CN103655459A - Multifunctional microemlusion gel preparation and preparation process thereof - Google Patents
Multifunctional microemlusion gel preparation and preparation process thereof Download PDFInfo
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Abstract
The invention discloses a multifunctional microemlusion gel preparation and a preparation process thereof, and belongs to the technical field of medicines. The preparation mainly comprises bulk pharmaceutical chemicals (such as non-steroidal anti-inflammatory drugs-diclofenac sodium, ibuprofen, indometacin, antifungal drugs-ornidazole, antiviral drugs-ganciclovir, hormone drugs-dexamethasone, local anesthesia drugs-lidocaine and irritants-menthol), a cationic polymer and a microemlusion, can further comprise gel or a thickener, and can be used for transdermal drug delivery and local drug delivery. The preparation process is simple, convenient, good in stability and pollution-free. Compared with existing cream and gel, the preparation has the advantages that a novel action mechanism is adopted, the accumulative penetration amount of unit area of drugs is remarkably increased, a certain slow-release effect is achieved, and the drug delivery frequency and the drug delivery amount can be reduced; a chemical penetration enhancer and a conventional preservative are not added, a certain bacterial inhibition effect is achieved, the skin irritation is avoided, and the use safety of the drugs is improved.
Description
Technical field
The present invention relates to a kind of multi-functional micro emulsion gel and preparation method thereof, belong to medical technical field.
Background technology
Diclofenac sodium, ibuprofen and indomethacin are NSAID (non-steroidal anti-inflammatory drug).Diclofenac sodium is usually used in joint inflammation, periostitis, skeleton myositis, arthritis, gout, rheumatism.Ibuprofen is often used to releasing arthritis, dysmenorrhoea, the symptoms such as heating.In addition ibuprofen is also a kind of analgesic, the pain causing especially for inflammation.It is obvious that indomethacin is alleviated inflammatory pain effect, therefore can be used for acute and chronic rheumatic arthritis, gouty arthritis.Although it is higher that these three kinds of medicines are considered to safety conventionally, orally uses also and can produce series of side effects.Long-term taking diclofenac sodium may cause stomachache, and diarrhoea is felt sick, dyspepsia, abdominal distention, vomiting, gastritis, constipation, erythra, dizziness, headache, menorrhagia.Excessive use ibuprofen can cause nausea, dyspepsia, diarrhoea, epistaxis, giddy and hypertension, and uncommon side effect comprises esophageal ulcer, heart failure, renal failure etc.Take indomethacin untoward reaction have gastrointestinal reaction (feel sick, vomiting, stomachache, diarrhoea, ulcer, sometimes and cause gastrorrhagia and perforation).A result of study of 2010 shows regularly to take NSAID (non-steroidal anti-inflammatory drug) and also can promote to shave one's head.For overcoming above untoward reaction, it is a kind of practicable selection that the NSAID (non-steroidal anti-inflammatory drug) such as diclofenac sodium, ibuprofen and indomethacin are prepared as to external preparation, in addition, makes topical formulations also can make medicine directly act on affected part, accelerates onset speed.
Fungal infection can be divided into table shallow fungal infection and deep fungal infection two classes, shows shallow infection and is invaded skin, hair, referred to that (toe) first-class body surface position causes by tinea bacterium, and sickness rate is high, and hazardness is less.Deep fungal infection invades internal organs by candidiasis and cryptococcus and deep tissue causes, and sickness rate is low, and hazardness is large.Conventional antifungal agent is divided into treatment superficial fungal infection medicine according to site of action salicylic acid, griseofulvin, nystatin, cannitracin, clotrimazole, miconazole, econazole, bifonazole, ketoconazole etc.Anti-deep fungal infection medicine has fluconazol, itraconazole etc.Itraconazole is a kind of lipotropy triazole broad-spectrum antifungal medicine, and deep fungal and superficial fungi are all had to antibacterial action.There are capsule, oral liquid, injection in commercial preparation at present.Itraconazole oral administration biaavailability is relatively low, and after auf nuechternen Magen einnehmen, absorbance is very low especially.In oral liquid, contain cyclodextrin and may cause osmotic diarrhea diarrhoea.Other side effect comprise nauseating, vomiting inappetence etc.
Minoxidil is for intractable hypertension, renal hypertension.These product can make hair hypertrophy, as made, solution external smears can hair growth disease, as alopecia areata and male baldness etc.Commercial preparation majority is tincture and suspensoid at present, is unfavorable for that medicine sticks on skin, and action time is short, needs frequent drug administration, and required drug level is higher.Minoxidil is almost insoluble in water, conventionally contains a large amount of ethanol and propylene glycol in commercial preparation, has potential safety hazard.
Local anesthetic is divided into lipid local anaesthetics and local anesthetics of amide derivatives.What belong to lipid local anaesthetics has procaine, chloroprocaine, tetracaine, a cocaine; Local anesthetics of amide derivatives's lignocaine, mepivacaine, Bupivacaine, etidocaine, prilocaine, ropivacaine.Commercial preparation is mainly injection, gel, emulsifiable paste at present.
Antiviral agents is that a class is for preventing and treat the medicine of viral infection.Can suppress rdrp virus in vitro, at infection cell or animal body, suppress virus replication or breeding, treat clinically the effective medicine of virosis.Open loop uncleosides as antiviral agents has acyclovir, ganciclovir, penciclovir etc., and this type of medicine is mainly used in anti-herpesvirus.Acyclovir is the open loop uncleosides as antiviral agents of first listing, is broad-spectrum antiviral medicament, now as the choice drug of anti-herpesvirus.Commercial preparation mostly is gel at present.
Glucocorticoid is a class steroid hormone of zona fasciculata secretion in adrenal cortex, is mainly hydrocortisone, has the sugar of adjusting, fat and the biosynthesis of protein and the effect of metabolism, also has that Immunosuppression is replied, an antiinflammatory, antitoxin, Antishock function.Local topical glucocorticoid is one of critical treatment means of department of dermatologry, is mainly to utilize its antiinflammatory action, immunosuppressive action and anti-proliferative effect etc.Existing glucocorticoid is mainly synthetic, and change its natural structure, comprise dexamethasone, triamcinolone, betamethasone, mometasone, halometasone etc., indication comprises neurodermatitis, chronic eczema, pruritus ani, contact dermatitis, insect dermatitis etc.
Microemulsion is to be mixed by proper proportion by water, oil, surfactant and cosurfactant, the isotropism of spontaneous formation, transparent, thermodynamically stable dispersion, and particle diameter is less than 100nm.Microemulsion transdermal drug delivery system is better than general Emulsion, stable and obvious to the solubilization of insoluble drug, can obviously improve the content of medicine in preparation, increases the Concentraton gradient of medicine, and its transdermal diffusion rate is increased, and absorbs obviously and accelerates.In addition, the nanostructured of microemulsion may produce inhibitory action to microbial growth.But microemulsion, as a kind of liquid, is unfavorable for being detained at skin surface, can produce harmful effect to the continuous action of medicine.
Micro emulsion gel is that microemulsion is added to people to gel-type vehicle (as macromolecular materials such as natural polymers, cellulose derivative, block polymers), and transparent, the homogenizing of formation, stable gel networks, contain microemulsion drop in network structure.Microemulsion gel inherited microemulsion can increase the dissolubility of insoluble drug, reduce skin diffusion barrier, increase the advantages such as transdermal penetration amount of medicine.Meanwhile, because the attached property of firewood of gel is fine, the intermediate forms of this preparation capable of permeating skin of microemulsion is made to gel, can solve most of microemulsion formulation viscosity too little, on skin, be difficult to coating, be detained the problems such as action time is short.In addition, microemulsion gel can overcome microemulsion to be stored because of long-term, and moisture easily evaporation causes surfactant concentration to raise, and the shortcoming that skin irritation is strong, increases preparation stability, reduces untoward reaction.Therefore,, with conventional microemulsion phase ratio, microemulsion gel is preferably as percutaneous dosing carrier.
Because micro emulsion gel possess advantage, this technology has been subjected to and has paid close attention to.There have been at present the Patents such as hydrochloric acid Granisetron micro emulsion gels and preparation method thereof (CN101933902A), a kind of Oxiconazole Nitrate microemulsion gel preparation (CN102423293A), but in these patents, generally there is the interpolation of chemical enhancers, traditional preservatives, affected product quality.
The present invention improves above-mentioned technology, by above-mentioned NSAID (non-steroidal anti-inflammatory drug), antifungal agent, local anaesthetics, antiviral agents, hair growth promoter, hormone medicine, antipruritic agent is prepared into microemulsion gel preparation, high-quality formula and preparation method have particularly been filtered out, make product not need to contain chemical enhancers and antiseptic, reduce the zest to skin, reduce side effect.Under the prerequisite of not using chemical enhancers, realized good drug transdermal effect, improved properties of product simultaneously.Having realized the two of drug effect effect and safety guarantees.
Summary of the invention
For the deficiencies in the prior art, the invention provides a kind of multi-functional microemulsion gel preparation and preparation method thereof, improve percutaneous absorption rate, the transdermal amount of medicine, and do not add chemical enhancers, traditional preservatives, improve the safety of preparation.Microemulsion nanometer system and cationic polymer coexist in this technique, combined effect, realized the object that significantly improves drug accumulation infiltration capacity, it is the pattern that a kind of new promotion medicine sees through skin barrier, compare transdermal effect and be all far superior to commercial preparation and self-control cation-containing copolymer hydrogel, illustrate that microemulsion and cationic polymer exist synergism.At the system Chinese medicine that has gel to exist, discharge and generally all can be delayed, and the micro emulsion gel transdermal effect that this technology makes is not even weaker than the microemulsion of liquid, guarantee good skin adherence simultaneously, and be not the effect based on chemical enhancers, realized technically innovation.In addition, the nanometer system of microemulsion is unfavorable for bacterial growth, cationic polymer add the further bacteriostasis that strengthened, make this preparation without adding traditional antiseptic.
Technical scheme of the present invention is as follows:
A kind of multi-functional micro emulsion gels, the suitable external used medicine (as NSAID (non-steroidal anti-inflammatory drug) diclofenac sodium, ibuprofen, indomethacin, antifungal drug ornidazole, tinidazole, ketoconazole, antiviral drugs ganciclovir, hormone medicine dexamethasone, local anaesthesia medicine lignocaine, hair restorer minoxidil, stimulant menthol) of take is crude drug, adopt cationic polymer, the micro emulsion gel that microemulsion (being comprised of surfactant, cosurfactant, oil phase and water) and gel or thickening agent form is as pharmaceutical carrier.
Crude drug is the effective ingredient of medicament, comprises by prepared various medicinal powder, crystallization, the extractum etc. of being used as of chemosynthesis, plant extract or biotechnology.
Above-mentioned multi-functional microemulsion gel preparation, preferred weight percentages of components (W/W) is as follows:
Crude drug of the present invention includes but not limited to one of following medicine or combination: NSAID (non-steroidal anti-inflammatory drug) diclofenac sodium, ibuprofen, indomethacin; Antifungal agent ornidazole, tinidazole, miconazole, ketoconazole, itraconazole, terbinafine; Local anaesthetics procaine, tetracaine, Li Kayin; Aciclovir, ganciclovir, penciclovir; Hair growth promoter minoxidil; Hormone medicine dexamethasone, triamcinolone, betamethasone, mometasone, halometasone; Antipruritic composition menthol, Oleum menthae, Borneolum Syntheticum, Camphora; Preferred water dissolubility is poor, and (dissolubility is less than the NSAID (non-steroidal anti-inflammatory drug) of 10g (ml)/100ml as crude drug.
Cationic polymer of the present invention comprises but is not limited to one of following or combination: polylysine, polyacrylamide, chitosan, polyquaternary ammonium salt.Polylysine preferred molecular weight is 3600-4300.The preferred deacetylation of chitosan is more than 90%, and molecular weight is below 100,000.
Described polyquaternary ammonium salt of the present invention is selected from: guar hydroxypropyltrimonium chloride, hydroxypropyl guar hydroxypropyltrimonium chloride, polyquaternary ammonium salt-6, polyquaternary ammonium salt-7, Polyquaternium-10, Merquat 280, polyquaternary ammonium salt-37, polyquaternary ammonium salt-39, polyquaternary ammonium salt-44, polyquaternary ammonium salt-51, polyquaternary ammonium salt-53;
Microemulsion of the present invention comprises surfactant, cosurfactant, and oil phase and water, and have but be not limited to following characteristics:
A. microemulsion particle diameter, between 0-100nm, is preferably between 20-60nm.
B. the ratio of surfactant and cosurfactant is at 1:1-9:1(W/W) between, be preferably in 3:1-9:1(W/W) between and preferably its summation account for the 5%-35%(W/W of microemulsion total amount).This than regular meeting to microemulsion molding, particle diameter, drug transdermal effect exerts an influence.
C. the ratio of surfactant and cosurfactant sum and oil phase is at 1:9-9:1(W/W) between, be preferably in 1:1-9:1(W/W) between, preferably at 2:1-4:1(W/W) between, this produces significance impact than regular meeting to the transdermal effect of medicine.
D. surfactant, the ratio of cosurfactant and oil phase sum and water is at 1:9-9:1(W/W) between, be preferably in 1:9-3:7(W/W) between, this produces significance impact than regular meeting to the transdermal effect of medicine.
Gel of the present invention or thickening agent are selected from one of following or combination: carbomer, hyetellose, aluminium-magnesium silicate, sodium carboxymethyl cellulose, sodium alginate, bentonite, poloxamer188, xanthan gum, guar gum, methylcellulose, ethyl cellulose, hypromellose.
Described surfactant of the present invention is selected from one of following or combination: Polysorbate, poloxamer, polyoxyethylene octyl 2, 2-Oxydiphenol, polyoxyethylene hydrogenated Oleum Ricini, polyoxyethylene castor oil, sad/certain herbaceous plants with big flowers acid polyethylene glycol glyceride, Solutol HS15.
It is one of following that poloxamer of the present invention is selected from: Pluronic/Lutrol F 44, PLURONICS F87, poloxamer 237, Pluronic/Lutrol F 108, poloxamer188.
It is one of following that Polysorbate of the present invention is selected from: polysorbate 20, polysorbate 40, polysorbate 60, polyoxyethylene sorbitan monoleate, polysorbate 85.
Cosurfactant of the present invention is selected from one of following or combination: ethanol, isopropyl alcohol, 1,2-PD, n-butyl alcohol, butanediol, pentanediol, PEG400, glycerol, polyglyceryl fatty acid ester, TC, single sad propylene glycol ester, mono laurate propylene glycol ester, oleic acid PVOH-6 glyceride.
It is one of following that polyglyceryl fatty acid ester of the present invention is selected from: polyglycereol-3 dioleic acid ester, Natrulon H-10 oleate, polyglycereol-6 oleate, polyglycereol-2 oleate, polyglycereol-2 stearate, polyglycereol-4 oleate, polyglycereol-4 stearate, polyglycereol-6 laurate, polyglycereol-6 myristinate, polyglycereol-4 five stearate, , polyglycereol-6 tristearate, polyglycereol-6 five stearate, ricinoleate is gathered in polyglycereol-6, Natrulon H-10 laurate, Natrulon H-10 myristinate, Natrulon H-10 stearate, Natrulon H-10 five oleates, Natrulon H-10 five stearates.
Oil phase of the present invention is selected from one of following or combination: soybean oil, isopropyl palmitate, myristic acid isopropyl ester, olive oil, Oleum Ricini, oleic acid, ethyl oleate, Ethyl linoleate, MCT Oil, isopropyl laurate.
The present invention preferably fills a prescription as follows:
The preparation method step of multi-functional micro emulsion gel of the present invention is as follows:
(1) surfactant is mixed homogeneously with cosurfactant, add oil phase, by stirring, concussion, ultrasonic or vortex mode, mix, add crude drug, by stirring, concussion, ultrasonic or vortex mode, crude drug is dissolved completely, add water, obtain homogeneous transparent or light blue microemulsion.
(2) gel or thickening agent, cationic polymer are added to the water, stir 20min-720min, make its fully dissolve/swelling, be uniformly dispersed, mix, obtain hydrogel.
(3) (1) is mixed mutually with the product of (2) gained, and stir, regulate pH5-8 and get final product, if pH own can not regulate pH within the scope of 5-8.
Or
(4) surfactant is mixed homogeneously with cosurfactant, add oil phase, by stirring, concussion, ultrasonic or vortex mode, mix, add crude drug, by stirring, concussion, ultrasonic or vortex mode, crude drug is dissolved completely, add water, obtain homogeneous transparent or light blue microemulsion.
(5) gel or thickening agent are directly added in (1) gained microemulsion, stir 20min-720min, make its fully dissolve/swelling, be uniformly dispersed, cationic polymer is added, mix, obtain micro emulsion gel.
(6) pH own (2) regulated to pH5-8 and get final product, if can not regulate pH within the scope of 5-8.
Rats in vitro transdermal experiment shows: the prepared multi-functional micro emulsion gel transdermal penetration speed of the present invention, apparently higher than market milk colloid and self-control hydrogel adhesive, can significantly improve the Transdermal absorption of crude drug.
The preparation of the multi-functional microemulsion gel preparation of the present invention is simple, adopt stir, the mode such as ultrasonic, vortex mixes each component, medicine is fully dissolved, then adds water can obtain crude drug emulsion.Gel or thickening agent are added to the water, stir, make its fully dissolve/swelling, be uniformly dispersed, regulate pH5-8, obtain hydrogel, hydrogel is mixed homogeneously and be get final product with crude drug microemulsion.Gained micro emulsion gel outward appearance is even, good stability.
The present invention, by nanometer system and the cationic polymer combined effect of microemulsion, realizes the inhibitory action of preparation to gram positive bacteria and negative bacterium, can not add traditional antiseptic.Owing to not adding traditional antiseptic, as parabens, benzalkonium chloride etc., eliminated the hidden danger of antiseptic to dermal toxicity.In addition, because preparation itself has good osmotic effect, without adding the chemical enhancers such as azone, further improved safety.
Slow releasing preparation refers to by delaying the rate of release of medicine from this dosage form, reduces medicine and enters the absorption rate of body, thereby play better therapeutic effect.The multi-functional microemulsion gel preparation of the present invention is after being applied to skin, not only see through skin speed fast, and preparation from removing, skin is still had high amount of drug active component be stored in skin, as drug-reservoir, continuing to see through skin discharges, realized certain slow release effect, in transdermal test in vitro experiment, compare with commercial preparation, the residual dose of skin of microemulsion gel preparation is higher.
Accompanying drawing explanation
Fig. 1 is diclofenac sodium microemulsion transmission electron microscope photo of the present invention.
Fig. 2 is the drug accumulation transdermal amount comparison diagram of the rats in vitro transdermal experiment of diclofenac sodium micro emulsion gel and market milk colloid and self-control gel in the present invention.
Fig. 3 is the inhibitory action figure of diclofenac sodium micro emulsion gel to Staphylococcus aureus growth in the present invention, and matched group is physiological saline solution.
Fig. 4 is the residual dose comparison diagram of skin of the rats in vitro transdermal experiment of diclofenac sodium micro emulsion gel and market milk colloid and self-control gel in the present invention.Note: MBGa, MBGb is micro emulsion gel, VOL is commercial preparation.
the specific embodiment
Below in conjunction with embodiment, the present invention is described in detail, but be not limited to this.
Embodiment 1 diclofenac sodium microemulsion gel preparation, component is as follows:
Preparation method is as follows:
(1) take ethyl oleate 5g, polyoxyethylene hydrogenated Oleum Ricini 20g, PEG400 25g, diclofenac sodium 1g, mix homogeneously, adds water and stirs 40min, obtains clear microemulsion A liquid.
(2) take Carbopol 1g, chitosan 0.1g stirs respectively 60min in water, and then swelling 12h mixes, and stirs, and regulates pH to 6-8, obtains clear gel B.
(3) A liquid is mixed with B gel, stir, obtain.
Preparation method is as follows:
(1) take isopropyl myristate 4g, polyoxyethylene sorbitan monoleate 20g, 1,2-PD 25g, ibuprofen 3g, mix homogeneously, adds water and stirs 40min, takes polylysine 0.1g and adds, and stirs 10min, obtains clear microemulsion A liquid.
(2) take carbomer ETD20201g, stir 60min in water, swelling 12h, then mixes, and stirs, and regulates pH to 6-8, obtains clear gel B.
(3) A liquid is mixed with B gel, stir, obtain.
Embodiment 3 menthol microemulsion gel preparations, component is as follows:
Preparation method is as follows:
(1) take MCT Oil 4g, sad/certain herbaceous plants with big flowers acid polyethylene glycol glyceride 25g, polyglycereol-2 oleate 3g, menthol 0.8g, mix homogeneously, adds water and stirs 40min, takes polylysine 0.1g and adds, and stirs 10min, obtains clear microemulsion A liquid.Under transmission electron microscope, observe as Fig. 1.
(2) take sodium alginate 3g, chitosan 0.5g stirs respectively 60min in water, and then swelling 12h mixes, and stirs, and regulates pH to 6-8, obtains clear gel B.
(3) A liquid is mixed with B gel, stir, obtain.
Preparation method is as follows:
(1) take MCT Oil 5g, polyoxyethylene hydrogenated Oleum Ricini 7g, polyglycereol-3 dioleic acid ester 1g, diclofenac sodium 1g, mix homogeneously, adds water and stirs 40min, obtains clear microemulsion A liquid.
(2) take Carbopol 1g, chitosan 0.5g stirs respectively 60min in water, and then swelling 12h mixes, and stirs, and regulates pH to 6-8, obtains clear gel B.
(3) A liquid is mixed with B gel, stir, obtain.
According to the diclofenac sodium micro emulsion gel of embodiment 4 preparations, in the unit are of 8h, accumulating infiltration capacity is 901.6 μ g/cm2, is 1.65 times of market milk colloid, and 6.06 times of making hydrogel by oneself, are shown in Fig. 2;
Diclofenac sodium micro emulsion gel according to embodiment 4 preparations, carries out growth inhibition test to staphylococcus aureus, and result is compared with normal saline, and 24h can reduce by 3595 times of clump counts, presents good fungistatic effect.See Fig. 3.
Preparation method is as follows:
(1) take ethyl oleate 10g, polyoxyl 40 hydrogenated castor oil 14g, sad/certain herbaceous plants with big flowers acid polyethylene glycol glyceride 26g, indomethacin 1g, ethyl oleate 10g, mix homogeneously, adds water and stirs 40min, obtains yellow transparent microemulsion A liquid.
(2) take Carbopol 1g, chitosan 0.5g stirs respectively 60min in water, and then swelling 12h mixes, and stirs, and regulates pH to 6-8, obtains clear gel B.
(3) A liquid is mixed with B gel, stir, obtain.
Preparation method is as follows:
(1) take MCT Oil 5g, polyoxyl 40 hydrogenated castor oil 12g, polyglycereol monoleate 2g, propylene glycol 7g, MCT Oil 5g, ornidazole 3g, mix homogeneously, adds water and stirs 40min, obtains light blue clear microemulsion A liquid.
(2) take ethyl cellulose 2g, chitosan 0.5g stirs respectively 60min in water, and then swelling 12h mixes, and stirs, and regulates pH to 6-8, obtains clear gel B.
(3) A liquid is mixed with B gel, stir, obtain.
Preparation method is as follows:
(1) take MCT Oil 5g, polyoxyl 40 hydrogenated castor oil 15g, polyglycereol monoleate 3g, propylene glycol 9g, MCT Oil 5g, tinidazole 3g, mix homogeneously, adds water and stirs 40min, obtains light blue clear microemulsion A liquid.
(2) take ethyl cellulose 2g, chitosan 0.5g stirs respectively 60min in water, and then swelling 12h mixes, and stirs, and regulates pH to 6-8, obtains clear gel B.
(3) A liquid is mixed with B gel, stir, obtain.
Preparation method is as follows:
(1) take sad/certain herbaceous plants with big flowers acid polyethylene glycol glyceride 13.75g, propylene glycol 6.5g, ethanol 15g, minoxidil 3g, oleic acid 2.5g, mix homogeneously, adds water and stirs 40min, obtains clear microemulsion A liquid.
(2) take hydroxyethyl-cellulose 4g, add A liquid, swelling 2h, obtains clear gel B.
(3) take polylysine 0.5g, add in suitable quantity of water and dissolve, mix with B gel, stir, obtain.
Embodiment 9 itraconazole microemulsion gel preparations, component is as follows:
Preparation method is as follows:
(1) take polyoxyethylene castor oil 22.5g, TC 7.5g, benzyl alcohol 15g, itraconazole 1g, mix homogeneously, adds water and stirs 40min, obtains clear microemulsion A liquid.
(2) take hydroxyethyl-cellulose 4g, add A liquid, swelling 2h, obtains clear gel B.
(3) take polylysine 0.5g, add in suitable quantity of water and dissolve, mix with B gel, stir, obtain.
Preparation method is as follows:
(1) take polyoxyethylene castor oil 22.5g, TC 7.5g, benzyl alcohol 15g, itraconazole 1g, mix homogeneously, adds water and stirs 40min, obtains light blue clear microemulsion A liquid.
(2) take hydroxyethyl-cellulose 4g, add A liquid, swelling 2h, obtains clear gel B.
(3) take polylysine 0.5g, add in suitable quantity of water and dissolve, mix with B gel, stir, obtain.
Embodiment 11 acyclovir microemulsion gel preparations, component is as follows:
Preparation method is as follows:
(1) take polyoxyethylene sorbitan monoleate 20g, glycerol 4g, glyceryl monostearate 2g, acyclovir 0.3g, mix homogeneously, adds water and stirs 40min, obtains clear microemulsion A liquid.
(2) take xanthan gum 3g, chitosan 0.5g stirs respectively 60min in water, and then swelling 12h mixes, and stirs, and regulates pH to 6-8, obtains clear gel B.
(3) A liquid is mixed with B gel, stir, obtain.
Embodiment 12 lignocaine breast gel preparations, component is as follows:
Preparation method is as follows:
(1) take Solutol HS15 21g, ethanol 7g, myristic acid isopropyl ester 2g, lignocaine 2g, mix homogeneously, adds water and stirs 40min, obtains faint yellow clear microemulsion A liquid.
(2) take aluminium-magnesium silicate 4g, chitosan 0.5g stirs respectively 60min in water, and then swelling 12h mixes, and stirs, and regulates pH to 5-8, obtains clear gel B.
(3) A liquid is mixed with B gel, stir, obtain.
Embodiment 13 menthol microemulsion gel preparations, component is as follows:
Preparation method is as follows:
(1) take Solutol HS15 21g, ethanol 7g, myristic acid isopropyl ester 2g, menthol 1g, mix homogeneously, adds water and stirs 40min, obtains light blue clear microemulsion A liquid.
(2) take chitosan 4g and in water, stir 60min, swelling 12h, stirs, and regulates pH to 5-8, obtains clear gel B.
(3) A liquid is mixed with B gel, stir, obtain.
Claims (21)
1. a multi-functional microemulsion gel preparation, is characterized in that comprising crude drug, cationic polymer and microemulsion.
2. multi-functional microemulsion gel preparation according to claim 1, is characterized in that it can further comprise gel or thickening agent.
3. multi-functional microemulsion gel preparation according to claim 1, the content that it is characterized in that telling crude drug is 0.5%-5%(w/w).
4. multi-functional microemulsion gel preparation according to claim 1, is characterized in that the content of the cationic polymer told is 0.1%-3%(w/w).
5. crude drug multi-functional microemulsion gel preparation according to claim 1, it is characterized in that described under crude drug including but not limited to one of following or combination: NSAID (non-steroidal anti-inflammatory drug) diclofenac sodium, ibuprofen, indomethacin; Antifungal agent ornidazole, tinidazole, miconazole, ketoconazole, itraconazole, terbinafine; Local anaesthetics procaine, tetracaine, Li Kayin; Aciclovir, ganciclovir, penciclovir; Hair growth promoter minoxidil; Hormone medicine dexamethasone, triamcinolone, betamethasone, mometasone, halometasone; Antipruritic composition menthol, Oleum menthae, Borneolum Syntheticum, Camphora.
6. multi-functional microemulsion gel preparation according to claim 1, is characterized in that the NSAID (non-steroidal anti-inflammatory drug) of preferred water dissolubility poor (dissolubility is less than 10g (ml)/100ml) is as crude drug.
7. multi-functional microemulsion gel preparation according to claim 1, is characterized in that described cationic polymer comprises but is not limited to one of following or combination: polylysine, polyacrylamide, chitosan, polyquaternary ammonium salt.
8. multi-functional microemulsion gel preparation according to claim 1, is characterized in that described microemulsion comprises surfactant, cosurfactant, oil phase and water.
9. multi-functional microemulsion gel preparation according to claim 7, is characterized in that polyquaternary ammonium salt in described cationic polymer is selected from one of following or combination: guar hydroxypropyltrimonium chloride, hydroxypropyl guar hydroxypropyltrimonium chloride, polyquaternary ammonium salt-6, polyquaternary ammonium salt-7, Polyquaternium-10, Merquat 280, polyquaternary ammonium salt-37, polyquaternary ammonium salt-39, polyquaternary ammonium salt-44, polyquaternary ammonium salt-51, polyquaternary ammonium salt-53.
10. multi-functional microemulsion gel preparation according to claim 8, is characterized in that surfactant in described microemulsion, and the ratio of cosurfactant and oil phase sum and water is at 1:9-9:1(W/W) between.
11. multi-functional microemulsion gel preparations according to claim 8, the ratio that it is characterized in that surfactant and cosurfactant sum and oil phase in described microemulsion is at 1:1-9:1(W/W) between.
12. multi-functional microemulsion gel preparations according to claim 8, in the microemulsion described in it is characterized in that, the ratio of surfactant and cosurfactant is at 1:3-9:1(W/W) between.
13. multi-functional microemulsion gel preparations according to claim 8, it is characterized in that the described preferred following scheme of microemulsion: the ratio of surfactant and cosurfactant is at 2:1-6:1(W/W) between, its summation accounts for the 5%-35%(W/W of microemulsion total amount), the ratio of surfactant and cosurfactant sum and oil phase is at 2:1-4:1(W/W) between, surfactant, the ratio of cosurfactant and oil phase sum and water is at 3:7-1:9(W/W) between, microemulsion particle diameter is preferably in 20-60nm.
14. multi-functional microemulsion gel preparation according to claim 2, is characterized in that described gel or thickening agent are selected from one of following or combination: carbomer, hyetellose, aluminium-magnesium silicate, sodium carboxymethyl cellulose, sodium alginate, bentonite, poloxamer188, xanthan gum, guar gum, methylcellulose, ethyl cellulose, hypromellose.
15. multi-functional microemulsion gel preparations according to claim 8, the surfactant that it is characterized in that described microemulsion is selected from one of following or combination: Polysorbate, poloxamer, polyoxyethylene octyl 2, 2-Oxydiphenol, polyoxyethylene hydrogenated Oleum Ricini, polyoxyethylene castor oil, sad/certain herbaceous plants with big flowers acid polyethylene glycol glyceride, Solutol HS15.
16. multi-functional microemulsion gel preparations according to claim 15, is characterized in that in described surfactant that poloxamer is selected from one of following: Pluronic/Lutrol F 44, PLURONICS F87, poloxamer 237, Pluronic/Lutrol F 108, poloxamer188.
17. multi-functional microemulsion gel preparations according to claim 15, is characterized in that in described surfactant that Polysorbate is selected from one of following: polysorbate 20, polysorbate 40, polysorbate 60, polyoxyethylene sorbitan monoleate, polysorbate 85.
18. multi-functional microemulsion gel preparations according to claim 15, it is characterized in that in described cosurfactant that polyglyceryl fatty acid ester is selected from one of following: polyglycereol-3 dioleic acid ester, Natrulon H-10 oleate, polyglycereol-6 oleate, polyglycereol-2 oleate, polyglycereol-2 stearate, polyglycereol-4 oleate, polyglycereol-4 stearate, polyglycereol-6 laurate, polyglycereol-6 myristinate, polyglycereol-4 five stearate, , polyglycereol-6 tristearate, polyglycereol-6 five stearate, ricinoleate is gathered in polyglycereol-6, Natrulon H-10 laurate, Natrulon H-10 myristinate, Natrulon H-10 stearate, Natrulon H-10 five oleates, Natrulon H-10 five stearates.
19. multi-functional microemulsion gel preparations according to claim 8, it is characterized in that in described microemulsion that cosurfactant is selected from one of following or combination: ethanol, isopropyl alcohol, 1,2-PD, n-butyl alcohol, butanediol, pentanediol, PEG400, glycerol, polyglyceryl fatty acid ester, TC, single sad propylene glycol ester, mono laurate propylene glycol ester, oleic acid PVOH-6 glyceride.
20. multi-functional microemulsion gel preparations according to claim 8, the oil phase that it is characterized in that described microemulsion is selected from one of following or combination: soybean oil, isopropyl palmitate, myristic acid isopropyl ester, olive oil, Oleum Ricini, oleic acid, ethyl oleate, Ethyl linoleate, MCT Oil, isopropyl laurate.
The preparation technology of 21. multi-functional microemulsion gel preparations comprises following content:
1) preparation of microemulsion: by crude drug, oil phase, surfactant, cosurfactant, water mixes.
2) by microemulsion, gel or thickening agent, cationic polymer, water mixes.
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