CN108143717A - A kind of menthol nanoemulsion and preparation method thereof - Google Patents
A kind of menthol nanoemulsion and preparation method thereof Download PDFInfo
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- CN108143717A CN108143717A CN201810143695.7A CN201810143695A CN108143717A CN 108143717 A CN108143717 A CN 108143717A CN 201810143695 A CN201810143695 A CN 201810143695A CN 108143717 A CN108143717 A CN 108143717A
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- menthol
- nanoemulsion
- polyoxyethylene
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- distilled water
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
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- 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
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- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
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- 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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- 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
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Abstract
The present invention relates to pharmaceutical technology fields, and in particular to a kind of menthol nanoemulsion and preparation method thereof.The present invention includes menthol, medium-chain fatty glyceride, polyoxyethylene-type surfactant, polysorbate, sucrose fatty ester, preservative, pH adjusting agent and distilled water.Menthol nanoemulsion provided by the invention can be effectively increased solubility of the menthol in aqueous solvent, and it without ethyl alcohol, emulsion products appearance clear obtained, applied widely, Clinical practice is safe and effective, and can preserve steadily in the long term.
Description
Technical field
The present invention relates to medical solubilization technique fields, and in particular to a kind of menthol nanoemulsion and preparation method thereof.
Background technology
Menthol, also known as l-menthol, its chemical name is：L-1- methyl -4- isopropyl cyclohexanols -3
Its structural formula is：
Molecular formula：C10H20O
Molecular weight：156.26
Physico-chemical property：White crystal has peppermint fragrance, and solubility is extremely low in water.
Menthol is a kind of saturation cyclic terpene alcohol being present in peppermint and Peppermint essential oil, can also be obtained by chemical synthesis.
Menthol is a kind of white column or acicular crystal, has antipruritic, analgesic, refrigerant and slight local anaesthesia with inhibiting peristalsis of the digest tract etc.
Effect, is widely used as daily chemical product and pharmaceuticals, and the scope of application is related to tobacco, cosmetics, odorant, fragrance and medical inside and outside
Section's drug etc. has high use value.But solubility is extremely low in water for menthol, less than 0.5mg/ml, this defect
Greatly limit the application of menthol.
Existing technology often uses ethyl alcohol or poly yamanashi esters to solve solubility of the menthol in aqueous solvent
To carry out solubilising.This method improves dissolubility of the menthol in aqueous solvent to a certain extent, Unfortunately, gathers
Sorb ester can be degraded by autoxidation or hydrolysis, when polysorbate molecular degradation, generate a variety of degradation by-products,
So that product appearance obtained is muddy, stability is poor including such as aliphatic acid, alkyl acid etc., storage process is easily destroyed,
Menthol is caused to be precipitated；And using ethanol as solvent, product can not take orally, be unsuitable for other non-alcohol conditions, the scope of application by
To limitation.
Therefore, for above-mentioned technical problem, it is necessary to provide a kind of menthol solubility height, without ethyl alcohol and its stability
Strong menthol nanoemulsion.
Invention content
The present invention is intended to provide a kind of menthol nanoemulsion and preparation method thereof is to solve menthol water in the prior art
The problem of dissolubility is low, and product stability obtained is poor.
Technical problem of the present invention is realized by following technical scheme：A kind of menthol nanoemulsion, each group in the emulsion
The mass ratio (w/w) divided is as follows：Menthol 0.5~5%, medium-chain fatty glyceride 0.5~5%, polyoxyethylene-type surface are lived
Property agent 2.5~40%, polysorbate 0.2~20%, sucrose fatty ester 0~2%, preservative 0.05~0.2% and surplus
Distilled water, with pH adjusting agent adjust pH to 4.0~7.0.
Further, the mass ratio (w/w) of each component is as follows in the emulsion：Menthol 0.8%, medium-chain fatty glyceride
0.8%th, polyoxyethylene-type surfactant 6%, polysorbate 2%, sucrose fatty ester 0.2%, preservative 0.05% and
The distilled water of surplus adjusts pH to 5.0 with pH adjusting agent.
Further, the medium-chain fatty glyceride include but not limited to Capmul MCM C8, two glycerol caprylates and
One or more of tricaprylin.
Further, the polyoxyethylene-type surfactant is selected from polyoxyl 40 hydrogenated castor oil, polyoxyethylene 50
Rilanit special, Cremophor RH60, Emulsifier EL-35, Emulsifier EL-60, polyoxyethylene 80
One or more of castor oil, Emulsifier EL-90 and Emulsifier EL-100.
Further, the polysorbate be selected from one or both of polysorbate60, polysorbate65, Tween 80 and polysorbate85 with
On.
Further, the preservative is selected from one or both of potassium sorbate and sodium benzoate.
Further, the grain size of the menthol nano-emulsion is 20~100nm.
Further, the mass ratio (w/w) of each component is as follows in the emulsion：Menthol 0.5~5%, tricaprylin
0.5~5%, polyoxyl 40 hydrogenated castor oil 2.5~40%, polyoxyethylene sorbitan monoleate 0.5~20%, sucrose fatty ester 0~
2%th, potassium sorbate 0.05~0.2% and the distilled water of surplus adjust pH to 4.0~7.0 with pH adjusting agent.
Further, the mass ratio (w/w) of each component is as follows in the emulsion：Menthol 0.8%, tricaprylin
0.8%th, polyoxyl 40 hydrogenated castor oil 6%, polyoxyethylene sorbitan monoleate 2%, sucrose fatty ester 0.2%, potassium sorbate 0.05%
And the distilled water of surplus, adjust pH to 5.0 with pH adjusting agent.
Further, the menthol nanoemulsion is oral preparations.
Correspondingly, the present invention also provides a kind of method for preparing above-mentioned menthol nanoemulsion, include the following steps：
A menthol, medium-chain fatty glyceride, polyoxyethylene-type surfactant, polysorbate, sucrose fat) are weighed
Acid esters, mixed grinding to menthol all dissolve, and obtain transparent slightly sticky solution；
B) by step A) made from solution be slowly added to distilled water while stirring to the 80% of full dose, nanosizing processing；
C) in step B) made from add in preservative in solution, with pH adjusting agent tune pH to 5.0 or so, determined with distilled water
Hold to get.
Compared with prior art, advantageous effect of the present invention is：
1) compared with existing menthol nanoemulsion, the present invention can take orally, Clinical practice is safer, has without ethyl alcohol
Effect.
2) this product provides a kind of new solubilizing systems, by polyoxyethylene-type surfactant, sucrose fatty ester and spits
Temperature composition, one side can significantly improve the solubility in water phase of menthol, and need not add ethyl alcohol, can be prepared into
Oral preparations use；On the other hand, inventor on the basis of tween it was unexpectedly observed that add in polyoxyethylene-type surfactant
The oxidation and degradation of tween itself can be overcome with sucrose fatty ester, emulsion products active ingredient containing menthol obtained is more
More, appearance is more clarified, stability higher；Simultaneously this product handled through nanosizing, uniform particle sizes are tiny, concentrate on 20~100nm with
Under.
Specific embodiment
The present invention is illustrated, but be not limited to following embodiment below by embodiment.
Embodiment one, menthol nanoemulsion
Preparation method：More than prescription accurate weighing material is pressed, menthol, tricaprylin, polyoxyethylene 40 is taken to hydrogenate
Castor oil, Tween 80, sucrose fatty ester, mixed grinding to menthol all dissolve, and obtain transparent slightly sticky solution；To mixed
It closes liquid to carry out magnetic agitation and be slowly added to distilled water to 80ml, ultrasonic nano handles 10min, sorbic acid is added in into solution
Potassium, with citric acid tune pH to 5.0 or so, with distilled water be settled to 100ml to get.
Embodiment two, menthol nanoemulsion
Preparation method reference implementation example one.
Embodiment three, menthol nanoemulsion
Preparation method reference implementation example one.
Example IV, menthol nanoemulsion
Preparation method reference implementation example one.
Embodiment five, menthol nanoemulsion
Preparation method reference implementation example one.
Comparative example one, menthol nanoemulsion
Difference lies in do not contain polyoxyl 40 hydrogenated castor oil, the dosage of Tween 80 to comparative example one with embodiment one
8.0g is increased to, remaining parameter and operation reference implementation example one.
Comparative example two, menthol nanoemulsion
Difference lies in do not contain polyoxyl 40 hydrogenated castor oil and sucrose-fatty to comparative example two with embodiment one
Ester, the dosage of Tween 80 increase to 8.2g, remaining parameter and operation reference implementation example one.
Comparative example three, menthol nanoemulsion
Difference lies in do not contain sucrose fatty ester, the dosage of Tween 80 increases to comparative example three with embodiment one
1.1g, remaining parameter and operation reference implementation example one.
Test example one, quality evaluation
One to three sample of Example one to five and comparative example, to the progress such as content of its grain size, appearance, pH and menthol
It measures, measurement result is as shown in table 1.
1 measurement result of table
Result of the test shows that one to three average grain diameter of the embodiment of the present invention is less than 80nm, and narrowly distributing, impurity content is few, greatly
Emulsion droplet content meets the requirements, and example IV and five average grain diameters are real slightly larger than embodiment one also between 60.00-80.00nm
Applying the menthol nanoemulsion of example one to five, all indicators are better than comparative examples one to three.
Test example two, estimation of stability
Example one to five and one to three sample of comparative example are placed in 25 DEG C, under the conditions of relative humidity 60%, carry out long-term
Stability test, result of the test are as shown in table 2.
2 long-term stable experiment result table of table
Result of the test shows embodiment one to five after storage 18 months, remains to keep clarification without cloudy state, stability
Higher, comparative example one begin to turbid phenomenon occur after 12 months, and comparative example two begins to muddiness occur after six months, and 18
It is even more bulk precipitation occur after a month, quality is significantly unstable；There is slight turbid phenomenon after 9 months in comparative example three, and 18
There is bulk precipitation to occur after a month.
The above content is the preferred embodiment of the present invention, it is impossible to assert that the specific implementation of the present invention is only limited to these and says
It is bright, it should be pointed out that：For those of ordinary skill in the art, without departing from the principle of the present invention, it can also do
Go out several improvements and modifications, these improvements and modifications also should be regarded as protection scope of the present invention.
Claims (10)
1. a kind of menthol nanoemulsion, it is characterised in that：The mass ratio (w/w) of each component is as follows in the emulsion：Menthol 0.5
~5%, medium-chain fatty glyceride 0.5~5%, polyoxyethylene-type surfactant 2.5~40%, polysorbate 0.2~
20%th, the distilled water of sucrose fatty ester 0~2%, preservative 0.05~0.2% and surplus, with pH adjusting agent adjust pH to
4.0~7.0.
2. menthol nanoemulsion according to claim 1, it is characterised in that：Mass ratio (the w/ of each component in the emulsion
W) it is as follows：Menthol 0.8%, medium-chain fatty glyceride 0.8%, polyoxyethylene-type surfactant 6%, polysorbate 2%,
The distilled water of sucrose fatty ester 0.2%, preservative 0.05% and surplus adjusts pH to 5.0 with pH adjusting agent.
3. menthol nanoemulsion according to claim 1 or 2, it is characterised in that：The medium-chain fatty glyceride choosing
From one or more of Capmul MCM C8, two glycerol caprylates and tricaprylin.
4. menthol nanoemulsion according to claim 1 or 2, it is characterised in that：The polyoxyethylene-type surface-active
Agent is selected from polyoxyl 40 hydrogenated castor oil, Nikkol HCO50, Cremophor RH60, polyoxyethylene
35 castor oil, Emulsifier EL-60,100 castor-oil plant of Emulsifier EL-80, Emulsifier EL-90 and polyoxyethylene
One or more of oil.
5. menthol nanoemulsion according to claim 1 or 2, it is characterised in that：The polysorbate be selected from polysorbate60,
One or more of polysorbate65, Tween 80 and polysorbate85.
6. menthol nanoemulsion according to claim 1 or 2, it is characterised in that：The preservative is selected from potassium sorbate
One or both of with sodium benzoate.
7. menthol nanoemulsion according to claim 1 or 2, it is characterised in that：The grain size of the menthol nano-emulsion
For 20~100nm.
8. menthol nanoemulsion according to claim 1, it is characterised in that：Mass ratio (the w/ of each component in the emulsion
W) it is as follows：Menthol 0.5~5%, tricaprylin 0.5~5%, polyoxyl 40 hydrogenated castor oil 2.5~40%, poly- mountain
Pear ester 80 0.5~20%, sucrose fatty ester 0~2%, potassium sorbate 0.05~0.2% and surplus distilled water, use pH
Conditioning agent adjusts pH to 4.0~7.0.
9. menthol nanoemulsion according to claim 1 or 2, it is characterised in that：The menthol nanoemulsion is interior
Formulation.
A kind of 10. method for preparing menthol nanoemulsion according to claim 1 or 2, it is characterised in that：Including following
Step：
A menthol, medium-chain fatty glyceride, polyoxyethylene-type surfactant, polysorbate, sucrose fatty ester) are weighed,
Mixed grinding is all dissolved to menthol, obtains transparent slightly sticky solution；
B) by step A) made from solution be slowly added to distilled water while stirring to the 80% of full dose, nanosizing processing；
C) in step B) made from add in preservative in solution, with pH adjusting agent tune pH to 5.0 or so, with distilled water constant volume, i.e.,
.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810143695.7A CN108143717A (en) | 2018-02-12 | 2018-02-12 | A kind of menthol nanoemulsion and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810143695.7A CN108143717A (en) | 2018-02-12 | 2018-02-12 | A kind of menthol nanoemulsion and preparation method thereof |
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| Publication Number | Publication Date |
|---|---|
| CN108143717A true CN108143717A (en) | 2018-06-12 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201810143695.7A Pending CN108143717A (en) | 2018-02-12 | 2018-02-12 | A kind of menthol nanoemulsion and preparation method thereof |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112602876A (en) * | 2020-12-30 | 2021-04-06 | 湖南农业大学 | Nanoemulsion based on natural bacteriostatic agent eutectic solvent and preparation and application thereof |
| CN113317431A (en) * | 2021-06-11 | 2021-08-31 | 扬州大学 | Oil-in-water carvacrol nanoemulsion and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1893982A (en) * | 2003-06-30 | 2007-01-10 | 日本制药株式会社 | Menthol-containing preparation |
-
2018
- 2018-02-12 CN CN201810143695.7A patent/CN108143717A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1893982A (en) * | 2003-06-30 | 2007-01-10 | 日本制药株式会社 | Menthol-containing preparation |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112602876A (en) * | 2020-12-30 | 2021-04-06 | 湖南农业大学 | Nanoemulsion based on natural bacteriostatic agent eutectic solvent and preparation and application thereof |
| CN113317431A (en) * | 2021-06-11 | 2021-08-31 | 扬州大学 | Oil-in-water carvacrol nanoemulsion and preparation method thereof |
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Application publication date: 20180612 |
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