The specific embodiment
Below in conjunction with instantiation the present invention is described in further detail.
One, function and the function of each raw material in this medicine cures mainly
1. the function of various raw materials in this medicine:
Rhizoma Coptidis: the nature and flavor bitter cold, heat clearing and damp drying, eliminating fire and detoxication is monarch drug;
Fructus Mume or Fructus Mume: the astringing intestine to stop diarrhea of astringing the lung, relieving colic caused by ascaris promotes the production of body fluid;
Pericarpium Papaveris: astringe the lung, astringing intestine to stop diarrhea pain relieving;
Fructus Mume or Fructus Mume, Pericarpium Papaveris two medicines can strengthen the merit of monarch drug treatment chronic diarrhea chronic dysentery, are ministerial drug altogether.
Rhizoma Zingiberis: the warming middle-JIAO recuperating depleted YANG, warming the lung to resolve fluid-retention can prevent Rhizoma Coptidis bitter cold damage gastric qi, with being corrigent;
The Radix Aucklandiae: promoting the circulation of QI to relieve pain;
Rhizoma Corydalis: promoting the circulation of QI to relieve pain.
The two is messenger drug the Radix Aucklandiae, Rhizoma Corydalis.
2. function cures mainly:
The spleen and stomach regulating, the astringing intestine to stop diarrhea pain relieving.Be used for incoordination between the liver and spleen, dysentery stomachache, chronic non-specific ulcerative colitis disease person.
3. usage and dosage:
Oral, three times on the one, one time 4 gram.
Two, preparation method
1. concentrated pill: get Fructus Mume or Fructus Mume, clean, water decocts secondary (1.5 hours, 1 hour), filters, and merging filtrate, being concentrated into relative density is that 1.10 (60 ℃) back is standby; Get Rhizoma Coptidis, Rhizoma Zingiberis, the Radix Aucklandiae, Pericarpium Papaveris, Rhizoma Corydalis and be ground into 100 order fine powders, fine powder after the pulverizing and above-mentioned concentrated solution add suitable quantity of water and mix, sterilizing-drying, and bag charcoal clothing, polishing, packing, promptly.
2. the watered pill: get Six-elements such as Fructus Mume, Rhizoma Coptidis and clean, cold drying is ground into 100 order fine powders, mixing, and the general pill of water, sterilizing-drying, packing is promptly.
3. water-honeyed pill: get Six-elements such as Fructus Mume, Rhizoma Coptidis and clean, cold drying is ground into 100 order fine powders, and mixing, every 100kg powder add refined honey 35~50kg and an amount of general water-honeyed pill of making of water, and sterilizing-drying is packed promptly.
Said medicine also can be made into other dosage forms.
Three, pharmacodynamic experiment
1. to the therapeutical effect of Radix Et Rhizoma Rhei type model of spleen deficiency mice
60 of healthy male ICR mouses, body weight 22-25 gram is divided into 6 groups immediately, 10 every group, surveys and respectively organizes mice body weight and body temperature.Irritate stomach 1ml/d distilled water for first group, only irritate stomach 100% Radix Et Rhizoma Rhei 1ml/d, continuous irrigation stomach eight days for all the other five groups.Respectively organize mice body weight and body temperature with repeating in the 9th day to survey, irritate stomach water, Spleen Invigorating and Intestine Tonifying Pill and Colic disease treating medicine bolus by following dosage then: 1. distilled water; 2. distilled water; 3. Spleen Invigorating and Intestine Tonifying Pill 7g/kg; 4. Colic disease treating medicine bolus 8g/kg; Colic disease treating medicine bolus 4g/kg; 6. Colic disease treating medicine bolus 2g/kg.After 30 minutes, 2., 3., 4., 5., 6. each group is only all irritated stomach 100% Radix Et Rhizoma Rhei decocting liquid 0.8ml/, from 1h, survey 1,3,5,6h mice loose stool number of times, since the tenth day 2., 3., 4., 5., 6. first administration or water, only irritate stomach 100% Radix Et Rhizoma Rhei 0.8ml/ every 1h, the 1. group only still only irritate stomach distilled water 1ml/, respectively organize mice body weight and body temperature, anus temperature, loose stool number of times with surveying again in the 15th day, to the results are shown in Table 1, table 2, table 3.
The influence (n=10) of table 1 pair mice body weight
Group | Dosage | Before giving Radix Et Rhizoma Rhei | After giving Radix Et Rhizoma Rhei |
The 9th day | The 15th day |
1. distilled water group | —— | ??24.0±1.50 | ??27.0±1.94 | ??31.5±4.19 |
2. Radix Et Rhizoma Rhei+water group | 1ml | ??23.8±1.63 | ??20.3±2.45 | ??17.7±3.27 |
3. Radix Et Rhizoma Rhei+Spleen Invigorating and Intestine Tonifying Pill | 0.8ml+7g/kg | ??24.4±1.64 | ??20.2±1.87 | ??24.8±2.62 |
4. Radix Et Rhizoma Rhei+JIECHANGYAN WAN | 0.8ml+8g/kg | ?24.3±1.72 | ?19.8±1.87 | ?25.6±3.72 |
5. Radix Et Rhizoma Rhei+JIECHANGYAN WAN | 0.8ml+4g/kg | ?23.4±1.90 | ?20.1±2.64 | ?25.2±2.68 |
6. Radix Et Rhizoma Rhei+JIECHANGYAN WAN | 0.8ml+2g/kg | ?23.5±1.92 | ?19.9±1.66 | ?25.6±2.80 |
The influence (n=10) of table 2 pair mice anus temperature
Group | Dosage | Before giving Radix Et Rhizoma Rhei | After giving Radix Et Rhizoma Rhei |
The 9th day | The 15th day |
1. distilled water group | —— | ?37.4±0.90 | ?37.1±0.92 | ?37.00±0.71 |
2. Radix Et Rhizoma Rhei+water group | 0.8ml | ?37.0±0.36 | ?36.3±0.89 | ?36.18±0.64 |
3. Radix Et Rhizoma Rhei+Spleen Invigorating and Intestine Tonifying Pill | 0.8ml+7g/kg | ?37.0±0.58 | ?36.4±0.89 | ?37.00±0.59 |
4. Radix Et Rhizoma Rhei+JIECHANGYAN WAN | 0.8ml+8g/kg | ?37.1±0.52 | ?36.3±1.18 | ?37.10±0.58 |
5. Radix Et Rhizoma Rhei+JIECHANGYAN WAN | 0.8ml+4g/kg | ?37.0±0.90 | ?36.5±0.43 | ?36.90±0.68 |
6. Radix Et Rhizoma Rhei+JIECHANGYAN WAN | 0.8ml+2g/kg | ?37.0±0.50 | ?36.3±1.13 | ?37.10±0.46 |
The influence (n=10) of table 3 pair mice with spleen deficiency loose stool number of times
Group dosage is to different time (h) loose stool cumulative number behind the Radix Et Rhizoma Rhei
1h??????????2h??????????3h??????????4h??????????5h??????????6h
1. distilled water group
2. Radix Et Rhizoma Rhei+water group 0.8ml 1.4 ± 1.35 4.2 ± 2.66 7.8 ± 3.12 12.5 ± 2.76 18.6 ± 2.63 23.6 ±
3.10
3. Radix Et Rhizoma Rhei+Spleen Invigorating and Intestine Tonifying Pill 0.8ml+7g/kg 0.9 ± 1.10 2.0 ± 1.49 3.4 ± 1.17 7.2 ± 1.99 11.3 ± 2.45 14.5 ± 2.22
4. Radix Et Rhizoma Rhei+JIECHANGYAN WAN 0.8ml+8g/kg 0.9 ± 0.74 2.2 ± 1.39 3.8 ± 1.32 7.2 ± 2.86 11.3 ± 3.2 14.2 ± 4.21
5. Radix Et Rhizoma Rhei+JIECHANGYAN WAN 0.8ml+4g/kg 0.9 ± 0.88 2.1 ± 1.29 3.6 ± 0.70 9.0 ± 1.33 12.3 ± 2.49 14.1 ± 3.28
6. Radix Et Rhizoma Rhei+JIECHANGYAN WAN 0.8ml+2g/kg 1.0 ± 1.05 2.4 ± 1.07 4.3 ± 1.16 8.2 ± 1.69 13.2 ± 2.74 16.2 ± 3.58
The result shows that this medicine can obviously increase the mice with spleen deficiency body weight, significantly reduces mice with spleen deficiency loose stool number of times, to mice with spleen deficiency body temperature is on the low side slightly restitution is arranged.
2. immunization
(1) nonspecific immunity---to the influence of RES phagocytic function
Get 50 of 18-22g male and female mices, be divided into 5 groups at random, grouping and dosage see Table 4, continuous irrigation stomach 7 days, and behind last administration 30min, tail vein injection 0.2ml india ink, respectively at 5min, 15min respectively gets eye socket venous plexus blood 20ul, is added on 2ml 1%Na
2CO
3Shake up in the test tube, put 600nm place colorimetric, calculate phagocytic index K value, the results are shown in Table 4.
The influence of table 4 pair RES phagocytic function
Group dosage number of animals phagocytic index K * 10
-2The P value
Matched group 10 1.12 ± 0.409
Spleen Invigorating and Intestine Tonifying Pill 7g/kg 10 1.79 ± 0.479<0.01
This medicine 8g/kg 10 2.07 ± 0.5427<0.001
This medicine 4g/kg 10 1.69 ± 0.715<0.01
This medicine 2g/kg 10 1.15 ± 0.147>0.05
The result shows that this medicine 8g/kg and 4g/kg have obvious potentiation to mice reticuloendothelial system phagocytic function.
(2) humoral immunization---to the influence of serum hemolysin generation
Get 50 of 18-22g male and female mices, grouping and administration are the same.Every mouse peritoneal is injected 5% normal saline chicken red blood cell suspension 0.2ml and is carried out immunity, and perfusion or water are 7 days then, pluck eyeball and get blood in the 7th day, centrifugal, get serum with 100 times of normal saline dilutions, get dilute serum 1ml, with 5% chicken red blood cell suspension 0.5ml, 10% complement 0.5ml mixes, in 37 ℃ of calorstats behind the insulation 30min, and stopped reaction in 0 ℃ of refrigerator, centrifugal, get supernatant in 721 spectrophotometer 540nm place colorimetrics, recording light density value (OD) the results are shown in Table 5.
The influence that table 5 pair serum hemolysin generates
Group dosage number of animals OD value * 100 P values
Matched group 10 12.1 ± 1.61
Spleen Invigorating and Intestine Tonifying Pill 7g/kg 10 16.2 ± 3.67<0.05
This medicine 8g/kg 10 18.4 ± 4.77<0.01
This medicine 4g/kg 10 16.8 ± 3.77<0.05
This medicine 2g/kg 10 14.6 ± 2.88>0.05
The result shows that this medicine 8g/kg and 4g/kg can obviously improve the humoral immunity of organism ability.
3. antiinflammatory action
(1) to the bullate influence of mouse ear
Get 50 of mices, press shown in the table 6 abundant, the subcutaneous pig house of indometacin, this medicine gavages, 1h behind the medicine, soak into dimethylbenzene with the circular filter paper of 0.5min diameter and be affixed on the mouse right ear inboard, put to death behind the 15min, cut ears along the auricle line, left ear is a matched group, with heavy poor (mg) expression swelling degree of two ears, see Table 6.
The bullate influence of table 6 xylol induced mice ear
Group dosage number of animals ear (mg) P value that swells
Matched group (water) 10 7.4 ± 3.4
Indometacin 25g/kg 10 3.0 ± 1.9<0.01
This medicine 8g/kg 10 3.9 ± 1.9<0.05
This medicine 4g/kg 10 4.4 ± 2.8<0.05
This medicine 2g/kg 10 6.1 ± 2.2>0.05
The result shows that this medicine 8g/kg and 4g/kg xylol induced mice ear swell obvious inhibitory action.
(2) to the granulomatous influence of mouse subcutaneous injection agar
Get 60 of mices, it is the same to divide into groups.All mices all under the rib of left side subcutaneous injection 2% agar 0.2ml/ only and, put to death mice on the 7th day in the 2nd day beginning successive administration 6 days, carefully peel off agar granulation lump, and claim weight in wet base (mg), the results are shown in Table 7.
The table 7 pair granulomatous influence of mice agar
Group dosage number of animals granuloma (mg) P value
Matched group (water) 12 99.5 ± 30.8
Indometacin 8g/kg 12 55.1 ± 16.5<0.001
This medicine 8g/kg 12 73.6 ± 21.4<0.05
This medicine 4g/kg 12 81.1 ± 26.6<0.05
This medicine 2g/kg 12 89.0 ± 22.6>0.05
The result shows: growth has obvious inhibitory action to mouse subcutaneous injection agar granuloma for this medicine 8g/kg and 4g/kg.
4. analgesic activity
The influence of the mouse writhing reaction that (1) acetic acid is caused
Get 50 of mices, press shown in the table 8 abundantly, dolantin subcutaneous injection, this medicine gavage back 1h, and every mouse peritoneal is only injected 0.7% acetic acid 0.2ml/, writes down mouse writhing number of times in 15 minutes, the results are shown in Table 8.
Table 8 pair acetic acid causes the influence of mouse writhing
Group dosage number of animals is turned round body number of times suppression ratio (%) P value
Matched group (water) 10 47.5 ± 12.01
Dolantin 25g/kg 10 13.9 ± 7.54 70.6<0.001
This medicine 8g/kg 10 23.5 ± 15.66 50.5<0.01
This medicine 4g/kg 10 33.5 ± 18.23 29.5>0.05
This medicine 2g/kg 10 38.2 ± 11.06 24.0>0.05
The result shows: this medicine 8g/kg can significantly reduce the mouse writhing number of times that acetic acid causes.
(2) hot plate method is caused the influence of the mice threshold of pain bitterly
Get 60 of female mices, body weight 18-22g, 12 every group, grouping and administration are the same.Experiment GJ8402 type hot plate dolorimeter, 55 ℃ of temperature, licking metapedes with the mice mouth is the pain index, record is put into mice to licking the sufficient time (s), is the painful threshold value of this mice.Selecting threshold of pain 5S for use is qualified to person between the 30S.Experiment Pretesting 2 times, meansigma methods are as normal value, and test in per 30 minutes once to compare (t check) before each group and the administration, the results are shown in Table 9 after the administration.
Table 9 pair hot plate method causes the influence (n=12) of the pain mice threshold of pain
Pain threshold before the group dosed administration
30min??????????60min?????????90min??????????120min
Matched group 21.25 ± 4.20 22.33 ± 6.89 23.08 ± 4.72 22.41 ± 12.01 20.50 ± 9.13
Dolantin 25g/kg 22.75 ± 4.86 32.08 ± 10.04 32.25 ± 5.72 37.33 ± 10.50 35.83 ± 4.84
This medicine 8g/kg 23.50 ± 4.19 25.25 ± 4.09 27.75 ± 4.28 33.00 ± 10.52 31.09 ± 8.14
This medicine 4g/kg 21.75 ± 3.76 23.33 ± 3.65 26.33 ± 5.07 32.75 ± 11.75 24.92 ± 11.80
This medicine 2g/kg 22.17 ± 4.49 23.00 ± 11.97 23.56 ± 7.56 25.83 ± 9.08 26.70 ± 5.81
The result shows: this medicine 8g/kg and 4g/kg can obviously prolong the mice pain threshold.
5. experiment conclusion
Find that by experimental study this medicine can obviously improve symptoms such as mice with spleen deficiency weight loss, body temperature descend, loose stool increases, strengthen mice nonspecific immunity and humoral immunization, and have antiinflammatory and analgesic activity, the effective Chinese patent medicine of this medicine for the treatment chronic non-specific ulcerative colitis is described.
Four, toxicity test
Animal subject: ICR mice, body weight 20 ± 2g.
Test method: irritate stomach 3 times through trial test in 0.35ml/10g24h, mice does not have death, does not have obvious toxic reaction yet, and with getting 20 of mices, male and female half and half are given in the mice 24h by trial test dosage and to be irritated stomach 3 times, observes in 7 days to have or not poisoning symptom and death condition.
Result of the test: the mice activity does not have abnormal phenomenas such as shouting, tremble, faint from fear, shed tears freely after the administration, and diet, two is just normal, and fur is smooth.Body weight 21.2 ± 1.4g before the administration, body weight 25.7 ± 1.45g after 7 days, none is only dead.Put to death all mices after 7 days, dissect main organs such as perusal mouse core, liver, spleen, lung, kidney, Non Apparent Abnormality changes.
Conclusion (of pressure testing): this medicine maximum tolerated dose is 31.5g/kg, amounts to crude drug in whole 35.6g/kg, and 157.5 times of the clinical consumption per day of quite being grown up show that this medicine does not have the overt toxicity effect.
Five, clinical observation
Through 256 routine clinical observations, cure rate is 56.6%, and effective percentage reaches 98.4%, and proof is controlled in clinical examination, and this medication is imitated really, and is comparatively stable, no obvious adverse reaction.Male's 164 examples wherein, women's 92 examples, the oldest 67 years old, minimum 6 years old; 20-50 year is 224 people, and the course of disease is the longest 32 years, the shortest 3 months.Dosage is the each consumption 5g of adult, and three times on the one, one month is a course of treatment.Learn by statistics and handle, it the results are shown in following table:
Table 10 pair hot plate method causes the influence (n=12) of the pain mice threshold of pain
Symptom and sign
Abdomen diarrhoea constipation bloody purulent stool tenesmus abdominal tenderness
1-5 time/day 6-10 time/day of pain is more than 11 times
Treat preceding 237 195 29 5 27 208 141 178
Control and disappear 159 116 24 3 26 183 141 142
Treatment alleviates 75 78 411 22 0 27
Back no change 31110309
After various symptoms and sign are learned processing by statistics, improve situation difference highly significant
Table 11 efficacy result statistics (constituent ratio)
Therapeutic outcome both sexes percentage ratio %
Fully recover 95 50 145 56.6
Produce effects 50 27 77 30.1
Take a turn for the better 17 13 30 11.7
Invalid 224 1.6
Amount to 164 92 256 100.0
Curative effect shows efficient and reaches 98.4%, and cure rate is 56.6%, and two groups of therapeutic effect of men and women are learned processing by statistics, and difference is not remarkable, no matter the men and women is described, take this medicine after, the effect of receiving is the comparison unanimity.
Embodiment 1
Take by weighing raw material (gram) by following proportioning:
Fructus Mume 470 (35%) Rhizoma Coptidis 268 (20%) Rhizoma Zingiberiss 268 (20%)
The Radix Aucklandiae 134 (10%) Pericarpium Papaveriss 134 (10%) Rhizoma Corydalis 67 (5%)
Method for making is as follows: get Fructus Mume 470 grams and clean, water decocted 1.5 hours for the first time, decocted 1 hour for the second time, filter, and merging filtrate, it is standby to concentrate the back; Get Rhizoma Coptidis 268 gram, Rhizoma Zingiberis 268 grams, the Radix Aucklandiae 134 grams, Pericarpium Papaveris 134 grams, Rhizoma Corydalis 67 grams and be ground into 100 order fine powders, fine powder after the pulverizing and above-mentioned concentrated solution mix, and oven dry promptly.
Embodiment 2
Take by weighing raw material (gram) by following proportioning:
Fructus Mume 470 (35%) Rhizoma Coptidis 134 (10%) Rhizoma Zingiberiss 134 (10%)
The Radix Aucklandiae 201 (15%) Pericarpium Papaveriss 201 (15%) Rhizoma Corydalis 201 (15%)
Method for making such as embodiment 1.
Embodiment 3
Take by weighing raw material (gram) by following proportioning:
Fructus Mume 671 (50%) Rhizoma Coptidis 107 (8%) Rhizoma Zingiberiss 107 (8%)
The Radix Aucklandiae 107 (8%) Pericarpium Papaveriss 161 (12%) Rhizoma Corydalis 188 (14%)
Method for making such as embodiment 1.
Embodiment 4
Take by weighing raw material (gram) by following proportioning:
Fructus Mume 658 (49%) Rhizoma Coptidis 242 (18%) Rhizoma Zingiberiss 242 (18%)
The Radix Aucklandiae 67 (5%) Pericarpium Papaveriss 67 (5%) Rhizoma Corydalis 67 (5%)
Method for making such as embodiment 1.
Embodiment 5
Take by weighing raw material (gram) by following proportioning:
Fructus Mume 537 (40%) Rhizoma Coptidis 268 (20%) Rhizoma Zingiberiss 268 (20%)
The Radix Aucklandiae 67 (5%) Pericarpium Papaveriss 67 (5%) Rhizoma Corydalis 134 (10%)
Method for making such as embodiment 1.
Embodiment 6
Take by weighing raw material (gram) by following proportioning:
Fructus Mume 150 (15%) Rhizoma Coptidis 120 (12%) Rhizoma Zingiberiss 130 (13%)
The Radix Aucklandiae 200 (20%) Pericarpium Papaveriss 200 (20%) Rhizoma Corydalis 200 (20%)
Method for making is as follows: get Fructus Mume 150, Rhizoma Coptidis 120, Rhizoma Zingiberis 130, the Radix Aucklandiae 200, Pericarpium Papaveris 200, Rhizoma Corydalis 200 five tastes, be ground into 100 order fine powders, water is drying to obtain after mixing.
Embodiment 7
Take by weighing raw material (gram) by following proportioning:
Fructus Mume 300 (30%) Rhizoma Coptidis 200 (20%) Rhizoma Zingiberiss 200 (20%)
The Radix Aucklandiae 100 (10%) Pericarpium Papaveriss 100 (10%) Rhizoma Corydalis 100 (10%)
Method for making such as embodiment 6.
Embodiment 8
Take by weighing raw material (gram) by following proportioning:
Fructus Mume 250 (25%) Rhizoma Coptidis 150 (15%) Rhizoma Zingiberiss 150 (15%)
The Radix Aucklandiae 150 (15%) Pericarpium Papaveriss 150 (15%) Rhizoma Corydalis 150 (15%)
Method for making such as embodiment 6.
Embodiment 9
Take by weighing raw material (gram) by following proportioning:
Fructus Mume 200 (20%) Rhizoma Coptidis 250 (25%) Rhizoma Zingiberiss 180 (18%)
The Radix Aucklandiae 120 (12%) Pericarpium Papaveriss 150 (15%) Rhizoma Corydalis 100 (10%)
Method for making such as embodiment 6.
Embodiment 10
Take by weighing raw material (gram) by following proportioning:
Fructus Mume 180 (18%) Rhizoma Coptidis 130 (13%) Rhizoma Zingiberiss 220 (22%)
The Radix Aucklandiae 170 (17%) Pericarpium Papaveriss 130 (13%) Rhizoma Corydalis 170 (17%)
Method for making such as embodiment 6.