CN107157922A - A kind of otoginsenoside gel and preparation method thereof - Google Patents
A kind of otoginsenoside gel and preparation method thereof Download PDFInfo
- Publication number
- CN107157922A CN107157922A CN201710212957.6A CN201710212957A CN107157922A CN 107157922 A CN107157922 A CN 107157922A CN 201710212957 A CN201710212957 A CN 201710212957A CN 107157922 A CN107157922 A CN 107157922A
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- Prior art keywords
- aescinate
- gel
- otoginsenoside
- gross weight
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Classifications
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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
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- 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
-
- 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
Abstract
The invention discloses a kind of otoginsenoside gel, its active component is Aescinate A and Aescinate B, and the Aescinate A accounts for the 0.3 1.5% of gel gross weight, and the Aescinate B accounts for the 0.1 0.8% of gel gross weight, and remaining is gel-type vehicle.Fully, speed is fast, and onset time is short, and compared with Sodium Aescinate external preparation, quality is more controllable for Transdermal absorption of the present invention, and more preferably, the excitant to skin is smaller for stability.
Description
Technical field
The invention belongs to pharmaceutical field, and in particular to a kind of otoginsenoside gel and preparation method thereof.
Background technology
Otoginsenoside be also known as otoginsenoside acid, be from Hippocastanaceae buckeye seed extract obtain total saposins,
The general name of β-otoginsenoside or different otoginsenoside etc., belongs to triterpene saponin.The water solubility of otoginsenoside is poor, to increase it
Solubility, is often made into sodium salt, and research has shown that, the higher composition of content is Aescinate A, B, C, D in Sodium Aescinate.Seven
Leaf saponin(e sodium can reduce pathologic capillary permeability and increase, and increase intravenous tension, reduce Inflammatory substances and ooze out, with anti-
The effects such as inflammation, detumescence, analgesic, improvement blood circulation, the recovery of promotion acute and closed soft tissue injury.
Sodium Aescinate oral administration biaavailability is not high, injects larger to blood vessel irritation, and topical administration leads to medicine
The osmosis for crossing skin reaches internal body, has the following advantages that：1. percutaneous dosing can avoid the first pass effect and medicine of liver
Degraded of the thing in intestines and stomach, drug absorption is not influenceed by gastrointestinal factors, reduces the individual difference of medication；2. single administration
Medicine can be made to enter internal with constant speed for a long time, administration number of times is reduced, extend dosing interval；3. avoid orally to
Blood concentration peak valley phenomenon, reduces toxicity caused by medicine etc..
The exterior-applied formulations such as Sodium Aescinate ointment, aerosol, liniment are had at present to come out, still, existing Sodium Aescinate
External preparation has the disadvantages that：1. very well, Determination of oil-water partition coefficient is very low, Transdermal absorption effect for Sodium Aescinate water-soluble
Difference；2. Sodium Aescinate complicated component, property is unstable, the exterior-applied formulation less stable being made；3. Sodium Aescinate external application
Preparation is larger to skin irritation.
The content of the invention
The purpose of the present invention is for drawbacks described above there is provided a kind of using Aescinate A and Aescinate B as active component
Otoginsenoside gel, because Aescinate A and Aescinate B than Sodium Aescinate have higher Determination of oil-water partition coefficient, therefore
Transdermal absorption effect is more preferable.The otoginsenoside gel quality that the present invention is provided is more controllable, and skin irritation is smaller.
The otoginsenoside gel that the present invention is provided, its active component is Aescinate A and Aescinate B, seven leaf
Saponin A accounts for the 0.3-1.5% of gel gross weight, and the Aescinate B accounts for the 0.1-0.8% of gel gross weight, and remaining is gel
Matrix.
Preferably, the Aescinate A accounts for the 0.6% of gel gross weight, and the Aescinate B accounts for gel gross weight
0.4%.
Preferably, the matrix is consisted of the following composition, and the percentage that each composition accounts for gel gross weight is respectively：
It is further preferred that the percentage that each composition accounts for gel gross weight is respectively：
The present invention further provides the preparation method of otoginsenoside gel：Carbomer is taken, sodium alginate adds 20-40% second
Alcoholic solution stirring is fully swelled, then takes Aescinate A, Aescinate B, isopropanol, Tween 80, azone, propane diols, ultrasonic dissolution
Afterwards, add in the solution after above-mentioned be swelled, watery hydrochloric acid is added dropwise after stirring and adjusts pH to 5-7, stirs, produces.
Preferably, the pH is that Aescinate A, B more stablize in the range of 5.5-6.5, the pH.
The beneficial effects of the invention are as follows：
1) because Aescinate A, Aescinate B than Sodium Aescinate have more preferable Determination of oil-water partition coefficient, thus it is transdermal
Absorb more abundant, faster, onset time is shorter for speed, better efficacy.
2) present invention is made up of two kinds of active components, and compared with Sodium Aescinate, quality is more controllable, and stability is more preferable,
Excitant to skin is smaller.
3) test of pesticide effectiveness result shows, the present invention have good anti-swelling, it is impervious go out effect, and the work with simple compared with
Property is stronger.
Brief description of the drawings
Fig. 1 is accumulation transmitance-time graph of Aescinate A.
Fig. 2 is accumulation transmitance-time graph of Aescinate B.
Embodiment
The present invention is described in detail by the following examples.
Embodiment 1
Preparation method：Carbomer 0.8g, sodium alginate 0.3g are taken, (weight concentration) ethanol solution 86.2g of plus 30%, stirring
Fully it is swelled, then takes Aescinate A 0.6g, Aescinate B 0.4g, isopropanol 10g, Tween 80 0.2g, azone 1g, the third two
After alcohol 0.5g, ultrasonic dissolution, add in the carbomer after above-mentioned be swelled, watery hydrochloric acid is added dropwise after stirring and adjusts pH to 6.2, stirs
Mix uniform, produce.
Embodiment 2
Preparation method：Carbomer 0.5g, sodium alginate 0.5g are taken, (weight concentration) ethanol solution 89.6g of plus 20%, stirring
Fully it is swelled, then takes Aescinate A 0.5g, Aescinate B 0.8g, isopropanol 5g, Tween 80 0.1g, azone 2g, propane diols
After 1g, ultrasonic dissolution, add in the carbomer after above-mentioned be swelled, watery hydrochloric acid regulation pH to 6 is added dropwise after stirring, stirring is equal
It is even, produce.
Embodiment 3
Preparation method：Carbomer 1g, sodium alginate 0.2g, plus 40% ethanol solution 80.3g are taken, stirring is fully swelled, then
Aescinate A 1.2g, Aescinate B 0.2g are taken, isopropanol 15g, Tween 80 0.4g, azone 1.5g, propane diols 0.2g surpass
After sound dissolving, add in the carbomer after above-mentioned be swelled, watery hydrochloric acid is added dropwise after stirring and adjusts pH to 5.5, stirs, i.e.,
.
Embodiment 4
Preparation method：Carbomer 1g, sodium alginate 0.3g, plus 30% ethanol solution 85.3g are taken, stirring is fully swelled, then
Take Aescinate A 1.5g, Aescinate B 0.5g, isopropanol 8g, Tween 80 0.4g, azone 2.5g, propane diols 0.5g, ultrasound
After dissolving, add in the carbomer after above-mentioned be swelled, watery hydrochloric acid is added dropwise after stirring and adjusts pH to 5, stirs, produces.
Embodiment 5
Preparation method：Carbomer 1.2g, sodium alginate 0.2g, plus 30% ethanol solution 75.6g are taken, stirring is fully swelled,
Aescinate A 1g, Aescinate B 0.4g are taken again, and isopropanol 20g, Tween 80 0.3g, azone 0.5g, propane diols 0.8g surpass
After sound dissolving, add in the carbomer after above-mentioned be swelled, watery hydrochloric acid is added dropwise after stirring and adjusts pH to 7, stirs, i.e.,
.
Test example
1. Transdermal absorption is tested
SD rats are taken, using 10%Na2The S aqueous solution is taken off except back wool, and next day, disconnected neck was put to death, and skin of back is cut immediately,
Hypodermis and fat are rejected, after physiological saline is rinsed well repeatedly, appropriately sized, inspection skin integrity is cut into.Using changing
(effective area is 2.92cm to good Franz vertical double-chambers diffusion cell2), the rat skin handled well is fixed on to two Room of diffusion cell
Between, stratum corneum side is to supply chamber.Gel precision prepared by embodiment 1~5 takes 0.5mL to be placed in supply chamber, into receiving chamber
7mL reception liquids are added, reception liquid is PBS (0.01M, pH7.4).Water bath with thermostatic control is set as 32 DEG C, with 150r/min magnetic
Power is stirred.0.5mL reception liquids are taken respectively at 0.5,1,2,4,6,8,12,24h, while 0.5mL PBSs are supplemented, through 0.45
After μm membrane filtration, take 20 μ L sample introductions to determine Aescinate A, B peak areas, calculate drug concentration.
HPLC chromatogram condition is as follows：Stationary phase is Ultimate C18 (5 μm, 4.6 × 250mm), and mobile phase is acetonitrile：
0.55% phosphate aqueous solution (38：62), Detection wavelength 220nm, flow velocity 1.0mL/min, 35 DEG C of column temperature, the μ L of sample size 20.
Accumulation transmitance-time graph result is shown in Fig. 1 and Fig. 2, and percutaneous penetration is shown：
The Aescinate A of embodiment 1 can reach 31% accumulation transmitance in 4h or so, and Aescinate B can reach in 6h or so
To 30% accumulation transmitance；
The Aescinate A of embodiment 2 can reach 25% accumulation transmitance in 4h or so, and Aescinate B can reach in 6h or so
To 24% accumulation transmitance；
The Aescinate A of embodiment 3 can reach 18% accumulation transmitance in 4h or so, and Aescinate B can reach in 6h or so
To 22% accumulation transmitance；
The Aescinate A of embodiment 4 can reach 28% accumulation transmitance in 4h or so, and Aescinate B can reach in 6h or so
To 22% accumulation transmitance；
The Aescinate A of embodiment 5 can reach 33% accumulation transmitance in 4h or so, and Aescinate B can reach in 6h or so
To 28% accumulation transmitance.
Result above proves, medicine of the present invention can through skin rapid osmotic in vivo, with existing Sodium Aescinate ointment,
Aerosol, liniment are compared, Transdermal absorption more fully, speed faster, so as to ensure that the rapid performance of drug effect.
2. stability test
According to the requirement of bulk drug and pharmaceutical preparation stability test guideline, carried out the high temperature of this product, high humidity and
The stability test research of strong light, is below specific experimental result.
(1) hot test takes test sample, removes outer packing, is placed 10 days under the conditions of 60 DEG C, in 0, sampling inspection in 5,10 days
Survey.It the results are shown in Table 1.
The hot test measurement result of table 1
(2) high wet test takes test sample, removes outer packing, is placed 10 days under the conditions of 25 DEG C, RH92.5% ± 5%,
0th, 5, sampling detection in 10 days.It the results are shown in Table 2.
The high wet test measurement result of table 2
(3) strong illumination experiment takes test sample, removes outer packing, and 10 are placed under the conditions of illumination is 4500lx ± 500lx
My god, 0, sampling detection in 5,10 days.It the results are shown in Table 3.
The highlight test measurement result of table 3
Test result indicates that, the present invention relatively stablizes to strong light, high temperature and high humidity.
3. skin irritation test
Healthy rabbits (2.0 ± 0.2kg) 20 are taken, 5 groups are randomly divided into, every group of male and female half and half are investigated embodiment 1~5 and made
The skin irritation of standby gel.In 24h before administration, animal backbone diamond wool is taken off with 10% sodium sulfide solution, gone per side
Hair scope about 3cm × 3cm, can not damage epidermis.Experiment uses consubstantiality left and right sides Self-control method.Distinguish in left and right side unhairing area
Give gel and water.2 times a day, successive administration one week, residual test medicine was washed away with warm water in the 8th day.Respectively at removal medicine
1 after thing, 6,12,24h observation medicine-feeding part whether there is erythema and oedema situation, no erythema or oedema are set to 0 grade, there is erythema or oedema
Then by being set to 1-4 grades from light to heavy.
The rabbit skin irritation test result (n=5) of table 4
As can be seen from the above tests, skin wound repair incidence of the present invention is relatively low, and only slight erythema or oedema go out
It is existing, and can be completely eliminated after drug withdrawal in 24 hours, treatment is not influenceed, and adverse reaction rate and release rate are significantly better than that
Existing Sodium Aescinate ointment, aerosol, liniment, illustrate that the security of the present invention is fine.
4. anti-swelling/it is impervious go out experiment
Using mice ear model, if blank group, Aescinate A group, Aescinate B group, Aescinate A+B groups (are pressed
The proportioning of embodiment 1), every group of 10 animals coating and determine swelling after bulk drug is dissolved with a small amount of ethanol, the results are shown in Table
5。
The anti-swelling Experiment on Function result of table 5
As a result show, Aescinate A, Aescinate B, Aescinate A+B can reduce the swelling of mice ear model
Degree, wherein only Aescinate A+B groups have pole significant difference (P compared with feminine gender group<0.01).
Using the animal model on the granulomatous influence of rat acute croton oil, if negative control group, Aescinate A group,
Aescinate B group, Aescinate A+B groups (proportioning for pressing embodiment 1), every group of 10 animals are molten with a small amount of ethanol by bulk drug
Coating and seepage discharge is determined after solution, the results are shown in Table 6.
Table 6 it is impervious go out Experiment on Function result
| Group | Dosage | Acute seepage discharge (ml) |
| Negative group | / | 5.36±2.90 |
| Aescinate A gel | 5mg/kg | 4.78±2.02 |
| Aescinate B gel | 5mg/kg | 4.32±1.90 |
| Aescinate A+B gels | 5mg/kg | 2.36±2.07 |
As a result show, Aescinate A, Aescinate B, Aescinate A+B can reduce oozing out for mice ear model
Amount, wherein only Aescinate A+B groups have pole significant difference (P compared with feminine gender group<0.01).
Claims (6)
1. a kind of otoginsenoside gel, its active component is Aescinate A and Aescinate B, the Aescinate A accounts for gel
The 0.3-1.5% of gross weight, the Aescinate B accounts for the 0.1-0.8% of gel gross weight, and remaining is gel-type vehicle.
2. otoginsenoside gel as claimed in claim 1, it is characterised in that：The Aescinate A accounts for gel gross weight
0.6%, the Aescinate B accounts for the 0.4% of gel gross weight.
3. otoginsenoside gel as claimed in claim 1, it is characterised in that：The matrix is consisted of the following composition, respectively into
The percentage for point accounting for gel gross weight is respectively：
4. otoginsenoside gel as claimed in claim 3, it is characterised in that：Each composition accounts for the percentage score of gel gross weight
It is not：
5. a kind of method for preparing otoginsenoside gel described in claim 3 or 4, it is characterised in that：Take carbomer, alginic acid
Sodium adds the stirring of 20-40% ethanol solutions to be fully swelled, then takes Aescinate A, Aescinate B, isopropanol, Tween 80, azone, third
After glycol, ultrasonic dissolution, add in the solution after above-mentioned be swelled, watery hydrochloric acid regulation pH to 5-7 is added dropwise after stirring, stirring is equal
It is even, produce.
6. the preparation method of otoginsenoside gel as claimed in claim 5, it is characterised in that：The pH is 5.5-6.5.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710212957.6A CN107157922A (en) | 2017-04-01 | 2017-04-01 | A kind of otoginsenoside gel and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710212957.6A CN107157922A (en) | 2017-04-01 | 2017-04-01 | A kind of otoginsenoside gel and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107157922A true CN107157922A (en) | 2017-09-15 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710212957.6A Pending CN107157922A (en) | 2017-04-01 | 2017-04-01 | A kind of otoginsenoside gel and preparation method thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113476640A (en) * | 2021-06-11 | 2021-10-08 | 中南大学 | Preparation method of antibacterial hydrogel dressing containing heterogeneous ion doped metal sulfide |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104622740A (en) * | 2015-01-14 | 2015-05-20 | 武汉爱民制药有限公司 | Application of semen aesculi extract in preparation of pharmaceutical cosmetic |
-
2017
- 2017-04-01 CN CN201710212957.6A patent/CN107157922A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104622740A (en) * | 2015-01-14 | 2015-05-20 | 武汉爱民制药有限公司 | Application of semen aesculi extract in preparation of pharmaceutical cosmetic |
Non-Patent Citations (1)
| Title |
|---|
| 石召华: "娑罗子药材的化学品质研究", 《中国实验方剂学杂志》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113476640A (en) * | 2021-06-11 | 2021-10-08 | 中南大学 | Preparation method of antibacterial hydrogel dressing containing heterogeneous ion doped metal sulfide |
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Application publication date: 20170915 |