JPH08259445A - Medicinal composition for improving gastric emptying performance - Google Patents

Abstract

PURPOSE: To obtain a medicinal composition for improving gastric emptying performances, containing carnitine chloride and having promoting actions on positive emptying of gastric contents into an enteric canal. CONSTITUTION: This composition contains carnitine chloride in which the d-, l-isomer, a racemic modification or a mixture thereof as an active ingredient and is obtained by further blending a Chinese medicine formulation having effects on symptoms of the digestive organs, a herb medicine and a medicine for controlling intestinal functions having stomachic actions, an antacid or a digestive agent, etc., in combination and adding a sweetening agent, a flavoring agent, a spice, an aromatic agent, a colorant, etc., and providing a medicine excellent in feeling of administration and refreshing feeling after the administration. The carnitine chloride is effective in alleviating symptoms of depressive symptoms due to antidepressat actions and treating symptoms of digestive organs such as a pain in the stomach and pyrosis, etc., due to accelerating actions on gastric emptying and improving the symptoms of the digestive organs caused by stress, anxiety, overeating, excessive ingestion of alcohols and administration of medicines, etc. The composition can be prepared into a solid pharmaceutical preparation, a solution, etc., for peroral administration.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a composition containing carnitine chloride for improving the reduction of gastric emptying ability. Furthermore, the present invention not only utilizes the gastric emptying improving effect of carnitine chloride, but also the feeling of taking the drug, the taste, and the taste of the drug by combining a herbal medicine or a herbal medicine having an effect on the symptoms of the digestive organs with the carnitine chloride.
Provided is a pharmaceutical composition having improved gastric emptying ability, which is excellent in aroma and the like.

[0002]

2. Description of the Related Art Carnitine chloride was introduced in 1905 by Gulewisch.
) Et al., And a chloride of a nitrogen-containing compound isolated from mammalian muscle extract for the first time separately by Kutscher et al., Carnitine being 3-carboxy-
It has the compound name of 2-hydroxy-N, N, N-trimethyl-1-propanammonium.hydroxide.inner salt. Subsequent studies revealed that it exists widely from humans to microorganisms including animals and plants, and showed that carnitine plays an important role in fatty acid oxidation in mammals in the late 1950s. When a long-chain fatty acid is taken into mitochondria, it cannot pass unless it is in the form of acylcarnitine, and then β-
It is well known that it undergoes oxidation and is involved in the production of ATP. Since most of myocardial energy requirements are satisfied by fatty acid oxidation, carnitine plays a large role in normal cardiac energy metabolism, and myocardial ischemia causes a decrease in the amount of carnitine in the heart and long-chain fatty acids of CoA and carnitine. It is also reported that carnitine administration has a protective effect on ischemic hearts because it causes ester accumulation.
Carnitine also has parasympathetic nerve stimulation and has been found to promote secretion of digestive fluids (saliva, gastric juice, pancreatic juice, bile, intestinal fluid). However, there are many unclear points about the pharmacological action of carnitine, such as the gastric emptying enhancing action,
Nothing is known about the activity suggesting antidepressant action.

In daily life, it is common to often experience gastrointestinal symptoms such as "stomach pain" and "heartburn", and the causes thereof are stress, anxiety, overeating, and excessive intake of alcohol. And taking medications. Chronic gastrointestinal symptoms such as stomach pain, heartburn, nausea / vomiting, stomach upset, and stomach weight have fallen into depression due to stress and anxiety caused by work and social environment in a complicated social structure, and side effects caused by taking drugs in recent years. There are many cases of complaining about that and causing a great hindrance to daily life, which is one social problem. Report by Miyahara et al. (Medicina 31, 1, 2
4-28: 1994), those who present with indefinite complaints of upper abdomen represented by such symptoms as "stomach lean" and "stomach weight" are more depressed than healthy people. In recent years, it has been considered that such symptoms are caused by a decrease in gastric emptying ability, and it has been pointed out that the presence of a depressive state is a background factor.

Conventionally, for this kind of gastrointestinal symptoms,
Over-the-counter gastrointestinal drugs are widely known and used in large numbers. And most of them are antacids, crude stomach medicines, digestive agents,
It is a combination of intestinal medicine, analgesic / spasmodic agent, and mucosal repair agent,
Of these, antacids and crude stomach medicines are especially widely used because they have the effect of relieving early symptoms. However, although these drugs can temporarily relieve symptoms,
For the depressive symptoms due to stress and anxiety that are the cause of the symptoms, the effect is insufficient, and there are almost no preparations prescribed with a drug having a pharmacological action supporting the causative therapy. In addition, at present, at best, it can only be used for drug development to the extent that it simply promotes movements of the stomach and the like to promote digestion, and in the present situation, it takes a step further and actively promotes the active discharge of gastric contents to the intestinal tract. There is a need for a drug that can be treated by using the drug. In addition, since these drugs are often administered frequently, they must be extremely safe, have no side effects, and be easy to take. The gastrointestinal medicine for this kind of gastrointestinal symptoms that has been conventionally used for such a purpose is, as described above, heartburn,
Since it is used for symptoms such as nausea / vomiting, stomach upset, and stomach weight, it must have favorable characteristics in terms of refreshing feeling during or after taking, and overall feeling of taste and aroma. It was very important.
Therefore, in developing such a preparation, it is important not only that it be excellent in its pharmacological action, but also that it should give a feeling of taking and a refreshing feeling after taking.

[0005]

[Means for Solving the Problems] Based on the above-mentioned idea, the present inventor diligently uses an evaluation system for a drug having gastric emptying ability in order to search for a component having an effect on the improvement of symptoms. I did a research. As a result, it was found that carnitine chloride has an excellent effect of improving gastric emptying upon oral administration. The present inventor further conducted a study and found a result suggesting that carnitine chloride exhibits its activity also for antidepressant action, and since it is excellent as a drug for improving the above-mentioned symptoms, We started development. That is, carnitine chloride can be expected to relieve depressive symptoms due to antidepressant action and improve symptoms due to gastric emptying, and is excellent as a pharmaceutical composition for treating the above-mentioned pathological conditions. Thus, the present invention further comprises (1) a pharmaceutical composition for improving gastric emptying ability, characterized by containing carnitine chloride, and (2) a herbal medicine having an effect on symptoms of the digestive organs. (1) The composition according to (1), (3) The composition according to (1) or (2) above, which further comprises at least one selected from the group consisting of a crude drug having stomachic activity and an intestinal regulator. ) A composition according to any one of (1) to (3) above, which further comprises a sweetener, (5) an antacid, a digestive agent, an antidiarrheal agent, an analgesic / spasmodic agent, a mucosal repair agent, a flavoring agent, and a flavoring agent. The composition according to any one of the above (1) to (4), further comprising at least one selected from the group consisting of: a flavoring agent, a flavoring agent, and an excipient.

(6) At least one selected from the group consisting of carnitine chloride d-form, l-form, and racemic form, Anchu-san, Kosandaira-san, Goku-fu, Gyorei-to, Uncho-to , Ennenkatsu-to, Origo-goto, Oren-gedoku-to, Oren-to, Kasoku-yoku-to,
Kakka Shoki-san, Kakkon Oren-gou-to, Kami-nen-to, Kami-Kai-to, Kami-Hei-san, Ginseng-Ginseng Hange-maru, Kanzo-Shinshin-to, Kisui-to, Keishika-Keakuyaku-Ginseng-to, Keishikashakuyakudaioto, Keishikashakuyakuto, Keishikaryukotsu-oyster, Keishijinjinto, Keisuito, Kenchu-to, Kosago-Rikkunshi-to, Kosago-shito, Koboku ginger half-summer Ginseng kanzo-to, gorei-yu, goshoku-san, gorei-san, saiko-karyukotsu-oyster-tou, saiko-keishi-kanzoku-to, saiko-keishi-to, saishakurokukuniko-to, saikorei-to, sojuninito, shigyakusan , Shikimiko-to, Shiryo-to, Ginger Ginseng-to, Kokenchu-to, Kosaiko-to, Kohankaka-Kairei-to, Sanrei-Hakushu-san, Shinbu-to, Daikenchu-to, Taikininko, Dai-Saiko-yu, Most of Natsuyu, Nichenyu, Ginseng hot spring, Hangekobokuyu, Hangeshashinto, Hangeka Sakushu Tenmayu, Fukakin Seisan, Furei-in, Kairei-inhansai-koin, Keireisawayu, Hiraisan, Yokukan. Select from the group consisting of Sansan, Yokukansanka Hempenka, and Rikkunshito At least one and dry aluminum hydroxide gel, magnesium aluminate silicate, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, magnesium hydroxide alumina, aluminum hydroxide gel, aluminum hydroxide / carbonic acid Sodium hydrogen coprecipitation product, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / magnesium carbonate / calcium carbonate coprecipitation product, magnesium hydroxide, sodium hydrogen carbonate,
At least one selected from the group consisting of magnesium carbonate, magnesium aluminometasilicate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, crow bones, stone determination, oysters, aminoacetic acid, and dihydroxyaluminum aminoacetate. The composition according to any one of (1) to (5) above,

(7) Herbal medicines having a stomachic effect include anise fruit, aloe, scent, euphoria, mulberry, enmeisou, and scuttlefish (scut).
ellariae radix), yellow oak, yellow ream, processed garlic, incense (po
gostemiherba), Karamus root, psoriasis, pickled husk, corn, cinnamon bark, gentian, ginseng, cabbage, gourd mushroom, pepper, colombo, conzulango, sansho, yamana, perilla, curd sand, ginger, ginger, azuku, stone sardine , Centaurium grass, senburi, soyaku, soba, large incense, large yellow, bamboo shoot carrot, Ding,
Chen peel, chili pepper, spruce, animal gall, oyster, nutmeg, carrot, light weight, hihatsu, white jelly, hops, homika extract, hyacinth leaf, woody incense, michichi, gall, ginger, lemon oil, 1-menthol, and d1- At least one selected from the group consisting of menthol, wherein the intestinal regulating agent is at least one selected from the group consisting of intestinal viable bacterial components, red bud, Asenyaku, ume, ketsumeishi, and genosho. (2) The composition according to any one of (6), (8) d of carnitine chloride as an active ingredient for promoting gastric emptying.
At least one selected from the group consisting of body, l-body, and racemic body, and at least one selected from the group consisting of the following: a stomachic herb, licorice, cinnamon, gentian, and magnolia A group consisting of, sand sand, ginger, senburi, soy sauce, clove, crust, carrot, and ginger. Dry aluminum hydroxide gel, magnesium aluminate silicate, synthetic hydrotalcite, magnesium hydroxide, sodium bicarbonate. , Magnesium carbonate, precipitated calcium carbonate, magnesium aluminometasilicate, and dihydroxyaluminum aminoacetate As a digestive agent, starch digestive enzyme, protein digestive enzyme, fat digestive enzyme, and ursodeoxycholic acid group, and mucosal repair agent As azulene sulfonate sodium, aldioxa, copper chlorophyllin potassium And a pharmaceutical composition for improving gastric emptying according to the above (1), characterized in that a group consisting of sodium, methylmethionine sulfonium chloride, licorice, and sucrose sulfate aluminum salt is blended.

(9) Carnitine chloride 3-5 parts by weight, synthetic hydrotalcite 6-8 parts by weight, magnesium hydroxide 3
-5 parts by weight, dihydroxyaluminum aminoacetate (aluminum glycinate) 2-4 parts by weight, licorice powder 1-2 parts by weight, dried skin extract 1-2 parts by weight, soy sauce powder 1.5-2.5 parts by weight, thickness Pak dried extract 0.1-0.5
Parts by weight, ginger powder 0.5 to 1.5 parts by weight, clove powder 0.1 to
1.0 parts by weight, 3 to 5 parts by weight of synthetic aluminum silicate,
0.1 to 1.0 parts by weight of light anhydrous silicic acid, containing at least mannitol and sorbitol, or 3 to 5 parts by weight of carnitine chloride, 2 to 4 parts by weight of sodium hydrogen carbonate, 1 to 3 parts by weight of precipitated calcium carbonate, 1-3 parts by weight of magnesium aluminometasilicate, 1-2 parts by weight of oyster,
1-2 parts by weight of keel, 0.8-2 parts by weight of cinnamon, 0.5 ginseng
~ 1.5 parts by weight, lactic acid bacteria 0.1 to 0.2 parts by weight, red mega wrinkles 0.4 to 1.0 parts by weight, riboflavin 0.01 to
0.2 parts by weight, copper chlorophyll potassium 1-2 parts by weight,
It contains at least mannitol and sorbitol, or 2 to 4 parts by weight of carnitine chloride, 10 to 14 parts by weight of sodium hydrogen carbonate, 6 to 8 parts by weight of magnesium metasilicate aluminate, 2 to 4.5 parts by weight of magnesium carbonate, and cinnamon bark 5. ~ 7 parts by weight, fragrance 2-4 parts by weight, carrot 8 ~
17 parts by weight, assembly 0.1-0.6 parts by weight, compacted sand 3-
6 parts by weight, biodiastase (1000) 0.7-1.
5 parts by weight, lipase (AP6), crimped sand 3 to 6 parts by weight, aldioxa 1 to 2 parts by weight, mannitol and sorbitol at least, and the gastric emptying ability improving property according to (1) above. A pharmaceutical composition is provided.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention provides a pharmaceutical composition for improving gastric emptying, which comprises carnitine chloride. As the carnitine chloride used in the present invention, a racemic body which is commonly used can be used, but d-form, l-form or a mixture thereof may be used. There is no particular limitation. Furthermore, the present inventors, in the process of developing a gastric emptying ability improving pharmaceutical composition containing carnitine chloride having such an action, for the purpose of sufficiently obtaining a more preferable action for the above-mentioned pathological conditions, Excellent safety due to the combination of existing ingredients widely used in gastrointestinal medicine
We have succeeded in developing a pharmaceutical composition with an excellent scent. That is, the present invention also relates to a gastric emptying-improving pharmaceutical composition comprising carnitine chloride. Such a pharmaceutical composition of the present invention has an excellent action of improving a decrease in gastric emptying ability, and is excellent in improving a decrease in gastric emptying ability due to a depressive state which is associated with stress / anxiety. The pharmaceutical composition of the present invention further comprises a herbal medicine having an effect on symptoms of the digestive organs, a crude drug having a stomachic effect, other crude drugs, an intestinal preparation, an antacid, a digestive agent, an antidiarrheal agent, an analgesic / spasmodic agent, and mucosal repair. Agents, Chinese herbs and the like can be combined with carnitine chloride. A sweetener can be further added to the pharmaceutical composition of the present invention. In addition, at least one selected from the group consisting of flavoring agents, flavoring agents, flavoring agents, aromatic agents, coloring agents and excipients can be further added to the pharmaceutical composition of the present invention. In particular, the drug used for the above-mentioned symptoms should be satisfying such as a feeling of ingestion such as refreshing by taking it when taking it, that the mood is improved, or that residual scent is preferable, taste, etc.
Even in this respect, it has an unexpected action effect, that is, an action effect that is excellent in ingestion sensation such as taste, scent, texture, sensation, and residual aroma.

[0010] Examples of Kampo medicines having effects on digestive organ symptoms include Anchu-san, Kosandaira-san, Santo-futo, Gyorei-to, Uncho-to, Enenhanka-to, Ogo-goto, Oren-gedoku-to, Oren-to, Kyokuyo-sui-to, Kakko-shoiki-san, Kakkon-Oren-go-to, Kami-nen-to, Kami-kihi-to, Kami-hiragasi-san, Ginseng Ginsengmaru, Licorice Rishinto, Kihito, Keishikashiyakuyaku ginger ginseng, Keishikashakuyakudaioto, Keishikashiyakuyu, Keishikaryukyo oyster, Keishininjinto, Keisuito, Kenchutou, Kosago Rikkunshito, Kosago Yoshoto, Koboku ginger half summer ginseng licorice, Kureiyu, Goshokusan, Goreisan, Saiko Karyu Oyster oyster, Saiko Keishi ginseng, Saiko Keishito, Shiba sage Rikkunshiyu,
Sarei-to, Soto-nin-to, Shigyaku-san, Shikunshi-to, Shiryo-to, Ginger Ginseng-yu, Kokenchu-to, Shosaiko-to, Kohankaka-Kairei-to, Sanrei-Shirayu-san, Shinbu-yu, Daikenchu Hot water, anti-gold drink, Daisaiko hot water, most summer hot water, Nichinyu hot water, carrot hot water, half summer koboku hot spring, half summer shinshin hot water, half summer white shakutenmayu, fiat money Seikansan, 茓 萓 萓, 茯苓 洗 合 Halfsummer hot spring. Hot water, Keireizawa-reiyu, Hiraishan, Yokukansan, Yokukansan Kachinsemihanka,
And those selected from the group consisting of Rikkunshito. In addition, since the Kampo medicine which is a mixture of crude drugs has different activities and ingredients from the crude drug alone, they are treated as different in this application.

As the herbal medicines, Anchu-san, Hira-to-san, Kosana-hira-to-san, Shinbu-to, Shikunshi-to, Ginger-soshin-to, Ginseng-to, Hange-Sakushuten-Ama-to, Hange-soshin-to, Keiryo-in, Roku Kimiko-to, Kimin-inko, etc. are mentioned as particularly preferable prescriptions, and it is possible to obtain a medicinal composition which is excellent in refreshing feeling upon or after taking, and in taking feeling such as overall taste and aroma. These are preferably used in the form of powder, extract, extract powder, or extract-adsorbed powder. In particular, the pharmaceutical composition obtained by blending Anchu-san, Kosang-hiragyo-san, etc. in combination with carnitine chloride is also excellent in refreshing feeling at the time of or after taking, and overall feeling of taste and aroma. ing. The Kampo medicine used in the present invention is a commonly used formulation prepared by a conventional method. Anchusan includes, for example, Keishi, Enryaku, Oyster, Incense, Cured Sand, Licorice, and Ginger,
Depending on the case, it is a mixture of peony, which is, for example, 3-5 Katsura, 3-4 Enryaku, 3-4 oysters, 1.5-smell scent.
2, crimped sand 1-2, licorice 1-2, and ginger 0.5-1 and, in some cases, 而 苓 5, but the blending ratio of the ingredients varies within the allowable range beyond the above range. It can be used. Kasandaira-san is, for example, 朮, Kabushi, Koboku,
Ginger, Chen skin, large jujube, licorice, and curd sand, and in some cases, incense (pogostemi herba) is mixed, and the combination is, for example, 4 to 6, Kazushi 2 to 4, Koboku 3 to 4.5, Ginger 2
~ 3, Chen skin 3 ~ 4.5, Oomu2 ~ 3, Licorice 1 ~ 1.5,
And, it is assumed that the condensed sand is 1.5 to 2 and, in some cases, the incense 1, but the compounding ratio of the components can be varied within the allowable range beyond the above range.

As the antacid, dried aluminum hydroxide gel, magnesium aluminate silicate, magnesium silicate, synthetic aluminum silicate, hydrotalcite, magnesium hydroxide, magnesium hydroxide alumina, aluminum hydroxide gel, hydroxide Aluminum / sodium hydrogen carbonate coprecipitation product, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / magnesium carbonate / calcium carbonate coprecipitation product, magnesium oxide, sodium hydrogen carbonate, magnesium carbonate, magnesium aluminometasilicate, There may be mentioned those selected from the group consisting of anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, squid bones, Ishigaki, oysters, aminoacetic acid, and dihydroxyaluminum aminoacetate. Among them, preferable compounds such as dried aluminum hydroxide gel, synthetic hydrotalcite, magnesium oxide, magnesium hydroxide, sodium hydrogen carbonate, magnesium carbonate, precipitated calcium carbonate, magnesium aluminometasilicate, and dihydroxyaluminum aminoacetate are preferred as antacids. As. Dihydroxyaluminum aminoacetate is mentioned as a particularly preferred compound. These antacids may be used alone or in combination of two or more, and preferably used in combination.

When hydrotalcite and dihydroxyaluminum aminoacetate are used in combination, high antacid and fast-acting properties are obtained, and side effects are suppressed. In other words, it can be dissolved in the acidic region to quickly neutralize stomach acid, and the increase in pH can be suppressed in the neutral region. Furthermore, a more preferable effect can be obtained by adding a fast-acting antacid component such as magnesium hydroxide to the above two components. Hydrotalcite belongs to the basic carbonate of magnesium and has the characteristic that it is highly durable in terms of antacid. The hydrotalcite may be either natural or synthetic. Preferred hydrotalcites include synthetic hydrotalcites. Examples of the synthetic hydrotalcite include those sold under the trade name Alkamak (Kyowa Chemical Co., Ltd.).
A typical hydrotalcite has the composition formula Mg ₆ Al ₂
(OH) ₁₆ CO ₃ , at least part of Al is F
It may be substituted with another metal such as e. Hydrotalcite may be used as a mixture of hydrotalcite containing Al and hydrotalcite containing another metal such as Fe in the above formula. Dihydroxyaluminum aminoacetate has the characteristic of exhibiting a long-lasting antacid effect. Dihydroxyaluminum aminoacetate is, for example, a product name glycinal (Kyowa Chemical Co., Ltd.)
The commercially available products are listed.

When hydrotalcite and dihydroxyaluminum aminoacetate are blended and used, it is preferable to select the blending amount of both so as not to impair the antacid and fast-acting properties. For example, hydrotalcite / dihydroxyaluminum aminoacetate = 30. / 70-90 / 10
(Weight ratio), preferably 40/60 to 80/20 (weight ratio), and more preferably about 45/55 to 70/30 (weight ratio). The fast-acting antacid component can be preferably added to the above two components, and examples of such a fast-acting antacid component include magnesium hydroxide, magnesium oxide, magnesium carbonate, sodium carbonate, sodium hydrogen carbonate and the like. These can be used alone or in combination of two or more. The preferred fast-acting antacid component includes magnesium hydroxide. Examples of magnesium hydroxide include those commercially available under the trade name Kyowa Suimag (Kyowa Chemical Co., Ltd.).
The fast-acting antacid component is preferably selected so as not to impair the fast-acting property. For example, 10 to 50% by weight, preferably about 20 to 40% by weight is selected in the total amount of the antacid component.

Crude drugs which can be incorporated in the preparation of the present invention include:
For example, those known as those having psychotropic action, those known as those having stomachic action, those known as sweet crude drugs, pungency crude drugs, bitter crude drugs, aromatic crude drugs and the like can be mentioned. Examples of the crude drug having a psychotropic action include oysters, keels, enthusiasts, koboku, tenma, tiannansei, agarwood, gyozato, sonojutsu, chrysanthemums and the like. Examples of the crude drug having a stomachic effect include anise fruit, aloe, scent, depression,
Oyaku, Enmeisou, Yellow sardine (scutellariae radix), Yellow oak,
Yellow lantern, processed garlic, cucumber (pogostemi herba), columbus root, ginkgo, husk, corn, cinnamon, gentian, ginger, cabbage, ginger, walnut, pepper, colombo, konzurango, sansho, yamana, shiso, curly Sand, ginger, oleander, blue skin, iris root, centaurium grass, senburi, soy sauce, soybean leaf, large incense, rhubarb, bamboo ginseng, clove, rind, chili pepper, spruce, animal gall, bittern, nutmeg, carrot, light load, hihatsu, White,
Examples include those selected from the group consisting of hops, homica extract, hyacinth leaves, woody incense, michichi, gall, ginger, lemon oil, 1-menthol, and d1-menthol.
Preferred examples include gentian, koboku, crimped sand, ginger, senburi, soy sauce, Ding, rind, carrot, and ginger.

[0016] Examples of the sweet crude drug include sweet tea powder, licorice and the like. Examples of the aromatic crude drug include scent, cinnamon, lightly-packed scent, and scent. These crude drugs are
It can be used as an extract or powder. The galenical component may be in the form of a dip, a decoction, a tincture, a flow extract and the like. The digestive agents include starch digestive enzymes, protein digestive enzymes,
Fat digestive enzymes, fibrin digestive enzymes, ursodeoxycholic acid, oxycholanic acid hydrochloride, cholic acid, bile powder, bile extract, dehydrocholic acid, animal gall, etc., such as starch digestive enzymes, protein digestive enzymes, fats. Enzymes such as digestive enzymes, fibrin digestive enzymes and ursodesoxycholic acid are mentioned as preferred components. Examples of the enzyme include diastase, pancreatin, pepsin, β-galactosidase, amylase, protease, lipase,
Cellulase and the like can be used, and those derived from animals, plants, and microorganisms can be appropriately used.

Examples of the intestinal regulating agent include live intestinal bacterium components, red bud,
Examples thereof include those selected from the group consisting of Asenyaku, Karasume, Ketsumeishi, Genshosho, and the like, and for example, a component of live intestinal rectifying bacteria and Akarashi Kashiwa are more preferable components. Examples of the intestinal viable bacteria component include, for example, multidrug-resistant Lactobacillus
Examples thereof include a live bacterial preparation of Acidophilus, a live bacterial preparation of Streptococcus faecalis, a live bacterial preparation of resistant lactic acid bacteria, a dry live bacterial preparation of Lactobacillus bifidus, and an anti-septic butyric acid spore preparation.

Examples of antidiarrheal agents include acrinol, berberine chloride, guaiacol, gleosort, phenyl salicylate, guaiacol carbonate, berberine tannate, bismuth subsalicylate, bismuth subnitrate, and bismuth subcarbonate.
Bismuth subgallate, tannic acid, albumin tannate, methylene thymol tannin, kaolin, natural aluminum silicate, aluminum hydroxynaphthoate, pectin, medicinal charcoal, precipitated calcium carbonate, calcium lactate, calcium hydrogen phosphate, Asan medicine, ume, Examples include yellow oak, yellow lantern, bitter gourd, ginseng, genus ginseng, quintet, yamabiko, senburi, eubayich, and the like, and preferred examples include berberine chloride, phenyl salicylate, berberine tannate, gennoshoko, quintet, and eubayich. Examples of the analgesic and antispasmodic include papaverine hydrochloride, ethyl aminobenzoate, chopped cord, licorice, magnolia, peony and the like. Papaverine hydrochloride and chord cord are preferable components.

Examples of mucosal repair agents include sodium azulene sulfonate, aldioxa, glycyrrhizic acid and salts thereof, licorice extract, L-glutamine, potassium copper chlorophyllin, sodium copper chlorophyllin, histidine hydrochloride, porcine stomach wall pepsin decomposition product, and porcine stomach wall acid. Hydrolyzate, methylmethionine sulfonium chloride, red bud, Encho, licorice, sucrose sulfate aluminum salt (sucralfate), cetraxate hydrochloride, sulfurcon, ornoprostil, sulpiride, cyclohexanecarboxylic acid esters such as cetraxate hydrochloride, gefarnate, teprenone , Terpenoid compounds such as plaunotol, aceglutamide aluminum, methylmethionine sulfonium chloride, and the like. For example, sucrose sulfate ester Aluminum salt (sucralfate), cetraxate hydrochloride azulene sulfonate sodium, aldioxa, copper chlorophyllin potassium, methylmethionine sulfonium chloride, licorice, sucrose sulfate aluminum salt (sucralfate), cetraxate hydrochloride, glycyrrhizic acid and salts thereof are particularly preferred compounds. As.

As the sweetener, mannitol (mannitol), glucose (glucose), maltose (maltose), starch syrup, malt extract, maltitol, sorbitol (sorbit), white sugar, brown sugar, fructose, lactose, honey,
Xylitol, licorice, licorice, glycyrrhizic acid, saccharin, aspartyl phenylalanine ester, and other such oligosaccharides such as maltooligosaccharide, maltosyl sucrose, fructooligosaccharide, lactulose, isomaltose, isomaltulose, reduced isomaltulose, and raffinose. Is mentioned. Preferred examples include mannitol (mannitol), sorbitol (sorbit), licorice, licorice extract, glycyrrhizic acid, and licorice powder. Mannitol (mannitol), sorbitol (sorbit) and the like are particularly preferable.

The composition of the present invention comprises tablets, powders, fine granules,
Oral solid preparations such as granules, suspensions, troches, capsules, chewable preparations and liquid preparations including elixirs, syrups and the like can be prepared. Particularly, for improving chronic gastrointestinal symptoms such as stomach pain, heartburn, nausea / vomiting, stomach upset, and stomach weight, powders, granules and the like can be used from the viewpoints of immediate effect, feeling of administration and the like. Chewable agents and the like are also preferable formulation forms. With powders, granules, chewable agents, etc., it is possible to provide a formulation excellent in refreshing feeling upon or after taking, and overall feeling such as taste and aroma.

These preparations can be carried out by any of the methods known in the art, conventional methods and ordinary methods depending on the preparation form, and preparations of various forms can be prepared. You can As a reference, edited by Yoshinori Nakai, Development of Pharmaceuticals, Volume 11, "Unit Operation and Machines for Pharmaceuticals", Hirokawa Shoten Co., Ltd., All descriptions issued and cited therein. Can be mentioned. Powdered and granular preparations such as powders, fine granules and granules can be appropriately prepared according to the purpose in consideration of properties such as dispersibility and adhesiveness. For example, in consideration of physical properties such as bulk, scattering, adhesion, hygroscopicity, chargeability, wettability and solubility, particle size, surface area, shape, etc. of powder, sustained action of drug, sustained release of drug It is preferable to prepare the compound after considering its ability and bioavailability.

The particle size of the granular drug is not necessarily small, and it is convenient for handling, moisture absorption, decomposition, deterioration,
In order to prevent discoloration and the like, it is preferable to adjust the size of the particles to a certain size. Grinding is generally carried out for the preparation of the powder, and mechanical operations are generally carried out so as not to give a negative influence such as alteration to the material. For the crushing operation, use an appropriate crushing method depending on the physical properties such as hardness, brittleness, presence of fibrous tissue, water content, etc. of the raw material, the size of the raw material, the size of the target crushed product, and the amount to be handled. You can choose and do it. As the pulverizing method, a dry pulverizing method, a wet pulverizing method, a low temperature pulverizing method, a jet pulverizing method, a batch pulverizing method, a continuous open circuit pulverizing method, a continuous closed circuit pulverizing method, etc. are known. They can be selected or combined depending on the purpose.

In the preparation of the preparation, if necessary, grouping may be carried out in order to stabilize the active ingredient. The term "grouped compounding" as used herein refers to a method in which components having poor mixability are separately granulated and then compounded later to reduce the contact area of the components and stabilize them. When mixing or blending the powdered ingredients, the ingredients should be screened (classified) so that they can be mixed evenly with each other so that the particle size of each ingredient to be mixed is as uniform as possible. Alternatively, crushing, mixing, and sieving may be repeated, or these operations may be arbitrarily selected and combined, and may be performed sequentially or simultaneously. In the case of crude drug raw materials, there are cases where there are portions that are easily crushed and portions that resist fibrous or woody hard crushing, so sufficient mixing treatment can be appropriately performed.

In preparing the preparation, diluents such as fillers, fillers, binders, excipients, moisturizers, disintegrants, surfactants, lubricants, sustained-release agents and the like which are usually used, Excipients can be used. Other solubilizers, buffers, preservatives, solubilizers, isotonic agents, emulsifiers, suspending agents, dispersants, thickeners, gel agents, curing agents, absorbents, adhesives, if necessary. , Elastic agents, plasticizers, adsorbents, fragrances, coloring agents, flavoring agents,
Antioxidants, preservatives, humectants, light-shielding agents, brighteners, antistatic agents, coating agents and the like can be used. More specifically, as excipients, lactose, corn starch, mannitol, D-sorbitol, crystalline cellulose, erythritol, sucrose, etc., as binders, hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose, polyvinylpyrrolidone, methylcellulose, pregelatinized. As a disintegrant such as starch, carmellose calcium, croscarmellose sodium, cross-linked polyvinylpyrrolidone and the like, as a lubricant magnesium stearate, talc and the like, and as a fragrance, 1-menthol, vanillin, lemon oil, cinnamon oil, peppermint Flavors such as oils and aromatic oils can be mentioned, preferably 1-menthol and the like, and it is preferable to add synthetic aluminum silicate, light anhydrous silicic acid, porous calcium silicate or the like as an adsorbent. The formulation of the present invention can also be a coating formulation. The coating can be performed by a known method,
As the coated tablet, a commonly used coating agent (for example, hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, polyvinylpyrrolidone, etc.) is used. In coating, a coating aid may be used by a conventional method, and as such a coating aid, pigments such as polyethylene glycol 6000, polysorbate (for example, Tween 80, etc.), titanium oxide, red iron oxide and the like are used.

In the present invention, preferably, (1) at least one selected from the group consisting of d-form, l-form and racemic carnitine chloride as the gastric emptying-promoting active ingredient, and the following (2)-( At least one selected from the group consisting of 5): (2) As a gastric herbal medicine, licorice, cinnamon, gentian, magnolia,
A group consisting of crimped sand, ginger, assembly, soy sauce, clove, crust, carrot, and ginger (3) Dry aluminum hydroxide gel, magnesium aluminate silicate, synthetic hydrotalcite, magnesium hydroxide, carbonic acid as an antacid Group consisting of sodium hydrogen, magnesium carbonate, precipitated calcium carbonate, magnesium aluminometasilicate, and dihydroxyaluminum aminoacetate (4) Composed of starch digestive enzyme, protein digestive enzyme, fat digestive enzyme, and ursodesoxycholic acid as digestive agent group,
(5) A gastric emptying-improving pharmaceutical composition containing a group consisting of sodium azulene sulfonate, aldioxa, potassium copper chlorophyllin, methylmethionine sulfonium chloride, licorice, and sucrose sulfate aluminum salt as a mucosal repair agent. It
The respective active ingredients of (2) to (5) can be blended with each other. An antidiarrheal agent, a mucous membrane repair agent, and the like can be added to these, and also known as adsorbents and coating agents can be added. Pharmaceutical compositions which additionally contain a sweetening agent, for example at least one selected from the group consisting of mannitol, maltose, sorbitol and honey, are preferred. These gastric emptying ability-improving pharmaceutical compositions are also excellent as compositions for improving the decrease in gastric emptying ability due to a depressive state that can appear with stress / anxiety. These combination products are extremely safe, have few side effects, and
It excels in the action of actively expelling gastric contents into the intestinal tract, has a prompt effect of improving depressive symptoms, and is well-balanced in the feeling of exhilaration at the time of or after taking the drug and the overall taste and aroma. , Shows excellent properties.

In the present invention, in particular, (1) at least one selected from the group consisting of d-form, l-form and racemic carnitine chloride as the gastric emptying-promoting active ingredient; At least one selected from the group consisting of cinnamon bark, gentian, koboku, crimped sand, ginger, senburi, soy sauce, clove, chin peel, carrot, and ginger, (3) dry aluminum hydroxide gel as an antacid, At least one selected from the group consisting of magnesium aluminate silicate, synthetic hydrotalcite, magnesium hydroxide, sodium hydrogen carbonate, magnesium carbonate, precipitated calcium carbonate, magnesium aluminometasilicate, and dihydroxyaluminum aminoacetate, ( 4) Starch-digesting enzymes, protein-digesting enzymes, fat-digesting enzymes, and Ursodes oxycord as digestive agents At least one selected from the group consisting of acids, and (5) a mucosa repairing agent comprising sodium azulene sulfonate, aldioxa, copper chlorophyllin potassium, methylmethionine sulfonium chloride, licorice, and sucrose sulfate aluminum salt. Including at least one selected, further sweeteners such as mannitol, maltose, sorbitol,
And a gastric emptying-improving pharmaceutical composition containing at least one selected from the group consisting of honey and honey. It is also excellent as a composition for improving a decrease in gastric emptying due to a depressive state that may appear with stress / anxiety. These combination products are extremely safe, have few side effects, are excellent in the action of actively expelling gastric contents into the intestinal tract, have a prompt depressive symptom-improving action, and are refreshing during or after administration. It has a good balance of feeling, overall taste, aroma and other ingestion feeling, and exhibits excellent properties.

Particularly (1) 3-5 parts by weight of carnitine chloride,
Synthetic hydrotalcite 6-8 parts by weight, magnesium hydroxide 3-5 parts by weight, dihydroxyaluminum aminoacetate (aluminum glycinate) 2-4 parts by weight, licorice powder 1-2 parts by weight (or licorice dry extract 0.8- Two
Parts by weight; 4 to 6 parts by weight of the crude drug equivalent), dried skin extract 1
~ 2 parts by weight (10 to 14 parts by weight of crude drug equivalent), Soso powder 1.5 to 2.5 parts by weight (or soybean dry extract 0.1)
.About.0.5 parts by weight; 1.5 to 3 parts by weight of crude drug, 0.1 to 0.5 parts by weight of dried magnolia extract (2 to 3 parts by weight of crude drug), ginger powder 0.5 to 1 .5 parts by weight (or 0.05 to 0.4 parts by weight of ginger dried extract;
2 parts by weight), the end of the letter 0.1 to 1.0 parts by weight, 3 to 5 parts by weight of synthetic aluminum silicate, and light anhydrous silicic acid 0.1 to
1.0 parts by weight, a pharmaceutical composition comprising mannitol and sorbitol, and (2) 3 to 5 parts by weight of carnitine chloride, 2 to 4 parts by weight of sodium hydrogen carbonate, 1 of precipitated calcium carbonate.
~ 3 parts by weight, magnesium aluminometasilicate 1-3
Parts by weight, oysters 1 to 2 parts by weight, keel 1 to 2 parts by weight, cinnamon bar 0.8 to 2 parts by weight, ginseng 0.5 to 1.5 parts by weight, lactic acid bacteria 0.1 to 0.2 parts by weight, red agate wrinkles 0 4 to 1.0 parts by weight, riboflavin 0.01 to 0.2 parts by weight, copper chlorophyll potassium 1 to 2 parts by weight, a pharmaceutical composition comprising mannitol and sorbitol, or (3) carnitine chloride 2 to 4 parts by weight. , Sodium hydrogencarbonate 10 to 14 parts by weight, magnesium metasilicate aluminate 6 to 8 parts by weight, magnesium carbonate 2 to 4.5 parts by weight, cinnamon bark 5 to 7 parts by weight, incense 2 to 4 parts by weight, carrot 8 to 17 parts by weight. Parts, assembly 0.1 to 0.6 parts by weight, compressed sand 3 to 6 parts by weight, biodiastase (1000) 0.7 to 1.5 parts by weight, lipase (AP6), compressed sand 3 to 6 parts by weight, aldioxa 1-2 parts by weight, mannitol and Pharmaceutical composition comprising sorbitol, and refreshing feeling after ingestion or during taking the overall flavor, balanced in ingestion feel such as smell, it shows excellent properties. It is also excellent as a composition for improving a decrease in gastric emptying due to a depressive state that may appear with stress / anxiety.

The present invention relates to carnitine chloride and one or more active ingredients selected from antacids, herbal medicines, digestive agents, intestinal preparations, antidiarrheals, analgesic / spasmodic agents and mucosal repair agents, or at least one or more Kampo medicines or a combination thereof. Disclosed is a composition containing a Chinese herb medicine, which improves the reduction of gastric emptying due to a depressive state that may appear with stress / anxiety. The gastric emptying promoting action of carnitine chloride can be confirmed by animal experiments as follows. As a gastric emptying test animal evaluation system, a gravimetric method of barium sulfate liquid diet in rats and a dog gastric motility measuring method equipped with a chronic strain gauge can be used. These methods are generally used, and for example, as a model for gastric emptying ability reduction, a drug can be evaluated using an experimental animal (rat, dog) pretreated with atropine. In addition, use of an experimental system capable of evaluating gastric emptying ability is not hindered. As a result, the carnitine chloride 100 mg / kg oral administration group has a higher gastric emptying enhancing effect as compared with the non-administration group. The effects on the depressive symptoms that are the cause of decreased gastric emptying can also be examined using the forced swimming test animal evaluation system. Evaluation is, for example, 0 to 5 minutes after drug administration, and 5
It can be performed at 3 points for 10 minutes and 10 to 15 minutes, and can be performed by measuring the rat immobility time at each evaluation time. The immobility time (mean ± standard error) of the carnitine chloride non-administered group at each evaluation time was 41.9 ±
7.7 seconds, 120.7 ± 20.5 seconds, 165.3 ± 2
0.8 seconds, whereas carnitine chloride 100 mg
/ Kg oral administration group, 33.7 ± 8.7 seconds, 82.9 ±
The results are 12.8 seconds and 125.8 ± 16.9 seconds, which shows that the immobility time of the rat is shortened and that carnitine chloride suggests an antidepressant action.

From these results, it is considered that carnitine chloride can be expected to relieve depressive symptoms due to antidepressant action and improve symptoms due to gastric emptying enhancing action, and is highly useful for the above-mentioned pathological conditions. In other words, it can be expected to be effective in treating gastrointestinal symptoms such as “stomach pain” and “heartburn”, and digestion caused by stress, anxiety, overeating, excessive alcohol intake, and drug administration. It can be used for the improvement of organ symptom, and is depressed due to stress / anxiety caused by work and social environment, and side effects caused by taking drugs, which causes stomach pain, heartburn, nausea / vomiting, stomach upset, stomach weight, etc. Improvement of chronic gastrointestinal symptoms
It can be used as a therapeutic agent. In particular, it can be used for symptoms such as upper abdominal indefinite complaints typified by symptoms such as "stomach leaning" and "stomach weight", and those caused by decreased gastric emptying ability. . Carnitine chloride has an action of normalizing a state of decreased digestive function, and can be expected to further have antidepressant-like anti-fatigue effect, enhance gastrointestinal function such as gastric emptying, improve mild psychosomatic disorder,
Further, it can be used for treating gastritis due to mild psychosomatic disorder, treatment of mental and physical stress, weakness and malaise due to psychosomatic stress, etc. As an active ingredient used in combination with carnitine chloride, antacids, crude drugs, digestive agents, intestinal agents, antidiarrheals,
Examples include analgesic / spasmodic agents, mucosal repair agents, Chinese herbal medicines, etc., and it is preferable to use one or more of these. The compounding amount of carnitine chloride is 30 to 1,200 mg per day for an adult, and preferably 60 to 600 mg. The active ingredients other than carnitine chloride include antacids, crude drugs, digestive agents, intestinal agents, antidiarrheals, analgesic / spasmodic agents, mucosal repair agents, herbal medicines and the like.

[0031]

EXAMPLES Examples of formulation of the present invention will be specifically described below, but the present invention is not limited to the following examples. [Example 1] Tablet (daily dose) Carnitine chloride 450 mg Dried extract 20 mg (amount of crude drug equivalent 240 mg) Ginger extract 10 mg (amount of original drug equivalent 100 mg) Soujutsu dry extract 60 mg (amount of original drug equivalent 200 mg) Clove powder 30mg Chinpi dry extract 150mg (raw drug equivalent 1,200mg) Synthetic hydrotalcite 700mg Magnesium hydroxide 450mg Dihydroxyaluminum aminoacetate 300mg Licorice dry extract 125mg (raw drug equivalent amount 500mg) Synthetic aluminum silicate 350mg Light anhydrous silicic acid 79.5mg Ac -Di-Sol 1,199.5mg Constarch 164mg HPC-L 120mg 1-Menthol 13mg Magnesium stearate 19mg

In a kneader (manufactured by Hata Tekko Co., Ltd.), 350 g of powder of synthetic aluminum silicate and 30 g of powder of light anhydrous silicic acid were charged, and 450 g of d1-carnitine chloride.
Is dissolved in 240 ml of water and adsorbed on the powder. After drying this with a vacuum dryer (Kusu Seisakusho),
It is pulverized using an atomizer (Fuji Paudal; KII-2) to produce an adsorption powder (preformulation). The adsorption powder 830
g, light anhydrous silicic acid 49.5 g, synthetic hydrotalcite (VF) 700 g, magnesium hydroxide 450 g, dihydroxyaluminum aminoacetate 300 g, licorice dry extract 125 g, chimpi dry extract 150 g,
Sojutsu dried extract 60g, Koboku dried extract 20
g, dried ginger extract 10g, clove powder 30
g, Ac-Di-Sol 99.5 g, Constarch 1
64 g and HPC-L 120 g are granulated using a high speed mixer (manufactured by Fukae Kogyo). This is dried with a flow coater (Freund) and then sized with a power mill (P-3S, Showa Kagaku Kikai). 1-menthol 1 at the end of sizing
Perfume with 3 g of dissolved alcohol. To 3,031 g of this sized powder, 19 g of magnesium stearate (lubricant) and 1,100 g of Ac-Di-Sol were added and a tumbler mixer (TM-1 manufactured by Showa Kagaku Kikai) was added.
Mix in 5). Using a rotary tablet machine (Correct 19k manufactured by Kikusui Seisakusho Co., Ltd.), 9,000 tablets are produced using a 9.5 mmφ ordinary surface.

Example 2 Synthetic aluminum silicate, light anhydrous silicic acid, HPC-
L, cornstarch, actisol (Ac-Di-So
1) and magnesium stearate are blended as in Example 1 to give tablets of the invention. Prescription: Adults in 9 tablets per day d1-carnitine chloride 450 mg Sodium hydrogencarbonate 300 mg Precipitated calcium carbonate 200 mg Magnesium aluminometasilicate 200 mg Oyster 150 mg Keels 150 mg Cinnamon 120 mg Ginseng 100 mg Lactomin (lactic acid bacteria) 18 mg Red sprout wrinkle extract (extracted from 520 mg red bud) 65mg Riboflavin 6mg Copper chlorophyllium potassium 150mg

[Example 3] Powder (daily dose) Carnitine chloride 450 mg Dried extract 20 mg (amount of crude drug equivalent 240 mg) Ginger end powder 100 mg Soujutsu end 200 mg Clove powder 30 mg Chinpi dry extract 150 mg (amount crude drug equivalent 1,200 mg) Synthetic hydrotalcite 700 mg Magnesium hydroxide 450 mg Dihydroxyaluminum aminoacetate 300 mg Licorice powder 150 mg D-sorbitol 1,000 mg Mannitol 74 mg Synthetic aluminum silicate 450 mg Light anhydrous silicic acid 25 mg HPC 80 mg 1-Menthol 16 mg

A kneader (manufactured by Hata Tekko Co., Ltd.) was charged with 450 g of a powder of synthetic aluminum silicate and 25 g of a powder of light anhydrous silicic acid, and 450 g of d1-carnitine chloride.
Was added to 700 ml of water and adsorbed on the powder. This was dried with a vacuum dryer (manufactured by Kusunoki Seisakusho) and then pulverized using an atomizer (manufactured by Fuji Paudal; KII-2) to produce an adsorbed powder (preformulation). The adsorption powder 92
5g and synthetic hydrotalcite (VF) 700g, magnesium hydroxide 450g, dihydroxyaluminum aminoacetate 300g, licorice powder 150g, chinpi dry extract 150g, Soujutsu powder 200g, Koboku dried extract 20g, ginger powder 100g, clove powder 30g, D -Sorbitol (1,000 g), mannitol (74 g) and HPC (80 g) were placed in a vertical granulator FM-G25 (manufactured by Paulec) and mixed, and then an alcohol in which 1-menthol (16 g) was dissolved was added for granulation. Then, after drying using a fluidized bed dryer FD5S (manufactured by Paulec), 5 g of light anhydrous silicic acid as a fluidizing agent was added to and mixed with the sieved product to obtain 4,200 g of a product.

[Example 4] [Sensory evaluation test] Example 3 was conducted by five expert panelists.
A sensory comparison was performed to compare the powder prepared in 1. with a formulation lacking a galenical component. The comparative drug product is carnitine chloride 450 mg, synthetic hydrotalcite 700 mg, magnesium hydroxide 450 mg, dihydroxyaluminum aminoacetate 300 mg, D-sorbitol 1,000 mg, synthetic aluminum silicate 450 mg, light anhydrous silicic acid 25 mg, HPC. With respect to the comparative preparation, all five panelists evaluated that the taste was extremely sour and unacceptable, and the taken feeling was evaluated to be difficult due to its dry texture. Regarding the scent, it is said that it does not have a desirable scent. On the other hand, in the case of the powder prepared in Example 3, all five panelists evaluated that the taste, the scent, and the feeling of ingestion were very favorable. The sweetness is also evaluated to be favorable without any discomfort. Example 3
It has been evaluated that the powder prepared in (1) feels refreshed after taking.

[Example 5] [Pharmacological experiment 1] Gastric emptying promoting activity I. Experimental Materials and Experimental Methods 1 Experimental Materials As animals, 5-week-old or 8-week-old male SD rats (CLEA Japan, Inc.) and male Beagle dogs weighing 9.0-12.6 kg (OBC Co., Ltd.) were used. Drugs used in this experiment: carnitine chloride (DL body, Kongo Chemical), atropine (Wako Pure Chemical Industries). The drug was dissolved in distilled water or physiological saline and orally administered (0.5 ml / 100 g body weight) or intravenously injected (1.0 ml / 100 g body weight). 2 Experimental method (1) Effect on gastric emptying suppression rat by atropine Rat fasted for 24 hours (8 weeks old, 240 to 270 g)
Was used as 14 animals per group. Atropine (3mg / k
g, orally), and 60 minutes later, carnitine chloride (pH)
(Adjusted to 6.0-6.5) was orally administered. 60 minutes later, test meal was orally administered (3 ml / rat), and test m
60 minutes after the administration of eal, the animals were killed with carbon dioxide gas, the stomach was excised together with the contents, and the weight thereof was measured. Further, the stomach contents were washed out, the stomach weight was measured again, and the remaining amount of test meal was calculated. Gastric emptying capacity (%) is calculated by [(test meal weight-test meal remaining amount) / test meal weight] x 100.

(2) Effect on dog gastric motility The dog gastric motility was determined by the method of Inatomi et al. (Inatomi N, et a.
l., Journal of Pharmacology and Experimental Therapeutics (J. Pharm. Exp.
Ther.), 251: 707-712, 1989). Dogs are anesthetized with sodium pentobarbital (30 mg / kg, IV) and laparotomy is performed along the midline. Stomach pylorus (3 cm from the pylorus to the back of the mouth), duodenum (1 from the pylorus
Force tr to measure the cricoid muscle contraction on the serosal surface of the 0 cm tail) and jejunum (30 cm caudal from Treiz ligament)
ansducer (F-12.IS-60. Star Medical)
Attach. The lead wire and cannula of the force transducer were introduced from the back through the chest to the outside of the body. A postoperative jacket (Star Medical) was used to protect the surgical wound, leads and cannula. Two weeks after the operation, it was used in the experiment. Exercise in each part of the digestive tract pressure amps
It was recorded on a recorder (FW123701, Graphtec) by connecting to an lifier (PA-001, Star Medical). For quantitative analysis of gastric motility, the signal of the gastric pylorus was analyzed by a pressuer amplifier every 100 msec.
It was input to the gnal procerssor and the amount of exercise was measured every 10 minutes. The experiment was performed 2 hours after feeding 20 / kg of the solid food for dogs. The results are displayed with the exercise amount for 10 minutes before drug administration as 100%.

II. Results (1) Effect of atropine on suppression of gastric emptying in rats The gastric emptying of rats was reduced by about 40% by administration of atropine (3 mg / kg, orally) (33.0% ± 2.9: control group 54.1% ± 3.4) done. Carnitine chloride (30 and 1
As a result of administration (00 mg / kg, orally), gastric emptying showed a dose-dependent improvement effect (30 mg / kg administration group 4
0.0% ± 2.9, 100 mg / kg administration group 43.0
% ± 3.0), especially at an oral dose of 100 mg / kg, a significant improving effect was observed. The results are shown in Table 1 and FIG.

[0040]

[Table 1]

(2) Effect on gastric motility of dogs under treatment with atropine When 30 μg / kg of atropine sulfate was intravenously administered during the postprandial period, gastric and intestinal tract motility was strongly suppressed. The gastric motility gradually recovered, but the amount of motility before administration was not reached even after 90 minutes. Oral administration of carnitine chloride 100 mg / kg 20 minutes after the administration of atropine sulfate increased gastric motility, and after 10 minutes the change was significant (control group 15%
± 2, carnitine chloride 100 mg / kg administration group 41%
± 7), and thereafter, gastric motility was greater when carnitine chloride was administered than when it was not administered, but no significant difference was observed. The results are shown in Figure 2.

[Example 6] [Pharmacological experiment 2] Anti-fatigue action and antidepressant action The experimental materials were the same as those in the pharmacological experiment 1, and 5 animals were used as experimental animals.
A week-old or 8-week-old male SD rat (CLEA Japan, Inc.) was used. (1) Effect on rat forced swimming test The forced swimming test is performed by the method of Porsolt et al. (Porsolt, RD, e.
Tal., Nature, 266: 730-732, 1977), 1 group of rats (5 weeks old, 131 to 177 g)
Used as an animal. In a cylindrical glass beaker (5 liters) with a height of 40 cm and a diameter of 19.5 cm, a depth of 19.5 cm
Up to 25 ± 1 ° C. was added. The drug was orally administered, and one hour later, the animals were placed in cylindrical glass beakers one by one.
Immobility time (seconds) was measured at 15 minute intervals until after 15 minutes. The effect was determined by comparing the immobility time (second) in each 5 minutes of the control group and the drug administration group.

(2) Effect of the rat on the rotating rod method The rotating rod method is the method of Dunhan et al. (Dunhan, NW, et al.,
Journal of the American Pharmaceutical Association (J. Am. Pharm. Ass.), 4
6: 208-209, 1957), rat (5 weeks old, 12
9 to 162 g) was used as 6 animals per group. 6 animals per minute
5 per animal on a rotating wooden rod 1.2 cm in diameter
Randomly placed ~ 6 times. After that, the time (seconds) until the animal dropped from the rotating rod was measured, and the drug was orally administered by selecting an animal with a reaction time of 2 to 3 times being almost constant. 30 minutes, 1 hour, and 2 hours after drug administration, the time (seconds) until the animal fell from the rotating rod was measured. The time before the administration of the drug to the animals was set to 100%, and the effect of the drug was examined from the change rate between the control group and the drug administration group at each time. The maximum extension time was 180 seconds. Stunning comparison test of Dunnett's was used for statistical processing.

[Results] (1) Action on rat forced swimming test Carnitine chloride showed a tendency to shorten immobility time at a dose of 100 mg / kg orally administered. The results are shown in Fig. 3.

(2) Action on the rotating rod method in rats Carnitine chloride was administered at 30 mg / kg orally and 10 times.
It showed a dose-dependent increasing effect on the rate of change from 0 mg / kg orally administered until it dropped from the rotating rod, especially at 100 mg / kg, orally, 30 minutes after administration. A significant increase was observed.
FIG. 4 shows the results. [Example 7] Powder (daily dose) Carnitine chloride 450 mg, Kosandou stomach acid extract powder 1,800 mg Light anhydrous silicic acid 625 mg Synthetic aluminum silicate 1,446.5 mg Lactose 353.5 mg Synthetic aluminum silicate in a kneader (manufactured by Hata Tekko Co., Ltd.) 450 g of powder and 25 g of light anhydrous silicic acid powder were charged, and 450 g of d1-carnitine chloride was added to 700 m of water.
The solution dissolved in 1 is added and adsorbed on the powder.
This is dried with a vacuum dryer (Kusu Seisakusho) and then pulverized with an atomizer (Fuji Paudal; KII-2) to produce adsorption (preformulation). 925 g of the adsorbed powder, 1,800 g of citrus sand stomach acid extract powder, 300 g of light anhydrous silicic acid, 500 g of synthetic aluminum silicate, and 150.5 g of lactose were added to Vertical Granulator FM-25 (manufactured by Paulec).
Pour into the mixture and mix, then granulate. Then fluidized bed dryer FD
After drying using 5S (manufactured by Paulec), 5 g of light anhydrous silicic acid as a fluidizing agent is added to the sieved product and mixed to obtain 4,200 g of a product. In addition, as the citrus sand stomach acid extract powder, an extract powder having the following formulation (amount of crude drug) according to a conventional method was used. Soy sauce 2,000 mg Bamboo grass 1,500 mg Chen peel 1,500 mg Licorice 500 mg Ginger 500 mg Otsume 1,000 mg Kafuzi 1,000 mg Shrink sand 1,000 mg [Example 8] According to the following prescription, a tablet of the present invention was obtained in the same manner as in Example 1. Tablets (daily dose) Carnitine chloride 450 mg Dried extract 20 mg (active substance equivalent 240 mg) Ginger dry extract 10 mg (active substance equivalent 100 mg) Soujutsu dry extract 60 mg (active substance equivalent 200 mg) Clove powder 30 mg Chinpi dry extract 150 mg (Abundance of crude drug 1,200 mg) Synthetic hydrotalcite 700 mg Magnesium hydroxide 450 mg Dihydroxyaluminum aminoacetate 300 mg Licorice dried extract 125 mg (Amount of crude drug equivalent 500 mg) Synthetic aluminum silicate 350 mg Light anhydrous silicic acid 79.5 mg Ac-Di-Sol 1,199.5 mg Constarch 164mg HPC-L 120mg 1-Menthol 15mg Magnesium stearate 19mg

[0046]

INDUSTRIAL APPLICABILITY Carnitine shows a significant improving effect on the gastric emptying ability decreased by pretreatment with atropine, normalizes the decline of gastrointestinal function, and can be expected as a gastric emptying agent. The pharmaceutical composition of the present invention showed an excellent effect in the pharmacological test method regarding the antidepressant action between the forced swimming method and the rotating rod method, but the expression of the effect by the rotating rod method is a drug having a mild antidepressant action. Shows remarkable efficacy as a composition [Nippon Pharmacologic Journal (F
olia Pharmacol. Jpn. ), 104,
39-49 (1994)]. Carnitine chloride shows a tendency to shorten the immobility time in the forced swimming test of rats and shows a significant increase activity in the rotating rod method. In the rotating rod method, compounds showing antidepressant action show a significant increase action, and therefore carnitine chloride is considered to exhibit antidepressant-like anti-fatigue action. In this way, it can be expected to be effective against weakness and malaise due to gastritis due to mild psychosomatic disorder and psychosomatic stress, and can be expected to be effective in treating gastrointestinal symptoms such as stomach pain and heartburn, stress, anxiety, and overeating. , It can be used to improve digestive tract symptoms caused by excessive intake of alcohol and taking drugs, and it is caused by stress and anxiety caused by work and social environment, and depression caused by side effects of taking drugs. It can be used as a remedy for chronic gastrointestinal symptoms such as stomach pain, heartburn, nausea / vomiting, stomach upset, and stomach weight. In particular, it can be used for symptoms such as upper abdominal indefinite complaints typified by symptoms such as stomach upset and stomach weight, and symptoms caused by a decrease in gastric emptying ability.

Carnitine chloride has the effect of normalizing the state of decreased digestive function, and can be expected to have antidepressant-like anti-fatigue effect. It also has an effect of enhancing gastrointestinal function such as gastric emptying and a mild psychosomatic disorder. It can be expected to be used for improvement, treatment of gastritis due to mild psychosomatic disease, treatment of psychosomatic stress, treatment of weakness and malaise due to psychosomatic stress, etc. The thus-obtained preparation of the present invention, in combination with the action of carnitine chloride and the action of the compounding ingredients other than carnitine chloride, with respect to a decrease in gastric emptying due to a depressive state appearing due to stress, etc., a gastric emptying enhancing action. By improving the symptoms caused by and the depression state by the antidepressant action, it is effective in treating the gastrointestinal symptoms caused by the functional decline. By mixing a Kampo medicine having an effect on the symptoms of the digestive organs with the carnitine chloride, a gastric emptying-improving pharmaceutical composition excellent in the feeling of taking the medicine can be obtained.

[Brief description of drawings]

FIG. 1 shows the effect of D, L-carnitine chloride on rats whose gastric emptying is suppressed by atropine. In the figure *: P <0.05 vs control group #: P <0.05 vs atropine administration group

FIG. 2 shows the effect of D, L-carnitine chloride on dogs whose gastric motility is suppressed by atropine. In the figure *: P <0.05 vs control group

FIG. 3 shows the effect of D, L-carnitine chloride on the forced swimming test in rats. The data in the figure are shown as the exercise time of the rats who were forced to swim.

FIG. 4 shows the action effect of D, L-carnitine chloride on rats by the rotating rod method. The data in the figure shows the percentage change with time before the drug administration. In the figure *: P <0.05 vs control group

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Office reference number FI technical display part // (A61K 31/205 35:78)

Claims (9)

[Claims] 1. A gastric emptying-improving pharmaceutical composition comprising carnitine chloride. 2. The composition according to claim 1, further comprising a Kampo medicine having an effect on symptoms of the digestive organs. 3. The composition according to claim 1, further comprising at least one selected from the group consisting of a crude drug having a stomachic effect and an intestinal regulating agent. 4. The method according to claim 1, further comprising a sweetener.
The composition according to any one of 1. 5. An antacid, digestive agent, antidiarrheal agent, analgesic / spasmodic agent,
The composition according to any one of claims 1 to 4, further comprising at least one selected from the group consisting of a mucous membrane repairing agent, a flavoring agent, a flavoring agent, a flavoring agent, an aromatic agent, and an excipient. 6. (1) At least one selected from the group consisting of d-form, l-form and racemic carnitine chloride; (2) Anchu-san, Kosandaira-san-san, Gokufu-to, Gyorei. Hot water, Oncho-to, Yonkan-totsu-to, Orago-goto, Orengedoku-to, Oreng-to, Kaishoku-yotsu-to, Kakko-sanki-san, Kakkon-Oreng-go-to, Kami-nen-to, Kamikisuito, Kamihirashinsan, Ginseng Ginseng Hanatsumaru, Kanzo Ryoshinto, Kisuito, Keishikashakuyaku Ginger Ginsengtou, Keishikashakuyakudaioto, Keishikashakuyakuto, Keishikaryukyu oyster Hot water, Keishininjinto, Keisetsuto, Kenchuto, Kosago Rikkunshito, Kosago Yohoto, Koboku ginger and half-summer ginseng licorice, Gojuyuyu, Gojusan, Goreisan, Saiko Gouryu bone oyster bath, Saiko keishi ginger bath, saiko keishi bath, saishakurikukunikoto,
Sarei-to, Soto-nin-to, Shigyaku-san, Shikunshi-to, Shiryo-to, Ginger Ginseng-yu, Kokenchu-to, Shosaiko-to, Kohankaka-Kairei-to, Sanrei-Shirayu-san, Shinbu-yu, Daikenchu Hot water, anti-gold drink, Daisaiko hot water, most summer hot water, Nichin hot water, carrot hot water, Hangekobokuyu, Hangekishinshinyu, Hangeakusakutenmayu, Fukokukinseikan, Furayen, Horeiboingo Hot water, Keireizawa-reiyu, Hiraishan, Yokukansan, Yokukansan Kachinsemihanka,
And at least one selected from the group consisting of Rikkunshito and (3) dry aluminum hydroxide gel, magnesium aluminate silicate, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, hydroxide Alumina magnesium, aluminum hydroxide gel, aluminum hydroxide / sodium hydrogen carbonate coprecipitation product, aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / magnesium carbonate / calcium carbonate coprecipitation product, magnesium hydroxide, hydrogen carbonate A small amount selected from the group consisting of sodium, magnesium carbonate, magnesium aluminometasilicate, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate, crow bone, stone determination, oysters, aminoacetic acid, and dihydroxyaluminum aminoacetate. The composition according to any one of claims 1 to 5, characterized in that are mixed with one Kutomo. 7. Herbal medicines having a stomachic effect include anise, aloe, scent, euphoria, mulberry, enmeisou and scutellari.
ae radix), yellow oak, yellow lantern, processed garlic, incense (pogostem)
i herba), Karamus root, licorice, husk, corn, cinnamon, gentian, ginseng, magnolia, gut mushroom, pepper, colombo,
Conzulango, Sansho, Yamana, Shiso, Cured sand, Ginger, Owl, Blue skin, Iris root, Centaurium grass, assembly,
Soyaku, Soha, Daihako, Daihoku, Takebushi Ginseng, Choji, Chen skin, pepper, spruce, animal gall, nigaki, nutmeg, carrot, light load, hihatu, white bean, hops, homika extract, hyuga leaf, woody incense, michichi, At least one selected from the group consisting of long gall, good ginger, lemon oil, 1-menthol, and d1-menthol, wherein the intestinal regulating agent is an intestinal regulating intestinal bacterial component, red bud, Assenyaku, Karasu, ketsumeishi, and genoshoko. 7. At least one selected from the group consisting of
The composition according to any one of 1. 8. (1) At least one selected from the group consisting of carnitine chloride d-form, l-form, and racemic form as a gastric emptying-promoting active ingredient, and among the following (2) to (5): At least one selected from the group consisting of: (2) As a gastric herbal medicine, licorice, cinnamon, gentian, and magnolia;
A group consisting of crimped sand, ginger, assembly, soy sauce, clove, crust, carrot, and ginger (3) Dry aluminum hydroxide gel, magnesium aluminate silicate, synthetic hydrotalcite, magnesium hydroxide, carbonic acid as an antacid Group consisting of sodium hydrogen, magnesium carbonate, precipitated calcium carbonate, magnesium aluminometasilicate and dihydroxyaluminum aminoacetate (4) Group consisting of starch digestive enzyme, protein digestive enzyme, fat digestive enzyme and ursodeoxycholic acid as digestive agent And (5) as a mucosal repair agent, a group consisting of sodium azulene sulfonate, aldioxa, potassium copper chlorophyllin, methylmethionine sulfonium chloride, licorice, and sucrose sulfate aluminum salt is blended. Gastric emptying as described Tolerance improving pharmaceutical composition. 9. Carnitine chloride 3 to 5 parts by weight, synthetic hydrotalcite 6 to 8 parts by weight, magnesium hydroxide 3 to 5
Parts by weight, dihydroxyaluminum aminoacetate (aluminum glycinate) 2 to 4 parts by weight, licorice powder 1
~ 2 parts by weight, dried skin extract 1-2 parts by weight, soy sauce 1.
5 to 2.5 parts by weight, dried magnolia extract 0.1 to 0.5 parts by weight, ginger powder 0.5 to 1.5 parts by weight, clove powder 0.1 to 1.
0 parts by weight, 3 to 5 parts by weight of synthetic aluminum silicate, 0.1 to 1.0 parts by weight of light anhydrous silicic acid, at least mannitol and sorbitol, or 3 to 5 parts by weight of carnitine chloride, sodium hydrogen carbonate 2 ~ 4 parts by weight, precipitated calcium carbonate 1 to 3 parts by weight, magnesium aluminometasilicate 1 to 3 parts by weight, oysters 1 to 2 parts by weight, keel 1
.About.2 parts by weight, cinnamon skin 0.8 to 2 parts by weight, carrot 0.5 to 1.
5 parts by weight, lactic acid bacteria 0.1 to 0.2 parts by weight, red mega wrinkles 0.4 to 1.0 parts by weight, riboflavin 0.01 to 0.2
Parts by weight, copper chlorophyll potassium 1 to 2 parts by weight, mannitol and sorbitol at least contained, or carnitine chloride 2 to 4 parts by weight, sodium hydrogen carbonate 10 to 14 parts by weight, magnesium aluminometasilicate 6 to 8 parts by weight, 2 to 4.5 parts by weight of magnesium carbonate, 5 to 7 parts by weight of cinnamon, 2 to 4 parts by weight of incense, 8 to 17 parts by weight of carrot, 0.1 to 0.6 parts by weight of assembly, 3 to 6 parts by weight of compressed sand, Biodiastase (1000) 0.7 to 1.5 parts by weight, lipase (AP6), condensed sand 3 to 6 parts by weight, aldioxa 1 to 2 parts by weight, mannitol and sorbitol are contained at least. The pharmaceutical composition for improving gastric emptying according to claim 1.