CN107693484A - A kind of rifampin gel and preparation method thereof - Google Patents
A kind of rifampin gel and preparation method thereof Download PDFInfo
- Publication number
- CN107693484A CN107693484A CN201710819662.5A CN201710819662A CN107693484A CN 107693484 A CN107693484 A CN 107693484A CN 201710819662 A CN201710819662 A CN 201710819662A CN 107693484 A CN107693484 A CN 107693484A
- Authority
- CN
- China
- Prior art keywords
- rifampin
- gel
- carbomer
- glycerine
- preparation
- 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
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 title claims abstract description 74
- 229960001225 rifampicin Drugs 0.000 title claims abstract description 74
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 238000001879 gelation Methods 0.000 title abstract description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims abstract description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 20
- 235000011187 glycerol Nutrition 0.000 claims abstract description 18
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims abstract description 17
- 229920002125 Sokalan® Polymers 0.000 claims abstract description 17
- 229960001631 carbomer Drugs 0.000 claims abstract description 17
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical class OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000000203 mixture Substances 0.000 claims abstract description 14
- ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical class CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 claims abstract description 14
- AXTGDCSMTYGJND-UHFFFAOYSA-N 1-dodecylazepan-2-one Chemical compound CCCCCCCCCCCCN1CCCCCC1=O AXTGDCSMTYGJND-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229960003639 laurocapram Drugs 0.000 claims abstract description 9
- 239000012153 distilled water Substances 0.000 claims abstract description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000003756 stirring Methods 0.000 claims abstract description 7
- 238000000034 method Methods 0.000 claims abstract description 6
- 238000002156 mixing Methods 0.000 claims abstract description 3
- 230000008595 infiltration Effects 0.000 claims description 15
- 238000001764 infiltration Methods 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 150000002576 ketones Chemical class 0.000 claims description 4
- 229940049638 carbomer homopolymer type c Drugs 0.000 claims description 3
- 229940043234 carbomer-940 Drugs 0.000 claims description 3
- 239000003292 glue Substances 0.000 claims description 3
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims description 2
- 230000035515 penetration Effects 0.000 abstract description 9
- 239000003814 drug Substances 0.000 abstract description 7
- 238000012360 testing method Methods 0.000 abstract description 6
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 4
- 238000011160 research Methods 0.000 abstract description 4
- 239000000499 gel Substances 0.000 description 35
- 238000009825 accumulation Methods 0.000 description 14
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 239000007788 liquid Substances 0.000 description 7
- 239000007791 liquid phase Substances 0.000 description 6
- 239000013558 reference substance Substances 0.000 description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen(.) Chemical compound [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 230000035699 permeability Effects 0.000 description 4
- 239000012488 sample solution Substances 0.000 description 4
- 201000008827 tuberculosis Diseases 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 206010067484 Adverse reaction Diseases 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 230000006838 adverse reaction Effects 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 230000002365 anti-tubercular Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- AEUTYOVWOVBAKS-UWVGGRQHSA-N ethambutol Chemical compound CC[C@@H](CO)NCCN[C@@H](CC)CO AEUTYOVWOVBAKS-UWVGGRQHSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 231100000435 percutaneous penetration Toxicity 0.000 description 2
- 208000008128 pulmonary tuberculosis Diseases 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid group Chemical class C(CC(O)(C(=O)O)CC(=O)O)(=O)O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 229940072185 drug for treatment of tuberculosis Drugs 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229960000285 ethambutol Drugs 0.000 description 1
- 238000000105 evaporative light scattering detection Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 229960003350 isoniazid Drugs 0.000 description 1
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229960005206 pyrazinamide Drugs 0.000 description 1
- IPEHBUMCGVEMRF-UHFFFAOYSA-N pyrazinecarboxamide Chemical compound NC(=O)C1=CN=CC=N1 IPEHBUMCGVEMRF-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 210000004003 subcutaneous fat Anatomy 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Dermatology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention provides a kind of rifampin gel and preparation method thereof.The rifampin gel, including rifampin, glycerine, propane diols, carbomer, Laurocapram, absolute ethyl alcohol and two drop triethanolamines；The preparation method of the rifampin gel is included under the conditions of lucifuge soaks rifampin with 10% propane diols；Add 15% absolute ethyl alcohol；1% carbomer is spread in distilled water, heats and stirs 30 minutes in 60 DEG C of water-bath, it is fully swelled, and adds two drop triethanolamines；By the mixture of mixture caused by step 2 and 3 and step 4, the gel-type vehicle mixing of glycerine and Laurocapram is added, and adds 100g distilled water and stirs and obtain uniform and stable rifampin gel.Compared with correlation technique, the preparation method of rifampin gel provided by the invention has preferable transdermal penetration effect by what repetition test research was drawn, and transdermal characteristic is good, and medicine, which penetrates into, easily and effectively meets bactericidal effect.
Description
Technical field
The present invention relates to pharmaceutical technology field, more particularly to a kind of rifampin gel and preparation method thereof.
Background technology
Tuberculosis is common infectious disease, the most common with pulmonary tuberculosis.Because tuberculosis has great infectiousness, having must
Early treatment is carried out to it, it is therefore desirable to the antituberculotic of selection efficiently, sensitive, less toxic.Clinically typically by isoniazid
With rifampin as most basic medicine, with pyrazinamide, ethambutol or remaining Drug combination, germ is killed to reach
Purpose with palindromia is reduced, turns into most basic antituberculous chemotherapy scheme.Wherein rifampin is semi-synthetic broad spectrum antibiotic,
Possess the antibacterial activity of height, there is obvious antibacterial action to tubercle bacillus, be clinically used to treat various tuberculosis, it is oral to inhale
Keep well, but the excessive often toxic side effect of oral dose.
The rifampin formulation used at present is mostly injection and oral formulations, based on Formulations for systemic administration, exist renal toxicity and
Hepatotoxicity wind agitation.For pulmonary tuberculosis focus with extensive fibroplasia, surrounding vessels distribution is less, influences blood circulation, causes medicine to penetrate into
Difficulty, drug concentration are difficult to reach effective bacteriocidal concentration, antituberculosis drugs treat course for the treatment of length, and treatment needs Long term combined medication,
It is also easy to produce many adverse reactions.
Therefore, improve concentration of the rifampin in lung has turned into one of focus for the treatment of tuberculosis research, such as lung-targeted microspheres, receives
The novel forms such as the grain of rice, aerosolized liposomes and inhalation aerosol, but these medicines using when can be distributed to other organs, cause bad
Reaction.
The content of the invention
Its percutaneous abilities is studied by preparing rifampin gel it is an object of the invention to provide one kind, is improved to reach
The preparation method of the rifampin gel of adverse reaction, reduction dosage and administration number of times and other effects.
The present invention provides a kind of rifampin gel, including：Rifampin, glycerine, propane diols, carbomer, Laurocapram, nothing
Water-ethanol and two drop triethanolamines.
Preferably, the proportioning of each composition is：1.5% rifampin, 10% glycerine, 10% propane diols, 1% carbomer,
1.0% Laurocapram, 15% absolute ethyl alcohol and two drop triethanolamines.
The present invention also provides a kind of method for preparing rifampin gel, comprises the following steps：
1) rifampin is soaked with 10% propane diols under the conditions of lucifuge；
2) 15% absolute ethyl alcohol is added；
3) 1% carbomer is spread in distilled water, heats and stir 30 minutes in 60 DEG C of water-bath, make it fully molten
It is swollen, and add two drop triethanolamines；
4) by the mixture of mixture caused by step 2 and 3 and step 4, the gel of glycerine and Laurocapram is added
Matrix mixes, and adds 100g distilled water and stir；
5) uniform and stable rifampin glue is obtained.
Preferably, 24 hours accumulation infiltration capacity average value of the rifampin is 204.14 ± 8.96 μ g/cm2, average infiltration
Speed is 7.40 ± 0.47 μ g/cm2·h。
Preferably, the gel-type vehicle in the step 5 is Carbomer-940.
Compared with correlation technique, the preparation method of rifampin gel provided by the invention passes through what repetition test research was drawn
With preferable transdermal penetration effect, transdermal characteristic is good, and medicine, which penetrates into, easily and effectively meets bactericidal effect.
Brief description of the drawings
Fig. 1 is efficient liquid phase reference substance solution chromatogram；
Fig. 2 is efficient liquid phase sample solution chromatogram；
Fig. 3 is efficient liquid phase negative control chromatogram；
Fig. 4 is the influence figure of carbomer content accumulation infiltration capacity percutaneous to rifampin；
Fig. 5 is the influence figure of content of propylene glycol accumulation infiltration capacity percutaneous to rifampin；
Fig. 6 is the influence figure of content of dispersion accumulation infiltration capacity percutaneous to rifampin；
Fig. 7 is the influence figure of Laurocapram content accumulation infiltration capacity percutaneous to rifampin.
Embodiment
Describe the present invention in detail below with reference to accompanying drawing and in conjunction with the embodiments.
A kind of rifampin gel provided by the invention includes：1.5% rifampin, 10% glycerine, 10% propane diols, 1%
Carbomer, 1.0% Laurocapram, 15% absolute ethyl alcohol and two drop triethanolamines.
One kind provided by the invention prepares rifampin gel method and comprised the following steps：
S1 is equipped with following composition by proportioning：1.5% rifampin, 10% glycerine, 10% propane diols, 1% carbomer,
1.0% bay nitrogenKetone, 15% absolute ethyl alcohol and two drop triethanolamines.
24 hours accumulation infiltration capacity average value of rifampin is (204.14 ± 8.96) μ g/cm2, average release rate is
(7.40±0.47)μg/cm2·h。
S2 soaks rifampin under the conditions of lucifuge with 10% propane diols.
S3 adds 15% absolute ethyl alcohol.
1% carbomer is spread in distilled water by S4, is heated and is stirred 30 minutes in 60 DEG C of water-bath, makes it fully molten
It is swollen, and add two drop triethanolamines.
The mixture of mixture caused by step 2 and 3 and step 4 is added glycerine and bay nitrogen by S5The gel of ketone
Matrix mixes, and adds 100g distilled water and stir.Gel-type vehicle is Carbomer-940.
S6 obtains uniform and stable rifampin glue.
This method is drawn by following experimental verification：
1st, laboratory apparatus and reagent
High performance liquid chromatograph (Agilent-1260-DAD-ELSD)；Chromatographic column (Agilent ZORBAX SB-C18)；
1/10000 electronic balance (FA2004N)；NDJ-1A rotation viscometers；TK-24BL type percutaneous dispersion test instrument.Main agents are shown in
Table 1.
The main agents of table 1 and raw material list
2nd, experimental animal is healthy male SPF levels SD mouse 20 (18~22g).
3rd, chromatographic condition
Agilent ZORBAX SB-C18 (4.6 × 250mm, 5 μm), with acetonitrile-(0.075molL-1 biphosphates
Potassium -1.0molL-1 citric acids (9: 1) (45: 55) are mobile phase, Detection wavelength 254nm, flow velocity 1.0mLmin-1, sample introduction
10 μ L are measured, theoretical cam curve is calculated with rifampin should be not less than 2000.
4th, the preparation of rifampin gel
Rifampin gel is made as stated above.
5th, the preparation of isolated skin
With 10% chloraldurate by after SD mouse anesthesias, with electric shaver shaving, skin is peeled off, removes subcutaneous fat group
Knit, with normal saline flushing, until cleaning fluid is haze-free, is put into 4 DEG C of refrigerators and preserves.Using belly skin in this experiment
Skin.
6th, percutaneous penetration
Take the isolated skin to have thawed to carry out skin penetration test in vitro, made with the slow middle liquid (pH value 7.4) of 8mL phosphate
Osmotic cell is added for acceptable solution.Osmotic cell temperature is maintained at (32 ± 0.1) DEG C, and 1 stirrer, electromagnetic agitation rotating speed are placed in pond
200rpm, diffusion area 3.14cm2.2.0mL is taken respectively at 1h, 3h, 5h, 7h, 9h, 11h, 24h time point, while adds equivalent
Reception liquid.Using concentration of the HPLC measure rifampins in reception liquid, unit area accumulation infiltration capacity is obtained.To accumulate infiltration
It is ordinate to measure (Qn), and the time (t) is abscissa, obtains the accumulation penetration curve of rifampin gel, curve obtained is returned
Return, obtain the permeability J (μ g/cm2h) of rifampin gel.
7th, result
It is as shown in Figure 1 efficient liquid phase reference substance solution chromatogram, Fig. 2 is efficient liquid phase sample solution chromatogram, and Fig. 3 is
Efficient liquid phase negative control chromatogram.
7.1 specificities are tested
Reference substance solution, sample solution, Blank gel solution determine according to chromatographic condition, the material in Blank gel and profit
The flat separating degree of good fortune is good, and the appearance time of rifampin is 11.0min.
7.2 prepare standard curve
Precision weighs rifampin reference substance 0.103g, is 4.12,20.6,41.2 with mobile phase dissolved dilution to concentration,
82.4,123.6,164.8,329.6 μ g/ml need testing solution, high performance liquid chromatograph measure record peak area, respectively with peak
Area A and concentration c (μ g/ml) are mapped for transverse and longitudinal coordinate, and obtaining calibration curve equation is：Y=19.137x-24.059, R2=
0.9995, illustrate rifampin in the range of 4.12~329.6 μ g/ml, its concentration and peak area are in good linear relationship.
7.3 relaxation shrinkages are tested
Compound concentration is that 82.4 μ g/ml rifampins reference substance solutions are added in Blank gel solution, is determined 6 times, average to return
Yield is 103.81%, specific data such as table 2.
The determination of recovery rates result of table 2
7.4 precision determine
With the standard liquid that mobile phase compound concentration is 80.0,100.0,320.0 μ gmL-1, take 1mL and 1mL empty respectively
White gel solution mixes, and takes mixed solution injection liquid chromatograph, records chromatogram, compareed after mixing containing various concentrations
Three sample solution continuous sample introductions of product 6 times, withinday precision is calculated, three test samples containing low middle and high concentration reference substance
RSD values are respectively 0.83%, 0.18%, 0.24%, specific data such as table 3.
The precision measurement result of table 3
Comparative example one
It is illustrated in figure 4 the influence figure of carbomer content accumulation infiltration capacity percutaneous to rifampin.With 10% glycerine, 10% the third
Glycol, 1% rifampin, 10% ethanol, two drop triethanolamines, various concentrations carbomer prepare gel, investigate various concentrations card ripple
Influence of the nurse content (0.5%, 1%, 1.5%) to rifampin gel transdermal penetration, as can be seen from the figure 1.0% carbomer
For matrix when permeability it is best.
Comparative example two
It is illustrated in figure 5 the influence figure of content of propylene glycol accumulation infiltration capacity percutaneous to rifampin.With 10% glycerine, 1.5%
Rifampin, 15% ethanol, two drop triethanolamines, 1% carbomer, various concentrations glycerine prepare gel, investigate various concentrations glycerine
Influence of the content (5%, 10%, 15%) to rifampin gel transdermal penetration.Content of propylene glycol is as can be seen from the figure
When 10% and 15%, the difference of the accumulation infiltration capacity of rifampin gel is smaller, is examined for the result from resource-effective angle
Consider, the propane diols of final choice 10% prepares gel as cosolvent.
Comparative example three
It is illustrated in figure 6 the influence figure of content of dispersion accumulation infiltration capacity percutaneous to rifampin.With 10% glycerine, 10% the third two
Alcohol, 1% carbomer, two drop triethanolamines, various concentrations rifampin prepare gel, investigate various concentrations rifampin content
The influence of (1.5%, 1.8%, 2.0%) to rifampin gel transdermal penetration, it is 1.0% and 1.5% preparation by rifampin content
Rifampin gel transdermal experiment result draw, it will be apparent from this figure that rifampin content be 1.5% when gel it is transdermal
Property is best.
Comparative example four
It is illustrated in figure 7 bay nitrogenThe influence figure of ketone content accumulation infiltration capacity percutaneous to rifampin.With 10% glycerine,
10% propane diols, 1.5% rifampin, 15% ethanol, two drop triethanolamines, various concentrations bay nitrogenKetone prepares gel, investigates
Various concentrations bay nitrogenInfluence of the ketone content (0.5%, 1%, 1.5%, 2.0%) to rifampin gel transdermal penetration, from this
The azone of it can be seen from the figure that 1.0% is more preferable to gel transdermal performance.
The best prescription drawn according to research prepares 3 parts of rifampin gels, completes percutaneous penetration and calculates accumulation respectively
The RSD values of transit dose and transmitance, it the results are shown in Table 4.
The percutaneous abilities checking of the rifampin gel of table 4
1.5% rifampin, 1% card ripple are finally filtered out by the Percutaneous permeability and permeability that compare rifampin gel
Nurse, 15% absolute ethyl alcohol, 10% glycerine, 10% propane diols and 1.0% permeation enhancers bay nitrogenKetone is final prescription, and it has
Preferable transdermal penetration effect.
Embodiments of the invention are the foregoing is only, are not intended to limit the scope of the invention, it is every to utilize this hair
The equivalent structure or equivalent flow conversion that bright specification and accompanying drawing content are made, or directly or indirectly it is used in other related skills
Art field, is included within the scope of the present invention.
Claims (5)
- A kind of 1. rifampin gel, it is characterised in that including：Rifampin, glycerine, propane diols, carbomer, Laurocapram, nothing Water-ethanol and two drop triethanolamines.
- 2. rifampin gel according to claim 1, it is characterised in that the proportioning of each composition is：1.5% rifampin, 10% glycerine, 10% propane diols, 1% carbomer, 1.0% Laurocapram, 15% absolute ethyl alcohol and two drop triethanolamines.
- A kind of 3. method for preparing rifampin gel as claimed in claim 1 or 2, it is characterised in that comprise the following steps：1) rifampin is soaked with 10% propane diols under the conditions of lucifuge；2) 15% absolute ethyl alcohol is added；3) 1% carbomer is spread in distilled water, heats and stir 30 minutes in 60 DEG C of water-bath, it is fully swelled, And add two drop triethanolamines；4) by mixture caused by step 2 and 3 and the mixture of step 4, glycerine and bay nitrogen are addedThe gel-type vehicle of ketone Mixing, and add 100g distilled water and stir；5) uniform and stable rifampin glue is obtained.
- 4. the preparation method of rifampin gel according to claim 1, it is characterised in that the rifampin is accumulated for 24 hours Infiltration capacity average value is 204.14 ± 8.96 μ g/cm2, average release rate is 7.40 ± 0.47 μ g/cm2·h。
- 5. the preparation method of rifampin gel according to claim 1, it is characterised in that the gel base in the step 5 Matter is Carbomer-940.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710819662.5A CN107693484B (en) | 2017-09-06 | 2017-09-06 | Rifampicin gel and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710819662.5A CN107693484B (en) | 2017-09-06 | 2017-09-06 | Rifampicin gel and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN107693484A true CN107693484A (en) | 2018-02-16 |
| CN107693484B CN107693484B (en) | 2021-02-12 |
Family
ID=61172577
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710819662.5A Expired - Fee Related CN107693484B (en) | 2017-09-06 | 2017-09-06 | Rifampicin gel and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107693484B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108653133A (en) * | 2018-06-15 | 2018-10-16 | 吉林化工学院 | A kind of preparation method of the anti-oxidant gelling agent of Maize silk flavones |
| CN108904812A (en) * | 2018-08-27 | 2018-11-30 | 邛崃市医疗中心医院 | With the external drug of the high transdermal characteristic prevention and treatment scapulohumeral periarthritis of carbomer collaboration transdermal agent |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100381124C (en) * | 2004-09-09 | 2008-04-16 | 江苏正大天晴药业股份有限公司 | Magnesium iso-glycyrrhetate gel and its preparing method and use |
| CN101138560B (en) * | 2007-08-17 | 2010-08-25 | 深圳海创医药科技发展有限公司 | Nitrofuran gelling agent and method of preparing the same |
| CN102266340B (en) * | 2010-06-04 | 2014-05-14 | 梁建琴 | Anti-tuberculosis gel preparation |
| RU2014154395A (en) * | 2014-12-30 | 2016-07-27 | Общество С Ограниченной Ответственностью "Научно-Производственный Центр "Амфион" | HYDROGEL MATERIALS WITH AN ADJUSTABLE DATE OF BIODEGRADATION AND PRODUCTS BASED ON THEM |
-
2017
- 2017-09-06 CN CN201710819662.5A patent/CN107693484B/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108653133A (en) * | 2018-06-15 | 2018-10-16 | 吉林化工学院 | A kind of preparation method of the anti-oxidant gelling agent of Maize silk flavones |
| CN108904812A (en) * | 2018-08-27 | 2018-11-30 | 邛崃市医疗中心医院 | With the external drug of the high transdermal characteristic prevention and treatment scapulohumeral periarthritis of carbomer collaboration transdermal agent |
Also Published As
| Publication number | Publication date |
|---|---|
| CN107693484B (en) | 2021-02-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102988291B (en) | Flurbiprofen axetil fat emulsion injection composition and preparation method thereof | |
| Yang et al. | A novel drug delivery gel of terbinafine hydrochloride with high penetration for external use | |
| CN114870016B (en) | Micro-emulsion foaming agent of JAK inhibitor and application thereof | |
| CN106619486A (en) | Propranolole hydrochloride gel and preparation method thereof | |
| Xu et al. | Novel therapeutic modalities and drug delivery–erlotinib liposomes modified with galactosylated lipid: In vitro and in vivo investigations | |
| CN107303263B (en) | Tripterygium glycosides nanoemulsion gel and preparation method thereof | |
| Pichayakorn et al. | Transdermal nicotine mixed natural rubber-hydroxypropylmethylcellulose film forming systems for smoking cessation: in vitro evaluations | |
| Wu et al. | Microemulsions vs chitosan derivative-coated microemulsions for dermal delivery of 8-methoxypsoralen | |
| CN107693484A (en) | A kind of rifampin gel and preparation method thereof | |
| CN102657602B (en) | 3,5-dyhydroxyl-4-isopropyl diphenylethene chitosan gel and preparation method thereof | |
| CN109718228A (en) | The antitumor Lymph Node Metastasis of mitoxantrone acts on and its pharmaceutical preparation | |
| CN109481404A (en) | A kind of preparation method of pH sensitivity imidazoles liposome | |
| CN108721218A (en) | A kind of alkannin liposome and preparation method thereof | |
| CN101439083A (en) | Chinese medicine soft capsules for clearing wind heat and clearing nasal passage, as well as preparation method and quality control method | |
| CN111789828A (en) | Etimicin sulfate liposome inhalant and preparation method thereof | |
| CN101601652A (en) | Momestasone furoate lipidosome cream | |
| CN104274826B (en) | A kind of oil-in-water type compound colistin nano-emulsion | |
| Petrov et al. | Chromatographic profile and redox-modulating capacity of methanol extract from seeds of Ginkgo biloba L. originating from plovdiv region in Bulgaria | |
| CN101485632B (en) | Nimodipine lipid microsphere injection and preparation method thereof | |
| CN106727503A (en) | A kind of medicine and its quality determining method for treating cardiovascular and cerebrovascular disease | |
| CN103284975B (en) | Metformin hydrochloride enteric capsule and preparation method thereof | |
| AU2016346203A1 (en) | Isotretinoin formulations and uses and methods thereof | |
| Amnuaikit et al. | Enhancement of Mycophenolate Mofetil Permeation for Topical Use by Eucalyptol and N‐Methyl‐2‐pyrrolidone | |
| CN105919974B (en) | Salmon calcitonin phosphatide complexes and its lipid nano particle and preparation method | |
| Li et al. | Toxicokinetics and toxicity of potassium 2-(1-hydroxypentyl)-benzoate in beagle dogs |
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 | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20210212 Termination date: 20210906 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |