WO2004112810A1 - Composition pharmaceutique utilisee en tant qu'antidiarrheique - Google Patents

Composition pharmaceutique utilisee en tant qu'antidiarrheique Download PDF

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Publication number
WO2004112810A1
WO2004112810A1 PCT/KR2004/001556 KR2004001556W WO2004112810A1 WO 2004112810 A1 WO2004112810 A1 WO 2004112810A1 KR 2004001556 W KR2004001556 W KR 2004001556W WO 2004112810 A1 WO2004112810 A1 WO 2004112810A1
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WO
WIPO (PCT)
Prior art keywords
lyophilizate
loperamide hydrochloride
lactobacillus
ratio
pharmaceutical compositions
Prior art date
Application number
PCT/KR2004/001556
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English (en)
Inventor
Seung-Ryul Lee
Seung-Kyoo Seong
Hee-Jin Sung
Se-Hee Hwang
Original Assignee
Dong Wha Pharm. Ind. Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dong Wha Pharm. Ind. Co., Ltd. filed Critical Dong Wha Pharm. Ind. Co., Ltd.
Publication of WO2004112810A1 publication Critical patent/WO2004112810A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis

Definitions

  • the present invention relates to pharmaceutical compositions, for relieving intestinal disorder and treating diarrhea, that are a mixture of lactobacillus lyophilizate with loperamide hydrochloride. More particularly, the present invention relates to pharmaceutical compositions that loperamide hydrochloride for treating diarrhea and lactobacillus lyophilizate for relieving intestinal disorder are mixed by weight in a ratio, wherein the ratio is greater than or equal to about 1:340, such that the pharmaceutical compositions have effects of relieving intestinal disorder and treating diarrhea regardless of etiology.
  • Diarrheas induce a loss of moisture and mineral in a body, which may induce conversion and central stimulation due to concentration of blood. Continual diarrheas induce malnutrition such that the diarrheas needed to be treated. Diarrheas are classified according to etiology -diarrhea caused by indigestion, diarrhea caused by stomach, diarrhea caused by neurosis, diarrhea caused by toxins and bacteria, diarrhea caused by parasites, diarrhea caused by abnormal contents of blood and diarrhea caused by chemical stimulus (Korea Pharmaceutical University Society division of Pharmacology, Pharmacology, 1986), and according to duration of diarrhea -acute diarrhea and chronic diarrhea.
  • the diarrheas are caused by toxins such as viruses, bacteria, parasites, etc., by deterioration of digestive functions, by a change of osmotic pressure of water across the intestinal mucosa, by mechanical and physical stimulation, by perverted fermentation of internal materials, etc.
  • the loperamide hydrochloride according to the present invention belongs to a category of drugs known as opioid analgesics. Also, the loperamide hydrochloride prevents intestinal vermiculation due to act selectively at intestines, restrains intestinal moisture and electrolyte from secreting, and promotes moisture and electrolyte for an absorption such that the loperamide hydrochloride has an effect on diarrhea and is usually used for treating acute diarrhea.
  • the loperamide hydrochloride prevents not only antidiarrheal acting but also eliminating the intestinal toxins or stimulus due to restrain intestinal vermiculation such that symptoms of intestinal infection grow worse and may be injurious to health.
  • the loperamide hydrochloride may be used for treating the chronic diarrhea due to highly effective as antidiarrhea, but has problems of bloated sensations in the abdomen or aneilema due to deterioration of digestive functions, etc., thereby giving a rise to side effects such as constipation, etc.
  • compositions containing the loperamide hydrochloride for antidiarrhea have been in demand, in order to have a pharmaceutical effect on diarrhea even with a small amount of the loperamide hydrochloride administrated.
  • the lactobacillus lyophilizate as lactic ferments for relieving intestinal disorder maintains homeostasis of intestinal normal bacterial flora, and prevents propagation of bacterial and virus inducing diarrhea.
  • the lactobacillus lyophilizate may not come into an effect fast such that the effect is faint, and the lactobacillus lyophilizate has an effect on chronic diarrhea when the lactobacillus lyophilizate is taken for long such that a problem of stopping administering often occurs.
  • the present inventors carried out an experiment on a mixture causing no side effects even when conventional antidiarrheal compositions having different chemical reaction in a body are administrated.
  • Pharmaceutical compositions that mix lactobacillus lyophilizate with loperamide hydrochloride in a predetermined ratio have an excellent effect on infective and non-infective diarrheas without generating bloated sensations in the abdomen or constipation.
  • the pharmaceutical compositions come into effects on alleviating symptom of diarrhea fast.
  • the present invention may treat acute diarrhea and chronic diarrhea better than a treatment using only lactobacillus lyophilizate or loperamide hydrochloride.
  • the present invention provides pharmaceutical compositions for relieving intestinal disorder and treating diarrhea, which have loperamide hydrochloride and lactobacillus lyophilizate mixed by weight in a ratio.
  • the loperamide hydrochloride to the lactobacillus lyophilizate ratio is greater than or equal to about 1:340.
  • the present invention also provides pharmaceutical compositions for relieving intestinal disorder and treating diarrhea, which may be used regardless of etiology.
  • the present invention still provides pharmaceutical compositions for relieving intestinal disorder and treating diarrhea, which may be used regardless of etiology and loperamide hydrochloride and lactobacillus lyophilizate are mixed by weight in a ratio greater than or equal to about 1 :340.
  • Antidiarrheal efficiency of loperamide hydrochloride is increased in accordance with an increase of mixing ratio of lactobacillus lyophilizate to the compositions of the present invention for treating diarrhea.
  • pharmaceutical compositions of the present invention contain lactobacillus lyophilizate such that side effects of loperamide hydrochloride may be decreased due to a relative dose reduction of loperamide hydrochloride.
  • loperamide hydrochloride and lactobacillus lyophilizate may be mixed by weight in a ratio about 1:2000 that is maximum. It is not practical when the ratio by weight is greater than or equal to about 1:2000.
  • the loperamide hydrochloride may not have an effect on diarrhea when the ratio by weight is less than about 1:340.
  • a formulation of the compositions is not restricted to a specific form, preferably selected from coated-tablets, powders, granules or capsules.
  • the coated-tablets are processed by adding talc, hydroxyprophyl methylcellulose, and polyethyleneglycol as inert ingredients to lactobacillus lyophilizate and loperamide hydrochloride as active ingredients and mixture- tabletting by published methods, preferably adding lactose, magnesium stearate, colloidal silicon dioxide, hydroxyprophyl methylcellulose, polyethyleneglycol, and titanium oxide.
  • the powders are processed by adding sucrose, lactose, or microcrystalline cellulose as inert ingredients to lactobacillus lyophilizate and loperamide hydrochloride as active ingredients and published methods, preferably adding mannitol, corn starch and colloidal silicon dioxide.
  • the granules are processed by adding sucrose and corn starch as inert ingredients to lactobacillus lyophilizate and loperamide hydrochloride as active ingredients and published methods, preferably adding mannitol, lactose, povidone and colloidal silicon dioxide
  • the capsules are processed by adding microcrystalline cellulose, corn starch, hydroxyprophyl cellulose, or magneisuim stearate as inert ingredients to lactobacillus lyophilizate and loperamide hydrochloride as active ingredients and published methods, preferably adding lactose, povidone, colloidal silicon dioxide, talc and magneisuim stearate.
  • compositions of the present invention for relieving intestinal disorder and treating diarrhea contain the lactobacillus lyophilizate and the loperamide hydrochloride such that antidiarrheal efficiency of the loperamide hydrochloride is increased and the side effects of the loperamide hydrochloride are decreased due to the dose reduction of the loperamide hydrochloride.
  • the loperamide hydrochloride is usually administered in a dose of about 1 to about 2mg a day and in division once or twice when the loperamide hydrochloride is only used for treating diarrhea, but the pharmaceutical compositions of the present invention contain the lactobacillus lyophilizate such that dose of the loperamide hydrochloride may be decreased to a dose of about 1/2 of usual dose of the loperamide hydrochloride.
  • compositions of the present invention for relieving intestinal disorder and treating diarrhea contain lactobacillus lyophilizate and loperamide hydrochloride, and bring out merits of each of the lactobacillus lyophilizate and the loperamide hydrochloride.
  • the pharmaceutical compositions of the present invention maintain homeostasis of intestinal normal bacterial flora; prevent propagation of bacterial and virus inducing a diarrhea; come into a fast effect on alleviating symptoms of diarrhea preventing from side effects such as bloated sensations in the abdomen, aneilema, constipation, etc.; and have excellent effects on diarrhea better than administrating only the lactobacillus lyophilizate or the loperamide hydrochloride and even when a small dose of the loperamide hydrochloride is administrated. Further, the pharmaceutical compositions of the present invention have an effect on treating diarrhea regardless of etiology. Best Mode For Carrying Out the Invention
  • mice were starved for 16 hours before performing the experiment, dissolved about 2mg, about 4mg, about 8mg of the loperamide hydrochloride per weight of mouse in 5% Tween20/saline was oral-administrated to the mouse, about 0.3ml of caster oil was oral-administrated to the mouse after about 30 minutes to induced the mouse with diarrheas, the mouse was observed for about 3 hours whether the mouse would be prevented from diarrhea.
  • Table 1 The results were shown in Table 1.
  • efficiency percentages of the experiment were about 60% and about 80% when about 4mg/kg and about 8mg/kg of the loperamide hydrochloride were administrated to the mouse, respectively.
  • antidiarrheal efficiency percentages increased by greater than or equal to about 20% when pharmaceutical compositions including the loperamide hydrochloride and the lactobacillus acidophilus lyophilizate mixed by weight in a ratio greater than or equal to about 1:85 were administrated, and increased by about 100% when pharmaceutical compositions including the loperamide hydrochloride and the lactobacillus acidophilus lyophilizate mixed by weight in a ratio greater than or equal to about 1 :340 were administrated.
  • the antidiarrheal efficiency percentage of the pharmaceutical compositions of a mixture of the loperamide hydrochloride and the lactobacillus acidophilus lyophilizate is much higher than an antidiarrheal efficiency percentage of pharmaceutical compositions of the loperamide hydrochloride only.
  • compositions had the best antidiarrheal efficiency when the loperamide hydrochloride and the lactobacillus acidophilus lyophilizate were mixed by weight in a ratio about 1:340(4/1360 mg/kg).
  • Experiment 3 was carried out to measure an antidiarrheal efficiency and a decreasing rate of weight in case of administrating the pharmaceutical compositions including the loperamide hydrochloride and the lactobacillus acidophilus lyophilizate mixed by weight in a ratio about 1:340 and pharmaceutical compositions containing only the loperamide hydrochloride or the lactobacillus acidophilus lyophilizate as a control to mouse with diarrhea induced by the same method of Experiment 1 and Experiment 2. The results were shown in Table 3. [Table 3]
  • Antidiarrheal efficiency percentages were increased by greater than or equal to about 100% when pharmaceutical compositions including the loperamide hydrochloride and the lactobacillus acidophilus lyophilizate mixed by weight in a ratio about 1:340(4/1360 mg/kg) were administrated like Experiment 2. Efficiency percentages of the pharmaceutical compositions were increased by about 30%) and about 100%) than antidiarrheal efficiency of group of administrating equal dose of the loperamide hydrochloride and the lactobacillus acidophilus lyophilizate, respectively, and were equal to antidiarrheal efficiency of group of administrating twice dose of the loperimide hydrochloride (8mg/kg).
  • compositions including the lactobacillus acidophilus lyophilizate and the loperamide hydrochloride mixed resulted decreasing rates of weight about 1.7 times, about 3times and about 4 times compared with group of administrating loperamide hydrochloride, group of administrating lactobacillus lyophilizate and solvent control. Accordingly, antidiarrheal efficiency of the pharmaceutical compositions containing both of the loperamide hydrochloride and the lactobacillus acidophilus lyophilizate was increased.
  • the pharmaceutical compositions for relieving intestinal disorder and treating diarrhea have excellent effect on diarrhea than each of conventional lactobacillus acidophilus lyophilizate and loperamide hydrochloride.
  • dose of the loperamide hydrochloride is decreased, antidiarrheal efficiency of the pharmaceutical compositions is equal to or greater than antidiarrheal efficiency of same dose of the loperamide hydrochloride.
  • the pharmaceutical compositions prevent side effects such as bloated sensations in the abdomen, aneilema, constipation and etc., due to administrating even a small amount of the loperamide hydrochloride.
  • the pharmaceutical compositions according to the present invention also prevent toxins such as harmful bacillus and rotavirus etc., from adhering to intestinal epituelium, so that antidiarrheal efficiency of the pharmaceutical compositions is increased, thereby successively treating acute diarrhea.
  • toxins such as harmful bacillus and rotavirus etc.
  • compositions that may be used regardless of etiology for diarrhea.
  • composition including the loperamide hydrochloride and lactobacillus acidophilus lyophilizate mixed by weight in a ratio about 1 :340 was mixture-tabletted as coated-tablet.
  • composition including the loperamide hydrochloride and lactobacillus acidophilus lyophilizate mixed by weight in a ratio about 1 :340 was mixture-tabletted as coated-tablet.
  • composition including the loperamide hydrochloride and lactobacillus acidophilus lyophilizate mixed by weight in a ratio about 1:340 was processed as powder.
  • composition including the loperamide hydrochloride and lactobacillus acidophilus lyophilizate mixed by weight in a ratio about 1:340 was processed as powder.
  • composition including the loperamide hydrochloride and lactobacillus acidophilus lyophilizate mixed by weight in a ratio about 1:340 was processed as granules.
  • composition including the loperamide hydrochloride and lactobacillus acidophilus lyophilizate mixed by weight in a ratio about 1 :340 was processed as granules.
  • composition including the loperamide hydrochloride and lactobacillus acidophilus lyophilizate mixed by weight in a ratio about 1:340 was processed as capsules. [Table 10]
  • composition including the loperamide hydrochloride and lactobacillus acidophilus lyophilizate mixed by weight in a ratio about 1:340 was processed as capsules.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Mycology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Microbiology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Molecular Biology (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne des compositions pharmaceutiques, permettant de soulager des troubles intestinaux et la diarrhée, comprenant du chlorhydrate de lopéramide et un lyophilisat de lactobacille mélangés dans un rapport en poids, le rapport étant supérieur ou égal à 1 :340. Lesdites compositions sont utilisées en tant que médicament pour traiter l'hypomyxie et stopper les maladies vermiculaires. Les compositions pharmaceutiques de l'invention présentent une efficacité anti-diarrhéique permettant de soulager des troubles intestinaux et traiter la diarrhée sans tenir compte de l'étiologie.
PCT/KR2004/001556 2003-06-25 2004-06-25 Composition pharmaceutique utilisee en tant qu'antidiarrheique WO2004112810A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020030041738A KR20050001548A (ko) 2003-06-25 2003-06-25 항설사용 약제학적 조성물
KR10-2003-0041738 2003-06-25

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007132359A2 (fr) * 2006-05-12 2007-11-22 Danisco A/S Composition

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Publication number Priority date Publication date Assignee Title
KR101166798B1 (ko) 2011-12-19 2012-07-26 김대현 락토바실러스 애시도필러스 엘비의 사균을 포함하는 알레르기 질환의 치료 또는 예방용 의약 조성물
KR102177371B1 (ko) * 2019-06-24 2020-11-12 에스비신일(주) 클로르테트라사이클린, 네오마이신 및 로페라마이드를 유효성분으로 포함하는 동물용 항균제 조성물

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992000082A1 (fr) * 1990-06-22 1992-01-09 The Procter & Gamble Company Compositions et methodes pour le traitement de la diarrhee
JPH04159223A (ja) * 1990-10-24 1992-06-02 Ss Pharmaceut Co Ltd 止瀉剤組成物
JP2002142719A (ja) * 2000-11-07 2002-05-21 Yutaka Sanbonmatsu 整腸栄養食品

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992000082A1 (fr) * 1990-06-22 1992-01-09 The Procter & Gamble Company Compositions et methodes pour le traitement de la diarrhee
JPH04159223A (ja) * 1990-10-24 1992-06-02 Ss Pharmaceut Co Ltd 止瀉剤組成物
JP2002142719A (ja) * 2000-11-07 2002-05-21 Yutaka Sanbonmatsu 整腸栄養食品

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
FARTHING M.J.: "Review article: prevention and treatment of travellers'diarrhoea", ALIMENT. PHARMACOL. THER., vol. 5, no. 1, February 1991 (1991-02-01), pages 15 - 30 *
PIETRUSKO R.G.: "Drug therapy reviews: Pharmacotherapy of diarrhea", AM. J. HOSP. PHARM., vol. 36, no. 6, June 1979 (1979-06-01), pages 757 - 767 *
SACH J.A. & CHANG L.: "Irritable bowel syndrome", CURRENT TREATMENT OPTIONS IN GASTROENTEROLOGY, vol. 5, 2002, pages 267 - 278 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007132359A2 (fr) * 2006-05-12 2007-11-22 Danisco A/S Composition
WO2007132359A3 (fr) * 2006-05-12 2008-08-14 Danisco Composition

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