HK1132190B - Liquid preparation for internal use - Google Patents

Abstract

A liquid preparation internal use which is composed of swertia extracts, pharmaceutical components having effect on the digestive system selected from ginger extract, ginseng extract, tumeric extract, cinnamic oil, eugenol, thymol or carnitine chloride, and remainder of auxiliary ingredients, and is adjusted to pH 4-7. The pharmaceutical activity of the liquid preparation internal use of the present invention continues over a long period of time, because the active ingredients in the swertia extracts are kept stable for a long time.

Description

Liquid preparation for oral administration

The present invention is a divisional application with the title of "liquid oral preparation" on application number 02141424.6, application date 2002, 8/30/h.

Technical Field

The present invention relates to a liquid oral preparation which can stably maintain the active ingredients of swertia japonica Makino extract for a long period of time.

Background

The crude drug Swertia japonica (Swertia Herb) is a whole plant of Swertia japonica Makino in flowering period, is classified as bitter stomachic, and has medicinal effects of treating gastritis, hyperacidity, anorexia, etc. The swertia japonica Makino contains Swertiamarin (Swertiamarin), Swertiamarin, red pelatarin, swertia pseudochinensis, oleanolic acid, and gentisic.

The preparations containing the stomach-invigorating crude drugs such as swertia japonica, etc. have been known from old times as powder preparations, tablets, etc. and in recent years, rapid absorption after administration is expected to result in quick-acting properties, so that liquid oral preparations have been marketed.

However, once swertia japonica Makino is incorporated into a liquid oral preparation, it is found that the content of swertiamarin, which is one of the active ingredients thereof, is decreased with the lapse of time.

It is therefore an object of the present invention to provide a liquid oral preparation which can stably retain swertia japonica Makino extract for a long period of time.

Disclosure of Invention

The present inventors have studied the cause of the decrease in swertia japonica Makino extract content from various viewpoints such as temperature, concentration, and pH, and as a result, have found that: the pH is extremely important for the stability of the swertiamarin content in swertia japonica Makino extract in a liquid preparation over time, and further, if the pH is adjusted to 4 to 7, a liquid internal preparation having excellent stability of the swertiamarin content over time can be obtained, and the present invention has been completed.

That is, the present invention provides a liquid internal preparation containing swertia japonica Makino extract and having a pH adjusted to 4 to 7.

Detailed Description

The liquid oral preparation of the present invention contains swertia japonica Makino extract having a bitter stomach-invigorating component. The swertia japonica Makino extract is obtained by extracting swertia japonica Makino with solvent such as cold water, hot water, ethanol, and water-ethanol mixture, preferably water-ethanol mixture.

The content of swertia japonica Makino extract in the liquid oral preparation of the present invention is 5 to 3000mg in terms of crude drug as 1 daily dose, and particularly preferably 10 to 1500 mg.

The pH of the liquid oral preparation of the present invention is required to be 4 to 7, preferably 4.4 to 6.3, more preferably 4.5 to 6.0, and particularly preferably 4.8 to 5.8, from the viewpoint of stability of the swertiamarin content in swertia japonica Makino extract over time.

When the pH is adjusted to 4 to 7, a buffer having a pH in this range is suitably used, and examples of the buffer include buffers containing citric acid, succinic acid, acetic acid, tartaric acid, hydrochloric acid, sulfuric acid, gluconic acid, lactic acid, fumaric acid, boric acid, maleic acid, phosphoric acid, methanesulfonic acid, malic acid, salts thereof, and the like, and among them, citric acid, sodium citrate, tartaric acid, sodium tartrate, malic acid, sodium malate, and the like are preferable, and these buffers are blended in an amount to adjust the pH to the above range. Furthermore, such acids can also be used in combination with alkali metal hydroxides, in particular sodium hydroxide, to form buffer systems.

The liquid oral preparation of the present invention may contain other effective components than the swertia herb extract, and the effective components may be those acting on the digestive system, and examples of the effective components include anise fruit, aloe, fennel, turmeric, lindera root, plectranthus, scutellaria, phellodendron bark, coptidis japonica, processed garlic, curcuma zedoary, ageratum, ramie root, goose skin, poncirus trifoliate, immature bitter orange, cinnamon bark, gentian, red ginseng, magnolia bark, evodia fruit, pepper, african tetrandra, curdlan, zanthoxylum, kaempferia galangal, perilla, amomum shreddatum, dried ginger, cardamom, green tangerine peel, pholidota herb, atractylis lancea, perilla leaf, anise, rhubarb, panax japonicus, clove, dried orange peel, capsicum, lime, animal gall, quassia, nutmeg, ginseng, mint, long pepper, atractylodes rhizome, hop, nux vomica, sleeping leaf, yunna, alpinia oxyphylla, costus, galangal fruit, and the like, Stomach invigorating crude drug extract such as Japanese gentian and rhizoma Alpiniae Officinarum; stomachic agents such as betaine hydrochloride, glutamic acid hydrochloride, carnitine chloride, bethanechol chloride, and dried yeast; antacids such as dried aluminum hydroxide gel, magnesium silicate aluminate, magnesium silicate, synthetic aluminum magnesium carbonate, magnesium oxide, aluminum magnesium hydroxide, aluminum hydroxide gel, aluminum hydroxide-sodium bicarbonate coprecipitate product, aluminum hydroxide-magnesium carbonate mixed dried gel, aluminum hydroxide-magnesium carbonate-silicon carbonate coprecipitate product, magnesium hydroxide, sodium bicarbonate, magnesium carbonate, precipitated calcium carbonate, magnesium metasilicate aluminate, anhydrous calcium hydrogen phosphate, cuttle bone, concha haliotidis, oyster shell, glycine, dihydroxyaluminum aminoacetate salt, and scopolia extract; digestants such as starch digestive enzyme, protein digestive enzyme, fat digestive enzyme, cellulose digestive enzyme, ursodeoxycholic acid, oxycholate, cholic acid, bile powder, bile extract (powder), dehydrocholic acid, and animal gallbladder; intestine regulating agent such as red cedar bud, Catechu, mume fructus, semen Cassiae, and herba Erodii Nepalensis; an antidiarrheal agent such as rivanol, berberine chloride, guaiacol, creosote, phenyl salicylate, guaiacol carbonate, berberine tannate, bismuth subsalicylate, bismuth subnitrate, bismuth subcarbonate, bismuth subgallate, tannic acid, albumin tannate, methylene thymol tannate, kaolin, natural aluminum silicate, aluminum hydroxynaphthoate, pectin, medicinal carbon, precipitated calcium carbonate, calcium lactate, calcium hydrogen phosphate, catechu, dark plum, phellodendron, Japanese coptis, sophora flavescens, geranium nepalense, gallnut, hawthorn, and bayberry; hydrobenraline hydrochloride, dicyclomine hydrochloride, mesterone hydrochloride, scopolamine bromate, methyl atropine bromide, methyl octyl tropine bromide, scopolamine methobromide, methyl 1-ranolazine bromide, methyl benactyzine bromide, belladonna extract, iprodione iodide, diphenyl piperidyl methyl dioxolane hyoscyamine iodide extract, scopine root total alkaloid citrate, papaverine hydrochloride, ethyl aminobenzoate, corydalis tuber, licorice, magnolia cortex, peony and other analgesic and antispasmodic medicines; sodium glycyrrhizate, sodium sulfocellulose, aluminum allantoinate, glycyrrhizic acid and its salts, Glycyrrhrizae radix extract, L-glutamic acid, copper potassium chlorophyll, copper sodium chlorophyll, histidine hydrochloride, pig stomach wall pepsin decomposition product, pig stomach wall acid hydrolysis product, vitamin U, fructus Sorbi Pohuashanensis, rhizoma corydalis, Glycyrrhrizae radix, etc.

In addition, the liquid oral preparation of the present invention may contain stabilizers such as sodium aspartate, sodium alginate, disodium edetate, sodium sulfite, sodium bisulfite and the like; sorbitol, white sugar and other sweeteners; sodium chloride, L-sodium glutamate, Mel, and apple juice; coloring agents such as caramel; flavoring agent such as L-menthol, peppermint flavor, chicory flavor, etc., and essential oil such as lemon oil, orange oil, spearmint oil, etc.; preservatives such as sodium benzoate and butyl p-hydroxybenzoate; polyoxyethylene hardened castor oil ester, a cosolvent of ethanol, and the like.

The liquid oral preparation of the invention is very useful as a liquid oral gastrointestinal drug, and the dosage is usually 20 to 100ml for one time, preferably 1 to 3 times per day.

Examples

The present invention will be described in more detail with reference to the following examples, which, however, are not intended to limit the scope of the invention.

Examples 1 to 2 and comparative examples 1 and 2

A liquid internal preparation containing swertia japonica Makino extract was prepared by the processes shown in tables 1 and 2, wherein the crude drugs in the tables are shown below.

(1) Swertia Japonica Makino extractive solution (1 ml stock solution equivalent to 1g crude drug, extraction solvent; ethanol water solution)

(2) Ginger extract (1 ml of original liquid is equivalent to 1g of crude drug, extraction solvent is ethanol water solution)

(3) Ginseng extract (1 ml of original liquid is equivalent to 4g of original medicine, extraction solvent is ethanol water solution)

(4) Curcuma rhizome extract (1 ml crude liquid equivalent to 1g crude drug, extraction solvent: ethanol water solution)

(5) Cinnamon oil (volatile oil obtained by steam distillation of cinnamon)

(6) Clove oil (volatile oil obtained by steam distillation of clove)

(7) Oleum Foeniculi (volatile oil obtained by steam distilling oleum Foeniculi)

The amounts indicated in the formulations in tables 1 and 2 refer to the amount of 1 vial of 30ml, and citric acid and sodium hydroxide were used to adjust the pH.

TABLE 1

Composition (I)	Example 1	Example 2	Example 3	Example 4	Example 5	Example 6	Example 7
								Swertia Japonica Makino extractive solution (ml)	0.05	0.05	0.05	0.05	0.05	0.05	0.05
Ginger extract (ml)	-	0.1	0.1	0.1	0.1	-	0.1
								Ginseng extract (mg)	50	50	-	50	50	-	50
Turmeric extract (ml)	0.1	0.1	0.1		0.1	0.1	-
								Cinnamon oil (mg)	-	10	10	-	10	10	10
Clove oil (mg)	2		2	2		2	2
								Fennel oil (mg)	2	2	2	2	2	2	-
Carnitine chloride (mg)	120	-	-	120	-	120	120
								Refined white sugar (mg)	1600	1600	1600	1600	1600	1600	1600
D-sorbitol solution (70% by weight) (mg)	900	900	900	900	900	900	900
								Polyoxyalkene hardened Castor oil ester (mg)	100	100	100	100	100	100	100
Sodium benzoate (mg)	20	20	20	20	20	20	20
								Caramel (mg)	34	34	34	34	34	34	34
Refined water	Proper amount of	Proper amount of	Proper amount of	Proper amount of	Proper amount of	Proper amount of	Proper amount of
								Total amount (ml)	30	30	30	30	30	30	30
pH	4.2	4.45	4.7	4.95	5.2	5.45	5.7

TABLE 2

Composition (I)	Example 8	Example 9	Example 10	Example 11	Example 12	Comparative example 1	Comparative example 2
								Swertia Japonica Makino extractive solution (ml)	0.05	0.05	0.05	0.05	0.05	0.05	0.05
Ginger extract (ml)	0.1	0.1	-	0.1	0.1	0.1	-
								Ginseng extract (mg)	50	-	50	50	-	50	50
Turmeric extract (ml)	0.1	0.1	-	0.1	0.1	-	0.1
								Cinnamon oil (mg)	-	10	10	-	10	10	10
Clove oil (mg)	2	-	2	2	2	-	-
								Fennel oil (mg)	2	2	2	2		2	2
Carnitine chloride (mg)		120	120		120	120	120
								Refined white sugar (mg)	1600	1600	1600	1600	1600	1600	1600

Composition (I)	Example 8	Example 9	Example 10	Example 11	Example 12	Comparative example 1	Comparative example 2
								D-sorbitol solution (70% by weight) (mg)	900	900	900	900	900	900	900
Polyoxyalkene hardened Castor oil ester (mg)	100	100	100	100	100	100	100
								Sodium benzoate (mg)	20	20	20	20	20	20	20
Caramel (mg)	34	34	34	34	34	34	34
								Refined water	Proper amount of	Proper amount of	Proper amount of	Proper amount of	Proper amount of	Proper amount of	Proper amount of
Total amount (ml)	30	30	30	30	30	30	30
								pH	5.95	6.2	6.45	6.7	6.95	3.5	7.2

Stability test over time

After the liquid preparations of examples 1 to 12 and comparative examples 1 and 2 were stored at 70 ℃ for 3 days, the remaining amount of swertiamarin in the preparations was measured by high performance liquid chromatography.

As a result, as shown in Table 3, even under a severe condition of 70 ℃ and at a pH of 4 to 7, swertiamarin in the swertia japonica Makino-containing liquid preparation remained stable, and even under a severe condition of 70 ℃ and at a pH of 4.4 to 6.3, the stable residual rate of swertiamarin was 50% or more, while at a pH of 4.5 to 6.0, the stable residual rate of swertiamarin was 60% or more, and at a pH of 4.8 to 5.8, the stable residual rate of swertiamarin was 70% or more.

TABLE 3

Liquid preparation	Residual rate of swertiamarin (%)
		Comparative example 1	0
Example 1	25.0
		Example 2	52.1
Example 3	63.0
		Example 4	74.7
Example 5	81.2
		Example 6	81.5
Example 7	75.9
		Example 8	68.9
Example 9	55.8
		Example 10	41.3
Example 11	31.6
		Example 12	12.5
Comparative example 2	8.2

Industrial applicability of the invention

The liquid internal preparation of the present invention can stably maintain the active ingredients of swertia japonica Makino extract for a long period of time, and thus can maintain the drug effect for a long period of time.

Claims (3)

1. A liquid oral preparation comprises swertia Japonica Makino extract, effective component selected from rhizoma Zingiberis recens extract, Ginseng radix extract, Curcuma rhizome extract, oleum Cinnamomi, oleum Caryophylli, oleum Foeniculi or carnitine chloride, and adjuvant component in balance, and has pH of 4-7.

2. The oral liquid preparation according to claim 1, wherein the pH is adjusted to 4.4 to 6.3.

3. The oral liquid preparation according to claim 1 or 2, wherein the auxiliary ingredients are refined white sugar, sorbitol, caramel, sodium benzoate, and polyoxyethylene hardened castor oil.