CN110123739A - Non-ionic precursor gel preparation and preparation method thereof before a kind of Rupatadine fumarate - Google Patents
Non-ionic precursor gel preparation and preparation method thereof before a kind of Rupatadine fumarate Download PDFInfo
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- CN110123739A CN110123739A CN201910402206.XA CN201910402206A CN110123739A CN 110123739 A CN110123739 A CN 110123739A CN 201910402206 A CN201910402206 A CN 201910402206A CN 110123739 A CN110123739 A CN 110123739A
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- 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
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Abstract
The present invention relates to non-ionic precursor gel preparations before a kind of Rupatadine fumarate and preparation method thereof.Rupatadine fumarate, stabilizer, nonionic surfactant, film coating material are added in organic solvent, sealed, heating water bath ultrasound, it sets the above heating water bath of rotary evaporation and flings to organic solvent, dried powder is obtained, is dried in vacuum overnight to get I phase；Carbomer is dissolved in distilled water again, obtains phase II；Weigh glycerol, propylene glycol is added in II phase under the conditions of magnetic stirrer, stirs evenly, obtain III phase；Transdermal enhancer azone is added in III phase, is stirred evenly, and is 6-7 with appropriate triethanolamine tune pH value, is added distilled water, is sufficiently stirred evenly using magnetic stirring apparatus, is obtained IV phase.I is added in IV phase, is stirred evenly, de-bubbled is fitted into light resistant container to get non-ionic precursor gel preparation before Rupatadine fumarate, is placed at shady and cool drying.
Description
Technical field
It is non-before especially a kind of novel drug carriers formulations Rupatadine fumarate the present invention relates to field of pharmaceutical preparations
Gas ions gel preparation and preparation method thereof.
Background technique
Rupatadine fumarate chemical name is the chloro- 6,11- dihydro -11- of 8- [1- [(5- methyl -3- pyridyl group) methyl] -
4- perperidylidene] -5H- benzo [5,6] cycloheptane simultaneously [1,2-b] pyridine fumarate salt, for treating seasonal and perennially mistake
Quick property rhinitis, nettle rash.Clinically there was only Rupatadine fumarate piece, for treat seasonal or catarrhus perennialis and
Related indication treatment, without the dosage form of percutaneous dosing or mucosa delivery.Percutaneous dosing can overcome classical hormonal class antiallergy
The disadvantages of drug is easy to recur, side effect is big after being discontinued.Rupatadine is second generation antihistamine drug, is a kind of long-acting, selectivity
Peripheral H1-receptor antagonist.But its poorly water-soluble and Rupatadine fumarate piece child and coma patient are not easy to swallow；When tabletting
The auxiliary material of addition influences the dissolution and bioavilability of Rupatadine, greatly limits its use and curative effect.
The existing dosage form of Rupatadine fumarate administration at present only has tablet, in order to overcome Rupatadine fumarate dosage form list
Non-ionic precursor gel preparation before Rupatadine fumarate is made in conjunction with preparation technique and newtype drug transmission system in one defect.
Preceding non-ionic precursor is a kind of drug-reservoir type that one kind after liposome, nonionic surfactant vesicle is novel
Dosage form, it is to can produce non-ionic surface active using preceding hydration using nonionic surfactant as utricule made of auxiliary material
The aqueous dispersion of agent vesica.Applied in transdermal delivery system, have the advantage that 1. raw material is easy to get, price more just
Preferably, stability is good, easy to industrialized production；2. nonionic surfactant molecule both ends have hydrophily and lipophilicity, can
Encapsulate amphipathic drug and nontoxic；3. having delayed drug release by drug encapsulation in nonionic surfactant vesicle, can mention
High drug bioavailability；4. be effectively improved liposome, nonionic surfactant vesicle during storage vesica easily assemble,
The problems such as fusion and drug are revealed, and have a clear superiority in transport, storage, use aspect.
Gelling agent means that form the auxiliary material of gel and drug is made the glop or half of suspension or emulsion type admittedly
Body preparation.Gel has good stability and biocompatibility, and has sustained-release and controlled release effect to drug, improves drug office
The concentration in portion, the release or diffusion process for extending drug, can be a variety of from skin, eye mucosa, oral cavity, nasal cavity, vagina, rectum etc.
Approach administration, has good application value and prospect in clinic.
It will be rich in conjunction with preceding non-ionic precursor and the common advantage of gelling agent according to Rupatadine fumarate therapeutic effect feature
Horse acid Rupatadine is prepared into external transdermal drug-delivery preparation, can more achieve the effect that treat disease, and easy to use.
Using preceding non-ionic precursor gel percutaneous dosing, have the advantage that 1. can solve Rupatadine bulk pharmaceutical chemicals is insoluble in
The problem of water；2. after percutaneous dosing, drug depot, slow release drug, stabilised blood medicine in keeping body can be formed in local skin
Concentration plays efficient, long-acting；3. being not easy to reach there is local drug concentration when overcoming common external preparation percutaneous dosing
It arrives, the problems such as dosage is big, curative effect is unobvious.
Summary of the invention
The purpose of the present invention is to provide non-ionic precursor gel preparations before a kind of Rupatadine fumarate, are semi-solid
State had not only solved the problems, such as that Rupatadine fumarate dosage form was single, but when overcoming common external preparation percutaneous dosing there is
The problems such as local drug concentration is not easy to reach, dosage is big, curative effect is unobvious.
It is a further object to provide the systems of non-ionic precursor gel preparation before a kind of above-mentioned Rupatadine fumarate
Preparation Method.
In order to achieve the above objectives, the invention provides the following technical scheme: non-ionic precursor is solidifying before a kind of Rupatadine fumarate
Glue preparation, it is characterised in that: calculate by weight, formula includes following components: 0.5-2 parts of Rupatadine fumarate, stabilizer
2-10 parts, it is 20-50 parts of nonionic surfactant, 2-10 parts of film coating material, 4-8 parts of organic solvent, 1-3 parts of carbomer, sweet
20-40 parts oily, 30-60 parts of propylene glycol, 3-6 parts of transdermal enhancer, distilled water are to 120-240 parts.
The stabilizer is the mixing of one or both of cholesterol, phosphatide.
The phosphatide is mixed selected from one or both of soybean lecithin, egg yolk lecithin, hydrolecithin.
The organic solvent is dehydrated alcohol, propyl alcohol, isopropanol or butanol.
The nonionic surfactant is selected from Arlacel-20, Arlacel-40, Arlacel-60, Arlacel-80, Tween-20, spits
The mixing of one or both of temperature -60, Tween-80.
The film coating material is the mixing of one or both of sucrose stearate, sorbierite, maltodextrin.
The carbomer is the mixing of one or both of carbomer 934,940,941.
The transdermal enhancer is the mixing of one or both of dimethyl sulfoxide, azone, propylene glycol, peppermint oil.
The preparation method of non-ionic precursor gel preparation before above-mentioned Rupatadine fumarate, it is characterised in that including following step
It is rapid: (1) Rupatadine fumarate, stabilizer, nonionic surfactant and film coating material to be added in organic solvent, added
Lid sealing, heating water bath ultrasound, sets heating water bath on Rotary Evaporators and flings to organic solvent, obtain dried powder, be dried in vacuo
Night is to get non-ionic precursor before Rupatadine fumarate；(2) carbomer is dissolved in distilled water, by glycerol, propylene glycol, magnetic force
It is added, stirs evenly under blender stirring condition；(3) transdermal enhancer is added in (2), is stirred evenly, with appropriate triethanolamine tune
PH value is 6-7, and distilled water is added sufficiently to be stirred evenly with magnetic stirring apparatus.(4) (3) are mixed with (1), is stirred evenly, de-bubbled obtains rich
Non-ionic precursor gel preparation before horse acid Rupatadine.
Water bath heating temperature in the step (1) is 55-65 DEG C.
Possessed by of the invention the utility model has the advantages that
Before Rupatadine fumarate of the invention non-ionic precursor gelling agent be a kind of semi-solid gel state, solve it is non-from
Vesica easily assemble, merges and the problems such as drug leakage, and is being transported during daughter surfactants vesicles solution state and storage
Defeated, storage, use aspect have apparent advantage, are suitable for industrialized production, are a kind of extremely promising newtype drugs
Carrier formulation.Non-ionic precursor gelling agent has good stability and biocompatibility before Rupatadine fumarate of the invention,
And there is sustained-release and controlled release effect to drug, improve the concentration of drug part, extend the release or diffusion process of drug, Ke Yicong
The administration of the number of ways such as skin, eye mucosa, oral cavity, nasal cavity, vagina, rectum, has good application value with before in clinic
Scape.
Preceding non-ionic precursor gel of the invention is a kind of semi-solid state, while inheriting pair of preceding non-ionic precursor and gel
Weight advantage, vesica was easily assembled, was merged and medicine during both having solved non-ionic precursor surfactants vesicles solution state and storage
The problems such as object is revealed provides an effective method, and has apparent advantage in transport, storage, use aspect, fits
It is not easy to reach there is local drug concentration for industrialized production, and when overcoming common external preparation percutaneous dosing, medication
The problems such as amount is big, curative effect is unobvious.It is a kind of extremely promising novel carriers preparation.
Non-ionic precursor gel may be directly applied on skin or mucous membrane before Rupatadine fumarate of the invention.
Specific embodiment
Combined with specific embodiments below, the present invention is further clarified.The experiment of actual conditions is not specified in embodiment
Method, usually according to normal condition and condition described in handbook, or according to the normal condition proposed by manufacturer；Used is logical
With equipment, material, reagent etc., it is commercially available unless otherwise specified.
The present invention is non-ionic precursor gel preparation before a kind of Rupatadine fumarate, is calculated by weight, formula include with
Lower component: 0.5-2 parts of Rupatadine fumarate, 2-10 parts of stabilizer, 20-50 parts of nonionic surfactant, film coating material
2-10 parts, 4-8 parts of organic solvent, 1-3 parts of carbomer, 20-40 parts of glycerol, 30-60 parts of propylene glycol, 3-6 parts of transdermal enhancer, distilled water
To 120-240 parts.
Rupatadine fumarate is main ingredient in formula；Nonionic surfactant is as the carrier for containing drug, selected from department
The mixing of one or both of disk -20, Arlacel-40, Arlacel-60, Arlacel-80, Tween-20, Tween-60, Tween-80；Phosphatide,
Cholesterol is membrane stabilizer, wherein lecithin can selected from one of soybean lecithin, egg yolk lecithin, hydrolecithin or
Two kinds of mixing；Organic solvent is dehydrated alcohol, propyl alcohol, isopropanol or butanol.Film coating material is sucrose stearate, sorb
The mixing of one or both of alcohol, maltodextrin；Carbomer is gel-type vehicle, one in carbomer 934,940,941
Kind or two kinds of mixing.Transdermal enhancer is the mixing of one or both of dimethyl sulfoxide, azone, propylene glycol, peppermint oil.
Non-ionic precursor before the present invention first uses suspension method to be prepared into Rupatadine fumarate, is further prepared into fumaric acid
Non-ionic precursor gel before Rupatadine.Specific preparation method the following steps are included: (1) by Rupatadine fumarate, stabilizer, non-
Ionic surface active agent and film coating material are added in organic solvent, are sealed, and heating water bath ultrasound sets Rotary Evaporators
Upper heating water bath flings to organic solvent, obtains dried powder, is dried in vacuum overnight to get non-ionic precursor before Rupatadine fumarate；
(2) carbomer is dissolved in distilled water, by glycerol, propylene glycol, is added, stirs evenly under the conditions of magnetic stirrer；(3)
Transdermal enhancer is added in (2), is stirred evenly, and is 6-7 with appropriate triethanolamine tune pH value, is added distilled water magnetic stirring apparatus abundant
It stirs evenly.(4) (3) are mixed with (1), is stirred evenly, de-bubbled obtains non-ionic precursor gel preparation before Rupatadine fumarate.Step
Suddenly the water bath heating temperature in (1) is preferably 55-65 DEG C.
Below by way of specific embodiment, the present invention is further elaborated, but the present invention is not limited thereto specific examples.
Embodiment 1
1 part of Rupatadine fumarate, 40 parts of sorbester p18,5 parts of soybean lecithin, 3 parts of sorbierite are added to 5 parts of ethyl alcohol
In, it seals, 55 DEG C of heating water bath ultrasounds, sets 60 DEG C of heating water baths on Rotary Evaporators and fling to ethyl alcohol, obtain dried powder, very
Sky is dried overnight to get non-ionic precursor before Rupatadine fumarate；Again by 1 part of Carbomer-940, it is dissolved in 12 parts of distilled water
In；20 parts of glycerol are weighed, 30 parts of propylene glycol, is added in above-mentioned matrix, stirs evenly under the conditions of magnetic stirrer；Add azone
It 3 parts, stirs evenly, is 6-7 with appropriate triethanolamine tune pH value, add distilled water to 120 parts, sufficiently stirred using magnetic stirring apparatus
It is even, add non-ionic precursor before Rupatadine fumarate, stir evenly, de-bubbled is solidifying to get non-ionic precursor before Rupatadine fumarate
Glue preparation, is fitted into light resistant container, places at shady and cool drying.
Embodiment 2
0.5 part of Rupatadine fumarate, 50 parts of polysorbas20,6 parts of egg yolk lecithin, 2 parts of sucrose stearate are added to
It in the mixed solution (2:1) of 6 parts of ethyl alcohol and propyl alcohol, seals, 60 DEG C of heating water bath ultrasounds set 65 DEG C of water on Rotary Evaporators
Organic solvent is flung in bath heating, is obtained dried powder, is dried in vacuum overnight to get non-ionic precursor before Rupatadine fumarate；Again will
It 2 parts of carbomer -941, is dissolved in 20 parts of distilled water；Weigh 25 parts of glycerol, 30 parts of propylene glycol, magnetic stirrer condition
It is lower to be added in above-mentioned matrix, it stirs evenly；Add azone and 3 parts of propylene glycol (2:1), stir evenly, with appropriate triethanolamine tune pH
Value is 6-7, adds distilled water to 150 parts, is sufficiently stirred evenly using magnetic stirring apparatus, add non-ionic precursor before Rupatadine fumarate, stir
It mixes uniformly, de-bubbled is fitted into light resistant container to get non-ionic precursor gel preparation before Rupatadine fumarate, is placed shady and cool dry
Dry place.
Embodiment 3
By 50 parts of 2 parts of Rupatadine fumarate, span 40 and Tween 80 mixture (1:1), 4 parts of cholesterol, 4 parts of sorbierite
It is added in 5 parts of isopropanols, seals, 60 DEG C of heating water bath ultrasounds set 60 DEG C of heating water baths on Rotary Evaporators and fling to second
Alcohol obtains dried powder, is dried in vacuum overnight to get non-ionic precursor before Rupatadine fumarate；It is molten again by 3 parts of Carbomer-940
Solution is in 30 parts of distilled water；35 parts of glycerol are weighed, 45 parts of propylene glycol, is added under the conditions of magnetic stirrer in above-mentioned matrix,
It stirs evenly；Add azone and 3 parts of mint oil mixtures (2:1), stir evenly, is 6-7 with appropriate triethanolamine tune pH value, adds steaming
Distilled water is sufficiently stirred evenly to 200 parts, using magnetic stirring apparatus, is added non-ionic precursor before Rupatadine fumarate, is stirred evenly, degassing
Bubble is fitted into light resistant container to get non-ionic precursor gel preparation before Rupatadine fumarate, is placed at shady and cool drying.
Embodiment 4
By 1.5 parts of Rupatadine fumarate, sorbester p18 and 40 parts of Tween 80 mixture (1:1), hydrogenated soy phosphatidyl choline 8
Part, 6 parts of sorbierite be added in 6 parts of butanol, seal, 55 DEG C of heating water bath ultrasounds set 55 DEG C of water-baths on Rotary Evaporators
Butanol is flung in heating, is obtained dried powder, is dried in vacuum overnight to get non-ionic precursor before Rupatadine fumarate；Again by carbomer-
It 940 1.5 parts, is dissolved in 15 parts of distilled water；28 parts of glycerol are weighed, 36 parts of propylene glycol, is added under the conditions of magnetic stirrer
In above-mentioned matrix, stir evenly；Add 2 parts of peppermint oil, stir evenly, is 6-7 with appropriate triethanolamine tune pH value, adds distilled water extremely
160 parts, sufficiently stirred evenly using magnetic stirring apparatus, add non-ionic precursor before Rupatadine fumarate, stir evenly, de-bubbled to get
Non-ionic precursor gel preparation before Rupatadine fumarate, is fitted into light resistant container, places at shady and cool drying.
Embodiment 5
By 2 parts of Rupatadine fumarate, 25 parts of sorbester p17, soybean lecithin and 6 parts of cholesterol (1:1), maltodextrin
5 parts are added in 4 parts of ethyl alcohol, seal, 60 DEG C of heating water bath ultrasounds, set 60 DEG C of heating water baths on Rotary Evaporators and fling to second
Alcohol obtains dried powder, is dried in vacuum overnight to get non-ionic precursor before Rupatadine fumarate；It is molten again by 2 parts of Carbomer-940
Solution is in 16 parts of distilled water；30 parts of glycerol are weighed, 30 parts of propylene glycol, is added under the conditions of magnetic stirrer in above-mentioned matrix,
It stirs evenly；Add 3 parts of dimethyl sulfoxide, stir evenly, is 6-7 with appropriate triethanolamine tune pH value, adds distilled water to 160 parts, make
It is sufficiently stirred evenly with magnetic stirring apparatus, adds non-ionic precursor before Rupatadine fumarate, stir evenly, de-bubbled is to get fumaric acid Lu
Non-ionic precursor gel preparation before Pa Tading, is fitted into light resistant container, places at shady and cool drying.
Embodiment 6
By 1.5 parts of Rupatadine fumarate, sorbester p18 and 30 parts of sorbester p17 (2:1), soybean lecithin and egg yolk lecithin
5 parts of (2:1), sorbierite and 3 parts of maltodextrin (1:1) are added in 5 parts of propyl alcohol, are sealed, 55 DEG C of heating water bath ultrasounds,
It sets 55 DEG C of heating water baths on Rotary Evaporators and flings to propyl alcohol, obtain dried powder, be dried in vacuum overnight to get Rupatadine fumarate
Preceding non-ionic precursor；Again by 1 part of Carbomer-940, it is dissolved in 12 parts of distilled water；Weigh 20 parts of glycerol, 30 parts of propylene glycol, magnetic force
It is added in above-mentioned matrix, stirs evenly under blender stirring condition；Add 3 parts of azone, stir evenly, with appropriate triethanolamine tune pH
Value is 6-7, adds distilled water to 130 parts, is sufficiently stirred evenly using magnetic stirring apparatus, add non-ionic precursor before Rupatadine fumarate, stir
It mixes uniformly, de-bubbled is fitted into light resistant container to get non-ionic precursor gel preparation before Rupatadine fumarate, is placed shady and cool dry
Dry place.
Embodiment 7
1.5 parts of Rupatadine fumarate, 45 parts of polysorbate40,5 parts of soybean lecithin, 4 parts of sorbierite are added to 4 parts of second
It in alcohol, seals, 60 DEG C of heating water bath ultrasounds, sets 60 DEG C of heating water baths on Rotary Evaporators and fling to ethyl alcohol, obtain dried powder,
It is dried in vacuum overnight to get non-ionic precursor before Rupatadine fumarate；Again by 1.5 parts of Carbomer-940, it is dissolved in 20 parts of distillations
In water；25 parts of glycerol are weighed, 40 parts of propylene glycol, is added in above-mentioned matrix, stirs evenly under the conditions of magnetic stirrer；Add nitrogen
It 1 part of ketone, stirs evenly, is 6-7 with appropriate triethanolamine tune pH value, add distilled water to 125 parts, sufficiently stirred using magnetic stirring apparatus
It is even, add non-ionic precursor before Rupatadine fumarate, stir evenly, de-bubbled is solidifying to get non-ionic precursor before Rupatadine fumarate
Glue preparation, is fitted into light resistant container, places at shady and cool drying.
Embodiment 8
By 50 parts of 2 parts of Rupatadine fumarate, polysorbate60 and sorbester p18 (1:1), 2 parts of soybean lecithin, maltodextrin
It is added in 8 parts of ethyl alcohol, seals with 3 parts of sorbierite (1:2), 60 DEG C of heating water bath ultrasounds set on Rotary Evaporators 60 DEG C
Heating water bath flings to ethyl alcohol, obtains dried powder, is dried in vacuum overnight to get non-ionic precursor before Rupatadine fumarate；It again will card
It 2 parts of Bo Mu -940, is dissolved in 20 parts of distilled water；Weigh 30 parts of glycerol, 30 parts of propylene glycol, under the conditions of magnetic stirrer
It is added in above-mentioned matrix, stirs evenly；Add 2.5 parts of azone, stir evenly, is 6-7 with appropriate triethanolamine tune pH value, adds distillation
Water is sufficiently stirred evenly to 180 parts, using magnetic stirring apparatus, is added non-ionic precursor before Rupatadine fumarate, is stirred evenly, de-bubbled,
It up to non-ionic precursor gel preparation before Rupatadine fumarate, is fitted into light resistant container, places at shady and cool drying.
Embodiment 9
By 25 parts of 1 part of Rupatadine fumarate, polysorbate60 and span 40 (1:2), hydrolecithin and cholesterol (2:1) 6
3 parts of part, sucrose stearate and sorbierite (2:1) are added in 6 parts of butanol and alcohol mixeding liquid (1:1), are sealed, 60 DEG C
Heating water bath ultrasound, sets 60 DEG C of heating water baths on Rotary Evaporators and flings to organic solvent, obtain dried powder, be dried in vacuum overnight,
Up to non-ionic precursor before Rupatadine fumarate；Again by 2 parts of carbomer -934, it is dissolved in 15 parts of distilled water；Weigh glycerol 25
Part, it 30 parts of propylene glycol, is added in above-mentioned matrix, stirs evenly under the conditions of magnetic stirrer；Add dimethyl sulfoxide and azone
3 parts of (2:1), stirs evenly, and is 6-7 with appropriate triethanolamine tune pH value, adds distilled water to 120 parts, filled using magnetic stirring apparatus
Divide and stir evenly, adds non-ionic precursor before Rupatadine fumarate, stir evenly, de-bubbled is to get nonionic before Rupatadine fumarate
Body gel preparation, is fitted into light resistant container, places at shady and cool drying.
Embodiment 10
1 part of Rupatadine fumarate, 40 parts of polysorbate60,4 parts of soybean lecithin, 4 parts of sorbierite are added to 4 parts of ethyl alcohol
In, it seals, 55 DEG C of heating water bath ultrasounds, sets 50 DEG C of heating water baths on Rotary Evaporators and fling to ethyl alcohol, obtain dried powder, very
Sky is dried overnight to get non-ionic precursor before Rupatadine fumarate；Again by 1 part of Carbomer-940, it is dissolved in 15 parts of distilled water
In；20 parts of glycerol are weighed, 35 parts of propylene glycol, is added in above-mentioned matrix, stirs evenly under the conditions of magnetic stirrer；Add azone
It 1.5 parts, stirs evenly, is 6-7 with appropriate triethanolamine tune pH value, add distilled water to 125 parts, sufficiently stirred using magnetic stirring apparatus
It is even, add non-ionic precursor before Rupatadine fumarate, stir evenly, de-bubbled is solidifying to get non-ionic precursor before Rupatadine fumarate
Glue preparation, is fitted into light resistant container, places at shady and cool drying.
Embodiment 11
By 1 part of Rupatadine fumarate, 40 parts of sorbester p18,5 parts of egg yolk lecithin, sucrose stearate and sorbierite (1:
2) it is added in ethyl alcohol for 3 parts, seals, 60 DEG C of heating water bath ultrasounds set 60 DEG C of heating water baths on Rotary Evaporators and fling to second
Alcohol obtains dried powder, is dried in vacuum overnight to get non-ionic precursor before Rupatadine fumarate；Again by 2.5 parts of Carbomer-940,
It is dissolved in 20 parts of distilled water；25 parts of glycerol are weighed, 30 parts of propylene glycol, above-mentioned matrix is added under the conditions of magnetic stirrer
In, it stirs evenly；Add 3 parts of azone, stir evenly, be 6-7 with appropriate triethanolamine tune pH value, add distilled water to 150 parts, uses
Magnetic stirring apparatus sufficiently stirs evenly, and adds non-ionic precursor before Rupatadine fumarate, stirs evenly, and de-bubbled is to get fumaric acid Lu's pa
Non-ionic precursor gel preparation, is fitted into light resistant container before he is fixed, places at shady and cool drying.
Embodiment 12
0.5 part of Rupatadine fumarate, 40 parts of sorbester p18,5 parts of soybean lecithin, 2 parts of sorbierite are added to 5 parts of second
It in alcohol, seals, 60 DEG C of heating water bath ultrasounds, sets 60 DEG C of heating water baths on Rotary Evaporators and fling to ethyl alcohol, obtain dried powder,
It is dried in vacuum overnight to get non-ionic precursor before Rupatadine fumarate；Again by 1.5 parts of Carbomer-940, it is dissolved in 15 parts of distillations
In water；20 parts of glycerol are weighed, 35 parts of propylene glycol, is added in above-mentioned matrix, stirs evenly under the conditions of magnetic stirrer；Add nitrogen
It 2 parts of ketone, stirs evenly, is 6-7 with appropriate triethanolamine tune pH value, add distilled water to 210 parts, sufficiently stirred using magnetic stirring apparatus
It is even, add non-ionic precursor before Rupatadine fumarate, stir evenly, de-bubbled is solidifying to get non-ionic precursor before Rupatadine fumarate
Glue preparation, is fitted into light resistant container, places at shady and cool drying.
The above content is a further detailed description of the present invention in conjunction with specific preferred embodiments, and it cannot be said that
Specific implementation of the invention is only limited to these instructions.For those of ordinary skill in the art to which the present invention belongs, exist
Under the premise of not departing from present inventive concept, a number of simple deductions or replacements can also be made, all shall be regarded as belonging to of the invention
Protection scope.
Claims (10)
1. non-ionic precursor gel preparation before a kind of Rupatadine fumarate, it is characterised in that: calculate by weight, formula includes
Following components: 0.5-2 parts of Rupatadine fumarate, 2-10 parts of stabilizer, 20-50 parts of nonionic surfactant, film coating material
2-10 parts of material, 4-8 parts of organic solvent, 1-3 parts of carbomer, 20-40 parts of glycerol, 30-60 parts of propylene glycol, 3-6 parts of transdermal enhancer, distillation
Water is to 120-240 parts.
2. non-ionic precursor gel preparation before a kind of Rupatadine fumarate according to claim 1, it is characterised in that: institute
The stabilizer stated is the mixing of one or both of cholesterol, phosphatide.
3. non-ionic precursor gel preparation before a kind of Rupatadine fumarate according to claim 1, it is characterised in that: institute
The phosphatide stated is mixed selected from one or both of soybean lecithin, egg yolk lecithin, hydrolecithin.
4. non-ionic precursor gel preparation before a kind of Rupatadine fumarate according to claim 1, it is characterised in that: institute
The organic solvent stated is dehydrated alcohol, propyl alcohol, isopropanol or butanol.
5. non-ionic precursor gel preparation before a kind of Rupatadine fumarate according to claim 1, it is characterised in that: institute
The nonionic surfactant stated is selected from Arlacel-20, Arlacel-40, Arlacel-60, Arlacel-80, Tween-20, Tween-60, tween-
One or both of 80 mixing.
6. non-ionic precursor gel preparation before a kind of Rupatadine fumarate according to claim 1, it is characterised in that: institute
The film coating material stated is the mixing of one or both of sucrose stearate, sorbierite, maltodextrin.
7. non-ionic precursor gel preparation before a kind of Rupatadine fumarate according to claim 1, it is characterised in that: institute
The carbomer stated is the mixing of one or both of carbomer 934,940,941.
8. non-ionic precursor gel preparation before a kind of Rupatadine fumarate according to claim 1, it is characterised in that: institute
The transdermal enhancer stated is the mixing of one or both of dimethyl sulfoxide, azone, propylene glycol, peppermint oil.
9. the preparation method of non-ionic precursor gel preparation, feature before Rupatadine fumarate described in a kind of claim 1-8
It is the following steps are included: (1) adds Rupatadine fumarate, stabilizer, nonionic surfactant and film coating material
Enter into organic solvent, seal, heating water bath ultrasound sets the above heating water bath of rotary evaporation and flings to organic solvent, obtains dry
Dry powder is dried in vacuum overnight to get non-ionic precursor before Rupatadine fumarate；(2) carbomer is dissolved in distilled water, it will
Glycerol, propylene glycol are added under the conditions of magnetic stirrer, stir evenly；(3) transdermal enhancer is added in above-mentioned matrix, stirring
Uniformly, it is 6-7 with appropriate triethanolamine tune pH value, distilled water is added sufficiently to be stirred evenly with magnetic stirring apparatus；(4) (3) and (1) are mixed
It closes, stirs evenly, de-bubbled, obtain non-ionic precursor gel preparation before Rupatadine fumarate, be fitted into light resistant container, place shady and cool
At dry.
10. the preparation method of non-ionic precursor preparation, feature exist before a kind of Rupatadine fumarate according to claim 9
In: the water bath heating temperature in the step (1) is 55-65 DEG C.
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|---|---|---|---|---|
| EP2402012A2 (en) * | 2010-06-30 | 2012-01-04 | J. Uriach y Compania S.A. | Liquid formulations of rupatadine fumarate |
| CN102958926A (en) * | 2010-06-30 | 2013-03-06 | J·乌里亚奇·Y股份有限公司 | Rupatadine salt as an antihistaminic agent |
| CN103340823A (en) * | 2013-06-05 | 2013-10-09 | 南方医科大学 | Formulation of paeonol proniosomes and preparing method thereof |
| CN108992398A (en) * | 2018-09-04 | 2018-12-14 | 广州君博医药科技有限公司 | A kind of gel for eye and preparation method thereof containing Rupatadine fumarate |
-
2019
- 2019-05-14 CN CN201910402206.XA patent/CN110123739A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2402012A2 (en) * | 2010-06-30 | 2012-01-04 | J. Uriach y Compania S.A. | Liquid formulations of rupatadine fumarate |
| CN102958926A (en) * | 2010-06-30 | 2013-03-06 | J·乌里亚奇·Y股份有限公司 | Rupatadine salt as an antihistaminic agent |
| CN103340823A (en) * | 2013-06-05 | 2013-10-09 | 南方医科大学 | Formulation of paeonol proniosomes and preparing method thereof |
| CN108992398A (en) * | 2018-09-04 | 2018-12-14 | 广州君博医药科技有限公司 | A kind of gel for eye and preparation method thereof containing Rupatadine fumarate |
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