CN102488686B - Compound a-keto acid tablet and preparation processes thereof - Google Patents
Compound a-keto acid tablet and preparation processes thereof Download PDFInfo
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- CN102488686B CN102488686B CN 201110437147 CN201110437147A CN102488686B CN 102488686 B CN102488686 B CN 102488686B CN 201110437147 CN201110437147 CN 201110437147 CN 201110437147 A CN201110437147 A CN 201110437147A CN 102488686 B CN102488686 B CN 102488686B
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Abstract
The invention relates to a compound a-keto acid tablet and preparation processes thereof. One of the preparation processes comprises the following steps of respectively mixing and granulating slightly alkaline medicines and slightly acidic medicines, mixing the slightly alkaline medicines and the slightly acidic medicines together and carrying out tabletting and coating, and the process enables dissolubility of the compound a-keto acid tablet to be enhanced and stability of the medicines to be improved. The other of the preparation processes comprises the following steps of granulating calcium 3-methyl-2-oxovalerate and ketoleucine calcium under a dark condition, respectively granulating other slightly alkaline medicines and slightly acidic medicines, mixing all the medicines together and carrying out tabletting and coating, and the process enables dissolubility of the compound a-keto acid tablet and stability of the medicines to be further improved.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, relate to a kind of compound recipe a-keto acid sheet and preparation technology thereof.
Background technology
In modern society, the chronic renal disease sickness rate raises increasingly, and chronic renal disease finally can worsen into uremia greatly.The medicine for the treatment of chronic renal disease is subject to people's extensive concern.
Compound recipe a-keto acid sheet is a kind of medicine of good treatment chronic renal disease.Compound recipe a-keto acid sheet can replenish compound alpha-ketoacid and essential amino acids, and it is disorderly to improve vivo acid and Proteometabolism, promotes albumen synthetic; Cooperate low protein diet, the height that alleviates glomerule filters, and the protection nephron slows down chronic renal failure and worsens.
It is found that in actual applications this disintegration of tablet speed is slower, drug dissolution is low.The people of pharmacy knows: drug dissolution is low, often so that medicine is low in the absorption of human body, affects the therapeutic effect of medicine, and simultaneously, this tablet is the compound preparation of multi-medicament, medicine stable undesirable.
Summary of the invention
Purpose of the present invention is exactly the defective for prior art, and a kind of compound recipe a-keto acid sheet and new preparation process thereof are provided, and it is on the low side to solve compound recipe a-keto acid sheet drug dissolution, the stable bad difficult problem of medicine.
We find: in the ingredients of compound recipe a-keto acid sheet, some medicine meta-alkalescence is such as keto-valine calcium, racemic ketoprofen isoleucine calcium, keto-leucine calcium, racemization hydroxyl Methionine calcium salt., Phenylalanine calcium salt., lysine acetate, histidine; Some medicine slant acidity is such as threonine, tryptophan, tyrosine.The disclosed preparation technology of compound recipe a-ketonic acid preparation always mixes granulation, tabletting with above-mentioned meta-alkalescence and slant acidity medicine.
We find pleasantly surprisedly: with meta-alkalescence medicine and slant acidity medicine difference mixing granulation, and then mix, and tabletting, the result is the dissolution that has greatly improved compound recipe a-keto acid sheet, its beneficial effect is seen embodiment 2.
We also find: with meta-alkalescence medicine and slant acidity medicine difference mixing granulation, also improved the stability of medicine.Its beneficial effect is seen embodiment 3.
Its reason may be: mixing granulation is granulated relatively with total mixing respectively, and its basic group and acidic-group touch opportunity are less, have reduced the adhesion between them, and is useful to improving dissolution,
Mixing granulation has respectively avoided alkalescent medicine and acidic drug to mix, produce impurity in the heating process granulating, and behind total mixed pressure sheet, minimizing contacts, and is conducive to improve the stability of medicine.
We also find through overtesting: racemic ketoprofen isoleucine calcium, keto-leucine calcium to its independent granulation, are granulated to keto-valine calcium, racemization hydroxyl Methionine calcium salt. ketone, Phenylalanine calcium salt., lysine acetate, histidine respectively under the lucifuge condition to photo-labile; Threonine, tryptophan, tyrosine are granulated, and then 3 kinds of total mixed pressure sheets of granule are not only useful to improving dissolution, and its beneficial effect of stability that greatly improves medicine is seen embodiment 3
We have invented compound recipe a-keto acid sheet, and its label is comprised of the stock and adjunct of following mass fraction:
Keto-valine calcium 86
Racemic ketoprofen isoleucine calcium 67
Keto-leucine calcium 101
Racemization hydroxyl Methionine calcium salt. 59
Ketone Phenylalanine calcium salt. 68
Lysine acetate 105
Histidine 38
Threonine 53
Tryptophan 23
Tyrosine 30
Starch 35-45
Cross-linked pvp 35-45
PVP 33
Pulvis Talci 10-12
Magnesium stearate 8-10
Compound recipe a-keto acid sheet, one of preparation technology:
Be characterized in: preparation method is that the meta-alkalescence medicine is keto-valine calcium, racemic ketoprofen isoleucine calcium, keto-leucine calcium, racemization hydroxyl Methionine calcium salt., Phenylalanine calcium salt., lysine acetate, histidine with meta-alkalescence medicine and slant acidity medicine difference mixing granulation; The slant acidity medicine is threonine, tryptophan, tyrosine.Preparation technology is as follows in detail:
1) above-mentioned mass fraction supplementary material is crossed respectively 80 mesh sieves;
2) with above-mentioned mass fraction keto-valine calcium, racemic ketoprofen isoleucine calcium, keto-leucine calcium, racemization hydroxyl Methionine calcium salt., Phenylalanine calcium salt., lysine acetate, histidine mixing, add the starch of mass fraction 25-30, the cross-linked pvp of mass fraction 30-35, further mixing gets mixture;
The PVP of mass fraction 28 is joined in the 360ml isopropyl alcohol, stir evenly, after stirring evenly, join in the said mixture, 20 orders are granulated, and 70 ℃ of forced air dryings 2 hours get granule 1;
3) with above-mentioned mass fraction threonine, tryptophan, tyrosine mixing, add the starch of mass fraction 10-15, the cross-linked pvp of mass fraction 5-10, further mixing gets mixture;
The PVP of mass fraction 5 is joined in the 64ml isopropyl alcohol, stir evenly, after stirring evenly, join in the said mixture, 20 orders are granulated, and 70 ℃ of forced air dryings 2 hours get granule 2;
4) granule 1,2 is mixed after, add mass fraction 10-12 Pulvis Talci, add the magnesium stearate of mass fraction 8-10, mixed pressuring plate, 60 ℃ of forced air dryings 2 hours get label;
5) tabletting: heavy according to the actual sheet of result of calculation gained, it is heavy to regulate sheet, tabletting.
6) coating: the stomach dissolution type Opadry of mass fraction 7 is dissolved in 80% ethanol of mass fraction 93, makes coating solution, in coating pan label is carried out coating, 60 ℃ of forced air drying half an hour, label increases weight about 3% behind the coating behind the coating.
7) detect qualified after, packing.
80% ethanol: the ethanol for moisture 20%
Compound recipe a-keto acid sheet, preparation technology's two:
Be characterized in: preparation method is with racemic ketoprofen isoleucine calcium, keto-leucine calcium mixing granulation under the lucifuge condition, racemization hydroxyl Methionine calcium salt., Phenylalanine calcium salt., lysine acetate, histidine mixing granulation, threonine, tryptophan, tyrosine mixing granulation.Preparation technology is as follows in detail:
1) above-mentioned mass fraction supplementary material is crossed respectively 80 mesh sieves;
2) under the lucifuge condition, with above-mentioned mass fraction racemic ketoprofen isoleucine calcium, keto-leucine calcium mixing, add the starch of mass fraction 8-10, the cross-linked pvp of mass fraction 10-12, further mixing gets mixture;
The PVP of mass fraction 9.3 is joined in the 120ml isopropyl alcohol, stir evenly, after stirring evenly, join in the said mixture, 20 orders are granulated, and 70 ℃ of forced air dryings 2 hours get granule 1, and whole technical process requires lucifuge;
3) with above-mentioned mass fraction keto-valine calcium, racemization hydroxyl Methionine calcium salt., Phenylalanine calcium salt., lysine acetate, histidine mixing, add the starch of mass fraction 17-20, the cross-linked pvp of mass fraction 20-23, further mixing gets mixture;
The PVP of mass fraction 18.7 is joined in the 240ml isopropyl alcohol, stir evenly, after stirring evenly, join in the said mixture, 20 orders are granulated, and 70 ℃ of forced air dryings 2 hours get granule 2;
4) with above-mentioned mass fraction threonine, tryptophan, tyrosine mixing, add the starch of mass fraction 10-15, the cross-linked pvp of mass fraction 5-10, further mixing gets mixture;
The PVP of mass fraction 5 is joined in the 64ml isopropyl alcohol, stir evenly, after stirring evenly, join in the said mixture, 20 orders are granulated, and 70 ℃ of forced air dryings 2 hours get granule 3;
5) granule 1,2,3 is mixed after, add mass fraction 10-12 Pulvis Talci, add the magnesium stearate of mass fraction 8-10, mixed pressuring plate, 60 ℃ of forced air dryings 2 hours get label, and are heavy according to the actual sheet of result of calculation gained, regulate sheet and weigh tabletting;
6) coating: the stomach dissolution type Opadry of mass fraction 7 is dissolved in 80% ethanol of mass fraction 93, makes coating solution, in coating pan label is carried out coating, 60 ℃ of forced air drying half an hour, label increases weight about 3% behind the coating behind the coating;
7) detect qualified after, packing.
The specific embodiment
Following embodiment is used for further narration the present invention, but does not impose any restrictions.
1 of the preparation of embodiment 1 compound recipe a-keto acid sheet
Prescription: (1000)
Keto-valine calcium 86g
Racemic ketoprofen isoleucine calcium 67g
Keto-leucine calcium 101g
Racemization hydroxyl Methionine calcium salt. 59g
Ketone Phenylalanine calcium salt. 68g
Lysine acetate 105g
Histidine 38g
Threonine 53g
Tryptophan 23g
Tyrosine 30g
Starch 40g
Cross-linked pvp 40g
PVP 33g
Pulvis Talci 10g
Magnesium stearate 8g
Preparation technology:
1) above-mentioned mass fraction supplementary material is crossed respectively 80 mesh sieves;
2) with above-mentioned mass fraction keto-valine calcium, racemic ketoprofen isoleucine calcium, keto-leucine calcium, racemization hydroxyl Methionine calcium salt., Phenylalanine calcium salt., lysine acetate, histidine mixing, add the cross-linked pvp of 30g starch, 35g, further mixing gets mixture;
The PVP of 28g joins in the 360ml isopropyl alcohol, stirs evenly, and after stirring evenly, joins in the said mixture, and 20 orders are granulated, and 70 ℃ of forced air dryings 2 hours get granule 1;
3) with above-mentioned mass fraction threonine, tryptophan, tyrosine mixing, add the starch of 10g, the cross-linked pvp of 5g, further mixing gets mixture;
The PVP of 5g is joined in the 64ml isopropyl alcohol, stir evenly, after stirring evenly, join in the said mixture, 20 orders are granulated, and 70 ℃ of forced air dryings 2 hours get granule 2;
4) granule 1,2 is mixed after, add mass fraction 10g Pulvis Talci, add the magnesium stearate of 8g, mixed pressuring plate, 60 ℃ of forced air dryings 2 hours get label; Heavy according to the actual sheet of result of calculation gained, it is heavy to regulate sheet, tabletting.
5) coating: the stomach dissolution type Opadry of mass fraction 7 is dissolved in 80% ethanol of mass fraction 93, makes coating solution, in coating pan label is carried out coating, 60 ℃ of forced air drying half an hour, label increases weight about 3% behind the coating behind the coating.
6) detect qualified after, packing.
2 of the preparation of embodiment 2 compound recipe a-keto acid sheets
Prescription: (1000)
Keto-valine calcium 86g
Racemic ketoprofen isoleucine calcium 67g
Keto-leucine calcium 101g
Racemization hydroxyl Methionine calcium salt. 59g
Ketone Phenylalanine calcium salt. 68g
Lysine acetate 105g
Tyrosine 30g
Histidine 38g
Threonine 53g
Tryptophan 23g
Tyrosine 30g
Starch 40g
Cross-linked pvp 40g
PVP 33g
Pulvis Talci 10g
Magnesium stearate 8g
Preparation technology:
1) above-mentioned mass fraction supplementary material is crossed respectively 80 mesh sieves;
2) under the lucifuge condition, with racemic ketoprofen isoleucine calcium 67g, keto-leucine calcium 101g mixing, add 10 g starch, 12 g cross-linked pvps, further mixing gets mixture;
9.3gPVP is joined in the 120ml isopropyl alcohol, stir evenly, after stirring evenly, join in the said mixture, 20 orders are granulated, and 70 ℃ of forced air dryings 2 hours get granule 1, and whole technical process requires lucifuge;
3) with keto-valine calcium 86g, racemization hydroxyl Methionine calcium salt. 59g, Phenylalanine calcium salt. 68g, lysine acetate 105g, histidine 38g mixing, add 20g starch, 20g cross-linked pvp, further mixing gets mixture;
18.7gPVP is joined in the 240ml isopropyl alcohol, stir evenly, after stirring evenly, join in the said mixture, 20 orders are granulated, and 70 ℃ of forced air dryings 2 hours get granule 2;
4) with threonine 53g, tryptophan 23g, tyrosine 30g mixing, add 10g starch, 8g cross-linked pvp, further mixing gets mixture;
5gPVP is joined in the 64ml isopropyl alcohol, stir evenly, after stirring evenly, join in the said mixture, 20 orders are granulated, and 70 ℃ of forced air dryings 2 hours get granule 3;
5) granule 1,2,3 is mixed after, add 10g Pulvis Talci, add mass fraction 8g magnesium stearate, mixed pressuring plate, 60 ℃ of forced air dryings 2 hours get label, and are heavy according to the actual sheet of result of calculation gained, regulate sheet and weigh tabletting;
6) coating: the stomach dissolution type Opadry of mass fraction 7 is dissolved in 80% ethanol of mass fraction 93, makes coating solution, in coating pan label is carried out coating, 60 ℃ of forced air drying half an hour, label increases weight about 3% behind the coating behind the coating;
7) detect qualified after, packing.
The comparative study of embodiment 3 compound recipe a-keto acid sheets
1, we prepare compound recipe a-keto acid sheet according to embodiment 1 prescription, technique, obtain the A sample.
2, we are according to embodiment 1 prescription, and technique obtains the B sample according to total mixed mode of granulating, and its preparation technology is as follows:
1) above-mentioned mass fraction supplementary material is crossed respectively 80 mesh sieves;
2) with the above-mentioned keto-valine calcium that sieves, racemic ketoprofen isoleucine calcium, keto-leucine calcium, racemization hydroxyl Methionine calcium salt. ketone, Phenylalanine calcium salt., lysine acetate, histidine, threonine, tryptophan, tyrosine mixing, the cross-linked pvp that adds 40g starch, 40g, further mixing gets mixture;
The PVP of 33g joins in the 424ml isopropyl alcohol, stirs evenly, and after stirring evenly, joins in the said mixture, and 20 orders are granulated, and 70 ℃ of forced air dryings 2 hours get granule;
3) granule is added mass fraction 10g Pulvis Talci, add the magnesium stearate of 8g, mixed pressuring plate, 60 ℃ of forced air dryings 2 hours get label; Heavy according to the actual sheet of result of calculation gained, it is heavy to regulate sheet, tabletting.
4) coating: the stomach dissolution type Opadry of mass fraction 7 is dissolved in 80% ethanol of mass fraction 93, makes coating solution, in coating pan label is carried out coating, 60 ℃ of forced air drying half an hour, label increases weight about 3% behind the coating behind the coating.
3, we prepare compound recipe a-keto acid sheet according to embodiment 2 prescriptions, technique, obtain the C sample.
4, to A, B, C sample carry out Comparative Study on Dissolution simultaneously
According to the method for Chinese Pharmacopoeia version regulation in 2010, in simulated gastric fluid (0.1mol/L hydrochloric acid solution), result of the test sees Table 1:
| Sample | Dissolution (meansigma methods) |
| Sample A | ８8％ |
| Sample B | 76％ |
| Sample C | 9５％ |
As can be seen from the above table: with meta-alkalescence medicine and slant acidity medicine difference mixing granulation, and then mix, tabletting, the result is the dissolution that has improved compound recipe a-keto acid sheet, with racemic ketoprofen isoleucine calcium, keto-leucine calcium mixing granulation under the lucifuge condition, racemization hydroxyl Methionine calcium salt., Phenylalanine calcium salt., lysine acetate, histidine mixing granulation, the mode of threonine, tryptophan, tyrosine mixing granulation, the dissolution of compound recipe a-keto acid sheet is best.
5, to A, the B sample carries out the long-time stability comparative test simultaneously:
The long term test condition
:Sample is put in the carton and is deposited, and is placed in the stability test case, and condition is 25 ± 2 ℃ of humidity RH60 ± 5% of temperature, and commercially available back is placed.
Long term test: 0 month, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months. to A, the B sample carries out the long-time stability comparative test simultaneously, the variation of its its related substances (%)
See the following form:
| Sample | 0 month | 3 months | 6 months | 9 months | 12 months | 18 months |
| A | 0.27 | 0.29 | 0.31 | 0.39 | 0.43 | 0.49 |
| B | 0.35 | 0.44 | 0.48 | 0.58 | 0.65 | 0.85 |
| C | 0.19 | 0.21 | 0.25 | 0.29 | 0.33 | 0.39 |
As can be seen from the above table: with meta-alkalescence medicine and slant acidity medicine difference mixing granulation, and then mix, tabletting, the result is that its related substances reduces, and has improved the stability of medicine.
With racemic ketoprofen isoleucine calcium, keto-leucine calcium mixing granulation under the lucifuge condition, racemization hydroxyl Methionine calcium salt., Phenylalanine calcium salt., lysine acetate, histidine mixing granulation, the mode of threonine, tryptophan, tyrosine mixing granulation, medicine stable best.
Claims (2)
1. compound recipe a-keto acid sheet is characterized in that its label is comprised of the stock and adjunct of following mass fraction:
Keto-valine calcium 86
Racemic ketoprofen isoleucine calcium 67
Keto-leucine calcium 101
Racemization hydroxyl Methionine calcium salt. 59
Ketone Phenylalanine calcium salt. 68
Lysine acetate 105
Histidine 38
Threonine 53
Tryptophan 23
Tyrosine 30
Starch 35-45
Cross-linked pvp 35-45
PVP 33
Pulvis Talci 10-12
Magnesium stearate 8-10;
To be prepared from by following methods:
1) above-mentioned mass fraction supplementary material is crossed respectively 80 mesh sieves;
2) with above-mentioned mass fraction keto-valine calcium, racemic ketoprofen isoleucine calcium, keto-leucine calcium, racemization hydroxyl Methionine calcium salt., Phenylalanine calcium salt., lysine acetate, histidine mixing, add the starch of mass fraction 25-30, the cross-linked pvp of mass fraction 30-35, further mixing gets mixture;
The PVP of mass fraction 28 is joined in the 360ml isopropyl alcohol, stir evenly, after stirring evenly, join in the said mixture, 20 orders are granulated, and 70 ℃ of forced air dryings 2 hours get granule 1;
3) with above-mentioned mass fraction threonine, tryptophan, tyrosine mixing, add the starch of mass fraction 10-15, the cross-linked pvp of mass fraction 5-10, further mixing gets mixture;
The PVP of mass fraction 5 is joined in the 64ml isopropyl alcohol, stir evenly, after stirring evenly, join in the said mixture, 20 orders are granulated, and 70 ℃ of forced air dryings 2 hours get granule 2;
4) granule 1,2 is mixed after, add mass fraction 10-12 Pulvis Talci, add the magnesium stearate of mass fraction 8-10, mixed pressuring plate, 60 ℃ of forced air dryings 2 hours get label, and are heavy according to the actual sheet of result of calculation gained, regulate sheet and weigh tabletting;
5) coating: the stomach dissolution type Opadry of mass fraction 7 is dissolved in 80% ethanol of mass fraction 93, makes coating solution, in coating pan label is carried out coating, 60 ℃ of forced air drying half an hour, label increases weight about 3% behind the coating behind the coating;
6) detect qualified after, packing.
2. compound recipe a-keto acid sheet is characterized in that its label is comprised of the stock and adjunct of following mass fraction:
Keto-valine calcium 86
Racemic ketoprofen isoleucine calcium 67
Keto-leucine calcium 101
Racemization hydroxyl Methionine calcium salt. 59
Ketone Phenylalanine calcium salt. 68
Lysine acetate 105
Histidine 38
Threonine 53
Tryptophan 23
Tyrosine 30
Starch 35-45
Cross-linked pvp 35-45
PVP 33
Pulvis Talci 10-12
Magnesium stearate 8-10;
To be prepared from by following methods:
1) above-mentioned mass fraction supplementary material is crossed respectively 80 mesh sieves;
2) under the lucifuge condition, with above-mentioned mass fraction racemic ketoprofen isoleucine calcium, keto-leucine calcium mixing, add the starch of mass fraction 8-10, the cross-linked pvp of mass fraction 10-12, further mixing gets mixture;
The PVP of mass fraction 9.3 is joined in the 120ml isopropyl alcohol, stir evenly, after stirring evenly, join in the said mixture, 20 orders are granulated, and 70 ℃ of forced air dryings 2 hours get granule 1, and whole technical process requires lucifuge;
3) with above-mentioned mass fraction keto-valine calcium, racemization hydroxyl Methionine calcium salt., Phenylalanine calcium salt., lysine acetate, histidine mixing, add the starch of mass fraction 17-20, the cross-linked pvp of mass fraction 20-23, further mixing gets mixture;
The PVP of mass fraction 18.7 is joined in the 240ml isopropyl alcohol, stir evenly, after stirring evenly, join in the said mixture, 20 orders are granulated, and 70 ℃ of forced air dryings 2 hours get granule 2;
4) with above-mentioned mass fraction threonine, tryptophan, tyrosine mixing, add the starch of mass fraction 10-15, the cross-linked pvp of mass fraction 5-10, further mixing gets mixture;
The PVP of mass fraction 5 is joined in the 64ml isopropyl alcohol, stir evenly, after stirring evenly, join in the said mixture, 20 orders are granulated, and 70 ℃ of forced air dryings 2 hours get granule 3;
5) granule 1,2,3 is mixed after, add mass fraction 10-12 Pulvis Talci, add the magnesium stearate of mass fraction 8-10, mixed pressuring plate, 60 ℃ of forced air dryings 2 hours get label, and are heavy according to the actual sheet of result of calculation gained, regulate sheet and weigh tabletting;
6) coating: the stomach dissolution type Opadry of mass fraction 7 is dissolved in 80% ethanol of mass fraction 93, makes coating solution, in coating pan label is carried out coating, 60 ℃ of forced air drying half an hour, label increases weight about 3% behind the coating behind the coating;
7) detect qualified after, packing.
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| CN102961378B (en) * | 2012-11-27 | 2016-06-01 | 贵州信邦制药股份有限公司 | A kind of compound a-ketone acid sheet and its preparation method and detection method |
| CN103520156B (en) * | 2013-09-23 | 2015-09-30 | 沈阳药科大学 | One is not containing talcous α keto acid compound and preparation technology thereof |
| CN105311017A (en) * | 2014-07-06 | 2016-02-10 | 天津金耀集团有限公司 | Compound [alpha]-keto acid composition and preparation method of same |
| CN105311018A (en) * | 2014-07-06 | 2016-02-10 | 天津金耀集团有限公司 | Stable compound [alpha]-keto acid tablet composition and preparation method thereof |
| CN104607410A (en) * | 2014-12-23 | 2015-05-13 | 上海景峰制药有限公司 | Method for washing compound alpha-ketoacid tablet particles left on oven tray or oven screen |
| CN107549803B (en) * | 2017-09-20 | 2021-06-01 | 精晶药业股份有限公司 | Effervescent tablet containing alpha-ketoacid and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101416947A (en) * | 2007-10-23 | 2009-04-29 | 江苏信孚药业有限公司 | Compound alpha-ketoacid chewing tablet and preparation method |
| CN101773497A (en) * | 2010-02-02 | 2010-07-14 | 北京世纪博康医药科技有限公司 | Compound alpha-keto acid tablet and preparation method thereof |
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| CN101991570B (en) * | 2009-08-14 | 2014-06-18 | 上海秀新臣邦医药科技有限公司 | Stable compound keto acid preparation and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101416947A (en) * | 2007-10-23 | 2009-04-29 | 江苏信孚药业有限公司 | Compound alpha-ketoacid chewing tablet and preparation method |
| CN101773497A (en) * | 2010-02-02 | 2010-07-14 | 北京世纪博康医药科技有限公司 | Compound alpha-keto acid tablet and preparation method thereof |
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