CN104546759A - Primidone composition lyophilized tablet and preparation method thereof - Google Patents
Primidone composition lyophilized tablet and preparation method thereof Download PDFInfo
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- CN104546759A CN104546759A CN201410828233.0A CN201410828233A CN104546759A CN 104546759 A CN104546759 A CN 104546759A CN 201410828233 A CN201410828233 A CN 201410828233A CN 104546759 A CN104546759 A CN 104546759A
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- primidone
- tablet
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- starch
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- 229960002393 primidone Drugs 0.000 title claims abstract description 58
- DQMZLTXERSFNPB-UHFFFAOYSA-N primidone Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NCNC1=O DQMZLTXERSFNPB-UHFFFAOYSA-N 0.000 title claims abstract description 58
- 239000000203 mixture Substances 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 239000003814 drug Substances 0.000 claims abstract description 26
- 238000004108 freeze drying Methods 0.000 claims abstract description 21
- 229940079593 drug Drugs 0.000 claims abstract description 20
- 229920002472 Starch Polymers 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 12
- 239000008107 starch Substances 0.000 claims abstract description 12
- 235000019698 starch Nutrition 0.000 claims abstract description 12
- 229920002261 Corn starch Polymers 0.000 claims abstract description 10
- 229930006000 Sucrose Natural products 0.000 claims abstract description 10
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims abstract description 10
- 239000008120 corn starch Substances 0.000 claims abstract description 10
- 230000008569 process Effects 0.000 claims abstract description 8
- 238000003756 stirring Methods 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 239000007788 liquid Substances 0.000 claims description 17
- 239000005720 sucrose Substances 0.000 claims description 15
- 238000010792 warming Methods 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 11
- 239000012153 distilled water Substances 0.000 claims description 8
- 239000008213 purified water Substances 0.000 claims description 8
- 210000000582 semen Anatomy 0.000 claims description 8
- 229920000742 Cotton Polymers 0.000 claims description 4
- 206010013786 Dry skin Diseases 0.000 claims description 4
- 239000005030 aluminium foil Substances 0.000 claims description 4
- 239000000706 filtrate Substances 0.000 claims description 4
- 238000007710 freezing Methods 0.000 claims description 4
- 230000008014 freezing Effects 0.000 claims description 4
- 239000003002 pH adjusting agent Substances 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
- 238000007789 sealing Methods 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- 239000002994 raw material Substances 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 abstract description 14
- 230000000694 effects Effects 0.000 abstract description 6
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 230000007547 defect Effects 0.000 abstract description 2
- 238000005516 engineering process Methods 0.000 abstract description 2
- 238000010438 heat treatment Methods 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract 3
- 229960004793 sucrose Drugs 0.000 abstract 3
- 229940032147 starch Drugs 0.000 abstract 1
- 239000002671 adjuvant Substances 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 2
- 239000000853 adhesive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 229960002036 phenytoin Drugs 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 208000033001 Complex partial seizures Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 206010063006 Facial spasm Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 208000034308 Grand mal convulsion Diseases 0.000 description 1
- 208000002033 Myoclonus Diseases 0.000 description 1
- 208000037158 Partial Epilepsies Diseases 0.000 description 1
- 206010034759 Petit mal epilepsy Diseases 0.000 description 1
- 208000005793 Restless legs syndrome Diseases 0.000 description 1
- 206010040703 Simple partial seizures Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 1
- 229960000623 carbamazepine Drugs 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 238000011978 dissolution method Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229960002695 phenobarbital Drugs 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
The invention provides a primidone composition lyophilized tablet and a preparation method thereof, and relates to the technical field of medicines and medicine production. The primidone composition lyophilized tablet is prepared from primidone, starch and cane sugar, and prepared by the following steps: using starch and cane sugar as auxiliary materials, performing heating process treatment to the ordinary corn starch to improve the bonding and disintegration functions of starch in the tablet and the formability of the tablet, wherein the primidone composition lyophilized tablet only needs the two auxiliary materials including starch and cane sugar. The primidone composition lyophilized tablet is prepared by the two-temperature-rising two-temperature-decrease lyophilization technology; the two-temperature-rising process and the two-temperature-decrease process can facilitate better formability and improve the dissolution rate of the tablet, so as to improve the bioavailability of the tablet; the tablet overcomes the defects of the common primidone, is high in dissolution rate and high in bioavailability, and ensures the curative effect and the safety of the clinical medication; the preparation method can reduce the varieties and the dosage of the auxiliary materials in primidone.
Description
Technical field
The present invention relates to medicine and medical production technical field, be specifically related to a kind of primidone composition freeze-drying sheet and preparation method thereof.
Background technology
This medicine can be used for treating epilepsy grand mal, simple partial seizures and complex partial seizures, but not as first-line drug.Only at phenytoin, phenobarbital, carbamazepine are alone or consider when share invalid to use.If this medicine share better effects if with phenytoin.Primidone is to petit mal weak curative effect, but effective to child's myoclonus.The treatment that this medicine also can be used for Q-T interval prolongation syndrome, facial spasm, restless legs syndrome, benign familial are trembled.
molecular weight: 218.26
In common primidone sheet containing supplementary product kind and quantity more, generally to use filler, lubricant, disintegrating agent, adhesive, correctives etc., according to Chinese Pharmacopoeia (2010 editions) second primidone tablet quality standard, the dissolution of primidone sheet reached more than 70% for qualified 60 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 primidone sheet, improve dissolution and the bioavailability of primidone sheet, 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 primidone 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 primidone 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 primidone composition freeze-drying sheet, does adjuvant with starch and sucrose, produces with freeze-dry process, this tablet overcomes the shortcoming of above-mentioned common primidone sheet, decreases supplementary product kind and consumption in primidone sheet, and this sheet dissolution is large, bioavailability is high, ensure that curative effect and the safety of clinical application.
A kind of primidone composition freeze-drying sheet, is prepared from by following raw material:
A preparation method for primidone 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 5-7.5, 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 primidone 50 grams, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;
Medicinal liquid is sub-packed in drug-containing dish after measuring primidone 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 primidone 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 primidone 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 primidone composition freeze-drying sheet, dosage of sucrose is 8.5% (W/V), it is the hardness reinforcer of this tablet, and plays flavored action.Primidone composition freeze-drying sheet only needs starch and sucrose two kinds of adjuvants.The freeze-dry process of two liters falls in primidone 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 primidone 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 5-7.5, 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 primidone 50g, add in 1L Semen Maydis-sucrose solution, stir 30 minutes.
Medicinal liquid is sub-packed in drug-containing dish after measuring primidone 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 primidone composition freeze-drying sheet.
Embodiment 2
A, take the corn starch of 130g, the purified water adding 900ml stirs, and controls at 5-7.5, 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 primidone 50 grams (by 1000 calculations), add 1L Semen Maydis-sucrose solution, stir 30 minutes.
Medicinal liquid is sub-packed in drug-containing dish after measuring primidone 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 primidone composition freeze-drying sheet.
Experimental data
The primidone composition freeze-drying sheet that above-described embodiment is obtained carries out following quality research test:
1, hardness, friability contrast test
Get primidone composition freeze-drying sheet prepared by above-described embodiment respectively and primidone 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 | 69 | <1％ |
| Execute example 2 | 67 | <1％ |
| Ordinary tablet | 64 | <1％ |
Experimental data shows, primidone 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 primidone sheet (commercially available) and each 6 of primidone 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 50 turns per minute, operate in accordance with the law, respectively through 10min, 20min, 30min, 40min, during 60min, get solution to filter, get continuous worry liquid, according to Chinese Pharmacopoeia (2010 editions) second annex IV A ultraviolet visible spectrophotometry, absorbance is measured at the wavelength place of 257nm, another precision takes primidone reference substance and is about 25mg, puts in 100mL measuring bottle, and add water appropriate, supersound process makes dissolving, lets cool, and is diluted to scale, is measured in the same method, and calculates the stripping quantity of every sheet.Result is as follows:
One, primidone sheet (commercially available)
Two, primidone 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 primidone tablet quality standard, the dissolution of primidone sheet (commercially available) reached more than 70% for qualified 60 minutes time, actual measurement is 85.4%, and primidone lyophilizing sheet dissolution 30 minutes time reaches 86.5%.It can thus be appreciated that the time that primidone lyophilizing sheet dissolution reaches 86.5% decreased for about 85.4% (30 minutes) time than primidone sheet (commercially available).So the primidone lyophilizing sheet blood drug level peaking time is shorter than primidone sheet (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 primidone composition freeze-drying sheet, is characterized in that, is prepared from by following raw material:
2. a preparation method for primidone 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 5-7.5, 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 primidone 50 grams, add in 1L Semen Maydis-sucrose solution, stir 25 ~ 35 minutes;
Medicinal liquid is sub-packed in drug-containing dish after measuring primidone 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 primidone composition freeze-drying sheet.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410828233.0A CN104546759A (en) | 2014-12-25 | 2014-12-25 | Primidone composition lyophilized tablet and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410828233.0A CN104546759A (en) | 2014-12-25 | 2014-12-25 | Primidone composition lyophilized tablet and preparation method thereof |
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| Publication Number | Publication Date |
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| CN104546759A true CN104546759A (en) | 2015-04-29 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201410828233.0A Pending CN104546759A (en) | 2014-12-25 | 2014-12-25 | Primidone composition lyophilized tablet and preparation method thereof |
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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 |
| CN104224737A (en) * | 2010-02-24 | 2014-12-24 | 硕腾有限责任公司 | Veterinary compositions |
-
2014
- 2014-12-25 CN CN201410828233.0A patent/CN104546759A/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 |
| CN104224737A (en) * | 2010-02-24 | 2014-12-24 | 硕腾有限责任公司 | Veterinary compositions |
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 * |
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Application publication date: 20150429 |