CN1238042C - Shoulder pain treating Chinese medicine and its prepn process - Google Patents
Shoulder pain treating Chinese medicine and its prepn process Download PDFInfo
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Abstract
The present invention relates to traditional Chinese medicine for alleviating shoulder pain and a preparation process thereof. 283 to 383 portions of angelica, 283 to 383 portions of corydalis tuber, 283 to 383 portions of wenyujin concise rhizome, 70.6 to 95.5 portions of notoginseng, 28.3 to 38.3 portions of olibanum and 283 to 383 portions of beautiful sweetgum fruit are used as raw medicinal materials matched with excipient auxiliary materials of microcrystalline cellulose, polyvidone, sodium carboxyl methylstarch, magnesium stearate and a coating auxiliary material of opadry used during film coated tablet manufacture. The traditional Chinese medicine of the present invention has the functions of activating the blood circulation to dissipate blood stasis, relieve inflammation and alleviating pain. Novel technologies of a supercritical extraction method and a dry granulation method are adopted in the preparation process, so active ingredients are completely extracted and reserved, and the continuous large-scale production under the GMP condition is convenient. The traditional Chinese medicine of the present invention can be made into various solid preparations such as tablets, capsule capsules, granules, etc., and has the advantages of high stability, convenient administration, accurate dosage and good curative effect.
Description
Technical field:
The present invention relates to a kind of medicine that is used for the treatment of scapulohumeral periarthritis and preparation method thereof, belong to the field of Chinese medicines.
Background technology:
Scapulohumeral periarthritis is a kind of commonly encountered diseases, is mainly in person in middle and old age, has a strong impact on normal work of people and life.In existing, Western medicine, and the physical therapy method of present more employing etc. is all not ideal enough on curative effect, Western medicine is used some downerns and antiinflammation pain-stopping pharmaceutical such as indometacin, piroxicam etc. more, toxic and side effects is bigger, and cure the symptoms, not the disease, physical therapy is many based on hot compress, exercise, and onset is slower.
Summary of the invention:
Technical problem to be solved by this invention is to avoid existing weak point in the above-mentioned prior art, and a kind of Chinese medicine that has better curative effect for scapulohumeral periarthritis is provided, and logical shoulder pain Chinese medicine relaxes.And the preparation technology of this solid preparation of Chinese medicine is provided, take, carry inconvenient drawback with what solid preparation overcame that decoction exists.
The technical scheme that technical solution problem of the present invention is adopted is:
The present invention is relaxed and is led to shoulder pain Chinese medicine, is characterized in being made by following bulk drugs:
283～383 parts of 283～383 parts of Radix Angelicae Sinensis, 283～383 parts of Rhizoma Corydalis, 283～383 parts of Rhizoma Wenyujin Concisum, 70.6～95.5 parts of Radix Notoginseng, 28.3～38.3 parts of Olibanums and Fructus Liquidambaris.
The present invention makes tablet then needs to join in addition 2.7～3.7 parts of 113.1～153 parts of figuration microcrystalline cellulose excipients, 16.2～21.9 parts of polyvidones, 13.6～18.4 parts of carboxymethylstach sodium and magnesium stearate, and 7.7～10.4 parts of coating adjuvant Opadries.
Preparation technology's of the present invention characteristics are to have following steps:
A, get Radix Angelicae Sinensis, Rhizoma Wenyujin Concisum two flavors, be ground into coarse powder, add ethanol and place supercritical extraction equipment, CO
2Supercritical extraction gets the reserve liquid that supercritical extraction goes out;
B, get Rhizoma Corydalis, Olibanum and Fructus Liquidambaris, alcohol reflux filters, and medicinal residues add ethanol again, and reflux, extract, filters, and merges alcohol extract, and alcohol extract merges with above-mentioned steps a gained reserve liquid, and decompression recycling ethanol gets alcohol-extracted extract after concentrating;
C, get Radix Notoginseng powder and be broken into fine powder, with step b gained alcohol-extracted extract and microcrystalline Cellulose, polyvidone, mix homogeneously, oven dry is pulverized, dry extract is standby;
D, in step c gained dry extract, add carboxymethyl starch sodium and magnesium stearate, through granulate, tabletting, film coating, promptly.
Preparation method of the present invention also can be following steps:
A, identical with above-mentioned steps a gets the reserve liquid that supercritical extraction goes out
B, get Rhizoma Corydalis, Olibanum, Fructus Liquidambaris, alcohol reflux filters, and medicinal residues add ethanol again, and reflux, extract, filters, and the alcohol extract of merging merges with above-mentioned steps a gained reserve liquid, and recovery ethanol is concentrated into 50 ℃ of following relative densities and is 1.08～1.10 extractum; This extractum and microcrystalline Cellulose mix homogeneously, spray drying gets spray powder;
C, Radix Notoginseng are pulverized, and cross 60 mesh sieves, with spray powder, dimension ketone, carboxymethylstach sodium and magnesium stearate, mix homogeneously, dry granulation, tabletting, film coating.
Radix Angelicae Sinensis sweet in the mouth suffering, warm in nature, the key medicine of invigorating blood circulation for enriching blood.Its pharmacological action of modern study: have the promotion immunologic function, good interferon-induced activity; Anti-inflammatory and antalgic and anti-damaging action.The Radix Notoginseng sweet and slightly bitter taste is warm in nature, the dissipating blood stasis hemostasis, and subduing swelling and relieving pain, and the strong effect of tonify deficiency is arranged, for controlling the good merchantable brand of all cards of blood stasis.Pharmacological action: suppress central action; Analgesic activity; Antiinflammatory action; Improve immunologic function.Rhizoma Corydalis is warm in nature, promoting blood circulation to remove blood stasis, promoting the circulation of QI to relieve pain.Its pharmacological action: to cental system analgesia, anesthetic action; Urge the people, calm and stable effect; The Olibanum blood-activating and qi-promoting, reducing swelling and alleviating pain, pharmacological action: reduce plasma viscosity and analgesic activity.Fructus Liquidambaris is flat, kind wind-damp dispelling, and soothing liver-QI is active, the tool resist inflammation on repercussive function.Be classified as monarch drug to work as, Radix Notoginseng and Rhizoma Corydalis close and are minister, and auxilliary monarch drug is strengthened the power of blood-activating and qi-promoting pain relieving; Fructus Liquidambaris and Olibanum are combined into adjuvant drug, the blood stasis dispelling double wind-damp dispelling that stimulates the menstrual flow; Rhizoma Wenyujin Concisum circulation of qi promoting warm in nature has the merit of uniqueness especially to shoulder arm pain, and it has antiinflammatory action modern pharmacological research, use for making, draw all medicines and go upward to disease institute.Full side closes 5, plays nourshing blood and promoting blood circulation altogether, the merit of promoting the circulation of QI to relieve pain.
Compared with the prior art, beneficial effect of the present invention is embodied in:
1, show by the Pharmacodynamic test of active extract result: the easypro logical shoulder pain sheet of the present invention can obviously suppress the mice ear degree that dimethylbenzene causes, obviously reduce the rat granulation hyperplasia tissue weight that plastic sheet causes, obviously reduce the whole blood viscosity under granuloma rat platelet maximum agglutination rate and low shear rate 1s-1, the 5s-1, obviously reduce the number of times that acetic acid brings out the mouse writhing reaction, obviously increase mice hot plate pain threshold, prove that this medical instrument has antiinflammatory action, function of promoting blood circulation to disperse blood clots and analgesic activity.
2, Chinese medicine of the present invention can make the medicine good stability by making tablet (solid preparation), easily storage, and taking convenience, dosage are accurate, easy to carry, and said preparation does not contain antiseptic, takes safety and has no side effect.
3, the present invention has adopted the extraction process of supercritical CO 2 extraction in preparation technology.The supercritical fluid extraction noresidue, speed is fast, cost is low, effective ingredient is not destroyed, and after extracting solution and alcohol extract merge reclaim under reduced pressure and concentrate, adds and adds the adjuvant dry granulation again after the excipient oven dry and form.Preparation technology of the present invention makes effective ingredient be obtained to greatest extent keeping.The preparation method operating process is simple, is convenient to large-scale production under the seriality GMP condition.
The specific embodiment:
283～383 parts of Radix Angelicae Sinensis, 283～383 parts of Rhizoma Corydalis, 283～383 parts of Rhizoma Wenyujin Concisum, 70.6～95.5 parts of Radix Notoginseng, 28.3～38.3 parts of Olibanums, 283～383 parts of Fructus Liquidambaris, 113.1～153 parts of microcrystalline Cellulose, 16.2～21.9 parts of polyvidones, 13.6～18.4 parts of carboxymethylstach sodium, 2.7～3.7 parts of magnesium stearate, 7.7～10.4 parts of coating adjuvant Opadries.
The preferred value of making tablet is:
333 parts of Radix Angelicae Sinensis, 333 parts of Rhizoma Corydalis, 333 parts of Rhizoma Wenyujin Concisum sheets, Radix Notoginseng 83 minutes, 33.3 parts of Olibanums, 333 parts of Fructus Liquidambaris; The figuration adjuvant: 133 parts of microcrystalline Cellulose, 19 parts of polyvidones, 16 parts of carboxymethylstach sodium, U.S. 3.2 parts of stearic acid, other has 9 parts of coating adjuvant Opadries.
Preparation method one:
A, get Radix Angelicae Sinensis, Rhizoma Wenyujin Concisum, be ground into coarse powder, add 0.5～1.2 times of medical material amount 90～95% ethanol and place supercritical extraction equipment, CO
2Supercritical extraction, extract 40～60 ℃ of still temperature, 25～45 kilograms of pressure, 40～60 ℃ of separation reactor I temperature, 9～15 kilograms of pressure, 40～60 ℃ of separation reactor I I temperature, 9～15 kilograms of pressure, extracted altogether 0.5～2.0 hour, and got the reserve liquid that supercritical extraction goes out.
B, get Rhizoma Corydalis, Olibanum, Fructus Liquidambaris, add 4～10 amounts, 50～90% alcohol reflux 1～2 hour, filter, medicinal residues add 3～7 times of amount 50～90% alcohol reflux 1～2 hour again, filter merging filtrate, this filtrate and above-mentioned reserve liquid merge, decompression recycling ethanol, after alcohol-extracted extract; Being concentrated to relative density is 1.0～1.7 (40～60 ℃).
C, get Radix Notoginseng powder and be broken into 60 purpose fine powders, with alcohol-extracted extract and microcrystalline Cellulose, polyvidone mix homogeneously, oven dry is pulverized, dry extract is standby.
Add carboxymethyl starch sodium in d, the above-mentioned dry extract, magnesium stearate mixing granulate, tabletting, the coating adjuvant is bundled into veneer coated tablet, packing, label, packing, promptly.
Preparation method two:
A, Radix Angelicae Sinensis, Rhizoma Wenyujin Concisum are ground into coarse powder, add 0.8 times of medical material amount of entrainment reagent 95% ethanol, place supercritical extraction equipment, supercritical CO
250 ℃ of still temperature, 35 kilograms of pressure are extracted in extraction, 35 ℃ of separation reactor I temperature, 12 kilograms of pressure, and 35 ℃ of separation reactor I I temperature, 12 kilograms of pressure extracted 1 hour altogether, and it is standby to get supercritical extraction liquid;
B, Rhizoma Corydalis, Olibanum, Fructus Liquidambaris add 70% alcohol reflux twice, each 1.5 hours, add 7 times of amounts for the first time, add for the second time 5 times of amounts, merge alcohol extract, filter, filtrate and above-mentioned standby medicinal liquid merge, and reclaim ethanol, are concentrated into the extractum of relative density 1.08～1.10 (50 ℃); This extractum and microcrystalline Cellulose mix homogeneously, spray drying gets spray powder;
C, Radix Notoginseng are pulverized, and cross 60 mesh sieves, with spray powder, dimension ketone, carboxymethylstach sodium and magnesium stearate, mix homogeneously, dry granulation, tabletting, film coating.
Radix Angelicae Sinensis and Rhizoma Wenyujin Concisum all contain volatile oil, effective ingredient ferulic acid in the Radix Angelicae Sinensis is heated and very easily decomposes, for fully extracting the medical material effective ingredient and guaranteeing its stable components, adopt the super critical extraction of extract at low temperature, be the extraction that entrainment reagent will be more conducive to liposoluble constituent with 95% ethanol again, the extraction told alcohol liquid is mainly with volatile oil such as ligustilide, ferulic acid, and organic acid compositions such as curcumin are main.
In order to select the condition of best CO2 supercritical extraction Radix Angelicae Sinensis, Rhizoma Wenyujin Concisum, the design orthogonal test.Selecting L9 (34) orthogonal table for use, serves as to investigate index with composition in the extract (ferulic acid), has carried out 9 tests, result of the test shows, the optimised process of Radix Angelicae Sinensis, Rhizoma Wenyujin Concisum supercritical extraction: pressure is 35Mpa, and temperature is 50 ℃, extraction time is 1 hour, and the entrainment reagent consumption is 0.8 times of amount.The Radix Angelicae Sinensis extraction ratio can reach 77.4% under this condition.
Mainly contain alkaloids in the Rhizoma Corydalis, Olibanum is mainly resinous, gummy, the volatile oil composition, and Fructus Liquidambaris contains terpenoid, sterols composition, and the alcohol extraction effect is better, pretends to be alcohol extraction group medical material ethanol extraction.
In order to select the optimum condition of alcohol reflux, the design orthogonal test.Select L9 (34) orthogonal table for use, respectively with the content of the tetrahydropalmatine in the alcohol extract as investigating index, carried out 9 tests.Result of the test shows that the optimum extraction process of Rhizoma Corydalis, Olibanum, Fructus Liquidambaris is: 70% ethanol that 7+5 doubly measures, reflux extracting time are 1.5 hours+1.5 hours.The Rhizoma Corydalis extraction ratio can reach 82.2% under this condition.
The selection of the condition of concentrating
Main effective ingredient among this side is a ferulic acid, tetrahydropalmatine etc.Tetrahydropalmatine is more stable, and it is little to concentrate influence, and the ferulic acid case of thermal instability.In order to reduce the loss of ferulic acid, medicinal liquid concentrates and reaches when reclaiming solvent, and all (0.08Mpa) carry out under the condition, temperature is no more than 70 ℃ in decompression.
The selection of baking temperature
Extractum is dried after adding Radix Notoginseng powder, and temperature can not be too high, otherwise volatile ingredient can lose, and the ferulic acid instability, meets heat and can decompose, and moisture must be controlled within the specific limits and could guarantee the tabletting effect simultaneously.
The tabletting result of the test shows, the granule water content is at 4.0～6.0% o'clock, press tablet smooth, hardness suitable;
And water content is lower than at 4.0% o'clock, press tablet loose sheet, sliver phenomenon easily take place; Water content is higher than at 8.0% o'clock, and mobility of particle is relatively poor, needs to increase lubricant this moment.Therefore should control 70 ℃ of baking temperatures, 24 hours drying times.
Adjuvant is selected
The selection of adjuvant should make its when wafers not sticking, good moldability, sheet smooth surface, hardness is suitable, disintegration time is suitable, and supplementary product consumption is less.
The present invention is relaxed and is led to shoulder pain sheet Pharmacodynamic test of active extract result:
Influence to the wet rat scapulohumeral periarthritis that causes of wind and cold:
Test objective: observe being subjected to of the influence of reagent thing, determine whether medicine has the effect of treatment scapulohumeral periarthritis to the wet rat scapulohumeral periarthritis lesion degree that causes of wind and cold.
Experimental control;
(1) model group: select 0.5%CMC-Na solution for use.
(2) positive drug group: select sinomenine hydrochloride for use, because of it is present effectively medicine commonly used.
Test grouping and dosage;
(1) model group: 0.5%CMC-Na solution.
(2) positive drug group: 0.4% sinomenine hydrochloride suspension solution (0.04g/kg).
(3) low dose group: 7.5% relaxes leads to shoulder pain sheet suspension solution (0.75g/kg).
(4) dosage group in: 15% relaxes leads to shoulder pain sheet suspension solution (1.5g/kg).
(5) high dose group: 30% relaxes leads to shoulder pain sheet suspension solution (3g/kg).
(6) normal control group: 0.5%CMC-Na solution.
Administration volume: 10ml/kg.Route of administration: oral administration gavage administration (ig).
Test operation:
Get healthy rat, random packet.Each is organized rat and anaesthetizes with 10% chloral hydrate solution (0.4g/kg) ip, gets the right side shoulder and loses hair or feathers with 8% sodium sulfide solution.The right side shoulder wind and cold that lost hair or feathers in the 1st day is wet to stimulate, and faces upward the position and fixes, and stimulus intensity is 5～7 ℃ of temperature, relative humidity＞95%, frozen water cylinder pressure 5kg/cm
2, air outlet is irritated the stomach syringe needle No. 18, and the continued stimulus time is 8 hours; The right side shoulder cold-damp of losing hair or feathers in the 2nd day stimulates, and it is fixing to face upward the position, with the plastic bag rubble ice of packing into after with water-soaked, spreads on depilation right side shoulder outward, will use up when ice cube melts, and in time changes, and continues 8 hours.Animal was normally raised in the 3rd day, beginning administration in the 4th day, administration every day 1 time, continuous 14 days.After the last administration 24 hours, observe animal right fore limitation of activity and grab thing limited degree situation, be recorded in the record special table; Draw the neck dislocation to put to death animal, get right side subcutaneous tissue of shoulder, 10% formalin fixed, paraffin embedding, conventional section, histology's microscopy is made in HE dyeing.Be recorded in the record special table, and t method of inspection and model group are carried out the significance test comparison between the employing group.
Result of the test:
The result shows: the wet weight of thrombus of the logical shoulder pain sheet 0.25g/kg treated animal that relaxes and model group be not statistically signigicant (P＞0.05) relatively, 0.5g/kg, the wet weight of thrombus of 1g/kg treated animal is starkly lower than model group, learn by statistics and handle, be significant difference (P＜0.05, P＜0.01=, drug effect strengthens with dosage; The thrombosis dry weight of promoting blood circulation to remove obstruction in the collateral injection 0.25g/kg treated animal and model group be not statistically signigicant (P＞0.05) relatively, 0.5g/kg, the dried model group that is starkly lower than of thrombosis of 1g/kg treated animal, learn by statistics and handle, be significant difference (P＜0.01, P＜0.01=, and drug effect also strengthens with dosage; Weight in wet base suppression ratio and dry weight suppression ratio also obviously increase.The results are shown in Table 1.
Table 1: the influence of the mice ear degree that xylol causes (X ± S)
| Group | Dosage (g/kg) | Animal (only) | Left side auricle heavy (mg) | Auris dextra sheet heavy (mg) | Left and right sides ear weight difference (mg) | Swelling suppresses % |
| The easypro easypro easypro shoulder pain of leading to of shoulder pain sheet of leading to of the easypro logical shoulder pain sheet of shoulder pain sheet of leading to of model group prednisolone acetate is loose | -- 0.005 0.25 0.5 1.0 1.0 | 10 10 10 10 10 10 | 20.5±1.6 20.2±1.5 20.2±1.7 20.7±1.5 20.1±1.9 20.3±1.3 | 22.6±4.6 16.1±2.9 **19.8±3.5 18.5±2.5 *16.3±3.2 **18.7±2.0 * | 9.1±5.3 2.9±2.6 ** 6.6±3.3 4.8±2.3 * 3.2±2.7 ** 5.4±1.1 * | 68.1 27.5 47.3 64.8 40.7 |
Compare with model group: U:P＜0.05,
*: P＜0.01.
The influence of the mice ear degree that xylol causes:
Test objective: observe the influence be subjected to the mice ear degree that reagent thing xylol causes, determine whether medicine has antiinflammatory action.
Experimental control;
(1) model group: select 0.5%CMC-Na solution for use.
(2) positive drug group: select prednisolone acetate for use, because of it is present effectively medicine commonly used.
Test grouping and dosage;
(1) model group: 0.5%CMC-Na solution.
(2) positive drug group: 0.025% prednisolone acetate suspension solution (0.005g/kg).
(3) low dose group: 7.5% relaxes leads to shoulder pain sheet suspension solution (1.5g/kg).
(4) dosage group in: 15% relaxes leads to shoulder pain sheet suspension solution (3g/kg).
(5) high dose group: 30% relaxes leads to shoulder pain sheet suspension solution (6g/kg).
Administration volume: 20ml/kg.Route of administration: oral administration gavage administration (ig).
Test operation:
Get male mice, body weight 20～22g, random packet, 10 every group.Every day, the ig administration was 1 time, for three days on end.After the last administration 1 hour, each Mus auris dextra is coated with xylene solution 0.05ml.Put to death animal after 1 hour, dash in the same position of the left and right ear of each Mus with diameter 8mm circle and to sweep away 1 circle auricle respectively, weigh, deducting left auricle weight with auris dextra sheet weight is the poor of left and right auricle weight, index as the swelling degree, by formula calculate inhibitory rate of intumesce, and t method of inspection and model group are carried out significance test relatively between the employing group.
Result of the test:
The result shows: the left and right sides ear weight difference of the easypro logical shoulder pain sheet 3g/kg of ig, 6g/kg treated animal is starkly lower than model group, learn by statistics and handle, be significant difference (P＜0.05, P＜0.01), show that the logical shoulder pain sheet that relaxes can obviously suppress the mice ear degree that dimethylbenzene causes.The results are shown in Table 2.
Table 2: the influence of the mice ear degree that xylol causes (X ± S)
| Group | Dosage (g/kg) | Animal (only) | Left side auricle heavy (mg) | Auris dextra sheet heavy (mg) | Left and right sides ear weight difference (mg) | Swelling suppresses % |
| The model group prednisolone acetate is relaxed and leads to the easypro logical shoulder pain sheet of the easypro logical shoulder pain sheet of shoulder pain sheet | -- 0.005 1.5 3.0 6.0 | 10 10 10 10 10 | 13.6±1.0 13.7±1.5 13.3±1.3 13.5±1.6 13.2±1.7 | 22.8±4.6 17.0±2.7 ** 20.1±2.9 18.5±2.6 * 17.3±2.3 ** | 9.2±4.9 3.3±1.6 ** 6.8±3.2 5.0±2.1 * 4.1±2.2 ** | 64.1 26.1 45.7 55.4 |
Compare with model group:
*: P＜0.05,
*: P＜0.01.
To the granulomatous influence of rat plastic sheet:
Test objective: observe the influence be subjected to the rat granulation tissue hyperplasia that the reagent thing causes plastic sheet, determine whether medicine has antiinflammatory action.
Experimental control;
(1) model group: select 0.5%CMC-Na solution for use.
(2) positive drug group: select aspirin for use, because of it is present effectively medicine commonly used.
Test grouping and dosage;
(1) model group: 0.5%CMC-Na solution.
(2) positive drug group: 2% aspirin solution (0.2g/kg).
(3) high dose group: 30% relaxes leads to shoulder pain sheet suspension solution (3g/kg).
(4) dosage group in: 15% relaxes leads to shoulder pain sheet suspension solution (1.5g/kg).
(5) low dose group: 7.5% relaxes leads to shoulder pain sheet suspension solution (0.75g/kg).
Administration volume: 10ml/kg.Route of administration: oral administration gavage administration (ig).
Test operation:
Get male rat, body weight 210～270g, random packet, 10 every group.After the ip pentobarbital sodium 30mg/kg anesthesia, at the left and right sides of every Mus pars inguinalis iodine disinfection, after 75% cotton ball soaked in alcohol takes off iodine, respectively cut the long osculum of 1cm, with the ophthalmology tweezer sterilization plastic sheet (there are 4 through holes the centre) of diameter 10mm, heavy 110mg is implanted from incision subcutaneous, skin suture immediately.Each Mus ip penicillin 20,000 unit/only.From performing the operation the same day administration every day 1 time, continuous 7 days.After the last administration 24 hours, each Mus sacrificed by exsanguination, take out plastic sheet, to separate with muscular fasciae totally attached to the blood crusts on the granuloma, blot with filter paper, weigh, gained weight deducts plastic sheet and heavily promptly gets pure granuloma heavily behind the 110mg, and the meansigma methods that two granulomas about each Mus are heavy is as rat granuloma weight in wet base; Then granuloma is put into 60 ℃ of baking ovens and toasted 24h, take out the title dry weight.Granuloma is wet, dry weight and body weight ratio as wet, the dry weight index; By formula calculate the heavy suppression ratio of granuloma, and the t method of inspection carries out the significance test comparison with model group between the employing group.
Result of the test
The result shows:
The granuloma weight in wet base and the weight in wet base index of the easypro logical shoulder pain sheet 1.5g/kg of ig, 3g/kg treated animal are starkly lower than model group, learn by statistics and handle, and are significant difference (P＜0.05, P＜0.01 and P＜0.05, P＜0.01=; The granuloma dry weight and the dry weight index of the easypro logical shoulder pain sheet 3g/kg of ig, 1.5g/kg treated animal also are starkly lower than model group, learn by statistics and handle, and are significant difference (P＜0.05, P＜0.01 and P＜0.05, P＜0.01=; Show that the logical shoulder pain sheet that relaxes can obviously reduce the rat granulation hyperplasia tissue weight that plastic sheet causes.The results are shown in Table 3-1,3-2.
Table 3-1: to the influence of rat plastic sheet granuloma weight in wet base, weight in wet base index and weight in wet base suppression ratio (X ± S)
| Group | Dosage (g/kg) | Animal (only) | The granuloma counterpoise (mg) that wets | Weight in wet base index (mg/g) | Weight in wet base suppression ratio (%) |
| The model group aspirin relaxes and leads to the easypro logical shoulder pain sheet of the easypro logical shoulder pain sheet of shoulder pain sheet | -- 0.2 0.75 1.5 3 | 10 10 10 10 10 | 719.3±450.9 257.2±187.9 ** 387.5±246.3 332.3±247.1 * 289.9±129.8 ** | 2.94±1.84 1.07±0.77 ** 1.62±1.00 1.38±1.02 * 1.16±0.52 ** | 64.2 46.1 53.8 59.7 |
Compare with model group:
*: P＜0.05,
*: P＜0.01.
Table 3-2: to the influence of rat plastic sheet granuloma dry weight, dry weight index and dry weight suppression ratio (X ± S)
| Group | Dosage (g/kg) | Animal (only) | The dried counterpoise of granuloma (mg) | Dry weight index (mg/g) | Dry weight suppression ratio (%) |
| The model group aspirin relaxes and leads to the easypro logical shoulder pain sheet of the easypro logical shoulder pain sheet of shoulder pain sheet | -- 0.2 0.75 1.5 3 | 10 10 10 10 10 | 136.5±73.7 52.2±41.7 ** 80.1±46.3 64.3±42.1 * 61.1±32.3 ** | 0.56±0.31 0.22±0.17 ** 0.34±0.19 0.27±0.18 * 0.24±0.13 ** | 61.8 41.3 52.9 55.2 |
Compare with model group:
*: P＜0.05,
*: P＜0.01.
Influence to rat platelet aggregation:
Test objective: observe and be subjected to of the influence of reagent thing, determine whether medicine has the effect that suppresses rat platelet aggregation to platelet maximum agglutination rate in the granulation tissue hyperplasia rat body.
Experimental control:
(1) model group: select 0.5%CMC-Na solution for use.
(2) positive drug group: select aspirin for use, because of it is present effectively medicine commonly used.
Test grouping and dosage;
(1) model group: 0.5%CMC-Na solution.
(2) positive drug group: 2% aspirin solution (0.2g/kg).
(3) high dose group: 30% relaxes leads to shoulder pain sheet suspension solution (3g/kg).
(4) dosage group in: 15% relaxes leads to shoulder pain sheet suspension solution (1.5g/kg).
(5) low dose group: 7.5% relaxes leads to shoulder pain sheet suspension solution (0.75g/kg).
(6) normal group: 0.5%CMC-Na solution.
Administration volume: 10ml/kg.Route of administration: oral administration gavage administration (ig).
Test operation:
Get granulation tissue hyperplasia rat in the 2.3 experiment items, after the last administration 24 hours, after each Mus ip pentobarbital sodium 30mg/kg anesthesia, it is fixing to face upward the position, the blood-letting of carotid artery intubate, with 3.8% sodium citrate anticoagulant, centrifugal 5 minutes of low speed (1000rpm), draw upper strata rich platelet (PRP), its platelet count is at 18～200,000/mm
3Between, to be measured.With last blood (3000rpm) centrifugal 10 minutes at a high speed, the absorption supernatant is platelet poor plasma (PPP) again.With ADP (ultimate density is 2nmol/L) is derivant, by literature method (father-in-law ties up the good chief editor of Denging. Hemorheology Study method and use front page Beijing: Science Press, 1989:224), measure platelet aggregation rate with PAPER-I type platelet aggregation and blood clotting analyzer (Beijing Steellex Scientific Instrument Company).By formula calculate the gathering suppression ratio, and t method of inspection and model group are carried out significance test relatively between the employing group.
Result of the test
The result shows:
The platelet maximum agglutination rate of ig easypro logical shoulder pain sheet 0.75g/kg, 1.5g/kg, 3g/kg treated animal is starkly lower than model group, learns by statistics and handles, and is significant difference (P＜0.05, P＜0.01, P＜0.001); The maximum gathering time of the easypro logical shoulder pain sheet 1.5g/kg of ig, 3g/kg treated animal also is starkly lower than model group, learns by statistics and handles, and is significant difference (P＜0.05, P＜0.001); Show that the logical shoulder pain sheet that relaxes can obviously reduce rat platelet aggregation.
The results are shown in Table 4.
Table 4: to the influence of rat platelet aggregation (X ± S)
| Group | Dosage (g/kg) | Number of animals (only) | Maximum agglutination rate (%) | The maximum gathering time (S) | Assemble suppression ratio (%) |
| Normal group model group aspirin relaxes and leads to the easypro logical shoulder pain sheet of the easypro logical shoulder pain sheet of shoulder pain sheet | -- -- 0.2 0.75 1.5 3 | 10 10 10 10 10 10 | 33.5±10.1 ** 49.7±8.5 33.3±8.8 *** 42.2±6.8 * 37.2±6.1 ** 33.9±6.3 *** | 132.7±47.6 *** 211.2±37.3 120.6±27.5 *** 180.3±45.8 162.9±41.2 * 137.2±34.9 *** | 32.60 33.00 15.09 25.15 31.79 |
Compare with model group:
*: P＜0.05,
*: P＜0.01,
* *: P＜0.001.
Experimental control:
(1) model group: select 0.5%CMC-Na solution for use.
(2) positive drug group: select aspirin for use, because of it is present effectively medicine commonly used.
Test grouping and dosage;
(1) model group: 0.5%CMC-Na solution.
(2) positive drug group: 2% aspirin solution (0.2g/kg).
(3) high dose group: 30% relaxes leads to shoulder pain sheet suspension solution (3g/kg).
(4) dosage group in: 15% relaxes leads to shoulder pain sheet suspension solution (1.5g/kg).
(5) low dose group: 7.5% relaxes leads to shoulder pain sheet suspension solution (0.75g/kg).
(6) normal group: 0.5%CMC-Na solution.
Administration volume: 10ml/kg.Route of administration: oral administration gavage administration (ig).
Test operation:
Get granulation tissue hyperplasia rat in the 2.2 experiment items, after the last administration 24 hours, each Mus pentobarbital sodium 30mg/kg, after the ip anesthesia, face upward the position and fix the blood-letting of carotid artery intubate, with the anticoagulant in 1: 9 of 3.8% sodium citrate, measure whole blood viscosity and plasma viscosity with LG-R-80 computer blood viscosity tester, measure erythrocyte sedimentation rate, packed cell volume, and the t method of inspection carries out the significance test comparison with model group between the employing group with Wen Shi pipe method.
Result of the test:
The result shows: ig relaxes and leads to shoulder pain sheet 0.75g/kg, 1.5g/kg, 3g/kg group thing animal low shear rate 1s
-1, 5s
-1Under whole blood viscosity be starkly lower than model group, learn to handle by statistics, be significant difference (equal P＜0.05=; Show that the logical shoulder pain sheet that relaxes can obviously reduce the rat whole blood viscosity.The results are shown in Table 5-1,5-2.
Table 5-1: to the influence of rat whole blood viscosity (X ± S)
| Group | Dosage (g/kg) | Animal (only) | Whole blood viscosity (mPas) | |||
| 200s -1 | 60s -1 | 5s -1 | 1s -1 | |||
| Normal group model group aspirin relaxes and leads to the easypro logical shoulder pain sheet of the easypro logical shoulder pain sheet of shoulder pain sheet | -- -- 0.2 0.75 1.5 3 | 10 10 10 10 10 10 | 3.00±0.28 3.16±0.39 2.75±0.36 * 3.07±0.37 3.05±0.38 2.92±0.30 | 3.56±0.43 3.88±0.50 3.25±0.43 ** 3.66±0.42 3.65±0.36 3.58±0.40 | 7.54±0.80 * 8.49±0.73 6.90±0.71 *** 7.82±0.63 * 7.75±0.49 * 7.52±0.71 ** | 17.80±2.41 ** 20.97±2.47 16.68±1.77 *** 18.78±1.75 * 18.50±1.86 * 18.41±1.93 * |
Compare with model group:
*: P＜0.05,
*: P＜0.01,
* *: P＜0.001.
Table 5-2 is to the influence of rat plasma viscosity, erythrocyte sedimentation rate, packed cell volume (X ± S)
| Group normal group model group aspirin relaxes and leads to the easypro logical shoulder pain sheet of the easypro logical shoulder pain sheet of shoulder pain sheet | Dosage (g/kg)----0.2 0.75 1.5 3 | Animal (only) 10 10 10 10 10 10 | Plasma viscosity (mPas) | Erythrocyte sedimentation rate (mm/h) | Packed cell volume (%) |
| 1.41±0.16 1.49±0.09 1.40±0.13 1.47±0.10 1.48±0.11 1.45±0.10 | 4.5±3.9 7.4±4.5 6.7±4.4 6.1±5.2 4.9±2.7 6.6±5.2 | 36.0±4.6 35.7±2.0 32.8±3.0 * 35.8±3.8 35.9±2.0 34.0±2.6 |
Compare with model group:
*: P＜0.05.
Dichlorodiphenyl Acetate brings out the influence of mouse writhing reaction times:
Test objective: observe being subjected to reagent thing Dichlorodiphenyl Acetate to bring out the influence of mouse writhing reaction times, determine whether medicine has analgesic activity.
Experimental control:
(1) model group: select 0.5%CMC-Na solution for use.
(2) positive drug group: select aspirin for use, because of it is present effectively medicine commonly used.
Test grouping and dosage:
(1) model group: 0.5%CMC-Na solution.
(2) positive drug group: 1% aspirin solution (0.2g/kg).
(3) low dose group: 7.5% relaxes leads to shoulder pain sheet suspension solution (1.5g/kg).
(4) dosage group in: 15% relaxes leads to shoulder pain sheet suspension solution (3g/kg).
(5) high dose group: 30% relaxes leads to shoulder pain sheet suspension solution (6g/kg).
Administration volume: 20ml/kg.Route of administration: oral administration gavage administration (ig).
Test operation:
Get mice, body weight 18～22g, random packet, 10 every group, male and female half and half.Every day, the ig administration was 1 time, for three days on end.After the last administration 1 hour, each Mus lumbar injection 0.6% acetum 02ml/ only." turning round body " reaction (abdominal part indent takes place in 15 minutes behind each Mus lumbar injection acetum of observed and recorded, open trunk and back leg Shen, hips up) number of times by formula calculates the pain suppression ratio, and t method of inspection and model group are carried out significance test relatively between the employing group.
Result of the test:
The result shows: the number of times that the acetic acid of the easypro logical shoulder pain sheet 3g/kg of ig, 6g/kg treated animal brings out the mouse writhing reaction is starkly lower than model group, learns by statistics and handles, and is significant difference (P＜0.05, P＜0.05); Show that the logical shoulder pain sheet that relaxes has certain analgesic activity.The results are shown in Table 6.
Table 6: Dichlorodiphenyl Acetate brings out the influence (X ± S) of mouse writhing reaction times
| Group | Dosage (g/kg) | Animal (only) | Turn round the body number of times (inferior/15min) | Pain suppression ratio (%) |
| The model group aspirin relaxes and leads to the easypro logical shoulder pain sheet of the easypro logical shoulder pain sheet of shoulder pain sheet | -- 0.2 1.5 3.0 6.0 | 10 10 10 10 10 | 26.7±9.6 14.6±7.3 ** 20.1±8.8 17.0±8.4 * 15.7±8.6 * | 45.3 24.7 36.3 41.2 |
Compare with model group:
*: P＜0.05,
*: P＜0.01.
Influence to mice hot plate method pain threshold:
Test objective: observe and be subjected to of the influence of reagent thing, determine whether medicine has analgesic activity to mice hot plate method pain threshold.
Experimental control;
(1) model group: select 0.5%CMC-Na solution for use.
(2) positive drug group: select tramadol hydrochloride for use, because of it is present effectively medicine commonly used.
Test grouping and dosage;
(1) model group: 0.5%CMC-Na solution.
(2) positive drug group: 0.2% tramadol hydrochloride suspension solution (0.04g/kg).
(3) low dose group: 7.5% relaxes leads to shoulder pain sheet suspension solution (1.5g/kg).
(4) dosage group in: 15% relaxes leads to shoulder pain sheet suspension solution (3g/kg).
(5) high dose group: 30% relaxes leads to shoulder pain sheet suspension solution (6g/kg).
Administration volume: 20ml/kg.Route of administration: oral administration gavage administration (ig).
Test operation:
1. regulate temperature controlled water bath:
Temperature controlled water bath pot bath topped up with water is regulated temperature regulating device and is made water temperature be controlled at 55 ± 0.75 ℃, puts into the 1000ml beaker, and makes beaker bottom immerse in the water as hot plate preheating 10 minutes.
2. screen qualified mice:
Get female mice, body weight 19～21g, on each 1 heat liberation board, with mice on heat liberation board to the pain threshold of metapedes required time (second) occurring licking as this Mus, allly lick the metapedes time less than 5 seconds or give it up greater than 30 seconds or leaper.
3. observe drug effect:
Qualified female mice, random packet, 10 every group.After the administration 0.5,1,2,3 hour, be placed on each Mus on the hot plate once more, with mice from the heat liberation board to metapedes required time (second) threshold of pain value added and after calculating medicine occurring licking for pain threshold behind the medicine of this Mus, by formula calculate threshold of pain increment rate, and t method of inspection and model group are carried out significance test relatively between the employing group.
Result of the test:
The result shows: the hot plate pain threshold of the easypro logical shoulder pain sheet 3g/kg of ig, 6g/kg treated animal is learned by statistics and is handled apparently higher than model group, is significant difference (P＜0.05, P＜0.001=; Show that the logical shoulder pain sheet that relaxes has certain analgesic activity.
Conclusion: Pharmacodynamic test of active extract result shows: the logical shoulder pain sheet that relaxes can obviously suppress the mice ear degree that dimethylbenzene causes, obviously reduce the rat granulation hyperplasia tissue weight that plastic sheet causes, obviously reduce the whole blood viscosity under granuloma rat platelet maximum agglutination rate and low shear rate 1s-1, the 5s-1, obviously reduce the number of times that acetic acid brings out the mouse writhing reaction, obviously increase mice hot plate pain threshold, prove that this medical instrument has antiinflammatory action, function of promoting blood circulation to disperse blood clots and analgesic activity.
Chinese medicine of the present invention also can be other solid preparations such as capsule, granule.
Claims (8)
1, easypro logical shoulder pain Chinese medicine is characterized in that being made by following bulk drugs:
283～383 parts of Radix Angelicae Sinensis, 283～383 parts of Rhizoma Corydalis, 283～383 parts of Rhizoma Wenyujin Concisum, 70.6～95.5 parts of Radix Notoginseng, 28.3～38.3 parts of Olibanums, 283～383 parts of Fructus Liquidambaris.
2, the logical shoulder pain Chinese medicine that relaxes according to claim 1, it is characterized in that having in addition 2.7～3.7 parts of 113.1～153 parts of figuration microcrystalline cellulose excipients, 16.2～21.9 parts of polyvidones, 13.6～18.4 parts of carboxymethylstach sodium and magnesium stearate, and 7.7～10.4 parts of coating adjuvant Opadries.
3, the preparation technology of the described logical shoulder pain Chinese medicine that relaxes of a kind of claim 2 is characterized in that step is as follows:
A, get Radix Angelicae Sinensis, Rhizoma Wenyujin Concisum, be ground into coarse powder, add ethanol and place supercritical extraction equipment, CO
2Supercritical extraction gets the reserve liquid that supercritical extraction goes out;
B, get Rhizoma Corydalis, Olibanum and Fructus Liquidambaris, alcohol reflux filters, and medicinal residues add ethanol again, and reflux, extract, filters, and the alcohol extract of merging merges with above-mentioned steps a gained reserve liquid, and decompression recycling ethanol gets alcohol-extracted extract after concentrating;
C, get Radix Notoginseng powder and be broken into fine powder, with step b gained alcohol-extracted extract and microcrystalline Cellulose, polyvidone, mix homogeneously, oven dry is pulverized, dry extract is standby;
D, in step c gained dry extract, add carboxymethyl starch sodium and magnesium stearate, through granulate, tabletting, film coating promptly gets tablet.
4, the preparation technology of the described logical shoulder pain Chinese medicine that relaxes of a kind of claim 2 is characterized in that step is as follows:
A, Radix Angelicae Sinensis, Rhizoma Wenyujin Concisum are ground into coarse powder, add entrainment reagent ethanol and place supercritical extraction equipment, supercritical CO
2Extraction, it is standby to get supercritical extraction liquid;
B, get Rhizoma Corydalis, Olibanum, Fructus Liquidambaris, alcohol reflux filters, and medicinal residues add ethanol again, and reflux, extract, filters, and the alcohol extract of merging merges with above-mentioned steps a gained reserve liquid, and recovery ethanol is concentrated into 50 ℃ of following relative densities and is 1.08～1.10 extractum; This extractum and microcrystalline Cellulose mix homogeneously, spray drying gets spray powder;
C, Radix Notoginseng are pulverized, and cross 60 mesh sieves, with spray powder, dimension ketone, carboxymethylstach sodium and magnesium stearate, mix homogeneously, dry granulation, tabletting, film coating.
5,, it is characterized in that in step a used concentration of alcohol is 90～95%, consumption is 0.5～1.2 times of medical material amount according to the preparation technologies of claim 3 or the 4 described logical shoulder pain Chinese medicines that relax; Extract 40～60 ℃ of still temperature, 25～45 kilograms of pressure; Extracted altogether 0.5～2.0 hour.
6, according to the preparation technology of claim 3 or the 4 described logical shoulder pain Chinese medicines that relax, it is characterized in that the twice alcohol reflux time among the described step b is 1～2 hour.
7, lead to the preparation technology of shoulder pain Chinese medicines according to claim 3 or 4 described relaxing, it is characterized in that among the step b that twice concentration of alcohol in the alcohol reflux is 50～95%, the ethanol consumption is 4～10 times of medical material amounts for the first time, the ethanol consumption is 3～7 times of medical material amounts for the second time.
8, the logical shoulder pain Chinese medicine that relaxes according to claim 2 is characterized in that each crude drug consumption is:
Radix Angelicae Sinensis, Rhizoma Corydalis, Rhizoma Wenyujin Concisum sheet and Fructus Liquidambaris are respectively done for oneself 333 parts, 83 parts of Radix Notoginseng, 33.3 parts of Olibanums; The figuration adjuvant: 133 parts of microcrystalline Cellulose, 19 parts of polyvidones, 16 parts of carboxymethylstach sodium, U.S. 3.2 parts of stearic acid, other has 9 parts of coating adjuvant Opadries.
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