Summary of the invention the purpose of this invention is to provide the new pharmaceutical applications of stachyose, and promptly stachyose is used for the treatment of application in the medicine of diabetes in preparation.Another object of the present invention provides stachyose and is used for the treatment of application process in the medicine of diabetes in preparation.The medicine of the treatment diabetes of this application stachyose preparation is the Chinese medicine medicine that has blood sugar lowering, blood fat reducing, increase insulin sensitivity, has no side effect.
Realize that technical scheme of the present invention is such: the application of stachyose in preparation treatment diabetes medicament, its active component of stachyose that it is characterized in that treating in the medicine of diabetes has following chemical structural formula:
The medicine of the treatment diabetes of stachyose preparation be in content of stachyose be 0.01~99.99% with pharmaceutical carrier content be that 99.99~0.01% ratio is made.
Stachyose is used for the treatment of manufacture method in the medicine of diabetes in preparation: make the medicine of forming as active ingredient and pharmaceutical carrier with stachyose of the present invention, can be according to conventional pharmaceutical methods, make clinically for oral administration or injection type of said routine in acceptable, the pharmaceutics, as tablet, capsule, powder and injection etc.
Stachyose of the present invention can be the stachyose preparation that extracts from stachyose platymiscium such as Chinese artichoke, Rhizoma Lycopi Lucidi, Rhizoma Humatae Tyermanni, snail dish, cutworm etc., and wherein stachyose purity is greater than 90%; Also can be from the Chinese medicine that contains stachyose such as Radix Rehmanniae, to extract to obtain.Preparation or produce the stachyose method from stachyose platymiscium such as Chinese artichoke, Rhizoma Lycopi Lucidi, Rhizoma Humatae Tyermanni, snail dish, cutworm etc., can number be 98100020.7,99124982.8 according to Chinese patent application, in 00123630.X and the 01109692.6 4 pieces of documents disclosed from stachyose platymiscium such as Chinese artichoke, Rhizoma Lycopi Lucidi, Rhizoma Humatae Tyermanni, snail dish, cutworm etc. preparation or the method for producing stachyose make extraction.Extracting stachyose from the Chinese medicine Radix Rehmanniae also has document openly to report, can make stachyose purity greater than 90% extract.Stachyose of the present invention also can be obtained by commercially available.Pharmaceutical carrier of the present invention is conventional pharmaceutical carrier.
Inventor's process discovers that above-mentioned stachyose pharmaceutical preparation has the effect of blood sugar lowering, blood fat reducing and increase insulin sensitivity, thereby has developed the new purposes of treatment diabetes.The present invention does not see any bibliographical information and use as yet.Stachyose composition of the present invention source is abundant, safe and reliable, has no side effect, and low price is a kind of novel blood sugar reducing preparation, has good social benefit and economic benefit.
The pharmacodynamic study result of the active ingredient stachyose of experimental example 1 treatment diabetes medicament of the present invention
1. stachyose is to the regulating action of glucose hyperglycemic rat blood glucose
1.1 experiment material is subjected to the reagent thing: Herba Stachydis Japonicae Icing Sugar (purity is greater than 90%); Animal subject: the Wistar rat, ♀, ♂ half and half, body weight 180~220g, Lanzhou medical college Experimental Animal Center provides.
1.2 method and result be animal subject Wistar rat, ♀, ♂ half and half, and body weight 180~220g is divided into 3 groups at random, and every group of 8-10 only is respectively normal control group, glucose hyperglycemia matched group and stachyose administration group.Normal control group and glucose hyperglycemia matched group distilled water are irritated stomach, once a day, and continuous 7 days; Stachyose administration group gives stachyose 200mg/kg and irritates stomach, once a day, and continuous 7 days.After the last administration, fasting 7h, blood glucose value (0 minute) is measured in eyeball rear vein beard blood sampling, lumbar injection glucose solution (2.5g/kg) afterwards, the blood glucose value of giving behind the glucose 30 minutes, 60 minutes and 120 minutes is measured in the blood sampling of eyeball rear vein beard.The result is with the t of two groups of means check and see Table 1.
1.3 discuss: the fasting glucose there was no significant difference of (0 minute) each group before the injection.30 minutes, 60 minutes and 120 minutes blood sugar concentration in the glucose tolerance test have significance to reduce in the stachyose group than glucose hyperglycemia matched group.The expression stachyose can reduce the glucose hyperglycemia.
Table 1 stachyose is to the influence of glucose hyperglycemic rat blood sugar level
Group | Dosage (mg/g) | Blood glucose value (mg/dl) |
0 minute | 30 minutes | 60 minutes | 120 minutes |
Normal control glucose contrast glucose+stachyose | 0 0 200 | 89.4±15.4 90.6±19.3 88.7±17.8 | 87.8±21.5 185.6±7.2
*** 121.5±28.0
## | 89.6±20.4 144.2±12.9
*** 122.8±26.2
# | 95.4±22.5 152.6±18.7
*** 130.4±29.2
|
x±SD,n=8-10。
* *P<0.001, vs normal control group;
#P<0.05,
##P<0.01, vs glucose hyperglycemia matched group.
2. stachyose is to the regulating action of adrenal gland's disposition hyperglycemic rat blood glucose
2.1 experiment material is subjected to the reagent thing: Herba Stachydis Japonicae Icing Sugar (purity is greater than 90%); Animal subject: the Wistar rat, ♀, ♂ half and half, body weight 180~220g is provided by Lanzhou medical college Experimental Animal Center.
2.2 method and result be animal subject Wistar rat, ♀, ♂ half and half, and body weight 180~220g is divided into 3 groups at random, and every group of 8-10 only is respectively normal control group, adrenal gland's disposition hyperglycemia matched group, stachyose administration group.Normal control group and adrenal gland's disposition hyperglycemia matched group distilled water are irritated stomach, once a day, and continuous 7 days; Stachyose administration group gives stachyose 200mg/kg and irritates stomach, once a day, and continuous 7 days.After the last administration, fasting 7h, blood glucose value (0 minute) is measured in eyeball rear vein beard blood sampling, subcutaneous injection epinephrine (300 μ g/kg) afterwards, the blood sampling of eyeball rear vein beard is measured and is given behind the epinephrine 30 minutes, 90 minutes blood glucose value.The result is with the t of two groups of means check and see Table 2.
2.3 discuss: the fasting glucose there was no significant difference of (0 minute) each group before the injection.30 minutes, 60 minutes and 120 minutes blood sugar concentration in the test of epinephrine hyperglycemia have significance to reduce in the stachyose group than glucose hyperglycemia matched group.The expression stachyose can reduce adrenal gland's disposition hyperglycemia.
Table 2 stachyose is to the influence of adrenal gland's disposition hyperglycemic rat blood sugar level
Group | Dosage (mg/kg) | Blood glucose value (mg/dl) |
0 minute | 30 minutes | 90 minutes |
Normal control epinephrine contrast epinephrine+stachyose | 0 0 200 | 98.2±7.4 96.0±4.9 94.5±7.1 | 100.3±15.2 313.9±50.6
*** 256.8±42.5
# | 99.8±10.7 303.2±59.4
*** 201.3±41.6
# |
x±SD,n=8-10。,
* *P<0.001vs normal control group;
#P<0.05vs adrenal gland disposition hyperglycemia matched group.
3. stachyose is to the adjusting of alloxan diabetes rats blood glucose, blood fat and plasma insulin
3.1 experiment material is subjected to the reagent thing: Herba Stachydis Japonicae Icing Sugar (purity is greater than 90%); Animal subject: the Wistar rat, ♀, ♂ half and half, body weight 180~220g is provided by Lanzhou medical college Experimental Animal Center.
3.2 method and result cause the rat diabetes model with alloxan.With the dosage once abdominal cavity injection of alloxan 150mg/kg, injection alloxan fasting 10h after 3 days, the blood sampling of eyeball rear vein beard selects the rat of fasting plasma blood glucose value more than 250mg/dl to be defined as diabetes rat.Normal control group, diabetic model group, diabetes model+stachyose group and diabetes model+metformin matched group are established in experiment.Normal control group and diabetic model group are irritated stomach and are only given normal saline 2.0ml/, and the stachyose group is pressed 200mg/kg dosage and irritated stomach, and the metformin matched group is irritated stomach with metformin 500mg/kg.Below respectively organize equal successive administration 7 days.After finishing the course of treatment, fasting 10h, blood glucose, plasma insulin, plasma cholesterol, triglyceride and HDL-C are measured in the blood sampling of eye socket venous sinus.The results are shown in Table 3, table 4.
3.3 discuss: stachyose group treatment back fasting glucose reduces than the diabetic model group significance, and treatment back fasting plasma insulin increases than the diabetic model group significance.The expression stachyose can reduce the blood glucose value under the diabetic disease states and increase plasma insulin level.In addition, stachyose treatment back cholesterol, triglyceride all have obvious reduction, and treatment back HDL-C significantly raises.Illustrate that stachyose also can improve the hyperlipidemia state of diabetes rat.
Table 3 stachyose is to the influence of alloxan diabetes rats blood glucose, plasma insulin
Group | Dosage (mg/kg) | Blood glucose value (mg/dl) | Plasma insulin (mIU/L) |
Normal control diabetes model diabetes+stachyose diabetes+metformin | 0 0 200 500 | 94.4±16.9 390.6±59.3
*** 150.1±34.2
## 96.8±25.2
## | 13.3±5.9 4.2±1.2
*** 8.2±2.6
# 11.2±3.2
## |
x±SD,n=8-10。
* *P<0.001vs normal control group;
#P<0.05,
##P<0.01vs diabetic model group.
Table 4 stachyose is to the influence of three of alloxan diabetes rats blood fat
Group | Dosage (mg/kg) | Cholesterol (mg/dl) | Triglyceride (mg/dl) | High density lipoprotein (mg/dl) |
Normal control diabetes model diabetes+stachyose diabetes+metformin | 0 0 200 500 | 94.4±16.9 190.6±29.3
*** 130.1±34.2
# 112.6±26.3
## | 37.1±4.8 355.3±65.8
*** 146.7±32.3
### 99.5±21.7
### | 13.3±5.9 4.2±1.2
** 10.2±2.6
## 13.5±3.8
## |
x±SD,n=8-10。
*P<0.01,
* *P<0.001vs normal control group:
#P<0.05,
##P<0.01,
###P<0.001vs diabetic model group.
The acute oral toxicity result of the test of experimental example 2 stachyose
1. experiment material is subjected to the reagent thing: Herba Stachydis Japonicae Icing Sugar (purity is greater than 90%).Animal: Kunming kind white mice, body weight 18~22g, female, hero half and half is provided by Lanzhou medical college Experimental Animal Center.
2. the shared Kunming of method and result kind white mice is 40, is divided into 4 groups at random: normal control group and stachyose administration group (three dosage groups), 10 every group, female, hero half and half.Three dosage groups of stachyose are: 5g/kg, 10g/kg and 20g/kg are equivalent to 125 times, 250 times and 500 times of clinical adult's every day of oral 3g (being dosage 0.04g/kg every day) respectively.Tried the thing dissolved in distilled water, irritated stomach by every mice 0.5ml.Matched group is irritated the distilled water of stomach equivalent.Observed 14 days, each dosage group white mice of stachyose all survives as a result, and is movable normal, do not see the toxic reaction, shows that stachyose belongs to safety non-toxic class material.It is 20g/kg that the white mice of stachyose is once irritated stomach maximum dosage-feeding (dosis tolerata).
The Preliminary Clinical Observation of experimental example 3 stachyose treatment type 2 diabetes mellitus
2002 7 with month in March, 2003, stachyose treatment type 2 diabetes mellitus is carried out clinical observation on the therapeutic effect, it is existing that stachyose is treated the observation of curative effect brief summary of 30 routine type 2 diabetes mellitus is as follows:
1 materials and methods
1.1 object choice
Diagnostic criteria: (1) tcm diagnosis standard: with reference to the dialectical standard of syndrome of deficiency of both qi and yin in " the clinical research guideline of Chinese medicine (new drug) treatment diabetes (diabetes) ".
Western medicine diagnose standard: adopt the type 2 diabetes mellitus diagnostic criteria that The World Health Organization (WHO) determined in 1999.
Case is selected: all trainings that meets the type 2 diabetes mellitus of above-mentioned Chinese and western medicine diagnostic criteria regularly go to a doctor patient and inpatient, all can include the observation case in.
Exclusion standard: (1) patient before medication/suddenly blood glucose is higher than normally, by diet control, increase activity etc., fasting glucose<7.8mmol/L or 2h blood glucose<11.1mmol/L after the meal.(2) age is under-18s or gestation and women breast-feeding their children, and to this medicine incompatibility person.(3) can not cooperate diet control or the medication person of affecting the treatment in accordance with regulations not.(4) severe cardiac Liver and kidney complication or merge other serious primary diseases, psychotic is arranged.(5) in nearly 1 month diabetes ketosis, ketoacidosis and the infected are arranged.(6) therapy discontinued less than the regulation observation period can't be judged the infull person of curative effect or data.
The training that is diagnosed as type 2 diabetes mellitus through clinical and lab testing regularly go to a doctor patient and inpatient, through simple Diet Therapy of 1 week, hyperglycemia state is failed the effector and is the object of observation.
1.2 clinical data
Stachyose treatment group type 2 diabetes mellitus patient 30 examples, male's 16 examples wherein, women's 14 examples, 36~72 years old age, 57.7 ± 9.7 years old mean age (x ± SD, down with), course of disease two weeks~20 year, average 3.8 ± 1.1 years.Fasting glucose<8.3mmol/L person's 10 examples, 8.4-11.1mmol/L person's 30 examples,>11.2mmol/L person 10 examples.The routine number that merges hyperlipidemia, coronary heart disease, peripheral neuropathy is respectively 14,2,4 examples.Chinese medicine (JINQI JIANGTANG PIAN) matched group 20 examples, male's 12 examples wherein, women's 8 examples, 31~82 years old age, 57.3 ± 10.1 years old mean age, course of disease February~15 year, average 4.0 ± 1.2 years, fasting glucose<8.3mmol/L person's 5 examples, 8.4-11.1mmol/L person's 12 examples,>11.2mmol/L person 3 examples.The routine number that merges hyperlipidemia, coronary heart disease, peripheral neuropathy is respectively 8,3,2 examples.Two groups of case sources, sex, age and course of disease analyses do not have obvious significant difference (P>0.05).
1.3 Therapeutic Method
1.3.1 stachyose group: give the stachyose group after diagnosis is clear and definite and give stachyose (purity is greater than 90%) 1.0g, tid, clothes, and other oral antidiabetic drug of stopping using before the meal.Instruct patient's diet control and physical training in the therapeutic process.Being a course of treatment January, 2~3 courses of treatment of overview.
1.3.2 Chinese medicine matched group: give JINQI JIANGTANG PIAN after diagnosis is clear and definite, 7 (every 0.3g), tid, clothes, and other oral antidiabetic drug of stopping using before the meal.Instruct patient's diet control and physical training in the therapeutic process.Being a course of treatment January, 2~3 courses of treatment of overview.
1.4 observation index and method
All make fasting glucose (FBG), 2 hours after the meal blood glucose (PBG) before and after observing treatment.The observation that hematuria conventional sense and clinical main symptom change.Some cases has been done the detection of plasma insulin (IRI) and blood fat (cholesterol TC, glycerol triplet TG, HDL-C HDL-C).
1.5 criterion of therapeutical effect
According to the curative effect judging standard in " the clinical research guideline of Chinese medicine (new drug) treatment diabetes (diabetes) " of Ministry of Public Health promulgation in 1993.Produce effects: treatment back symptom disappears substantially, fasting glucose<7.2mol/L, 2h blood glucose<8.3mmol/L after the meal, twenty-four-hour urine sugar quantitatively<10g or blood glucose 24h glucose in urine be quantitatively than descending more than 30% before the treatment; Effectively: treatment back symptom is obviously improved, fasting glucose<8.3mmol/L, the glucose in urine of 2h blood glucose<10.0mmol/L, or 24h after the meal quantitatively<25.0g, or blood glucose, 24h glucose in urine quantitatively descend more than 10% before the treatment.Invalid: treatment back symptom does not have obvious improvement, and blood glucose, glucose in urine descend and do not reach effective standard.
1.6 statistical method
Adopt SPSS software to carry out statistical analysis, the treatment front and back are relatively checked with the t of own control mean relatively on the same group.
2 results
2.1 clinical efficacy: stachyose treatment is to type 2 diabetes mellitus patient's therapeutic effect: produce effects 11 examples, and effective 15, invalid 4 examples.Total effective rate 86%.JINQI JIANGTANG PIAN group therapeutic effect: produce effects 14 examples, effective 2, invalid 4 examples, total effective rate 80%.
2.2 clinical symptoms: symptoms such as stachyose group treatment back polydipsia, polyphagia, polyuria and spiritlessness and weakness, the soreness of waist, few clothes all have clear improvement.
2.3 stachyose is to the influence of type 2 diabetes mellitus patient blood glucose and plasma insulin: see Table 5.
As seen from Table 5, stachyose treatment back fasting glucose and after the meal 2h blood glucose with treat before compare, decline is all arranged, there was a significant difference (P<0.05).
2.3 stachyose is to the influence of type 2 diabetes mellitus patient blood fat: see Table 6.
As seen from Table 6, TC and TG difference also have significance (P<0.05) before and after the stachyose treatment.HDL-C does not then have significance and changes.
2.4 side effect
The stachyose group there is no reactions such as diarrhoea, stomachache, vomiting, drug eruption and hypoglycemia.
Table 5 stachyose is to type 2 diabetes mellitus patient fasting glucose, the influence of 2h blood glucose and plasma insulin after the meal
Group | The example number | Fasting glucose (mmol/L) | 2h blood glucose (mmol/L) after the meal | Plasma insulin (mIU/L) |
Before the treatment | After the treatment | Before the treatment | After the treatment | Before the treatment | After the treatment |
Stachyose group Chinese medicine matched group | 30 20 | 10.18±2.48 10.50±2.36 | 7.39±1.29* 8.56±1.54* | 15.45±4.23 15.66±5.06 | 12.80±3.35* 13.10±3.63* | 13.71±4.46 13.03±4.51 | 13.56±1.94 13.56±1.85 |
Annotate:
*P<0.05, relatively preceding with treatment.x±SD。
Table 6 stachyose is to the influence (mmol/L) of type 2 diabetes mellitus patient plasma cholesterol, triglyceride and high density lipoprotein
Group | The example number | Cholesterol | Triglyceride | High density lipoprotein |
Before the treatment | After the treatment | Before the treatment | After the treatment | Before the treatment | After the treatment |
Stachyose group Chinese medicine matched group | 30 20 | 6.59±0.87 6.65±1.10 | 4.66±0.55* 5.39±0.59* | 2.06±0.47 2.12±0.60 | 1.67±0.18* 1.80±0.35* | 1.18±0.26 1.21±0.33 | 1.38±0.20 1.32±0.23 |
Annotate:
*P<0.05, relatively preceding with treatment.x±SD。
3 conclusions
By stachyose treatment type 2 diabetes mellitus 30 routine clinical observation result are shown that stachyose has following outstanding feature: (1) stachyose truly has curative effect, treatment effective percentage to type 2 diabetes mellitus is 86%, and senile diabetes (fasting glucose is about 7~9mmol/L) patient's blood glucose is generally being reduced to normally about a course of treatment after the medication; Middle and high diabetes mellitus type (general two to three purposes that can reach blood sugar control the course of treatment of medication of blood glucose>10mmol/L).(2) invalid patient had effect to stachyose to using Western medicine antidiabetic drug such as metformin, sulphanylureas etc., also can play a role with the Western medicine antidiabetic drug is collaborative, and curative effect is more singly with for well; (3) observe the characteristics that stachyose has increases patient's insulin sensitivity clinically.(4) stachyose has reduction effect preferably for hyperlipidemia except blood sugar lowering, and this also is a distinguishing feature of stachyose.(5) up to the present, do not find that stachyose has apparent side effect, this is significantly to be different from the Western medicine antidiabetic drug.