Nanoemulsion composition for repairing scald wound, preparation method and application

Abstract

The invention provides a nano-emulsion composition for repairing a scald wound, a preparation method and application, and belongs to the technical field of pharmaceutical preparations. The composition comprises madecassoside raw material medicine, lemon essential oil, an emulsifying agent and water. The preparation method comprises the following steps: dissolving madecassoside powder in water, adding the madecassoside powder into lemon essential oil containing a W / O type emulsifier after the madecassoside powder is completely dissolved, crushing under a cell crusher to form primary emulsion, adding the primary emulsion into a solution containing an O / W type emulsifier, and continuously crushing and stirring to obtain the madecassoside nano-emulsion. The fat solubility of madecassoside can be improved, the permeation effect of madecassoside on the skin is enhanced, the absorption of madecassoside is greatly improved, and the madecassoside has a good application prospect in scald repair.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations and relates to a nanoemulsion composition for repairing scald wounds, a preparation method and an application thereof. Background Art

[0002] Burns are common accidental injuries in daily life, with a higher incidence rate among children, who are one of the high-risk groups for burns. Because children are still in childhood, their minds have not yet matured and they have not formed a solid sense of safety, burns often occur inadvertently. If the scar area caused by burns is too large, it will affect the appearance and may have a series of physiological or psychological effects on human health.

[0003] Physiological effects: Burns can cause pain in the wound area, which can last for hours or even days, affecting the patient's daily activities and sleep. As the burn deepens, blisters may form, increasing the risk of infection and prolonging wound healing. Deep burns may also leave permanent scars or scar hyperplasia, affecting the overall appearance and function of the skin.

[0004] In more serious burns, the heat generated by the burn can damage the nerves under the skin, causing abnormal or loss of nerve sensation, such as tingling, numbness or itching. Nerve damage not only increases the patient's pain, but may also affect the patient's quality of life.

[0005] Psychological impact: The pain caused by burns can cause patients to feel anxious, fearful or inferior. The change in the appearance of scars after burns affects the patient's self-confidence, causing social barriers or withdrawal. Long-term self-isolation further aggravates the patient's psychological problems. Therefore, it is urgent to strengthen timely and effective intervention treatment for burns and reduce the adverse effects of burns. Summary of the invention

[0006] The purpose of the present invention is to provide a burn repair nanoemulsion composition in view of the above-mentioned problems existing in the prior art. The technical problem to be solved by the present invention is to provide a pharmaceutical composition for burn repair.

[0007] The components include madecassoside raw material, lemon essential oil, emulsifier, co-emulsifier and water. The emulsifier is Span 80, the co-emulsifier is sodium lauryl sulfate, the weight ratio of Span 80 to sodium lauryl sulfate is 1-1.5:1, the weight ratio of lemon essential oil to Span 80 is 1-1.5:1, and the weight ratio of lemon essential oil to sodium lauryl sulfate is 1-1.5:1.

[0008] One of the optional solutions is composed, by weight, of 2% madecassoside, 10%-20% lemon essential oil, 20%-30% Span 80, 20%-30% sodium lauryl sulfate, and the balance is water.

[0009] One of the optional solutions is composed, by weight, of 1% madecassoside, 15%-20% lemon essential oil, 20%-25% Span 80, 20%-25% sodium lauryl sulfate, and the balance is water.

[0010] One of the optional solutions is composed, by weight, of 1.5% madecassoside, 20%-26% lemon essential oil, 25%-30% Span 80, 20%-25% sodium lauryl sulfate, and the balance is water.

[0011] One of the optional solutions is composed, by weight, of 1.2% madecassoside, 14%-18% lemon essential oil, 25%-30% Span 80, 25%-30% sodium lauryl sulfate, and the balance is water.

[0012] Further, the W / O type emulsifier may be a mixture of one or more of Span-80, Span-20, Span-40, Span-60, Span-65 and Span-85.

[0013] Furthermore, the O / W emulsifier can be a mixture of one or more of sodium dodecyl sulfate (SDS), poloxamer 188, Tween and tween emulsifiers.

[0014] Madecassoside has good wound repairing ability, but its disadvantage is that it is easily soluble in water and difficult to be absorbed through the skin when applied externally because it contains more hydrophilic groups in its structure. The present invention applies for a method for preparing a madecassoside nanoemulsion composition, which solves the problems of low fat solubility, poor bioavailability, and difficulty in transdermal absorption of madecassoside.

[0015] The preparation method comprises the following steps:

[0016] Preparation of colostrum: Madecassoside powder is dissolved in water (inner aqueous phase), and after complete dissolution, it is added to lemon essential oil containing a W / O type emulsifier (oil phase), and crushed in a cell crusher to form colostrum.

[0017] Preparation of double emulsion: Add colostrum into a solution containing an O / W emulsifier (external aqueous phase) and continue to crush and stir.

[0018] The weight ratio of the inner water phase to the oil phase is 0.5-1:1, and the weight ratio of the colostrum to the outer water phase is 0.2-1:1.

[0019] The cell disruptor has a disruption time of 1-10 minutes, with ultrasound for 1 second and an interval of 2 seconds. The power of the cell disruptor is 150W-195W.

[0020] Madecassoside nanoemulsion has the ability to repair wounds and has good application prospects in burn repair.

[0021] The optional specific preparation steps are as follows:

[0022] Take 200 mg of madecassoside API, dissolve it in 1 mL of water, then slowly drop 1 mL of oil phase lemon essential oil, which contains 1.5 mL of surfactant Span 80. Use a cell disruptor to disrupt for 1 minute to make colostrum, then add it to 3% sodium dodecyl sulfate solution, and disrupt the cells for another minute to form a double emulsion.

[0023] Beneficial effects: The madecassoside composite emulsion prepared by the preparation method can be directly applied to the skin burns, has no obvious irritation, is easy to apply, convenient to carry, and has a simple preparation process. The obtained nanoemulsion composition has a small particle size and a narrow particle size distribution, and performs well in wound repair in quality evaluation. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 This is a real sample appearance diagram that reflects the stable properties of the nanoemulsion.

[0025] Figure 2 Figure (A) shows the particle size of the madecassoside nanoemulsion composition of Example 1; Figure 2 Figure (B) is a physical picture of the madecassoside nanoemulsion composition; Figure 2 Figure (C) is the zeta potential diagram of the madecassoside nanoemulsion composition.

[0026] Figure 3 A diagram showing the repair of burn wounds in rats at the same dose.

[0027] Figure 4 Skin pathological sections stained with HE at 0, 7, 14, and 21 days under the same administration dose. DETAILED DESCRIPTION

[0028] The following are specific embodiments of the present invention and the accompanying drawings to further describe the technical solution of the present invention, but the present invention is not limited to these embodiments.

[0029] The specific preparation steps are as follows:

[0030] (1) Madecassoside is dissolved in deionized water to form an aqueous phase, i.e., phase W1.

[0031] (2) Slowly add the oil phase containing the emulsifier Span 80 into the W phase by ultrasonic dripping to prepare the colostrum W1 / O.

[0032] (3) The emulsifier SDS is made into the external water phase, namely the W2 phase.

[0033] (4) The colostrum W1 / O is added dropwise to the W2 phase by ultrasonic method to obtain a composite emulsion W1 / O / W2 phase.

[0034] In step (1), deionized water and madecassoside are loaded drugs with a mass of 200 mg, and the mass ratio of deionized water to drug is 50:1.

[0035] In step (2), the emulsifier Span 80 is a W / O type emulsifier, including Span-80, Span-20, Span-40, Span-60, Span-65 and Span-85. Finally, Span-80 is selected, and the concentration of Span-80 is 1-2 g / mL.

[0036] In step (2), the ultrasound is provided by an ultrasonic cell disruptor with a power of 195 W and an ultrasound time of 1 minute.

[0037] In step (3), the concentration of SDS was 1%-3%, and 3% SDS was finally selected.

[0038] In step (3), the ratio of the external aqueous phase to the internal aqueous phase is 1:1.5-3.5:1.

[0039] Step (4), ultrasonic treatment for 1 minute, ultrasonic power is 195W.

[0040] Example 1

[0041] Prescription: By weight, madecassoside 1%, lemon essential oil 20%, Span-80 30%, sodium lauryl sulfate 30%, water 19%.

[0042] Example 2

[0043] Prescription: By weight, madecassoside 1.5%, lemon essential oil 23%, Span-80 22.5%, sodium lauryl sulfate 23%, water 30%.

[0044] Example 3

[0045] Prescription: By weight, madecassoside 1.2%, lemon essential oil 25%, Span-80 26.8%, sodium lauryl sulfate 25%, water 22%.

[0046] Example 4

[0047] Prescription: By weight, madecassoside 2%, lemon essential oil 19%, Span-80 26%, sodium lauryl sulfate 27%, water 26%.

[0048] According to the above example, a burn repair nanoemulsion was evaluated for quality:

[0049] Table 1: Particle size, potential, and PDI under different examples

[0050]

[0051] In the quality evaluation experiment, the prepared nanoemulsion had a particle size of 158.2 nm, a PDI of 0.141, a potential of -46.1 mv, a uniform appearance, and no obvious centrifugal stratification after 60 minutes at 8000 r / min. Figure 1 , indicating that the prepared nanoemulsion is stable in nature and can ensure the stability of the Centella asiatica nanoemulsion after meeting the quality requirements of the nanoemulsion. The above examples have a good emulsion state, and no oil-water separation occurs in the 30 days after the test.

[0052] Preliminary screening of nanoemulsions for burn repair

[0053] (1) Screening of colostrum for composite emulsion

[0054] Colostrum was compounded with 1% SDS, lemon essential oil, deionized water, Tween 80, Span 80, 1% poloxamer 188, and 1% polyvinyl alcohol in a ratio of 1:1-1:10. Ultimately, 1.5 mL of Span 80, 1 mL of lemon essential oil, and 1 mL of water were determined to be the optimal formula for colostrum.

[0055] (2) Screening of oil phase: lemon essential oil, soybean oil, and finally lemon essential oil.

[0056] (3) Screening of external aqueous phase: Polyvinyl alcohol, Tween 80, Poloxamer 188, SDS, and finally 3% SDS (sodium dodecyl sulfate) were selected as the external aqueous phase.

[0057] Screening of dosage of nanoemulsion for burn repair

[0058] (1) Screening of the dosage of W / O emulsifier: Take 0.5g of lemon essential oil and water phase respectively, and screen the dosage of W / O emulsifier, and prepare under the same experimental conditions and the same preparation steps. By observing the appearance, dispersibility and stability of the emulsion, the most suitable emulsion dosage of the emulsifier is screened. The results are shown in Table 2. Under the same experimental conditions, as the dosage of emulsifier Span 80 increases, the viscosity of the emulsion increases first and then decreases. When the dosage of the emulsifier is 1.5-2.5g, the appearance of the emulsion is more uniform and the color is full, indicating that the dispersion effect of the emulsion is better at this dosage. After centrifugation of 1g and 1.5g Span 80, no obvious stratification is observed, indicating that the stability and dispersion performance of the emulsion are better. Therefore, the dosage of emulsifier Span 80 of 1.5-2.5g is selected as the standard for further research.

[0059] Table 2: Screening of dosage of W / O emulsifier

[0060]

[0061] (2) Screening of the dosage of O / W emulsifier: After determining the W / O type emulsifier, oil phase and water phase through the above experiment, under the same experimental conditions, the concentration of O / W emulsifier was changed, the appearance of the emulsion was observed, and the particle size of the emulsion was measured. The results are shown in Table 3.

[0062] Table 3: Screening effect of O / W emulsifier concentration

[0063]

[0064] Characterization of burn repair nanoemulsion

[0065] (1) After preparing a blank nanoemulsion according to the optimized formula, 200 mg of the purified madecassoside was slowly added to 50 μL of the blank nanoemulsion, and the mixture was stirred and 3.5 mL of deionized water was added to completely dissolve the mixture, thereby preparing a double emulsion.

[0066] (2) Particle size analysis of madecassoside composite emulsion

[0067] The particle size of emulsion droplets is an important characteristic parameter of nanoemulsion and one of the most important properties for evaluating the stability of nanoemulsion. The particle size of samples was measured using a Malvern laser particle size analyzer. The results showed that the appearance of madecassoside emulsion was uniform, a white emulsion without obvious precipitation, an average particle size of 150-188nm, and a surface Zeta potential of -46.1mV. Figure 2 shown.

[0068] Evaluation of the pharmacodynamics of madecassoside nanoemulsion on Ⅱ degree burns in rats

[0069] (1) Changes in wound surface of rats: After scalding, rats were treated with madecassoside lemon oil nanoemulsion (MA group), Jingwanhong scald ointment (Scald ointment group), normal saline (no treatment), and blank emulsion without drug encapsulation (without MA). The results are as follows: Figure 3 As shown, the degree of reduction in wound surface area in the madecassoside nanoemulsion group was significantly better than that in the normal saline group and the blank nanoemulsion group.

[0070] (2) HE staining of pathological sections: The wound skin of rats in four groups was taken at 0, 7, 14, and 21 days, and HE staining was used to prepare pathological sections. The changes in the internal structure of the skin were observed through pathological sections. The results are as follows Figure 4 As shown, pathological sections showed that blood vessels and collagen in the four experimental groups had a certain degree of hyperplasia, but the epidermal hyperplasia effect in the Centella asiatica nanoemulsion group was more significant, indicating that the treatment significantly repaired scars.

[0071] Repair and treatment of burn wounds: The rats were given the drug for 21 days after the burn, each time was about 0.2g / time, and the interval between the drugs was 24h / time. The specific changes in each group are as follows Figure 3 shown.

[0072] Pathological section analysis: On day 0, the epidermis of the four groups was completely necrotic, indicating that the burns were caused by a homemade burn instrument. The burn wounds had regular incisions and the degree of burns was consistent (HE, ×40).

[0073] On the 7th day after scalding, the blood vessels in the four groups showed inflammatory necrosis on the wound surface, as well as tissue edema caused by infiltration of vascular proliferative cells (HE, ×40).

[0074] On the 14th day after administration, the wound surface was obviously hardened and scab formed. The pathological sections of the four groups showed epidermal hyperplasia and inflammatory cell infiltration (HE, ×40).

[0075] On the 21st day after administration, collagen was deposited in the dermis of the wound in the Centella asiatica nanoemulsion group and the commercially available scald ointment group, basically covering the wound edge surface. At the same time, the number of fibroblasts decreased, the cell nuclei became elongated, and the number of capillary proliferation gradually decreased, indicating that the inflammatory stage gradually eased. From the appearance, the skin treated with Centella asiatica nanoemulsion had a certain elasticity, which was basically the same as the normal skin tissue structure, and the surface repair of the wound was obvious (HE, ×40).

[0076] The specific embodiments described herein are merely examples of the spirit of the present invention. Those skilled in the art may make various modifications or additions to the specific embodiments described or replace them in similar ways, but they will not deviate from the spirit of the present invention or exceed the scope defined by the appended claims.

Claims

1. A burn repair nanoemulsion composition, comprising madecassoside raw material, lemon essential oil, W / O emulsifier, O / W emulsifier and water; the weight ratio of the W / O emulsifier to the O / W emulsifier is 1-1.5:1, the weight ratio of the lemon essential oil to the W / O emulsifier is 1-1.5:1, and the weight ratio of the lemon essential oil to the O / W emulsifier is 1-1.5:

1.

2. The burn repair nanoemulsion composition according to claim 1, characterized in that: The composition is as follows by weight: 2% of madecassoside, 10%-20% of lemon essential oil, 20%-30% of W / O emulsifier, 20%-30% of O / W emulsifier, and the balance is water.

3. The burn repair nanoemulsion composition according to claim 1, characterized in that: The composition is as follows by weight: 1% of madecassoside, 15%-20% of lemon essential oil, 20%-25% of W / O type emulsifier, 20%-25% of O / W type emulsifier, and the balance is water.

4. The burn repair nanoemulsion composition according to claim 1, characterized in that: The composition is as follows by weight: 1.5% of madecassoside, 20%-26% of lemon essential oil, 25%-30% of W / O type emulsifier, 20%-25% of O / W type emulsifier, and the balance is water.

5. The burn repair nanoemulsion composition according to claim 1, characterized in that: The composition is as follows by weight: 1.2% of madecassoside, 14%-18% of lemon essential oil, 25%-30% of W / O emulsifier, 25%-30% of O / W emulsifier, and the balance is water.

6. The composition according to claim 1, characterized in that: The W / O type emulsifier is a mixture of one or more of Span-80, Span-20, Span-40, Span-60, Span-65 and Span-85.

7. The composition according to claim 1, characterized in that: The O / W emulsifier is a mixture of one or more of sodium lauryl sulfate, poloxamer 188, Tween and tween emulsifiers.

8. A method for preparing the madecassoside nanoemulsion composition according to any one of claims 1 to 7, characterized in that: The steps include: Preparation of colostrum: dissolving madecassoside powder in water to form an inner water phase, adding it to the oil phase after it is completely dissolved, the oil phase being lemon essential oil containing a W / O type emulsifier, and crushing it under a cell crusher to form colostrum; Preparation of double emulsion: adding colostrum to the external water phase and continuing to crush, the external water phase is a solution containing an O / W type emulsifier, stirring to obtain a double emulsion; The weight ratio of the inner water phase to the oil phase is 0.5-1:1, and the weight ratio of the colostrum to the outer water phase is 0.2-1:

1.

9. The method for preparing the madecassoside nanoemulsion composition according to claim 8, characterized in that: The cell disruptor has a disruption time of 1-10 minutes, with ultrasound for 1 second and an interval of 2 seconds. The power of the cell disruptor is 150W-195W.

10. Use the madecassoside nanoemulsion described in claims 1 to 9 for repairing burns in skin tissue.

Images