CN115414320A - 1,8-eucalyptol nanoemulsion gel with antifungal effect - Google Patents
1,8-eucalyptol nanoemulsion gel with antifungal effect Download PDFInfo
- Publication number
- CN115414320A CN115414320A CN202211117548.5A CN202211117548A CN115414320A CN 115414320 A CN115414320 A CN 115414320A CN 202211117548 A CN202211117548 A CN 202211117548A CN 115414320 A CN115414320 A CN 115414320A
- Authority
- CN
- China
- Prior art keywords
- eucalyptol
- nanoemulsion
- gel
- skin
- antifungal effect
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 229960005233 cineole Drugs 0.000 title claims abstract description 107
- 239000007908 nanoemulsion Substances 0.000 title claims abstract description 86
- 230000000843 anti-fungal effect Effects 0.000 title claims abstract description 19
- WEEGYLXZBRQIMU-UHFFFAOYSA-N Eucalyptol Chemical compound C1CC2CCC1(C)OC2(C)C WEEGYLXZBRQIMU-UHFFFAOYSA-N 0.000 claims abstract description 39
- 238000002360 preparation method Methods 0.000 claims abstract description 25
- 239000004094 surface-active agent Substances 0.000 claims abstract description 14
- 239000004064 cosurfactant Substances 0.000 claims abstract description 9
- 238000002156 mixing Methods 0.000 claims description 16
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol group Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 12
- 239000011159 matrix material Substances 0.000 claims description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 239000008367 deionised water Substances 0.000 claims description 6
- 229910021641 deionized water Inorganic materials 0.000 claims description 6
- 239000012752 auxiliary agent Substances 0.000 claims description 5
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical group [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims description 4
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical group [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 4
- 239000002738 chelating agent Substances 0.000 claims description 4
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 claims description 4
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 claims description 4
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 claims description 4
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical group CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 claims description 4
- 239000003906 humectant Substances 0.000 claims description 4
- 239000003755 preservative agent Substances 0.000 claims description 4
- 230000002335 preservative effect Effects 0.000 claims description 4
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 4
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 4
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 3
- 239000004359 castor oil Substances 0.000 claims description 3
- 235000019438 castor oil Nutrition 0.000 claims description 3
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 claims description 3
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 3
- -1 polyoxyethylene Polymers 0.000 claims description 3
- 239000013543 active substance Substances 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims description 2
- 238000000034 method Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 28
- 230000000694 effects Effects 0.000 abstract description 14
- 230000008021 deposition Effects 0.000 abstract description 9
- 230000009471 action Effects 0.000 abstract description 7
- 230000008901 benefit Effects 0.000 abstract description 6
- 239000002674 ointment Substances 0.000 abstract description 6
- 206010059866 Drug resistance Diseases 0.000 abstract description 5
- 206010017533 Fungal infection Diseases 0.000 abstract description 4
- 208000024386 fungal infectious disease Diseases 0.000 abstract description 4
- 208000031888 Mycoses Diseases 0.000 abstract description 3
- 230000008685 targeting Effects 0.000 abstract description 3
- 229940124350 antibacterial drug Drugs 0.000 abstract 1
- 239000000499 gel Substances 0.000 description 62
- 210000003491 skin Anatomy 0.000 description 53
- 238000000338 in vitro Methods 0.000 description 16
- 241000700159 Rattus Species 0.000 description 13
- 210000001519 tissue Anatomy 0.000 description 9
- 230000000844 anti-bacterial effect Effects 0.000 description 7
- 210000004207 dermis Anatomy 0.000 description 7
- 238000012360 testing method Methods 0.000 description 6
- 241001045770 Trichophyton mentagrophytes Species 0.000 description 5
- 230000006399 behavior Effects 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 4
- 241000893980 Microsporum canis Species 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 229940044949 eucalyptus oil Drugs 0.000 description 4
- 239000010642 eucalyptus oil Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000012466 permeate Substances 0.000 description 4
- 241001480043 Arthrodermataceae Species 0.000 description 3
- WEEGYLXZBRQIMU-WAAGHKOSSA-N Eucalyptol Chemical compound C1C[C@H]2CC[C@]1(C)OC2(C)C WEEGYLXZBRQIMU-WAAGHKOSSA-N 0.000 description 3
- 241000893976 Nannizzia gypsea Species 0.000 description 3
- 230000037304 dermatophytes Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 210000000434 stratum corneum Anatomy 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 208000007163 Dermatomycoses Diseases 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- 241000243190 Microsporidia Species 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000009395 breeding Methods 0.000 description 2
- 230000001488 breeding effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 210000002808 connective tissue Anatomy 0.000 description 2
- 201000003929 dermatomycosis Diseases 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000003640 drug residue Substances 0.000 description 2
- 210000002615 epidermis Anatomy 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 230000010494 opalescence Effects 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 231100000245 skin permeability Toxicity 0.000 description 2
- 125000002006 1,8-cineol group Chemical group 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 206010003399 Arthropod bite Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000282465 Canis Species 0.000 description 1
- 241000905957 Channa melasoma Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 208000001840 Dandruff Diseases 0.000 description 1
- 241001480035 Epidermophyton Species 0.000 description 1
- 241001480037 Microsporum Species 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 206010039509 Scab Diseases 0.000 description 1
- 241000447727 Scabies Species 0.000 description 1
- 206010053262 Skin swelling Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000223238 Trichophyton Species 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000005352 clarification Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000032798 delamination Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 206010048282 zoonosis Diseases 0.000 description 1
Images
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
-
- 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
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Dermatology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biophysics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Molecular Biology (AREA)
- Dispersion Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cosmetics (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
The invention discloses a 1,8-eucalyptol nanoemulsion gel with an antifungal effect, and relates to the field of antibacterial drug preparation; the formula comprises the following components in percentage by volume: 10 to 15 percent of 1,8-cineole, 1 to 3 percent of tackifier, 8 to 12 percent of surfactant and 2 to 3 percent of cosurfactant; the nanoemulsion gel penetrates the skin, so that 1,8-eucalyptol enters the skin, the problems that an ointment medicine stays in a skin cuticle layer, the medicine is wiped off by clothes, the action time of the medicine is shortened, foreign matters are polluted are solved, a protection device is not required to be additionally arranged, the effect of continuous action of the medicine is achieved, the administration is convenient, 1,8-eucalyptol penetrates the skin through the nanoemulsion gel, the deposition amount of the medicine in the skin is improved, the nanoemulsion gel acts on a superficial skin fungus infection position, and has targeting effect on the skin, and the effect of treating superficial skin mycosis is achieved; has the advantages of no residue, no drug resistance and the like.
Description
Technical Field
The invention relates to the field of antibacterial medicine preparation, and in particular relates to a 1,8-eucalyptol nanoemulsion gel with an antifungal effect.
Background
Superficial dermatomycosis is a kind of contagious zoonosis with strong infection ability caused by dermatophyte. The dermatophytes causing the diseases mainly comprise microsporum, trichophyton and epidermophyton. After the host is infected, the symptoms of dandruff increase, hair loss, scabbing, pruritus and the like can appear, secondary bacterial and parasitic infection is easy to occur, the health and the growth performance of animals are seriously influenced, huge economic loss is caused to the breeding industry, and the health of breeding producers is seriously threatened while the animals are harmed because the disease is an infectious disease which is shared by human and livestock. As chemically synthesized drugs and antibiotics are gradually limited and forbidden due to the development of drug resistance and severe drug residues; the traditional Chinese medicine market is developed.
In conclusion, the current superficial skin mycosis treatment process has the following technical problems: 1,8-cineole is the main component of eucalyptus oil, is a colorless liquid, has remarkable antibacterial effect, and has good antibacterial effect on trichophyton mentagrophytes, microsporum canis, microsporum gypseum and other fungi. But 1,8-eucalyptol has poor water solubility and volatility, and the retention time in the skin layer is too short, which is not beneficial to the treatment of dermatophytes; at present, 1,8-eucalyptol preparations related to the treatment of skin diseases mainly comprise solutions, oils, ointments and the like, such as eucalyptus oil solutions for the treatment of animal scabies and mite diseases, eucalyptus oil for the treatment of skin swelling and pain caused by mosquito bites, eucalyptus oil urea ointments for the treatment of rhagadia manus et pedis and the like. The preparation process of each preparation is mature, but certain disadvantages still exist, for example, the solution preparation belongs to a liquid preparation, but the liquid preparation has the disadvantages of large dispersion degree of the medicine, poorer chemical stability, easy decomposition failure of the medicine, easy mildewing and rancidity, unstable tendency of heterogeneous liquid medicine, large volume, inconvenient carrying, transportation and storage and the like; the oil agent has mild action and low irritation, but has poor adhesion; the ointment is uneven in coating, easy to rub off, easy to stay in the horny layer of the skin, poor in using effect, strong in infectivity of superficial dermatomycosis, serious in harm, and the currently commonly used antibiotic treatment has the problems of drug residues, serious drug resistance and the like.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides a 1,8-eucalyptol nanoemulsion gel with an antifungal effect, which solves the problems of inconvenience in medication, volatility, incapability of staying on a large number of skin layers and the like in direct use of 1,8-eucalyptol based on the properties, biological activity, production practice use characteristics and other factors of 1,8-eucalyptol.
In order to achieve the technical purpose and achieve the technical effect, the invention is realized by the following technical scheme:
a1,8-eucalyptol nanoemulsion gel with antifungal effect comprises the following components by volume percent:
10-15% of 1,8-cineole, 1-3% of tackifier, 8-12% of surfactant, 2-3% of cosurfactant and 70-75% of auxiliary agent.
Preferably, the volume percentage of 1,8-eucalyptol is 12.1%, the volume percentage of tackifier is 1.5%, the volume percentage of surfactant is 10.08%, the volume percentage of cosurfactant is 2.52%, and the volume percentage of adjuvant is 73.8%.
Preferably, the auxiliary agent is other preparations which can be added in the prescription in a pharmaceutically acceptable way, and the auxiliary agent comprises a preservative, a chelating agent and a humectant.
Preferably, the viscosity increasing agent is sodium carboxymethyl cellulose.
Preferably, the surfactant is polyoxyethylene castor oil EL-35.
Preferably, the cosurfactant is absolute ethyl alcohol.
Preferably, the preservative is ethylparaben; the ratio of ethylparaben to 1,8-eucalyptol is 0.2g:100ml.
Preferably, the chelating agent is disodium edetate; the ratio of the disodium ethylene diamine tetraacetate to the 1,8-cineole is 0.02g:100ml.
Preferably, the humectant is glycerol; the ratio of the glycerol to the 1,8-cineole is 8ml:100ml.
A preparation method of 1,8-eucalyptol nanoemulsion gel with antifungal effect comprises the following steps:
s1: mixing the tackifier and deionized water according to the proportion, standing for 24 hours to enable the mixture to be fully swelled to obtain a gel matrix;
s2: mixing a surfactant and a cosurfactant according to a ratio to obtain a mixed surfactant;
s3: mixing the mixed expression active agent with 1,8-cineole according to the proportion to obtain 1,8-cineole nanoemulsion system;
s4: mixing the 1,8-eucalyptol nanoemulsion system obtained in the step S3 with deionized water according to a ratio to obtain 1,8-eucalyptol nanoemulsion;
s5: mixing the gel matrix in the S1 with 1,8-cineole nanoemulsion according to the proportion to obtain 1,8-cineole nanoemulsion gel.
The invention has the beneficial effects that:
a1,8-eucalyptol nanoemulsion gel with antifungal effect is in the form of semisolid preparation, has no toxic and side effects in preparation substances and contents, and is safe to human, animals and environment; the 1,8-eucalyptol nanoemulsion gel is prepared by basic mixing operation at normal temperature, the preparation process is simple, the prepared 1,8-eucalyptol nanoemulsion gel is smeared on an affected part, the nanoemulsion gel permeates skin, 1,8-eucalyptol enters skin, the problems that ointment medicine stays at the cuticle layer of the skin, the medicine is wiped off by clothes, the action time of the medicine is shortened, and foreign matters are polluted are solved, a protection device is not required to be additionally arranged, the effect of medicine continuous action is achieved, the administration is convenient, 1,8-eucalyptol permeates the skin by the nanoemulsion gel, the deposition amount of the medicine in the skin is improved, the medicine acts on the superficial skin fungus infection position, the targeting effect is achieved, and the effect of treating superficial skin mycosis is achieved; has the advantages of no residue, no drug resistance and the like.
Of course, it is not necessary for any product in which the invention is practiced to achieve all of the above-described advantages at the same time.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art that other drawings can be obtained according to the drawings without creative efforts.
FIG. 1 is Qn-T curve of isolated rat skin of 1,8-eucalyptol nanoemulsion gel and 1,8-eucalyptol according to the embodiment of the present invention;
FIG. 2 shows the deposition of 1,8-eucalyptol nanoemulsion gel and 1,8-eucalyptol in skin at 12h of example 12;
FIG. 3 is a section of skin HE stained tissue from a drug-administered portion of rats collected from a placebo group according to an embodiment of the invention;
FIG. 4 is a tissue section of HE stained skin after treatment of 1,8-eucalyptol group for 2 hours according to an embodiment of the present invention;
FIG. 5 is a section of skin HE stained tissue after treatment of the 1,8-eucalyptol group for 6 hours according to an embodiment of the present invention;
FIG. 6 is a sample of the 1,8-eucalyptol group after 12h treatment of skin HE stained tissue sections according to an embodiment of the present invention;
FIG. 7 is a 1,8-eucalyptol nanoemulsion gel set treated for 2h with skin HE stained tissue sections according to an embodiment of the present invention;
FIG. 8 is a 1,8-eucalyptol nanoemulsion gel set of the present invention, processed for 6h and then processed into skin HE stained tissue sections;
fig. 9 is a 1,8-eucalyptol nanoemulsion gel set treated for 12h and then processed into skin HE stained tissue sections according to the embodiment of the invention.
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.
Example 1
(1) Preparation of gel matrix: and (3) dissolving 1.5g of sodium carboxymethylcellulose in 10mL of deionized water, and standing for 24h to fully swell the sodium carboxymethylcellulose to obtain the gel matrix.
(2) Preparation of mixed surfactant: and uniformly mixing the polyoxyethylene castor oil EL-3510.08mL and 2.52mL of absolute ethyl alcohol to obtain the mixed surfactant.
(3) 1,8-preparation of eucalyptol nanoemulsion System: mixing 12.6mL of mixed surfactant with 1,8-eucalyptol 12.1mL to obtain 1,8-eucalyptol nanoemulsion system.
(4) 1,8-preparation of eucalyptol nanoemulsion: and (3) dropwise mixing the 1,8-eucalyptol nanoemulsion system with deionized water until the total volume is 80mL to obtain 1,8-eucalyptol nanoemulsion.
(5) 1,8-preparation of eucalyptol nanoemulsion gel: and (3) fully and uniformly mixing the gel matrix obtained in the step (1) and the 1,8-eucalyptol nanoemulsion obtained in the step (4) to obtain 1,8-eucalyptol nanoemulsion gel.
Through detection, the nano-emulsion gel is a clear and semitransparent semisolid with light blue opalescence, and the dispersity, the particle size, the pH value, the viscosity and the content are all qualified.
The following pharmacodynamic tests were performed on the nanoemulsion gel prepared in example 1;
the 1,8-eucalyptol nanoemulsion gel and 1,8-eucalyptol prepared in the example 1 respectively study the in vitro antibacterial activity of trichophyton mentagrophytes, microsporum gypseum and microsporum canis;
table 1 results of the detection of the minimum inhibitory concentration:
note: the minimum inhibitory concentration is 1,8-eucalyptol content.
The results of the in vitro antibacterial activity of 1,8-eucalyptol nano-emulsion gel and 1,8-eucalyptol prepared in example 1 on 3 kinds of fungi are shown in table 1, the 1,8-eucalyptol nano-emulsion gel has an antibacterial effect on trichophyton mentagrophytes, microsporidia gypseum and microsporidia canis, and the nano-emulsion gel does not destroy the antibacterial effect of 1,8-eucalyptol medicine; after 1,8-eucalyptol is prepared into the nanoemulsion gel in the embodiment 1 according to the proportion, the bacteriostatic effect on trichophyton mentagrophytes, microsporum gypseum and microsporum canis is obviously better than that of 1,8-eucalyptol.
Example 2
In-vitro transdermal test of skin permeability of 1,8-eucalyptol nanoemulsion gel prepared in example 1;
in vitro transdermal tests of 1,8-eucalyptol nanoemulsion gel and 1,8-eucalyptol prepared in example 1 are carried out by adopting a Franz diffusion cell, and the transdermal penetration of 1,8-eucalyptol and 1,8-eucalyptol in 1,8-eucalyptol nanoemulsion gel within 12h is detected by taking 1,8-eucalyptol content as a detection index.
Table 21,8-eucalyptol nanoemulsion gels and 1,8-eucalyptol in vitro rat skin transdermal absorption parameters:
at 12h in fig. 2, 1,8-eucalyptol nanoemulsion gel was <0.05 and P <0.01 compared to 1,8-eucalyptol group.
The results can be seen from fig. 1 and table 2, the permeability of 1,8-eucalyptol nanoemulsion gel (450.85 mug/cm 2/h) is less than that of 1,8-eucalyptol (672.45 mug/cm 2/h), and the cumulative permeability per unit area of the two also shows obvious regularity between 4 and 12 h: 1,8-eucalyptol nanoemulsion gel <1,8-eucalyptol. The results show that the preparation of the nanoemulsion gel can reduce the transdermal penetration of 1,8-eucalyptol.
Then, 1,8-eucalyptol nanoemulsion gel and 1,8-eucalyptol transdermal permeation mechanisms are further discussed, and a zero-order kinetic model, a first-order kinetic model and a Higuchi model are adopted to fit the in-vitro skin permeation behaviors of the gel and the in-vitro skin permeation mechanisms, and the results are shown in the following table 3;
table 31,8-eucalyptol nanoemulsion gel and 1,8-eucalyptol ex vivo skin permeation curve fit results:
1,8-eucalyptol in vitro skin permeation behavior fitting results show that the value of a regression equation R2 of a zero order kinetic model is the largest, which indicates that 1,8-eucalyptol in vitro skin permeation behavior conforms to the zero order kinetic model; the fitting result of the in vitro skin permeation behavior of the 1,8-eucalyptol nanoemulsion gel prepared in the example 1 shows that the regression equation R2 value of the first-order kinetic model is the largest, which shows that the in vitro skin permeation behavior of the 1,8-eucalyptol nanoemulsion gel prepared in the example 1 accords with the first-order kinetic model, and the preparation of the nanoemulsion gel can change the in vitro skin permeation mechanism of 1,8-eucalyptol.
Example 3
The 1,8-eucalyptol nanoemulsion gel prepared in the embodiment 1 is used for detecting the deposition amount in the skin permeability;
the 1,8-eucalyptol nanoemulsion gel and 1,8-eucalyptol prepared in example 1 with the same volume are coated on the surface of in-vitro skin, and the content of 1,8-eucalyptol in the skin is measured 12 hours after the skin is treated in a Franz diffusion pool. The results are shown in FIG. 2 and Table 4 below;
table 41,8-eucalyptol nanoemulsion gel and 1,8-eucalyptol deposition in vitro skin test results:
note: p <0.05, P <0.01 compared to 1,8-cineole group.
1,8-eucalyptol nanoemulsion gel has a drug deposition amount in skin of 1455.662 + -442.514 μ g/cm2;1,8-eucalyptol is deposited in the skin in an amount of 212.650 + -137.699 mug/cm 2. The result shows that compared with 1,8-cineole, the 1,8-cineole nano-emulsion gel has obviously improved deposition amount in skin (P is less than 0.01). The preparation of the nanoemulsion gel significantly increased the amount of 1,8-eucalyptol deposited in the skin.
Example 4
Histological observation of rat skin treated with 1,8-eucalyptol nanoemulsion gel and 1,8-eucalyptol prepared in example 1
Selecting 9 healthy rats, and dividing each group into 1,8-eucalyptol nanoemulsion gel group, 1,8-eucalyptol group and normal saline group, wherein each group comprises 3 healthy rats. The rats in each group are respectively coated with the same volume of medicine, and one rat is randomly selected for 2h, 6h and 12h respectively to collect the skin of the medicine-feeding part for HE staining observation.
3-9, 12h, HE stained tissue sections of rat skin treated with 1,8-eucalyptol and 1,8-eucalyptol nanoemulsion gels, "→" pointed at the stratum corneum; "Green arrow" points to the epidermal layer; the "purple arrow" points to the dermis.
The results are shown in fig. 3, and from fig. 3, the structures of the skin layers of the rats in the blank control group are clear, and the stratum corneum, the epidermis layer and the dermis layer are clear and compact; the structure of the horny layer is complete; no inflammatory cell infiltration was seen in the dermis; the skin accessory structure is normal; connective tissues in the dermis are distributed compactly and orderly.
Compared with a blank control group, in the 1,8-eucalyptol group, within 12h, the cuticle layer is loosened and layered and is irregularly curled, gaps between inner layers of the cuticle layer are enlarged, and meanwhile, a part of the cuticle layer is broken; irregular collagen fiber bundle cracks appear in the dermis; as treatment time was extended, crevices in the dermal layer became more pronounced (fig. 4-6); the rat skin layers treated with the 1,8-eucalyptol nanoemulsion gel groups of 2h and 6h are clear and complete in structure, inflammatory cells are not infiltrated in the dermis layer, and the skin accessory structure is normal (fig. 7 and 8); after 12h of treatment, the 1,8-eucalyptol nanoemulsion gel group rats showed local loose delamination of the stratum corneum (fig. 9);
compared with the 1,8-eucalyptol group, the 1,8-eucalyptol nanoemulsion gel group has the advantage that the cuticle tissue and the dermis layer connective tissue of the skin of the rats are firmer.
In conclusion, the 1,8-eucalyptol nanoemulsion gel with the antifungal effect is a semisolid preparation, has no toxic or side effect when participating in preparation of substances and contents, and is safe to human, animals and the environment; the 1,8-eucalyptol nanoemulsion gel is prepared by basic mixing operation at normal temperature, the preparation process is simple, the prepared 1,8-eucalyptol nanoemulsion gel is smeared on an affected part, the nanoemulsion gel permeates skin, 1,8-eucalyptol enters skin, the problems that ointment medicine stays at the cuticle layer of the skin, the medicine is wiped off by clothes, the action time of the medicine is shortened, and foreign matters are polluted are solved, a protection device is not required to be additionally arranged, the effect of medicine continuous action is achieved, the administration is convenient, 1,8-eucalyptol permeates the skin by the nanoemulsion gel, the deposition amount of the medicine in the skin is improved, the medicine acts on the superficial skin fungus infection position, the targeting effect is achieved, and the effect of treating superficial skin mycosis is achieved; has the advantages of no residue, no drug resistance and the like; the nano-emulsion gel prepared by the invention has the advantages of uniform dispersion of main drugs, bluish opalescence, clarification and translucency, convenient administration, long-lasting effect, small toxic and side effects, accordance with the requirements of Chinese pharmacopoeia and controllable quality; the in vitro bacteriostasis test and in vitro transdermal test research show that the invention has obvious inhibiting effect on trichophyton mentagrophytes, gypsum-like microspores and microsporum canis and can obviously improve the deposition amount of the invention on the skin layer.
In the description herein, references to the description of "one embodiment," "an example," "a specific example" or the like are intended to mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above do not necessarily refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
The preferred embodiments of the invention disclosed above are intended to be illustrative only. The preferred embodiments are not intended to be exhaustive or to limit the invention to the precise embodiments disclosed. Obviously, many modifications and variations are possible in light of the above teaching. The embodiments were chosen and described in order to best explain the principles of the invention and the practical application, to thereby enable others skilled in the art to best utilize the invention. The invention is limited only by the claims and their full scope and equivalents.
Claims (10)
1. A1,8-eucalyptol nanoemulsion gel with antifungal effect is characterized in that: the formula comprises the following components in percentage by volume: 10-15% of 1,8-cineole, 1-3% of tackifier, 8-12% of surfactant, 2-3% of cosurfactant and 70-75% of auxiliary agent.
2. The 1,8-eucalyptol nanoemulsion gel with antifungal effect of claim 1, wherein: according to the volume percentage, 1,8-eucalyptol accounts for 12.1%, tackifier accounts for 1.5%, surfactant accounts for 10.08%, cosurfactant accounts for 2.52% and adjuvant accounts for 73.8%.
3. The 1,8-eucalyptol nanoemulsion gel with antifungal effect of claim 1, wherein: the auxiliary agent is other preparations which can be added in the formula pharmaceutically, and comprises a preservative, a chelating agent and a humectant.
4. The 1,8-eucalyptol nanoemulsion gel with antifungal effect of claim 1, wherein: the tackifier is sodium carboxymethyl cellulose.
5. The 1,8-eucalyptol nanoemulsion gel with antifungal effect of claim 1, wherein: the surfactant is polyoxyethylene castor oil EL-35.
6. The 1,8-eucalyptol nanoemulsion gel with antifungal effect of claim 1, wherein: the cosurfactant is absolute ethyl alcohol.
7. The 1,8-eucalyptol nanoemulsion gel with antifungal effect of claim 3, wherein: the preservative is ethylparaben; the ratio of the ethylparaben to the 1,8-eucalyptol is 0.2g:100ml.
8. The 1,8-eucalyptol nanoemulsion gel with antifungal effect of claim 3, wherein: the chelating agent is disodium ethylene diamine tetraacetate; the ratio of the disodium ethylene diamine tetraacetate to the 1,8-cineole is 0.02g:100ml.
9. The 1,8-eucalyptol nanoemulsion gel with antifungal effect of claim 3, wherein: the humectant is glycerol; the ratio of the glycerol to the 1,8-cineole is 8ml:100ml.
10. A method for preparing the 1,8-eucalyptol nanoemulsion gel with antifungal effect of claim 1, which is characterized by comprising the following steps: comprises the following steps;
s1: mixing the tackifier and deionized water according to the proportion, standing for 24 hours to fully swell the mixture to obtain a gel matrix;
s2: mixing a surfactant and a cosurfactant according to a ratio to obtain a mixed surfactant;
s3: mixing the mixed expression active agent with 1,8-cineole according to the proportion to obtain 1,8-cineole nanoemulsion system;
s4: mixing the 1,8-eucalyptol nanoemulsion system obtained in the step S3 with deionized water according to a ratio to obtain 1,8-eucalyptol nanoemulsion;
s5: mixing the gel matrix in the S1 with 1,8-cineole nanoemulsion according to the proportion to obtain 1,8-cineole nanoemulsion gel.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202211117548.5A CN115414320A (en) | 2022-09-14 | 2022-09-14 | 1,8-eucalyptol nanoemulsion gel with antifungal effect |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202211117548.5A CN115414320A (en) | 2022-09-14 | 2022-09-14 | 1,8-eucalyptol nanoemulsion gel with antifungal effect |
Publications (1)
Publication Number | Publication Date |
---|---|
CN115414320A true CN115414320A (en) | 2022-12-02 |
Family
ID=84202924
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202211117548.5A Pending CN115414320A (en) | 2022-09-14 | 2022-09-14 | 1,8-eucalyptol nanoemulsion gel with antifungal effect |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN115414320A (en) |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2004283431A1 (en) * | 2003-10-10 | 2005-05-06 | Antares Pharma Ipl Ag | Transdermal pharmaceutical formulation for minimizing skin residues |
CN101941075A (en) * | 2009-07-03 | 2011-01-12 | 北京印刷学院 | Synthetic method of antibacterial agent containing nano-silver |
CN112263542A (en) * | 2020-10-19 | 2021-01-26 | 澳美制药厂有限公司 | Desonide nanoemulsion gel composition and preparation method thereof |
-
2022
- 2022-09-14 CN CN202211117548.5A patent/CN115414320A/en active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2004283431A1 (en) * | 2003-10-10 | 2005-05-06 | Antares Pharma Ipl Ag | Transdermal pharmaceutical formulation for minimizing skin residues |
CN101941075A (en) * | 2009-07-03 | 2011-01-12 | 北京印刷学院 | Synthetic method of antibacterial agent containing nano-silver |
CN112263542A (en) * | 2020-10-19 | 2021-01-26 | 澳美制药厂有限公司 | Desonide nanoemulsion gel composition and preparation method thereof |
Non-Patent Citations (1)
Title |
---|
LIXIA LI等: "Preparation, characterization,ex vivo transdermal properties and skin irritation evaluation of 1,8-cineole nanoemulsion gel", 《INTERNATIONAL JOURNAL OF PHARMACEUTICS》, vol. 624, pages 1 - 12 * |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US8333981B2 (en) | Antifungal treatment of nails | |
RU2538729C2 (en) | Using alpha 2 adrenergic receptor agonists for treating or preventing psoriasis | |
CN105848719A (en) | Anti-infective methods, compositions, and devices | |
CN102065851A (en) | Nanoemulsions for treating fungal, yeast and mold infections | |
CN104306358B (en) | Antipruritic scar liniment of dispelling | |
EP1450771B1 (en) | Pharmaceutical preparations useful for treating lesions of the skin and the mucous membranes and methods and kits using same | |
CN108888646B (en) | Wormwood paste and preparation method thereof | |
CN104983675B (en) | A kind of Tretinoin ethosome gel and preparation method thereof | |
CN101129378A (en) | Medicament spraying agent used for accelerating growth of hair | |
CN116637069B (en) | Honokiol liposome transdermal gel and preparation method and application thereof | |
CN115414320A (en) | 1,8-eucalyptol nanoemulsion gel with antifungal effect | |
CN108158975A (en) | Antimycotic sustained release thermo-responsive hydro gel of stannic oxide/graphene nano silver Terbinafine and its preparation method and application | |
JP2023089178A (en) | Topical montelukast formulations | |
CN105581924A (en) | Compound cassia oil nanoemulsion and preparation method thereof | |
CN112263544B (en) | Lidocaine hydrochloride gel and preparation method thereof | |
CN113143788A (en) | Multi-effect composition and face cream with moisturizing, repairing and relieving functions | |
CN114601959A (en) | Medical skin care dressing and preparation method and application thereof | |
CN107441071A (en) | A kind of application of ar-turmerone in treatment and/or prevention psoriasis is prepared | |
CN104274494B (en) | A kind of American cockroach external preparation and preparation method thereof | |
CN112315988A (en) | Radix Ilicis Pubescentis extract gel for promoting skin ulcer wound repair and its preparation method | |
CN111281851A (en) | PH-targeted flexible nanoliposome with acne removing effect and preparation method thereof | |
CN103330679B (en) | Film coating agent for treating pigeon ectozoa and preparation method thereof | |
CN112807353B (en) | Econazole nitrate spray and preparation method thereof | |
CN107822978A (en) | A kind of jelly film surface film containing growth factor and preparation method thereof | |
KR102376314B1 (en) | Pharmaceutical compositions for topical administration in the form of solution comprising itraconazole and processes for the preparation thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20221202 |