CN1813905A - Coated magnolia fargesii volatile oil nano liposome nasal drops - Google Patents
Coated magnolia fargesii volatile oil nano liposome nasal drops Download PDFInfo
- Publication number
- CN1813905A CN1813905A CN 200510111347 CN200510111347A CN1813905A CN 1813905 A CN1813905 A CN 1813905A CN 200510111347 CN200510111347 CN 200510111347 CN 200510111347 A CN200510111347 A CN 200510111347A CN 1813905 A CN1813905 A CN 1813905A
- Authority
- CN
- China
- Prior art keywords
- liposome
- volatile oil
- drop according
- nasal drop
- nasal
- 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.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
Abstract
The present invention relates to a kind of covered magnolia flower-bud volatile oil nano liposome nose drops. Its preparation method includes the following steps: (a), mixing magnolia flower-bud volatile oil, phospholipids, cholesterol, antioxidant and liposome membrane regulating agent and dissolving them in solvent; (b), making the mixed solvent obtained by step a undergo the process of constant temperature reduced pressure evaporation treatment; (c), adding the lipid membrane obtained by step b into buffer solution, making oscillation and salvation, regulating pH value and adding auxiliary material; (d), making the liposome dispersing solution obtained by step c undergo the process of ice-water bath ultrasonic treatment and be passed through microporous filter membrane to make filtration; and (e), filtering the liposome mixed suspension solution obtained by steps d and adding the stabilizing agent into filtrate so as to obtain the invented nose drops.
Description
Technical field
The present invention relates to a kind of nasal drop, especially relate to a kind of coated magnolia fargesii volatile oil nano liposome nasal drops.
Background technology
Flos Magnoliae volatile oil contains multiple composition, wherein except containing main effective ingredient cineole, also contains australene, linalool, geraniol, alpha-terpineol, consumption geraniol, farnesol, eugenol, Coumarins, compositions such as lignanoids.Flos Magnoliae nature and flavor suffering, temperature have dispersing wind-cold, the effect of clearing the nasal passage.Extraction quintessence oil-the Flos Magnoliae volatile oil of Flos Magnoliae is more to the target spot of allergic rhinitis treatment; can pass through antihistamine; antiallergic; antiinflammatory and to a plurality of links such as the protective effects of mastocyte and allergic rhinitis is made a difference; treatment to allergic rhinitis is the synergism of several mechanism, thereby can obtain better therapeutic effect.
Liposome is the different arrangement terms of a description by some very wide chemical compounds of chemistry and change in physical scope.It and micelle, microemulsion, liquid crystal, monomolecular film, multimolecular film, host and guest's system etc. are referred to as " molecular assembly assembly ", liposome be actually a kind of amphipathic molecule can spontaneous formation in water by the membrane material of the capsule of the spherical little complete closed of bimolecular film parcel.It can make the higher liposome of envelop rate with water solublity or fat-soluble medicine, drug encapsulation has the class cellularity at this nano_scale particle, thereby reach effects such as reducing toxicity, slow release, lasting curative effect, reduce the toxicity of the therapeutic dose and the reduction medicine of medicine.
Because liposome easily prepares, and has good biocompatibility and hypotoxicity, so be widely used as living model and pharmaceutical carrier in recent years.Wrapping kmedicine by liposome is a physical process, does not change drug molecular structure, can reduce drug toxicity after medicine is wrapped, and reduces the drug use amount, has slow release and controlled-release function, and the medicine of various molecular sizes all can be wrapped.The liposome that can prepare property carries out target administration as immunoliposome, various condition responsive liposome, improves effect of drugs.
The primary raw material phospholipid of liposome is the main composition material of liposome bimolecular film, and wherein lecithin is the Main Ingredients and Appearance that constitutes the human body cell film, is one of life basic substance that keeps cell normal morphology and function.The compatibility of liposome and human body is good, is decomposed the afterproduct totally nontoxic by enzyme in human body.The diameter of liposome is generally in the 25-1000nm scope, and according to liposome morphosis difference, primary structure has two kinds: unilamellar liposome and multilamellar liposome.Unilamellar liposome is formed liposome and is had only monofilm, and multilamellar liposome is made up of the multilamellar monomolecular film.Unilamellar liposome is divided into three kinds of small unilamellar vesicle, middle unilamellar liposome and big unilamellar liposomes again.
Liposome causing the very big interest of scientific circles aspect the drug encapsulation material.In the research of liposome nasal-cavity administration, domestic existing people carries out the research of this respect, Dong Zemin [(research [J] Chinese Journal of Pharmaceuticals 1995 of Dong Ze people's aspisol liposome nasal-cavity administration, 26 (5): 199-202)] prepared the reconstruction type with freeze-thaw method and relied an amine woods liposome, mean diameter is 1.29 μ m.The continuous nasal-cavity administration of rabbit 20mg/kg 20 days is harmless to nasal mucosa.
People's Republic of China's patent publication No. is that G Gregory Ai Disi of 1200668 etc. has invented the liposome that a kind of formation diameter 0.1 μ m to 50 μ m that comprises water-insoluble or undissolved particulate matter has the single or multiple lift structure.
People's Republic of China's patent publication No. is 1446534 to have introduced a kind of Chinese traditional medicine biology bases liposome and preparation thereof, and it can improve effective blood drug concentration.
People's Republic of China's patent publication No. is 1080523 to have introduced a kind of slow release formulation of nasal-cavity administration, is that drying is handled afterwards and made with the sponge-like vector absorption medicine of hollow and the mixed liquor of adjuvant.
At present, the domestic and international patent report that does not also have about the Flos Magnoliae volatile oil liposome.The present nasal drop of Flos Magnoliae on the market all is to adopt common mode, directly acts on nasal mucosa, and difference is that composition is different with preparation method.
Summary of the invention
The object of the present invention is to provide a kind of coated magnolia fargesii volatile oil nano liposome nasal drops.
The objective of the invention is to realize by following technical method: the present invention adopts common reverse evaporation and injection and supersound process to prepare nanometer liposome, makes liposome and nanotechnology and has started wide application prospect in the application aspect the Chinese traditional treatment mode Chinese medicine nasal drop.
A kind of coated magnolia fargesii volatile oil nano liposome nasal drops makes by following method:
A Flos Magnoliae volatile oil, phospholipid, cholesterol, antioxidant, liposome membrane regulator mix, and are dissolved in the dissolution solvent;
The mixed solvent constant temperature reduction vaporization that b obtains step a;
The lipid membrane that c obtains step b adds concussion dissolving in the buffer, regulates pH value, adds adjuvant;
The Liposomal dispersion that d obtains step c, the ice-water bath supersound process is through filtering with microporous membrane;
The liposome turbid liquor that e obtains steps d adds stabilizing agent and is prepared into nasal cavity administrated preparation in filtrate;
Wherein said dissolution solvent is selected from one or more solvents in chloride alkanes, alcohols solvent and the ethers,
Wherein said adjuvant be selected from controlled slow-release preparation, antiseptic one or more.
Flos Magnoliae volatile oil, phospholipid, cholesterol ratio are 15-8: 6-1: 2-1 in step a.
Phospholipid is selected from one or more in soybean lecithin, the Ovum Gallus domesticus Flavus lecithin.
Antioxidant is selected from one or more in collagen protein, vitamin A acetate, the vitamin E in step a, and the antioxidant addition accounts for the 0.1-5% of phospholipid weight.
The liposome membrane regulator is selected from sodium cholate, sodium deoxycholate, Triton-100 in step a, and liposome membrane regulator addition accounts for the 0.001-2.5% of phospholipid weight.
The temperature of evaporating in step b is 28-65 ℃.
Regulating pH value in step c is 5.5-7.5.
The control slow releasing agent is selected from one or more in Stearyl Amine, the diacetyl phosphoric acid in step c, and control slow releasing agent addition accounts for the 3-25% of phospholipid weight.
Antiseptic is selected from one or more in polyoxyethylene sorbitan monoleate, methyl methyl hydroxybenzoate, the phenyl methyl hydroxybenzoate in step c, and the antiseptic addition accounts for the phospholipid weight ratio less than 0.025%.
Ultransonic temperature is at 0-10 ℃ in steps d, and supersonic frequency is at 200-1000Hz, ultransonic effective time 0.5-20min.
Stabilizing agent is selected from one or more in phosphatidyl glycerol, phosphatidic acid, the stearylamine in step e, and the stabilizing agent addition accounts for the 0.9-4.25% of phospholipid weight.
The disclosed a kind of coated magnolia fargesii volatile oil nano liposome nasal drops of the present invention, its advantage shows:
(1) the present invention adopts the form of nasal drop, than conventional nasal drop bigger specific surface area is arranged, increased the contact area of it and nasal membrane, the time of contact and the mucosa infiltration rate of it and nasal membrane have been prolonged relatively, and it is easy to use, can avoid simultaneously because the drug loss that causes in the process of using improves effective rate of utilization.
(2) the liposome nasal drop of the present invention's employing, the compatibility than conventional nasal drop and body is better, can promote to absorb, and can isolate medicine and absorb body, prevent drug induced injury that absorption site is caused, can reduce the be decomposed loss of medicine in absorption process simultaneously.
(3) liposome of the present invention has certain flexibility and morphotropism, absorbs by mucosa than the conventional liposome of same particle size is easier, thereby has better permeability.
(4) particle diameter of liposome of the present invention can conveniently be regulated by changing one or two condition in certain scope.Find that after deliberation particle diameter is can drug absorption under nanoscale rapider in the Flos Magnoliae volatile oil liposome, the mucosa infiltration rate of requirement, particle diameter effect when 100nm is following is better.
Description of drawings
Fig. 1 shows the liposome shape appearance figure that coats Flos Magnoliae volatile oil under the tem observation.
The specific embodiment
Below in conjunction with embodiment the present invention is further described.
Embodiment 1
The preparation of coated magnolia fargesii volatile oil nano liposome nasal drops (one)
200mg soybean lecithin, 750mg Flos Magnoliae volatile oil, 100mg cholesterol, 0.2mg sodium cholate, 1mg collagen protein are dissolved in the mixed solvent of 2: 1 methanol/chloroforms of 20ml.38 ℃ of constant temperature, reduction vaporizations form lipid membrane, add the phosphate buffer concussion dissolving of 20ml, and regulating pH value is 5.5, adds 10mg Stearyl Amine, 0.05mg polyoxyethylene sorbitan monoleate, obtains big multicell Liposomal dispersion.10 ℃ of ultrasonic temperature, the ice-water bath supersound process is 20 minutes under the supersonic frequency 200Hz condition, forms the liposome turbid liquor of uniform monolayer through 0.15 μ m filtering with microporous membrane, adds the 8.5mg phosphatidyl glycerol and be prepared into nasal cavity administrated preparation in filtrate.Measure that entrapped drug carrier liposome mean diameter is 73nm in the suspension, envelop rate is 94.8%, and room temperature was preserved 60 days down, and the solution physicochemical properties are stable, and low temperature was preserved uniform and stable no layering of solution and denaturalization phenomenon 150 days down for 4 ℃.
Embodiment 2
The preparation of coated magnolia fargesii volatile oil nano liposome nasal drops (two)
200mg Ovum Gallus domesticus Flavus lecithin, 330mg Flos Magnoliae volatile oil, 66mg cholesterol, 0.01mg sodium deoxycholate, 10mg vitamin A acetate are dissolved in the mixed solvent of 30ml methanol.28 ℃ of constant temperature, reduction vaporizations form lipid membrane, add the phosphate buffer concussion dissolving of 20ml, and regulating pH value is 7.0, adds 100mg diacetyl phosphoric acid, 0.1mg methyl methyl hydroxybenzoate, obtains big multicell Liposomal dispersion.1 ℃ of ultrasonic temperature, the ice-water bath supersound process is 10 minutes under the supersonic frequency 600Hz condition, forms the liposome turbid liquor of uniform monolayer through 0.15 μ m filtering with microporous membrane, adds the 4mg phosphatidic acid and be prepared into nasal cavity administrated preparation in filtrate.Measure that entrapped drug carrier liposome mean diameter is 56nm in the suspension, envelop rate is 93.6%, and room temperature was preserved 60 days down, and the solution physicochemical properties are stable, and low temperature was preserved uniform and stable no layering of solution and denaturalization phenomenon 150 days down for 4 ℃.
Embodiment 3
The preparation of coated magnolia fargesii volatile oil nano liposome nasal drops (three)
The 200mg soybean lecithin, the 1600mg Flos Magnoliae volatile oil, the 200mg cholesterol, 5mgTriton-100, the 5mg vitamin E is dissolved in 40ml chloroform mixed solvent, 65 ℃ of reduction vaporizations form lipid membrane, the phosphate buffer concussion dissolving that adds 20ml, regulating pH value is 7.5, add the 20mg Stearyl Amine, 50mg diacetyl phosphoric acid, 0.1mg phenyl methyl hydroxybenzoate, obtain big multicell Liposomal dispersion, 5 ℃ of ultrasonic temperature, the ice-water bath supersound process is 1 minute under the supersonic frequency 1000Hz condition, form the liposome turbid liquor of uniform monolayer through 0.15 μ m filtering with microporous membrane, in filtrate, add the 2mg stearylamine and be prepared into nasal cavity administrated preparation.Measure that entrapped drug carrier liposome mean diameter is 66nm in the suspension, envelop rate is 95.8%, and room temperature was preserved 60 days down, and the solution physicochemical properties are stable, and low temperature was preserved uniform and stable no layering of solution and denaturalization phenomenon 150 days down for 4 ℃.
Embodiment 4
Influence to the allergic rhinitis Cavia porcellus
40 of 300～350g Cavia porcelluss are got in Cavia porcellus allergic rhinitis model preparation, and male and female half and half are divided equally 5 groups, and 8 every group, except that staying one group to do the normal control, all the other four groups, with 24 toluene-2,4-diisocyanates (TDL) collunarium sensitization.Be about to 10%TDL olive oil solution 10 μ l, splash into Cavia porcellus bilateral nostril (every side 5 μ l) with sample injector, once a day, 7d after model is judged successfully, keeps the next day of changing into 1 time continuously, finishes until observing medicine; Matched group drips the same model group of method, dosage of olive oil.
Model judges that rhinocnesmus scratching, sneeze, watery nasal discharge to occur serve as to judge index, gives sensitizer TDL the beginning first, as seen rhinocnesmus scratching in various degree, sneeze in the 30min, see watery nasal discharge behind the 3d, with the sensitization time lengthening, symptom gradually increases the weight of, the time of starting shortens, and presents the above symptom of typical case.The curative action effect is scratched number of times with rhinocnesmus, and sneeze number of times, watery nasal discharge degree (flowing to anterior nares is 1 minute, and surpassing anterior nares is 2 minutes, and watery nasal discharge completely is 3 minutes) be as observation index, and be that last is given behind the TDI in the 30min observing time.
After experimental technique and results model are set up, in grouping administration in the 8th day, every day secondary, in the nostril administration of Cavia porcellus bilateral, matched group gives distilled water with sample injector, continuously 7d, 30min after the last administration, give TDL, respectively organize scratching of Cavia porcellus rhinocnesmus and sneeze number of times, watery nasal discharge degree in the observation 30min, the results are shown in Table 1.
Table 1 Flos Magnoliae volatile oil nanometer liposome nasal-cavity administration is to the effect (x ± s of Cavia porcellus allergic rhinitis symptom; N=8)
| Group | Dosage μ l only | Scratching (inferior) | Sneeze (inferior) | Watery nasal discharge (branch) |
| Normal control | 100 | 0.3±0.4 | 0.5±0.6 | 0 |
| The model contrast | 100 | 5.2±1.2△ | 12.2±3.6△ | 2.6±1.0△ |
| The ketotifen nasal drop | 100 | 1.9±0.6 ** | 4.3±1.8 ** | 1.0±0.7 ** |
| Flos Magnoliae volatile oil | 100 | 3.6±1.4 * | 8.7±2.8 * | 1.5±0.9 * |
| The nanometer Flos Magnoliae volatile oil | 100 | 2.4±1.2 ** | 5.2±1.4 ** | 0.8±0.8 ** |
Annotate: compare △ P＜0.01 with the normal control group, compare * P＜005, * * P＜001 with model group
Above-mentioned result of experiment shows: Flos Magnoliae volatile oil nanometer nasal drop can effectively resist the symptom of rhinocnesmus that the Cavia porcellus allergic rhinitis produced, sneeze, watery nasal discharge.Therapeutic effect is better than in conventional Flos Magnoliae volatile oil medicine.
Claims (11)
1, a kind of coated magnolia fargesii volatile oil nano liposome nasal drops is characterized in that making by following method:
A, Flos Magnoliae volatile oil, phospholipid, cholesterol, antioxidant, liposome membrane regulator mix, and are dissolved in the dissolution solvent;
B, the mixed solvent constant temperature reduction vaporization that step a is obtained;
C, the lipid membrane that step b is obtained add concussion dissolving in the buffer, regulate pH value, add adjuvant;
D, the Liposomal dispersion that step c is obtained, the ice-water bath supersound process is through filtering with microporous membrane;
E, the liposome turbid liquor that steps d is obtained add stabilizing agent and are prepared into nasal cavity administrated preparation in filtrate;
Wherein said dissolution solvent is selected from one or more solvents in chloride alkanes, alcohols solvent and the ethers,
Wherein said adjuvant be selected from controlled slow-release preparation, antiseptic one or more.
2, nasal drop according to claim 1 is characterized in that: Flos Magnoliae volatile oil, phospholipid, cholesterol ratio are 15-8: 6-1: 2-1 in step a.
3, nasal drop according to claim 3 is characterized in that: phospholipid is selected from one or more in soybean lecithin, the Ovum Gallus domesticus Flavus lecithin.
4, nasal drop according to claim 1 is characterized in that: antioxidant is selected from one or more in collagen protein, vitamin A acetate, the vitamin E in step a, and the antioxidant addition accounts for the 0.1-5% of phospholipid weight.
5, nasal drop according to claim 1 is characterized in that: the liposome membrane regulator is selected from sodium cholate, sodium deoxycholate, Triton-100 in step a, and liposome membrane regulator addition accounts for the 0.001-2.5% of phospholipid weight.
6, nasal drop according to claim 1 is characterized in that: the temperature of evaporating in step b is 28-65 ℃.
7, nasal drop according to claim 1 is characterized in that: regulating pH value in step c is 5.5-7.5.
8, nasal drop according to claim 1 is characterized in that: the control slow releasing agent is selected from one or more in Stearyl Amine, the diacetyl phosphoric acid in step c, and control slow releasing agent addition accounts for the 3-25% of phospholipid weight.
9, nasal drop according to claim 1 is characterized in that: antiseptic is selected from one or more in polyoxyethylene sorbitan monoleate, methyl methyl hydroxybenzoate, the phenyl methyl hydroxybenzoate in step c, and the antiseptic addition accounts for the phospholipid weight ratio less than 0.025%.
10, nasal drop according to claim 1 is characterized in that: ultransonic temperature is at 0-10 ℃ in steps d, and supersonic frequency is at 200-1000Hz, ultransonic effective time 0.5-20min.
11, nasal drop according to claim 1 is characterized in that: stabilizing agent is selected from one or more in phosphatidyl glycerol, phosphatidic acid, the stearylamine in step e, and the stabilizing agent addition accounts for the 0.9-4.25% of phospholipid weight.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005101113474A CN100467013C (en) | 2005-12-09 | 2005-12-09 | Coated magnolia fargesii volatile oil nano liposome nasal drops |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005101113474A CN100467013C (en) | 2005-12-09 | 2005-12-09 | Coated magnolia fargesii volatile oil nano liposome nasal drops |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1813905A true CN1813905A (en) | 2006-08-09 |
| CN100467013C CN100467013C (en) | 2009-03-11 |
Family
ID=36906337
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2005101113474A Expired - Fee Related CN100467013C (en) | 2005-12-09 | 2005-12-09 | Coated magnolia fargesii volatile oil nano liposome nasal drops |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100467013C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112569193A (en) * | 2019-09-27 | 2021-03-30 | 深圳光彩生命工程技术有限公司 | Magnolia liliflora volatile oil nano liposome freeze-dried powder |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1634346A (en) * | 2004-10-27 | 2005-07-06 | 上海大学 | Preparation method of amomum fruit volatile oil nanometer liposome turbid liquor medicament |
-
2005
- 2005-12-09 CN CNB2005101113474A patent/CN100467013C/en not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112569193A (en) * | 2019-09-27 | 2021-03-30 | 深圳光彩生命工程技术有限公司 | Magnolia liliflora volatile oil nano liposome freeze-dried powder |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100467013C (en) | 2009-03-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0317120B1 (en) | Improved amphotericin b liposome preparation | |
| EP2879502B1 (en) | Cochleates made with soy phosphatidylserine | |
| US20050208122A1 (en) | Biodegradable biocompatible implant and method of manufacturing same | |
| JP2017226691A (en) | Novel formulations of volatile anesthetics and methods of use thereof for reducing inflammation | |
| CN101209348A (en) | Elastic nano vesicle carrier and preparation and application thereof | |
| WO2008130137A1 (en) | Anionic lipid nanosphere and preparation method of the same | |
| CH684308A5 (en) | Liposomes containing an allylamine. | |
| CN101011354B (en) | Asarone submicron emulsion and its preparation method | |
| CN101209251A (en) | Elastic nano vesicle preparations containing paclitaxel or docetaxel and preparation thereof | |
| KR20050105445A (en) | Asiaticoside-liposome and its use | |
| US20130189352A1 (en) | Liposome comprising combination of chloroquine and adriamycin and preparation method thereof | |
| CN100350912C (en) | Nanometer partical administration system of prostaglandin E1 coated with polyglycol derived phospholipid | |
| CN100493530C (en) | Method for preparing coated magnolia fargesii volatile oil nano liposome nasal drops | |
| CN100467013C (en) | Coated magnolia fargesii volatile oil nano liposome nasal drops | |
| CN106309370A (en) | Paclitaxel pH-sensitive long-circulation liposome and preparation method thereof | |
| EP2680821B1 (en) | Liposome formulation comprising an anti-tumour active substance, method for its preparation and pharmaceutical compositions comprising it | |
| CN1813906A (en) | Incense-fuming solid-state formulation for treating nasitis and reagent bottle equipped with same | |
| CN101147728A (en) | 6-methocy bideoxy bideoxy guanosine long circulating liposome preparation and preparing method | |
| US20040175417A1 (en) | Amphotericin B liposome preparation | |
| CN103040723B (en) | Xiyanping lipidosome injection | |
| CN103040744B (en) | Propyl gallate liposome injection | |
| CN101190183B (en) | Clonidine hydrochloride multi-vesicular liposome and preparation method thereof | |
| CN116440080A (en) | Safflower yellow nanometer flexible liposome and preparation method thereof | |
| RU42953U1 (en) | LIPOSOMAL NANOCAPSULE WITH DOXORUBICIN |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20090311 Termination date: 20121209 |