CN105147596A - Water-soluble supramolecular salicylic acid gel technology - Google Patents
Water-soluble supramolecular salicylic acid gel technology Download PDFInfo
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Abstract
The invention discloses a water-soluble supramolecular salicylic acid gel technology. After a salicylic acid alcoholic solution, a starch nanocrystalline poloxamer suspension, an alpha-cyclodextrin aqueous solution and a lower-molecular fish collagen aqueous solution are mixed, and after ultrasonic treatment is carried out for 3 min, and still standing is carried out for 90 min, water-soluble supramolecular salicylic acid gel is obtained after treatment. The water-soluble supramolecular salicylic acid gel is composed of several kinds of active ingredients, all the ingredients achieve the synergic effect, the effect of salicylic acid for treating acne is effectively achieved, and the unexpected advantages of being high in transdermal efficiency, stable in dosage form, resistant to heat and the like are further achieved.
Description
Technical field
The invention belongs to the preparing technical field of supramolecular techniques field water soluble drug clathrate.
Background technology
Supramolecular chemistry is the chemistry of research intermolecular interaction, and two or more molecule is combined by intermolecular force thus realizes complicated height systematism polymolecular entity.Host molecule has special selectivity to guest molecule, and the key of supramolecular chemistry is exactly the Synthesis and application of host molecule.Along with the development of supramolecular chemistry has successively occurred three generations's supramolecular system, they are based on the supramolecular system of crown ether, cyclodextrin and calixarenes respectively.This three generations's supramolecular system respectively has feature: first generation supramolecular system utilizes crown ether compound the peculiar property of optionally complexing alkali metal ion, alkaline-earth metal ions and primary amine salt to grow up; Cyclodextrin, as second filial generation supermolecule main block compound, has interior hydrophobic, outer hydrophilic cavity structure, the most of aromatic compound of alternative enclose and aliphatic compound; The calixarenes of the third generation is the class cyclic oligomer generated through composite reaction by phenol and formaldehyde.This kind of compound molecule has the adjustable hydrophobic cavity of size, and selectivity is good, can and metal ion and neutral organic molecule form super molecule inclusion compound.
And cyclodextrin (Cyclodextrin, letter is CD) is as the representative of second filial generation supermolecule main block molecule, be generally by 6,7,8 D-glucopyranose units are with a class cyclic oligosaccharide of а-Isosorbide-5-Nitrae bonding, because its output is high, cheap, be widely used.Cyclodextrin has the hydrophobic cavity of certain size, can the optionally multiple organic guest molecule of enclose, thus forms super molecular compound.Its cavity structure effectively can form clathrate by enclose drug molecule, simultaneously due to the outside polyhydric hydrophilic of cyclodextrin, makes clathrate have good water solublity, thus reaches the effect to insoluble drug solubilising.
Salicylic acid is a kind of fat-soluble organic acid.Poplar acid starting material is that China and American Pharmacopeia include kind.Abroad, relevant salicylic formulation products is a lot, and dosage form has: gel, ointment, patch, shampoo, lotion, cleaning agent etc., specification (Determination of Salicylic Acid) also has multiple, is mainly used in Acne treatment, wart and seborrheic dermatitis.Research shows that it is better than benzoyl peroxide to the curative effect of acne and blackhead; Salicylic acid Transdermal absorption does not affect by skin condition, absorbs best in hydrophilic alcoholic substrate; The salicylic acid of 1 ~ 4% removes surface horny, and the concentration of more than 5% can be used for deep layer keratinization.According to " clinical medicine is complete works of ", the salicylate treatment acne of 0.5 ~ 2% concentration, safe and effective, be mainly used in mild to moderate acne, therefore Salicylic Acid Formulations is widely used abroad.
At home, salicylic preparation has unguentum acidi salicylici, and performing Ministry of Public Health ministry standard 1989, is Cidex-7, solubilized horny layer.With reference to Chinese Pharmacopoeia version two " clinical application notice " in 2000, salicylic acid is used for acne vulgaris, seborrheic dermatitis etc.
Other the active ingredient ratio of Acne treatment of salicylic acid and some, has the following advantages: (1) effective percentage is high: research shows: the curative effect of salicylic acid to acne and blackhead is better than benzoyl hydroperoxide; The curative effect of salicylate treatment skin aging and wrinkle removing stricture of vagina, is obviously better than glycolic, and side effect is lower than glycolic.(2) safety is good: research shows: local uses the hydrophilic alcoholic water solublity supermolecule salicylic acid gel of 2% not only to absorb well, and uses the side effect not having general continuously.(3) there is skin-care function: as wrinkle removing and decolouring, FDA has recommended salicylic acid as OTC medicine for wrinkle removing, and the salicylic acid of high concentration can be used safely in coloured skin: as pigmentation, melasma, skin is thick, and oiliness also has the decolouring of gross porosity and remission to treat.
The present invention is intended to invent a kind of novel water solublity supermolecule salicylic acid gel, and it is made up of several active ingredients, and each composition plays synergy, not only effectively play the effect of salicylate treatment acne, also there is beyond thought transdermal efficiency high, stable dosage forms, the advantage such as heat-resisting.
Summary of the invention
Based on the technical problem that background technology exists, the present invention is directed to background technology Problems existing, a kind of novel water solublity supermolecule salicylic acid gel is provided, it is made up of several active ingredients, each composition plays synergy, not only effectively plays the effect of salicylate treatment acne, also has beyond thought transdermal efficiency high, stable dosage forms, the advantage such as heat-resisting.
Object of the present invention is achieved through the following technical solutions:
A novel water solublity supermolecule salicylic acid gel, it is prepared from by following methods:
The following stated mark is mark meter all by weight;
(1) solution of salicylic acid and alcohol is prepared:
1 part of salicylic acid is added alcohol liquid (mixed liquor of 10-12 part 95% ethanol and 25-32 part 1,2-PD) stirring and dissolving, obtain solution of salicylic acid and alcohol;
(2) nanometer starch crystal is prepared:
By 3-4 part tapioca, 0.2-0.6 part acetate starch, 2-3 part corn starch, is scattered in the 3.2M sulphuric acid of 100 parts, then in 35 DEG C, reaction 3 days under 120rpm condition, then Heat thermostability 50s at 60 DEG C, obtained suspension;
Described suspension is by repeatedly washing and centrifugal extremely neutrality, and obtained nanometer starch crystal suspension, obtains nanometer starch crystal after lyophilization composition;
(3) nanometer starch crystal poloxamer suspension is prepared:
Get nanometer starch crystal 4 parts, adding 50-80 part molecular weight is successively 13000, the content of polyethylene glycol oxide is the poloxamer of 81%, the molecular weight of 120-130 part is 6200, the content of polyethylene glycol oxide is the poloxamer of 78%, deionized water 500 parts also stirs, and makes nanometer starch crystal aaerosol solution;
(4) the alpha-cyclodextrin aqueous solution of 200mg/mL mass percent concentration is prepared;
(5) low molecule fish collagen aqueous solution is prepared:
Get the low molecule fish collagen that molecular weight is 800-1000, be prepared into saturated aqueous solution;
(6) by solution of salicylic acid and alcohol, the aaerosol solution of nanometer starch crystal and alpha-cyclodextrin aqueous solution, fish collagen aqueous solution, now salicylic acid, nanometer starch crystal, the mass concentration of fish collagen in mixed aqueous solution is respectively 2wt%, 0.03wt%, the ultrasonic 3min of 0.05-0.08wt%, obtains water solublity supermolecule salicylic acid gel after leaving standstill 90min.
Described supersound process refers to: be 180w at ultrasonic output, and output frequency is ultrasonic disperse under the environment of 40kHz.
The technology point of water solublity supermolecule salicylic acid gel of the present invention is mainly: 1., when preparing nanometer starch crystal, optimize the recipe ingredient of starch, and after mild temperature reaction, heat shock at relatively high temperatures; 2., when preparing nanometer starch crystal poloxamer suspension, add two kinds of poloxamers successively; 3. add the fish collagen etc. of trace.Described technique is totally optimized, after synergism, and the advantages such as obtained water solublity supermolecule salicylic acid gel not only good water solubility, effectively plays the effect of salicylate treatment acne, also have beyond thought transdermal efficiency high, stable dosage forms, heat-resisting.
Usefulness of the present invention is:
1. pair skin irritation is extremely low, and the therapeutic effect of acne is good.
2. phase transdermal absorption factor is high.
3. stable performance, at 40 ± 2 DEG C, under RH75% ± 5% condition, accelerated test 8 months, the quality of water solublity supermolecule salicylic acid gel does not have significant change.
4. human experimentation proves, the mass effect that improve acne that the optimization of multifactor lower technique is unexpected, and also has significant facilitation on transdermal absorption factor.
5. also to have preparation process simple and convenient for this method, constant product quality, and large-scale industrial is produced and conveniently waited beneficial effect.
Detailed description of the invention
Embodiment 1:
Raw material of the present invention is commercially available purchase and obtains.
Novel water solublity supermolecule salicylic acid gel, it is prepared from by following methods:
The following stated mark is mark meter all by weight;
(1) solution of salicylic acid and alcohol is prepared:
1 part of salicylic acid is added alcohol liquid (mixed liquors of 10 part of 95% ethanol and 32 parts of 1,2-PDs) stirring and dissolving, obtain solution of salicylic acid and alcohol;
(2) nanometer starch crystal is prepared:
By 3 portions of tapiocas, 0.2 part of acetate starch, 3 parts of corn starchs, are scattered in the 3.2M sulphuric acid of 100 parts, then in 35 DEG C, reaction 3 days under 120rpm condition, then Heat thermostability 50s at 60 DEG C, obtained suspension;
Described suspension is by repeatedly washing and centrifugal extremely neutrality, and obtained nanometer starch crystal suspension, obtains nanometer starch crystal after lyophilization composition;
(3) nanometer starch crystal poloxamer suspension is prepared:
Get nanometer starch crystal 4 parts, adding 50 parts of molecular weight is successively 13000, and the content of polyethylene glycol oxide is the poloxamer of 81%, the molecular weight of 130 parts is 6200, the content of polyethylene glycol oxide is the poloxamer of 78%, and deionized water 500 parts also stirs, and makes nanometer starch crystal aaerosol solution;
(4) the alpha-cyclodextrin aqueous solution of 200mg/mL mass percent concentration is prepared;
(5) low molecule fish collagen aqueous solution is prepared:
Get the low molecule fish collagen that molecular weight is 800, be prepared into saturated aqueous solution;
(6) by solution of salicylic acid and alcohol, the aaerosol solution of nanometer starch crystal and alpha-cyclodextrin aqueous solution, fish collagen aqueous solution, now salicylic acid, nanometer starch crystal, the mass concentration of fish collagen in mixed aqueous solution is respectively 2wt%, 0.03wt%, the ultrasonic 3min of 0.08wt%, obtains water solublity supermolecule salicylic acid gel after leaving standstill 90min.
Described supersound process refers to: be 180w at ultrasonic output, and output frequency is ultrasonic disperse under the environment of 40kHz.
Embodiment 2:
Novel water solublity supermolecule salicylic acid gel, it is prepared from by following methods:
The following stated mark is mark meter all by weight;
(1) solution of salicylic acid and alcohol is prepared:
1 part of salicylic acid is added alcohol liquid (mixed liquors of 12 part of 95% ethanol and 25 parts of 1,2-PDs) stirring and dissolving, obtain solution of salicylic acid and alcohol;
(2) nanometer starch crystal is prepared:
By 4 portions of tapiocas, 0.6 part of acetate starch, 2 parts of corn starchs, are scattered in the 3.2M sulphuric acid of 100 parts, then in 35 DEG C, reaction 3 days under 120rpm condition, then Heat thermostability 50s at 60 DEG C, obtained suspension;
Described suspension is by repeatedly washing and centrifugal extremely neutrality, and obtained nanometer starch crystal suspension, obtains nanometer starch crystal after lyophilization composition;
(3) nanometer starch crystal poloxamer suspension is prepared:
Get nanometer starch crystal 4 parts, adding 80 parts of molecular weight is successively 13000, and the content of polyethylene glycol oxide is the poloxamer of 81%, the molecular weight of 120 parts is 6200, the content of polyethylene glycol oxide is the poloxamer of 78%, and deionized water 500 parts also stirs, and makes nanometer starch crystal aaerosol solution;
(4) the alpha-cyclodextrin aqueous solution of 200mg/mL mass percent concentration is prepared;
(5) low molecule fish collagen aqueous solution is prepared:
Get the low molecule fish collagen that molecular weight is 1000, be prepared into saturated aqueous solution;
(6) by solution of salicylic acid and alcohol, the aaerosol solution of nanometer starch crystal and alpha-cyclodextrin aqueous solution, fish collagen aqueous solution, now salicylic acid, nanometer starch crystal, the mass concentration of fish collagen in mixed aqueous solution is respectively 2wt%, 0.03wt%, the ultrasonic 3min of 0.05wt%, obtains water solublity supermolecule salicylic acid gel after leaving standstill 90min.
Described supersound process refers to: be 180w at ultrasonic output, and output frequency is ultrasonic disperse under the environment of 40kHz.
Embodiment 3:
Novel water solublity supermolecule salicylic acid gel, it is prepared from by following methods:
The following stated mark is mark meter all by weight;
(1) solution of salicylic acid and alcohol is prepared:
1 part of salicylic acid is added alcohol liquid (mixed liquors of 11 part of 95% ethanol and 30 parts of 1,2-PDs) stirring and dissolving, obtain solution of salicylic acid and alcohol;
(2) nanometer starch crystal is prepared:
By 3 portions of tapiocas, 0.3 part of acetate starch, 3 parts of corn starchs, are scattered in the 3.2M sulphuric acid of 100 parts, then in 35 DEG C, reaction 3 days under 120rpm condition, then Heat thermostability 50s at 60 DEG C, obtained suspension;
Described suspension is by repeatedly washing and centrifugal extremely neutrality, and obtained nanometer starch crystal suspension, obtains nanometer starch crystal after lyophilization composition;
(3) nanometer starch crystal poloxamer suspension is prepared:
Get nanometer starch crystal 4 parts, adding 60 parts of molecular weight is successively 13000, and the content of polyethylene glycol oxide is the poloxamer of 81%, the molecular weight of 125 parts is 6200, the content of polyethylene glycol oxide is the poloxamer of 78%, and deionized water 500 parts also stirs, and makes nanometer starch crystal aaerosol solution;
(4) the alpha-cyclodextrin aqueous solution of 200mg/mL mass percent concentration is prepared;
(5) low molecule fish collagen aqueous solution is prepared:
Get the low molecule fish collagen that molecular weight is 900, be prepared into saturated aqueous solution;
(6) by solution of salicylic acid and alcohol, the aaerosol solution of nanometer starch crystal and alpha-cyclodextrin aqueous solution, fish collagen aqueous solution, now salicylic acid, nanometer starch crystal, the mass concentration of fish collagen in mixed aqueous solution is respectively 2wt%, 0.03wt%, the ultrasonic 3min of 0.07wt%, obtains water solublity supermolecule salicylic acid gel after leaving standstill 90min.
Described supersound process refers to: be 180w at ultrasonic output, and output frequency is ultrasonic disperse under the environment of 40kHz.
Embodiment 4:
Novel water solublity supermolecule salicylic acid gel, it is prepared from by following methods:
The following stated mark is mark meter all by weight;
(1) solution of salicylic acid and alcohol is prepared:
1 part of salicylic acid is added alcohol liquid (mixed liquors of 10 part of 95% ethanol and 27 parts of 1,2-PDs) stirring and dissolving, obtain solution of salicylic acid and alcohol;
(2) nanometer starch crystal is prepared:
By 4 portions of tapiocas, 0.5 part of acetate starch, 2 parts of corn starchs, are scattered in the 3.2M sulphuric acid of 100 parts, then in 35 DEG C, reaction 3 days under 120rpm condition, then Heat thermostability 50s at 60 DEG C, obtained suspension;
Described suspension is by repeatedly washing and centrifugal extremely neutrality, and obtained nanometer starch crystal suspension, obtains nanometer starch crystal after lyophilization composition;
(3) nanometer starch crystal poloxamer suspension is prepared:
Get nanometer starch crystal 4 parts, adding 70 parts of molecular weight is successively 13000, and the content of polyethylene glycol oxide is the poloxamer of 81%, the molecular weight of 121 parts is 6200, the content of polyethylene glycol oxide is the poloxamer of 78%, and deionized water 500 parts also stirs, and makes nanometer starch crystal aaerosol solution;
(4) the alpha-cyclodextrin aqueous solution of 200mg/mL mass percent concentration is prepared;
(5) low molecule fish collagen aqueous solution is prepared:
Get the low molecule fish collagen that molecular weight is 800, be prepared into saturated aqueous solution;
(6) by solution of salicylic acid and alcohol, the aaerosol solution of nanometer starch crystal and alpha-cyclodextrin aqueous solution, fish collagen aqueous solution, now salicylic acid, nanometer starch crystal, the mass concentration of fish collagen in mixed aqueous solution is respectively 2wt%, 0.03wt%, the ultrasonic 3min of 0.06wt%, obtains water solublity supermolecule salicylic acid gel after leaving standstill 90min.
Described supersound process refers to: be 180w at ultrasonic output, and output frequency is ultrasonic disperse under the environment of 40kHz.
Embodiment 5:
Novel water solublity supermolecule salicylic acid gel, it is prepared from by following methods:
The following stated mark is mark meter all by weight;
(1) solution of salicylic acid and alcohol is prepared:
1 part of salicylic acid is added alcohol liquid (mixed liquors of 12 part of 95% ethanol and 31 parts of 1,2-PDs) stirring and dissolving, obtain solution of salicylic acid and alcohol;
(2) nanometer starch crystal is prepared:
By 3 portions of tapiocas, 0.4 part of acetate starch, 3 parts of corn starchs, are scattered in the 3.2M sulphuric acid of 100 parts, then in 35 DEG C, reaction 3 days under 120rpm condition, then Heat thermostability 50s at 60 DEG C, obtained suspension;
Described suspension is by repeatedly washing and centrifugal extremely neutrality, and obtained nanometer starch crystal suspension, obtains nanometer starch crystal after lyophilization composition;
(3) nanometer starch crystal poloxamer suspension is prepared:
Get nanometer starch crystal 4 parts, adding 53 parts of molecular weight is successively 13000, and the content of polyethylene glycol oxide is the poloxamer of 81%, the molecular weight of 129 parts is 6200, the content of polyethylene glycol oxide is the poloxamer of 78%, and deionized water 500 parts also stirs, and makes nanometer starch crystal aaerosol solution;
(4) the alpha-cyclodextrin aqueous solution of 200mg/mL mass percent concentration is prepared;
(5) low molecule fish collagen aqueous solution is prepared:
Get the low molecule fish collagen that molecular weight is 900, be prepared into saturated aqueous solution;
(6) by solution of salicylic acid and alcohol, the aaerosol solution of nanometer starch crystal and alpha-cyclodextrin aqueous solution, fish collagen aqueous solution, now salicylic acid, nanometer starch crystal, the mass concentration of fish collagen in mixed aqueous solution is respectively 2wt%, 0.03wt%, the ultrasonic 3min of 0.08wt%, obtains water solublity supermolecule salicylic acid gel after leaving standstill 90min.
Described supersound process refers to: be 180w at ultrasonic output, and output frequency is ultrasonic disperse under the environment of 40kHz.
Embodiment 6:
Comparative example of the present invention is exemplary exemplifying, and in fact, from the time of heat shock, the formula of starch, the character of poloxamer, the many factors such as the source of collagen protein and molecular weight selection are all most important, and slight change is all difficult to reach effect of the present invention.
Comparative example 1: do not carry out Heat thermostability:
Novel water solublity supermolecule salicylic acid gel, it is prepared from by following methods:
The following stated mark is mark meter all by weight;
(1) solution of salicylic acid and alcohol is prepared:
1 part of salicylic acid is added alcohol liquid (mixed liquors of 11 part of 95% ethanol and 26 parts of 1,2-PDs) stirring and dissolving, obtain solution of salicylic acid and alcohol;
(2) nanometer starch crystal is prepared:
By 3 portions of tapiocas, 0.2 part of acetate starch, 2 parts of corn starchs, are scattered in the 3.2M sulphuric acid of 100 parts, then in 35 DEG C, reaction 3 days obtained suspensions under 120rpm condition;
Described suspension is by repeatedly washing and centrifugal extremely neutrality, and obtained nanometer starch crystal suspension, obtains nanometer starch crystal after lyophilization composition;
(3) nanometer starch crystal poloxamer suspension is prepared:
Get nanometer starch crystal 4 parts, adding 77 parts of molecular weight is successively 13000, and the content of polyethylene glycol oxide is the poloxamer of 81%, the molecular weight of 123 parts is 6200, the content of polyethylene glycol oxide is the poloxamer of 78%, and deionized water 500 parts also stirs, and makes nanometer starch crystal aaerosol solution;
(4) the alpha-cyclodextrin aqueous solution of 200mg/mL mass percent concentration is prepared;
(5) low molecule fish collagen aqueous solution is prepared:
Get the low molecule fish collagen that molecular weight is 888, be prepared into saturated aqueous solution;
(6) by solution of salicylic acid and alcohol, the aaerosol solution of nanometer starch crystal and alpha-cyclodextrin aqueous solution, fish collagen aqueous solution, now salicylic acid, nanometer starch crystal, the mass concentration of fish collagen in mixed aqueous solution is respectively 2wt%, 0.03wt%, the ultrasonic 3min of 0.05wt%, obtains water solublity supermolecule salicylic acid gel after leaving standstill 90min.
Described supersound process refers to: be 180w at ultrasonic output, and output frequency is ultrasonic disperse under the environment of 40kHz.
Comparative example 2: active component does not add fish collagen:
Novel water solublity supermolecule salicylic acid gel, it is prepared from by following methods:
The following stated mark is mark meter all by weight;
(1) solution of salicylic acid and alcohol is prepared:
1 part of salicylic acid is added alcohol liquid (mixed liquors of 10 part of 95% ethanol and 28 parts of 1,2-PDs) stirring and dissolving, obtain solution of salicylic acid and alcohol;
(2) nanometer starch crystal is prepared:
By 4 portions of tapiocas, 0.6 part of acetate starch, 3 parts of corn starchs, are scattered in the 3.2M sulphuric acid of 100 parts, then in 35 DEG C, reaction 3 days under 120rpm condition, then Heat thermostability 50s at 60 DEG C, obtained suspension;
Described suspension is by repeatedly washing and centrifugal extremely neutrality, and obtained nanometer starch crystal suspension, obtains nanometer starch crystal after lyophilization composition;
(3) nanometer starch crystal poloxamer suspension is prepared:
Get nanometer starch crystal 4 parts, adding 66 parts of molecular weight is successively 13000, and the content of polyethylene glycol oxide is the poloxamer of 81%, the molecular weight of 127 parts is 6200, the content of polyethylene glycol oxide is the poloxamer of 78%, and deionized water 500 parts also stirs, and makes nanometer starch crystal aaerosol solution;
(4) the alpha-cyclodextrin aqueous solution of 200mg/mL mass percent concentration is prepared;
(5) by solution of salicylic acid and alcohol, the aaerosol solution of nanometer starch crystal and alpha-cyclodextrin aqueous solution, fish collagen aqueous solution, now salicylic acid, nanometer starch crystal, the mass concentration of fish collagen in mixed aqueous solution is respectively 2wt%, 0.03wt%, the ultrasonic 3min of 0.07wt%, obtains water solublity supermolecule salicylic acid gel after leaving standstill 90min.
Described supersound process refers to: be 180w at ultrasonic output, and output frequency is ultrasonic disperse under the environment of 40kHz.
(1) transdermal absorption factor:
Water solublity supermolecule salicylic acid gel the present invention prepared carries out mice percutaneous penetration, and experimental apparatus used is the vertical Transdermal diffusion cell of Franz, and the structure of vertical Transdermal diffusion cell comprises supply chamber, drug-supplying system, receiving chamber and sample tap.Wherein, supply chamber is for placing laboratory sample, and receiving chamber is equipped with receiving liquid, and receiving liquid is water, is provided with magnetic stirring apparatus bottom receiving chamber.
Before carrying out mice percutaneous penetration, the neck that first broken by mice is put to death, then immediately with the hair of electric hair cutter removing mouse back, clip mouse back skin, and remove the subcutaneus adipose tissue of mouse back skin, and after rinsing well with clear water, the mouse back skin removing subcutaneus adipose tissue is placed in normal saline, and cold preservation is for subsequent use.
Respectively mice percutaneous penetration is carried out to above-mentioned 7 kinds of water solublity supermolecule salicylic acid gels, through calculating after experiment, in 7 kinds of water solublity supermolecule salicylic acid gels, the salicylic acid Transdermal absorption amount of embodiment 5 is significantly higher than comparative example, is comparative example 1 and comparative example 2 1.3 times and 2.1 times respectively.
(2) stability test:
Through influence factor's test, preliminary proof water solublity supermolecule salicylic acid gel to light and high temperature (60 DEG C) and low temperature basicly stable; Through accelerated test investigate, water solublity supermolecule salicylic acid gel at 40 ± 2 DEG C, under RH75% ± 5% condition, accelerated test 8 months, the quality of water solublity supermolecule salicylic acid gel does not have significant change; Water solublity supermolecule salicylic acid gel is under listing terms of packing, and long term test investigates 24 months, constant product quality.If with composite soft tube packaging, and at 40 ± 2 DEG C, do that accelerated test investigates 8 months, the investigation of long-term stable experiment under RH75% ± 5% condition, the quality of water solublity supermolecule salicylic acid gel does not significantly change.
According to every stability test result, and dosage form, prescription feature, determine that preservation condition is: sealing, preserve in the cool; Tentative 3 years of effect duration.
And the stability of comparative example 1 and 2 is obviously worse than embodiments of the invention, at 40 ± 2 DEG C, under RH75% ± 5% condition, preserve under accelerated test, start layering respectively at 1 month and 3 months.
(3) zest research:
Experiment is tested with regard to the zest of water solublity supermolecule salicylic acid gel to guinea pig skin, result shows: Cavia porcellus normal skin and damaged skin once with continuous 7 days painting water solublity supermolecule salicylic acid gels after, have no skin irritation reaction, show that water solublity supermolecule salicylic acid gel reacts without obvious irritation skin.
Experiment has carried out allergic reaction on guinea pigs to water solublity supermolecule salicylic acid gel, and result shows: have no anaphylaxis after Cavia porcellus local skin repeated multiple times painting water solublity supermolecule salicylic acid gel.
(4) Clinical practice effect:
Clinical trial has been carried out to the efficacy and saferry of 2% water solublity supermolecule salicylic acid gel treatment acne vulgaris prepared by embodiment 3.Each embodiment selects 100 routine satisfactory experimenters to participate in this test.Treat the equal no difference of science of statistics of the order of severity of the age of each experimental group, sex and the state of an illness, shown in the following form of result of the test:
Conclusion: light, the moderate acne safety of 2% salicylic acid supermolecular gel treatment of the present invention based on acne, effectively, the probability of especially desquamation generation is significantly lower than matched group.Especially the formula of embodiment 1, instant effect, effective percentage is high, and untoward reaction is few.
Above-mentioned description of test, novel water solublity supermolecule salicylic acid gel of the present invention, it is made up of several active ingredients, each composition plays synergy, not only effectively play the effect of salicylate treatment acne, also there is beyond thought transdermal efficiency high, stable dosage forms, heat-resisting, the advantages such as adverse reaction rate is low.Also find in the experiment in later stage, relative to comparative example 1-2, the formula of embodiment 2 also has the effect of beyond thought significantly higher desalination mottle.
The above; be only the present invention's preferably detailed description of the invention; but protection scope of the present invention is not limited thereto; anyly be familiar with those skilled in the art in the technical scope that the present invention discloses; be equal to according to technical scheme of the present invention and inventive concept thereof and replace or change, all should be encompassed within protection scope of the present invention.
Claims (3)
1. a novel water solublity supermolecule salicylic acid gel, it is prepared from by following methods:
The following stated mark is mark meter all by weight;
(1) solution of salicylic acid and alcohol is prepared:
1 part of salicylic acid is added alcohol liquid (mixed liquor of 10-12 part 95% ethanol and 25-32 part 1,2-PD) stirring and dissolving, obtain solution of salicylic acid and alcohol;
(2) nanometer starch crystal is prepared:
By 3-4 part tapioca, 0.2-0.6 part acetate starch, 2-3 part corn starch, is scattered in the 3.2M sulphuric acid of 100 parts, then in 35 DEG C, reaction 3 days under 120rpm condition, then Heat thermostability 50s at 60 DEG C, obtained suspension;
Described suspension is by repeatedly washing and centrifugal extremely neutrality, and obtained nanometer starch crystal suspension, obtains nanometer starch crystal after lyophilization composition;
(3) nanometer starch crystal poloxamer suspension is prepared:
Get nanometer starch crystal 4 parts, adding 50-80 part molecular weight is successively 13000, the content of polyethylene glycol oxide is the poloxamer of 81%, the molecular weight of 120-130 part is 6200, the content of polyethylene glycol oxide is the poloxamer of 78%, deionized water 500 parts also stirs, and makes nanometer starch crystal aaerosol solution;
(4) the alpha-cyclodextrin aqueous solution of 200mg/mL mass percent concentration is prepared;
(5) low molecule fish collagen aqueous solution is prepared:
Get the low molecule fish collagen that molecular weight is 800-1000, be prepared into saturated aqueous solution;
(6) by solution of salicylic acid and alcohol, the aaerosol solution of nanometer starch crystal and alpha-cyclodextrin aqueous solution, fish collagen aqueous solution, now salicylic acid, nanometer starch crystal, the mass concentration of fish collagen in mixed aqueous solution is respectively 2wt%, 0.03wt%, 0.05-0.08wt%, ultrasonic 3min, obtain water solublity supermolecule salicylic acid gel after leaving standstill 90min.
2. water solublity supermolecule salicylic acid gel according to claim 1, is characterized in that:
Described supersound process refers to: be 180w at ultrasonic output, and output frequency is ultrasonic disperse under the environment of 40kHz.
3. the water solublity supermolecule salicylic acid gel described in claim 1-2, is characterized in that:
(1) solution of salicylic acid and alcohol is prepared:
1 part of salicylic acid is added alcohol liquid (mixed liquors of 10 part of 95% ethanol and 32 parts of 1,2-PDs) stirring and dissolving, obtain solution of salicylic acid and alcohol;
(2) nanometer starch crystal is prepared:
By 3 portions of tapiocas, 0.2 part of acetate starch, 3 parts of corn starchs, are scattered in the 3.2M sulphuric acid of 100 parts, then in 35 DEG C, reaction 3 days under 120rpm condition, then Heat thermostability 50s at 60 DEG C, obtained suspension;
Described suspension is by repeatedly washing and centrifugal extremely neutrality, and obtained nanometer starch crystal suspension, obtains nanometer starch crystal after lyophilization composition;
(3) nanometer starch crystal poloxamer suspension is prepared:
Get nanometer starch crystal 4 parts, adding 50 parts of molecular weight is successively 13000, and the content of polyethylene glycol oxide is the poloxamer of 81%, the molecular weight of 130 parts is 6200, the content of polyethylene glycol oxide is the poloxamer of 78%, and deionized water 500 parts also stirs, and makes nanometer starch crystal aaerosol solution;
(4) the alpha-cyclodextrin aqueous solution of 200mg/mL mass percent concentration is prepared;
(5) low molecule fish collagen aqueous solution is prepared:
Get the low molecule fish collagen that molecular weight is 800, be prepared into saturated aqueous solution;
(6) by solution of salicylic acid and alcohol, the aaerosol solution of nanometer starch crystal and alpha-cyclodextrin aqueous solution, fish collagen aqueous solution, now salicylic acid, nanometer starch crystal, the mass concentration of fish collagen in mixed aqueous solution is respectively 2wt%, 0.03wt%, the ultrasonic 3min of 0.08wt%, obtains water solublity supermolecule salicylic acid gel after leaving standstill 90min.
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| CN114028265A (en) * | 2021-12-16 | 2022-02-11 | 爱西美(珠海)生物技术有限公司 | Supermolecule embedded salicylic acid and preparation method thereof |
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