CN104288235A - Tea-tree-oil nanometer inhalant and application thereof to treat bacterial and fungal pneumonia - Google Patents
Tea-tree-oil nanometer inhalant and application thereof to treat bacterial and fungal pneumonia Download PDFInfo
- Publication number
- CN104288235A CN104288235A CN201410373918.0A CN201410373918A CN104288235A CN 104288235 A CN104288235 A CN 104288235A CN 201410373918 A CN201410373918 A CN 201410373918A CN 104288235 A CN104288235 A CN 104288235A
- Authority
- CN
- China
- Prior art keywords
- tea tree
- tree oil
- tea
- inhalant
- nanometer
- 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
Classifications
-
- 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)
- A61K36/61—Myrtaceae (Myrtle family), e.g. teatree or eucalyptus
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/28—Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
-
- 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
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
-
- 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
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Dispersion Chemistry (AREA)
- Otolaryngology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pulmonology (AREA)
- Biotechnology (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Botany (AREA)
- Physics & Mathematics (AREA)
- Alternative & Traditional Medicine (AREA)
- Biomedical Technology (AREA)
- Nanotechnology (AREA)
- Optics & Photonics (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a tea-tree-oil nanometer inhalant and application thereof to treat bacterial and fungal pneumonia. The tea-tree-oil nanometer inhalant is prepared by a tea-tree-oil nanometer drug delivery system, and the tea-tree-oil nanometer drug delivery system is selected from a tea-tree-oil nano-emulsion, a tea-tree-oil microemulsion, tea-tree-oil liposome, a tea-tree-oil nonionic surfactant vesicle, a tea-tree-oil nanoparticle and a tea-tree-oil nanocapsule. The dosage form of the tea-tree-oil nanometer inhalant is selected from an aerosol, an aqueous aerosol and a powder aerosol. The tea-tree-oil nanometer preparation is capable of increasing stability of tea tree oil and reducing irritation, can easily deeply enter lung tissue and position a lesion location in a targeting manner, is beneficial for treatment on bacterial and fungal pneumonia, and is convenient to carry and use. The bacterial and fungal pneumonia means pulmonary infection caused by bacteria and fungi.
Description
Technical field
The present invention relates to biomedicine field, be specifically related to containing the nanometer inhalant of tea tree oil and the application in treatment microbiological contamination pneumonia thereof.
Background technology
Tea tree oil (TTO) is the volatile oil extracted from myrtle Melaleuca Alternifolia tree branches and leaves.Melaleuca Alternifolia originates in Australia, is included by European Pharmacopoeia at present.Tea tree oil has 100 Multiple components, main component is 4-terpineol, γ-terpineol, alpha-terpineol, 1, cyclenes hydro carbons such as 8-cineole, α-terpinene and enols used, there is stronger antibacterial, antiinflammatory, antioxidation, antiviral, acaricide, antitussive, antitumor, promotion wound healing and immunity moderation isoreactivity, there is great medical value.Tea tree oil antibacterial spectrum is wide; suppression effect is had to 57 kinds of pathogenic bacterium; antibacterial activity is strong; as staphylococcus aureus, escherichia coli, Candida albicans etc.; be used to treatment by fungus, bacterial relevant disease, being expected to exploitation becomes the natural antibacterial agent that one can alleviate the whole world " antibacterials crisis ".
Tea tree oil is a kind of quintessence oil containing multiple alkene terpenoid, under light or oxygen effect, easily generates and has irritating p-cumene.Tea tree oil poorly water-soluble in addition, unstable, volatile and there is strong impulse abnormal smells from the patient.These features greatly limit its application, application especially pharmaceutically.
Pulmonary infection pathogen is varied, and have antibacterial, virus, mycoplasma, rickettsia, chlamydia, fungus, spirillum and parasite etc., wherein bacteriological infection is the most common, accounts for 80% of pneumonia sum.Pulmonary Fungal Infections is also increasing year by year, this and Prolonging Human Average Life, and the immune deficient patients such as chemotherapy of tumors, organ transplantation increase, and the extensive use of the medicine such as broad ectrum antibiotic, adrenocortical hormone and immunosuppressant is closely related.The application of a large amount of broad-spectrum antibiotic in recent years, pathogenic flora transition and drug resistance, even there is multidrug resistant (MDR, refer to and tolerance produced to 2 kinds or antibacterials of more than two kinds) bacterial strain and general drug resistance (PDR, refer to and Tetracyclines, carbapenems, cephalosporins, fluoroquinolones and enzyme inhibitor compound preparation all tolerated) bacterial strain, causes the example of clinical experience medication Endodontic failure of common occurrence.
The particle diameter of administration nano-drug administration system is nanoscale, and specific surface area is very big, very big with the contact area of site of action after entering human body, greatly can increase stripping and the absorption of medicine.Administration nano-drug administration system also can solve the problems such as many medicine poorly water-solubles, absorption difference, instability.The material major part preparing nanosystems is biocompatibility macromolecular carrier, by medicine parcel wherein, reduces drug degradation, improves stability; Promote that medicine enters in cell, increase and absorb.Administration nano-drug administration system is used for lung inhalation outstanding advantage.It can enter lung tissue deep after inhalation, directly contact with alveolar, and contact area is large.Therefore medicine increases greatly in the concentration of alveolar tissue, can fast onset drug effect.Administration nano-drug administration system comprises the dosage forms such as liposome, nanoparticle, microemulsion, nano-emulsion.
Nano-emulsion refers to the system of the emulsion droplet composition of particle diameter below 200 nanometers, fat-soluble medicine can be wrapped in emulsion droplet.Nano-emulsion is high dispersion, is improved the feature such as drug bioavailability, intensifier target tropism as pharmaceutical carrier.Nano-emulsion can make fat-soluble medicine content in the formulation enlarge markedly, and the absorption of active substance also can be made obviously to accelerate.Microemulsion refers to the system of the emulsion droplet composition of particle diameter below 100 nanometers, has the feature of nano-emulsion equally.
Liposome is the vesicle that phospholipid bilayer is formed.Medicine can be encapsulated in interior aqueous phase or lipid film according to character.Liposome is made up of biodegradable material (phospholipid and cholesterol), and to human non-toxic, histocompatibility is good.Liposome and cell membrane affinity by force, can increase the ability being wrapped medicine permeates cell membranes.Liposome technology can solve the difficult problem that some fat-soluble medicine is insoluble in water.Nonionic surfactant vesicle (Niosomes) refers to that some non-ionic surface active agent (as sorbester p18) is self-assembled into imitated vesicle structure under certain condition in water, similar liposome.It as pharmaceutical carrier, can have some inside and outside features of similar liposome equally.
Nanoparticle refers generally to be the solids of nano-scale dispersion, and due to its high dispersion, it is improved the feature such as drug bioavailability, intensifier target tropism as pharmaceutical carrier.Solid lipid nanoparticle adopts the compatible matrix material of human body to form nanoparticle as major auxiliary burden, and have the feature of common nanoparticle and the feature of good biocompatibility, Recent study is more.Nanocapsule refers in particular to pharmaceutical pack and is rolled in the nanoparticle formed in filmogen, has the inside and outside feature of nanoparticle equally.
Lung sucks preparation and is developed rapidly in recent years.Except obtaining effective general action, lung inhalation approach is the most direct therapeutic modality of the pulmonary disease such as asthma, emphysema, chronic obstructive pulmonary disease.Medicine can be directly to and reaches target site, rapid-action, reduces dosage and toxicity and untoward reaction.There are more than one hundred million alveolars in pulmonary, and absorption area is large; Blood flow is large, is conducive to the absorption of medicine; Medicine directly enters blood circulation after lung absorbs, and avoids the first pass effect of liver, improves the bioavailability of medicine, at present multiple pulmonary inhalation listing.Lung sucks preparation formulation and mainly contains 3 kinds: (1) aerosol; (2) water smoke agent; (3) powder spray.
Summary of the invention
The invention discloses a kind of tea tree oil nanometer inhalant, and the application of tea tree oil nanometer inhalant in treatment microbiological contamination pneumonia.
The preparation process of tea tree oil nanometer inhalant does not limit, as long as obtain corresponding tea tree oil administration nano-drug administration system, and prepares tea tree oil nanometer inhalant and just can meet requirement of the present invention.Usually, the preparation of tea tree oil nanometer inhalant can adopt following steps:
(1) tea tree oil administration nano-drug administration system is prepared;
(2) tea tree oil administration nano-drug administration system is prepared into tea tree oil nanometer inhalant.
Tea tree oil administration nano-drug administration system is selected from tea tree oil nanoemulsion, tea tree oil microemulsion, tea tree oil liposome, tea tree oil nonionic surfactant vesicle, tea tree oil nanoparticle, tea tree oil nanocapsule, preferably tea tree oil nanoemulsion, tea tree oil liposome, more preferably tea tree oil nanoemulsion.The tea tree oil nanometer inhalant of different dosage form can be obtained by the various dosage forms of tea tree oil administration nano-drug administration system, specifically be selected from tea tree oil nanoemulsion inhalant, tea tree oil microemulsion inhalant, tea tree oil liposome inhalant, tea tree oil nonionic surfactant vesicle inhalant, tea tree oil nanoparticle inhalant, tea tree oil nanocapsule inhalant, preferably tea tree oil nanoemulsion inhalant, tea tree oil liposome inhalant, more preferably tea tree oil nanoemulsion inhalant.
The preparation method of tea tree oil nanoemulsion can with reference to pertinent literature and professional technique data.Usually, tea tree oil nanoemulsion contains emulsifying agent, co-emulsifier, oil phase, aqueous phase, tea tree oil.Emulsifying agent and co-emulsifier are selected from ethylene glycol monostearate, ethylene glycol monolaurate, ethylene glycol monoleate, glycol monopalmitate, ethylhydroxyethylcellulose, acetylated monoglyceride, diethylene glycol distearate, triethylene glycol dilaurate, triethylene glycol list cinnamate, triethylene glycol monolaurate, triethylene glycol monostearate, triethylene glycol dicaprylate, N, N-diethyl lauramide, diacetyl monoglyceride, diacetyl tartaric acid is (single, two) glyceride, diisopropanolamine (DIPA), sodium lauryl sulphate, Stepanol MG, sodium tetradecyl sulfate, sodium cetostearylsulphate, Emulphor FM, Triglycerol Caprylate-Caprate TCC, trihydroxy aminomethane, casein, N-9, Emulsifier LM-102, xylitan monostearate, ethoxylated lanolin, ethoxylated hydrogenated lanoline, Hamposyl L, Hamposyl C, Semen Myristicae sarcosine, hard ester acylsarcosine, sodium laurate, lauric acid amine, potassium laurate, lauric isopropropanolamide, lauric acid diethyl amide, propylene glycol diacetate, propylene glycol monostearate, chitose, methylcellulose, glycerol three rosin ester, triolein, tripalmitin, glycerol tristearate, triacetin, glyceryl monostearate, glycerin mono-fatty acid ester, Monooctamoin, four butanoic acid aldehyde, sorbitan mono-laurate, sorbitan monopalmitate, sorbitan monooleate, sorbitan trioleate, sorbitan sesquioleate, sorbitan monostearate, anhydrous sorbitol tristearate, sesbania gum, his that glue, Ficus elastica, carbomer, isobutylated lanolin acid esters, isopropanolamine, Furcellaran, lactide ricinoleic acid polyglycerin ester, tragacanth, ethoxylated lanolin alcohol, self-emulsifying monostearate, Resina persicae, malt extract, octoxynol 9, Bentonite, Bentonite magnesium, carrageenin, tamarind gum, lecithin, hydrogenated soybean lecithin, emulsifing wax, lactic acid fatty acid propylene glycol glyceride mixture, lactic acid fatty glyceride, pectin, pine glue, enuatrol, single double glyceride, POLY-karaya, soft soap, poloxamer, citric acid fatty glyceride, cholesteryl palmitat, cholesterol ester stearic acid, gallbladder acid, sodium cholate bile acid sodium, deoxycholic acid, alginic acid, propylene glycol alginate, sodium alginate, calcium alginate, potassium alginate, Sargassum acid amide, fatty acid lactoyl ester, polyglycerol fatty acid ester, diglycerol list-2-hexyldecanoic acid ester, two triglycerol monostearates, two triglycerol monoleates, two triglycerol monolaurates, five contracting six glyceryl monostearates, five contracting six glycerol distearates, nine contracting ten glycerol four oleates, nine contracting ten glycerol eight oleates, nine contracting SY-Glyster DAO 750s, nine contracting ten glycerol ten stearates, like raw blue, hydroxyethylmethyl-cellulose, hydroxylated lecithin, hydroxyethyl-cellulose, hydroxypropyl emthylcellulose, Xanthan gum is former, scleroglucan, choline chloride, stearmide, palmitamide, stearic acid sodium lactate, lactic acid myristyl ester, lactic acid cetyl ester, sodium stearate, hard soap, curdled milk soap, potassium stearate, stearyl alcohol, coconut monoethanolamide, coconut oil diethanol amide, general Shandong is blue, acetyl kip Shandong is blue, sodium palmitate, microbial alginate, Carboxymethyl cellulose sodium, sodium caseinate, guaiac gum, polyethyleneglycol bacteria ether emulsifing wax, Cetomacrogol 1000, polyvinyl alcohol, polysorbate-20, polysorbate-40, polysorbate-60, polysorbate-65, Polyoxyethylene Sorbitan Monooleate, polysorbate-85, polyoxyethylene (4) laurate, polyoxyethylene (8) laurate, polyoxyethylene (12) laurate, polyoxyethylene (24) laurate, polyoxyethylene (40) laurate, polyoxyethylene (100) laurate, Polyethylene Glycol (200) monolaurate, Polyethylene Glycol (400) monolaurate, Polyethylene Glycol (600) monolaurate, Polyethylene Glycol (1000) monolaurate, Polyethylene Glycol (6000) monolaurate, polyoxyethylene lauryl ether, polyoxyethylene cetostearyl ether, polyoxyethylene (30EO) sorbitol four oleyl ether, polyoxyethylene (60EO) sorbitol four stearyl ether, polyoxyethylene (40EO) sorbitol four oleate ether, polyoxyethylene (60EO) sorbitol four oleate, Emulsifier LT-60M, polyoxyethylene alkyl ether, , Emulsifier BY Emulsifier MOA, Emulsifier O, Brij-30, Brij-35, Brij-52, Brij-56, Brij-58, Brij-76, Brij-28, Brij-92, Brij-96, Brij-98, polyoxyethylene (10) oleyl ether, polyoxyethylene (8) stearate, polyoxyethylene (12) stearate, polyoxyethylene (24) stearate, polyoxyethylene (100) stearate, polyoxyethylene (110) stearate, polyoxyethylene (40) stearate, polyoxyethylene (50) stearate, polyoxyethylene (40) castor oil hydrogenated, polyoxyethylene (10) castor oil hydrogenated, polyoxyethylene (30) castor oil hydrogenated, polyoxyethylene (50) castor oil hydrogenated, polyoxyethylene (60) castor oil hydrogenated, polyoxyethylene (40) Oleum Ricini, polyoxyethylene (10) Oleum Ricini, polyoxyethylene (35) Oleum Ricini, polyoxyethylene (60) Oleum Ricini, polyoxyethylene (80) Oleum Ricini, polyoxyethylene (90) Oleum Ricini, polyoxyethylene (100) Oleum Ricini, polyoxyethylene (300) monoleate, polyoxyethylene (400) monoleate, polyoxyethylene (600) monoleate, sucrose fatty acid ester, sucrose monolaurate, sucrose palmitic acid ester, locust bean gum, sulfonated castor oil, sulfonation castor oil hydrogenated, sodium dioctyl sulfosuccinate, dioctyl sulphosuccinate calcium, dioctyl sulphosuccinate potassium, PHOSPHATIDYL ETHANOLAMINE, Phosphatidylserine, phosphocholine.Generally after selecting suitable prescription, easily can form tea tree oil nanoemulsion.If select suitable prescription, generally comprise emulsifying agent, co-emulsifier, oil phase, can also form tea tree oil from nanometer emulsified system, after adding suitable quantity of water solution, system can become tea tree oil nanoemulsion by self-dispersing.After oil phase, aqueous phase, emulsifying agent and co-emulsifier determine, find out nano-emulsion region by accurate ternary phase diagrams.Tea tree oil nanoemulsion in the present invention, its particle diameter is 1 ~ 1000 nanometer, preferably 10 ~ 500 nanometers, more preferably 10 ~ 100 nanometers.In tea tree oil nanoemulsion, the amount of tea tree oil, the amount of adjuvant do not limit, as long as the formulation requirements and the treatment that meet tea tree oil nanometer inhalant require just passable, preferred tea tree oil content is 0.1% ~ 30% weight ratio, preferred tea tree oil content is 0.3% ~ 10% weight ratio, and preferred tea tree oil content is 1% ~ 5% weight ratio further.The adjuvant of tea tree oil nanoemulsion inhalant is except emulsifying agent, co-emulsifier; also can contain other pharmaceutically acceptable adjuvant, and be selected from one or more in adsorbent, solubilizing agent, cosolvent, antiseptic, stabilizing agent, freeze drying protectant, surfactant.
The preparation method of tea tree oil microemulsion can with reference to pertinent literature and professional technique data.Usually, tea tree oil microemulsion contains emulsifying agent, co-emulsifier, cosolvent, oil phase, aqueous phase, medicine.Emulsifying agent and the co-emulsifier of preparing microemulsion can with reference to the emulsifying agent of tea tree oil nanoemulsion selection and co-emulsifier.Generally after selecting suitable prescription, can easily form tea tree oil microemulsion.If select suitable prescription, generally comprise emulsifying agent, co-emulsifier, cosolvent, oil phase, can also form tea tree oil self-microemulsifying system, after adding suitable quantity of water solution, system can become tea tree oil microemulsion by self-dispersing.After oil phase, aqueous phase, emulsifying agent and co-emulsifier determine, find out microemulsion region by accurate ternary phase diagrams.
The preparation method of tea tree oil liposome is selected from film dispersion method, reverse phase evaporation, multi-emulsion method, fusion method, injection method, freeze-drying, surfactant facture, centrifuging, pro-liposome method, pressurization extrusion molding, calcium fusion method, preferably from film dispersion method, reverse phase evaporation, injection method, pressurization extrusion molding, more preferably film dispersion method.These preparation methoies can with reference to relevant speciality books and document, is designed and operation completes by professional and technical personnel.If adopt film dispersion method to prepare liposome, the film materials such as glycerol backbone anti-tumor predrug and phospholipid can be dissolved in organic solvent jointly, contain in flask, decompression rotary evaporation, obtains thin film, then adds water or suitable buffer, carry out vibration and ultrasonic, until form uniform suspension.If ultrasonic time extends, also nano-scale dispersion system may be obtained.Liposome turbid liquor can also be selected suitable prescription and carry out lyophilization or spraying dry under proper condition, and form solid powdery, can ensure the stability of preparation like this, adding aqueous solution jolting before use can obtain liposome turbid liquor.Use same technology can obtain tea tree oil nonionic surfactant vesicle.
The particle diameter of the tea tree oil liposome in the present invention is 1 ~ 1000 nanometer, preferably 10 ~ 600 nanometers, more preferably 20 ~ 300 nanometers.In tea tree oil liposome, the amount of tea tree oil, the amount of adjuvant do not limit, as long as the formulation requirements and the treatment that meet tea tree oil nanometer inhalant require just passable, preferred tea tree oil content is 0.1% ~ 30% weight ratio, preferred tea tree oil content is 0.3% ~ 10% weight ratio, and preferred tea tree oil content is 1% ~ 5% weight ratio further.The adjuvant of tea tree oil liposome inhalant is except emulsifying agent, co-emulsifier; also can contain other pharmaceutically acceptable adjuvant, and be selected from one or more in adsorbent, solubilizing agent, cosolvent, antiseptic, stabilizing agent, freeze drying protectant, surfactant.
The lipid contained in tea tree oil liposome is selected from lecithin, PHOSPHATIDYL ETHANOLAMINE, soybean phospholipid, cholesterol, cephalin, cholesterol acetyl fat, cupreol, natrii tauroglycocholas, Yolk lecithin, DLPC, dimyristoyl phosphatidyl choline, dipalmitoyl phosphatidyl choline, distearoyl phosphatidylcholine, DPPG, DSPG, DPPA, Phosphatidylserine, phosphatidylinositols, sphingomyelin, sphingo, two Cetyl Phosphates, stearmide, preferably from lecithin, soybean phospholipid, cholesterol, DLPC, dimyristoyl phosphatidyl choline, dipalmitoyl phosphatidyl choline, distearoyl phosphatidylcholine, more preferably from lecithin, soybean phospholipid, cholesterol, dipalmitoyl phosphatidyl choline, most preferably from soybean phospholipid and cholesterol.When adopting soybean phospholipid and cholesterol to prepare tea tree oil liposome, the molar ratio of soybean phospholipid and cholesterol is selected from 100: 1 ~ 1: 2, preferably from 20: 1 ~ 1: 1, more preferably from 10: 1 ~ 2: 1.Can also add other additives in tea tree oil liposome, concrete kind is unrestricted, such as vitamin E, 18-amine..
The preparation method of tea tree oil nanoparticle has a variety of, different with requirement according to the material of nanoparticle, can with reference to pertinent literature and professional technique books.Tea tree oil nanoparticle is selected from tea tree oil polymer nanoparticle, tea tree oil solid lipid nanoparticle, tea tree oil inorganic nano-particle, preferably from tea tree oil solid lipid nanoparticle.The preparation method of tea tree oil polymer nanoparticle is selected from polymerization, the sedimentation method, solvent evaporation method, salting out method.The preparation method of tea tree oil solid lipid nanoparticle is selected from film ultrasound, high-pressure stripping, melting breast even method, the even method of freezing breast, emulsification-evaporation method, nano-emulsion method.The preparation method of tea tree oil inorganic nano-particle can adopt the sedimentation method.The method of tea tree oil nanocapsule is selected from monomer interface polymerization and polymer interface nano-precipitation method.
In the preparation method of tea tree oil solid lipid nanoparticle, usually, by being solid-state lipid under tea tree oil and room temperature, as phospholipid, fatty acid, glyceride, common heating and melting, then water or suitable buffer is added, under heating state in high pressure dispersing emulsification machine cocycle emulsifying repeatedly, form the emulsion droplet of nano-dispersed, cool rapidly, make it solidification, namely obtain tea tree oil solid lipid nanoparticle.Also tea tree oil solid lipid nanoparticle can be obtained by microemulsion method.
Tea tree oil administration nano-drug administration system directly as tea tree oil nanometer inhalant, or can prepare tea tree oil nanometer inhalant after being applicable to technical process process.Tea tree oil administration nano-drug administration system, when carrying out technical process process, can not add adjuvant and directly obtain tea tree oil nanometer inhalant; Also can as required with the difference of dosage form, add adjuvant and obtain tea tree oil nanometer inhalant.
The concrete dosage form of tea tree oil nanometer inhalant is selected from aerosol, water smoke agent, powder spray.Aerosol is mixed with propellant by medicine, and pressurization pours in pressure vessel, and when opening valve, propellant carries medicine and gasifies rapidly and enter respiratory tract and lung.Water smoke agent is, by ultrasonic or high pressure draught, the solution of medicine or suspension are atomized into superfine droplet, is then inhaled into respiratory tract and lung.Powder spray is by the powder of drug containing by Diskus, is initiatively drawn in respiratory tract and lung.Therefore, corresponding different dosage form, tea tree oil nanometer inhalant is selected from tea tree oil nano aerosol, the agent of tea tree oil nanometer water smoke, tea tree oil nanometer powder spray.
Tea tree oil administration nano-drug administration system can directly be prepared into tea tree oil nano aerosol, is specifically selected from tea tree oil nanoemulsion aerosol, tea tree oil microemulsion aerosol, tea tree oil liposome aerosol, tea tree oil nonionic surfactant vesicle aerosol, tea tree oil nanoparticle aerosol, tea tree oil nanocapsule aerosol.Tea tree oil administration nano-drug administration system can mix with propellant by the preparation process of tea tree oil nano aerosol, and pressurization pours in pressure vessel and just can obtain.Propellant is selected from dichlorodifluoromethane, Dichloromonofluoromethane, F-22, dichlorotetra-fluoroethane, a chloropentafluoroethane, chlorodifluoroethane, Difluoroethane, trichorotrifluoroethane, Perfluorocyclobutane, isceon.
Tea tree oil administration nano-drug administration system directly can be prepared into the agent of tea tree oil nanometer water smoke, is specifically selected from the agent of tea tree oil nanoemulsion water smoke, the agent of tea tree oil microemulsion water smoke, the agent of tea tree oil liposome water smoke, the agent of tea tree oil nonionic surfactant vesicle water smoke, the agent of tea tree oil nanoparticle water smoke, the agent of tea tree oil nanocapsule water smoke.
Tea tree oil nanometer powder spray is selected from tea tree oil nanoemulsion powder spray, tea tree oil microemulsion powder spray, tea tree oil liposome powder spray, tea tree oil nonionic surfactant vesicle powder spray, tea tree oil nanoparticle powder spray, tea tree oil nanocapsule powder spray.The preparation process of tea tree oil nanometer powder spray does not limit, as long as obtain corresponding tea tree oil administration nano-drug administration system, and prepares tea tree oil nanometer powder spray and just can meet requirement of the present invention.Usually, the preparation of tea tree oil nanometer powder spray can adopt following steps:
(1) tea tree oil administration nano-drug administration system is prepared;
(2) tea tree oil administration nano-drug administration system is dried to powder;
(3) tea tree oil administration nano-drug administration system powder is mixed with carrier.
Above-mentioned steps (2), when drying, according to the character of tea tree oil administration nano-drug administration system, can be added or not add suitable adjuvant, for the purpose of the powder obtaining the thin good fluidity of granule; Dry method is selected from lyophilization and spraying dry.
In some cases, do not need carrier to participate in, independent tea tree oil administration nano-drug administration system powder just can as tea tree oil nanometer powder spray.Therefore, the preparation of tea tree oil nanometer powder spray also can adopt following steps:
(1) tea tree oil administration nano-drug administration system is prepared;
(2) tea tree oil administration nano-drug administration system is dried to powder.
The explanation of above-mentioned steps (2) is identical with aforesaid preparation process with requirement.
Adjuvant above described in preparation process is selected from saccharide, alcohols, amino acids, phospholipid, pulmonary surfactant, cyclodextrin, polymer substance, fluidizer, antioxidant, citric acid and salt, phosphate.Saccharide is selected from lactose, galactose, glucose, fructose, sucrose, trehalose, Raffinose.Alcohols is selected from mannitol, xylitol, maltose alcohol, sorbitol.Amino acids recited above, is selected from glycine, Aspartic Acid, alanine, tryptophan, threonine, glutamic acid, phenylalanine, leucine, isoleucine, cystine, lysine, proline, arginine.Phospholipid is selected from soybean phospholipid, lecithin, phosphatidylcholine, PHOSPHATIDYL ETHANOLAMINE, synthetic phospholipid.Pulmonary surfactant is selected from dipalmitoyl phosphatidyl choline, DLPC, cholesterol.Cyclodextrin is selected from alpha-cyclodextrin, beta-schardinger dextrin-, gamma-cyclodextrin, large cyclodextrin, the alpha-cyclodextrin derivant of various substitution value, the beta-cyclodextrin derivative of various substitution value, the gamma-cyclodextrin derivant of various substitution value, HP-β-CD, sulfobutyl ether-beta-cyclodextrin, branched cyclodextrin, methylated cyclodextrin, dimethyl-β-cyclodextrin, hydroxyethyl cyclodextrin, low-molecular-weight beta cyclo dextrin polymer (molecular weight is 3000-6000), ethyl cyclodextrin, acetyl group cyclodextrin, ionic cyclodextrin derivative, carboxymethyl cyclodextrin, sulfuric ester cyclodextrin.Polymer substance is selected from biodegradable polymer substance such as albumin, dextrin, polyvinylpyrrolidone, cellulose derivative, starch derivatives, polylactic acid, poly lactic-co-glycolic acid, Polyethylene Glycol, poloxamer, hyaluronic acid, hyaluronate sodium, sodium alginate.Fluidizer is selected from micropowder silica gel, Pulvis Talci, hard magnesium, stearic acid, hard ester fumaric acid sodium.Antioxidant is selected from vitamin C, sodium L-ascorbate-2-phosphate, each analog derivative of vitamin C, coenzyme Q10, vitamin E, polyethylene glycol 1000 vitamin E succinic acid ester, each analog derivative of vitamin E.
Carrier above described in preparation process is selected from lactose, arabic gum, xylitol, glucosan, mannitol, trehalose, preferably from lactose, mannitol, most preferably lactose.The weight ratio of tea tree oil administration nano-drug administration system powder and carrier does not have strict regulations, as long as meet good fluidity, pulmonary deposition effect higher position is passable.Usually, the part by weight of tea tree oil administration nano-drug administration system powder and carrier is 1: 50 ~ 50: 1, preferably 1: 20 ~ 10: 1, most preferably 1: 10 ~ 5: 1.
Tea tree oil nanometer powder spray is packaged in capsule or bubble-cap or Diskus, just can carries easily and use.
Tea tree oil nanometer inhalant is used for the treatment of microbiological contamination pneumonia.Microbiological contamination pneumonia comprises antibacterial, fungus-caused pulmonary infection.The strain of antibacterial is unrestricted, can be selected from staphylococcus aureus, streptococcus pneumoniae, hemophilus influenza, Pseudomonas aeruginosa, acinetobacter calcoaceticus, Enterobacter, proteus vulgaris, bacillus subtilis, Streptococcus sobrinus, Branhamella catarrhalis, streptococcus pyogenes, Actinomycesviscosus, Streptococcus mutans, Klebsiella Pneumoniae genus, escherichia coli, Acinetobacter bauamnnii, Fusobacterium nucleatum, lactobacillus, Methicillin-resistant Staphylococcus aureus.The strain of fungus is unrestricted, optional from Candida albicans, Candida parapsilosis, Cryptococcus histolyticus, trichophyton, saccharomyces albicans, acrothesium floccosum, Fusarium spp., Sabouraudites lanosus, malassezia furfur, microsporon gypseum, penicillium, Trichosporon Behrend, Aspergillus flavus, Aspergillus fumigatus, aspergillus niger, trichophyton tonsurans, Candida parapsilosis, Candida glabrata, Oidium tropicale.
Through inside and outside, antibacterial tests result proves, tea tree oil nanometer inhalant disclosed by the invention, has stronger antibacterial effect.Particularly there is stronger killing action to fungus.
Accompanying drawing explanation
Fig. 1. tea tree oil nanoemulsion outward appearance photo (A is the common breast of tea tree oil, and B is tea tree oil nanoemulsion)
Fig. 2. the transmission electron microscope photo of tea tree oil nanoemulsion
Fig. 3. tea tree oil nanoemulsion particle size determination result
Fig. 4. tea tree oil nanoemulsion places the particle size determination result after 2 months
Fig. 5. the Zeta potential measurement result of tea tree oil nanoemulsion
Fig. 6. tea tree oil nanoemulsion in-vitro antibacterial effect (A: Klebsiella Pneumoniae, B: escherichia coli, C: Acinetobacter bauamnnii, D: staphylococcus aureus, E: Candida albicans)
Fig. 7. tea tree oil nanoemulsion to dye pathological section photo (× 200) (A is tea tree oil high dose group, B is dosage group in tea tree oil, C is tea tree oil low dose group, the blank group of D positive drug (fluconazol) group, E model group, F) to lung tissue HE after the treatment of fungus (Candida albicans) pneumonia rats
Fig. 8. tea tree oil nanoemulsion to dye pathological section photo (× 200) (A is tea tree oil high dose group, B is dosage group in tea tree oil, C is tea tree oil low dose group, the blank group of D positive drug (penicillin) group, E model group, F) to lung tissue HE after the treatment of antibacterial (Acinetobacter bauamnnii) pneumonia rats
detailed description of the invention
Embodiment 1. tea tree oil nanoemulsion
Get tea tree oil 2g, polyoxyethylene (35) Oleum Ricini 4g, water 34ml are placed in beaker mix homogeneously, make formation colostrum by 1000rpm mechanical agitation, under high pressure homogenizer 15000psi, homogenizing 3 times, obtains tea tree oil nanoemulsion.The outward appearance of tea tree oil nanoemulsion is the clear transparent solutions having light blue opalescence, and the common newborn outward appearance of tea tree oil is milky, opaque dirty solution (Fig. 1).Under transmission electron microscope, observe tea tree oil nanoemulsion distribution comparatively even, great majority are in spherical shape (Fig. 2).The particle diameter peak value recording tea tree oil nanoemulsion with Malvern laser particle analyzer is 13.06nm (Fig. 3), and mean diameter is about 24.39nm, and PDI is 0.468, and particle size range compares and concentrates between 10 ~ 28nm.Place after 2 months, its particle diameter peak value is 13.19nm (Fig. 4), with basically identical before, still clear, the light blue opalescence of tool, without layering, without flocculation, without demulsifying phenomenon, illustrate that tea tree oil nanoemulsion is more stable.The Zeta potential of tea tree oil nanoemulsion is-14.1mV (Fig. 5).
Embodiment 2. tea tree oil liposome
Get tea tree oil 100mg, soybean phospholipid 320mg, cholesterol 30mg is placed in eggplant type flask, add 5ml oxolane and dissolve completely, rotary evaporation in 35 DEG C of water-baths, removing organic solvent, forms skim uniform films at eggplant type flask inwall; Add in eggplant type flask by the phosphate buffer of the 200ml pH5.0 being dissolved with 2.26g lactose, be placed in 37 DEG C of 100 revs/min of constant temperature oscillations 1 hour, make its abundant hydration, ultrasonic disperse 10min after taking out, obtains tea tree oil liposome.
Embodiment 3. tea tree oil solid lipid nanoparticle
Get vitamin E 0.1g, cetyl palmitate 2.0g, caprylic/capric glyceride 0.4g are heated to melting in 53 DEG C of water-baths, mix as oil phase with tea tree oil 1.0g, injection fabaceous lecithin 1.5g, polyoxyethylene 660-12 hydroxy stearic acid ester 1.8g are injected by water 100mL stirring and dissolving, be heated to 53 DEG C, as aqueous phase; Stir and logical nitrogen condition under, be added drop-wise to by aqueous phase in synthermal oil phase, continue to stir certain hour and form colostrum, Probe Ultrasonic Searching 5min, 0 ~ 2 DEG C airtight stirs 2h, and 0.22 μm of microporous filter, obtains tea tree oil solid lipid nanoparticle.Observe under a scanning electron microscope, mostly be the particle of below 100 nanometers.
Embodiment 4. tea tree oil microemulsion
Get tea tree oil 50mg to be dissolved in 5ml ethyl oleate/tetrahydrochysene furan food in one's mouth mixed solvent, add appropriate polyoxyethylene castor oil and monoglyceride, heated and stirred becomes solution, under high-speed stirred condition, add about 4ml water, Keep agitation, obtain transparence dispersing liquid, obtain tea tree oil microemulsion.Granulometry result shows that most of particle is at below 100nm.
The agent of embodiment 5. tea tree oil nanoemulsion water smoke
Get tea tree oil 2g, polyoxyethylene (35) Oleum Ricini 4g, water 34ml are placed in beaker mix homogeneously, make formation colostrum by 1000rpm mechanical agitation, under high pressure homogenizer 15000psi, homogenizing 3 times, obtains tea tree oil nanoemulsion; Tea tree oil nanoemulsion is loaded in the special nebulizer for lung suction, obtain the agent of tea tree oil nanoemulsion water smoke.
Embodiment 6. tea tree oil nanoemulsion aerosol
Getting tea tree oil 2g is added in polyoxyethylene (35) Oleum Ricini 4g, dissolve, add 40ml water again, stir, become colostrum, under high pressure homogenizer 15000psi, homogenizing obtains tea tree oil nanoemulsion 3 times, and embedding is in the dichlorodifluoromethane 20g of the sorbester p37 and 0.5g ethyl oleate that are dissolved with 0.5g, mixing, obtains tea tree oil nanoemulsion aerosol.
Embodiment 7. tea tree oil nanoemulsion powder spray
Get tea tree oil 2g, polyoxyethylene (35) Oleum Ricini 4g, water 34ml are placed in beaker mix homogeneously, formation colostrum is made by 1000rpm mechanical agitation, homogenizing 3 times under high pressure homogenizer 15000psi, obtain translucent tea tree oil nanoemulsion, granulometry result shows that most of particle is at below 120nm; Get 100mg mannitol to add in 4ml tea tree oil nanoemulsion and dissolve, lyophilization in freeze dryer, obtains the white loose tea tree oil nanoemulsion powder of good fluidity; Get tea tree oil nanoemulsion powder 100mg to mix with Inhalac230 model lactose 100mg, obtain tea tree oil nanoemulsion powder spray.
Experimental example 1. tea tree oil nanoemulsion Antimicrobial test
Material: the tea tree oil nanoemulsion prepared according to embodiment 1.
Method and result: investigate the external antibacterial effect to escherichia coli, Candida albicans, Acinetobacter bauamnnii, staphylococcus aureus, Klebsiella Pneumoniae of tea tree oil nanoemulsion.After bacterium liquid cryopreservation tube dissolves, draw bacterium liquid 5 μ l (Candida albicans is absorption 20 μ l) and join in the test tube containing 5ml LB culture fluid, in 37 DEG C, in the constant temperature gas bath shaking table of 200rpm, cultivate about 20h.Get the fresh bacterium liquid of 5 μ l more respectively to join in 5 test tubes containing the culture fluid of tea tree oil nanoemulsion, in 37 DEG C, in the constant temperature gas bath shaking table of 200rpm, cultivate about 20h.Be coated on flat board with the inoculating loop bacterium of getting in the pastille culture fluid of variable concentrations, in 37 DEG C of constant incubators, cultivate about 20h, observe colony growth situation.Result display tea tree oil nanoemulsion all has good antibacterial action (Fig. 6) to experimental strain, wherein the minimal inhibitory concentration (MIC) of tea tree oil nanoemulsion to Klebsiella Pneumoniae is 7.03mg/ml, being 1.76mg/ml to colibacillary MIC, is all 3.52mg/ml to the MIC of Acinetobacter bauamnnii, staphylococcus aureus and Candida albicans.Therefore tea tree oil nanoemulsion is escherichia coli > Candida albicans ~ Acinetobacter bauamnnii ~ staphylococcus aureus > Klebsiella Pneumoniae to different bacterium anti-microbial property size order.
Experimental example 2. tea tree oil nanoemulsion is to the therapeutic effect of Fungal Pneumonia rat
Material: tea tree oil nanoemulsion, the fluconazol prepared according to embodiment 1.
Method: 60 healthy SD rats are divided into 6 groups at random, often organizes 10, is respectively tea tree oil high dose (70.31mgml
-1) treatment group, dosage (35.16mgml in tea tree oil
-1) treatment group, tea tree oil low dosage (7.03mgml
-1) treatment group, positive drug (fluconazol, 10mg/ml) treatment group, model group (not administration) and blank group.Except blank group, the first intraperitoneal injection of cyclophosphamide of other 5 groups of rats, then contaminate pneumonia of rats through the disposable Candida albicans bacterium liquid inductance that sprays into of trachea.Model group gives normal saline.Within 1st day, spray into administration through trachea after modeling success, dosage converts with reference to adult's routine dose every day.Blank group and model group normal saline 0.2ml, fluconazol 10mg/ml, every day 2 times, tea tree oil nanoemulsion 35mg/mg, every day 2 times, successive administration 2d.After administration 2d, each group of rat is put to death in dislocation in batches, often organizes 5 at every turn.Opening breast by complete for lung taking-up is separated, and left lung makes pathological section.
Result: normal rats vivaciously active, strong big and fleshy, fur gloss is shinny, breathe steadily, body weight increases gradually.Model group rats, in 7d, appearance activity and feed water obviously reduce, and curl in cage corner, the messy tarnish of hair, rapid breathing with sound of stridulating, body weight obviously declines, have obvious bony, eye portion secretions.Tea tree oil nanoemulsion group is also slightly rapid in breathing upon administration, and gloss owed by fur, and diet is general, and active state is slightly poor, but all good than model group.The symptoms such as fluconazol group rat also has rapid breathing, lassitude upon administration, lazyness is moved, be better than model group, but comparatively tea tree oil nanoemulsion are poor.The two lung of normal group is pale pink, smooth surface, good springiness.Model group lung color is dark red, and lobe of the lung profile is unclear, and quality is hardening, and lung volume slightly reduces, visible strip, rough pale stove, and what surface differed in size as seen bleeds profusely a little.Tea tree oil nanoemulsion group and fluconazol group, lung color shows slightly dark, and surface is slightly coarse, and the elasticity touched is fair, and volume is without obviously reducing.The local lung field that lung tissue of rats pathological section (Fig. 7) shows positive drug fluconazol group oozes out (in alveolar space visible pink transudate), hemorrhage as seen, and mononuclear phagocyte showed increased, companion's partial airway exuviation necrosis (based on larger bronchus and bronchioles); And tea tree oil high dose group to ooze out degree slightly light, in tea tree oil, dosage group oozes out scope and all slightly light and visible antibacterial of degree deposits in interstitial and alveolar space, visible a small amount of transudate in tea tree oil low dose group part alveolar space.So tea tree oil nanoemulsion comparatively positive drug fluconazol there is good therapeutic effect, middle dosage is best, and low concentration nano-emulsion is suitable with Fluconazole treating effect.
Experimental example 3. tea tree oil nanoemulsion is to the therapeutic effect of Acinetobacter bauamnnii pneumonia rats
Material: tea tree oil nanoemulsion, the penicillin prepared according to embodiment 1.
Method: laboratory animal grouping and therapeutic scheme are with experimental example 2.Positive drug is selected the good penicillin 240mg/ml of Acinetobacter bauamnnii killing effect.Lung tissue of rats pathological section (Fig. 8) shows, and sees a small amount of transudate in the minority alveolar of positive drug treatment group lung tissue of rats, the intact symptom of indivedual appearance; A small amount of transudate is seen in tea tree oil high dose group minority alveolar; See a small amount of transudate in dosage group minority alveolar in tea tree oil, macrophage increases more obvious; See a small amount of transudate in tea tree oil low dose group part alveolar and visible more bacterial deposition in interstitial or alveolar space.Suitable with positive drug penicillin to the antibacterial effect of Acinetobacter bauamnnii in visible tea tree oil nanoemulsion body.
Acinetobacter is in gram-negative bacteria, and the cell wall of this bacterium has special multiple structure, and outside whole cell peptidoglycan layer, also have lipopolysaccharide, double-layer of lipoid and lipoprotein three part special composition, adds the infiltration difficulty of tea tree oil composition.In nano-emulsion, the content of tea tree oil is not high, limited to the medicine liquid volume of rat.The concentration (240mg/ml) of penicillin is much larger than the concentration of tea tree oil nanoemulsion (Cmax is 70.31mg/ml).But during Antimicrobial test, tea tree oil nanoemulsion has very strong antibacterial action to Acinetobacter bauamnnii, although and the concentration of tea tree oil nanoemulsion far below penicillin, its therapeutic effect is suitable with penicillin.The general Resistant strain of current Acinetobacter bauamnnii and multiple antibiotic resistant strain increasing, mostly be that abusing of heavy dose of antibacterials causes, and the nano-emulsion of the broad spectrum antimicrobicide tea tree oil of pure natural is when relatively low dosage, just there is fine antibacterial action, so the antibacterial feature of tea tree oil nanoemulsion is that dosage is little, antimicrobial agent.
Claims (10)
1. a tea tree oil nanometer inhalant.
2. tea tree oil nanometer inhalant as claimed in claim 1, its preparation can adopt following steps:
(1) tea tree oil administration nano-drug administration system is prepared;
(2) tea tree oil administration nano-drug administration system is prepared into tea tree oil nanometer inhalant.
3. tea tree oil nanometer inhalant as claimed in claim 2, wherein tea tree oil administration nano-drug administration system is selected from tea tree oil nanoemulsion, tea tree oil microemulsion, tea tree oil liposome, tea tree oil nonionic surfactant vesicle, tea tree oil nanoparticle, tea tree oil nanocapsule.
4. tea tree oil nanometer inhalant as claimed in claim 2, wherein tea tree oil administration nano-drug administration system is tea tree oil nanoemulsion.
5. tea tree oil nanometer inhalant as claimed in claim 4, wherein in tea tree oil nanoemulsion, tea tree oil content is 0.1% ~ 30% weight ratio.
6. tea tree oil nanometer inhalant as claimed in claim 1, dosage form is selected from aerosol, water smoke agent, powder spray.
7. tea tree oil nanometer inhalant as claimed in claim 1, is tea tree oil nanometer powder spray, and its preparation adopts following steps:
(1) tea tree oil administration nano-drug administration system is prepared;
(2) tea tree oil administration nano-drug administration system is dried to powder;
(3) tea tree oil administration nano-drug administration system powder is mixed with carrier;
Above-mentioned steps (2), when drying, according to the character of tea tree oil administration nano-drug administration system, can be added or not add suitable adjuvant, for the purpose of the powder obtaining the thin good fluidity of granule; Dry method is selected from lyophilization and spraying dry.
8. tea tree oil nanometer inhalant as claimed in claim 7, the adjuvant used in step (2) is selected from saccharide, alcohols, amino acids, phospholipid, pulmonary surfactant, cyclodextrin, polymer substance, fluidizer, antioxidant, citric acid and salt, phosphate.
9. tea tree oil nanometer inhalant as claimed in claim 7, the carrier used in step (3) is selected from lactose, arabic gum, xylitol, glucosan, mannitol, trehalose.
10. tea tree oil nanometer inhalant as claimed in claim 1, is used for the treatment of microbiological contamination pneumonia.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410373918.0A CN104288235A (en) | 2014-08-01 | 2014-08-01 | Tea-tree-oil nanometer inhalant and application thereof to treat bacterial and fungal pneumonia |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410373918.0A CN104288235A (en) | 2014-08-01 | 2014-08-01 | Tea-tree-oil nanometer inhalant and application thereof to treat bacterial and fungal pneumonia |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104288235A true CN104288235A (en) | 2015-01-21 |
Family
ID=52308347
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410373918.0A Pending CN104288235A (en) | 2014-08-01 | 2014-08-01 | Tea-tree-oil nanometer inhalant and application thereof to treat bacterial and fungal pneumonia |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104288235A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104586822A (en) * | 2015-02-16 | 2015-05-06 | 中国人民解放军军事医学科学院放射与辐射医学研究所 | Dimeticone nanometer inhalant and application thereof in treating acute dropsy |
| CN105536031A (en) * | 2016-02-03 | 2016-05-04 | 常州市奥普泰科光电有限公司 | Preparation method of tea tree oil liposome anti-inflammatory and antibacterial medical dressing |
| US10076551B2 (en) | 2016-11-14 | 2018-09-18 | FREDRICK COBBLE, Jr. | Method for treating interstitial lung disease |
| CN112451508A (en) * | 2020-12-10 | 2021-03-09 | 中国人民解放军军事科学院军事医学研究院 | Application of essential oil nanoemulsion atomization inhalation liquid in treatment of allergic rhinitis |
| CN112592772A (en) * | 2020-12-23 | 2021-04-02 | 广州市柏菲化妆品有限公司 | Tea tree cleaning solution and preparation method thereof |
| CN113633614A (en) * | 2021-09-08 | 2021-11-12 | 中国人民解放军陆军军医大学 | Efficient antibacterial natural tea tree essential oil nanoemulsion preparation for treating intractable dental ulcer and preparation method and application thereof |
| CN115581242A (en) * | 2022-08-10 | 2023-01-10 | 上海明涌新材料有限公司 | Water-soluble tea tree oil disinfectant, and raw material composition, preparation method and application thereof |
-
2014
- 2014-08-01 CN CN201410373918.0A patent/CN104288235A/en active Pending
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104586822A (en) * | 2015-02-16 | 2015-05-06 | 中国人民解放军军事医学科学院放射与辐射医学研究所 | Dimeticone nanometer inhalant and application thereof in treating acute dropsy |
| CN104586822B (en) * | 2015-02-16 | 2019-10-15 | 中国人民解放军军事科学院军事医学研究院 | Dimeticone nanometer inhalant and its application for treating acute pulmonary edema |
| CN105536031A (en) * | 2016-02-03 | 2016-05-04 | 常州市奥普泰科光电有限公司 | Preparation method of tea tree oil liposome anti-inflammatory and antibacterial medical dressing |
| CN105536031B (en) * | 2016-02-03 | 2018-12-11 | 浙江康诚工业产品设计有限公司 | A kind of preparation method of the anti-inflammatory antibacterial medical dressing of tea tree oil liposome |
| US10076551B2 (en) | 2016-11-14 | 2018-09-18 | FREDRICK COBBLE, Jr. | Method for treating interstitial lung disease |
| CN112451508A (en) * | 2020-12-10 | 2021-03-09 | 中国人民解放军军事科学院军事医学研究院 | Application of essential oil nanoemulsion atomization inhalation liquid in treatment of allergic rhinitis |
| CN112592772A (en) * | 2020-12-23 | 2021-04-02 | 广州市柏菲化妆品有限公司 | Tea tree cleaning solution and preparation method thereof |
| CN113633614A (en) * | 2021-09-08 | 2021-11-12 | 中国人民解放军陆军军医大学 | Efficient antibacterial natural tea tree essential oil nanoemulsion preparation for treating intractable dental ulcer and preparation method and application thereof |
| CN113633614B (en) * | 2021-09-08 | 2023-04-07 | 中国人民解放军陆军军医大学 | Efficient antibacterial natural tea tree essential oil nanoemulsion preparation for treating intractable dental ulcer and preparation method and application thereof |
| CN115581242A (en) * | 2022-08-10 | 2023-01-10 | 上海明涌新材料有限公司 | Water-soluble tea tree oil disinfectant, and raw material composition, preparation method and application thereof |
| CN115581242B (en) * | 2022-08-10 | 2024-05-24 | 上海明涌新材料有限公司 | Water-soluble tea tree oil disinfectant, and raw material composition, preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104288235A (en) | Tea-tree-oil nanometer inhalant and application thereof to treat bacterial and fungal pneumonia | |
| CN101474155B (en) | Lung-targeted medicine carrying precursor liposome for injection and method of use thereof | |
| Pastor et al. | Sodium colistimethate loaded lipid nanocarriers for the treatment of Pseudomonas aeruginosa infections associated with cystic fibrosis | |
| TW201124425A (en) | Parenteral formulations of gemcitabine derivatives | |
| KR102656823B1 (en) | An improved formulation of levosimendan for intravenous administration as an infusion or solution for injection and as a concentrate for infusion. | |
| CN104173290A (en) | Solid lipid nanoparticle or liposome and preparation method thereof | |
| CN104337851A (en) | Preparation method of oleum fructus bruceae nano structure lipid carrier and freeze-dried powder thereof | |
| WO2021057007A1 (en) | Rapamycin nanoscale sustained-release agent and preparation method thereof | |
| CN105902525A (en) | Application of chlorogenic acid nano powder inhalation in medicine for treating acute lung injury | |
| US20110020428A1 (en) | Gel-stabilized liposome compositions, methods for their preparation and uses thereof | |
| EP3388055A1 (en) | Method for preparing liposome | |
| CN104224717A (en) | Application of oridonin powder aerosol in treatment of acute lung injury | |
| WO2004082668A1 (en) | Coenzyme q10-containing proliposome and preparation thereof | |
| US20230270676A1 (en) | Rapamycin (rapa) formulation and preparation method thereof | |
| CN104415016A (en) | Application of dry curcumin nano-powder inhalant in treatment of acute lung injury | |
| CN109562068B (en) | Liposome composition containing weakly acidic agent | |
| CN102397242A (en) | Hydrogel containing coenzyme Q10, and cataplasm prepared by hydrogel | |
| CN101810610B (en) | Amoxicillin sodium flucloxacillin sodium medicine compound liposome injection | |
| CN107412172A (en) | A kind of suspension freeze-dried powder of taxol albumin nano and its preparation technology | |
| CN103735508A (en) | Polymyxin lipidosome and preparation process thereof | |
| CN103859395A (en) | Self-emulsifying drug release system of coenzyme Q10 with high absorptivity and preparation method and application thereof | |
| CN107095799A (en) | Complex liposome and its preparation method and application | |
| CN106580928A (en) | Andrographolide nanometer inhalant and application thereof to treatment of bacterial pneumonia | |
| CN109125302A (en) | Application of resveratrol in medicine for treating bacterial pneumonia | |
| CN104586822B (en) | Dimeticone nanometer inhalant and its application for treating acute pulmonary edema |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20150121 |