CN102579322B - Externally applied hydrogel agent and preparation method and application thereof - Google Patents
Externally applied hydrogel agent and preparation method and application thereof Download PDFInfo
- Publication number
- CN102579322B CN102579322B CN 201210087733 CN201210087733A CN102579322B CN 102579322 B CN102579322 B CN 102579322B CN 201210087733 CN201210087733 CN 201210087733 CN 201210087733 A CN201210087733 A CN 201210087733A CN 102579322 B CN102579322 B CN 102579322B
- Authority
- CN
- China
- Prior art keywords
- parts
- dihydroxy
- exterior
- weight portion
- liquid medicine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Abstract
The invention relates to a 3, 5-dyhydroxy-4-isopropyl diphenylethene externally-applied hydrogel agent and a preparation method and application thereof. The externally-applied hydrogel agent consists of carbomer, 3, 5-dyhydroxy-4-isopropyl diphenylethene, a permeation enhancer, a gel agent, a bacteriostatic agent, solvent and water. The externally-applied hydrogel agent is used for preparing medicine for curing psoriasis or eczema. The externally-applied hydrogel agent has the characteristics of strong adhesive force and easiness in cleaning, the skin permeability can be improved very remarkably and can be improved by 400 times approximately, the biocompatibility is good, the toxicity is low and the curative efficacy exertion of the medicine is greatly facilitated.
Description
[technical field]
The invention belongs to technical field of pharmaceuticals.More specifically, the present invention relates to a kind ofly 3,5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel also relates to the preparation method of described exterior-applied liquid medicine gel, relates to the purposes of described exterior-applied liquid medicine gel.
[background technology]
People know that 3,5-dihydroxy-4-isopropyl toluylene has good antifungal activity.CN200910075295 discloses a kind of (E)-3, the clean method for preparing of 5-dihydroxy-4-isopropyl toluylene.This preparation method is by 3; the 5-resorcylic acid by methylate, isopropylation (or through isopropylation, methylate) preparation 3; 5-dimethoxy-4 '-cumene methanol; and then synthesize medicine benzene alkene i.e. (E)-3 of moral not with antifungal activity, 5-dihydroxy-4-isopropyl toluylene through steps such as reduction, halo, Wittig-Horner condensation, deprotections.CN 200910074292 discloses a kind of Chitosan-coated 3, sustained-release micro-spheres of 5-dihydroxy-4-isopropyl toluylene and preparation method thereof.This microsphere is nucleocapsid structure, and its center is Powdered 3, and 5-dihydroxy-4-isopropyl toluylene layer, shell are the crosslinked condensation substance layer of chitosan and glutaraldehyde.It can improve the stability of medicine, improves percutaneous permeability, can reach the purpose to medicine sustained and controlled release simultaneously.It is a kind of 3 that CN 200910227909 discloses, cyclodextrin clathrate of 5-dihydroxy-4-isopropyl toluylene and preparation method thereof.The present invention is with the cyclodextrin inclusion compound medicine, and this dosage form increases the dissolubility of medicine and dissolution, and has improved stability and the bioavailability of medicine, can reach the purpose of medicine sustained and controlled release simultaneously.It is a kind of 3 that CN 200910074674 discloses, and 5-dihydroxy-4-isopropyl toluylene-succinic anhydride-polyethylene glycol complex, former medicine are 3,5-dihydroxy-4-isopropyl toluylene, and trim is Polyethylene Glycol, and linking arm is succinic anhydride; This complex is compared with former medicine, and water solublity and stability increase greatly, changes drug distribution, improves simultaneously bioavailability.It is a kind of 3 that CN 200910074673 discloses, and 5-dihydroxy-4-isopropyl toluylene-bromoacetate-polyethylene glycol complex, former medicine are 3,5-dihydroxy-4-isopropyl toluylene, and trim is Polyethylene Glycol, and linking arm is bromoacetate; This complex is compared with former medicine, and water solublity and stability increase greatly, changes drug distribution, improves simultaneously bioavailability.
3,5-dihydroxy-4-isopropyl toluylene can be used for treating the diseases such as intractable psoriasis.The existing dosage form of this medicine is mainly the vaseline ointment, its defective be oiliness greatly, easily come off, not easy cleaning, easy pollution clothes, use inconvenient etc.
The exterior-applied gel that uses in the prior art is transparent semisolid, homogeneous exquisiteness, and easily coating is coated on the skin and can forms transparent thin film after launching, tack is strong, and performance of keeping humidity is good, can keep for a long time the affected part moistening, without unhappy sensation, release is fast, and the holdup time is long; Fine and smooth and without greasy feeling when hydrogel is coated on the skin, easily eccysis, pollution clothes to skin and mucosa nonirritant, is fit to the local skin external.Carbomer is the excellent substrates of transdermal delivery system, and the exterior-applied gel of preparation is widely used at medicine and cosmetic field take it as main matrix.
Hydrogel is a kind of macromolecular material that can produce swelling in water, it is a kind of hydrophilic net high-polymer swelling body that can absorb and keep large quantity of moisture and don't be dissolved in water in water, because its biocompatibility is good, all be widely used in biological, engineering in medicine neck city at present.Because gel has good swellability, permeability and cohesive, therefore, in the local topical preparation, people utilize these gelling properties can realize medicament-carried with gel and the control drug release; Simultaneously the gel dosage form is because contain a large amount of water, and is soft and similar bio-tissue has good histocompatibility with skin, therefore is beneficial to the absorption of medicine.Carbomer (Carbomer also is called carbopol, Carbopol) is to be formed by acrylic acid and allyl sucrose copolymerization, have hydratability strong, discharge fast, without the characteristics of greasy and emulsibility, can effectively reduce interfacial tension, thereby make preparation stabilization.Simultaneously, exterior-applied gel can be kept stable, lasting blood drug level, and that can be scheduled to and long action time are provided, and reduces drug toxicity and side effect, improves curative effect and reduces administration number of times.
However, at present, also there is not the report of relevant 3,5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel gel.Therefore, the inventor by lot of experiments work, has finished the present invention finally on the basis of summing up prior art.
[summary of the invention]
[technical problem that will solve]
The purpose of this invention is to provide a kind of 3,5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel.
Another object of the present invention provides the preparation method of described exterior-applied liquid medicine gel.
Another object of the present invention provides the purposes of described exterior-applied liquid medicine gel.
[technical scheme]
The present invention is achieved through the following technical solutions.
The present invention relates to a kind of medicine 3, the novel form of 5-dihydroxy-4-isopropyl toluylene, it is exterior-applied liquid medicine gel gel dosage form, it is to utilize carbomer to make substrate, utilize its good hydrophilic, improve percutaneous permeability, simultaneously this dosage form is had without greasy feeling, the characteristics that adhesion is strong are conducive to medicine performance curative effect.
The present invention relates to a kind of 3,5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel.
This exterior-applied liquid medicine gel is composed as follows: in weight portion
5～50 parts of carbomers,
5～50 parts of 3,5-dihydroxy-4-isopropyl toluylene,
0～200 part of solvent orange 2 A,
5～350 parts of transdermal enhancers,
5～25 parts of gellant,
100～600 parts of solvent B,
0～50 part of antibacterial,
200～1500 parts in water;
Wherein:
Described solvent orange 2 A is glycerol, propylene glycol or their mixture;
Described solvent B is that one or more are selected from the solvent in ethanol, propylene glycol or the isopropyl alcohol.
A preferred embodiment of the invention, described transdermal enhancer are one or more transdermal enhancers that are selected from laurocapram, dimethyl sulfoxide (DMSO), decyl methyl sulfoxide, dimethyl acetylamide, oleic acid or menthol.
According to another kind of preferred implementation of the present invention, described gellant is one or more gellant that are selected from triethanolamine, ammonia, sodium hydroxide or sodium carbonate.
According to another kind of preferred implementation of the present invention, described antibacterial is one or more antibacterial that are selected from chlorocresol, mersalyl, ethyl hydroxybenzoate, benzalkonium chloride or Kazon.
Preferably, this 3,5-dihydroxy-4-isopropyl toluylene hydrogel adhesive is composed as follows: in weight portion
10～40 parts of carbomers,
10～40 parts of 3,5-dihydroxy-4-isopropyl toluylene,
50～150 parts of solvent orange 2 As,
80～260 parts of transdermal enhancers,
10～20 parts of gellant,
180～520 parts of solvent B,
0～20 part of antibacterial,
600～1200 parts in water.
More preferably, this 3,5-dihydroxy-4-isopropyl toluylene hydrogel adhesive is composed as follows: in weight portion
15～30 parts of carbomers,
15～40 parts of 3,5-dihydroxy-4-isopropyl toluylene,
80～120 parts of solvent orange 2 As,
120～200 parts of transdermal enhancers,
12～18 parts of gellant,
240～450 parts of solvent B,
10～15 parts of antibacterial,
800～1000 parts in water.
The invention still further relates to the preparation method of 3,5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel.
The step of this preparation method is as follows:
5～50 weight portion carbomers are joined stirring among 0～200 parts by weight solvent A, infiltrate, add again an amount of water, then placing spends the night under the room temperature makes its abundant swelling, then toward wherein dripping 5～25 weight portion gellant, use alkali with pH regulator to 4.5～8.0, make it become gel, stir; With 5～50 weight portions 3,5-dihydroxy-4-isopropyl toluylene, 0～50 weight portion antibacterial and 5～350 weight portion transdermal enhancers are dissolved among the solvent B, the solution that obtains is added in the described gel again, stir, add again entry, make Total Water reach 200～1500 weight portions, use again the homogenizer homogenize, so obtain 3 of transparent semi-solid, 5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel.
The invention still further relates to the preparation method of 3,5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel.
The step of this preparation method is as follows:
5～50 weight portion carbomers are joined infiltration among 0～200 parts by weight solvent A, grind, add an amount of water again, then placing spends the night under the room temperature makes its abundant swelling, makes it become gel, stirs; With 5～50 weight portions 3,5-dihydroxy-4-isopropyl toluylene, 0～50 weight portion antibacterial and 5～350 weight portion transdermal enhancers are dissolved among the solvent B, the solution that obtains is added in the described gel, then toward wherein dripping 5～25 weight portion gellant, use alkali with pH regulator to 4.5～8.0, add again entry, make Total Water reach 200～1500 weight portions, use again the homogenizer homogenize, so obtain 3 of transparent semi-solid, 5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel.
According to another kind of preferred implementation of the present invention, described alkali is one or more alkali that are selected from sodium hydroxide, potassium hydroxide, triethanolamine or ammonia.
The invention still further relates to described 3, the purposes of 5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel in preparation treatment psoriasis or eczema medicine.
The below will describe the present invention in more detail.
The present invention relates to a kind of 3,5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel and preparation method thereof and its purposes.
Of the present invention 3,5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel is to be effective ingredient with 3,5-dihydroxy-4-isopropyl toluylene, and carbomer is made substrate, add the compositions such as cutaneous permeable agent, antibacterial, wetting agent, under the gellant effect, prepare.
Hydrogel be a kind of can be in water swelling, absorption and keep large quantity of moisture and don't be dissolved in the hydrophilic net high-polymer swelling body of water, smooth surface, good biocompatibility.Gel has swellability, dewatering shrinkage, permeability and cohesive, in the local topical preparation, often utilizes these character of gel to control drug release or its adhesiveness to skin comes percutaneous to transmit medicine.
People know that 3,5-dihydroxy-4-isopropyl toluylene has good antibiotic property.
Carbomer is a kind of commodity, and it is formed by acrylic acid and allyl sucrose copolymerization, wherein also has a large amount of carboxyls, can be neutralized into by alkali the gel of transparent semi-solid.For example use in the sodium hydroxide solution and during carbomer solution, its toughness increases, and utilizes this character can prepare gel.Carbomer has good suspending ability, increases the denseness of continuous phase and makes Emulsion stable, reduces layering and flocculation phenomenon, also has emulsibility, reduces surface tension, thereby makes preparation stabilization.
Carbomer is joined in the solvent orange 2 A, under agitation allow solvent orange 2 A infiltrate carbomer 1-2 hour, carbomer is fully infiltrated by solvent orange 2 A present pasty state, then water carries out abundant swelling, make it become gel, until the carbomer particle size can not increase, carbomer carries out the normally 6-24 hour time of abundant swelling.
Described solvent orange 2 A is glycerol, propylene glycol or their mixture.Wherein glycerol can be the mixture that mixes with any ratio with propylene glycol.
When the amount of carbomer was 5～50 weight portion, the amount of solvent orange 2 A was 0～200 weight portion.If solvent is too high in the hydrogel that the amount of solvent orange 2 A greater than 200 weight portions, then can cause making, therefore, the amount of solvent orange 2 A is that 0～200 weight portion is suitable.
After the abundant swelling of carbomer, toward wherein dripping 5～25 weight portion gellant, use alkali with pH regulator to 4.5～8.0, make it become gel, stir.
In the present invention; described gellant should be appreciated that it is a kind of additional substance that can make latex be transformed into gradually uniform semi-rigid solid gel and keep original shape; therefore; every have this character and don't can damage 3; the material of 5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel performance may be used to the present invention, all within protection scope of the present invention.
Particularly, described gellant is one or more gellant that are selected from triethanolamine, ammonia, sodium hydroxide or sodium carbonate.
When the amount of carbomer was 5～50 weight portion, the amount of gellant was 10～25 weight portions.If the amount of gellant less than 10 weight portions, then can not make acid carbomer become suitable salt, so thickening effect is undesirable; If the amount of gellant greater than 25 weight portions, then can cause the pH value of system excessive, affect the stability of medicine, the hydrogel that causes simultaneously making produces stimulation to skin.Therefore, the amount of gellant is that 10～25 weight portions are suitable.
When the dropping gellant was regulated its pH with alkali, employed alkali was one or more alkali that are selected from sodium hydroxide, potassium hydroxide, triethanolamine or ammonia.
Preferably, described alkali is one or more alkali that are selected from sodium hydroxide, triethanolamine or ammonia.
More preferably, described alkali is sodium hydroxide or triethanolamine.
The concentration of described alkali is not crucial, normally 0.1～2N.
In addition, with 5～50 weight portions 3,5-dihydroxy-4-isopropyl toluylene, 0～50 weight portion antibacterial and 5～350 weight portion transdermal enhancers are dissolved among the solvent B, obtain a kind of solution.
Described solvent B is that one or more are selected from the solvent in ethanol, propylene glycol or the isopropyl alcohol.
According to the present invention, described antibacterial should be appreciated that it is the material of energy bacteria growing inhibiting.Antibacterial possibly can't killing bacteria, but the growth that it can anti-bacteria, stop bacteria breed too much, health risk.Therefore, every material that has this character and don't can damage 3,5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel performance may be used to the present invention, all within protection scope of the present invention.
Particularly, described antibacterial is one or more antibacterial that are selected from chlorocresol, mersalyl, ethyl hydroxybenzoate, benzalkonium chloride or Kazon.Chlorocresol, mersalyl, ethyl hydroxybenzoate, benzalkonium chloride or Kazon all are the antibacterial products of selling in the market.
Preferably, described antibacterial is one or more antibacterial that are selected from chlorocresol, mersalyl, ethyl hydroxybenzoate or Kazon.
More preferably, described antibacterial is one or more antibacterial that are selected from chlorocresol, mersalyl or Kazon.
According to the present invention, described transdermal enhancer should be appreciated that it is a kind ofly can promote that active component in the pharmaceutical preparation is faster, penetrate in the skin more or see through skin and enter in the body-internal-circulation system, thereby the material of performance part or whole body therapeutic effect, this material should have good biocompatibility, excellent physicochemical property, the character such as quick-acting and long-lasting.Therefore, every material that has this character and don't can damage 3,5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel performance may be used to the present invention, all within protection scope of the present invention.
Being fit to cutaneous permeable agent of the present invention for example is one or more transdermal enhancers that are selected from laurocapram, dimethyl sulfoxide (DMSO), decyl methyl sulfoxide, dimethyl acetylamide, oleic acid or menthol.
Laurocapram all has the effect of oozing of well urging to multiple hydrophilic and lipophilic drugs.Generally speaking, its short effect of oozing is closely related with concentration, does not increase with concentration.
Dimethyl sulfoxide (DMSO) has the promotion Drug Percutaneous Absorption, also have antiinflammatory, relieve the pain, antipruritic, promote the wound healing effect.
Decyl methyl sulfoxide has good transdermal and promotes performance, and zest and toxicity are all low.
Menthol has the transdermal facilitation, and the Transdermal absorption of multiple hydrophilic and lipophilic drugs is all had significant facilitation.
In the present invention, when the amount of 3,5-dihydroxy-4-isopropyl toluylene was 5～50 weight portion, the amount of carbomer was 5～50 weight portions, and is uneven if the amount of carbomer during less than 5 weight portion, then can cause owing to substrate is very few medicine to disperse; If the amount of carbomer during greater than 50 weight portion, then can make drug loading become low; Therefore, the amount of carbomer is that 5～50 weight portions are suitable.
Similarly, 3, when the amount of 5-dihydroxy-4-isopropyl toluylene is 5～50 weight portion, the amount of described antibacterial is 0～50 weight portion, if the amount of antibacterial greater than 50 weight portions, then might be covered the effect of main medicine, and, because 3,5-dihydroxy-4-isopropyl toluylene itself has certain bactericidal action, too much antibacterial there is no need; Therefore, the amount of described antibacterial is that 0～50 weight portion is suitable.
When the amount of 3,5-dihydroxy-4-isopropyl toluylene was 5～50 weight portion, the amount of described transdermal enhancer was 5～350 weight portions, if the amount of transdermal enhancer less than 5 weight portions, then can not have obvious mechanism; If the amount of transdermal enhancer greater than 350 weight portions, then can cause unnecessary waste; Therefore, the amount of described transdermal enhancer is that 5～350 weight portions are suitable.
Described solution is added in the described gel again, stirs, add entry again, make Total Water reach 200～1500 weight portions, grinding stirs evenly again, so obtain 3 of transparent semi-solid, 5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel.
Can also adopt following method to prepare 3,5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel.The step of this preparation method is as follows:
5～50 weight portion carbomers are joined infiltration among 0～200 parts by weight solvent A, grind, add an amount of water again, then placing spends the night under the room temperature makes its abundant swelling, makes it become gel, stirs; With 5～50 weight portions 3,5-dihydroxy-4-isopropyl toluylene, 0～50 weight portion antibacterial and 5～350 weight portion transdermal enhancers are dissolved among the solvent B, the solution that obtains is added in the described gel, then toward wherein dripping 5～25 weight portion gellant, with pH regulator to 4.5～8.0, add again entry, make Total Water reach 200～1500 weight portions, use again the homogenizer homogenize, so obtain 3 of transparent semi-solid, 5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel.
The exterior-applied liquid medicine gel that adopts the inventive method to obtain has following composition: in weight portion
5～50 parts of carbomers,
5～50 parts of 3,5-dihydroxy-4-isopropyl toluylene,
0～200 part of solvent orange 2 A,
5～350 parts of transdermal enhancers,
5～25 parts of gellant,
100～600 parts of solvent B,
0～50 part of antibacterial,
200～1500 parts in water;
Wherein:
Described solvent orange 2 A is glycerol, propylene glycol or their mixture;
Described solvent B is that one or more are selected from the solvent in ethanol, propylene glycol or the isopropyl alcohol.
This exterior-applied liquid medicine gel dosage form has that adhesion is strong, the characteristics of easy cleaning, can improve percutaneous permeability, good biocompatibility, and toxicity is low, is conducive to medicine performance curative effect.
Preferably, this 3,5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel is composed as follows: in weight portion
10～40 parts of carbomers,
10～40 parts of 3,5-dihydroxy-4-isopropyl toluylene,
50～150 parts of solvent orange 2 As,
80～260 parts of transdermal enhancers,
10～20 parts of gellant,
180～520 parts of solvent B,
0～20 part of antibacterial,
600～1200 parts in water.
More preferably, this 3,5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel is composed as follows: in weight portion
15～30 parts of carbomers,
15～40 parts of 3,5-dihydroxy-4-isopropyl toluylene,
80～120 parts of solvent orange 2 As,
120～200 parts of transdermal enhancers,
12～18 parts of gellant,
240～450 parts of solvent B,
10～15 parts of antibacterial,
800～1000 parts in water.
The invention still further relates to the purposes of 3,5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel in preparation treatment psoriasis or eczema medicine.
Its curing psoriasis method is that the psoriasis affected part is cleaned with clear water, and the sterilization towel gently dips in and makes the affected part dry, and the exterior-applied liquid medicine gel that the present invention is contained 3,5-dihydroxy-4-isopropyl toluylene with the cotton swab of drying directly is coated on the affected part and gets final product.Can repeatedly use every day, and the antipruritic and skin in affected part begins to become smooth after 2-3 days.
Its eczema treatment method is to clean the affected part with clear water, and the exterior-applied liquid medicine gel that after the dried the present invention is contained 3,5-dihydroxy-4-isopropyl toluylene directly is coated on the affected part and gets final product.
Use of the present inventionly 3,5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel has carried out the Transdermal Absorption experiment.
Experimental technique: get Kunming mouse, slough the hair of white mice abdominal part after putting to death with 8 % by weight sodium sulfide solutions, peel off Corium Mus, with the fat deposit Ex-all of Corium Mus, repeatedly wash with distilled water, normal saline, soak with normal saline at last, put into 4 ℃ of refrigerator and cooled and hide, stand-by.
Use is carried out this experiment by Shanghai Huanghai Sea medicine inspection company with the drug transdermal diffusion test instrument that trade name RYJ-12B sells.
This experimental facilities is rational in infrastructure, use rectilinear Franz diffusion cell, in solid dry type thermostatic container case, under the duty of magnetic force uniform stirring, slowly permeate by animal skins, having reproduced objectively the preparation of the present invention speed of permeating and pharmacology process of degree in the solvent of regulation, is one of detection method of the present current international practice.
This experiment is carried out according to the condition of this tester operation instructions explanation, and this experiment is implemented convenient and easy, and the data of mensuration are accurate.
The Kunming mouse skin is fixed between supply pool and the reception tank, makes stratum corneum side to supply chamber, effective infiltrating area of diffusion cell is 1.5cm
2, receiving liquid is saturated saline solution, the reception tank volume is 16mL.
It is of the present invention 3 to take by weighing 0.5g, and 5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel sample is applied to the Kunming mouse skin surface, and bath temperature is controlled at 37 ± 0.5 ℃, and agitator is with rotating speed 120r/min constant revolution.Respectively at 0.5,1,2,4,6,8,12h takes out whole receiving liquids, replenishes simultaneously isopyknic acceptable solution.
Adopt in the described acceptable solution of HPLC chromatography determination 3,5-dihydroxy-4-isopropyl toluylene content.
HPLC coefficients data measured by chromatography fixed condition: the high performance liquid chromatograph (HPLC that uses Japanese Shimadzu company, LC-10AT VP), Phenomenexluna-C18 (250 * 4.6mm, 5 μ m) chromatographic column, UV-detector, detect wavelength 316nm, mobile phase is methanol and redistilled water (V/V=80/20), and flow velocity is 1.0mL/min, sample size 10 μ L.
With above-mentioned same condition under carried out former medicine 3, the transdermal experiment of 5-dihydroxy-4-isopropyl toluylene.
By in the described acceptable solution 3,5-dihydroxy-4-isopropyl toluylene content calculates respectively former medicine 3 according to following formula, the accumulation infiltration capacity Q of 5-dihydroxy-4-isopropyl toluylene and 3,5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel:
Q＝∑CnV
In the formula:
Cn is the concentration of n sub-sampling,
V represents the volume of reception tank,
To time t mapping, it the results are shown in accompanying drawing 1 with Q.
With reference to the accompanying drawings 1, with Q t is carried out linear regression and obtain 3, the linear equation of 5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel is: Q=54.32t-18.67, r=0.9921, show 3,5-dihydroxy-4-isopropyl toluylene sees through skin with first order kinetics, and infiltration rate is 54.32 μ gcm
-2, 12h accumulation infiltration capacity is 638.2 μ gcm
-2
Similarly, former medicine 3, the linear equation of 5-dihydroxy-4-isopropyl toluylene is: Q=0.5t+1.63, r=0.9975 illustrates its former medicine 3, the 12h accumulation infiltration capacity of 5-dihydroxy-4-isopropyl toluylene only is 1.63 μ gcm
-2
This shows, of the present invention 3,5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel penetrating power is higher than former medicine 3 far away, the penetrating power of 5-dihydroxy-4-isopropyl toluylene, high about 400 times, therefore, exterior-applied liquid medicine gel therapeutic effect of the present invention will be much better than the therapeutic effect of former medicine.
[beneficial effect]
The invention has the beneficial effects as follows: exterior-applied liquid medicine gel of the present invention has that adhesion is strong, the characteristics of easy cleaning, can improve extremely significantly percutaneous permeability, improves about 400 times, good biocompatibility, and toxicity is low, is very beneficial for medicine performance curative effect.
[description of drawings]
Fig. 1 is the present invention 3,5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel medicine permeability test former with it result.
[specific embodiment]
Can understand better the present invention by following embodiment.
Embodiment 1:3, the preparation of the exterior-applied liquid medicine gel dosage form of 5-dihydroxy-4-isopropyl toluylene
This embodiment implementation step is as follows:
15 weight portion carbomers are joined stirring in the 80 weight portion glycerol, infiltrate, make into pasty state, add again an amount of water, then placing spends the night under the room temperature makes its abundant swelling, and the carbomer particle size can not increase, and stirs, then toward wherein dripping 10 weight portion triethanolamine gellant, use 0.5NNaOH solution with pH regulator to 6.5, make it become gel, stir; With 25 weight portions 3,5-dihydroxy-4-isopropyl toluylene, 12 weight portion chlorocresol antibacterial and 20 weight portion laurocapram transdermal enhancers are dissolved among the 400 parts by weight of ethanol solvent B, the solution that obtains is added in the described gel again, stir, add again entry, make Total Water reach 600 weight portions, re-use Wenzhou biotic experiment equipment company limited and carry out homogenize with the totally-enclosed intelligent Syrup-homogenizing instrument of trade name ZW-800G, so obtain 3 of transparent semi-solid, 5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel.
Determine that by Transdermal Absorption experiment the exterior-applied liquid medicine gel of this embodiment preparation is in 12h 3,5-dihydroxy-4-isopropyl toluylene accumulation infiltration capacity is 638.2 μ g/cm
2
Embodiment 2:3, the preparation of the exterior-applied liquid medicine gel dosage form of 5-dihydroxy-4-isopropyl toluylene
This embodiment implementation step is as follows:
20 weight portion carbomers are joined stirring in the 100 weight portion propylene glycol, infiltrate, make into pasty state, add an amount of water again, then placing spends the night under the room temperature makes its abundant swelling until the carbomer particle size can not increase, and stirs; Then with 20 weight portions 3,5-dihydroxy-4-isopropyl toluylene, 10 weight portion mersalyl antibacterial and 20 weight portion menthol+DMSO (its weight ratio 1: 2) transdermal enhancer are dissolved among 300 parts by weight of ethanol+isopropyl alcohol (volume ratio 2: 1) solvent B, the solution that obtains is added in the described gel again, toward wherein dripping 20 weight portion sodium hydroxide gellant, use 1.0N NaOH solution with pH regulator to 6.5, add again entry, make Total Water reach 800 weight portions, re-use Wenzhou biotic experiment equipment company limited and carry out homogenize with the totally-enclosed intelligent Syrup-homogenizing instrument of trade name ZW-800G, so obtain 3 of transparent semi-solid, 5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel.
Determine that by Transdermal Absorption experiment the exterior-applied liquid medicine gel of this embodiment preparation is in 12h 3,5-dihydroxy-4-isopropyl toluylene accumulation infiltration capacity is 625.3 μ g/cm
2
Embodiment 3:3, the preparation of the exterior-applied liquid medicine gel dosage form of 5-dihydroxy-4-isopropyl toluylene
This embodiment is to carry out with embodiment 1 same way as, just preparation condition is done following change: 5 weight portion carbomers, 15 weight portions 3,5-dihydroxy-4-isopropyl toluylene, 60 weight portion glycerol solvent orange 2 As, 400 weight portion propylene glycol solvent B, 10 weight portion benzalkonium chloride antibacterial, 40 weight portion dimethyl acetylamide transdermal enhancers, 5 weight portion sodium carbonate gellant, pH8 and 500 weight parts waters.
Determine that by Transdermal Absorption experiment the exterior-applied liquid medicine gel of this embodiment preparation is in 12h 3,5-dihydroxy-4-isopropyl toluylene accumulation infiltration capacity is 608.4 μ g/cm
2
Embodiment 4:3, the preparation of the exterior-applied liquid medicine gel dosage form of 5-dihydroxy-4-isopropyl toluylene
This embodiment is to carry out with embodiment 1 same way as, just preparation condition is done following change: 25 weight portion carbomers, 10 weight portions 3,5-dihydroxy-4-isopropyl toluylene, 90 weight portion propylene glycol+glycerol (volume ratio 2: 1) solvent orange 2 A, 600 parts by weight of ethanol+propylene glycol (volume ratio 1: 2) solvent B, 5 weight portion ethyl hydroxybenzoate+Kazon (weight ratio 1: 4) antibacterial, 5 weight portion decyl methyl sulfoxide transdermal enhancers, 15 weight portion triethanolamine gellant, pH4.5 and 1000 weight parts waters.
Determine that by Transdermal Absorption experiment the exterior-applied liquid medicine gel of this embodiment preparation is in 12h 3,5-dihydroxy-4-isopropyl toluylene accumulation infiltration capacity is 611.7 μ g/cm
2
Embodiment 5:3, the preparation of the exterior-applied liquid medicine gel dosage form of 5-dihydroxy-4-isopropyl toluylene
This embodiment is to carry out with embodiment 1 same way as, just preparation condition is done following change: 10 weight portion carbomers, 5 weight portions 3,5-dihydroxy-4-isopropyl toluylene, solvent-free A, 100 parts by weight of ethanol solvent B, 50 weight portion Kazon antibacterial, 35 weight portion oleic acid transdermal enhancers, 20 weight portion ammonia gellant, pH7.0 and 200 weight parts waters.
Determine that by Transdermal Absorption experiment the exterior-applied liquid medicine gel of this embodiment preparation is in 12h 3,5-dihydroxy-4-isopropyl toluylene accumulation infiltration capacity is 588.1 μ g/cm
2
Embodiment 6:3, the preparation of the exterior-applied liquid medicine gel dosage form of 5-dihydroxy-4-isopropyl toluylene
This embodiment is to carry out with embodiment 2 same way as, just preparation condition is done following change: 35 weight portion carbomers, 50 weight portions 3,5-dihydroxy-4-isopropyl toluylene, 180 weight portion propylene glycol solvent A, 200 weight portion isopropanol solvent B, 50 weight portion ethyl hydroxybenzoate antibacterial, 350 weight portion DMSO transdermal enhancers, 20 weight portion sodium carbonate gellant, pH5.0 and 1300 weight parts waters.
Determine that by Transdermal Absorption experiment the exterior-applied liquid medicine gel of this embodiment preparation is in 12h 3,5-dihydroxy-4-isopropyl toluylene accumulation infiltration capacity is 601.2 μ g/cm
2
Embodiment 7:3, the preparation of the exterior-applied liquid medicine gel dosage form of 5-dihydroxy-4-isopropyl toluylene
This embodiment is to carry out with embodiment 2 same way as, just preparation condition is done following change: 50 weight portion carbomers, 45 weight portions 3,5-dihydroxy-4-isopropyl toluylene, 200 weight portion glycerol solvent orange 2 As, 600 parts by weight of ethanol+propylene glycol (volume ratio 2: 1) solvent B, without antibacterial, 25 weight portion menthol transdermal enhancers, 25 weight portion triethanolamine gellant, pH6.0 and 1500 weight parts waters.
Determine that by Transdermal Absorption experiment the exterior-applied liquid medicine gel of this embodiment preparation is in 12h 3,5-dihydroxy-4-isopropyl toluylene accumulation infiltration capacity is 592.1 μ g/cm
2
Claims (2)
1. one kind 3,5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel is characterized in that this exterior-applied liquid medicine gel is composed as follows: in weight portion
10～40 parts of carbomers,
10～40 parts of 3,5-dihydroxy-4-isopropyl toluylene,
50～150 parts of solvent orange 2 As,
80～260 parts of transdermal enhancers,
10～20 parts of gellant,
180～520 parts of solvent B,
0～20 part of antibacterial,
600～1200 parts in water;
Wherein:
Described solvent orange 2 A is glycerol, propylene glycol or their mixture;
Described solvent B is that one or more are selected from the solvent in ethanol, propylene glycol or the isopropyl alcohol;
Described gellant is one or more gellant that are selected from triethanolamine, ammonia, sodium hydroxide or sodium carbonate;
Described transdermal enhancer is one or more transdermal enhancers that are selected from laurocapram, dimethyl sulfoxide, decyl methyl sulfoxide, dimethyl acetylamide, oleic acid or menthol;
Described antibacterial is one or more antibacterial that are selected from chlorocresol, ethyl hydroxybenzoate, benzalkonium chloride or Kazon.
2. according to claim 13,5-dihydroxy-4-isopropyl toluylene exterior-applied liquid medicine gel is characterized in that this exterior-applied liquid medicine gel is composed as follows: in weight portion
15～30 parts of carbomers,
15～40 parts of 3,5-dihydroxy-4-isopropyl toluylene,
80～120 parts of solvent orange 2 As,
120～200 parts of transdermal enhancers,
12～18 parts of gellant,
240～450 parts of solvent B,
10～15 parts of antibacterial,
800～1000 parts in water.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210087733 CN102579322B (en) | 2012-03-29 | 2012-03-29 | Externally applied hydrogel agent and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210087733 CN102579322B (en) | 2012-03-29 | 2012-03-29 | Externally applied hydrogel agent and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102579322A CN102579322A (en) | 2012-07-18 |
| CN102579322B true CN102579322B (en) | 2013-10-23 |
Family
ID=46468935
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201210087733 Active CN102579322B (en) | 2012-03-29 | 2012-03-29 | Externally applied hydrogel agent and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102579322B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104306186A (en) * | 2013-09-05 | 2015-01-28 | 安徽万邦医药科技有限公司 | Coix seed beauty gel and preparation method thereof |
| CN109010260A (en) * | 2018-07-24 | 2018-12-18 | 株洲千金药业股份有限公司 | A kind of metronidazole vagina gel preparation |
| CN114569586B (en) * | 2022-01-28 | 2023-12-05 | 鲁奕诗 | Benzenimod enema and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101721713A (en) * | 2009-12-01 | 2010-06-09 | 河北科技大学 | Cyclodextrin inclusion compound of 3,5-dyhydroxyl-4-isopropyl toluylene and preparation method thereof |
| CN101822638A (en) * | 2009-12-01 | 2010-09-08 | 河北科技大学 | Nano-emulsion of stilbene compound and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7321050B2 (en) * | 1999-12-06 | 2008-01-22 | Welichem Biotech Inc. | Anti-inflammatory and psoriasis treatment and protein kinase inhibition by hydroxy stilbenes and novel stilbene derivatives and analogues |
| ES2334635T3 (en) * | 1999-12-06 | 2010-03-15 | Welichem Biotech Inc. | POLYHYDROXIESTILBEN AND STILBENE OXIDES AS ANTIPSORIASIC AGENTS AND INHIBITORS OF PROTEIN KINASE. |
-
2012
- 2012-03-29 CN CN 201210087733 patent/CN102579322B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101721713A (en) * | 2009-12-01 | 2010-06-09 | 河北科技大学 | Cyclodextrin inclusion compound of 3,5-dyhydroxyl-4-isopropyl toluylene and preparation method thereof |
| CN101822638A (en) * | 2009-12-01 | 2010-09-08 | 河北科技大学 | Nano-emulsion of stilbene compound and preparation method thereof |
Non-Patent Citations (4)
| Title |
|---|
| Jane S. Williams et al.The gene stlA encodes a phenylalanine ammonia-lyase that is involved in the production of a stilbene antibiotic in Photorhabdus luminescens TT01.《Microbiology》.2005,第151卷2543-2550页. |
| The gene stlA encodes a phenylalanine ammonia-lyase that is involved in the production of a stilbene antibiotic in Photorhabdus luminescens TT01;Jane S. Williams et al;《Microbiology》;20051231;第151卷;2543-2550页 * |
| The preparation of 3,5-dihydroxy-4-isopropylstilbene nanoemulsion and in vitro release;Yue Zhang et al;《International Journal of Nanomedicine》;20110331(第6期);649-657页 * |
| YueZhangetal.Thepreparationof3 5-dihydroxy-4-isopropylstilbene nanoemulsion and in vitro release.《International Journal of Nanomedicine》.2011 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102579322A (en) | 2012-07-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Kathe et al. | Film forming systems for topical and transdermal drug delivery | |
| CA2309688C (en) | Penetration enhancing and irritation reducing systems | |
| KR102378645B1 (en) | Topical gel compositions including polycaprolactone polymer and methods for enhancing the topical application of a benefit agent | |
| JP5487461B2 (en) | Adhesive skin-forming formulation for skin delivery of drugs and method of using the same | |
| US6280764B1 (en) | Device for topical treatment of acne and its method of manufacture | |
| RU2437680C2 (en) | Application of film-forming polymers from group of polyurethanes for hair care and pharmaceutical preparations, which contain these polymers | |
| CN103717213B (en) | The transdermal composition of ibuprofen and using method thereof | |
| AU2014365791A1 (en) | Topical gel compositions including poly(monostearoyl glycerol-co-succinate) polymer and methods for enhancing the topical application of a benefit agent | |
| CN102256666B (en) | A composition and method of treating skin conditions | |
| CN106344956A (en) | Chitosan antibacterial gel with effect of promoting healing and method for preparing chitosan antibacterial gel | |
| JP2018048140A (en) | Diclofenac formulation | |
| Rasool et al. | Development and evaluation of ibuprofen transdermal gel formulations | |
| JP6778220B2 (en) | Application of mussel adhesive protein products in the treatment and prevention of melanin-related diseases | |
| CN103476396B (en) | Comprise the topical formulations of the suspendible type of cyclic depsipeptide | |
| CN102579322B (en) | Externally applied hydrogel agent and preparation method and application thereof | |
| CN102639127A (en) | Composition for skin improvement comprising hexamidines and retinoids | |
| JPS6112621A (en) | Cataplasma | |
| CN102018696B (en) | Skin external preparation containing lidocaine or pharmaceutical salt thereof | |
| CN102657602B (en) | 3,5-dyhydroxyl-4-isopropyl diphenylethene chitosan gel and preparation method thereof | |
| KR102631501B1 (en) | Compositions and methods for treating skin conditions using light and polycarboxylic acids | |
| AU732330B2 (en) | Device for topical treatment of acne and its method of manufacture | |
| CN101618030B (en) | Triptolide transdermal patch and preparation method thereof | |
| CN104208042B (en) | A kind of transdermal absorption formulation | |
| JPS6112614A (en) | Drug for external use | |
| JPS60163811A (en) | External application pharmaceutical containing propranolol |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C53 | Correction of patent for invention or patent application | ||
| CB03 | Change of inventor or designer information |
Inventor after: Zhang Yue Inventor after: Yu Yifeng Inventor after: Shang Zhenhua Inventor after: Chen Aibing Inventor after: Lv Haijun Inventor before: Zhang Yue Inventor before: Yu Yifeng |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: INVENTOR; FROM: ZHANG YUE YU YIFENG TO: ZHANG YUE YU YIFENG SHANG ZHENHUA CHEN AIBING LV HAIJUN |
|
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |