CN107080733A - A kind of miconazole nitrate chitosan vagina slowly-releasing gel and preparation method thereof - Google Patents
A kind of miconazole nitrate chitosan vagina slowly-releasing gel and preparation method thereof Download PDFInfo
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- CN107080733A CN107080733A CN201710251971.7A CN201710251971A CN107080733A CN 107080733 A CN107080733 A CN 107080733A CN 201710251971 A CN201710251971 A CN 201710251971A CN 107080733 A CN107080733 A CN 107080733A
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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
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4174—Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
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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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- 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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
-
- 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
Abstract
The present invention relates to a kind of miconazole nitrate chitosan vagina slowly-releasing gel and preparation method thereof, sustained-release gel is grouped into by following group：Miconazole nitrate, chitosan, Polycarbophil, glycerine, Compritol 888 ATO, sodium benzoate, triethanolamine, mass fraction are 2% acetum and water for injection.Method includes preparing chitosan-acetic acid solution, prepares polymer phase, the acquisition for preparing oil phase, preparing aqueous phase and spansule.Present invention linear relationship in the range of 0.050 0.80mg/mL is good, and mean sample recovery rate is 97.91% (RSD=0.24%), and has carried out precision test in a few days and in the daytime, as a result shows that withinday precision and day to day precision are good；Obtained sustained-release gel is respectively 35.54%, 56.02% and 93.92% in 1h, 2h and 12h Accumulation dissolution；Shown through clinical data, sustained-release gel of the present invention is 95.83% to the effective percentage for treating monilial vaginitis.
Description
Technical field
The present invention relates to a kind of miconazole nitrate chitosan vagina slowly-releasing gel and preparation method thereof, belong to medical science neck
Domain.
Background technology
Miconazole nitrate is 1- phenethyl imdazole derivatives, and its active component is Miconazole, belongs to antifungal, blastomycete
Category, tissue milk born of the same parents Pseudomonas, Cryptococcus, Mycotoruloides, Coccidioides etc. are sensitive to this product, draw available for gynaecology candida albicans etc.
Superinfection caused by the vagina infection risen and gram-positive bacterium.Miconazole nitrate may interfere with fungal cytochrome P450's
Activity, suppresses the biosynthesis of fungal cell membrane ergosterol, changes the permeability of film, causes intracellular matter to leak outside；Also may be used
Suppress the triacylglycerol of fungi and the biosynthesis ethyl oxidizing ferment and the activity of peroxidase of phosphatide, cause intracellular peroxidation
Oxygen is gathered, and causes cell submicroscopic structure to be denatured and meronecrosis.Application No. 200810243197.6, a kind of entitled nitre
Sour Miconazole film and preparation method thereof and the application in pharmacy, are disclosed a kind of for treating female genital fungal infection
Miconazole nitrate film, its raw material include miconazole nitrate, filmogen, plasticizer, membrane material lytic agent and preservative, pass through
Effect experiment proves that miconazole nitrate film has preferable therapeutic action to monilial vaginitis, with Gyno-Daktarin in symptom
Improvement and fungi clearance rate on have identical curative effect, and simultaneously, when mouse is administered, film is kneaded and fills in mouse vagina
Depths, its occupation mode with suppository is essentially identical.Miconazole nitrate oral preparation medicament is difficult that a large amount of genital tracts that come together in glue
Film, it is necessary to which heavy dose is used, could produce curative effect, therefore cause larger toxic side effect, liniment, creme, and existing solidifying
Glue, it is short using the later lasting period, preferable effect is extremely difficult to, and suppository drugloading rate is big, long-term use is also easy to produce the resistance to the action of a drug.
Chitosan is chitin deacetylase product, is one of maximum marine resources of China's yield, with nontoxic, stingless
Swash, the features such as with degradable, good biocompatibility.
The content of the invention
It is an object of the invention to a kind of miconazole nitrate chitosan vagina slowly-releasing gel and preparation method thereof, the present invention with
Chitosan, Polycarbophil are that vagina sustained-release gel is made in mixed-matrix, can continue 12h and slowly discharge, and reach reduction administration
The purpose of number of times.Technical scheme is as follows：
A kind of miconazole nitrate chitosan vagina slowly-releasing gel, it is composed of the following components：
Miconazole nitrate, chitosan, Polycarbophil, glycerine, Compritol 888 ATO, sodium benzoate, triethanolamine, quality point
Number is 2% acetum and water for injection.
Further, sustained-release gel is made up of the following component counted by weight：
1-3 parts of miconazole nitrate, 0.3-0.8 parts of chitosan, 0.5-1.5 parts of Polycarbophil, 4-7 parts of glycerine, behenic acid are sweet
1-3 parts of grease, 0.2-0.5 parts of sodium benzoate, 0.1-0.3 parts of triethanolamine, mass fraction are 2% 12-18 parts of acetum,
Inject water to 100 parts.
Further, sustained-release gel is made up of the following component counted by weight：
2 parts of miconazole nitrate, 0.5 part of chitosan, 1 part of Polycarbophil, 5 parts of glycerine, 2 parts of Compritol 888 ATO, benzoic acid
0.3 part of sodium, 0.2 part of triethanolamine, mass fraction are 2% 15 parts of acetum, inject water to 100 parts.
The method for preparing miconazole nitrate chitosan vagina slowly-releasing gel, is comprised the following steps that：
(1) chitosan-acetic acid solution is prepared：Chitosan is weighed, the burning for filling the acetum that mass fraction is 2% is added
In cup, stirring to dissolving；
(2) polymer phase is prepared：Polycarbophil plus appropriate water for injection soaked overnight are sufficiently stirred for until complete swelling
Into uniform gellike polymer, the chitosan-acetic acid solution of step (1) preparation is slowly added under high-speed stirred；
(3) oil phase is prepared：Heating glycerin, Compritol 888 ATO make fusing, are sufficiently stirred for obtaining uniform oil phase；
(4) aqueous phase is prepared：Sodium benzoate, triethanolamine and miconazole nitrate are mixed in remaining water for injection, plus
Heat is to 65 DEG C；
(5) oil phase is added in the aqueous phase of heat, stirring is sufficiently mixed two-phase, uniform dirty solution is obtained, in 60 DEG C of bars
Under part, polymer phase is added in dirty solution rapidly and stirred and evenly mixed, while stirring, adjust pH so that pH 3.5-5.5 it
Between.
Further, pH is adjusted from sodium hydroxide；It is preferred that, it is adjusted from 10mg/mL sodium hydrate aqueous solutions
pH。
Further, regulation pH is between 4.5-5；It is preferred that, regulation pH is 4.8.
The present invention has advantages below compared with prior art：
The vagina gel that the present invention is made using chitosan, Polycarbophil as matrix, compared with suppository, the present invention more can
Fully contacted with vaginal mucosa gauffer, not only increase contact area, also make medicine retention time lengthening, the present invention both ensure that
Curative effect reduces administration number of times again, and without greasy feeling, using comfortable.
Brief description of the drawings
Fig. 1 is ultraviolet absorpting spectrum, wherein, 1 is miconazole nitrate solution；2 be auxiliary material solution；
Fig. 2 is sustained-release gel Accumulation dissolution curve map of the present invention.
Embodiment
The invention will now be further described with reference to specific embodiments, advantages of the present invention and feature will be with description and
It is apparent.But embodiment is only exemplary, does not constitute any limitation to the scope of the present invention.Those skilled in the art should
It should be appreciated that, the details and form of technical solution of the present invention can be repaiied without departing from the spirit and scope of the invention
Change or replace, but these modifications and replacement are each fallen within protection scope of the present invention.
A kind of miconazole nitrate chitosan vagina slowly-releasing gel of embodiment 1
Sustained-release gel is made up of the following component counted by weight：
2 parts of miconazole nitrate, 0.5 part of chitosan, 1 part of Polycarbophil, 5 parts of glycerine, 2 parts of Compritol 888 ATO, benzoic acid
0.3 part of sodium, 0.2 part of triethanolamine, mass fraction are 2% 15 parts of acetum, inject water to 100 parts.
The method for preparing miconazole nitrate chitosan vagina slowly-releasing gel, is comprised the following steps that：
(1) chitosan-acetic acid solution is prepared：Chitosan is weighed, the burning for filling the acetum that mass fraction is 2% is added
In cup, stirring to dissolving；
(2) polymer phase is prepared：Polycarbophil plus appropriate water for injection soaked overnight are sufficiently stirred for until complete swelling
Into uniform gellike polymer, the chitosan-acetic acid solution of step (1) preparation is slowly added under high-speed stirred；
(3) oil phase is prepared：Heating glycerin, Compritol 888 ATO make fusing, are sufficiently stirred for obtaining uniform oil phase；
(4) aqueous phase is prepared：Sodium benzoate, triethanolamine and miconazole nitrate are mixed in remaining water for injection, plus
Heat is to 65 DEG C；
(5) oil phase is added in the aqueous phase of heat, stirring is sufficiently mixed two-phase, uniform dirty solution is obtained, in 60 DEG C of bars
Under part, polymer phase is added in dirty solution rapidly and stirred and evenly mixed, while stirring, from 10mg/mL sodium hydrate aqueous solutions
It is 4.8 to adjust pH.
A kind of miconazole nitrate chitosan vagina slowly-releasing gel of embodiment 2
Sustained-release gel is made up of the following component counted by weight：
1.2 parts of miconazole nitrate, 0.3 part of chitosan, 0.7 part of Polycarbophil, 4.5 parts of glycerine, Compritol 888 ATO 1.3
Part, 13 parts of the acetum that 0.3 part of sodium benzoate, 0.15 part of triethanolamine, mass fraction are 2%, inject water to 100
Part.
The method for preparing miconazole nitrate chitosan vagina slowly-releasing gel, is comprised the following steps that：
(1) chitosan-acetic acid solution is prepared：Chitosan is weighed, the burning for filling the acetum that mass fraction is 2% is added
In cup, stirring to dissolving；
(2) polymer phase is prepared：Polycarbophil plus appropriate water for injection soaked overnight are sufficiently stirred for until complete swelling
Into uniform gellike polymer, the chitosan-acetic acid solution of step (1) preparation is slowly added under high-speed stirred；
(3) oil phase is prepared：Heating glycerin, Compritol 888 ATO make fusing, are sufficiently stirred for obtaining uniform oil phase；
(4) aqueous phase is prepared：Sodium benzoate, triethanolamine and miconazole nitrate are mixed in remaining water for injection, plus
Heat is to 65 DEG C；
(5) oil phase is added in the aqueous phase of heat, stirring is sufficiently mixed two-phase, uniform dirty solution is obtained, in 60 DEG C of bars
Under part, polymer phase is added in dirty solution rapidly and stirred and evenly mixed, while stirring, from 10mg/mL sodium hydrate aqueous solutions
It is 3.5 to adjust pH.
A kind of miconazole nitrate chitosan vagina slowly-releasing gel of embodiment 3
Sustained-release gel is made up of the following component counted by weight：
3 parts of miconazole nitrate, 0.7 part of chitosan, 1.5 parts of Polycarbophil, 6.5 parts of glycerine, 2.8 parts of Compritol 888 ATO,
0.5 part of sodium benzoate, 0.3 part of triethanolamine, mass fraction are 2% 16 parts of acetum, inject water to 100 parts.
The method for preparing miconazole nitrate chitosan vagina slowly-releasing gel, is comprised the following steps that：
(1) chitosan-acetic acid solution is prepared：Chitosan is weighed, the burning for filling the acetum that mass fraction is 2% is added
In cup, stirring to dissolving；
(2) polymer phase is prepared：Polycarbophil plus appropriate water for injection soaked overnight are sufficiently stirred for until complete swelling
Into uniform gellike polymer, the chitosan-acetic acid solution of step (1) preparation is slowly added under high-speed stirred；
(3) oil phase is prepared：Heating glycerin, Compritol 888 ATO make fusing, are sufficiently stirred for obtaining uniform oil phase；
(4) aqueous phase is prepared：Sodium benzoate, triethanolamine and miconazole nitrate are mixed in remaining water for injection, plus
Heat is to 65 DEG C；
(5) oil phase is added in the aqueous phase of heat, stirring is sufficiently mixed two-phase, uniform dirty solution is obtained, in 60 DEG C of bars
Under part, polymer phase is added in dirty solution rapidly and stirred and evenly mixed, while stirring, from 10mg/mL sodium hydrate aqueous solutions
It is 5.5 to adjust pH.
The measure of miconazole nitrate content in the present invention of test example 1
1st, it is 0.25mg/mL's that the determination of measure wavelength, which takes miconazole nitrate plus methanol to dissolve and become mass concentration,
Solution.Separately chitosan, Polycarbophil and other auxiliary material methanol is taken to dissolve by prescription example, respectively by above two solution in 250-
Scanning absorbs collection of illustrative plates in 300nm wave-length coverages, and as a result ultraviolet absorpting spectrum as shown in figure 1, show miconazole nitrate at 272nm
Have an absorption maximum, and matrix and other auxiliary materials at this wavelength almost without absorption, therefore selection 272nm is used as and determines wavelength.
2nd, the preparation precision of standard curve is weighed dries to the miconazole nitrate reference substance 0.25g of constant weight in 105 DEG C, puts
In 50mL measuring bottles, plus methanol dissolves and is diluted to scale, shakes up, is used as stock solution.Respectively precision measure stock solution 0.50,
1.0th, 2.0,3.0,4.0,5.0,6.0,8.0mL is put in 50mL measuring bottles, with methanol dilution to scale, is shaken up.Using methanol as blank,
Trap A is determined at 272nm wavelength, linear regression is carried out to trap A with concentration C, as a result miconazole nitrate is in 0.050-
In the range of 0.80mg/mL, the linear relationship of trap and concentration is good, and the regression equation tried to achieve is A=1.4213C+0.046, r
=0.9994.
3rd, sample size determines the sustained-release gel sample for taking 3 batches to prepare altogether.The sustained-release gel for therefrom taking 1 batch to prepare
Sample, precision weighs about 3.0g, is placed in 50mL volumetric flasks, makes sample melted in the bath that discharges water, and adding proper amount of methanol makes its complete
Dissolving, is settled to scale.Precision measures 5mL, puts in 50mL volumetric flasks, with methanol constant volume to scale, shakes up.Using methanol as sky
In vain, in determination sample solution at 272nm miconazole nitrate trap, substitute into regression equation, concentration is calculated, so as to calculate
Go out the content of the batch sustained-release gel sample.Ibid method, determines the content of other 2 batch sample.
4th, average recovery experiment weighs 105 DEG C of dryings by 80%, 100%, the 120% of prescription main ingredient amount, respectively precision
To the miconazole nitrate of constant weight, and in the ratio of each component in sustained-release gel prescription, precision weighs matrix and other prescribed materials,
It is appropriate with methanol dissolving each component, determine miconazole nitrate content according to sample size method for measuring.Each Specimen Determination 3 times,
Average value is calculated, average recovery is calculated, 1 is the results are shown in Table.
The average recovery result of the test (n=3) of table 1
The precision test of test example 2
By method under the preparation of the standard curve of test example 1, miconazole nitrate 0.20,0.40,0.60mg/mL are prepared
Solution, in different time (0,2,4,6,8,10h) in a few days and in the daytime, (1,2,3,4d) determines trap respectively, calculates in a few days
And day to day precision, it the results are shown in Table 2.
The Precision test result of table 2
The stability test of the present invention of test example 3
Centrifugal test takes sustained-release gel 5g or so, is fitted into centrifuge tube with a scale, is centrifuged with 2500r/min rotating speeds
30min, observes its appearance character, and as a result gel does not occur lamination.
Reserved sample observing places packaged sample 3,6 months at room temperature, is examined with foregoing quality control standard
Survey, as a result indices do not find significant change.
The drug release determination of the present invention of test example 4
Simulation vaginal secretion accurately weighs NaCl 3.51g, KOH 1.4g, Ca (OH)20.222g, bovine serum albumin(BSA)
0.018g, lactic acid 2.00g, acetic acid 1.00g, glycerine 0.16g, urea 0.4g and glucose 5.0g, are added in 1000mL water, use
PH is adjusted to 4.2 by HCl.
Assay method takes the present invention about 3.0g to be placed in dissolution sample cell bank, closes sample with nylon membrane, covers pond
Lid, is closely screwed on.Sample cell is put into stripping rotor, bank upward, height is starched with place kick adjustment, with simulation vaginal secretion
900mL is as dissolution medium, and the rotating speed of slurry is 60r/min, and temperature is (37 ± 0.5) DEG C, 0.1,0.3,0.5,1,2,3,4,
6th, 8,10,12h takes solution 5mL respectively, while supplementing dissolution medium 5mL immediately, determines Accumulation dissolution.Obtain the tired of the present invention
Product release curve, as shown in Fig. 2 as a result showing, obtained sustained-release gel 1h discharges 35.54%, 2h and discharges 56.02%, 12h
Release is up to 93.92%, from release profiles as can be seen that medicine is first discharged rapidly to valid density, Ran Houhuan in dissolution medium
On The Drug Release, so as to reach quick-acting slow release effects.
The clinical test of test example 5
1st, case history standard is included：
25-46 Sui, meet the married woman of gynaecologic vaginal monilial infection diagnosis.
2nd, case inclusive criteria:
(1) symptom：Obvious pruritus vulvue, leucorrhea increasing slightly stink, vagina burn feeling, can be with urgent urination, odynuria and property
Hand over the symptoms such as pain；
(2) sign inspection：Vagina mucosa is red and swollen, and edema of vulva, flush might have vulva excoriation；
(3) microscopy：Vaginal fluid can find brood cell and false mattress silk under the microscope；
(4) case is excluded:Gestation and women breast-feeding their children；To miconazole nitrate allergy；Have a serious organ disease, such as the heart, liver,
The diseases such as kidney and Pregnant Patients；The similar medicine for treating the disease was used in selected first 1 month；It is unwilling to coordinate investigation
Patient；
(5) standard is exited：Due to the adverse reaction person that needs termination test；Patient's compliance is bad, it is impossible to continuous use
7d person；Patient is late for further consultation and person lost to follow-up；Period has used the similar medicine person for treating the disease simultaneously；Merge other reproductions
Device infection needs curer.
3rd, treatment method：
(1) treatment group：After clean period 3d, vagina is cleaned with warm water before sleeping, it is then with medicator that present invention sustained release is solidifying
About 3 grams of glue squeezes into vagina depths, once a night, continuous use 7 days, prohibitive life during treatment.
(2) control group 1：Cleaned with warm water after vagina before sleeping, miconazole nitrate for vagina embolism is entered into vagina depths, every night one
Grain, continuous use 7 days；
(3) control group 2：Cleaned with warm water after vagina before sleeping, Miconazole nitrate cream is applied to vagina affected part, every night one
It is secondary, 7 days as one therapeutic course is used in conjunction.
4th, observation item after treating：
(1) symptom：Whether take a turn for the better or disappear；
(2) sign inspection：Including vulva, vagina, uterine neck and vaginal fluid inspection；
(3) microscopy：Microscopy is carried out to vaginal fluid.
(4) compliance：Understand research object by inquiring patient and withdrawing unspent medicine and medicine box
Drug compliance.
5th, the standard of curative effect evaluation
(1) cure：Symptom, sign disappear, microscopy (-)；
(2) it is effective：Bed symptom, sign improve, microscopy (-)；
(3) effectively：Symptom, sign are alleviated, microscopy (+)；
(4) it is invalid：Symptom, sign do not improve or even aggravated, microscopy (+).
Total effective rate=(curing number+effective number+efficiently individual quantity)/total number of persons × 100%
6th, result
(1) general information：This experiment is screened into group case 134 altogether, is late for further consultation and person lost to follow-up 14, continuous use
Less than 7d person 5, similar medicine (JIEERYIN XIYE) person 1 for treating the disease has during which been used simultaneously；Merge other reproductions
Device infection needs curer to exit experimenter 1；So the case load for actually accomplishing experiment is 113.
(2) curative effect statistical result, as shown in table 3：
The therapeutic effect of 3 three groups for the treatment of monilial vaginitis of table compares
| Group | Case load | Cure | It is effective | Effectively | It is invalid | Efficient (%) |
| Treatment group | 48 | 35 | 7 | 4 | 2 | 95.83 |
| Control group 1 | 32 | 19 | 6 | 4 | 3 | 90.62 |
| Control group 2 | 33 | 20 | 6 | 2 | 5 | 84.85 |
Claims (8)
1. a kind of miconazole nitrate chitosan vagina slowly-releasing gel, it is characterised in that sustained-release gel is composed of the following components：
Miconazole nitrate, chitosan, Polycarbophil, glycerine, Compritol 888 ATO, sodium benzoate, triethanolamine, mass fraction are
2% acetum and water for injection.
2. miconazole nitrate chitosan vagina slowly-releasing gel according to claim 1, it is characterised in that sustained-release gel by with
Under count by weight component composition：
1-3 parts of miconazole nitrate, 0.3-0.8 parts of chitosan, 0.5-1.5 parts of Polycarbophil, 4-7 parts of glycerine, Compritol 888 ATO
1-3 parts, 0.2-0.5 parts of sodium benzoate, 0.1-0.3 parts of triethanolamine, mass fraction be 2% 12-18 part of acetum, fill
Penetrate with water to 100 parts.
3. miconazole nitrate chitosan vagina slowly-releasing gel according to claim 2, it is characterised in that sustained-release gel by with
Under count by weight component composition：
2 parts of miconazole nitrate, 0.5 part of chitosan, 1 part of Polycarbophil, 5 parts of glycerine, 2 parts of Compritol 888 ATO, sodium benzoate 0.3
Part, 15 parts of the acetum that 0.2 part of triethanolamine, mass fraction are 2%, inject water to 100 parts.
4. the method for the above-mentioned miconazole nitrate chitosan vagina slowly-releasing gel as described in claim any one of 1-3 is prepared, specifically
Step is as follows：
(1) chitosan-acetic acid solution is prepared：Chitosan is weighed, is added in the beaker for filling the acetum that mass fraction is 2%,
Stirring is extremely dissolved；
(2) polymer phase is prepared：Polycarbophil plus appropriate water for injection soaked overnight are sufficiently stirred for until complete swelling Cheng Jun
The chitosan-acetic acid solution of step (1) preparation is slowly added under even gellike polymer, high-speed stirred；
(3) oil phase is prepared：Heating glycerin, Compritol 888 ATO make fusing, are sufficiently stirred for obtaining uniform oil phase；
(4) aqueous phase is prepared：Sodium benzoate, triethanolamine and miconazole nitrate are mixed in remaining water for injection, are heated to
65℃；
(5) oil phase is added in the aqueous phase of heat, stirring is sufficiently mixed two-phase, obtains uniform dirty solution, under the conditions of 60 DEG C,
Polymer phase is added in dirty solution rapidly and stirred and evenly mixed, while stirring, pH is adjusted so that pH is between 3.5-5.5.
5. method according to claim 4, it is characterised in that in the step (5), pH is adjusted from sodium hydroxide.
6. method according to claim 5, it is characterised in that in the step (5), from 10mg/mL sodium hydroxide water
PH is adjusted in solution.
7. method according to claim 6, it is characterised in that in the step (5), from 10mg/mL sodium hydroxide water
Solution adjusts pH between 4.5-5.
8. method according to claim 7, it is characterised in that in the step (5), from 10mg/mL sodium hydroxide water
Solution regulation pH is 4.8.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005074883A1 (en) * | 2004-01-29 | 2005-08-18 | Sinclair Pharmaceuticals Limited | Aqueous compositions containing mixtures of synthetic polymers and biopolymers, useful in the treatment of skin and mucosal tissues dryness, and suitable as vehicles of active ingredients |
| CN106266037A (en) * | 2016-08-19 | 2017-01-04 | 吉安市御美丽健康产业股份有限公司 | A kind of liquid gel and preparation method thereof |
| CN106265486A (en) * | 2016-08-18 | 2017-01-04 | 滨州医学院附属医院 | A kind of miconazole nitrate sustained-release gel and preparation method thereof |
-
2017
- 2017-04-17 CN CN201710251971.7A patent/CN107080733A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005074883A1 (en) * | 2004-01-29 | 2005-08-18 | Sinclair Pharmaceuticals Limited | Aqueous compositions containing mixtures of synthetic polymers and biopolymers, useful in the treatment of skin and mucosal tissues dryness, and suitable as vehicles of active ingredients |
| CN106265486A (en) * | 2016-08-18 | 2017-01-04 | 滨州医学院附属医院 | A kind of miconazole nitrate sustained-release gel and preparation method thereof |
| CN106266037A (en) * | 2016-08-19 | 2017-01-04 | 吉安市御美丽健康产业股份有限公司 | A kind of liquid gel and preparation method thereof |
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