CN105287420A - Leflunomide tablet for treating adult rheumatoid arthritis - Google Patents
Leflunomide tablet for treating adult rheumatoid arthritis Download PDFInfo
- Publication number
- CN105287420A CN105287420A CN201510874476.2A CN201510874476A CN105287420A CN 105287420 A CN105287420 A CN 105287420A CN 201510874476 A CN201510874476 A CN 201510874476A CN 105287420 A CN105287420 A CN 105287420A
- Authority
- CN
- China
- Prior art keywords
- leflunomide
- rheumatoid arthritis
- tablet
- adult rheumatoid
- starch
- 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.)
- Pending
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a leflunomide tablet for treating adult rheumatoid arthritis, and belongs to the technical field of medicines. The composition is prepared from leflunomide, lactose, starch, hydroxy propyl cellulose, lauryl sodium sulfate, superfine silica powder, polyethylene glycol 6,000, sodium carboxymethyl starch and magnesium stearate. The leflunomide is a novel crystal compound. An experiment shows that the medicine is fast to dissolve, simple in preparation technology and applicable to mass production.
Description
Technical field
The invention belongs to medical art, relate to a kind of leflunomide tablet for the treatment of adult rheumatoid arthritis.
Background technology
Leflunomide (leflunomide) is the new drug that first of ratifying in recent ten years is specifically designed to treatment rheumatoid arthritis.This product has immunosuppressant and antiinflammatory action, its mechanism of action is novel, and its T suppression cell sticks the activity with acid kinase, affects the Information Conduction of cytokine, suppress the activity of dihydroorate dehydrogenase, thus inhibit the propagation of relevant activated lymphocytes of falling ill to rheumatoid arthritis.Zoopery and clinical effectiveness display, leflunomide suppresses local inflammation and connective tissue proliferation and arthritic general reaction, it is effective medicine of first this chronic disease of rheumatoid arthritis progress that can slow down, it can not only lower various indication and the symptom of Patients With Rheumatoid Arthritis, and the structure that rheumatoid arthritis can be stoped to cause is downright bad.X-ray result shows, this product is used all to be significantly improved in joint erosions and joint space narrow etc., this is different from existing resisting rheumatoid disease arthritis drug and comprises methotrexate and willow sulfoamide pyridine etc., first medicine showing definite curative effect in objective indicator, and have that rapid-action, use safety, toleration are good, patient can the feature such as long-term taking.
Leflunomide poorly water-soluble, adopts conventional tablet prescription and preparation method, is difficult to improve its dissolution, also affects its bioavailability and curative effect thus.
Summary of the invention
Goal of the invention of the present invention is to provide a kind of leflunomide tablet for the treatment of adult rheumatoid arthritis.
In order to complete object of the present invention, the technical scheme of employing is:
A kind of leflunomide tablet for the treatment of adult rheumatoid arthritis, consist of the following composition: 10-15g leflunomide, 40-50g lactose, 40-50g starch, 15-20g hydroxypropyl cellulose, 5-7g sodium lauryl sulphate, 3-5g micropowder silica gel, 1-3g polyethylene glycol 6000, 2-4g carboxymethyl starch sodium, 0.5-0.7g magnesium stearate, described leflunomide is crystal, measure by powder X-ray diffraction algoscopy, the X-ray powder diffraction pattern represented with the 2 θ ± 0.2 ° angle of diffraction is at 26.6 °, 30.02 °, 33.16 °, 34.02 °, 35.5 °, 35.56 °, 44.1 °, 53.34 ° and 72.9 ° of places demonstrate characteristic diffraction peak.
The leflunomide tablet of described treatment adult rheumatoid arthritis, preparation method is, leflunomide is pulverized, take after leflunomide and lactose, starch, sodium lauryl sulphate, polyethylene glycol 6000 mix, the hydroxypropyl cellulose aqueous solution adding weight concentration 8 ~ 10% is appropriate, soft material processed, granulation, forced air drying, granulate, add magnesium stearate and the micropowder silica gel of recipe quantity, mixing, tabletting, to obtain final product.
The leflunomide tablet of described treatment adult rheumatoid arthritis, consists of the following composition: 12g leflunomide, 45g lactose, 45g starch, 18g hydroxypropyl cellulose, 6g sodium lauryl sulphate, 4g micropowder silica gel, 2g polyethylene glycol 6000,3g carboxymethyl starch sodium, 0.6g magnesium stearate.
The application of leflunomide tablet in preparation treatment adult rheumatoid arthritis medicine of described treatment adult rheumatoid arthritis.
The present inventor obtains a kind of leflunomide novel crystal forms structure being different from prior art through a large amount of tests, and by test, show that the leflunomide tablet stability that this novel crystal forms structure makes the present invention prepare strengthens, dissolution improves, preparation technology is comparatively simple, is applicable to industrialized great production.
Accompanying drawing explanation
Fig. 1 is the X-ray powder diffraction that the leflunomide crystal of the embodiment of the present invention 1 preparation uses the measurement of Cu-K alpha ray to obtain.
Detailed description of the invention
Now further describe preparation process of the present invention and implementation result by following examples, embodiment is only for the object of illustration, do not limit the scope of the invention, the simultaneously apparent change made according to the present invention of those of ordinary skill in the art and modification are also contained within the scope of the invention.
Embodiment 1: the preparation of leflunomide crystal
(1) leflunomide is dissolved in the solvent of N-methylacetamide, and the solvent load that needs of every g leflunomide is 100ml; (2), after being heated to 40 DEG C of dissolvings, after cool to room temperature, crystal seed is added; (3) be cooled to less than 0 DEG C, stirring and crystallizing, the temperature of crystallize is-10 DEG C, filters, dry, collects crystal and namely obtains leflunomide crystal.
The leflunomide crystal powder X-ray diffraction algoscopy prepared measures, and the X-ray powder diffraction pattern represented with the 2 θ ± 0.2 ° angle of diffraction demonstrates characteristic diffraction peak at 26.6 °, 30.02 °, 33.16 °, 34.02 °, 35.5 °, 35.56 °, 44.1 °, 53.34 ° and 72.9 ° of places.
Embodiment 2
Get 10g leflunomide, 50g lactose, 40g starch, 20g hydroxypropyl cellulose, 5g sodium lauryl sulphate, 5g micropowder silica gel, 1g polyethylene glycol 6000, 4g carboxymethyl starch sodium, 0.5g magnesium stearate, preparation method is, leflunomide is pulverized, take leflunomide and lactose, starch, sodium lauryl sulphate, after polyethylene glycol 6000 mixing, the hydroxypropyl cellulose aqueous solution adding weight concentration 8 ~ 10% is appropriate, soft material processed, granulate, forced air drying, granulate, add magnesium stearate and the micropowder silica gel of recipe quantity, mixing, tabletting, obtain 1000 leflunomide tablets.
Described leflunomide is crystal, measure by powder X-ray diffraction algoscopy, the X-ray powder diffraction pattern represented with the 2 θ ± 0.2 ° angle of diffraction demonstrates characteristic diffraction peak at 26.6 °, 30.02 °, 33.16 °, 34.02 °, 35.5 °, 35.56 °, 44.1 °, 53.34 ° and 72.9 ° of places.
Embodiment 3
Get 15g leflunomide, 40g lactose, 50g starch, 15g hydroxypropyl cellulose, 7g sodium lauryl sulphate, 3g micropowder silica gel, 3g polyethylene glycol 6000, 2g carboxymethyl starch sodium, 0.7g magnesium stearate, preparation method is, leflunomide is pulverized, take leflunomide and lactose, starch, sodium lauryl sulphate, after polyethylene glycol 6000 mixing, the hydroxypropyl cellulose aqueous solution adding weight concentration 8 ~ 10% is appropriate, soft material processed, granulate, forced air drying, granulate, add magnesium stearate and the micropowder silica gel of recipe quantity, mixing, tabletting, obtain 1000 leflunomide tablets.
Described leflunomide is crystal, measure by powder X-ray diffraction algoscopy, the X-ray powder diffraction pattern represented with the 2 θ ± 0.2 ° angle of diffraction demonstrates characteristic diffraction peak at 26.6 °, 30.02 °, 33.16 °, 34.02 °, 35.5 °, 35.56 °, 44.1 °, 53.34 ° and 72.9 ° of places.
Embodiment 4
Get 12g leflunomide, 45g lactose, 45g starch, 18g hydroxypropyl cellulose, 6g sodium lauryl sulphate, 4g micropowder silica gel, 2g polyethylene glycol 6000, 3g carboxymethyl starch sodium, 0.6g magnesium stearate, preparation method is, leflunomide is pulverized, take leflunomide and lactose, starch, sodium lauryl sulphate, after polyethylene glycol 6000 mixing, the hydroxypropyl cellulose aqueous solution adding weight concentration 8 ~ 10% is appropriate, soft material processed, granulate, forced air drying, granulate, add magnesium stearate and the micropowder silica gel of recipe quantity, mixing, tabletting, obtain 1000 leflunomide tablets.
Described leflunomide is crystal, measure by powder X-ray diffraction algoscopy, the X-ray powder diffraction pattern represented with the 2 θ ± 0.2 ° angle of diffraction demonstrates characteristic diffraction peak at 26.6 °, 30.02 °, 33.16 °, 34.02 °, 35.5 °, 35.56 °, 44.1 °, 53.34 ° and 72.9 ° of places.
Comparative example 1: embodiment 1 method being CN101816637B according to public announcement of a patent application number prepares leflunomide tablet.
Comparative example 2: the embodiment method being CN103989675B according to public announcement of a patent application number prepares leflunomide tablet.
The dissolution determination experiment of embodiment 5 leflunomide tablet
According to dissolution method (Chinese Pharmacopoeia version in 2010 two annex XC second methods).Respectively with 0.1mol/L hydrochloric acid solution 900mL for dissolution medium, rotating speed is 75 turns per minute, operate in accordance with the law, solution 10mL (adding synthermal dissolution medium 10mL after every sub-sampling) is respectively got respectively at 5min, 15min, filter, precision measures subsequent filtrate 2mL (40mg specification) or 1mL (80mg specification), put in 10mL measuring bottle, scale is diluted to dissolution medium, shake up, according to high performance liquid chromatography (Chinese Pharmacopoeia two annex IV A in 2010), adopt AgilentODS (4.6mm3250mm, 5 μm) chromatographic column; Mobile phase: acetonitrile-methanol-0.02mol2L-1KH2PO4 solution (15:20:55); Flow velocity: 1.5mL2min-1; Determined wavelength 254nm; Separately get leflunomide reference substance, accurately weighed, add stripping medium dissolves and quantitatively dilute the solution made about containing 10 μ g in every 1 milliliter, being measured in the same method, calculating the stripping quantity of every sheet, in table 1.
Leflunomide tablet dissolution determination result prepared by each embodiment of table 1
| Sample source | 5min dissolution (%) | 5min dissolution (%) |
| Embodiment 2 | 97.1 | 99.6 |
| Embodiment 3 | 97.8 | 99.9 |
| Embodiment 4 | 96.2 | 99.3 |
| Comparative example 1 | 58.9 | 72.4 |
| Comparative example 2 | 65.7 | 78.3 |
As can be seen from the experimental result of table 1, leflunomide tablet stripping prepared by various embodiments of the present invention is rapid, the basic stripping completely of 5min; Comparative example 1 and comparative example 2 stripping slow.
Claims (4)
1. treat the leflunomide tablet of adult rheumatoid arthritis for one kind, it is characterized in that consisting of the following composition: 10-15g leflunomide, 40-50g lactose, 40-50g starch, 15-20g hydroxypropyl cellulose, 5-7g sodium lauryl sulphate, 3-5g micropowder silica gel, 1-3g polyethylene glycol 6000, 2-4g carboxymethyl starch sodium, 0.5-0.7g magnesium stearate, described leflunomide is crystal, measure by powder X-ray diffraction algoscopy, the X-ray powder diffraction pattern represented with the 2 θ ± 0.2 ° angle of diffraction is at 26.6 °, 30.02 °, 33.16 °, 34.02 °, 35.5 °, 35.56 °, 44.1 °, 53.34 ° and 72.9 ° of places demonstrate characteristic diffraction peak.
2. treat the leflunomide tablet of adult rheumatoid arthritis as claimed in claim 1, it is characterized in that preparation method is, leflunomide is pulverized, take after leflunomide and lactose, starch, sodium lauryl sulphate, polyethylene glycol 6000 mix, the hydroxypropyl cellulose aqueous solution adding weight concentration 8 ~ 10% is appropriate, soft material processed, granulation, forced air drying, granulate, add magnesium stearate and the micropowder silica gel of recipe quantity, mixing, tabletting, to obtain final product.
3. treat the leflunomide tablet of adult rheumatoid arthritis as claimed in claim 1, it is characterized in that consisting of the following composition: 12g leflunomide, 45g lactose, 45g starch, 18g hydroxypropyl cellulose, 6g sodium lauryl sulphate, 4g micropowder silica gel, 2g polyethylene glycol 6000,3g carboxymethyl starch sodium, 0.6g magnesium stearate.
4. treat the application of leflunomide tablet in treatment adult rheumatoid arthritis medicine of adult rheumatoid arthritis as claimed in claim 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510874476.2A CN105287420A (en) | 2015-12-03 | 2015-12-03 | Leflunomide tablet for treating adult rheumatoid arthritis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510874476.2A CN105287420A (en) | 2015-12-03 | 2015-12-03 | Leflunomide tablet for treating adult rheumatoid arthritis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105287420A true CN105287420A (en) | 2016-02-03 |
Family
ID=55185719
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510874476.2A Pending CN105287420A (en) | 2015-12-03 | 2015-12-03 | Leflunomide tablet for treating adult rheumatoid arthritis |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105287420A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109180599A (en) * | 2018-09-03 | 2019-01-11 | 深圳市新阳唯康科技有限公司 | A kind of leflunomide crystal compound and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101816637A (en) * | 2009-02-26 | 2010-09-01 | 江苏亚邦爱普森药业有限公司 | Leflunomide tablet preparation and preparation method thereof |
| WO2014096464A1 (en) * | 2013-01-31 | 2014-06-26 | Alfred E. Tiefenbacher (Gmbh & Co. Kg) | Pharmaceutical composition comprising leflunomide |
| CN103989675A (en) * | 2014-05-20 | 2014-08-20 | 王俊国 | Leflunomide tablet and preparation technology thereof |
-
2015
- 2015-12-03 CN CN201510874476.2A patent/CN105287420A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101816637A (en) * | 2009-02-26 | 2010-09-01 | 江苏亚邦爱普森药业有限公司 | Leflunomide tablet preparation and preparation method thereof |
| WO2014096464A1 (en) * | 2013-01-31 | 2014-06-26 | Alfred E. Tiefenbacher (Gmbh & Co. Kg) | Pharmaceutical composition comprising leflunomide |
| CN103989675A (en) * | 2014-05-20 | 2014-08-20 | 王俊国 | Leflunomide tablet and preparation technology thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109180599A (en) * | 2018-09-03 | 2019-01-11 | 深圳市新阳唯康科技有限公司 | A kind of leflunomide crystal compound and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103641822B (en) | A kind of Ka Gelie purifies compound and pharmaceutical composition thereof | |
| CN105503872B (en) | A kind of Li Gelieting impurity and its preparation method and application | |
| CN102920674A (en) | Technology for preparing hydroxychloroquine sulfate tablets | |
| CN102688252A (en) | Acarbose oral solid preparation composition and preparation method thereof | |
| CN106138012B (en) | A kind of preparation method of Isosorbide Mononitrate spansule | |
| CN105496941A (en) | Folic acid solid preparation and preparation method thereof | |
| CN105287420A (en) | Leflunomide tablet for treating adult rheumatoid arthritis | |
| CN105769872B (en) | A kind of mosapride citrate composition of Fast Stripping | |
| CN102429912B (en) | Pharmaceutical composition prepared with micronized prasterone or sodium prasterone sulfate and use thereof | |
| CN110946834B (en) | Tofacitinib citrate tablet and preparation process thereof | |
| CN106420637B (en) | A kind of Determination of Ketotifen Fumarate Tablets and preparation method thereof | |
| CN104116743A (en) | Folic acid pharmaceutical composition for preventing administration | |
| CN110420188A (en) | A method of improving Entecavir tablet uniformity of dosage units | |
| CN105168169A (en) | Gefitinib tablet and preparation method thereof | |
| CN107569504B (en) | Ambroxol hydrochloride dispersible tablet and preparation method thereof | |
| CN106214646B (en) | A kind of silibinin meglumine preparation | |
| CN110907583B (en) | Method for separating related substances in loxoprofen or sodium salt thereof | |
| CN105287418A (en) | Simvastatin tablets with effect of reducing blood lipid | |
| CN103284975B (en) | Metformin hydrochloride enteric capsule and preparation method thereof | |
| CN103432090B (en) | Cyclovirobuxine D sublingual tablet as well as preparation method and application thereof | |
| CN104324013B (en) | The preparation technology of indapamide slow release agent | |
| CN104352465B (en) | Prucalopride succinate pharmaceutical composition free of silicon dioxide and preparation method of prucalopride succinate pharmaceutical composition | |
| CN106749174A (en) | A kind of sitafloxacin dihydrate crystal formation, preparation method and combinations thereof tablet | |
| CN102188386B (en) | Nimesulide sustained-release pellets and preparation method thereof | |
| CN112851726A (en) | Arbutin-carbamide eutectic crystal and preparation method, preparation and application 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 | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20160203 |
|
| RJ01 | Rejection of invention patent application after publication |