CN102018704A - Compound preparation used for treating chronic kidney diseases and preparation method thereof - Google Patents
Compound preparation used for treating chronic kidney diseases and preparation method thereof Download PDFInfo
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Abstract
The invention relates to a compound preparation used for treating chronic kidney diseases and a preparation method thereof. The preparation has the advantages of beautiful appearance, fast disintegration speed, high dissolution rate and high and stable content of active ingredients. The method that calcium ketonate and amino acid are respectively granulated is adopted, interaction of components is avoided, and the contents of active ingredients can be ensured to be stable. The calcium ketonate part contains anti-viscosity ingredients and an anhydrous wetting agent, the granulation problem caused by the facts that the calcium ketonate is easy to agglomerate due to high viscosity is solved, and meanwhile the disintegration speed and dissolution rate of the preparation are improved, the product quality can be ensured, and the requirement of large scale production can be met.
Description
Technical field
The present invention relates to a kind of compound preparation for the treatment of chronic kidney disease and preparation method thereof, belong to field of pharmaceutical preparations.
Background technology
In recent years, chronic kidney disease (CKD) presents the sickness rate height, and is tending towards the situation of rejuvenation, is subject to people's attention day by day.The concealment of CKD course of disease progress, in case enter late period, the expense of medicine and nursing all will be increased sharply.Fu Fangα-Tong Suanpian cooperates low protein diet can delay the renal failure progress, has important value in the CKD treatment, has become the core means of CKD treatment gradually.
Compound alpha-ketoacid is to comprise 4 kinds of ketone for amino acid calcium, the a kind of hydroxyl compound preparation for amino acid calcium and five kinds of ten kinds of active component such as essential amino acids, be respectively α-racemic ketoprofen isoleucine calcium, alpha-keto-leucine-calcium, α-ketone Phenylalanine calcium salt., α-keto-valine calcium, α-racemization hydroxyl Methionine calcium salt., L-lysine acetate, L-threonine, L-tryptophan, L-histidine, L-tyrosine.The principal agent composition can be divided into calcium picrolonate and two parts of aminoacid by its chemical constitution, and the two character has than big-difference.Traditional preparation process technology is that ten kinds of principal agent compositions are mixed with adjuvant, wet granulation, and tabletting, coating, there is following problems in this technology:
1. calcium picrolonate directly mixes easily generation interaction with aminoacid, and reactions such as calcium picrolonate and amino acid degradation take place, and causes the principal agent component content to reduce, and related substance increases.
2. calcium picrolonate has big viscosity, particularly meet water after, viscosity is bigger, serious agglomerating phenomenon can appear in wet granulation, can't make satisfactory granule, influence tabletting, is not suitable for amplifying production.
3. it is slow that material viscosity causes the product disintegration rate greatly, and dissolution is low.
200710163357.1 disclose a kind of compound alpha-ketoacid chewing tablet and preparation method thereof, adopt the technology of calcium picrolonate, aminoacid and pharmaceutic adjuvant mixing granulation, no resistance to bond composition in the prescription, and binding agent is moisture, it is big to overcome calcium picrolonate viscosity, easily agglomerating defective.200810224131.2 disclose a kind of compound alpha-ketoacid dispersible tablet and preparation method thereof, this technology is only granulated to the principal agent composition, adjuvant directly joins in the particle, carry out tabletting again, this technology is directly mixed granular principal agent composition with pulverous adjuvant, the two particle diameter differs greatly, and can't guarantee mixing, and easily produces interaction.In addition, though there is not moisture in the pelletization,, still can't solve the tough problem of pelletization owing to do not add the resistance to bond composition.
Summary of the invention
An object of the present invention is to provide stable in properties, outward appearance grace, high-quality compound preparation, another purpose provides the preparation method of this compound preparation.
Concrete technical scheme is as follows:
A kind of compound preparation for the treatment of chronic kidney disease comprises calcium picrolonate part and amino acid moiety, and this compound preparation is tablet, capsule,
Wherein calcium picrolonate partly comprises
α-racemic ketoprofen isoleucine calcium 60-70g
Alpha-keto-leucine-calcium 95-105g
α-ketone Phenylalanine calcium salt. 65-73g
α-keto-valine calcium 80-90g
α-racemization hydroxyl Methionine calcium salt. 55-62g
Polyethylene Glycol 20-50g
Pulvis Talci 20-50g
Wetting agent 20-50g
Filler 15-50g
Disintegrating agent 5-20g
Lubricant 2-20g
Preferred calcium picrolonate partly comprises
α-racemic ketoprofen isoleucine calcium 67g
Alpha-keto-leucine-calcium 101g
α-ketone Phenylalanine calcium salt. 68g
α-keto-valine calcium 86g
α-racemization hydroxyl Methionine calcium salt. 59g
Polyethylene Glycol 20-40g
Pulvis Talci 25-45g
Wetting agent 20-45g
Filler 20-45g
Disintegrating agent 5-15g
Lubricant 2-10g
Amino acid moiety comprises
L-lysine acetate 100-112g
L-threonine 52-59g
L-tryptophan 21-28g
L-histidine 31-41g
L-tyrosine 26-34g
Filler 30-70g
Disintegrating agent 2-20g
Binding agent 2-25g
Lubricant 1-15g
Preferred amino acid partly comprises
L-lysine acetate 105g
L-threonine 53g
L-tryptophan 23g
L-histidine 38g
L-tyrosine 30g
Filler 30-60g
Disintegrating agent 2-15g
Binding agent 5-18g
Lubricant 2-10g
Wherein wetting agent is selected from one or more in ethanol, isopropyl alcohol, the acetone; Filler is selected from one or more in pregelatinized Starch, microcrystalline Cellulose, starch, lactose, dextrin, the mannitol; Disintegrating agent is one or more in carboxymethyl starch sodium, cross-linked carboxymethyl cellulose, crospolyvinylpyrrolidone, the low-substituted hydroxypropyl cellulose; Binding agent is one or both in polyvidone, the hypromellose; Lubricant is one or both in magnesium stearate, the micropowder silica gel.
Preparation method may further comprise the steps:
(1) preparation calcium picrolonate part
Take by weighing α-racemic ketoprofen isoleucine calcium, alpha-keto-leucine-calcium, α-ketone Phenylalanine calcium salt., α-keto-valine calcium, α-racemization hydroxyl Methionine calcium salt., Polyethylene Glycol, Pulvis Talci, filler, the disintegrating agent mix homogeneously of recipe quantity, add wetting agent system soft material, the 10-30 mesh sieve is granulated, 50 ℃ of aeration-dryings are to moisture＜3%, 10-30 mesh sieve granulate, add lubricant, mixing gets the calcium picrolonate part;
(2) preparation amino acid moiety
Take by weighing L-lysine acetate, L-threonine, L-tryptophan, L-histidine, L-tyrosine, filler, the disintegrating agent mix homogeneously of recipe quantity, add binding agent system soft material, the 10-30 mesh sieve is granulated, 50 ℃ of aeration-drying 2 hours, 10-30 mesh sieve granulate, add lubricant, mixing gets amino acid moiety;
(3) above-mentioned two parts mix homogeneously, tabletting, coating gets tablet; Incapsulate, get capsule.
The invention has the advantages that:
1. the method that adopts calcium picrolonate and aminoacid to granulate has respectively been stopped calcium picrolonate and aminoacid and has been interacted, and guarantees preparation principal agent component content height, avoids related substance to increase.
2. calcium picrolonate has partly added Polyethylene Glycol and Pulvis Talci resistance to bond composition, substitute binding agent with wetting agent, utilize the viscosity of calcium picrolonate itself to reach adherent purpose, overcome because big, the easy agglomerating granulation difficult problem of bringing of calcium picrolonate viscosity satisfies big production demand.
3. Polyethylene Glycol and Pulvis Talci are united use, and not only the resistance to bond effect is remarkable, help promoting the disintegrate of tablet simultaneously, improve dissolution, and the two effect of uniting use significantly is better than using separately wherein any.
The specific embodiment
Formulation and technology 1 (the invention provides)
The calcium picrolonate part
α-racemic ketoprofen isoleucine calcium 67g
Alpha-keto-leucine-calcium 101g
α-ketone Phenylalanine calcium salt. 68g
α-keto-valine calcium 86g
α-racemization hydroxyl Methionine calcium salt. 59g
Polyethylene Glycol 29g
Pulvis Talci 33g
Microcrystalline Cellulose 20g
Pregelatinized Starch 11g
Carboxymethyl starch sodium 10g
Dehydrated alcohol 32g
Magnesium stearate 4g
Amino acid moiety
L-lysine acetate 105g
L-threonine 53g
L-tryptophan 23g
L-histidine 38g
L-tyrosine 30g
Microcrystalline Cellulose 22g
Carboxymethyl starch sodium 4g
Pregelatinized Starch 24g
Polyvidone 8g
Magnesium stearate 3g
Preparation process is as follows:
1. prepare the calcium picrolonate part: the five kinds of calcium picrolonates, Polyethylene Glycol, Pulvis Talci, microcrystalline Cellulose, pregelatinized Starch, the carboxymethyl starch sodium that take by weighing recipe quantity, add dehydrated alcohol system soft material, 30 mesh sieves are granulated, 50 ℃ of C aeration-dryings are to moisture＜3%, 24 mesh sieve granulate, add magnesium stearate, mixing gets the calcium picrolonate part.
2. preparation amino acid moiety: five seed amino acids, microcrystalline Cellulose, carboxymethyl starch sodium, the pregelatinized Starch mix homogeneously that take by weighing recipe quantity, polyvidone alcoholic solution system soft material, 30 mesh sieves are granulated, 50 ℃ of aeration-drying 2 hours, cross 24 mesh sieve granulate, add magnesium stearate, mixing gets the calcium picrolonate part.
3. with above-mentioned two parts mix homogeneously, tabletting, coating gets tablet, incapsulate capsule.
Formulation and technology 2 (granulating a kind of resistance to bond composition respectively)
The calcium picrolonate part
α-racemic ketoprofen isoleucine calcium 67g
Alpha-keto-leucine-calcium 101g
α-ketone Phenylalanine calcium salt. 68g
α-keto-valine calcium 86g
α-racemization hydroxyl Methionine calcium salt. 59g
Pulvis Talci 42g
Microcrystalline Cellulose 29g
Carboxymethyl starch sodium 15g
Pregelatinized Starch 13g
Dehydrated alcohol 30g
Magnesium stearate 5g
Amino acid moiety
L-lysine acetate 105g
L-threonine 53g
L-tryptophan 23g
L-histidine 38g
L-tyrosine 30g
Microcrystalline Cellulose 24g
Carboxymethyl starch sodium 7g
Pregelatinized Starch 22g
Polyvidone 10g
Magnesium stearate 5g
Preparation method such as formulation and technology 1
Formulation and technology 3 (granulating a kind of resistance to bond composition respectively)
The calcium picrolonate part
α-racemic ketoprofen isoleucine calcium 67g
Alpha-keto-leucine-calcium 101g
α-ketone Phenylalanine calcium salt. 68g
α-keto-valine calcium 86g
α-racemization hydroxyl Methionine calcium salt. 59g
Polyethylene Glycol 38g
Microcrystalline Cellulose 26g
Carboxymethyl starch sodium 14g
Pregelatinized Starch 15g
Dehydrated alcohol 34g
Magnesium stearate 6g
Amino acid moiety
L-lysine acetate 105g
L-threonine 53g
L-tryptophan 23g
L-histidine 38g
L-tyrosine 30g
Microcrystalline Cellulose 26g
Carboxymethyl starch sodium 8g
Pregelatinized Starch 21g
Polyvidone 9g
Magnesium stearate 4g
Preparation technology such as formulation and technology 1
Formulation and technology 4 (mixing granulation, a kind of resistance to bond composition)
α-racemic ketoprofen isoleucine calcium 67g
Alpha-keto-leucine-calcium 101g
α-ketone Phenylalanine calcium salt. 68g
α-keto-valine calcium 86g
α-racemization hydroxyl Methionine calcium salt. 59g
L-lysine acetate 105g
L-threonine 53g
L-tryptophan 23g
L-histidine 38g
L-tyrosine 30g
Microcrystalline Cellulose 49g
Pregelatinized Starch 35g
Carboxymethyl starch sodium 21g
Pulvis Talci 35g
Polyvidone 15g
Magnesium stearate 10g
Preparation process is as follows:
1. take by weighing α-racemic ketoprofen isoleucine calcium, alpha-keto-leucine-calcium, α-ketone Phenylalanine calcium salt., α-keto-valine calcium, α-racemization hydroxyl Methionine calcium salt., L-lysine acetate, L-threonine, L-tryptophan, L-histidine, L-tyrosine, microcrystalline Cellulose, pregelatinized Starch, carboxymethyl starch sodium, the Pulvis Talci mix homogeneously of recipe quantity, add polyvidone alcoholic solution system soft material, crossing 30 mesh sieves granulates, 50 ℃ of aeration-dryings are crossed 24 mesh sieve granulate to moisture＜3%.
2. with above-mentioned granule and magnesium stearate mix homogeneously, tabletting, coating.
Prescription 5 (mixing granulation, a kind of resistance to bond compositions)
α-racemic ketoprofen isoleucine calcium 67g
Alpha-keto-leucine-calcium 101g
α-ketone Phenylalanine calcium salt. 68g
α-keto-valine calcium 86g
α-racemization hydroxyl Methionine calcium salt. 59g
L-lysine acetate 105g
L-threonine 53g
L-tryptophan 23g
L-histidine 38g
L-tyrosine 30g
Microcrystalline Cellulose 46g
Pregelatinized Starch 37g
Carboxymethyl starch sodium 17g
Polyethylene Glycol 39g
Polyvidone 12g
Magnesium stearate 11g
Preparation process is as writing out a prescription 4
Prescription 6 (mixing granulation, no resistance to bond compositions)
α-racemic ketoprofen isoleucine calcium 67g
Alpha-keto-leucine-calcium 101g
α-ketone Phenylalanine calcium salt. 68g
α-keto-valine calcium 86g
α-racemization hydroxyl Methionine calcium salt. 59g
L-lysine acetate 105g
L-threonine 53g
L-tryptophan 23g
L-histidine 38g
L-tyrosine 30g
Microcrystalline Cellulose 49g
Pregelatinized Starch 45g
Carboxymethyl starch sodium 24g
Polyvidone 13g
Magnesium stearate 9g
Preparation technology is as writing out a prescription 4
Interpretation of result:
Formulation and technology 1 pelletization modest viscosity provided by the invention does not have agglomerating phenomenon, and particle size is evenly distributed, and good fluidity satisfies the tabletting demand, and tablet appearance is complete bright and clean, and color and luster is even.Writing out a prescription 2 adds a kind of anti-stick composition of Pulvis Talci, and pelletization viscosity is big, and agglomerating phenomenon is arranged, the particle size skewness, and tablet surface is rough, spottiness.Prescription only adds a kind of anti-stick composition of Polyethylene Glycol in 3, and it is 2 bigger that the pelletization viscosity ratio is write out a prescription, and agglomerating phenomenon is obvious, the particle size skewness, and tablet surface is rough, spottiness.Formulation and technology 4,5 mixing granulations add a kind of resistance to bond composition, and agglomerating phenomenon is obvious in the pelletization, particle size skewness, tablet surface spottiness.6 mixing granulations of writing out a prescription do not add any anti-stick composition, and agglomerating phenomenon is serious in the pelletization, and particle size distributes seriously inhomogeneous, and the tablet surface that makes is rough, spottiness.
The tablet that write out a prescription 1 tablet that makes and capsule and prescription 4,5,6 are made carries out the accelerated test in high temperature (45 ℃), high humidity (RH75%) 0 month, January, February, selects the least stable α-ketone Phenylalanine calcium salt. of character to carry out assay.The results are shown in Table 1.
Table 1
| Project (α-ketone phenylalanine calcium content) | Prescription 1 (tablet) | Prescription 1 (capsule) | Prescription 4 | Prescription 5 | Prescription 6 |
| 0 month | 99.8％ | 99.6％ | 97.2％ | 98.0％ | 95.5％ |
| January | 99.6％ | 99.0％ | 93.2％ | 95.7％ | 91.1％ |
| February | 98.9％ | 98.2％ | 87.9％ | 88.7％ | 84.9％ |
Accelerated tests result shows, the formulation products that prescription 1 is produced owing to adopt granulating process respectively, is avoided each interaction between component, and principal agent component content height through after the accelerated test, can keep stable content.And the product of mixing granulation, drug content is low, and through behind the high temperature and humidity test, content descends rapidly, the stability that can't ensure drug quality.
The tablet that whole prescriptions are made carries out quality research, investigates the disintegration of tablet, and α-ketone Phenylalanine calcium salt. of selecting indissoluble to go out surveys its dissolution, as table 2.Test shows that prescription 1 pelletization modest viscosity provided by the invention does not have agglomerating phenomenon; The tablet appearance grace that makes, disintegration is reasonable, and dissolution is significantly higher than other formulation and technology products, has guaranteed the high-quality of product.
Table 2
| Test item | Prescription 1 (tablet) | Prescription 2 | Prescription 3 | Prescription 4 | Prescription 5 | Prescription 6 |
| Pelletization | Do not have agglomerating phenomenon, particle size is evenly distributed, and good fluidity satisfies the tabletting demand | Viscosity is big, and agglomerating phenomenon is arranged, the particle size skewness | It is 2 bigger that viscosity is write out a prescription, and agglomerating phenomenon is obvious, the particle size skewness | Agglomerating phenomenon is very obvious, the particle size skewness | Agglomerating phenomenon is very obvious, the particle size skewness | Agglomerating serious, particle size distributes seriously inhomogeneous |
| The label outward appearance | Off-white color, complete bright and clean, color and luster is even | Off-white color, unilateral spottiness | Off-white color, unilateral spottiness | Off-white color, unilateral spottiness | Off-white color, unilateral spottiness | Off-white color, unilateral spottiness |
| Disintegration | 36min | 45min | 48min | 56min | 59min | 65min |
| α-ketone Phenylalanine calcium salt. dissolution | 99.8％ | 90.6％ | 89.1％ | 83.7％ | 81.9％ | 79.8％ |
Claims (12)
1. a compound preparation for the treatment of chronic kidney disease is characterized in that described compound preparation comprises calcium picrolonate part and amino acid moiety.
2. compound preparation according to claim 1 is characterized in that, described compound preparation is tablet, capsule.
3. compound preparation according to claim 1 is characterized in that, described calcium picrolonate partly comprises:
α-racemic ketoprofen isoleucine calcium 60-70g
Alpha-keto-leucine-calcium 95-105g
α-ketone Phenylalanine calcium salt. 65-73g
α-keto-valine calcium 80-90g
α-racemization hydroxyl Methionine calcium salt. 55-62g
Polyethylene Glycol 20-50g
Pulvis Talci 20-50g
Wetting agent 20-50g
Filler 15-50g
Disintegrating agent 5-20g
Lubricant 2-20g
4. compound preparation according to claim 3 is characterized in that, described calcium picrolonate partly comprises:
α-racemic ketoprofen isoleucine calcium 67g
Alpha-keto-leucine-calcium 101g
α-ketone Phenylalanine calcium salt. 68g
α-keto-valine calcium 86g
α-racemization hydroxyl Methionine calcium salt. 59g
Polyethylene Glycol 20-40g
Pulvis Talci 25-45g
Wetting agent 20-45g
Filler 20-45g
Disintegrating agent 5-15g
Lubricant 2-10g
5. compound preparation according to claim 1 is characterized in that, described amino acid moiety comprises:
L-lysine acetate 100-112g
L-threonine 52-59g
L-tryptophan 21-28g
L-histidine 31-41g
L-tyrosine 26-34g
Filler 30-70g
Disintegrating agent 2-20g
Binding agent 2-25g
Lubricant 1-15g
6. compound preparation according to claim 5 is characterized in that, described amino acid moiety comprises:
L-lysine acetate 105g
L-threonine 53g
L-tryptophan 23g
L-histidine 38g
L-tyrosine 30g
Filler 30-60g
Disintegrating agent 2-15g
Binding agent 5-18g
Lubricant 2-10g
7. according to claim 3 or 4 arbitrary described compound preparations, it is characterized in that described wetting agent is one or more in ethanol, isopropyl alcohol, the acetone.
8. according to the arbitrary described compound preparation of claim 3-6, it is characterized in that described filler is one or more in pregelatinized Starch, microcrystalline Cellulose, starch, lactose, dextrin, the mannitol.
9. according to the arbitrary described compound preparation of claim 3-6, it is characterized in that described disintegrating agent is one or more in carboxymethyl starch sodium, cross-linked carboxymethyl cellulose, crospolyvinylpyrrolidone, the low-substituted hydroxypropyl cellulose.
10. according to the arbitrary described compound preparation of claim 3-6, it is characterized in that described binding agent is one or both in polyvidone, the hypromellose.
11., it is characterized in that described lubricant is one or both in magnesium stearate, the micropowder silica gel according to the arbitrary described compound preparation of claim 3-6.
12. a preparation method for preparing the arbitrary described compound preparation of claim 1-11 is characterized in that, may further comprise the steps:
(1) preparation calcium picrolonate part
Take by weighing α-racemic ketoprofen isoleucine calcium, alpha-keto-leucine-calcium, α-ketone Phenylalanine calcium salt., α-keto-valine calcium, α-racemization hydroxyl Methionine calcium salt., Polyethylene Glycol, Pulvis Talci, filler, the disintegrating agent mix homogeneously of recipe quantity, add wetting agent system soft material, the 10-30 mesh sieve is granulated, 50 ° of ℃ of aeration-dryings are to moisture＜3%, 10-30 mesh sieve granulate, add lubricant, mixing gets the calcium picrolonate part;
(2) preparation amino acid moiety
Take by weighing L-lysine acetate, L-threonine, L-tryptophan, L-histidine, L-tyrosine, filler, the disintegrating agent mix homogeneously of recipe quantity, add binding agent system soft material, the 10-30 mesh sieve is granulated, 50 ℃ of aeration-drying 2 hours, 10-30 mesh sieve granulate, add lubricant, mixing gets amino acid moiety;
(3) with above-mentioned two parts mix homogeneously, tabletting, coating gets tablet; Incapsulate, get capsule.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102988357A (en) * | 2011-09-14 | 2013-03-27 | 北大方正集团有限公司 | Compound alpha keto acid medicine composition and preparation method thereof |
| CN103463014A (en) * | 2013-09-23 | 2013-12-25 | 沈阳药科大学 | Compound alpha-ketoacid tablet and preparation method thereof |
| CN105640950A (en) * | 2015-12-21 | 2016-06-08 | 南京生命能科技开发有限公司 | Compound alpha-keto acid tablet and preparation technology thereof |
| CN107549803A (en) * | 2017-09-20 | 2018-01-09 | 精晶药业股份有限公司 | A kind of effervescent tablet containing α ketone acids and preparation method thereof |
| CN107997182A (en) * | 2017-11-02 | 2018-05-08 | 上海市杨浦区市东医院 | The fixation nutritional agents that a kind of kidney failure dialysis patient uses |
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| CN1308939A (en) * | 2000-02-14 | 2001-08-22 | 江骥 | Ketonic acid preparation for treating nephrosis |
| CN1981584A (en) * | 2005-11-17 | 2007-06-20 | 卡夫食品集团公司 | A cheese flavor composition and process for making same |
| CN101623271A (en) * | 2008-10-17 | 2010-01-13 | 佟兵 | Compound alpha-keto acid dispersible tablet and preparation method thereof |
| CN101646358A (en) * | 2007-04-04 | 2010-02-10 | 赢创德固赛有限责任公司 | The food supplement that contains 2-ketoacid |
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| CN1308939A (en) * | 2000-02-14 | 2001-08-22 | 江骥 | Ketonic acid preparation for treating nephrosis |
| CN1981584A (en) * | 2005-11-17 | 2007-06-20 | 卡夫食品集团公司 | A cheese flavor composition and process for making same |
| CN101646358A (en) * | 2007-04-04 | 2010-02-10 | 赢创德固赛有限责任公司 | The food supplement that contains 2-ketoacid |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102988357A (en) * | 2011-09-14 | 2013-03-27 | 北大方正集团有限公司 | Compound alpha keto acid medicine composition and preparation method thereof |
| CN102988357B (en) * | 2011-09-14 | 2014-05-21 | 北大方正集团有限公司 | Compound alpha keto acid medicine composition and preparation method thereof |
| CN103463014A (en) * | 2013-09-23 | 2013-12-25 | 沈阳药科大学 | Compound alpha-ketoacid tablet and preparation method thereof |
| CN103463014B (en) * | 2013-09-23 | 2015-08-05 | 沈阳药科大学 | A kind of α keto acid compound and preparation technology thereof |
| CN105640950A (en) * | 2015-12-21 | 2016-06-08 | 南京生命能科技开发有限公司 | Compound alpha-keto acid tablet and preparation technology thereof |
| CN105640950B (en) * | 2015-12-21 | 2018-05-25 | 南京生命能科技开发有限公司 | A kind of preparation method of α keto acid compound |
| CN107549803A (en) * | 2017-09-20 | 2018-01-09 | 精晶药业股份有限公司 | A kind of effervescent tablet containing α ketone acids and preparation method thereof |
| CN107997182A (en) * | 2017-11-02 | 2018-05-08 | 上海市杨浦区市东医院 | The fixation nutritional agents that a kind of kidney failure dialysis patient uses |
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|---|---|
| CN102018704B (en) | 2012-02-22 |
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