CN104546764A - Calcium folinate composition freezing-drying tablet and preparation method thereof - Google Patents
Calcium folinate composition freezing-drying tablet and preparation method thereof Download PDFInfo
- Publication number
- CN104546764A CN104546764A CN201410829360.2A CN201410829360A CN104546764A CN 104546764 A CN104546764 A CN 104546764A CN 201410829360 A CN201410829360 A CN 201410829360A CN 104546764 A CN104546764 A CN 104546764A
- Authority
- CN
- China
- Prior art keywords
- calcium folinate
- tablet
- solution
- drying
- hours
- 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
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a calcium folinate composition freezing-drying tablet and a preparation method thereof, and relates to the technical field of medicine and medicine production. The calcium folinate composition freezing-drying tablet comprises calcium folinate, starch and saccharose, wherein the starch and saccharose are taken as auxiliary materials. Heating process treatment is carried out on ordinary corn starch, so that the adhesion and disintegration effects of the starch in the tablet can be improved, the formability of the tablet is improved, and the calcium folinate composition freezing-drying tablet only needs the two auxiliary materials of starch and saccharose. The calcium folinate composition freezing-drying tablet adopts a twice-cooling and twice-warming freezing-drying technology, the formability of the tablet can be better through twice cooling and twice warming, the dissolution rate of the tablet is improved, and the bioavailability of the tablet is improved; the tablet overcomes the defects of an ordinary calcium folinate tablet, the types and using amounts of the auxiliary materials in the calcium folinate tablet are reduced, the tablet is great in dissolution rate and high in bioavailability, and the curative effect and safety of clinical medication are guaranteed.
Description
Technical field
The present invention relates to medicine and medical production technical field, be specifically related to a kind of calcium folinate composition freeze-drying sheet and preparation method thereof.
Background technology
Calcium folinate (being called for short CF or LV) is the calcium salt of Calcium leucovorin formyl derivative, is folic acid activated form in vivo.Be commonly used for aminopterin and methotrexate excessive time antidote.In addition still can be used for megaloblastic anemia and leukopenia.Calcium folinate is anti-anemic drug, is also antineoplastic adjuvant drug.There is the effect of antagonism antifol (as medicines such as methotrexate, pyrimethamine and trimethoprims) toxicity, and can treat due to folic acid deficiency, the megaloblastic anemia caused, promote the differentiation of myeloid element, ripe and release.
structural formula
Molecular weight: 601.61
In common calcium folinate in tablets containing supplementary product kind and quantity more, generally to use filler, lubricant, disintegrating agent, adhesive, correctives etc., according to Chinese Pharmacopoeia (2010 editions) second calcium folinate in tablets quality standard, the dissolution of calcium folinate in tablets reached more than 75% for qualified 30 minutes time, and increasing research shows that impurity in the incompatibility of the toxic and side effects of adjuvant itself, adjuvant and principal agent, adjuvant etc. all can have an impact to the safety of medicine.
Therefore, provide one can overcome above-mentioned shortcoming, select suitable adjuvant and technique, reduce supplementary product kind and consumption in calcium folinate in tablets, improve dissolution and the bioavailability of calcium folinate in tablets, ensure that the safety of clinical application all has positive effect.
Traditional lyophilizing tablet can improve dissolution and bioavailability, but still need use the adjuvant such as mannitol, gelatin.And mannitol has certain biological activity, gelatin resource-constrained and perishable.
Starch is the basic adjuvant of oral solid formulation, it is polymerized by glucose molecule, and be commonly used for adhesive, diluent and disintegrating agent in tablets, it is cheap and easy to get, to human-body safety, but being used alone starch has no report as adjuvant freeze-dry process production calcium folinate lyophilizing sheet.
Summary of the invention
Technical problem to be solved by this invention is the defect overcoming prior art, and propose a kind of calcium folinate composition freeze-drying sheet and preparation method thereof further, said preparation adjuvant is few, good stability, and bioavailability is high.
Technical problem to be solved by this invention realizes by the following technical solutions:
A kind of calcium folinate composition freeze-drying sheet, adjuvant is done with starch and sucrose, produce with freeze-dry process, this tablet overcomes the shortcoming of above-mentioned common calcium folinate in tablets, decrease supplementary product kind and consumption in calcium folinate in tablets, this sheet dissolution is large, and bioavailability is high, ensure that curative effect and the safety of clinical application.
A kind of calcium folinate composition freeze-drying sheet, is prepared from by following raw material:
A preparation method for calcium folinate composition freeze-drying sheet, comprises step as follows:
A, take the starch of component amount, add a certain amount of purified water and stir, by pH adjusting agent, the pH value of solution is controlled between 5.0-6.5, be then heated to 72 DEG C, be incubated 20 minutes, make the corn starch solution of 5 ~ 15% (W/V);
B, measure purified water 45ml, boil, add 85g sucrose, stir, after dissolving, continue to be heated to 100 DEG C, filter with purified cotton, the appropriate hot distilled water of filter is cleaned, and washing liquid and filtrate merge, and let cool, add appropriate distilled water, make full dose become 100mL, stir evenly, obtain B solution;
The solution that C, the solution and the step B that steps A are obtained obtain mixes, and fully stirs 30 minutes, is down to room temperature and obtains Semen Maydis-sucrose solution;
D, take calcium folinate 15 grams, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;
Medicinal liquid is sub-packed in drug-containing dish after measuring calcium folinate content by E, medicinal liquid, each drug-containing dish dress 1.0ml;
F, the drug-containing dish that medicinal liquid is housed is put into vacuum freezing drying oven, be cooled to subzero 45 DEG C, keep 2 hours, evacuation, then 0 DEG C is warming up to gradually, keep 2 hours, then be cooled to subzero 45 DEG C, keep 2 hours, be warming up to 0 DEG C gradually again, keep 2 ~ 4 hours, then be warming up to 28 ~ 32 DEG C of dryings 4 ~ 6 hours gradually, whole process vacuum remains on 10 handkerchiefs; Finally the drug-containing dish lid of powder charge is covered tightly, and load aluminium foil bag and carry out sealing and obtain calcium folinate composition freeze-drying sheet.
Described starch selects corn starch, preferably the corn starch solution of 10% (W/V).
Beneficial effect of the present invention is:
The preparation method of a kind of calcium folinate composition freeze-drying sheet of the present invention, heating process process is carried out to common corn starch, starch bonding in tablets, disintegration can be improved, improve the mouldability of tablet, in calcium folinate composition freeze-drying sheet, dosage of sucrose is 8.5% (W/V), it is the hardness reinforcer of this tablet, and plays flavored action.Calcium folinate composition freeze-drying sheet only needs starch and sucrose two kinds of adjuvants.The freeze-dry process of two liters falls in calcium folinate composition freeze-drying sheet employing two, and twice cooling, twice intensification can make sheet mouldability better, which increase the dissolution of tablet, thus improve the bioavailability of tablet.
Accompanying drawing explanation
Fig. 1 is the dissolution correlation curve figure of calcium folinate in experiment.
Detailed description of the invention
The technological means realized to make the present invention, creation characteristic, reaching object and effect is easy to understand, below in conjunction with specific embodiment, set forth the present invention further, but following embodiment being only the preferred embodiments of the present invention, and not all.Based on the embodiment in embodiment, those skilled in the art under the prerequisite not making creative work obtain other embodiment, all belong to the protection domain of this patent.
Embodiment 1
A, take the corn starch of 100g, the purified water adding 900ml stirs, and controls at 5.0-6.5, is then heated to 72 DEG C, keep 120 minutes, make the corn starch solution of 9% (W/V) by pH adjusting agent by the pH value of solution.
B, measure purified water 45ml, boil, add 85g sucrose, stir, after dissolving, continue to be heated to 100 DEG C, filter with purified cotton, the appropriate hot distilled water of filter is cleaned, and washing liquid and filtrate merge, and let cool, add appropriate distilled water, make full dose become 100mL, stir evenly, obtain B solution.
The solution that C, the solution and the step B that steps A are obtained obtain mixes, and fully stirs 30 minutes, after solution be down to room temperature obtain Semen Maydis-sucrose solution.
D, take calcium folinate 15g, add in 1L Semen Maydis-sucrose solution, stir 30 minutes.
Medicinal liquid is sub-packed in drug-containing dish after measuring calcium folinate content by E, medicinal liquid, each drug-containing dish dress 1.0ml.
F, the drug-containing dish that medicinal liquid is housed is put into vacuum freezing drying oven, be cooled to subzero 45 DEG C, keep 2 hours, evacuation, then 0 DEG C is warming up to gradually, keep 2 hours, then be cooled to subzero 45 DEG C, keep 2 hours, be warming up to 0 DEG C gradually again, keep 2 ~ 4 hours, then be warming up to 28 ~ 32 DEG C of dryings 4 ~ 6 hours gradually, whole process vacuum remains on 10 handkerchiefs.Finally the drug-containing dish lid of powder charge is covered tightly, and load aluminium foil bag and carry out sealing and obtain calcium folinate composition freeze-drying sheet.
Embodiment 2
A, take the corn starch of 130g, the purified water adding 900ml stirs, and controls at 5.0-6.5, is then heated to 72 DEG C, keep 120 minutes, make the corn starch solution of 13% (W/V) by pH adjusting agent by the pH value of solution.
B, measure purified water 45ml, boil, add 85g sucrose, stir, after dissolving, continue to be heated to 100 DEG C, filter with purified cotton, the appropriate hot distilled water of filter is cleaned, and washing liquid and filtrate merge, and let cool, add appropriate distilled water, make full dose become 100mL, stir evenly, obtain B solution.
The solution that C, the solution and the step B that steps A are obtained obtain mixes, and fully stirs 30 minutes, after solution be down to room temperature obtain Semen Maydis-sucrose solution.
D, take calcium folinate 15 grams (by 1000 calculations), add 1L Semen Maydis-sucrose solution, stir 30 minutes.
Medicinal liquid is sub-packed in drug-containing dish after measuring calcium folinate content by E, medicinal liquid, each drug-containing dish dress 1.0ml.
F, the drug-containing dish that medicinal liquid is housed is put into vacuum freezing drying oven, be cooled to subzero 45 DEG C, keep 2 hours, evacuation, then 0 DEG C is warming up to gradually, keep 2 hours, then be cooled to subzero 45 DEG C, keep 2 hours, be warming up to 0 DEG C gradually again, keep 2 ~ 4 hours, then be warming up to 28 ~ 32 DEG C of dryings 4 ~ 6 hours gradually, whole process vacuum remains on 10 handkerchiefs.Finally the drug-containing dish lid of powder charge is covered tightly, and load aluminium foil bag and carry out sealing and obtain calcium folinate composition freeze-drying sheet.
Experimental data
The calcium folinate composition freeze-drying sheet that above-described embodiment is obtained carries out following quality research test:
1, hardness, friability contrast test
Get calcium folinate composition freeze-drying sheet prepared by above-described embodiment respectively and calcium folinate ordinary tablet (commercially available) detects friability and hardness by " Chinese Pharmacopoeia " version in 2010 two annex X G inspection techniques, carried out comparative study, the results are shown in following table:
| Sample | Hardness/N | Friability |
| Execute example 1 | 65 | <1％ |
| Execute example 2 | 67 | <1％ |
| Ordinary tablet | 69 | <1％ |
Experimental data shows, calcium folinate composition freeze-drying sheet and ordinary tablet (commercially available) without significant difference, meet " Chinese Pharmacopoeia " version in 2010 to the requirement of tablet on friability and hardness.
2, dissolution contrast test
(No. 1 to No. 3 is embodiment 1 to get calcium folinate in tablets (commercially available) and each 6 of calcium folinate composition freeze-drying sheet, No. 4 to No. 6 is embodiment 2), press Chinese Pharmacopoeia (2010 editions) second dissolution method annex X C second method respectively, with water 900mL for dissolution medium, rotating speed is 100 turns per minute, operate in accordance with the law, respectively through 5min, 10min, 20min, 30min, during 60min, get solution to filter in right amount, precision measures continuous worry liquid, make in every 1ml about containing folinic acid 10ug with the dilution of 0.2mol/L sodium hydroxide solution, according to Chinese Pharmacopoeia (2010 editions) second annex IV A ultraviolet visible spectrophotometry, absorbance is measured at the wavelength place of 282nm, be 575 calculating by the absorptance (E1cm1%) of C20H21CaN7O7, and result 0.9256 is multiplied, calculate the stripping quantity of every sheet.Result is as follows:
One, calcium folinate in tablets (commercially available)
Two, calcium folinate lyophilizing sheet (No. 1 to No. 3 is embodiment 1, and No. 4 to No. 6 is embodiment 2)
Respectively with catch cropping Dissolution profiles during average dissolution pair, as Fig. 1.
Four, result judges
Judge according to Chinese Pharmacopoeia (2010 editions) second calcium folinate in tablets quality standard, the dissolution of calcium folinate in tablets (commercially available) reached more than 75% for qualified 30 minutes time, actual measurement is 76.4%, and calcium folinate lyophilizing sheet dissolution 10 minutes time reaches 77.25%.It can thus be appreciated that the time that calcium folinate lyophilizing sheet dissolution reaches 75% decreased for about 66.7% (20 minutes) time than calcium folinate in tablets (commercially available).So the calcium folinate lyophilizing sheet blood drug level peaking time is shorter than calcium folinate in tablets (commercially available), and bioavailability is higher, better efficacy.
More than show and describe ultimate principle of the present invention, principal character and advantage of the present invention.The technical staff of the industry should understand; the present invention is not restricted to the described embodiments; what describe in above-described embodiment and description is only preference of the present invention; be not used for limiting the present invention; without departing from the spirit and scope of the present invention; the present invention also has various changes and modifications, and these changes and improvements all fall in the claimed scope of the invention.Application claims protection domain is defined by appending claims and equivalent thereof.
Claims (2)
1. a calcium folinate composition freeze-drying sheet, is characterized in that, is prepared from by following raw material:
2. a preparation method for calcium folinate composition freeze-drying sheet according to claim 1, is characterized in that, comprise step as follows:
A, take the starch of component amount, add a certain amount of purified water and stir, by pH adjusting agent, the pH value of solution is controlled between 5.0-6.5, be then heated to 72 DEG C, be incubated 20 minutes, make the corn starch solution of 5 ~ 15% (W/V);
B, measure purified water 45ml, boil, add 85g sucrose, stir, after dissolving, continue to be heated to 100 DEG C, filter with purified cotton, the appropriate hot distilled water of filter is cleaned, and washing liquid and filtrate merge, and let cool, add appropriate distilled water, make full dose become 100mL, stir evenly, obtain B solution;
The solution that C, the solution and the step B that steps A are obtained obtain mixes, and fully stirs 30 minutes, is down to room temperature and obtains Semen Maydis-sucrose solution;
D, take calcium folinate 15 grams, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;
Medicinal liquid is sub-packed in drug-containing dish after measuring calcium folinate content by E, medicinal liquid, each drug-containing dish dress 1.0ml;
F, the drug-containing dish that medicinal liquid is housed is put into vacuum freezing drying oven, be cooled to subzero 45 DEG C, keep 2 hours, evacuation, then 0 DEG C is warming up to gradually, keep 2 hours, then be cooled to subzero 45 DEG C, keep 2 hours, be warming up to 0 DEG C gradually again, keep 2 ~ 4 hours, then be warming up to 28 ~ 32 DEG C of dryings 4 ~ 6 hours gradually, whole process vacuum remains on 10 handkerchiefs; Finally the drug-containing dish lid of powder charge is covered tightly, and load aluminium foil bag and carry out sealing and obtain calcium folinate composition freeze-drying sheet.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410829360.2A CN104546764A (en) | 2014-12-25 | 2014-12-25 | Calcium folinate composition freezing-drying tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410829360.2A CN104546764A (en) | 2014-12-25 | 2014-12-25 | Calcium folinate composition freezing-drying tablet and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104546764A true CN104546764A (en) | 2015-04-29 |
Family
ID=53064548
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410829360.2A Pending CN104546764A (en) | 2014-12-25 | 2014-12-25 | Calcium folinate composition freezing-drying tablet and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104546764A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108392470A (en) * | 2018-04-13 | 2018-08-14 | 健进制药有限公司 | A kind of production technology of injection Calcium Levofolinate freeze-dried powder |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61242556A (en) * | 1985-04-19 | 1986-10-28 | Hatoya Seika:Kk | Preparation of snack using fruits |
| US20020173016A1 (en) * | 2001-03-27 | 2002-11-21 | Helmut Wurst | High-throughput nucleic acid polymerase devices and methods for their use |
| CN1456163A (en) * | 2003-04-01 | 2003-11-19 | 杭州华卫制药技术开发有限公司 | Oral medicine of leucovocin calcium and its preparing method |
-
2014
- 2014-12-25 CN CN201410829360.2A patent/CN104546764A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61242556A (en) * | 1985-04-19 | 1986-10-28 | Hatoya Seika:Kk | Preparation of snack using fruits |
| US20020173016A1 (en) * | 2001-03-27 | 2002-11-21 | Helmut Wurst | High-throughput nucleic acid polymerase devices and methods for their use |
| CN1456163A (en) * | 2003-04-01 | 2003-11-19 | 杭州华卫制药技术开发有限公司 | Oral medicine of leucovocin calcium and its preparing method |
Non-Patent Citations (1)
| Title |
|---|
| 刘晓睿: "《口腔速溶片的研究进展》", 《中南药学》, vol. 2, no. 5, 31 May 2004 (2004-05-31), pages 296 - 298 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108392470A (en) * | 2018-04-13 | 2018-08-14 | 健进制药有限公司 | A kind of production technology of injection Calcium Levofolinate freeze-dried powder |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104546764A (en) | Calcium folinate composition freezing-drying tablet and preparation method thereof | |
| CN104546766A (en) | Mercaptopurine composition freeze-drying tablet and preparation method thereof | |
| CN104490753A (en) | Furosemide composition freeze-dried tablet and preparation method thereof | |
| CN104490750A (en) | Spirolactone composition freeze-dried tablets and preparation method thereof | |
| CN104490759A (en) | Cobamamide composition freeze-dried tablets and preparation method thereof | |
| CN104490751A (en) | Hydrochlorothiazide composition freeze-dried tablets and preparation method thereof | |
| CN104546675A (en) | Estazolam composition freeze-dried tablet and preparation method thereof | |
| CN104490831A (en) | Ferrous sulfate composition freeze-dried tablets and preparation method thereof | |
| CN104586749A (en) | Metronidazole composition freeze-dried tablet and preparation method thereof | |
| CN104546859A (en) | Dimenhydrinate composition freeze-dried tablets and preparation method thereof | |
| CN104490754A (en) | Lyophilized tablet prepared from captopril composition and preparation method thereof | |
| CN104586781A (en) | Ribavirin composition freeze-dried tablet and preparation method thereof | |
| CN104546676A (en) | Cimetidine composition freeze-drying tablet and preparation method thereof | |
| CN104586790A (en) | Methotrexate composition freeze-dried tablet and preparation method thereof | |
| CN104434776A (en) | Meloxicam composition lyophilized tablet and preparation method thereof | |
| CN104546677A (en) | Inosine composition freeze-drying tablet and preparation method thereof | |
| CN104546752A (en) | Dipyridamole composition freeze-drying tablet and preparation method thereof | |
| CN104434835A (en) | Calcium gluconate composition freeze-dried tablet and preparation method thereof | |
| CN104473863A (en) | Benzbromarone composition lyophilized tablet and preparation method thereof | |
| CN104490825A (en) | Zinc gluconate composition freeze-dried tablets and preparation method thereof | |
| CN104490758A (en) | Leflunomide composition freeze-dried tablets and preparation method thereof | |
| CN104586746A (en) | Propylthiouracil composition freeze-dried tablet and preparation method thereof | |
| CN104586743A (en) | Clozapine compound freeze-dried tablet and preparation method thereof | |
| CN104434775A (en) | Carvedilol composition freeze-dried tablet and preparation method thereof | |
| CN104546760A (en) | Thiamazole composition freeze-drying tablet 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 | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20150429 |