AU2005242204B2 - Remedies for diabetes mellitus - Google Patents

Remedies for diabetes mellitus Download PDF

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AU2005242204B2
AU2005242204B2 AU2005242204A AU2005242204A AU2005242204B2 AU 2005242204 B2 AU2005242204 B2 AU 2005242204B2 AU 2005242204 A AU2005242204 A AU 2005242204A AU 2005242204 A AU2005242204 A AU 2005242204A AU 2005242204 B2 AU2005242204 B2 AU 2005242204B2
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Australia
Prior art keywords
sucrose
arabinose
diabetes mellitus
weight
sugar
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AU2005242204A
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AU2005242204A1 (en
Inventor
Makoto Fujii
Susumu Hizukuri
Shigemitsu Ohsaki
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Sanwa Kousan Co Ltd
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Sanwa Kousan Co Ltd
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Priority to AU2001210984 priority
Priority to PCT/JP2001/009542 priority patent/WO2002040035A1/en
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Publication of AU2005242204A1 publication Critical patent/AU2005242204A1/en
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AUSTRALIA Patents Act 1990 COMPLETE SPECIFICATION STANDARD PATENT Applicant (s): SANWA KOSAN KABUSHIKI KAISHA MAKOTO FUJII SUSUMU HIZUKURI Invention Title: REMEDIES FOR DIABETES MELLITUS The following statement is a full description of this invention, including the best method of performing it known to me/us; REMEDY FOR. DIABETES MELLITUS Background of the Invention 1. Field of the Invention The present invention relates to remedy for diabetes mellitus in which interaction of L-arabinose with sucrose is utilized, to food or beverage for improvement of diabetes mellitus and also to use of L-arabinose for the treatment of diabetes mellitus. 2. Description of the Related Art Although the great part of saccharides in food is starch, a lot of sucrose is taken as the most preferable sweetener throughout the world. In 1996 for example, 67 g and 1BSg of sucrose/person/day were consumed in Japan and in the United States, respectively. Ingestion of much sucrose tends to induce hyperglycemia and obesity. Obesity is a well-known dangerous factor for non-insulin-dependent diabetes mellitus (NIDDM'. Many of diabetics are persons suffering from NIDDM. In addition to administration of insulin or administration of an SU agent which accelerates the secretion of insulin, administration of an inhibitor of a-glucosidase, etc. is available for the therapy of NIDDM. The former two agents promote the ingestion of saccharide from blood into cells whereby blood-sugar level is lowered while, in the latter, action of enzyme (glucosidase) which digests and decomposes the saccharide is suppressed and digestion and absorption of the saccharide in small intestine are delayed and/or suppressed to inhibit the ingestion of the saccharide from intestine into blood whereupon a rise in blood-sugar level after meal is suppressed. On the other hand, L-arabinose has been known to have an action of inhibition of sucrase which is a sucrose-decomposing enzyme in small intestine and it has been recognized that such an action of L-arabinose is utilized to partially inhibit the decomposition of sucrose and to reduce the energy of sucrose. For example, in the Japanese Patent Laid-Open No. Hei-6/650 8 0 , there is disclosed that L-arabinose has an action of suppressing the rise of blood-sugar level in mice during 30 to 120 minutes after loading with sucrose. However, that which is disclosed therein is only the above-mentioned action of sucrase-inhibiting of L-arabinose, action of suppression of increase in blood-sugar level aftermeal and action of suppression of bodyweight increase caused thereby and, with regard to efficacy of improvement and treatment diabetes mellitus by lowering the blood-sugar level, it is not made clear. The present invention has been invented in view of the current state of the prior art as such and it would be advantageous to provide a remedy for diabetes mellitus effective to diabetic patient utilizing L-arabinose which results in hypoglycaemic action, food or beverage for improvement of diabetes mellitus and method for 2 - 3 using L-arabinose for the therapy of diabetes mellitus. In order to achieve such an advantage, the present inventors have carried out various studies and, as a result, they have 5 unexpectedly found that, although the. sole use of L-arabinose shows only a transient suppressive action to hypoglycemia due to its sucrase-inhibiting action, blood-sugar level of mice is 10 drastically lowered and diabetes mellitus is improved and cured when feed in which L-arabinose is mixed in a specific rate with sucrose which is a causing substance for diabetes mellitus is continuously administered to mice KK-AY which is a model for 15 non-insulin-dependent diabetes mellitus whereupon the present invention has been achieved. Summary of the Invention 20 The present invention provides the following items (1) to (18): (1) Use of L-arabinose and sucrose in the manufacture of a medicament for the treatment of diabetes mellitus. 25 (2) The use according to item (1), wherein the medicament is in two parts, the first part being a composition containing L-arabinose and the second part being a composition containing sucrose. (3) The use according to any preceding item, wherein 30 the medicament is an oral preparation. (4) The use according to any preceding item, wherein sugar or sugar-containing food or beverage is used as a source for sucrose. N:\Sydney\Casos\Patent\49000-49999\P49520.AU.1\Specis\P49520.AU.1 Specification 2009-1-22.doc 22/01/09 - 3A (5) The use according to any preceding item, wherein L arabinose is present in a ratio of 0.5% to 90% by weight to sucrose. (6) The use according to any preceding item, wherein L 5 arabinose is present in a ratio of 1% to 50% by weight to sucrose. (7) The use of L-arabinose and sucrose in the manufacture of a food or beverage for the treatment of diabetes mellitus. 10 (8) The use according to item (7), wherein L-arabinose is present in a ratio of 0.5% to 90% by weight to sucrose. (9) The use according to item (7) or (8), wherein L-arabinose is present in a ratio of 1% to 50% by weight to sucrose. 15 (10) A method for the treatment of diabetes mellitus, comprising administering to a patient suffering from diabetes mellitus an effective amount of L-arabinose and an effective amount of sucrose. (11) The method according to item (10), comprising 20 administering a first part being a composition containing L-arabinose, and a second part being a composition containing sucrose. (12) The method according to item (10), wherein the L-arabinose and sucrose are administered orally. 25 (13) The method according to any one of items (10) to (12), wherein sugar or sugar-containing food or beverage is used as a source for sucrose. (14) The method according to any one of items (10) to (13), wherein L-arabinose is administered in a ratio of 30 0.5% to 90% by weight to sucrose. (15) The method according to any one of items (10) to (14), wherein L-arabinose is administered in a ratio of 1% to 50% by weight to sucrose. N:\Sydney\Cases\PatentW9000-49999\P49520.AU.1\Specis\P49520.AU.1 Specification 2009-1-22.doc 29/01109 - 3B (16) A method for the treatment of diabetes mellitus, comprising administering to a patient suffering from diabetes mellitus a food or beverage containing an effective amount of L-arabinose and an effective amount of 5 sucrose. (17) A method according to item (16), wherein the L-arabinose is present in a ratio of 0.5% to 90% by weight to sucrose (18) The method according to item (16), wherein the 10 L-arabinose is present in a ratio of 1% to 50% by weight to sucrose. Thus, the present invention relates to a remedy for 15 diabetes mellitus which is characterized in containing L-arabinose and sucrose (for example, sugar or sugar-containing food or beverage is used as a source for sucrose) as effective 20 ingredients. The present invention further relates to food or beverage for improvement of diabetes mellitus which is characterized in 2s containing L-arabinose and sucrose (for example, sugar or sugar-containing foodorbeverage is usedas a source for sucrose) as effective ingredients. The present invention still further relates to a method N \SydneCases\Patent\9000-49999\P49520.AU \Specis\P49520.AU. 1 Specification 2009-1-22.doc 29/01/09 for using L-arabin'ose which is characterized in that, for the treatment of diabetes mellitus, L-arabinose is taken together with or prior to ingestion of sucr-o-s-e (for example, sugar or sugar-containing food or beverage is used as a source for sucrose). Brief Description of the Drawings Fig. 1 shows the changes in blood-sugar level (mg/dl) during the raising period of group A and group B for 30 days. Fig. 2 shows the changes in blood-sugar level (mg/dl) during the raising period of group C and group D for 30 days. Detailed Description of the Preferred Embodiments Remedy for diabetes mellitus and food or beverage for the improvement of diabetes mellitus according to the present disclosure will be specifically illustrated hereinafter. With regard to L-arabinose used in the present invention, that which is manufactured by various known methods can be used. For example, there may be used that which is manufactured in high purity and in high efficiency where plant fiber containing L-arabinose as a part of the constituting saccharides is contacted to an acid of low concentration to subject to an acid hydrolysis whereupon L-arabinose is selectively produced as disclosed, for example, in the Japanese Patent Laid-Open No. 4 Hei-ll/31 37 00 . With regardto sucrose usedinthepresent invention, there may be used chemically purified sucrose as well as sucrose-containing substance as a source for sucrose such as sugar or sugar-containing food or beverage. There are various sugar products depending upon material, manufacturing method, degree of purification, color, processed form, etc. thereof and any of them may be used in the present invention so far as it contains sucrose. With regard to the remedy for diabetes mellitus and the food or beverage for improvement of diabetes mellitus described herein, L-arabinose and sucrose maybe ingested separately with time intervals provided that it is possible to result in a state where L-arabinose and sucrose simultaneously are present in intestine. However, since L-arabinose is slowly absorbed from intestinal tract and remains for long time in intestine while sucrose shows quick digestion and absorption, it is effective for the therapy or the improvement of diabetes mellitus that L-arabinose is ingested together with or prior to ingestion of sucrose (sugar or sugar-containing food or beverage) . In the remedy for diabetes mellitus or the food or beverage for improvement of diabetes mellitus described herein, it is preferred that L-arabinose is present in a ratio of 0.5~90% by weight or, preferably, 1-5O% by weight to sucrose. When the used amount of L-arabinose is less than 5 the above lower limit, it is not preferred because the effect by the joint use of L-arabinose with sucrose is hardly expressed while, when it is more than the above upper limit, it is not preferred in view of economy since an effect due to its amount cannot be expected. In addition to the use of L-arabinose and sucrose only, the remedy for diabetes mellitus described herein may also be easily manufactured by combining them with known pharmaceutical carriers to give pharmaceutical preparations. Manufacture of such pharmaceutical preparations is usually conducted in such a manner that L-arabinose and sucrose are compounded with pharmaceutically acceptable liquid or solid carrier and, if necessary, solvent, dispersingagent, emulsifier, buffer, stabilizer, filler, binder, disintegrating agent, lubricant, etc. are added thereto to give solid preparations such as tablets, granules, diluted powder, powder and capsules or liquid preparations such as normal liquid, suspension and emulsion. It is also possible to prepare a dried preparation which can be made into liquid by addition of appropriate carrier thereto before use. It is preferred that the remedy for diabetes mellitus is an oral preparation so as to effectively express the effect by the joint use of L-arabinose and -sucrose. With regard to a pharmaceutical carrier for the oralpreparation, theremaybeused, forexample, 6 starch, lactose, white sugar, mannitol, carboxymethyl cellulose, corn starch and inorganic salt. For the manufacture of the oral preparation, it is also possible to further compound binder, disintegrating agent, surface-active agent, lubricant, fluidity promoter, corrigent, coloring agent, perfume, etc. therewith. Dose of the remedy for diabetes mellitus, described herein maybe appropriately determined depending upon dosage form, administering method, object of use and age, body weight and symptom of the patient applied therewith and, although it is not definite, the amount of L-arabinose contained in the preparation is usually from 1 mg to 10 g/kg per day for adults. It goes without saying that the dose varies depending upon various conditions and, in some cases, less dose than above may be sufficient while, in some other cases,. more dose than the above range may be necessary. The remedy for diabetes mellitus described herein may be daily ingested by adding to any food or beverage as well as oral administration. Although there is no particular limitation for the manufacturing method of the food or beverage for improvement of diabetes mellitus according to the present invention, there may be exemplified the manufacture by means of cooking, processing and commonly used manufacturing method for food or beverage provided that the mianuf actured food or beverage contains L-arabinose and sucrose having an improving action for diabetes 7 mellitus as an effective ingredient. With regard to the food or beverage for improvement of diabetes mellitus, there is no particular limitation for its form so far as sucrose and L-arabinose having an improving action fordiabetesmellitus arecontainedtherein, addedthereto and/or diluted therein and it covers orally applicable forms such as tablets, granules, capsules, gel and sol. Although the reason why the joint use of L-arabinose and sucrose in the remedy for diabetes mellitus and the food or beverage forimprovingdiabetesmellitus described herein is effective for treatment and improvement of diabetes mellitus has not been clearly elucidated, it is judged that numbers of specific enterobacteria are increased or activated due to the presence of L-arabinose and sucrose at the same time in intestine and that those bacteria produce a substance which is effective for reducing sugar-blood level by promoting the incorporation of saccharide from blood into cells. Examples Effect of the joint use of L-arabinose and sucrose used in the present invention for the therapy or improvement of diabetes mellitus will be illustrated as hereunder. Example 1 Twenty model mice for non-insulin-depending diabetes mellitus showinghyperglycemia (260-270mg/liter) (KK-A , male, 8 8 weeks age, Nippon Clair) were preliminarily .raised for one week, divided into two groups (group A and group B) and used for the test. Each of the mice was placed in a plastic cage separately and raised by keeping at 23 ± 1C under a 12-hour bright-and-dark cycle (bright environment from 7 a.m. to 7 p.m. and dark environment from 7 p.m. to 7 a.m. of the next day) where feed and water were freely.taken by the mice. Blood-sugar level (concentration of glucose in blood). was measured by a glucose oxidase method after collecting the blood from venous plexus of the eyeground at 9 a.m. The feed A mentioned in Table 1 (a feed containing ct-corn starch, sucrose and cellulose as carbohydrate sources but containing no L-arabinose) was given to the mice of group Awhile the feedBmentionedin Table 1 'a feedcontaininq a-corn starch, sucrose and cellulose as carbohydrate sources and also containing L-arabino.se) was given to the mice of group B and raising was carried out for 30 days. 9 Table 1 Composition of the Feed Composition Feed (% by weight) A B C D a-Cdrn starch 35,85 35.85 55.85 55.85 Sucrose 20 20 0 0 L-Arabinose 0 2.5 0 2.5 Cellulose 5.0 2.5 5.0 2.5 Corn oil 6 6 6 6 Mixture of.minerals * 6 6 6 6 Mixture of vitamins 2 2 2 2 Choline chloride 0.15 0.15 0.15 0.15 Casein 25 25 25 25 41: L-Arabinose (purity: 98%) manufactured by Sanwa Dempun Bogyo K. K. *2: manufactured by Oriental Yeast K. K. Changes. in blood-sugar level (mg/dl) of the groups A and B raised as such for a raising period of 30 days are shown in Fig. 1. As will be apparent from Fig. 1, in the group A where there was given the feed A containing sucrose but containing no L-arabinose, blood-sugar level continued in increasing from the 7th day while, in the group B where there was given the feed B containing sucrose and'also containing L-arabinose, lower blood-sugar level than the group A was continuously noted from the 7th day, lower blood-sugar level than that at the start of the experiment was noted after the 21st day and, from the 25th day until 30th day, a continuous decrease in the sugar-blood level was apparently noted whereupon an effect of improving and treating diabetes mellitus was expressed. 10 Result of Example 1 shows an effect of improving and treating the blood-sugar level is expressed as the joint action by simultaneous administration of sucrose and L-arabinose but, onlybywayof Example 1, there is still apossibilitythat addition of L-arabinose only may have the same effect. In order to make the possibility clear, an experiment was carried nut in the following Reference Example 1 where no sucrose was added to the feed but a-corn starch was added instead of sucrose. Reference Example 1 As same as in Example 1, a feed C mentioned in Table 1 (containing a-corn starch and cellulose as carbohydrate sources but containing neither sucrose nor L-arabinose) was given to themice of group Cwhile, to theimice of group D, a feedDmentioned in Table 1 (containing a-corn starch and cellulose as catbohydrate sources and also containing L-arabinose but containing no sucrose) was given and raising was carried out for 30 days. Changes in blood-sugar level (mg/dl) of the groups C and D raised as such for 30 days are shown in Fig. 2. As will be apparent from-Fig. 2, mice of both groups C and D continued in increasing the blood-sugar level as same as in the case of the group A of Example 1 during a period of the experiment whereby no improving effect for blood-sugar level was noted. That shows no decrease in blood-sugar level takes place even when only L-arabinos awas givenwithout additionof sucrose. Now results 11 - 12 of Example 1 and Reference Example 1 show that high blood-sugar level in model mice for non-insulin-independent diabetes mellitus can be continuously lowered and improved by a simultaneous ingestion of a mixture of sucrose and L-arabinose s whereby that is effective for remedy for diabetes mellitus. Incidentally, it is not always necessary that sucrose and L-arabinose are administered as a mixture thereof but, for example, with regard to sucrose, food or beverage containing sucrose may be ingested separately. In that case, L-arabinose 10 may be ingested either before or after sucrose although the early ingestion is effective. Advantage of the Invention In accordance with the present invention, a 15 continuous decrease in blood-sugar level can be achieved by a joint use of sucrose and L-arabinose and that is very useful as a remedy for diabetes mellitus and as food or beverage for improvement of diabetes mellitus. 20 In the claims which follow and in the preceding description of the invention, except where the context requires otherwise due to express language or necessary implication, the word "comprise" or variations such as "comprises" or "comprising" is used in an inclusive sense, i.e. to specify the 25 presence of the stated features but not to preclude the presence or addition or further features in various embodiments of the invention. It is to be understood that a reference herein to a prior art publication does not constitute an admission that the 30 publication forms a part of the common general knowledge in the art in Australia, or any other country. N:\Sydney\Cases\Patent\49000-49999\P49520.AU.1\Specis\P49520AU.1 Specification 2009-1-22.doc 22/01109

Claims (19)

1. Use of L-arabinose and sucrose in the manufacture of a medicament for the treatment of diabetes mellitus.
2. The use according to claim 1, wherein the 5 medicament is in two parts, the first part being a composition containing L-arabinose and the second part being a composition containing sucrose.
3. The use according to any preceding claim, wherein the medicament is an oral preparation. 10
4. The use according to any preceding claim, wherein sugar or sugar-containing food or beverage is used as a source for sucrose.
5. The use according to any preceding claim, wherein L-arabinose is present in a ratio of 0.5% to 90% by weight 15 to sucrose.
6. The use according to any preceding claim, wherein L-arabinose is present in a ratio of 1% to 50% by weight to sucrose.
7. The use of L-arabinose and sucrose in the 20 manufacture of a food or beverage for the treatment of diabetes mellitus.
8. The use according to claim 7, wherein L-arabinose is present in a ratio of 0.5% to 90% by weight to sucrose.
9. The use according to claim 7 or 8, wherein 25 L-arabinose is present in a ratio of 1% to 50% by weight to sucrose. N:\Sydney\Cases\Patent\490O0-49999\P49520.AU 1 \Spects\P49520.AU. 1 Specification 2009-1-22.doc 22/01/09 - 14
10. A method for the treatment of diabetes mellitus, comprising administering to a patient suffering from diabetes mellitus an effective amount of L-arabinose and an effective amount of sucrose. 5
11. The method according to claim 10, comprising administering a first part being a composition containing L-arabinose, and a second part being a composition containing sucrose.
12. The method according to claim 10, wherein the L 10 arabinose and sucrose are administered orally.
13. The method according to any one of claims 10 to 12, wherein sugar or sugar-containing food or beverage is used as a source for sucrose.
14. The method according to any one of claims 10 to 13, 1s wherein L-arabinose is administered in a ratio of 0.5% to 90% by weight to sucrose.
15. The method according to any one of claims 10 to 14, wherein L-arabinose is administered in a ratio of 1% to 50% by weight to sucrose. 20
16. A method for the treatment of diabetes mellitus, comprising administering to a patient suffering from diabetes mellitus a food or beverage containing an effective amount of L-arabinose and an effective amount of sucrose. 25
17. A method according to claim 16, wherein the L-arabinose is present in a ratio of 0.5% to 90% by weight to sucrose N:\Sydney\Cases\Patent\49000-49999\P49520.AU.1\Specis\P49520.AU.1 Specification 2009-1-22.doc 29/01/09 - 15
18. The method according to claim 16, wherein the L-arabinose is present in a ratio of 1% to 50% by weight to sucrose.
19. The use of claim 1, or the method of claim 10, 5 substantially as hereinbefore described with reference to the Examples. N:\Sydney\Cases\Patent\49000-49999\P49520.AU 1\Specis\P49520.AU 1 Specification 2009-1-22doc 29/01/09
AU2005242204A 2000-11-15 2005-12-09 Remedies for diabetes mellitus Ceased AU2005242204B2 (en)

Priority Applications (3)

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JP2000-347372 2000-11-15
AU2001210984 2001-10-31
PCT/JP2001/009542 WO2002040035A1 (en) 2000-11-15 2001-10-31 Remedies for diabetes

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CN101797007B (en) 2009-12-08 2012-07-25 济南圣泉唐和唐生物科技有限公司 Bloom inhabiting chocolate

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0560284A1 (en) * 1992-03-10 1993-09-15 Godo Shusei Co., Ltd. Prophylactic and remedial preparation for diseases attendant on hyperglycemia, and wholesome food
WO1994012057A1 (en) * 1992-11-25 1994-06-09 Fujisawa Pharmaceutical Co., Ltd. Diet sweetener

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0560284A1 (en) * 1992-03-10 1993-09-15 Godo Shusei Co., Ltd. Prophylactic and remedial preparation for diseases attendant on hyperglycemia, and wholesome food
WO1994012057A1 (en) * 1992-11-25 1994-06-09 Fujisawa Pharmaceutical Co., Ltd. Diet sweetener

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