CN114796115B - Dendrobium candidum polysaccharide external preparation and preparation method and application thereof - Google Patents
Dendrobium candidum polysaccharide external preparation and preparation method and application thereof Download PDFInfo
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Abstract
The invention provides an external preparation of dendrobium candidum polysaccharide and a preparation method and application thereof, wherein the preparation is a w/o/w type emulsion prepared by taking dendrobium candidum polysaccharide as an active ingredient and adding pharmaceutically acceptable auxiliary materials, the preparation method is simple, the preparation stability is good, and concentric vesicles which are formed by alternately multiple layers of water and oil phases and have onion-like structures can realize the slow release and long-acting functions of active substances; meanwhile, the preparation can improve the stability of the medicine, has high medicine carrying capacity and encapsulation efficiency, can effectively increase the transdermal absorbability of dendrobium candidum polysaccharide, and has excellent clinical application prospect as an external preparation for treating skin photoaging.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and in particular relates to an external preparation of dendrobium candidum polysaccharide, and a preparation method and application thereof.
Background
Photoaging of skin is the damage caused by long-term exposure of the skin to sunlight. Manifesting as rough, thickened, dry skin exposed areas, loose skin, thickened wrinkles, localized hyperpigmentation or telangiectasia, and possibly even various benign or malignant tumors (e.g., solar keratosis, squamous cell carcinoma, malignant melanoma, etc.).
Studies have shown that the underlying mechanism of skin photoaging is related to ROS production and subsequent oxidative stress. ROS are produced by mitochondria, ultraviolet radiation and other external factors. ROS can activate various intracellular kinases, including MAPK, AKT and ERK, in a direct or indirect manner, resulting in the production of activin 1 (AP-1) and nuclear factor- κB (NF-kB). Activated AP-1 and NF-kB regulate transcription of Matrix Metalloproteinases (MMPs). Four members of MMPs, including MMP1, MMP2, MMP3, and MMP9, can completely degrade collagen. Notably, MMPs are members of the elastase family, with the ability to degrade elastin and reduce elastin levels. At the same time, activated AP-1 and NF-kB can also increase the expression of MMP Tissue Inhibitor (TIMP). Nevertheless, MMP activation is still more advantageous than TIMP activity, leading to degradation of collagen, elastin, fibrils and some other dermal extracellular matrix. In addition, NF-kB is the primary activator of inflammatory cell infiltration by inducing the production of the pro-inflammatory cytokines TNF- α, interleukin (IL) -1, IL-6 and VEGF, which stimulate further MMP production. ROS-induced AP-1 also reduced collagen biosynthesis. The reduction of type I and type III collagen results from AP-1 down-regulating the transforming growth factor-b receptor and compromising the subsequent cascade and pathway. Eventually, collagen and elastin levels in the dermis layer decrease, thus accelerating skin aging.
Dendrobium officinale is a perennial herb of Dendrobium genus of Orchidaceae, and has reputation of "Chinese Mesona herb". In recent years, research results show that dendrobium candidum contains substances such as polysaccharide, flavonoid, phenols, vitamins, amino acids and the like, wherein dendrobium candidum polysaccharide (DOP) is the main component of the activity of the dendrobium candidum polysaccharide. Dendrobium candidum polysaccharide has effects of keeping moisture, resisting oxidation, and inhibiting inflammatory reaction. Specifically, dendrobium candidum polysaccharide can effectively reduce oxidative stress load by inhibiting ROS production, enhancing antioxidant enzyme system, inhibiting inflammatory reaction and other ways. Yang Kaiye et al found that Dendrobium candidum polysaccharide has a certain anti-photoaging effect and better effect than brown algae polysaccharide, ganoderan or Dictyophora indusiata polysaccharide in the process of studying compound polysaccharide to inhibit ultraviolet-induced photoaging of skin cells. However, the study is only carried out at the level of the effect of the polysaccharide solution on cells, which is not advantageous for practical use.
Because of the relatively low transdermal absorbability of Dendrobium candidum polysaccharides, a suitable carrier for transdermal administration needs to be found. The emulsion is a liquid preparation composed of water phase, oil phase, emulsifying agent and medicine, and is a relatively mature medicine transmission system, which can stably transmit the contained active ingredients to the skin so as not to change. In addition, certain components in the emulsion have the function of promoting penetration, and the type and the dosage of the oil phase can change the affinity of the medicine and the skin, thereby being beneficial to the medicine entering into the stratum corneum. Therefore, the research on the external dendrobium candidum polysaccharide emulsion with high stability and long-acting slow release and high-efficiency transdermal absorption has very important value in the field of medicaments for treating skin photoaging. However, for the preparation of the emulsion, the selection of different raw medicines, auxiliary materials and proportions can greatly influence the stability and actual drug effect of the emulsion, and no emulsion which has good stability, good transdermal administration effect and can effectively treat skin photoaging and takes dendrobium candidum polysaccharide as an active ingredient has been reported at present.
Disclosure of Invention
The invention aims to provide an external preparation of dendrobium candidum polysaccharide, and a preparation method and application thereof.
The invention provides a preparation for treating skin photoaging, which is prepared by taking dendrobium candidum polysaccharide as an active ingredient and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients.
Further, the preparation is an external preparation.
Further, the external preparation is a solution, powder, tincture, spirit, lotion, oil, emulsion, ointment, plaster, cream, paste, film, cataplasm, gel, liniment, aerosol, patch or emplastrum, preferably an emulsion.
Further, the emulsion is a multilayer emulsion, preferably a w/o/w multilayer emulsion.
Further, the w/o/w type multilayer emulsion comprises an inner water phase, an oil phase, an outer water phase and an emulsifier, wherein the weight ratio of the inner water phase to the oil phase to the outer water phase to the emulsifier is as follows: 1: (1-4): (2-5): (1 to 3), preferably 1: (3-4): (4-5): (1.6-2.3).
Furthermore, the inner water phase is formed by dissolving dendrobium candidum polysaccharide and an aqueous phase thickener A in water, and the outer water phase is formed by dissolving an aqueous phase thickener B in water; the mass ratio of the dendrobium candidum polysaccharide to the water phase thickener is (0.1-5) to (0.1-3); preferably (0.5 to 5): 0.25; the mass of the aqueous phase thickener is the total mass of the aqueous phase thickener A and the aqueous phase thickener B.
Further, the aqueous phase thickener a and the aqueous phase thickener B are each independently selected from at least one of hyaluronic acid, xanthan gum, carbomer, gelatin or acacia.
Further, the oil phase is one or more of capric triglyceride, polydimethylsiloxane, polyoxyethylene castor oil, soybean oil and ceramide or a mixture of the capric triglyceride, the polydimethylsiloxane, the polyoxyethylene castor oil, the soybean oil and the ceramide and an oil phase thickener, wherein the oil phase thickener is hydrogenated grease or cetyl alcohol, and preferably cetyl alcohol; the oil phase thickener accounts for 3-8wt% of the oil phase.
Further, the emulsifying agent includes a colostrum emulsifying agent and a multiple emulsion emulsifying agent; the colostrum emulsifier is a composite emulsifier of linear alkyl quaternary ammonium salt and fatty alcohol, and the composite emulsifier is a composite emulsifier of polysorbate-20 and lauroyl lactyl sodium lactate.
Further, the linear alkyl quaternary ammonium salt is behenyl trimethyl ammonium methyl sulfate, and the fatty alcohol is cetylstearyl alcohol; the mass ratio of the linear alkyl quaternary ammonium salt to the fatty alcohol is 1 (1-6), and is preferably 1:3.
Further, the mass ratio of the polysorbate-20 to the sodium lauroyl lactylate is (8-15): 1, preferably 9:1.
Further, the w/o/w type multilayer emulsion also contains a humectant and a preservative.
Further, the humectant is at least one of sodium hyaluronate, glycerin, allantoin, propylene glycol, polyethylene glycol, and sorbitol.
Further, the preservative is at least one of ethylhexyl glycerol, phenoxyethanol or sorbitol.
Further, the mass fraction of the dendrobium candidum polysaccharide is 0.1% -5%, and the pharmaceutically acceptable auxiliary materials or auxiliary components comprise: 0.1-3% of water phase thickener, 1-5% of oil phase thickener, 5-15% of colostrum emulsifier and 5-15% of multiple emulsion emulsifier; preferably, the composition further comprises 2-10% by mass of humectant and/or 0.01-3% by mass of preservative.
Preferably, the mass fraction of the water phase thickener is 3%, the mass fraction of the oil phase thickener is 2%, the mass fraction of the colostrum emulsifier is 5.6%, and the mass fraction of the double emulsion emulsifier is 11.8%.
The invention also provides a method for preparing the preparation: the method comprises the following steps:
(1) Weighing the colostrum emulsifier according to the amount, adding the colostrum emulsifier into an oil phase, heating to 60-80 ℃ for dissolution, and preserving heat to obtain a standby liquid;
(2) Dissolving dendrobium candidum polysaccharide and a water phase thickener in water to prepare an inner water phase, heating to the same temperature as the standby liquid in the step (1), adding the standby liquid obtained in the step (1), and stirring and dispersing uniformly at 60-80 ℃ to prepare primary emulsion;
(3) Dissolving the aqueous phase thickener in water to obtain an external aqueous phase, adding the compound emulsion emulsifier into the external aqueous phase to dissolve, adding the external aqueous phase thickener into the colostrum obtained in the step (2), and stirring and dispersing uniformly to obtain the external aqueous phase thickener.
Further, the temperature of step (1) and/or step (2) is 80 ℃.
Further, the stirring and dispersing speed in the step (2) is 12000-15000 rpm, and the stirring time is 5-20 min; preferably, the stirring speed is 14500rpm, and the time is 10-15 min.
Further, the stirring and dispersing speed in the step (3) is 10000-12000 rpm, and the stirring time is 5-20 min; preferably, the stirring speed is 11500rpm, and the time is 10-15 min.
The invention also provides application of the preparation in preparing a medicament for treating skin photoaging.
Further, the above-mentioned drugs for treating skin photoaging are drugs for topical administration through the skin.
Experimental results show that the multi-layer emulsion of dendrobium candidum polysaccharide provided by the invention has concentric vesicles which are formed by alternately multiple layers of water and oil phases and similar to onion structures, can be observed under a microscope, and can realize the slow-release long-acting function of active substances; the multi-layer emulsion of the dendrobium candidum polysaccharide can effectively increase the transdermal absorbability of the dendrobium candidum polysaccharide, improve the stability of the medicine, and the preparation has excellent stability, thereby being beneficial to clinical application and popularization.
The invention relates to a w/o/w type multilayer emulsion which is a water-in-oil-in-water type double emulsion.
"colostrum emulsifier" refers to an emulsifier used in the process of preparing colostrum, i.e. an emulsifier dissolved in the oil phase or the internal water phase; "multiple emulsion emulsifier" refers to an emulsifier used in the preparation of w/o/w multiple emulsion from colostrum, i.e. an emulsifier that is dissolved in the external aqueous phase.
It should be apparent that, in light of the foregoing, various modifications, substitutions and alterations can be made herein without departing from the spirit and scope of the invention as defined by the appended claims.
The above-described aspects of the present invention will be described in further detail below with reference to specific embodiments in the form of examples. It should not be understood that the scope of the above subject matter of the present invention is limited to the following examples only. All techniques implemented based on the above description of the invention are within the scope of the invention.
Drawings
Fig. 1 shows the appearance of the dendrobium candidum polysaccharide (DOP) multilayer emulsion prepared by the invention (examples 1-3 are in turn from left to right).
Fig. 2 shows the appearance of emulsions prepared in comparative examples (comparative examples 2 to 7 in order from left to right).
Fig. 3 is a microstructure observation (examples 1 to 3 in order from left to right) of dendrobium candidum polysaccharide (DOP) multi-layer emulsion prepared by the present invention.
Fig. 4 is a microstructure observation of the single emulsion prepared in comparative example 1.
FIG. 5 is a microstructure observation of emulsions prepared in comparative examples 2 to 7.
FIG. 6 is a microstructure observation of the emulsion prepared in comparative example 8.
FIG. 7 shows the property change condition of the Dendrobium Officinale Polysaccharide (DOP) multi-layer emulsion prepared by the invention at 70 ℃ (examples 1-3 are in sequence from left to right).
FIG. 8 shows the results of measuring the temperature characteristics of the Dendrobium candidum polysaccharide (DOP) multi-layer emulsion prepared in examples 1 to 3 according to the present invention.
FIG. 9 is a DOP concentration-UV absorbance standard curve.
Fig. 10 shows the transdermal release experimental results of the dendrobium candidum polysaccharide (DOP) multi-layer emulsion prepared in examples 1 to 3 of the present invention.
Detailed Description
The raw materials and equipment used in the invention are all known products and are obtained by purchasing commercial products.
Example 1 preparation of Dendrobium candidum polysaccharide emulsion of the present invention
The preparation method comprises the following steps:
(1) Preparation of an oil phase: the method comprises the steps of weighing a colostrum emulsifier (a composite emulsifier formed by 0.07g of behenyl trimethyl ammonium methyl sulfate and 0.21g of cetostearyl alcohol), adding an oil phase (1.8 mL of caprylic capric triglyceride, 0.1mL of polydimethyl silicone oil and 0.1g of oil phase thickener cetyl alcohol), heating in a water bath, performing ultrasonic treatment to dissolve the mixture, and preserving the temperature at 80 ℃ for later use;
(2) Preparation of the inner aqueous phase: 0.025g of dendrobium candidum polysaccharide (DOP) is taken and evenly mixed with 0.5mL of 0.5wt% aqueous solution of aqueous phase thickener xanthan gum.
(3) Preparation of an external aqueous phase: the multiple emulsion emulsifier (compound emulsifier made of 0.53g polysorbate-20 and 0.06g lauroyl lactyl sodium lactate) was mixed with 2.5ml of 0.5wt% aqueous solution of aqueous phase thickener xanthan gum.
(4) Preparation of colostrum: slowly adding the oil phase into an internal water phase heated to the same temperature (the mass ratio of the internal water phase to the oil phase is 1:4), and uniformly stirring the mixture in a water bath at 80 ℃ by using a dispersing machine to prepare the colostrum, wherein the stirring speed is 14500rpm, and the time is 10-15 min;
(5) Slowly adding the external water phase (the mass ratio of the external water phase to the oil phase is 5:4) into the colostrum, and stirring by a dispersing machine to obtain the multilayer emulsion; the stirring speed is 11500rpm, the stirring time is 10-15min, and the emulsion with the dendrobium candidum polysaccharide mass fraction of 0.5% is prepared.
Example 2 preparation of Dendrobium candidum polysaccharide emulsion of the present invention
The preparation method comprises the following steps:
(1) Preparation of an oil phase: the method comprises the steps of weighing a colostrum emulsifier (a composite emulsifier formed by 0.07g of behenyl trimethyl ammonium methyl sulfate and 0.21g of cetostearyl alcohol), adding an oil phase (1.8 mL of caprylic capric triglyceride, 0.1mL of polydimethyl silicone oil and 0.1g of oil phase thickener cetyl alcohol), heating in a water bath, performing ultrasonic treatment to dissolve the mixture, and preserving the temperature at 80 ℃ for later use;
(2) Preparation of the inner aqueous phase: mixing herba Dendrobii polysaccharide (DOP) 0.05g with water phase thickener (xanthan gum) 0.5mL 0.5%.
(3) Preparation of an external aqueous phase: the multiple emulsion emulsifier (compound emulsifier made of polysorbate-20 (0.53 g) and sodium lauroyl lactylate (0.06 g)) was mixed with 2.5ml of 0.5% aqueous phase thickener (xanthan gum).
(4) Preparation of colostrum: slowly adding the oil phase into an internal water phase heated to the same temperature (the mass ratio of the internal water phase to the oil phase is 1:4), and uniformly stirring the mixture in a water bath at 80 ℃ by using a dispersing machine to prepare the colostrum, wherein the stirring speed is 14500rpm, and the time is 10-15 min;
(5) Taking the external water phase (the mass ratio of the external water phase to the oil phase is 5:4), slowly adding the colostrum, and stirring by a dispersing machine to obtain the multilayer emulsion; the stirring speed is 11500rpm, the stirring time is 10-15min, and the emulsion with the dendrobium candidum polysaccharide mass fraction of 1% is prepared.
Example 3 preparation of Dendrobium candidum polysaccharide emulsion of the invention
The preparation method comprises the following steps:
(1) Preparation of an oil phase: the method comprises the steps of weighing a colostrum emulsifier (a composite emulsifier formed by 0.07g of behenyl trimethyl ammonium methyl sulfate and 0.21g of cetostearyl alcohol), adding an oil phase (1.8 mL of caprylic capric triglyceride, 0.1mL of polydimethyl silicone oil and 0.1g of oil phase thickener cetyl alcohol), heating in a water bath, performing ultrasonic treatment to dissolve the mixture, and preserving the temperature at 80 ℃ for later use;
(2) Preparation of the inner aqueous phase: mixing herba Dendrobii polysaccharide (DOP) 0.25g with water phase thickener (xanthan gum) 0.5mL 0.5%.
(3) Preparation of an external aqueous phase: the multiple emulsion emulsifier (compound emulsifier made of polysorbate-20 (0.53 g) and sodium lauroyl lactylate (0.06 g)) was mixed with 2.5ml of 0.5% aqueous phase thickener (xanthan gum).
(4) Preparation of colostrum: slowly adding the oil phase into an internal water phase heated to the same temperature (the mass ratio of the internal water phase to the oil phase is 1:4), and uniformly stirring the mixture in a water bath at 80 ℃ by using a dispersing machine to prepare the colostrum, wherein the stirring speed is 14500rpm, and the time is 10-15 min;
(5) Taking the external water phase (the mass ratio of the external water phase to the oil phase is 5:4), slowly adding the colostrum, and stirring by a dispersing machine to obtain the multilayer emulsion; the stirring speed is 11500rpm, the stirring time is 10-15min, and the emulsion with the dendrobium candidum polysaccharide mass fraction of 5% is prepared.
Comparative example 1 preparation of O/W type Single emulsion
[ formula ]
Oil-water phase mass ratio O: w=1:3.5
An oil phase: caprylic capric triglyceride, adding an oil phase thickener: 5wt% cetyl alcohol (mass fraction of oil phase)
Aqueous phase: water, 0.5wt% of dendrobium candidum polysaccharide, and adding an aqueous phase thickener: 0.5wt% xanthan gum (mass fraction of the inner aqueous phase)
Emulsifying agent: 4% (Behenyltrimethylammonium methyl sulfate (BTMS): cetostearyl alcohol=1:3)
The emulsifier is added into the oil phase to be dispersed evenly, the water phase and the oil phase are heated to 75 ℃ respectively on a water bath to dissolve, and the two phases are mixed under the stirring of a dispersing machine and stirred to be condensed.
[ As a result ], milky semisolid was thicker, had poor stability, and had flocs. The emulsion droplets are uneven in size, large in size of about 45 μm, small in size of about 5 μm, and the surface of some droplets is crushed.
Comparative example 2 preparation of W/O/W type double emulsion
[ formula ]
Oil-water phase mass ratio W1 (inner water phase) O: W (outer water phase) =1:1:1
An oil phase: caprylic capric triglyceride, oil phase thickener: 5wt% cetyl alcohol (mass fraction of oil phase)
Inner aqueous phase: water, 0.5wt% of dendrobium candidum polysaccharide (the mass fraction of the total emulsion is the final concentration), 0.5wt% of xanthan gum (the mass fraction of the internal water phase)
Outer aqueous phase: water, 0.5wt% xanthan gum (mass fraction of the outer aqueous phase)
Colostrum emulsifier: 4wt% (behenyl trimethyl ammonium methyl sulfate (BTMS): cetostearyl alcohol=1:3) (mass fraction of colostrum)
Mixing cetyl alcohol, BTMS and cetyl stearyl alcohol and caprylic capric triglyceride (as oil phase), heating in water bath to 75deg.C, slowly adding the oil phase into the inner water phase heated to the same temperature, stirring at normal temperature with a disperser to obtain colostrum, slowly adding the outer water phase at 75deg.C into colostrum, and stirring with disperser until it is condensed.
Comparative example 3 preparation of W/O/W type double emulsion
Oil phase thickener: 10wt% cetyl alcohol (mass fraction of the oil phase); the remaining formulation and preparation method were the same as comparative example 2.
Comparative example 4 preparation of W/O/W type double emulsion
Oil phase thickener: 15wt% cetyl alcohol (mass fraction of the oil phase); the remaining formulation and preparation method were the same as comparative example 2.
Comparative example 5 preparation of W/O/W type double emulsion
The formulation was the same as comparative example 2, but 4wt% (behenyl trimethylammonium methylsulfate (BTMS): cetostearyl alcohol=1:3) was used as a multiple emulsion emulsifier.
[ PREPARATION METHOD ]: mixing cetyl alcohol and caprylic/capric triglyceride (as oil phase), heating in water bath to 75deg.C, slowly adding the oil phase into the inner water phase heated to the same temperature, stirring at room temperature to obtain colostrum, dissolving BTMS and cetylstearyl alcohol in the outer water phase, slowly adding colostrum into the outer water phase at 75deg.C, and stirring until condensation.
Comparative example 6 preparation of W/O/W type double emulsion
Oil phase thickener: 10wt% cetyl alcohol (mass fraction of the oil phase); the remaining formulation and preparation method were the same as comparative example 5.
Comparative example 7 preparation of W/O/W type double emulsion
Oil phase thickener: 15wt% cetyl alcohol (mass fraction of the oil phase); the remaining formulation and preparation method were the same as comparative example 5.
Comparative example 8 preparation of W/O/W type double emulsion
Oil-water phase mass ratio W1 (inner water phase): O: W (outer water phase) =1:3.5:2.5
An oil phase: caprylic capric triglyceride, oil phase thickener: 10wt% cetyl alcohol (mass fraction of oil phase)
Inner aqueous phase: water, 0.5wt% of dendrobium candidum polysaccharide (the mass fraction of the total emulsion is the final concentration), 0.5wt% of xanthan gum (the mass fraction of the internal water phase)
Outer aqueous phase: water, 0.5wt% xanthan gum (mass fraction of the outer aqueous phase)
Colostrum emulsifier: 2wt% (behenyl trimethyl ammonium methyl sulfate (BTMS): cetostearyl alcohol=1:3) (mass fraction of colostrum)
Mixing cetyl alcohol, BTMS, cetostearyl alcohol and caprylic/capric triglyceride (as oil phase), heating in water bath to 75deg.C, slowly adding the oil phase into the inner water phase heated to the same temperature, stirring at normal temperature with a disperser to obtain colostrum, slowly adding colostrum into the outer water phase at 75deg.C, and stirring with the disperser until it is condensed.
Comparative example 9 preparation of W/O/W type double emulsion
Oil-water phase mass ratio W1 (inner water phase): O: W (outer water phase) =1:2:2
An oil phase: caprylic capric triglyceride, oil phase thickener: 12wt% cetyl alcohol ((mass fraction of oil phase)
Inner aqueous phase: water, 0.5wt% of dendrobium candidum polysaccharide (the mass fraction of the total emulsion is the final concentration), 0.5wt% of xanthan gum (the mass fraction of the internal water phase)
Outer aqueous phase: water, 0.5wt% xanthan gum (mass fraction of the outer aqueous phase)
Colostrum emulsifier: 2wt% (behenyl trimethyl ammonium methyl sulfate (BTMS): cetostearyl alcohol=1:3) (mass fraction of colostrum)
Mixing cetyl alcohol, BTMS, cetostearyl alcohol and caprylic/capric triglyceride (as oil phase), heating in water bath to 80deg.C, slowly adding the oil phase into the inner water phase heated to the same temperature, stirring in water bath with a disperser to obtain colostrum (14500 rpm,10-15 min) (not taking out, standing in water bath), adding the colostrum into the outer water phase at 80deg.C, and stirring with the disperser (11500 rpm,10-15 min) until condensation.
Comparative example 10 preparation of W/O/W type double emulsion
Colostrum emulsifier: 4wt% (behenyl trimethylammonium methylsulfate (BTMS): cetostearyl alcohol=1:3) (mass fraction of colostrum); the remaining formulation and preparation method were the same as comparative example 9.
Comparative example 11 preparation of W/O/W type double emulsion
Colostrum emulsifier: 4wt% (behenyl trimethylammonium methylsulfate (BTMS): cetostearyl alcohol=1:3) (mass fraction of colostrum); the mass fraction of the xanthan gum in the inner water phase and the outer water phase is 0.5wt%; the remaining formulation and preparation method were the same as comparative example 9.
Comparative example 12 preparation of W/O/W type double emulsion
The mass fraction of the xanthan gum in the inner water phase and the outer water phase is 0.5wt%; the remaining formulation and preparation method were the same as comparative example 9.
The beneficial effects of the dendrobium candidum polysaccharide emulsion disclosed by the invention are proved by experimental examples.
Experimental example 1 DOP multilayer emulsion was observed with naked eyes and under a mirror
1. Experimental method
Taking a part of the emulsion prepared in the examples and the comparative examples to photograph, and observing the characteristics of the emulsion, such as properties, texture, fluidity, fineness and the like; a small amount of emulsion was diluted with ultrapure water and the microstructure of the emulsion was observed under a microscope.
2. Experimental results
2.1 As shown in figure 1, the multilayer emulsion prepared by the embodiment of the invention has uniform characteristics of colostrum in the preparation process, and the further prepared compound emulsion is in the form of cream, is smooth and fine, has good continuity, has no obvious particles, has no layering and has no oil bloom. The emulsion of example 1 was milky white, and the multi-layer emulsions of examples 2 and 3 appeared ginger yellow and dark brown, respectively, as the content of dendrobium candidum increased.
The single-layer emulsion prepared in comparative example 1 was milky white semi-solid, thicker, and had poor stability, and flocculated.
The colostrum of comparative examples 2, 3, 4 and 6 shows phase separation, one phase is liquid, the other phase is milky cotton-like substance, but after stopping stirring, the liquid phase disappears, and after adding the external water phase, the emulsion with uniform dispersion can be formed. The colostrum of comparative examples 5 and 7 showed the state of oil condensation, heated oil-water separation, and after the external water phase was added, the emulsion was uniformly dispersed. However, the emulsions of comparative examples 2 to 7 were inferior to examples 1 to 3 in shape and had a low general viscosity in spite of the good fineness, and had very many bubbles (fig. 2, comparative examples 2 to 7 in order from left to right). The emulsion of comparative example 8 was poor in fineness.
The emulsion prepared in comparative examples 9-12 has uniform colostrum character and is in a milky white solid state, and the fact that the colostrum is prepared under the condition of heat preservation in a water bath is proved to be the key of uniform colostrum dispersion. However, the compound emulsions finally obtained in comparative examples 9 to 12 were thin, unevenly dispersed, and had flocs.
2.2, the emulsion droplets of the emulsions prepared in examples 1 to 3 were observed under a microscope to show multilayer concentric vesicles similar to onion structures, and the alternate multilayer composite structure was confirmed to be uniform and stable in structure (FIG. 3).
The emulsion droplets observed in comparative example 1 were uneven in size, large in size of about 45 μm and small in size of about 5 μm, and a part of the droplet surface was crushed (FIG. 4).
As can be seen from FIG. 5, the emulsion droplet sizes of comparative examples 2 to 7 are related to the amount of cetyl alcohol, and the larger the amount of cetyl alcohol, the smaller the emulsion droplet size; and when BTMS and cetostearyl alcohol are used as the colostrum emulsifier, the emulsion drops are dispersed more uniformly. However, in general, the emulsions of comparative examples 2 to 7 were inferior in emulsion droplet dispersion effect to the emulsions of examples 2 to 4, had larger particle diameters, and did not form a distinct multilayer structure, and were unstable in structure.
As can be seen from FIG. 6, the emulsion prepared in comparative example 8 has a small number of droplets, a large particle size, and poor dispersion effect, although there are several layers of droplets.
Therefore, the emulsion with the specific composition prepared by the invention has optimal properties, is smooth and fine, has good continuity, and has no obvious floccules, precipitates, particles, oil flowers, layering and the like through the exploration of a large amount of emulsion auxiliary materials by the inventor; the skin-care product has obvious characteristic multilayer vesicle structure, is uniform and stable, and has the particle size suitable for skin absorption.
Experimental example 2, stability investigation of DOP multilayer emulsion
1. Experimental method
The emulsions prepared in examples 2 to 4 were placed at 4 ℃, 25 ℃ and 70 ℃ for 6 hours, respectively, and the change in appearance was observed and the change in the multilayer structure was observed under a microscope.
2. Experimental results
The multilayer emulsion provided by the invention is placed at the temperature of 4 ℃ and the temperature of 25 ℃ for 6 hours, the appearance form is not obviously changed, and layering phenomenon is not generated; after being placed in the environment of 70 ℃ for 6 hours, dendrobium candidum polysaccharide (DOP) has layering phenomenon in low, medium and high dose multi-layer emulsion, floccule is deposited, and liquid precipitation is not compatible with the original emulsion (figure 7). The above phenomenon shows that the high temperature can damage the composite water-oil structure of the multi-layer emulsion w/o/w. The DOP multi-layer emulsion with three dose gradients is placed in an environment of 4 ℃ and 25 ℃ and has stable microstructure without obvious change, and clear concentric vesicles can be seen. Under the high temperature of 70 ℃, the DOP multi-layer emulsion microstructure is destroyed, wherein the DOP low-dose multi-layer emulsion microscope and the DOP medium-dose multi-layer emulsion microscope can hardly see complete concentric circle structures, and the DOP high-dose multi-layer emulsion microscope can see a large amount of broken emulsion droplet fragments, and only a small amount of the DOP high-dose multi-layer emulsion microscope can keep the normal concentric circle structures (figure 8).
The results show that the emulsion has good stability at low temperature to room temperature and is easy to manufacture and transport.
Experimental example 3 determination of drug-loading and encapsulation Rate of the multilayered emulsion of the present invention
1. Experimental method
Precisely weighing DOP 10mg in a 10ml volumetric flask, dissolving with 2ml of aqueous solution, diluting with water to obtain standard solution with constant volume of 1mg/ml, and obtaining standard curve of DOP by measuring absorbance at 268nm wavelength with mass concentration as abscissa and absorbance as ordinate, wherein the total of 5 groups is 0.1mg/ml,0.05mg/ml,0.02mg/ml,0.01mg/ml and 0.005 mg/ml. The encapsulation efficiency of the emulsion was determined by centrifugation. Taking a proper amount of the multilayer emulsions prepared in examples 2-4 respectively, centrifuging the multilayer emulsions in a centrifuge tube at 12000rpm for 20 minutes, sucking the lower liquid and moderately diluting the lower liquid, measuring the light absorption value at a wavelength of 268nm, calculating according to a standard curve to obtain the drug content, and calculating according to the following formula to obtain the drug loading and encapsulation efficiency: drug loading = drug amount contained in emulsion/total mass of emulsion x 100%; encapsulation efficiency = (amount of encapsulated drug in emulsion/total amount of encapsulated and unencapsulated drug in emulsion) ×100%; the amount of drug contained in the emulsion=m measurement value x dilution.
2. Experimental results
Drawing a standard curve according to ultraviolet absorbance values corresponding to DOP solutions with different concentrations to obtain a curve regression equation of y=0.0283x+0.0011, R 2 =0.9989 (fig. 9). According to calculation, the drug loading rate of the DOP low-dose multi-layer emulsion is 0.46%, and the encapsulation rate is 93.58%; the drug loading rate of the multi-layer emulsion in DOP is 0.92%, and the encapsulation rate is 92.03%; the drug loading of the DOP high-dose multi-layer emulsion is 4.69%, and the encapsulation efficiency is 93.91%.
The results show that the drug loading rate of the emulsion can reach more than 4%, the encapsulation efficiency is more than 90%, and the emulsion has good application prospect.
Experimental example 4 transdermal delivery assay of the multilayer emulsion of the invention
1. Experimental method
The transdermal penetration test was performed on DOP solutions and the multi-layer emulsions of examples 2 to 4 using a Franz diffusion cell device. The spare mouse skin was held between the supply chamber and the receiving chamber of the diffusion cell with the stratum corneum facing the supply chamber. The effective diffusion area of the diffusion cell is 2.27cm 2 The magnetic stirring speed is 300r/min. Accurately adding DOP emulsion and DOP multi-layer emulsion 0.3g into a dosing tank, uniformly distributing the DOP emulsion and DOP multi-layer emulsion on the surface of mouse skin, putting the diffusion tank into a water bath at 32 ℃, adding 14mL of PBS buffer solution preheated to 32 ℃ into a receiving tank as receiving solution, sampling respectively at 0.5,1,2,4 and 6 hours, taking out the receiving solution, and rapidly supplementing the receiving solution preheated by equal amount. The absorbance was then measured at 268nm and the drug content was obtained according to a standard curve.
2. Experimental results
The experimental results show that the transdermal absorption of the DOP multi-layer emulsion prepared by the invention for six hours is far higher than that of the DOP solution (equivalent mass fraction) with high dosage (figure 10).
The results show that the DOP emulsion prepared by the invention obviously increases the transdermal absorbability of DOP, has excellent transdermal administration effect and is beneficial to clinical application.
In summary, the invention provides the multi-layer emulsion of dendrobium candidum polysaccharide and the preparation method thereof, the preparation method is simple and convenient to operate, the prepared emulsion has concentric vesicles which are similar to onion structures and are formed by alternately multiple layers of water and oil phases, the concentric vesicles can be observed under a microscope, and the slow release and long-acting functions of active substances can be realized; the multi-layer emulsion of dendrobium candidum polysaccharide can improve the stability of the medicine, has excellent stability, high drug-loading rate and encapsulation efficiency, can effectively increase the transdermal absorbability of the dendrobium candidum polysaccharide, and has excellent clinical application prospect as an external preparation for treating skin photoaging.
Claims (11)
1. A preparation for treating skin photoaging is characterized in that the preparation is a w/o/w type multilayer emulsion prepared by taking dendrobium candidum polysaccharide as an active ingredient and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients; the w/o/w type multilayer emulsion comprises an inner water phase, an oil phase, an outer water phase and an emulsifying agent, wherein the weight ratio of the inner water phase to the oil phase to the outer water phase to the emulsifying agent is as follows: 1: (1-4): (2-5): (1-3);
the inner water phase is formed by dissolving dendrobium candidum polysaccharide and a water phase thickener A in water, and the outer water phase is formed by dissolving a water phase thickener B in water; the water phase thickener A and the water phase thickener B are xanthan gum;
the mass ratio of the dendrobium candidum polysaccharide to the water phase thickener is (0.1-5): (0.1-3), and the mass of the water phase thickener is the total mass of the water phase thickener A and the water phase thickener B;
the oil phase is a mixture of caprylic capric triglyceride and polydimethylsiloxane, and the oil phase thickener is cetyl alcohol; the oil phase thickener accounts for 3-8wt% of the oil phase;
the emulsifying agent comprises a colostrum emulsifying agent and a double emulsion emulsifying agent, wherein the colostrum emulsifying agent is a composite emulsifying agent of behenyl trimethyl ammonium methyl sulfate and cetostearyl alcohol, and the double emulsion emulsifying agent is a composite emulsifying agent of polysorbate-20 and sodium lauroyl lactylate;
the preparation process comprises the step of uniformly stirring and dispersing the internal water phase, the oil phase and the colostrum emulsifier at 60-80 ℃ to prepare colostrum.
2. The formulation of claim 1, wherein the internal aqueous phase, oil phase, external aqueous phase and emulsifier are present in a weight ratio of 1: (3-4): (4-5): (1.6-2.3).
3. The preparation of claim 1, wherein the mass ratio of the dendrobium candidum polysaccharide to the aqueous phase thickener is (0.5-5) to 0.25.
4. A formulation according to claim 1, wherein the mass ratio of behenyl trimethylammonium methylsulfate to cetostearyl alcohol is 1 (1-6);
and/or the mass ratio of the polysorbate-20 to the sodium lauroyl lactylate is (8-15): 1.
5. the formulation of claim 1, wherein the w/o/w type multi-layer emulsion further comprises a humectant and/or preservative.
6. The formulation of claim 5, wherein the humectant is at least one of sodium hyaluronate, glycerin, allantoin, propylene glycol, polyethylene glycol, and sorbitol; the preservative is at least one of ethylhexyl glycerol, phenoxyethanol or sorbitol.
7. The preparation of any one of claims 1-6, wherein the dendrobium candidum polysaccharide has a mass fraction of 0.1% -5%, and the pharmaceutically acceptable auxiliary materials or auxiliary components comprise 0.1% -3% of water phase thickener, 1% -5% of oil phase thickener, 5% -15% of colostrum emulsifier and 5% -15% of multiple emulsion emulsifier.
8. The formulation of claim 7, wherein the pharmaceutically acceptable excipients or auxiliary ingredients further comprise a humectant in an amount of 2-10% by mass and/or a preservative in an amount of 0.01-3% by mass.
9. A method of preparing the formulation of any one of claims 1 to 8, comprising the steps of:
(1) Weighing a colostrum emulsifier according to the amount, adding the colostrum emulsifier into an oil phase, heating to 60-80 ℃ for dissolution, and preserving heat to obtain a standby liquid;
(2) Dissolving dendrobium candidum polysaccharide and a water phase thickener in water to prepare an inner water phase, heating to the same temperature as the standby liquid in the step (1), adding the standby liquid obtained in the step (1), and stirring and dispersing uniformly at 60-80 ℃ to prepare primary emulsion;
(3) Dissolving the aqueous phase thickener in water to obtain an external aqueous phase, adding the compound emulsion emulsifier into the external aqueous phase to dissolve, adding the external aqueous phase thickener into the colostrum obtained in the step (2), and stirring and dispersing uniformly to obtain the external aqueous phase thickener.
10. Use of a formulation according to any one of claims 1 to 8 for the preparation of a medicament for the treatment of skin photoaging.
11. The use according to claim 10, wherein the medicament for treating photoaging of the skin is a medicament for topical administration through the skin.
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| CN105434350A (en) * | 2015-12-24 | 2016-03-30 | 中国药科大学 | Diclofenac sodium frozen compound emulsion transdermal delivery preparation and preparation method thereof |
| CN106692692A (en) * | 2015-08-21 | 2017-05-24 | 中国科学院昆明植物研究所 | Dendrobium officinale extract and preparation method thereof |
| CN107157872A (en) * | 2017-05-08 | 2017-09-15 | 宁波易中禾生物技术有限公司 | A kind of oxidation resistant dendrobium candidum facial treatment milk of moisturizing and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106692692A (en) * | 2015-08-21 | 2017-05-24 | 中国科学院昆明植物研究所 | Dendrobium officinale extract and preparation method thereof |
| CN105434350A (en) * | 2015-12-24 | 2016-03-30 | 中国药科大学 | Diclofenac sodium frozen compound emulsion transdermal delivery preparation and preparation method thereof |
| CN107157872A (en) * | 2017-05-08 | 2017-09-15 | 宁波易中禾生物技术有限公司 | A kind of oxidation resistant dendrobium candidum facial treatment milk of moisturizing and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 杨凯业等.复合多糖抑制紫外线诱导皮肤细胞的光老化.《中国组织工程研究》.2019,第23卷(第23期),第4710页左栏第1段，右栏第1段. * |
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