CN1733089A - Medicine for treating diabetes and its complications and process for preparing the same - Google Patents

Abstract

The invention relates to a Medicine for treating diabetes and its complications and process for preparation, which comprises (by weight portions) ginseng 2-20, leech 1-10, ground beetle 2-20, earthworm 2-21, notoginseng 1-25, radix salvia miltiorrhiza 4-30, red peony root 4-23, ligustrum japonicum 3-28, root of balloonflower 2-20, arctium fruit 4-22, atractylodes rhizome 1-20. The invention also relates to the process for preparing various preparations of the medicament.

Description

Medicine of treatment diabetes and complication and preparation method thereof

Technical field

The present invention relates to a kind of Chinese medicine medicine, specifically relate to medicine for the treatment of diabetes and preparation method thereof.

Background technology

Diabetes are endocrine metabolism diseases that one group of cause of disease and pathogeny are not illustrated as yet fully.Because insulin secretion is absolute or relative deficiency and target cell reduce insulin sensitivity, causes water, the metabolic disturbance of electrolyte of sugar, protein, fat and secondary.Along with productivity's development, scientific and technological progress, growth in the living standard, life pattern change and social aging, no matter be developed country or development country, the sickness rate of diabetes is all increasing year by year.According to statistics, nearly 100,000,000 people in the whole world 6% of the population of promptly growing up suffers from diabetes, and in industrialized country, diabetes are factors of the third-largest common death, are only second to heart disease and cancer ^[1]The sickness rate of China's diabetes by 1980 0.609% ^[2]Rise to about 2.5% of nineteen ninety-five ^[3], be about 3.5% according to the recent statistics sickness rate, and this growth trend is carried out still continuing.The chronic complicating diseases (cardiovascular, kidney, retina, neuropathy) that diabetes produce then becomes the lethal main cause that disables.Bibliographical information, American-European diabetic 75% is died from cardiovascular disease ^[4]The annual newfound diabetic nephropathy patients with terminal of the U.S. has 4000 examples approximately, and diabetes are again one of principal diseases of blinding.The diabetes B lower limb gangrene can cause the hardship of amputation.Diabetes and complication thereof constitute a serious threat to human health!

Modern medicine treatment primary disease adopts antidiabetic drug and insulin preparation, though blood glucose is descended rapidly, prolonged application easily develops immunity to drugs and dependency, and particularly after complication produced, simple blood sugar control can not stop the continuation of its pathology process fully.WHO diabetologist committee points out: many areas are effective with the treatment by Chinese herbs diabetes, need carry out coherent research to these therapies, treat the mechanism of diabetes to determine them.Therefore, Chinese scholars is all at the Glucovance of being devoted to seek efficient, safety, taking convenience.

Diabetes spp is in Chinese medicine diabetes category, and " diabetes " of traditional Chinese medical science successive dynasties medical book record promptly mainly refers to diabetes.From the grand piece of writing of vast as the open sea Chinese medicine monumental work, the comprehensive induction-arrangement of comparison system can confirm motherland's medical science has abundant document record and treatment experience to primary disease.At first, the more complete record of diabetes is arranged promptly in " interior warp ", in " gold is deficient ", shown the special piece of writing of diabetes.Song dynasty has then been founded the theory that three types of diabetes is divided and ruled, and gold dollar has formed scorching and the deficiency of YIN two big theories period.Bright clear pathology content of further having enriched the deficiency of vital energy, deficiency of spleen-YANG and kidneyYANG and phlegm-damp has again later been opened up the beginning of controlling from the liver opinion.Obtained many achievements modern age in a large amount of clinical researches and experimentation, established the comparatively unified dialectical standard and the corresponding rule of treatment and the square medicine that are divided into hyperactivity of fire caused by deficiency of YIN, deficiency of both QI and YIN, deficiency of both YIN and YANG, stagnation of QI and blood etc., drug research has also proved the blood sugar reducing function of plurality of Chinese, reduced the dosage of Western medicine hypoglycemic medicine clinically effectively, improved the utilization rate of body to insulin, especially the science and the superiority of Chinese medicine diabetes have further been showed in the utilization of activating blood and removing stasis Method, the kidney invigorating method.We are by clinical observation for many years, and realizing the deficiency of YIN is the pathogenetic key of glycosuria, and the deficiency of vital energy is the crux of its delay, and blood stasis is the major reason that its complication takes place, and the clinical diabetes patient deficiency of both QI and YIN blood stasis of holding concurrently more.In view of this, we have established the principle of treatment of supplementing QI and nourishing YIN, activating blood and resolving stasis and treating type ii diabetes syndrome of deficiency of both qi and yin, clinical observation and experimentation by system, prove the good efficacy of its treatment diabetes, and disclosed it and treated the mechanism of diabetes, for the Chinese medicine prevention diabetes provide scientific basis.

Summary of the invention

Purpose of the present invention is exactly in order to address the above problem, and provides a kind of medicine for the treatment of diabetes according to Chinese medical theory, and this Drug therapy type ii diabetes effect is remarkable, has no side effect, and blood sugar lowering is fast, and dose is little, lasting medicine.Prevention and therapeutic effect to diabetic complication are obvious, and be especially more remarkable to diabetes complicated hyperlipemia, high blood viscosity, peripheral neuropathy, cardiovascular and cerebrovascular disease prevention, therapeutic effect.

The present invention also aims to provide the preparation method of the various preparations of described medicine.

The parts by weight of the medicine of treatment diabetes of the present invention are composed as follows: Radix Ginseng Rubra 2～20, Hirudo 1～10, Eupolyphaga Seu Steleophaga 2～20, Pheretima 2～21, Radix Notoginseng 1～25, Radix Salviae Miltiorrhizae 4～30, Radix Paeoniae Rubra 4～23, Fructus Ligustri Lucidi 3～28, Radix Platycodonis 2～20, Fructus Arctii 4～22, Rhizoma Atractylodis 1～20

Best composed as follows: Radix Ginseng Rubra 3～9, Hirudo 3～10, Eupolyphaga Seu Steleophaga 2～10, Pheretima 4～11, Radix Notoginseng 2～9, Radix Salviae Miltiorrhizae 15～20, Radix Paeoniae Rubra 15～23, Fructus Ligustri Lucidi 9～15, Radix Platycodonis 4～10, Fructus Arctii 6～10, Rhizoma Atractylodis 6～10

For consumption per capita, the unit of above-mentioned composition is gram.

The Main Ingredients and Appearance of medicine each component of the present invention comprises:

Radix Ginseng Rubra: ginsenoside's class (ginsenoside), organic acid, sterols, vitamins, saccharide etc.

Hirudo: hirudin (hirudin), aminoacid etc.

Eupolyphaga Seu Steleophaga: aminoacid, trace element etc.

Pheretima: aminoacid, cholesterol (cholesterol) etc.

Radix Notoginseng: ginsenoside's class (ginsenoside), sterols, amino acids, saccharide etc.

Radix Salviae Miltiorrhizae: tanshinone (tanshinone), danshensu, Radix Salviae Miltiorrhizae acid (danshensuan), protocatechuic acid (protocatechuic acid) etc.;

Radix Paeoniae Rubra: peoniflorin (paeoniflorin) etc.

Fructus Ligustri Lucidi: oleandrin (olearopein), oleanolic acid (oleanolic acid), Fructus Ligustri Lucidi glycosides (nuzhenide), ursolic acid (ursolicacid) mannitol (mannitol) etc.

Radix Platycodonis: steroidal class, polysaccharide, saponins, vitamins etc.

Fructus Arctii: Arctiin (arctiin), Fructus Arctii acids (arctic acid), triterpenes, steroidal and fatty acid, polysaccharide etc.

Rhizoma Atractylodis: volatile oil etc.

Medicine of the present invention can be pulverized solid preparations such as making powder, pill, tablet, capsule, or water decocts or with making various oral formulations behind alcohol extraction or the water extract-alcohol precipitation.

The concrete preparation method of the oral liquid of medicine of the present invention is: the water or the ethanol that add 6～13 times of suitable medicine gross weights in the medicine extract; 1～3 hour time of extracting, extract 1～3 time; Medicinal liquid after the extraction carries out vacuum concentration after filtering, places, and precipitation is got liquid and is prepared into liquid preparations such as mixture, oral liquid;

The concrete preparation method of the solid preparation of medicine of the present invention is: the water or the ethanol that add 6～13 times of amounts of suitable medicine gross weight in the medicine extract; 1～3 hour time of extracting, extract 1～3 time; Medicinal liquid after the extraction carries out vacuum concentration after filtering, and the relative density of 60 ℃ of following concentrated solutions is 1.01～1.30, and spray drying obtains dry extract, dry granulation, and mix homogeneously is prepared into solid preparations such as granule, tablet, capsule.

The present invention compared with prior art has following advantage:

(1) this prescription therapeutic type ii diabetes effect is remarkable, has no side effect, and blood sugar lowering is fast, and dose is little, lasting medicine.Prevention and therapeutic effect to diabetic complication are obvious, and be especially more remarkable to diabetes complicated hyperlipemia, high blood viscosity, peripheral neuropathy, cardiovascular and cerebrovascular disease prevention, therapeutic effect.This medicine has supplementing QI and nourishing YIN, and the activating blood circulation to dissipate blood stasis function cures mainly II diabetes syndrome of deficiency of both qi and yin, and by 300 routine clinical observations, this observed drug group 200 routine clinical obvious effective rates are 49.5%, and total effective rate is 88.5%; The diabetes pill matched group is respectively 52%, 87%, the two there was no significant difference (P＞0.05), and the curative effect that is combined disease, in this observed drug group 140 examples, produce effects accounts for 19.3%, and is effective 62.9%, and total effective rate is 82.1%; In matched group 74 examples, produce effects accounts for 13.5%, effectively accounts for 52.7%, and total effective rate is 66.2%, learns by statistics and handles, and observation group's curative effect is better than matched group (P＜0.01).This medicine can significantly improve cardinal symptoms such as the thirsty polydipsia of diabetics, polyorexia, urinary micturition, and its effect is similar to diabetes pill; Simultaneously, the improvement to fatigue and weakness, spontaneous perspiration, dizziness, dysphoria with feverish sensation in the chest palms and soles, cardio palmus shape obviously is better than matched group; This medicine has remarkable reduction diabetics blood glucose, blood fat and improves the hemorheological property effect, its hypoglycemic activity and diabetes pill are suitable, and effect for reducing blood fat is better than diabetes pill, the serum insulin release test is pointed out this medicine to have to improve the beta Cell of islet hypofunction and is promoted the effect of initial stage insulin secretion, safety indexes is observed and is shown that this medicine property of medicine is gentle, not finding toxic and side effects, is safe Chinese medicine preparation.The experimentation proof can significantly reduce the hyperglycemia of Alloxan diabetes rat, and its blood sugar reducing function and diabetes pill are suitable; And can obviously increase diabetes rat liver glycogen content due to the Alloxan, promote the beta Cell of islet excreting insulin and suppress alpha Cell of islet secretion glucagon.In a word,, proved the good efficacy of this Drug therapy type ii diabetes, and disclosed the mechanism of its treatment type ii diabetes, provide scientific basis for Chinese medicine prevents diabetes by the clinical observation and the experimentation of system.

(2) its prescription of oral formulations of the present invention is precise and appropriate, and by conventional Chinese medicine is formed, the medicine source is clear, and wide material sources are cheap and easy to get;

(3) preparation is simple, adopted advanced technologies such as spray drying, dry granulation, taking convenience, and dosage is accurate, and is economical and practical.

The specific embodiment

Embodiment 1, production pill medicine

Form (unit gram): Radix Ginseng Rubra 9, Hirudo 6, Eupolyphaga Seu Steleophaga 6, Pheretima 9, Radix Notoginseng 5, Radix Salviae Miltiorrhizae 15, Radix Paeoniae Rubra 15, Fructus Ligustri Lucidi 11, Radix Platycodonis 6, Fructus Arctii 7, Rhizoma Atractylodis 8

Earlier will above-mentioned ten Chinese medicine simply, assort by the recipe quantity weighing, drying (below 80 ℃), be ground into powder, sieve (more than 80 mesh sieves), mixing, every 100g powder add refined honey 90～110g and make honeyed pill, promptly.This method preparation technology is easy, and effect relaxes lasting, takes, easy to carry.

Embodiment 2, production mixture

Form (unit gram): Radix Ginseng Rubra 7, Hirudo 7, Eupolyphaga Seu Steleophaga 7, Pheretima 10, Radix Notoginseng 5, Radix Salviae Miltiorrhizae 21, Radix Paeoniae Rubra 22, Fructus Ligustri Lucidi 13, Radix Platycodonis 7, Fructus Arctii 7, Rhizoma Atractylodis 8

Earlier will above-mentioned ten Chinese medicine simply, assort by the recipe quantity weighing, put into extraction pot, add the extraction of 6～13 water gagings, extract 1～3 time, each 1～3 hour, filter, merging filtrate, extracting solution to the clear paste shape, adds correctives through vacuum concentration, antiseptic is an amount of, leave standstill, filter, stir evenly, packing, promptly.This method preparation technology is easy, and oral post-absorption is fast, the bioavailability height.

Embodiment 3, production capsule

Form (unit gram): Radix Ginseng Rubra 6, Hirudo 6, Eupolyphaga Seu Steleophaga 6, Pheretima 9, Radix Notoginseng 5, Radix Salviae Miltiorrhizae 20, Radix Paeoniae Rubra 20, Fructus Ligustri Lucidi 12, Radix Platycodonis 6, Fructus Arctii 9, Rhizoma Atractylodis 9

Earlier will above-mentioned ten Chinese medicine simply, assort by the recipe quantity weighing, put into extraction pot, add 6～13 times of amounts of dose, 50～80% ethanol extractions once, filter, the filtrate vacuum concentration reclaims ethanol, it is standby to get alcohol extract.Medicinal residues add 6～10 times of water gagings and extracted 1～2 hour, filter, and filtrate merges with the alcohol extraction concentrated solution through vacuum concentration, mixing, and the concentrated solution spray drying gets dry extract, and the dry extract mixing is made granule through dry method, incapsulates, promptly.

This method preparation technology advanced person has adopted spray drying and dry granulation technology, and technology is rationally feasible, the medicine stability height, and it is fast to take post-absorption, the bioavailability height.

Embodiment 4, production granule

Form (unit gram): Radix Ginseng Rubra 10, Hirudo 8, Eupolyphaga Seu Steleophaga 8, Pheretima 11, Radix Notoginseng 3, Radix Salviae Miltiorrhizae 18, Radix Paeoniae Rubra 17, Fructus Ligustri Lucidi 10, Radix Platycodonis 5, Fructus Arctii 7, Rhizoma Atractylodis 8

Earlier will above-mentioned ten Chinese medicine simply, assort by the recipe quantity weighing, put into extraction pot, add 6～13 times of water gagings of dose and extract, extracting solution obtains concentrated solution through vacuum concentration, the concentrated solution spray drying, dry extract, the dry extract mixing is granulated, packing, promptly.

Embodiment 5, production tablet

Form (unit gram): Radix Ginseng Rubra 10, Hirudo 6, Eupolyphaga Seu Steleophaga 8, Pheretima 10, Radix Notoginseng 7, Radix Salviae Miltiorrhizae 23, Radix Paeoniae Rubra 22, Fructus Ligustri Lucidi 16, Radix Platycodonis 9, Fructus Arctii 10, Rhizoma Atractylodis 10

, assort earlier, put into extraction pot by the recipe quantity weighing with above-mentioned ten Chinese medicines simply, add 6～13 times of amounts of dose, 30～80% ethanol extractions 1～3 time, each 1～3 hour, filter merge extractive liquid,, extracting solution is through vacuum concentration, obtain concentrated solution, the concentrated solution spray drying gets dry extract, the dry extract mixing, granulation, tabletting, promptly.

Clinical observation

One, physical data

1. sex, age, the course of disease: NIDDM patient's 300 examples of selecting to meet the object of observation, male's 203 examples, women's 97 examples, age reckling 32 years old, the maximum 65 years old, the course of disease is the longest 13 years, and is the shortest 1 year, outpatient's 80 examples wherein, inpatient's 220 examples are divided into observation group's 200 examples at random, matched group 100 examples.Two groups of sexes, age, courses of disease distribute through the X2 check, and there was no significant difference (P＞0.05) has comparability.See table for details

Table 1 liang group sex, age, course of disease distribution (example)

Group	The example number	Sex		The age course of disease
										The man	The woman	32～40	41～50	51～65	1～5	6～10	14～13
		Observation group's matched group adds up to	200 100 300	134 69 203	66 31 97	19 8 27	96 47 143	85 45 130	103 49 152									66 40 106	31 11 42

2. complication: among the 300 routine patients, main complication has hyperlipemia, coronary heart disease, retinopathy, hypertension, peripheral neuritis etc.Through the X2 check, two groups of complication distribution there was no significant differences (P＞0.05) have comparability, see table 2 for details.

Table 2 liang group complication distribution situation example (%)

Group	The example number	Hyperlipemia	Coronary heart disease	Hypertension	Retinopathy	Peripheral neuritis
							Observation group's matched group	140 74	50(35.7) 26(35.1)	40(28.6) 22(29.7)	12(8.6) 7(9.5)	23(164) 13(17.6)	15(10.7) 6(8.1)

Two, case is selected:

(1). diagnostic criteria:

1. the diabetes diagnosis standard [5] that WHO1982 determines is pressed in Western medicine diagnose standard NIDDM (type ii diabetes) diagnostic criteria.

(1). diabetic symptom is arranged, blood glucose 〉=11.1mmol/L (200mg/dl), or fasting glucose 〉=7.8mmol/L (140mg/dl) any time.

(2). diabetic symptom is arranged and blood glucose does not reach above-mentioned standard, carry out the oral glucose tolerance test of 75g (OGTT), 2 hours blood glucose 〉=11.1mmol/L (200mg/dl),

(3). as the non-diabetic symptom, remove above-mentioned standard exterior palpi and add a standard in addition, be OGTT1 hour blood glucose 〉=11.1mmol/L (200mg/dl), or another time OGTT2 hour blood glucose 〉=11.1mmol/L (200mg/dl), or another time fasting glucose 〉=7.8mmol/L (140mg/dl).

2. Chinese medical discrimination standard: the dialectical standard of syndrome of deficiency of both qi and yin is carried out about diabetes differentiation of symptoms and signs for classification of syndrome deficiency of both QI and YIN standard according to Ministry of Public Health bureau of drug administration " new Chinese medicine clinical research guideline ".

Syndrome of deficiency of both qi and yin: fatigue and weakness, spontaneous sweating, the lazy speech of breathing hard, thirst and liking drink, dysphoria with feverish sensation in the chest palms and soles, cardiopalmus is lost the people, the red constipation of urinating, red tongue soaks less, and corpulent tongue is big, thin fur or flower stripping, stringy and thready pulse or count accurately.

(2). include the case standard in

I. meet Western medicine diagnose standard and differential diagnosis in tcm syndrome of deficiency of both qi and yin, all can include the test case in;

2. all cases are NIDDM, can partner treatment, and diet, live and work are basicly stable;

(3). get rid of case standard (comprising inadaptation or rejecting standard)

1. though patient's blood glucose before medication is higher than normally, by back fasting glucose≤7.8mmol/L (140mg/dl) such as diet control, increase activities, or 2 hours after the meal blood glucose≤11.1mmol/L (200mg/dl).

2. age under-18s or over-65s patient, gestation or women breast-feeding their children are to this medicine allergy sufferers.

3. noncooperationist's (refer to mismatch diet control or not medication and the person of affecting the treatment in accordance with regulations).

4. complication such as severe cardiac, liver, kidney are arranged, or merge and other serious primary disease, psychotic arranged.

5. in nearly 1 month the diabetes ketosis is arranged, ketoacidosis and the infected.

6. the therapy discontinued less than the regulation observation period can't be judged the infull person of curative effect or data.

Three, treatment and observational technique

(1). this medicine of Therapeutic Method observation group, this medicine is produced by Guangzhou Lanyun Medicine Research Co., Ltd., specification 0.5g/ grain, lot number: 991013.The matched group diabetes pill, this medicine is by Guangzhou No.1 Chinese Pharmacy Factory production.Oral medicine of observation group, each 1.5g, every day 3 times; The oral diabetes pill of matched group is looked state of an illness weight, each 8～10, every day 2～3 times, all obeys half an hour ante cibum.Per 4 weeks were 1 course of treatment, observed 3 courses of treatment.The patient is during medication, and stopping using, other treats the medicine of diabetes.

(2). observational technique

1. work out strict unified clinical observation on the therapeutic effect table, and conscientiously fill on time;

2. record main clinic symptoms, the variation of complication and tongue, pulse condition; Quantitatively indexs such as (being limited to the inpatient), blood fat, blood pressure, body weight, hemorheology of fasting glucose, twenty-four-hour urine sugar are measured in before the treatment and treatment back; Part patient does the serum insulin release test, looks into optical fundus, electrocardiogram, hepatic and renal function, blood, routine urinalysis.

3. statistical procedures selects for use X2 check, Ridit inspection thing, t check to be analyzed according to situation the gained data.

Four, curative effect determinate standard

With reference to efficacy assessment standard in the bureau of drug administration of Ministry of Health of the People's Republic of China " new drug (Chinese medicine) treatment diabetes (diabetes) face clinical research guideline ", be divided into three grades:

1. produce effects treatment back symptom disappears substantially, fasting glucose 7.2mmol/L (130mg/dl), 2 hours after the meal blood glucose＜8.3mmol/L (150mg/dl), twenty-four-hour urine sugar quantitatively＜10.0g; Or blood glucose twenty-four-hour urine sugar descends more than 30% before the treatment.

2. effectively treatment back symptom is obviously improved, fasting glucose＜8.3mmol/L (150mg/dl), 2 hours after the meal blood glucose＜10.0g mmol/L (180mg/dl), twenty-four-hour urine sugar quantitatively＜25.0g; Or blood glucose, twenty-four-hour urine sugar quantitatively descends more than 109% before the treatment.

3. symptom does not have obvious improvement, blood glucose, glucose in urine and descends and do not reach above-mentioned standard after the futile treatment.

Five, result and analysis

(1). two groups of clinical curative effect analysis: see table 3 for details

Table 3 liang group clinical curative effect analysis example (%)

Group	The example number	Produce effects	Effectively	Invalid	Total effective rate
						Observation group's matched group	200 100	99(495) 52(52)	78(39) 35(35)	23(11.5) 13(13)	177(88.5) 87(87)

Therapeutic outcome, observation group's total effective rate are 88.5%, and matched group is 87%, analyze through Ridit, and total effects compares there was no significant difference (P＞0.05) between two groups, shows that the curative effect of this medicine is similar substantially to the diabetes pill matched group.

(2). two groups of complication clinical efficacies compare: see table 4 for details

Table 4 liang group complication clinical efficacy comparative example (%)

Group	The example number	Produce effects	Effectively	Invalid	Total effective rate
						Observation group's matched group	140 74	27(19.3) 10(13.5)	88(62.9) 39(52.7)	25(17.9) 25(33.8)	98(82.1) 49(66.2)

After treating 3 courses of treatment, in observation group's complication 140 examples, produce effects accounts for 19.3%, and is effective 62.9%, and total effective rate is 82.1%; In matched group complication 74 examples, produce effects accounts for 13.5%, and is effective 52.7%, and total effective rate is 66.2%.Learn by statistics and handle, observation group's curative effect is better than matched group (P＜0.01).

(3). the improvement situation of two groups of clinical cardinal symptoms: see table 5 for details

The improvement situation example (%) of the table 5 liang clinical cardinal symptom of group

Observation group (200)					Matched group (100)
										Symptom	Disappear	Take a turn for the better	No change	Effective percentage (%)	Disappear	Take a turn for the better	No change	Effective percentage (%)	The P value
Thirsty polydipsia	170	26	2	98.9	79	15	2	97.9	＞0.05
										Polyorexia	150	21	24	87.7	58	14	11	86.7	＞0.05
Urinary micturition	172	11	10	94.8	68	6	8	90.2	＞0.05
										Fatigue and weakness	180	11	5	97.4	35	16	20	71.8	＜0.05
Spontaneous perspiration	100	22	8	93.9	32	22	36	60.0	＜0.01
										Dizzy	33	29	14	82.1	7	6	27	32.5	＜0.01
Dysphoria with feverish sensation in the chest palms and soles	167	6	4	97.7	35	32	22	75.3	＜0.05
										Cardiopalmus	43	34	7	91.7	2	9	19	36.7	＜0.01

By table 5 as seen, this medicine is to thirsty polydipsia, and the improvement of polyorexia, urinary micturition and matched group relatively do not have significantly grand sesame different (P＞0.05); And to the improvement of fatigue and weakness, spontaneous perspiration, dizziness, dysphoria with feverish sensation in the chest palms and soles, cardio palmus shape, there were significant differences (P＜0.05～0.01) through the Ridit analysis with matched group, shows that this medicine obviously is better than the diabetes pill matched group to the improvement of symptoms such as fatigue and weakness, spontaneous perspiration, dysphoria with feverish sensation in the chest palms and soles.

(4), two groups of treatment front and back fasting glucose change relatively: see table 6 for details

Fasting glucose variation comparison (mmol/L) before and after table 6 treatment (X ± s)

Group	The example number	Before the treatment	After the treatment	Difference
					Observation group's matched group	200 100	15.45±4.12 14.57±3.67	8.25±2.22 ※※ 7.56±2.15 ※※	7.24±1.12 ▲ 7.55±1.66 ▲

Annotate: ※ ※ and preceding relatively P＜0.01 of treatment; ▲ compare P＞0.05 with matched group

Table 6 shows through the t check, all significantly decline of blood pressure sugar on an empty stomach before and after two groups of treatments, self compare with treatment is preceding, significant difference (P＜0.01), this medicine is compared with the diabetes pill matched group the reduction amplitude of fasting glucose, no significant difference (P＞0.05) shows that this medicine has hypoglycemic activity preferably.

(5). twenty-four-hour urine sugar Quantitative Comparison before and after two groups of treatments: see table 7 for details

Quantitative (g/4h) (X ± s) relatively of twenty-four-hour urine sugar before and after the treatment of table 7 liang group

Group	The example number	Before the treatment	After the treatment	Difference
					Observation group's matched group	110 60	12.95±2.29 12.64±1.48	6.13±1.15 ※※ 6.33±1.37 ※※	6.45±1.13 ▲ 6.29±1.01

Annotate: ※ ※ and preceding relatively P＜0.01 of treatment; ▲ compare P＞0.05 with matched group

By table 7 as seen, treat back twenty-four-hour urine sugar for two groups and quantitatively all descend, self compare, notable difference (P＜0.01) is arranged, show that this medicine and diabetes pill all have the effect of positive third constellations glucose in urine with treatment is preceding.Observation group and matched group compare, and no significant difference (P＞0.05) shows that the effect of two groups of reduction glucoses in urine is similar.

(6). Blood Lipid is relatively before and after two groups of treatments: see table 8～9 for details

TC (mmol/L) variation comparison before and after table 8 treatment (X ± s)

Group	The example number	Before the treatment	After the treatment	Difference
					Observation group's matched group	200 100	5.863±1.246 6.027±2.040	4.161±1.041 ※※ 5.312±1.345 ※	1.621±1.010 ▲ 0.566±0.414

Annotate: preceding than ※ P＜0.05 with treatment; ※ ※ P＜0.01; ▲ compare P＜0.05 with matched group

TG (mmol/L) variation comparison before and after table 9 treatment (X ± s)

Group	The example number	Before the treatment	After the treatment	Difference
					Observation group's matched group	200 100	2.056±0.359 2.134±0.278	1.471±0.120 ※※ 1.819±0.103 ※※	0.599±0.119 ▲▲ 0.302±0.112

Annotate: ※ ※ and preceding relatively P＜0.01 of treatment; ▲ ▲ compare P＜0.01 with matched group

By table 8,9 as can be known, two make up also, and hyperlipidemia patient treatment back TC, TG level significantly reduce, and compare significant difference (P＜0.01) with treatment is preceding; Its difference, observation group compares with matched group that there were significant differences (P＜0.01), show that diabetics has tangible abnormalities of sugar/lipid metabolism, and this medicine and diabetes pill all have certain blood fat reducing effect, and this drug effect is better than the diabetes pill matched group.

(7). this medicine is to the influence of serum insulin release test: see table 10 for details

The variation of table 10 90 routine serum I NS (uu/ml) release values (X ± s)

Minute	Before the treatment	After the treatment	The P value
				Empty stomach 1h 2h 3h	16.97±6.76 29.66±13.76 38.55±16.21 32.56±13.56	18.55±6.45 40.45±16.34 35.32±15.07 22.17±9.78	＞0.05 ＜0.05 ＞0.05 ＜0.05

Table 10 shows that through t check after the treatment, serum insulin increases to some extent on an empty stomach, but not statistically significant, and 1h serum insulin secretion level obviously improves, with treat before compared significant difference (P＜0.05), 2h, 3h insulin level descend gradually; Relatively there were significant differences (P＜0.05) before 3h insulin secretion level and the treatment; As seen from table, treatment proinsulin peak value appears at clothes sugar back 2h, insulin discharges and is delayed response, show insulin β emiocytosis insufficiency of function, treatment back insulin peak moves to 1 clothes sugar back 1h, insulin discharges and is normal reaction, points out this medicine to have and improves the effect that insulin β cell function lowly reaches promotion initial stage insulin secretion.

(8). hemorheology index is relatively before and after two groups of treatments: see table 11 for details

Hemorheology index comparison before and after table 11 treatment (X ± s)

Group	Time	Whole blood viscosity (mpa.s)		Plasma viscosity (mpa.s)	Packed cell volume (%)	Fibrinogen (g/l)	Erythrocyte sedimentation rate K value (m/h)
								Height is cut	Low cutting
		Observation group	Before the treatment							△△	△△	△	△△	△	△
6.28±0.63	5.02±2.05			2.82±0.41	49.32±3.29	4.20±0.63	96.89±11.39
								After the treatment	※※	※▲	※▲	※※▲▲	※※	※※▲
5.68±0.38	13.78±1.49		2.15±0.34	45.47±3.68	3.24±0.69	84.13±7.29
							Matched group		Before the treatment	△△	△	△	△△	△	△
3.19±0.59	15.23±2.23	2.68±0.64	49.54±4.31	3.75±0.75	95.89±9.57
						After the treatment		※						※
5.63±0.32	15.02±2.14	2.51±0.36	49.4g±4.82	3.14±0.43	92.39±11.67
								Normal healthy controls		5.32±0.48	9.86±1.54	1.75±0.51	43.15±2.56	2.91±0.12	79.02±10.21

Annotate: with the normal healthy controls group than △ P＜0.01 △ △ P＜0.001; With treat before compare ※ P＜0.05

※ ※ P＜0.01; With matched group treat the back than ▲ P＜0.05 ▲ ▲ P＜0.01

Table 11 is checked as can be known through t, and the every indexs of hemorheology illustrate that all apparently higher than normal healthy controls group (P＜0.01～0.001) diabetes patient's blood ripple close to degree raises before two groups of patient treatments, is still close to, high doubtful, blood stasis state.Self relatively has significant difference (P＜0.05～0.01) before observation group every finger border, treatment back and the treatment.Notable difference (P＜0.01) is relatively arranged, no significant difference (P＞0.05) before and after all the other every treatments after the treatment of control group before whole blood viscosity, Fibrinogen and the treatment.Show that this medicine improves significantly to the rising of diabetes blood viscosity.

(9). toxic and side effects 200 routine patients take this medicine after 4～12 weeks, through detections such as routine blood test, routine urinalysis, hepatic and renal functions, do not find any untoward reaction and toxic and side effects.

Experimentation

One, experiment material

1. laboratory animal Wistar rat, male and female half and half, body weight 180～220g is provided by Guangdong Province's Experimental Animal Center.

2. this medicine of experimental drug is provided by Guangzhou Lanyun Medicine Research Co., Ltd..Specification: 0.5g/ capsule; Lot number 991013; Every gram is equivalent to the 1.8g crude drug: diabetes pill, and by Guangzhou No.1 Chinese Pharmacy Factory production.

3. main agents alloxan; Hydrochloric acid chlore-ammonia ketone injection, Shanghai first pharmaceutical factory produces; The blood glucose test kit, Beijing Zhongsheng Biological Engineering High Technology Company produces; The insulin radioimmunological kit, China Atomic Energy Science Research Institute provides; The glucagon radioimmunological kit, China Atomic Energy Science Research Institute provides.

4. instrument SFB-1 automatic colorimeter, Shanghai medical analytical instrument factory; 721-1 type spectrophotometer, extra large medical analytical instrument three factories; The automatic γ immunity of FJ-2008G enumerator, Xi'an 262 factories; Centrifuge, Beijing Medical Centrifugal Machine Factory.

Two, experimental technique

(1). modeling, grouping and medication

1. the preparation [6] of alloxan (AIloxan) diabetes pathological model

Choose 80 of the wistar rats of body weight 180～220g, be divided into normal control group (10) and alloxan group (70) at random.Per 10 is that a cage is fed, and weighs the dyeing label.Rat fasting (can't help water) 6h before the experiment, each Mus is with the dosage lumbar injection hydrochloric acid chlore-ammonia ketone injection (2ml:0.1g chlore-ammonia ketone) of 2ml/kg, after the anesthesia fully, ethanol wiping rat tails is in order to vasodilation, four oxygen sprays pyrimidine group tail vein (being no more than 30 ') is rapidly injected 2% alloxan solution (with PH is that 4.003 Potassium Hydrogen Phthalate is a solvent, face with existing molten), dosage is 40mg/kg; 0.9% sterile saline of normal control group tail intravenous injection equal volume.

2. group technology

Behind the modeling 48h, fasting (can't help water) 6h, each Mus changes in the fixedly letter, is fixed on the test tube rack, and the about 1ml of blood is got in docking in the hot environment about 37 ℃, uses the determination of glucose oxidase fasting glucose.Choose blood glucose in the modeling group and be higher than the diabetes pathological model of 9.99mmol/L (180mg/dl) person as success, and according to the blood sugar level layering, be divided into level Four more at random: normal saline group, this medicine high dose group, this medicine low dose group, diabetes pill group, 10 every group, each is organized rat average blood sugar difference and is no more than 1.11mmol/L (20mg/dl), and label again dyes; 10 of normal control groups, when after the merit grouping is formed in modeling, taking a blood sample for the first time, index determinings such as the preceding blood glucose of same blood sampling do treatment.Each group is all fed with normal feedstuff (total amount of heat 3.7keal/g, carbohydrate containing 53%, fat 9%, protein 20%), and appetite is not limit, and freely drinks water, and changes cage every day 1 time, changes water twice, weighs once weekly

3. medication

1. normal control group: irritate stomach, every day 1 time with 0.9% sterile saline 20ml/kg consumption.

2. normal saline group: irritate stomach, every day 1 time with 0.9% sterile saline 20ml/kg consumption.

3. this medicine high dose group: this drug suspension 20ml/kg consumption with 50% is irritated stomach, every day 1 time.Its metering is for this medicine (crude drug) 10g/kg, quite with 10 times of adult's consumption.

4. this medicine low dose group: this drug suspension 20ml/kg consumption with 25% is irritated stomach, every day 1 time.Its dosage is this medicine 5g/kg, quite with 5 times of adult's consumption.

5. diabetes pill group: the diabetes pill suspension 20ml/kg consumption with 3.5% is irritated stomach, every day 1 time.Its dosage is diabetes pill 0.7g/kg, is equivalent to into 5 times of population amount.

More than five groups after diabetes animal model duplicates successfully grouping, promptly began gastric infusion the same day, every day 1 time, continuous 4 weeks.Indexs such as 4 weeks back blood sampling check blood glucose.Disconnected neck is put to death animal, wins liver, is used to detect liver glycogen content.

(2). observation index and assay method

1. blood glucose (BG) content: glucose oxidase method, press the test kit description operation.

2. liver glycogen content: anthrone method is measured [7].

3. plasma insulin content: radioimmunology, press the test kit description operation.

4. blood plasma glucagon content; Radioimmunology is pressed the test kit description operation.

(3). statistical procedures: variance analysis, t check.

Three, result and analysis

(1). this medicine is to the influence of blood glucose in diabetic rats (BG): see table 12 for details

This medicine of table 12 is to the influence of diabetes rat BG (mmol/L) level (X ± s)

Group	The example number	Before the treatment	After the treatment	Difference
					Normal control group normal saline group this medicine group (height) this medicine group (low) diabetes pill group	10 10 10 9 9	537±0.68 21.51±2.43 ※ 20.45±2.77 ※ 19.27±3.22 ※ 19.89±1.68 ※	5.43±0.72 ※※ 20.77±1.31 10.32±2.06▲△○☆ 14.21±1.23▲△ 10.52±2.67▲△○	0.41±0.38 10.32±0.21△○☆ 6.37±1.15△ 9059±0.72△○

Annotate: with preceding relatively ※ P＜0.01 of treatment; With comparison ▲ P＜0.05 before the treatment; Compare △ P＜0.01 with the normal saline group;

With low dose group than zero P＜0.01; With the diabetes pill group than ☆ P＞0.05.

As shown in Table 12, the diabetes rat FBG level due to the Alloxan significantly increases, and relatively there were significant differences (P＜0.01) with the normal control group, shows the diabetes rat model success due to the Alloxan.High and low dose group rat is after this medicine is irritated around the stomach, and the FBG level descends, with treat before own control and treat back normal saline group relatively, all have utmost point significant difference (P＜0.01), show that this medicine has the effect of tangible reduction hyperglycemia; This medicine high dose group is compared with the diabetes pill group, there was no significant difference (P＞0.05); The blood sugar reducing function and the diabetes pill that show this medicine are suitable; This medicine high and low dose group is compared, and significant difference (P＜0.05) is arranged, and shows the increase along with this drug dose, and its blood sugar reducing function strengthens.

(2). this medicine is to the influence of diabetes rat liver glycogen content: see table 13 for details

The influence of diabetes rat liver glycogen content during this medicine of table 13 (X ± s)

Group	The example number	Liver glycogen content (mg/g weight in wet base)
			Normal control group normal saline group this medicine group (height) this medicine group (low) diabetes pill group	10 10 9 10 9	19.52±6.45 11.42±4.33※※ 18.51±5.31▲▲▲△ 16.59±3.45▲▲ 13.65±3.77▲

Annotate: with the normal control group than ※ ※ P＜0.01; With normal saline group ratio ▲ P＞0.05; ▲ ▲ P＜0.05, ▲ ▲ ▲ P＜0.01; Compare △ P＜0.05 with low dose group

As shown in Table 13, the obvious f of liver glycogen content of normal saline group looks up with eyes wide open normal control group (P＜0.01), illustrating that diabetes rat exists tangible liver glycogen complex functionality due to the Alloxan weakens, low dose group rats'liver glycogen content raises, relatively there were significant differences (P＜0.05～0.01) with the normal saline group, the diabetes pill group changes not obvious to the rats'liver glycogen, there is not significant difference (P＞0.05) with the normal saline group, this medicine high dose group is better than low dose group, show the effect that this medicine has increases liver glycogen content, along with the increase of dosage, effect strengthens.

(3). this medicine is to the influence of diabetes rat serum insulin: see table 14 for details

This medicine of table 14 is to the influence of diabetes rat serum I NS (X ± s)

Group	The example number	Serum I NS (mmol/L)
			This organizes this medicine group (height) this medicine group (low) diabetes pill group normal control group normal saline	10 10 9 10 9	21.76±5.68 6.89±3.81※※ 14.76±2.59△△▲○ 11.23±3.24△ 15.64±2.56△△▲

Annotate: compare ※ ※ P＜0.01 with the normal control group; Compare △ P＜0.05 △ △ P＜0.01 and low dose group ratio ▲ P＜0.05 with the normal saline group; With the diabetes pill group than zero P＜0.05.

Table 14 shows, diabetes rat serum insulin levels with the Alloxan modeling obviously descends, compared significant difference (P＜0.01) with the normal control group, serum insulin levels rises after the relative medicine treatment, and it is the most remarkable to raise with diabetes pill, and this medicine high dose group is taken second place, and low dose group is taken second place again, comparing with the normal saline group all has significant difference (P＜0.05～0.01), shows that this medicine has the effect that promotes insulin secretion.

Toxicological experiment research

This medicine be the treatment diabetes the efficacious prescriptions medicine arranged, for median lethal dose(LD 50) (LD50) and the maximum tolerated dose of inquiring into medicine, observe the toxic reaction and the order of severity that animal produces because of continuous use, sure evaluation is made in the safety of this medicine, we have done this medicine to animal acute toxicity test and long term toxicity test research according to " provisions for new drugs approval ", " new Chinese medicine toxicologic study guide " pertinent regulations.The result shows that this safety of medicine is reliable, and is without any side effects.

Animal acute toxicity test research

One, test objective: for median lethal dose(LD 50) (LD50) and the maximum tolerated dose of inquiring into medicine, we have done the acute toxicity test of this medicine to animal.

Two, claimed by the reagent name: this medicine.The unit of providing: Guangzhou Lanyun Medicine Research Co., Ltd..Lot number: 991013. content: every gram contains crude drug 1.8 grams.Compound method: this drug suspension that is mixed with Cmax (100%) with 0.5% cellulose acetate sodium.

Three, animal origin, kind and the unit of providing: the Kunming kind, mice, Guangdong Province's Experimental Animal Center provides.Body weight: 18～20g.Sex: male and female half and half.Number of animals: 30.Room temperature: feeding environment temperature 19 ± 10C, relative humidity 50%～60%.

Four, experimental technique and result: get 10 of mices, body weight 18～20g, male and female half and half, fasting (can't help water) is 12 hours before the experiment, every Mus is pressed this medicine of Cmax and irritates with maximum gastric capacity (0.4ml/10g body weight), behind the filling stomach, gives animal with normal diet, observed 7 days continuously, do not see that animal has any untoward reaction.Get 20 of mices again, body weight 18～20g, male and female half and half, fasting (can't help water) 12 hours before the experiment, every Mus press this medicine thing Red filling of Cmax with maximum gastric capacity (0.4ml/10g body weight), in 1 day behind the continuous irrigation stomach 3 times, give animal with normal diet, observed again 7 days, do not see animal dead.Rarely seen just irritate stomach to animal after, animal activity reduces, and recovers normal in general about 1 hour, after weighing in the 7th day, puts to death mice, cores, liver, spleen, lung, kidney, stomach, intestinal, brain, perusal does not have macroscopic pathological abnormalities.By pertinent regulations, this poison of drug is very little, can not ask LD50.Its, maximum tolerated dose was 21g/kg every day, was more than 360 times of clinical consumption, therefore thought this medicine clinical practice safety non-toxic.

List of references

1. Ministry of Public Health bureau of drug administration. " new Chinese medicine toxicologic study guide " .P203.

2. Ministry of Health of the People's Republic of China. " provisions for new drugs approval " " (about the revision of Chinese medicine part and mend regulation) .P18

Long-term toxicity test for animals research

One, test objective

This medicine be the treatment diabetes the efficacious prescriptions medicine arranged, in order to observe the toxic reaction and the order of severity that animal produces because of continuous use, the safety member of this medicine is made sure evaluation, and we have done long term toxicity test research according to " provisions for new drugs approval ", " new Chinese medicine toxicologic study guide " pertinent regulations.

Two, claimed by the reagent name: this medicine.The unit of providing: Guangzhou Lanyun Medicine Research Co., Ltd..Lot number: 991013.Content: every gram contains crude drug 1.8 grams.Collocation method: usefulness cellulose acetate sodium deployment cost drug suspension (1.8g/ml, 0.9g/ml).Medication: gastric infusion.

Three, animal origin, kind and the unit of providing: the SD rat, Guangdong Province's Experimental Animal Center provides.Body weight: 122.73 ± 11.14g, Mus 9 weeks of age, sex: male and female half and half, 60 of number of animals.Room temperature: 19 ± 10 ℃ of feeding environment temperature, relative humidity 50%～60%.

Four, get 60 of rat, body weight 122.73 ± 11.14g, male and female half and half, every group of each drug withdrawal in 10 days of male and female only is divided into high and low two dosage groups and normal saline matched group.High dose group administration 36g/kg.d, low dose group administration 18g/kg.d, (be respectively clinical consumption 60 times, 30 times), gastric infusion is 1 month continuously, weigh in weekly 1 time, adjust dosage according to body weight, after last 1 administration 24 hours, the part animal is killed in every group of work, get blood and do routine blood test, liver function, kidney Seedling energy, alkali phosphatase (ALP), total protein, albumin, total bilirubin, T-CHOL inspection, and get animal brain, the heart, lung, thymus, liver, spleen, stomach, intestinal, adrenal gland, kidney, testis, ovary and do the pathological tissue inspection.Remaining animal continues medication drug withdrawal in 60 days, continues to observe for 2 weeks, lives and detects every index extremely.

Five, result of the test

1. first animal testing result

1. rat ordinary circumstance: each dosage group of this medicine is in continuous 1 month filling stomach process, fur gloss, aspect and normal saline group comparison no significant differences such as activity situation, diet, sleep, defecation show that this medicine long-term prescription has no adverse effects to animal.

2. to the influence of rat body weight: before this medicine is irritated stomach to animal, two weeks, 1 month body weight carry out statistical analysis, the result shows that this medicine does not have harmful effect to rat body weight.The results are shown in Table 1.

This medicine of table 1 is to the influence of rat body weight (g, X ± s)

Group	n	Dosage (g/Kg)	After the administration
						Before the administration	Two weeks	1 month
			High dose low dosage matched group	10 10 10	36 18 -				122.4±9.68* 122.9±12.35* 122.9±11.78	148.6±10.01* 147.3±13.06* 145.9±13.94	182.0±10.52* 180.0±15.11* 176.1±17.14

Compare with the normal saline matched group: * P＞0.05

3. to the influence of rat main organs coefficient (organ weights is than body weight): this medicine is after irritating stomach to animal, get the main organs heart, liver, spleen, lung, kidney, thymus, adrenal gland, claim its weight, calculate organ coefficient, the result shows that this medicine does not have harmful effect to rat main organs coefficient.The results are shown in Table 2,3.

This medicine of table 2 is to the influence of rat main organs coefficient (g/100g, X ± s)

Group	n	Dosage (g/Kg)	The heart	Liver	Lung	Kidney (two)
							High dose low dosage matched group	10 10 10	36 18 -	0.48±0.06* 0.45±0.04* 0.44±0.08	5.28±0.71* 4.99±0.57* 4.97±0.65	1.03±0.17* 0.98±0.15* 1.00±0.16	0.89±0.04* 0.87±0.05* 0.87±0.06

Compare with the normal saline matched group: * P＞0.05

This medicine of table 3 is to the influence of rat main organs coefficient (X ± s)

Group	n	Dosage (g/Kg)	Spleen (g/10 ton)	Thymus (g/100g)	Adrenal gland (mg/100g)
						High dose low dosage matched group	10 10 10	36 18 -	0.42±0.03* 0.42±0.03* 0.40±0.05	0.23±0.05* 0.21±0.06* 0.20±0.06	34.04±3.96* 32.25±3.86* 30.39±6.48

Compare with the normal saline matched group: * P＞0.05

4. to the influence of rat hemogram: this medicine is got blood examination and is surveyed hemoglobin (Hb), erythrocyte sum (RBC), total white blood cells (WBC) and classification (DBC), platelet (BPC) after irritating stomach to animal, the results are shown in Table 4,5.Statistical result illustrates that this medicine has no adverse effects to the rat hemopoietic organ.

This medicine of table 4 is to the influence of rat hemogram (X ± s)

Group	n	Dosage (g/Kg)	Hb (g/L)	RBC (×10.12/L)	BPC (×109/L)
						High dose low dosage matched group	10 10 10	36 18 -	128.5±10.81* 124.0±13.29* 123.5±12.70	8.13±0.95* 7.93±0.94* 7.97±1.26	906.0±176.58* 850.0±122.47* 870.0±141.97

This medicine of table 5 is to the influence of rat hemogram (X ± s)

Group	n	Dosage (g/Kg)	WBC (×109/L)	N (％)	L (％)
						High dose low dosage matched group	10 10 10	36 18 -	8.96±1.69* 8.36±1.50* 8.61±1.23	60.7±6.52* 65.2±6.89* 65.3±5.21	39.3±6.52* 34.8±6.89 34.7±5.21

Bury the saline control group relatively with living: * P＞0.05

5. to the influence of rats'liver, renal function: this medicine gives rat oral gavage after 1 month, detect serum glutamic pyruvic transminase (GPT), glutamic oxaloacetic transaminase, GOT (GOT),, blood urea nitrogen (BUN), creatinine (Cr), the results are shown in Table 6.Credit is analysed by statistics, compares there was no significant difference (P＞0.05) with the normal saline group, illustrates that this medicine has no adverse effects to liver, renal function.

This medicine of table 6 is to the influence of rat blood serum GPT, GOT, BUN, Cr (X ± s)

Group	n	Dosage (g/Kg)	GPT(u/L)	GOT(u/L)	BUN(mmol/L)	Q(umol/L)
							High dose low dosage matched group	10 10 10	36 18 -	51.4±6.45* 52.5±5.64* 53.5±5.10	156.5±17.06* 164.1±18.15* 165.5±10.99	7.14±0.49* 6.94±0.48* 6.98±0.44	105.5±14.45* 10.54±10.83* 112.3±12.16

Compare with the normal saline matched group: * P＞0.05

3. to the influence of rat blood serum alkali phosphatase (ALP), T-CHOL (Ch), total bilirubin (TBIL): blue rhythm hypoglycemic instant powder gives rat oral gavage after 1 month, detects serum levels of ALP, T-CHOL, total bilirubin, the results are shown in Table 7.Credit is analysed by statistics, compares there was no significant difference (P＞0.05) with the normal saline group, illustrates that this medicine has no adverse effects to ALP, T-CHOL, total bilirubin.

This medicine of table 7 is to the influence of rat blood serum ALP, CH, TBIL (X ± s)

Group	n	Dosage (g/Kg)	ALP(u/L)	ch(mmol/L)	TBiL(mmol/L)
						High dose low dosage matched group	10 10 10	36 18 -	180.9±27.05* 175.4±17.41* 167.4±11.15	1.59±0.29* 1.56±0.26* 1.58±0.20	6.47±0.51* 6.35±0.46* 6.46±0.44

The saline control group compares with supervising the cooking: * P＞0.05

7. to rat blood serum total protein, albuminous influence: this medicine gives rat oral gavage after 1 month, detects total serum protein, albumin, the results are shown in Table 8.Credit is analysed by statistics, compares there was no significant difference (P＞0.05) with the normal saline group, illustrates that this medicine has no adverse effects to total protein, blood glucose.

This medicine of table 8 is to rat blood serum total protein, albuminous influence (X ± s)

Group	n	Dosage (g/Kg)	Total protein (g/L)	Albumin (g/L)
					High dose low dosage matched group	10 10 10	36 18 -	89.4±5.54* 86.3±5.74* 86.4±5.62	50.1±4.25* 47.3±3.62* 46.4±3.31

Compare with the normal saline matched group: * P＞0.05

3. to the influence of rat main organs: high and low two the dosage groups of this medicine are given rat continuous irrigation stomach 1 month, after the off-test, put to death animal and cut open internal organs such as getting brain, the heart, lung, thymus, liver,spleen,kidney, adrenal gland, stomach, intestinal, testis, ovary, carried out careful gross examination of skeletal muscle, no abnormal pathological change.Existing side by side soon, internal organs such as brain, the heart, lung, thymus, liver,spleen,kidney, adrenal gland, stomach, intestinal, testis, ovary are fixed in 10% formalin, conventional dehydration, specimens paraffin embedding slices, HE dyeing, observe under light microscopic, the result proves the tissue slice of two dosage groups and normal saline matched group, and its organizational structure, cellular morphology all belong to normally, the reactive pathological change of no accumulate poisoning shows that this medicine is taken for a long time the internal organs major organs is had no adverse effects.

2. second batch of animal testing result

The drug withdrawal in 60 days that continues to take medicine of remaining animal continues normal the nursing for 2 weeks, lives in getting blood examination extremely and survey These parameters, and cuts open and get main organs and carry out histological examination, to observe the situation of accumulating and the reversibility of drug toxicity reaction.

1. to the influence of rat hemogram: after stopping 2 weeks of perfusion, put to death animal, get the blood danger and survey hemoglobin (Hb), erythrocyte sum (RBC), total white blood cells (WBC) and classification (DBC), platelet (BPC), the results are shown in Table 9,10.Statistical result illustrates that this medicine does not have the cumulative toxicity reaction to the rat hemopoietic organ.

This medicine of table 9 is to the influence of rat hemogram (X ± s)

Group	n	Dosage (g/Kg)	Hb (g/L)	RBC (×1012/L)	BPC (×109/L)
						High dose low dosage matched group	10 10 10	36 18 -	127.0±11.35* 124.5±10.66* 122.0±11.11	7.77±1.22* 8.16±1.05* 7.40±0.98	782.0±101.19* 768.0±110.53* 760.0±93.81

This medicine of table 10 is to the influence of rat hemogram (X ± s)

Group	n	Dosage (g/Kg)	WBC (×109/L)	N (％)	L (％)
						High dose low dosage matched group	10 10 10	36 18 -	7.53±1.13* 7.54±1.11* 7.49±0.63	59.1±7.64* 59.5±6.04* 57.9±7.89	40.9±7.64* 40.5±6.04* 42.1±7.89

Compare with the normal saline matched group: * P＞0.05

2. to rats'liver, the influence of renal function: after stopping 2 weeks of perfusion, the execution animal is got blood examination and surveys serum glutamic pyruvic transminase (GPT), glutamic oxaloacetic transaminase, GOT (GOT), blood urea nitrogen (BUN), creatinine (Cr), the results are shown in Table 11.Credit is analysed by statistics, compares there was no significant difference (P＞0.05) with the normal saline group and illustrates that this medicine does not have the cumulative toxicity reaction to liver, renal function.

This medicine of table 11 is to the influence of rat blood serum GPI, GOT, BUN, Cr (X ± s)

Group	n	Dosage (g/Kg)	GPT(u/L)	GOT(u/L)	BUN(mmol/L)	CI(umol/L)
							High dose low dosage matched group	10 10 10	36 18 -	50.8±3.94* 50.5±5.30* 51.2±4.31	150.2±13.64* 153.5±12.49* 157.6±13.46	6.62±0.55* 6.63±0.48* 6.61±0.41	107.3±15.00* 108.9±11.62* 114.7±11.65

Compare * P＞0.05 with the normal saline matched group

3. for the influence of rat blood serum ALP, T-CHOL, total bilirubin: after stopping 2 weeks of perfusion, put to death animal, get blood examination and survey serum levels of ALP, T-CHOL, total bilirubin, the results are shown in Table 12.Credit is analysed by statistics, compares there was no significant difference (P＞0.05) with the normal saline group, illustrates that this medicine does not have the cumulative toxicity reaction to rat ALP, T-CHOL, total bilirubin.

This medicine of table 12 is to the influence of rat blood serum ALP, ch, TBiL (X ± s)

Group	n	Dosage (g/Kg)	ALP(u/L)	ch(mmol/L)	TBiL(mmol/L)
						High dose low dosage matched group	10 10 10	36 18 -	150.2±13.57* 147.2±22.26* 153.3±14.17	1.54±0.17* 1.55±0.16* 1.63±0.23	6.87±6.12* 7.61±0.61* 6.99±0.66

Compare * P＞0.05 with the normal saline matched group

4. to rat blood serum total protein, albuminous influence: after stopping 2 weeks of perfusion, before the execution, get blood examination and survey total serum protein, albumin, the results are shown in Table 13.Credit is analysed by statistics, compares there was no significant difference (P＞0.05) with the normal saline group, illustrates that this medicine does not have the cumulative toxicity reaction to rat total protein, albumin.

This medicine of table 13 is to rat blood serum total protein, albuminous influence (X ± s)

Group	n	Dosage (g/Kg)	Total protein (g/L)	Albumin (g/L)
					High dose low dosage matched group	10 10 10	36 18 -	85.8±6.20* 82.0±5.62* 82.6±7.46	44.7±5.48* 42.8±3.42* 43.0±3.86

Compare * P＞0.05 with the normal saline matched group

5. to the influence of rat main organs: high and low two dosage of this medicine are given rat continuous irrigation stomach 3 months, after the off-test, discontinue medication and observe 15 days again, put to death animal and cut open internal organs such as getting brain, the heart, lung, thymus, liver,spleen,kidney, adrenal gland, stomach, intestinal, testis, ovary, carried out careful gross examination of skeletal muscle, no abnormal pathological change.Existing side by side soon, internal organs such as brain, the heart, lung, thymus, liver,spleen,kidney, adrenal gland, stomach, intestinal, testis, ovary are fixed in 10% formalin, conventional dehydration, specimens paraffin embedding slices, HE dyeing, observe under light microscopic, the result proves the tissue slice of two dosage groups and normal saline matched group, and its organizational structure, cellular morphology all belong to normally, the reactive pathological change of no accumulate poisoning shows that this medicine is taken for a long time the internal organs major organs is had no adverse effects.

Claims (4)

1, a kind of medicine for the treatment of diabetes is characterized in that being made up of following Chinese medicine:

Radix Ginseng Rubra, Hirudo, Eupolyphaga Seu Steleophaga, Pheretima, Radix Notoginseng, Radix Salviae Miltiorrhizae, Radix Paeoniae Rubra, Fructus Ligustri Lucidi, Radix Platycodonis, Fructus Arctii, Rhizoma Atractylodis.

2, the medicine of treatment diabetes according to claim 1 is characterized in that the parts by weight of each Chinese medicine are composed as follows:

Radix Ginseng Rubra 2～20, Hirudo 1～10, Eupolyphaga Seu Steleophaga 2～20, Pheretima 2～21, Radix Notoginseng 1～25, Radix Salviae Miltiorrhizae 4～30, Radix Paeoniae Rubra 4～23, Fructus Ligustri Lucidi 3～28, Fructus Citri tangerinae are hard 2～20, Fructus Arctii 4～22, Rhizoma Atractylodis 1～20.

3, the preparation method of the medicine oral liquid of the described treatment diabetes of claim 1 is characterized in that the water or the ethanol that add 6～13 times of suitable medicine gross weights in the medicine extract; 1～3 hour time of extracting, extract 1～3 time; Medicinal liquid after the extraction carries out vacuum concentration after filtering, and concentrated solution or add ethanol is placed, and precipitation is got the supernatant packing, promptly.

4, the preparation method of the medical solid preparation of the described treatment diabetes of claim 1 is characterized in that the water or the ethanol that add 6～13 times of amounts of suitable medicine gross weight in medicine extract; 1～3 hour time of extracting, extract 1～3 time; Medicinal liquid after the extraction carries out vacuum concentration after filtering, and the relative density of concentrated solution is 1.01～1.30, and spray drying obtains dry extract, dry granulation, mix homogeneously.