GB2182558A - Oral fructo-oligosaccharide pharmaceutical compositions - Google Patents

Abstract

Pharmaceutical compositions for encouraging the increase of beneficial intestinal flora (eg. Lactobacillus bifidus) comprise fructo-oligosaccharide in the form of tablets or granules each containing an appropriate amount of the fructo-oligosaccharide for oral administration at each mealtime.

Description

SPECIFICATION Preventive against senile change This invention relates to a preventive for oral ingestion against senile change. This preventive against senile change is not a medicineforthe cure of any specific disease. This invention relates to a substance which, when taken continually, i.e. at each mealtime, will suppress intestinal microorganisms, thesourne for harmful substances promoting senile changes ofthe organs and cells of a human body.

Mankind,forseveral million years since his origination on the earth, has been seeking a "wonderful medicine" hopefully expected to keep him from senility and death forever, only in vain.

FirstEmperorShin Haung Ti of Chin (an ancient dynasty of China) is famed to have sent his men out in search of a medicine of this nature.

An object of this invention is to develop an edible substance capable of preventing senile changes and realize mankind's natural term of existence which is claimed to be about seven scores of years.

By the expression "prevention of senile changes" as used herein is substantially meantthe utmost retardation ofthe progress of senile changes.

The technical achievement which underlies this invention resides in the realization of commercial production offructoligosaccharide by Meiji Seika Kaisha, Ltd.

As a publication dealing with the use of this sugar, a book titled "A weak intestine is caused by a dec rease ofthe population of bifidus microbes",written byAtsushi Okada and published in October, 1984 by the Seishun Press can be cited.

In the explanatory note published by Health Industry Department of Meiji Seika Kaisha, Ltd., there is a passage, reading: "Meioligo is a health syrup using fructoligosaccharide as its main component. It can be directly ingested and enabled to nourish bifidus microbes without causing the user's anxiety about excess calorie or tooth decay. It is a convenient and trustworthy help matching the needs of the time of intestine". Underthetitle "direction on use",there is a mention reading: "Use it as admixed with coffee, blacktea, milk, oryogurt in much the samewayas sugar".

This product comes in three forms; liquid, minute granules closely resembling powder, and cubic can dies. The liquid contains 9 g offructoligosaccharide per packet, the granules 4.5 g of the sugar per packet, and the candies 4.3 g ofthe sugar per piece. The effect and usage ofthe fructoligosaccharide whose production has been commercialized byMeiji Seika Kaisha, Ltd. are shown in the aforementioned book. The contents of this book are as follows.

Chapter 1 "Yourweak intestine is caused byshortage of bifidus microbes".

Chapter2 "Dreadful harms are done to persons who relyforcure of constipation upon vegetables, water, and medicines".

Chapter 3 "Ciinical report: Persons suffering from chronic constipation experience three times as rapid senile changes as healthy persons".

Chapter4 "The new substance (fructoligosaccharide) cures constipation by only 7 days' medication and gives a healthy body".

In Chapter I, the author explains the microorganism, bifidus, as follows.

"I have already stated that bifidus microbes are the so-called good ones. The expression 'good microbes' as used herein means that these microbes fulfill useful parts in our bodies. It should be also noted that they produce absolutely no harmful matter in our bodies".

"The bad microbes led by colon bacilli are regarded as harmful entities because they decompose proteins with liberation of such putrefying components as ammonia, amines, and hydrogen sulfide".

"For the prevention of constipation, . . . (Irrelevant passage omitted) . . ., it is essential that the army of good bifidus microbes predominates over the army of bad microbes".

"The charm pointofthe bifidus microbes resides in the fact that these microbes in the intenstine decompose sugars and produce lactic acid and acetic acid in a ratio of :1.... (Irrelevant passage omitted) . . . . . In short, theyform a favorable cycle in which the acids so produced enable bifidus microbes to enjoy supremacy over the bad microbes all the more in proportion tothe population of bifidus microbes".

"What is more, there exists the mechanism in which the peristaltic movement of the intestine gains in vigor when the intestinal pH inclines toward ac- idity".

"lnfactyourconstipation is caused bythe loss of balance ofthe intestinal colony. What should be doneforthe cure of constipation? The best way is to increase the intestinal population of bifidus microbes. I believe you have followed me up to this point".

"Tojustifytheconclusionthatthefructoligosaccharide serves to increase bifidus microbes, two problems to be solved remain".

"One ofthe problems is whether or not other microbes will not feed on the fructoligosaccharide at all.

. . . . . (Irrelevant passage omitted) . . . It has been es- tabu fished that it is the bifidus microbes that utilize the frutoligosaccharide most effectively".

"This sugar is utilized also by lactic acid bacteria, bacteroides, and entric cocci, though not so much as by the bifidus microbes. It has been demonstrated that the sugar is never utilized by colon bacilli and Welch bacilli which may well be classified as bad microbes".

"We still have the other problem to explore. This problem is whether or not the fructoligosaccharide, when orally ingested, is digested and absorbed en route to the small intestine and is prevented from reaching the large intestine inhabited by the bifidus microbes or barely allowed to reach the large intest ine in a very small amount.... (Irrelevant passage omitted) . . fortunately, it has been ex- perimentally established that the fructoligosaccharide is not absorbed within the enteric canal (inclusive ofthe small and large intestines)".

Inthefinal partofthebook,thefollowingdirection on the use of the fructoligosaccharide is found.

"Asconcernstheamountofthesugarto betaken daily and the duration ofthe use ofthis sugar, it is fairly difficult to fix them generally because they are variable from one person to another, depending on the seriousness of constipation. One safe standard is one week's use of 5 g per day. Most average cases of constipation will be cured satisfactorily by this prescription in terms of-both amount and duration. When this prescription fails to give a satisfactory cure, it may be advisable to increase the amount of the sugar taken dailyapproximatelytothe level of10g andto extend the duration of use.... (Irrelevant passage omitted) . . .Afterthe cure of constipation is obtained as desired, it may be wise for you to continue the habit of using this sugarforthe purpose of preventing constipation and maintaining the intestinal health as well. Although thefructoiigosaccharide is effective in curing constipation, it is nota medicine but a foodstuff in category".

An objectofthis invention isto provide a subst ancewhich, when ingested, will enable bifidus to prevent occurrence of substances promoting intestinal senile changes.

The object described above is accomplished by a granular preventive against senile change, containing fructoligosaccharide in an amount in the range of 0.1 to 1.0 g, pergranule.

Thefructoligosaccharide is a substance such that when it is ingested, it will not be absorbed by either the human bodyorharmful microbes butabsorbed only by bifidus microbes and harmless microbes.

The method which effects propagation of intestinal bifidus microbes by making the mostofthis behavior ofthe fructoligosaccharide has been known to the art. A certain company has achieved a great success in realizing commercial prodution ofthis desirable substance, fructoligosaccharide. Studies on the dev- elopmentof applications and the establishment of methods of utilization of the produced fructoligosaccharide are delayed.To be specific, the question asto whatfunction the bifidus microbes are expected to fulfill when the intenstinal bifidus microbes are propagated by the use of the fructoligosaccharide and the question as to how the fructoligosaccharide is to be use din effecting the propagation ofthe bifidus microbes so asto suit the purpose are subject matters of study which have notyet been explored to any appreciable extent. The method of ingestion ofthefructoligosaccharide recommended by the producer and the researchers is one week's continued use of 5 g per day as already described above.

By this method of ingestion, since the amount of bifidus microbes in the intestine widely varies im mediatelyafterthe ingestion ofthefructoligosaccharide and sometime afterthe ingestion, the occurrence of substances promoting senile changes in the intestine cannot be prevented effectively.

The inventor has sought a way of preventing the occurrence of substances promoting senile changes in the intestine and has formed a conclusion that a user should take the fructoligosaccharide at each mealtime and, as a result, the bifidus microbes in the intestine should be retained in a fixed amount at all times.

This invention, in accordance with the conclusion described above, aims to provide a granular product which has a fructoligosaccharide suitable for continued ingestion at each mealtime.

This invention is directedtoagranularsubstance for oral ingestion, containing fructoligosacchariode, an oligosaccharide resulting from the action of a fructosetransferase upon sucrose and having 1 to3 fructose units bonded to the fructose residue ofthe sucrose, in a fixed amount in the range of 0.1 to 1.0 g per granule.

The invention will be described more specifically below.

Heretofore, the fructoligosaccharide has been marketed in various forms as described above; the liquid containing 9 g ofthefructoligosaccharide per packet, the minute granules 4.5 g of the sugar per granule, and the candies 4.3 g per piece. These sugar contents agree with the directions of use indicated in the aforementioned booktotheeffectthatwhenthe sugar is taken in an amount of about 5 g once daily for the preservation of health, the liquid preparation should be taken so many large cooling spoonfuls.

From the description to be given afterward, it is understood thatthis method of use is effective when the sugar is intended to prevent constipation, i.e. to adjust the condition of the intestine.

The present invention,forthe purpose of using the frutoligosaccharide as a preventive against senile changes and not as a foodstuffforthe adjustment of the intestinal condition, prepares this sugar in the form of granules containing the sugar in a fixed amount in the range of 0.1 to 1.0 g per granule. The term "granules" as used herein is intended to referto all solid preparations including tablets, peliets, and capsules which can be ingested directly. The fructoligosaccharide which used to be contained in an amount of 4.3 to 9 g per packet is now contained in the granules ofthis invention in an amount of 0.1 to 1.0 g per granule. What new effects this simple change offructoligosaccharide content has brought aboutwill be described below.

Of the feces discharged from the human body, a proportion of 10 to 20% is accounted for by live microbes. If bifidus microbes account for 10% of the intestinal colon, bifidus microbes are daily discharged in such a large proportion of 1 to 2% ofthe amount of feces. Even when the fructoligosaccharide is not ingested daily, the same amount of bifidus microbes are produced by daily propagation using as the source of nutrient the remnant of food brought down to the large intestine. Thus, a substantially fixed amount of bifidus microbes are maintained within the intestine.

In the condition just described,the following phenomenon occurs when the fructol igosaccharide is generously ingested once daily as described above.

First, the frucloligosaccharide is diffused in the food inside the stomach and then forwarded downwardly toward the intestine. While the remnant ofthe food is passing through the large intestine, the bifidus microbes in the intestine are vigorously propagated.

Consequently, a larger amount of bifidus microbes than before are carried to the rectum and discharged out of the system. In the meantime, afairamountof propagated bifidus microbes remain insidethe large intestine. Since the food taken in the subsequent meal contains no fructoligosaccharide, then the re mnantofthisfood is passingthroughthe large in testine,the bifidus microbes propagated and retained insidethe intestine are carried outtowardthe rectum and discharged from the system. When the fructoligosaccharide is ingested once daily, the amount of bifidus microbes in the intestine describes a daily cycle consisting of one ridge and one groove.

During the phase of the ridge, namely when bifidus microbes are produced in a large amount, the acids in the intestine are increased and the peristaltic movement ofthe intestine is enhanced, with theresuit that the cure of the constipation will be effectively promoted.

From the standpoint of preventing senile changes, this method of ingestion is not effective because putrefying microbes is not effective because putrefying microbes and other microbes producing substances which accelerate senile changes are suppressed when bifidus mirobes exist in a large amount but the substances responsible for senile changes are suffered to occur as vigorously as before when the amount of bifidus microbes is decreased.

In the case ofthe granule preparation ofthis invention which contains the fructoligosaccharide in a small fixed amount since it is ingested at each mealtime as easily as any medicine and, consequently, the remnant offood passing through the large intest inealwayscontainsasubstantiallyfixed amountof the fructoligosaccharide, there is virtually no time when the substances responsibleforsenilechanges are allowed to form.

When the fructoligosaccharide is ingested, since the amount of bifidus microbes retained in the intestine before the ingestion is increased by addition of the amountofbifidus microbes propagated (though part of the propagated microbes are discharged out of the system) owing to the optimum source of nutrient, fructoligosaccharide, and is retained afterthe ingestion, the action of the bifidus microbes to sup p- ress the other microbes is enhanced and the diffusion ofthe substances responsibleforsenile changes within the system is decreased. This decrease of the substances responsible for senile changes either impedes or decreasesthe phe- nomenon of senile changes ofthe parts and cells of the human body.

The actions of the bifidus microbes, as excerpted from the "Handbookon Nutrition" published by Gihodo, will be enumerated below.

"I:Bifidus microbes have absolutely no path- ogenesis and do no harm to the host.

il: Bifidus microbes prevent intestinal propagation of microbes of other species.

Ill:Bifidus microbes, by constantly producing acids in the intestine, not only suppress the other mic robes but also stimulate the intestine, suitably enhance the peristaltic movement ofthe intest ine and facilitate the absorption of calcium and iron salts.

IV: Bifidus microbes synthesize vitamin B.

V:The colon of bifidus microbes inducesthe phen- omenon of intestinal putrefaction onlywith dif ficulty.

As products of the intestinal putrefaction, there may be cited ammonia, hydrogen sulfide, indole, skatole, amines, methane, methyl mercaptan, etc. or iginating in the decomposition of proteins".

When the fructoligosaccharide is ingested at each mealtime, the remnant of food which passes through the large intestine always containsthefruc- toligosaccharide. As a result, the amount of bifidus microbes propagated surpasses that of bifidus microbes discharged out ofthe system and the gradual increase of the intestinal population of bifidus microbes is consequently continued. Unless other detrimental conditions develop, the bifidus microbes and other harmless microbes capable of assimilatefructoligosaccharide expel harmful microbes from the intestine.

As a test on human subjects, the inventor himself, hisfamily, and employees orallyingestedthecom- mercially availablefructoligosaccharide liquid continually at each mealtime in a fixed amount of 1 g apiece. Since all the subjects were healthy, it was not easy to rate the effects precisely. They all felt refreshed both mentally and physically as though stagnant feces was expelled in consequence offasting.

It is safely concluded that theyfeltthe same sensation as when this invention manifested its effect on person using the fructoligosaccharide in the light of the fact that the stagnent feces fi I led with harmful microbes was expelled and the intestinal release of harmful substances was discontinued.

The granule preparation of this invention differs from the existing commercially available produce only in respect that the amount offruc- toligosaccharide contained in each granule is re markablysmall in the former as compared with that in the latter. The effect of this difference in the change ofthe manner of ingestion of the fructoligosaccharide from one ingestion per day to ingestion at each mealtime is profound from the standpoint of prevention of the senile changes. Con ventionally, since the fructoligosaccharide was taken only once daily, though in a large amount, the action ofthe sugarto suppress harmful microbes was manifested intermittently and the effect in preventing senile changes was poor. In accordance with this invention, since the fructoligosaccharide is ingested at each mealtime, though in a relatively small amount, the remnant of food in the intestine is always enriched and the intestinal population of bifidus microbes is maintained at a high level. As a result, the action of suppressing harmful microbes is effectively maintained and the action of preventing senile changes is constantly carried out.

Natural death due to senile changes is prevented by promoting the protection against senile changes.

The present invention, therefore, may well be regarded as the firstto realize the mankind's long dream of obtaining a wonderful medicine for keeping mankind from senile changes and eventually death.

The granular preparation for oral ingestion con tainsfructoligosaccharide in a fixed amount in the range of 0.1 to 1.0 g per granule and can beconveni- entlytaken at each mealtime. When a person ingests this granular preparation at each mealtime,thein- testnal population of bifidus microbes can be kept constant and the occurrence of substances responsible for senile changes is precluded or remarkable suppressed.

Claims (2)

1. A granular preventive for oral ingestion against senile changes, containing fruc toligosaccharide, which is an oligosaccharide resulting from the action of a fructose transferase upon sucrose and having 1 to 3 fructose units bonded to the fructose residue of sucrose, in a fixed amountfalling in the range of0.1 to 1.0 g pergranule.

2. A preventive as claimed in Claiml and sub- stantially as described in the Examples.