CN105031564B - A kind ofly treat Chinese medicine preparation of acute soft tissue bruise and preparation method thereof - Google Patents

Abstract

The invention provides and a kind ofly treat Chinese medicine preparation of acute soft tissue bruise and preparation method thereof.The Chinese medicine preparation of described treatment acute soft tissue bruise is made up of the crude drug of following weight proportioning: Radix Angelicae Sinensis 20-40%, Rhizoma Chuanxiong 20-40%, Flos Carthami 20-40%, Flos Caryophylli 2-6%, Rhizoma Zingiberis Recens 7-15%, Camphora 1-3%, Oleum Terebinthinae 2-6%.Described preparation is preferably aerosol or liniment.This Chinese medicine preparation is not only rapid-action, easy to use, and toxic and side effects is little, determined curative effect, can effectively treat acute soft tissue bruise.

Description

A kind ofly treat Chinese medicine preparation of acute soft tissue bruise and preparation method thereof

Technical field

The invention belongs to field of medicaments, relate to a kind of Chinese medicine preparation and preparation method thereof, particularly relate to and a kind ofly treat Chinese medicine preparation of acute soft tissue bruise and preparation method thereof.

Background technology

Acute soft tissue bruise refer to certain or multiple position of body because of certain external force cause based on the local response of damaging inflammation with based on the general reaction of the neuroendocrine system effect after wound.Show as local swelling, pain, skin are crimson or livid purple, functional activity is limited.

Acute soft tissue bruise very easily occurs in the activities such as routine work, life, sports, and the diseases such as common cyanosis of the skin ecchymosis, hematoma pain, at home and abroad sickness rate is high, is common motion sickness, external wounds disease.As treated not in time, very easily cause sequela, part likely causes unnecessary complication.Therefore should treat in time, and be the basic rule for the treatment of with blood circulation promoting and blood stasis dispelling, reducing swelling and alleviating pain.

The method of current treatment acute soft tissue bruise is more, as embrocated ZHENGHONGHUA YOU, bone-setting liquor, mercurochrome, pastes rubber unguentum etc.Although these methods have certain curative effect, often occur the shortcomings such as onset is slow, it is inconvenient to use, it is attractive in appearance to affect, the easy skin allergy of life-time service, cause the poor compliance of user, therapeutic effect is not very desirable.Therefore, still need to find the Chinese medicine preparation that energy is safe, convenient, effectively treat acute soft tissue bruise.

Summary of the invention

The object of the invention is to overcome defect of the prior art, provide a kind of and treat Chinese medicine preparation of acute soft tissue bruise and preparation method thereof.This Chinese medicine preparation is not only rapid-action, easy to use, and toxic and side effects is little, determined curative effect.

The present invention is by adopting following technical scheme to realize.

On the one hand, the invention provides a kind of Chinese medicine preparation for the treatment of acute soft tissue bruise, is be made up of the crude drug of following weight proportioning: Radix Angelicae Sinensis 20-40%, Rhizoma Chuanxiong 20-40%, Flos Carthami 20-40%, Flos Caryophylli 2-6%, Rhizoma Zingiberis Recens 7-15%, Camphora 1-3%, Oleum Terebinthinae 2-6%.

Preferably, the Chinese medicine preparation for the treatment of acute soft tissue bruise of the present invention is be made up of the crude drug of following weight proportioning: Radix Angelicae Sinensis 25-30%, Rhizoma Chuanxiong 25-30%, Flos Carthami 25-30%, Flos Caryophylli 4-6%, Rhizoma Zingiberis Recens 10-15%, Camphora 1-3%, Oleum Terebinthinae 2-5%.

More preferably, the Chinese medicine preparation for the treatment of acute soft tissue bruise of the present invention is be made up of the crude drug of following weight proportioning: Radix Angelicae Sinensis 26%, Rhizoma Chuanxiong 26%, Flos Carthami 26%, Flos Caryophylli 5%, Rhizoma Zingiberis Recens 12%, Camphora 2%, Oleum Terebinthinae 3%.

The present invention is used for the treatment of the Chinese medicine preparation of acute soft tissue bruise by adding pharmaceutically acceptable any adjuvant, make the pharmaceutical dosage form of this area routine, comprise aerosol, liniment, spray, tincture, ointment, ointment, gel or emplastrum etc.Preferably, the present invention is used for the treatment of the Chinese medicine preparation of acute soft tissue bruise is aerosol or liniment.

Chinese medicine preparation of the present invention is made up of the Radix Angelicae Sinensis of specified weight ratio, Rhizoma Chuanxiong, Flos Carthami, Flos Caryophylli, Rhizoma Zingiberis Recens, Camphora and Oleum Terebinthinae, wherein:

Radix Angelicae Sinensis is the dry root of umbelliferae angelica Angelicasinensis (Oliv.) Diels.Having enriches blood invigorates blood circulation, menstruction regulating and pain relieving, the effect of loosening bowel to relieve constipation.For blood deficiency and yellow complexion, dizzy cardiopalmus, menoxenia, amenorrhea dysmenorrhea, asthenia cold abdominalgia, rheumatic arthralgia, traumatic injury, ulcer sores, dryness of the intestine constipation.

Rhizoma Chuanxiong is the dry rhizome of samphire Rhizoma Chuanxiong LigusticumchuanriongHort..There is blood-activating and qi-promoting, the effect of wind-expelling pain-stopping.For obstruction of qi in the chest and cardialgia, the twinge of the breast side of body, tumbling and swelling, menoxenia, amenorrhea dysmenorrhea ， mass in the abdomen is suffered from abdominal pain, headache, rheumatic arthralgia.

Flos Carthami is the dried floral of Flos Chrysanthemi section Plant Carthamus Tinctorius L CarthamustinctoriusL.There is promoting blood circulation to restore menstrual flow, the effect of eliminating stasis to stop pain.For amenorrhea, dysmenorrhea, lochia ， mass in the abdomen mass in the abdomen, obstruction of qi in the chest and cardialgia, the stagnant stomachache of the stasis of blood, the twinge of the breast side of body, injury from falling down, skin infection swells and ache.

Flos Caryophylli is the dry flower of myrtle EugeniacaryophllataThunb..There is warming middle-JIAO to send down the adverse QI, the effect of reinforcing the kidney and supporting YANG.For Deficiency and coldness of spleen and stomach, singultus is vomitted, lack of appetite and vomiting, trusted subordinate's cold type of pain, impotence due to deficiency of the kidney.

Rhizoma Zingiberis Recens is the fresh rhizome of zingiber ZingiberofficinaleRosc..There is the cold expelling that induces sweat, warming middle-JIAO to arrest vomiting, preventing phlegm from forming and stopping coughing, the effect of solving toxin of fish and crab.For anemofrigid cold, gastrofrigid vomiting, cold-phlegm is coughed, and fish Eriocheir sinensis is poisoning.

Camphora, for the dry branch of canella Cinnamomumcamphora (L.) Presl, leaf and root extract obtained crystallization through processing.There is orifice opening, qi stagnation removing, ward off foul, killing parasites for relieving itching, reducing swelling and alleviating pain effect.Be mainly used to the symptoms such as treatment scabies pruritus, traumatic pain, toothache.

Oleum Terebinthinae is the oleoresin oozed out in Pinaceae Pinus several plants, through the volatile oil that distillation or additive method are extracted.For alleviating myalgia, arthralgia, neuralgia and spraining.

Radix Angelicae Sinensis in formula of the present invention, Rhizoma Chuanxiong Flos Carthami have effect of eliminating stasis to stop pain, are aided with Flos Caryophylli, Rhizoma Zingiberis Recens, Camphora and Oleum Terebinthinae, and principal agent can be assisted to strengthen analgesic effect.In addition, the present inventor is surprised to find that, above-mentioned raw material of Chinese medicine medicine is carried out compatibility with specific weight ratio, mutually reaches synergy between each medicine, can realize effect of better blood circulation promoting and blood stasis dispelling, reducing swelling and alleviating pain.

Present invention also offers the preparation method of the Chinese medicine preparation of described treatment acute soft tissue bruise, comprise following steps:

(1), by Rhizoma Zingiberis Recens thinly slice, add 70 ﹪ ethanol of 3-20 times of volume, dipping 48-60 hour, filter, filtrate is for subsequent use;

(2), Flos Carthami, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Flos Caryophylli powder are broken into coarse powder, merge with the medicinal residues in step (1), with 70 ﹪ ethanol as solvent, to flood after 48-60 hour slowly percolation, collect percolate, removing ethanol, then merge with impregnation liquid in step (1), be concentrated into appropriate, filter;

(3), by Camphora, Oleum Terebinthinae respectively with joining in the filtrate of step (2) after dissolve with ethanol, mix homogeneously, then adds pharmaceutically acceptable adjuvant and makes regular dosage form.

In order to accelerate the onset time of medicine further, and the drug effect of Chinese medicine preparation of the present invention being performed to best, preferably Chinese medicine preparation of the present invention having been made aerosol and liniment by the adjuvant of specific consumption.

Medicine preparation is in the embodiment of aerosol in the present invention, consisting of of crude drug: Radix Angelicae Sinensis 26g, Rhizoma Chuanxiong 26g, Flos Carthami 26g, Flos Caryophylli 5g, Rhizoma Zingiberis Recens 12g, Camphora 2g, Oleum Terebinthinae 3g.The preparation method of aerosol is:

(1), by Rhizoma Zingiberis Recens thinly slice, add 70 ﹪ ethanol of 3-20 times of volume, dipping 48-60 hour, filter, filtrate is for subsequent use;

(2), Flos Carthami, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Flos Caryophylli powder are broken into coarse powder, merge with the medicinal residues in step (1), with 70 ﹪ ethanol as solvent, to flood after 48-60 hour slowly percolation, collect percolate, removing ethanol, then merge with impregnation liquid in step (1), be concentrated into appropriate, filter;

(3), by Camphora, Oleum Terebinthinae use dissolve with ethanol respectively, then join in the filtrate of step (2), mix homogeneously, by 70 ﹪ ethanol adjustment total amounts to 1000ml, subpackage, sealing, press-in propellant, packaging, to obtain final product; Described propellant is selected from tetrafluoroethane, heptafluoro-propane, propane, normal butane, iso-butane, dimethyl ether or carbon dioxide.

Medicine preparation is in the embodiment of liniment in the present invention, consisting of of crude drug: Radix Angelicae Sinensis 26g, Rhizoma Chuanxiong 26g, Flos Carthami 26g, Flos Caryophylli 5g, Rhizoma Zingiberis Recens 12g, Camphora 2g, Oleum Terebinthinae 3g.The preparation method of liniment is:

(1), by Rhizoma Zingiberis Recens thinly slice, add 70 ﹪ ethanol of 3-20 times of volume, dipping 48-60 hour, filter, filtrate is for subsequent use;

(2), Flos Carthami, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Flos Caryophylli powder are broken into coarse powder, merge with the medicinal residues in step (1), with 70 ﹪ ethanol as solvent, to flood after 48-60 hour slowly percolation, collect percolate, removing ethanol, then merge with impregnation liquid in step (1), be concentrated into appropriate, filter;

(3), by Camphora, Oleum Terebinthinae use dissolve with ethanol respectively, then join in the filtrate of step (2), mix homogeneously, by 70 ﹪ ethanol adjustment total amounts to 1000ml, subpackage, sealing, packaging, to obtain final product.

On the other hand, the invention provides the Chinese medicine preparation of the treatment acute soft tissue bruise prepared by said method.

Further, the purposes of Chinese medicine preparation of the present invention in the medicine of preparation treatment acute soft tissue bruise is additionally provided.

Below by embodiment, the present invention is described in more detail, but these embodiments can not be interpreted as limitation of the present invention.

Accompanying drawing explanation

Fig. 1 is the effect diagram of Fig. 1 invention product to rat formaldehyde arthritis foot thickness;

Fig. 2 invention product is to the effect diagram of rat formaldehyde arthritis foot Zhou Jing;

Fig. 3 invention product is on the impact (first) of rat Ovum Gallus domesticus album arthritis thickness;

Fig. 4 invention product is on the impact (first) of rat Ovum Gallus domesticus album arthritis Zhou Jing;

Fig. 5 invention product is on the impact (second batch) of rat Ovum Gallus domesticus album arthritis thickness;

Fig. 6 invention product is on the impact (second batch) of rat Ovum Gallus domesticus album arthritis Zhou Jing.

Detailed description of the invention

Embodiment 1: the preparation of aerosol

Crude drug: Radix Angelicae Sinensis 26g, Rhizoma Chuanxiong 26g, Flos Carthami 26g, Flos Caryophylli 5g, Rhizoma Zingiberis Recens 12g, Camphora 2g, Oleum Terebinthinae 3g.

Preparation method: thinly sliced by Rhizoma Zingiberis Recens, adds 70 ﹪ ethanol of 6 times of volumes, floods 48 hours, and filter, filtrate is for subsequent use; Flos Carthami, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Flos Caryophylli powder are broken into coarse powder, merge with aforesaid medicinal residues, with 70 ﹪ ethanol as solvent, to flood after 48 hours slowly percolation, collect percolate, removing ethanol, then merges with aforesaid impregnation liquid, is concentrated into appropriate, filters; Camphora, Oleum Terebinthinae are used dissolve with ethanol respectively, then joins in aforesaid filtrate, mix homogeneously, by 70 ﹪ ethanol adjustment total amounts to 1000ml, subpackage, sealing, press-in tetrafluoroethane, packaging, to obtain final product.

Embodiment 2: the preparation of aerosol

Crude drug: Radix Angelicae Sinensis 26g, Rhizoma Chuanxiong 26g, Flos Carthami 26g, Flos Caryophylli 5g, Rhizoma Zingiberis Recens 12g, Camphora 2g, Oleum Terebinthinae 3g.

Preparation method: thinly sliced by Rhizoma Zingiberis Recens, adds 70 ﹪ ethanol of 10 times of volumes, floods 60 hours, and filter, filtrate is for subsequent use; Flos Carthami, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Flos Caryophylli powder are broken into coarse powder, merge with aforesaid medicinal residues, with 70 ﹪ ethanol as solvent, to flood after 60 hours slowly percolation, collect percolate, removing ethanol, then merges with aforesaid impregnation liquid, is concentrated into appropriate, filters; Camphora, Oleum Terebinthinae are used dissolve with ethanol respectively, then joins in aforesaid filtrate, mix homogeneously, by 70 ﹪ ethanol adjustment total amounts to 1000ml, subpackage, sealing, press-in heptafluoro-propane, packaging, to obtain final product.

Embodiment 3: the preparation of aerosol

Crude drug: Radix Angelicae Sinensis 30g, Rhizoma Chuanxiong 30g, Flos Carthami 30g, Flos Caryophylli 5g, Rhizoma Zingiberis Recens 15g, Camphora 3g, Oleum Terebinthinae 4g.

Preparation method: thinly sliced by Rhizoma Zingiberis Recens, adds 70 ﹪ ethanol of 15 times of volumes, floods 50 hours, and filter, filtrate is for subsequent use; Flos Carthami, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Flos Caryophylli powder are broken into coarse powder, merge with aforesaid medicinal residues, with 70 ﹪ ethanol as solvent, to flood after 50 hours slowly percolation, collect percolate, removing ethanol, then merges with aforesaid impregnation liquid, is concentrated into appropriate, filters; Camphora, Oleum Terebinthinae are used dissolve with ethanol respectively, then joins in aforesaid filtrate, mix homogeneously, by 70 ﹪ ethanol adjustment total amounts to 1000ml, subpackage, sealing, press-in normal butane, packaging, to obtain final product.

Embodiment 4: the preparation of liniment

Crude drug: Radix Angelicae Sinensis 26g, Rhizoma Chuanxiong 26g, Flos Carthami 26g, Flos Caryophylli 5g, Rhizoma Zingiberis Recens 12g, Camphora 2g, Oleum Terebinthinae 3g.

Preparation method: thinly sliced by Rhizoma Zingiberis Recens, adds 70 ﹪ ethanol of 4 times of volumes, floods 48 hours, and filter, filtrate is for subsequent use; Flos Carthami, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Flos Caryophylli powder are broken into coarse powder, merge with aforesaid medicinal residues, with 70 ﹪ ethanol as solvent, to flood after 48 hours slowly percolation, collect percolate, removing ethanol, then merges with aforesaid impregnation liquid, is concentrated into appropriate, filters; Camphora, Oleum Terebinthinae are used dissolve with ethanol respectively, then joins in aforesaid filtrate, mix homogeneously, by 70 ﹪ ethanol adjustment total amounts to 1000ml, subpackage, sealing, packaging, to obtain final product.

Embodiment 5: the preparation of liniment

Crude drug: Radix Angelicae Sinensis 20g, Rhizoma Chuanxiong 20g, Flos Carthami 20g, Flos Caryophylli 3g, Rhizoma Zingiberis Recens 8g, Camphora 3g, Oleum Terebinthinae 2g.

Preparation method: thinly sliced by Rhizoma Zingiberis Recens, adds 70 ﹪ ethanol of 10 times of volumes, floods 50 hours, and filter, filtrate is for subsequent use; Flos Carthami, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Flos Caryophylli powder are broken into coarse powder, merge with aforesaid medicinal residues, with 70 ﹪ ethanol as solvent, to flood after 48 hours slowly percolation, collect percolate, removing ethanol, then merges with aforesaid impregnation liquid, is concentrated into appropriate, filters; Camphora, Oleum Terebinthinae are used dissolve with ethanol respectively, then joins in aforesaid filtrate, mix homogeneously, by 70 ﹪ ethanol adjustment total amounts to 1000ml, subpackage, sealing, packaging, to obtain final product.

Test example 1: rat acute soft tissue contusion model test

(1) test specimen

Of the present invention group: the liniment prepared according to the embodiment of the present application 4.

Positive controls 1: ZHENGHONGHUA YOU, very imperial board, Pharma Inc. of Singapore produces.

Positive controls 2: spasmolysis and analgesia tincture.

Solvent control group: 70% ethanol.

(2) experimental animal

SD rat 40, body weight 240 ~ 250g, male and female half and half.

(3) test method

After hair outside hypomere in Rat Right thigh being cut short in 24 hours before administration, with 8% sodium sulfide solution, depilation process is carried out to it, depilation area is 2.5 × 2.5cm, and the 2nd day by depilation and unabroken rat is placed on contusion models platform, with 1% penthiobarbital 0.4ml lumbar injection.After anesthesia comes into force, hit at rat depilation position from the height free-falling of 20cm with 200g counterweight, continued operation 3 times, causes acute contusion models.Rat is divided into 5 groups at random, often organizes 10, male and female half and half.Liniment 1.0ml/kg of the present invention is smeared for of the present invention group in rat depilation place; Positive controls 1 smears ZHENGHONGHUA YOU 1.0ml/kg in rat depilation place; Positive controls 2 smears spasmolysis and analgesia tincture 1.0ml/kg in rat depilation place; The solvent 70% ethanol 1.0ml/kg of liniment of the present invention is smeared in solvent control group rat depilation place lacking invention medicine.Daily 2 times, successive administration 5 days, medication and the time identical.Observe the redness of contusion place, blood stasis situation every day.

(4) observation index and tentative standard is dampened

A, skin temperature: rat normal skin temperature is variant because position and temperature etc. are different, and outside this group experimental rat right thigh, mean skin temperature is 34.8 ± 0.6 DEG C, local makes local skin temperature raise because of damaging inflammatory reaction after dampening.

B, swelling degree: normal without swelling phenomenon, skin is glossy, flexible.Injuredly to increase because of angiorrhexis or vascular permeability and damaging inflammatory reaction etc. causes local organization swelling afterwards.Tentative standard is: slight, compared with normal week footpath increase by 2 ~ 5mm; Moderate, compared with normal week footpath increase by 6 ~ 10mm; Severe, compared with normal week footpath increase more than 10mm.

C, functional activity: normal rat each portion functional activity is without exception.Injuredly make functional activity limited because of local swelling and pain afterwards; Limited degree and damaged degree proportional.Tentative standard is: normal (-), and activity freely; Slightly (+), activity is slightly limited, walks not nimble; Moderate (++), limitation of activity, walks lamely; Severe (+++), functional activity is obviously limited, and suffering limb can not be walked.

D, skin color: normal rat skin is baby pink, the injured rear local skin that makes because blood vessel injury is hemorrhage becomes red or livid purple color, even occurs large stretch of ecchymosis and hematoma.Tentative standard: slight, skin is crimson red or slightly livid purple; Moderate, cyanosis of the skin; Severe, skin is obviously livid purple, ecchymosis or subcutaneous hemorrhage.

E, microcirculating state: under normal circumstances, healthy white rat blood capillary is clear, and without oozing out, the changes such as hemorrhage and vasospasm, fluidised form is grain linear flow.After injured, cause hemorrhage because blood capillary is impaired, ooze out and tissue edema, therefore blood capillary is smudgy, occur the change such as vasospasm or overdistension, fluidised form also becomes the even blood flow stopping of the stagnant shape of the stasis of blood.This experiment adopts Mesentery microcirculation to observe: alternative body weight 240 ~ 250g healthy rat 8, after ventral seta is cut short, with 8% sodium sulfide solution, depilation process is carried out to it, with 1% penthiobarbital 0.4ml lumbar injection, after anesthesia comes into force, prepare area skin 75% ethanol disinfection, cut abdomen, amplify 50 times by under mesenteric pull to microscope, find clear and be convenient to the blood capillary of observation and be fixed on microscope slide, examining the situation of change before and after blood capillary medication.

F, pathologic finding: within the 3rd day and the 6th day, respectively get a rat after experiment and carry out affected part biopsy, tissue of getting comprises skin, subcutaneous tissue and part muscular tissue.The Mus of having got living tissue excludes other and observes within item statistical number.

(5) on the impact of rat acute soft tissue contusion effect

By each sample to the administration of acute soft tissue contusion rat model after, the situation of change after the medication of rat compromised skin is observed, to observe drug effect.

A, skin temperature change: within after wound one week, respectively group rat pars affecta skin variations in temperature is in table 1, and preparing position skin temperature before experiment is 34.8 ± 0.6 DEG C.

Table 1 four groups of rat pars affecta skin temperature compare (DEG C)

Note: of the present invention group with solvent control group ratio, * P > 0.05, * * P < 0.05, * * * P < 0.01;

Of the present invention group with positive controls 1 ratio, △ P > 0.05, △ △ P < 0.05, △ △ △ P < 0.01;

Of the present invention group with positive controls 2 ratio, ● P > 0.05, ● ● P < 0.05, ● ● ● P < 0.01.

Of the present invention group is compared with ZHENGHONGHUA YOU group and antipyretic and analgesic tincture group, P > 0.05, skin temperature change no significant difference; Invention group compares with solvent (70% ethanol) matched group, and from the 4th day, there were significant differences (0.01 < P < 0.05) in skin temperature change.

B, swelling degree: within after wound one week, respectively organize rat affected part swelling degree and compare in table 2, preparing position Zhou Jing before experiment is 46.2 ± 1.5mm.

Table 2 four groups of rat affected part swelling degree compare (mm)

Note: of the present invention group with solvent control group ratio, * P > 0.05, * * P < 0.05, * * * P < 0.01;

Of the present invention group with positive controls 1 ratio, △ P > 0.05, △ △ P < 0.05, △ △ △ P < 0.01;

Of the present invention group with positive controls 2 ratio, ● P > 0.05, ● ● P < 0.05, ● ● ● P < 0.01.

Invention group compares with ZHENGHONGHUA YOU group, except second day (P < 0.05) is except there were significant differences, and other no significant differences; Invention group compares with antipyretic and analgesic tincture group, and just started there were significant differences (P < 0.05) from the 4th day; Invention group compares with solvent (70% ethanol) matched group, has the difference (P < 0.01) of highly significant from second day.

C, functional activity: after four groups of rat wounds, the functional rehabilitation time compares in table 3, and effective time is the time of severe dysfunction (+++) to slight dysfunction (+); Complete recovery time is that severe dysfunction (+++) is to the time of recovering normal (-) completely.

Four groups of rat suffering limb functional rehabilitation times of table 3 compare (hr)

Note: ※ P > 0.05, ※ ※ P < 0.05, ※ ※ ※ P < 0.01.

Invention group compares with ZHENGHONGHUA YOU group and antipyretic and analgesic tincture group, and P > 0.05, all without significant difference; Invention group compares with solvent (70% ethanol) matched group, effective time and completely recovery time P < 0.01, the equal highly significant of difference.

D, skin color: four groups of rat pars affecta skin color recovery times are in table 4.

Table 4 four groups of rat pars affecta skin colors compare (hr) recovery time

Note: of the present invention group with solvent control group ratio, ※ ※ ※ P < 0.001;

Of the present invention group with positive controls 1 ratio, △ △ △ P < 0.01;

Of the present invention group with positive controls 2 ratio, ● ● ● P < 0.01.

Invention group compares with ZHENGHONGHUA YOU group and antipyretic positive pain tincture group, all has < 0.01; Compare with solvent (70% ethanol) matched group, P < 0.001, all has the difference of highly significant.

E, microcirculating state: product of the present invention and ZHENGHONGHUA YOU are on the microvascular impact of rat mesentery in table 5, and microcirculatory fluidised form and definition are because excluding in table without obviously changing before and after medication.

Table 5 invention product and ZHENGHONGHUA YOU are on the microvascular impact of rat mesentery

Note: ※ P > 0.05, ※ ※ P < 0.05, ※ ※ ※ P < 0.01.

F, pathologic finding: in pathological examination, invention group compares with ZHENGHONGHUA YOU group, without significant difference.

(6) brief summary is tested

In the important indicator that above-mentioned experiment is observed, invention group is slightly better than ZHENGHONGHUA YOU group, is obviously better than antipyretic and analgesic tincture group.Compare with solvent (70% ethanol) group, every important indicator all has highly significant difference.Illustrate that product of the present invention has obvious relaxing muscles and tendons to promote blood circulation, reducing swelling and alleviating pain, promote skin temperature, skin color and suffering limb functional rehabilitation, improving the microcirculatory effect of affected part, is a kind of external used medicine of ideal treatment acute soft tissue injury.

Test example 2: rat formaldehyde arthritis model is tested

(1) test specimen

Of the present invention group: the liniment prepared according to the embodiment of the present application 4.

Positive controls: ZHENGHONGHUA YOU, very imperial board, Pharma Inc. of Singapore produces.

Solvent control group: 70% ethanol.

(2) experimental animal

SD rat 15, body weight 150 ~ 170g, male and female dual-purpose, often organizes 5 by random point 3 groups.

(3) test method

Get healthy qualified test rat, in the right back toes of every Mus subcutaneous injection 2% formalin 0.1ml, within 1,4,8,24,36,48,96 hour after causing model, be coated with different tests sample respectively.Before coating, causing the face of model foot and bottom to be labelling with dyestuff, fixed measuring point, measures sufficient thickness with slide calliper rule, measures sufficient Zhou Jing with cord, as the whether effective observation index of medicine.The sample amount of embrocating is 0.2ml//time.

(4) result of the test

In three groups of experimental animals, invention sample sets has good curative effect, from causing after model in the of 8 hours, the thickness of swollen joint and all footpaths start to reduce, redness faded away, red and swollen slight to local when 52 hours, to the 11st day (264 hours), arthroncus obviously disappears, and close to the normal level caused before arthritis model.

The arthritic therapeutical effect of very imperial board safflower oil PARA FORMALDEHYDE PRILLS(91,95) is undesirable, and redness and swelling of joints disappears slowly, and to the 11st day (264 hours), arthroncus degree was still close with 70% ethanol group.

Product of the present invention and ZHENGHONGHUA YOU on the impact of rat formaldehyde arthritis model in table 6, table 7, Fig. 1 and Fig. 2.

Table 6 invention product is on the impact of rat formaldehyde arthritis thickness

Note: of the present invention group with solvent control group ratio, * P > 0.05, * * P < 0.05, * * * P < 0.01.

The impact of table 7 invention product rat formaldehyde arthritis Zhou Jing

Note: of the present invention group with solvent control group ratio, * * P < 0.05, * * * P < 0.01.

Test example 3: rat Ovum Gallus domesticus album Arthritis Assay

(1) test specimen

Of the present invention group: the liniment prepared according to the embodiment of the present application 4.

Positive controls: ZHENGHONGHUA YOU, very imperial board, Pharma Inc. of Singapore produces.

Solvent control group: 70% ethanol.

(2) experimental animal

SD rat 10, body weight 130 ~ 160g, male and female dual-purpose, by body weight random packet, first often organizes 4, and second batch often organizes 6.

(3) test method

Get Fresh Egg clear, be made into the concentration (V/V) of 15% with distilled water, to Rat Right metapedes toe subcutaneous injection 0.1ml, cause rat arthritis model.First is tested and within latter 0.5 hour, starts medication in injection, measures 0.5,1,2,4,6, the 24 little thickness of joint constantly and all footpaths after causing arthritis model and changes, and coating, altogether administration 5 times after each measurement, each 0.1ml, the 24th little no longer administration constantly.Second batch is tested and namely start administration after being caused model, and measure joint thickness and the change of all footpaths in time causing after model 0.25,0.5,1,2,6,24 hour respectively, and coating, altogether administration 5 times after each measurement, each 0.15ml, the 24th little no longer administration constantly; Invention sample sets separately establishes each administration 0.1ml matched group.

(4) result of the test

Statistical analysis, two batches of experimental results all show, invention sample has good inhibitory action to rat albumen arthritis, and arthroncus degree and inflammation disappearance speed are all better than blank group and 70% alcohol solvent matched group.Second batch experiment embrocates ZHENGHONGHUA YOU, increased frequency, embrocates ZHENGHONGHUA YOU total amount and reach 0.9ml/ only in 24 hours, in 6 animals dead 4, because the animal of other experimental grouies is all normal, therefore caused by the toxicity being thought of as ZHENGHONGHUA YOU.

First experimental data is in table 8, table 9, Fig. 3 and Fig. 4; Second batch experimental data is in table 10, table 11, Fig. 5 and Fig. 6.

Table 8 invention product is on the impact (first) of rat Ovum Gallus domesticus album arthritis thickness

Note: measure not yet administration during 30min, starts first time administration after measurement.Of the present invention group with blank group ratio, * P > 0.05, * * P < 0.05, * * * P < 0.01.

Table 9 invention product is on the impact (first) of rat Ovum Gallus domesticus album arthritis Zhou Jing

Note: measure not yet administration during 30min, starts first time administration after measurement.Of the present invention group with blank group ratio, * P > 0.05, * * P < 0.05, * * * P < 0.01.

Table 10 invention product is on the impact (second batch) of rat Ovum Gallus domesticus album arthritis thickness

Of the present invention group with blank group ratio, * P > 0.05, * * P < 0.05, * * * P < 0.01.

Of the present invention group with blank group ratio, P > 0.05, P < 0.05, P < 0.01.

Table 11 invention product is on the impact (second batch) of rat Ovum Gallus domesticus album arthritis Zhou Jing

Of the present invention group with blank group ratio, * P > 0.05, * * P < 0.05, * * * P < 0.01.

Of the present invention group with blank group ratio, P > 0.05, P < 0.05, P < 0.01.

Above-mentioned experiment shows, invention product all has good therapeutical effect to the Ovum Gallus domesticus album arthritis of rat and formaldehyde arthritis; The arthritic therapeutical effect of the Ovum Gallus domesticus album of invention product to rat of various dose is similar, but the effect of high dose group is more better than low dose group.

Test example 4: clinical study results

The liniment of application the embodiment of the present application 4 contrasts with bone-setting liquor, adopts Multicenter controlled study, observes the Clinical efficacy and safety of liniment treated acute soft tissue injury of the present invention, observes 480 examples altogether, wherein treatment group 360 example, matched group 120 example.

(1) object and method

Whole patient is and treats at hospital year October in May, 2004 to 2004,18 ~ 65 years old age, male or female, traditional Chinese medical science cardinal symptom is that wound strain is fallen ill, multiplely be born in damage period,, there is livid purple ecchymosis or have larger hematoma, joint motion limited in local swelling, twinge, localized pain.Doctor trained in Western medicine standard for having obvious trauma history, sharp ache, local rapidly swelling, limb activity dysfunction; Injury tenderness is obvious, and can occur the livid purple ecchymosis in local, ecchymosis appears in severe patient, and the positive is levied in fluctuation; Latter about 2 weeks of damage, transfer yellowish-brown to during congestive edema major part disappears, pain fades away, functional rehabilitation or slight obstacle; Minority damages heavier patient, and convalescent period is grown, local still has swelling or has scleroma, and have a dull ache, limb activity has limited in various degree; X-ray ray examination, mainly gets rid of fracture, dislocation and osteopathia etc.

(2) Therapeutic Method

Of the present invention group of liniment exterior coating treatment by the embodiment of the present application 4,3 times on the one, affected part is coated with and puts on the skin.The bone-setting liquor exterior coating treatment that matched group is produced with Guangxi Yulin pharmaceutical Co. Ltd, 3 times on the one.

(3) curative effect judging standard

Recovery from illness: pain disappears, and muscular tone and spasm disappear, and joint motion is normal.Without pressure pain point, can recover original functional activity, suffering limb swelling is disappeared completely.

Effective: pain disappears substantially, swelling is disappeared substantially, and without tenderness or slight tenderness, major joint activity is not limited, and functional activity is normal or normal, occasionally now slightly aches after tired.

Effective: pain obviously alleviates, swelling is obviously disappeared, the limited improvement of joint motion, can participate in comparatively light work and move.

Invalid: symptom and sign are improved less or without improvement.

(4) result

The clinical efficacy data results of of the present invention group and matched group is in table 12.

The clinical efficacy data of of the present invention group of table 12 and matched group

(5) conclusion

The result of table 4 shows, all there were significant differences for the symptom and sign integration before and after of the present invention group and treatment of control group, and the total effective rate of of the present invention group is higher than matched group.Of the present invention group, during clinical research, all there is not untoward reaction in matched group.Therefore product of the present invention is that one is treated acute soft tissue injury curative effect and shown, the medicine that safety is high.

Test example 5: drug toxicology test and damaged skin irritant experiment

(1) acute toxicity test

1, the mensuration of an oral administration LD50 (half number lethal dose)

Test specimen: the liniment prepared according to the embodiment of the present application 4.

Experimental animal: mice 50, body weight 18 ~ 22g, male and female half and half, by body weight random packet.

Test method: get body weight 18 ~ 22 grams of healthy mices, be divided into 5 groups at random by body weight, often organizes 10, male and female half and half.By equal proportion dosage distance and the weight of animals, fill with respectively with the liniment of the invention product embodiments 4 of different volumes.Observe each treated animal death toll in 7 days (168hr) after single administration, calculate mortality rate.

Result of the test: (1) poisoning symptom: the symptom such as all occur instability of gait after each treated animal gavage, wave, heavy dose of group most animals starts lethargy, rapid breathing after gavage in 10min, within 4 ~ 6 hours, start to occur dead; Small dose group most animals 60min after gavage starts lethargy, and 4 ~ 6 hours after gavage start to revive, and death appears in minority animals administer after 24 hours, within after most animals administration 6 hours, recovers normal activity.Dissect each group of dead animal, the perusal heart, liver, kidney, lung, have no obvious pathological change.

(2) date processing: calculate with simplification probit method, the results are shown in Table 13.

Table 13 invention product acute toxicity test tables of data

As calculated, LD50=12.16ml/kg, it 95% is crediblely limited to 11.08 ~ 13.24ml/kg.

2, the outer wiping of invention product does not cause dead mouse, therefore cannot measure the LD50 of external method.

3, invention product solvent for use 70% ethanol oral administration LD50 measures

Test specimen: 70% ethanol.

Experimental animal: mice 50, body weight 18 ~ 22g, male and female half and half, by body weight random packet.

Test method: get body weight 18 ~ 22 grams of healthy mices, be divided into 5 groups at random by body weight, often organizes 10, male and female half and half.By equal proportion dosage distance and the weight of animals, fill with respectively with the liniment of the invention product embodiments 4 of different volumes solvent 70% ethanol used.Observe each treated animal death toll in 7 days (168hr) after single administration, calculate mortality rate.

Result of the test: (1) poisoning symptom: each treated animal, with the symptom such as all occur instability of gait after 70% ethanol gavage, wave, occurs the symptoms such as lethargy then, heavy dose of group starts to occur dead for 6 hours in administration; Middle dosage group occurs dead in 24 hours after administration; Small dose group recovers normal activity in 6 hours upon administration.Dissect each group of dead animal, the perusal heart, liver, kidney, lung, have no obvious pathological change.

(2) date processing: calculate with simplification probit method, the results are shown in Table 14.

Table 1470% acute ethanol toxicity test tables of data

As calculated, LD50=13.34ml/kg, it 95% is crediblely limited to 12.16 ~ 14.32ml/kg.

4, acute toxicity test brief summary

(1) performance after the Symptoms of invention product acute toxicity and the solvent 70% ethanol gavage of this product is consistent, and two groups of LD50 values of simultaneously testing are comparatively close, therefore can think that this toxicity is relevant with 70% ethanol.

(2) this medicine external safety coefficient is large, but due to ethanol content high, therefore should avoid taking orally.

(2) irritated and long term toxicity test

Test specimen: the liniment prepared according to the embodiment of the present application 4.

Experimental animal: Cavia porcellus, body weight 200 ~ 240g16,250 ~ 300g12, male and female half and half; 350 ~ 400g3 is only, female; Kunming mouse 60, male and female half and half; SD rat 26, body weight 140 ~ 170g.

Test method:

1, Cavia porcellus allergic experiment: get body weight 200 ~ 240g Cavia porcellus 16, male and female half and half.The next day lumbar injection product 0.5ml of the present invention, totally three sensitization.The 14th day after first time administration and the 21st day, get 8 Cavia porcelluss respectively and inject product 1.0ml of the present invention in fibular veins, two treated animals all illustrate existing dysphoria, pant and grab the anaphylaxis such as ear, excitement.

2, guinea pig skin allergic experiment: get body weight 250 ~ 300g Cavia porcellus 12, mixes invention product 5ml and Freund's complete adjuvant 5ml, in every Cavia porcellus back of the body shoulder blade portion injection suspension 0.1ml/ point, injects 2 points altogether.In latter 7th day of injection, hair 20% sodium sulfide in injection site is deviate from 5cm × 5cm, expose skin, product of the present invention and paraffin oil intermixture (V/V:1:1) 1ml/ sheet are embrocated in local, observe local skin after 24 hours, except two guinea pig skins have slightly infrared, be showed no exception, after 36 hours, skin recovers normal, without anaphylaxiss such as redness, diabrosis, depilations.

3, skin irritation test: get 350 ~ 400g Female guinea pigs 3, with 20% sodium sulfide depilation after the cropping of back, expose 6cm × 7cm skin, every sheet is coated with product 2ml of the present invention, and totally twice, local skin when observing 24,48,72 hours, vacuum response symptom.

4, cumulative toxicity experiment: Kunming mouse 60, male and female half and half.40 mices give product of the present invention once, continuous 30 days by 1/3 amount 5ml/kg gavage every day of LD50; Another 20 mices give 70% ethanol 5ml/kg, continuous 30 days every day; The animal dead number 3/20 of 70% ethanol group 30 days; Invention product treated animal death toll is 6/40.The death toll of two treated animals is through X ²inspection, X ²value is 0.0001634, does not have significant difference.Illustrate that this death toll is relevant with solvent 70% ethanol of invention product, and other compositions in invention product are safer to animal at the dosage that experiment is used.

5, long term toxicity test: get body weight 140 ~ 170gSD rat 26, male and female half and half, be divided into two groups at random by body weight.Organize 1 every animal and embrocate product 0.6ml of the present invention at tail skin every day, group 2 every animals embrocate 70% ethanol 0.6ml at tail skin every day, and embrocating area is 4cm × 5cm.Separately establish blank treated animal 5.Before administration, animal is taken out painstaking effort and looks into SGDT (glutamate pyruvate transaminase) and BUN (blood urea nitrogen).Embrocate and put to death half animal afterwards in 15 days, get hepatic tissue and carry out pathological examination.Administration 30 days is place's residue half animal afterwards, blood of coring before execution check SGDT (glutamate pyruvate transaminase) and BUN (blood urea nitrogen), and get liver, nephridial tissue does pathological examination.Various check result is in table 15.

Table 15 invention product is on the impact of SGDT, BUN in rat body weight and blood

After rat embrocates product of the present invention, SGDT, BUN in blood are not affected significantly.The internal organs such as the when dissected perusal heart, liver, kidney, lung, gastrointestinal, do not have obvious pathological change.

Toxicology test brief summary: no matter this product is external or injection, does not all cause allergic reaction to Cavia porcellus; The death condition that this product shows in the experiment of mice cumulative toxicity is relevant with its solvent 70% ethanol; This product wipes 30 days outward, does not significantly affect on local skin and on the liver of rat, nephridial tissue; In long term toxicity test, the measurement result of serum SGDT (glutamate pyruvate transaminase) and BUN (blood urea nitrogen) proves that product of the present invention does not have obvious toxicity to rat, is safer.

(3) damaged skin irritant experiment

Get healthy guinea pig 12, wherein female 5, male 7, body weight 240 ~ 350g, the depilation of Mao Houyong 20% sodium sulfide is shaved at back, each side exposes 3cm × 4cm skin.With No. 1 scalpel by right side exposed region people for causing epidermis breach 2cm × 3.Divide 4 groups at random by above-mentioned animal, often organize 3 Cavia porcelluss.One group is matched group, embrocates 70% ethanol; Other three groups are all coated with product of the present invention.Dosage used is respectively each exposed region 0.5ml, 1.0ml, 2.0ml.Test first is at bilateral each district coating secondary, and the medication interval time is 7 hours.Local change of skin situation when 24,48,72 hours after observation coating.Coating was shown in that matched group wound had a small amount of oozing of blood at that time, and three groups of medication are showed no oozing of blood.Within 24 hours, observe four treated animal wounds all to form a scab, local is without obviously red and swollen.Within 48 hours, observe four treated animals test skin-colors light red, wound incrustation district has no empyema under sepage and crust.Within 72 hours, observe all visible fine hair on birds or animals hair growth in four treated animal coating districts, crust is dry and hard.By observe, product of the present invention to damaged skin without obvious stimulation effect.

Claims (1)

1. a preparation method for preparation, is characterized in that described preparation is aerosol, wherein, and consisting of of the middle spice medicine of former treatment acute soft tissue bruise: Radix Angelicae Sinensis 26g, Rhizoma Chuanxiong 26g, Flos Carthami 26g, Flos Caryophylli 5g, Rhizoma Zingiberis Recens 12g, Camphora 2g, Oleum Terebinthinae 3g;

The preparation method of described aerosol is:

(1), by Rhizoma Zingiberis Recens thinly slice, add 70 ﹪ ethanol of 3-20 times of volume, dipping 48-60 hour, filter, filtrate is for subsequent use;

(2), Flos Carthami, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Flos Caryophylli powder are broken into coarse powder, merge with the medicinal residues in step (1), with 70 ﹪ ethanol as solvent, to flood after 48-60 hour slowly percolation, collect percolate, removing ethanol, then merge with impregnation liquid in step (1), be concentrated into appropriate, filter;

(3), by Camphora, Oleum Terebinthinae use dissolve with ethanol respectively, then join in the filtrate of step (2), mix homogeneously, by 70 ﹪ ethanol adjustment total amounts to 1000ml, subpackage, sealing, press-in propellant, packaging, to obtain final product; Described propellant is dimethyl ether.