CN109464381A - Gram vertical boron sieve cubic liquid crystal gel preparation and preparation method thereof - Google Patents
Gram vertical boron sieve cubic liquid crystal gel preparation and preparation method thereof Download PDFInfo
- Publication number
- CN109464381A CN109464381A CN201811643203.7A CN201811643203A CN109464381A CN 109464381 A CN109464381 A CN 109464381A CN 201811643203 A CN201811643203 A CN 201811643203A CN 109464381 A CN109464381 A CN 109464381A
- Authority
- CN
- China
- Prior art keywords
- liquid crystal
- preparation
- gram
- boron sieve
- vertical boron
- 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.)
- Granted
Links
Classifications
-
- 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
-
- 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
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1274—Non-vesicle bilayer structures, e.g. liquid crystals, tubules, cubic phases, cochleates; Sponge phases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Dermatology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a kind of gram vertical boron sieve cubic liquid crystal gel preparations and preparation method thereof.Gram vertical boron sieve cubic liquid crystal gel preparation of the invention, on the basis of the gross mass of preparation, including following components in percentage by weight: LCD vector material: 20-60%；Gram vertical boron sieve: 0.1%-5%；1,2- propylene glycol: 0-20%；Remaining is water；The LCD vector material is selected from Monoolein.Gram vertical boron sieve cubic liquid crystal gel preparation of the invention has many advantages, such as that non-stimulated, cuticula transmitance is high, slow release effect is significant, skin targeting is good.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, more particularly to a kind of gram vertical boron sieve cubic liquid crystal gel preparation and its preparation
Method.
Background technique
Gram vertical boron sieve, the entitled Crisaborole of English, chemical structural formula are as follows:
Gram vertical boron sieve is approved listing by U.S. FDA on December 14th, 2016, by Anacor pharmaceutical development, trade nameGram vertical boron sieve is a kind of phosphodiesterase-4 (PDE-4) inhibitor, and this inhibition leads to intracellular loops phosphoric acid gland
Glycosides (cAMP) level increases；For 2 years old and the slight local treatment to moderate allergic dermatitis of the above patient,
The dosage form of listing is a kind of local topical ointment.
The approach that traditional ointment preparation capable of permeating skin absorbs mainly has cutaneous appendages and cuticula, due to skin accessory organ
The ratio of (such as hair follicle, sebaceous glands) only accounts for the 0.1% of skin area, to the contribution very little of absorption.Therefore cuticula approach is medicine
The main path of object Transdermal absorption, but since the cuticula of epidermis is a kind of very fine and close " brick wall " structure, drug is direct
Penetrate that horn cell diffusional resistance is larger, the drug molecule of only only a few diffuses through cuticula through space between cells.Due to angle
It is lower that the special nature of matter layer causes Traditional transdermal preparation to absorb, and leads to relatively large number of medicine due to not having skin targeting
Object enters blood to generate unnecessary side effect.Additionally, due to big vaseline is contained in traditional ointment of listing, make
With there is strong greasy feeling in the process, patient's usage experience is poor.Therefore, however it remains certain toxic side effect and use according to
The problems such as poor from property, limits gram popularization and use of vertical boron sieve ointment clinically.Further screening low toxicity, efficient, Gao Shun
Gram vertical boron sieve transdermal formulation of answering property is still of great significance.
Liquid crystal (liquid crystalline) is long-range order, short at unordered molecular aggregate, be the three states of matters it
The 4th outer state is the thermodynamically stable mesophase between solid-state and liquid, on the one hand it has as liquid
Mobility and continuity, on the other hand there is anisotropy as crystal again, be a kind of substance with special construction.
Amphipathic lipids body liquid crystal material generally first spontaneously forms thermodynamically stable double-layer of lipoid after contacting with water, then reassembles into and have
Various shape and structured liquid crystal system, such as layered liquid crystal structure, cubic structure etc..Wherein, cubic liquid crystal gel has uniqueness
The double channel structures in inside, constitute similar " honeycomb " structure of the co-continuous of three-dimensional extension.
Summary of the invention
Based on this, the present invention provides a kind of gram vertical boron sieve cubic liquid crystal gel preparations and preparation method thereof, existing to overcome
Have the shortcomings that skin permeability existing for technology is poor, skin targeting is poor.
Specific technical solution is as follows:
A kind of gram vertical boron sieve cubic liquid crystal gel preparation, on the basis of the gross mass of preparation, including following weight percent
Component:
LCD vector material: 20-60%；
Gram vertical boron sieve: 0.1-5%；
1,2- propylene glycol: 0-20%；
Remaining is water；
The LCD vector material is Monoolein.
It is a further object of the present invention to provide a kind of preparation methods of above-mentioned gram of vertical boron sieve cubic liquid crystal gel preparation, including
Following steps:
(1) both LCD vector material and propylene glycol being mixed in 35~85 DEG C, gram vertical boron sieve is added, stirring is extremely dissolved,
Obtain mixture A；
(2) mixture A is mixed with water, obtains mixture B；
(3) mixture B 20-40 DEG C placement 5-10 days, i.e., formation gram vertical boron sieve cubic liquid crystal gel.
Gram vertical boron sieve cubic liquid crystal gel preparation of the invention has the following advantages and beneficial effects:
It was found by the inventors of the present invention that in gram preparation process of vertical boron sieve gel with liquid crystal structure, the selection of organic phase and liquid crystal
The selection of carrier material is very crucial.The present invention selects propylene glycol for organic phase, selects Monoolein as LCD vector
Material.Propylene glycol can form liquid crystal interface with LCD vector material；The cubic liquid crystal internal structure that Monoolein is formed
It is three-dimensional extension, belongs to the network structure of co-continuous, there are the double channel structures in unique inside, in abundant swelling,
Viscosity and film-strength are all very big, are conducive to cubic liquid crystal packaging medicine, improve the stability of drug.By propylene glycol and glycerol list oil
Acid esters and water obtain that transparent, quality is uniform, the cubic liquid crystal of the significant ternary system of slow release effect is solidifying by specific proportion mixing
Glue preparation.
The cubic liquid crystal gel that propylene glycol, water, Monoolein are formed has huge surface area and unique three-dimensional
Lattice structure has good dissolubility and stabilization to gram vertical boron sieve.The cubic liquid crystal gel preparation for carrying medicine can be through molecule
Gap penetrates fine and close " cuticula brick wall ", and forms drug depot in skin corium, and sustained release reaches skin targeting and delays
The effect of On The Drug Release.Gram vertical boron sieve gel with liquid crystal structure preparation of the invention also has a biology in situ high-adhesiveness, liquid crystal layer to ulcer,
Predisposing infection area has temporary protection effect, non-stimulated to skin.
In addition, the preparation method simple process of gram vertical boron sieve cubic liquid crystal gel preparation of the invention, good process repeatability,
Lower production costs are conducive to industrialized production, have a good application prospect.
Detailed description of the invention
Fig. 1 is gram vertical boron sieve cubic liquid crystal gel release profiles in vitro；
Fig. 2 is that gram vertical boron sieve cubic liquid crystal gel and ointment add up infiltration capacity curve.
Specific embodiment
To facilitate the understanding of the present invention, it below with reference to embodiment to invention is more fully described, is given below
Presently preferred embodiments of the present invention.But the invention can be realized in many different forms, however it is not limited to described herein
Embodiment.Purpose of providing these embodiments is makes the disclosure of the present invention more thorough and comprehensive.
Unless otherwise defined, all technical and scientific terms used herein and belong to technical field of the invention
The normally understood meaning of technical staff is identical.Used term is intended merely to describe specific reality in the description of the invention
Apply the purpose of example, it is not intended that in the limitation present invention.Term as used herein "and/or" includes one or more relevant institutes
Any and all combinations of list of items.
A kind of gram vertical boron sieve cubic liquid crystal gel preparation, on the basis of the gross mass of preparation, including following weight percent
Component:
LCD vector material: 20-60%；
Gram vertical boron sieve: 0.1%-5%；
1,2- propylene glycol: 0-20%；
Remaining is water；
The LCD vector material is Monoolein.
Preferably, gram vertical boron sieve cubic liquid crystal gel preparation of the invention, on the basis of the gross mass of preparation, including it is following
The component of weight percent:
LCD vector material: 20-60%；
Gram vertical boron sieve: 0.5-5%；
1,2- propylene glycol: 5-15%；
Remaining is water.
Preferably, gram vertical boron sieve cubic liquid crystal gel preparation of the invention, on the basis of the gross mass of preparation, including it is following
The component of weight percent:
LCD vector material: 20-60%；
Gram vertical boron sieve: 0.5-1.5%；
1,2- propylene glycol: 5-15%；
Remaining is water.
It is further preferred that gram vertical boron sieve cubic liquid crystal gel preparation of the invention, on the basis of the gross mass of preparation, packet
Include following components in percentage by weight:
LCD vector material: 20-40%；
Gram vertical boron sieve: 0.8-1.2%；
1,2- propylene glycol: 8-12%；
Remaining is water.
The proportion of LCD vector material, gram vertical boron sieve, 1,2-PD, water is advanced optimized, obtained gram
Vertical boron sieve cubic liquid crystal gel preparation has better texture and slow-release capability.
In some embodiments, the weight ratio of LCD vector material and 1,2-PD is preferably (2.5-3.5:1)；Thus
Gram vertical boron sieve cubic liquid crystal gel preparation that ratio is prepared has more preferably quality and sustained release performance.
In wherein some embodiments, gram vertical boron sieve cubic liquid crystal gel preparation of the invention further includes antioxidant, anti-corrosion
At least one of agent；Specifically, the preservative includes following at least one: methyl p-hydroxybenzoate, para hydroxybenzene
Propyl formate, butyl p-hydroxybenzoate, sorbic acid and benzyl alcohol；The antioxidant includes following at least one: galla turcica
Propyl propionate, butylated hydroxy anisole, dibutyl hydroxy toluene, citric acid, EDTA and its esters and tocopherol.
The preparation process of gram vertical boron sieve cubic liquid crystal gel preparation of the invention, comprising the following steps:
(1) both LCD vector material and propylene glycol being mixed in 35~85 DEG C, gram vertical boron sieve is added, stirring is extremely dissolved,
Obtain mixture A；
(2) mixture A is mixed with water, obtains mixture B；
(3) mixture B 20-40 DEG C placement 5-10 days, i.e., formation gram vertical boron sieve cubic liquid crystal gel.
Preferably, in step (1), LCD vector material and propylene glycol are mixed in 35~65 DEG C.
Preferably, in step (3), the time that the mixture B is placed at 20-40 DEG C is -9 days 7 days.
Specifically, in step (2), the hybrid mode is vortex, hand operated mixing or motor-driven stirring.
Below in conjunction with specific embodiment and attached drawing to gram vertical boron sieve cubic liquid crystal gel and preparation method thereof of the invention
It is described in further detail.
Material used in following embodiment, reagent etc. are commercially available unless otherwise specified.
One, the preparation of gram vertical boron sieve cubic liquid crystal gel
1 gram of table vertical boron sieve cubic liquid crystal gel prescription (%: weight percent)
The preparation of each prescription in table 1:
Prescription 1-3: the preparation of gram vertical boron sieve cubic liquid crystal gel of binary system
Suitable Monoolein and Ke Li boron sieve are weighed in sufficiently dissolution is mixed in 45 DEG C of water-baths by the mass ratio in table 1
The purified water for uniformly adding recipe quantity and/or preservative and antioxidant are closed, is uniformly mixed in oscillator, 25 DEG C are placed 7 days,
Obtain the cubic liquid crystal gel of prescription 1-3.
Prescription 4-10, comparative example 1,4,5: the preparation of gram vertical boron sieve cubic liquid crystal gel of ternary system
Suitable LCD vector material, propylene glycol, gram vertical boron sieve are weighed in abundant in 45 DEG C of water-baths by the mass ratio in table 1
Dissolution is uniformly mixed, and adds the purified water and/or preservative, antioxidant of recipe quantity, is uniformly mixed in oscillator, 25 DEG C of placements
7 days, obtain cubic liquid crystal gel.
LCD vector material described in prescription 4-10, comparative example 4,5 is Monoolein.
LCD vector material described in prescription 11-16 in comparative example 1 is successively are as follows: phytantriol, two glyceryl oleates, phosphorus
Acyl ethanol amine, two sub- oleoyl rouge ethanol amines, 1-palmitoyl-2-oleoylphosphatidylcholine, two myristoyl phosphatidylcholines.
Antioxidant described in prescription 7-9 is successively are as follows: butylated hydroxy anisole, dibutyl hydroxy toluene, tocopherol.
Prescription 4,6, preservative described in 7-9 are successively are as follows: methyl p-hydroxybenzoate, propylparaben, to hydroxyl
Yl benzoic acid butyl ester, benzyl alcohol, sorbierite.
Comparative example 2:
The raw material prescription of gram vertical boron sieve cubic liquid crystal gel of this comparative example is substantially identical as the raw material prescription of prescription 5, area
It is not to replace propylene glycol with glycerine, preparation method is the same as prescription 5.
Comparative example 3:
The raw material prescription of gram vertical boron sieve cubic liquid crystal gel of this comparative example is substantially identical as the raw material prescription of prescription 5, area
It is not to replace propylene glycol with ethyl alcohol, preparation method is the same as prescription 5.
Two, the characterization of gram vertical boron sieve cubic liquid crystal gel structure:
Table 2: the characterization result of gram vertical boron sieve cubic liquid crystal gel
| Prescription number | Form | Prescription number | Form |
| Prescription 1 | It is homogeneous transparent solution, sticky | Prescription 2 | It is homogeneous transparent solution, sticky |
| Prescription 3 | It is homogeneous transparent solution, sticky | Prescription 4 | Homogeneous transparent solution |
| Prescription 5 | Homogeneous transparent solution | Prescription 6 | Homogeneous transparent solution |
| Prescription 7 | Homogeneous transparent solution | Prescription 8 | Homogeneous transparent solution |
| Prescription 9 | Homogeneous transparent solution | Prescription 10 | Homogeneous transparent solution |
| Prescription 11 | Clear solution, quality are poor | Prescription 12 | Clear solution, quality are poor |
| Prescription 13 | Clear solution, quality are poor | Prescription 14 | Clear solution, quality are poor |
| Prescription 15 | Clear solution, quality are poor | Prescription 16 | Clear solution, quality are poor |
| Comparative example 2 | Gel with liquid crystal structure cannot be formed | Comparative example 3 | Gel with liquid crystal structure cannot be formed |
| Comparative example 4 | White opacity shape | Comparative example 5 | Gel with liquid crystal structure cannot be formed |
From prescription 4-6, it can be seen that, You Keli boron sieve, LCD vector material, propylene glycol and water pass through specific optimum organization
The transdermal gel preparation of the cubic liquid crystal of ternary system can be prepared, quality is uniform.From prescription 1-3 it can be seen that, You Keli
Boron sieve, LCD vector material and water cooperate gram vertical boron sieve cube liquid that a kind of binary system can also be prepared at a specific ratio
Brilliant gel preparation, quality is uniform, but more more sticky than the gel with liquid crystal structure of above-mentioned ternary system, and use feeling is slightly worse.
From prescription 5, comparative example 1 prescription 11-16 it can be seen that, in plurality of liquid crystals carrier material, with Monoolein
Quality it is best, the cubic liquid crystal internal structure formed by Monoolein is three-dimensional extension, belongs to the network of co-continuous
Structure has the double channel structures in unique inside, and in abundant swelling, viscosity and film-strength are all very big, is conducive to cube
Liquid crystal packaging medicine improves the stability of drug.It is prepared when Monoolein is substituted for other LCD vector materials
For obtained gram vertical boron sieve cubic liquid crystal gel although still transparent, quality homogeneity is obviously poor.
From comparative example 2 and 3 it is found that propylene glycol has very great influence to cubic liquid crystal gel of the invention, as general
When 1,2-PD replaces with glycerine or ethyl alcohol, gel with liquid crystal structure can not be formed, because glycerine or alcohol structure make its nothing
Method and LCD vector material form liquid crystal interface.
From comparative example 4 it is found that the content of drug also has influence to the gel with liquid crystal structure being formed by, when the content of drug is
When 12%, the gel being formed by is white opacity shape, it may be possible to which drug does not dissolve completely, cannot form homogeneous and transparent knot
Brilliant gel.
From comparative example 5, it can be seen that, the content of LCD vector material is to preparation-obtained gram of vertical boron sieve cubic liquid crystal gel
Quality have larger impact.When the content of LCD vector material is 80%, when content of propylene glycol is 10%, cannot be formed
Gel with liquid crystal structure.It is screened by the mass ratio to LCD vector material and propylene glycol, finds LCD vector material and propylene glycol
Preferred mass ratio be 3:1, preparation-obtained cubic liquid crystal gel is transparent, uniform within this range, and quality is more excellent.
Three, different temperatures prepares gram vertical boron sieve cubic liquid crystal gel
Suitable Monoolein, propylene glycol and Ke Li boron sieve are weighed by prescription 5, is respectively placed in 35 DEG C, 40 DEG C, 45
DEG C, 55 DEG C, 65 DEG C, 75 DEG C, by Monoolein and mixed with propylene glycol in 85 DEG C of water-baths, remaining step is the same as the preparation gram of prescription 5
Vertical boron sieve cubic liquid crystal gel, and gram vertical boron sieve impurity content is detected, gram vertical boron sieve impurity content does not find apparent increase.
Four, the skin irritation test of gel with liquid crystal structure prescription
Investigate the cubic gel preparation obtained of prescription 5, skin irritation after single-dose.
Experimental animal: healthy rabbits.
Experiment purpose: cubic liquid crystal gel preparation and blank cubic gel preparation group are investigated to the shadow of rabbit skin irritation
It rings.
Experimental method: each experimental preparation is applied on the healthy skin and damage skin of a rabbit back 24 hours, according to
The standards of grading of table 1 carry out range estimation judgement to the skin symptom after removing 1 hour, 24 hours, 48 hours, calculate each experimental preparation
Stimulus index.Skin irritatin intensity is determined according to table 3.
Stimulus index calculation method: skin irritatin sex index=total irritation value/number of observation
1. every rabbit will be removed the value observed after 1 hour, 24 hours, 48 hours after patch and be added, with determination
The irritation value of erythema or eschar forming portion subtotaling.
2. every rabbit will be removed the value observed after 1 hour, 24 hours, 48 hours after patch and be added, with determination
The irritation value of oedema forming portion subtotaling.
3. for every rabbit, by the irritation value of erythema or eschar total irritation value and oedema forming portion subtotaling
It is added, calculates total irritation value of every rabbit.
3. skin irritation of table reacts standards of grading
4. experimental result of table
| Test prescription | Prescription 5 | Blank cubic gel |
| Stimulate sex index | 0.16 | 0 |
By table 3 and table 4 it is found that cubic liquid crystal gel preparation of the invention is to rabbit no skin irritation.
Five, the Ligustrazine hydrochloride behavior of gram vertical boron sieve cubic liquid crystal gel is investigated
Using Franz diffusion cell carry out transdermal experiment, 37 DEG C of bath temperature, mixing speed 300rpm, transdermal area
10cm2, reception tank volume 1ml.SD rat abdomen skin is fixed between the supply chamber of diffusion cell and receiving chamber, stratum corneum side to
Supply chamber and medicament contact.Gram vertical boron sieve cubic liquid crystal gel and the self-control of prescription 5 are given in experimentation, in supply chamber respectively
Specification is all 1% gram vertical boron sieve ointment, the ethanol solution that receiving liquid is 20%.Take 1 gram of each sample to be placed in supply chamber, sample with
Rat skin close contact is placed in 37 DEG C of water-baths, is opened magnetic stirring apparatus (300rpm), 1,2,3,4,5,6,7,8,9,
10,11,12,24 hours point in time sampling 1mL, mend 1mL blank receiving liquid immediately, and the sample after sampling crosses 0.45 μm of miillpore filter
HPLC measures the content of gram vertical boron sieve afterwards, calculates the accumulation infiltration capacity (being shown in Table 5) of skin unit area.
After experiment, skin is removed, with normal saline flushing skin surfaces externally and internally, and is dried with cotton swab, measurement gram is vertical
Hold-up of boron sieve drug in cuticula and living Epidermis's layer.Mouse skin is shredded, is placed in 10mL band plug centrifuge tube, is added
5mL methanol, with cell crushing instrument ultrasonic extraction 10min, 5mL methanol constant volume.Test liquid through 15000rpm ultracentrifugation 10min,
Supernatant after taking centrifugation, 0.45 μm of filtering with microporous membrane, HPLC method measure gram vertical boron sieve content in test liquid, calculate in mouse skin
The hold-up of drug.The In-vitro release curves of cubic liquid crystal gelling agent are shown in attached drawing 1；The body of ointment and cubic liquid crystal gelling agent
Outer accumulation infiltration capacity curve is shown in attached drawing 2.
Table 5: experimental result
| Prescription | Skin hold-up (μ g) |
| Cubic liquid crystal gel | 32.36 |
| Make ointment by oneself | 2.17 |
It can be seen from the above result that gram vertical boron sieve cubic liquid crystal gelling agent of the invention has higher skin stagnant than cream
Allowance, it is soft that accumulation permeability curve reflects that gram vertical boron sieve cubic liquid crystal gelling agent is significantly less than by the amount that skin enters blood
Paste.The above result shows that gram vertical boron sieve cubic liquid crystal gel has better skin targeting and slow release compared with ointment
Can, it is particularly suited for the local administration of skin disease class disease.
Each technical characteristic of embodiment described above can be combined arbitrarily, for simplicity of description, not to above-mentioned reality
It applies all possible combination of each technical characteristic in example to be all described, as long as however, the combination of these technical characteristics is not deposited
In contradiction, all should be considered as described in this specification.
The embodiments described above only express several embodiments of the present invention, and the description thereof is more specific and detailed, but simultaneously
It cannot therefore be construed as limiting the scope of the patent.It should be pointed out that coming for those of ordinary skill in the art
It says, without departing from the inventive concept of the premise, various modifications and improvements can be made, these belong to protection of the invention
Range.Therefore, the scope of protection of the patent of the invention shall be subject to the appended claims.
Claims (10)
1. a kind of gram vertical boron sieve cubic liquid crystal gel preparation, which is characterized in that on the basis of the gross mass of preparation, including it is following heavy
Measure the component of percentage:
LCD vector material: 20-60%；
Gram vertical boron sieve: 0.1-5%；
1,2- propylene glycol: 0-20%；
Remaining is water；
The LCD vector material is Monoolein.
2. according to claim 1 gram of vertical boron sieve cubic liquid crystal gel preparation, which is characterized in that be with the gross mass of preparation
Benchmark, including following components in percentage by weight:
LCD vector material: 20-60%；
Gram vertical boron sieve: 0.5-1.5%；
1,2- propylene glycol: 5-15%；
Remaining is water.
3. according to claim 2 gram of vertical boron sieve cubic liquid crystal gel preparation, which is characterized in that be with the gross mass of preparation
Benchmark, including following components in percentage by weight:
LCD vector material: 20-40%；
Gram vertical boron sieve: 0.8-1.2%；
1,2- propylene glycol: 8-12%；
Remaining is water.
4. according to claim 1 gram of vertical boron sieve cubic liquid crystal gel preparation, which is characterized in that the LCD vector material
Weight ratio with 1,2- propylene glycol is (2.5-3.5): 1.
5. according to claim 1-4 gram of vertical boron sieve cubic liquid crystal gel preparation, which is characterized in that further include resisting
Oxygen agent, at least one of the preservatives.
6. according to claim 5 gram of vertical boron sieve cubic liquid crystal gel preparation, which is characterized in that the preservative is to hydroxyl
At least one of yl benzoic acid methyl esters, propylparaben, butyl p-hydroxybenzoate, sorbic acid and benzyl alcohol.
7. according to claim 5 gram of vertical boron sieve cubic liquid crystal gel preparation, which is characterized in that the antioxidant is not eat
At least one in sub- propyl propionate, butylated hydroxy anisole, dibutyl hydroxy toluene, citric acid, EDTA and its esters and tocopherol
Kind.
8. a kind of preparation method of described in any item grams of claim 1-7 vertical boron sieve cubic liquid crystal gel preparations, feature exist
In, comprising the following steps:
(1) LCD vector material and propylene glycol are mixed in 35~85 DEG C, gram vertical boron sieve is added, stirring is mixed to dissolving
Object A；
(2) mixture A is mixed with water, obtains mixture B；
(3) mixture B 20-40 DEG C placement 5-10 days, i.e., formation gram vertical boron sieve cubic liquid crystal gel.
9. the preparation method of according to claim 8 gram of vertical boron sieve cubic liquid crystal gel preparation, which is characterized in that step
(1) in, LCD vector material and propylene glycol are mixed in 35~65 DEG C.
10. the preparation method of according to claim 8 gram of vertical boron sieve cubic liquid crystal gel preparation, which is characterized in that step
(2) in, the mixing is that mode is vortex, hand operated mixing or motor-driven stirring；In step (3), mixture B is placed at 20-40 DEG C
Time be -9 days 7 days.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811643203.7A CN109464381B (en) | 2018-12-29 | 2018-12-29 | Kelibong Roche liquid crystal gel preparation and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811643203.7A CN109464381B (en) | 2018-12-29 | 2018-12-29 | Kelibong Roche liquid crystal gel preparation and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109464381A true CN109464381A (en) | 2019-03-15 |
| CN109464381B CN109464381B (en) | 2021-12-28 |
Family
ID=65678318
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811643203.7A Active CN109464381B (en) | 2018-12-29 | 2018-12-29 | Kelibong Roche liquid crystal gel preparation and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109464381B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108451898A (en) * | 2018-04-03 | 2018-08-28 | 苏州尚宜佳生物科技有限公司 | One kind gram vertical boron sieve thermo-sensitive gel agent and its preparation method and application |
-
2018
- 2018-12-29 CN CN201811643203.7A patent/CN109464381B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108451898A (en) * | 2018-04-03 | 2018-08-28 | 苏州尚宜佳生物科技有限公司 | One kind gram vertical boron sieve thermo-sensitive gel agent and its preparation method and application |
Non-Patent Citations (2)
| Title |
|---|
| HANNE EVENBRATT ET AL.: "Phase behavior, rheology, and release from liquid crystalline phases containing combinations of glycerol monooleate, glyceryl monooleyl ether, propylene glycol, and water", 《RSC ADVANCES》 * |
| 陈琰 等: "立方晶及其在药剂学中的研究进展", 《第二军医大学学报》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109464381B (en) | 2021-12-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JAIN | Formulation Development And Evaluation Of Fluconazole Gel In Various Polymer Basesformulation Development And Evaluation Of Fluconazole Gel In Various Polymer BaseS | |
| Cao et al. | A combination of a microemulsion and a phospholipid complex for topical delivery of oxymatrine | |
| CN112315846B (en) | Schizophyllum commune polysaccharide liposome and preparation method and application thereof | |
| CN103520006A (en) | Flexible nano liposome as well as preparation method and application of flexible nano liposome | |
| CN104983675B (en) | A kind of Tretinoin ethosome gel and preparation method thereof | |
| CN111973494B (en) | Long-acting moisturizing facial cream and preparation method thereof | |
| CN109069418A (en) | topical composition comprising tacrolimus | |
| CN103301188A (en) | Nanoemulsion gel made of radix sophorae flavescentis and earthworm and preparation method of nanoemulsion gel | |
| CN106491519A (en) | Cubic liquid crystal in-situ gel injection agent of local anesthetic and preparation method thereof | |
| CN108078912A (en) | A kind of excretion body with long preservation period repairs gel and preparation method thereof | |
| CN103450368A (en) | Preparation method of silanized hyaluronate compound | |
| CN102579437B (en) | Tacrolimus composition containing alcohol and preparation method of tacrolimus composition | |
| CN1457253A (en) | External application for enhancing skin permeability of active components therein | |
| CN108478607B (en) | Preparation method of sarcandra glabra extract liposome hydrogel | |
| Kozaka et al. | Lyotropic liquid crystal-based transcutaneous peptide delivery system: Evaluation of skin permeability and potential for transcutaneous vaccination | |
| CN109820814A (en) | A kind of Tacrolimus paste and preparation method thereof | |
| CN109464381A (en) | Gram vertical boron sieve cubic liquid crystal gel preparation and preparation method thereof | |
| CN108158979A (en) | A kind of Tacrolimus paste composition | |
| CN110448525A (en) | A kind of external application Finasteride lipid nanometer preparation and preparation method thereof prevented hair loss with growth-promoting hair | |
| CN107320699A (en) | A kind of Chinese medicine compound prescription micro emulsion gels and its production and use | |
| JPS6218526B2 (en) | ||
| CN114588108B (en) | Oil-soluble solution containing insect repellent and preparation method and application thereof | |
| CN108498849A (en) | A kind of gel with liquid crystal structure hepatic artery embolism agent and preparation method thereof | |
| CN113041169A (en) | Salidroside liposome freeze-dried powder and preparation method and application thereof | |
| Kim et al. | A microemulsion-based hydrogel formulation containing voriconazole for topical skin delivery |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20221123 Address after: Unit 501, Building C31, No. 218, Xinghu Street, Suzhou City, Jiangsu Province, 215000 Patentee after: Suzhou gaomai Pharmaceutical Co.,Ltd. Address before: 511458 room 612, No. 26, Jinlong Road, Nansha District, Guangzhou City, Guangdong Province, self compiled a003 (office use only) Patentee before: GUANGZHOU MAIKANG PHARMACEUTICAL TECHNOLOGY Co.,Ltd. |