CN113952292A - Rosemary essential oil nanoemulsion gel, preparation method and application thereof - Google Patents

Rosemary essential oil nanoemulsion gel, preparation method and application thereof Download PDF

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CN113952292A
CN113952292A CN202111263335.9A CN202111263335A CN113952292A CN 113952292 A CN113952292 A CN 113952292A CN 202111263335 A CN202111263335 A CN 202111263335A CN 113952292 A CN113952292 A CN 113952292A
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essential oil
rosemary essential
nanoemulsion
rosemary
gel
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CN113952292B (en
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黄海英
朱艳慧
余海艳
薛丙权
李康
吕田田
崔荣洽
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Yuzhou Hetongtai Pharmaceutical Co ltd
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Henan University of Traditional Chinese Medicine HUTCM
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/06Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/53Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/10Dispersions; Emulsions
    • A61K9/107Emulsions ; Emulsion preconcentrates; Micelles
    • A61K9/1075Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10Antimycotics
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention provides rosemary essential oil nanoemulsion gel, and belongs to the technical field of medicaments. The feed is prepared from the following raw materials in percentage by weight: 1-3.5 wt% of carbomer, 5-15 wt% of glycerol, 5.5-10.5 wt% of propylene glycol, 0.5-2.0 wt% of rosemary essential oil nanoemulsion and the balance of water. The rosemary essential oil nanoemulsion gel provided by the invention has the advantages of moisture retention, easiness in spreading and good skin feeling, and plays an important role in a transdermal drug delivery system. Compared with rosemary essential oil products, the prepared gel preparation has small irritation, strong stability and greatly improved bioavailability; it has swelling property, thixotropy and adhesiveness, so that the adhesion of the nanoemulsion to the skin can be enhanced.

Description

Rosemary essential oil nanoemulsion gel, preparation method and application thereof
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, the name of Latin (Rosmarinus officinalis), is a plant shrub of the family Labiatae, the genus Rosmarinus, of the class Dicotyledoneae, prefers warm climates, native European regions and the coast of the Mediterranean region of Africa. Rosemary is documented to be introduced into China in the seventeen West region of the three kingdoms. Rosemary is an important perfume, and its essential oil also has strong anti-inflammatory and antioxidant effects. Rosemary Essential Oil (REO) is a volatile component extracted from Rosemary, and mainly comprises monoterpene, sesquiterpene, etc. At present, REO is mainly applied to the fields of daily chemical industry, food, health care and the like.
REO is colorless to yellowish volatile liquid, has antiinflammatory, antioxidant, antifungal, and cardiovascular protecting effects. However, REO has a more specific odor and is excessively irritating to the skin; the solubility in water is extremely low, the REO is hardly dissolved in water, the storage stability at normal temperature is low, the volatility is high, the stability is weak, and the use of REO products is limited.
At present, in order to improve the bioavailability and stability of essential oil drugs, a nanoemulsion (nanoemulsion) is usually used as a novel drug delivery system, and the nanoemulsion (nanoemulsion) is a homogeneous dispersion system which is composed of oil, water, a surfactant and a cosurfactant, has a particle size of 1-100 nm, has isotropy, is clear and transparent in appearance and is thermodynamically stable. The nanoemulsion as a novel drug-loading 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 concerned and researched in multiple industries such as medicines, cosmetics, foods and the like. In the prior art, the essential oil medicines are prepared into the nanoemulsion, so that the bioavailability of the essential oil medicines can be improved, but the nanoemulsion has strong liquidity 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. The gel has the advantages of moisture retention, easy spreading and good skin feeling, and plays an important role in a transdermal drug delivery system. It has swelling property, thixotropy and adhesiveness, so that the adhesion of the nanoemulsion to the skin can be enhanced.
The first purpose of the invention is to provide rosemary essential oil nanoemulsion gel which is prepared from the following raw materials in parts by weight: 1-3.5 wt% of carbomer, 5-15 wt% of glycerol, 5.5-10.5 wt% of propylene glycol, 0.5-2.0 wt% 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: 12-18 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.
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 polyoxyethylene castor oil, and the cosurfactant is absolute ethyl alcohol.
More preferably, the rosemary essential oil is extracted according to the following steps: dispersing coarse rosemary powder in 6-10 times of water, and performing reflux extraction for 5-8 hours by using a steam distillation method, wherein the extraction temperature is 100-105 ℃, so as to obtain rosemary essential oil.
The second object of the invention provides a preparation method of rosemary essential oil nano-emulsion 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 to obtain the rosemary essential oil nanoemulsion gel.
Preferably, the preservative is potassium sorbate.
The third purpose of the invention is to provide the application of the 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 preparation provided by the invention is a plaster for external use, can reduce irritation, has a good anti-inflammatory effect, is well evaluated in the aspects of moisture retention, smell, aesthetic property and the like, does not find toxic or side effect and adverse reaction in a test, achieves a satisfactory effect, and 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 hydrophilic polymer water absorption swelling, and the network skeleton of the rosemary essential oil nanoemulsion gel has good drug loading capacity, so that drugs can be dispersed in the gel and slowly and stably released. The gel has the advantages of moisture retention, easy spreading and good skin feeling, and plays an important role in a transdermal drug delivery system. It has swelling property, thixotropy and adhesiveness, so that the adhesion of the nanoemulsion to the skin can be enhanced.
The invention mainly utilizes the antibacterial and anti-inflammatory properties of rosemary essential oil, prepares the nanoemulsion through the design and blending of a formula, and selects a reasonable gel matrix and components to obtain the rosemary essential oil nanoemulsion gel.
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 structural diagram of rosemary essential oil nanoemulsion provided by the invention.
Fig. 2 is a photograph showing the appearance of the rosemary essential oil nanoemulsion provided in example 1.
Fig. 3 is a uv full-wavelength scanning curve diagram of the rosemary essential oil nanoemulsion and the rosemary essential oil-free nanoemulsion without rosemary essential oil provided in example 1.
Fig. 4 shows the particle size and polymer dispersibility index of the rosemary essential oil nanoemulsion provided in example 1.
Fig. 5 is a bar of bacteriostatic activity test results of the rosemary essential oil nanoemulsion, the rosemary essential oil and the blank nanoemulsion provided in example 1.
Fig. 6 is a photograph of bacteriostatic activity zones of the rosemary essential oil nanoemulsion, the rosemary essential oil and the blank nanoemulsion provided in example 1.
Fig. 7 is a cell migration diagram of the rosemary essential oil nanoemulsion, the rosemary essential oil and the blank nanoemulsion provided in example 1.
Figure 8 is a photograph of the appearance of the rosemary essential oil nanoemulsion gel provided in example 4.
Fig. 9 is a photograph of the rosemary essential oil nanoemulsion gel, rosemary essential oil and blank set of skin irritation tests provided in example 4.
Fig. 10 is a photograph of rosemary essential oil nanoemulsion gel, blank gel and model group anti-inflammatory provided in example 4.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The invention is further described below with reference to the accompanying drawings and examples.
It should be noted that the reagents and materials used in the following examples are commercially available unless otherwise specified; the experimental methods are all conventional methods unless otherwise specified.
Carbomer 940 is used as carbomer;
the rosemary essential oil adopted in the following embodiments is 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 in a 1000mL round-bottom flask, adding 8 times of distilled water, and performing reflux extraction for 5 hours by a steam distillation method at the extraction temperature of 105 ℃ to obtain rosemary essential oil.
Example 1
A rosemary essential oil nanoemulsion is shown in figure 1 and is prepared from the following raw materials in parts by weight: 15.5 percent of polyoxyethylene castor oil, 15.5 percent of absolute ethyl alcohol, 6.9 percent of rosemary essential oil and 62.1 percent of water.
The rosemary essential oil nanoemulsion is prepared by 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 phase transition on the solution to change the solution from clear to turbid and clear so as to obtain the rosemary essential oil nanoemulsion.
Example 2
The same as example 1 except that rosemary oil 13.8 wt%, water 55.2 wt%; 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 example 1, except that tween 20 was used instead of the polyoxyethylene castor oil, and 1, 2-propanediol was used instead of the absolute ethanol.
Example 4
The rosemary essential oil nanoemulsion gel is prepared from the following raw materials in parts by weight: carbomer 1.0 wt%, glycerin 10 wt%, propylene glycol 8.4 wt%, rosemary essential oil nanoemulsion 1.0 wt% provided in example 1, and the balance water.
The rosemary essential oil nanoemulsion gel is prepared by the following method:
weighing 40.0g of 2.5% carbomer which is completely dissolved, putting the carbomer into a 250mL beaker, adding 60.0mL of water, and uniformly stirring to obtain a phase I; weighing 12.4g of glycerol and 10.4g of propylene glycol, and adding into the phase I under magnetic stirring to obtain a phase II; adding 1.24g of the rosemary essential oil nanoemulsion provided by the embodiment 1 into the phase II, and uniformly stirring to obtain a phase III; adding 0.6% potassium sorbate water solution 3.0g, stirring well to obtain rosemary essential oil nanoemulsion gel, wherein 1ml of the gel preparation is equivalent to REO nanoemulsion containing about 1%.
Example 5
The material is the same as the material in the embodiment 4, except that the material is prepared from the following raw materials in percentage by weight: carbomer 1 wt%, glycerin 5 wt%, propylene glycol 8.4 wt%, rosemary essential oil nanoemulsion 1.0 wt% provided in example 1, and the balance water.
Example 6
The material is the same as the material in the embodiment 4, except that the material is prepared from the following raw materials in percentage by weight: 3.5 wt% of carbomer, 15 wt% of glycerol, 8.4 wt% of propylene glycol, 1.0 wt% of rosemary essential oil nanoemulsion provided in example 1 and the balance of water.
Example 7
The material is the same as the material in the embodiment 4, except that the material is prepared from the following raw materials in percentage by weight: 2.5 wt% of carbomer, 5 wt% of glycerol, 5.5 wt% of propylene glycol, 0.5 wt% of rosemary essential oil nanoemulsion provided in example 1 and the balance of water.
Example 8
The material is the same as the material in the embodiment 4, except that the material is prepared from the following raw materials in percentage by weight: carbomer 1.5 wt%, glycerin 12 wt%, propylene glycol 10.5 wt%, rosemary essential oil nanoemulsion 2.0 wt% provided in example 1, and the balance water.
To illustrate the properties of the rosemary essential oil nanoemulsion and rosemary essential oil nanoemulsion gel provided by the invention, the rosemary essential oil nanoemulsion provided in the example 1 and the rosemary essential oil nanoemulsion gel provided in the example 4 are tested.
Relevant performance tests are carried out on the rosemary essential oil nanoemulsion provided in example 1
(1) The appearance of the REO nanoemulsion, as shown in figure 2,
fig. 2 is a photograph showing the appearance of the rosemary essential oil nanoemulsion provided in example 1, and it can be seen from fig. 2 that the REO nanoemulsion is colorless, clear and transparent and has good fluidity and can generate the tyndall effect. In fig. 2(B), the nanoemulsion is irradiated by a beam of light, so that the beam of light can be clearly seen to pass through the nanoemulsion, further illustrating that the REO nanoemulsion should be colorless, clear and transparent in appearance.
(2) Ultraviolet full wavelength scanning, as shown in FIG. 3
Fig. 3 is a graph of ultraviolet full-wavelength scanning of the rosemary essential oil nanoemulsion and the rosemary essential oil-free nanoemulsion, which are provided in example 1, and specifically shows that absolute ethanol is used as a solvent in the rosemary essential oil nanoemulsion and the rosemary essential oil-free nanoemulsion, and the REO, REO nanoemulsion and blank nanoemulsion are subjected to ultraviolet full-wavelength scanning. As can be seen in FIG. 3, the blank nanoemulsion with the wavelength of 200-400nm has no interference to REO, and simultaneously shows that REO becomes a new substance after being prepared into the REO nanoemulsion.
(3) Particle size and PDI of REO nanoemulsion are shown in FIG. 4
Fig. 4 shows the particle size and Polymer Dispersibility Index (PDI) of the rosemary essential oil nanoemulsion provided in example 1, which is measured by a specific testing method, 100 μ L of prepared REO nanoemulsion is taken, diluted with 900 μ L of ultrapure water, and after 2min of room temperature equilibrium, the particle size and PDI of the REO nanoemulsion are detected by a malvern laser particle size analyzer and repeated for 3 times. As can be seen from FIG. 4, the average particle size of the prepared REO nanoemulsion is 18.43 +/-0.5 nm, and the PDI is 0.086 +/-0.03, which indicates that the particle size meets the requirements and the REO nanoemulsion is uniformly dispersed.
(4) Investigation of stability of REO nanoemulsion
Centrifugal stability
And (3) placing a proper amount of prepared REO nano-emulsion in a centrifuge tube, centrifuging for 15min at 10000rpm, observing the appearance of the REO nano-emulsion, and if the REO nano-emulsion still keeps clear and transparent and no precipitation phenomenon occurs, proving that the centrifugal stability is good.
(ii) thermal stability
Taking appropriate amount of REO nanoemulsion, heating at 40 deg.C, 50 deg.C, 60 deg.C, 70 deg.C, and 80 deg.C for 15min, observing its appearance, and if it is still clear and transparent, and no precipitation occurs, it proves that its thermal stability is good.
Cold stability
And (3) refrigerating a proper amount of REO nano-emulsion at 4 ℃ for 30min, observing the appearance of the REO nano-emulsion, and if the REO nano-emulsion still keeps clear and transparent and no precipitation phenomenon occurs, proving that the cold stability is good.
(5) Antibacterial activity of REO and REO nanoemulsion
Measuring the diameters of the inhibition zones of REO, REO nano-emulsion and blank nano-emulsion by adopting an agar diffusion method; specifically, the test bacteria are grown on nutrient agar for 18-24 hours at 37 ℃. One loop was picked and inoculated into sterilized medium to prepare a bacterial suspension, and 100. mu.L of the bacterial suspension was spread on solid nutrient agar medium. Dividing the culture medium into 3 areas, placing sterilized 6mm filter paper sheets in the middle of each area, soaking in REO, blank nanoemulsion, penicillin, rosemary aqueous extract, rosemary alcohol extract, REO nanoemulsion (equivalent REO in terms of REO content) and 10% DMSO solution for 30min, and rapidly covering the culture dish. And the dishes were incubated at 37 ℃ for 24 h. The diameter of the zone of inhibition was measured by a cross method, the experiment was repeated 3 times, and the average value was taken. See FIG. 5, and Table 1;
table 1 shows the results of the bacteriostatic experiments
Figure BDA0003326227610000081
Table 1 shows the bacteriostatic activity test results of the rosemary essential oil nanoemulsion, the rosemary essential oil and the blank nanoemulsion provided in example 1. It can be seen that REO and REO nanoemulsion have relatively obvious bacteriostatic effects on staphylococcus aureus and escherichia coli, and also have certain bacteriostatic effects on staphylococcus epidermidis and candida albicans, and the blank nanoemulsion has no bacteriostatic circle, which indicates that the blank nanoemulsion has no influence on experimental results.
Fig. 5 is a bar of bacteriostatic activity test results of the rosemary essential oil nanoemulsion, the rosemary essential oil and the blank nanoemulsion provided in example 1;
fig. 6 is a photograph of bacteriostatic activity of the rosemary essential oil nanoemulsion, the rosemary essential oil and the blank nanoemulsion provided in example 1, wherein fig. 6(a) is a diagram of bacteriostatic effect of the rosemary essential oil nanoemulsion, the rosemary essential oil and the blank nanoemulsion provided in example 1 on staphylococcus aureus, and fig. 6(B) is a diagram of bacteriostatic effect of the rosemary essential oil nanoemulsion, the rosemary essential oil and the blank nanoemulsion provided in example 1 on escherichia coli; in fig. 6(a) and 6(B), 1.REO nanoemulsion; 2, REO; 3 blank nanoemulsion.
As can be seen from fig. 5 to 6 and table 1, REO and REO nanoemulsions have a significant bacteriostatic effect on staphylococcus aureus and escherichia coli, while blank nanoemulsions have no bacteriostatic circle, which indicates that blank nanoemulsions have no influence on experimental results.
(6) Cell migration assay
HEK-a cells were cultured at 5X 105After the cells/wells are planted in a 6-well plate marked by a transverse line on the back surface for 24 hours, a sterile gun head is used for vertically scratching the transverse line on the back surface, PBS is used for washing for 3 times, a serum-free culture medium, 4 mu L of REO 4 mu L, REO nano emulsion and blank nano emulsion are respectively added, and the mixture is placed at 37 ℃ and 5% CO2The culture is carried out in a constant-temperature and constant-humidity sterile incubator, and pictures are observed and taken at 12h and 24 h. As shown in FIG. 7;
FIG. 7 is a graph of the cell migration of the rosemary essential oil nanoemulsion, rosemary essential oil and blank nanoemulsion provided in example 1; wherein, fig. 7(a) blank nanoemulsion; FIG. 7(B) addition of REO24 h; FIG. 7(C) addition of REO nanoemulsion for 24h, FIG. 7(D) bar graph of increment rate;
as can be seen from FIG. 7, the scratch test was performed using HEK-a cells (human epidermal keratinocytes), 4. mu.L of REO nanoemulsion was added, and photographs were observed at 12h and 24h, respectively. As can be seen, the spacing of the scratches becomes narrower, indicating that REO nanoemulsion can promote the proliferation of skin cells.
Secondly, relevant performance tests are carried out on the rosemary essential oil nanoemulsion gel provided in the example 4
(1) A photograph of the appearance of rosemary essential oil nanoemulsion gel, shown in fig. 8;
as can be seen from FIG. 8, the obtained product is semisolid with smooth surface, luster, clarity, moderate viscosity, appropriate odor, uniform product, good viscosity, good spreadability, and stable property.
(2) Skin irritation test
Taking 15 adult male healthy mice, dividing the mice into an REO group, an REO nanoemulsion gel group and a blank group, respectively coating REO and REO nanoemulsion on the outer sides of the left ears of the mice in the REO group and the REO nanoemulsion gel group, wherein the blank group is not treated, observing the auricle state of the mice every 5min, and taking a picture for recording. As shown in FIG. 9
FIG. 9 is a photograph of the skin irritation test of the rosemary essential oil nanoemulsion gel, the rosemary essential oil and the blank group provided in example 4; among them, FIG. 9(A) blank group; FIG. 9(B) REO group; FIG. 9(C) REO nanoemulsion gel set
As can be seen from fig. 9, when two groups of mice were simultaneously coated with REO nanoemulsion gel and REO and photographed at the same time point, it can be seen that auricles of the mice coated with REO are 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 assay
15 adult male healthy mice were divided into a model group, an REO nanoemulsion gel administration group and a blank gel group, and xylene was applied to the outer side of the left ear of each mouse. After 10min, the REO nanoemulsion is smeared on the left ear of the mouse in the administration group, and the physiological saline is smeared on the left ear of the mouse in the model group to serve as a blank control. The auricle status of the mice was observed every 5min and recorded by photographing. As shown in FIG. 10;
fig. 10 is a photograph of rosemary essential oil nanoemulsion gel, blank gel and model group anti-inflammatory provided in example 4; FIG. 10(A) is a set of models; FIG. 10(B) blank gel; FIG. 10(C) REO nanoemulsion gel administration group
As can be seen from fig. 10, the REO nanoemulsion administration group and the model group mice are simultaneously coated with xylene, after 5min, the experimental group mice are coated with REO nanoemulsion gel, and the images are observed and photographed at the same time point, so that the swelling degree of the REO nanoemulsion administration group mice is obviously reduced, which indicates that the REO nanoemulsion has an obvious anti-inflammatory effect.
The matrix adopted by the invention is 2.0 percent of carbomer 940; the content of glycerin is 10%; the propylene glycol content was 8.4%; the content of REO nanoemulsion is 1%, and an anti-inflammatory experiment shows that the REO nanoemulsion gel has a certain anti-inflammatory effect. Skin irritation experiments show that the irritation to the skin is obviously reduced after the REO is prepared into the REO nano-emulsion gel.
In conclusion, the rosemary essential oil nanoemulsion gel provided by the invention is a plaster for external use, can reduce irritation, has a good anti-inflammatory effect, is well commented on the aspects of moisture retention, smell, aesthetic property and the like, does not find toxic or side effect and adverse reaction in a test, achieves a satisfactory effect, and 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 hydrophilic polymer water absorption swelling, and the network skeleton of the rosemary essential oil nanoemulsion gel has good drug loading capacity, so that drugs can be dispersed in the gel and slowly and stably released. The gel has the advantages of moisture retention, easy spreading and good skin feeling, and plays an important role in a transdermal drug delivery system. It has swelling property, thixotropy and adhesiveness, so that the adhesion of the nanoemulsion to the skin can be enhanced.
The invention mainly utilizes the antibacterial and anti-inflammatory properties of rosemary essential oil, prepares the nanoemulsion through the design and blending of a formula, and selects a reasonable gel matrix and components to obtain the rosemary essential oil nanoemulsion gel.
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. Therefore, it is intended that the appended claims be interpreted as including 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 changes and modifications may be made in the present invention without departing from the spirit and scope of the invention. Thus, if such modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include such modifications and variations.

Claims (8)

1. The rosemary essential oil nanoemulsion gel is characterized by being prepared from the following raw materials in parts by weight: 1-3.5 wt% of carbomer, 5-15 wt% of glycerol, 5.5-10.5 wt% of propylene glycol, 0.5-2.0 wt% of rosemary essential oil nanoemulsion and the balance of water.
2. Rosemary essential oil nanoemulsion gel according to claim 1, wherein the rosemary essential oil nanoemulsion is prepared from the following raw materials in weight ratio: 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.
3. Rosemary essential oil nanoemulsion gel according to claim 2, wherein the surfactant is one or more of tween 80, tween 20, cremophor; the cosurfactant is one or more of 1, 2-propylene glycol, polyethylene glycol 400 and absolute ethyl alcohol.
4. Rosemary essential oil nanoemulsion gel according to claim 3, wherein the surfactant is polyoxyethylated castor oil and the co-surfactant is absolute ethanol.
5. Rosemary essential oil nanoemulsion gel according to claim 2, wherein the rosemary essential oil was extracted according to the following steps: dispersing coarse rosemary powder in 6-10 times of water, and performing reflux extraction for 5-8 hours by using a steam distillation method, wherein the extraction temperature is 100-105 ℃, so as to obtain rosemary essential oil.
6. A method of preparing rosemary essential oil nanoemulsion gel as claimed in claim 1, comprising 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 to obtain the rosemary essential oil nanoemulsion gel.
7. A method of preparing a rosemary essential oil nanoemulsion gel according to claim 6, wherein the preservative is potassium sorbate.
8. Use of rosemary essential oil nanoemulsion gel as claimed in claim 1 for anti-bacterial and anti-inflammatory purposes.
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