CN104138353A - Tazarotene gelata and preparation method thereof - Google Patents
Tazarotene gelata and preparation method thereof Download PDFInfo
- Publication number
- CN104138353A CN104138353A CN201310401701.1A CN201310401701A CN104138353A CN 104138353 A CN104138353 A CN 104138353A CN 201310401701 A CN201310401701 A CN 201310401701A CN 104138353 A CN104138353 A CN 104138353A
- Authority
- CN
- China
- Prior art keywords
- tazarotene
- solution
- gel
- preparation
- gel agent
- 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
Abstract
The invention discloses a tazarotene gelata and a preparation method thereof. The preparation is prepared form the active ingredient tazarotene and auxiliary materials. The auxiliary materials include methyl cyclodextrin and sodium alginate. The preparation method includes: dissolving methyl cyclodextrin in water, adding a prescribed amount of quantity of tazarotene, conducting stirring for dissolving so as to obtain a solution I; dissolving sodium alginate and a bacteriostatic agent in water to obtain a solution II; and mixing the two solutions and stirring the mixture evenly, thus obtaining the gelata. The tazarotene gelata provided by the invention has the advantages of simple preparation process, good gel stability, few variety of auxiliary materials, and easy coating.
Description
Technical field
The invention belongs to technical field of medicine, in particular to a kind of medicine external preparation, relate in particular to a kind of Tazarotene gel agent and preparation method thereof.
Background technology
Acne is the chronic pilosebaceous unit disease due to many factors comprehensive function.First Histological change is dyskeratosis.At infundibulum of hair follicle portion cutin, pile up and form thromboembolism, cause micropowder thorn to form.Sebum increases and adds that horn cell is further piled up and make micropowder thorn become opening or closed comedones, i.e. blackhead or hoary hair's acne (non-inflammatory acne).Above-mentioned environment is conducive to the breeding of propionibacterium acnes.The latter discharges chemotactic factor, causes neutrophil infiltration, causes acne to be broken, and develops into inflammatory pimple or pustule (acne).Therefore, rapidly effectively the formation of containment micropowder thorn is to stop the state of an illness to further develop and the key of Acne treatment.
Tazarotene is a kind of novel specific receptor-selective tretinoin medicines.The mechanism of external tazarotene Acne treatment is: suppress sebum secretion, hair follicle stimulating epithelium conversion ratio increases, and causes horn cell cohesive strength to reduce, and makes acne become flexible and get rid of.Due to anti-cutinization, destroy anaerobic environment, thereby destroyed the existence of the propionibacterium acnes of anaerobism, indirectly bring into play antiinflammatory action, suppress cicatrization simultaneously.Therefore, tazarotene can be at a plurality of link Acne treatments, and especially its strong effective anti-acne forms ability.Tazarotene topical application is retained in skin surface or skin mostly, system absorbtivity is limited, local topical 0.1% Tazarotene gel treatment facial acne 26d, blood plasma top level is 0.14ng/mL, after tazarotene Transdermal absorption, can be metabolized to rapidly water soluble metabolites, get rid of rapidly drug safety.
The chemistry of tazarotene is by name: 6-[(3,4-dihydro-4,4-dimethyl-2H-1-benzo thiapyran-6-yl) acetenyl]-Niacin Nicitinic Acid ethyl ester.The carboxylic acid, ethyl ester group of this compound is easy to hydrolysis, affects curative effect of medication and drug safety.In addition, tazarotene is easily molten in benzyl alcohol, in ethyl acetate, dissolves, slightly molten in acetonitrile, and slightly soluble in ethanol is almost insoluble in water.Because tazarotene is insoluble in water, cause medicine dissolubility in substrate low, be difficult for being uniformly dispersed, gel particle diameter skewness and particle diameter are larger, and stability is bad, is easy to occur the underproof phenomenon of particle diameter in storing process.
CN1528313A discloses a kind of psoriatic complex external medicine for the treatment of, and contains following effective active composition (percentage by weight): tazarotene 0.025～0.1%, 17-hydroxy-11-dehydrocorticosterone 0.01～0.2%; This external used medicine is made gel, ointment by above-mentioned effective active composition and conventional substrate carrier.
CN1528328A discloses a kind of complex external medicine that is used for the treatment of a skin ulcer, contains tazarotene 0.01～2%, antimicrobial drug 0.25～5%.This external used medicine is made gel, ointment by above-mentioned effective active composition and conventional substrate carrier.
CN102988987A
Disclose a kind of pharmaceutical composition and preparation thereof that is used for the treatment of hyperproliferative epidermal diseases, contain calcipotriol 0.001～0.01%(W/W), tazarotene 0.05～2%(W/W), adrenal cortex hormones drug 0.05～2%(W/W).The prescription of its gel and preparation technology are: the carbomer of recipe quantity or sodium carboxymethyl cellulose are joined to 30ml distilled water with polyoxyethylene sorbitan monoleate and mix, after the sodium hydroxide of getting recipe quantity is dissolved in 10ml distilled water, add liquid to stir evenly, then the ethyl hydroxybenzoate of recipe quantity is dissolved in add gradually to stir evenly after the ethanol of recipe quantity and obtains gel-type vehicle; A small amount of glycerol porphyrize, the dispersion for calcipotriol, tazarotene and adrenal cortex hormones drug of separately getting recipe quantity, be mixed in gel-type vehicle, regulates after pH to 7.0, and distilled water adds to 100g and stirs evenly and get final product.
In prior art, gel matrix material is selected complexity, as adopt hexadecanol, vaseline, liquid paraffin, glyceryl monostearate, glycerol, solubilizing agent, emulsifying agent, ethyl hydroxybenzoate etc., but all the carboxylic acid, ethyl ester group hydrolysis how effectively suppressing in medicine is not proposed to solution.
Summary of the invention
For the deficiencies in the prior art, first object of inventor is by the lot of experiments research of writing out a prescription, and provides that a kind of technique is simple, good stability, Tazarotene gel agent that supplementary product kind is few.
The a large amount of creative experiments of inventor's process, are surprised to find that, when selecting sodium alginate as gel-type vehicle, gel not only denseness is suitable, is easy to coating, and more making us unforeseeable is that medicine stability significantly improves.Concrete, inventor studies and unremitting thinking by lot of experiments, has finally obtained following technical scheme:
A Tazarotene gel agent, is prepared from by active component tazarotene and adjuvant, and described adjuvant comprises Methyl flamprop and sodium alginate.
Preferably, above-mentioned Tazarotene gel agent, wherein the weight ratio of tazarotene and Methyl flamprop is 1:30-100.
Further preferably, above-mentioned Tazarotene gel agent, wherein the weight ratio of tazarotene and Methyl flamprop is 1:40-70.
Preferably, above-mentioned Tazarotene gel agent, wherein the quality volumn concentration of sodium alginate in gel is 2%-8%.
Further preferably, above-mentioned Tazarotene gel agent, wherein the quality volumn concentration of sodium alginate in gel is 3%-5%.
Again further preferably, above-mentioned Tazarotene gel agent, wherein said adjuvant is comprised of Methyl flamprop, sodium alginate, antibacterial and water.
In embodiment preferred for this invention, the quality volumn concentration of each component of above-mentioned Tazarotene gel agent is in following scope:
Again further preferably, above-mentioned Tazarotene gel agent, wherein said antibacterial is selected from following one or more: methyl parahydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, sodium benzoate.
Second object of the present invention is to provide a kind of preparation method of above-mentioned Tazarotene gel agent, and the method comprises the steps:
(1) Methyl flamprop is dissolved in water, adds recipe quantity tazarotene, be stirred to dissolve, obtain solution I;
(2) sodium alginate and antibacterial are dissolved in water, obtain solution II;
(3) solution I is mixed with solution II, stir, obtain Tazarotene gel.
Preferably, the preparation method of above-mentioned Tazarotene gel agent, wherein said antibacterial is selected from following one or more: methyl parahydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, sodium benzoate.
Tazarotene gel technique of the present invention is simple, good stability, and supplementary product kind is few, is easy to coating.Be embodied in: tazarotene, with adding with solution form after Methyl flamprop solubilising, has avoided medicine to be difficult to the problem of mix homogeneously, and Methyl flamprop has also improved medicine stability simultaneously; Select sodium alginate as gel-type vehicle, prepared gel not only denseness is suitable, is easy to coating, and has suppressed the hydrolysis of medicine, has obtained stay-in-grade Tazarotene gel.
The specific embodiment
Now by following examples, further describe preparation process of the present invention and implementation result, embodiment is only for the object of illustration, do not limit the scope of the invention, within the apparent change that those of ordinary skills make according to the present invention simultaneously and modification are also contained in the scope of the invention.
Embodiment 1 Tazarotene gel agent prescription and preparation technology
Preparation technology:
(1) Methyl flamprop of recipe quantity is dissolved in 20ml water, adds recipe quantity tazarotene, be stirred to dissolve, obtain solution I;
(2) sodium alginate of recipe quantity, ethylparaben are dissolved in 60ml water, obtain solution II;
(3) solution I is mixed with solution II, add water to 100ml, stir, obtain gel.
Embodiment 2 Tazarotene gel agent prescription and preparation technologies
Preparation technology:
(1) Methyl flamprop of recipe quantity is dissolved in 15ml water, adds recipe quantity tazarotene, be stirred to dissolve, obtain solution I;
(2) sodium alginate of recipe quantity, ethylparaben are dissolved in 70ml water, obtain solution II;
(3) solution I is mixed with solution II, add water to 100ml, stir, obtain gel.
Embodiment 3 Tazarotene gel agent prescription and preparation technologies
Preparation technology:
(1) Methyl flamprop of recipe quantity is dissolved in 20ml water, adds recipe quantity tazarotene, be stirred to dissolve, obtain solution I;
(2) sodium alginate of recipe quantity, sodium benzoate are dissolved in 60ml water, obtain solution II;
(3) solution I is mixed with solution II, add water to 100ml, stir, obtain gel.
Comparative example 1 Tazarotene gel agent prescription and preparation technology
Preparation technology:
(1) HYDROXYPROPYL BETA-CYCLODEXTRIN of recipe quantity is dissolved in 20ml water, adds recipe quantity tazarotene, be stirred to dissolve, obtain solution I;
(2) sodium alginate of recipe quantity, sodium benzoate are dissolved in 60ml water, obtain solution II;
(3) solution I is mixed with solution II, add water to 100ml, stir, obtain gel.
Comparative example 2 Tazarotene gel agent prescription and preparation technologies
Preparation technology:
(1) Methyl flamprop of recipe quantity is dissolved in 20ml water, adds recipe quantity tazarotene, be stirred to dissolve, obtain solution I;
(2) hydroxypropyl emthylcellulose of recipe quantity, sodium benzoate are dissolved in 60ml water, obtain solution II;
(3) solution I is mixed with solution II, add water to 100ml, stir, obtain gel.
Comparative example 3 Tazarotene gel agent prescription and preparation technologies
Preparation technology:
Tazarotene is dissolved in propylene glycol; Hexadecanol, octadecanol, glyceryl monostearate heating and melting, add vaseline, liquid paraffin, sorbester p18, stirs; Two kinds of solution are mixed, add benzyl alcohol, be stirred to dissolve, add water to recipe quantity, stir, obtain gel.
The experimental study of embodiment 4 Tazarotene gel agent stability
1. related substance: it is appropriate to get this product, adds mobile phase and makes in every 1ml approximately solution containing 16 μ g as need testing solution; Precision measures 1.5ml, puts in 100ml measuring bottle, adds mobile phase and is diluted to scale, shakes up, in contrast solution.According to the chromatographic condition under assay item, get contrast solution 20 μ l injection liquid chromatographies, regulate detection sensitivity, make the peak height at main constituent peak be about 20% of full scale, precision measures need testing solution and each 20 μ l injection liquid chromatographies of contrast solution again, records chromatogram to 2 times of main constituent peak retention time.In need testing solution chromatogram, if any impurity peaks, the area sum of each impurity peaks must not be greater than the main peak area (1.0%) of contrast solution.
2. assay: measure according to high performance liquid chromatography (two appendix V D of Chinese Pharmacopoeia version in 2010).Chromatographic condition and system suitability: with octadecylsilane chemically bonded silica, be filler; Isopropyl alcohol-acetonitrile-water (530:380:90) is mobile phase; Detect wavelength 325nm.Number of theoretical plate calculates and should be not less than 5000 by tazarotene peak, and the separating degree of tazarotene peak and adjacent impurity peaks should be up to specification.
Algoscopy: precision takes at 60 ℃ of drying under reduced pressure appropriate to the tazarotene reference substance of constant weight, adds mobile phase and dissolves and dilute and make in every 1ml approximately containing the solution of 16 μ g, and precision measures 20 μ l injection liquid chromatographies, records chromatogram; Separately get this product appropriate, be measured in the same method, by external standard method, with calculated by peak area, obtain.
Table 1 tazarotene content and determination of related substances result (40 ℃, 75%RH accelerates 6 months)
The variation of Tazarotene gel state before and after table 2 accelerated test
According to the experimental result of table 1, table 2, show, Tazarotene gel prepared by embodiment of the present invention 1-3 is after accelerating investigation, and content and related substance are substantially constant, and outward appearance is uniform solution; Comparative example's 1 use HYDROXYPROPYL BETA-CYCLODEXTRIN replaces Methyl flamprop, content declines soon compared with the present invention, related substance increases obviously, has a small amount of particulate matter to occur, may be because Methyl flamprop more can effectively be protected relevant with solubilize drugs compared with HYDROXYPROPYL BETA-CYCLODEXTRIN; Comparative example 2 adopts hydroxypropyl emthylcellulose to replace sodium alginate, and medicament contg declines, and related substance increases significantly; The gel of comparative example's 3 preparations is through accelerating investigation, and related substance increases obviously, and content declines more, occurs a large amount of particulate matters, illustrates that prior art not can solve the problem of separating out that medicine causes because of poor solubility, and stability is also poor.
Claims (10)
1. a Tazarotene gel agent, is prepared from by active component tazarotene and adjuvant, it is characterized in that: described adjuvant comprises Methyl flamprop and sodium alginate.
2. Tazarotene gel agent according to claim 1, is characterized in that: the weight ratio of tazarotene and Methyl flamprop is 1:30-100.
3. Tazarotene gel agent according to claim 2, is characterized in that: the weight ratio of tazarotene and Methyl flamprop is 1:40-70.
4. Tazarotene gel agent according to claim 1, is characterized in that: the quality volumn concentration of sodium alginate in gel is 2%-8%.
5. Tazarotene gel agent according to claim 4, is characterized in that: the quality volumn concentration of sodium alginate in gel is 3%-5%.
6. according to the Tazarotene gel agent described in claim 1-5 any one, it is characterized in that: described adjuvant is comprised of Methyl flamprop, sodium alginate, antibacterial and water.
7. Tazarotene gel agent according to claim 6, is characterized in that: the quality volumn concentration of each component is:
8. Tazarotene gel agent according to claim 6, is characterized in that: described antibacterial is selected from following one or more: methyl parahydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, sodium benzoate.
9. a preparation method for Tazarotene gel agent according to claim 6, is characterized in that comprising the steps:
(1) Methyl flamprop is dissolved in water, adds recipe quantity tazarotene, be stirred to dissolve, obtain solution I;
(2) sodium alginate and antibacterial are dissolved in water, obtain solution II;
(3) solution I is mixed with solution II, stir, obtain Tazarotene gel.
10. the preparation method of Tazarotene gel agent according to claim 9, is characterized in that: described antibacterial is selected from following one or more: methyl parahydroxybenzoate, ethylparaben, propyl p-hydroxybenzoate, sodium benzoate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310401701.1A CN104138353B (en) | 2013-09-05 | 2013-09-05 | A kind of Tazarotene gel agent and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310401701.1A CN104138353B (en) | 2013-09-05 | 2013-09-05 | A kind of Tazarotene gel agent and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104138353A true CN104138353A (en) | 2014-11-12 |
| CN104138353B CN104138353B (en) | 2016-06-22 |
Family
ID=51847808
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310401701.1A Expired - Fee Related CN104138353B (en) | 2013-09-05 | 2013-09-05 | A kind of Tazarotene gel agent and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104138353B (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6730308B1 (en) * | 1999-03-08 | 2004-05-04 | Allergan, Inc. | Tazarotene and alpha hydroxy acid treatment for psoriasis and/or photodamage |
| CN1528328A (en) * | 2003-09-29 | 2004-09-15 | 中国医学科学院皮肤病研究所 | Complex external medicine for treating acne |
| CN1989956A (en) * | 2005-12-29 | 2007-07-04 | 北京德众万全医药科技有限公司 | Adapalene gel composition and its preparation |
| WO2008017914A2 (en) * | 2006-08-08 | 2008-02-14 | Fernando Ahumada Ayala | Topical antiacne preparations containing retinoid (tazarotene or adapalene), antibiotic (clindamycin phosphate) and/or keratolytic (miscrosponged benzoyl peroxide) |
| CN102988987A (en) * | 2012-12-13 | 2013-03-27 | 西安力邦制药有限公司 | Pharmaceutical composition for treating hyperproliferative skin disease and preparation of pharmaceutical composition |
-
2013
- 2013-09-05 CN CN201310401701.1A patent/CN104138353B/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6730308B1 (en) * | 1999-03-08 | 2004-05-04 | Allergan, Inc. | Tazarotene and alpha hydroxy acid treatment for psoriasis and/or photodamage |
| CN1528328A (en) * | 2003-09-29 | 2004-09-15 | 中国医学科学院皮肤病研究所 | Complex external medicine for treating acne |
| CN1989956A (en) * | 2005-12-29 | 2007-07-04 | 北京德众万全医药科技有限公司 | Adapalene gel composition and its preparation |
| WO2008017914A2 (en) * | 2006-08-08 | 2008-02-14 | Fernando Ahumada Ayala | Topical antiacne preparations containing retinoid (tazarotene or adapalene), antibiotic (clindamycin phosphate) and/or keratolytic (miscrosponged benzoyl peroxide) |
| CN102988987A (en) * | 2012-12-13 | 2013-03-27 | 西安力邦制药有限公司 | Pharmaceutical composition for treating hyperproliferative skin disease and preparation of pharmaceutical composition |
Non-Patent Citations (3)
| Title |
|---|
| DINA N. ANDERSON等: "Topical Tazarotene in Acne Vulgaris:Treatment Approaches", 《CUTIS》 * |
| 张爱军等: "他扎罗汀壳聚糖凝胶的制备与质量标准研究", 《中国药业》 * |
| 阮健等: "痤疮外用凝胶治疗研究进展", 《中南药学》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104138353B (en) | 2016-06-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Hasa et al. | Drug salt formation via mechanochemistry: the case study of vincamine | |
| CN102151242A (en) | In-situ gel slow-release preparation for anti-tuberculosis drugs and preparation method thereof | |
| CN102657602B (en) | 3,5-dyhydroxyl-4-isopropyl diphenylethene chitosan gel and preparation method thereof | |
| CN103181923A (en) | Medicinal preparation containing repaglinide and preparation of medicinal preparation | |
| CN101292991A (en) | Compound gelling agent containing clindamycinum | |
| CN104138353B (en) | A kind of Tazarotene gel agent and preparation method thereof | |
| TW201513894A (en) | A pharmaceutical composition for skin external use comprising icotinib and the application thereof | |
| CN103405780B (en) | Ointment containing tretinoin inclusion compound and clobetasol propionate and preparation method thereof | |
| CN104667258A (en) | Octreotide acetate tablet and preparation method thereof | |
| CN102846572A (en) | Diclofenac sodium sustained release tablet and preparation method thereof | |
| CN103405383B (en) | Clindamycin phosphate gel and preparation method thereof | |
| Zhang et al. | Comprehensive Bioanalysis of Ultrahigh Molecular Weight, Highly Disperse Poly (ethylene oxide) in Rat via Microsolid Phase Extraction and RPLC-QQ-TOF Coupled with the MSALL Technique | |
| CN102920651A (en) | Flurbiprofen axetil micro-emulsion gel preparation and preparation method thereof | |
| D’Alessandro et al. | Competitive binding of aqueous perfluoroctanesulfonic acid and ibuprofen with bovine serum albumin studied by electrospray ionization mass spectrometry | |
| CN102697703B (en) | Piroxicam gel preparation and preparation method thereof | |
| CN102813624B (en) | Lidocaine ethosome and preparation method thereof | |
| CN102846624B (en) | Compound telmisartan hydrochlorothiazide pharmaceutical composition and preparation method thereof | |
| CN103040843B (en) | Solid dispersion containing clobetasol propionate and tretinoin and preparation method thereof | |
| BasuSarkar et al. | Chemical stability of compounded spironolactone suspension in proprietary oral MixTM over a 90-day period at two controlled temperatures in different storage containers | |
| Veerareddy et al. | Preparation and evaluation of mucoadhesive cefdinir microcapsules | |
| CN104173278A (en) | Subcutaneous injection administration system based on Brij97 liquid crystal and preparation method of subcutaneous injection administration system based on Brij97 liquid crystal | |
| CN108815174A (en) | A kind of modified form fat-soluble compositions and preparation method thereof | |
| Adibkia et al. | Serum concentrations and hypoglycemic effect of gliclazide: Crosspovidone solid dispersion on streptozotocin induced diabetic rats | |
| CN103877073B (en) | A kind of disodium cantharidinate controlled release preparation and preparation method thereof | |
| CN110124046B (en) | Diclofenac diethylamine loaded on graphene oxide and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CP03 | Change of name, title or address |
Address after: 225400 No. 8, Zhong Dan Road, Hongqiao Town, Taixing, Jiangsu. Patentee after: Jiangsu Xiaolin Pharmaceutical Co., Ltd. Address before: 225453 No. 8, Zhong Dan Road, Hongqiao Town, Taixing City, Taizhou, Jiangsu. Patentee before: Jiangsu Zhongdan Pharmaceutical Co., Ltd. |
|
| CP03 | Change of name, title or address | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20160622 Termination date: 20200905 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |