Pharmaceutical composition containing sodium aescinate and preparation method thereof

Abstract

The invention relates to a pharmaceutical composition containing sodium aescinate and a preparation method thereof, and belongs to the technical field of pharmaceutical compositions. In order to solve the problems that the existing medicine for treating lower limb lymphedema is not obvious in treatment effect and easy to cause gastrointestinal discomfort, the invention provides a pharmaceutical composition taking sodium aescinate, herba lycopi volatile oil, tanshinol and mirabilite as effective components. A plurality of targets of resisting inflammation, promoting venous return, reducing capillary permeability, promoting blood circulation to remove blood stasis and the like jointly act on elimination treatment of lower limb lymphedema, and the treatment effect is enhanced. The medicine composition is further prepared into a viscous gel preparation, the viscous gel preparation is tightly attached to the skin surface for a long time, it is ensured that the medicine directly acts on edema tissue, and the first-pass effect and side effects of oral medicine are avoided. The viscous gel can maintain a moist environment of the skin at the edema part, promote skin barrier repair, relieve symptoms of the lower limb lymphedema skin and improve the life quality of a patient.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical compositions, and in particular relates to a pharmaceutical composition containing sodium aescinate and a preparation method thereof. Background Art

[0002] Lower limb lymphedema is a chronic progressive disease, which refers to a pathological state in which soft tissue fluid accumulates abnormally on the body surface and in the cavity due to obstruction of lymphatic reflux. Due to obstruction of lymphatic reflux, lymphatic fluid accumulates in the subcutaneous tissue, causing fibrosis and fat sclerosis. In the later stage, limb swelling, skin thickening and roughness occur, which is also called "elephantiasis". Lower limb lymphedema can occur at any age, often due to abnormal development of lymphatic vessels, surgery or trauma.

[0003] Physical therapy uses specific massage techniques to promote the return of lymph fluid to normal lymphatic vessels according to the anatomical and physiological pathways of the lymphatic system. This non-invasive treatment method can effectively reduce limb swelling, but the treatment effect is short-lived and edema may recur quickly.

[0004] Through surgery, the lymphatic return channel is reconstructed and the lymphatic vessels are anastomosed with the nearby small veins, so that the lymph fluid flows directly into the venous system, thereby reducing the pressure on the lymphatic system, which can effectively improve the return of lymph fluid and reduce limb swelling. However, surgical treatment may not be ideal for patients with lymphatic dysplasia or extensive lymphatic vessel damage, and complications such as anastomotic thrombosis and infection are prone to occur.

[0005] Oral benzopyrone drugs can enhance the activity of macrophages, promote protein decomposition, and reduce the protein content in interstitial fluid, thereby reducing limb swelling. However, the effect of using drugs alone to treat lower limb lymphedema is often not obvious, and long-term use is required. Adverse reactions such as gastrointestinal discomfort and allergies may occur. Summary of the invention

[0006] In order to solve the problem that the existing drugs for treating lower limb lymphedema have insignificant therapeutic effects and are prone to gastrointestinal discomfort, the present invention provides a pharmaceutical composition containing sodium aescinate and a preparation method thereof.

[0007] The technical solution of the present invention:

[0008] A pharmaceutical composition containing sodium aescinate comprises the following active ingredients in parts by weight: 20-30 parts of sodium aescinate, 10-20 parts of danshensu, 5-15 parts of zedoaria volatile oil and 5-10 parts of mirabilite.

[0009] Furthermore, the invention contains the following active ingredients in parts by weight: 25 parts of sodium aescinate, 16 parts of danshensu, 15 parts of zedoaria volatile oil and 6 parts of mirabilite.

[0010] Furthermore, the pharmaceutical composition is a viscous gel preparation, and further contains the following components in parts by weight:

[0011] 1-3 parts of Tween-80, 5-10 parts of glycerol, 2-3 parts of amidation reagent, 5-6 parts of dopamine hydrochloride, 100-120 parts of sodium hyaluronate aqueous solution with a mass concentration of 2-3% and 100 parts of deionized water.

[0012] Furthermore, the amidation reagent is NHS (N-hydroxysuccinimide) and EDC·HCl (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride) in a mass ratio of 2:3.

[0013] A method for preparing a pharmaceutical composition containing sodium aescinate, wherein the pharmaceutical composition is a viscous gel preparation, and the preparation method comprises the following steps:

[0014] Step 1: Preparation of Ze Lan volatile oil:

[0015] The dried whole herb of Zedoaria is crushed, mixed with distilled water, heated and distilled, the volatile oil obtained by distillation is collected, and the purified Zedoaria volatile oil is obtained after drying with anhydrous sodium sulfate;

[0016] Step 2: Preparation of drug-loaded microemulsion:

[0017] Dissolve 10-20 parts of danshensu, 1-3 parts of Tween-80 and 5-10 parts of propylene glycol in 100 parts of deionized water, and fully stir at a first speed to obtain a water phase; use 5-15 parts of zedoaria volatile oil as an oil phase, add the oil phase to the water phase under stirring at a first speed, stir at a second speed for a certain period of time, and then perform ultrasonic treatment to obtain a drug-loaded microemulsion;

[0018] Step 3: Preparation of viscous gel preparation:

[0019] To 100 to 120 parts of a sodium hyaluronate aqueous solution with a mass concentration of 2 to 3%, the drug-loaded microemulsion prepared in step 1, 20 to 30 parts of sodium aescinate and 5 to 10 parts of mirabilite are added, and after being fully stirred at a third speed, 2 to 3 parts of an amidation reagent are added to the obtained mixed system, and the stirring is continued at the third speed for a certain time, and then 5 to 6 parts of dopamine hydrochloride are added under an inert atmosphere, and the mixture is stirred at the third speed for a certain time and then homogenized to obtain a viscous excipient preparation.

[0020] Furthermore, in step 1, the first rotation speed is 200-300 rpm, the stirring time for fully stirring the water phase is 30-45 min, and the oil phase is added to the water phase by slowly dropping the oil phase into the water phase at 0.5-1.0 mL / min.

[0021] Furthermore, in step 1, the second rotation speed is 600-800 rpm, the stirring time at the second rotation speed is 10 min, the power of the ultrasonic treatment is 100-150 W, and the ultrasonic treatment time is 20-30 min.

[0022] Furthermore, the sodium aescinate and mirabilite in step 2 are both ground and sieved through a 20-mesh or 30-mesh sieve.

[0023] Furthermore, the third rotation speed in step 2 is 800-1000 rpm, the time for sufficient stirring at the third rotation speed is 1-3 h, the stirring time after adding the amidation reagent is 1-2 h, and the stirring time after adding dopamine hydrochloride is 12-18 h.

[0024] Furthermore, the homogenization speed in step 2 is 2000-2200 rpm, and the homogenization time is 30-60 min.

[0025] Beneficial effects of the present invention:

[0026] The invention provides a pharmaceutical composition with sodium aescinate, zedoaria volatile oil, danshensu and mirabilite as effective ingredients, and the pharmaceutical composition is used for treating lower limb lymphedema. Sodium aescinate has an anti-inflammatory effect, can promote venous blood return, reduce capillary permeability, inhibit macroglobulin release, increase lymph return speed, and promote lymphatic circulation, thereby achieving the purpose of detumescence. Zedoaria volatile oil has the effect of promoting blood circulation and removing blood stasis, can promote local blood circulation, accelerate the absorption and disappearance of edema, has the effect of promoting water and detumescence, can directly treat the edema site, and alleviate the symptoms of lower limb lymphedema. Danshensu can alleviate inflammatory response, help treat lower limb lymphedema, and can also scavenge free radicals, reduce the damage of free radicals to cells, and promote tissue repair. Mirabilite has the effect of clearing heat and detumescence, can alleviate the pain and swelling caused by lower limb lymphedema, and indirectly promote the disappearance of lower limb lymphedema. The effective ingredients from these four natural medicines work together in the pharmaceutical composition to eliminate lower limb lymphedema through multiple targets such as anti-inflammation, promoting venous return, reducing capillary permeability, promoting blood circulation and removing blood stasis, thereby enhancing the therapeutic effect and comprehensively improving the pathological and physiological process of lower limb lymphedema. The pharmaceutical composition provided by the present invention is suitable for lower limb lymphedema caused by various reasons such as surgery, trauma, and infection.

[0027] The present invention further prepares the pharmaceutical composition into a viscous gel preparation, and forms a viscous gel dressing by self-polymerization of dopamine and cross-linking with sodium hyaluronate, which can evenly disperse the drug molecules and embed them in its network structure, and ensure that the drug directly acts on the edematous tissue by closely fitting to the skin surface for a long time, thereby avoiding the first-pass effect and side effects of oral drugs. The drug is slowly released by the viscous gel to ensure the continuous release of the drug, maintain the effective concentration of the drug in the treatment area, and improve the bioavailability and therapeutic effect of the drug. The hyaluronic acid in the viscous gel dressing helps to maintain the moist environment of the skin in the edematous part, alleviates the problem of dry skin in the lower limb lymphedema part, promotes skin barrier repair, helps to alleviate the symptoms of lower limb lymphedema skin, and improves the quality of life of patients. DETAILED DESCRIPTION

[0028] The technical solution of the present invention is further described below in conjunction with the embodiments, but it is not limited thereto. Any modification or equivalent replacement of the technical solution of the present invention without departing from the spirit and scope of the technical solution of the present invention shall be included in the protection scope of the present invention. The process equipment or devices not specifically noted in the following embodiments are all conventional equipment or devices in the art. If not specifically specified, the raw materials used in the embodiments of the present invention can be obtained commercially; if not specifically specified, the technical means used in the embodiments of the present invention are all conventional means well known to those skilled in the art.

[0029] Example 1

[0030] This embodiment provides a pharmaceutical composition containing sodium aescinate and a preparation method thereof.

[0031] The dosage form of the pharmaceutical composition containing sodium aescinate in this embodiment is a viscous gel preparation, which contains the following components in two parts:

[0032] 25 parts of sodium aescinate, 16 parts of danshensu, 15 parts of zedoaria volatile oil, 6 parts of mirabilite, 2 parts of Tween-80, 8 parts of glycerol, 1 part of amidation reagent N-hydroxysuccinimide NHS, 1.5 parts of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDC·HCl, 6 parts of dopamine hydrochloride, 110 parts of 3% sodium hyaluronate aqueous solution and 100 parts of deionized water, wherein the sodium aescinate and mirabilite are ground separately and then passed through a 30-mesh sieve to obtain sodium aescinate powder and mirabilite powder.

[0033] The preparation method of the pharmaceutical composition containing sodium aescinate in this embodiment comprises the following steps:

[0034] Step 1: Preparation of Ze Lan volatile oil:

[0035] The dried whole herb of Zedoaria was crushed, mixed with 10 times the mass of distilled water, heated and distilled, and the volatile oil obtained by distillation was collected and dried over anhydrous sodium sulfate to obtain pure Zedoaria volatile oil;

[0036] Step 2: Preparation of drug-loaded microemulsion:

[0037] Danshensu, Tween-80 and glycerol were dissolved in deionized water and stirred at 200 rpm for 45 min to obtain an aqueous phase; Zedoaria volatile oil was used as an oil phase, and the oil phase was slowly added to the aqueous phase at a rate of 0.5 mL / min under stirring at 200 rpm, stirred at 700 rpm for 10 min, and then ultrasonically treated at 120 W power for 20 min to obtain a microemulsion;

[0038] Step 3: Preparation of viscous gel preparation:

[0039] The microemulsion prepared in step 1, sodium aescinate powder and mirabilite powder were added to the sodium hyaluronate aqueous solution, and the mixture was stirred at 800 rpm for 2 h. NHS and EDC·HCl were added to the mixed system, and the mixture was stirred at 800 rpm for 1 h. Then, dopamine hydrochloride was added to the obtained mixed system under a nitrogen atmosphere, and the mixture was stirred at 800 rpm for 16 h. The mixture was homogenized at a speed of 2200 rpm for 45 min to obtain a viscous gel preparation.

[0040] Example 2

[0041] This embodiment provides a pharmaceutical composition containing sodium aescinate and a preparation method thereof.

[0042] The dosage form of the pharmaceutical composition containing sodium aescinate in this embodiment is a viscous gel preparation, which contains the following components in two parts:

[0043] 20 parts of sodium aescinate, 106 parts of danshensu, 10 parts of zedoaria volatile oil, 8 parts of sodium sulfate, 1 part of Tween-80, 5 parts of glycerol, 1 part of amidating agent N-hydroxysuccinimide NHS, 1.5 parts of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDC·HCl, 6 parts of dopamine hydrochloride, 110 parts of sodium hyaluronate aqueous solution with a mass concentration of 3% and 100 parts of deionized water, wherein the sodium aescinate and sodium sulfate are ground separately and then passed through a 30-mesh sieve to obtain sodium aescinate powder and sodium sulfate powder.

[0044] The preparation method of the pharmaceutical composition containing sodium aescinate in this embodiment comprises the following steps:

[0045] Step 1: Preparation of Ze Lan volatile oil:

[0046] The dried whole herb of Zedoaria was crushed, mixed with 10 times the mass of distilled water, heated and distilled, and the volatile oil obtained by distillation was collected and dried over anhydrous sodium sulfate to obtain pure Zedoaria volatile oil;

[0047] Step 2: Preparation of drug-loaded microemulsion:

[0048] Danshensu, Tween-80 and glycerol were dissolved in deionized water and stirred at 200 rpm for 45 min to obtain a water phase; Zedoaria volatile oil was used as the oil phase, and the oil phase was slowly added to the water phase at a rate of 0.8 mL / min under stirring at 200 rpm, stirred at 600 rpm for 10 min, and then ultrasonically treated at 100 W power for 30 min to obtain a microemulsion;

[0049] Step 3: Preparation of viscous gel preparation:

[0050] The microemulsion prepared in step 1, sodium aescinate powder and mirabilite powder were added to the sodium hyaluronate aqueous solution, and the mixture was stirred at 800 rpm for 1 h. NHS and EDC·HCl were added to the mixed system, and the mixture was stirred at 800 rpm for 1 h. Then, dopamine hydrochloride was added to the obtained mixed system under a nitrogen atmosphere, and the mixture was stirred at 800 rpm for 12 h. The mixture was homogenized at a speed of 2200 rpm for 45 min to obtain a viscous gel preparation.

[0051] Example 3

[0052] This embodiment provides a pharmaceutical composition containing sodium aescinate and a preparation method thereof.

[0053] The dosage form of the pharmaceutical composition containing sodium aescinate in this embodiment is a viscous gel preparation, which contains the following components in two parts:

[0054] 30 parts of sodium aescinate, 15 parts of danshensu, 15 parts of zedoaria volatile oil, 8 parts of mirabilite, 3 parts of Tween-80, 5 parts of glycerol, 1 part of amidation reagent N-hydroxysuccinimide NHS, 1.5 parts of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDC·HCl, 6 parts of dopamine hydrochloride, 110 parts of 3% sodium hyaluronate aqueous solution and 100 parts of deionized water, wherein the sodium aescinate and mirabilite are ground separately and then passed through a 30-mesh sieve to obtain sodium aescinate powder and mirabilite powder.

[0055] The preparation method of the pharmaceutical composition containing sodium aescinate in this embodiment comprises the following steps:

[0056] Step 1: Preparation of Ze Lan volatile oil:

[0057] The dried whole herb of Zedoaria was crushed, mixed with 10 times the mass of distilled water, heated and distilled, and the volatile oil obtained by distillation was collected and dried over anhydrous sodium sulfate to obtain pure Zedoaria volatile oil;

[0058] Step 2: Preparation of drug-loaded microemulsion:

[0059] Danshensu, Tween-80 and glycerol were dissolved in deionized water, and stirred at 300 rpm for 30 min to obtain a water phase; Zedoaria volatile oil was used as the oil phase, and the oil phase was slowly added to the water phase at 1.0 mL / min under stirring at 300 rpm, stirred at 600 rpm for 10 min, and then ultrasonically treated at 100 W power for 30 min to obtain a microemulsion;

[0060] Step 3: Preparation of viscous gel preparation:

[0061] The microemulsion prepared in step 1, sodium aescinate powder and mirabilite powder were added to the sodium hyaluronate aqueous solution, and the mixture was stirred at 800 rpm for 2 h. NHS and EDC·HCl were added to the mixed system, and the mixture was stirred at 800 rpm for 2 h. Then, dopamine hydrochloride was added to the obtained mixed system under a nitrogen atmosphere, and the mixture was stirred at 800 rpm for 14 h. The mixture was homogenized at a speed of 2200 rpm for 45 min to obtain a viscous gel preparation.

[0062] Example 4

[0063] This embodiment provides a pharmaceutical composition containing sodium aescinate and a preparation method thereof.

[0064] The dosage form of the pharmaceutical composition containing sodium aescinate in this embodiment is a viscous gel preparation, which contains the following components in two parts:

[0065] 26 parts of sodium aescinate, 20 parts of danshensu, 10 parts of zedoaria volatile oil, 8 parts of mirabilite, 2 parts of Tween-80, 6 parts of glycerol, 1 part of amidation reagent N-hydroxysuccinimide NHS, 1.5 parts of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDC·HCl, 6 parts of dopamine hydrochloride, 110 parts of 3% sodium hyaluronate aqueous solution and 100 parts of deionized water, wherein the sodium aescinate and mirabilite are ground separately and then passed through a 30-mesh sieve to obtain sodium aescinate powder and mirabilite powder.

[0066] The preparation method of the pharmaceutical composition containing sodium aescinate in this embodiment comprises the following steps:

[0067] Step 1: Preparation of Ze Lan volatile oil:

[0068] The dried whole herb of Zedoaria was crushed, mixed with 10 times the mass of distilled water, heated and distilled, and the volatile oil obtained by distillation was collected and dried over anhydrous sodium sulfate to obtain pure Zedoaria volatile oil;

[0069] Step 2: Preparation of drug-loaded microemulsion:

[0070] Danshensu, Tween-80 and glycerol were dissolved in deionized water, and stirred at 300 rpm for 40 min to obtain a water phase; Zedoaria volatile oil was used as the oil phase, and the oil phase was slowly added to the water phase at 0.5 mL / min under stirring at 300 rpm, stirred at 700 rpm for 10 min, and then ultrasonically treated with 100 W power for 25 min to obtain a microemulsion;

[0071] Step 3: Preparation of viscous gel preparation:

[0072] The microemulsion prepared in step 1, sodium aescinate powder and mirabilite powder were added to the sodium hyaluronate aqueous solution, and the mixture was stirred at 800 rpm for 1 h. NHS and EDC·HCl were added to the mixed system, and the mixture was stirred at 800 rpm for 1 h. Then, dopamine hydrochloride was added to the obtained mixed system under a nitrogen atmosphere, and the mixture was stirred at 800 rpm for 12 h. The mixture was homogenized at a speed of 2200 rpm for 45 min to obtain a viscous gel preparation.

[0073] Example 5

[0074] This embodiment provides a pharmaceutical composition containing sodium aescinate and a preparation method thereof.

[0075] The dosage form of the pharmaceutical composition containing sodium aescinate in this embodiment is a viscous gel preparation, which contains the following components in two parts:

[0076] 25 parts of sodium aescinate, 15 parts of danshensu, 10 parts of zedoaria volatile oil, 5 parts of mirabilite, 1 part of Tween-80, 6 parts of glycerol, 1 part of amidating agent N-hydroxysuccinimide NHS, 1.5 parts of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDC·HCl, 6 parts of dopamine hydrochloride, 110 parts of sodium hyaluronate aqueous solution with a mass concentration of 3% and 100 parts of deionized water, wherein the sodium aescinate and mirabilite are respectively ground and then passed through a 30-mesh sieve to obtain sodium aescinate powder and mirabilite powder.

[0077] The preparation method of the pharmaceutical composition containing sodium aescinate in this embodiment comprises the following steps:

[0078] Step 1: Preparation of Ze Lan volatile oil:

[0079] The dried whole herb of Zedoaria was crushed, mixed with 10 times the mass of distilled water, heated and distilled, and the volatile oil obtained by distillation was collected and dried over anhydrous sodium sulfate to obtain pure Zedoaria volatile oil;

[0080] Step 2: Preparation of drug-loaded microemulsion:

[0081] Danshensu, Tween-80 and glycerol were dissolved in deionized water and stirred at 200 rpm for 45 min to obtain a water phase; Zedoaria volatile oil was used as the oil phase, and the oil phase was slowly added to the water phase at a rate of 0.5 mL / min under stirring at 200 rpm, stirred at 700 rpm for 10 min, and then ultrasonically treated at 120 W power for 25 min to obtain a microemulsion;

[0082] Step 3: Preparation of viscous gel preparation:

[0083] The microemulsion prepared in step 1, sodium aescinate powder and mirabilite powder were added to the sodium hyaluronate aqueous solution, and the mixture was stirred at 900 rpm for 1 h. NHS and EDC·HCl were added to the mixed system, and the mixture was stirred at 900 rpm for 1 h. Then, dopamine hydrochloride was added to the obtained mixed system under a nitrogen atmosphere, and the mixture was stirred at 900 rpm for 12 h. The mixture was homogenized at a speed of 2200 rpm for 45 min to obtain a viscous gel preparation.

[0084] Example 6

[0085] This embodiment provides a pharmaceutical composition containing sodium aescinate and a preparation method thereof.

[0086] The dosage form of the pharmaceutical composition containing sodium aescinate in this embodiment is a viscous gel preparation, which contains the following components in two parts:

[0087] 28 parts of sodium aescinate, 18 parts of danshensu, 15 parts of zedoaria volatile oil, 10 parts of mirabilite, 3 parts of Tween-80, 8 parts of glycerol, 1 part of amidating agent N-hydroxysuccinimide NHS, 1.5 parts of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDC·HCl, 6 parts of dopamine hydrochloride, 110 parts of sodium hyaluronate aqueous solution with a mass concentration of 3% and 100 parts of deionized water, wherein the sodium aescinate and mirabilite are ground separately and then passed through a 30-mesh sieve to obtain sodium aescinate powder and mirabilite powder.

[0088] The preparation method of the pharmaceutical composition containing sodium aescinate in this embodiment comprises the following steps:

[0089] Step 1: Preparation of Ze Lan volatile oil:

[0090] The dried whole herb of Zedoaria was crushed, mixed with 10 times the mass of distilled water, heated and distilled, and the volatile oil obtained by distillation was collected and dried over anhydrous sodium sulfate to obtain pure Zedoaria volatile oil;

[0091] Step 2: Preparation of drug-loaded microemulsion:

[0092] Danshensu, Tween-80 and glycerol were dissolved in deionized water and stirred at 200 rpm for 45 min to obtain an aqueous phase; Zedoaria volatile oil was used as the oil phase, and the oil phase was slowly added to the aqueous phase at a rate of 0.8 mL / min under stirring at 200 rpm, stirred at 800 rpm for 10 min, and then ultrasonically treated at 130 W power for 20 min to obtain a microemulsion;

[0093] Step 3: Preparation of viscous gel preparation:

[0094] The microemulsion prepared in step 1, sodium aescinate powder and mirabilite powder were added to the sodium hyaluronate aqueous solution, and the mixture was stirred at 1000 rpm for 1 h. NHS and EDC·HCl were added to the mixed system, and the mixture was stirred at 1000 rpm for 2 h. Then, dopamine hydrochloride was added to the obtained mixed system under a nitrogen atmosphere, and the mixture was stirred at 1000 rpm for 16 h. The mixture was homogenized at a speed of 2200 rpm for 45 min to obtain a viscous gel preparation.

[0095] Example 7

[0096] This embodiment provides a pharmaceutical composition containing sodium aescinate and a preparation method thereof.

[0097] The dosage form of the pharmaceutical composition containing sodium aescinate in this embodiment is a viscous gel preparation, which contains the following components in two parts:

[0098] 30 parts of sodium aescinate, 20 parts of danshensu, 15 parts of zedoaria volatile oil, 10 parts of sodium sulfate, 3 parts of Tween-80, 10 parts of glycerol, 1 part of amidation reagent N-hydroxysuccinimide NHS, 1.5 parts of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDC·HCl, 6 parts of dopamine hydrochloride, 110 parts of sodium hyaluronate aqueous solution with a mass concentration of 3% and 100 parts of deionized water, wherein the sodium aescinate and sodium sulfate are ground separately and then passed through a 30-mesh sieve to obtain sodium aescinate powder and sodium sulfate powder.

[0099] The preparation method of the pharmaceutical composition containing sodium aescinate in this embodiment comprises the following steps:

[0100] Step 1: Preparation of Ze Lan volatile oil:

[0101] The dried whole herb of Zedoaria was crushed, mixed with 10 times the mass of distilled water, heated and distilled, and the volatile oil obtained by distillation was collected and dried over anhydrous sodium sulfate to obtain pure Zedoaria volatile oil;

[0102] Step 2: Preparation of drug-loaded microemulsion:

[0103] Danshensu, Tween-80 and glycerol were dissolved in deionized water and stirred at 300 rpm for 40 min to obtain a water phase; Zedoaria volatile oil was used as the oil phase, and the oil phase was slowly added to the water phase at 1.0 mL / min under stirring at 300 rpm, stirred at 800 rpm for 10 min, and then ultrasonically treated at 130 W power for 25 min to obtain a microemulsion;

[0104] Step 3: Preparation of viscous gel preparation:

[0105] The microemulsion prepared in step 1, sodium aescinate powder and mirabilite powder were added to the sodium hyaluronate aqueous solution, and the mixture was stirred at 1000 rpm for 2 h. NHS and EDC·HCl were added to the mixed system, and the mixture was stirred at 1000 rpm for 2 h. Then, dopamine hydrochloride was added to the obtained mixed system under a nitrogen atmosphere, and the mixture was stirred at 1000 rpm for 18 h. The mixture was homogenized at a speed of 2200 rpm for 45 min to obtain a viscous gel preparation.

[0106] Comparative Example 1

[0107] This comparative example provides a blank gel without any drug component.

[0108] The blank gel of this comparative example contains the following components in parts by mass: 1 part of amidation reagent N-hydroxysuccinimide NHS, 1.5 parts of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDC·HCl, 6 parts of dopamine hydrochloride, 110 parts of sodium hyaluronate aqueous solution with a mass concentration of 3%, and 100 parts of deionized water.

[0109] The preparation method of the blank gel of this comparative example comprises the following steps:

[0110] Deionized water was added to the sodium hyaluronate aqueous solution, and NHS and EDC·HCl were added after stirring at 800 rpm. The mixture was stirred for 30 min at 800 rpm, and then dopamine hydrochloride was added to the obtained mixture under nitrogen atmosphere. The mixture was stirred at 800 rpm for 12 h and homogenized at 2000 rpm for 60 min to obtain a blank gel.

[0111] Test Example 1

[0112] This test example verifies the effects of the microemulsion prepared in Example 1, the viscous gel prepared in step 2 of Example 1, and the blank viscous gel in treating lower limb lymphedema through animal experiments.

[0113] 1. Experimental Animals:

[0114] Forty healthy SD rats weighing 200±10g were selected, half of which were male and half were female.

[0115] 2. Construction of tail lymphedema model rats:

[0116] SD rats were anesthetized with isoflurane, and 1 cm of the tail skin was cut 15 cm away from the end of the tail. The lymphatic vessels on both sides of the tail were separated and ligated, and care was taken not to damage the blood vessels. The local area was disinfected and bandaged, and water and feed were freely available and raised normally; after one week, the tail of the rat was observed to be obviously swollen, and the model was successfully established.

[0117] 3. Grouping

[0118] The rats with tail lymphedema model were randomly divided into 4 groups, 10 rats in each group, and the medication conditions of each group were as follows:

[0119] Drug-loaded gel group: The viscous gel prepared in Example 1 was applied to the edematous part of the rat tail, and the amount of the drug applied was enough to cover the swollen part of the rat tail. The drug was administered once a day;

[0120] Drug-loaded microemulsion group: The microemulsion prepared in step 1 of Example 1 was applied to the edematous part of the rat tail, and the amount of the drug applied was enough to cover the swollen part of the rat tail. The drug was administered once a day;

[0121] Blank gel group: The blank gel prepared in Comparative Example 1 was applied to the edematous part of the rat tail, and the amount of the application was enough to cover the swollen part of the rat tail, and the drug was administered once a day;

[0122] Blank control group: no treatment.

[0123] 4. Experimental Results

[0124] The degree of swelling and circumference of the rat tails of each group of rats were observed and recorded daily. The results showed that after 2 weeks of treatment, the symptoms of rat tail edema in the drug-loaded gel group were significantly alleviated and basically recovered to normal circumference. The symptoms of rat tail edema in the drug-loaded microemulsion group were also alleviated, but the circumference was only restored to half of the normal circumference. This is because sodium aescinate, danshensu, zedoaria volatile oil and mirabilite in the drug-loaded gel prepared by the present invention can produce a synergistic effect, enhance anti-inflammatory and anti-edema effects, and can also improve microcirculation and promote lymph circulation, thereby accelerating the regression of lymphedema.

[0125] The edema symptoms in both the blank gel group and the blank control group were not relieved, but the tail skin of the rats in the blank control group showed symptoms of darkening and thickening, while the appearance of the edematous skin of the tail of the rats in the blank gel group remained basically unchanged. This is because the hyaluronic acid in the sticky gel dressing helps maintain a moist environment for the skin in the edematous area, relieves the problem of dry skin in the lower limb lymphedema area, and promotes skin barrier repair.

Claims

1. A pharmaceutical composition containing sodium aescinate, characterized in that: The invention contains the following effective ingredients in parts by weight: 20-30 parts of sodium aescinate, 10-20 parts of danshensu, 5-15 parts of zedoaria volatile oil and 5-10 parts of mirabilite.

2. A pharmaceutical composition containing sodium aescinate according to claim 1, characterized in that: The invention contains the following active ingredients in parts by weight: 25 parts of sodium aescinate, 16 parts of danshensu, 15 parts of zedoaria volatile oil and 6 parts of mirabilite.

3. A pharmaceutical composition containing sodium aescinate according to claim 1 or 2, characterized in that: The pharmaceutical composition is a viscous gel preparation, and further contains the following components in parts by weight: 1-3 parts of Tween-80, 5-10 parts of glycerol, 2-3 parts of amidation reagent, 5-6 parts of dopamine hydrochloride, 100-120 parts of sodium hyaluronate aqueous solution with a mass concentration of 2-3% and 100 parts of deionized water.

4. A pharmaceutical composition containing sodium aescinate according to claim 3, characterized in that: The amidation reagent is NHS and EDC·HCl in a mass ratio of 2:

3.

5. A method for preparing a pharmaceutical composition containing sodium aescinate, characterized in that: The pharmaceutical composition is a viscous gel preparation, and the preparation method comprises the following steps: Step 1: Preparation of Ze Lan volatile oil: The dried whole herb of Zedoaria is crushed, mixed with distilled water, heated and distilled, the volatile oil obtained by distillation is collected, and the purified Zedoaria volatile oil is obtained after being dried with sewage sodium sulfate; Step 2: Preparation of drug-loaded microemulsion: Dissolve 10-20 parts of danshensu, 1-3 parts of Tween-80 and 5-10 parts of propylene glycol in 100 parts of deionized water, and fully stir at a first speed to obtain a water phase; use 5-15 parts of zedoaria volatile oil as an oil phase, add the oil phase to the water phase under stirring at a first speed, stir at a second speed for a certain period of time, and then perform ultrasonic treatment to obtain a drug-loaded microemulsion; Step 3: Preparation of viscous gel preparation: To 100 to 120 parts of a sodium hyaluronate aqueous solution with a mass concentration of 2 to 3%, the drug-loaded microemulsion prepared in step 1, 20 to 30 parts of sodium aescinate and 5 to 10 parts of mirabilite are added, and after being fully stirred at a third speed, 2 to 3 parts of an amidation reagent are added to the obtained mixed system, and the stirring is continued at the third speed for a certain time, and then 5 to 6 parts of dopamine hydrochloride are added under an inert atmosphere, and the mixture is stirred at the third speed for a certain time and then homogenized to obtain a viscous excipient preparation.

6. A method for preparing a pharmaceutical composition containing sodium aescinate according to claim 5, characterized in that: Step 1: The first rotation speed is 200-300 rpm, the stirring time for fully stirring the water phase is 30-45 min, and the oil phase is added to the water phase by slowly dropping the oil phase into the water phase at 0.5-1.0 mL / min.

7. A method for preparing a pharmaceutical composition containing sodium aescinate according to claim 5 or 6, characterized in that: In step 1, the second rotation speed is 600-800 rpm, the stirring time at the second rotation speed is 10 min, the power of the ultrasonic treatment is 100-150 W, and the ultrasonic treatment time is 20-30 min.

8. A method for preparing a pharmaceutical composition containing sodium aescinate according to claim 7, characterized in that: In step 2, the sodium aescinate and mirabilite are ground and sieved through a 20-mesh or 30-mesh sieve.

9. A method for preparing a pharmaceutical composition containing sodium aescinate according to claim 8, characterized in that: In step 2, the third rotation speed is 800-1000 rpm, the time for sufficient stirring at the third rotation speed is 1-3 hours, the stirring time after adding the amidation reagent is 1-2 hours, and the stirring time after adding dopamine hydrochloride is 12-18 hours.

10. A method for preparing a pharmaceutical composition containing sodium aescinate according to claim 9, characterized in that: The homogenization speed in step 2 is 2000-2200 rpm, and the homogenization time is 30-60 min.