CN101180065A - A composition containing timosaponin A-III for prevention and treatment of type 2 diabetes mellitus - Google Patents

A composition containing timosaponin A-III for prevention and treatment of type 2 diabetes mellitus Download PDF

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CN101180065A
CN101180065A CNA2006800174863A CN200680017486A CN101180065A CN 101180065 A CN101180065 A CN 101180065A CN A2006800174863 A CNA2006800174863 A CN A2006800174863A CN 200680017486 A CN200680017486 A CN 200680017486A CN 101180065 A CN101180065 A CN 101180065A
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timosaponin
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diabetes mellitus
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韩昌均
林光津
宣垣硕
韩蕙英
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SK Chemicals Co Ltd
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Abstract

The present invention relates to a composition for the prevention or treatment of type 2 diabetes mellitus, which comprises timosaponin A-III, and in particular, it relates to a composition for the prevention or treatment of type 2 diabetes mellitus comprising timosaponin A-III as an active ingredient, which is completed by finding that timosaponin A-III is superior in preventing or treating type 2 diabetes mellitus while is poor in preventing or treating type 1 diabetes mellitus, in contrary to what has been known.

Description

Be used to prevent and treat the compositions that comprises timosaponin A-III of type 2 diabetes mellitus
Technical field
The present invention relates to be used to prevent or treat the compositions of type 2 diabetes mellitus, described compositions comprises 1-timosaponin A-1-III, relate to the compositions that is used to prevent or treat type 2 diabetes mellitus especially, described compositions comprises the 1-timosaponin A-1-III as the composition of living, and this can prevent and treat to have excellent effect in the type 2 diabetes mellitus and discovery (opposite with the known knowledge) support of poor effect in prevention or treatment type 1 diabetes by 1-timosaponin A-1-III.
Background technology
According to NIH (NIH), nearly 1,570 patient's [evidence reports: clinical guideline on theidentification that suffer type 2 diabetes mellitus (obesity-related disease a kind of), evaluation, and treatment of overweight andobesity in adults, 1999, NIH].
In addition, the number of WHO expection diabetics in 2025 will reach about 300,000,000 people.Especially, suffer the patient of type 2 diabetes mellitus (the wherein function of insulin deficit glucose level control) to amount to the people such as 5.9%[A.S.Wagman that are approximately U.S. population, CurrentPharmaceutical Design, 7,417,2001].
Diabetes relate to the metabolic disease of Hydrocarbon and show the symptom of hyperglycemia level.This disease is divided into type 1 diabetes (insulin dependent diabetes mellitus (IDDM); Be approximately total patient 10%) and type 2 diabetes mellitus (noninsulindependent diabetes; Be approximately total patient 90%) [B.Set, Clin Therapeu., 25,1895,2003; S.N.Davis, JDiabetes Complications., 18,367,2004].Thereby because the pancreatic damage that causes the destruction of β cell in the pancreas to be caused owing to heredity or virus infraction, type 1 diabetes patient has the ability of very low excreting insulin or does not have the ability of excreting insulin.In addition, these patients show that very high blood glucose blood is flat, and this hyperglycemia level may further develop to the symptom of ketoacidosis and ketoacidosis (ketoasidosis).The childhood period that type 1 diabetes mainly occurring in, must come glucose level control by administration of insulin.On the contrary, type 2 diabetes mellitus in the adult, find usually and because of heredity, obesity, pressure, hormone secretion unusually and the use of medicine take place.The patient can secrete but cause imbalance with non-usually low amount excreting insulin or because of the secretion of unfavorable active hormones increase.Type 2 diabetes mellitus comes from the insulin resistance that the generation of endogenous glucose in the obstruction of appropriate insulin secretion, the liver is increased or causes owing to glucose utilization lower in the surrounding tissue according to reports.Although this disease also can be developed to the hyperglycemia level, the patient can not resemble the type 1 diabetes patient ketoacidosis and ketoacidosis sensitivity.Under the situation of type 1 diabetes, can control by meals, exercise and insulin medicament treatment blood sugar lowering level.Yet type 2 diabetes mellitus requires to use extraly the horizontal medicine of blood sugar lowering.
Hypoglycemic drug can be divided into three classes according to mechanism of action.Sulfonylurea or be the first kind based on the medicine of meglitinide, the β cell in its stimulating pancreas is to improve insulin secretion.Second class is that insulin sensitizer is for example based on the medicine of biguanide or thiazolidinediones.Acarbose or miglitol are included in the 3rd apoplexy due to endogenous wind, the absorption that it suppresses the degraded of saccharide and reduce saccharide in intestinal.The preferred horizontal medicine of blood sugar lowering should suppress the excessive increase of blood sugar level fast after dining, and also loses activity and do not cause the hypoglycemia level.In addition, it should improve the abnormal metabolism that diabetes are followed.Aspect this, aforementioned medicine is not suitable fully, therefore must develop Orally administered suitably to treat the horizontal medicine of stable blood sugar lowering of the diabetes that worldwide increasing.
In the type 1 diabetes animal model, exist to use the drug-induced model of alloxan or streptozotocin and the number of animals by cultivating diabetes-induced for the natural inductive model that produces for example NOD (non-obese diabetes) mice and BB (bio breeding) rat.On the contrary, the model that genetic engineering produces is widely used for the type 2 diabetes mellitus animal model, and representative example is db/db mice (diabetes model that produces because of the defective of Leptin receptor), ob/ob mice (the obesity model that causes because of the defective of Leptin receptor), zucker (adiposis disease model) rat, OLETF (The Otsuka Long-Evans Tokushima fatty; Fat and glucose resistance diabetes model) rat, KK (obese diabetes model) mice, KK-Ay (obese diabetes, hyperinsulinemia model) mice [people such as S.Makino, Exp Anim., 29,1,1980; People such as A.F.Nakhooda, Diabetes, 26,100,1977; People such as M.Nakamura, Diabetol, 3,121,1967; People such as K.Kawano, Diabetes, 41,1422,1992; People such as D.A.Rees, Diabetic Medicine, 22,359,2005].Therefore, understand the character of each animal model (1 type, 2 types) and to select optimal model be very important.
Relevant prior art
People such as N.Nakashima have reported the effect of pseudo-timosaponin (pseudotimosaponin) A-III, former timosaponin (prototimosaponin) A-III, 1-timosaponin A-1-III blood sugar lowering level in rat, in described rat, diabetes are induced by alloxan and streptozotocin, described medicine is the representative drugs [people such as N.Nakashima who is used for the experimental diabetes disease model, J.Nat.Prod. the 56th roll up, 345,1994].In addition, 1-timosaponin A-1-III has the activity of anticoagulant [people such as A.Niwa, YakugakuZasshi 108 (6), 555,1988] and vasodilator [people such as G.Wang, Life Sci.71,1081,2002] according to reports.
Alloxan and streptozotocin are as the representative drugs of inducing type 1 diabetes, because its expression by glucose transporter (GLUT-2) enters the β cell in the pancreas, the destruction of inducing DNA or NAD+ exhaust, thereby cause the programmed cell death of the β cell in the pancreas.[people such as K.Bloch, Diabetes Metab Res Rev 21,253,2005; People such as D.A.Rees, Diabetic Medicine, 22,359,2005; People such as J.Kawada, YakugakuZasshi, 112,773,1992; People such as V.M.F.Rastelli, Inflamm Res., 54,173,2005; People such as R.K.Cuman, Inflamm Res.50,460,2001; With reference to figure 1].
Alloxan (5,5-dihydroxy-2,4,6 (1H, 3H, 5H)-and pyrimidine trione) be the oxidation product or the pyrimidine derivatives of uric acid.The alloxan anion is destroyed β cell in the pancreas [people such as K.Bloch, Diabetes Metab ResRev 21,253,2005 by the radical reaction of cytochrome P-450 mediation; Yakugaku Zasshi, 112,773,1992].Yet, reported the high mortality that alloxan has toxicity and causes animal.People such as I.F.Federiuk try to find out and make the mortality rate in the inductive diabetes model of alloxan be reduced to the minimum best approach by route of administration or the dosage that changes alloxan.As a result, the intraperitoneal of the alloxan of high dose (200mg/kg) is used and is reduced mortality rate 10%, and induces the type 1 diabetes [I.F.Federiuk, Compara Med, 54,252,2004] above 70%.
Streptozotocin (2-deoxidation-2-(3-methyl-3-nitroso-group urea groups)-D-Glucopyranose .) (glucosan derivative) enters the β cell and produces superoxide radical based on strong alkylating, thereby causes the oxidation of described β cell is destroyed.The generation of superoxide radical is by the indirect activation of XOD (xanthine oxidase) (this activation is caused by the ADP when the cell middle and high concentration that suppresses to produce when mitochondrion produces ATP) or by the direct activation of XOD (xanthine oxidase) [people such as D.A.Rees, Diabetic Medicine, 22,359,2005; Yakugaku Zasshi, 112,773,1992] induce.
Although reported by using streptozotocin to induce type 2 diabetes mellitus, the great majority of these reports disclose need with the medicament administration of inducing type 2 diabetes mellitus extra drug dexamethasone [people such as S.J.Giddings, Diabetes for example for example, 34,235,1985], niacin amide [people such as S.Ozyazgan, Pharmacol., 74,119,2005] or the high fat diet at least 1 to 2 week [people such as R.de Souza Santos, Clin Chim Acta., 2005, Epubahead of print; People such as M.J.Reed, Metabolism., 49,1390,2000; People such as F.Zhang, Exp Anim., 52,401,2003] use the extra measurement of carrying out together.That is, be type 1 diabetes by the inductive disease of independent streptozotocin (no matter dosage or route of administration), this is seemingly unquestionable.The inductive diabetes animal model of this streptozotocin should be different from introduction stage streptozotocin (being called ' n-streptozotocin ' hereinafter) inductive diabetes model [people such as I.Degirmenci in two day age rat, J EthnopharmacoL, 97,555,2005; People such as D.N.Umrani, Clin Exp Hypertens., 25,221,2003].N-streptozotocin-inductive diabetes rat model is widely used type 2 diabetes mellitus model, in fact, described report also described clearly in adult rat the inductive diabetes model of streptozotocin be 1 pattern type and in neonate rat n-streptozotocin-inductive diabetes model be 2 pattern types [B.M.Kim., Diabetol., 44,2192,2001; People such as V.M.F.Rastelli, Inflamm Res., 54,173,2005; People such as R.K.Cuman, Inflamm Res.50,460,2001; People such as U.A.Shinde, J Cell Mol Med., 7,322,2003; People such as U.A.Shindea, J Trace Elem Med Biol., 18,23,2004].
In a word, [people such as N.Nakashima, the J.Nat.Prod of people such as N.Nakashima report, the 56th volume, 345,1994] effect of 1-timosaponin A-1-III in reducing blood level only is applicable to the type 1 diabetes model, this with described type 2 diabetes mellitus herein in the activity of blood sugar lowering level irrelevant.In addition, people such as N.Nakashima only disclose the comparison activity of blood sugar lowering level, and do not describe the absolute effect of blood sugar lowering level at all.Therefore, people such as N.Nakachima fail to show, have than the former 1-timosaponin A-1-III described herein or the more weak active fact of pseudo-1-timosaponin A-1-III based on 1-timosaponin A-1-III, 1-timosaponin A-1-III has excellent effect in the blood sugar lowering level in the type 2 diabetes mellitus model.
Therefore the object of the present invention is to provide the new purposes of 1-timosaponin A-1-III in prevention or treatment type 2 diabetes mellitus.
Detailed Description Of The Invention
The present invention relates to be used to prevent or treat the compositions of type 2 diabetes mellitus, it comprises the timosaponin as active component.
In addition, the present invention relates to comprise 1-timosaponin A-1-III as active component, be health food effective for type 2 diabetes mellitus.
Detailed description of the present invention is provided hereinafter.
The present invention supports by following discovery, and described discovery is, and is opposite with known knowledge, 1-timosaponin A-1-III effect in prevention or treatment type 2 diabetes mellitus excellent and in prevention or treatment type 1 diabetes effect relatively poor.
In the present invention, isolate 1-timosaponin A-1-III (3-O-β-D-glucopyranosyl-(1 → 2)-β-D-galactopyranose base) Sarsasapogenin of formula (I) from the Rhizoma Anemarrhenae.
Figure S2006800174863D00051
Be used for comprising from the method for Rhizoma Anemarrhenae rhizome (Rhizoma Anemarrhenae) separation 1-timosaponin A-1-III:
(a) in aqueous solution of alcohol, obtain the extract (hereinafter being called ' Rhizoma Anemarrhenae ') of Rhizoma Anemarrhenae rhizome and reclaim extract with tri-distilled water;
(b) make the extract layering of recovery with the hexane of same amount, remove the upper strata then;
(c) water layer below the washed with dichloromethane of same amount is with the ethyl acetate layering of same amount, separating ethyl acetate layer then; With
(d) use silica gel column chromatography that isolating ethyl acetate layer is carried out fractionated, separate and the acquisition timosaponin by the recrystallization that uses the diox aqueous solution.
The present invention determined, and is opposite with known knowledge, and the effect of 1-timosaponin A-1-III in prevention or treatment type 2 diabetes mellitus is very excellent and effect in prevention or treatment type 1 diabetes is relatively poor.
Therefore, the present invention relates to be used to prevent or treat type 2 diabetes mellitus, comprise compositions as the 1-timosaponin A-1-III of active component.
Compositions herein (when accepting Clinical detection) can by oral or parenteral for example by intravenous, subcutaneous, peritoneum and topical is used and can medicine or the form of health food use.
Compositions herein can be mixed with tablet, pill, Emulsion or liquid dosage form, aerosol, tablet, contain ingot, water or oil suspension, preparation, powder, granule, Emulsion, hard or soft capsule, syrup or elixir.Tablet or capsule preparations can comprise binding agent for example lactose, sucrose, Sorbitol, mannitol, starch, amylopectin, cellulose or gelatin; Excipient is dicalcium phosphate for example; Disintegrating agent is corn starch or sweet potato starch for example; Lubricant is magnesium stearate, calcium stearate, sodium stearyl fumarate or polyethylene glycol wax for example.Capsule preparations also can comprise liquid-carrier.In addition, but parenteral is for example subcutaneous, compositions herein is used in intravenous, intramuscular or chest (pectoral) injection.Can be by compositions herein be mixed in water with stabilizing agent or buffer agent, the one-pack type that is mixed with ampoule or bottle is then produced parenteral formulation.
Suitable carriers, excipient and diluent example are aluminum salt, phenyl phenol, water, normal saline solution, lactose, glucose, Sorbitol, mannitol, calcium silicates, cellulose, methylcellulose, Celluloasun Microcrystallisatum, polyvinylpyrrolidone, methyl hydroxybenzoate, propyl hydroxybenzoate, Talcum, magnesium stearate and mineral oil.
In addition, any preparation of compositions also can comprise filler, anti-agent, lubricant, wetting agent, flavoring agent, suspending agent or the antiseptic of assembling herein.
Simultaneously, can be by considering that for example absorption level, inactivation rate, excretion rate or patient's age, sex, the physical condition of active component wait the proper dosage level of determining active component herein to various information.In preferred embodiments, adult's dosage level is 0.1-15g every day.
Compositions herein can be formulated as food or medicine and can take every day 1 time or 2 twice according to aforesaid daily dose.
As used herein, ' health food ' is meant the food that the form with capsule, powder or suspending agent exists, by for example thereby beverage, tea, flavoring agent, natural gum, point add herein active component in the heart and provide the effect of wanting (simultaneously different with medicine, without any side effects for a long time after taking) to prepare described health food at different foods.
Summary of drawings
Fig. 1 shows the destructive process of the β cell that is produced by alloxan and streptozotocin.
Fig. 2 shows Rhizoma Anemarrhenae ethyl acetate fraction (AA-EA) and its subfraction (figure of the effect of blood sugar lowering level in the db/db mouse model of EA-I～EA-V).
Fig. 3 is the figure that shows 1-timosaponin A-1-III effect of blood sugar lowering level in the db/db mouse model.
Fig. 4 is the figure that shows 1-timosaponin A-1-III effect of blood sugar lowering level in the KK-Ay mouse model.
Fig. 5 is the figure that shows 1-timosaponin A-1-III effect of blood sugar lowering level in the inductive diabetes rat model of streptozotocin.
Embodiment
By the following example the present invention is described more clearly.Embodiments herein just is used to illustrate of the present invention, and endlessly any way limits the present invention.
Preparation embodiment 1: from the preparation of the active EA fraction of the Rhizoma Anemarrhenae
The Rhizoma Anemarrhenae of 3kg is immersed in the ethanol of 20L 50% and carried out 4 hours, carry out 2 times.Under 80 ℃, under condition of stirring, carry out this process to obtain effective extraction.After 4 hours,, remove final floating material with funnel and absorbent cotton with solid precipitation.Distill filtrate with rotary evaporator, take by weighing the weight of thus obtained extract.The 100g extract is recovered in the 500mL tri-distilled water, repeats this process.With the n-hexane of the extract that obtains and same amount (Jinchemicals pharmaceutical Co.Ltd., Korea) mixing, and in separatory funnel, stirring.After 24 hours, remove top hexane layer, repeat this process 2 or 3 times.
With the method identical with said method with the remaining water layer 3 of dichloromethane (Jin chemicalspharmaceutical Co.Ltd., Korea is called " MC " hereinafter) washing of same amount or 4 times.The ethyl acetate (Jin chemicalspharmaceutical Co.Ltd., Korea is called " EA " hereinafter) of remaining water layer and same amount is mixed, and place separatory funnel.After 24 hours, remove top EA layer.By carry out the Rhizoma Anemarrhenae EA fraction (AA-EA) that 2 or 3 fractionated acquisitions are wanted with EA, under the pressure that reduces, it is concentrated then.Store with to be used down with its atomizing and at-20 ℃.
Preparation embodiment 2: the inferior fractionated of Rhizoma Anemarrhenae EA fraction
290g Rhizoma Anemarrhenae EA fraction (AA-EA) is accepted to use silica gel column chromatography, and (the 170-230 order, series classification 3kg) is separated.By using the following solvent of 15L: EA (15L), EA: MeOH=20 respectively: 1 (20L), EA: MeOH: water=20: 2: 0.1 (20L), EA: MeOH: water=10: 2: 0.2 (20L) obtains 5 kinds of different fraction.Described fraction is called EA-I, EA-II, EA-III, EA-IV and EA-V in proper order according to this.Concentrate each fraction under the pressure that reduces, described fraction and store with to be used down at-20 ℃ atomizes.
Preparation embodiment 3: the separation of active component and structural characterization
40mL 70% De diox aqueous solution is added 1g Rhizoma Anemarrhenae EA subfraction (EA-V), it is dissolved fully by water-bath and supersound process.Dissolved EA-V fraction is at room temperature placed 24 hours, thereby the white needles material is provided.(Rf 0.38,90% MeOH is at 5% ethanolic H to be called Compound I by the material that filters the white needles material preparation 2SO 4Spraying back carbonization, RP-18 F254s, MERCK).
Use H 1-NMR, C 13-NMR and ESI-MS carry out structural characterization to isolated compound I, and determine that described chemical compound is the people such as 1-timosaponin A-1-III[S.Saito that report in the past, Chem.Pharm.Bull.2342.1994].In addition, the commercially available acquisition of standardized product (SKF 7862, WAKO pure chemical industries.LTD.), and the material identical materials that is defined as and uses HPLC to obtain.
Embodiment 1: the effect of blood sugar lowering level in the db/db mouse model
The db/db male mice (C57BL/Ks-db/db) in age in 8-9 week is used for this experiment.The rising of and experience blood sugar level fat by C57BL/Ks-db/db mice 4-5 week beginning after birth of the Jackson laboratory of U.S. development is because the shortage of Leptin receptor and by anomalous signals transmission system inducing obesity dependency diabetes in the hypothalamus.Because this character, it is with the representative type 2 diabetes mellitus animal model [people such as D.A.Rees, Diabetic Medicine, 22,359,2005 that act on the mechanism of analyzing and find diabetes, obesity and its complication or be used to screen the medicine of blood sugar lowering level; People such as G.H.Lee, Nature, 379,632,1996; People such as S.C.Chua, Science, 271,994,1996; People such as J.K.Naggert, Mamm Genome., 6,131,1995].
Every afternoon, use detection of drugs to experimental group, make negative control group and positive controls accept intraperitoneal or Orally administered 0.5% carboxymethyl cellulose (CMC) solution and the rosiglitazone that is dissolved in 0.5% carboxymethyl cellulose (CMC) solution respectively.In the afternoon just in time before the time of application of plan, come measurement of glucose levels with 3-4 days intervals by cutting tail vein.Just in time before using, take by weighing the weight of mice and feedstuff with 2 days intervals.After using, weigh and measure, carried out 10 days, separation of serum from the blood of gathering, and measure various biochemical parameters to analyze the lipid and the function of liver or kidney.
Fig. 2 is presented at the effect of 300mg/kg subfraction (EA-I, EA-II, EA-III, EA-IV, EA-V) the back blood sugar lowering level of using the Rhizoma Anemarrhenae EA fraction (AA-EA) for preparing among the 300mg/kg preparation embodiment 1 and preparing in preparation embodiment 2.
As a result, determined to compare with Rhizoma Anemarrhenae EA fraction (AA-EA), EA-V shows more excellent activity.In addition, owing to described activity equates with positive control, so this fraction is accepted the screening of active component.
Fig. 3 is presented at respectively the effect of the blood sugar lowering level behind the 1-timosaponin A-1-III of preparation among the preparation embodiment 3 of using with the dosage of 100mg/kg, 200mg/kg and 3000mg/kg.The figure illustrates effect identical with positive control on the dosage of 200mg/kg, shown the blood sugar lowering level even more excellent effect on the dosage of 300mg/kg, this has determined that 1-timosaponin A-1-III is the main active in the EA-V fraction.
Embodiment 2: the effect of 1-timosaponin A-1-III blood sugar lowering in the KK-Ay mice
The KK-Ay male mice (C57BL/Ks) in age in 9-10 week is used for this experiment.Produce the KK-Ay mice by ob gene being imported the KK mice, described KK mice comes from KaskabeSaitamihyun Japan and is used for genetic research by Takeda Pharmaceutical IndustryCorporation development.It is as the type 2 diabetes mellitus model that shows obesity and hyperinsulinemia (because hyperglycemia level cause) in early days [people such as M.Okazaki, Exp Anim., 51,191,2002; People such as J.Suto, Eur J Endocrinol., 139,654,1998].
Make every afternoon negative control group and experimental group accept 0.5% carboxymethyl cellulose (CMC) solution respectively and be dissolved in to be subjected to the Orally administered of reagent thing in 0.5% carboxymethyl cellulose (CMC).In the afternoon just in time before the time of application of plan, come measurement of glucose levels with 3-4 days intervals by cutting tail vein.Just in time before using, take by weighing the weight of mice and feedstuff with 2 days intervals.After using, weigh and measure, carried out 8 days, separation of serum from the blood of gathering is measured various biochemical parameters to analyze the lipid and the function of liver or kidney.
Fig. 4 shows respectively the effect of the blood sugar lowering level behind the 1-timosaponin A-1-III of preparation among the preparation embodiment 3 of using with the dosage of 100mg/kg and 200mg/kg.On the dosage of 200mg/kg, determined strong blood sugar decreasing effect.
Embodiment 3: the effect of 1-timosaponin A-1-III blood sugar lowering level in the inductive diabetes rat of streptozotocin
Be dissolved in the 50mM citrate buffer solution (pH 4.5) streptozotocin (STZ:40mg/kg) to 7 the week ages the wistar male rat (body weight: 180-200g) intraperitoneal is used once.Used back 5 days at STZ, select to show the rat of the stable blood sugar level that is higher than 400mg/dl and use it for experiment.
Use to experimental group and be subjected to the reagent thing every afternoon, makes negative control group and positive controls accept 0.5% carboxymethyl cellulose (CMC) solution respectively and be dissolved in the Orally administered of glibenclamide in 0.5% carboxymethyl cellulose (CMC) solution, carried out 8 days.In the afternoon just in time before the time of application of plan, come measurement of glucose levels with 3-4 days intervals by cutting tail vein.Just in time before using, take by weighing the weight of mice and feedstuff with 2 days intervals.
1-timosaponin A-1-III that Fig. 5 is presented at preparation among the preparation embodiment 3 is the effect of blood sugar lowering level in the type 1 diabetes model at the inductive diabetes rat of streptozotocin.Opposite with people's such as N.Nakashima people such as [, J.Nat.Prod, the 56th volume, 345,1994] N.Nakashima report, the uncertain effect of 1-timosaponin A-1-III (150mg/kg) with significant blood sugar lowering level on the statistical significance.
Based on the result of previous embodiment 1-3, the present inventor determines that 1-timosaponin A-1-III has very strong and effect selectivity blood sugar lowering level in type 2 diabetes mellitus.
Embodiment 4: the toxicity of 1-timosaponin A-1-III in the ICR mice detects
For carrying out toxicity research, under the situation of the repeated doses (1g) of 1-timosaponin A-1-III, the ICR mice (every group of 5 mices) in 4-5 age in week of selecting 16-hour-fasting is as the experimenter.Orally administered 1g is dissolved in 1-timosaponin A-1-III of 0.5% carboxymethyl cellulose (CMC), carries out 5 days.There is not dead experimenter not have anomaly for example to the damage of internal organs yet.
Preparation embodiment 1: the preparation of powder and capsule
100mg 1-timosaponin A-1-III is mixed with 14.8mg lactose, 3mg microcrystalline Cellulose and 0.2mg magnesium stearate.By using suitable device that described mixture is packed in No. 5 gelatine capsules.
Preparation embodiment 2: the preparation of ointment
As shown below by using 1-timosaponin A-1-III to prepare ointment:
The distilled water and the phosphoric acid of active component 5g, cetyl palmitate 20g, spermol 40g, stearyl alcohol 40g, isopropyl myristate 80g, sorbitan monostearate 20g, polysorbate60 g, propyl p-hydroxybenzoate 1g, methyl parahydroxybenzoate 1g and appropriate amount.
Embodiment 3: the preparation of injection
As follows by using 1-timosaponin A-1-III to prepare injection:
Active component 100mg, mannitol 180mg, sodium hydrogen phosphate 25mg, distilled water for injection 2974mg.
Preparation embodiment 4: the preparation of health food
As follows, by using 0.3g 1-timosaponin A-1-III, preparing health food based on vitamin E, ferrous lactate, zinc oxide, niacin amide, vitamin A, vitamin B1 and the vitamin B2 of the powderization of daily dose.The content of health food following (based on daily dose):
Active component 300mg
Radix Ginseng extract 100mg
Green tea extract 100mg
Vitamin C 100mg
Powder vitamin E 120mg
Ferrous lactate 2mg
Zinc oxide 2mg
Niacin amide 20mg
Vitamin A 5mg
Vitamin B1 2mg
Vitamin B2 2mg
Corn starch 200mg
Magnesium stearate 20mg
As mentioned above, the present invention is being used for preventing or to treat the medicine or the health food of type 2 diabetes mellitus very useful, because opposite with known knowledge, the effect of 1-timosaponin A-1-II in prevention or treatment type 2 diabetes mellitus very excellent and in prevention or treatment type 1 diabetes effect relatively poor.

Claims (3)

1. be used to prevent or treat the compositions of type 2 diabetes mellitus, said composition comprises the chemical compound of the formula (1) as active component
Figure S2006800174863C00011
2. the compositions of claim 1 is oral or the parenteral formulation form.
3. the health food that comprises the chemical compound of the formula (1) as active component, this food are effective for type 2 diabetes mellitus
Figure S2006800174863C00012
CNA2006800174863A 2005-08-24 2006-08-24 A composition containing timosaponin A-III for prevention and treatment of type 2 diabetes mellitus Pending CN101180065A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105616435A (en) * 2016-02-20 2016-06-01 通化华夏药业有限责任公司 Timosaponin AI serving as dipeptidyl peptidase IV inhibitor and preparation method and application
CN110025717A (en) * 2019-05-20 2019-07-19 上海中医药大学 Timosaponin digests conversion product and inhibits the application in skin superficial fungi drug in preparation

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20040063290A (en) * 2003-01-06 2004-07-14 에스케이케미칼주식회사 Preparation method of Anemarrhena asphodeloides Bunge extracts and pharmaceutical composition for diabetes therapeutics using thereof
KR100661397B1 (en) * 2004-01-02 2006-12-27 한국 한의학 연구원 Composition comprising timosaponin A-? for promoting release of growth hormone

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105616435A (en) * 2016-02-20 2016-06-01 通化华夏药业有限责任公司 Timosaponin AI serving as dipeptidyl peptidase IV inhibitor and preparation method and application
CN110025717A (en) * 2019-05-20 2019-07-19 上海中医药大学 Timosaponin digests conversion product and inhibits the application in skin superficial fungi drug in preparation
CN110025717B (en) * 2019-05-20 2022-02-08 上海中医药大学 Application of timosaponin enzymatic hydrolysate in preparation of medicines for inhibiting skin superficial fungi

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KR20070023425A (en) 2007-02-28
KR101235115B1 (en) 2013-02-20

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