A pharmaceutical composition containing sodium aescinate and its preparation method

Abstract

The present 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 problem that the existing drug treatment effect of lower limb lymphedema is not obvious and gastrointestinal discomfort is prone to occur, the present invention provides a pharmaceutical composition with sodium aescinate, zedoaria volatile oil, danshensu and mirabilite as effective ingredients, which acts on multiple targets such as anti-inflammatory, promoting venous return, reducing capillary permeability, and promoting blood circulation and removing blood stasis to eliminate lower limb lymphedema, thereby enhancing the therapeutic effect. The present invention further prepares the pharmaceutical composition into a viscous gel preparation, which ensures that the drug directly acts on the edematous tissue by being tightly adhered to the skin surface for a long time, thereby avoiding the first-pass effect and side effects of oral drugs. The viscous gel can maintain a moist environment of the skin of the edematous part, promote skin barrier repair, help alleviate the symptoms of lower limb lymphedema skin, and improve the quality of life of patients.

Description

Technical Field

[0001] The present 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 extremity lymphedema is a chronic, progressive condition characterized by abnormal accumulation of soft tissue fluid on the body's surface and within cavities due to impaired lymphatic drainage. This impaired lymphatic drainage leads to accumulation of lymph in the subcutaneous tissue, causing fibroplasia and liposclerosis. Later, it can lead to limb swelling, thickening, and roughening of the skin, also known as elephantiasis. Lower extremity lymphedema can occur at any age and is often caused by abnormal lymphatic vascular development, surgery, or trauma.

[0003] Physical therapy uses specific massage techniques to promote the return of lymph to normal lymphatic channels 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] Surgery reconstructs lymphatic drainage pathways by anastomosing lymphatic vessels with nearby small veins, allowing lymph to flow directly into the venous system. This reduces pressure on the lymphatic system, effectively improving lymphatic return and alleviating 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 more likely to occur.

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

[0006] In order to solve the problem that existing drugs for treating lower limb lymphedema are ineffective and 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 zedoary volatile oil, and 5-10 parts of mirabilite.

[0009] Furthermore, the invention contains the following active ingredients in parts by mass: 25 parts of sodium aescinate, 16 parts of danshensu, 15 parts of zedoary 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 2-3% sodium hyaluronate aqueous solution 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 Zedoaria volatile oil:

[0015] The dried whole herb of Zedoariae rhizome is crushed, mixed with distilled water, heated and distilled, the volatile oil obtained by distillation is collected, and dried over anhydrous sodium sulfate to obtain the pure Zedoariae rhizome volatile oil;

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

[0017] Dissolving 10-20 parts of danshensu, 1-3 parts of Tween-80, and 5-10 parts of glycerol in 100 parts of deionized water, and stirring thoroughly at a first speed to obtain an aqueous phase; adding 5-15 parts of zedoaria volatile oil as an oil phase to the aqueous phase while stirring at the first speed, stirring at a second speed for a certain period of time, and then ultrasonically treating to obtain a drug-loaded microemulsion;

[0018] Step 3: Prepare 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 sodium sulfate are added; after fully stirring at a third speed, 2 to 3 parts of an amidation reagent are added to the resulting mixed system; stirring is continued at the third speed for a certain time; then, 5 to 6 parts of dopamine hydrochloride are added under an inert atmosphere; 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 to obtain the aqueous phase is 30-45 min, and the oil phase is added to the aqueous phase by slowly dropping the oil phase into the aqueous 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 speed in step 2 is 800-1000 rpm, the time for sufficient stirring at the third 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 present invention provides a pharmaceutical composition comprising sodium aescinate, zedoaria volatile oil, danshensu and mirabilite as active ingredients, and the composition is used to treat lower limb lymphedema. Sodium aescinate has an anti-inflammatory effect, can promote venous blood return, reduce capillary permeability, inhibit macroglobulin release, increase lymph return rate, and promote lymphatic circulation, thereby achieving the purpose of reducing swelling. 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 circulation and reducing swelling, can directly treat the edematous area, and alleviate the symptoms of lower limb lymphedema. Danshensu can alleviate inflammatory reactions, help treat lower limb lymphedema, and can also scavenge free radicals, reduce free radical damage to cells, and promote tissue repair. Mirabilite has the effect of clearing heat and reducing swelling, can alleviate the pain and swelling caused by lower limb lymphedema, and indirectly promote the disappearance of lower limb lymphedema. These four active ingredients, derived from natural medicines, work synergistically in the pharmaceutical composition to treat lower limb lymphedema through multiple targets, including anti-inflammatory, venous evacuation, capillary permeability reduction, and blood circulation and stasis removal. This enhances the therapeutic effect and comprehensively improves the pathophysiology of lower limb lymphedema. The pharmaceutical composition provided by this invention is suitable for treating lower limb lymphedema caused by various causes, including 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. By closely fitting to the skin surface for a long time, it is ensured that the drug directly acts on the edematous tissue, thereby avoiding the first-pass effect and side effects of oral medications. The drug is slowly released by the viscous gel to ensure the sustained 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. Hyaluronic acid in the viscous gel dressing helps to maintain a moist environment on the skin of the edema part, alleviates the problem of dry skin at the lower limb lymphedema part, promotes skin barrier repair, helps to alleviate the symptoms of the skin of the lower limb lymphedema, and improves the quality of life of the patient. DETAILED DESCRIPTION

[0028] The technical solution of the present invention is further described below with reference to the embodiments, but 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 scope of protection of the present invention. The process equipment or devices not specifically noted in the following examples are all conventional equipment or devices in the art. Unless otherwise specified, the raw materials used in the examples of the present invention can be obtained commercially; unless otherwise specified, the technical means used in the examples 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 pharmaceutical composition containing sodium aescinate in this embodiment is in the form of a viscous gel preparation, comprising two portions of the following components:

[0032] 25 parts of sodium aescinate, 16 parts of danshensu, 15 parts of zedoaryl essential oil, 6 parts of sodium sulfate, 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 a 3% sodium hyaluronate aqueous solution, and 100 parts of deionized water, wherein the sodium aescinate and sodium sulfate are separately ground and then passed through a 30-mesh sieve to obtain sodium aescinate powder and sodium sulfate powder.

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

[0034] Step 1: Preparation of Zedoaria 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 the oil phase, and the oil phase was slowly added dropwise to the aqueous phase at a rate of 0.5 mL / min while stirring at 200 rpm. The mixture was stirred at 700 rpm for 10 min, and then ultrasonicated at 120 W for 20 min to obtain a microemulsion.

[0038] Step 3: Prepare viscous gel preparation:

[0039] The microemulsion prepared in step 1, sodium aescinate powder, and Glauber's salt powder were added to the sodium hyaluronate aqueous solution and stirred at 800 rpm for 2 h. NHS and EDC·HCl were added to the mixture, and stirring was continued at 800 rpm for 1 h. Then, dopamine hydrochloride was added to the resulting mixture under a nitrogen atmosphere, and stirring was continued at 800 rpm for 16 h. The mixture was homogenized at 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 pharmaceutical composition containing sodium aescinate in this embodiment is in the form of a viscous gel preparation, comprising two portions of the following components:

[0043] 20 parts of sodium aescinate, 106 parts of danshensu, 10 parts of zedoary volatile oil, 8 parts of sodium sulfate, 1 part 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 a 3% sodium hyaluronate aqueous solution, and 100 parts of deionized water, wherein the sodium aescinate and sodium sulfate are separately ground 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 Zedoaria 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 an aqueous phase. Zedoaria volatile oil was used as the oil phase, and the oil phase was slowly added dropwise to the aqueous phase at a rate of 0.8 mL / min while stirring at 200 rpm. The mixture was stirred at 600 rpm for 10 min, and then ultrasonicated at 100 W power for 30 min to obtain a microemulsion.

[0049] Step 3: Prepare viscous gel preparation:

[0050] The microemulsion prepared in step 1, sodium aescinate powder, and Glauber's salt powder were added to the sodium hyaluronate aqueous solution and stirred at 800 rpm for 1 hour. NHS and EDC·HCl were added to the mixture and stirred at 800 rpm for another 1 hour. Dopamine hydrochloride was then added to the mixture under a nitrogen atmosphere and stirred at 800 rpm for 12 hours. The mixture was homogenized at 2200 rpm for 45 minutes 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 pharmaceutical composition containing sodium aescinate in this embodiment is in the form of a viscous gel preparation, comprising two portions of the following components:

[0054] 30 parts of sodium aescinate, 15 parts of danshensu, 15 parts of zedoary volatile oil, 8 parts of sodium sulfate, 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 a 3% sodium hyaluronate aqueous solution, and 100 parts of deionized water, wherein the sodium aescinate and sodium sulfate are separately ground and then passed through a 30-mesh sieve to obtain sodium aescinate powder and sodium sulfate powder.

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

[0056] Step 1: Preparation of Zedoaria 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 an aqueous phase. Zedoaria volatile oil was used as the oil phase, and the oil phase was slowly added dropwise to the aqueous phase at a rate of 1.0 mL / min while stirring at 300 rpm. The mixture was stirred at 600 rpm for 10 min, and then ultrasonicated at 100 W power for 30 min to obtain a microemulsion.

[0060] Step 3: Prepare viscous gel preparation:

[0061] The microemulsion prepared in step 1, sodium aescinate powder, and Glauber's salt powder were added to the sodium hyaluronate aqueous solution and stirred at 800 rpm for 2 h. NHS and EDC·HCl were added to the mixture and stirred at 800 rpm for another 2 h. Dopamine hydrochloride was then added to the mixture under a nitrogen atmosphere and stirred at 800 rpm for 14 h. The mixture was homogenized at 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 pharmaceutical composition containing sodium aescinate in this embodiment is in the form of a viscous gel preparation, comprising two portions of the following components:

[0065] 26 parts of sodium aescinate, 20 parts of danshensu, 10 parts of zedoary volatile oil, 8 parts of sodium sulfate, 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 a 3% sodium hyaluronate aqueous solution, and 100 parts of deionized water, wherein the sodium aescinate and sodium sulfate are separately ground and then passed through a 30-mesh sieve to obtain sodium aescinate powder and sodium sulfate powder.

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

[0067] Step 1: Preparation of Zedoaria 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 an aqueous phase. Zedoaria volatile oil was used as the oil phase, and the oil phase was slowly added dropwise to the aqueous phase at a rate of 0.5 mL / min while stirring at 300 rpm. The mixture was stirred at 700 rpm for 10 min, and then ultrasonicated at 100 W power for 25 min to obtain a microemulsion.

[0071] Step 3: Prepare viscous gel preparation:

[0072] The microemulsion prepared in step 1, sodium aescinate powder, and Glauber's salt powder were added to the sodium hyaluronate aqueous solution and stirred at 800 rpm for 1 hour. NHS and EDC·HCl were added to the mixture and stirred at 800 rpm for another 1 hour. Dopamine hydrochloride was then added to the mixture under a nitrogen atmosphere and stirred at 800 rpm for 12 hours. The mixture was homogenized at 2200 rpm for 45 minutes 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 pharmaceutical composition containing sodium aescinate in this embodiment is in the form of a viscous gel preparation, comprising two portions of the following components:

[0076] 25 parts of sodium aescinate, 15 parts of danshensu, 10 parts of zedoary volatile oil, 5 parts of mirabilite, 1 part 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 a 3% sodium hyaluronate aqueous solution, and 100 parts of deionized water, wherein the sodium aescinate and mirabilite are separately ground and 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 Zedoaria 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 an aqueous phase. Zedoaria volatile oil was used as the oil phase, and the oil phase was slowly added dropwise to the aqueous phase at a rate of 0.5 mL / min while stirring at 200 rpm. The mixture was stirred at 700 rpm for 10 min, and then ultrasonicated at 120 W for 25 min to obtain a microemulsion.

[0082] Step 3: Prepare viscous gel preparation:

[0083] The microemulsion prepared in step 1, sodium aescinate powder, and Glauber's salt powder were added to the sodium hyaluronate aqueous solution and stirred at 900 rpm for 1 h. NHS and EDC·HCl were added to the mixture and stirred at 900 rpm for another 1 h. Dopamine hydrochloride was then added to the mixture under a nitrogen atmosphere and stirred at 900 rpm for 12 h. The mixture was homogenized at 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 pharmaceutical composition containing sodium aescinate in this embodiment is in the form of a viscous gel preparation, comprising two portions of the following components:

[0087] 28 parts of sodium aescinate, 18 parts of danshensu, 15 parts of zedoary volatile oil, 10 parts of sodium sulfate, 3 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 a 3% sodium hyaluronate aqueous solution, and 100 parts of deionized water, wherein the sodium aescinate and sodium sulfate are separately ground and then passed through a 30-mesh sieve to obtain sodium aescinate powder and sodium sulfate powder.

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

[0089] Step 1: Preparation of Zedoaria 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 dropwise to the aqueous phase at a rate of 0.8 mL / min while stirring at 200 rpm. The mixture was stirred at 800 rpm for 10 min, and then ultrasonicated at 130 W for 20 min to obtain a microemulsion.

[0093] Step 3: Prepare viscous gel preparation:

[0094] The microemulsion prepared in step 1, sodium aescinate powder, and Glauber's salt powder were added to the sodium hyaluronate aqueous solution and stirred at 1000 rpm for 1 h. NHS and EDC·HCl were added to the mixture and stirred at 1000 rpm for 2 h. Dopamine hydrochloride was then added to the mixture under a nitrogen atmosphere and stirred at 1000 rpm for 16 h. The mixture was homogenized at 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 pharmaceutical composition containing sodium aescinate in this embodiment is in the form of a viscous gel preparation, comprising two portions of the following components:

[0098] 30 parts of sodium aescinate, 20 parts of danshensu, 15 parts of zedoary 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 a 3% sodium hyaluronate aqueous solution, and 100 parts of deionized water, wherein the sodium aescinate and sodium sulfate are separately ground 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 Zedoaria 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 an aqueous phase. Zedoaria volatile oil was used as the oil phase, and the oil phase was slowly added dropwise to the aqueous phase at a rate of 1.0 mL / min while stirring at 300 rpm. The mixture was 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: Prepare viscous gel preparation:

[0105] The microemulsion prepared in step 1, sodium aescinate powder, and Glauber's salt powder were added to the sodium hyaluronate aqueous solution and stirred at 1000 rpm for 2 h. NHS and EDC·HCl were added to the mixture and stirred at 1000 rpm for another 2 h. Dopamine hydrochloride was then added to the mixture under a nitrogen atmosphere and stirred at 1000 rpm for 18 h. The mixture was homogenized at 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 a 3% sodium hyaluronate aqueous solution, 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 the mixture was stirred at 800 rpm. NHS and EDC·HCl were then added, and stirring was continued at 800 rpm for 30 min. Then, dopamine hydrochloride was added to the resulting mixture under a nitrogen atmosphere, and the mixture was stirred at 800 rpm for 12 h. The mixture was homogenized at 2000 rpm for 60 min to obtain a blank gel.

[0111] Test Example 1

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

[0113] 1. Experimental Animals

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

[0115] 2. Establishment of rat tail lymphedema model:

[0116] Sprague-Dawley rats were anesthetized with isoflurane. A 1-cm circumferential cut was made to the tail skin 15 cm from the end of the tail. Lymphatic vessels on both sides of the tail were isolated and ligated, taking care not to damage the blood vessels. The area was disinfected and bandaged. The rats were allowed free access to water and feed and maintained as normal. One week later, significant swelling of the tail was observed, indicating successful modeling.

[0117] 3. Grouping

[0118] 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 area of ​​the rat tail. The amount of drug applied was sufficient to cover the swollen area 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 area of ​​the rat tail. The amount of drug applied was sufficient to cover the swollen area 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 area of ​​the rat tail. The amount of the gel applied was sufficient to cover the swollen area of ​​the rat tail. 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 in each group were observed and recorded daily. The results showed that after 2 weeks of treatment, the symptoms of tail edema in the drug-loaded gel group were significantly alleviated and basically returned to normal circumference. The symptoms of 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 at the same time improve microcirculation and promote lymph circulation, thereby accelerating the disappearance 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 skin at the edema site 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 at the edema site, relieves the problem of dry skin at the lower limb lymphedema site, and promotes skin barrier repair.

Claims

1. A pharmaceutical composition containing sodium aescinate, characterized in that: The pharmaceutical composition comprises the following active ingredients in parts by weight: 20-30 parts of sodium aescinate, 10-20 parts of danshensu, 5-15 parts of zedoary volatile oil, and 5-10 parts of sodium sulfate; 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 an amidation reagent, 5-6 parts of dopamine hydrochloride, 100-120 parts of a 2-3% aqueous sodium hyaluronate solution, and 100 parts of deionized water; the amidation reagent is NHS and EDC·HCl in a mass ratio of 2:3; The preparation method of the pharmaceutical composition comprises the following steps: Step 1: Preparation of Zedoaria volatile oil: The dried whole herb of Zedoariae rhizome is crushed, mixed with distilled water, heated and distilled, the volatile oil obtained by distillation is collected, and dried over anhydrous sodium sulfate to obtain the pure Zedoariae rhizome volatile oil; Step 2: Preparation of drug-loaded microemulsion: 10-20 parts of danshensu, 1-3 parts of Tween-80, and 5-10 parts of glycerol were dissolved in 100 parts of deionized water, and the mixture was stirred at 200-300 rpm for 30-45 minutes to obtain an aqueous phase; 5-15 parts of zedoaria volatile oil were used as an oil phase, and the oil phase was added to the aqueous phase at a rate of 0.5-1.0 mL / min while stirring at 200-300 rpm. The mixture was stirred at 600-800 rpm for 10 minutes, and then ultrasonicated at 100-150 W for 20-30 minutes to obtain a drug-loaded microemulsion; Step 3: Prepare viscous gel preparation: To 100-120 parts of a 2-3% sodium hyaluronate aqueous solution, the drug-loaded microemulsion prepared in step 1, 20-30 parts of sodium aescinate, and 5-10 parts of thenardite are added, wherein the sodium aescinate and then the thenardite are ground and passed through a 20-mesh or 30-mesh sieve. After being fully stirred at 800-1000 rpm for 1-3 hours, 2-3 parts of an amidation reagent are added to the resulting mixture, and stirring is continued at 800-1000 rpm for 1-2 hours. Then, 5-6 parts of dopamine hydrochloride are added under an inert atmosphere, and the mixture is stirred at 800-1000 rpm for 12-18 hours, followed by homogenization at a speed of 2000-2200 rpm for 30-60 minutes to obtain a viscous gel preparation; The pharmaceutical composition containing sodium aescinate is used for treating lower limb lymphedema.

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