CN105726465A - Preparation method of pectic matrix oridonin nano lipid gel - Google Patents
Preparation method of pectic matrix oridonin nano lipid gel Download PDFInfo
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- CN105726465A CN105726465A CN201610198005.9A CN201610198005A CN105726465A CN 105726465 A CN105726465 A CN 105726465A CN 201610198005 A CN201610198005 A CN 201610198005A CN 105726465 A CN105726465 A CN 105726465A
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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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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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
- A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
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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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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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
- A61K9/127—Liposomes
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Abstract
The invention discloses a preparation method of a pectic matrix oridonin nano lipid gel, and belongs to the field of gels. The method comprises the following steps: extracting and preparing pectin from pitaya; preparing a nano lipid from oridonin, lecithin and cholesterol; and preparing a gel mixed solution from the pectin and sodium alginate, mixing the mixed solution with the oridonin nano lipid and concentrating to prepare the pectic matrix oridonin nano lipid gel. The oridonin with poor water solubility is coated with a pectin lipid carrier, so that the permeability ad the absorptivity of the oridonin on the skin are improved; and the prepared gel has the characteristics of being good in air permeability, high in bioavailability, good in stability, free of thrill to skin, convenient to medicate for the skin and the like.
Description
Technical field
The preparation method that the invention discloses a kind of pectic matrix rubescensin nano-lipid gel, belongs to gel field.
Background technology
Gel is a kind of novel pharmaceutical formulation of rising in recent years, and relatively early, development is very fast in external research.Domestic development is started to walk from hospital preparation, there is now multiple gel and obtains country's certification, shows the more advantage effectiveness of gel.Gel is divided into hydrophilic gel, lipophilic gel and emulsion-type gel by matrix type, and the host material of hydrophilic gel is adopted with the most use at present, common are carbomer, chitosan, calcium alginate, sodium carboxymethyl cellulose etc..Gel compared with frequently with route of administration be percutaneous dosing, oral administration, dosing eyes, nasal-cavity administration etc..Different route of administration all can receive drug level height, action time lasting promising result.Along with the application of new skill, also have developed the new products such as environmental sensitivity gel, lipidosome gel, Benexate Hydrochloride gel, improve clinical efficacy.
Liposome belongs to new colloidal drug-supplying system, has good biocompatibility, be possible not only to well with skin surface contact, and epidermis layer depth people can be passed through to deep skin, increase the medicine accumulation at local skin, performance slow releasing function.Gel is the semi-solid preparation that a class contains dissolving, suspendible or emulsion state medicine, can closely slit with site of action in a long time attached, has biological attached property of slitting preferably, and preparation is simple, it is comfortable to use.Gel means that medicine and the adjuvant that can form gel make glop or the semi-solid preparation of homogeneous, suspendible or emulsion type.Have that breathability is good, bioavailability is high, the feature such as good stability, untoward reaction are few, easy to use.
Rubescensin is a kind of diterpene-kind compound that first China find from traditional herbal medicine Rabdosia rubescens, there is parasite killing heat-clearing and toxic substances removing, anti-inflammatory analgetic, stomach invigorating invigorate blood circulation and etc. effect.Current clinical application mainly has Rabdosia rubescens tablet and syrup, but the rubescensin concentration of oral rear blood drug level and near tumor cells is low, constrains the performance of curative effect.
Summary of the invention
nullThe technical problem that present invention mainly solves: smear for current ointment，Life-time service is bigger to the zest of skin、Assimilation effect is slow，And the composition of poorly water-soluble such as rubescensin，Directly it is added in oral drugs，Constrain the problem that curative effect plays，The preparation method providing a kind of pectic matrix rubescensin nano-lipid gel，The present invention extracts from Hylocereus undatus and is prepared into pectin，Again by Oridonin and lecithin、Cholesterol prepares into nanometer liposome，By prepared pectin、Gel mixed liquor prepared into by sodium alginate，Mix with rubescensin nanometer liposome again、Concentrate，The present invention utilizes pectin lipid carrier that slightly solubility rubescensin carries out bag load effect，To improve rubescensin to the permeability of skin and absorbability，It is good that the gel prepared has breathability、Bioavailability is high、Good stability、To no skin irritation、Facilitate the features such as dermatologic.
In order to solve above-mentioned technical problem, the technical solution adopted in the present invention is:
(1) take to put into after pitaya peel dries naturally after jet mill is pulverized and cross 80 mesh standard sieves, the pitaya peel powder sieved 40～60 DEG C of warm water of its volume 8～10 times are rinsed 3～5 times repeatedly to remove soluble sugar and pigment, it is that 1:8 joins in mixed acid solution by the peel after washing by solid-to-liquid ratio again, move in 50～60 DEG C of water-baths, be incubated acidolysis 5～6h；
(2) acidolysis terminates rear isolated by filtration and obtains filtrate, the saturated aluminum sulfate solution of filtrate cumulative volume 1/3 is dropwise instilled in filtrate, pH to 7～8 is regulated again with the ammonia that mass concentration is 10%, staticly settle overnight under the ice-water bath of 4～6 DEG C, buchner funnel is put into after being filtrated to get pectin precipitation, dry with vacuum drier with after dehydrated alcohol filtering and washing 3～5 times, obtain self-control pectin, standby；
(3) 100～200g rubescensin and 20～30g ovum lipoid and 3～5g cholesterol are dissolved in 300～400mL acetic acid, stir prepared oil phase, again 3～5g sucrose ester is dissolved in the warm water that 400～500g temperature is 40～50 DEG C, it is placed on magnetic stirrer and is stirred with 300～400r/min rotating speed, oil phase is dropwise instilled by the process of stirring, controls rate of addition and make to dropwise in its 20～30min；
(4) after oil phase dropwises, 65～75 DEG C it are continuously heating to, stirring and emulsifying reaction 4～5h also evaporates acetic acid, the mixed liquor obtained is poured into rapidly in 4～6 DEG C of distilled water after terminating by emulsion reaction, stirring solidification 1～2h, and be centrifugally separating to obtain lower sediment with high speed centrifuge with 2000～3000r/min rotating speed and be rubescensin nanometer liposome；
(5) pour in 1～2L distilled water after weighing the standby self-control pectin of 15～20g and 5～10g sodium alginate mix homogeneously, be placed on shaking table vibration dissolve overnight gel mixed liquor, 50～100mL glycerol is added after above-mentioned prepared rubescensin nanometer liposome and gel mixed liquor being mixed for 1:2 by volume again, it is placed in vortex oscillation instrument with the vibration mixing of 30～40W power vortex, after concentration, namely obtains pectic matrix rubescensin nano-lipid gel.
Described mixed acid solution is to prepare for 1:2 is composite by volume for 0.03mol/L hydrochloric acid with concentration for 0.5mol/ phosphoric acid and concentration.
The method of the application of the present invention: the pectic matrix rubescensin nano-lipid gel uniform application present invention prepared is on the local skin needing anti-inflammation, use 5 days is a course for the treatment of, use 3～5 every day, using for 1～2 course for the treatment of, this gel therapeutic effect is good, and skin irritation is less, for wound, having significantly high Healing, through test, invented liposomes gel 24h transdermal test in vitro rate is 68～72 μ g cm-2·h-1, and common gel is 21.8 μ g cm-2·h-1, the good penetrability of skin, absorption rate is fast.
The invention has the beneficial effects as follows:
(1) present invention utilizes pectin lipid carrier that slightly solubility rubescensin carries out bag load effect, to improve rubescensin to the permeability of skin and absorbability；
(2) gel prepared has that breathability is good, bioavailability is high, good stability, to no skin irritation, facilitate the features such as dermatologic.
Detailed description of the invention
First take to put into after pitaya peel dries naturally after jet mill is pulverized and cross 80 mesh standard sieves, the pitaya peel powder sieved 40～60 DEG C of warm water of its volume 8～10 times are rinsed 3～5 times repeatedly to remove soluble sugar and pigment, it is that 1:8 joins in mixed acid solution by the peel after washing by solid-to-liquid ratio again, move in 50～60 DEG C of water-baths, be incubated acidolysis 5～6h；Acidolysis terminates rear isolated by filtration and obtains filtrate, the saturated aluminum sulfate solution of filtrate cumulative volume 1/3 is dropwise instilled in filtrate, pH to 7～8 is regulated again with the ammonia that mass concentration is 10%, staticly settle overnight under the ice-water bath of 4～6 DEG C, buchner funnel is put into after being filtrated to get pectin precipitation, dry with vacuum drier with after dehydrated alcohol filtering and washing 3～5 times, obtain self-control pectin, standby；100～200g rubescensin and 20～30g ovum lipoid and 3～5g cholesterol are dissolved in 300～400mL acetic acid, stir prepared oil phase, again 3～5g sucrose ester is dissolved in the warm water that 400～500g temperature is 40～50 DEG C, it is placed on magnetic stirrer and is stirred with 300～400r/min rotating speed, oil phase is dropwise instilled by the process of stirring, controls rate of addition and make to dropwise in its 20～30min；65～75 DEG C it are continuously heating to after oil phase dropwises, stirring and emulsifying reaction 4～5h also evaporates acetic acid, the mixed liquor obtained is poured into rapidly in 4～6 DEG C of distilled water after terminating by emulsion reaction, stirring solidification 1～2h, and be centrifugally separating to obtain lower sediment with high speed centrifuge with 2000～3000r/min rotating speed and be rubescensin nanometer liposome；Pour in 1～2L distilled water after weighing the standby self-control pectin of 15～20g and 5～10g sodium alginate mix homogeneously, be placed on shaking table vibration dissolve overnight gel mixed liquor, 50～100mL glycerol is added after above-mentioned prepared rubescensin nanometer liposome and gel mixed liquor being mixed for 1:2 by volume again, it is placed in vortex oscillation instrument with the vibration mixing of 30～40W power vortex, after concentration, namely obtains pectic matrix rubescensin nano-lipid gel.
Described mixed acid solution is to prepare for 1:2 is composite by volume for 0.03mol/L hydrochloric acid with concentration for 0.5mol/ phosphoric acid and concentration.
Example 1
First take to put into after pitaya peel dries naturally after jet mill is pulverized and cross 80 mesh standard sieves, the pitaya peel powder sieved 40 DEG C of warm water of its volume 8 times are rinsed 3 times repeatedly to remove soluble sugar and pigment, it is that 1:8 joins in mixed acid solution by the peel after washing by solid-to-liquid ratio again, move in 50 DEG C of water-baths, be incubated acidolysis 5h；Acidolysis terminates rear isolated by filtration and obtains filtrate, the saturated aluminum sulfate solution of filtrate cumulative volume 1/3 is dropwise instilled in filtrate, pH to 7 is regulated again with the ammonia that mass concentration is 10%, staticly settle overnight under the ice-water bath of 4 DEG C, buchner funnel is put into after being filtrated to get pectin precipitation, dry with vacuum drier with after dehydrated alcohol filtering and washing 3 times, obtain self-control pectin, standby；100g rubescensin and 20g ovum lipoid and 3g cholesterol are dissolved in 300mL acetic acid, stir prepared oil phase, again 3g sucrose ester is dissolved in the warm water that 400g temperature is 40 DEG C, it is placed on magnetic stirrer and is stirred with 300r/min rotating speed, oil phase is dropwise instilled by the process of stirring, controls rate of addition and make to dropwise in its 20min；65 DEG C it are continuously heating to after oil phase dropwises, stirring and emulsifying reaction 4h also evaporates acetic acid, the mixed liquor obtained is poured into rapidly in 4 DEG C of distilled water after terminating by emulsion reaction, stirring solidifies 1h, and is centrifugally separating to obtain lower sediment with high speed centrifuge with 2000r/min rotating speed and is rubescensin nanometer liposome；Pour in 1L distilled water after weighing the standby self-control pectin of 15g and 5g sodium alginate mix homogeneously, be placed on shaking table vibration dissolve overnight gel mixed liquor, 50mL glycerol is added after above-mentioned prepared rubescensin nanometer liposome and gel mixed liquor being mixed for 1:2 by volume again, it is placed in vortex oscillation instrument with the vibration mixing of 30W power vortex, after concentration, namely obtains pectic matrix rubescensin nano-lipid gel.
Described mixed acid solution is to prepare for 1:2 is composite by volume for 0.03mol/L hydrochloric acid with concentration for 0.5mol/ phosphoric acid and concentration.
The pectic matrix rubescensin nano-lipid gel uniform application present invention prepared is on the local skin needing anti-inflammation, use 5 days is a course for the treatment of, use 3 every day, using for 1 course for the treatment of, this gel therapeutic effect is good, and skin irritation is less, for wound, having significantly high Healing, through test, invented liposomes gel 24h transdermal test in vitro rate is 68 μ g cm-2·h-1, and common gel is 21.8 μ g cm-2·h-1, the good penetrability of skin, absorption rate is fast.
Example 2
First take to put into after pitaya peel dries naturally after jet mill is pulverized and cross 80 mesh standard sieves, the pitaya peel powder sieved 50 DEG C of warm water of its volume 9 times are rinsed 4 times repeatedly to remove soluble sugar and pigment, it is that 1:8 joins in mixed acid solution by the peel after washing by solid-to-liquid ratio again, move in 55 DEG C of water-baths, be incubated acidolysis 5.5h；Acidolysis terminates rear isolated by filtration and obtains filtrate, the saturated aluminum sulfate solution of filtrate cumulative volume 1/3 is dropwise instilled in filtrate, pH to 7.5 is regulated again with the ammonia that mass concentration is 10%, staticly settle overnight under the ice-water bath of 5 DEG C, buchner funnel is put into after being filtrated to get pectin precipitation, dry with vacuum drier with after dehydrated alcohol filtering and washing 4 times, obtain self-control pectin, standby；150g rubescensin and 25g ovum lipoid and 4g cholesterol are dissolved in 350mL acetic acid, stir prepared oil phase, again 4g sucrose ester is dissolved in the warm water that 450g temperature is 45 DEG C, it is placed on magnetic stirrer and is stirred with 350r/min rotating speed, oil phase is dropwise instilled by the process of stirring, controls rate of addition and make to dropwise in its 25min；70 DEG C it are continuously heating to after oil phase dropwises, stirring and emulsifying reaction 4.5h also evaporates acetic acid, the mixed liquor obtained is poured into rapidly in 5 DEG C of distilled water after terminating by emulsion reaction, stirring solidifies 1.5h, and is centrifugally separating to obtain lower sediment with high speed centrifuge with 2500r/min rotating speed and is rubescensin nanometer liposome；Pour in 1.5L distilled water after weighing the standby self-control pectin of 17g and 7.5g sodium alginate mix homogeneously, be placed on shaking table vibration dissolve overnight gel mixed liquor, 75mL glycerol is added after above-mentioned prepared rubescensin nanometer liposome and gel mixed liquor being mixed for 1:2 by volume again, it is placed in vortex oscillation instrument with the vibration mixing of 35W power vortex, after concentration, namely obtains pectic matrix rubescensin nano-lipid gel.
Described mixed acid solution is to prepare for 1:2 is composite by volume for 0.03mol/L hydrochloric acid with concentration for 0.5mol/ phosphoric acid and concentration.
The pectic matrix rubescensin nano-lipid gel uniform application present invention prepared is on the local skin needing anti-inflammation, use 5 days is a course for the treatment of, use 4 every day, using for 1 course for the treatment of, this gel therapeutic effect is good, and skin irritation is less, for wound, having significantly high Healing, through test, invented liposomes gel 24h transdermal test in vitro rate is 70 μ g cm-2·h-1, and common gel is 21.8 μ g cm-2·h-1, the good penetrability of skin, absorption rate is fast.
Example 3
First take to put into after pitaya peel dries naturally after jet mill is pulverized and cross 80 mesh standard sieves, the pitaya peel powder sieved 60 DEG C of warm water of its volume 10 times are rinsed 5 times repeatedly to remove soluble sugar and pigment, it is that 1:8 joins in mixed acid solution by the peel after washing by solid-to-liquid ratio again, move in 60 DEG C of water-baths, be incubated acidolysis 6h；Acidolysis terminates rear isolated by filtration and obtains filtrate, the saturated aluminum sulfate solution of filtrate cumulative volume 1/3 is dropwise instilled in filtrate, pH to 8 is regulated again with the ammonia that mass concentration is 10%, staticly settle overnight under the ice-water bath of 6 DEG C, buchner funnel is put into after being filtrated to get pectin precipitation, dry with vacuum drier with after dehydrated alcohol filtering and washing 5 times, obtain self-control pectin, standby；200g rubescensin and 30g ovum lipoid and 5g cholesterol are dissolved in 400mL acetic acid, stir prepared oil phase, again 5g sucrose ester is dissolved in the warm water that 500g temperature is 50 DEG C, it is placed on magnetic stirrer and is stirred with 400r/min rotating speed, oil phase is dropwise instilled by the process of stirring, controls rate of addition and make to dropwise in its 30min；75 DEG C it are continuously heating to after oil phase dropwises, stirring and emulsifying reaction 5h also evaporates acetic acid, the mixed liquor obtained is poured into rapidly in 6 DEG C of distilled water after terminating by emulsion reaction, stirring solidifies 2h, and is centrifugally separating to obtain lower sediment with high speed centrifuge with 3000r/min rotating speed and is rubescensin nanometer liposome；Pour in 2L distilled water after weighing the standby self-control pectin of 20g and 10g sodium alginate mix homogeneously, be placed on shaking table vibration dissolve overnight gel mixed liquor, 100mL glycerol is added after above-mentioned prepared rubescensin nanometer liposome and gel mixed liquor being mixed for 1:2 by volume again, it is placed in vortex oscillation instrument with the vibration mixing of 40W power vortex, after concentration, namely obtains pectic matrix rubescensin nano-lipid gel.
Described mixed acid solution is to prepare for 1:2 is composite by volume for 0.03mol/L hydrochloric acid with concentration for 0.5mol/ phosphoric acid and concentration.
The pectic matrix rubescensin nano-lipid gel uniform application present invention prepared is on the local skin needing anti-inflammation, use 5 days is a course for the treatment of, use 5 every day, using for 2 courses for the treatment of, this gel therapeutic effect is good, and skin irritation is less, for wound, having significantly high Healing, through test, invented liposomes gel 24h transdermal test in vitro rate is 72 μ g cm-2·h-1, and common gel is 21.8 μ g cm-2·h-1, the good penetrability of skin, absorption rate is fast.
Claims (2)
1. the preparation method of a pectic matrix rubescensin nano-lipid gel, it is characterised in that concrete preparation process is:
(1) take to put into after pitaya peel dries naturally after jet mill is pulverized and cross 80 mesh standard sieves, the pitaya peel powder sieved 40～60 DEG C of warm water of its volume 8～10 times are rinsed 3～5 times repeatedly to remove soluble sugar and pigment, it is that 1:8 joins in mixed acid solution by the peel after washing by solid-to-liquid ratio again, move in 50～60 DEG C of water-baths, be incubated acidolysis 5～6h；
(2) acidolysis terminates rear isolated by filtration and obtains filtrate, the saturated aluminum sulfate solution of filtrate cumulative volume 1/3 is dropwise instilled in filtrate, pH to 7～8 is regulated again with the ammonia that mass concentration is 10%, staticly settle overnight under the ice-water bath of 4～6 DEG C, buchner funnel is put into after being filtrated to get pectin precipitation, dry with vacuum drier with after dehydrated alcohol filtering and washing 3～5 times, obtain self-control pectin, standby；
(3) 100～200g rubescensin and 20～30g ovum lipoid and 3～5g cholesterol are dissolved in 300～400mL acetic acid, stir prepared oil phase, again 3～5g sucrose ester is dissolved in the warm water that 400～500g temperature is 40～50 DEG C, it is placed on magnetic stirrer and is stirred with 300～400r/min rotating speed, oil phase is dropwise instilled by the process of stirring, controls rate of addition and make to dropwise in its 20～30min；
(4) after oil phase dropwises, 65～75 DEG C it are continuously heating to, stirring and emulsifying reaction 4～5h also evaporates acetic acid, the mixed liquor obtained is poured into rapidly in 4～6 DEG C of distilled water after terminating by emulsion reaction, stirring solidification 1～2h, and be centrifugally separating to obtain lower sediment with high speed centrifuge with 2000～3000r/min rotating speed and be rubescensin nanometer liposome；
(5) pour in 1～2L distilled water after weighing the standby self-control pectin of 15～20g and 5～10g sodium alginate mix homogeneously, be placed on shaking table vibration dissolve overnight gel mixed liquor, 50～100mL glycerol is added after above-mentioned prepared rubescensin nanometer liposome and gel mixed liquor being mixed for 1:2 by volume again, it is placed in vortex oscillation instrument with the vibration mixing of 30～40W power vortex, after concentration, namely obtains pectic matrix rubescensin nano-lipid gel.
2. the preparation method of a kind of pectic matrix rubescensin nano-lipid gel according to claim 1, it is characterised in that: described mixed acid solution is to prepare for 1:2 is composite by volume for 0.03mol/L hydrochloric acid with concentration for 0.5mol/ phosphoric acid and concentration.
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|---|---|---|---|
| CN201610198005.9A CN105726465A (en) | 2016-03-31 | 2016-03-31 | Preparation method of pectic matrix oridonin nano lipid gel |
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| CN201610198005.9A CN105726465A (en) | 2016-03-31 | 2016-03-31 | Preparation method of pectic matrix oridonin nano lipid gel |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108926525A (en) * | 2018-09-14 | 2018-12-04 | 南方医科大学 | A kind of arthritis externally applied transdermal absorption preparation |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108926525A (en) * | 2018-09-14 | 2018-12-04 | 南方医科大学 | A kind of arthritis externally applied transdermal absorption preparation |
| CN108926525B (en) * | 2018-09-14 | 2021-08-31 | 南方医科大学 | External transdermal absorption preparation for arthritis |
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Application publication date: 20160706 |