CN102961388A - Medicine capable of promoting secretion of glp-1 and restraining secretion of gip - Google Patents
Medicine capable of promoting secretion of glp-1 and restraining secretion of gip Download PDFInfo
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- CN102961388A CN102961388A CN2012100851993A CN201210085199A CN102961388A CN 102961388 A CN102961388 A CN 102961388A CN 2012100851993 A CN2012100851993 A CN 2012100851993A CN 201210085199 A CN201210085199 A CN 201210085199A CN 102961388 A CN102961388 A CN 102961388A
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- sucrose
- medicament
- secretion
- gip
- glp
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- 235000011962 puddings Nutrition 0.000 description 1
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- 238000003756 stirring Methods 0.000 description 1
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- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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Images
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/52—Adding ingredients
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/30—Foods or foodstuffs containing additives; Preparation or treatment thereof containing carbohydrate syrups; containing sugars; containing sugar alcohols, e.g. xylitol; containing starch hydrolysates, e.g. dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7016—Disaccharides, e.g. lactose, lactulose
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/328—Foods, ingredients or supplements having a functional effect on health having effect on glycaemic control and diabetes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Abstract
The invention provides an incretin-associated medicine capable of restraining secretion of GIP completely and promoting secretion of GLP-1 and highly safe. The medicine capable of promoting the secretion of GLP-1 (glucagon-like peptide-1) and restraining the secretion of the GIP (glucose-dependent insulinotropic peptide) comprises non-antagonistic inhibitor of clastic enzyme of cane sugar, such as L-gum sugar, D-wood sugar and D-tagatose, as an active ingredient.
Description
[technical field]
The present invention relates to the related medicine of incretin useful in the prevention of the treatment of impaired glucose tolerance or diabetes.
[background technology]
The diabetes of Japan to suffer from patient's number be about 7,400,000 people in whole nation statistics (2004), comprise that its excessive risk person is about 1,620 ten thousand people (MHLW's real attitude investigation of diabetes in 2002), compares last time that investigation (1997) increases about 20%.As the cause of death, directly be the 10th in the male, be the 9th (overview of MHLW's population vital statistics in 2005) in the women, if comprise that then quantity is more surprising by trunk obstacle that brings out with the complication of diabetes etc.
As diabetes excessive risk person's initial stage symptom and what pay close attention to is impaired glucose tolerance.Impaired glucose tolerance refers to the symptom that blood glucose value after the meal is difficult to descend, and usually uses 75g glucosieloading test (75gOGTT) to judge.
In recent years, for treating diabetes, paid close attention to the related medicine of incretin (the dependence on the glucose insulin secretion stimulates polypeptide (GIP), glucagon-like-peptide-1 (GLP-1)).Mainly by the stimulation of the K cell that exists in upper intestines is secreted, on the other hand, GLP-1 is mainly secreted by the stimulation of the L cell that lower intestine is existed GIP.Incretin acts on pancreas and the increase of amount of insulin secretion when promoting hyperglycemia, when blood glucose value is not high, owing to do not increase amount of insulin secretion, thus cause that hypoglycemic risk is low.But incretin has the shortcoming of the enzyme that is decomposed (DPP-4) fast decoupled.Thereby, develop the material (inhibitor of catabolic enzyme or be not subjected to the exendin-4 of enzyme effect) of the effect that suppresses its decomposition as the related medicine of incretin.Expect that such medicine is the material of few side effects.But the related medicine of any incretin is the non-existent material of occurring in nature, requires the strict doctor's of prescription control, and its preparation cost is also not very cheap.
Among the 2 kinds above-mentioned incretin, GLP-1 also has food rcstriction effect (non-patent literature 1) except increasing insulin secretion, so prevent also effectively for obesity, expects the promotion of its secretion.On the other hand, GIP also has lipopexia effect (non-patent literature 2) except increasing insulin secretion, so not preferred in the prevention of the treatment of the impaired glucose tolerance that requires body weight control or diabetes, preferably its secretion is suppressed.
Except DPP-4 inhibitor or GLP-1 analog medicine as the related medicine of general incretin, know the disaccharides catabolic enzyme depressant (α-GI agent) of acarbose, voglibose, miglitol etc. as the related medicine of incretin that the secretion that promotes GLP-1 and the effect of the secretion that suppresses GIP are arranged.But, although α in the past-GI agent can suppress the GIP secretory volume to a certain degree, secretion inhibitor (acarbose: non-patent literature 3, voglibose: non-patent literature 4, miglitol: non-patent literature 5) fully.In addition, although α in the past-GI agent can be along with the together oral uptake of having dinner of every day, but still need doctor's prescription.
[prior art document]
[non-patent literature]
[non-patent literature 1] Turton MD, et al., Nature, 379, p69,1996.
[non-patent literature 2] Miyawaki, K., et al., Proc.Acad.Sci.USA, 96, p14843,1999.
[non-patent literature 3] Seifarth, C., et al., Diabetic Med., 15, p485,1998.
[non-patent literature 4]
B., et al., Digestion, 50, p493,1995.
[non-patent literature 5] Aoki, K., et al., Endocrine J., 57, p667,2010.
[summary of the invention]
[technical task that invention will solve]
The present invention is the invention of making in view of the present situation of conventional art, and its objective is provides the secretion that can fully suppress GIP, and promotes the secretion of GLP-1, and the good related medicine of incretin of safety.
[solving the technical scheme of problem]
The inventor is in order to solve the problem that relates to, when checking the mechanism of action of in the past α-GI agent, find since in the past α-the GI agent is antagonism type inhibitor, its disaccharides catabolic enzyme inhibitory action exists uneven, particularly not too effective in the upper intestines inhibitory action, the K cell of upper intestines is stimulated and is secreted GIP.Then, replace the use of antagonism type inhibitor with respect to the inhibitor of the non-antagonism type more than the sucrose specified quantitative, then nothing is uneven in the disaccharides catabolic enzyme inhibitory action, effective in the upper intestines inhibitory action, carry out digesting and assimilating slowly of disaccharides in lower intestine, found that, can not give the K cytositimulation of upper intestines, and give the L cell stimulation for a long time of lower intestine, can not exclusively secrete GIP and increase the GLP-1 secretion.Confirm in addition in the α of non-antagonism type-GI agent, how to be used as food additives, so also to human-body safety all the time.
The present invention is based on these opinions and finish, consisted of by following (1)～(6).
(1) medicament, it is characterized in that, it is the medicament that promotes the secretion of GLP-1 (glucagon-like-peptide-1) and suppress the secretion of GIP (the dependence on the glucose insulin secretion stimulates polypeptide), its non-antagonism type inhibitor that contains the sucrose decomposition enzyme is as effective ingredient, and the non-antagonism type inhibitor of described sucrose decomposition enzyme is L-arabinose, D-xylose and/or D-Tag.
(2) (1) described medicament, it is characterized in that, the mixing ratio of the non-antagonism type inhibitor of the sucrose decomposition enzyme of sucrose is 4.5～99 % by weight in the situation of L-arabinose or D-xylose relatively, is 25～99 % by weight in the situation of D-Tag.
(3) (1) described medicament is characterized in that, also contains sucrose.
(4) medicament, it is characterized in that, it is (1) the described medicament that does not contain sucrose, itself and sucrose or the picked-up that contains the food of sucrose are taken simultaneously, take with interior at sucrose or front 90 minutes of picked-up containing the food of sucrose, perhaps take with interior at sucrose or rear 15 minutes of picked-up containing the food of sucrose.
(5) (4) described medicament is characterized in that, the food that contains sucrose is Japanese Western-style pastry class, milk product, beverage or drinking water.
(6) each described medicament of (1)～(5) is for the preparation of the purposes of the medicine that uses in the prevention of the treatment of impaired glucose tolerance or diabetes.
[invention effect]
Medicament of the present invention since with the α of non-antagonism type-GI agent as effective ingredient, fully be suppressed at the secretion of the GIP that does not expect in the prevention of the treatment of impaired glucose tolerance or diabetes, can only promote the secretion of the GLP-13 that expects.In addition, the α of non-antagonism type-GI agent is generally speaking how to be used as food additives all the time, and is good to human safety.
[description of drawings]
Fig. 1 shows that sucrose+L-arabinose (relatively sucrose 5%) uses group and sucrose and use the coordinate diagram of rheological parameters' change with time that group and arabinose are used the blood glucose value that using front and back of group.
Fig. 2 shows that sucrose+L-arabinose (relatively sucrose 5%) uses group and sucrose and use the coordinate diagram that group and arabinose are used the rheological parameters' change with time of the amount of insulin in the serum that using front and back of group.
Fig. 3 shows that sucrose+L-arabinose (relatively sucrose 5%) uses group and sucrose and use the coordinate diagram of rheological parameters' change with time that group and arabinose are used the amount of the active form GLP-1 in the blood plasma that using front and back of group.
Fig. 4 shows that sucrose+L-arabinose (relatively sucrose 5%) uses group and sucrose and use the coordinate diagram of rheological parameters' change with time that group and arabinose are used the amount of the total GLP-1 in the blood plasma that using front and back of group.
Fig. 5 shows that sucrose+L-arabinose (relatively sucrose 5%) uses group and sucrose and use the coordinate diagram that group and arabinose are used the rheological parameters' change with time that the GIP in the blood plasma that using front and back of group measures.
Fig. 6 shows that sucrose+L-arabinose (relatively sucrose 1%, 2.5%, 4%, 5%, 10%, 20%) uses the coordinate diagram of rheological parameters' change with time that group and sucrose are used the amount of the active form GLP-1 in the blood plasma that using front and back of group.
Fig. 7 shows that sucrose+L-arabinose (relatively sucrose 1%, 2.5%, 4%, 5%, 10%, 20%) uses the coordinate diagram that group and sucrose are used the rheological parameters' change with time that the GIP in the blood plasma before and after the using of group measures.
Fig. 8 shows that sucrose+D-xylose (relatively sucrose 1%, 2.5%, 4%, 5%, 10%, 20%) uses the coordinate diagram of rheological parameters' change with time that group and sucrose are used the amount of the active form GLP-1 in the blood plasma that using front and back of group.
Fig. 9 shows that sucrose+D-xylose (relatively sucrose 1%, 2.5%, 4%, 5%, 10%, 20%) uses the coordinate diagram that group and sucrose are used the rheological parameters' change with time that the GIP in the blood plasma before and after the using of group measures.
Figure 10 shows that sucrose+D-Tag (relatively sucrose 10%, 20%, 30%, 40%, 50%) uses the coordinate diagram of rheological parameters' change with time that group and sucrose are used the amount of the active form GLP-1 in the blood plasma that using front and back of group.
Figure 11 shows that sucrose+D-Tag (relatively sucrose 10%, 20%, 30%, 40%, 50%) uses the coordinate diagram that group and sucrose are used the rheological parameters' change with time that the GIP in the blood plasma before and after the using of group measures.
[embodiment]
Medicament of the present invention is among the antagonism type inhibitor of sucrose decomposition enzyme and non-antagonism type inhibitor, by using non-antagonism type inhibitor, do not give the K cytositimulation of upper intestines, and only give the L cytositimulation of lower intestine, promote the secretion of the GIP that the secretion and suppressing of the GLP-1 of expectation or not, from but to the treatment of impaired glucose tolerance or the exceedingly useful material of prevention of diabetes.
Non-antagonism type inhibitor as the effective ingredient of medicament of the present invention, can use in the past known any material, but from the viewpoint of safety, preferred occurring in nature exists, and the viewpoint of testing from cuisine canon, the general preferred plant origin that uses as food.In addition, when using occurring in nature to exist hardly, preferably use added to the food of public institution's approval.The preference of non-antagonism type inhibitor can be enumerated L-arabinose, D-xylose and D-Tag, and these can be used alone or as a mixture.
In order to make medicament of the present invention bring into play its effect, be necessary to make the non-antagonism type inhibitor of sucrose decomposition enzyme of effective ingredient and sucrose at the simultaneous state of patient's enteral.For this reason, preferably make medicament contain sucrose from body, perhaps with medicament and sucrose or contain the food coupling of sucrose.
Make medicament when body contains sucrose, have identical effect when other non-antagonism type inhibitor is taken simultaneously with sucrose with inciting somebody to action.The mixing ratio of the relative sucrose of the non-antagonism type inhibitor in the medicament of this moment is aspect sucrose decomposition enzymeinhibition effect, more than preferred 4.5 % by weight.The mixing ratio of non-antagonism type inhibitor begins more than above-mentioned lower limit, and inhibitor can suppress the sucrose decomposition enzyme significantly.Limit on the mixing ratio for non-antagonism type inhibitor to be not particularly limited, but the above also indifference of effect that increases to a certain degree, so from the viewpoint of the balance of economy and flavor matter, preferred maximum is 200 % by weight.Non-antagonism type inhibitor is that the mixing ratio of its relative sucrose is 4.5～99 % by weight preferably in the situation of L-arabinose or D-xylose, is more preferably 4.5～75 % by weight.In addition, in the situation of D-Tag 25～99 % by weight preferably, be more preferably 25～75 % by weight.
The dosage form of medicament of the present invention is not particularly limited, and can have such as lamellar, graininess, Powdered, capsule shape, gel, colloidal sol shape etc.In addition, preparation gets final product according to known method, can be by with the non-antagonism type inhibitor of effective ingredient and sucrose together, mix with permissible carrier such as the pharmacy of starch, mannitol, carboxymethyl cellulose etc., add as required again stabilizing agent, excipient, bonding agent, disintegrating agent etc. and carry out.
With other sucrose or when containing the food coupling of sucrose, the taking of medicament is necessary at sucrose or carries out in the rear certain hour when containing the picked-up of food of sucrose or before the picked-up with medicament.Taking simultaneously medicament with sucrose or the picked-up that contains the food of sucrose has certain effect, but considers the intestinal holdup time of sucrose or non-antagonism type inhibitor, and preferably both picked-up time is separated by not far.Particularly, the taking too early of medicament is then at picked-up sucrose or contain the worry that has non-antagonism type inhibitor not exist in the food of sucrose in intestinal, so taking the earliest also preferably front 90 minutes of picked-up of medicament carried out with interior.In addition, sucrose or contain the picked-up of food of sucrose after the sucrose that arrives first intestinal of taking of medicament decomposed by the sucrose decomposition enzyme, analyte stimulates the K cell of upper intestines and the worry of secreting GIP, so preferably avoid as far as possible, but so long as absorb in rear 15 minutes, tolerable under the behaviour in service of reality then.
With medicament and other sucrose or the mixing ratio of the relative sucrose of the non-antagonism type inhibitor when containing the food coupling of sucrose can be basically same from the situation that body contains sucrose with medicament.
The food that contains sucrose that together uses with medicament of the present invention, as long as contain fully sucrose, then be not particularly limited, for example can enumerate, maltosemalt sugar, chewing gum, cookies, cake, pudding, fruit jelly, Bavaria dessert, mousse, red bean jelly, steamed bun, bean filling glutinous rice pie, bronze gong burns, madai is burnt, burn in modern river, battercake, bush clover cake, the Japanese Western-style pastry class of large good fortune, dumpling, fine cake etc.; The milk product of ice cream, yogurt etc.; The beverage of coffee, black tea etc.; Refrigerant drinking water, carbonic acid drinking water, put into the drinking water of the drinking water etc. of fruit juice.
When medicament of the present invention is taken simultaneously with the picked-up that contains the food of sucrose, add in advance medicament of the present invention to these food, the form of getting the food that contains medicament also can.At this moment, for the reduction of the flavor matter of the food that prevents from resulting from non-antagonism type inhibitor, also can add the replacement sweetening material of sucralose, maltose alcohol, xylitol, erythritol, aspartame, acesulfame K etc.In addition, as required, in order to keep the food form, also can add the viscosifier of carrageenin, agar, plant gum (guar gum, arabic gum etc.), other insoluble dietary fiber, water solublity dietary fiber etc.
[embodiment]
Next the good effect (effect of the secretion of the secretion of promotion GLP-1 and inhibition GIP) of specifically showing medicament of the present invention.Have, the record of embodiment is intended to help the understanding of inventing purely again, and the present invention is not limited by these embodiment.
[embodiment 1: the demonstration test of the effect when using L-arabinose as non-antagonism type inhibitor]
[test method]
For the situation that sucrose and L-arabinose is applied to rat, sucrose independent (contrast) is applied to the situation of rat, reach the situation that L-arabinose independent (contrast) is applied to rat, by the secretory volume of research GLP-1 and GIP, check the inhibition of blood glucose value and insulin value.
At first, utilizing 12 SD heros of taming for 1 week with conventional food is rat (4 age in week), these are divided into 3 groups with each 4, to each group dosage forms for oral administration sucrose 2.5g/ body weight kg+L-arabinose 125mg/ body weight kg (relatively sucrose 5%), sucrose 2.5g/ body weight kg or L-arabinose 125mg/ body weight kg.
Use front, use 30 minutes after, and after using 60 minutes, gather portal Blood and venous blood from each rat.Prepare to inject in advance the blood taking tube of DPP-4 inhibitor and EDTA, ice-cooled immediately after the stirring to the portal Blood of wherein putting into collection, rear 30 minutes of collection with interior centrifugalize blood plasma.Next, from then on blood plasma uses the active form GLP-1 of each sample of ELISA standard measure, total GLP-1 and GIP.In addition, the venous blood that gathers is put into test tube for blood sample, centrifugalize and obtain serum.Next, from then on serum uses the insulin value in the ELISA standard measure serum, uses enzymatic assays Glucose in serum value (blood glucose value).Each characteristic value to the record value of the coordinate diagram meansigma methods as the measured value that obtains from 4 rat.
[result]
Measurement result is shown in Fig. 1～5.Fig. 1 shows that sucrose+L-arabinose uses group and sucrose and use the coordinate diagram of rheological parameters' change with time that group (contrast) and L-arabinose are used the blood glucose value that using front and back of group (contrast), and Fig. 2～5 are respectively naturally about the amount of the insulin value in the serum, active form GLP-1, the always amount, coordinate diagram amount and that Fig. 1 is same of GIP of GLP-1.
Know from Fig. 1 and 2, use simultaneously sucrose and L-arabinose, compare when only using sucrose, the rising of the insulin value in blood glucose value and the serum is suppressed.In addition, know from Fig. 3 and 4 that by using of sucrose and L-arabinose, the secretion of active form GLP-1 and total GLP-1 is promoted that the secretory volume of active form GLP-1 is also remarkable after 60 minutes.On the other hand, know from Fig. 5 that GIP is also hardly secretion when using sucrose and L-arabinose.Have, know from Fig. 1～5, only use L-arabinose, the insulin value in blood glucose value, the serum, the amount of active form GLP-1, the amount of total GLP-1, the amount of GIP all do not change yet.
[embodiment 2: the checkout facility of the effect when changing the consumption of L-arabinose]
[test method]
Change the L-arabinose amount that is administered to rat among the embodiment 1, the variation of the secretory volume of research GLP-1 and GIP.
At first, utilizing 24 SD heros of taming for 1 week with conventional food is rat (4 age in week), these are divided into 6 groups with each 4, to each group dosage forms for oral administration sucrose 2.5g/ body weight kg+L-arabinose 25mg/ body weight kg (relatively sucrose 1%), sucrose 2.5g/ body weight kg+L-arabinose 62.5mg/ body weight kg (relatively sucrose 2.5%), sucrose 2.5g/ body weight kg+L-arabinose 100mg/ body weight kg (relatively sucrose 4%), sucrose 2.5g/ body weight kg+L-arabinose 250mg/ body weight kg (relatively sucrose 10%), sucrose 2.5g/ body weight kg+L-arabinose 500mg/ body weight kg (relatively sucrose 20%), perhaps sucrose 2.5g/ body weight kg.Processing after using is to measure active form GLP-1 and GIP as embodiment 1.
[result]
Measurement result is shown in Fig. 6 and 7.Fig. 6 shows that sucrose+L-arabinose uses the coordinate diagram of rheological parameters' change with time of amount that group and sucrose are used the active form GLP-1 that using front and back of group (contrast), and Fig. 7 shows that sucrose+L-arabinose is used to organize and sucrose is used the coordinate diagram of rheological parameters' change with time of amount of the GIP that using front and back of group (contrast).Have, Fig. 6 and 7 is the data of note relative sucrose 5% of mensuration in embodiment 1 also again.
Know from Fig. 6 and 7, use 1%, 2.5% or 4% L-arabinose with respect to sucrose, then compare when only using sucrose, active form GLP-1 increased after 60 minutes significantly, and GIP is some increases also.In addition, use 10% or 20% L-arabinose with respect to sucrose, then active form GLP-1 increases, and knows on the other hand, though GIP does not increase, its degree is roughly the same when using 5% L-arabinose with respect to sucrose.
[embodiment 3: the demonstration test of the effect when using the D-xylose as non-antagonism type inhibitor]
[test method]
For sucrose and D-xylose are applied to the situation of rat with various mixing ratios, and with sucrose separately (contrast) be applied to the situation of rat, study the secretory volume of GLP-1 and GIP.
At first, utilizing 28 SD heros of taming for 1 week with conventional food is rat (4 age in week), these are divided into 7 groups with each 4, to each group dosage forms for oral administration sucrose 2.5g/ body weight kg+D-xylose 25mg/ body weight kg (relatively sucrose 1%), sucrose 2.5g/ body weight kg+D-xylose 62.5mg/ body weight kg (relatively sucrose 2.5%), sucrose 2.5g/ body weight kg+D-xylose 100mg/ body weight kg (relatively sucrose 4%), sucrose 2.5g/ body weight kg+D-xylose 125mg/ body weight kg (relatively sucrose 5%), sucrose 2.5g/ body weight kg+D-xylose 250mg/ body weight kg (relatively sucrose 10%), sucrose 2.5g/ body weight kg+D-xylose 500mg/ body weight kg (relatively sucrose 20%), perhaps sucrose 2.5g/ body weight kg.Processing after using is to measure active form GLP-1 and GIP as embodiment 1.
[result]
Measurement result is shown in Fig. 8 and 9.Fig. 8 shows that sucrose+D-xylose uses the coordinate diagram of rheological parameters' change with time of amount that group and sucrose are used the active form GLP-1 that using front and back of group (contrast), and Fig. 9 shows that sucrose+D-xylose is used to organize and sucrose is used the coordinate diagram of rheological parameters' change with time of amount of the GIP that using front and back of group (contrast).
Know from Fig. 8 and 9, use 1%, 2.5% or 4% D-xylose with respect to sucrose, then compare when only using sucrose, active form GLP-1 promoted to increase significantly after 60 minutes, and GIP is some increases also.Know in addition, use 5%, 10% or 20% D-xylose with respect to sucrose, then active form GLP-1 increases, and on the other hand, GIP does not increase.
[embodiment 4: the demonstration test of the effect when using D-Tag as non-antagonism type inhibitor]
[test method]
For sucrose and D-Tag are applied to the situation of rat with various mixing ratios, and with sucrose separately (contrast) be applied to the situation of rat, study the secretory volume of GLP-1 and GIP.
At first, utilizing 24 SD heros of taming for 1 week with conventional food is rat (4 age in week), these are divided into 6 groups with each 4, to each group dosage forms for oral administration sucrose 2.5g/ body weight kg+D-Tagatose 250mg/ body weight kg (relatively sucrose 10%), sucrose 2.5g/ body weight kg+D-Tagatose 500mg/ body weight kg (relatively sucrose 20%), sucrose 2.5g/ body weight kg+D-Tagatose 750mg/ body weight kg (relatively sucrose 30%), sucrose 2.5g/ body weight kg+D-Tagatose 1000mg/ body weight kg (relatively sucrose 40%), sucrose 2.5g/ body weight kg+D-Tagatose 1250mg/ body weight kg (relatively sucrose 50%), perhaps sucrose 2.5g/ body weight kg.Processing after using is to measure active form GLP-1 and GIP as embodiment 1.
[result]
Measurement result is shown in Figure 10 and 11.Figure 10 shows that sucrose+D-Tag uses the coordinate diagram of rheological parameters' change with time of amount that group and sucrose are used the active form GLP-1 that using front and back of group (contrast), and Figure 11 shows that sucrose+D-Tag is used to organize and sucrose is used the coordinate diagram of rheological parameters' change with time of amount of the GIP that using front and back of group (contrast).
Know from Figure 10 and 11, use 10% or 20% D-Tag with respect to sucrose, then compare when only using sucrose, active form GLP-1 increased after 60 minutes significantly, and GIP is some increases also.Know in addition, use 30%, 40% or 50% D-Tag with respect to sucrose, then active form GLP-1 increases, and on the other hand, GIP does not increase.
Know from above result, L-arabinose, D-xylose, and D-Tag all can be used as the non-antagonism type inhibitor of sucrose decomposition enzyme, effectively promote the secretion of GLP-1 while the secretion that suppresses GIP, and the mixing ratio of the non-antagonism type inhibitor of the sucrose decomposition enzyme of relative sucrose is just enough more than 4.5 % by weight in the situation of L-arabinose or D-xylose, is just enough more than 25 % by weight in the situation of D-Tag.
[industrial applicibility]
Medicament of the present invention can be among incretin, also fully suppresses the secretion of the GIP that do not expect in impaired glucose tolerance or the diabetes, only promotes simultaneously the secretion of the GLP-1 of expectation.In addition, as the non-antagonism type of the effective ingredient of medicament of the present invention α-generally speaking the GI agent is used more, therefore good to the safety of human body all the time as food additives.Thereby medicament of the present invention is extremely suitable for the daily picked-up of the prevention of the treatment that is used for impaired glucose tolerance or diabetes.
Claims (6)
1. medicament is characterized in that,
To promote the secretion of glucagon-like-peptide-1 and suppress the medicament that the dependence on the glucose insulin secretion stimulates the secretion of polypeptide,
Contain the non-antagonism type inhibitor of sucrose decomposition enzyme as effective ingredient, the non-antagonism type inhibitor of described sucrose decomposition enzyme is L-arabinose, D-xylose and/or D-Tag.
2. medicament claimed in claim 1 is characterized in that, relatively the mixing ratio of the non-antagonism type inhibitor of the sucrose decomposition enzyme of sucrose
In the situation of L-arabinose or D-xylose, be 4.5～99 % by weight,
25～99 % by weight in the situation of D-Tag.
3. medicament claimed in claim 1 is characterized in that, also contains sucrose.
4. medicament is characterized in that,
● described medicament is the medicament claimed in claim 1 that does not contain sucrose, and
● described medicament
■ and sucrose or the food picked-up that contains sucrose are taken simultaneously,
■ absorbs at sucrose or the food that contains sucrose and took with interior in front 90 minutes, perhaps
■ absorbs at sucrose or the food that contains sucrose and took with interior in rear 15 minutes.
5. medicament claimed in claim 4 is characterized in that, the food that contains sucrose is Japanese Western-style pastry class, milk product, beverage or drinking water.
6. each described medicament of claim 1～5 is for the preparation of the purposes of the medicine that uses in the prevention of the treatment of impaired glucose tolerance or diabetes.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2011-186869 | 2011-08-30 | ||
| JP2011186869 | 2011-08-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102961388A true CN102961388A (en) | 2013-03-13 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012100851993A Pending CN102961388A (en) | 2011-08-30 | 2012-03-28 | Medicine capable of promoting secretion of glp-1 and restraining secretion of gip |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JP2013063947A (en) |
| KR (1) | KR20130027075A (en) |
| CN (1) | CN102961388A (en) |
| TW (1) | TW201315472A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104739848A (en) * | 2015-04-07 | 2015-07-01 | 福州乾正药业有限公司 | Composition containing L-arabinose and tagatose as well as preparation method and drug application of composition |
| CN106133519A (en) * | 2014-03-24 | 2016-11-16 | 花王株式会社 | The evaluation of GIP compound or system of selection |
| CN108135918A (en) * | 2015-07-29 | 2018-06-08 | 学校法人自治医科大学 | GLP-1 secernents |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109152382A (en) | 2016-05-04 | 2019-01-04 | Cj第制糖株式会社 | For inhibiting the functional health-care food comprising coffee and Tagatose of blood glucose rise |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5468734A (en) * | 1992-03-10 | 1995-11-21 | Godo Shusei Co., Ltd. | Prophylactic and remedial preparation for diseases attendant on hyperglycemia, and wholesome food |
-
2012
- 2012-03-28 CN CN2012100851993A patent/CN102961388A/en active Pending
- 2012-04-20 KR KR1020120041440A patent/KR20130027075A/en not_active Application Discontinuation
- 2012-05-11 JP JP2012108986A patent/JP2013063947A/en active Pending
- 2012-08-29 TW TW101131272A patent/TW201315472A/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5468734A (en) * | 1992-03-10 | 1995-11-21 | Godo Shusei Co., Ltd. | Prophylactic and remedial preparation for diseases attendant on hyperglycemia, and wholesome food |
Non-Patent Citations (2)
| Title |
|---|
| T.W.DONNER: "D-tagatose, a novel hexose: acute effects on carbohydrate tolerance in subjects with and without type 2 diabetes", 《DIABETES，OBESITY AND METABOLISM》 * |
| 周克夫，等: "L-阿拉伯糖对高糖高脂喂养小鼠体重及耐糖量的影响", 《中国医药导刊》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106133519A (en) * | 2014-03-24 | 2016-11-16 | 花王株式会社 | The evaluation of GIP compound or system of selection |
| US10132795B2 (en) | 2014-03-24 | 2018-11-20 | Kao Corporation | Method for evaluating or selecting agent for suppressing GIP level elevation |
| CN104739848A (en) * | 2015-04-07 | 2015-07-01 | 福州乾正药业有限公司 | Composition containing L-arabinose and tagatose as well as preparation method and drug application of composition |
| CN108135918A (en) * | 2015-07-29 | 2018-06-08 | 学校法人自治医科大学 | GLP-1 secernents |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2013063947A (en) | 2013-04-11 |
| TW201315472A (en) | 2013-04-16 |
| KR20130027075A (en) | 2013-03-14 |
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