle shell [0016] ■■■

Claims (1)

[Claims] 1. A growth promoter comprising at least one selected from 1-carnitine, acyl-1-carnitine, and physiologically acceptable salts thereof as an active ingredient.