CN105983101A - Application of essential oil of alpinia oxyphylla miq. as penetration enhancer in fields of drug transdermal delivery and cosmetics - Google Patents
Application of essential oil of alpinia oxyphylla miq. as penetration enhancer in fields of drug transdermal delivery and cosmetics Download PDFInfo
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Abstract
According to the invention, essential oil of alpinia oxyphylla miq. is taken as a major research object, and the effect of the essential oil on promoting drug transdermal permeation is investigated. On the basis of systematic investigation, both fruit essential oil and leaf essential oil of the alpinia oxyphylla miq. are relatively strong in penetration enhancing effect; and when the concentration of the essential oil is 3%, the penetration enhancing effect of the fruit essential oil and the leaf essential oil on drugs is obviously better than that of a common skin penetration enhancer, namely azone. Based upon GC-MS analysis, as for major ingredients, the fruit essential oil and the leaf essential oil are different in contents of alkane terpene and oxy-terpene ingredients; therefore, the fruit essential oil and the leaf essential oil keep a certain difference in drug penetration enhancing effect. In addition, the result of a skin irritation test proves that the fruit essential oil and the leaf essential oil, at an appropriate concentration, can avoid any erythema or edema in animal skin. Therefore, the essential oil of the alpinia oxyphylla miq., with the significant penetration enhancing effect and safety to the skin, has a broad development and application prospect in the fields of drug delivery and cosmetics.
Description
Technical field
The present invention relates to the quintessence oil research method as dermal osmosis accelerator of a kind of Hainan genuine medicinal materials Fructus Alpiniae Oxyphyllae, steam distillation is used to extract Fructus Alpiniae Oxyphyllae fruit and leaf quintessence oil respectively, with healthy rat back isolated skin as permeability barrier, indomethacin is to be promoted drug model, external Franz diffusion cell is permeability apparatus, UPLC-PDA is that detection technique carries out content analysis, with two kinds of derived essential oils of GC-MS com-parison and analysis, carrying out irritation test with New Zealand's large ear rabbit and investigate the safety of quintessence oil, it belongs to medicine and cosmetic technical field.
Background technology
The barrier action of keratodermatitis makes the transdermal penetration rate of most medicine be difficult to meet treatment needs.Percutaneous absorption enhancer (penetration enhancer), it is possible to reversible change keratodermatitis barrier function and don't damage any competent cell, it is possible to the transdermal capability strengthening medicine improves drug transdermal amount.Transdermal absorption in cosmetics, referring to the neutraceutical active ingredients in cosmetics can act on skin surface according to the effectiveness of product or enter epidermis or corium, and gathers at this position and play a role；If nutritional labeling can not be fully absorbed by skin, skin surface nutritional labeling then can be caused superfluous, parasitic bacteria amount reproduction, thus cause skin infection, penetration enhancer importance in cosmetics as can be seen here, conventional penetration enhancer mainly has natural penetration enhancer and synthesis penetration enhancer.But, toxicity and the zest of some synthesis penetration enhancer (such as: dimethyl sulfoxide) limit its clinical practice.Therefore, natural penetration enhancer is by the extensive concern of researcher, especially rich in the volatile oil of terpenes composition.Research shows, the volatile oil of the Chinese traditional herbs such as Rhizoma Chuanxiong, Rhizoma Zingiberis, Radix Angelicae Sinensis, Fructus Cnidii has significant transdermal enhancing effect.
Fructus Alpiniae Oxyphyllae (Alpinia oxyphylla Miq.) is Zingiberaceae Alpinia herbaceos perennial, is mainly distributed on the ground such as Hainan, Guangdong, Guangxi, for one of China four great Nan medicine and Hainan Province's genuine medicinal materials.Volatile oil is the important component of Fructus Alpiniae Oxyphyllae, and content is about 1-2%, is made up of multiple terpenoid.High spot reviews of the present invention Fructus Alpiniae Oxyphyllae fruit and the leaf quintessence oil transdermal enhancing effect to medicine and the safety to skin, develop Fructus Alpiniae Oxyphyllae medical material and have important directive significance in the application of medicine transmission and cosmetic field.
Summary of the invention
It is contemplated that research Fructus Alpiniae Oxyphyllae fruit and leaf quintessence oil are as dermal osmosis accelerator application in medicine transmission and cosmetics.With indomethacin as drug model, healthy rat back isolated skin is permeability barrier, and external Franz diffusion cell is permeability apparatus, UPLC-PDA analytical technology detection drug osmotic content；The cutaneous safety of irritation test checking quintessence oil is carried out with New Zealand's large ear rabbit for animal model.Efficient and rational transdermal enhancing effect and cutaneous safety make Fructus Alpiniae Oxyphyllae quintessence oil have broad application prospects in terms of medicine transmission field and cosmetic actives absorption.
Technical solution
The technical solution used in the present invention is: steam distillation extracts the quintessence oil of Fructus Alpiniae Oxyphyllae fruit and leaf respectively；With healthy Wistar skin of rat as permeability barrier, with indomethacin for being promoted drug model, Franz diffusion cell permeability apparatus, combined U PLC-PDA analytical tool detection different time points is applied to receive the content of liquid Chinese medicine；Analyzed the composition of fruit essential oil and leaf quintessence oil by GC-MS, and carry out irritation test with New Zealand's large ear rabbit.
Technology Roadmap is shown in Fig. 1
Technical essential:
(1) drug osmotic experimental technique, is carried out as steps described below:
A. prepared by skin of rat: selects healthy Wistar rat, 10% chloral hydrate solution, intraperitoneal injection of anesthesia, after fixing limbs, carefully cuts off back hair with surgical scissors, then carefully peeled off by this partial skin, removes subcutaneous fat and tissue；Ensure skin without impaired, after repeatedly rinsing well with normal saline, the fritter of clip suitable size, with masking foil parcel to be placed on-20 DEG C of Refrigerator stores standby, use in Yu Yizhou；
B. supply mutually and receives liquid and prepares: supply be mutually 2% (w/v) sodium carboxymethyl cellulose the most swelling in water after, room temperature stands overnight, indomethacin (3mg/ml) ethanol (10%, v/v) after dissolving, join in gained gel, stirring, positive controls adds the azone (Azone) of variable concentrations, and experimental group adds the quintessence oil of variable concentrations；Receiving liquid is ethanol/pH 7.4PBS (1: 1, v/v)；
C. the processing mode of experimental group skin: skin uses the quintessence oil of variable concentrations and Azone to process removing after 2h respectively, after cleaning up, adds the gel containing osmotic drug indomethacin；
(2) irritation test method, is carried out as steps described below:
A. choosing New Zealand's large ear rabbit, often group four, male and female half and half, before experiment, 24h loses hair or feathers in both sides, back, and depilatory is 8g sodium sulfide, and 7g starch dissolution (is first cut short hair, then used depilatory 2-3min) in 100mL water, and unhairing scope is 3 × 3cm2, after depilation, clean epilating area with appropriate warm water；
B. with clear water as blank, the base oil of dilution quintessence oil is negative control, and each consumption is 0.5mL, cleans up with warm water after smearing four hours, and continuously at same regional administration in one week, each administration time is identical, observation experiment result.
The effectiveness of this study tour quintessence oil and safety, developing further and providing in the application of medicine transmission and cosmetic field and ensure reliably for Fructus Alpiniae Oxyphyllae medical material.
Detailed description of the invention
By following example, the present invention is further described.Set forth below for embodiment be construed as limiting never in any form.
Solution is prepared: the PBS buffer solution of 0.1moL/L, pH 7.4: 8g NaCl, 1.2g Na2HPO4, 0.2g KH2PO4, 0.2g KCl is dissolved in 1000mL water；
Embodiment 1: permeability test
(1) prepared by quintessence oil:
Fructus Alpiniae Oxyphyllae fruits and the leaf powder of crossing No. two sieves after the most accurately weighing 300g pulverizing are placed in 5L round-bottomed flask, add 10 times amount water, soak 6 hours；Round-bottomed flask is heated in heating mantle, keeps micro-boiling, with extraction by steam distillation 6 hours；Standing a moment after stopping heating, water is slowly released by the piston opening determinator lower end, arriving at scale 5mm to oil reservoir upper end；Placing more than 1h, it is the most concordant with scale 0 that unlatching piston makes oil reservoir drop to its upper end, reads volatilization oil mass, calculates volatile oil yield；
B. quintessence oil stores: quintessence oil extraction obtained is placed in centrifuge tube, adds appropriate anhydrous sodium sulfate and is dried；It is placed in a centrifuge with 13000rpm, centrifugal 5min；With liquid-transfering gun, volatile oil is transferred in brown sample injection bottle, is placed in-4 DEG C of refrigerators, stand-by；
(2) prepared by skin:
A. choose healthy Wistar rat, give 10% chloral hydrate solution, intraperitoneal injection of anesthesia, carefully reject back hair with surgical scissors, then this partial skin is carefully peeled off, remove subcutaneous fat and tissue；
B. skin physiological saline is rinsed well repeatedly, the fritter of clip suitable size, is placed in-20 DEG C of Refrigerator stores, uses in Yu Yizhou；
C. before permeability test starts, take out skin from refrigerator, naturally thaw in room temperature normal saline；
(3) supply phase and the preparation of reception liquid:
A. supply phase: take 0.2g sodium carboxymethyl cellulose, be dissolved in while stirring in 9mL PBS, the most swelling after, room temperature stands overnight, and accurately weighs 30.0mg indomethacin, is dissolved in 1mL ethanol, adds solution in gained gel while stirring；
B. liquid is received: for ethanol/pH7.4PBS (1: 1, v/v)；
(4) permeability test:
Skin filter paper after naturally thawing is dried gently, and stratum corneum side is fixed between diffusion cell and reception tank upward, it is ensured that bubble-free between skin and reception liquid；The temperature receiving liquid is 37 ± 0.1 DEG C, and magneton rotating speed is 600rpm；Sampling time point is 1,2,4,6,8,10,12,24h, every sub-sampling 1mL, adds the equal volume reception liquid with equitemperature after sampling immediately；Sample i.e. can use UPLC-PDA to detect medicament contg after 0.22 μm membrane filtration.
(5) chromatographic condition: Waters ACQUITYH-Class Ultra Performance Liquid Chromatography instrument, PDA detector；Waters ACQUITYBEH Shield RP 18 (50 × 2.1mm, 1.7 μm) chromatographic column；Detection wavelength: 268nm；Sample size: 1 μ L；Column temperature: 30 DEG C；Flowing phase: methanol/0.05% acetic acid water (65/35, v/v)；Flow velocity: 0.2mL/min.
Medicine transdermal enhancing effect comparison diagram is shown in Fig. 2 by fruit, leaf quintessence oil and Azone (3%)
Embodiment 2:GC-MS analyzes fruit and the composition of leaf quintessence oil
1. sample treatment: using steam distillation to respectively obtain fruit and leaf quintessence oil, precision measures 10 μ L quintessence oils, is placed in 1mL volumetric flask, is diluted to scale by ethyl acetate (chromatographic grade), shakes up.
2. chromatographic condition: Thermo GC-MS gas chromatograph-mass spectrometer, AI/AS3000 sample introduction tower；Carrier gas: nitrogen (purity 99.99%)；GC chromatographic column TR-5MS (30m × 0.25mm i.d., 0.32 μm)；Injector temperature: 250 DEG C；Sample size: 1.0 μ L；Splitless injecting samples；Temperature programming, initial temperature 50 DEG C, keep 3min, be warming up to 90 DEG C with 6 DEG C/min, keep 5min, then be warming up to 140 DEG C with 6 DEG C/min, be then warming up to 145 DEG C with 0.2 DEG C/min, keep 2min, then be warming up to 260 DEG C with 15 DEG C/min, keep 6min.Ionization mode (EI), sweep time 0.2s/Scan, sweep limits: 40.0-500.0u.
The GC-MS spectrogram of fruit essential oil and leaf quintessence oil is shown in Fig. 3
Embodiment 3: fruit essential oil and the leaf quintessence oil safety testing to rabbit skin
1. choosing healthy New Zealand large ear rabbit, often group four, male and female half and half, before experiment, 24h loses hair or feathers in both sides, back, and depilatory is 8g sodium sulfide, and 7g starch dissolution (is first cut short hair, then used depilatory 2-3min) in 100mL water, and unhairing scope is 3 × 3cm2, after depilation, clean epilating area with appropriate warm water.
2., with clear water as blank, the base oil of dilution quintessence oil is negative control, and each consumption is 0.5mL, cleans up with warm water after smearing four hours, and continuously at same regional administration in one week, each administration time is identical, observation experiment result.
Irritation test result figure is shown in Fig. 4
Accompanying drawing illustrates:
Fig. 1 is the technology of the present invention route map
Fig. 2 is that fruit, leaf quintessence oil and Azone (3%) are to medicine transdermal enhancing effect comparison diagram
Fig. 3 is the GC-MS spectrogram of fruit essential oil and leaf quintessence oil
Fig. 4 is irritation test result figure.
Claims (2)
1. Fructus Alpiniae Oxyphyllae quintessence oil transmits and the application of cosmetic field at drug transdermal as penetration enhancer, it is characterised in that:
(1) extraction by steam distillation Fructus Alpiniae Oxyphyllae fruit and leaf quintessence oil；
(2) with healthy male Wistar rat skin of back as permeability barrier, external Franz diffusion cell is tested；
(3) with indomethacin as drug model, UPLC-PDA is that detection technique sets up drug detection method；
(4) compare and the composition of discrimination fruit essential oil Yu leaf quintessence oil with GC-MS；
(5) with New Zealand's large ear rabbit as animal model, irritation test is carried out.
2. transmit and the application of cosmetic field at drug transdermal as penetration enhancer according to claim 1 Fructus Alpiniae Oxyphyllae quintessence oil, it is characterised in that the method includes following
Step:
(1) Fructus Alpiniae Oxyphyllae fruit and the preparation process of leaf quintessence oil:
Weigh Fructus Alpiniae Oxyphyllae fruit respectively and blade 300g (pulverizing, cross No. 2 sieves) be placed in 5L round-bottomed flask, extract volatile oil, extracting method:
10 times of water yields, soak 8h, extract 6h.Quintessence oil adds appropriate anhydrous sodium sulfate and removes water, is stored in-4 DEG C of refrigerators, standby；
(2) preparation process of rat skin:
A. select healthy Wistar rat through 10% chloral hydrate intraperitoneal injection of anesthesia, carefully reject back hair with surgical scissors, then by this portion
Divide skin carefully to peel off, carefully remove subcutaneous fat and tissue；
B. repeatedly rinse skin, clip optimum plot size with normal saline well, be placed on-20 DEG C of Refrigerator stores, in Yu Yizhou with what masking foil wrapped up
Use；
(3) permeability test step:
A. before vitro permeation assay starts, take out skin from refrigerator, naturally thaw in room temperature normal saline；Stratum corneum side upward, is fixed on supply
Between pond and diffusion cell, receiving liquid is ethanol/PBS (pH=7.4) (1: 1, v/v), discharges skin and the bubble received between liquid, in disperser
The temperature of water is maintained at 37 ± 0.1 DEG C, rotor speed 600rpm；
B. the Fructus Alpiniae Oxyphyllae quintessence oil of variable concentrations and positive control azone (Azone) process skin respectively and remove after 2 hours, add 1g and contain indole U.S.
Pungent supply phase, receiving liquid sampling time point is 1h, and 2h, 4h, 6h, 8h, 10h, 12h, 24h add equivalent isothermal immediately after sampling
Fresh reception liquid；
C. acceptable solution crosses 0.22 μm filter membrane, and UPLC-PDA carries out content analysis.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108497440A (en) * | 2018-03-27 | 2018-09-07 | 广州城市职业学院 | A kind of natural longan flavouring and preparation method thereof |
| CN113416608A (en) * | 2021-06-29 | 2021-09-21 | 中国热带农业科学院热带作物品种资源研究所 | Extraction method of intelligence-developing essential oil for inhibiting listeria monocytogenes and intelligence-developing essential oil |
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| CN102688163A (en) * | 2012-06-13 | 2012-09-26 | 中国医学科学院药用植物研究所海南分所 | Anti-skin aging skin care compound essential oil |
| TWI463997B (en) * | 2013-09-26 | 2014-12-11 | Univ Hungkuang | Antioxidant, whitening and antibacterial function of the benefits of intellectual oil and its Method |
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2015
- 2015-02-03 CN CN201510057924.XA patent/CN105983101A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102688163A (en) * | 2012-06-13 | 2012-09-26 | 中国医学科学院药用植物研究所海南分所 | Anti-skin aging skin care compound essential oil |
| TWI463997B (en) * | 2013-09-26 | 2014-12-11 | Univ Hungkuang | Antioxidant, whitening and antibacterial function of the benefits of intellectual oil and its Method |
Non-Patent Citations (2)
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| J.Y. FANG: "Development of sesquiterpenes from Alpinia oxyphylla as novel skin permeation enhancers", 《EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES》 * |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108497440A (en) * | 2018-03-27 | 2018-09-07 | 广州城市职业学院 | A kind of natural longan flavouring and preparation method thereof |
| CN113416608A (en) * | 2021-06-29 | 2021-09-21 | 中国热带农业科学院热带作物品种资源研究所 | Extraction method of intelligence-developing essential oil for inhibiting listeria monocytogenes and intelligence-developing essential oil |
| WO2023272797A1 (en) * | 2021-06-29 | 2023-01-05 | 中国热带农业科学院热带作物品种资源研究所 | Method for extracting alpinia oxyphylla miq essential oil for inhibiting listeria monocytogenes, and alpinia oxyphylla miq essential oil |
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Application publication date: 20161005 |