CN1141086C - Hypoglycemic Chinese medicine 'yanzizhang' and its preparing process - Google Patents
Hypoglycemic Chinese medicine 'yanzizhang' and its preparing process Download PDFInfo
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Abstract
The present invention relates to a Yanzizhang Chinese medicine blood sugar reduction preparation and a preparation method thereof. A main blood sugar reduction ingredient in the preparation is 3-methyl-2-butanyl isoguanidine which is firstly discovered and is a natural blood sugar reduction compound. The molecular formula of the 3-methyl-2-butanyl isoguanidine is C6H13N3, the molecular weight is 127.18, and the melting point is 108 DEG C. The preparation also contains an auxiliary ingredient for treating diabetes and a mixture of beta-sitosterol, D-mannitol, potassium chloride and sodium chloride. The preparation technology can adopt a boiling method in water, a boiling alcohol deposition method in water, and a macroporous resin desorption method. A preparation prepared by each method is the blood sugar reduction preparation of the present invention. However, the methods are different, and the yield and the content are different. When the blood sugar reduction preparation is prepared, a method can be adopted as required. The effect of blood sugar reduction of the preparation is obvious, and the improvement of patient's integral functions is obvious.
Description
The present invention relates to a kind of Crassula argentea Thunb traditional Chinese medicine antidiabetic preparations and preparation method thereof, is the traditional Chinese medicine antidiabetic preparations of feedstock production with Crassulaceae jade plant genus, Crassula argentea Thunb Chinese crude drug-decoction pieces specifically, belongs to hypoglycemic Chinese medicine preparation technical field.
The types of drugs of treatment diabetes is various at present, but the side effect of some Western medicine is big, and later stage secondary failure problem is arranged; The Chinese patent medicine kind is quite a few, but effect is all not too obvious, contain sugar-lowering components in the Crassula argentea Thunb, on March 19th, 1991, the fourth celebrating was once crossed patent in Japanese publication, application number is 3-81585, publication number is 5-178749 (seeing Appendix 1), name is called " Hypoylycemic agents ", think to contain effective blood sugar reducing component in the Hypoylycemic agents, have a kind of of its described two kinds of chemical compounds at least, and provide two kinds of compound structures, but do not provide more scientific basis and name in the description, its structural formula complexity, molecular weight is big, is to extract from the greenery of bright Crassula argentea Thunb.
November 24 nineteen ninety-five, the fourth mirror was 95117499.1 at Chinese application number, name is called " new technology of extracting blood sugar lowering and nutrient substance from plants such as Crassula argentea Thunb ", the technology that is adopted is ethanol ultrasonic extraction technology, and the active substance that is extracted is the former powder of DSP (seeing Appendix 2) of not knowing which kind of chemical constituent; It is 97112555.5 that fourth celebratings in 1997 application name again is called " Crassula argentea polgsaccharide " application number, and this Crassula argentea polgsaccharide also is a kind of material (seeing Appendix 3) of not principal component.They mention two kinds of chemical compounds in the not mentioned again first application in China's application.
This problem is extracted the different guanidine of a kind of blood sugar lowering active chemical 3-methyl-2-butene base through a large amount of careful research works in Crassula argentea Thunb, through domestic and international 51 data bases of Chinese science and technology information institute retrieval center online information retrieval, do not find same chemical compound (seeing Appendix 4).
The objective of the invention is from Crassula argentea Thunb, to extract hypoglycemic active chemical, determine its chemical constituent and structure, and be prepared into Chinese medicine preparation, be used for the treatment of type ii diabetes and control of diabetes complication with Crassula argentea Thunb.
The objective of the invention is to realize with following proposal:
The main blood sugar lowering chemical compound of this preparation is the natural blood sugar lowering chemical compound of finding first, the different guanidine of 3-methyl-2-butene base, and molecular formula is C
6H
13N
3, molecular weight is 127.18, fusing point is 108 ℃, chemical structural formula:
Still contain the composition that the treatment diabetes is had assosting effect in the preparation, be cupreol, content is 0.23%～0.42%, D-mannitol, content is 0.95%～1.35%, the mixture of potassium chloride, sodium chloride, the content of the different guanidine of natural blood sugar lowering chemical compound 3-methyl-2-butene base is 4%～30% in the preparation.
Noval chemical compound carries out animal experiment through institute of Chinese materia medica, Sichuan pharmacological room by the technical specification in " new drug research guide " and proves effective blood sugar lowering chemical compound for finding first by retrieval, its animal pharmacology, and toxicological experiment result such as table 1 are listed:
Table one: the continuous different guanidine (C of ig3-methyl-2-butene base
6H
13N
3) 7 days blood sugar influences to alloxan hyperglycemia Mus
| Animal varieties | Group | Animal (only) | Dosage (mg/kgd) | Blood glucose (mmo1/LX ± SD |
| The hybrid mice | Normal control | 10 | Equivalent ig Calculus Bovis from Northwest of China glue | 2.58±1.12 |
| Model group | 10 | - | 5.76±0.84 | |
| Heavy dose of group | 10 | 25 | 2.21±1.296″ | |
| Small dose group | 10 | 12.5 | 3.11±1.675′ | |
| Purebred mice | Normal control | 10 | Equivalent ig Calculus Bovis from Northwest of China glue | 3.49±1.75 |
| Model group | 10 | - | 22.02±0.875 | |
| Heavy dose of group | 10 | 25 | 5.226±3.59″ | |
| Small dose group | 10 | 12.5 | 10.24±0.50″ |
Annotate:
1. heavy dose of group is the different guanidine of oral 3-methyl-2-butene base, 25 milligrams of per kilogram every days
2. small dose group is the different guanidine of oral 3-methyl-2-butene base, 12.5 milligrams of per kilogram every days
3. compare with model ' P＜0.05; " P＜0.01.
Modern medicine proof chemical compound cupreol has blood fat reducing, reduces blood cholesterol, pharmacological actions such as cough-relieving, anticancer, antiinflammatory; Compound D-mannitol has dehydration, diuresis and prevent and treat pharmacological actions such as early stage renal insufficiency.Inorganic salt potassium chloride has the pharmacological action that brings high blood pressure down, and therefore comprises that the Crassula argentea Thunb preparation of above several chemical compounds is orally-taken blood sugar reducing medicines of comparatively ideal treatment type ii diabetes and complication.With its treatment diabetes the time, need be with the different guanidine of purified 3-methyl-2-butene base, as long as the different guanidine content of 3-methyl-2-butene base reaches more than 4% in the extract, and cupreol wherein, D-mannitol, potassium chloride can play the effect of control diabetic complication.
The step of preparation process of Crassula argentea Thunb traditional Chinese medicine antidiabetic preparations is as follows:
1, preparation Crassula argentea Thunb decoction pieces, the medicinal all herbal medicine of answering of Crassula argentea Thunb, the Crassula argentea Thunb plant is connected root dialled, bright grass removes 30% left and right sides moisture through dry in the sun, cleans with clear water and is cut into long 5-8cm, the strip and block of wide 2-3cm, in the sun or send in the drying machine and carry out the vibratory liquefaction drying to be lower than 60 ℃ of temperature, make moisture content be lower than 10%, impurity content is lower than 3% technical specification, make the bright product of Crassula argentea Thunb be processed into the prepared slices of Chinese crude drugs by above processing, yield is about 5%.
2, boiled process and preparation
The Crassula argentea Thunb decoction pieces was crushed to 10 mesh sieves, and the water retting of 2 times of weight of adding 4 hours adds 10 times of water gagings again, boils 2 hours, collects filtrate for the first time; Filtering residue adds 8 times of water gagings for the first time, boils 2 hours after-filtration, collects filtrate for the second time, and filtering residue adds 5 times of water gagings for the second time again, boils 2 hours after-filtration, collects filtrate for the third time; Merge filtrate for the third time, in water-bath, be concentrated into maltose shape fluid extract, with fluid extract 60 ° of reduced vacuum dryings, powder gets dry extract, dried cream powder was crushed to 60 mesh sieves, yield is 35-37%, adds excipient and is prepared into capsule or tablet, and containing the different guanidine amount of effective sugar-lowering components 3-methyl-2-butene base is 4%-7%.
3, decocting in water alcohol precipitation process and preparation
It is 95% ethanol that decocting in water fluid extract in 2 is added content, make the concentration of alcohol in the fluid extract reach 60%, after leaving standstill 24 hours, filtration under diminished pressure leaves standstill liquid, behind the filter and remove residue, reclaim under reduced pressure is ethanol to the greatest extent, again the medicinal liquid water-bath being concentrated the back is dried cream powder 60 ℃ of reduced vacuum dryings, and dried cream powder is crushed to this 60 mesh sieve, and yield is 10.5-12.5%, encapsulated or tablet forming, containing the different guanidine amount of effective sugar-lowering components 3-methyl-2-butene base is 10%-15%.
4, macroporous resin adsorption technology and preparation:
After three decocting in water filtrates in 2 are merged, make filtrate pass through macroporous adsorbent resin (resin demand is 2 times of decoction pieces), flow velocity 2ml/min, cm
2, wash adsorption resin column (water yield is about 10 times of decoction pieces amount) with water, treat that the water liquid stream is done after, the ethanol elution with 70% (the ethanol consumption is about 7 times of raw material dose), flow velocity 1ml/min, cm
2Collect ethanol elution, decompression recycling ethanol gets fluid extract, it is 1.38-1.40 that fluid extract is concentrated into relative density, yield is 0.8%, and vacuum drying under 60 ℃ of temperature conditions was crushed to 60 mesh sieves then, encapsulated or make tablet, containing the different guanidine amount of effective sugar-lowering components 3-methyl-2-butene base is 20%-30%.
The chemical constituent separation and Extraction of Crassula argentea Thunb and structure are identified
With 100 grams of the extractum in the step 3, admix equivalent silica gel (100 orders-160 order), the apparatus,Soxhlet's of packing into is used chloroform respectively, ethyl acetate, acetone, four kinds of solvents of methanol carry out extracting, concentrate then and get extract 60 grams, 15 grams, 8 grams, 6 grams respectively.
1, chloroform portion extract is further separated, purification, the white needle-like crystals chemical compound, be accredited as cupreol.
Chemical name: Stigmast-5-en-3-ol, (3 β)-
Molecular formula: C
29H
50O
Molecular weight: 414.69
Fusing point: measured value 134-136 ℃
Literature value 134-136 ℃
Chemical structural formula:
Structure is identified:
Infrared absorption spectroscopy (IR) Timeing Detection Table
IR
KBR(cm-1) literature value 3424 (OH) 2931 (OH) 2863 (OH) 1461 (OH) measured values 3429 (OH) 2935 (OH) 2868 (OH) 1460 (OH) literature values 1370 (CH
3CH
2) 1053 (CH
3CH
2) 956 (CH
3CH
2) measured value 1379.2 (CH
3CH
2) 1059 (CH
3CH
2) 956 (CH
3CH
2)
Proton nmr spectra (
1HNMR) determination data table
1HNMR data literature value 0.68 (S, CH3) 0.8 (3H, S) 0.82 (3H, S) 0.87 (3H, S, CH3) measured value 0.67 (3H, S, CH3) 0.8 (3H, S, CH3) 0.81 (3H, S, CH3) 0.86 (3H, S, CH3) literature value 1.0 (3H, S, CH3) 1.01 (3H, S, CH3) 5.35 (1H, D, 6-H) 3.53 (1H, m, 3-H) measured value 0.99 (3H, S, CH3) 1.00 (3H, S, CH3) 5.35 (3H, S, CH3) 3.53 (1H, M, 3-H) 0.87 (3H, S, CH
3)
Mass spectrum (MS) determination data table
EI-MS literature value 414 (M
+) 396 (M-H2O) 381 (M-CH3-H2O) 329 (M-CH3-H2O) measured values, 414 (M
+) 396 (M-H2O) 381 (M-CH3-H2O) 329 (M-CH3-H2O) literature values, 303 (M-CH3-H2O) 273 (M-CH3-H2O), 255 (M-CH3-H2O) 231 (M-CH3-H2O) measured values, 303 (M-CH3-H2O) 273 (M-CH3-H2O), 255 (M-CH3-H2O) 231 (M-CH3-H2O) literature values, 213 (M-CH3-H2O) 145 (M-CH3-H2O), 95 (M-CH3-H2O) 81 (M-CH3-H2O) measured values, 213 (M-CH3-H2O) 145 (M-CH3-H2O), 95 (M-CH3-H2O) 81 (M-CH3-H2O)
2, methanol portion extract is further separated, purification gets the white particulate crystalline solid, is accredited as mannitol.Must a white particulate crystallization in separation process this, be accredited as Kcl and Nacl mixture.
Mannitol chemical name: D-Mannitol
Chemical structural formula:
Molecular formula: C
6H
14O
6
Molecular weight: 182.17
Fusing point: survey 166-168 ℃
Reference substance 166-169 ℃
Structure is identified:
Infrared absorption spectroscopy (IR) determination data table
Oscillatory type group intensity measurement 3391, strong standard specimen 3396, the 3279 flexible-OH actual measurement 1460 flexible-C-CH of 3288 flexible-OH
3Standard specimen 1421 flexible-C-CH
3
Proton nmr spectra (
1HNMR) determination data table
(
1HNMR) data
Carbon-13 nmr spectra (
13CNMR) determination data table
| Contrast performance number (ppM) | 3.66 | 3.79 | 3.88 |
| Sample value ppM | 3.67 | 3.79 | 3.87 |
| Contrast performance number (ppM) | 66.0685 | 72.0991 | 73.6692 |
| Sample value ppM | 66.0761 | 72.1252 | 73.6776 |
Elementary analysis
Reference substance: Tianjin chemical reagent two factory's products, analytical pure
| Theoretical value | C：39.52 | H：7.68 |
| Sample value | C：39.73 | H：7.65 |
3. ethyl acetate portion extract is further separated respectively with acetone portion extract, purification, obtain two kinds of white needle-like crystals respectively, be chemical compound of the same race through evaluation: the different guanidine of 3-methyl-2-butene base.
The different guanidine of chemical name 3-methyl-2-butene base
Chemical structural formula:
Molecular formula: C
6H
13N
3
Molecular weight: 127.18
Fusing point: 108 ℃ (measured value)
Chemical constitution is identified:
Infrared absorption spectroscopy (IR) Timeing Detection Table
Proton nmr spectra
1H NMR) determination data table
| Absworption peak (cm -1) 3402 1666 1334 | Oscillatory type stretching vibration stretching vibration stretching vibration | Fundamental frequency N-H C=C C-N | Absorption peak strength is strong strong |
1H NMR) data
| The proton sequence number | Chemical shift (ppm) | Proton number | Remarks |
| CH3(1) | Measured value | Do not see bibliographical information 1H composes data | |
| 1.7009 | 3 | ||
| CH3(2) | 1.7606 | 3 | D 2The O exchange |
| CH2 | 3.7840 | 2 | |
| CH | 5.2643 | 4 |
Carbon-13 nmr spectra (
13C NMR) determination data table
| The carbon sequence number | Chemical shift (ppm) | Remarks |
| 1 2 3 4 5 6 | Measured value 19.9186 27.4945 41.9822 120.0766 142.1471 159.5966 | Do not see bibliographical information 13C composes data |
The mass spectroscopy tables of data
The determination data tabulation
Mass-to-charge ratio (m/z) relative abundance remarks
Measured value 127 (M
+) 126 (M-H)
+112 (M-CH
3)
+
112(M-CH
3)
+
84 (M-CH
3N
2)
+70 (M-CH
3N
2)
+Animal pharmacology, toxicological experiment
The present invention carries out pharmacology, toxicological experiment in strict accordance with " the study of tcm new drug guide " of the promulgation of bureau of drug policy ﹠ administration of Ministry of Health of the People's Republic of China by the technical specification of Chinese medicine kind new medicine research.
1, toxicity test result:
Acute toxicity LD50=11.63g/kg is 1400 times of people's informal dress dosage.
Chronic toxicity (long term toxicity) result
The Crassula argentea Thunb preparation influence to the various organ coefficients of rat in 90 days of ig various dose continuously
| Group | Crassula argentea Thunb preparation group | The blank group | |
| Experimental mouse number (only) | 10 | 10 | |
| Dosage (g/kg.d) | 0.2 | 1g 1% Calculus Bovis from Northwest of China glue | |
| Thymus ♀ ♂ | 0.18 6±0.018″ 0.162±0.042′ | 0.146±0.019 0.110±0.029 | |
| Heart ♀ ♂ | 0.396±0.083 0.408±0.068 | 0.420±0.060 0.376±0.064 | |
| Organ coefficient X ± SD | Lungs ♀ ♂ | 0.708±0.082 0.627±0.078 | 0.896±0.023 0.945±0.051 |
| Liver ♀ ♂ | 3.320±0.482 2.730±0.154 | 3.264±0.280 2.988±0.336 | |
| The ♀ spleen | 0.510±0.093 0.510±0.093 | 0.766±0.116 0.766±0.116 | |
| ♀ kidney ♂ | 0.440±0.082 0.560±0.087 | 0.518±0.111 0.624±0.071 | |
| Adrenal gland ♀ ♂ | 0.043±0.013 0.034±0.040 | 0.099±0.020 0.152±0.025 | |
| Ovary ♀ | 0.086±0.026 | 0.071±0.011 | |
| Prostate ♂ | 0.260±0.086 | 0.270±0.072 | |
| Uterus ♀ | 0.139±0.040 | 0.152±0.025 | |
| Testis ♂ ♀ | 1.430±0.120 0.603±0.090 | 1.472±0.169 0.592±0.021 | |
| Full brain ♂ ♀ | 0.590±0.060 0.648±0.083 | 0.570±0.079 0.659±0.117 | |
| Stomach ♂ | 0.642±0.110 | 0.750±0.036 | |
With matched group ratio '＜0.05; " P＜0.01 organ coefficient=internal organs weight in wet base/body weight when cuing open * 100%
In the slow poison test, the thymus coefficient of animal subject (Crassula argentea Thunb preparation group and blank group are relatively) significantly improves, and indicates that preparation of the present invention has good potentiation to diabetes patient's function of immune system.
Special toxicity:
1. it is negative to cause the gene mutation experimental result.
2. the reproductive toxicity testing result is negative.
3. according to " new drug research guide " regulation: it is prominent negative to cause gene, can exempt to do carcinogenic test.
2, pharmacological experiment result
The Crassula argentea Thunb preparation is to the therapeutical effect (continuous oral administration 20 days) of alloxan diabetes mouse blood sugar.
| Group | Experimental mouse number (only) | Dosage mg/kgd | Measure Mus number (only) | Blood glucose (mmol/L X ± SD) |
| Model group | 20 | Ig equivalent Calculus Bovis from Northwest of China glue | 14 | 6.02±1.95 |
| The glyburide group | 20 | 1.5 | 10 | 5.48±1.41′ |
| The Crassula argentea Thunb group | 20 | 100 | 16 | 3.88±1.81″ |
| Normal group | 2 0 | - | 17 | 5.01±1.40′ |
With model group ratio ' P＜0.05; "＜0.01
The Crassula argentea Thunb preparation is to the therapeutical effect (continuous oral administration 20 days) of alloxan diabetes rats blood glucose.
| Group | Experimental mouse number (only) | Dosage mg/kgd | Measure Mus number (only) | Blood glucose (mmol/L X ± SD) |
| Normal group | 8 | - | 8 | 3.03±0.48′ |
| Model group | 10 | Ig equivalent Calculus Bovis from Northwest of China glue | 10 | 3.63±0.40 |
| The Crassula argentea Thunb group | 10 | 100 | 9 | 3.06±0.25″ |
| The excellent grain group of falling | 10 | 1.5 | 10 | 2.04±0.61″ |
With model group ratio ' P＜0.05; " P＜0.01
The Crassula argentea Thunb preparation is to the blood fat influence (continuous oral administration 20 days) of alloxan hyperglycemic rat.
| Group | Experimental mouse number (only) | Dosage mg/kgd | Measure Mus number (only) | Blood cholesterol (mmol/L) | Triglyceride in the blood (mmol/L) |
| Blank group | 8 | - | 8 | 2.08±0.32′ | 1.28±0.32′ |
| Model group | 10 | Ig equivalent Calculus Bovis from Northwest of China glue | 10 | 2.55±0.28 | 1.66±0.26 |
| The glyburide group | 10 | 1.5 | 10 | 2.37±0.50 | 1.60±0.39 |
| The Crassula argentea Thunb group | 10 | 100 | 9 | 1.63±0.23″ | 0.90±0.22″ |
With model group ratio, ' P＜0.05; " P＜0.01
Chinese crude drug Crassula argentea Thunb and the preparation thereof that the present invention relates to; prove by zoopery: blood glucose, body weight, a month survival rate to the large and small Mus of alloxan all have significant protection (treatment) effect; particularly the thymus to the large and small Mus of alloxan has obvious protection therapeutical effect; test of many times proof is to reversing the blood sugar increasing due to the alloxan; immune organ suppresses; weight loss; blood cholesterol, triglyceride rising all have protection therapeutical effect in various degree, and whole synthesis protection effect obviously is better than orally-taken blood sugar reducing medicines such as Western medicine glyburide and Chinese medicine TANGMAIKANG.
The clinical experiment result:
Crassula argentea Thunb that the present invention relates to and preparation thereof are pressed WHO definite type ii diabetes diagnostic criteria in 1985 through attached new bridge hospital of Military Medical Univ No.3, P.L.A (entire PLA clinical pharmacology base), and differential diagnosis in tcm carries out clinical experiment with reference to " traditional Chinese medical science Clinical Researches of New Drugs technological guidance principle " that Ministry of Health of the People's Republic of China formulates.Its result is as follows:
1, said preparation is to the treatment of type ii diabetes and complication, and obvious effective rate is 44%, and effective percentage is 46.9%, total effective rate 90.9%.
2, said preparation is in the process of treatment diabetes, and along with the decline of blood glucose, its blood cholesterol, triglyceride also descend thereupon, and blood middle-high density ester gp APOA1 is raise more significantly, and low-density ester gp APOB descends gradually.
3, be difficult for producing hypoglycemic reaction.
4, share treatment severe diabetes with the orally-taken blood sugar reducing Western medicine, curative effect is good.To the oral said preparation of type i diabetes patient, can reduce insulin dosage.
5, the treatment diabetic complication is evident in efficacy.
6, the protection islet function alleviates and delays the medicine secondary failure.
7, in therapeutic process, observe patient's blood, routine urinalysis, the heart, liver, the no abnormal discovery of renal function.Take place to feel sick in the drug administration process, untoward reaction such as vomiting, stomachache.Also do not find hypoglycemic reaction.
Conclusion: oral Chinese medicine antihypelipidemic preparation blood sugar lowering effect of the present invention is obvious, and patient's allomeric function is improved significantly, and coordinative role is arranged, and the diabetes patient below the state of an illness moderate is single good with hypoglycemic effect, and stable.The ApOA1 of raising is arranged and reduce the APOB effect, oral this medicine has no adverse reaction.
Advantage of the present invention:
By intensive research work, find blood sugar lowering effective ingredient in the Crassula argentea Thunb first, the different guanidine of 3-methyl-2-butene base; And isolate other organic and inorganic constituentss that contain in the Crassula argentea Thunb, the complication that these compositions can the partner treatment diabetes; And preparation made a large amount of animal pharmacologies, toxicological experiment and clinical experiment prove: blood glucose, body weight, a month survival rate to the large and small Mus of alloxan all have significant protection effect; Clinical experiment, oral Crassula argentea Thunb antihypelipidemic preparation blood sugar lowering effect is obvious, and is remarkable to the whole motor-driven improvement of patient, coordinative role is arranged, and the diabetes patient below the state of an illness moderate is single good with hypoglycemic effect, has no side effect, the ApOA1 of raising is arranged and reduce the ApOB effect, preparation technology of the present invention makes decoction pieces earlier, makes Chinese medicine preparation by the traditional Chinese medicine technology standard again, steady quality, controlled, curative effect is reliable, safety.Different with above-mentioned Crassula argentea polgsaccharide of mentioning or the former powder of DSP, blood sugar lowering chemical substance of the present invention is the noval chemical compound of finding first, the different guanidine of 3-methyl-2-butene base, clear and definite name, molecular formula, structural formula and fusing point are arranged, in addition, other compositions of control diabetic complication are still arranged, and its content, molecular formula, structural formula, chemical property and molecule are all clear and definite; Be worth to propose that be that preparation technology of the present invention uses is Chinese medicine preparation technology, the present invention makes decoction pieces with the Crassula argentea Thunb herb by prepared slices of Chinese crude drugs preparation technology earlier, decoction pieces is a kind of stable raw material, have and be convenient to transportation, store, advantage such as undergo no deterioration has three kinds of different technologies, the preparation that can be numerous can letter make, the content of the different guanidine of 3-methyl-2-butene base is also different, can be made into different dosage form, is used for the different cases of weight.And the structure of matter that extracts is clear and definite, and molecular weight is little, than polysaccharide, and compounding substances such as DSP raw material, blood sugar lowering and to prevent and treat the mechanism of complication clear is generally acknowledged.Be that science and technology and the traditional Chinese medicine theory of uses advanced and practice combine and the new medicine developed.It is clear and definite to have kept the Western medicine effective ingredient, and the mechanism of action is clear, the quality control index strictness, and the plurality of active ingredients of stable curative effect and Chinese medicine is also deposited, and the characteristics of Comprehensive Treatment have been inherited the pure natural essence of Chinese medicine, the characteristics that toxic and side effects is little.
The Chinese crude drug that embodiment 1 the present invention relates to---Crassula argentea Thunb belongs to for the Crassulaceae jade plant, South Africa, original producton location, widely cultivation all over the world, ornamental plant, formal name used at school: Crassulaargentea Thunb) be documented in (InBailey, mauu PL, 456,1949), " Beijing plant magazine " has a detailed description.The applicant has begun the scale plantation at present.With high temperature, high humidity, high ultraviolet condition and reasonable cultivation management, behind the planting season 2-3, in the greenhouse canopy, bloom, the applicant is for measuring the content of the different guanidine of the contained effective blood sugar lowering chemical constituent 3-methyl-2-butene base of Crassula argentea Thunb plant, to determine medicinal part and the collecting time of plant, use the high-efficient liquid phase technique measurement result shown in table one, table two.
Table one: the different guanidine content of each position 3-methyl-2-butene base of Crassula argentea Thunb plant decoction pieces
| The content position | Growth time | ||
| 1 year | 2 years | 3 years | |
| The tender point of stem fibrous root root head branch and leaf | 3.33％ 0.91％ 3.80％ 3.36％ 0.49％ 0.49％ | 7.37％ 0.45％ 2.69％ 6.0％ 0.74％ 0.51％ | 6.70％ 0.67％ 2.98％ 5.12％ 0.31％ 0.76％ |
Table two: South Africa (Namibia) originates in the different guanidine content of 3-methyl-2-butene base in the annual decoction pieces branch of plant Crassula argentea Thunb, the leaf.
| Plant parts | The different guanidine content of 3-methyl-2-butene base |
| Leaf branch | 0.23％ 0.18％ |
By assay: the medicinal all herbal medicine of answering of Crassula argentea Thunb plant, can find out that also the active constituent content of the Crassula argentea Thunb plant blood sugar lowering of cultivation surpasses the active constituent content that South Africa originates in Crassula argentea Thunb plant blood sugar lowering.Annual herb plant total content average is that 2.06%, two year living herb plant total content average is that 2.96%, three year living herb plant total content average is 2.76%.Because this plant belongs to undershrub, the position that has after a year begins lignifying, and per mu yield is not greatly improved.Therefore, it is considered herein that: collecting time, no matter from the active constituent content evaluation, or the comprehensive economic index evaluation, be advisable with the annual plant all herbal medicine.
Embodiment 2, effective different guanidine (C of blood sugar lowering chemical compound 3-methyl-2-butene in the different process preparation
6H
13N
3) assay.
Effective different guanidine (C of blood sugar lowering chemical compound 3-methyl-2-butene base in the different process preparation
6H
13N
3) assay.
Instrument:
France's (GILSON company high pressure liquid chromatograph); HoLOCHROME UV, visible light ripple detector; 303 type high-pressure pumps.
Chromatographic column:
1.50 the stainless steel column of * 4.6mm;-NH
2Base ion-type 7 μ m filler high-pressure columns.
Solvent:
Deionized water, methanol-analytical pure; Sulphuric acid-top grade is pure.
Chromatographic condition
Mobile phase: 5mmod aqueous sulfuric acid, flow velocity: 1.0ml/min; Detect wavelength: 200nm.
The sample mouth is handled:
Accurately take by weighing sample in dissolve measuring bottle, standardize solution is diluted to scale.Ultrasonoscope heating for dissolving 20 minutes.
Computational methods:
The standard curve external standard method is calculated regression equation, will record several substitutions and calculate.
Measurement result:
1, equation of linear regression: Y=4.06108 * 10
6-614418.872
Regression coefficient: r=0.99789
2, measurement result:
| Sample | Sample size (mg) | The peak area integration | C 6H 13N 3Content | Percentage composition (%) |
| Boiled process decocting in water alcohol precipitation process macroporous resin technology | 49.04 50.15 11.88 | 13283486 26593204 16725807 | 3.42 6.70 4.27 | 6.97 13.36 36.19 |
Annotate: computing formula in the table:
1.Y＝4.06108×10
6X-614418.872
Y-detected peaks integral area; Different guanidine (the C of X-3-methyl-2-butene base
6HON
3) content μ g
2. percentage composition=C
6H
13N
3Content (μ g)/sample size (μ g) * 100%.
Embodiment 3, the preparation method of the pure product of the different guanidine of 3-methyl-2-butene base:
Extractum with three decocting in water of Crassula argentea Thunb, filtration, after concentrating, with 2 times when extractum 75% soak with ethanol 9 after, filter also collection filtrate.Then, again with filtering residue with 75% soak with ethanol 9 hours (amount of alcohol is 2 times of filtering residue amount), filter and also collect filtrate.5 times so repeatedly, to collect 5 times and merge alcoholic solution, decompression recycling ethanol gets extractum.Extractum is scattered in the water, adds strong aqua ammonia in water, make pH value reach 11.Use ethyl acetate and n-butanol extraction respectively, the extract concentrating under reduced pressure is got extractum, with acetone extractum will be dissolved once more, remove insoluble matter, reclaim under reduced pressure acetone gets extractum.Gained extractum is mixed the alkaline silica gel H (200-300 order) of last 2.5 times of amounts, with 1kg alkaline silica gel upper prop.Use earlier chloroform: methanol: the solvent elution of water=80: 10: 1, flow velocity 2ml/min, cm
2, collect eluent.Reuse chloroform: methanol: the solvent elution of water=7: 3: 1, flow velocity 1ml/mincm
2, merge eluent twice, through condensing crystallizing, get white, needle-shaped crystals body-different guanidine of 3-methyl-2-butene base (purity is more than 97%).
Claims (2)
1, a kind of Crassula argentea Thunb traditional Chinese medicine antidiabetic preparations, the main blood sugar lowering chemical compound that it is characterized in that this antihypelipidemic preparation is the natural blood sugar lowering chemical compound of finding first, the different guanidine of 3-methyl-2-butene base, molecular formula is C
6H
13N
3, molecular weight is 127.18, fusing point is 108 ℃, chemical structural formula:
Contain the composition that the treatment diabetes is had assosting effect in the preparation in addition, be cupreol, content is at 0.23%-0.42%, D-mannitol, and content is at the mixture of 0.95%-1.35%, potassium chloride, sodium chloride; The content of the different guanidine of natural blood sugar lowering chemical compound 3-methyl-2-butene base is at 4%-30% in the preparation.
2, a kind of preparation method of Crassula argentea Thunb traditional Chinese medicine antidiabetic preparations as claimed in claim 1, its processing step division is as follows:
(1) preparation Crassula argentea Thunb decoction pieces, the medicinal all herbal medicine of answering of Crassula argentea Thunb, bright grass removes 30% left and right sides moisture through dry in the sun, cleans with clear water, is cut into long 5-8cm, the strip and block of wide 2-3cm, in the sun or send in the drying machine and carry out the vibratory liquefaction drying to be lower than 60 ℃ of temperature, make moisture content be lower than 10%, impurity content is lower than 3% technical specification, make the bright product of Crassula argentea Thunb be processed into the prepared slices of Chinese crude drugs by above processing, yield is about 5%;
(2), boiled process and preparation
The Crassula argentea Thunb decoction pieces was crushed to 10 mesh sieves, and the water retting of 2 times of weight of adding 4 hours adds 10 times of water gagings again, boils 2 hours, collects filtrate for the first time; Filtering residue adds 8 times of water gagings for the first time, boils 2 hours after-filtration, collects filtrate for the second time, and filtering residue adds 5 times of water gagings for the second time again, boils 2 hours after-filtration, collects filtrate for the third time; Merge filtrate for the third time, in water-bath, be concentrated into maltose shape fluid extract, with fluid extract 60 ° of reduced vacuum dryings, powder gets dry extract, dried cream powder was crushed to 60 mesh sieves, yield is 35-37%, adds excipient and is prepared into capsule or tablet, and containing the different guanidine amount of effective sugar-lowering components 3-methyl-2-butene base is 4%-7%;
(3), decocting in water alcohol precipitation process and preparation
It is 95% ethanol that decocting in water fluid extract in (2) is added content, make the concentration of alcohol in the fluid extract reach 60%, after leaving standstill 24 hours, filtration under diminished pressure leaves standstill liquid, behind the filter and remove residue, decompression recycling ethanol, again the medicinal liquid water-bath being concentrated the back is dried cream powder 60 ℃ of reduced vacuum dryings, and dried cream powder is crushed to this 60 mesh sieve, and yield is 10.5-12.5%, encapsulated or tablet forming, containing the different guanidine amount of effective sugar-lowering components 3-methyl-2-butene base is 10%-15%;
(4), macroporous resin adsorption technology and preparation:
After three decocting in water filtrates merging in (2), make filtrate pass through macroporous adsorbent resin (resin demand is 2 times of decoction pieces), flow velocity 2ml/min, cm
2, wash adsorption resin column (water yield is about 10 times of decoction pieces amount) with water, treat that the water liquid stream is done after, the ethanol elution with 70% (the ethanol consumption is about 7 times of raw material dose), flow velocity 1ml/min, cm
2Collect ethanol elution, decompression recycling ethanol gets fluid extract, it is 1.38-1.40 that extractum is concentrated into relative density, yield is 0.8%, and vacuum drying under 60 ℃ of temperature conditions was crushed to 60 mesh sieves then, encapsulated or make tablet, containing the different guanidine amount of effective sugar-lowering components 3-methyl-2-butene base is more than the 20%-30%.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB001358863A CN1141086C (en) | 2000-12-21 | 2000-12-21 | Hypoglycemic Chinese medicine 'yanzizhang' and its preparing process |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB001358863A CN1141086C (en) | 2000-12-21 | 2000-12-21 | Hypoglycemic Chinese medicine 'yanzizhang' and its preparing process |
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| Publication Number | Publication Date |
|---|---|
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| CN1141086C true CN1141086C (en) | 2004-03-10 |
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ID=4596943
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|---|---|---|---|
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Country Status (1)
| Country | Link |
|---|---|
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2000
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