CN1785410A - Preparation method of ready prepared chinese medicinal granules for treathing pains - Google Patents

Abstract

A Chinese medicine in the form of particles for treating the pain diseases is prepared from 6 Chinese-medicinal materials including white peony root, liquorice root, curcuma root, notoginseng, etc. Its preparing process is disclosed.

Description

A kind of preparation method for the treatment of the Chinese patent medical granule of pain disease

Technical field

The present invention relates to a kind of preparation method for the treatment of the Chinese patent medical granule of pain disease.

Background technology

JINFO ZHITONG WAN is to be that crude drug is made by the Radix Paeoniae Alba, Radix Glycyrrhizae, Radix Notoginseng, Rhizoma Corydalis, Fructus Citri Sarcodactylis, Rhizoma Curcumae Longae and Radix Curcumae.This medical instrument has dispersing the stagnated liver-QI for regulating the stomach, promoting tissue regeneration by removing blood stasis, and the effect of promoting the circulation of QI to relieve pain can be used for treating stomachache due to hyperactive liver-QI attacking the stomach, ecchymoma due to internal injury, menstrual pain, digestive tract ulcer, the pain that chronic gastritis causes.The preparation method of former pill is that the seven flavor medicine material is pulverized, and gets the part Radix Paeoniae Alba, Radix Curcumae, Rhizoma Curcumae Longae, Radix Glycyrrhizae and decocts with water twice, adds Fructus Citri Sarcodactylis for the second time and decocts, and filters, and merging filtrate is condensed into thick paste; Get the remaining Radix Paeoniae Alba again, Rhizoma Corydalis (vinegar system), Radix Notoginseng are ground into coarse powder altogether, with thick paste mix homogeneously, drying, are ground into 80-120 order fine powder, sieve, and mixing obtains medicated powder, and the powder water of getting it filled is general to be ball, drying, and pill is made in the primary colors polishing.This pill uses does not see obvious toxic-side effects, good analgesic effect, but the suitable crude drug amount of Unit Weight is not high, is to guarantee curative effect, and it is more once to take quantity.

Summary of the invention

The purpose of this invention is to provide a kind ofly conveniently take, the suitable crude drug amount of Unit Weight increases reduces the particulate preparation method of golden Buddhist pain relieving of taking quantity.

Technical solution of the present invention is:

(1) gets the Radix Paeoniae Alba, Radix Glycyrrhizae, Radix Curcumae, Rhizoma Curcumae Longae, Fructus Citri Sarcodactylis and Radix Notoginseng Six-element crude drug, add water 10-14 for the first time doubly, decocted 1-3 hour; Add for the second time water 6-12 doubly, decocted 1-3 hour; Merge extracted twice liquid, filter, filtrate is concentrated into the extractum that relative density is 1.20-1.25 (75-80 a ℃);

(2) above-mentioned extractum adds 80-95% ethanol to containing the alcohol amount for the 50-70% precipitation, leaves standstill 12-36 hour, gets pure molten supernatant, filters, and is standby;

(3) the Rhizoma Corydalis (processed with vinegar) medicinal material coarse powder broken after, add for the first time 50-70% ethanol 5-7 doubly, reflux, extract, 1-3 hour; Add for the second time 50-70% ethanol 3-5 doubly, reflux, extract, 1-3 hour, filter, standby;

(4) merge above-mentioned two parts solution, mix homogeneously, being concentrated into relative density is 1.25, measures dry solids content, adds the maltodextrin that is equivalent to dry solids content gross weight 3-5% and carries out drying, gets dry extract;

(5) with behind the get dry extract mill 100-140 order, granulate, cross 16 mesh sieves and 60 mesh sieves, make granule.

Preferred version of the present invention is: it takes following steps:

(1) gets the Radix Paeoniae Alba, Radix Glycyrrhizae, Radix Curcumae, Rhizoma Curcumae Longae, Fructus Citri Sarcodactylis and Radix Notoginseng Six-element crude drug, add 12 times in water for the first time, decocted 2 hours; For the second time add 10 times in water, decocted 1.5 hours; Merge extracted twice liquid, filter, filtrate is concentrated into the extractum that relative density is 1.20-1.25 (75-80 a ℃);

(2) to add 95% ethanol to the alcohol amount of containing be 60% precipitation to above-mentioned extractum, left standstill 12-36 hour, pure molten supernatant, filter, standby;

(3) the Rhizoma Corydalis (processed with vinegar) medicinal material coarse powder broken after, add for the first time 6 times of 60% ethanol, reflux, extract, 2 hours; For the second time add 4 times of 60% ethanol, reflux, extract, 1.5 hours filters, and is standby;

(4) merge above-mentioned two parts solution, mix homogeneously, being concentrated into relative density is 1.25, measures dry solids content, adds the maltodextrin that is equivalent to dry solids content gross weight 4% and carries out vacuum drying, gets dry extract;

(5) with behind get dry extract mill 120 orders, carry out one-step palletizing, cross 16 mesh sieves and 60 mesh sieves, make granule.

Advantage of the present invention is: aspect dried cream yield, adopt former technology to be about 28%, use the dried cream yield of new technology of the present invention to be about 7% (10 batches of pilot scale data), 3 times have been reduced nearly than former technology, but be to use the prepared golden Buddhist pain relieving granule of the inventive method in pain relieving, spasmolytic, drug effect such as antiinflammatory and anti-gastric mucosa injury aspect, compare with the prepared pill of former technology, have approaching, equivalence even slightly excellent effect, the suitable crude drug amount of Unit Weight medicine increases greatly, has onset speed faster, taking convenience, the misery of reduction of patient quickly.

Below, beneficial effect of the present invention is described by some effect experiment data:

1 experiment material

1.1 animal

The NIH mice, SPF level, body weight 18～22g, male and female dual-purpose, the quality certification number: 2004A018; The SD rat, SPF level, body weight 180～200g, male and female dual-purpose, the quality certification number: 2004A021; New zealand rabbit, regular grade, body weight 2～2.5kg, male and female dual-purpose, the quality certification number: 2004A001; Cavia porcellus, regular grade, body weight 300～500g, male and female dual-purpose, the quality certification number: 2004A023.Above animal provides by Guangdong Medical Lab Animal Center.

1.2 zoopery environmental facility: the herbal pharmacology laboratory is three grades of State Administration of Traditional Chinese Medicine Chinese medicine scientific experiment chambers.

1.3 medicine and main agents

JINFO ZHITONG WAN, the suitable crude drug amount of every g 3.59g is provided lot number by Guangzhou Zhongyi Medicine Industry Co., Ltd: 99050012, adult's (by 60kg) consumption per day is 10-30g (by 30g); Gold Buddhist pain relieving granule (new technology) vacuum drying medicated powder, the suitable crude drug amount of every g medicated powder 13.274g is provided lot number by Guangzhou Zhongyi Medicine Industry Co., Ltd: 030809, following experimental drug amount is all shown with the crude drug scale; The rotundine hydrochloride sheet: Nanning Pharmaceutical Engerprise (Group) Corp., Guangxi produces, lot number: 0708; Indometacin enteric-coated tablet, Shi Qi pharmaceutical factory in Guangdong produces, lot number: 981218; Sucralfate; Jiangsu vast stretch of wooded country pharmaceutcal corporation, Ltd makes branch company, lot number: 0211052; Acetylcholine: east, Beijing ring amalgamation factory, 980210; Barium chloride: chemical plant, the Taishan, Guangdong produces, analytical pure, lot number: 790401; Diethylstilbestrol injection: bright emerging pharmaceutical factory, Guangzhou, lot number: 020901; Oxytocin inj: 10u/ml, Mingxing Pharmaceutical Factory, Guangzhou, lot number: MC3202; Indometacin, U.S. SIGMA company, lot number: 314-771-5750.

2 methods and result

2.1 analgesic test

2.1.1 hot plate method female mice fasting 12 hours is at first screened, and mice is placed on the hot plate (55 ± 0.5 ℃), the record mice licks the metapedes time (s) for the first time, and as pain threshold, the threshold of pain was less than 5 seconds or discard greater than 30 seconds and leaper need not.Get qualified mice, stratified random is divided into seven groups, be respectively distilled water group, little, the middle dosage group of JINFO ZHITONG WAN, JINFO ZHITONG WAN new technology little, in, heavy dose of group and positive drug rotundine group.The administration before measurement threshold of pain 2 times, get average as administration before pain threshold.Each is organized mice and gives corresponding reagent thing and the water of being subjected to, JINFO ZHITONG WAN is little, in, heavy dose of by 0.5 times, 1 times of adult's clinical equivalent amount and 2 times of designs, medicine is made into 395g crude drug/L, 790g crude drug/L and 1580g crude drug/L, rotundine is by the administration of adult's clinical equivalent amount, medicine is made into 2.4g/L, the administration volume is 25ml/kg, and the distilled water group is given the equal-volume distilled water.Animal administration in advance 3 days, every day 1 time.Fasting is 12 hours before the last administration, surveys pain threshold in 30,60,90 and 120 minutes after the administration, and pain threshold surpasses 60 seconds the mice taking-up was calculated by 60 seconds, to prevent the mice scald.Adopt the sided t check to compare the significant difference of administration group and each time point pain threshold of distilled water group.

Experimental result shows, it is close that each organizes the basic threshold of pain, no difference of science of statistics between group (p＞0.05), in the former technology of JINFO ZHITONG WAN in dosage and the new technology, after heavy dose of administration each time point pain threshold and distilled water group relatively pain threshold all obviously raise, point out golden Buddhist pain relieving granule, two kinds of dosage forms of ball that analgesic effect (table 1) is arranged.

Table 1, JINFO ZHITONG WAN hot-plate analgesic test

Group	Number of animals (n)	The threshold of pain, basis (s, x ± s)	The different time threshold of pain after the administration (s, x ± s)
							30min	60min	90min	120min
			Big rotundin during the little middle new technology of the former technology of distilled water group is little	15 15 14 14 14 14 14	13.0±2.3 12.4±1.8 13.4±2.2 13.1±3.0 13.2±3.4 13.6±2.4 13.3±3.2	13.1±2.1 13.9±3.9 19.3±7.9 ** 15.8±4.4 18.6±8.1 * 22.0±8.0 ** 51.1±10.7 **					12.1±3.0 14.3±4.0 22.1±7.7 ** 14.5±3.5 20.4±8.8 ** 24.8±9.9 ** 51.8±11.5 **	13.3±3.0 14.6±4.2 22.8±5.2 ** 16.7±8.3 22.2±7.3 ** 27.6±11.6 ** 52.6±12.5 **	13.4±2.5 15.6±6.1 24.1±8.6 ** 18.5±8.2 * 21.0±7.5 ** 25.9±11.0 ** 48.0±15.0 **

Compare with the distilled water group: ^*P＜0.05; ^*P＜0.01

2.1.2 acetic acid twisting method mice fasting 12 hours, stratified random grouping, grouping are with the hot plate method experiment, each treated animal dosage is identical with the hot plate method test with method.Fasting is 12 hours before the last administration, and after the administration 1 hour, lumbar injection 0.6% acetic acid 0.1ml/10g body weight was counted 20 minutes mouse writhing number of times and writhing response and incubation period occurred.Carry out statistical analysis with the sided t check.

Experimental result shows, in two dosage of the former technology of JINFO ZHITONG WAN and the new technology, heavy dose of group mouse writhing number of times obviously reduces than the distilled water group, significance meaning (p＜0.05 or p＜0.01) has been analysed in credit by statistics, points out two kinds of technologies that significant analgesia role (table 2) is arranged.

Table 2, JINFO ZHITONG WAN writhing method analgesic test

Group	Number of animals (n)	Dosage (g/kg)	Incubation period (s, x ± s)	Turn round body number of times (x ± s)
					Big rotundine during the little middle new technology of the former technology of distilled water group is little	14 14 14 14 15 15 15	Equal-volume water 9.87 19.75 9.87 19.75 39.49 0.06	4.52±1.27 4.04±3.34 5.14±2.30 5.96±3.27 6.84±3.55 * 5.10±4.21 6.94±6.84	21.9±7.2 13.9±10.7 * 13.9±8.0 * 18.6±9.7 14.1±12.4 * 11.3±9.8 ** 2.5±2.7 **

Compare with the distilled water group: ^*P＜0.05, ^*P＜0.01

2.1.3 JINFO ZHITONG WAN is to the effect of dysmenorrhea model in mice

Get that the female mice stratified random is divided in normal group, model group, the large, medium and small dosage group of JINFO ZHITONG WAN new technology, the former technology, small dose group, rotundine group, except that normal group, all the other only respectively organize mice subcutaneous injection every day diethylstilbestrol injection 0.2mg/, continuous 10 days.Beginning administration on the 11st, the same analgesic test of dosage, normal group is given the equal-volume distilled water, and be administered once every day, successive administration 3 days.Fasting is 12 hours before the last administration, and 30min after the administration, lumbar injection oxytocin inj 0.3u/ only count 20 minutes mouse writhing number of times and writhing response and incubation period occurs.Carry out statistical analysis with the sided t check.

Experimental result shows, in the former technology of JINFO ZHITONG WAN in dosage and the new technology, heavy dose of group mouse writhing number of times obviously reduces than the distilled water group, significance meaning (p＜0.05 or p＜0.01) has been analysed in credit by statistics, and obviously prolong the incubation period that writhing response appears in the new technology heavy dose.Point out two kinds of technology preparations that the dysmenorrhea model mice is had significantly analgesic effect (table 3).

Table 3, JINFO ZHITONG WAN are to the effect of dysmenorrhea model in mice

Group	Number of animals (n)	Dosage (g/kg)	Incubation period (s, x ± s)	Turn round body number of times (x ± s)
					It is big during the little middle new technology of the former technology of normal group model group is little	15 14 15 15 15 15 15	Equal-volume water equal-volume water 9.87 19.75 9.87 19.75 39.49	- 5.03±4.44 3.83±1.39 5.06±4.49 5.99±5.82 6.27±5.71 11.17±6.71 **	0 27.6±13.3 22.6±13.7 17.1±13.6 * 23.1±15.2 14.9±11.8 * 5.1±7.0 **

Rotundine

15

0.06

17.43±4.87 **

1.7±3.0 **

Compare with model group: ^*P＜0.05, ^*P＜0.01

2.2 antiinflammatory action

2.2.1 mouse peritoneal capillary permeability test

The grouping of mice stratified random, except that positive drug changed indomethacin into, all the other groupings were identical with the analgesic test with dosage, and indomethacin is by 2 times of administrations of clinical adult's equivalent, and medicine is made into 1g/L.1 administration is adopted in experiment, fasting is 12 hours before the administration, after the administration 1 hour, the equal tail vein injection 0.5% azovan blue normal saline solution 0.1ml/10g body weight of each Mus, lumbar injection 0.6%HAc 0.1ml/10g body weight is taken off cervical vertebra and is put to death after 20 minutes immediately, cut off skin of abdomen muscle, divide several to wash the abdominal cavity with the 6ml normal saline, suction pipe sucking-off cleaning mixture, merging back add normal saline to 10ml, centrifugal 15 minutes of 3000rpm; Get supernatant in 590nm colorimetric determination OD value, organize a t check relatively.

The result shows that dosage and three dosage groups of new technology OD value are starkly lower than the distilled water group in the former technology of JINFO ZHITONG WAN, and the inflammation of pointing out two kinds of preparations that acetic acid is caused the mouse peritoneal blood capillary is oozed out inhibitory action (table 4) is arranged.

Table 4, JINFO ZHITONG WAN are to the influence of mouse peritoneal capillary permeability

Group	Number of animals (n)	Dosage (g/kg)	Eluate OD value (x ± s)
				Big Indomethacin during the little middle new technology of the former technology of distilled water is little	13 13 13 13 14 14 13	Equal-volume water 9.87 19.75 9.87 19.75 39.49 25mg/kg	0.580±0.127 0.482±0.135 0.438±0.154 * 0.431±0.207 * 0.443±0.150 * 0.447±0.107 * 0.264±0.176 **

Compare with the distilled water group: ^*P＜0.05, ^*P＜0.01

2.2.2 influence to the foot swelling of rat Ovum Gallus domesticus album

Get the SD male rat, be divided into eight groups at random: normal group, model group, little, the middle dosage group of the former technology of JINFO ZHITONG WAN, new technology be little, in, heavy dose of group, positive drug indomethacin group.The basic, normal, high dosage of JINFO ZHITONG WAN is by 0.5 times, 1 times and 2 times of designs of adult's clinical equivalent amount, medicine is made into 485g crude drug/L, 969g crude drug/L and 1939 crude drug g/L, indomethacin is by 2 times of administrations of adult's clinical equivalent amount, medicine is made into 1.25g/L, the administration volume is 10ml/kg, and normal group and model group are given the equal-volume distilled water.The animal fasting is 24 hours before the administration.Measure every sufficient volume in an animal left side respectively by " volumetric method ", as the basic value before the administration.After the administration 1 hour, every animal was measured sufficient volume respectively at causing after the inflammation 1-6 hour with method in parapodum plantar subcutaneous injection fresh albumen 0.1ml except that normal group.Deduct the difference that causes the preceding basic value of inflammation with each time point determining value and multiply by 100% as the swelling degree divided by basic value, relatively the significant difference of each administration group and model group adopts the t check analysis.

The result shows, changes not obvious before and after the normal group administration.The former technology low dose of JINFO ZHITONG WAN has 2 time points, middle dosage to have 3 time point paw swellings all obviously to descend than model group, and dose-effect relationship is not obvious; New technology is little, heavy dose respectively has 2 time points, whole 4 the time point paw swellings of middle dosage obviously descend than model group, and dose-effect relationship is not obvious, and is best with middle dosage effect.Point out two kinds of preparations that acute exudative inflammation is had certain inhibitory action (table 5).

Table 5, JINFO ZHITONG WAN cause the influence of rat paw edema to Ovum Gallus domesticus album

Group	Number of animals (n)	Dosage (g/kg)	Cause scorching back different time paw swelling (%, x ± s)
							1	2	4	6(h)
			Big Indomethacin group during the little middle new technology of the former technology of normal group model group is little	10 10 10 10 10 10 10 10	Equal-volume water equal-volume water 4.85 9.69 4.85 9.69 19.39 12.5mg/kg	-1.9±3.7 68.1±7.4 59.5±10.7 * 61.5±7.8 57.5±10.0 * 51.5±16.0 ** 55.4±9.4 ** 53.8±8.0 **					-2.2±3.5 66.4±7.4 57.6±8.1 * 57.2±9.7 * 52.9±9.6 ** 46.1±14.2 ** 52.2±12.4 ** 52.0±9.2 **	-2.4±3.7 53.3±6.0 47.0±8.8 45.8±7.7 * 48.8±5.8 41.4±12.3 ** 46.8±11.4 41.9±6.5 **	0.4±1.5 40.5±6.4 35.6±8.5 31.4±5.5 ** 36.2±5.4 32.3±10.4 * 37.4±8.9 31.1±6.7 **

Compare with model group: ^*P＜0.05, ^*P＜0.01

2.3 gastric mucosal protective effect

2.3.1 the effect of anti-chmice acute gastric mucosa injury

Mice stratified random grouping administration.Outside positive drug sucralfate (by the administration of adult's clinical equivalent amount, medicine is made into 15g/L), all the other groupings and administration are with the hot plate method analgesic experiment.Be administered once every day, and for three days on end, fasting is 12 hours before the last administration, prohibits water 2 hours.Only irritated gastric hydrochloric acid alcoholic solution (every 100ml contains 60ml dehydrated alcohol and 15mmol hydrochloric acid) 0.3ml/ in 1 hour after the administration, put to death animal after 1 hour, get stomach, ligation pylorus and cardia are put into concentration formalin after gastric injects 1% formalin 2ml and are fixed 10 minutes, cut off along greater gastric curvature afterwards, tap water is rinsed well, is tiled on the blank sheet of paper, measures damaged length,, compare between organizing as damage index with damaged length sum (mm).

The result shows: the former process-induced damage index of JINFO ZHITONG WAN has to a certain degree minimizing than matched group, but does not have significant difference (P＞0.05); In the new technology, heavy dose of damage index obviously reduces than matched group.The effect (table 6) of pointing out it that anti-gastric mucosa injury is arranged.

Table 6, the effect of the anti-chmice acute gastric mucosa injury of JINFO ZHITONG WAN

Group	Number of animals (n)	Dosage (g/kg)	Damage incidence rate (%)	Damage index (mm, x ± s)	Suppression ratio (%)
						During the little middle new technology of the former technology of distilled water group is little	10 10 10 10 10	Equal-volume water 9.87 19.75 9.87 19.75	100 100 80 100 90	17.1±6.7 14.0±10.0 11.4±8.4 17.5±15.3 9.6±6.4 *	18.1 33.3 -2.3 43.9

Big sucralfate

10 10

39.49 0.375

70 70

7.5±9.5 * 3.8±3.3 **

56.1 77.8

Compare with the distilled water group: ^*P＜0.05, ^*P＜0.01

2.3.2 the effect of Chinese People's Anti-Japanese Military and Political College's Mus acute gastric mucosal lesion

Get the SD male rat, be divided into seven groups at random: distilled water group, little, the middle dosage group of the former technology of JINFO ZHITONG WAN, new technology be little, in, heavy dose of group, positive drug sucralfate group.JINFO ZHITONG WAN is little, in, heavy dose of 0.5 times, 1 times and 2 times of designs by adult's clinical equivalent amount, medicine is made into 485g crude drug/L, 969g crude drug/L and 1939 crude drug g/L, sucralfate is by 2 times of administrations of adult's equivalent, medicine is made into 50g/L, the administration volume is 10ml/kg, and the distilled water group is given the equal-volume distilled water.Be administered once every day, for three days on end, fasting is 24 hours before the last administration, prohibited water 2 hours, 1 hour rat skin lower injection indometacin 5% sodium bicarbonate aqueous solution 30mg/kg after the administration, put to death animal after 7 hours, get stomach, ligation pylorus and cardia are put into concentration formalin after gastric injects 1% formalin 10ml and are fixed 10 minutes, cut off along greater gastric curvature afterwards, tap water is rinsed well, is tiled on the blank sheet of paper, measures damaged length,, compare between organizing as damage index with damaged length sum (mm).

The result shows: the heavy dose of group of little, middle dosage group of the former technology of JINFO ZHITONG WAN and new technology damage index obviously reduces than the distilled water group, points out two kinds of technology preparations that the effect (table 7) of certain Chinese People's Anti-Japanese Military and Political College's Mus acute gastric mucosal lesion is arranged.

Table 7, the Mus acute gastric mucosal lesion effect of the JINFO ZHITONG WAN Chinese People's Anti-Japanese Military and Political College

Group	Number of animals (n)	Dosage (g/kg)	Damage incidence rate (%)	Damage index (mm, x ± s)	Suppression ratio (%)
						Big ulcerlmin during the little middle new technology of the former technology of distilled water group is little	11 10 10 10 10 10 10	Equal-volume water 4.85 9.69 4.85 9.69 19.39 50mg/kg	100 80 70 100 100 80 100	28.0±10.5 14.3±14.5 * 7.2±9.0 ** 21.3±12.5 23.9±12.9 16.0±15.0 * 13.4±12.7 *	- 48.9 74.3 23.9 14.6 42.9 52.1

Compare with the distilled water group: ^*P＜0.05, ^*P＜0.01

2.4 spasmolysis

2.4.1 spasmolytic test to rabbit, guinea pig in vitro intestinal tube

Get healthy new zealand rabbit (and Cavia porcellus), the mallet portion of tapping the head causes death, taking out rabbit duodenum and ileum (Cavia porcellus is got small intestinal) immediately puts in the tyrode's solution, wash out the enteric cavity content with tyrode's solution, get the intestinal tube that is about 2.0cm, hang in the maxwell bath pipe that fills the 20ml tyrode's solution 37 ± 0.5 ℃ of constant temperature, and bubbling air, trace curve movement with the WXT-self-balancing recorder.Treat that the basicly stable back of intestinal tube motion adds acetylcholine or barium chloride (small intestine of guinea pig adds histamine), produce strong spastic contraction, add institute's reagent thing behind the 5min, the variation of record administration anterioposterior curve, and calculate and suppress percentage rate or antagonism percentage rate.

The result shows: the exsomatize spastic contraction of ileum and histamine of the rabbit that two technologies of JINFO ZHITONG WAN cause acecoline or barium chloride causes that the spastic contraction of small intestine of guinea pig all has antagonism, the tension force that mainly shows as the dosing metagaster obviously descends, and tangible dose-effect relationship is arranged.Point out two kinds of technology preparations that tangible spasmolysis (table 8) is all arranged.

The influence that table 8, two kinds of technologies of JINFO ZHITONG WAN are moved to intestine in vitro

Medicine	Dosage ※ (mg/mL)	Medicine is caused the tetanic property of small intestinal contraction antagonism percentage rate (%)
					Acetylcholine	Barium chloride	Histamine
		Former technology I II new technology I II III	7.0 14.0 7.0 14.0 28.0	48.0±22.3(10) 65.6±20.6(8) 25.9±10.7(10) 56.6±11.1(12) 75.2±14.8(8)				39.7±11.2(9) 66.8±10.0(8) 28.2±10.3(8) 38.0±12.3(8) 69.8±15.3(8)	57.0±20.2(9) 89.5±10.8(8) 54.6±17.3(9) 75.5±24.1(10) 91.3±17.4(9)

Annotate: number is the intestinal tube number in the bracket. ^※For bathing pipe Chinese medicine concentration.

2.4.2 isolated rat uterus movement test

Get female sd inbred rats, in preceding 3 days of experiment, intramuscular injection diethylstilbestrol injection 0.54mg/kg body weight was tested on the 3rd day once a day, and animal dislocation is put to death, and cut open the belly, and careful separating uterus is peelled off the fatty tissue and the mesentery that adhere to, put into that to wear Crohn liquid standby.Bathe in the pipe and wear Crohn liquid 20ml, 37 ± 0.5 ℃ of water temperatures feed O ₂The about 1.5cm of clip uterus experimentizes by rabbit intestinal tube exercise testing same procedure.Treat that uterus movement adds oxytocin 0.25 unit after stable, shrink the adding of stable back and respectively be subjected to the reagent thing, observe the variation of curve movement.

Experimental result shows that two technologies of JINFO ZHITONG WAN cause that to oxytocin the spastic contraction of rat uterus has tangible antagonism, mainly show as dosing after uterine contraction tension force significantly descend, its effect is strengthened with the increasing of dosage.Point out two kinds of technology preparations that tangible spasmolysis (table 9) is arranged.

Table 9, JINFO ZHITONG WAN cause the antagonism of the spastic contraction of rat uterus to oxytocin

Medicine	Dosage ※ (mg/mL)	Uterus hop count (n)	The antagonism percentage rate (%, x ± s)
				The former technology I II gold of gold Buddhist Buddhist new technology I II III rotundine	7.0 14.0 7.0 14.0 28.0 1.0	7 8 6 8 8 7	22.9±10.6 58.8±32.3 18.0±3.9 58.8±19.7 90.5±17.3 90.9±15.5

Annotate: ^※For bathing pipe Chinese medicine concentration.

3 brief summaries

3.1 analgesic activity

3.1.1 hot plate method and acetic acid twisting method analgesic test show, what gold Buddhist pain relieving granule (new technology preparation) and JINFO ZHITONG WAN (former preparation) can both reduce obviously that acetic acid causes mice turns round the body number of times, improve the pain threshold of hot plate method experiment mice, both action intensities are similar, point out both that analgesic activity is arranged.

3.1.2 the dysmenorrhea model in mice analgesic test shows, two kinds of preparations of gold Buddhist pain relieving granule (new technology preparation) and JINFO ZHITONG WAN (former preparation) are irritated the administration of stomach therapeutic, have obvious reduction oxytocin to cause the effect of dysmenorrhea model mouse writhing number of times, both action intensities are similar.

3.2 spasmolysis

3.2.1 isolated rabbit small intestinal and isolated guinea pig ileum exercise test show, gold Buddhist pain relieving granule (new technology preparation) and two kinds of preparations of JINFO ZHITONG WAN (former preparation) cause that to acecoline, barium chloride the stripped spastic contraction of jejunum of rabbit all has tangible antagonism, same dose compares, and former technology slightly is better than new technology; Two kinds of preparations cause that to histamine the spastic property of the ileum contraction of exsomatizing also has tangible antagonism, and both action intensities are similar.Point out two kinds of preparations that tangible spasmolysis is all arranged.

3.2.2 the test of isolated rat uterus movement shows, clear liquid all has the obvious suppression effect to the spastic contraction of isolated rat uterus muscle bar that oxytocin causes on the aqueous solution of gold Buddhist pain relieving granule (new technology preparation) and two kinds of preparations of JINFO ZHITONG WAN (former preparation), same dose compares, and both action intensities are similar.

3.3 antiinflammatory action

3.3.1 test of mouse peritoneal hair cell vascular permeability and rat acute foot swelling test show that acute the oozing out that golden Buddhist pain relieving granule (new technology preparation) and two kinds of preparation gastric infusion Dichlorodiphenyl Acetates of JINFO ZHITONG WAN (former preparation) cause the mouse peritoneal blood capillary has the obvious suppression effect; The impatient property of rat Ovum Gallus domesticus album foot swelling model is had the effect of obvious reduction paw swelling, same dose relatively, new technology slightly is better than former technology.Point out two kinds of preparations that anti-acutely inflamed effect is arranged.

3.4 anti-acute gastric mucosal lesion effect

3.4.1 rat, the test of chmice acute gastric mucosa injury show; gold Buddhist pain relieving granule (new technology preparation) and two kinds of preparation gastric infusions of JINFO ZHITONG WAN (former preparation) have the certain protection effect to the chmice acute gastric mucosa injury that acidic alcohol causes; can reduce the gastric mucosa injury index, more obvious with the effect of new technology preparation.The rat pipe film injury that indometacin is caused has significant protective effect, and same function compares, and former technology preparation action intensity is better than new technology.

Sum up: as can be seen by above-mentioned data, the prepared particulate drug action of golden Buddhist pain relieving of adopting new technology is suitable with original JINFO ZHITONG WAN preparation, but the dried cream yield of new technology is lower than former technology, the suitable crude drug amount of the prepared dried cream of the particulate Unit Weight of golden Buddhist pain relieving of new technology is far above the prepared pill of former technology, the amount that the patient once takes has reduced, and uses more convenient.

The specific embodiment

Embodiment 1: the particulate preparation method of golden Buddhist pain relieving, and it takes following steps:

(1) gets the Radix Paeoniae Alba, Radix Glycyrrhizae, Radix Curcumae, Rhizoma Curcumae Longae, Fructus Citri Sarcodactylis and Radix Notoginseng Six-element crude drug, add 10 times in water for the first time, decocted 1 hour; For the second time add 6 times in water, decocted 1.5 hours; Merge extracted twice liquid, filter, filtrate is concentrated into the extractum that relative density is 1.20-1.25 (75-80 a ℃);

(2) to add 95% ethanol to the alcohol amount of containing be 60% precipitation to above-mentioned extractum, left standstill 12 hours, pure molten supernatant, filter, standby;

(3) the Rhizoma Corydalis (processed with vinegar) medicinal material coarse powder broken after, add for the first time 5 times of 60% ethanol, reflux, extract, 1 hour; For the second time add 3 times of 50% ethanol, reflux, extract, 1.5 hours filters, and is standby;

(4) merge above-mentioned two parts solution, mix homogeneously, being concentrated into relative density is 1.25, measures dry solids content, adds the maltodextrin that is equivalent to dry solids content gross weight 4% and carries out vacuum drying, gets dry extract;

(5) with behind get dry extract mill 100 orders, carry out one-step palletizing, cross 16 mesh sieves and 60 mesh sieves, make granule.

Embodiment 2: the particulate preparation method of golden Buddhist pain relieving, and it takes following steps:

(1) gets the Radix Paeoniae Alba, Radix Glycyrrhizae, Radix Curcumae, Rhizoma Curcumae Longae, Fructus Citri Sarcodactylis and Radix Notoginseng Six-element crude drug, add 12 times in water for the first time, decocted 2 hours; For the second time add 10 times in water, decocted 1.5 hours; Merge extracted twice liquid, filter, filtrate is concentrated into the extractum that relative density is 1.20-1.25 (75-80 a ℃);

(2) to add 95% ethanol to the alcohol amount of containing be 60% precipitation to above-mentioned extractum, left standstill 24 hours, pure molten supernatant, filter, standby;

(3) the Rhizoma Corydalis (processed with vinegar) medicinal material coarse powder broken after, add for the first time 6 times of 60% ethanol, reflux, extract, 2 hours; For the second time add 4 times of 60% ethanol, reflux, extract, 1.5 hours filters, and is standby;

(4) merge above-mentioned two parts solution, mix homogeneously, being concentrated into relative density is 1.25, measures dry solids content, adds the maltodextrin that is equivalent to dry solids content gross weight 4% and carries out vacuum drying, gets dry extract;

(5) with behind get dry extract mill 120 orders, carry out one-step palletizing, cross 16 mesh sieves and 60 mesh sieves, make granule.

Embodiment 3: the particulate preparation method of golden Buddhist pain relieving, and it takes following steps:

(1) gets the Radix Paeoniae Alba, Radix Glycyrrhizae, Radix Curcumae, Rhizoma Curcumae Longae, Fructus Citri Sarcodactylis and Radix Notoginseng Six-element crude drug, add 14 times in water for the first time, decocted 2 hours; For the second time add 12 times in water, decocted 3 hours; Merge extracted twice liquid, filter, filtrate is concentrated into the extractum that relative density is 1.20-1.25 (75-80 a ℃);

(2) to add 95% ethanol to the alcohol amount of containing be 70% precipitation to above-mentioned extractum, left standstill 36 hours, pure molten supernatant, filter, standby;

(3) the Rhizoma Corydalis (processed with vinegar) medicinal material coarse powder broken after, add for the first time 7 times of 70% ethanol, reflux, extract, 3 hours; For the second time add 4 times of 70% ethanol, reflux, extract, 3 hours filters, and is standby;

(4) merge above-mentioned two parts solution, mix homogeneously, being concentrated into relative density is 1.25, measures dry solids content, adds the maltodextrin that is equivalent to dry solids content gross weight 4% and carries out vacuum drying, gets dry extract;

(5) with behind get dry extract mill 140 orders, carry out one-step palletizing, cross 16 mesh sieves and 60 mesh sieves, make granule.

Claims (2)

1, a kind of preparation method for the treatment of the Chinese patent medical granule of pain disease, it is characterized in that: it takes following steps:

(1) gets the Radix Paeoniae Alba, Radix Glycyrrhizae, Radix Curcumae, Rhizoma Curcumae Longae, Fructus Citri Sarcodactylis and Radix Notoginseng Six-element crude drug, add water 10-14 for the first time doubly, decocted 1-3 hour; Add for the second time water 6-12 doubly, decocted 1-3 hour; Merge extracted twice liquid, filter, filtrate is concentrated into the extractum that relative density is 1.20-1.25 (75-80 a ℃);

(2) above-mentioned extractum adds 80-95% ethanol to containing the alcohol amount for the 50-70% precipitation, leaves standstill 12-36 hour, gets pure molten supernatant, filters, and is standby;

(3) the Rhizoma Corydalis (processed with vinegar) medicinal material coarse powder broken after, add for the first time 50-70% ethanol 5-7 doubly, reflux, extract, 1-3 hour; Add for the second time 50-70% ethanol 3-5 doubly, reflux, extract, 1-3 hour, filter, standby;

(4) merge above-mentioned two parts solution, mix homogeneously, being concentrated into relative density is 1.25, measures dry solids content, adds the maltodextrin that is equivalent to dry solids content gross weight 3-5% and carries out drying, gets dry extract;

(5) with behind the get dry extract mill 100-140 order, granulate, cross 16 mesh sieves and 60 mesh sieves, make granule.

2, the preparation method of the Chinese patent medical granule of treatment pain disease according to claim 1, it is characterized in that: it takes following steps:

(1) gets the Radix Paeoniae Alba, Radix Glycyrrhizae, Radix Curcumae, Rhizoma Curcumae Longae, Fructus Citri Sarcodactylis and Radix Notoginseng Six-element crude drug, add 12 times in water for the first time, decocted 2 hours; For the second time add 10 times in water, decocted 1.5 hours; Merge extracted twice liquid, filter, filtrate is concentrated into the extractum that relative density is 1.20-1.25 (75-80 a ℃);

(2) to add 95% ethanol to the alcohol amount of containing be 60% precipitation to above-mentioned extractum, left standstill 12-36 hour, pure molten supernatant, filter, standby;

(3) the Rhizoma Corydalis (processed with vinegar) medicinal material coarse powder broken after, add for the first time 6 times of 60% ethanol, reflux, extract, 2 hours; For the second time add 4 times of 60% ethanol, reflux, extract, 1.5 hours filters, and is standby;

(4) merge above-mentioned two parts solution, mix homogeneously, being concentrated into relative density is 1.25, measures dry solids content, adds the maltodextrin that is equivalent to dry solids content gross weight 4% and carries out vacuum drying, gets dry extract;

(5) with behind get dry extract mill 120 orders, carry out one-step palletizing, cross 16 mesh sieves and 60 mesh sieves, make granule.