CN1290529C - Medicine for treating gout, hyperuricemia and hyperlipemia and preparation method thereof - Google Patents
Medicine for treating gout, hyperuricemia and hyperlipemia and preparation method thereof Download PDFInfo
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- CN1290529C CN1290529C CNB2004100523570A CN200410052357A CN1290529C CN 1290529 C CN1290529 C CN 1290529C CN B2004100523570 A CNB2004100523570 A CN B2004100523570A CN 200410052357 A CN200410052357 A CN 200410052357A CN 1290529 C CN1290529 C CN 1290529C
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Abstract
The present invention relates to a medicine for treating gout, hyperuricemic nephropathy and hyperlipemia. The present invention is composed according to weight portions of 3 to 19 portions of cassia seed, 9 to 30 portions of plantain herb, 6 to 25 portions of glossy privet fruit, 3 to 19 portions of garter snake, 5 to 15 portions of honeycombs of paper wasps and 10 to 30 portions of gynostemma pentaphylla. The present invention also relates to a method for preparing various preparations of the medicine. The medicine of the present invention has the advantages of evident effect of treating the gout, no toxic and side effect, quick pain alleviation, small dosage and lasting medicinal effect.
Description
Technical field
The present invention relates to a kind of Chinese medicine medicine, specifically relate to medicine for the treatment of gout, hyperuricemia and hyperlipemia and preparation method thereof.
Background technology
Chinese medicine is thought the generation of gout, hyperuricemia and hyperlipemia, mainly is owing to have a liking for the food greasy and surfeit flavour, so that retention of damp-heat in the interior, double again affection of exogenous wind-cold, the invasion and attack meridians, the qi-blood-body fluid operation is obstructed, then make the damp and hot expectorant that decocts into, the stasis of blood is coagulated the network road, causes the redness and swelling of joints causalgia.Also have because of the natural endowment deficiency, or aged debility, visceral dysfunction is especially with the two dirty dysfunctions of spleen kidney, dysfunction of the spleen in transportation, ascending the clear and descending the turbid is had no right, and the kidney flatusization is distinguished not turbid mistake department, gives birth in damp and hot, accumulate heat-transformation of a specified duration, poly-expectorant stays the stasis of blood, and causes the winddamp phlegm stasis of blood, and numbness hinders due to the meridians.
Modern medicine thinks that then gout continues the disease that raises and cause owing to heritability or the acquired cause of disease cause purine metabolism obstacle and blood uric acid.It is one group of disease of tissue injury due to long-term purine metabolic disturbance, blood uric acid increase.Clinical characters comprises that hyperuricemia, gouty acute arthritis show effect etc. repeatedly, treat untimely, course of disease delay, gout complication such as hypertension, hyperlipidemia, coronary heart disease, diabetes, renal calculus often occur together.In China, gout was relatively more rare in the past, but in recent years, because the improvement of medical condition and medical worker are to the raising of gout understanding, make that to be failed to pinpoint a disease in diagnosis with mistaken diagnosis be the gout of rheumatic arthritis, rheumatoid arthritis, erysipelas, osteoarthritis, tuberculous arthritis, allergic arthritis, can in time be diagnosed; Simultaneously, along with high development of social economy, the change of life style, the sickness rate of gout significantly improves.The human appearance arranged on earth, just have gout to exist.Promptly adopt gout one speech about Europe in 1270 greatly, English is gout.Its implication is " deposition ", " gathering ".At that time to goat because of it be unclear that.Because of its pain as wind, come soon, go also soon, therefore be called as gout.Today, gout has become one of disease of serious harm human health, but thoroughly effective at present medicine does not almost have.
Summary of the invention
Purpose of the present invention is exactly in order to address the above problem, provide a kind of medicine for the treatment of gout, hyperuricemia and hyperlipemia according to Chinese medical theory, this medicine can reach the effect of pain, mitigation symptoms, uric acid reducing and blood fat due to quick alleviation or the elimination gout.
The present invention also aims to provide the preparation method of the various preparations of described medicine.
The crude drug and the parts by weight thereof of medicine active ingredient that make treatment gout of the present invention, hyperuricemia and hyperlipemia are as follows: Semen Cassiae 3～19, Herba Plantaginis 9～30, Fructus Ligustri Lucidi 6～25, Zaocys 9～19, Nidus Vespae 5～15, Herb Gynostemmae Pentaphylli 10～30.
Preferred plan is as follows: Semen Cassiae 12～15, Herba Plantaginis 17～25, Fructus Ligustri Lucidi 11～13, Zaocys 13～16, Nidus Vespae 9～13, Herb Gynostemmae Pentaphylli 16～23.
For consumption per capita, the unit of above-mentioned composition is gram.The Main Ingredients and Appearance of crude drug comprises:
Semen Cassiae: chrysophanol (Chrysophanol), emodin-6-methyl ether (Emodin-6-methyl ether), obtusin (Obtusin)
Herba Plantaginis: aucubin (Aucubin), plantagin (Plantaginin), ursolic acid (Ursolic acid) etc.
Fructus Ligustri Lucidi: oleandrin (Olearopein), oleanolic acid (Oleanolic acid), Fructus Ligustri Lucidi glycosides (Nuzhenide), ursolic acid (Ursolic acid) mannitol (Mannitol) etc.
Zaocys: protein, aminoacid, fat etc.
Nidus Vespae: volatile oil, protein, calcium, ferrum etc.
Herb Gynostemmae Pentaphylli: gypenoside class (Gypenosides), trace element, aminoacid, carbohydrate content etc.
The inventor through investigative test, finds out the medicine of specific composition, specific consumption, its clinical efficacy highly significant at the etiology and pathogenesis of gout, hyperuricemia and hyperlipemia.Semen Cassiae, Herba Plantaginis, Herb Gynostemmae Pentaphylli heat clearing away, dampness removing in the side, reduce phlegm; Zaocys, Nidus Vespae dispelling wind and removing obstruction in the collateral, blood-activating analgetic; Fructus Ligustri Lucidi, Herb Gynostemmae Pentaphylli kidney and spleen invigorating.
Whole prescription is played the effect of clearing away heat-damp and promoting diuresis, dispelling pathogenic wind and eliminating phlegm, collateral dredging blood stasis dispelling, kidney and spleen invigorating, eliminating impediment pain relieving altogether.But the Herba Plantaginis diuresis promotes respiratory mucus secretion, dilution sputum; But Fructus Ligustri Lucidi human body immunity improving function has heart tonifying diuresis and hepatoprotective effect; But the Zaocys sedation and analgesia, blood vessel dilating; But the diuresis of Nidus Vespae heart tonifying, blood vessel dilating; But the Semen Cassiae antihypertensive diuretic reduces serum cholesterol; Herb Gynostemmae Pentaphylli can strengthen the human body cell vigor, and accelerate blood circulation enhances metabolism, and human body immunity improving power has defying age, blood pressure lowering, the fat of dispelling, antiinflammatory, many effects such as calm the nerves, be good for the stomach.All components are share the accelerate blood circulation, enhance metabolism, and blood fat reducing, sedation and analgesia, remarkable to the therapeutic effect of gout, hyperuricemia and hyperlipemia.
Medicine of the present invention directly be taken after can water decocting, and also can pulverize solid preparations such as making powder, pill, tablet, capsule, or water decocts or with making various oral formulations after the alcohol extraction.
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 crude drug gross weights in the crude drug 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 crude drug gross weight in the crude drug 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) Drug therapy gout effect of the present invention is remarkable, has no side effect, and pain relieving is fast, and dose is little, lasting medicine.Select for use uric acid sodium crystallization (MUS) to induce the acute gouty arthritis animal model and the intact animal of foot swelling, the result shows this prescription, and arthroncus has significant antagonism to the rat gouty; Show that with hot plate method, writhing method test this prescription has significant analgesia role, and comparison is more lasting according to the medicine effect.According to acute toxicity test, this poison of drug is very little, can not ask LD
50Its, maximum tolerated dose was the 7.2g/20g body weight every day, was more than 800 times of clinical consumption, therefore, and this medicine clinical practice safety non-toxic.Long term toxicity test finds no toxic action.The clinical observation total effective rate reaches 92%, and pain relieving is fast, dose is little.Took two months, blood uric acid obviously descends, and difference reaches 151.8 ± 139.2 before and after the treatment.In a word, this prescription has excellent curative to acute gouty arthritis and gouty arthritis,chronic acute attack, can reduce patient with gout blood uric acid content simultaneously, improves the joint movement function of patient with gout.Part weight in patients, blood pressure, blood glucose, blood triglyceride, cholesterolemia also reduce.Do not find any untoward reaction;
(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): Semen Cassiae 9, Herba Plantaginis 30, Fructus Ligustri Lucidi 15, Zaocys 12, Nidus Vespae 10, Herb Gynostemmae Pentaphylli 30.
, assort earlier by the recipe quantity weighing with above-mentioned Six-element Chinese medicine, dry (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): Semen Cassiae 12, Herba Plantaginis 19, Fructus Ligustri Lucidi 20, Zaocys 9, Nidus Vespae 15, stricture of vagina thigh indigo plant 15.
With above-mentioned Six-element Chinese medicine, assort earlier, put into extraction pot, add 6～13 water gagings and extract, extract 1～3 time by the recipe quantity weighing, 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): Semen Cassiae 9, Herba Plantaginis 25, Fructus Ligustri Lucidi 20, Zaocys 9, Nidus Vespae 15, Herb Gynostemmae Pentaphylli 20.
With above-mentioned Six-element Chinese medicine, assort by the recipe quantity weighing earlier, put into extraction pot, add 6～13 times of amounts of dose, 50～80% ethanol extractions once, filter, the filtrate vacuum concentration reclaims ethanol, and 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, and promptly gets gout capsule.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): Semen Cassiae 9, Herba Plantaginis 25, Fructus Ligustri Lucidi 20, Zaocys 9, Nidus Vespae 15, Herb Gynostemmae Pentaphylli 20.
With above-mentioned Six-element Chinese medicine, assort by the recipe quantity weighing earlier, put into extraction pot, add 6～13 times of water gagings of dose and extract, extracting solution obtains concentrated solution through vacuum concentration, and the concentrated solution spray drying gets dry extract, the dry extract mixing, and granulation, packing, promptly.
Embodiment 5, production tablet
Form (unit gram): Semen Cassiae 9, Herba Plantaginis 25, Fructus Ligustri Lucidi 20, Zaocys 9, Nidus Vespae 15, Herb Gynostemmae Pentaphylli 20
With above-mentioned Six-element Chinese medicine, assort by the recipe quantity weighing earlier, put into extraction pot, add 6～13 times of amounts of dose, 30～80% ethanol extractions, extracting solution obtains concentrated solution through vacuum concentration, and the concentrated solution spray drying gets dry extract, dry extract mixing, granulation, tabletting.
Animal experiment study
The pharmacodynamics animal experiment study
1. test objective: according to the function that cures mainly gout of the gout capsule of embodiment 3 preparations, select for use uric acid sodium crystallization (MUS) to induce the acute gouty arthritis animal model and the intact animal of foot swelling, the resist inflammation on repercussive function of thoroughly evaluating gout capsule and analgesic activity, to determine drug action, efficacy strength and the characteristics of gout capsule, for clinical research provides foundation.
2. the resist inflammation on repercussive function of gout capsule
2.1 summary: the equilibrium of regular grade SD rat is divided into 5 groups at random, i.e. normal saline negative control group, positive drug matched group, large, medium and small three the dosage groups of gout capsule, 10 every group.By the administration of each 0.72ml/100g body weight volume, irritate stomach and give gout capsule every day, experimentizes after 7 days.Cause inflammation in the right back sufficient plantar subcutaneous injection micro-crystal type uric acid sodium suspension of rat, adopt the rat foot claw volumetric type meter, mensuration causes the volumetrical variation of scorching forward and backward right back sufficient sole of the foot pawl (per hour detecting once continuous 6 times after causing inflammation), so that the difference of the sufficient volume in scorching front and back is as the swelling degree.After found that normal saline group rat injection uric acid, the 1h foot sole of the foot promptly begins swelling, and 3-4h swelling reaches the peak, and 5-6h swelling still clearly.Compare with the normal saline group, gout capsule and positive drug indometacin group all can significantly alleviate rat paw edema at each time point; Wherein the gout capsule low dose promptly shows as tangible anti-swelling effect.Compare with positive drug, gout capsule is better than the indometacin group in the effect of 1h time point, but is weaker than the indometacin group in the effect of 5h and two time points of 6h.Comprehensive The above results can think that gout capsule has the effect of good gout arthroncus.
2.2 experiment purpose: observe the influence of the rat gouty arthroncus that gout capsule causes uric acid.
2.3 the gout capsule that medicine: embodiment 3 obtains, the positive control drug indometacin is bought from hospital pharmacy.Uric acid is Shanghai chemical reagents corporation of Chinese Medicine group product, lot number: 990505.The clinical dosage that provides by producer and the clinical consumption intermediate value of positive control are converted out the middle dosage that rat is used in (pressing the body surface area method) experiment, and as heavy dose of, 1/2 times of this dosage as low dose with 1 times of this dosage.Above-mentionedly be subjected to reagent all to be mixed with the medicinal liquid of respective concentration with normal saline standby facing with preceding, press the administration of 0.72ml/100g body weight.
2.4 animal: 50 of regular grade SD rats, body weight 180 ± 20g, male, provide the animal quality certification number by No.1 Military Medical Univ.'s Experimental Animal Center: 000A046.
2.5 experimental technique: above-mentioned rat equilibrium is divided into 5 groups at random: normal saline negative control group, positive drug matched group, large, medium and small three the dosage groups of gout capsule, 10 every group.Irritate stomach and give gout capsule every day, experimentizes after 7 days.Cause inflammation in the right back sufficient plantar subcutaneous injection micro-crystal type uric acid sodium suspension of rat.Adopt the rat foot claw volumetric type meter, measure and cause the volumetrical variation of scorching forward and backward right back sufficient pawl (per hour detecting once continuous 6 times after causing inflammation), so that the difference of scorching metapedes volume is as the swelling degree.
2.6 experimental result: behind the normal saline group rat paw injection uric acid, the 1h foot sole of the foot promptly begins swelling, and 3-4h swelling reaches the peak, and 5-6h swelling still clearly.Compare with the normal saline group, gout capsule and positive drug indometacin group can significantly alleviate rat paw edema at each time point; Wherein the gout capsule low dose promptly shows as tangible anti-swelling effect.Compare with positive drug, gout capsule is better than the indometacin group in the effect of 1h time point, but is weaker than the indometacin group in the effect of 5h and two time points of 6h.The results are shown in Table 1.
The variation of table 1 rat paw edema degree (n=10, x ± SD)
| 1h | 2h | 3h | 4h | 5h | 6h | |
| Normal saline | 0.40±0.14 | 0.56±0.19 | 0.61±0.12 | 0.64±0.14 | 0.51±0.18 | 0.47±0.14 |
| Positive drug | 0.36±0.06 | 0.27±0.18 ** | 0.18±0.17 *** | 0.15±0.10 *** | 0.12±0.09 *** | 0.09±0.06 *** |
| Gout capsule-big | 0.10±0.1 *** | 0.25±0.15 *** | 0.32±0.1 *** | 0.20±0.13 *** | 0.27±0.1 ** | 0.24±0.1 ** |
| Gout capsule-in | 0.32±0.17 | 0.24±0.13 *** | 0.22±0.15 *** | 0.20±0.18 *** | 0.29±0.09 ** | 0.19±0.12 *** |
| Gout capsule-little | 0.11±0.11 *** | 0.21±0.10 *** | 0.21±0.09 *** | 0.16±0.11 *** | 0.26±0.13 ** | 0.22±0.14 *** |
Compare with the normal saline group:
*P＜0.01,
* *P＜0.001.
2.7 conclusion: arthroncus has significant antagonism to gout capsule to the rat gouty.
3. the analgesic activity of gout capsule
3.1 experiment material
(1) medicine: gout capsule, every capsule content is equivalent to crude drug in whole 3g; Etidocine tablet (indometacin tablets), the 25mg/ sheet, Linfen, Shanxi Province biochemical-pharmaceutical factory is produced, lot number: 98051345.
(2) animal: Kunming mouse, female, body weight 18-22g is provided by Guangdong Province's Experimental Animal Center.
(3) main agents: the analytical pure glacial acetic acid, content＞99.5%, east, Chongqing chemical reagent work produces, lot number: 950303-1.
(4) key instrument: GJ-8402 type hot plate dolorimeter, the white stone electronics medicine in Ninghai, Zhejiang instrument plant produces; The too suitable board stopwatch of PC9730 type, Tianfu Electronic Co., Ltd., Shenzhen produces.
3.2 experimental technique
(1) hot plate method: with hot plate dolorimeter screening mice, allly lick the metapedes time less than 5 seconds or all give it up, measure the normal pain threshold of each treated animal 2 times before the experiment greater than 30 seconds persons, get 2 times meansigma methods as this Mus administration before pain threshold.Qualified mice is divided into 5 groups at random, 10 every group.Each group is irritated stomach (ig) amount of liquid medicine and is 0.2ml/10g, matched group ig normal saline wherein, indometacin group ig indometacin suspension (0.025g/Kg), (the distilled water preparation of the high, medium and low dosage group of gout capsule ig gout capsule solution, dosage is respectively 2.25g/Kg, 1.35g/Kg, 0.45g/Kg, 5 times, 3 times, 1 times of the clinical dosage that is equivalent to be grown up).Each treated animal is by above-mentioned dosage ig administration, every day 1 time, continuous 6 days.After the administration in the 6th day, measure each treated animal pain threshold respectively at 30min, 60min.Pain threshold carries out statistical procedures before and after the administration.The results are shown in Table 2.
The influence pain caused to the mice hot plate method of table 2 gout capsule (x ± s, n=10)
| Group | The preceding threshold of pain of administration | The 30min threshold of pain after the administration in the 6th day | The 60min threshold of pain after the administration in the 6th day |
| Dosage group gout capsule low dose group in the matched group indometacin group gout capsule high dose group gout capsule | 18.73±4.95 18.63±5.21 18.90±4.58 18.81±5.28 18.81±4.93 | 18.82±5.19 38.64±10.21** 29.76±9.39* 28.77±8.89* 23.93±9.63 | 19.15±5.21 33.88±11.03* 39.84±11.17** 37.93±10.87** 30.19±10.85* |
Annotate: compare * P＜0.01, * * P＜0.05 with matched group.(down together)
Conclusion: indometacin, high, normal, basic three the dosage groups of gout capsule all have significant analgesia role, and the analgesic activity of indometacin is faster, and the analgesic activity of gout capsule is then more slow, but more lasting.
(2) writhing method: the same hot plate method of stating of animal grouping, dosage and time.After respectively organizing administration 30min on the 6th day, freshly prepared 0.6% glacial acetic acid of each Mus lumbar injection (0.2ml/ is only), mouse writhing number of times in the immediate record 30min.The results are shown in Table 3.
The influence of table 3 gout capsule Dichlorodiphenyl Acetate induced mice writhing response (x ± s, n=10)
| Group | Turn round the body number of times in the 30min | Reduce percentage rate (%) |
| Dosage group gout capsule low dose group in the matched group indometacin group gout capsule high dose group gout capsule | 27.67±3.04 14.28±2.08** 15.03±2.87** 17.04±3.02** 22.73±3.98* | 47.98 45.77 37.53 20.02 |
Conclusion: indometacin, high, normal, basic three the dosage groups of gout capsule all can suppress mice significantly and turn round the body number of times because of what the lumbar injection glacial acetic acid caused, and indometacin, the dosage group effect of gout capsule senior middle school are more remarkable.
Toxicity test
The gout capsule acute toxicity test
1. test objective: the acute toxicity test and the maximum tolerated dose of observing gout capsule.
2. be subjected to the reagent thing: gout capsule, every capsule contains crude drug 3g, is provided lot number by Guangzhou Lanyun Medicine Research Co., Ltd.: 990304.Concentrate before the test and be mixed with the Cmax (100%) that can irritate stomach, cold preservation is standby.
3. animal origin: 30 of Kunming kind closed colony mices, male and female half and half, body weight 18-22g is provided by medical faunae center, Guangdong Province.
4. experimental technique
4.1 acute toxicity test
Get 10 of mices, fasting (can't help water) 12 hours before the experiment after the gout capsule that every Mus press Cmax is irritated stomach with maximum gastric capacity (0.4ml/10g body weight),, was observed 7 days with normal diet continuously to animal.
4.2 maximum tolerance determination
Get 20 of mices, fasting (can't help water) 12 hours before the experiment, every Mus press the gout capsule solution of Cmax and irritates with maximum gastric capacity (0.4ml/10g body weight), in 1 day behind the continuous irrigation stomach 3 times, total dosage 7.2g/20g body weight.Give animal with normal diet, observed continuously 7 days.
5. experimental result
5.1 acute toxicity test
Laboratory animal was observed 7 days, did not see animal dead.And because of being subjected to drug level and volume restrictions, can not find to cause the dosage of dead mouse, so can't measure the LD that gout capsule solution is irritated stomach
50
5.2 maximum tolerance determination
Laboratory animal was observed 7 days, did not see animal dead, and rarely seen just to behind the animal filling stomach, animal activity reduces, recovered normal in general about 1 hour, after weighing in the 7th day, put to death mice, core, liver, spleen, lung, stomach, intestinal, brain, macroscopic pathological abnormalities is not seen in perusal.
Be calculated as follows the maximum tolerated dose of mice:
The dosis tolerata of maximum tolerated dose multiple=every mice of mice/mice average weight (20g) * adult's average weight (60000g)/adult's consumption every day
＝7.2×60000/20×27
=800 times
6. conclusion: according to acute toxicity test, this poison of drug is very little, can not ask LD
50Its, maximum tolerated dose was the 7.2g/20g body weight every day, was more than 800 times of clinical consumption.Therefore, this medicine clinical practice safety non-toxic.
The gout capsule long term toxicity test
1. experiment purpose
The safety of objective evaluation gout capsule.
2. be subjected to the reagent thing
Gout capsule, every capsule contains crude drug 3g, is provided lot number by Guangzhou Lanyun Medicine Research Co., Ltd.: 990304.Concentrate before the test and be mixed with the Cmax (100%) that can irritate stomach, cold preservation is standby.
3. laboratory animal
The Wistar rat, body weight 100 ± 12g is provided by medical faunae center, Guangdong Province.
4. test method
Get 80 of rats, arrange in pairs or groups at random by sex and body weight and to be divided into 4 groups, every group 20, respectively as the gout capsule height, in, low dose group and blank group, 3 dosage groups are respectively: 22.5g crude drug/kg, 11.25g crude drug/kg, 2.25g crude drug/kg (50 times of the clinical dosage that is equivalent to be grown up, 25 times, 5 times), matched group is irritated the stomach distilled water, administration and distilled water volume are 1ml/100g, every morning gastric infusion 1 time, successive administration and distilled water 3 months, claim the weight of animals weekly 1 time before the administration and during the administration, adjust dosage with the average weight of animal weekly.
Duration of test is observed rat general state, sign, food ration, drinking-water and feces character every day.It is heavy to write down each Mus that takes by weighing weekly, understands the influence of gout capsule to the weight of animals.Last administration 24 hours, every group is extracted rat each 14 (male and female half and half), from left external iliac vein blood-letting and collect blood and check animal as first.The rat of every group of remainder stops administration, and animal is checked as second batch in the conventional 2 all backs of raising.Blood to two batches of animals carries out following index determining: hematochrome (Hb), red blood cell count(RBC) (RBC), reticulocyte (Rct), platelet (PLT), numeration of leukocyte (WBC), leukocyte differential count (WDC), blood glucose (GLu), creatinine (CRE), blood urea nitrogen (BUN), T-CHOL (T-CH), total protein (TP), albumin (ALR), total bilirubin (T-BIL),, glutamate pyruvate transaminase (ALT), glutamic oxaloacetic transaminase, GOT (AST), have harmless to observe gout capsule to the hemogram and the hepatic and renal function of laboratory animal.After getting blood, each treated animal is put to death, get brain, the heart, liver, spleen, lung, kidney immediately and weigh, internal organs such as brain, the heart, liver, spleen, lung, kidney, adrenal gland, testis, epididymis, ovary, uterus carry out perusal, and make tissue slice, mirror checks that down pathology change.
5. experimental result
5.1 gout capsule is to the influence of rat ordinary circumstance and body weight
In 3 months of successive administration, each administration group and matched group relatively at aspect there was no significant differences such as activity, food ration, stool, fur and body weight gains, show no obvious abnormalities situation.The body weight gain situation sees Table 4.
The influence that table 4 gout capsule successive administration increased rat body weight in 3 months (n=20, x ± s, g)
| Group | Before the administration | 1W | 3W | 5W | 7W | 9W | 11W | 13W |
| Dosage group low dose group in the matched group high dose group | 101.23±5.21 102.64±6.54 100.26±5.65 104.65±7.38 | 115.06±8.32 117.08±7.87 116.45±7.88 118.33±8.82 | 161.39±10.54 164.89±12.01 163.54±1121 166.48±12.43 | 198.86±15.53 201.77±14.64 197.49±13.24 199.35±16.32 | 260.85±24.84 265.79±25.76 259.98±22.18 263.44±26.85 | 303.88±30.59 310.02±34.08 305.65±32.21 307.55±35.53 | 360.32±34.04 369.99±36.37 362.68±33.31 370.19±32.08 | 383.75±38.84 390.96±39.62 385.84±35.47 388.91±38.21 |
Annotate: it is wide to be limited to table, the weight of animals in unlisted 2,4,6,8,10,12 weeks; Each organize the administration group respectively with matched group relatively, p is all＞0.05.
5.2 gout capsule is to the influence of rat hemogram
In 2 weeks after successive administration 3 months and the drug withdrawal, each administration group and control rats hemogram be there was no significant difference relatively, and all in normal range.The results are shown in Table 5,6.The influence to the rat hemogram in 3 months of table 5 gout capsule successive administration (n=14, x ± s)
| Group | Hb (g/L) | RBC (×10 12/L) | Rct (％) | PLT (×10 9/L) | WBC (×10 9/L) | WDC(％) | |||
| N | L | E | M | ||||||
| Matched group | 135.22±7.20 | 7.06±0.89 | 2.38±1.56 | 598.83±75.53 | 10.88±2.85 | 23.38±3.54 | 76.36±8.14 | 0.85±0.84 | 0.60±0.68 |
Annotate: each administration group rat hemogram value compares with matched group respectively, and p all＞0.05.
Table 6 gout capsule successive administration after 3 months 2 weeks of drug withdrawal to the influence of rat hemogram (n=6, x ± s)
| Group | Hb (g/L) | RBC (×10 12/L) | Rct (％) | PLT (×10 9/L) | WBC (×10 9/L) | WDC(％) | |||
| N | L | E | M | ||||||
| Dosage group low dose group in the matched group high dose group | 132.45±6.28 137.65±7.54 132.54±6.65 131.32±7.43 | 6.77±0.87 7.88±1.28 7.27±0.98 6.29±1.21 | 2.01±1.76 2.43±2.12 2.21±1.54 2.08±1.36 | 587.6±70.98 598.76±83.23 578.88±78.54 583.43±71.48 | 10.14±2.34 11.98±2.69 11.08±2.43 10.01±2.87 | 21.96±3.46 24.76±3.04 23.98±2.95 23.67±3.43 | 75.77±7.87 78.67±8.32 76.32±7.65 74.89±6.87 | 0.87±0.87 1.21±0.97 0.96±0.89 0.87±0.89 | 0.76±0.65 0.78±0.85 0.76±0.81 0.70±0.56 |
Annotate: each administration group rat hemogram value compares with matched group respectively, and p all＞0.05.
5.3 gout capsule is to the influence of rat blood biochemical indicator
In 2 weeks after successive administration 3 months and the drug withdrawal, each administration group and control rats blood parameters be there was no significant difference relatively, and all in normal range.The results are shown in Table 7,8.
The influence to the rat blood biochemical indicator in 3 months of table 7 gout capsule successive administration (n=14, x ± s)
| Group | GLu (mmol/L) | CRE (mmol/L) | BUN (mmol/L) | T-CH (mmol/L) | TP (g/L) | ALR (g/L) | T-BIL (mmol/L) | ALT (IU/L) | AST (IU/L) |
| Dosage group low dose group in the matched group high dose group | 7.21±0.57 6.56±0.65 6.82±0.78 7.01±0.68 | 63.65±6.76 67.76±7.21 66.32±6.78 65.43±6.86 | 7.01±0.78 7.32±0.76 7.58±0.43 7.43±0.76 | 2.02±0.87 1.54±0.78 1.92±0.54 1.98±0.86 | 68.32±5.43 71.56±5.87 70.43±5.89 72.54±5.76 | 31.94±3.32 32.76±3.77 36.87±3.78 37.11±4.21 | 12.22±4.32 13.13±4.76 14.32±4.37 15.44±4.86 | 60.43±12.45 63.21±11.83 66.32±14.15 67.32±14.21 | 145.87±27.76 150.53±28.43 148.54±27.66 152.04±28.20 |
Annotate: each administration group rat blood biochemical indicator value compares with matched group respectively, and p all＞0.05.
Table 8 gout capsule successive administration after 3 months 2 weeks of drug withdrawal to the influence of rat blood biochemical indicator (n=6, x ± s)
| Group | GLu (mmol/L) | CRE (mmol/L) | BUN (mmol/L) | T-CH (mmol/L) | TP (g/L) | ALR (g/L) | T-BIL (mmol/L) | ALT (IU/L) | AST (IU/L) |
| Dosage group low dose group in the matched group high dose group | 7.02±0.65 6.98±0.68 7.06±0.76 7.12±0.69 | 60.43±6.21 64.65±6.76 65.67±6.54 65.87±6.75 | 6.82±0.67 7.03±0.68 7.23±0.61 7.45±0.76 | 1.87±0.76 1.78±0.81 1.78±0.46 1.89±0.87 | 64.65±5.13 70.83±5.69 70.43±5.89 72.54±5.76 | 30.43±3.31 31.87±3.65 33.52±3.91 35.45±4.23 | 11.57±4.43 12.67±4.21 13.42±4.45 15.13±4.87 | 62.43±11.43 60.28±12.55 65.78±13.68 66.66±15.14 | 144.66±26.98 147.55±27.62 147.83±27.78 150.67±27.06 |
Annotate: each administration group rat blood biochemical indicator value compares with matched group respectively, and p all＞0.05.
5.4 gout capsule is to the influence of rat important organ weight
In 2 weeks after successive administration 3 months and the drug withdrawal, each administration group and control rats main organs weight ratio are than there was no significant difference.The results are shown in Table 9,10.
The influence to rat main organs weight in 3 months of table 9 gout capsule successive administration (n=14, x ± s)
| Group | Brain | The heart | Liver | Spleen | Lung | Kidney |
| Dosage group low dose group in the matched group high dose group | 1.82±0.05 1.86±0.11 1.81±0.09 1.80±0.08 | 1.43±0.25 1.38±0.32 1.40±0.28 1.42±0.27 | 15.23±3.65 13.68±3.24 14.43±3.21 15.11±3.02 | 1.68±0.32 1.73±0.42 1.72±0.47 1.70±0.51 | 2.67±0.54 2.92±0.62 2.69±0.74 2.64±0.73 | 1.54±0.21 1.42±0.52 1.48±0.37 1.50±0.28 |
Annotate: each administration group rat body weight value compares with matched group respectively, and p all＞0.05.
Table 10 gout capsule successive administration after 3 months 2 weeks of drug withdrawal to the influence of rat main organs weight (n=6, x ± s)
| Group | Brain | The heart | Liver | Spleen | Lung | Kidney |
| Dosage group low dose group in the matched group high dose group | 1.88±0.12 1.99±0.21 1.96±0.15 1.92±0.17 | 1.51±0.32 1.47±0.47 1.49±0.45 1.52±0.68 | 16.46±3.68 14.79±3.75 15.43±3.85 16.38±3.77 | 1.80±0.43 1.79±0.48 1.75±0.52 1.74±0.46 | 2.83±0.75 3.15±0.66 2.85±0.68 2.71±0.62 | 1.61±0.34 1.48±0.45 1.52±0.51 1.56±0.38 |
Annotate: each administration group rat body weight value compares with matched group respectively, and p all＞0.05.
5.5 gout capsule is to the influence of rat important organ histopathology form
2 weeks after successive administration 3 months and the drug withdrawal, two batches of rats of getting are extremely dissected, each administration group important organ brain of perusal, the heart, liver, spleen, lung, kidney, adrenal gland, testis, epididymis, ovary, uterus etc. are no abnormal, then each group rat important organ is drawn materials in same area, fix with 10% formalin.The above-mentioned organ-tissue of each administration group and control rats is made tissue slice and carried out pathological examination, find that various organ structures are normal, cell dyeing is even, does not have obviously to change.
6 experiment conclusion
The result shows through the rat long term toxicity test, with gout capsule 22.5,11.25,2.25g three kinds of dosage of crude drug/kg (are respectively 50 times of adult's consumption, 25 times and 5 times), every day 1 time, continuous 3 months to 2 weeks after rat oral gavage administration and the drug withdrawal, compare with the blank group of irritating the stomach distilled water, each dosed administration is to the general state (mode of appearance of rat, movable, food ration, stool shape etc.), growth promoter (body weight gain), hemopoietic function (hematological examination), liver function (blood parameters), renal function (blood parameters), vitals weight and pathological examination all find no the overt toxicity effect.So can think that under prescribed dose to take gout capsule toxicity the longer course of treatment very low, take safety.Clinic trial can be provided, further examine or check it again and have or not toxicity.
The report of gout capsule clinical preliminary observation
Gout capsule of the present invention has that clearing away heat-damp and promoting diuresis, promoting blood circulation to remove obstruction in the collateral, circulation of qi promoting dispel the wind, the effect of anti-inflammatory analgetic, the liver and the kidney tonifying, prove that through pharmacodynamic study it has tangible resist inflammation on repercussive function to the gouty arthritis due to the crystallite urate, the pain that physicochemical irritation is caused has significant analgesia role.In order further to observe the clinical efficacy of gout capsule, we have carried out the clinical contrast observation than system, now are described as follows:
Physical data
1.1 general data
All observe case and be in hospital and the outpatient, totally 160 examples are divided into treatment group and matched group at random, and wherein 100 examples are organized in treatment, male's 95 examples, women's 5 examples; Age 18-68 year, average 55.3 years old; Course of disease 2-15, average 8.2 years; Matched group 60 examples, male's 57 examples, women's 3 examples; Age 18-64 year, average 54.9 years old; Course of disease 2-14, average 8.4 years.Through the homogeneity check, P＞0.1 has comparability.
1.2 it is disease accompanied
The coronary heart disease that occurs together in the treatment group 20 examples, diabetes 23 examples, hypertension 38 examples, hyperlipidemia 40 examples; The coronary heart disease that occurs together in the matched group 15 examples, diabetes 17 examples, hypertension 28 examples, hyperlipidemia 30 examples.
2 cases are selected
2.1 diagnostic criteria
" traditional Chinese medical science disease diagnosis criterion of therapeutical effect " and the American Rheumatism Association's diagnostic criteria of issuing according to State Administration of Traditional Chinese Medicine in 1977 (see Meng Zhaoheng. gout. combined publication society of China Concord Medical Science University of Beijing Medical University, 1997,120-121):
(1) in the joint fluid leukocyte urate crystal is arranged.
(2) suction of tophus pin or biopsy have urate crystal.
(3) have that 6 above persons also can make a definite diagnosis in following 12:
A.1 time above arthritis outbreak;
B. inflammation peaked within 1 day;
C. monarthritis outbreak;
D. arthremia swelling;
E. the 1st toe sole of the foot arthralgia or swelling;
F. one-sided the 1st toe sole of the foot arthralgia outbreak;
G. involve one-sided midtarsal joints;
H. suspicious tophus;
J. serum uric acid level raises;
K. asymmetric 1 arthralgia;
1.X line shows that the cystis degeneration accompanies bone to soak under the cortical bone;
M. arthritis is between stage of attack, joint fluid antibacterial culturing feminine gender.
(4) no above-mentioned 3 but have following 3 persons and also can make a definite diagnosis:
A. typical monarthritis has a symptom intermission thereupon;
B. after giving the colchicine treatment, synovitis can be alleviated rapidly, and the special treatment effect is arranged;
C. hyperuricemia.
2.2 standard of including in: constitutional acute gouty arthritis and gouty arthritis,chronic acute attack person; Chinese medical discrimination is a syndrome of accumulated dampness-heat; During morbidity not with other drug and method therapist; Age 18-70 one full year of life.
2.3 exclusion standard: can be suspected to have malignant disease, secondary gout person, with serious hepatic renal dysfunction person, with rheumatism, rheumatoid arthritis and cellulitis, erysipelas, suppurative arthritis, traumatic arthritis, chondrocalcinosis, psoriatic arthritis etc., can not cooperation person with psychosis, alzheimer disease etc.
3 Therapeutic Method: oral gout capsule is organized in treatment, every day 3 times, each 3 of acute stage, each 2 of catabasis, treats for 8 weeks continuously; Matched group is taken ZHONGHUA TONGFENGDING JIAONANG (being produced by banknotes-system medicine company in the China Academy of TCM), and every day 3 times, each 3, acute stage adds indometacin, each 25mg, every day 3 times.
4 observation index: clinical symptoms sign, the changes of function of the local joint of especially falling ill; Blood uric acid (UA), erythrocyte sedimentation rate (ERS), numeration of leukocyte (WBC); Body weight, blood pressure, blood glucose, blood fat (T-CHOL, triglyceride, high density lipoprotein, low density lipoprotein, LDL), ALT, BUN etc.
5 criterions of therapeutical effect
Curative effect determinate standard with reference to " new Chinese medicine clinical research guideline " formulated divides 4 grades.
Clinical recovery: the symptom complete obiteration, joint function recovery is normal, blood uric acid＜380 μ mol/L, erythrocyte sedimentation rate, numeration of leukocyte drop to normal level.
Produce effects: cardinal symptom disappears, and function of joint is recovered substantially, blood uric acid＜416 μ mol/L, and erythrocyte sedimentation rate, numeration of leukocyte are recovered the normal value level substantially.
Effectively: cardinal symptom disappears substantially, and function of joint makes moderate progress, and blood uric acid, erythrocyte sedimentation rate, numeration of leukocyte etc. descend to some extent.
Invalid: relatively preceding with treatment, each side does not all have improvement.
6 joint function disturbance criterion:
Joint function disturbance is divided into 4 grades.
The I level: comings and goings all can normally carry out.
The II level: moderate is limited, though there are not 2 or a plurality of joint not or limitation of activity, but still can be engaged in normal activity.
The III level: obviously limited, though take care of oneself, can not be engaged in general activity.
The IV level: bed or seat crouch, and can't take care of oneself.
I level 0 minute, II level 1 minute, III level 2 minutes, IV level 3 minutes.
Total mark compares before and after the treatment.
7 statistical method: ranked data are checked with Ridit, relatively with paired t check, relatively check the enumeration data X 2 test between group with two sample t before and after the treatment of dosage data.
8 therapeutic outcomes
8.1 gout capsule therapeutic effect.See Table 11.
The comparison of table 11 therapeutic effect (n, %)
| Group | Case load | Clinical recovery | Produce effects | Effectively | Invalid | Total effective rate |
| Treatment group matched group | 100 60 | 78(78) 33(55) | 10(10) 10(13.67) | 4(4) 6(10) | 8(8) 11(18.33) | 92(92) 48(81.67) |
Data are analyzed through Ridit in the table 1, and treatment group curative effect is better than matched group (P＜0.05).
8.2 gout capsule is to the influence of blood uric acid.See Table 12.
Blood uric acid compares (μ mol/L) before and after table 12 treatment
| Group | Case load | Before the treatment | After the treatment | Difference before and after the treatment |
| Treatment group matched group | 100 60 | 517.6±122.4 513.4±115.8 | 367.3±181.8** 401.9±151.7**△ | 151.8±139.2 112.6±133.6△ |
Annotate: * * is relatively preceding with treatment, P＜0.01; △ and treatment group compare, P＜0.05.
8.3 gout capsule is to the influence of joint movement function.See Table 13.
Function of joint integration comparison before and after table 13 treatment (x ± s)
| Group | Case load | Before the treatment | After the treatment | Difference before and after the treatment |
| Treatment group matched group | 100 60 | 2.67±0.12 2.64±0.09 | 0.48±0.08** 0.89±0.15**△ | 2.18±0.21 1.79±0.26△ |
Annotate: * * is relatively preceding with treatment, P＜0.01; △ and treatment group compare, P＜0.05.
8.4 gout capsule is to the influence of body weight, blood pressure, blood glucose, blood fat
After treatment group and the treatment of control group, part patient's body weight, blood pressure, blood glucose, blood fat have the reduction phenomenon, especially reduce more obviously with high triglyceride, hypercholesterolemia person, handle there was no significant difference before and after the treatment and between group but learn by statistics.
8.5 adverse reactions of patients is observed
Matched group part patient has poor appetite, abdominal distention, returns phenomenons such as acid after taking medicine 1 day, consideration may be the untoward reaction that indometacin causes; Treatment group patient does not have any abnormal response.Look into ALT, the variation of BUN no abnormality seen before and after all patient treatments.
9 discuss
Acute gouty arthritis and gouty arthritis,chronic acute attack belong to the category of the traditional Chinese medical science " pyretic arthralgia ", this type of patient's polymorph obesity, thick greasy, the greasy and surfeit flavour of preference for fat and sweet food, food and drink do not save usually, easily injure taste, cause transporting and transforming function of the spleen and stomach not normal, the unboiled water damp-phlegm is turbid then; Turbid the gathering of water damp-phlegm do not changed, and be strongly fragrant and heat-transformation then is a damp-heat accumulation; The water damp-phlegm is turbid to stagnate in meridians, and then QI-blood circulation is not smooth, stays and is the stasis of blood.So the patient shows as the red and swollen heat pain in morbidity joint.And the gouty arthritis,chronic patient often has the perennial root of deficiency of the liver and kindey.At above-mentioned pathogenesis, the gout capsule reasonable recipe strikes home, and gathers altogether that clearing away heat-damp and promoting diuresis, promoting blood circulation to remove obstruction in the collateral, circulation of qi promoting dispel the wind, the merit of anti-inflammatory analgetic, the liver and the kidney tonifying, with the card of treatment gout.
10 conclusions
Gout capsule has excellent curative to acute gouty arthritis and gouty arthritis,chronic acute attack, can reduce patient with gout blood uric acid content simultaneously, improves the joint movement function of patient with gout.Part weight in patients, blood pressure, blood glucose, blood triglyceride, cholesterolemia also reduce.Do not find any untoward reaction.
Claims (4)
1, a kind of medicine for the treatment of gout, hyperuricemia and hyperlipemia, the crude drug and the parts by weight thereof that it is characterized in that making this effective ingredient are as follows:
Semen Cassiae 3～19, Herba Plantaginis 9～30, Fructus Ligustri Lucidi 6～25, Zaocys 3～19, Nidus Vespae 5～15, Herb Gynostemmae Pentaphylli 10～30.
2, the medicine of treatment gout according to claim 1, hyperuricemia and hyperlipemia, the crude drug and the parts by weight thereof that it is characterized in that making this effective ingredient are as follows::
Semen Cassiae 12～15, Herba Plantaginis 17～25, Fructus Ligustri Lucidi 11～13, Zaocys 13～16, Nidus Vespae 9～13, Herb Gynostemmae Pentaphylli 16～23.
3, the preparation method of the oral liquid of the medicine of the described treatment gout of claim 1, hyperuricemia and hyperlipemia is characterized in that the water or the ethanol that add 6～13 times of suitable crude drug gross weights in crude drug 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.
4, the preparation method of the solid preparation of the medicine of the described treatment gout of claim 1, hyperuricemia and hyperlipemia is characterized in that the water or the ethanol that add 6～13 times of amounts of suitable crude drug gross weight in crude drug 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, mix homogeneously.
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| CN102908436B (en) * | 2012-11-12 | 2014-03-26 | 易春莲 | Particle type solid drink having curative effects on gout and preparation method thereof |
| CN104546987A (en) * | 2013-10-16 | 2015-04-29 | 浙江中医药大学 | Application of gynostemma pentaphyllum total saponins to prevention and cure of hyperuricemia |
| CN104644768A (en) * | 2015-02-07 | 2015-05-27 | 广州暨南生物医药研究开发基地有限公司 | Application of traditional Chinese medicine composition in preparation of medicine for treating kidney disease |
| CN107898947A (en) * | 2017-12-20 | 2018-04-13 | 何宝兰 | A kind of herb composition for treating gout, hyperuricemia and its preparation method and application |
| CN113679742A (en) * | 2021-08-30 | 2021-11-23 | 神农架林区蜜蜂天堂食品有限公司 | Preparation method and application of honeycomb alcohol extract |
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Owner name: GUANGZHOU LANYUN MEDICINE RESEARCH CO., LTD. Free format text: FORMER OWNER: ZHANG JING Effective date: 20100831 |
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Free format text: CORRECT: ADDRESS; FROM: 510632 ROOM 601, NO.15, HUAJING ROAD, TIANHE DISTRICT, GUANGZHOU CITY, GUANGDONG PROVINCE TO: 510663 D909, INTERNATIONAL BUSINESS INCUBATOR ZONE D, NO.3, JUQUAN ROAD, SCIENCE CITY OF HIGH-TECH INDUSTRIAL DEVELOPMENT AREA, GUANGZHOU |
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Effective date of registration: 20100831 Address after: 510663 high tech Industrial Development Zone of Guangzhou Science City skim Springs Road No. 3, Guangzhou international business incubator D D909 Patentee after: GUANGZHOU LANYUN MEDICINE RESEARCH Co.,Ltd. Address before: 510632 Guangdong city of Guangzhou province Tianhe District Hua Jing Lu No. 15 Room 601 Patentee before: Zhang Jing |
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Address after: 510663 Guangdong city of Guangzhou province high tech Industrial Development Zone of Guangzhou Science City skim Springs Road No. 3, Guangzhou international business incubator B District 301 Patentee after: GUANGZHOU HONGYUN MEDICAL SCIENTIFIC AND TECHNOLOGICAL CO.,LTD. Address before: Guangzhou hi tech Industrial Development Zone, Science City skim Springs Road No. 3, Guangzhou international business incubator D D909 Patentee before: GUANGZHOU LANYUN MEDICINE RESEARCH Co.,Ltd. |
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Effective date of registration: 20230627 Address after: 519000 Card slot 05, Room 408, Building 21, No. 1889 Huandao East Road, Hengqin New District, Zhuhai City, Guangdong Province Patentee after: Zhuhai Hengqin Hongtai Pharmaceutical Technology Co.,Ltd. Address before: 510663 No.301, zone B, Guangzhou International Business Incubator, No.3, Juquan Road, Science City, Guangzhou high tech Industrial Development Zone, Guangzhou City, Guangdong Province Patentee before: GUANGZHOU HONGYUN MEDICAL SCIENTIFIC AND TECHNOLOGICAL CO.,LTD. |
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Address after: Building D, 2nd Floor, No. 1168 Huanli Road, Zhenmei Community, Xinhu Street, Guangming District, Shenzhen City, Guangdong Province, 518107 Patentee after: Hongtai (Shenzhen) Pharmaceutical Technology Co.,Ltd. Address before: 519000 Card slot 05, Room 408, Building 21, No. 1889 Huandao East Road, Hengqin New District, Zhuhai City, Guangdong Province Patentee before: Zhuhai Hengqin Hongtai Pharmaceutical Technology Co.,Ltd. |