CN100353996C - Medicine composition for treating soft tissue damage and osteoarthropathy and its prepn process - Google Patents

Abstract

The invention discloses a pharmaceutical composition for treating tendons and soft tissue injuries and osteoarthritis. The pharmaceutical composition is prepared from the following raw materials in parts by weight: 1-50 parts of Panax notoginseng, 1-50 parts of Polygonum cuspidatum, 1-50 parts of Chuanwu, 1-50 parts of Araceae, 1-50 parts of Duhuo, 1-50 parts of Angelica, 1-50 parts of Dipsacus, 1-50 parts of dried ginger, 1-50 parts of pepper, 1-50 parts of clove basil oil 50 parts, turpentine 1-50 parts, menthol 1-50 parts, camphor 1-50 parts, borneol 1-50 parts. The medicine combination and the prepared preparation of the present invention have the effects of promoting blood circulation and dispelling blood stasis, dredging meridians and activating collaterals, reducing swelling and relieving pain, etc., and are used for treating tendons and soft tissue injuries and swelling and pain caused by osteoarthropathy, and the prepared medicine is in the form of Pale yellow semi-solid, with a delicate fragrance, the paste is delicate, easy to spread, easy to clean, and will not pollute clothes.

Description

A kind of pharmaceutical composition and preparation method for treating tendon soft tissue injury and osteoarthropathy

technical field

The invention relates to a pharmaceutical composition for treating swelling and pain and a preparation method thereof.

Background technique

Soft tissue injuries and bone and joint lesions in orthopedics and traumatology are often characterized by local swelling and pain. They are common pain syndromes in traditional Chinese medicine. Happens often in life. With the rapid development of transportation, construction, and industrial and mining industries, people's pace of life has accelerated, the incidence of various sprains, fractures, and dislocations has increased year by year, and the number of soft tissue injuries has increased. According to statistics, the number of patients with soft tissue injuries increases at a rate of 6-9% per year, causing huge economic losses to patients and the country. Therefore, patients have an urgent need for drugs for soft tissue injuries.

Traditional Chinese medicine for the treatment of soft tissue injuries and bone and joint lesions in orthopedics and traumatology is mainly in the form of black plaster. Heavy metals such as lead red are used in production, which pollutes the environment. In recent years, it has been impossible to arrange production. The rubber plaster produced in recent years uses gasoline as a solvent during production, which is explosive and requires an explosion-proof workshop for production, which also pollutes the environment. When used, it has poor air permeability and often causes allergies. Other existing dosage forms for external use also have the disadvantages that the paste is black and thick, difficult to spread, pollutes clothes, and difficult to clean. Therefore, the development of new dosage forms of drugs for the treatment of soft tissue injuries and osteoarthritis in orthopedics and traumatology has broad market prospects and huge social benefits.

Contents of the invention

The object of the present invention is to provide a pharmaceutical composition for treating tendon soft tissue injury and osteoarthropathy, which is easy to apply, has a light color and taste, is easy to clean and does not pollute clothes, and a preparation method.

In order to achieve the above-mentioned purpose, the pharmaceutical composition of the present invention is made of the following raw materials in parts by weight:

Panax notoginseng 1-50 parts, Polygonum cuspidatum 1-50 parts, Chuanwu 1-50 parts, Araceae 1-50 parts, Duhuo 1-50 parts, Angelica 1-50 parts, Dipsacus 1-50 parts, Dried ginger 1-50 parts 1-50 parts of pepper, 1-50 parts of clove basil oil, 1-50 parts of turpentine oil, 1-50 parts of menthol, 1-50 parts of camphor, and 1-50 parts of borneol.

The preferred version of the present invention is that the parts by weight of the bulk drug are:

25 parts of Panax notoginseng, 25 parts of Polygonum cuspidatum, 20 parts of Aconitum, 20 parts of Araceae, 16 parts of Duhuo, 10 parts of Angelica, 10 parts of Dipsacus, 10 parts of dried ginger, 10 parts of pepper, 10 parts of clove basil oil, 16 parts of turpentine oil, 26 parts of menthol, 13 parts of camphor, 13 parts of borneol.

In the prescription, Sanqi and Chuanwu are the two medicines. Sanqi is sweet and bitter but warm, enters the liver meridian, has the function of removing blood stasis and stopping bleeding, promoting blood circulation and relieving pain, can stop bleeding and dissipate blood stasis, stop bleeding without leaving stasis, remove blood stasis and relieve pain. It is suitable for various blood syndromes, especially those with stasis, and is an important medicine for promoting blood circulation, removing blood stasis and relieving pain; Chuanwu is hard and warm, enters the heart, liver and kidney meridians, and has the functions of expelling wind and dampness, dispelling cold and relieving pain, "Compendium of Materia Medica": "mainly strong wind and stubborn numbness." It is the key medicine for treating cold-damp arthralgia. Combination of two medicines, one is to relieve pain by promoting blood circulation, removing blood stasis and stopping bleeding, which is used for bruises, local torsion and swelling pain; the other is to relieve pain by dispelling wind, dispelling cold and dehumidification, and is used for pain caused by wind-cold-damp invasion and stagnation of meridians Heavy pain. Combined with clove oil, angelica, and Duhuo three medicines as ministers, among them, clove oil, pungent and warm, diffuses fragrance, moves qi and relieves pain, which means that blood is first promoted, and when qi moves, blood moves; Entering the Heart, Liver and Spleen Meridian, it can not only help Sanqi to promote blood circulation, reduce swelling and relieve pain, but also nourish blood and strengthen muscles. Returning to the liver and bladder meridian, it can not only bitterly dry the wind, cold and dampness of the joints, but also be good at expelling the pungent powder, so that the wind, cold and dampness can be relieved from the foot sun meridian. When used together with Chuanwu, it can dispel wind and dampness, dispel cold and relieve pain. In the prescription, Polygonum cuspidatum is bitter and cold, returns to the liver, gallbladder and lung meridian, and has the function of promoting blood circulation, removing blood stasis and relieving pain; Tiannan star is bitter and warm, returns to the lung, liver and spleen meridian, and is used externally to reduce swelling and relieve pain, and also has the function of dispelling wind and relieving spasm; Slightly warm, returns to the Liver and Kidney meridian, can pass through blood vessels, relieve swelling and relieve pain, and treat rheumatic arthralgia. It can also nourish the liver and kidney, strengthen muscles and bones, and heal wounds. Swelling and pain, etc. Dried ginger is pungent, hot and dry, and returns to the spleen, stomach, heart and lung meridians, warms the middle and dispels cold, restores yang and unblocks the meridians, whichever can "send the cold air of all meridians" to help Chuanwu alone live and eliminate evil; pepper is also pungent and hot The product for expelling cold and relieving pain, the above five flavors are used as adjuvant medicine. Turpentine oil, fragrant and pungent, expelling wind and cold, dredging collaterals and relieving pain; camphor, menthol is the essence of camphor tree and peppermint, with aroma, good at reaching muscles, smooth camp and health, penetrating joints, both expelling wind and dispersing evil Dredge the interstitial muscles, dredge the meridian and reach the collaterals, and have the effect of reducing swelling and relieving pain; borneol is the crystallization of dipterocarp, which is fragrant and resuscitating when taken internally, and relieves swelling and pain when used externally, and is good at treating various pains. Dehumidification, fragrance travels and dredges the meridian and collaterals, penetrates the interstitial muscles and heals injuries and relieves pain. It is also used as an adjuvant medicine. In addition, borneol and menthol are used for their fragrance and thoroughness, dredging camps and guards, and directing medicines to sick places, so they are also used as medicines. Taking a comprehensive view of the whole prescription, it emphasizes both promoting blood circulation, removing blood stasis and dredging collaterals, dispelling wind and cold, and removing dampness. Invigorating blood circulation without forgetting to promote qi, eliminating evils without forgetting to strengthen the body, the monarch and ministers are orderly, and the compatibility is strict. Collateral, the merit of reducing swelling and relieving pain, makes it accessible to the body and defense, harmonizes Qi and blood, removes pathogenic factors and promotes peace, then bruises and swellings will disappear, pain will be flat, and all diseases will be eliminated.

The above-mentioned pharmaceutical composition can be made into clinically acceptable dosage forms such as external ointment, atomizer, liniment, film, gel, etc. The composition can also be made into powder by adding appropriate auxiliary materials.

The preparation method of the pharmaceutical composition of the present invention comprises the following steps:

a), get lovage, angelica, and dried ginger in the above fourteen raw materials, grind them into 20-60 mesh coarse powder, use 6-8 times the amount of 80% ethanol as a solvent, soak it for 24 hours, and use 2-60% ethanol as a solvent per minute. Percolation at a speed of 5ml, collect 1 to 3 times the amount of the first decant liquid, store in another container, continue percolation, collect the subsequent percolation liquid, concentrate the subsequent percolation liquid below 60°C to a thick paste, add the initial dehydration liquid, and use 80% Dilute to 3 times the amount with ethanol to obtain an ethanol extract, and put it in a clean container for later use;

b) Take Polygonum cuspidatum, Panax notoginseng, Araceae, Aconitum, Dipsacus, and pepper, reflux extract with 6 times the amount of 50-80% ethanol for 3 times, each time for 0.5-1.5 hours, filter, combine the extracts, recover the ethanol, and concentrate Thick paste with a relative density of 1.10 to 1.25 at 50°C;

c), take the thick cream and mix it with the ethanol extracts of lovage, angelica, and dried ginger, adjust the volume to 3 times the amount, and mix well;

d) Mix the above mixed liquid with 10-80 parts of glycerin, 1-10 parts of sodium benzoate, and 10-50 parts of carbomer in water, heat to 60°C to form an aqueous phase, and use 20% triethanolamine aqueous solution to adjust the water phase pH to 6.5-7.0;

e) Mix 5-50 parts of azone and emulsifier polysorbate 80, heat to 60°C to form an auxiliary material oil phase, add turpentine, menthol, borneol, camphor, clove basil oil and mix to form an oil phase;

f) adding the oil phase into the water phase and stirring to room temperature to obtain a semi-solid drug.

The crude drug of the present invention passes through the above preparation process.

The preparation process of various commonly used dosage forms of pharmaceutical composition of the present invention is illustrated respectively below:

(1), preparation of ointment for external use: take the obtained semi-solid medicine, weigh, add appropriate amount of adjuvant, mix well, obtain ointment for external use. The commonly used auxiliary material is purified water.

(2) Preparation of the atomizer: take the obtained semi-solid medicine, weigh it, add appropriate amount of auxiliary materials, and make the atomizer. Commonly used auxiliary materials are propellants.

(3), preparation of liniment: the obtained semi-solid medicine is added with appropriate amount of auxiliary material to make liniment. The commonly used auxiliary material is ethanol with a concentration of 40-80%.

(4), preparation of film: the obtained semi-solid medicine is added with an appropriate amount of adjuvant to make a film. Commonly used auxiliary materials are polyvinyl alcohol, acrylic resins, cellulose and other natural polymer materials.

(5), preparation of gel: obtain the semi-solid medicine, add appropriate auxiliary material, make gel. The commonly used excipient is carbomer.

(6) Preparation of powder: a) Take the above fourteen herbs, and grind the lovage, angelica, dried ginger, knotweed, Sanqi, Araceae, Chuanwu, Dipsacus, and pepper into 100-200 mesh fine powder ;

b), Azone is mixed with turpentine, menthol, borneol, camphor, clove basil oil, etc. to form an oil phase;

c) Mix the oil phase with the fine powder of medicinal materials to make a powder.

The invention has the advantages that the prepared medicine is light yellow semi-solid, has a delicate smell, and the paste is fine and smooth, easy to spread and clean, and will not pollute clothes.

The pharmaceutical composition of the present invention has the following pharmacological effects: it has obvious analgesic effect on pain caused by intraperitoneal injection of acetic acid and heat stimulation in mice. It has obvious inhibitory effect on acute inflammation models such as increased permeability of mouse abdominal capillaries induced by acetic acid, swelling of rat carrageenan toes, and swelling of mouse auricles induced by xylene; it has obvious inhibitory effect on rat cotton ball granuloma The subacute inflammation model also has a certain inhibitory effect. It can promote the absorption of subcutaneous blood spots in mice, significantly reduce the area of blood spots and shorten the disappearance time of blood spots, and can shorten the time for the disappearance of traumatic ecchymosis in rats. It can reduce the whole blood viscosity and plasma viscosity of blood stasis model rats; it can also significantly expand the caliber of rabbit ear veins, and has the effect of improving microcirculation; the above pharmacological effects of this pharmaceutical composition are its clinical use for soft tissue injuries and osteoarthritis The resulting swelling and pain provide an experimental basis.

Further illustrate effect of the present invention below in conjunction with some experiments:

Experiment 1. Analgesic test

1.1 Test material

1.1.1 Test drug: external ointment of the pharmaceutical composition of the present invention: wherein 0.224g crude drug/g ointment; batch number: BN20040809; provided by the New Drug Center of Guangzhou University of Traditional Chinese Medicine. Bone-setting water: produced by Guangxi Yulin Pharmaceutical Co., Ltd., batch number 421117. Barium sulfide: Shanghai Sinopharm Chemical Reagent Co., Ltd., batch number: F20040529; blank control drug: blank matrix, provided by the New Drug Center of Guangzhou University of Traditional Chinese Medicine.

1.1.2 Test dosage: the external application ointment (0.224g crude drug/g) of pharmaceutical composition of the present invention, adult clinical every day 4 times, once 2g, promptly maximum dosage every day is 1.79g crude drug/d, calculate with adult's body weight 60kg , the average dosage was 0.0299g crude drug/kg/d. The low, medium and high dosage groups of the mice in this experiment were respectively set at 0.3, 0.6 and 1.2 g crude drug/kg, and the above-mentioned dosages were 10, 20 and 40 times (calculated by body weight) of the clinical dosage.

1.1.3 Animals: NIH mice, (Certificate No. 20030001), provided by the Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine. SPF grade, normal feeding after 3 days for testing.

1.2 Methods and results

1.2.1 Effects on pain induced by heat stimulation in mice (hot plate method)

60 NIH mice, female, weighing 18-22g, selected 60 mice with a basic pain threshold between 5 and 30s (from placing the mice on a hot plate at a temperature of 55±0.5°C until the mice started licking) foot time as the basic pain threshold) are randomly divided into 5 groups, i.e. blank matrix control group, Zhenggushui positive control group, ointment high, middle and low dose groups of the present invention, apply medicine 1 time every day (use 8% vulcanization agent one day before administration) Barium hair removal), the blank control group was coated with the same amount of matrix, for 3 consecutive days, after the last administration, the pain threshold of the mice was measured at 0.5, 1.0, and 2.0 h after the drug, the percentage increase of the pain threshold was calculated, and the differences among the groups were compared. The results are shown in Table 1.

Table 1 result shows: the external application ointment high dosage of pharmaceutical composition of the present invention can significantly improve 0.5～2h mouse pain threshold raising percentage (P＜0.05～0.01), and middle dose can significantly improve 1～2h mouse pain threshold after medicine Increase the percentage (P<0.05～0.01), and low dose can increase the percentage of pain threshold improvement in mice 1h after the drug (P<0.05); Zhenggushui can significantly increase the percentage of pain threshold improvement in mice 0.5～2h after the drug (P<0.05 ~0.01). It is suggested that the external ointment of the pharmaceutical composition of the present invention has analgesic effect.

Table 1 The effect of pharmaceutical composition ointment of the present invention on the pain of mice caused by thermal stimulation

group number of animals Dose g crude drug/kg Percentage increase in pain threshold (%) 0.5h 1h 2h Blank bone-setting water ointment of the present invention ointment of the present invention ointment of the present invention 1212121212 -10ml0.30.61.2 6.95±5.2312.85±7.98 ^* 11.13±5.5814.75±12.6518.15±11.42 ^** 7.21±4.01 2.28±15.70 ^** 12.45±6.29 ^* 18.21±9.83 ^** 22.13±13.05 ^** 15.30±11.4238.31±27.19 ^* 26.94±14.6328.66±15.15 ^* 31.91±19.18 ^*

Note: Compared with blank matrix group, ^* P<0.05, ^** P<0.01

1.2.2 Effects on pain induced by acetic acid in mice (twisting method)

Choose 60 healthy male mice, body weight is 18～22g, be divided into 5 groups at random, i.e. blank matrix control group, Zhenggushui positive control group, ointment high, middle and low dose groups of the present invention, apply medicine 1 time every day (administration The day before with 8% barium sulfide for depilation), the blank control group was coated with the same amount of substrate, for 3 consecutive days, after the last coating (during the experiment, the mice were fasted for 12 hours) and intraperitoneally injected 0.8% acetic acid saline solution 0.2 ml/mouse, observe and record the time from the injection of acetic acid to writhing and the number of times of writhing within 20 minutes, and compare the differences among the groups. The results are shown in Table 2.

Table 2 Ointment of the present invention is to the influence of mouse pain caused by acetic acid

group Number of animals Dose g crude drug/kg Appearance time (seconds) 20 minutes of writhing Blank bone-setting water ointment of the present invention ointment of the present invention ointment of the present invention 1212121212 -10ml0.30.61.2 243.83±48.46286.17±32.01 ^* 277.33±30.15284.33±28.59 ^* 320.42±83.58 ^* 41.25±7.331.25±12.10 ^* 34.83±7.73 ^* 33.33±7.80 ^* 32.33±11.70 ^*

Note: Compared with the blank matrix group, ^* P<0.05

As can be seen from the results in Table 2, the low, medium and high doses of ointment of the present invention can significantly reduce the number of times of writhing in mice caused by acetic acid (P < 0.05) and the medium and high doses can prolong the time that the writhing occurs (P < 0.05); Bone-setting water can also significantly reduce the number of writhing in mice and prolong the time of writhing (P<0.05). Prompt ointment of the present invention has analgesic effect.

Experiment 2. Anti-inflammatory test

2.1 Test material

2.1.1 Test drug: ointment of the present invention: 0.224g crude drug/g ointment; batch number: BN20040809; provided by the New Drug Center of Guangzhou University of Traditional Chinese Medicine, positive control drug: Fuqingqing ointment: specification: 2.5mg/10g, supplied by Tianjin Pharmaceutical Produced by Group Co., Ltd., batch number 04086005. Blank control drug: blank matrix, provided by the New Drug Center of Guangzhou University of Traditional Chinese Medicine; xylene: chemically pure, Guangzhou Chemical Reagent Factory, batch number: 0203428; carrageenan: a product of Sigma Company, Evans Blue: a product of Sigma Company; acetic acid : Produced by Shanghai Reagent No. 1 Factory, batch number: 0103521.

2.1.2 Test dose: the ointment of the present invention (0.224g crude drug/g), adult clinical 4 times a day, 2g once, that is, the maximum daily dosage is 1.79g crude drug/d, based on the adult body weight of 60kg, the average dosage is 0.0299 crude drug /kg/d. The low, medium and high dosage groups of the mice in this test were respectively set as 0.3, 0.6 and 1.2g crude drug/kg, and the above-mentioned dosages were 10, 20 and 40 times (calculated by body weight) of the clinical drug dosage; 1, 3, and 3 dosage groups, respectively set as 0.15, 0.3, 0.6g crude drug/kg, above-mentioned dosage is 5, 10, 20 times of clinical drug dosage (calculated by body weight).

2.1.3 Animals: NIH mice (Certificate No. 20030001); SD rats (Certificate No. 20030001), all provided by the Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine. SPF grade, normal feeding after 3 days for testing.

2.1.3 Instrument: BS110S electronic balance: product of Sartorius Company; 722 grating spectrophotometer: Shanghai Precision Scientific Instrument Co., Ltd. Capillary amplification measuring device.

2.2 Methods and results

2.2.1 Effect on increased permeability of mouse peritoneal capillaries

Get 60 NIH mice, body weight 18～22g, male, be divided into 5 groups at random, i.e. blank matrix control group, fluocinolone positive control group, high, middle and low dose groups of ointment of the present invention, apply medicine 1 time every day (administration The day before with 8% barium sulfide hair removal), the blank control group was coated with the same amount of matrix, for 3 consecutive days, 1h after the last administration, each rat was injected with 2% Evans blue normal saline solution 0.1ml/10g body weight through the tail vein, and immediately injected into the abdominal cavity. Inject 0.2ml/mouse of 0.8% acetic acid saline solution, kill the mice by dislocation after 20min, cut open the abdominal cavity, rinse several times with 5ml saline solution, collect the lotion, centrifuge, take the supernatant and measure the OD value at 590nm of the spectrophotometer , to compare the differences between the groups. The results are shown in Table 3.

Table 3 The effect of ointment of the present invention on the increase of mouse abdominal cavity capillary permeability caused by acetic acid

group Number of animals Dose g crude drug/kg OD value Blank base fluocinolone ointment of the present invention ointment of the present invention ointment of the present invention 1212121212 -1.25mg0.30.61.2 0.391±0.1450.242±0.077 ^** 0.289±0.058 ^* 0.260±0.063 ^** 0.253±0.064 ^**

Note: Compared with blank matrix group, ^* P<0.05, ^** P<0.01

Table 3 result shows: ointment high, middle and low dosage groups of the present invention can significantly suppress the mouse capillary permeability increase (P＜0.01～0.05) caused by acetic acid, and be dose-effect relationship; As a result, the capillary permeability of mice was increased (P<0.01). Prompt that ointment of the present invention has the effect of suppressing inflammatory exudation.

2.2.2 Effects on rat carrageenan toe swelling

Choose 50 SD rats, males, with a body weight of 150-160 g, randomly divided into 5 groups, i.e. blank matrix control group, fluocinolone positive control group, high, middle and low dose groups of ointment of the present invention, each mouse left hind paw before the test A clear horizontal line was drawn with a marker pen at the ankle joint, and the volume of the toe of the rat was measured by the capillary amplification method. Then apply the medicine once a day (with 8% barium sulfide for depilation the day before the administration), and the blank control group is coated with the same amount of matrix for 3 consecutive days. After the last administration 1h, each mouse is subcutaneously injected with 1% carrageenan on the left hind foot. Glue 0.1ml, measure the volume of the toes of the rats once in 1, 2, 3, 4, and 5 hours respectively, calculate the degree of paw swelling, and compare the differences among the groups. The results are shown in Table 4.

Paw swelling degree (ml) = foot volume at each time point after swelling (ml) - swelling forefoot volume (ml)

Table 4 The impact of ointment of the present invention on carrageenan rat paw swelling

group Number of animals (only) Dose (g crude drug/kg) degree of paw swelling (ml) 1h 2h 3h 4h 5h The present invention 101010 -0.625mg0.15 0.40±0.080.29±0.100.38±0.06 0.51±0.100.40±0.08 ^* 0.49±0.07 0.54±0.090.43±0.07 ^** 0.54±0.08 0.51±0.090.36±0.08 ^** 0.50±0.08 0.42±0.110.31±0.06 ^** 0.46±0.07

Ointment of the present invention Ointment of the present invention 1010 0.30.6 0.38±0.080.35±0.07 0.42±0.07 ^* 0.41±0.06 ^* 0.45±0.10 ^* 0.43±0.07 ^** 0.43±0.07 ^* 0.38±0.08 ^** 0.35±0.080.33±0.09 ^*

Note: Compared with blank matrix group, ^* P<0.05, ^** P<0.01

Table 4 result shows: the ointment middle dose group of the present invention can significantly suppress the foot swelling degree (P＜0.05) of 1～4h, and high dose can significantly suppress the foot swelling degree (P＜0.05～0.01) of 1～5h time point; Relaxation can also significantly inhibit the paw swelling at each time point of 2-5 hours (P<0.05-0.01). It is suggested that the ointment of the present invention has anti-inflammatory and detumescence effects.

2.2.3 Effect of xylene-induced ear swelling in mice

Get 65 NIH mice, body weight 18～22g, male, be divided into 5 groups at random, i.e. blank matrix control group, fluocinolone positive control group, high, middle and low dose groups of ointment of the present invention, then apply medicine 1 time every day (for 8% barium sulfide was used for hair removal the day before the medicine), and the blank control group was coated with the same amount of substrate for 3 consecutive days. After 1 hour of the last administration, 50 μl of xylene was dropped on both sides of the right ear of the mouse, and the left ear was not coated as a control, 0.5 After one hour, the mice were killed by dislodging the cervical vertebrae, and the round ear pieces were respectively punched in the same part of the left and right ears with a 6mm diameter punch, and weighed accurately. . The results are shown in Table 5.

The influence of table 5 ointment of the present invention on mouse auricle swelling caused by xylene

group Number of animals Dose (g crude drug kg) Degree of ear swelling (mg) Blank Fucainolone Ointment of the Invention Ointment of the Invention Ointment of the Invention 1313131313 -1.25mg0.30.61.2 6.12±2.474.25±1.61 ^* 5.15±1.164.59±0.97 ^* 4.62±0.56 ^*

Note: Compared with the blank matrix group, ^* P<0.05

The results in Table 5 show that: medium and high doses of the ointment of the present invention can significantly reduce the swelling degree of the auricle of the xylene-induced inflammation mice (P<0.05). Furelaxone can also significantly reduce ear swelling in mice (P<0.05). It is suggested that the ointment of the present invention has anti-inflammatory and detumescence effects.

2.2.4 The influence of ointment of the present invention on rat cotton ball granuloma

Get 50 male SD rats, body weight 140～160g, be divided into 5 groups at random, namely blank matrix control group, fluocinolone positive control group, high, middle and low dose groups of ointment of the present invention. Under light ether anesthesia, the abdomen was shaved and disinfected, and sterilized cotton balls (each cotton ball weighed 10±0.5mg, autoclaved, each added with ampicillin 1mg/0.1ml each, dried at 50°C) were implanted into the large intestine. Subcutaneously, and then sutured. On the day after the operation, the drug was applied once, and the blank control group was coated with the same amount of matrix for 7 consecutive days. On the eighth day, they were killed by dislocation, and the cotton balls were taken out, dried at 60°C for 12 hours, and weighed to obtain the weight of the cotton ball granuloma. The inhibition rate was calculated, and the results are shown in Table 6.

Table 6 The impact of ointment of the present invention on rat cotton ball granuloma

group Number of animals (only) Dosage (g crude drug kg) Granuloma weight (mg) Inhibition rate(%)   Blank Fucaolin ointment of the present invention Ointment of the present invention Ointment of the present invention   1010101010 -0.625mg0.150.30.6 25.04±3.8020.24±5.12 ^* 22.42±1.6921.71±2.36 ^* 21.12±2.77 ^* 19.1710.4613.3015.65

Note: Compared with the blank matrix group, ^* P<0.05

The results in Table 6 show that high and medium doses of the ointment of the present invention can significantly reduce the weight of granulation tissue (P<0.05), suggesting that the ointment of the present invention can inhibit the formation of granulation tissue in the proliferative phase of inflammation.

Experiment 3. Experiment of removing blood stasis and reducing swelling

3.1 Test material

3.1.1 Test drug: ointment of the present invention: 0.224g crude drug/g ointment; batch number: BN20040809; provided by New Drug Center of Guangzhou University of Traditional Chinese Medicine; positive control drug: Zhenggushui: produced by Guangxi Yulin Pharmaceutical Co., Ltd., batch number 421117; blank Control drug: blank matrix, provided by the New Drug Center of Guangzhou University of Traditional Chinese Medicine; heparin: produced by Xuzhou Wanbang Biochemical Pharmaceutical Co., Ltd., batch number: 0206108; barium sulfide: Shanghai Sinopharm Chemical Reagent Co., Ltd., batch number: F20040529.

3.1.2 Test dose: the ointment of the present invention (0.224g crude drug/g), adult clinical 4 times a day, 2g once, that is, the maximum daily dosage is 1.79g crude drug/d, based on the adult body weight of 60kg, the average dosage is 0.0299 crude drug /kg/d. The low, medium and high dosage groups of the mice in this test were respectively set as 0.3, 0.6 and 1.2g crude drug/kg, and the above-mentioned dosages were 10, 20 and 40 times (calculated by body weight) of the clinical drug dosage; 1, 3, and 3 dosage groups, respectively set as 0.15, 0.3, 0.6g crude drug/kg, above-mentioned dosage is 5, 10, 20 times of clinical drug dosage (calculated by body weight).

3.1.3 Animals: NIH mice (Certificate No. 20030001); SD rats (Certificate No. 20030001), all provided by the Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine. SPF grade, normal feeding after 3 days for testing.

3.2 Methods and results

3.2.1 Effect of ointment of the present invention on rat traumatic ecchymosis

Get 50 SD rats, body weight 180～200g, both male and female, be randomly divided into 5 groups, namely blank matrix control group, bone-setting water positive control group, high, middle and low dose groups of ointment of the present invention. The day before the experiment, the back of the rat was depilated with 8% barium sulfide, and then the skin was clamped with vise to cause subcutaneous hemorrhage (area 4cm × 4cm). After one hour, ecchymosis appeared, and the liquid was applied to the ecchymosis evenly, every day Twice, observe the disappearance of ecchymosis every day, the results are shown in Table 7.

Table 7 The impact of ointment of the present invention on rat traumatic ecchymosis

group Number of animals (only) Dose (g crude drug/kg) Days for ecchymosis to subside Blank bone-setting water ointment of the present invention ointment of the present invention ointment of the present invention   1010101010 -5ml0.150.30.6 8.2±0.796.9±1.10 ^** 7.3±0.95 ^* 7.2±1.03 ^* 7.0±1.05 ^**

Note: Compared with blank matrix group, ^* P<0.05, ^** P<0.01

The results in Table 7 show that the ointment of the present invention can significantly shorten the days for the ecchymosis to disappear, and there is an obvious dose-effect relationship. It is suggested that the ointment of the present invention has the effect of removing blood stasis and reducing swelling.

3.2.2 Experiment of ointment of the present invention on mouse blood stasis model

Preparation of subcutaneous blood spot model: use depilatory agent (8% barium sulfide) to depilate the back of each mouse 2cm × 3cm, and 1 day later, take 0.4ml of blood from the orbit, anticoagulate with 0.1ml of 50u/ml heparin saline, and subcutaneously inject it into the depilation of the back blood spots under the skin. 60 NIH mice made of subcutaneous blood spot models, half male and half male, were randomly divided into 5 groups, namely blank matrix group, three dosage groups of low, medium and high dosage groups of ointment of the present invention, and bone-setting water positive group. After 4 hours, the blood spot area was measured, and it was taken as the blood spot area before administration. Immediately administer the drug, and apply the medicine on the upper part of the blood spot every day, twice a day, for 7 consecutive days. And measure the blood spot area once a day until the blood spot disappears, if it has not disappeared within 7 days, it will be counted as 7 days. The blood spots of some mice disappeared from the 4th day. Therefore, only the blood spot disappearing time and the blood spot area on the 1st, 2nd, 3rd, and 4th day were compared, and the results are shown in Table 8.

n＝13)The impact of table 8 ointment of the present invention on mouse subcutaneous blood spot absorption (

n=13)

group Dose g crude drug/g Blood spot area (mm ² ) Blood spots disappearing time (d) Before administration 1d 2d 3d 4d Blank matrix bone-setting water ointment of the present invention ointment of the present invention ointment of the present invention -10ml0.30.61.2 47.32±8.5848.81±7.4750.49±12.0553.18±7.8046.38±10.79 50.45±7.8449.29±6.9944.40±11.70 ^* 49.76±8.5343.85±9.33 48.98±6.2843.60±5.68 ^* 41.82±11.0143.07±7.87 ^* 40.37±9.21 ^* 40.56±9.1232.18±8.35 ^* 32.36±10.05 ^* 32.37±9.78 ^* 31.75±7.25 ^* 28.66±12.0319.00±6.25 ^* 19.71±7.67 ^* 19.33±7.21 ^* 18.70±4.70 ^* 6.2±0.85.5±0.8 ^* 5.7±0.65.5±0.8 ^* 5.4±0.5 ^**

Compared with blank matrix group: *p<0.05; **p<0.01; t test

It can be seen from Table 8 that the ointment of the present invention can significantly reduce the area of blood spots and shorten the disappearance time of blood spots. And dose-dependent. It is suggested that the ointment of the present invention has the effect of removing blood stasis and reducing swelling.

Experiment 4. Effects on hemorheology

4.1 Test material

4.1.1 Drugs and Reagents

Ointment of the present invention: 0.224g crude drug/g ointment; batch number: BN20040809; provided by New Drug Center of Guangzhou University of Traditional Chinese Medicine. Positive control drug: Zhenggushui: produced by Guangxi Yulin Pharmaceutical Co., Ltd., batch number 421117. Epinephrine Hydrochloride Injection, produced by Beijing Yongkang Pharmaceutical Factory, batch number: 20010406. Heparin: produced by Nanjing Xinbai Pharmaceutical Co., Ltd., batch number: 030101.

4.1.2 Test dose: the ointment of the present invention (0.224g crude drug/g), adult clinical 4 times a day, 2g once, that is, the maximum daily dosage is 1.79g crude drug/d, based on an adult body weight of 60kg, the average dosage is 0.0299 crude drug /kg/d. The low, medium and high dose groups of the rats were respectively set at 0.15, 0.3 and 0.6 g crude drug/kg, and the above-mentioned doses were 5, 10 and 20 times (calculated by body weight) of the clinical drug dose.

4.1.3 Animals: SD rats (certificate number: 20030001), provided by the Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine. SPF grade, after three days of normal feeding, it was tested.

4.1.4 Instrument: LBY-N6B rotary blood viscometer (Prison)

4.2 Methods and results

Get 60 SD rats, be divided into 6 groups at random, namely normal control group, blood stasis model group control group, bone-setting water positive drug group, ointment low, middle and high dose groups of the present invention. The medicine was applied once a day, and the control group was given an equal amount of blank matrix. Except for the normal control group, each group was gavaged with cold boiled water (5ml/cause) every day for 7 consecutive days. On the seventh day, except the normal control group, the other groups were subcutaneously injected with epinephrine (0.08ml/100g), twice in total with an interval of 4h. Between the two injections of epinephrine (each interval of 2 hours before and after), the rats were immersed in ice In water for 5 minutes, fasting without water after treatment, blood was collected from the eyes of animals in each group on the eighth day, anticoagulated with heparin, and the viscosity of whole blood and plasma were measured respectively. The results are shown in Table 9.

It can be seen from Table 9 that after subcutaneous injection of epinephrine in rats, the whole blood viscosity and plasma viscosity both increased, which indicated the formation of the "blood stasis (high blood viscosity)" model. Different dosage groups of the ointment of the present invention can reduce whole blood viscosity and plasma viscosity. It is suggested that the ointment of the present invention has the effect of promoting blood circulation and removing stasis.

Table 9 The influence of ointment of the present invention on rat hemorheology

group Dose (g crude drug/kg) Number of animals (only) whole blood viscosity plasma viscosity Normal control group model bone-setting water ointment of the present invention ointment of the present invention --10ml0.150.30.6 101010101010 17.83±1.52 24.94±3.94 ^ 20.31±2.63 ^** 20.35±5.1619.84±4.91 ^* 19.02±1.98 ^** 1.06±0.05 1.39±0.11 ^ 1.15±0.07 ^** 1.28±0.11 ^* 1.11±0.08 ^** 1.14±0.07 ^**

Note: Compared with the normal control group: ^ P<0.05, ^ P<0.01; compared with the model group: *P<0.05 **P<0.01, t test

Experiment 5. Effect on microcirculation

5.1 Test material

5.1.1 Drugs and Reagents

Ointment of the present invention: 0.224g crude drug/g ointment; batch number: BN20040809; provided by New Drug Center of Guangzhou University of Traditional Chinese Medicine. Positive control drug: Zhenggushui: produced by Guangxi Yulin Pharmaceutical Co., Ltd., batch number 421117.

5.1.2 Test dose: the ointment of the present invention (0.224g crude drug/g), adult clinical 3 times a day, 2g once, that is, the maximum daily dosage is 1.79g crude drug/d, based on the adult body weight of 60kg, the average dosage is 0.0299 crude drug /kg/d. In this experiment, the low, medium and high dose groups of New Zealand rabbits were respectively set at 0.15, 0.3 and 0.6 g crude drug/kg, and the above doses were 5, 10 and 20 times of the clinical drug dose (calculated by body weight).

5.1.3 Animals: New Zealand rabbits, provided by the Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine, (certificate number: 20030001) ordinary grade.

5.2 Methods and results

Get 50 New Zealand rabbits with a body weight of 1.2-1.5 kg, and divide them into 5 groups at random, namely, a blank control group, a bone-setting water-positive drug group, and low, middle, and high-dose groups of the ointment of the present invention. Animals in each group were anesthetized by intraperitoneal injection of 40% urethane 2ml/kg before the experiment, and then pasted on the auricle with medical adhesive plaster to remove the hair. paraffin. The observation table is placed on the dissecting microscope stage, and under transmitted light, observe the change of the microcirculation capillary caliber of the auricle at the same position before and after the ointment of the present invention is smeared with a 15×5 magnification lens. The results are shown in Table 10.

μm)The influence of table 10 ointment of the present invention on New Zealand rabbit pinna vein capillary caliber (

μm)

group Dose (g crude drug/kg) Number of animals (only) Before administration After administration 5min difference 10min difference Blank control Bone-setting water Ointment of the present invention Ointment of the present invention Ointment of the present invention -10ml0.521.042.08 1010101010 28.3±6.826.1±4.429.0±9.533.1±11.533.1±11.5 29.7±6.830.1±6.130.9±10.235.8±11.636.1±11.7 1.39±0.714.19±3.29 ^* 1.85±1.122.72±1.31 ^* 3.24±1.87 ^** 29.3±6.929.8±5.530.5±9.735.4±11.635.8±11.7 1.03±0.393.72±2.89 ^** 1.46±0.662.28±1.15 ^** 2.95±1.52 ^**

Note: Compared with blank control group: **P<0.01, t test

As can be seen from Table 10, after giving the ointment of the present invention, the caliber of the auricular vein of New Zealand rabbits increases, which is significantly different from that of the control group. The results show that the ointment of the present invention can obviously improve the microcirculation of New Zealand rabbit auricle.

Experiment 6. Toxicological research on ointment of the present invention

6.1. Acute toxicity test

Apply rat, mouse to carry out acute toxicity test and show: rat normal skin, damaged skin give the ointment local application 4.48g crude drug/kg of the present invention of highest concentration, 2 times a day (maximum dosage is 8.96g crude drug/kg/d , which is 600 times the dosage of clinical adults), observed continuously for seven days. The results showed that there was no abnormality in the systemic reaction of the animals in each group, and the body weight gain, food intake, drinking water, and activities were all normal, and no animal died. The _LD50 of the present invention is 4.93g crude drug/kg (95% credible limit is 4.02～6.04g crude drug/kg) after oral gavage of mice, and the symptoms of poisoning begin to appear in 5 minutes after oral gavage of the present invention, and the symptoms of poisoning are shortness of breath , Unsteady gait, loss of righting reflex, the degree of poisoning is related to the dose, and the animals finally died due to respiratory depression, most of them died within 20-30 minutes, a few within 1-2 hours, and individual mice within 24 hours . Autopsy found no obvious abnormalities in tissues and organs. The surviving mice had normal diet, water intake and activities during the observation period. The clinical application of this product is topical administration for external use, and the dosage and the amount that can be absorbed into the whole body are small, so it can be considered that this product is safer for clinical external use.

6.2. Chronic toxicity test

Select SD rats for use, give the ointment of the present invention of different concentrations (0.6, 1.8, 3.6g crude drug/kg), apply on the back skin once every day, for 30 consecutive days, each group kills alive 10 animals (male and female) in 24 hours after the last administration. Half and half), and the remaining 10 animals were killed alive after continued observation for 2 weeks. During the test, observe the appearance, general behavior, and body weight changes of the animals, and conduct hematology (RBC, HCT, MCV, MCH, MCHC, HB, PLT, CT, WBC and classification, reticulocytes) 30 days after administration and 2 weeks after drug withdrawal. , coagulation time) and serum biochemical (AST, ALT, ALP, Glu, BUN, Crea, TP, T.BIL, ALB, GLOB, A/G, CHOL), urine biochemical, organ coefficient, histopathology and other indicators examine. The test results showed that the animals in each group were generally in good condition, and there were no abnormal changes in appearance signs, behavioral activities, and weight gain; the hematological examination, blood biochemical examination, and urine biochemical examination of the three dosage groups and the control group were all within the normal range, and there was no abnormal change in the three dose groups and the control group. There was no significant difference; there were no drug-related pathological changes in major organs and tissues in each group. The above indicators did not change after 2 weeks of drug withdrawal. The dosage of this test is respectively 120, 60, and 20 times of the dosage of clinical medication. According to the test results, it is shown that three dosages (0.6, 1.8, 3.6g crude drug/kg) of the ointment of the present invention are administered continuously for 30 days. There was no obvious effect on rats, and no delayed toxic reaction was observed in the observation period during the recovery period, suggesting that the dose safety of this product in clinical application is relatively high.

6.3. Local administration toxicity test

Select New Zealand rabbits and guinea pigs to study the irritation test and allergy test of the ointment of the present invention to normal and damaged skin. The results show that: New Zealand rabbits were given the ointment of the present invention, and no tissue abnormality was found, which proves that the ointment of the present invention has no obvious irritation to normal and damaged skin of rabbits. Simultaneously, the allergy test results on guinea pigs also show that the skin medication does not cause allergic reactions, suggesting that the clinical application of the ointment of the present invention is safer.

Detailed ways

Embodiment 1: the preparation method of the external use ointment of pharmaceutical composition of the present invention:

a) Take 25g Panax notoginseng, 25g Polygonum cuspidatum, 20g Aconitum, 20g Araceae, 16g Duhuo, 10g Angelica, 10g Dipsacus, 10g dried ginger, 10g pepper, 10g clove basil oil, 16g turpentine oil, 26g menthol, 13g camphor, Borneol 13g is a total of fourteen raw materials. Take lovage, angelica, and dried ginger among them, grind them into 20-mesh coarse powder, use 6 to 8 times the amount of 80% ethanol as a solvent, and soak them for 24 hours. Speed percolation, collect 1 to 3 times the amount of the initial eluent, store in another container, continue percolating, collect the secondary eluate, concentrate the secondary eluate below 60°C to a thick paste, add the initial eluent, and dilute with 80% ethanol to 3 times the amount to obtain the ethanol extract, and put it in a clean container for later use;

b) Take Polygonum cuspidatum, Panax notoginseng, Araceae, Aconitum, Dipsacus, and pepper, reflux extract with 6 times the amount of 50-80% ethanol for 3 times, each time for 0.5-1.5 hours, filter, combine the extracts, recover the ethanol, and concentrate Thick paste with a relative density of 1.10 to 1.25 at 50°C;

c), take the thick cream and mix it with the ethanol extracts of lovage, angelica, and dried ginger, adjust the volume to 3 times the amount, and mix well;

d) Mix the above mixed solution with 50 g of glycerin, 5 g of sodium benzoate and 35 g of carbomer in water, heat to 60° C. to form a water phase, and adjust the pH of the water phase to 6.5-7.0 with 20% triethanolamine aqueous solution;

e) Mix 30 g of azone and emulsifier polysorbate 80, heat to 60° C. to form an auxiliary material oil phase, add turpentine, menthol, borneol, camphor, clove basil oil and mix to form an oil phase;

f) Add the oil phase to the water phase and stir until room temperature to obtain a semi-solid drug, weigh it, add an appropriate amount of purified water, mix well, and obtain an ointment for external use.

Embodiment 2: Preparation of the pharmaceutical composition aerosol of the present invention:

a) Take 25g Panax notoginseng, 25g Polygonum cuspidatum, 20g Aconitum, 20g Araceae, 16g Duhuo, 10g Angelica, 10g Dipsacus, 10g dried ginger, 10g pepper, 10g clove basil oil, 16g turpentine oil, 26g menthol, 13g camphor, Borneol 13g is a total of fourteen raw materials. Take lovage, angelica, and dried ginger among them, grind them into 40-mesh coarse powder, use 6-8 times the amount of 80% ethanol as a solvent, and soak them for 24 hours. Speed percolation, collect 1 to 3 times the amount of the initial eluent, store in another container, continue percolating, collect the secondary eluate, concentrate the secondary eluate below 60°C to a thick paste, add the initial eluent, and dilute with 80% ethanol to 3 times the amount to obtain the ethanol extract, and put it in a clean container for later use;

b) Take Polygonum cuspidatum, Panax notoginseng, Araceae, Aconitum, Dipsacus, and pepper, reflux extract with 6 times the amount of 50-80% ethanol for 3 times, each time for 0.5-1.5 hours, filter, combine the extracts, recover the ethanol, and concentrate Thick paste with a relative density of 1.10 to 1.25 at 50°C;

c), take the thick cream and mix it with the ethanol extracts of lovage, angelica, and dried ginger, adjust the volume to 3 times the amount, and mix well;

d) Mix the above mixed solution with 30 g of glycerin, 10 g of sodium benzoate, and 40 g of carbomer, heat to 60° C. to form a water phase, and use 20% triethanolamine aqueous solution to adjust the pH of the water phase to 6.5-7.0;

e), 40g of azone and emulsifier polysorbate 80 were mixed, heated to 60°C to form an auxiliary material oil phase, and turpentine, menthol, borneol, camphor, and clove basil oil were added to form an oil phase;

f) Add the oil phase to the water phase and stir to room temperature to obtain a semi-solid drug, and add a propellant to make an atomizer.

Embodiment 3: the preparation of pharmaceutical composition liniment of the present invention:

a) Take 25g Panax notoginseng, 25g Polygonum cuspidatum, 20g Aconitum, 20g Araceae, 16g Duhuo, 10g Angelica, 10g Dipsacus, 10g dried ginger, 10g pepper, 10g clove basil oil, 16g turpentine oil, 26g menthol, 13g camphor, Borneol 13g has fourteen raw materials in total. Take lovage, angelica, and dried ginger among them, grind them into a 60-mesh coarse powder, use 6-8 times the amount of 80% ethanol as a solvent, and soak it for 24 hours. Speed percolation, collect 1 to 3 times the amount of the initial eluent, store in another container, continue percolating, collect the secondary eluate, concentrate the secondary eluate below 60°C to a thick paste, add the initial eluent, and dilute with 80% ethanol to 3 times the amount to obtain the ethanol extract, and put it in a clean container for later use;

b) Take Polygonum cuspidatum, Panax notoginseng, Araceae, Aconitum, Dipsacus, and pepper, reflux extract with 6 times the amount of 50-80% ethanol for 3 times, each time for 0.5-1.5 hours, filter, combine the extracts, recover the ethanol, and concentrate Thick paste with a relative density of 1.10 to 1.25 at 50°C;

c), take the thick cream and mix it with the ethanol extracts of lovage, angelica, and dried ginger, adjust the volume to 3 times the amount, and mix well;

d) Mix the above mixed solution with 80g of glycerin, 10g of sodium benzoate, and 50g of carbomer in water, heat to 60°C to form a water phase, and adjust the pH of the water phase to 6.5-7.0 with 20% triethanolamine aqueous solution;

e), 50g of azone and emulsifier polysorbate 80 were mixed, heated to 60°C to form an auxiliary material oil phase, and turpentine, menthol, borneol, camphor, and clove basil oil were added to form an oil phase;

f) adding the oil phase into the water phase and stirring to room temperature to obtain a semi-solid drug, adding an appropriate amount of ethanol with a concentration of 40-80% to make a liniment.

Embodiment 4: the preparation of pharmaceutical composition powder of the present invention:

a) Take 25g Panax notoginseng, 25g Polygonum cuspidatum, 20g Aconitum, 20g Araceae, 16g Duhuo, 10g Angelica, 10g Dipsacus, 10g dried ginger, 10g pepper, 10g clove basil oil, 16g turpentine oil, 26g menthol, 13g camphor, 13g of borneol, among which Duhuo, Angelica, dried ginger, Polygonum cuspidatum, Panax notoginseng, Araceae, Chuanwu, Dipsacus, and pepper are crushed into 100-mesh fine powder;

b), Azone is mixed with turpentine, menthol, borneol, camphor, clove basil oil, etc. to form an oil phase;

c) Mix the oil phase with the fine powder of medicinal materials to make a powder.

Embodiment 5: the preparation of pharmaceutical composition film of the present invention:

a) Take 25g Panax notoginseng, 25g Polygonum cuspidatum, 20g Chuanwu, 20g Araceae, 16g Duhuo, 10g Angelica, 10g Dipsacus, 10g dried ginger, 10g pepper, 10g clove basil oil, 16g turpentine oil, 26g menthol, 13g camphor , borneol 13g altogether fourteen kinds of raw materials, get among them lovage, angelica, dried ginger, grind into 60 mesh coarse powder, use 6-8 times the amount of 80% ethanol as solvent, after soaking for 24 hours, at 2-5ml per minute Percolation at a high speed, collect 1 to 3 times the amount of the initial decant liquid, save it in another device, continue percolation, collect the secondary percolation liquid, concentrate the secondary percolation liquid below 60°C to a thick paste, add the primary dehydration liquid, and use 80% ethanol Dilute to 3 times the amount to obtain an ethanol extract, and put it in a clean container for later use;

b) Take Polygonum cuspidatum, Panax notoginseng, Araceae, Aconitum, Dipsacus, and pepper, reflux extract with 6 times the amount of 50-80% ethanol for 3 times, each time for 0.5-1.5 hours, filter, combine the extracts, recover the ethanol, and concentrate Thick paste with a relative density of 1.10 to 1.25 at 50°C;

c), take the thick cream and mix it with the ethanol extracts of lovage, angelica, and dried ginger, adjust the volume to 3 times the amount, and mix well;

d) Mix the above mixed solution with 80g of glycerin, 10g of sodium benzoate, and 50g of carbomer in water, heat to 60°C to form a water phase, and adjust the pH of the water phase to 6.5-7.0 with 20% triethanolamine aqueous solution;

e), 50g of azone and emulsifier polysorbate 80 were mixed, heated to 60°C to form an auxiliary material oil phase, and turpentine, menthol, borneol, camphor, and clove basil oil were added to form an oil phase;

f) Adding the oil phase into the water phase and stirring to room temperature to obtain a semi-solid drug, adding an appropriate amount of polymer materials such as polyvinyl alcohol or acrylic resin or cellulose to prepare a film.

Embodiment 6: the preparation of pharmaceutical composition ointment of the present invention:

a) Take 25g Panax notoginseng, 25g Polygonum cuspidatum, 20g Aconitum, 20g Araceae, 16g Duhuo, 10g Angelica, 10g Dipsacus, 10g dried ginger, 10g pepper, 10g clove basil oil, 16g turpentine oil, 26g menthol, 13g camphor, Borneol 13g has fourteen raw materials in total. Take lovage, angelica, and dried ginger among them, grind them into a 60-mesh coarse powder, use 6-8 times the amount of 80% ethanol as a solvent, and soak it for 24 hours. Speed percolation, collect 1 to 3 times the amount of the initial eluent, store in another container, continue percolating, collect the secondary eluate, concentrate the secondary eluate below 60°C to a thick paste, add the initial eluent, and dilute with 80% ethanol to 3 times the amount to obtain the ethanol extract, and put it in a clean container for later use;

b) Take Polygonum cuspidatum, Panax notoginseng, Araceae, Aconitum, Dipsacus, and pepper, reflux extract with 6 times the amount of 50-80% ethanol for 3 times, each time for 0.5-1.5 hours, filter, combine the extracts, recover the ethanol, and concentrate Thick paste with a relative density of 1.10 to 1.25 at 50°C;

c), take the thick cream and mix it with the ethanol extracts of lovage, angelica, and dried ginger, adjust the volume to 3 times the amount, and mix well;

d) Mix the above mixed solution with 60g of glycerin, 5g of sodium benzoate, and 40g of carbomer in water, heat to 60°C to form a water phase, and use 20% triethanolamine aqueous solution to adjust the pH of the water phase to 6.5-7.0;

e), 40g of azone and emulsifier polysorbate 80 were mixed, heated to 60°C to form an auxiliary material oil phase, and turpentine, menthol, borneol, camphor, and clove basil oil were added to form an oil phase;

f) Add the oil phase to the water phase and stir to room temperature to obtain a semi-solid drug, weigh it, add an appropriate amount of purified water, and mix to obtain an ointment.

Embodiment 7: the preparation of pharmaceutical composition gel of the present invention:

a) Take 25g Panax notoginseng, 25g Polygonum cuspidatum, 20g Aconitum, 20g Araceae, 16g Duhuo, 10g Angelica, 10g Dipsacus, 10g dried ginger, 10g pepper, 10g clove basil oil, 16g turpentine oil, 26g menthol, 13g camphor, Borneol 13g has fourteen raw materials in total. Take lovage, angelica, and dried ginger among them, grind them into a 60-mesh coarse powder, use 6-8 times the amount of 80% ethanol as a solvent, and soak it for 24 hours. Speed percolation, collect 1 to 3 times the amount of the initial eluent, store in another container, continue percolating, collect the secondary eluate, concentrate the secondary eluate below 60°C to a thick paste, add the initial eluent, and dilute with 80% ethanol to 3 times the amount to obtain the ethanol extract, and put it in a clean container for later use;

b) Take Polygonum cuspidatum, Panax notoginseng, Araceae, Aconitum, Dipsacus, and pepper, reflux extract with 6 times the amount of 50-80% ethanol for 3 times, each time for 0.5-1.5 hours, filter, combine the extracts, recover the ethanol, and concentrate Thick paste with a relative density of 1.10 to 1.25 at 50°C;

c), take the thick cream and mix it with the ethanol extracts of lovage, angelica, and dried ginger, adjust the volume to 3 times the amount, and mix well;

d) Mix the above mixed solution with 60g of glycerin, 10g of sodium benzoate, and 50g of carbomer in water, heat to 60°C to form a water phase, and use 20% triethanolamine aqueous solution to adjust the pH of the water phase to 6.5-7.0;

e), 50g of azone and emulsifier polysorbate 80 were mixed, heated to 60°C to form an auxiliary material oil phase, and turpentine, menthol, borneol, camphor, and clove basil oil were added to form an oil phase;

f) Add the oil phase into the water phase and stir until room temperature to obtain a semi-solid drug, weigh it, add appropriate amount of carbomer and other auxiliary materials, and mix well to obtain a gel.

Embodiment 8: the preparation of pharmaceutical composition powder of the present invention:

a) Take 5g Panax notoginseng, 5g Polygonum cuspidatum, 5g Aconiti, 5g Araceae, 6g Duhuo, 5g Angelica, 5g Dipsacus, 5g dried ginger, 5g pepper, 5g clove basil oil, 5g turpentine oil, 5g menthol, 5g camphor, 5g of borneol, among which Duhuo, Angelica, Ginger, Polygonum cuspidatum, Panax notoginseng, Araceae, Chuanwu, Dipsacus, and pepper are crushed into 200-mesh fine powder;

b), Azone is mixed with turpentine, menthol, borneol, camphor, clove basil oil, etc. to form an oil phase;

c) Mix the oil phase with the fine powder of medicinal materials to make a powder.

Embodiment 9: the preparation of pharmaceutical composition powder of the present invention:

a) Take 45g Panax notoginseng, 45g Polygonum cuspidatum, 40g Aconitum, 40g Aracea, 46g Duhuo, 50g Angelica, 50g Dipsacus, 50g dried ginger, 50g pepper, 50g clove basil oil, 50g turpentine oil, 50g menthol, 50g camphor, 50g of borneol, among which Duhuo, Angelica, Ginger, Polygonum cuspidatum, Panax notoginseng, Araceae, Chuanwu, Dipsacus, and pepper are crushed into 200-mesh fine powder;

b), Azone is mixed with turpentine, menthol, borneol, camphor, clove basil oil, etc. to form an oil phase;

c) Mix the oil phase with the fine powder of medicinal materials to make a powder.

Claims (10)

1. A pharmaceutical composition for treating tendon and soft tissue injuries and osteoarthropathy, characterized in that: the active ingredients of the pharmaceutical composition are made of the following raw materials by weight: 1 to 50 parts of Panax notoginseng, 1 part of Polygonum cuspidatum ~50 parts, Chuanwu 1~50 parts, Araceae 1~50 parts, Duhuo 1~50 parts, Angelica 1~50 parts, Dipsacus 1~50 parts, dried ginger 1~50 parts, pepper 1~50 parts, cloves 1-50 parts of basil oil, 1-50 parts of turpentine oil, 1-50 parts of menthol, 1-50 parts of camphor, and 1-50 parts of borneol. 2. A kind of pharmaceutical composition for the treatment of tendons and soft tissue injuries and osteoarthropathy as claimed in claim 1, characterized in that: the parts by weight of the crude drug are: 25 parts of Panax notoginseng, 25 parts of Polygonum cuspidatum, Aconitum aconiti 20 parts, Tiannanxing 20 parts, Duhuo 16 parts, Angelica 10 parts, Dipsacus 10 parts, dried ginger 10 parts, pepper 10 parts, clove basil oil 10 parts, turpentine oil 16 parts, menthol 26 parts, camphor 13 parts, borneol 13 parts share. 3. as claimed in claim 1 or 2, be used for the treatment of tendon and soft tissue injury and the pharmaceutical composition of osteoarthropathy, it is characterized in that: this pharmaceutical composition can add skin absorption promoting agent, matrix and antiseptic adjuvant or excipient It can be made into clinically acceptable external ointment, nebulizer, liniment, film or gel and into powder. 4. a method for preparing the pharmaceutical composition for the treatment of tendon soft tissue injury and osteoarthropathy as claimed in claim 1, is characterized in that: it comprises the steps: a) Take Panax notoginseng, Polygonum cuspidatum, Aconitum aconitum, Araceae, lovage, angelica, Dipsacus, dried ginger, pepper, clove basil oil, turpentine oil, menthol, camphor, and borneol. Dried ginger, crushed into coarse powder of 20-60 meshes, using 6-8 times the amount of 80% ethanol as a solvent, soaking for 24 hours, percolating at a speed of 2-5ml per minute, collecting 1-3 times the amount of the initial eluent, Store in another container, continue to percolate, collect the secondary eluate, concentrate the secondary eluate below 60°C to a thick paste, add the primary eluate, dilute to 3 times the amount with 80% ethanol to obtain an ethanol extract, and put it in a clean container spare; b) Take Polygonum cuspidatum, Panax notoginseng, Araceae, Aconitum, Dipsacus, and pepper, reflux extract with 6 times the amount of 50-80% ethanol for 3 times, each time for 0.5-1.5 hours, filter, combine the extracts, recover the ethanol, and concentrate Thick paste with a relative density of 1.10 to 1.25 at 50°C; c), take the thick cream and mix it with the ethanol extracts of lovage, angelica, and dried ginger, adjust the volume to 3 times the amount, and mix well; d) Mix the above mixed solution with 10-80 parts of glycerin, 1-10 parts of sodium benzoate, and 10-50 parts of carbomer, heat to 60°C to form an aqueous phase, and use 20% triethanolamine aqueous solution Adjust the pH of the water phase to 6.5-7.0; e) Mix 5-50 parts of azone and emulsifier polysorbate 80, heat to 60°C to form an oil phase of auxiliary materials, add turpentine, menthol, borneol, camphor, clove basil oil and mix to form an oil phase; f) adding the oil phase into the water phase and stirring to room temperature to obtain a semi-solid drug. 5. The preparation method of the pharmaceutical composition as claimed in claim 4, characterized in that: take the obtained semi-solid drug, weigh it, add appropriate amount of excipients, mix well, and obtain an ointment for external use. 6. The preparation method of the pharmaceutical composition as claimed in claim 4, characterized in that: the obtained semi-solid drug is added with an appropriate amount of auxiliary materials to make an atomizer. 7. The preparation method of the pharmaceutical composition as claimed in claim 4, characterized in that: the obtained semi-solid drug is made into a liniment by adding appropriate amount of auxiliary materials 8. The preparation method of the pharmaceutical composition as claimed in claim 4, characterized in that: the obtained semi-solid drug is added with an appropriate amount of auxiliary materials to form a film. 9. The preparation method of the pharmaceutical composition as claimed in claim 4, characterized in that: the obtained semi-solid drug is made into a gel by adding an appropriate amount of auxiliary materials. 10. A method for preparing the powder of the pharmaceutical composition for treating tendon and soft tissue injuries and osteoarthritis as claimed in claim 1, characterized in that: a) Take fourteen medicines of Panax notoginseng, Polygonum cuspidatum, Aconitum aconitum, Araceae, lovage, angelica, Dipsacus, dried ginger, pepper, clove basil oil, turpentine, menthol, camphor, and borneol, and add lovage and angelica , dried ginger, knotweed, Panax notoginseng, Araceae, Chuanwu, Dipsacus, and chili are crushed into 100-200 mesh fine powder; b), Azone is mixed with turpentine, menthol, borneol, camphor, and clove basil oil to form an oil phase; c) Mix the oil phase with the fine powder of medicinal materials to make a powder.