CN100588409C - A kind of preparation method for the treatment of diabetes medicament - Google Patents
A kind of preparation method for the treatment of diabetes medicament Download PDFInfo
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- CN100588409C CN100588409C CN200610016490A CN200610016490A CN100588409C CN 100588409 C CN100588409 C CN 100588409C CN 200610016490 A CN200610016490 A CN 200610016490A CN 200610016490 A CN200610016490 A CN 200610016490A CN 100588409 C CN100588409 C CN 100588409C
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Abstract
The present invention discloses a kind of treatment diabetes medicament, and (trade name: preparation method JINQI JIANGTANG PIAN) is broken into fine powder with the prior art processes Rhizoma Coptidis powder and changes ethanol extraction, purification into; The Radix Astragali is with prior art processes 50% ethanol extraction three times, and 4,2,2 hours time changed 75% ethanol extraction secondary into, 2,2 hours time; Flos Lonicerae is pulverized prior art processes total amount 1/6, and 5/6 water temperature is soaked and changed that whole water temperatures are soaked, precipitate with ethanol improves technology makes this medicine taking dose be reduced to each 2-3 sheet by each 7-10 sheet into, has improved the compliance of patient's medication.
Description
Technical field
The present invention relates to a kind of medicine for the treatment of diabetes, particularly relating to a kind of is the preparation method of the tablet of the treatment diabetes made of raw material with the vegetable Chinese herbal medicine.
Background technology
The medicine of diabetes has license day for announcing 2000.5.17 at present, and it is prescription raw material and main component with Rhizoma Coptidis, the Radix Astragali, Flos Lonicerae, Lian Alice, Rhizoma Dioscoreae to authorize public CN1052419C " a kind of Chinese herb medicine for the treatment of diabetes ".Open day 2001.12.12, it is prescription raw material and main component with Rhizoma Coptidis, the Radix Astragali, Flos Lonicerae, Radix Panacis Quinquefolii, Radix Trichosanthis, Radix Rehmanniae, Margarita to publication number CN1325723A " Chinese herb medicine of treatment diabetes and preparation method thereof "." Yunnan Chinese medicine magazine " 1999.20 (1) record articles＜JINQI JIANGTANG PIAN treatment type ii diabetes evaluation of clinical curative effect〉it is prescription raw material and main component decoction with Gypsum Fibrosum, the Rhizoma Anemarrhenae, Rhizoma Coptidis, Rhizoma Dioscoreae, pollen, Radix Adenophorae (Radix Glehniae), the Radix Rehmanniae, Flos Lonicerae, the Radix Astragali, Rhizoma Polygonati, Fructus Lycii, Radix Ophiopogonis, Herba Taraxaci for unexposed prescription and " Hubei Journal of Traditional Chinese Medicine " 1993.15 (2) record articles " the golden yellow drink treatment of white tiger diabetes 34 examples ".
The preparation method of the tablet of diabetes, patent announcement day: 2005.01.05 is arranged at present, notification number: CN1559549, application number: 200410018739.1, " a kind of medicine for the treatment of diabetes and preparation method thereof " discloses with Rhizoma Coptidis, the Radix Astragali, Flos Lonicerae is prescription feedstock production (trade name: the JINQI JIANGTANG PIAN) method of tablet.But this medicine taking dose is bigger, each 7-10 sheet, and the patient takes very inconvenient.For this reason, need dwindle dosage, the standard of improving the quality of products research, satisfy patient's requirement.
Summary of the invention
The present invention will deal with problems: on the basis of fully investigation, to this medicine (trade name: JINQI JIANGTANG PIAN) carried out improvement technology, dwindle dosage, the Study on standards of improving the quality of products.
For reach the foregoing invention purpose we to this medicine carried out improvement technology, dwindled dosage, the Study on standards of improving the quality of products.
1. definite foundation of dosage form selection and specification
Because of the research is a process modification,, still be tablet so dosage form does not become.But specification changes, and calculates according to result of the test and the former crude drug amount of taking, and sheet heavily is 0.56g.
2. preparation technology and research contents
2.1 the comparison of existing technology and former technology
The main difference part of existing technology and former technology sees the following form.
| Project | Prior art processes | Technology of the present invention |
| The raw material that makes this effective ingredient is formed | The Rhizoma Coptidis 10.3 weight portion Radixs Astragali 15.4 weight portion Flos Loniceraes 61.8 weight portions | The Rhizoma Coptidis 10.3 weight portion Radixs Astragali 15.4 weight portion Flos Loniceraes 61.8 weight portions |
| Rhizoma Coptidis | Pulverize | 50% ethanol extraction, purification |
| The Radix Astragali | 50% ethanol extraction three times, 4,2,2 hours time | 75% ethanol extraction secondary, 2,2 hours time |
| Flos Lonicerae | Total amount 1/6 is pulverized, and 5/6 water temperature is soaked | Whole water temperatures are soaked, precipitate with ethanol |
| Taking dose | The 7-10 sheet | The 2-3 sheet |
2.2 preparation technology parameter and definite foundation
2.2.1 extraction process
Rhizoma Coptidis has heat clearing and damp drying, the eliminating fire and detoxication effect.Be used for damp and hotly, quench one's thirst etc.Be monarch drug in the prescription.According to the literature, its effective ingredient berberine has obvious hypoglycemic activity.Adopting orthogonal experiment, is the main index of investigating with the content of berberine, preferred optimum extraction process condition.According to the physicochemical property of berberine, ethanol extract is carried out purification process.For making purification condition reasonable, compare test, that is: the comparison of ethanol extract diluent water and 1% acetic acid; The selection of acid treatment pH value; The test that the acid treatment increase is saltoutd; The acidic precipitation thing is regulated the comparative test of pH value with alkali and washing; According to result of the test, determine Rhizoma Coptidis optimum extraction purifying process.
This extraction process is preferably come out through orthogonal test; The used acid-base method of purification is to extract the method that berberine is used always, more easily grasps in the operation, measures liquid PH value with the PH precision test paper, simple, easy row; So this technological design is reasonable, simple, the suitability is strong.
The Radix Astragali has invigorating QI to consolidate the body surface resistance, effects such as diuresis poison holding.Be used for interior-heat and quench one's thirst, diabetes etc.According to the literature, Radix Astragali main active is polysaccharide, astragaloside and flavonoid etc., has the effects such as secretion of blood sugar regulation, promotion insulin and C peptide.Adopting orthogonal experiment, is the main index of investigating with the Astragaloside content, preferred optimum extraction process condition.
Compare with former technology: existing technology Astragaloside content height, extraction time is short, and the extractum yield is low.
Flos Lonicerae has heat-clearing toxin-expelling functions, contains compositions such as chlorogenic acid, flavone.Because of the Flos Lonicerae petal is thin, composition easily leaches, so adopt the water temperature method of soaking to extract.For reducing dose, Flos Lonicerae is all extracted.On the basis of former technology, extractum has been carried out the precipitate with ethanol processing.Adopting orthogonal experiment, is the main index of investigating with the chlorogenic acid content, preferred Flos Lonicerae optimum extraction process.
Flos Lonicerae accounts for prescription ratio 70%, and its extractum amount is also bigger to the taking dose influence.So, pass through the preferred of orthogonal test, existing technology obviously reduces than the extractum yield of former technology, and chlorogenic acid content is also higher.
2.2.2 preparations shaping
By studying before the preparation prescription, the key property of the full extract powder of JINQI JIANGTANG PIAN to be analyzed, the emphasis of determining preparation research is to select the pharmaceutic adjuvant that flowability is strong, compressibility is good, solves the disintegration of tablet problem.The reference literature report selects for use five kinds of adjuvants such as microcrystalline Cellulose, pregelatinized Starch, cross-linked carboxymethyl cellulose to carry out multiple test.At first, determine method of granulating by the method for granulating test; By tablet molding adjuvant screening test, determine the supplementary product kind and the consumption of tablet molding; Through disintegrating agent kind, consumption screening and coating test, determine disintegrating agent kind and consumption; According to result of the test, determine preparation prescription.
Compare with former technology, existing technology method of granulating is simple, and the disintegration of tablet time is short.The long problem of disintegration time that has often occurred when having solved former explained hereafter.
2.2.3 pilot scale
Carry out three batches of pilot scales according to Rhizoma Coptidis, the Radix Astragali, the preferred extraction process of Flos Lonicerae and preparation process at the workshop of GMP compatible.Experimental scale is 58 times of recipe quantities.Result of the test (on average): extractum yield: Rhizoma Coptidis 11.0%; The Radix Astragali 12.0%; Flos Lonicerae 14.0%; Each extractum yield is relatively stable.The leading indicator composition extracts the rate of transform: berberine 65.2% in the Rhizoma Coptidis; Astragaloside 8204% in the Radix Astragali; Chlorogenic acid 57.1% in the Flos Lonicerae; All can reach more than 50%.Determine the concentrate drying temperature according to effective ingredient character in this medicine, temperature should be controlled at below 80 ℃, and wherein Flos Lonicerae is extracted thickening temperature and should be no more than 70 ℃.Yield rate: 94.6%.According to three batches of pilot-scale experiment,, calculate existing dose, and folded piece heavily reaches the sheet number in conjunction with former taking dose.Result of calculation: taking dose is reduced to the 2-3 sheet one time, the heavy 0.56g of sheet.Three batches of finished products all comply with relevant regulations through checking every index.
The pilot scale conclusion: this technology is reasonable, feasible, more stable.
3. quality research and quality standard
3.1 raw material, adjuvant quality standard
The supplementary material quality standard is carried out according to Chinese Pharmacopoeia version in 2000.Thin film dress material standard is seen data (5-3) adnexa.The result who adopts pharmacopeia method and HPLC method (finished product standard) to measure content to Rhizoma Coptidis, Radix Astragali raw material compares, and the measurement result error of HPLC method is little as a result.
3.2 intermediate quality standard
For guaranteeing end product quality,, formulated relative density, yield and the content limit of Rhizoma Coptidis, the Radix Astragali, Flos Lonicerae extractum respectively in conjunction with the different content of raw material according to pilot-scale experiment.
3.3 end product quality standard
3.3.1 differentiate
With berberine hydrochloride, chlorogenic acid, Radix Astragali control medicinal material and astragaloside is contrast, and finished product is done the thin layer chromatography discrimination test, and compares with the thin layer chromatography of former handicraft product, and each mainly detects the composition basically identical as a result.
3.3.2 check
Heavy metal detects according to appendix inspection of Chinese Pharmacopoeia version in 2000.The result: lead content≤5ppm in the test agent in three crowdes, arsenic content＜2ppm meets conventional criteria, so do not include in the routine examination standard.
3.3.3 assay
With high performance liquid chromatography the effective ingredient berberine hydrochloride and the first glycosides of Rhizoma Coptidis, the Radix Astragali in the finished product carried out assay.
Existing berberine hydrochloride content in the Rhizoma Coptidis proper mass standard, because of Rhizoma Coptidis in the primary standard is directly to be used as medicine with the crude drug powder, after changing technology, the extraction purification rate of transform according to berberine in the Rhizoma Coptidis is adjusted its content limit, according to three batches of lab scales and pilot scale sample determination result, formulate content limit: every content must not be less than 12mg.
The Radix Astragali is widely used as the quality control index of the Radix Astragali with astragaloside.For controlling product quality better, issue WS3-368 (Z-038)-2001 standard with reference to office, formulated the content assaying method and the content limit of astragaloside in the finished product.And done the methodology demonstration test.According to three batches of lab scales and pilot scale sample determination result, formulate content limit: every content must not be less than 0.17mg.
Flos Lonicerae according to the literature, chlorogenic acid composition less stable is subject to multiple factor affecting such as temperature, pH value, so undetermined chlorogenic acid component content in the finished product in the Flos Lonicerae.
By three batches of test agents in the above-mentioned quality standard check, its every result is all up to specification.
Quality standard is estimated this standard and is made up of raw material, intermediate and finished product three parts.May command production overall process.Wherein intermediate and end product quality standard increase than primary standard.The finished product standard is made up of qualitative, quantitative two parts.Wherein qualitative standard has been done the thin layer chromatography discriminating respectively to three flavor medicines in the finished product; Quantitative criterion is to the equal controlling content of effective ingredient berberine, astragaloside in wherein Rhizoma Coptidis, the Radix Astragali, so this quality standard can guarantee the curative effect of this medicine to a certain extent.
3. study on the stability
Investigate three batches in sample, accelerated stability test six months, item indexs such as the outward appearance of this product, character, discriminating, content, disintegrate, microorganism all do not have obvious change, meet relevant regulations.Sample adopts original packing-aluminium-plastic bubble plate packing, between probation in, this packing can satisfy the requirement of assurance product quality.
Conclusion: this constant product quality, but long preservation.
4. A+E
According to a result of the test such as optimal process, quality control, study on the stability, prove that this technological design is reasonable, raw material, production overall process and end product quality are all controlled, and product stability is good.Taking dose is reduced to each 2-3 sheet by each 7-10 sheet, has improved the compliance of patient's medication.
The invention provides a kind of preparation method for the treatment of diabetes medicament, comprise that the raw material that makes this effective ingredient consists of: the Rhizoma Coptidis 10.3 weight portion Radixs Astragali 15.4 weight portion Flos Loniceraes 61.8 weight portions, described medicine is a tablet, it is characterized in that Rhizoma Coptidis adds 50% alcohol reflux secondary, each 2 hours, filter, merging filtrate, being evaporated to relative density is the extractum of 1.15～1.20 (60 ℃), and it is an amount of to add 1% acetic acid, regulates pH value to 1～2 with hydrochloric acid, it is an amount of to add sodium chloride, left standstill 12 hours, and filtered, it is an amount of that precipitation adds water, regulate pH value to 6～7 with 20% sodium hydroxide, stirring makes dissolving, filters, and gets the precipitation drying under reduced pressure and pulverizes standby;
The Radix Astragali adds 75% alcohol reflux secondary, and each 2 hours, filter, merging filtrate, being evaporated to relative density is the extractum of 1.25～1.30 (60 ℃), drying under reduced pressure is pulverized standby;
Flos Lonicerae adds water temperature and soaks secondary, each 1 hour, merge extractive liquid, filtered, being evaporated to relative density is the extractum of 1.17～1.22 (60 ℃), when treating that temperature is reduced to 40 ℃, stir and slowly to add ethanol down, make to contain the alcohol amount and reach 70%, left standstill 24 hours, filter, being evaporated to relative density is the extractum of 1.22～1.28 (60 ℃), and drying under reduced pressure is pulverized standby;
With Rhizoma Coptidis, the Radix Astragali, 7.1 parts of adjuvants that add 2.9 parts of Flos Lonicerae extractum powder, make granule, compacting is wrapped film-coat, promptly in flakes.
The preparation method of described treatment diabetes medicament is characterized in that described adjuvant is 1.1 parts of pregelatinized Starch, 1.4 parts of microcrystalline Cellulose, 0.25 part of cross-linking sodium carboxymethyl cellulose, 0.15 part of composition of magnesium stearate.
Effect of the present invention: change ethanol extraction, purification into because the prior art processes Rhizoma Coptidis powder is broken into fine powder; Owing to use alcohol extraction, can will there be the material of blood sugar reducing function to propose, and a large amount of inert matters such as starch are rejected, therefore can reduce dose.
The Radix Astragali is with prior art processes 50% ethanol extraction three times, and 4,2,2 hours time changed 75% ethanol extraction secondary into, 2,2 hours time; Because sugar reducing substance more is dissolved in ethanol,,, still can reach good effect though shortened extraction time so improve concentration of alcohol.
Flos Lonicerae is pulverized prior art processes total amount 1/6, and 5/6 water temperature is soaked and changed that whole water temperatures are soaked, precipitate with ethanol into, carries and has rejected a lot of inert matters owing to all change water into, so can reduce dose.
Improve technology and make this medicine taking dose be reduced to each 2-3 sheet, improved the compliance of patient's medication by each 7-10 sheet.
The specific embodiment
Embodiment 1: the medicine (JINQI JIANGTANG PIAN) of preparation treatment diabetes
Prescription: Rhizoma Coptidis 343g Radix Astragali 513g Flos Lonicerae 2058g pregelatinized Starch 60g microcrystalline Cellulose 76g cross-linking sodium carboxymethyl cellulose 13.5g magnesium stearate 2.5g
Preparation method:
1, Rhizoma Coptidis adds 50% alcohol reflux secondary, each 2 hours, filters, merging filtrate, being evaporated to relative density is the extractum of 1.15～1.20 (60 ℃), it is an amount of to add 1% acetic acid, regulate pH value to 1～2 with hydrochloric acid, it is an amount of to add sodium chloride, leaves standstill 12 hours, filter, it is an amount of that precipitation adds water, regulates pH value to 6～7 with 20% sodium hydroxide, stirs and make dissolving, filter, get the precipitation drying under reduced pressure and pulverize standby; 2, the Radix Astragali adds 75% alcohol reflux secondary, and each 2 hours, filter, merging filtrate, being evaporated to relative density is the extractum of 1.25～1.30 (60 ℃), drying under reduced pressure is pulverized standby;
3, Flos Lonicerae adds water temperature and soaks secondary, each 1 hour, merge extractive liquid, filtered, being evaporated to relative density is the extractum of 1.17～1.22 (60 ℃), when treating that temperature is reduced to 40 ℃, stir and slowly to add ethanol down, make to contain the alcohol amount and reach 70%, left standstill 24 hours, filter, being evaporated to relative density is the extractum of 1.22～1.28 (60 ℃), and drying under reduced pressure is pulverized standby.Get above-mentioned three kinds of powder, add right amount of auxiliary materials, make granule, be pressed into 1000, the bag film-coat promptly gets JINQI JIANGTANG PIAN.
Embodiment 2: the medicine of new technology treatment diabetes (trade name: JINQI JIANGTANG PIAN) pharmacological toxicology test summary data:
JINQI JIANGTANG PIAN has been widely used in clinical at present, has the effect of aspects such as blood sugar lowering, blood fat reducing, adjusting immunity.On this basis, again former technology has been carried out improving and improved, the new technology JINQI JIANGTANG PIAN has been carried out pharmacodynamics, toxicology test research, confirmed the effectiveness and the safety of new technology preparation, now result of the test has been summarized as follows.
One, pharmacodynamic study:
1. new technology JINQI JIANGTANG PIAN 0.9,1.8, three dosage groups of 3.6g crude drug/kg every day is to normal rat oral gavage administration 1 time, continuous 7 days.As a result, each dosage group medicine is not seen significant change to normal rat blood sugar, and is identical with the former technology group effect of Isodose.
2. new technology JINQI JIANGTANG PIAN 0.9,1.8, three dosage groups of 3.6g crude drug/kg, streptozotocin is brought out diabetes model zoometry different dosing time blood glucose value, each administration treated animal blood glucose value is in administration in the time of 4 days as a result, do not see obvious reduction, administration beginning in the 7th day, middle and high dosage treated animal blood glucose value has obvious reduction, all shows tangible blood sugar reducing function to the 10th day each dosage group, and relatively there were significant differences with model control group.But do not drop to normal level as yet.
3. new technology JINQI JIANGTANG PIAN 0.9,1.8, three dosage groups of 3.6g crude drug/kg, to different time blood glucose value after the diabetes model zoometry administration of model induced by alloxan, result and model control group are relatively, the new technology low dose group is not seen obvious influence to rat blood sugar in administration in 8 days, high dose group is beginning in 5 days after administration, blood glucose value significance occurs and descends, and effect continues to the 8th day; In dosed administration group and former technology JINQI JIANGTANG PIAN group all administration after 8 days blood glucose value significance decline appears.The former slightly is better than the latter blood sugar reducing function of new technology JINQI JIANGTANG PIAN and former technology comparison.
4. new technology JINQI JIANGTANG PIAN 0.9,1.8, three dosage groups of 3.6g crude drug/kg, successive administration are after 8 days, measure the variation of blood glucose value behind the rat oral glucose.The result shows, though the blood sugar increasing statistics that this medicine causes after to oral glucose goes up there was no significant difference, shows certain inhibitory action trend.New technology is close with the effect of former technology group.
5. new technology JINQI JIANGTANG PIAN 0.9,1.8, three dosage groups of 3.6g crude drug/kg, successive administration 30 days and 28 days, can significance suppress rising, the rising of triglyceride is also demonstrated certain inhibitory action by hyperlipemia model rat T-CHOL model induced by alloxan and that bring out by lipomul; 1.8,3.6,7.2g crude drug/kg successive administration 7 days, can suppress the rising of acute hyperlipemia mice T-CHOL value.
6. new technology JINQI JIANGTANG PIAN 1.8,3.6g crude drug/kg, three dosage groups of 7.2g crude drug/kg successive administration are 9 days, can significantly reduce the insulin resistant effect that is caused by hydrocortisone.Isodose new technology drug effect is close with former technology drug effect.
7. new technology JINQI JIANGTANG PIAN 1.8,3.6, three dosage groups of 7.2g crude drug/kg successive administration are 16 days, the there was no significant difference that influences to thymus, but can increase the weight of spleen and pancreas in various degree, this may with the immune state of suitable adjusting body, it is relevant to improve the body function of blood sugar reduction.
8. new technology JINQI JIANGTANG PIAN 3.6, two dosage groups of 7.2g crude drug/kg successive administration are 7 days, can significantly improve the inductive humoral immunization of sheep red blood cell (SRBC), and this point is similar to former technology drug effect, shows that this product has certain humoral immunization effect.
In sum; the new technology JINQI JIANGTANG PIAN does not have obvious influence to normal body blood glucose; short application use can slightly reduce the blood sugar level of hyperglycemia model animal; prolonged application can obviously suppress the blood sugar increasing of diabetes model animal; obviously reduce cholesterol and the triglyceride levels of high fat animal; improve diabetes complicated dyslipidemia, and suitable enhancing body's immunological function, improve the immunity of body.Notable difference is not seen in new technology and former technology comparison drug action.
Two toxicologic studies
1 acute toxicity test
After disposable filling stomach gives the new technology JINQI JIANGTANG PIAN 96.9g crude drug/kg of Cmax in the mice 24 hours, observed 14 days continuously, indexs such as mice body weight, hair color state, moving situation, feces situation there is no unusually, and body weight gain is normal, death condition do not occur.All surviving animals dissection perusal main organs are not seen obvious pathological change after 14 days.New technology JINQI JIANGTANG PIAN gastric infusion maximum dosage-feeding is equivalent to the clinical plan of people 242 times with dosage approximately greater than 96.9g crude drug/kg.
2 long term toxicity tests
(1) 13 week
1. JINQI JIANGTANG PIAN is that 21.6g crude drug/kg, middle dosage group are that 10.8g crude drug/kg, low dose group are 5.4g crude drug/kg through rat oral gavage administration high dose group, is equivalent to 54,27 and 13.5 times of the daily dosage of the clinical plan of people respectively.In three 13 weeks of dosage group successive administration, male and female rat general signs is good, behavioral activity, urinate, defecation, drinking-water be all normal, body weight gain and food ration and matched group be no significant difference relatively all.
2. in 13 week of female, the male rat administration of high, medium and low three the dosage groups of the JINQI JIANGTANG PIAN back routine urianlysises, rarely seen male Mus individual animal protein is positive, and the male Mus of high dose group has 1 example urine to occult blood to be positive.Comprehensive hematology, blood biochemical are learned index analysis, and this result is not relevant with drug toxicity, also treat testing result and deciding in latter stage.
3. rarely seen female Mus hemoglobin slightly raises in female, the male rat administration 13 all hematological examinations of high, medium and low three the dosage groups of JINQI JIANGTANG PIAN, other indexs all with the matched group no significant difference.Show that this medicine does not have influence to the above-mentioned observation index of testing mid-term.
4. the reduction of female, the male rat glutamic oxaloacetic transaminase, GOT value of administration group, female Mus creatinine value and male Mus blood urea nitrogen value during female, the male rat administration of high, medium and low three the dosage groups of JINQI JIANGTANG PIAN 13 all blood biochemicals are learned and checked, though statistical significance is arranged, does not all have the clinical toxicology meaning.Female, male mouse blood glucose value is raise and the reduction of the albumin value of high dose group had not both had dose-effect relationship, and also asexuality relation is still waiting testing result and deciding in latter stage so change.
5. after 13 weeks of high, medium and low three the dosage groups of JINQI JIANGTANG PIAN administration, in rarely seen female Mus, low dose group liver weight and matched group be variant, but its coefficient does not see that difference is arranged, and consideration is that the difference by the weight of animals is caused, and is irrelevant with the toxic reaction of medicine.Other are respectively organized female male animal viscera weight and compare equal no significant difference with matched group with organ coefficient.Show that this medicine does not have influence to the internal organs of test animal in mid-term.
6. do not find the toxic reaction relevant in the histopathologic examination with medicine yet.
7. based on the above results, under this experiment condition, the rat oral gavage approach gives JINQI JIANGTANG PIAN after 13 weeks, does not find the tangible toxic reaction relevant with medicine.Because this medicine is being proceeded the administration toxicity test in 26 weeks, so after treating that its test is all over, again its result of the test is carried out final evaluation.
(2) 26 week and convalescent periods
1. general signs and body weight inspection: JINQI JIANGTANG PIAN is through 26 weeks of rat oral gavage administration, high dose group is that 21.6g crude drug/kg, middle dosage group are that 10.8g crude drug/kg, low dose group are 5.4g crude drug/kg, is equivalent to 54,27 and 13.5 times of the daily dosage of the clinical plan of people respectively.The high, medium and low dosage group of JINQI JIANGTANG PIAN male and female rat general signs is good as a result, behavioral activity, urinate, defecation, drinking-water be all normal, body weight gain and food ration and matched group be no significant difference relatively all.Show that this medicine does not have influence to above-mentioned observation.
2. routine urianlysis: detect in the different dosing phase, administration group and matched group all have individual animal protein and are positive.Being thought of as animal itself changes with the spontaneity that age growth occurs.
3. hematological examination: administration 26 week the back detect, erythrocyte and the hemoglobin value of the female tom of middle and high dosage group all have trend of rising, consider this kind variation may with this product in to contain the pharmacological action of compositions such as the Radix Astragali relevant.No toxicology meaning.
4. blood biochemical is learned and is checked: after 26 weeks of administration, fluctuation all appears becoming in indexs such as the blood glucose value of the female male animal of administration group, albumin value, paddy third transaminase, millet straw transaminase, but these change neither amount effect relationship, also asexuality concerns, and it detects numerical value all in normal range, so think that these variations do not have the toxicology meaning.But the middle and high dosage group of male Mus blood urea nitrogen value presents dose dependent ground to raise, and female Mus also shows same effect trend, does not see that just renal tissue has pathologic to change.This result and the administration of former technology JINQI JIANGTANG PIAN rat in the time of 3 months the reaction result of high dose group consistent, the report of relevant nephrotoxicity is not seen in two clinical practices.However, still advise when clinical use, should noting detecting at any time the variation of renal function.
5. organ weights and organ coefficient inspection: in 26 weeks of administration, female male animal viscera weight of each administration group and organ coefficient are compared no significant difference with matched group.Show that this medicine does not have obvious influence to above-mentioned observation index.
6. histopathology is observed: each treated animal of perusal there is no unusually; The mirror observation animal heart, liver, lung, spleen, kidney, adrenal gland, stomach, duodenum, sky, ileum, uterus, ovary, testis, epididymis, prostate, brain, cerebellum, hypophysis, thymus, thyroid, parathyroid gland down shows no obvious abnormalities.
7. comprehensive above-mentioned every testing result shows that under this experiment condition, 26 week of JINQI JIANGTANG PIAN rat oral gavage administration, low, middle dosage group there is no tangible toxic reaction, so its nontoxic amounts of reactants is 10.8g crude drug/kg, was equivalent to 27 times of dosage of the clinical plan of people.
Claims (1)
1, a kind of preparation method for the treatment of diabetes medicament, its raw material consists of: Rhizoma Coptidis 343g Radix Astragali 513g Flos Lonicerae 2058g pregelatinized Starch 60g microcrystalline Cellulose 76g cross-linking sodium carboxymethyl cellulose 13.5g magnesium stearate 2.5g, the dosage form of described medicine is a tablet, it is characterized in that preparation method is:
Rhizoma Coptidis adds 50% alcohol reflux secondary, each 2 hours, filters, merging filtrate, the relative densities that are evaporated to mensuration under 60 ℃ are 1.15～1.20 extractum, it is an amount of to add 1% acetic acid, regulate pH value to 1～2 with hydrochloric acid, it is an amount of to add sodium chloride, leaves standstill 12 hours, filter, it is an amount of that precipitation adds water, regulates pH value to 6～7 with 20% sodium hydroxide, stirs and make dissolving, filter, get the precipitation drying under reduced pressure and pulverize standby;
The Radix Astragali adds 75% alcohol reflux secondary, and each 2 hours, filter, merging filtrate, being evaporated in temperature is that 60 ℃ of relative densities of measuring down are 1.25～1.30 extractum, drying under reduced pressure is pulverized standby;
Flos Lonicerae adds water temperature and soaks secondary, each 1 hour, merge extractive liquid, filtered, the relative densities that are evaporated to mensuration under 60 ℃ are 1.17～1.22 extractum, when treating that temperature is reduced to 40 ℃, stir and slowly to add ethanol down, make to contain the alcohol amount and reach 70%, left standstill 24 hours, filter, the relative densities that are evaporated to mensuration under 60 ℃ are 1.22～1.28 extractum, and drying under reduced pressure is pulverized standby; Get above-mentioned three kinds of powder, add above-mentioned adjuvant, make granule, be pressed into 1000, the bag film-coat, promptly.
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| CN200610016490A CN100588409C (en) | 2006-11-01 | 2006-11-01 | A kind of preparation method for the treatment of diabetes medicament |
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| CN100588409C true CN100588409C (en) | 2010-02-10 |
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| CN101390966B (en) * | 2007-09-20 | 2013-04-10 | 中国医学科学院药物研究所 | Traditional Chinese medicine effective part compound recipe composition, preparation technique and anti-diabetes use thereof |
| CN101695520B (en) * | 2008-12-30 | 2013-01-16 | 天津医科大学 | Preparation method of medicament for treating diabetes |
| CN101837057A (en) * | 2009-03-19 | 2010-09-22 | 中国医学科学院药物研究所 | Components of compound formula of Chinese medicament active parts, preparation process thereof and anti-diabetic use thereof |
| CN102526243A (en) * | 2010-12-07 | 2012-07-04 | 天津中新药业集团股份有限公司隆顺榕制药厂 | Traditional Chinese medicine combination for clearing heat and tonifying qi and preparation method thereof |
| CN102552448A (en) * | 2010-12-07 | 2012-07-11 | 天津中新药业集团股份有限公司隆顺榕制药厂 | Chinese medicine composition for clearing heat and tonifying qi and preparation method thereof |
| CN102357131B (en) * | 2011-10-12 | 2013-09-25 | 吉林敖东延边药业股份有限公司 | Method for preparing astragalus polysaccharide glucose-lowering capsule |
| CN105596458A (en) * | 2016-03-16 | 2016-05-25 | 中国药科大学 | Jinqi glucose-lowering tablet for treating diabetic cardiovascular complications |
| CN108186636B (en) * | 2018-01-23 | 2019-01-04 | 首都医科大学附属北京世纪坛医院 | A kind of pharmaceutical composition for treating prediabetes |
| CN108245665A (en) * | 2018-02-22 | 2018-07-06 | 天津中新药业集团股份有限公司隆顺榕制药厂 | Pharmaceutical composition and its preparation method and application |
| CN109745372B (en) * | 2019-03-21 | 2021-06-18 | 广东药科大学 | Application of Jinqi hypoglycemic oral preparation in preparation of medicine for treating ulcerative colitis |
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| 黄连中小檗碱的提取工艺. 席国萍等.山地农业生物学报，第23卷第6期. 2004 |
| 黄连中小檗碱的提取工艺. 席国萍等.山地农业生物学报，第23卷第6期. 2004 * |
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Address after: No.21, 10th Street, Binhai New Area Economic and Technological Development Zone, Tianjin 300457 Patentee after: Jinyao Darentang Group Co.,Ltd. Longshunrong Pharmaceutical Factory Address before: 300457 No. tenth, 21 Avenue, Tianjin economic and Technological Development Zone, Tianjin Patentee before: Longshunrong Pharmaceutical Factory, Tianjin Zhongxin Pharmaceutical Group Co.,Ltd. |