CN111481607A - Medicine composition for treating wound-releasing compound wound and preparation method and application of lyotropic liquid crystal prepared from medicine composition - Google Patents

Abstract

The invention discloses a compound lyotropic liquid crystal for treating a wound-releasing compound wound, which comprises aloe extract, tea tree oil, water, absolute ethyl alcohol, lidocaine hydrochloride, glyceryl monooleate and poloxamer. The invention has the functions of easing pain, promoting healing and resisting bacteria, has higher viscosity and long local retention time, and is beneficial to sustained drug release. Animal experiment results show that the invention can obviously promote the wound healing speed of the mice of the wound-releasing compound wound model and reduce the death rate.

Description

A pharmaceutical composition for treating radiation-wound combined injury and lyotropic liquid prepared therefrom Crystal preparation method and use

technical field

The present invention relates to a compound lyotropic liquid crystal comprising aloe vera, tea tree oil and lidocaine hydrochloride, in particular to a preparation method thereof, and its curative effect for treating combined radiation and trauma injuries.

Background technique

Radiation trauma combined injury refers to nuclear radiation injury combined with trauma, and its most obvious feature is that the wound is repeatedly ulcerated and necrotic, which is prolonged and difficult to heal. The mechanism of whole body radiation injury delaying wound healing may be due to the direct effect of high-energy particles on the hematopoietic system, attacking hematopoietic cells, and reducing the number of repairing cells in the early stage of healing. In addition, radiation can also produce a large number of free radicals on the skin surface, resulting in decreased expression of cytokines and growth factors in the early stage of radiation, and high expression of related apoptosis genes. Complex factors such as low number of local fibroblasts, morphological damage, decreased function, and slow growth of granulation tissue in the lesion may also lead to impaired repair function and affect the healing of radio-injury combined injuries.

Aloe vera is a succulent herb of Liliaceae, containing a variety of chemical components, such as anthraquinones, organic acids, carbohydrates, proteins, calcium oxalate, cellulose, etc. Function. Aloe tincture in aloe vera extract has a killing effect on various microorganisms such as bacteria, fungi and viruses, and can prevent infection when applied locally.

Tea tree oil, also known as Melaleuca alternifolia oil, is a pure natural plant essential oil extracted from the leaves of Melaleuca alternifolia of the family Myrtaceae by distillation. It is a colorless to pale yellow liquid with antibacterial and anti-inflammatory properties. , repelling insects, killing mites, etc., non-polluting, non-corrosive, strong permeability. 1,8-Cineole is its main antibacterial ingredient. Currently, commonly used tea tree oil formulations include emulsions, creams, gels, creams, and the like.

A lyotropic liquid crystal is a liquid crystal formed by two or more compounds including a solvent compound after amphiphilic molecules are dissolved in a solvent. Lyotropic liquid crystals have many advantages as drug carriers: they can encapsulate drugs of different polarities and protect them from physical or enzymatic degradation; improve drug bioavailability; have bioadhesive properties; prolong drug release time; improve drug stability and reduce Drug side effects, etc. Due to the good bioadhesion of lyotropic liquid crystals, it can be directly applied to the affected area, which is convenient to prepare and use, and is particularly widely used in mucosal and transdermal administration.

SUMMARY OF THE INVENTION

Radiation trauma combined with local ischemia and hypoxia is very susceptible to infection, and the redness, swelling, and pain are severe and persistent for a long time. The purpose of the present invention is to develop a multifunctional compound lyotropic liquid crystal which integrates antibacterial, analgesic, and wound healing promotion functions, and is used for the treatment of radiation wound complex wounds.

The invention provides a compound lyotropic liquid crystal for treating radiation-induced combined wounds, which comprises aloe vera extract, tea tree oil, lidocaine hydrochloride, water, absolute ethanol, glycerol monooleate and poloxamer.

Further, a compound lyotropic liquid crystal for treating radiation-induced wounds and wounds is composed of the following medicines in parts by weight, including 100-1000 parts of water, 50-500 parts of poloxamer, 10-50 parts of aloe vera extract, 1-50 parts lidocaine hydrochloride, 100-500 parts glycerol monooleate, 25-100 parts anhydrous ethanol, 100-500 parts tea tree oil.

Preferably, in the above-mentioned compound lyotropic liquid crystal, the medicine is composed of 500-1000 parts by weight of water, 100-300 parts of poloxamer, 10-30 parts of aloe vera extract, and 1-20 parts of lidocaine hydrochloride , 250 to 500 parts of glycerol monooleate, 25 to 100 parts of absolute ethanol, and 250 to 500 parts of tea tree oil.

Further, in the above compound lyotropic liquid crystal, the lyotropic liquid crystal material is selected from polyoxyethylene/isopropyl myristate, chitosan/sodium tripolyphosphate, glycerol monooleate/absolute ethanol. any one or more.

Preferably, in the above compound lyotropic liquid crystal, the lyotropic liquid crystal material is glycerol monooleate/absolute ethanol.

More preferably, in the above pharmaceutical composition, the lyotropic liquid crystal material is glycerol monooleate/absolute ethanol, and the weight ratio of the glycerol monooleate to the absolute ethanol is 60:1～ 10:1, preferably 10:1.

The present invention provides a method for preparing the above compound lyotropic liquid crystal, which comprises the steps of mixing the aloe extract, tea tree oil, lidocaine hydrochloride, water, absolute ethanol, glycerol monooleate and poloxamer.

The present invention provides a lyotropic liquid crystal prepared from the above medicine.

The preparation method of compound lyotropic liquid crystal for treating radiation wound compound wounds according to the present invention comprises the following steps: (1) measuring an appropriate amount of water in a 50ml beaker, adding 0.08g aloe vera extract and 45mg lidocaine hydrochloride, ultrasound After dissolving, 1.00 g of poloxamer 407 was added, and it was fully swollen at 4°C overnight, and water was added to 5 ml as the water phase. (2) Weigh 2g of glycerol monooleate into a 10ml centrifuge tube, add 0.2ml of absolute ethanol to dissolve by ultrasonic, and then add 1.5g of tea tree oil and mix it as an oil phase. (3) Take 3ml of the above-mentioned water phase and pour it into the oil phase slowly and continuously under the vortex condition. After the oil phase gradually becomes viscous, stir evenly with a glass rod, continue to drop the remaining water phase, and leave at room temperature.

Further, in the above preparation method, it is fully swollen at a low temperature (ambient temperature is 0-5° C., preferably 4° C.), and placed at room temperature.

The invention provides the application of the above compound lyotropic liquid crystal in the preparation of a medicine for treating radiation-wound compound wounds.

The beneficial effects of the invention are as follows: the multifunctional compound lyotropic liquid crystal has high viscosity and long local residence time, which is conducive to continuous drug release, and has various effects of bacteriostasis, analgesia and wound healing promotion. Compared with the existing similar drugs on the market, the compound lyotropic liquid crystal of the present invention can obviously promote the wound healing speed and reduce the death rate of the radiation wound compound injury model mice after the radiation skin injury is treated, and is expected to become a therapeutic compound of the radiation wound compound injury. A highly effective preparation for wounding.

Description of drawings

Figure 1 shows the in vitro antibacterial results of tea tree oil against a single bacteria.

Figure 2 shows the appearance of the compound lyotropic liquid crystal.

FIG. 3 is a polarizing microscope photograph of the compound lyotropic liquid crystal.

Figure 4 is a small-angle X-ray scattering spectrum of a lyotropic liquid crystal sample.

Figure 5 shows the effects of wound and irradiation sequence on wound healing in mice.

Figure 6 is the wound healing photos of mice in the simple trauma group, the radiation/trauma compound injury model group (radiation wound compound injury model group), and the radiation/wound compound injury treatment group.

Figure 7 shows the survival curves of mice in the simple trauma group, the radiation/trauma compound injury model group (radiation wound compound injury model group), and the radiation/trauma compound injury treatment group.

Figure 8 shows the residual wound area and wound healing percentage of mice in the simple wound group, the radiation/trauma compound wound model group (radiation wound compound wound model group), and the radiation/wound compound wound treatment group.

Figure 9 shows the H.E. staining results of the skin of mice in the simple trauma group, the radiation/traumatic compound injury model group (radiation wound compound injury model group), and the radiation/trauma compound injury treatment group at different times.

Figure 10 shows the results of Masson staining of the skin of mice in the simple trauma group, the radiation/traumatic compound injury model group (radiation wound compound injury model group), and the radiation/trauma compound injury treatment group at different times.

Detailed ways

The invention provides a compound lyotropic liquid crystal for treating radiation-induced combined wounds, which comprises aloe vera extract, tea tree oil, lidocaine hydrochloride, water, absolute ethanol, glycerol monooleate and poloxamer.

In one embodiment of the present invention, a compound lyotropic liquid crystal for treating radiation-induced wounds and wounds is composed of the following medicines in parts by weight: 100-1000 parts of water, 50-500 parts of poloxamer, 10- 50 parts of aloe vera extract, 1 to 50 parts of lidocaine hydrochloride, 100 to 500 parts of glycerol monooleate, 25 to 100 parts of absolute ethanol, and 100 to 500 parts of tea tree oil.

In a preferred embodiment of the present invention, in the above-mentioned compound lyotropic liquid crystal, the pharmaceutical composition in parts by weight is 500-1000 parts by weight of water, 100-300 parts of poloxamer, 10-30 parts of aloe vera extract, 1-20 parts lidocaine hydrochloride, 250-500 parts glycerol monooleate, 25-100 parts anhydrous ethanol, 250-500 parts tea tree oil.

In one embodiment of the present invention, the lyotropic liquid crystal material is selected from any of polyoxyethylene/isopropyl myristate, chitosan/sodium tripolyphosphate, glycerol monooleate/absolute ethanol one or more.

In a preferred embodiment of the present invention, in the above compound lyotropic liquid crystal, the lyotropic liquid crystal material is glycerol monooleate/absolute ethanol.

In one embodiment of the present invention, the weight ratio of the glycerol monooleate to the absolute ethanol is 60:1 to 10:1.

In a preferred embodiment of the present invention, the weight ratio of the glycerol monooleate to the absolute ethanol is 10:1.

The present invention provides a method for preparing the above compound lyotropic liquid crystal, which comprises the steps of mixing the aloe extract, tea tree oil, lidocaine hydrochloride, water, absolute ethanol, glycerol monooleate and poloxamer.

The present invention provides a lyotropic liquid crystal prepared from the above medicine.

The preparation method of compound lyotropic liquid crystal according to the present invention comprises the following steps: (1) Measure an appropriate amount of water into a 50ml beaker, add 0.08g of aloe vera extract and 45mg of lidocaine hydrochloride, and add 1.00g of poise after ultrasonic dissolving Loxamer 407 was fully swollen at 4°C overnight, and water was added to 5 ml as an aqueous phase. (2) Weigh 2g of glycerol monooleate into a 10ml centrifuge tube, add 0.2ml of absolute ethanol to dissolve by ultrasonic, and then add 1.5g of tea tree oil and mix it as an oil phase. (3) Take 3ml of the above-mentioned water phase and pour it into the oil phase slowly and continuously under the vortex condition. After the oil phase gradually becomes viscous, stir evenly with a glass rod, continue to drop the remaining water phase, and leave at room temperature.

In the context of the present invention, the term "lyotropic liquid crystal" refers to a liquid crystal formed by two or more compounds (at a certain concentration) including a solvent compound, after the amphiphilic molecule is dissolved in a solvent. According to different internal structures, lyotropic liquid crystals can be divided into lamellar liquid crystals, cubic liquid crystals and hexagonal liquid crystals. Layered liquid crystals are prone to structural transformation in the presence of excess water, while cubic phase liquid crystal and hexagonal phase liquid crystal structures can coexist stably with excess water.

The technical solutions in the present invention will be further described below with reference to specific embodiments. It should be understood that the following examples are only used to explain and illustrate the present invention, but are not used to limit the protection scope of the present invention. Unless otherwise specified, the instruments, materials, reagents, etc. used in the following examples can be obtained by conventional commercial means.

Example 1: Antibacterial test of tea tree oil cubic liquid crystal.

The inhibitory effects of tea tree oil on Acinetobacter baumannii, Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 1705, and Candida albicans were investigated.

The culture medium with drug concentration of 0.98, 1.76, 3.52, 7.03 and 14.06 mg·ml ^-1 was prepared. Specific operation: Take 5 test tubes containing 5ml of LB culture solution (Saboteur culture solution for Candida albicans), numbered 1-5, absorb 0.07, 0.125, 0.25, 0.5, 1ml of culture solution respectively, and then make up the corresponding volume of tea tree oil, and mix well to obtain a drug-containing culture medium.

Take out the cryopreservation tube, dissolve it, and add 5 μl of bacterial liquid (20 μl for Candida albicans) into a test tube containing 5 ml of LB culture solution, and culture at 37°C and 200rpm in a constant temperature air-bath shaker for about 20h.

Take 5 μl of fresh bacterial solution and add it to 5 test tubes containing medicated culture solution, and culture in a constant temperature air-bath shaker at 37° C. and 200 rpm for about 20 hours (20 μl for Candida albicans).

The bacteria in the drug-containing culture solution were spread on the plate with an inoculation loop, and cultured in a constant temperature incubator at 36.5°C for about 20 hours to observe the growth of the colony.

Results: Tea tree oil had good antibacterial effect on the experimental strains (Fig. 1). The MIC of tea tree oil against Klebsiella pneumoniae was 7.03 mg·ml ^-1 , and the MIC against Escherichia coli was 1.76 mg·ml ^-1 , the MICs against Acinetobacter baumannii, Staphylococcus aureus and Candida albicans were all 3.52 mg·ml ^-1 . Therefore, the order of antibacterial properties of tea tree oil nanoemulsion against different bacteria is Escherichia coli>Candida albicans≈Acinetobacter baumannii≈Staphylococcus aureus>Klebsiella pneumoniae. Tea tree oil contains a lot of terpenes, terpenes can destroy and penetrate the lipid structure, so when tea tree oil acts on the microbial cell membrane, it forms perforations, and intracellular substances, especially potassium ions, seep out in large quantities, resulting in the occurrence of potential inside and outside the membrane. Changes, inducing hydrolase to degrade the cell wall to stimulate cell autolysis to play a bacteriostatic effect.

Example 2: Preparation of compound lyotropic liquid crystal.

In this example, water, aloe vera extract, lidocaine hydrochloride and poloxamer 407 are used as the water phase, glycerol monooleate, absolute ethanol and tea tree oil are used as the oil phase, the oil phase is added to the water phase, and the glass rod is stirred evenly, After the oil phase became viscous, the remaining water phase was continuously added dropwise to obtain compound lyotropic liquid crystals.

1. The present invention provides a compound lyotropic liquid crystal for the treatment of radiation-induced wounds and wounds. parts glycerol monooleate, 40 parts absolute ethanol, 300 parts tea tree oil.

2. The preparation method of compound lyotropic liquid crystal according to the present invention includes the following steps: (1) Measure an appropriate amount of water in a 50ml beaker, add 0.08g aloe vera extract and 45mg lidocaine hydrochloride, and add 1.00 g of water after ultrasonic dissolving. g Poloxamer 407, 4 ℃ overnight to make it fully swollen, add water to 5ml as the water phase. (2) Weigh 2g of glycerol monooleate into a 10ml centrifuge tube, add 0.2ml of absolute ethanol to dissolve by ultrasonic, and then add 1.5g of tea tree oil and mix it as an oil phase. (3) Take 3ml of the above-mentioned water phase and pour it into the oil phase slowly and continuously under the vortex condition. After the oil phase gradually becomes viscous, stir evenly with a glass rod, continue to drop the remaining water phase, and leave at room temperature. The compound lyotropic liquid crystal was obtained (as shown in Figure 2).

Experimental example 1: Characterization of compound lyotropic liquid crystals.

In this experimental example, the prepared liquid crystal gel preparation was characterized by polarizing microscope and small-angle X-ray scattering instrument.

1 Instruments and reagents:

1.1 Instruments:

X-ray small angle diffractometer (SAXSess, Anton Paar GmbH)

Polarizing microscope (DM2500P, Leica, Germany)

1.2 Materials and reagents:

Tea tree oil (Guangdong Fuyang Biotechnology Co., Ltd., batch number: SO1026)

Glycerol monooleate (GMO, Shanghai Zhenzhun Biotechnology Co., Ltd., batch number: ZZS16030906)

Poloxamer 407 (BASF, Germany, batch number: WRFT5338)

Lidocaine hydrochloride (Shanxi Xinbaoyuan Pharmaceutical Co., Ltd., batch number: 20130904)

Anhydrous ethanol (Sinopharm Chemical Reagent Co., Ltd., batch number: 20150917)

Curacao Aloe Vera Extract (Chengdu Croma Biotechnology Co., Ltd.)

Polylactic acid-glycolic acid (Jinan Daigang Technology Co., Ltd.)

Ultrapure water (made in laboratory).

2 Characterization of compound lyotropic liquid crystal:

2.1 Polarizing microscope: Take an appropriate amount of lyotropic liquid crystal samples on a glass slide and observe with a polarizing microscope at room temperature.

2.2 Small-angle X-ray scattering instrument: Take an appropriate amount of samples to observe the lyotropic liquid crystal structure under vacuum and room temperature conditions using a small-angle X-ray diffractometer. The photosensitive plate is taken out and placed in the detector, the detector is connected with the computer, and the signal on the photosensitive plate is read through the operation of the computer. Convert to Excel data table, and then use the software to plot, and then perform peak abscissa ratio analysis.

3 Experimental results:

3.1 Observation results of polarized light microscope: It can be seen from Figure 3 that the above compound solute liquid crystal is anisotropic and has a micellar structure, which has the relevant properties of liquid crystal products.

3.2 Test results of small-angle X-ray scattering instrument: It can be seen from Figure 4 that there is an obvious peak, which proves to be a single crystal structure.

4 Conclusion: The above two results show that the compound solute liquid crystal meets the index requirements.

Experimental Example 2: The treatment plan and pharmacodynamic evaluation of compound lyotropic liquid crystals for radio-traumatic combined injuries.

Using H.E. and Masson stained pathological sections as indicators, the prepared compound lyotropic liquid crystals were evaluated for pharmacodynamics to provide a basis for market application.

1 Instruments and reagents:

1.1 Instruments:

Co ⁶⁰ radioactive source (Cobalt source of Academy of Military Medical Sciences)

Small animal anesthesia machine (IC-R, Shanghai Yuyan Scientific Instrument Co., Ltd.)

1.2 Materials and reagents:

SD rats (Animal Center, Academy of Military Medical Sciences)

Glycerol monooleate (GMO, Shanghai Zhenzhun Biotechnology Co., Ltd., batch number: ZZS16030906)

Poloxamer 407 (BASF, Germany, batch number: WRFT5338)

Lidocaine hydrochloride (Shanxi Xinbaoyuan Pharmaceutical Co., Ltd., batch number: 20130904)

Anhydrous ethanol (Sinopharm Chemical Reagent Co., Ltd., batch number: 20150917)

2 methods and processes:

2.1 Grouping of experimental animals:

Thirty Kunming mice were randomly divided into 3 groups, pure trauma group, radiation/trauma compound injury model group (radiation/trauma compound injury model group), and radiation/trauma compound injury treatment group, with 10 mice in each group.

2.2 Construction of animal model:

Simple trauma group: After the mice were anesthetized, the back was shaved with a shaver, and a circular mark with a diameter of 1.5 cm was made. Lift the back skin with tissue forceps and hemostatic clips, and use ophthalmic scissors to excise full-thickness skin on the back without damaging the subcutaneous fascia and tissue.

Radiation/trauma model group: Mice were placed in a plexiglass box and irradiated with 5Gy γ-rays for a single whole body at a dose rate of 95.96cGy/min. After 0.5h, the back was injured.

Radiation/wound treatment group: After modeling, compound lyotropic liquid crystal was applied to the wound every day to cover the full thickness of the wound.

2.3 Processing process:

All mice wounds were not bandaged, and they drank and ate normally.

The mice in the administration group were smeared with compound lyotropic liquid crystal on the wound every day to cover the whole wound.

Neither the simple trauma group nor the radiation trauma combined trauma model group were treated.

2.4 The percentage of wound healing in mice:

All mice wound photos were taken 3 hours after injury, the photos were processed using Image Pro Plus software, and the wound area was calculated and recorded as A ₀ . After that, the images were taken at ₁ , 2, 4, 6, 8, 10, and 12 days, respectively, and the wound area was recorded as An, and the wound healing rate was calculated according to the following formula.

Wound healing rate=(A ₀ -A _n )/A _n ×100%

2.5 H.E. staining:

On the 7th and 14th day, 2 mice were randomly selected from each group and sacrificed. The skin around the wound was fixed in formalin, embedded in paraffin, and sectioned at 4 μm. After H.E. staining, the wound healing and inflammatory cell infiltration were observed.

2.6 Masson staining:

On the 7th and 14th day, 2 mice were randomly selected from each group and sacrificed. The skin around the wound was fixed in formalin, embedded in paraffin, and sectioned at 4 μm. After H.E. staining, the wound healing and inflammatory cell infiltration were observed. Collagen growth was observed after Masson staining.

3 Experimental results:

3.1 Treatment results:

Simple trauma group: 12d wound healing rate was over 90%.

Radiation trauma combined injury model group: the wound healing rate was significantly slower than that of the trauma group. The wound healing rate of the radiation trauma combined trauma model group was significantly lower than that of the trauma group at 6d (P<0.01), and the wound healing rate reached more than 90% at 18d.

In the radiation-wound combined wound treatment group: the wound healing rate was over 90% at 14d (Figures 5, 6, and 8).

There was no significant difference between the radio-traumatic combined trauma group and the simple trauma group (P>0.05).

The survival rate of animals in the trauma group and the treatment group was 100%, and the mice in the radio-traumatic combined injury model group had a higher mortality rate and a lower survival rate (Fig. 7).

3.2 H.E. staining and Masson staining results:

Simple trauma group: At 7 days, the epidermis structure was clear, but some collagen edema was seen, and the cells in the basal layer of the dermis were unevenly arranged; after 14 days, the collagen was dense, the cells in the dermis were arranged in an orderly manner, hair follicles were visible, and hair was formed.

In the model group of radiation trauma combined injury: at 7d, the cuticle of the epidermis was peeled off, the epidermis was incomplete, and the collagen was loose; after 14d, the epidermis showed obvious hyperplasia, uneven thickness, subcutaneous blood vessel bleeding, and infiltration of inflammatory cells.

Radiation trauma combined injury treatment group: the overall recovery was good, the collagen structure of the dermis was clear on 7d, hair growth was seen on 14d, and there was less inflammatory cell infiltration (as shown in Figures 9 and 10).

4 Conclusion:

Through animal experiments, it was determined that the simple wound group healed the fastest, followed by the radiotherapy combined trauma treatment group, and the radiotherapy combined trauma model group was the slowest. The overall recovery of the radiotherapy combined trauma treatment group was better. wound healing.

Experimental Example 3: Influence of wound and irradiation sequence on wound healing in mice.

1 Instruments and reagents:

1.1 Instruments:

Co ⁶⁰ radioactive source (Cobalt source of Academy of Military Medical Sciences)

Small animal anesthesia machine (IC-R, Shanghai Yuyan Scientific Instrument Co., Ltd.)

shaver

1.2 Materials and reagents:

SD rats (Animal Center, Academy of Military Medical Sciences)

2 methods and processes:

2.1 Grouping of experimental animals:

Twenty-four Kunming mice were randomly divided into 3 groups: pure trauma group, first trauma followed by irradiation group, and first irradiation followed by trauma group, with 8 mice in each group.

2.2 Processing process:

The backs of all mice were shaved with a shaver, and circular marks with a diameter of 1.3 cm were made with a marker.

Simple trauma group: After anesthesia, tissue forceps and hemostatic clips were used to lift the back skin, and ophthalmic scissors were used to excise the full-thickness skin on the back along the mark, without damaging the subcutaneous fascia and tissue.

First trauma and then irradiation group: the back was injured first (injury procedure was the same as that of the simple trauma group), and 0.5 hours later, the mice were placed in a plexiglass box, and 5Gy γ-rays were irradiated to the whole body (dose rate: 95.96 cGy/min) .

First irradiation followed by trauma group: mice were placed in a plexiglass box, irradiated with 5Gy γ-rays (dose rate: 95.96cGy/min), and wounded on the back after 0.5h (injury steps were the same as those of the simple trauma group).

3 Experimental results:

The pure wound group healed the fastest, and the 10-day wound healing rate was over 90%. The first trauma followed by irradiation group followed, and the first irradiation followed by trauma group healed the slowest. On the 12th day, the wound healing percentages in the first trauma and then irradiation group and the first irradiation and then trauma group were significantly lower than those in the simple trauma group (P<0.01), and the wound healing in the first irradiation and then trauma group was the slowest (as shown in Figure 5). ).

4 Conclusion

Through animal experiments, it was confirmed that irradiation caused damage to the skin repair mechanism and delayed the speed of wound healing. It is more conducive to the pharmacodynamic evaluation to establish a mouse model of combined radiation and trauma by the method of irradiation first and then trauma.

Claims (9)

1. A compound lyotropic liquid crystal for treating wound healing wound comprises Aloe extract, tea tree oil, lidocaine hydrochloride, water, anhydrous alcohol, glyceryl monooleate and poloxamer.

2. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises, by weight, 800 parts of water, 200 parts of poloxamer, 16 parts of aloe vera extract, 9 parts of lidocaine hydrochloride, 400 parts of glycerol monooleate, 40 parts of absolute ethanol, and 300 parts of tea tree oil.

3. The pharmaceutical composition according to claim 1 or 2, characterized in that: the lyotropic liquid crystal material is selected from any one or more of polyoxyethylene and isopropyl myristate, chitosan and sodium tripolyphosphate, glycerol monooleate and absolute ethyl alcohol.

4. The method of preparing a complex lyotropic liquid crystal according to any of claims 1 to 3, comprising the step of mixing the aloe vera extract, tea tree oil, lidocaine hydrochloride, water, absolute ethanol, glycerol monooleate and poloxamer.

5. A lyotropic liquid crystal prepared from the pharmaceutical composition of any of claims 1 to 4.

6. In the pharmaceutical composition, the lyotropic liquid crystal material is glycerol monooleate/absolute ethyl alcohol, and the weight ratio of the glycerol monooleate to the absolute ethyl alcohol is 60: 1-10: 1, preferably 10: 1.

7. The method for preparing the compound lyotropic liquid crystal according to claim 5, comprising the following steps: (1) weighing appropriate amount of water in a 50ml beaker, adding 0.08g of aloe extract and 45mg of lidocaine hydrochloride, dissolving with ultrasound, adding 1.00g of poloxamer 407, standing overnight at 4 deg.C for full swelling, and adding water to 5ml to obtain water phase. (2) Weighing 2g of glycerol monooleate, placing the glycerol monooleate into a 10ml centrifuge tube, adding 0.2ml of absolute ethyl alcohol for ultrasonic dissolution, adding 1.5g of tea tree oil, and uniformly mixing to obtain an oil phase. (3) And (3) slowly and continuously injecting the oil phase into the water phase under a vortex condition, stirring uniformly by using a glass rod after the oil phase gradually becomes viscous, continuously dropwise adding the residual water phase, and standing at room temperature to obtain the compound lyotropic liquid crystal.

8. Use of the compound lyotropic liquid crystal for treating a wound healing complex according to any one of claims 1 to 7 in the preparation of a medicament for treating a wound healing complex.

9. Use according to claim 7, characterized in that: the trauma is combined with a trauma by nuclear radiation injury.

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