CN109985000A - Gram vertical boron sieve micro emulsion composition - Google Patents
Gram vertical boron sieve micro emulsion composition Download PDFInfo
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- CN109985000A CN109985000A CN201711471716.XA CN201711471716A CN109985000A CN 109985000 A CN109985000 A CN 109985000A CN 201711471716 A CN201711471716 A CN 201711471716A CN 109985000 A CN109985000 A CN 109985000A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/69—Boron compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
Abstract
The invention discloses gram vertical boron sieve micro emulsion compositions, described gram of vertical boron sieve micro emulsion composition includes: by weight percentage, it include: gram vertical boron sieve 0.5%~5.0%, oily phase 5%~20%, emulsifier 10%~40%, assistant for emulsifying agent 5%~30%, water 30%~70%, wherein oil is mutually the fatty-acid monoester selected from C10-C18, one of triglyceride or a variety of combinations, and emulsifier is selected from tween system emulsifier.Gram vertical boron sieve microemulsion solution stability of the invention is good, has ideal micro emulsion partial size, can effectively improve drug penetration through skin；Gram vertical boron sieve micro emulsion gel compares gram vertical boron sieve microemulsion solution, can further improve percutaneous permeability and hold-up, allergic dermatitis clinical treatment compliance can be improved and play slow release effect.
Description
Technical field
The invention belongs to biomedicine fields, and in particular to a kind of gram vertical boron sieve microemulsion solution and micro emulsion gels and its system
Preparation Method, the micro emulsion composition can contain gram vertical boron sieve through keratoderma, have high percutaneous permeability, high dermal drug
The feature of hold-up, residue easy cleaning is mainly used for treating allergic dermatitis (eczema).
Background technique
Allergic dermatitis (AD, atopic dermatitis), is commonly called as eczema.It is one kind and the close phase of genetic anaphylactic predisposition
The dermal inflammatory disease of pass, patients are widely distributed.It is characterized in that pruitus, fash pleomorphism are simultaneously inclined to exudation.
In addition to the clinical manifestation with eczema, the family's tendency for being easy to suffer from asthma, allergic rhinitis, eczema is also had the following characteristics that；
To foreign protei allergy；Serum immune globulin E (IgE) increase and blood in eosinophilia.
The cause and onset of disease mechanism of allergic dermatitis is not yet completely clear.Being commonly referred to be is stimulated by various inside and outside factors
And interaction causes to fall ill, including inherent cause, immune factor and environmental factor etc..Allergic dermatitis has apparent family
Race's aggregation, and 60%~90% patient is obvious by seasonal effect, and the weight summer in winter is light.Hot and cold and amblent air temperature change dramatically,
A large amount of suddenly perspire also can be deterioration or risk factor.Contact the professional disease incidence of wool, textile, dust and high-temperature operation
It is higher.Allergic dermatitis is distributed in each age group, and baby is in the majority with teenager, and the allergic dermatitis of statistics display 60% presents early
The characteristics of phase occurs, and with lifelong.Developed country at present, the disease incidence of allergic dermatitis maintains 10~20%, and is in
Now increased trend year by year.
According to the result of study of disease feature and current predisposition thereto, the therapeutic modality of allergic dermatitis mainly includes being
System drug therapy, physiotherapy and topical medications.1) systemic drug is treated: the immunology morbidity machine based on allergic dermatitis
The systemic administration of system, including oral and drug administration by injection.Oral drugs mainly include ciclosporin A (CyA), mycophenolate (MMF) etc.,
Its main feature is that curative for effect reliable, as immunosuppressor, liver renal toxicity, serious gastrointestinal reaction and neutrophil leucocyte subtract
It greatly limits their application less, another kind of oral drugs are based on antibacterium and antifungal drug, primary limitation is that resistance to
The repeatability of pharmacological property and disease；Injecting class drug is mainly immunomodulator, and representing drug has interferon-γ and immune ball
Albumen (HdIVIG), its main feature is that rapid-action, effect is obvious, but long-term administration safety data is not perfect.2) physiotherapy: base
In pathological research, for the external physical means of intervention of the lesions position of allergic dermatitis, representation mode has phototherapy (middle and high
The ultraviolet lighting of dosage), its main feature is that it is safe without obvious adverse reaction, but exact curative effect greatly limits its clinical application.3)
Topical medications: allergic dermatitis is as locality lesion, because of its disease feature, headed by topical medications (external drug)
Select therapeutic scheme.At present the drug of local treatment mainly include tacrolimus, Meike do not take charge of, capsaicin, doxepin liniment.
The limitation of local treatment drug is that drug permeability is poor, and offer limited effectiveness, mechanism of drug action is indefinite, is easy recurrence.
Gram vertical boron sieve of listing in 2016 is as external application small molecule boron class drug, to the meaning weight of allergic dermatitis treatment
Greatly.Based on the research of allergic dermatitis pathogenesis, by inhibit phosphodiesterase 4 (PDE4) and pro-inflammatory cytokine this two
A inflammation target, thus reach the activity for inhibiting inflammation medium, cyclic adenosine monophosphate of degrading, to reach treatment allergic dermatitis
Effect.
Gram vertical boron sieve listing dosage form is cream (trade name: EUCRISA), need to be administered daily 2 times.According to allergic dermatitis
Disease feature, long lasting for administration, clinically poor compliance, cream are mainly oleaginous base, skin surface oil after administration
Soapy feeling is strong, after contacting with clothing etc., it is difficult to clean, clinical application poor compliance, the production technology of cream is complicated, and drug is prepared
And subpackage dress need to be heat-treated, and need special packaging material.
Ideal external preparation is, with the formulation and technology of simple and stable, to promote medicine in a manner of physics by preparation technique
Object passes through keratoderma, improves permeability to achieve the purpose that improve therapeutic efficiency, reduces drug toxic side effect itself, improve
Safety, and improve the clinical compliance of medication.
Micro emulsion (micro emulsion, ME) is water, and oil, surfactant and cosurfactant mix in appropriate proportion
It closes, the isotropism spontaneously formed is transparent, thermodynamically stable dispersion.Microemulsion first by discoveries such as schulman simultaneously
Name.It is known micro emulsion percutaneous drug administration preparation is made in drug to can be improved the drugloading rate and stability of preparation, extend drug effect
Time improves bioavilability, and micro emulsion surface tension is lower, is easily wetted skin, so that cuticula structure is changed, makes
Drug readily penetrates through cuticula and is absorbed by the body.Also has the successful case of micro emulsion percutaneous drug administration preparation currently on the market.However,
The effect of microemulsion formulation plays and specific drug ingedient, the close phase of the size of surfactant used and micro emulsion particle
It closes, in addition, the stability of microemulsion formulation itself is also extremely important, the oil in emulsion or creme occurred in the prior art is mutually general
For vaseline or fatty alcohol, however the preparation of above-mentioned oily phase is used, stability is bad, and percutaneous penetration is also poor.To Mr. Yu spy
Determine for drug, it is unexpected for can obtaining the microemulsion formulation with excellent stability and significant effect promotion.
Summary of the invention
Problems to be solved by the invention
It is good in view of the deficiencies of the prior art, it is an object of the present invention to provide a kind of stability and with ideal micro emulsion partial size
Gram vertical boron sieve micro emulsion composition.
The solution to the problem
A kind of gram vertical boron sieve micro emulsion composition, described gram of vertical boron sieve micro emulsion composition include: by weight percentage, it is gram vertical
Boron sieve 0.5%~5.0%, oily phase 5%~20%, emulsifier 10%~40%, assistant for emulsifying agent 5%~30%, water 30%~
70%, wherein oil is mutually the fatty-acid monoester selected from C10-C18, one of triglyceride or a variety of combinations, emulsification
Agent is selected from tween system emulsifier.The fatty-acid monoester is the fat that 1mol fatty acid and 1mol alcohol are formed by esterification
Acid esters, the triglyceride are formed by triglyceride by esterification for 3mol carboxylic acid and 1mol glycerol.
Further, described gram of vertical boron sieve micro emulsion composition is gram vertical boron sieve microemulsion solution or gram vertical boron sieve micro emulsion gel
Agent, wherein by weight percentage, described gram of vertical boron sieve microemulsion solution includes: gram vertical boron sieve 0.5%~5.0%, oily phase 5%
~20%, emulsifier 10%~40%, assistant for emulsifying agent 5%~30%, water 30%~70%, wherein oil is mutually for selected from C10-C18
Fatty-acid monoester, one of triglycerides or a variety of combinations, emulsifier is selected from one of Tween 80 and polysorbate60
Or a variety of combination；Described gram of vertical boron sieve micro emulsion gels include gram vertical boron sieve microemulsion solution and the gel rubber material.
Further, described gram of vertical boron sieve microemulsion solution, by weight percentage, gram vertical boron sieve 1.0%~2.0%, oil
Phase 8%~15%, emulsifier 15%~30%, assistant for emulsifying agent 10%~25%, water 40%~60%, preferably gram vertical boron sieve
1.5%~2.0%, oily phase 8%~10%, emulsifier 20%~30%, assistant for emulsifying agent 10%~20%, water 40%~50%.
Further, the oil is mutually one in oleate, triglyceride, palmitate and myristinate
Kind is a variety of, it is preferred that the oleate is oleic acid Arrcostab, and the alkyl is the alkyl of C1-C6, and the tricarboxylic acids is sweet
Grease is the carboxylic acid containing C1-C6, and the palmitate is alkyl palmitates, and the alkyl is the alkyl of C1-C6, described
Myristinate be myristyl ester, the alkyl be C1-C6 alkyl.
Further, the oil is mutually ethyl oleate, glyceryl triacetate, isopropyl palmitate and isopropyl myristate
One of or a variety of combinations.
Further, the assistant for emulsifying agent is selected from methanol, ethyl alcohol, propyl alcohol, isopropanol, propylene glycol and polyethylene glycol 400
One of or a variety of combinations.
Further, the oil is mutually ethyl oleate, and the emulsifier is Tween 80, and the assistant for emulsifying agent is ethyl alcohol, excellent
It is selected as dehydrated alcohol.
Further, the gel rubber material be one of carbomer, methylcellulose or sodium carboxymethylcellulose or
It is a variety of, preferably Acritamer 940, carbomer 934, Carbopol 941, more preferably Acritamer 940, the gel rubber material adds
Add weight is the 0.5%~2.5% of the addition weight of described gram of vertical boron sieve microemulsion solution.
Further, micro emulsion particle diameter is 5-50nm in gram vertical boron sieve microemulsion solution.
Further, micro emulsion particle diameter is 5-30nm in gram vertical boron sieve microemulsion solution.
The present invention also provides a kind of preparation methods of gram vertical boron sieve micro emulsion composition, and described method includes following steps:
(1) the oily phase, emulsifier, assistant for emulsifying agent are taken, is stirred evenly, gram vertical boron sieve is added, stirring adds water to get a gram vertical boron Luo Wei
Milk solution, (2) are optionally added into gel rubber material, are sufficiently swollen, and are uniformly mixed to get gram vertical boron sieve micro emulsion gels.
Further, step (1) is to take the oily phase, emulsifier, assistant for emulsifying agent, stirs evenly, gram vertical boron sieve is added, after
Purified water is added to dissolving in continuous stirring, stirring to clear and bright, to bubble disappear to the greatest extent clear transparent solutions, as gram vertical boron sieve micro emulsion
Solution, wherein when purified water is added, stirred using mechanical agitator, mixing speed is 500~5000rpm
Further, the reaction temperature of the reaction is 20-100 DEG C, preferably 20-80 DEG C.
The effect of invention
1) gram vertical boron sieve microemulsion solution stability of the invention is good, has ideal micro emulsion partial size, micro emulsion ion surface band is just
Charge, and it has been demonstrated experimentally the percutaneous permeability that can effectively improve pharmaceutical composition, it is expected to improve the treatment of gram vertical boron sieve
Effect；
2) for gram vertical boron sieve micro emulsion gel of the invention on the basis of gram vertical boron sieve microemulsion solution, the skin for improving micro emulsion is viscous
Attached property, stretchability and residence time problem increase drug in skin surface adhesiveness, raising drug skin hold-up, can mention
High allergic dermatitis clinical treatment compliance, and drug in micro emulsion can also be prevented to be precipitated simultaneously, medicine stability is improved, is extended
The release time of drug realizes slow release effect, has achieved the purpose that reduce medicine frequency.
3) gram vertical boron sieve micro emulsion of the invention or micro emulsion gel are O/W systems, drug system have both adhesiveness, stretchability and
While the advantages such as permeability, has and be readily cleaned, pollution clothes etc. a little, do not have good clinical application compliance.
4) gram vertical boron sieve microemulsion solution of the invention or micro emulsion gel prepare simple, process control.
Detailed description of the invention
Gram vertical boron sieve microemulsion solution size distribution stability of Fig. 1 embodiment 1-3.
Gram vertical boron sieve microemulsion solution size distribution stability of Fig. 2 embodiment 4-6 and comparative example 1.
Specific embodiment
Gram vertical boron sieve, the entitled Crisaborole of English, is approved listing by U.S. FDA, is a kind of di-phosphate ester for 2016
Enzyme -4 (PDE-4) inhibitor.
The present invention provides a kind of gram vertical boron sieve micro emulsion composition.Specifically, the composition is gram vertical boron sieve microemulsion solution
Or gram vertical boron sieve micro emulsion gels, wherein by weight percentage, the composition of raw materials of gram vertical boron sieve microemulsion solution includes: gram vertical
Boron sieve 1.0%~2.0%, oily phase 8%~15%, emulsifier 15%~30%, assistant for emulsifying agent 10%~25%, water 40%~
60%, wherein oil is mutually for selected from one of ethyl oleate, glyceryl triacetate, isopropyl palmitate and isopropyl myristate
Or a variety of combinations, emulsifier are selected from one of Tween 80, polysorbate60 or a variety of combinations, assistant for emulsifying agent is selected from anhydrous
One of ethyl alcohol, propylene glycol and polyvinyl alcohol 400 or a variety of combinations；The composition of raw materials of described gram of vertical boron sieve micro emulsion gels
Include gram vertical boron sieve microemulsion solution and a gel rubber material.
In a preferred embodiment, the composition of raw materials of described gram of vertical boron sieve microemulsion solution are as follows: gram vertical boron sieve 1.5%
~2.0%, oily phase 8%~10%, emulsifier 20%~30%, assistant for emulsifying agent 10%~20%, water phase 40%~50%.
In a preferred embodiment, the oil is mutually ethyl oleate, and emulsifier is Tween 80, and assistant for emulsifying agent is
Dehydrated alcohol.Under the formulation condition, the particle size of prepared gram vertical boron sieve microemulsion solution, stability is the most excellent, accordingly
Percutaneous permeability it is best and without any side effects simultaneously.Further, the composition of raw materials of gram vertical boron sieve microemulsion solution are as follows: gram
Vertical boron sieve about 2.0%, oil make an appointment 8%, emulsifier about 30%, assistant for emulsifying agent about 10%, water phase about 50%.
Gram vertical boron sieve microemulsion solution of the invention can be made according to the conventional method of microemulsion solution known in the art
It is standby, however, it is preferred that gram vertical boron sieve microemulsion solution of the invention is made by following steps: taking the oily phase, the emulsification of formula ratio
Agent, assistant for emulsifying agent stir evenly under room temperature or heating condition, and gram vertical boron sieve of formula ratio is added, and continue stirring to dissolving, so
Afterwards under lasting stirring condition, it is continuously added purified water, is stirred continuously to clear and bright, disappears to obtain clear transparent solutions to the greatest extent to bubble, i.e.,
For gram vertical boron sieve microemulsion solution.Gram vertical boron sieve microemulsion solution that this method is prepared is water oil-packaging type micro-emulsion, and micro emulsion drop
Surface has charge.
In a preferred embodiment, when purified water is added, stirred using mechanical agitator, mixing speed is
500~5000rpm, under this condition, the particle size of obtained micro emulsion particle is more satisfactory and homogeneity is preferable.
In a preferred embodiment, according to the present invention, micro emulsion particle in gram vertical boron sieve microemulsion solution
Diameter is between 5-50nm, preferably 5-30nm, more preferably 5-20nm.The wherein test method of size distribution are as follows: take micro emulsion molten
Liquid, purified water dilute one times, measure size distribution using Nicomp388 laser particle analyzer.P.I value is variance (Variance),
It is all examining report result with average particle size for the coefficient of variation repeatedly measured.
As a further preferred embodiment of the present invention, described gram of vertical boron sieve micro emulsion composition is gram vertical boron sieve micro emulsion gel
Agent can prevent drug in micro emulsion to be precipitated compared with gram vertical boron sieve microemulsion solution by the stable reticular structure of gel rubber material,
Increase adhesiveness of the drug system in skin surface, stretchability simultaneously, extend the medicine retention time, improves medication compliance.
Further, in gram vertical boron sieve micro emulsion gels, the addition weight of gel rubber material is that described gram of vertical boron sieve micro emulsion is molten
The 0.5%~2% of the addition weight of liquid.
Preferably, the gel rubber material is carbomer, such as Acritamer 940.
One kind of gram vertical boron sieve micro emulsion gels is simple the preparation method comprises the following steps: take gram vertical boron sieve microemulsion solution, is added
Gel rubber material, sufficiently be swollen, be uniformly mixed to get.
According to another aspect of the present invention, this gram of vertical boron sieve microemulsion solution the preparation method comprises the following steps: 1) taking gram of formula ratio
Vertical boron sieve, oily phase, emulsifier, assistant for emulsifying agent in room temperature or are heated to 60~80 DEG C to dissolution；2) continue under stirring condition, by water
It is mutually continuously added in oily phase, is stirred continuously, disappears to the greatest extent to bubble, obtain clear microemulsion solution.
Further, common bacteriostatic agent, essence etc. can also be added in micro emulsion composition provided by the present invention.
Carry out the technical solution during the present invention is further explained below with reference to specific embodiment.Under it should be understood that
Column embodiment is only used for the explanation and illustration present invention, and the protection scope being not intended to restrict the invention.Unless otherwise indicated, under
Instrument used in column embodiment, material and reagent etc. can be obtained by routine business means.
Embodiment 1-1: the preparation of gram vertical boron sieve microemulsion solution
By the formula composition and following preparation step preparation gram vertical boron sieve microemulsion solution in table 1:
1) ethyl oleate, Tween 80, dehydrated alcohol at room temperature, are taken, using efficient mechanical blender, mixing speed
500rpm is stirred evenly, and gram vertical boron sieve is added, and continues stirring to dissolution；
2) continue under stirring condition, purified water constantly added to oily phase, be stirred continuously to clear and bright, to bubble disappear to the greatest extent it is colourless
To faint yellow clear transparent solutions.
Table 1
The average particle size of gained microemulsion solution is 16.5 ± 0.6nm, P.I.0.127.
Embodiment 1-2: the preparation of gram vertical boron sieve microemulsion solution
The present embodiment substantially with embodiment 1-1, unlike, wherein Tween 80 is that polysorbate60 substitutes, and dehydrated alcohol is poly-
Ethylene glycol 400 substitutes, and gained microemulsion solution average particle size is 23.4 ± 0.7nm, P.I.0.185.
Embodiment 1-3: the preparation of gram vertical boron sieve microemulsion solution
The present embodiment substantially with embodiment 1-1, unlike, wherein Tween 80 is that lecithin substitutes, dehydrated alcohol third
Glycol substitution, gained microemulsion solution average particle size are 22.5 ± 0.8nm, P.I.0.215.
Embodiment 2: the preparation of gram vertical boron sieve microemulsion solution
By the formula composition and following preparation step preparation gram vertical boron sieve microemulsion solution in table 2:
1) ethyl oleate, Tween 80, dehydrated alcohol at room temperature, are taken, using efficient mechanical blender, mixing speed
2500rpm is stirred evenly, and gram vertical boron sieve is added, and continues stirring to dissolution；
2) continue under stirring condition, purified water constantly added to oily phase, be stirred continuously to clear and bright, to bubble disappear to the greatest extent it is colourless
To faint yellow clear transparent solutions.
Table 2
The average particle size of gained microemulsion solution is 7.7 ± 0.3nm, P.I.0.251.
Embodiment 3: the preparation of gram vertical boron sieve microemulsion solution
By the formula composition and following preparation step preparation gram vertical boron sieve microemulsion solution in table 3:
1) isopropyl myristate, Tween 80, polyethylene glycol 400, dehydrated alcohol at room temperature, are taken, is stirred using efficient mechanical
Device is mixed, mixing speed 3000rpm is stirred evenly, and gram vertical boron sieve is added, and continues stirring to dissolution；
2) continue under stirring condition, purified water constantly added to oily phase, be stirred continuously to clear and bright, to bubble disappear to the greatest extent it is colourless
To faint yellow clear transparent solutions.
Table 3
The average particle size of gained microemulsion solution is 16.8 ± 0.5nm, P.I.0.225.
Embodiment 4: the preparation of gram vertical boron sieve microemulsion solution
By the formula composition and following preparation step preparation gram vertical boron sieve microemulsion solution in table 4:
1) glyceryl triacetate, Tween 80, dehydrated alcohol at room temperature, are taken, using efficient mechanical blender, mixing speed
4000rpm is stirred evenly, and gram vertical boron sieve is added, and continues stirring to dissolution；
2) continue under stirring condition, purified water constantly added to oily phase, be stirred continuously to clear and bright, to bubble disappear to the greatest extent it is colourless
To yellow clear transparent solutions.
Table 4
The average particle size of gained microemulsion solution is 19.8 ± 0.8nm, P.I.0.187.
Comparative example 1The preparation of gram vertical boron sieve microemulsion solution
By the formula composition and following preparation step preparation gram vertical boron sieve microemulsion solution in table 5:
1) isopropyl palmitate, Crodaret 40, dehydrated alcohol are taken, oil bath heating is to 45 DEG C, using height
Mechanical agitator is imitated, mixing speed 4000rpm is stirred evenly, and gram vertical boron sieve is added, and continues stirring to dissolution；
2) continue under stirring condition, purified water constantly added to oily phase, be stirred continuously to clear and bright, to bubble disappear to the greatest extent it is colourless
To faint yellow clear transparent solutions.
Table 5
The average particle size of gained microemulsion solution is 257.0 ± 19.4nm, P.I.0.388, and after standing for 24 hours, solution occurs to divide
Layer has part oil droplet deposition and crystal to be precipitated.
Embodiment 5: the preparation of gram vertical boron sieve microemulsion solution
By the formula composition and following preparation step preparation gram vertical boron sieve microemulsion solution in table 6:
1) ethyl oleate, Tween 80, dehydrated alcohol are taken, using efficient mechanical blender, mixing speed 5000rpm stirring is equal
It is even, 60~80 DEG C are heated to, gram vertical boron sieve is added, continues stirring to dissolution；
2) continue under stirring condition, purified water constantly added to oily phase, be stirred continuously to clear and bright, to bubble disappear to the greatest extent it is colourless
To faint yellow clear transparent solutions.
Table 6
The average particle size of gained microemulsion solution is 17.4 ± 0.6nm, P.I.0.158.
Embodiment 6: the preparation of gram vertical boron sieve microemulsion solution
By the formula composition and following preparation step preparation gram vertical boron sieve microemulsion solution in table 7:
1) ethyl oleate, Tween 80, dehydrated alcohol are taken, using efficient mechanical blender, mixing speed 5000rpm stirring is equal
It is even, gram vertical boron sieve is added, continues stirring to dissolution；
2) continue under stirring condition, purified water constantly added to oily phase, be stirred continuously to clear and bright, to bubble disappear to the greatest extent it is colourless
To faint yellow clear transparent solutions.
Table 7
The average particle size of gained microemulsion solution is 26.5 ± 0.8nm, P.I.0.271.
Embodiment 7: the preparation of gram vertical boron sieve micro emulsion gels
By the formula composition and following preparation step preparation gram vertical boron sieve micro emulsion gels in table 8:
At room temperature, gram vertical boron sieve microemulsion solution is taken, formula ratio Acritamer 940 is added, after it is sufficiently swollen, mixing is equal
It is even.
Table 8
It is 3120 ± 60mPa.s that this example, which is formulated 1 resulting gram of vertical boron sieve micro emulsion gels viscosity, is formulated 2 resulting grams and stands
Boron sieve micro emulsion gels viscosity is 8780 ± 80mPa.s, be formulated 3 resulting grams of vertical boron sieve micro emulsion gels viscosity be 12370 ±
110mPa.s。
Embodiment 8: the preparation of gram vertical boron sieve micro emulsion gels
By the formula composition and following preparation step preparation gram vertical boron sieve micro emulsion gels in table 9:
At room temperature, gram vertical boron sieve microemulsion solution is taken, formula ratio Acritamer 940 is added, after it is sufficiently swollen, mixing is equal
It is even.
Table 9
It is 7960 ± 50mPa.s that this example, which is formulated 4 resulting grams of vertical boron sieve micro emulsion gels viscosity, is formulated 5 resulting grams and stands
Boron sieve micro emulsion gels viscosity is 13890 ± 430mPa.s, and being formulated 6 resulting grams of vertical boron sieve micro emulsion gels viscosity is 23000
±800mPa.s。
Embodiment 9: the preparation of gram vertical boron sieve micro emulsion gels
By the formula composition and following preparation step preparation gram vertical boron sieve micro emulsion gels in table 10:
At room temperature, gram vertical boron sieve microemulsion solution is taken, formula ratio Acritamer 940 is added, after it is sufficiently swollen, mixing is equal
It is even.
Table 10
Being formulated 7 resulting grams of vertical boron sieve micro emulsion gels viscosity is 14560 ± 290mPa.s, is formulated 8 resulting grams of vertical boron
Sieve micro emulsion gels viscosity is 24380 ± 690mPa.s, be formulated 9 resulting grams of vertical boron sieve micro emulsion gels viscosity be 42000 ±
1100mPa.s。
Embodiment 10: the skin permeation test in vitro of gram vertical boron sieve micro emulsion gels
Gram vertical boron sieve microemulsion solution of embodiment 1-1, gram vertical boron sieve microemulsion solution, embodiment 8 of comparative example 1 is respectively adopted
Particle boron sieve micro emulsion gels and refer to gram vertical boron sieve cream patent text prepared by middle formula 6
(US20170152273A1) 2% gram of vertical boron sieve cream that the cream preparation method in is prepared carries out isolated skin infiltration
Permeability test.
Artificial skin film permeability test is carried out with above-mentioned sample.Artificial skin film is taken, the supply of Franz diffusion cell is fixed on
7.4 phosphate buffer of pH of 20% polyethylene glycol 400 is added in receiving chamber as dissolution medium, keeps artificial membrane liner for room
With solution close contact.Quantitative sample is taken to set in supply chamber, adjusting water-bath makes jacket layer temperature be constant at 37 ± 1 DEG C, stirring speed
Degree is 100r/min, measures medicament contg in receiving chamber, the results are shown in Table 11.
Table 11
The result shows that: gram vertical boron sieve micro emulsion and its gelling agent have better percutaneous penetration.Gram vertical boron sieve microemulsion solution
Though the Transdermal absorption of drug can be promoted, due to agents area particularity, it is detained it in skin surface from longer, needs
It is administered continuously；Though gram vertical boron sieve cream can satisfy continued administration, percutaneous permeability is worse than micro emulsion and its gelling agent,
It is made of a large amount of oleaginous bases simultaneously, and medicine-feeding part cleaning and clothes cleaning trouble, medication compliance are poor.Therefore, comprehensive
Compare, gram vertical boron sieve micro emulsion gel has preferable skin adherence and percutaneous permeability and has certain slow releasing function, special
Property be conducive to improve clinical application compliance.
Embodiment 11The stability experiment of gram vertical boron sieve microemulsion solution
Gram vertical boron sieve microemulsion solution of preparation is stored at room temperature (25 ± 2 DEG C, 65 ± 5%RH), respectively at 5,10,30
It investigates microemulsion solution stability.Observe microemulsion solution character and cosmetic variation table 12, size distribution table 13 and Fig. 1 and Fig. 2.
12 grams of table vertical boron sieve microemulsion solution property stabilities
13 grams of table vertical boron sieve microemulsion solution size distribution stability
The result shows that: gram vertical boron sieve microemulsion solution has preferable stability.Under room temperature storage, the equal of clear is kept
Phase system.Size distribution is stablized, and emulsion droplet aggregation, rupture do not occur.Therefore, have by gram vertical boron sieve lotion of this technology preparation good
Good stability.
The above embodiments merely illustrate the technical concept and features of the present invention, and its object is to allow person skilled in the art
Scholar cans understand the content of the present invention and implement it accordingly, and it is not intended to limit the scope of the present invention.It is all according to the present invention
Equivalent change or modification made by Spirit Essence, should be covered by the protection scope of the present invention.
Claims (10)
1. a kind of gram vertical boron sieve micro emulsion composition, which is characterized in that described gram of vertical boron sieve micro emulsion composition includes: with weight percent
Than meter, comprising: gram vertical boron sieve 0.5%~5.0%, oily phase 5%~20%, emulsifier 10%~40%, assistant for emulsifying agent 5%~
30%, water 30%~70%, wherein oil is mutually the fatty-acid monoester selected from C10-C18, one of triglyceride or more
The combination of kind, emulsifier are selected from tween system emulsifier.
2. one kind gram vertical boron sieve micro emulsion composition as described in claim 1, which is characterized in that described gram of vertical boron sieve micro emulsion combination
Object is gram vertical boron sieve microemulsion solution or gram vertical boron sieve micro emulsion gels, wherein by weight percentage, described gram of vertical boron sieve micro emulsion
Solution includes: gram vertical boron sieve 0.5%~5.0%, oily phase 5%~20%, emulsifier 10%~40%, and assistant for emulsifying agent 5%~
30%, water 30%~70%, wherein oil is mutually the fatty-acid monoester selected from C10-C18, one of triglyceride or more
The combination of kind, emulsifier are selected from one of Tween 80 and polysorbate60 or a variety of combinations；Described gram of vertical boron sieve micro emulsion gel
Agent includes gram vertical boron sieve microemulsion solution and the gel rubber material.
3. according to claim 2 gram of vertical boron sieve micro emulsion composition, which is characterized in that described gram of vertical boron sieve microemulsion solution,
By weight percentage, comprising: gram vertical boron sieve 1.0%~2.0%, oily phase 8%~15%, emulsifier 15%~30% help cream
Agent 10%~25%, water 40%~60%, preferably gram vertical boron sieve 1.5%~2.0%, oily phase 8%~10%, emulsifier
20%~30%, assistant for emulsifying agent 10%~20%, water 40%~50%.
4. according to claim 1 or 2 gram of vertical boron sieve micro emulsion composition, which is characterized in that the oil is mutually for selected from oleic acid
One of ester, triglyceride, myristinate are a variety of；Preferably, the oleate is oleic acid Arrcostab, wherein institute
The alkyl stated is the alkyl of C1-C6, and the carboxylic acid in the triglyceride is the carboxylic acid containing C1-C6, the nutmeg
Acid esters is myristic acid Arrcostab, wherein the alkyl is the alkyl of C1-C6；The more preferably described oil is mutually ethyl oleate.
5. according to claim 1 or 2 gram of vertical boron sieve micro emulsion composition, which is characterized in that the assistant for emulsifying agent be selected from
One of methanol, ethyl alcohol, propyl alcohol, isopropanol, propylene glycol and polyethylene glycol 400 or a variety of combinations.
6. according to claim 2 gram of vertical boron sieve micro emulsion composition, which is characterized in that the gel rubber material is selected from card
One of wave nurse, methylcellulose or sodium carboxymethylcellulose are a variety of, the viscosity of gram vertical boron sieve micro emulsion gels
For 2000-30000mPa.s, preferably 3000-25000mPa.s.
7. according to claim 2 or 3 gram of vertical boron sieve micro emulsion composition, which is characterized in that the addition of the gel rubber material
Weight is the 0.5%~2.5% of the addition weight of described gram of vertical boron sieve microemulsion solution.
8. according to claim 2 gram of vertical boron sieve micro emulsion composition, which is characterized in that gram vertical boron sieve microemulsion solution
Middle micro emulsion particle diameter is 5-50nm, preferably 5-30nm.
9. a kind of preparation method of described in any item grams of claim 1-8 vertical boron sieve compositions, which is characterized in that the method
Include the following steps: that (1) takes the oily phase, emulsifier, assistant for emulsifying agent, stirs evenly, gram vertical boron sieve is added, stirring adds water, i.e.,
Gram vertical boron sieve microemulsion solution is obtained, (2) are optionally added into gel rubber material, are sufficiently swollen, and are uniformly mixed to get a gram vertical boron Luo Wei curdling
Jelly.
10. the preparation method of according to claim 9 gram of vertical boron sieve composition, which is characterized in that step (1) is described to take
Oily phase, emulsifier, assistant for emulsifying agent, stir evenly, addition gram vertical boron sieve, continue stirring to dissolving, purified water is added, stirs to clear
It is bright, disappear to bubble and use up to obtain clear transparent solutions, as gram vertical boron sieve microemulsion solution, wherein when purified water is added, is stirred using machinery
Device is mixed to stir, mixing speed is 500~5000rpm, and reaction temperature is 20-100 DEG C, preferably 20-80 DEG C.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN113504158A (en) * | 2021-07-14 | 2021-10-15 | 山东诺明康药物研究院有限公司 | In-vitro transdermal test method for medicament containing boron dermatitis |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20170152273A1 (en) * | 2015-11-30 | 2017-06-01 | Anacor Pharmaceuticals Inc. | Topical Pharmaceutical Formulations For Treating Inflammatory-Related Conditions |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20170152273A1 (en) * | 2015-11-30 | 2017-06-01 | Anacor Pharmaceuticals Inc. | Topical Pharmaceutical Formulations For Treating Inflammatory-Related Conditions |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113504158A (en) * | 2021-07-14 | 2021-10-15 | 山东诺明康药物研究院有限公司 | In-vitro transdermal test method for medicament containing boron dermatitis |
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