CN113952292B - Rosemary essential oil nanoemulsion gel, preparation method and application thereof - Google Patents
Rosemary essential oil nanoemulsion gel, preparation method and application thereof Download PDFInfo
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- CN113952292B CN113952292B CN202111263335.9A CN202111263335A CN113952292B CN 113952292 B CN113952292 B CN 113952292B CN 202111263335 A CN202111263335 A CN 202111263335A CN 113952292 B CN113952292 B CN 113952292B
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- 239000007908 nanoemulsion Substances 0.000 title claims abstract description 167
- 239000000341 volatile oil Substances 0.000 title claims abstract description 118
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 244000178231 Rosmarinus officinalis Species 0.000 title 1
- 241001529742 Rosmarinus Species 0.000 claims abstract description 124
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims abstract description 39
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 25
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims abstract description 12
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- 238000000034 method Methods 0.000 claims description 10
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- 238000001256 steam distillation Methods 0.000 claims description 4
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical group [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 claims description 3
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- 238000012360 testing method Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
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- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
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- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
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- 239000000243 solution Substances 0.000 description 2
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- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
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- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 241001530490 Salvia rosmarinus Species 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
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- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
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- General Health & Medical Sciences (AREA)
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- Natural Medicines & Medicinal Plants (AREA)
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Abstract
The invention provides rosemary essential oil nanoemulsion gel, and belongs to the technical field of medicaments. The material is prepared from the following raw materials in parts by weight: 1 to 3.5 weight percent of carbomer, 5 to 15 weight percent of glycerol, 5.5 to 10.5 weight percent of propylene glycol, 0.5 to 2.0 weight percent of rosemary essential oil nanoemulsion and the balance of water. The rosemary essential oil nanoemulsion gel provided by the invention has the effects of moisture preservation, easy spreading and good skin feel, and plays an important role in a percutaneous administration system. The prepared gel preparation has less irritation than rosemary essential oil product, strong stability and greatly improved bioavailability; it has swelling, thixotropic and adhesive properties, so that it can enhance adhesion of nanoemulsion to skin.
Description
Technical Field
The invention belongs to the technical field of medicaments, and particularly relates to rosemary essential oil nanoemulsion gel, a preparation method and application thereof.
Background
Rosemary, latin (Rosmarinus officinalis), is a dicotyledonous plant class, labiatae, rosemary plant shrub, is warm climate loving, is in European region of origin and is coastal in the North Mediterranean of Africa. According to literature, rosemary was introduced into China in the seventeen western regions of three countries Wei Wendi. Rosemary is an important spice, and the essential oil also has strong anti-inflammatory and antioxidant effects. The Rosemary Essential Oil (REO) is a volatile component extracted from rosemary, and mainly comprises monoterpenes, sesquiterpenes and the like. At present, REO is mainly applied to the fields of daily chemical industry, food, health care and the like.
REO is colorless to pale yellow volatile liquid, has antiinflammatory, antioxidant, antifungal, and cardiovascular protecting effects. REO, however, has a more specific smell and is too irritating to the skin; the solubility in water is extremely low, the REO product is hardly dissolved in water, and the REO product is unstable in storage at normal temperature, has strong volatility and weak stability, and is limited in use.
At present, in order to improve the bioavailability and stability of essential oil drugs, nanoemulsion is generally used as a novel drug delivery system, and the nanoemulsion (nanoemulsion) is a homogeneous dispersion system which consists of oil, water, a surfactant and a cosurfactant, has the particle size of 1-100 nm, and has isotropy, clear and transparent appearance and thermodynamic stability. The nanoemulsion as a novel drug delivery system has the advantages of good stability, small particle size, easy absorption, capability of improving the solubility of insoluble drugs and the like, and is widely focused and researched in a plurality of industries such as medicines, cosmetics, foods and the like. In the prior art, the essential oil medicine is prepared into the nanoemulsion, and although the bioavailability of the essential oil medicine can be improved, the nanoemulsion has strong fluidity and is not easy to adhere to skin in the using process.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides rosemary essential oil nanoemulsion gel, a preparation method and application thereof, wherein the emulsion gel is a three-dimensional network structure obtained by swelling hydrophilic polymers through water absorption, and the network skeleton of the emulsion gel has good drug carrying capacity, so that drugs can be dispersed in the gel to be released slowly and stably. The gel has the functions of moisturizing, is easy to spread and good in skin feel, and plays an important role in a percutaneous administration system. It has swelling, thixotropic and adhesive properties, so that it can enhance adhesion of nanoemulsion to skin.
The first aim of the invention is to provide rosemary essential oil nanoemulsion gel which is prepared from the following raw materials in parts by weight: 1 to 3.5 weight percent of carbomer, 5 to 15 weight percent of glycerol, 5.5 to 10.5 weight percent of propylene glycol, 0.5 to 2.0 weight percent of rosemary essential oil nanoemulsion and the balance of water.
Preferably, the rosemary essential oil nanoemulsion is prepared from the following raw materials in parts by weight: 12 to 18 weight percent of surfactant, 12 to 18 weight percent of cosurfactant, 6.9 to 13.8 weight percent of rosemary essential oil and 55.2 to 62.1 weight percent of water.
More preferably, the surfactant is one or more of tween 80, tween 20 and polyoxyethylene castor oil; the cosurfactant is one or more of 1, 2-propylene glycol, polyethylene glycol 400 and absolute ethyl alcohol.
More preferably, the surfactant is polyoxyethylated castor oil and the cosurfactant is absolute ethanol.
More preferably, the rosemary essential oil is extracted according to the following steps: dispersing the rosemary coarse powder in 6-10 times of water, and carrying out reflux extraction for 5-8 h by a steam distillation method at the extraction temperature of 100-105 ℃ to obtain rosemary essential oil.
The second object of the invention is to provide a preparation method of rosemary essential oil nanoemulsion gel, which comprises the following steps:
dispersing carbomer in water, swelling, sequentially adding glycerol and propylene glycol, mixing, adding rosemary essential oil nanoemulsion, adding a proper amount of preservative, and mixing uniformly to obtain the rosemary essential oil nanoemulsion gel.
Preferably, the preservative is potassium sorbate.
The third purpose of the invention is to provide an application of rosemary essential oil nanoemulsion gel in bacteriostasis and anti-inflammation.
Compared with the prior art, the invention has the beneficial effects that:
the rosemary essential oil nanoemulsion gel provided by the invention is an externally-taken plaster, can reduce the irritation and has good anti-inflammatory effect, the rosemary essential oil nanoemulsion gel is good in moisture retention, smell, aesthetic property and the like, no toxic or side effect or adverse reaction is found in the test, a satisfactory effect is achieved, and the rosemary essential oil nanoemulsion gel has a wide application prospect and remarkable economic and social benefits.
The rosemary essential oil nanoemulsion gel provided by the invention is of a three-dimensional network structure obtained by swelling hydrophilic polymers by water absorption, and the network skeleton of the rosemary essential oil nanoemulsion gel has good drug carrying capacity, so that drugs can be dispersed in the gel to be slowly and stably released. The gel has the functions of moisturizing, is easy to spread and good in skin feel, and plays an important role in a percutaneous administration system. It has swelling, thixotropic and adhesive properties, so that it can enhance adhesion of nanoemulsion to skin.
The invention mainly utilizes the antibacterial and anti-inflammatory properties of rosemary essential oil, the nanoemulsion is prepared through the design and the adjustment of a formula, and the rosemary essential oil nanoemulsion gel is prepared through selecting a reasonable gel matrix and components, so that the nanoemulsion gel has the advantages of gloss, clarity, moderate viscosity, proper odor, uniformity of a finished product, good viscosity, good spreadability, stable property and capability of effectively adhering to skin, and the anti-inflammatory experiment result shows that the gel preparation prepared from the rosemary essential oil can reduce the irritation and has good anti-inflammatory effect.
The rosemary essential oil nanoemulsion provided by the invention has good thermal stability, cold stability and centrifugal stability, so that the preparation of rosemary essential oil nanoemulsion gel is realized.
Drawings
Fig. 1 is a schematic diagram of a rosemary essential oil nanoemulsion structure provided by the invention.
Fig. 2 is a photograph of the external appearance of rosemary essential oil nanoemulsion provided in example 1.
Fig. 3 is a full-wavelength ultraviolet scanning graph of the nanoemulsion of rosemary essential oil and the nanoemulsion without rosemary essential oil provided in example 1.
Fig. 4 is a particle size and polymer dispersibility index of rosemary essential oil nanoemulsion provided in example 1.
Fig. 5 is a column of antibacterial results of antibacterial activity experiments of rosemary essential oil nanoemulsion, rosemary essential oil and blank nanoemulsion provided in example 1.
Fig. 6 is a photograph of a rosemary essential oil nanoemulsion, rosemary essential oil and a blank nanoemulsion provided in example 1, showing antibacterial activity.
Fig. 7 is a graph showing migration of rosemary essential oil nanoemulsion, rosemary essential oil and blank nanoemulsion cells provided in example 1.
Fig. 8 is a photograph showing the appearance of rosemary essential oil nanoemulsion gel provided in example 4.
Fig. 9 is a photograph of a rosemary essential oil nanoemulsion gel, rosemary essential oil and a blank skin irritation experiment provided in example 4.
Fig. 10 is an anti-inflammatory photograph of rosemary essential oil nanoemulsion gel, blank gel and model set provided in example 4.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
The invention is further described below with reference to the drawings and examples.
The reagents and materials used in the examples described below are commercially available unless otherwise specified; the experimental methods are all conventional methods unless otherwise specified.
The carbomer used below is carbomer 940;
the rosemary essential oil used in the following examples was prepared according to the following steps:
extracting rosemary essential oil by adopting a steam distillation method: weighing 50g of rosemary coarse powder, placing the rosemary coarse powder into a 1000mL round bottom flask, adding 8 times of distilled water, and carrying out reflux extraction for 5h by a steam distillation method, wherein the extraction temperature is 105 ℃, thus obtaining rosemary essential oil.
Example 1
A rosemary essential oil nanoemulsion, shown in figure 1, is prepared from the following raw materials in parts by weight: 15.5wt% of polyoxyethylene castor oil, 15.5wt% of absolute ethyl alcohol, 6.9wt% of rosemary essential oil and 62.1wt% of water.
The rosemary essential oil nanoemulsion is prepared according to the following steps:
slowly dripping rosemary essential oil and deionized water into a mixed solution of polyoxyethylene castor oil and absolute ethyl alcohol, and carrying out a phase transition process on the solution, so as to obtain the rosemary essential oil nanoemulsion from clear to turbid to clear.
Example 2
The same as in example 1, except that the essential oil of rosemary was 13.8wt% and water was 55.2wt%; tween 80 is used for replacing polyoxyethylene castor oil, and polyethylene glycol 400 is used for replacing absolute ethyl alcohol.
Example 3
The same as in example 1, except that tween 20 was used instead of polyoxyethylated castor oil and 1, 2-propanediol was used instead of absolute ethanol.
Example 4
A rosemary essential oil nanoemulsion gel is prepared from the following raw materials in parts by weight: 1.0wt% of carbomer, 10wt% of glycerol, 8.4wt% of propylene glycol, 1.0wt% of rosemary essential oil nanoemulsion provided in example 1 and the balance of water.
The rosemary essential oil nanoemulsion gel is prepared according to the following method:
40.0g of fully swelled 2.5% carbomer is weighed and placed in a 250mL beaker, 60.0mL of water is added, and the mixture is stirred uniformly to obtain phase I; 12.4g of glycerin and 10.4g of propylene glycol are weighed and added into the phase I under magnetic stirring to obtain phase II; 1.24g of rosemary essential oil nanoemulsion provided in example 1 is added into phase II, and is stirred uniformly to obtain phase III; adding 3.0g of 0.6% potassium sorbate aqueous solution, and stirring thoroughly to obtain rosemary essential oil nanoemulsion gel, wherein 1ml of gel preparation is equivalent to about 1% REO nanoemulsion.
Example 5
The same as in example 4, except that it was made from the following raw materials in weight ratio: carbomer 1wt%, glycerin 5wt%, propylene glycol 8.4wt%, rosemary essential oil nanoemulsion 1.0wt% provided in example 1, and the balance water.
Example 6
The same as in example 4, except that it was made from the following raw materials in weight ratio: 3.5wt% carbomer, 15wt% glycerin, 8.4wt% propylene glycol, 1.0wt% rosemary essential oil nanoemulsion provided in example 1, the balance being water.
Example 7
The same as in example 4, except that it was made from the following raw materials in weight ratio: carbomer 2.5wt%, glycerin 5wt%, propylene glycol 5.5wt%, rosemary essential oil nanoemulsion provided in example 10.5wt%, the balance being water.
Example 8
The same as in example 4, except that it was made from the following raw materials in weight ratio: 1.5% of carbomer, 12% of glycerol, 10.5% of propylene glycol, 2.0% of rosemary essential oil nanoemulsion provided in example 1 and the balance of water.
In order to illustrate various properties of the rosemary essential oil nanoemulsion and the rosemary essential oil nanoemulsion gel provided by the invention, the rosemary essential oil nanoemulsion provided by example 1 and the rosemary essential oil nanoemulsion gel provided by example 4 were tested.
1. Performance test on rosemary essential oil nanoemulsion provided in example 1
(1) The appearance of REO nanoemulsion, as shown in figure 2,
fig. 2 is a photograph showing the appearance of rosemary essential oil nanoemulsion provided in example 1, and as can be seen from fig. 2, REO nanoemulsion should be colorless, clear and transparent in appearance and have good fluidity, and can produce the tyndall effect. In fig. 2 (B), the nanoemulsion is irradiated by a light beam, so that the light beam can clearly pass through the nanoemulsion, further explaining that the REO nanoemulsion should be colorless, clear and transparent in appearance.
(2) Ultraviolet full wavelength scanning, see FIG. 3
Fig. 3 is a graph of ultraviolet full-wavelength scan of the rosemary essential oil nanoemulsion and rosemary essential oil and nanoemulsion without rosemary essential oil provided in example 1, specifically, see that the rosemary essential oil nanoemulsion and rosemary essential oil nanoemulsion without rosemary essential oil uses absolute ethanol as a solvent to perform ultraviolet full-wavelength scan on REO, REO nanoemulsion and blank nanoemulsion. As can be seen from fig. 3, the blank nanoemulsion has no interference to REO at the wavelength of 200-400nm, and also shows that REO becomes a new substance after being prepared into REO nanoemulsion.
(3) The particle size and PDI of REO nanoemulsion are shown in figure 4
Fig. 4 shows particle size and Polymer Dispersion Index (PDI) of rosemary essential oil nanoemulsion provided in example 1, and the specific test method is to take 100 μl of prepared REO nanoemulsion, dilute with 900 μl of ultrapure water, equilibrate at room temperature for 2min, and then detect REO nanoemulsion particle size and PDI with a malvern laser particle sizer, and repeat 3 times. As can be seen from FIG. 4, the average particle size of the REO nanoemulsion prepared was 18.43.+ -. 0.5nm, and the PDI was 0.086.+ -. 0.03, indicating that the particle size was satisfactory and the dispersion was uniform.
(4) Investigation of REO nanoemulsion stability
(1) Centrifugal stability
And (3) placing a proper amount of prepared REO nanoemulsion into a centrifuge tube, centrifuging for 15min at 10000rpm, observing the appearance of the REO nanoemulsion, and if the REO nanoemulsion still keeps clear and transparent and has no precipitation phenomenon, proving that the centrifugal stability of the REO nanoemulsion is good.
(2) Thermal stability
And heating proper REO nanoemulsion at 40 ℃, 50 ℃, 60 ℃, 70 ℃ and 80 ℃ for 15min respectively, observing the appearance of the REO nanoemulsion, and if the REO nanoemulsion still keeps clear and transparent and has no precipitation phenomenon, proving that the thermal stability is good.
(3) Cold stability
And (3) refrigerating a proper amount of REO nanoemulsion at 4 ℃ for 30min, observing the appearance of the REO nanoemulsion, and if the REO nanoemulsion still keeps clear and transparent and has no precipitation phenomenon, proving that the cold stability is good.
(5) Antibacterial Activity of REO and REO nanoemulsion
The diameter of a bacteriostasis ring of REO, REO nanoemulsion and blank nanoemulsion is measured by adopting an agar diffusion method; specifically, the bacteria to be tested are grown on nutrient agar for 18-24 h at 37 ℃. A loop of the culture medium was inoculated to the sterilized medium to prepare a bacterial suspension, and 100. Mu.L of the bacterial suspension was spread on a solid nutrient agar medium. The culture medium is divided into 3 areas, a sterilized 6mm filter paper sheet is placed in the middle of each area, and the culture medium is soaked in REO, blank nanoemulsion, penicillin, rosemary aqueous extract, rosemary alcohol extract (REO with equal amount of REO content) and 10% DMSO solution for 30min respectively, and a culture dish cover is quickly covered. And the dishes were incubated at 37℃for 24h. The diameter of the inhibition zone is measured by a crisscross method, the experiment is repeated 3 times, and an average value is obtained. See FIG. 5, and Table 1;
table 1 shows the results of the bacteriostasis test
Table 1 shows antibacterial results of antibacterial activity of rosemary essential oil nanoemulsion, rosemary essential oil and blank nanoemulsion provided in example 1. The REO and REO nanoemulsions have obvious antibacterial effects on staphylococcus aureus and escherichia coli, have a certain antibacterial effect on staphylococcus epidermidis and candida albicans, and a blank nanoemulsion has no antibacterial ring, so that the blank nanoemulsion has no influence on experimental results.
Fig. 5 is a column of antibacterial experimental results of antibacterial activity of rosemary essential oil nanoemulsion, rosemary essential oil and blank nanoemulsion provided in example 1;
fig. 6 is a photograph of a bacteriostatic activity zone of rosemary essential oil nanoemulsion, rosemary essential oil and blank nanoemulsion provided in example 1, wherein fig. 6 (a) is a graph of bacteriostatic effects of rosemary essential oil nanoemulsion, rosemary essential oil and blank nanoemulsion provided in example 1 on staphylococcus aureus, and fig. 6 (B) is a graph of bacteriostatic effects of rosemary essential oil nanoemulsion, rosemary essential oil and blank nanoemulsion provided in example 1 on escherichia coli; in fig. 6 (a) and 6 (B), 1.Reo nanoemulsion; reo;3 blank nanoemulsion.
From fig. 5 to 6 and table 1, it can be seen that REO and REO nanoemulsions have relatively obvious antibacterial effects on staphylococcus aureus and escherichia coli, and that blank nanoemulsions have no antibacterial ring, which indicates that the blank nanoemulsions have no influence on experimental results.
(6) Cell migration experiments
HEK-a cells were grown at 5X 10 5 After 24h of the cells/wells were seeded in a 6-well plate marked with a back transversal line, vertically scratched with a sterile gun head on the back transversal line, washed 3 times with PBS, and added with serum-free medium and REO 4 mu L, REO nanoemulsion 4 mu L and blank nanoemulsion, respectively, and placed at 37℃with 5% CO 2 Conventional culture is carried out in a constant temperature and constant humidity sterile incubator, and observation photographing is carried out at 12h and 24h. See fig. 7;
fig. 7 is a schematic diagram of rosemary essential oil nanoemulsion, rosemary essential oil and blank nanoemulsion cell migration provided in example 1; wherein, fig. 7 (a) blank nanoemulsion; FIG. 7 (B) REO24 h was added; FIG. 7 (C) REO nanoemulsion was added for 24h, and FIG. 7 (D) value-added rate bar graph;
as can be seen from FIG. 7, scratch experiments were performed using HEK-a cells (human epidermal keratinocytes), 4. Mu.L of REO nanoemulsion was added, and photographs were taken at 12h and 24h, respectively. From the figure, the pitch of the scratches is narrowed, indicating that REO nanoemulsion can promote proliferation of skin cells.
2. Performance test on rosemary essential oil nanoemulsion gel provided in example 4
(1) The external photograph of the rosemary essential oil nanoemulsion gel is shown in fig. 8;
from fig. 8, it can be seen that the finished product is a semi-solid with a relatively flat surface, gloss, clarity, moderate viscosity, and proper smell, and has relatively uniform product, relatively good viscosity, good spreadability, and stable properties.
(2) Skin irritation test
15 adult male healthy mice are taken and divided into REO groups, REO nanoemulsion gel groups and blank groups, REO nanoemulsion and REO nanoemulsion are respectively smeared on the outer sides of left ears of the REO groups and REO nanoemulsion gel groups, the blank groups are not treated, auricle states of the mice are observed every 5min, and photographing and recording are carried out. See FIG. 9
Fig. 9 is a photograph of a rosemary essential oil nanoemulsion gel, rosemary essential oil and blank skin irritation experiment provided in example 4; wherein, fig. 9 (a) blank group; fig. 9 (B) REO group; FIG. 9 (C) REO nanoemulsion gel group
As can be seen from fig. 9, two groups of mice are coated with REO nanoemulsion gel and REO at the same time point, and the eyes of the mice coated with REO are observed and photographed at the same time point, so that the auricle of the mice coated with REO is obviously red and swollen, which indicates that the irritation to skin is obviously reduced after REO is prepared into REO nanoemulsion gel.
(3) Anti-inflammatory experiment
15 adult male healthy mice were divided into a model group, a REO nanoemulsion gel administration group and a blank gel group, and xylene was applied to the outer side of the left ear of the mice, respectively. And (3) after 10min, coating REO nanoemulsion on the left ear of the mice in the administration group, and coating normal saline on the left ear of the mice in the model group as a blank control. The state of the auricle of the mouse was observed every 5min, and recorded by photographing. See fig. 10;
FIG. 10 is an anti-inflammatory photograph of rosemary essential oil nanoemulsion gel, blank gel and model set provided in example 4; wherein, FIG. 10 (A) model set; FIG. 10 (B) blank gel; FIG. 10 (C) REO nanoemulsion gel dosing group
As can be seen from fig. 10, the mice of the REO nanoemulsion administration group and the model group are simultaneously coated with xylene, the mice of the experimental group are coated with REO nanoemulsion gel after 5min, and the mice of the REO nanoemulsion administration group are observed and photographed at the same time point, so that the swelling degree of the mice of the REO nanoemulsion administration group is obviously reduced, which indicates that the REO nanoemulsion has a remarkable anti-inflammatory effect.
The matrix adopted by the invention is carbomer 940 with the concentration of 2.0 percent; the glycerol content is 10%; propylene glycol content 8.4%; the REO nanoemulsion content is 1%, and anti-inflammatory experiments show that REO nanoemulsion gel has a certain anti-inflammatory effect. Skin irritation experiments show that the irritation to skin is obviously reduced after REO is prepared into REO nanoemulsion gel.
In conclusion, the rosemary essential oil nanoemulsion gel provided by the invention is an externally-taken plaster, the rosemary essential oil nanoemulsion gel preparation can reduce the irritation and has good anti-inflammatory effect, the moisture retention, the smell, the aesthetic property and the like are all good, no toxic or side effect or adverse reaction is found in the test, the satisfactory effect is achieved, and the rosemary essential oil nanoemulsion gel preparation has wide application prospect and obvious economic and social benefits.
The rosemary essential oil nanoemulsion gel provided by the invention is of a three-dimensional network structure obtained by swelling hydrophilic polymers by water absorption, and the network skeleton of the rosemary essential oil nanoemulsion gel has good drug carrying capacity, so that drugs can be dispersed in the gel to be slowly and stably released. The gel has the functions of moisturizing, is easy to spread and good in skin feel, and plays an important role in a percutaneous administration system. It has swelling, thixotropic and adhesive properties, so that it can enhance adhesion of nanoemulsion to skin.
The invention mainly utilizes the antibacterial and anti-inflammatory properties of rosemary essential oil, the nanoemulsion is prepared through the design and the adjustment of a formula, and the rosemary essential oil nanoemulsion gel is prepared through selecting a reasonable gel matrix and components, so that the nanoemulsion gel has the advantages of gloss, clarity, moderate viscosity, proper odor, uniformity of a finished product, good viscosity, good spreadability, stable property and capability of effectively adhering to skin, and the anti-inflammatory experiment result shows that the gel preparation prepared from the rosemary essential oil can reduce the irritation and has good anti-inflammatory effect.
The rosemary essential oil nanoemulsion provided by the invention has good thermal stability, cold stability and centrifugal stability, so that the preparation of rosemary essential oil nanoemulsion gel is realized.
While preferred embodiments of the present invention have been described, additional variations and modifications in those embodiments may occur to those skilled in the art once they learn of the basic inventive concepts. It is therefore intended that the following claims be interpreted as including the preferred embodiments and all such alterations and modifications as fall within the scope of the invention.
It will be apparent to those skilled in the art that various modifications and variations can be made to the present invention without departing from the spirit or scope of the invention. Thus, it is intended that the present invention also include such modifications and alterations insofar as they come within the scope of the appended claims or the equivalents thereof.
Claims (4)
1. The preparation method of the rosemary essential oil nanoemulsion gel is characterized by comprising the following raw materials in parts by weight: 1 to 3.5 weight percent of carbomer, 5 to 15 weight percent of glycerol, 5.5 to 10.5 weight percent of propylene glycol, 0.5 to 2.0 weight percent of rosemary essential oil nanoemulsion and the balance of water;
the preparation method of the rosemary essential oil nanoemulsion gel comprises the following steps:
dispersing carbomer in water, swelling, sequentially adding glycerol and propylene glycol, mixing, adding rosemary essential oil nanoemulsion, adding a proper amount of preservative, and mixing uniformly to obtain rosemary essential oil nanoemulsion gel;
the rosemary essential oil nanoemulsion is prepared from the following raw materials in parts by weight: 12-18 wt% of surfactant, 12-18 wt% of cosurfactant, 6.9-13.8 wt% of rosemary essential oil and 55.2-62.1 wt% of water;
the surfactant is polyoxyethylene castor oil, and the cosurfactant is absolute ethyl alcohol.
2. The method for preparing rosemary essential oil nanoemulsion gel according to claim 1, wherein the rosemary essential oil is extracted according to the following steps: dispersing the rosemary coarse powder in 6-10 times of water, and carrying out reflux extraction for 5-8 h by a steam distillation method at the extraction temperature of 100-105 ℃ to obtain rosemary essential oil.
3. The method for preparing rosemary essential oil nanoemulsion gel according to claim 1, wherein the preservative is potassium sorbate.
4. Use of rosemary essential oil nanoemulsion gel according to claim 1 in the preparation of antibacterial and anti-inflammatory drugs.
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Inventor after: Zhang Xuelin Inventor after: Huang Haiying Inventor after: Zhu Yanhui Inventor after: Yu Haiyan Inventor after: Xue Bingquan Inventor after: Li Kang Inventor after: Lv Tiantian Inventor after: Cui Rongqia Inventor before: Huang Haiying Inventor before: Zhu Yanhui Inventor before: Yu Haiyan Inventor before: Xue Bingquan Inventor before: Li Kang Inventor before: Lv Tiantian Inventor before: Cui Rongqia |
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Effective date of registration: 20240112 Address after: No. 330, Yuwang Avenue, Yingchuan Street, Yuzhou City, Xuchang City, Henan Province, 461670 Patentee after: YUZHOU HETONGTAI PHARMACEUTICAL Co.,Ltd. Address before: 450000 No. 1, Jinshui East Road, Jinshui District, Zhengzhou City, Henan Province Patentee before: HENAN University OF CHINESE MEDICINE |