Title of Invention	FOOD FOR IMPROVING CLINICAL CONDITIONS CAPABLE OF LOWERING THE CONCENTRATIN OF LOW - MOLECULAR-WEIGHT NITROGEN-CONTAINING COMPOUNDS IN BLOOD
Abstract	The present invention aims at preventing or retarding a transition to hemodialysis treatment in kidney failure or decreasing the number of implementation of the hemodialysis therap and preventing or lessening occuirenceofaccompanyinghyperammonemiainhepaticinsufficiency. To accomlish the Voses described above, the pathological improvement food of the invention is featured by being composed chieflv of indigestible polysaccharides and having restricted addition of protein components. Energy produced by exporting the indigestible polysaccharides contributes to fungal protein synthesis using, asanN-source.ureaorammonia secretionintotheintestine andexcretionof toliferatedbacteriawith feces, so that nitrogen-containing low-molecular substances in the blood can be decreased, thereby to im^ovedisorderofthekidnepndliver.

Title of Invention

FOOD FOR IMPROVING CLINICAL CONDITIONS CAPABLE OF LOWERING THE CONCENTRATIN OF LOW - MOLECULAR-WEIGHT NITROGEN-CONTAINING COMPOUNDS IN BLOOD

Abstract

The present invention aims at preventing or retarding a transition to hemodialysis treatment in kidney failure or decreasing the number of implementation of the hemodialysis therap and preventing or lessening occuirenceofaccompanyinghyperammonemiainhepaticinsufficiency. To accomlish the Voses described above, the pathological improvement food of the invention is featured by being composed chieflv of indigestible polysaccharides and having restricted addition of protein components. Energy produced by exporting the indigestible polysaccharides contributes to fungal protein synthesis using, asanN-source.ureaorammonia secretionintotheintestine andexcretionof toliferatedbacteriawith feces, so that nitrogen-containing low-molecular substances in the blood can be decreased, thereby to im^ovedisorderofthekidnepndliver.

Full Text	FORM 2 THE PATENT ACT 1970 (39 of 1970) & The Patents Rules, 2003 PROVISIONAL/COMPLETE SPECIFICATION (See section 10 and rule 13) 1. FOOD FOR IMPROVING CLINICAL CONDITIONS CAPABLE OF LOWERING THE CONCENTRATIN OF LOW-MOLECULAR-WEIGHT NITROGEN-CONTAINING COMPOUNDS IN BLOOD 2. (A) CHEIRON JAPAN CO. (B) JAPAN (C) 202,25-1, Funabachi 3-chome, Setagaya-ku, Tokyo, Japan. The following specification particularly describes the invention and the manner in which it is to be performed. TECHNICALFIELD This invention relates to food suitable for improving clinical conditions of patients particularly with kidney failure or hectic failure, and more particular1y to pathological improvement food capable of being used for preventing or retarding a transition to hemodialysis treatment in kidney failure or decreasing the number of impementation of the hemodialysis therapy and preventing or lessening occurrence of accompanyinghyperammonemiainhepaticinsufficiency. BACKGROUNDART There has been so far known that dietary' fiber or nonfibrillary hydroscopi c carbon has a function of increasing the excretion amount of nitrogen into feces without digesting dietary fiber or non-fibrillary hydraulic carboninthe smallintestineofthehumanor animal. Thisisdisclosed in, fbrexample, Sealock, R. R., Basinski, D. H. & Murlin, J. R.: J. Nutrition, 22,589-596 (1941); Mason, V. C. & Palmer, R. M.: Proc. Nutr. Soc., 32, 82A, 83A(1973); Weber.F. L Gastroenterology: 77, 518-523(1979); and Steven, A., M. & Cummings,J.H.:Proc,Nutr.Soc.,38,141A(1979). An application example for applying the dietary fiber to renal disease is disclosed in Japanese Patent Application Publication HEI02-101016A. This publication discloses preparation for improving renal disease, which contains the dietary fiber as an active ingredient made from the hull of edible seed. The publication suggests that the dietary fiber made from the hull is effective at prolonging the life of a rat with acute kidney failure resulting from renal ligation. However, since the case of acute renal disorder of renal ligationhas no appicationto achronic disordercaseofa human andrtis uncertainwhetheromot the dietary fiber is effective in the treatment of renal disease, various kinds of dietary fibers are dealt with indusively in the publication. Thus, there is an undesirable possibility of side effects such as diarrhea due to dietary fiber intakeincreasedsimply. For the meanwhile, it has known that 40% to 70% of nitrogen in the feces are derived from fungal proteinwithinintestinal bacteria. whichmakes useofammoniaproducedbydecomposition ofureasecreted into the intestine to convert the fungal protein. -See Wrong, 0. M. & Vince, A.: Proc. Nutr. Soc, 43, pp.77-86(1984)- 2 kidney failure by positively using the urea secreted into the intestine for of fungal protein synthesis of the intestinalbacteriaintheintestine. The medical guideline recommended by Japanese Society of Nephrology provides restriction of proteinintake(0.5to0.6pykgbodyweight)forpreventifingcreaseofureanitrogeninthebiood(BloodUrea Nitrogen BUN) of a renal failure patient ("Lrfestyle guidance and dietary advice for patients with renal disease" combed by Japanese Society of Nphrology). In addition to the restriction of protein intake, ingestion of qualif protein having high biological value (such as animal protein, fishery product whole egg, etc.)isrecommended. To accomplish this purpose, low-gluten wheat is recommended as kidney failure diet, and therefore, there havebeendevelopeda gooddealoflow-protein foodofhigh-biologicalvalue. Further, variousdietar* suppements and elemental diets containing essential amino acid in a balanced manner have been devised andused. Although high-protein food of high-biological value is recommended for patients with hectic failure, high-calorie elemental diets containing branched-chain amino acids (valine, leucine and isoleucine) have been devised and used for hepatic disease, because such amino acids provide promotion of insulin secretion and suppression of formation of trypopan-derived serotonin or other brain amines by being antagonistic to trypcphan with respect to blood-brain barrier to prevent hpatic coma and cause awakening, and arginine containedintheaminoacidsactivatesureacycle. However, the aforesaid diets are mere food or enteral nutrient having a function of decreasing the supply of low-molecular-weight nitrogen-containing confounds such as urea and ammonia or raise hopes for producing sytomatic improvement through the provision of high-biological value protein or food composed of amino acid at an appropriate ratio of concentration designed in mixture. However, these diets do not fulfill the purpose and function of decreasing BUN since excretion of ingested nitrogen-containing confounds to the outside of the body through the route other than the principal metabolic excretion system orperipheralroute. As a result, when the low-molecular-weight nitrogen confounds such as urea derived from protein and amino acid in the diet are accumulated in the blood befond the filtering ability of the kidne" of a renal failureptientthenitrogencompundswillbedischargoutsideofthebodybyhemodifilltration Besides the dietetic treatment as noted above, there have been often used medicinal agents such as activated charcoal and cation-exchange resin for absorbing or inactivating ammonia drawn into the intestine to discharge or remove the ammonia as feces so as to decrease the blood ammonia level in the patient with hepaticfailur. 3 There have been the following guidelines of alimentaiy therap for accorrflishing the purposes describedabove. (l)Quantitativerestrictionanoqualitativeenrichmentoprotein: It isrecommendable to quantitatively restrict the intake of protein and qualitative^ enrich the quality of the protein in order for reducing the burden of nitric metabolite and preverrting decrease in kidne" function. In general, low-protein diets (0.6 g/kg bod1' weight for kidne5' feilure, and 1.2 to 1.5 g/kg body weight for hectic failure) bring about an effect of slowing the deterioration in kidne* failure or hepatic failure. Since the dietary treatment should extend over a long period of time, it is necessary to select the diets of high protein value protein score) so as to regulate the balance of essential amino acids ("Lifesyle guidance and dieted advice for patients with renal disease" confiled tfJaynese Socief of Nephrology, Tokyoigakusha (1998), and "Nutritional diagnostics of liver diseases / Liver disease and nutritional theray', Akiharu WatanabeandMisakoOkrta.DaHchiShiuppanpublisingCo.ltd pp.53-68(1992)) (2)Sufficientsupplyofdietaryenergy ltisthoughtthat35kcal/kgofdailvenergyisappropriateand daiFenen/intakesof 1800to2000kcal are recommended. ("Lifestyle guidance and dietary advice for patients with renal disease" combed by Japanese Society of Nephrology, Tokyoigakusha (1998), and "Nutritional diagnostics of liver diseases / Liver disease and nutritional thera^', Akiharu Watanabe and Misako Okita, DaMchi Shu^an Publishing Co-.Ltd.^.SS-68(1992)) (3)SodiumchlorideCNaCI)shouldberestrictediiracomplicatinofanasarcaandhigh-bloodpressure (4)Potassiumshouldberestrictedincausinghyperkalemia. (5) Water intake should be restricted with salt when developing signs of anasarca, whereas dehydration requiresattentioningeneral. It is general important to satisf the quantity and balance of required essential amino acids by low proteindiets. Under the conventional technology it is necessar* to give foods of high-biological value and having low total content of nitrogen to a patient with renal feilure so as to reduce protein intake, which foods are Wared in such a manner that the Wortion of better protein in the foods is increased for infroving the quality of protein intake and reducing the total content of nitrogen or by using amino acids, especially, essential amino acid confounds having desirable relative Wortions of the amino acids. However, when the concentration of low-molecular-weight nitrogen-containing confounds in the blood su^asses the renal fittrationca^bil^.th^atierrtmustunde 4 Thehemodialysistreatmentrequiresthe^atienttoattendahospitalthreeorfourtimes aweekandhave therawthree to five hours onattending occasions. Large temporal, financial and Penological burdens will be exerted on the patient undergoing the hemodiaPsis treatment, resulting in a major detriment at the individualandsociallevels. The medicine using the hemodialysis treatment for discharging the low-molecular-weight nitrogen-containing confounds from the blood will impose not only tremendous temporal, financial, Wsical and psycho!ogical burdens upon the patient, but also create more problems such as a large social burden of medical costs covered by a medical e^ense insurance. Such dialysis medical e^enses will tend tobeincreasingfromnowon. Hepaticcomainhepati(^ilurepatientsiscausedbydeCTeaseinactivftyofui^ Also, ammonia escalated in the blood due to the hepatic failure has a bearing on the drculation c^de of the intestine and blood. As a medical formula for discharging the ammonia to the outside of the body there has been recognized a dose of chemical absorbing agent such as activated charcoal and cation-exchange resin is effective as a medical su"5!7. However, heavy dosage of the absorbing agent having a possible side effect laces an enormous burden to the patient Under the drcumstances, a need has been felt for an effective solutioncapableofreducingtheburdensinvo!vedintreating. Thus, the present invention seeks to provide a superior solution of the aforementioned problems involvedintreatingapatientwithkidneyfai!ureomepaticfailure. DISCLOSUREOFTHEINVENTION The inventors of this invention has found the solution for attaining the objects described above, by administering indigestible polysaccharides as food having energy required for protein synthesis by bacteria, which isdiftlculttodigestaccordingtodigestiveenzyme and mavbe ingestedas foodaccordingtointestinal bacteria, for the Wose of making use of low-molecular-weight nitrogen-containing confounds that are drained into the intestine and drculated in the reingested state as ingredients for fungal protein synthesis of intestinal bacteria to reduce the finandal and tenforal burdens involved in undergoing the hemodialysis treatment without taking any drug medidnes having potential adverse effects. This invention could be achievedonthestrengthofthisbiochemicalknowtedge. That is, the present invention provides patho!ogical infrovement food composed chiefly of indigestible ^saccharides and having restricted addition of protein confonents, which contains trace metal.vrtaminand/orfatasrequired. 5 BESTMODEFORCARRYINGOUTTHEINVENTION Theinventionwillbedescribedhereinafterindetail. First, as to indigestible pol ysaccharides, starch and glycogen falling into polysaccharides are digested into glucose in the small intestine by digestive enzyme such as amylase in saliva or pancreatic fluid so as to be ingested into the bod1'. Meanwhile, the ^saccharides t^rfied by cellulose that isresistant to hydrolysis by the digestive enzyme have been known as dietary fiber (Dietar1' Fiber, M i ps\& 1953). However, lactic acid bacilli and bifidobacteria that belong to intestinal normal inhabitants in the large intestine can export certain dietary fiber, and specifically, these enterobacteria can easily take in water-soluble dietar7 fiber fectine, gum, oligosaccharide, alginic acid, chrtosan, etc.) The dietar7 fiber exported by the intestinal normal inhabitants is termed as indigestible ^saccharide. Polydextrose used in this invention is relative of oligosaccharideanctfallsintotheindigestibl^oPs^ Concretely speaking, the aforementioned indigestible polysaccharides include pectine, that is in an a^e, strawberry and citrus, seaweed-derived alginic acid, fucoidan, crustacean chitin, chitosan, gums such as acacia gum, arum root-derived mannan, agar, polydextrose that is glucose polymer, testa-derived water-soluble dietar7 fiber (hemicellulose) such as com, soybeans and psyllium, and sugar alcohol and polymersofsugaralcohol. Of these polysaccharides, a compound made up of polydextrose and pectine has been used suitably. The proportion of the confound is preferably 0.05 to 100 parts by weight of pectine to 100 "arts of polydextrose. The inventorshave knowledge that such a confound brings about the most prominent effect of lowering BUN without causing diarrhea in ingestion thereof. For unknown reasons, it is conceivable that the polydextrose and pectine are different in use-efficienc7 owing to intestinal bacteria such as lactic acid bacilli, consequent^ to further facilitate the activity of the lactic acid bacilli because of difference between theminmetabolicrate. Oftheaforesaid substances.the pectinecan easiPbemadefromana^leorcitrus fruitorobtainedas a co-productinthemakingofcitrusdrinks. There can be produced alginic acid and fucoidan from seaweeds, arid the chitin and chitosan from crustacean shells with sinfle operation. The polydextrose can be made by polymerizing a natural product such as glucose as a basic ingredient in the presence of citric acid. Avariety of testa-derived water-soluble dietaryfibersarecommerciallyavailable. The pathological irrfrovement food according to the invention contains more than 5% by weight, preferably, 40% to 70% by weight of indigestible ^saccharide as a chief ingredient relative to the solid 6' content of the food in terms of dried foodstuff. When exceeding 70% by weight, the food is like!y to be viscous1consequentlytomakefoodprocessingdifrlcurt The restriction of protein component in the food has a meaning of addition thereof within the range which does not raise blood urea nitrogen when ingesting with the indigestible polysaccharides and the proteincontentis50% oriessreiativetothefoodofakind. Tobe more specffic,theproportonoftheprotein component (i.e. protein and its partially hydrolyzed protein fe'Hide)) to the solid content is made to 8% or iessbyweight,preferablyaboul2%byweightintenTisofdriedfoodstufT. The indigestible polysaccharides according to the invention contains, as basic ingredients, singly the aforementioned indigestible polysaccharides or confounds combined with several kinds of indigestible ^saccharides controlled in sweetness and acerbity with sweetener such as sucrose, fructose, glucose and sugar alcohol or natural sweetener such as luohan fruit essence and citric acid. To strengthen the effect of a dietar* su^ement, the indigestible polysaccharides of the invention may additional? contain sodium salt, potassium sajt, magnesium salt and calcium sal and further the needed volume of trace metals such as Zn, Fe, Cu, Co, Mn, Cr and Se inthe formofthea^roved foodadditives. To further strengthen the effect ofthe dietary su^ement, the indigestible ^saccharides of the invention may additional? contain, as a primary body, substances fortified with a suitable quantfty of vitamins such as vitamin A, vitamin B family (e.g. B1, B2, B6,B12andnicotineacid),vitamin C,VrtaminE,andfolic aad,essentialfattyatidoromega-3fat. The indigestible polysaccharides of the invention may be produced in the form of a liquid (drink), jelly or cream or in a solid or semisolid form like a biscuit cookie, bread, noodles, cake, ice cream, and sherbet and can be givensing^orincdmbinationtoa^tientwrrjikidn^failureom^aticfailure. It may be preferable to make a variety ofthe indigestible ^saccharides according to the invention with variations so as to kee13 the patient from being bored by being flavored with fruit juice such as of an a^le, lemon, strawberry, blueberr* mandarin orange, orange, pomegranate, litchee, ^nea^e, papaya and banana.orflavoringagents. Through e^eriments using ^gs, it has been actually demonstrated the fact that the indigestible polysaccharides of the invention have a significant effect of reducing urinal excretion of nitrogen-containing low-molecular substances and excreting almost all the ingested nitrogen into faces (Lecture Abstract of 76th Meeting of The Japanese Society of Swine Science; Lecturers: Yamamoto et al., The Japanese Journal of Swine Science, Vol.38(4), p.227 (2001)). Yamamoto et al. announced in the meetingthaturinaryureaexcretionwas decreasedto one-tenthwhenraisehearth^gsfor sevendayswitha feed of low-protein feeding stuff (nitrogen intake 35.5 grams per day on an average) mixed with 30% by weightofapplejuicelees(dried foodstuff). The nitrogenequivalenttothesubstance takenupbyfeces could beretrieved. 7 The experimental results using the Pigs siPort the possibilrty that the diet containing indigestible polysaccharides brings about significant effects of lowering the concentration of nitrogen-containing low-molecular substances in the blood of a hectic failure patient so as to hold over treatments with hemodialysis or reduce the number of treatments with hemodialysis, or lowering the concentration of blood ammonia level of a kidney failure patient to prevent hePatic coma. However, the experimental results using the pigs do not always indicate the effectiveness of the pathological improvement food of the invention in treating the patients with kidne* failure and hepatic failure from the viewpoint of the dose of the indigestible Po^saccharidesaPPliedtothePigsforexPerimentalPurPose. To put it another way, the pathological improvement food of the invention, which chiefly contains indigestible polysaccharides, can take various forms such asdrink, cream, biscuit,bread, cake, ice creamand provide various textures by diversely combining different kinds of indigestible polysaccharides or determining the amount of each ingredient, or the pathological improvement food of the invention may be made in the form of powder composed ofrequired ingredients. Therefore, desirable diet food as mentioned abovemaybemadeinthehomeaccordingfothePatient The t^cal of indigestible ^saccharides is pectine. The pectine is contained in P\|enty in an aPPle and citrus fruit and remains in existence in high concentration in fruit juice lees. Thus, the pectine can be extracted from the lees and processed into a dry product upon being de-esterified with acid or alkali and purified. It may also be processed in such a manner of being extracted from the a^e, pericarP of citrus fruit or vegetable, de-esterified with acid or alkali, filtrated, concentrated, Precipitated with alcohol to be cleansed, dried and broken into powder. The pectine may be taken out bybeing refined for use in this invention in the manner described above, but a^e juice lees or fruit juice lees of citrus fruit (mandarin orange, orange, grapefruit, etc.) may be used as the1' are for the same Wose as the refined pectine because these juice lees arerichinpectine. Thatis.thePectinetermedinthisinventionindudesft^ lees. Likewise, alginic acids and fucoidan, which are made from seaweed, and polydextrose made from glucose as a basic ingredient in the presence of citric acid can be used as the indigestible polysaccharide. These indigestible polysaccharides for use in the invention should not necessarily be understood as being limiteo^otherefinedproducteaslongastheeffectoftheinventionisnotnjined. The ^saccharide becomes viscous when dissolving in water because it can absorb large volume of waterintoitspolymerstructure. Therefore,whentheindigestiblePolysaccharideisusedinthePreParationof a beverage, the concentration thereof is desirably 0.5% to 30% by weight Also, it is preferable to determine the concentration of the same to 2% to 30% by weight for creamy food, 2% to 30% by weight for je!lylike food,and5%to60%byweightforcakes,and5%to60%byweightforeJriedfoodssuchasbis 8 considered to be fundamental to maintenance of Wsical functioning, such as Mg, Zn, Fe, Cu, Co, Mn, Cr and Se due to unbalanced diet Likewise, a patient undergoing hemodialysis treatment often lacks ingestion of the trace metals due to exteriorize thereof during hemodialysis, consequently to possibly cause renal anemia. The pathological infrovement food of the invention may contain 0.01 % to 5.0% by weight of trace metalsina freestateor intheadditive formofmetal-containing yeast(e.g. "MineralYeasf'made ^Oriental Yeast Co., Ltd.) The pathological improvement food thus produced even containing such trace metals does not have a disagreeable smell endemic to metal nor nasty taste and can be made in safety. The su^lementation of trace metal condensates deficiency of the patient and activates the intestinal bacteria. Thus, the pathological improvement food composed chieflyofthe indigestible polysaccharides according to the invention can be further elevated in availability. To be more specific, the ingestion of the indigestible polysaccharidecontributes toreducethelevelof blood ureaandlow-moleculamitrogen compounds suchas ammonia, consequently to promote a^etite su^ression and eliminate a lowering factor for metabolic activrt/. lnaddffiontotheaforesaidprominenteffectsotttepatholog^ the essential nutrients such as the trace metals noted above are efficients added thereto, consequent^ to Produceas^ergistc^ectforimProvingthe^sicalconditions. TTiere may be further added lactobacillus spore, e.g. LACRIS (trade name), made by Sankyo Utetech Co.,Ltd.,totheaforesaidfoodinordertostimulategrowthoflacticacidbac!!li. TTte present invention provides effective means capable of decreasing the amount of nitrogen reabsorbed from the intestine into the bloodstream to su^ress the rise of concentration of the low-molecular-weight nitrogen-containing confounds in the blood through the exquisite biodynamic mechanism in which the low-molecular-weight nitrogen-containing confounds such as urea discharged from the blood (through the blood vessel) into the intestine are effected for protein sVrthesis of intestinal bacteria and passed out with feces. To accom^ish the intended means, the food prepared with the indigestible polysaccharide, which is not easily exported by digestive enzvme but is effective for the irrtestinalbacteria,therebytomakeuseofferesuFtert lntrinsically, the low-molecular-weight nitrogen-containing compounds in the blood such as urea and ammonia are secreted into the intestine with the bodily fluid and reabsorbed, thus being circulated between thefluidintheintestineandtheblood. Therefore.thenitrogen-containinglow-molecularsubstancessecreted into the intestine can be utilized as a nitrogen source working on the protein synthesis of intestinal bacteria and discharged to the outside of the 000* as feces upon prorrferating the fungus bodies, thereby to break off the circulation of nitrogen-containing confounds between the intestine and the blood, resulting in a lower concentration in the blood. Thus, the excretion of the confounds effects alleviating of a burden on the 9 kidne. The reduced burden of the kidney causes degeneration of kidney glomerulus to be retarded, so as to have an expectancv to retard a transition to hemodiaPsis treatment and decrease the number of hemodialysis. I f a kidne1' failure patient periodicallv takes the pathological improvement food of the invention after each meal and/or between meals, a part of the low-molecular-weight nitrogen-containing confound in the bloodis partiallyconvertedinto intestinalbacterial proteinand thenexcretedas feces.resurtinginloweringof thebloodcon centrationthereof, soastoenablethetransitiontohemodiaP'sistreatmenttoberetardedandthe number of required hemodiaFsis to be decreased. As a result the various problems posed by the hemodiaPsistreatmentcaneffectrvePl^olv^ Also, when the pathological improvement food having the function of driving the fungal protein synthesis of intestinal bacteria with ammonia secreted into the intestine and excreting the ammonia with feces is given to a patient with hepatic failure after each meal and/or between meals, the problems as above can be solved, so that distress involved in taking high doses of adsorbent agent can be relieved without producinganysideeffectaccordingtotheinvention. The nitrogen-containing compound, specifically ammonia, in the urine, emits urine odor, whereas the urineodorgwenoutduetoanesthesiaexcretionofabedridden^ The 'resent invention will be described hereinafter in more detail, demonstrating some medicafizing cases using the patho!ogical improvement food of the invention, but the invention does by no means contemplateimpc«inganylimitationtothecasesandcompositionsdescribedbelow. (Embodiment) Beverage Table 1 below shows solid contents of the essential constituent parts of the pathological improvement food of the invention per 100 grams of beverage made by adding water to the essential constituents. There was^aredlOOgramsofbeveragefroductJt^addingwaterthereto. 10 10 Basiclngredients Solidcontentsper1 OOgramsofbeverage PolydextrosePectineFructoseCitricadd-NaVitaminC VitaminBiVitamihB2 VrtaminBgVitaminBi Nicotinic-acidamideFolicaddDHACaldurngfcero^os^ateMgCI2Fe-containingmineralyeastZn-containingmineralyeastCu-containingmineralyeastMn-containingminera^eastArumroofowderorAgarFoodflavor (of a^dtrusandsoon)FrurijuiceorfruitessenceTextureimprovingagentSweetener ~20g ~20g ~5g - 400mg ~500mg ~20mg -20mg ~2mg ~1mg ~20mg ~5mg ~0.5g ~300mg ~200mg ~30mg ~50mg ~30mg -10mgq.s.q.s.q.s.q.s.qs. TABLE1 Waterisaddedtodefinethetotalasl 00. pH:4.5to5.5 / Viscosity:50to500mPas Color Lightyellow-lightbrown / Taste:Moderatelyadjustedwithsweetandacid Energy:30to80kcal/100g MineralYeast:Cr-orSe-containingmineralveastmaybeaddedarbitrarily. Table 1 exercises the daiy[ intake of the beverage. The beverage may be taken in dailv after each mealduringdialysistreatmentatonetimeorindivideddoses. Altematively)itmaybedrunkwithfooditems described in Embodiment 2 and Embodiment 3 in combination. The daily intake as exemplified herein may of course be increased, but calorie of the food according to the invention may be preferably reduced to notexceeding300kcalperdayforexample. Particulariyina caseofadiabeticpatientondialysis,thecaloric intake by the nutraceutical food of the invention should be reduced as low as possible to lessen the influence oncaloriecountofessentialstaplefood. 11 Apple juice lees can be substituted for pectine. The pectine derived from a^e juice, strawberry, citrous or other fruits or pectine-containing foodstuff may be used as an alternative thereto. Also, there may 12 be used other ingredients than pectine, such as acacia gum falling into indigestible polysaccharides, testa-derived hemicellubse, seaweed-derived alginic acids, arum root-derived mannan and so forth instead. Thepectinemaybedisplacedinpart Fmdosemaybrepacedwithoneofsucrose.sugaralcoholandothersweetenersoramixtureofthese. As the sweetener, there may also be used natural sweetener such as luohan frurt essence, stevia, licorice extract. AnarrjficialsweetenersuchasAspartamemaybeused. As to vitamins, there are added vitamin C that is easier to lack and vitamin B family that is losable duringthehemodialysistreatment lnspecrfic,sincemineralssuchastraceminerals{Fe,Zn,Cu,Mn,Cr,Se, etc.) essential for maintenance of body function have not been a^roved as food additives by Ministr of Health.Labour and Welfare, yeast containing some ofthese ingredients is added t^the quantityrequired for dailyrequirementforadultfomutritionalconsiderations. For inVYoving the texture of the pathological improvement food, 0.1 to 3 grams of agar powder or alimentarumroofowdermaybeaddedtomakethefoodjelly. When drinking200to 300grams (equivalentinsolidcontent) ofthe beverage thusprepared aday, 4to 8 grams of protein taken on the same day are fixed into intestinal bacterial protein, consequent!* to be excreted with feces. As a result, the blood concentration of low-molecular-weight nitrogen-containing confounds such as urea can be decreased corresp0nding to the amount of nitrogen content in the fungal protein,toalleviateaburdenonthekidnev. TheconditJonsatrJiatdmecanbefomiulatedr/thefollowino/ormula. That is, there can be proved e^erimentalF the following relation in which the intestinal bacteria gains energy by exporting indigestible polysaccharides using, as a nitrogen source, low-molecular-weight nitrogerHX)ntainingcompoundssuchasureasecretedintheintestineinfungalproteinsynthesis. (a) Assuming that the total energy content of indigestible polysaccharide is general 3.6 kcal/g and 50% of the energy is consumed by the fungus bod1', the energy at which the indigestible polysaccharide (Ag)areconsumedbythefungusbodyisAgx3.6kcal/gx0.5=1.8xA(kcal). (b) Assuming that the energy required for fungal protein synthesis is generally 5.66 kcal/g protein and the energy use effia'ency by the intestinal bacteria is 44%, the fungal protein synthesis of Bg necessitates Bg x 5.66 kcal x 0.44 = 12.8 x B(kcal). Accordingly, the a^roximate amount of bacterial protein (Bg) s^esized^oraladministrationofTiieindigestible^saccharideofAgisI .8xA/12.8. 13 (A) of 30 to 60 grams of the indigestible ^saccharides, and the fungal protein content (B) synthesized at thatrJmebecomes4.2to8.4grarns. Whenattdnyfailuipatient(50kgbodyweight)consumes30gramsfproteinaday(0.6g/kgbody weight), the intake of 300 grams of the beverage in terms of solid content brings about the same effect as intakereductionby4% to17% ofrotein. (Embodiment2)Jellvlikefood Table2belowshowspafeofrJieessentialconstrtuentsofthejellylikefood. TABLE2 Basiclngredients BlendingGuantity A^lejuiceleesPectinePolydextrose Arumroot-derivedmannan 3to20g 1to10g 10to20g 0.1to2g Waterisaddedtobe60to105grams. Fructose, citric acid, sodium citrate, vitamin C, vitamin B family (B1, B2, B6, nicotinic-acid amide, and B 12), trace metals, and mineral yeast all are contained in a similar manner in the beverage (former embodiment) and the jelMike food. Thus, the jelflike food can be produced by adding fructose and the subsequent ingredients shown in Table 1 to three ingredients shown in Table 2. The water content of the foodisiegulatedr/addingwaten^thefoodsoastomakeatotalof604o105gramsintotal. ThejelMike food Waredinthe aforementioned mannermaybe stored in containers of, forexample, 20,25or 35gramsinasterilecondition. Itmayofcoursebecontainedinalargercontaineror packager. The aforesaid jelfflike food (20-gram, 25-gram or 35-gram package) may be taken after each meal or during dialysis treatment as needed. When consuming one dose of food of the quantity described above three times a day, the daiP intake of indigestible polysaccharides becomes roughly 25 grams (20- Even i f the protein intake (or nitrogen intake) fluctuates from day to day, ft is equivalent to the total excretion amount of nitrogen. The intake of indigestible ^saccharides enhances the effect of introducing 14 the nitrogen into feces via the principal excreting route rather than feces routed through the kidne' or large intestine, thereby to lessen a burden infosed on the kidney and bring about an effect of detoxication and exdusionofhrrjogen-containingcompoundssuchasureasecretedintotheintestine. Incidental^ a hepatic failure patient may possibly be relieved from the sufferings from gastrointestinal disordersuchasdiarrheaduetoammoniasecretedintotheintestine. (Embodiment3)Confectionerysuchasbiscurtsorcookies Dry or semidry products such as cookies, biscuits bread or rice crackers may be produced by using indigestible polysaccharides as a chief constituent The confosition of the chief constituent of food will be showninTable3below. TABLE3 Basiclngredients % (Dryweight) . Polydextrose 5to25% A^ejuicelees 10to40% Pectine 3to15% Cellulosefiber 5to10% Oligosaccharide 15to30% Starch(Low-glutenwheat) 5to20% Butter(orShortening) 10to20% Others(-) 1to10% 1% to 10% of sweetener, food flavor, vitamins and minerals are added on the basisofEmbodiments1and2. As the indigestible polysaccharides, there may also be used not merely a^e juice lees, but also acacia gum, psyllium and water-soluble indigestible polysaccharides derived from cereal testa such as of soybeans andcom. Bacilluscoagulant(e.g.LACROSSE0"radename))maybeadded. As cellulose fiber, microsco'l c cellulose powder such as "SolcaFloc 300FCC" (Danisco Japan KK) maybeusedbywayofexample. As the starch, potato starch, com starch, kudzu starch, and low-gluten wheat which are is low in protein, may be preferably used. Soft wheat flour may be used within the realm of using the starch. In the caseofusingthea^ejuicelees inbakingthecomponents showninTable3tomadethebiscu"rtsorcookies, the pectine-rich a^e juice lees become like mud and hard to bake particular1y when they are enriched with polydextroseandpectine. Consequently1thecomponentscontainingalargeamountofectineisnotsurtable 15 for such baked products, but wheat flour may be added so as to be over 20% to the total amount to improve the Wsical properties of the components. In making the product in this embodiment low-gluten wheat is preferably used to restrict the protein ingredient to less than its specific quantity while preventing flour-derivedproteinglutenfromadmixing. As to the ingredients of cookie and biscuit the biscuit contains butter (or shortening) that is smaller in amount than in the cookie, and the cookie and biscuit both contain baking soda and citric acid or sodium citric acid to prevent hardening and thus to provide favorable texture. Although the cookies and biscuits are general baked by using a common baking device, baking of the cookies and biscuits by microwave heating brings about an effect of releasing moisture content from the dough ingredients to make numerous poresintheproductsandprovidefavorabletexture. The butter and shortening are edible oil and fat and solid at room temperature in a lot of cases. The butter and shortening may contain oleic acid, palmitic acid, linoleic acid, linolenic acid and/or fatty acids havingacarbonnumberof12or14. Theremayrjefurtheraddedpolyunsaturateo^ttyaddsu{^asDHAinorderfor protecng^e(»ntralnervoussystemsusceptibletodisorderofthekidneyor1iver. Thecookiesandbiscuits thusproduced can ensure protein contentofO.1 to 4grams per day. Thefood products of this kind provide 400 kcal per day available to a patient so that a large amount of indigestible polysaccharidecanbegivenwrthoutaffecfingthedieteryschedulefotheoatient(1800to2000kcalperday), consequently to decrease the blood level of urea or ammonia. Thus, the food products according to the inventionprovidesynergistica!lytherapeirticbenefitto When taking six articles of food (e.g. cookies) made from the ingredients described above every day theintakeofindigestiblepolysaccharidesis about 30 to 50 grams. As aresult,4 to 6grams ofdietar^rotein areb^assedthroughthefecalroute. The food products such as the beverage, jelly and cookies shown in Embodiments 1,2 and 3 may be taken singly or in combination so as to excrete substantial amount of dietary-derived nitrogen components with urine and feces. The combination of the pathological infrovement food of the invention and regular mea!sindudingdini(^ldietbringsaboutenoticeablesynergisticeffectwithease. When taking 100 grams of beverage (solid content equivalent), two packages of jellv (25 grams per package), and six cookies by mixture daiP in several divided intakes, fungal protein synthesis runs to 10 to 15grams,resultinginexcretionofrJielcw-molecular-we^^ tc^uaipartsofthefongalproteinsynthesisthro 16 (Embodiment4)0theifypeoffood Adiet food maybe made bymixing5% to 30% bVeightofindigestible polysaccharides into noodle while reducing starch as flour as small as equivalent to the indigestible ^saccharides. In this case, the amount of indigestible ^saccharides to be added should be adequately determined based on the protein content in the flour or cereal starch so as to moderate the intake of protein to 0.6 g/kg body weight or less or 1.2to1.5g/kgbodyweighferday. The indigestible polysaccharides may be used as the basic ingredients of frozen desserts and confectioner1'. There may be added 5% to 20% by weight of polydextrose of the indigestible ^saccharides. The semisweet ^Fdextrose is suitable for confectioner. Addition of 1% to 5% of citrus pectine such as of an a^le or strawberr gives the confectioner* more sweet taste. The quantities of the principle ingredients of the confectioner1' such as milk and egg or protein components derived therefrom should be moderated to acconrtfish the objects of the invention. Such being the case, in ^ace of 20% to 70% by weight of protein in the food, there may be used a substituting ingredient made by adding 5% to 30% by weight of soybean or egg-derived lecithin to emulsified soybean made by condensing supematant fluid obtained in coagulating soybean curd. The protein confonents derived from milk or egg may be substituted for an ingredient made by adding soybean or egg-derived lecithin to the emulsified sc/bean to have high affinity with water. Thus, the present invention can provide the pathological improvement food haringanoticeab]esynergistireffiectwithinidigestiblapolysaccharidesbysuppressingtheproteinntake (Embodiment5)Testforimprovementofclinicalconditions(Case1) Three packages of jellMike food (25 grams each) as described in Embodiment 2 and six cookies as described in Embodiment 3 were given to four healthy male volunteer subjects and four health* female volunteer subjects (eight subjects in total) a day. The total quantity of indigestible polysaccharides was 80 gramsperdayonaverage,andthedailyproteinintakewas0.6g/kgbodyweight The e^erimental subjects were divided into two graups by gender and subjected to a cross-over method. Tobe specific,twomale andtwo female subjectsinonegroupstartedeatingcontroldiet foodatthe outset of the dietar* test and took e^erimental diet food from the 5th day, and then, continued to eat the e^erimental diet food for 4 days. The other group composed of two male and two female subjects started eating^ee^erimentaldietfoodandtoatandcontinuedtoeatcontroldietfoodfrothe5thdayfor4days An emanation about the objectives of the dietar* test, the compositions of the food under test and safe^ofthefoodwasmadetothee^erimentalsubjec^ogaintheirOTnsentinwriting. 17 respective subjects was collected to provide measurement for urinar* nitrogen ever1' day. The experimental resuttsobtainedeventualiyareshowninTable4below. TABLE4 BUN NitrogenAmountftotalurinevolume/dav ControlGroup 20.8±5.3mg/dl 12.3±4.5g/day TestingGroup 14.5±6.5mg/dl 8.1±2.9g/day As showninTable4,the excretionamountofhitrogenintothe urinewasdecreasedb)'34% andBUN isimprovedby30%. (Embodiment6)Testforimprovementofclinicalconditions(Case2) An experiment on the influence of the pathological improvement food on nitrogen excreted into the feces, BUN, urinar* urea and ammonia was conducted by giving three jelNike food toducts (25 grams each) as shown in Embodiment 2 a day and six cookie-like food products in two to three divided doses a da. From kidne" failure patients who need not hemodialysis, but have higher BUN and have habitualF kidne^su^orting diets, five experimental subjects were selected with the written consent of the patients upon ex^aining the research "ureses, prescribed diet food and schedule of experiment. The experiment was conducted by collecting blood samTes from the patients at the same time each day to measure BUN anc!. collecting all urine fromthe respective Patients to measure the amounts ofurea and ammonia everW. All feces of the respective patients were collected on the 7th, 8th and 9th days during the test to measure the total nitrogen amounts. On 7th, 8th and 9th days, the same meals were Wared, and the total amount of nitrogenofeach meal and theintake ofhitrogen were calculated. TTie calculatedamountsthereofare shown inTable5below. TABLE5 (1)Feces Tesferiod ControPeriodfomon-dose Periodfordose l_apseddays 7 8 9 7 8 9 Fecalamount 95.2±32.8 98.5±29.1 103.8±43.7 93.7±28.3 102.9±40.2 126.1 ±53.2 Totalnitrogen amount(g/daO 1.90.45 2.0±0.21 2.1 ±0.28 2.50±o.50 2.62±0.45 2.80±0.23 18 (2)BloodandUrine Tesferiod Controlperiodfomon-dose Periodfordose Lapseddays 1 4 7 10 14 2 4 7 10 14 Blood BUN(mg/dl) 35.3 36.2 33.7 34.6 34.8 30.8 28.3 26.1 25.3 24.8 Urine VolumeCL/da") 1.51 1.39 1.46 1.53 1.48 1.43 1.56 1.38 152 1.48 Totalnitrogen (g/da*) 3.7 3.9 3.9 3.4 3.6 3.2 2.8 2.8 2.4 2.6 As seen from Table 5, increase in amount of the feces and nitrogen excreted into the feces was confirmed on 9th day of a course of the e^eriment by the possible cause considered to be formula of the sample diet food. It was also confirmed that BUN was decreased by 20% and the excretion amount of nitrogenintotheurinewasimprovedby30%to60%onadailybasis. (EmbKxJimentTJTestforinfrovementofcJinicalcondrtionstCaseS) From patients undergoing dialysis three times a week, five experimental subjects were selected with the written consent of the patients upon explaining the research Voses, prescribed diet food and schedule ofe^erimentinthe same manner asinEmbodiment 6. The experiment was conductedbygivingthesame diet food of the same amount as sifflied in Embodiment 6 to the patientst to measure the total amount of nrtrogenexcretedintc^efeces^ndBUN.TheresultsareshowninTable6below. TABEL6 Tesferiod Controlperiodfomon-dose Periodfordose Lapseddays 7 8 9 7 8 9 Fecalamount 75.8±22.8 81.3±29.1 78.8±43.7 73.7±22.3 82.9±30.2 86.1±53.2 Totalnitrogen amount(g/day) 1.30±12 1.43±23 1.35±18 1.49129 1.62±26 1.57±35 BUN(mg/dl) 48.5 53.2 46.6 34.8 37.3 32.4 As seen from Table 6, increase in amount of the feces and nitrogen excreted into the feces was confirmed on 9th day of a course of the e^eriment by the possible cause considered to be formula of the sample diet food. It was also confirmed that BUN was decreased by about 30% on the 9th day and signrficantimprovementoccurred. 19 INDUSTRIALAPPLICABILITY The pathological improvement food according to the invention has a function of decreasing reabsor^on of low-molecu!ar-weight nitrogen-containing compounds such as urea circulating in the blood and intestine and then excreting the nitrogen-containing compounds in the form of feces through the mechanismofusingnitrogenofingestedproteinasanagent^ AccordingP.thePathologicalimfavemen (1) The blood concentration of the nitrogen-containing low-molecular substances such as BUN and ammonia can be lowered. (2) It becomes possible to alleviate the burdens exerted on thekidney ofa kidne1' failurepatientandretard atransrtiontohemodiaFsisfreatmentonlVtakinga specifiedquantityofthe food of the invention every day. (3) The number ofrequired hemodialysis required for treating Wdney failure can be decreased to lessen the Penological, temporal and financial burdens upon the patient and heighten the quality of life of the patient while saving medical e^enses. (4) The blood ammonia level can be decreased so as to ke^ a patient with acute or chronic hematic failure from a danger of falling into hepatic coma and improvethemedicalconditionofthepatient 20 CLAIMS: 1. Pathologicalimprovementfbod fbrioweringbloodconcentrationoflow-molecular-weight nitrogen-containing confounds, which contains, as basic ingredients, indigestible po!ysaccharides and has restrictedadditionofroteincomponents. 2. Pathologicalimprovementfood forloweringbloodconcentrationoflow-molecular-weight nitrogen-containing confounds, which contains more than 5% by weight of indigestible polysaccharides in tenrisofdrieo1bodstuffandproteincomponentsrestrictedto8%ori 3. Pathologicalimprovementfbod forloweringbloodconcentrationoflow-molecular-weight nitrogen-containing compounds according to claim 1 or claim 2, wherein said indigestible polysaccharides are one kind selected from pectine, polydextrose, alginic acid, fucoidan, chitin, chitosan, testa-derived hemicellulose, acacia gum, arum root-derived mannan, agar, and sugar alcohol and polymers of sugar alcohol. 4. Patho!ogicalimprovementfood forioweringbloodconcentrationoflow-molecular-weight nitrogen-containing confounds according to claim 2, wherein said indigestible polysaccharides contains at least polvdextrose and pectine with a ratio of 0.05 to 100 parts by weight of pectine to 100 parts of polydextrose. 5. Pathologicalimprovementfbod forloweringbloodconcentrationoflow-molecular-weight nitrogen-containing compounds accordingto anyofc!aims 1,2 and 4, further containing at least one oftrace metal.vrtaminandfat. 6. Pathologicalinfrovementfood forloweringbloodconcentrationoflow-molecular-weight nitrogen-containing confounds according to claim 3, further containing at least one oftrace metal, vitamin andfat. 21 7. Patholcgicalimprovementfoodforioweringbloodconcentrationofw-molecular-weight nitrogen-containing confounds according to any of daims 1, 2 and 4, which food is formed in beverage, biscuit cookie,cake,icecream,sherbet,bread,noodleorjelP'. 8. Pathologicalimprovementfood forioweringbloodconcentrationoflow-molecular-weight nitrogen-containing confounds according to claim 3, which food is formed in beverage, biscuit cookie, cake1icecream,sherbetbread,noodleorjelly. 9. Pathologicalimprovementfood forloweringbloodconc^ntrationoflow-molecular-weight nitrogen-containing confounds according to claim 5, which food is formed in beverage, biscuit cookie, cake,icecream,sherbet,bread,noodleorjelly. 10. Pathologicalimprovementfood forioweringbloodconcentrationoflow-molecular-weight nitrogen-containing confounds according to daim 6, which food is formed in beverage, biscuit cookie, cake,icecream,sherbet,bread,noodleorjelly. 11. Food for improving clinical conditions capable oflowering the concentratin oflow-molecular-weight nitrogen-containing compoundsin blood as herein described with forgoing description and figures. Dated this 12th day of September 2005. 22 ABSTRACT The present invention aims at preventing or retarding a transition to hemodialysis treatment in kidney failure or decreasing the number of implementation of the hemodialysis thera^ and preventing or lessening occuirenceofaccompanyinghyperammonemiainhepaticinsufficiency. To accomlish the Voses described above, the pathological improvement food of the invention is featured by being composed chieflv of indigestible polysaccharides and having restricted addition of protein components. Energy produced by exporting the indigestible polysaccharides contributes to fungal protein synthesis using, asanN-source.ureaorammonia secretionintotheintestine andexcretionof toliferatedbacteriawith feces, so that nitrogen-containing low-molecular substances in the blood can be decreased, thereby to im^ovedisorderofthekidnepndliver.

Full Text

FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
PROVISIONAL/COMPLETE SPECIFICATION
(See section 10 and rule 13)
1. FOOD FOR IMPROVING CLINICAL CONDITIONS CAPABLE OF LOWERING THE CONCENTRATIN OF LOW-MOLECULAR-WEIGHT NITROGEN-CONTAINING COMPOUNDS IN BLOOD
2.
(A) CHEIRON JAPAN CO.
(B) JAPAN
(C) 202,25-1, Funabachi 3-chome, Setagaya-ku, Tokyo,
Japan.
The following specification particularly describes the invention and the manner in which it is to be performed.

TECHNICALFIELD
This invention relates to food suitable for improving clinical conditions of patients particularly with kidney failure or hectic failure, and more particular1y to pathological improvement food capable of being used for preventing or retarding a transition to hemodialysis treatment in kidney failure or decreasing the number of impementation of the hemodialysis therapy and preventing or lessening occurrence of accompanyinghyperammonemiainhepaticinsufficiency.
BACKGROUNDART
There has been so far known that dietary' fiber or nonfibrillary hydroscopi c carbon has a function of increasing the excretion amount of nitrogen into feces without digesting dietary fiber or non-fibrillary hydraulic carboninthe smallintestineofthehumanor animal. Thisisdisclosed in, fbrexample, Sealock, R. R., Basinski, D. H. & Murlin, J. R.: J. Nutrition, 22,589-596 (1941); Mason, V. C. & Palmer, R. M.: Proc. Nutr. Soc., 32, 82A, 83A(1973); Weber.F. L Gastroenterology: 77, 518-523(1979); and Steven, A., M. & Cummings,J.H.:Proc,Nutr.Soc.,38,141A(1979).
An application example for applying the dietary fiber to renal disease is disclosed in Japanese Patent Application Publication HEI02-101016A. This publication discloses preparation for improving renal disease, which contains the dietary fiber as an active ingredient made from the hull of edible seed. The publication suggests that the dietary fiber made from the hull is effective at prolonging the life of a rat with acute kidney failure resulting from renal ligation. However, since the case of acute renal disorder of renal ligationhas no appicationto achronic disordercaseofa human andrtis uncertainwhetheromot the dietary fiber is effective in the treatment of renal disease, various kinds of dietary fibers are dealt with indusively in the publication. Thus, there is an undesirable possibility of side effects such as diarrhea due to dietary fiber intakeincreasedsimply.
For the meanwhile, it has known that 40% to 70% of nitrogen in the feces are derived from fungal proteinwithinintestinal bacteria. whichmakes useofammoniaproducedbydecomposition ofureasecreted into the intestine to convert the fungal protein. -See Wrong, 0. M. & Vince, A.: Proc. Nutr. Soc, 43, pp.77-86(1984)-
2

kidney failure by positively using the urea secreted into the intestine for of fungal protein synthesis of the intestinalbacteriaintheintestine.
The medical guideline recommended by Japanese Society of Nephrology provides restriction of proteinintake(0.5to0.6pykgbodyweight)forpreventifingcreaseofureanitrogeninthebiood(BloodUrea Nitrogen
BUN) of a renal failure patient ("Lrfestyle guidance and dietary advice for patients with renal disease" combed by Japanese Society of Nphrology). In addition to the restriction of protein intake, ingestion of qualif protein having high biological value (such as animal protein, fishery product whole egg, etc.)isrecommended.
To accomplish this purpose, low-gluten wheat is recommended as kidney failure diet, and therefore, there havebeendevelopeda gooddealoflow-protein foodofhigh-biologicalvalue. Further, variousdietar* suppements and elemental diets containing essential amino acid in a balanced manner have been devised andused.
Although high-protein food of high-biological value is recommended for patients with hectic failure, high-calorie elemental diets containing branched-chain amino acids (valine, leucine and isoleucine) have been devised and used for hepatic disease, because such amino acids provide promotion of insulin secretion and suppression of formation of trypopan-derived serotonin or other brain amines by being antagonistic to trypcphan with respect to blood-brain barrier to prevent hpatic coma and cause awakening, and arginine containedintheaminoacidsactivatesureacycle.
However, the aforesaid diets are mere food or enteral nutrient having a function of decreasing the supply of low-molecular-weight nitrogen-containing confounds such as urea and ammonia or raise hopes for producing sytomatic improvement through the provision of high-biological value protein or food composed of amino acid at an appropriate ratio of concentration designed in mixture. However, these diets do not fulfill the purpose and function of decreasing BUN since excretion of ingested nitrogen-containing confounds to the outside of the body through the route other than the principal metabolic excretion system orperipheralroute.
As a result, when the low-molecular-weight nitrogen confounds such as urea derived from protein and amino acid in the diet are accumulated in the blood befond the filtering ability of the kidne" of a renal failureptientthenitrogencompundswillbedischargoutsideofthebodybyhemodifilltration
Besides the dietetic treatment as noted above, there have been often used medicinal agents such as activated charcoal and cation-exchange resin for absorbing or inactivating ammonia drawn into the intestine to discharge or remove the ammonia as feces so as to decrease the blood ammonia level in the patient with hepaticfailur.
3

There have been the following guidelines of alimentaiy therap for accorrflishing the purposes describedabove.
(l)Quantitativerestrictionanoqualitativeenrichmentoprotein:
It isrecommendable to quantitatively restrict the intake of protein and qualitative^ enrich the quality of the protein in order for reducing the burden of nitric metabolite and preverrting decrease in kidne" function. In general, low-protein diets (0.6 g/kg bod1' weight for kidne5' feilure, and 1.2 to 1.5 g/kg body weight for hectic failure) bring about an effect of slowing the deterioration in kidne* failure or hepatic failure. Since the dietary treatment should extend over a long period of time, it is necessary to select the diets of high protein value protein score) so as to regulate the balance of essential amino acids ("Lifesyle guidance and dieted advice for patients with renal disease" confiled tfJaynese Socief of Nephrology, Tokyoigakusha (1998), and "Nutritional diagnostics of liver diseases / Liver disease and nutritional theray', Akiharu WatanabeandMisakoOkrta.DaHchiShiuppanpublisingCo.ltd pp.53-68(1992))
(2)Sufficientsupplyofdietaryenergy
ltisthoughtthat35kcal/kgofdailvenergyisappropriateand daiFenen/intakesof 1800to2000kcal are recommended. ("Lifestyle guidance and dietary advice for patients with renal disease" combed by Japanese Society of Nephrology, Tokyoigakusha (1998), and "Nutritional diagnostics of liver diseases / Liver disease and nutritional thera^', Akiharu Watanabe and Misako Okita, DaMchi Shu^an Publishing Co-.Ltd.^.SS-68(1992))
(3)SodiumchlorideCNaCI)shouldberestrictediiracomplicatinofanasarcaandhigh-bloodpressure
(4)Potassiumshouldberestrictedincausinghyperkalemia.
(5) Water intake should be restricted with salt when developing signs of anasarca, whereas dehydration requiresattentioningeneral.
It is general important to satisf the quantity and balance of required essential amino acids by low proteindiets.
Under the conventional technology it is necessar* to give foods of high-biological value and having low total content of nitrogen to a patient with renal feilure so as to reduce protein intake, which foods are Wared in such a manner that the Wortion of better protein in the foods is increased for infroving the quality of protein intake and reducing the total content of nitrogen or by using amino acids, especially, essential amino acid confounds having desirable relative Wortions of the amino acids. However, when the concentration of low-molecular-weight nitrogen-containing confounds in the blood su^asses the renal fittrationca^bil^.th^atierrtmustunde
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Thehemodialysistreatmentrequiresthe^atienttoattendahospitalthreeorfourtimes aweekandhave
therawthree to five hours onattending occasions. Large temporal, financial and Penological burdens will be exerted on the patient undergoing the hemodiaPsis treatment, resulting in a major detriment at the individualandsociallevels.
The medicine using the hemodialysis treatment for discharging the low-molecular-weight nitrogen-containing confounds from the blood will impose not only tremendous temporal, financial, Wsical and psycho!ogical burdens upon the patient, but also create more problems such as a large social burden of medical costs covered by a medical e^ense insurance. Such dialysis medical e^enses will tend tobeincreasingfromnowon.
Hepaticcomainhepati(^ilurepatientsiscausedbydeCTeaseinactivftyofui^ Also, ammonia
escalated in the blood due to the hepatic failure has a bearing on the drculation c^de of the intestine and blood. As a medical formula for discharging the ammonia to the outside of the body there has been recognized a dose of chemical absorbing agent such as activated charcoal and cation-exchange resin is effective as a medical su"5!7. However, heavy dosage of the absorbing agent having a possible side effect laces an enormous burden to the patient Under the drcumstances, a need has been felt for an effective solutioncapableofreducingtheburdensinvo!vedintreating.
Thus, the present invention seeks to provide a superior solution of the aforementioned problems involvedintreatingapatientwithkidneyfai!ureomepaticfailure.
DISCLOSUREOFTHEINVENTION
The inventors of this invention has found the solution for attaining the objects described above, by administering indigestible polysaccharides as food having energy required for protein synthesis by bacteria, which isdiftlculttodigestaccordingtodigestiveenzyme and mavbe ingestedas foodaccordingtointestinal bacteria, for the Wose of making use of low-molecular-weight nitrogen-containing confounds that are drained into the intestine and drculated in the reingested state as ingredients for fungal protein synthesis of intestinal bacteria to reduce the finandal and tenforal burdens involved in undergoing the hemodialysis treatment without taking any drug medidnes having potential adverse effects. This invention could be achievedonthestrengthofthisbiochemicalknowtedge.
That is, the present invention provides patho!ogical infrovement food composed chiefly of indigestible ^saccharides and having restricted addition of protein confonents, which contains trace metal.vrtaminand/orfatasrequired.
5

BESTMODEFORCARRYINGOUTTHEINVENTION
Theinventionwillbedescribedhereinafterindetail.
First, as to indigestible pol ysaccharides, starch and glycogen falling into polysaccharides are digested into glucose in the small intestine by digestive enzyme such as amylase in saliva or pancreatic fluid so as to be ingested into the bod1'. Meanwhile, the ^saccharides t^rfied by cellulose that isresistant to hydrolysis by the digestive enzyme have been known as dietary fiber (Dietar1' Fiber, M i ps\& 1953). However, lactic acid bacilli and bifidobacteria that belong to intestinal normal inhabitants in the large intestine can export certain dietary fiber, and specifically, these enterobacteria can easily take in water-soluble dietar7 fiber fectine, gum, oligosaccharide, alginic acid, chrtosan, etc.) The dietar7 fiber exported by the intestinal normal inhabitants is termed as indigestible ^saccharide. Polydextrose used in this invention is relative of oligosaccharideanctfallsintotheindigestibl^oPs^
Concretely speaking, the aforementioned indigestible polysaccharides include pectine, that is in an a^e, strawberry and citrus, seaweed-derived alginic acid, fucoidan, crustacean chitin, chitosan, gums such as acacia gum, arum root-derived mannan, agar, polydextrose that is glucose polymer, testa-derived water-soluble dietar7 fiber (hemicellulose) such as com, soybeans and psyllium, and sugar alcohol and polymersofsugaralcohol.
Of these polysaccharides, a compound made up of polydextrose and pectine has been used suitably. The proportion of the confound is preferably 0.05 to 100 parts by weight of pectine to 100 "arts of polydextrose. The inventorshave knowledge that such a confound brings about the most prominent effect of lowering BUN without causing diarrhea in ingestion thereof. For unknown reasons, it is conceivable that the polydextrose and pectine are different in use-efficienc7 owing to intestinal bacteria such as lactic acid bacilli, consequent^ to further facilitate the activity of the lactic acid bacilli because of difference between theminmetabolicrate.
Oftheaforesaid substances.the pectinecan easiPbemadefromana^leorcitrus fruitorobtainedas a co-productinthemakingofcitrusdrinks.
There can be produced alginic acid and fucoidan from seaweeds, arid the chitin and chitosan from crustacean shells with sinfle operation. The polydextrose can be made by polymerizing a natural product such as glucose as a basic ingredient in the presence of citric acid. Avariety of testa-derived water-soluble dietaryfibersarecommerciallyavailable.
The pathological irrfrovement food according to the invention contains more than 5% by weight, preferably, 40% to 70% by weight of indigestible ^saccharide as a chief ingredient relative to the solid
6'

content of the food in terms of dried foodstuff. When exceeding 70% by weight, the food is like!y to be viscous1consequentlytomakefoodprocessingdifrlcurt
The restriction of protein component in the food has a meaning of addition thereof within the range which does not raise blood urea nitrogen when ingesting with the indigestible polysaccharides and the proteincontentis50% oriessreiativetothefoodofakind. Tobe more specffic,theproportonoftheprotein component (i.e. protein and its partially hydrolyzed protein fe'Hide)) to the solid content is made to 8% or iessbyweight,preferablyaboul2%byweightintenTisofdriedfoodstufT.
The indigestible polysaccharides according to the invention contains, as basic ingredients, singly the aforementioned indigestible polysaccharides or confounds combined with several kinds of indigestible ^saccharides controlled in sweetness and acerbity with sweetener such as sucrose, fructose, glucose and sugar alcohol or natural sweetener such as luohan fruit essence and citric acid. To strengthen the effect of a dietar* su^ement, the indigestible polysaccharides of the invention may additional? contain sodium salt, potassium sajt, magnesium salt and calcium sal and further the needed volume of trace metals such as Zn, Fe, Cu, Co, Mn, Cr and Se inthe formofthea^roved foodadditives. To further strengthen the effect ofthe dietary su^ement, the indigestible ^saccharides of the invention may additional? contain, as a primary body, substances fortified with a suitable quantfty of vitamins such as vitamin A, vitamin B family (e.g. B1, B2, B6,B12andnicotineacid),vitamin C,VrtaminE,andfolic aad,essentialfattyatidoromega-3fat. The indigestible polysaccharides of the invention may be produced in the form of a liquid (drink), jelly or cream or in a solid or semisolid form like a biscuit cookie, bread, noodles, cake, ice cream, and sherbet and can be givensing^orincdmbinationtoa^tientwrrjikidn^failureom^aticfailure.
It may be preferable to make a variety ofthe indigestible ^saccharides according to the invention with variations so as to kee13 the patient from being bored by being flavored with fruit juice such as of an a^le, lemon, strawberry, blueberr* mandarin orange, orange, pomegranate, litchee, ^nea^e, papaya and banana.orflavoringagents.
Through e^eriments using ^gs, it has been actually demonstrated the fact that the indigestible polysaccharides of the invention have a significant effect of reducing urinal excretion of nitrogen-containing low-molecular substances and excreting almost all the ingested nitrogen into faces (Lecture Abstract of 76th Meeting of The Japanese Society of Swine Science; Lecturers: Yamamoto et al., The Japanese Journal of Swine Science, Vol.38(4), p.227 (2001)). Yamamoto et al. announced in the meetingthaturinaryureaexcretionwas decreasedto one-tenthwhenraisehearth^gsfor sevendayswitha feed of low-protein feeding stuff (nitrogen intake 35.5 grams per day on an average) mixed with 30% by weightofapplejuicelees(dried foodstuff). The nitrogenequivalenttothesubstance takenupbyfeces could beretrieved.
7

The experimental results using the Pigs siPort the possibilrty that the diet containing indigestible polysaccharides brings about significant effects of lowering the concentration of nitrogen-containing low-molecular substances in the blood of a hectic failure patient so as to hold over treatments with hemodialysis or reduce the number of treatments with hemodialysis, or lowering the concentration of blood ammonia level of a kidney failure patient to prevent hePatic coma. However, the experimental results using the pigs do not always indicate the effectiveness of the pathological improvement food of the invention in treating the patients with kidne* failure and hepatic failure from the viewpoint of the dose of the indigestible Po^saccharidesaPPliedtothePigsforexPerimentalPurPose.
To put it another way, the pathological improvement food of the invention, which chiefly contains indigestible polysaccharides, can take various forms such asdrink, cream, biscuit,bread, cake, ice creamand provide various textures by diversely combining different kinds of indigestible polysaccharides or determining the amount of each ingredient, or the pathological improvement food of the invention may be made in the form of powder composed ofrequired ingredients. Therefore, desirable diet food as mentioned abovemaybemadeinthehomeaccordingfothePatient
The t^cal of indigestible ^saccharides is pectine. The pectine is contained in P|enty in an aPPle and
citrus fruit and remains in existence in high concentration in fruit juice lees. Thus, the pectine can be
extracted from the lees and processed into a dry product upon being de-esterified with acid or alkali and
purified. It may also be processed in such a manner of being extracted from the a^e, pericarP of citrus fruit or
vegetable, de-esterified with acid or alkali, filtrated, concentrated, Precipitated with alcohol to be cleansed,
dried and broken into powder. The pectine may be taken out bybeing refined for use in this invention in the
manner described above, but a^e juice lees or fruit juice lees of citrus fruit (mandarin orange, orange,
grapefruit, etc.) may be used as the1' are for the same Wose as the refined pectine because these juice lees
arerichinpectine. Thatis.thePectinetermedinthisinventionindudesft^ lees.
Likewise, alginic acids and fucoidan, which are made from seaweed, and polydextrose made from glucose as a basic ingredient in the presence of citric acid can be used as the indigestible polysaccharide. These indigestible polysaccharides for use in the invention should not necessarily be understood as being limiteo^otherefinedproducteaslongastheeffectoftheinventionisnotnjined.
The ^saccharide becomes viscous when dissolving in water because it can absorb large volume of waterintoitspolymerstructure. Therefore,whentheindigestiblePolysaccharideisusedinthePreParationof a beverage, the concentration thereof is desirably 0.5% to 30% by weight Also, it is preferable to determine the concentration of the same to 2% to 30% by weight for creamy food, 2% to 30% by weight for je!lylike food,and5%to60%byweightforcakes,and5%to60%byweightforeJriedfoodssuchasbis 8

considered to be fundamental to maintenance of Wsical functioning, such as Mg, Zn, Fe, Cu, Co, Mn, Cr and Se due to unbalanced diet Likewise, a patient undergoing hemodialysis treatment often lacks ingestion of the trace metals due to exteriorize thereof during hemodialysis, consequently to possibly cause renal anemia.
The pathological infrovement food of the invention may contain 0.01 % to 5.0% by weight of trace
metalsina freestateor intheadditive formofmetal-containing yeast(e.g. "MineralYeasf'made ^Oriental
Yeast Co., Ltd.) The pathological improvement food thus produced even containing such trace metals does
not have a disagreeable smell endemic to metal nor nasty taste and can be made in safety. The
su^lementation of trace metal condensates deficiency of the patient and activates the intestinal bacteria.
Thus, the pathological improvement food composed chieflyofthe indigestible polysaccharides according to
the invention can be further elevated in availability. To be more specific, the ingestion of the indigestible
polysaccharidecontributes toreducethelevelof blood ureaandlow-moleculamitrogen compounds suchas
ammonia, consequently to promote a^etite su^ression and eliminate a lowering factor for metabolic
activrt/. lnaddffiontotheaforesaidprominenteffectsotttepatholog^ the
essential nutrients such as the trace metals noted above are efficients added thereto, consequent^ to Produceas^ergistc^ectforimProvingthe^sicalconditions.
TTiere may be further added lactobacillus spore, e.g. LACRIS (trade name), made by Sankyo Utetech Co.,Ltd.,totheaforesaidfoodinordertostimulategrowthoflacticacidbac!!li.
TTte present invention provides effective means capable of decreasing the amount of nitrogen reabsorbed from the intestine into the bloodstream to su^ress the rise of concentration of the low-molecular-weight nitrogen-containing confounds in the blood through the exquisite biodynamic mechanism in which the low-molecular-weight nitrogen-containing confounds such as urea discharged from the blood (through the blood vessel) into the intestine are effected for protein sVrthesis of intestinal bacteria and passed out with feces. To accom^ish the intended means, the food prepared with the indigestible polysaccharide, which is not easily exported by digestive enzvme but is effective for the irrtestinalbacteria,therebytomakeuseofferesuFtert
lntrinsically, the low-molecular-weight nitrogen-containing compounds in the blood such as urea and ammonia are secreted into the intestine with the bodily fluid and reabsorbed, thus being circulated between thefluidintheintestineandtheblood. Therefore.thenitrogen-containinglow-molecularsubstancessecreted into the intestine can be utilized as a nitrogen source working on the protein synthesis of intestinal bacteria and discharged to the outside of the 000* as feces upon prorrferating the fungus bodies, thereby to break off the circulation of nitrogen-containing confounds between the intestine and the blood, resulting in a lower concentration in the blood. Thus, the excretion of the confounds effects alleviating of a burden on the
9

kidne*.
The reduced burden of the kidney causes degeneration of kidney glomerulus to be retarded, so as to have an expectancv to retard a transition to hemodiaPsis treatment and decrease the number of hemodialysis.
I f a kidne1' failure patient periodicallv takes the pathological improvement food of the invention after each meal and/or between meals, a part of the low-molecular-weight nitrogen-containing confound in the bloodis partiallyconvertedinto intestinalbacterial proteinand thenexcretedas feces.resurtinginloweringof thebloodcon centrationthereof, soastoenablethetransitiontohemodiaP'sistreatmenttoberetardedandthe number of required hemodiaFsis to be decreased. As a result the various problems posed by the hemodiaPsistreatmentcaneffectrvePl^olv^
Also, when the pathological improvement food having the function of driving the fungal protein synthesis of intestinal bacteria with ammonia secreted into the intestine and excreting the ammonia with feces is given to a patient with hepatic failure after each meal and/or between meals, the problems as above can be solved, so that distress involved in taking high doses of adsorbent agent can be relieved without producinganysideeffectaccordingtotheinvention.
The nitrogen-containing compound, specifically ammonia, in the urine, emits urine odor, whereas the urineodorgwenoutduetoanesthesiaexcretionofabedridden^
The 'resent invention will be described hereinafter in more detail, demonstrating some medicafizing cases using the patho!ogical improvement food of the invention, but the invention does by no means contemplateimpc«inganylimitationtothecasesandcompositionsdescribedbelow. (Embodiment) Beverage
Table 1 below shows solid contents of the essential constituent parts of the pathological improvement food of the invention per 100 grams of beverage made by adding water to the essential constituents. There was^aredlOOgramsofbeveragefroductJt^addingwaterthereto.
10
10

Basiclngredients Solidcontentsper1 OOgramsofbeverage
PolydextrosePectineFructoseCitricadd-NaVitaminC VitaminBiVitamihB2 VrtaminBgVitaminBi Nicotinic-acidamideFolicaddDHACaldurngfcero^os^ateMgCI2Fe-containingmineralyeastZn-containingmineralyeastCu-containingmineralyeastMn-containingminera^eastArumroofowderorAgarFoodflavor (of a^dtrusandsoon)FrurijuiceorfruitessenceTextureimprovingagentSweetener ~20g ~20g ~5g - 400mg ~500mg ~20mg -20mg ~2mg ~1mg ~20mg ~5mg ~0.5g ~300mg ~200mg ~30mg ~50mg ~30mg -10mgq.s.q.s.q.s.q.s.qs.
TABLE1
Waterisaddedtodefinethetotalasl 00. pH:4.5to5.5 / Viscosity:50to500mPas
Color Lightyellow-lightbrown / Taste:Moderatelyadjustedwithsweetandacid Energy:30to80kcal/100g
MineralYeast:Cr-orSe-containingmineralveastmaybeaddedarbitrarily.
Table 1 exercises the daiy[ intake of the beverage. The beverage may be taken in dailv after each
mealduringdialysistreatmentatonetimeorindivideddoses. Altematively)itmaybedrunkwithfooditems
described in Embodiment 2 and Embodiment 3 in combination. The daily intake as exemplified herein may of course be increased, but calorie of the food according to the invention may be preferably reduced to notexceeding300kcalperdayforexample. Particulariyina caseofadiabeticpatientondialysis,thecaloric intake by the nutraceutical food of the invention should be reduced as low as possible to lessen the influence oncaloriecountofessentialstaplefood.
11

Apple juice lees can be substituted for pectine. The pectine derived from a^e juice, strawberry, citrous or other fruits or pectine-containing foodstuff may be used as an alternative thereto. Also, there may
12

be used other ingredients than pectine, such as acacia gum falling into indigestible polysaccharides, testa-derived hemicellubse, seaweed-derived alginic acids, arum root-derived mannan and so forth instead. Thepectinemaybedisplacedinpart
Fmdosemaybrepacedwithoneofsucrose.sugaralcoholandothersweetenersoramixtureofthese. As
the sweetener, there may also be used natural sweetener such as luohan frurt essence, stevia, licorice extract. AnarrjficialsweetenersuchasAspartamemaybeused.
As to vitamins, there are added vitamin C that is easier to lack and vitamin B family that is losable duringthehemodialysistreatment lnspecrfic,sincemineralssuchastraceminerals{Fe,Zn,Cu,Mn,Cr,Se, etc.) essential for maintenance of body function have not been a^roved as food additives by Ministr* of Health.Labour and Welfare, yeast containing some ofthese ingredients is added t^the quantityrequired for dailyrequirementforadultfomutritionalconsiderations.
For inVYoving the texture of the pathological improvement food, 0.1 to 3 grams of agar powder or alimentarumroofowdermaybeaddedtomakethefoodjelly.
When drinking200to 300grams (equivalentinsolidcontent) ofthe beverage thusprepared aday, 4to 8 grams of protein taken on the same day are fixed into intestinal bacterial protein, consequent!* to be excreted with feces. As a result, the blood concentration of low-molecular-weight nitrogen-containing confounds such as urea can be decreased corresp0nding to the amount of nitrogen content in the fungal protein,toalleviateaburdenonthekidnev.
TheconditJonsatrJiatdmecanbefomiulatedr/thefollowino/ormula.
That is, there can be proved e^erimentalF the following relation in which the intestinal bacteria gains energy by exporting indigestible polysaccharides using, as a nitrogen source, low-molecular-weight nitrogerHX)ntainingcompoundssuchasureasecretedintheintestineinfungalproteinsynthesis.
(a) Assuming that the total energy content of indigestible polysaccharide is general 3.6 kcal/g and 50% of the energy is consumed by the fungus bod1', the energy at which the indigestible polysaccharide (Ag)areconsumedbythefungusbodyisAgx3.6kcal/gx0.5=1.8xA(kcal).
(b) Assuming that the energy required for fungal protein synthesis is generally 5.66 kcal/g protein and the energy use effia'ency by the intestinal bacteria is 44%, the fungal protein synthesis of Bg necessitates Bg x 5.66 kcal x 0.44 = 12.8 x B(kcal). Accordingly, the a^roximate amount of bacterial protein (Bg) s^esized^oraladministrationofTiieindigestible^saccharideofAgisI .8xA/12.8.
13

(A) of 30 to 60 grams of the indigestible ^saccharides, and the fungal protein content (B) synthesized at thatrJmebecomes4.2to8.4grarns.
Whenattdnyfailuipatient(50kgbodyweight)consumes30gramsfproteinaday(0.6g/kgbody weight),
the intake of 300 grams of the beverage in terms of solid content brings about the same effect as intakereductionby4% to17% ofrotein.
(Embodiment2)Jellvlikefood
Table2belowshowspafeofrJieessentialconstrtuentsofthejellylikefood.
TABLE2
Basiclngredients BlendingGuantity
A^lejuiceleesPectinePolydextrose Arumroot-derivedmannan 3to20g 1to10g 10to20g 0.1to2g
Waterisaddedtobe60to105grams.
Fructose, citric acid, sodium citrate, vitamin C, vitamin B family (B1, B2, B6, nicotinic-acid amide, and B 12), trace metals, and mineral yeast all are contained in a similar manner in the beverage (former embodiment) and the jelMike food. Thus, the jelflike food can be produced by adding fructose and the subsequent ingredients shown in Table 1 to three ingredients shown in Table 2. The water content of the foodisiegulatedr/addingwaten^thefoodsoastomakeatotalof604o105gramsintotal.
ThejelMike food Waredinthe aforementioned mannermaybe stored in containers of, forexample, 20,25or 35gramsinasterilecondition. Itmayofcoursebecontainedinalargercontaineror packager.
The aforesaid jelfflike food (20-gram, 25-gram or 35-gram package) may be taken after each meal or during dialysis treatment as needed. When consuming one dose of food of the quantity described above three times a day, the daiP intake of indigestible polysaccharides becomes roughly 25 grams (20- Even i f the protein intake (or nitrogen intake) fluctuates from day to day, ft is equivalent to the total excretion amount of nitrogen. The intake of indigestible ^saccharides enhances the effect of introducing
14

the nitrogen into feces via the principal excreting route rather than feces routed through the kidne*' or large intestine, thereby to lessen a burden infosed on the kidney and bring about an effect of detoxication and exdusionofhrrjogen-containingcompoundssuchasureasecretedintotheintestine.
Incidental^ a hepatic failure patient may possibly be relieved from the sufferings from gastrointestinal disordersuchasdiarrheaduetoammoniasecretedintotheintestine. (Embodiment3)Confectionerysuchasbiscurtsorcookies
Dry or semidry products such as cookies, biscuits bread or rice crackers may be produced by using indigestible polysaccharides as a chief constituent The confosition of the chief constituent of food will be showninTable3below.
TABLE3

Basiclngredients % (Dryweight)
. Polydextrose 5to25%
A^ejuicelees 10to40%
Pectine 3to15%
Cellulosefiber 5to10%
Oligosaccharide 15to30%
Starch(Low-glutenwheat) 5to20%
Butter(orShortening) 10to20%
Others(-) 1to10%
1% to 10% of sweetener, food flavor, vitamins and minerals are added on the basisofEmbodiments1and2.
As the indigestible polysaccharides, there may also be used not merely a^e juice lees, but also acacia gum, psyllium and water-soluble indigestible polysaccharides derived from cereal testa such as of soybeans andcom. Bacilluscoagulant(e.g.LACROSSE0"radename))maybeadded.
As cellulose fiber, microsco'l c cellulose powder such as "SolcaFloc 300FCC" (Danisco Japan KK) maybeusedbywayofexample.
As the starch, potato starch, com starch, kudzu starch, and low-gluten wheat which are is low in protein, may be preferably used. Soft wheat flour may be used within the realm of using the starch. In the caseofusingthea^ejuicelees inbakingthecomponents showninTable3tomadethebiscu"rtsorcookies, the pectine-rich a^e juice lees become like mud and hard to bake particular1y when they are enriched with polydextroseandpectine. Consequently1thecomponentscontainingalargeamountofectineisnotsurtable
15

for such baked products, but wheat flour may be added so as to be over 20% to the total amount to improve the Wsical properties of the components. In making the product in this embodiment low-gluten wheat is preferably used to restrict the protein ingredient to less than its specific quantity while preventing flour-derivedproteinglutenfromadmixing.
As to the ingredients of cookie and biscuit the biscuit contains butter (or shortening) that is smaller in amount than in the cookie, and the cookie and biscuit both contain baking soda and citric acid or sodium citric acid to prevent hardening and thus to provide favorable texture. Although the cookies and biscuits are general baked by using a common baking device, baking of the cookies and biscuits by microwave heating brings about an effect of releasing moisture content from the dough ingredients to make numerous poresintheproductsandprovidefavorabletexture.
The butter and shortening are edible oil and fat and solid at room temperature in a lot of cases. The butter and shortening may contain oleic acid, palmitic acid, linoleic acid, linolenic acid and/or fatty acids havingacarbonnumberof12or14. Theremayrjefurtheraddedpolyunsaturateo^ttyaddsu{^asDHAinorderfor protec*ng^e(»ntralnervoussystemsusceptibletodisorderofthekidneyor1iver.
Thecookiesandbiscuits thusproduced can ensure protein contentofO.1 to 4grams per day. Thefood products of this kind provide 400 kcal per day available to a patient so that a large amount of indigestible polysaccharidecanbegivenwrthoutaffecfingthedieteryschedulefotheoatient(1800to2000kcalperday),
consequently to decrease the blood level of urea or ammonia. Thus, the food products according to the inventionprovidesynergistica!lytherapeirticbenefitto
When taking six articles of food (e.g. cookies) made from the ingredients described above every day theintakeofindigestiblepolysaccharidesis about 30 to 50 grams. As aresult,4 to 6grams ofdietar^rotein areb^assedthroughthefecalroute.
The food products such as the beverage, jelly and cookies shown in Embodiments 1,2 and 3 may be taken singly or in combination so as to excrete substantial amount of dietary-derived nitrogen components with urine and feces. The combination of the pathological infrovement food of the invention and regular mea!sindudingdini(^ldietbringsaboutenoticeablesynergisticeffectwithease.
When taking 100 grams of beverage (solid content equivalent), two packages of jellv (25 grams per package), and six cookies by mixture daiP in several divided intakes, fungal protein synthesis runs to 10 to 15grams,resultinginexcretionofrJielcw-molecular-we^^ tc^uaipartsofthefongalproteinsynthesisthro
16

(Embodiment4)0theifypeoffood
Adiet food maybe made bymixing5% to 30% bVeightofindigestible polysaccharides into noodle while reducing starch as flour as small as equivalent to the indigestible ^saccharides. In this case, the amount of indigestible ^saccharides to be added should be adequately determined based on the protein content in the flour or cereal starch so as to moderate the intake of protein to 0.6 g/kg body weight or less or 1.2to1.5g/kgbodyweighferday.
The indigestible polysaccharides may be used as the basic ingredients of frozen desserts and confectioner1'. There may be added 5% to 20% by weight of polydextrose of the indigestible ^saccharides. The semisweet ^Fdextrose is suitable for confectioner*. Addition of 1% to 5% of citrus pectine such as of an a^le or strawberr* gives the confectioner* more sweet taste. The quantities of the principle ingredients of the confectioner1' such as milk and egg or protein components derived therefrom should be moderated to acconrtfish the objects of the invention. Such being the case, in ^ace of 20% to 70% by weight of protein in the food, there may be used a substituting ingredient made by adding 5% to 30% by weight of soybean or egg-derived lecithin to emulsified soybean made by condensing supematant fluid obtained in coagulating soybean curd. The protein confonents derived from milk or egg may be substituted for an ingredient made by adding soybean or egg-derived lecithin to the emulsified sc/bean to have high affinity with water. Thus, the present invention can provide the pathological improvement food haringanoticeab]esynergistireffiectwithinidigestiblapolysaccharidesbysuppressingtheproteinntake (Embodiment5)Testforimprovementofclinicalconditions(Case1)
Three packages of jellMike food (25 grams each) as described in Embodiment 2 and six cookies as described in Embodiment 3 were given to four healthy male volunteer subjects and four health* female volunteer subjects (eight subjects in total) a day. The total quantity of indigestible polysaccharides was 80 gramsperdayonaverage,andthedailyproteinintakewas0.6g/kgbodyweight
The e^erimental subjects were divided into two graups by gender and subjected to a cross-over method. Tobe specific,twomale andtwo female subjectsinonegroupstartedeatingcontroldiet foodatthe outset of the dietar* test and took e^erimental diet food from the 5th day, and then, continued to eat the e^erimental diet food for 4 days. The other group composed of two male and two female subjects started eating^ee^erimentaldietfoodandtoatandcontinuedtoeatcontroldietfoodfrothe5thdayfor4days
An emanation about the objectives of the dietar* test, the compositions of the food under test and safe^ofthefoodwasmadetothee^erimentalsubjec^ogaintheirOTnsentinwriting.
17

respective subjects was collected to provide measurement for urinar* nitrogen ever1' day. The experimental resuttsobtainedeventualiyareshowninTable4below.
TABLE4

BUN NitrogenAmountftotalurinevolume/dav
ControlGroup 20.8±5.3mg/dl 12.3±4.5g/day
TestingGroup 14.5±6.5mg/dl 8.1±2.9g/day
As showninTable4,the excretionamountofhitrogenintothe urinewasdecreasedb)'34% andBUN isimprovedby30%.
(Embodiment6)Testforimprovementofclinicalconditions(Case2)
An experiment on the influence of the pathological improvement food on nitrogen excreted into the feces, BUN, urinar* urea and ammonia was conducted by giving three jelNike food toducts (25 grams each) as shown in Embodiment 2 a day and six cookie-like food products in two to three divided doses a da*.
From kidne" failure patients who need not hemodialysis, but have higher BUN and have habitualF kidne^su^orting diets, five experimental subjects were selected with the written consent of the patients upon ex^aining the research "ureses, prescribed diet food and schedule of experiment. The experiment was conducted by collecting blood samTes from the patients at the same time each day to measure BUN anc!. collecting all urine fromthe respective Patients to measure the amounts ofurea and ammonia everW. All feces of the respective patients were collected on the 7th, 8th and 9th days during the test to measure the total nitrogen amounts. On 7th, 8th and 9th days, the same meals were Wared, and the total amount of nitrogenofeach meal and theintake ofhitrogen were calculated. TTie calculatedamountsthereofare shown inTable5below.
TABLE5
(1)Feces

Tesferiod ControPeriodfomon-dose Periodfordose
l_apseddays 7 8 9 7 8 9
Fecalamount 95.2±32.8 98.5±29.1 103.8±43.7 93.7±28.3 102.9±40.2 126.1 ±53.2
Totalnitrogen amount(g/daO 1.9*0.45 2.0±0.21 2.1 ±0.28 2.50±o.50 2.62±0.45 2.80±0.23
18

(2)BloodandUrine

Tesferiod Controlperiodfomon-dose Periodfordose
Lapseddays 1 4 7 10 14 2 4 7 10 14
Blood BUN(mg/dl) 35.3 36.2 33.7 34.6 34.8 30.8 28.3 26.1 25.3 24.8
Urine VolumeCL/da") 1.51 1.39 1.46 1.53 1.48 1.43 1.56 1.38 152 1.48
Totalnitrogen (g/da*) 3.7 3.9 3.9 3.4 3.6 3.2 2.8 2.8 2.4 2.6
As seen from Table 5, increase in amount of the feces and nitrogen excreted into the feces was confirmed on 9th day of a course of the e^eriment by the possible cause considered to be formula of the sample diet food. It was also confirmed that BUN was decreased by 20% and the excretion amount of nitrogenintotheurinewasimprovedby30%to60%onadailybasis. (EmbKxJimentTJTestforinfrovementofcJinicalcondrtionstCaseS)
From patients undergoing dialysis three times a week, five experimental subjects were selected with the written consent of the patients upon explaining the research Voses, prescribed diet food and schedule ofe^erimentinthe same manner asinEmbodiment 6. The experiment was conductedbygivingthesame diet food of the same amount as sifflied in Embodiment 6 to the patientst to measure the total amount of nrtrogenexcretedintc^efeces^ndBUN.TheresultsareshowninTable6below.
TABEL6

Tesferiod Controlperiodfomon-dose Periodfordose
Lapseddays 7 8 9 7 8 9
Fecalamount 75.8±22.8 81.3±29.1 78.8±43.7 73.7±22.3 82.9±30.2 86.1±53.2
Totalnitrogen amount(g/day) 1.30±12 1.43±23 1.35±18 1.49129 1.62±26 1.57±35
BUN(mg/dl) 48.5 53.2 46.6 34.8 37.3 32.4
As seen from Table 6, increase in amount of the feces and nitrogen excreted into the feces was confirmed on 9th day of a course of the e^eriment by the possible cause considered to be formula of the sample diet food. It was also confirmed that BUN was decreased by about 30% on the 9th day and
signrficantimprovementoccurred.
19
INDUSTRIALAPPLICABILITY
The pathological improvement food according to the invention has a function of decreasing reabsor^on of low-molecu!ar-weight nitrogen-containing compounds such as urea circulating in the blood and intestine and then excreting the nitrogen-containing compounds in the form of feces through the mechanismofusingnitrogenofingestedproteinasanagent^ AccordingP.thePathologicalimfavemen
(1) The blood concentration of the nitrogen-containing low-molecular substances such as BUN and ammonia can be lowered. (2) It becomes possible to alleviate the burdens exerted on thekidney ofa kidne1' failurepatientandretard atransrtiontohemodiaFsisfreatmentonlVtakinga specifiedquantityofthe food of the invention every day. (3) The number ofrequired hemodialysis required for treating Wdney failure can be decreased to lessen the Penological, temporal and financial burdens upon the patient and heighten the quality of life of the patient while saving medical e^enses. (4) The blood ammonia level can be decreased so as to ke^ a patient with acute or chronic hematic failure from a danger of falling into hepatic coma and improvethemedicalconditionofthepatient
20

CLAIMS:
1. Pathologicalimprovementfbod fbrioweringbloodconcentrationoflow-molecular-weight nitrogen-containing confounds, which contains, as basic ingredients, indigestible po!ysaccharides and has restrictedadditionofroteincomponents.
2. Pathologicalimprovementfood forloweringbloodconcentrationoflow-molecular-weight nitrogen-containing confounds, which contains more than 5% by weight of indigestible polysaccharides in tenrisofdrieo1bodstuffandproteincomponentsrestrictedto8%ori
3. Pathologicalimprovementfbod forloweringbloodconcentrationoflow-molecular-weight nitrogen-containing compounds according to claim 1 or claim 2, wherein said indigestible polysaccharides are one kind selected from pectine, polydextrose, alginic acid, fucoidan, chitin, chitosan, testa-derived hemicellulose, acacia gum, arum root-derived mannan, agar, and sugar alcohol and polymers of sugar alcohol.
4. Patho!ogicalimprovementfood forioweringbloodconcentrationoflow-molecular-weight nitrogen-containing confounds according to claim 2, wherein said indigestible polysaccharides contains at least polvdextrose and pectine with a ratio of 0.05 to 100 parts by weight of pectine to 100 parts of polydextrose.
5. Pathologicalimprovementfbod forloweringbloodconcentrationoflow-molecular-weight nitrogen-containing compounds accordingto anyofc!aims 1,2 and 4, further containing at least one oftrace metal.vrtaminandfat.
6. Pathologicalinfrovementfood forloweringbloodconcentrationoflow-molecular-weight nitrogen-containing confounds according to claim 3, further containing at least one oftrace metal, vitamin andfat.
21

7. Patholcgicalimprovementfoodforioweringbloodconcentrationofw-molecular-weight
nitrogen-containing confounds according to any of daims 1, 2 and 4, which food is formed in beverage, biscuit cookie,cake,icecream,sherbet,bread,noodleorjelP'.
8. Pathologicalimprovementfood forioweringbloodconcentrationoflow-molecular-weight nitrogen-containing confounds according to claim 3, which food is formed in beverage, biscuit cookie, cake1icecream,sherbetbread,noodleorjelly.
9. Pathologicalimprovementfood forloweringbloodconc^ntrationoflow-molecular-weight nitrogen-containing confounds according to claim 5, which food is formed in beverage, biscuit cookie, cake,icecream,sherbet,bread,noodleorjelly.
10. Pathologicalimprovementfood forioweringbloodconcentrationoflow-molecular-weight nitrogen-containing confounds according to daim 6, which food is formed in beverage, biscuit cookie, cake,icecream,sherbet,bread,noodleorjelly.
11. Food for improving clinical conditions capable oflowering the
concentratin oflow-molecular-weight nitrogen-containing compoundsin blood as herein described with forgoing description and figures.
Dated this 12th day of September 2005.

22

ABSTRACT
The present invention aims at preventing or retarding a transition to hemodialysis treatment in kidney failure or decreasing the number of implementation of the hemodialysis thera^ and preventing or lessening occuirenceofaccompanyinghyperammonemiainhepaticinsufficiency.
To accomlish the Voses described above, the pathological improvement food of the invention is featured by being composed chieflv of indigestible polysaccharides and having restricted addition of protein components.
Energy produced by exporting the indigestible polysaccharides contributes to fungal protein synthesis using, asanN-source.ureaorammonia secretionintotheintestine andexcretionof toliferatedbacteriawith feces, so that nitrogen-containing low-molecular substances in the blood can be decreased, thereby to im^ovedisorderofthekidnepndliver.

Documents:

995-mumnp-2005-abstract(19-09-2005).pdf

995-mumnp-2005-abstract.doc

995-mumnp-2005-abstract.pdf

995-mumnp-2005-cancelled pages(19-09-2005).pdf

995-mumnp-2005-claims(granted)(19-09-2005.pdf

995-mumnp-2005-claims.doc

995-mumnp-2005-claims.pdf

995-mumnp-2005-correspondence(05-12-2007).pdf

995-mumnp-2005-correspondence(ipo)-(07-12-2006).pdf

995-mumnp-2005-correspondence-others.pdf

995-mumnp-2005-correspondence-received-ver-081206.pdf

995-mumnp-2005-correspondence-received-ver-110905.pdf

995-mumnp-2005-correspondence-received.pdf

995-mumnp-2005-description (complete).pdf

995-mumnp-2005-form 1(19-09-2005).pdf

995-mumnp-2005-form 18(24-10-2005).pdf

995-mumnp-2005-form 2(granted)-(19-09-2005).pdf

995-mumnp-2005-form 3(12-09-2005).pdf

995-mumnp-2005-form 3(20-10-2005).pdf

995-mumnp-2005-form 5(12-09-2005).pdf

995-mumnp-2005-form 8(11-12-2006).pdf

995-mumnp-2005-form-1.pdf

995-mumnp-2005-form-18.pdf

995-mumnp-2005-form-2.doc

995-mumnp-2005-form-2.pdf

995-mumnp-2005-form-3.pdf

995-mumnp-2005-form-5.pdf

995-mumnp-2005-form-8.pdf

995-mumnp-2005-form-pct-ipea-409.pdf

995-mumnp-2005-pct-search report.pdf

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Patent Number

219595

Indian Patent Application Number

995/MUMNP/2005

PG Journal Number

33/2008

Publication Date

15-Aug-2008

Grant Date

09-May-2008

Date of Filing

12-Sep-2005

Name of Patentee

CHEIRON JAPAN CO

Applicant Address

Inventors:

#	Inventor's Name	Inventor's Address
1	FURUYA SHU
2	1) YUGARI YASUMI 2) KOBAYASHI TAKAAKI 3) FURUYA SHU
3	KOBAYASHI TAKKAKI

PCT International Classification Number

A61K 31/715

PCT International Application Number

PCT/JP2004/004319

PCT International Filing date

2004-03-26

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	2003-086141	2003-03-26	Japan