CN1383829A - Compound folic acid prepn for preventing and treating homocysteinemia and relevant diseases - Google Patents
Compound folic acid prepn for preventing and treating homocysteinemia and relevant diseases Download PDFInfo
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- CN1383829A CN1383829A CN 01115679 CN01115679A CN1383829A CN 1383829 A CN1383829 A CN 1383829A CN 01115679 CN01115679 CN 01115679 CN 01115679 A CN01115679 A CN 01115679A CN 1383829 A CN1383829 A CN 1383829A
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Abstract
The present invention relates to oral liquid or injection, which contains folic cid, vitamin B6 and vitamin B12 and is used in preventing and treating homocysteinemia and relevant diseases. Each unit of the preparation contains folic acid 0.1-5 mg. preferably 0.2-1 mg, vitamin B6 1-20 mg, preferably 5-10 mg, and vitamin B12 0.01-2 mg. perferably 0.1-1 mg. The preparation is used in adjusting the concentration of homocysteine in blood clinically.
Description
The present invention relates to prevent and treat the compound mormula folic acid preparation of hyperhomocysteinemiainjury and relevant disease thereof; Specifically, relate to and contain folic acid, vitamin B
6Vitamin B
12The oral or injection that is used to prevent and treat hyperhomocysteinemiainjury and relevant disease thereof.
Hyperhomocysteinemiainjury is the performance of biochemical metabolism disorder.The rising of homocysteine level in the blood is the indication of disturbance of sulphur-bearing aminoacid metabolism; Confirmed that now the disease relevant with hyperhomocysteinemiainjury has alcoholism, presenile dementia, cognitive function descends, coronary artery disease, dark venous thrombosis, depression, diabetic nephropathy, diabetic retinopathy, intermittent claudication, multiple sclerosis, myocardial infarction, neural tube defect, noninsulindependent diabetes, osteoporosis, parkinson, peripheral vascular disease, placental abruption, renal failure, the retinal vessel thromboembolism, rheumatic arthritis, schizophrenia, spontaneous abortion, apoplexy.As seen its harm is big, extensively.
Folic acid, vitamin B
6, vitamin B
12Be respectively the coenzyme of homocysteine different metabolic approach, homocysteine level often raises and body folate level, vitamin B
12Level, vitamin B
6It is relevant that level is on the low side; Suitably replenishing these three kinds of materials can make blood homocysteine concentration maintain normal level.Yet but there are not folic acid and vitamin B in the market
6, vitamin B
12Mixture sell, this with clinically to folic acid, vitamin B
6And vitamin B
12The understanding of effect deepen day by day, it is conflicting that the needs of its mixture are increased day by day, also is unfavorable for the clinical medical progress of China.
Folic acid is the single preparations of ephedrine that effectively reduces homocysteine most, and small dosage of folic acid (0.2mg/d, 0.4mg/d, 0.5mg/d, 0.65mg/d) similar to the effect of heavy dose of folic acid (5mg/d)." clinical application notice " record that a tree name China pharmacopeia committee publishes, the using dosage of folic acid is one day three times always, a 5～10mg; And the specification of YESUAN PIAN also has only every to contain one kind of folic acid 5mg.Versions in 2000 have increased the new spec of 0.4mg folic acid newly, but still do not have the record of compound mormula folic acid sheet.
The present invention is intended to folic acid, vitamin B
6, vitamin B
12With its suitable choosing amount proportioning,, make the preparation that is used to prevent and treat hyperhomocysteinemiainjury and relevant disease thereof of being convenient to clinical practice with the method that adapts with it.
For this reason, we are to folic acid, vitamin B
6, vitamin B
12The effective dosage ranges of treatment homocysteine mass formed by blood stasis is studied.At first, get large ear rabbit, subcutaneous injection homocysteine 20mg/kg is to set up rabbit hyperhomocysteinemiainjury model; And determine folic acid, vitamin B with this model
6, vitamin B
12The effective dosage ranges of symptomatic treatment and best of breed proportioning.
Concrete assay method is as follows:
Get fasting blood 2～3ml (0.1%EDTA anticoagulant), ice bath cooling immediately, and centrifugal in 30 minutes, collect blood plasma ,-20 ℃ of preservations.Working sample is 200 μ l blood plasma, adds acetylcysteine (final concentration 0.5mM) and makes internal reference, handles 30 minutes for 4 ℃ with 3-butyl phosphine (final concentration 60mM), abundant reduction sulfydryl, 0.6M perchloric acid Denatured protein, 2000g, centrifugal 10 minutes, get supernatant 50 μ l, add 1.55M NaOH 10 μ l, borate buffer 125 μ l (0.125M, PH9.5 contain 4mM EDTA), 50 μ l SBD-F (1mg/ml), 60 ℃ of water-baths 60 minutes, ice bath cooling, get 15 μ l, HPLC analyzes.
Instrument and analysis condition are as follows:
Adopt the HP1100 of Hewlett-Packard type high performance liquid chromatograph, HP1045 fluorescent probe, the reverse post of C18.Fluoroscopic examination condition: excitation wavelength 390nm, radiation wavelength 470nm; Mobile phase is the 0.08M acetate buffer solution, pH4.0,1% methanol, flow velocity 0.8ml/min, elution time 15min.
The result is as follows:
| Time (h) | ??0 | ?0.5 | ?1 | ?2 | ?4 | ?6 | ?7 | ?12 |
| ?tHcy(μmol/L) | ??19.5 | ?28.5 | ?38.0 | ?44.5 * | ?63.0 ** | ?56.5 ** | ?48.5 * | ?26.5 |
※ tHcy: homocysteine.
*: relatively preceding with injection, p＜0.05;
*: relatively preceding with injection, p＜0.01.
Determining of minimum effective dose: with reference to the acceptable daily intake (RDA) that the threpsology recommends, folic acid is 0.4mg, vitamin B
6Be 2mg, vitamin B
12Be 0.001mg, the people is in 50Kg, and respectively with RDA, 1/2 RDA amounts to into the per kilogram dosage, determines minimum effective dose.
The dosage design is as follows:
Folic acid: each administration is respectively 0.004mg/Kg, 0.008mg/Kg, 0.016mg/Kg, 0.032mg/Kg, 0.064mg/Kg, 0.128mg/Kg;
Vitamin B
6: each administration is respectively 0.04mg/Kg 0.08mgKg, 0.16mg/Kg, 0.32mgKg, 0.64mg/Kg, 1.28mg/Kg;
Vitamin B
12: each administration is respectively 0.0004mg/Kg, 0.002mg/Kg, 0.01mg/Kg, 0.05mg/Kg.
Adopt commercially available vitamin B
6Sheet, vitamin B
12Sheet and YESUAN PIAN give the White Rabbit model oral with various dose respectively, and clothes back different time is measured homocysteine concentration in the white rabbit blood before clothes.
Adopt commercially available vitamin B
6Injection, vitamin B
12Injection, folic acid inj are given White Rabbit model subcutaneous injection with various dose respectively, and injection back different time is measured homocysteine concentration in the white rabbit blood before injection.
Experimental technique: per eight (male and female half and half) are one group.Every subcutaneous injection homocysteine 20mg/kg, per os is irritated folic acid, the vitamin B of stomach or intramuscular injection various dose then
6, vitamin B
12Other establishes blank group (the subcutaneous normal saline 2ml/kg that gives) and model group (subcutaneous injection homocysteine 20mg/kg, and give normal saline 2ml/kg behind subcutaneous injection).Equal 2h behind (0h) and the subcutaneous injection before subcutaneous injection, 4h, 7h, 12h gets blood, adds the EDTA anticoagulant, centrifugal (6000 change 10 minutes), separated plasma.Measure homocysteine in blood plasma concentration.Relatively the difference of homocysteine in plasma concentration is organized in each time point prevention (or treatment), and does the t check.The results are shown in Table one to six.Table one. oral variable concentrations folic acid to the influence of homocysteine in plasma (μ mol/L, x ± D, n=8)
Table two. oral variable concentrations vitamin B
6To the influence of homocysteine in plasma (μ mol/L, x ± SD, n=8)
Table three. oral variable concentrations vitamin B
12To the influence of homocysteine in plasma (μ mol/L, x ± D, n=8)
Table four. injection variable concentrations folic acid to the influence of homocysteine in plasma (μ mol/L, x ± SD, n=8)
Table five. injection variable concentrations vitamin B
6To the influence of homocysteine in plasma (μ mol/L, x ± SD, n=8)
Table six. injection variable concentrations vitamin B
12To the influence of homocysteine in plasma (μ mol/L, x ± SD, n=8)
The effective range (people is in 50kg) of determining various vitamin B group control hyperhomocysteinemiainjuries in view of the above is as follows: folic acid: 0.2～5mg; Vitamin B
6: 2～2.5mg; Vitamin B
12: 0.002～2.5mg.The present invention is with following span prescription: folic acid: 0.1～5mg, preferentially select 0.2～1mg for use; Vitamin B
6: 1～20mg, preferentially select 5～10mg for use; Vitamin B
12: 0.01～2mg, preferentially select 0.01～1mg for use.Vitamin preparation of the present invention can add suitable adjuvant, for example add suitable adhesive such as starch, hydroxypropyl methylcellulose, ethanol etc., add suitable filler such as microcrystalline Cellulose, sucrose, lactose etc., add suitable disintegrating agent such as sodium carboxymethylstarch etc., add suitable lubricant such as magnesium stearate etc., add suitable fluidizer such as Pulvis Talci etc., add suitable opacifier such as titanium dioxide and add green etc. can be made into of suitable pigment such as pectin and be fit to industrial tablet.Interpolation is used to regulate acid or the alkali that allows on the physiology of pH value, local anaesthetics, and osmotic pressure regulators etc. can be made injection.
| Time (hour) | ?0 | ?2 | ?4 | ?7 | ?12 |
| Blank group concentration | ?12.43±01.93 | ?15.02±4.04 | ?12.99±1.99 | ?10.47±1.69 | ?12.12±4.67 |
| Model group concentration | ?15.72±5.69 | ?49.00±8.24 | ?59.06±6.33 | ?50.49±6.48 | ?32.02±8.17 |
| 0.004mg/ | ?15.28± | ?44.32±4.34 | ?49.10±8.34 | ?35.54±7.94 | ?28.59±8.83 |
| 0.008mg/kg | ?14.93±5.46 | ?42.73±5.51 | ?49.54±7.46 | ?34.57±8.18 | ?28.86±8.86 |
| 0.016mg/kg | ?15.54±6.01 | ?41.45±6.34 | ?47.69±8.18 | ?36.64±4.32 | ?27.51±5.05 |
| 0.032mg/kg | ?15.67±5.82 | ?41.92±7.03 | ?45.11±6.58 | ?28.55±7.95 | ?28.48±4.25 |
| 0.064mg/kg | ?14.89±6.93 | ?40.24±7.09 | ?44.04±5.99 | ?28.71±6.45 | ?28.57±7.64 |
| 0.128mg/kg | ?15.98±7.01 | ?41.52±6.67 | ?46.04±7.75 | ?28.32±7.73 | ?30.48±6.10 |
| Time (hour) | ?0 | ?2 | ?4 | ?7 | ?12 |
| Blank group concentration | ?12.43±1.93 | ?15.02±4.04 | ?12.99±1.99 | ?10.47±1.69 | ?12.12±4.67 |
| Model group concentration | ?15.72±5.69 | ?49.00±8.24 | ?59.06±6.33 | ?50.49±6.48 | ?32.02±8.17 |
| 0.04mg/kg | ?14.32±3.75 | ?40.15±8.05 | ?44.33±8.15 | ?36.69±9.31 | ?22.25±11.00 |
| 0.08mg/kg | ?13.97±2.86 | ?41.17±9.10 | ?49.25±9.96 | ?38.72±9.62 | ?24.47±8.76 |
| 0.16mg/kg | ?14.15±3.12 | ?44.54±7.13 | ?48.36±10.43 | ?34.56±8.44 | ?21.34±9.45 |
| 0.32mg/kg | ?13.86±2.88 | ?39.23±8.88 | ?46.51±11.23 | ?35.51±8.85 | ?25.32±11.11 |
| 0.64mg/kg | ?12.51±3.25 | ?42.75±9.66 | ?47.74±9.87 | ?33.97±11.39 | ?26.67±10.52 |
| 1.28mg/kg | ?14.01±3.00 | ?40.08±8.59 | ?48.99±10.01 | ?34.51±9.56 | ?20.18±11.46 |
| Time (hour) | ?0 | ?2 | ?4 | ?7 | ?12 |
| Blank group concentration | ?12.43±1.93 | ?15.02±4.04 | ?12.99±1.99 | ?10.47±1.69 | ?12.12±4.67 |
| Model group concentration | ?15.7±25.69 | ?49.00±8.24 | ?59.06±6.33 | ?50.49±6.48 | ?32.02±8.17 |
| 0.0004mg/kg | ?13.63±2.67 | ?45.09±6.34 | ?47.05±4.99 | ?30.21±4.34 | ?21.37±8.99 |
| 0.002mg/kg | ?12.27±3.67 | ?44.25±5.66 | ?48.91±7.71 | ?37.38±8.56 | ?25.62±9.28 |
| 0.01mg/kg | ?16.70±4.12 | ?43.59±5.14 | ?43.82±6.32 | ?35.47±7.65 | ?22.77±10.41 |
| 0.05mg/kg | ?15.87±3.39 | ?41.24±5.79 | ?45.86±5.43 | ?35.60±6.56 | ?20.73±9.05 |
| Time (hour) | ?0 | ?2 | ?4 | ?7 | ?12 |
| Blank group concentration | ?12.43±01.93 | ?15.02±4.04 | ?12.99±1.99 | ?10.47±1.69 | ?12.12±4.67 |
| Model group concentration | ?15.72±5.69 | ?49.00±8.24 | ?59.06±6.33 | ?50.49±6.48 | ?32.02±8.17 |
| 0.004mg/kg | ?12.72±4.01 | ?30.15±7.28 | ?49.18±9.01 | ?24.39±8.84 | ?10.83±9.34 |
| 0.008mg/kg | ?14.36±6.52 | ?40.76±6.96 | ?49.27±7.26 | ?21.57±6.41 | ?18.83±8.12 |
| 0.016mg/kg | ?14.47±6.67 | ?41.13±7.04 | ?48.79±8.23 | ?23.36±7.95 | ?14.06±9.03 |
| 0.032mg/kg | ?15.36±5.41 | ?36.43±6.51 | ?44.93±8.95 | ?22.19±8.53 | ?8.76±6.45 |
| 0.064mg/kg | ?15.64±6.32 | ?38.19±6.76 | ?45.80±7.34 | ?20.06±8.12 | ?10.21±6.32 |
| 0.128mg/kg | ?13.58±5.45 | ?40.26±7.31 | ?48.68±8.75 | ?24.13±7.40 | ?13.62±7.71 |
| Time (hour) | ?0 | ?2 | ?4 | ?7 | ?12 |
| Blank group concentration | ?12.43±1.93 | ?15.02±4.04 | ?12.99±1.99 | ?10.47±1.69 | ?12.12±4.67 |
| Model group concentration | ?15.72±5.69 | ?49.00±8.24 | ?59.06±6.33 | ?50.49±6.48 | ?32.02±8.17 |
| 0.04mg/kg | ?13.45±4.16 | ?38.43±5.70 | ?46.39±8.48 | ?36.56±7.34 | ?19.24±9.83 |
| 0.08mg/kg | ?12.95±5.67 | ?44.45±6.35 | ?44.98±8.88 | ?32.46±10.56 | ?20.74±12.47 |
| 0.16mg/kg | ?16.65±5.43 | ?39.27±6.87 | ?46.27±9.35 | ?30.16±9.44 | ?18.98±9.41 |
| 0.32mg/kg | ?15.56±3.82 | ?40.71±8.34 | ?45.09±10.71 | ?32.95±8.92 | ?20.55±10.55 |
| 0.64mg/kg | ?15.66±4.79 | ?38.45±7.19 | ?44.93±7.90 | ?34.41±8.77 | ?18.78±12.25 |
| 1.28mg/kg | ?14.02±3.49 | ?39.16±7.60 | ?45.76±8.12 | ?35.99±9.99 | ?19.39±11.13 |
| Time (hour) | ?0 | ?2 | ?4 | ?7 | ?12 |
| Blank group concentration | ?12.43±1.93 | ?15.02±4.04 | ?12.99±1.99 | ?10.47±1.69 | ?12.12±4.67 |
| Model group concentration | ?15.7±25.69 | ?49.00±8.24 | ?59.06±6.33 | ?50.49±6.48 | ?32.02±8.17 |
| 0.0004mg/kg | ?13.71±3.99 | ?42.28±7.24 | ?51.58±7.05 | ?35.00±7.65 | ?21.51±8.86 |
| 0.002mg/kg | ?14.57±4.29 | ?41.19±6.97 | ?47.05±9.91 | ?43.48±9.29 | ?22.16±9.44 |
| 0.01mg/kg | ?15.12±5.12 | ?40.32±5.06 | ?48.91±8.82 | ?31.23±6.56 | ?21.45±9.82 |
| 0.05mg/kg | ?12.09±3.67 | ?0.26±7.59 | ?45.86±8.86 | ?32.60±5.56 | ?20.88±7.43 |
Embodiment 1:(tablet) plain sheet: folic acid: 4.0g, vitamin B
6: 50.0g, vitamin B
12: 0.575g, microcrystalline Cellulose: 400g, starch: 200g, cane sugar powder: 100g, lactose: 400g, sodium carboxymethylstarch: 100g, 6% hydroxypropyl methylcellulose RT5 ethanol liquid: an amount of, Pulvis Talci: 10.0g, magnesium stearate: 5.0g; Gross weight 1270g; Make 10000.Coating fluid prescription: hypromellose 60RT5 100g, pectin green lake: 6g, titanium dioxide: 20g, glycerol: 20g, ethanol (95%): 300, water adds to 1000g.
Embodiment 2:(tablet) plain sheet: folic acid: 1.0g, vitamin B
6: 10.0g, vitamin B
12: 0.1g, microcrystalline Cellulose: 400g, starch: 200g, cane sugar powder: 100g, lactose: 400g, sodium carboxymethylstarch: 100g, 6% hydroxypropyl methylcellulose RT5 ethanol liquid: an amount of, Pulvis Talci: 10.0g, magnesium stearate: 5.0g; Gross weight 1270g; Make 10000.Coating fluid prescription: hypromellose 60RT5 100g, pectin green lake: 6g, titanium dioxide: 20g, glycerol: 20g, ethanol (95%): 300, water adds to 1000g.
Embodiment 3:(tablet) plain sheet: folic acid: 2.0g, vitamin B
6: 100.0g, vitamin B
12: 20g, microcrystalline Cellulose: 400g, starch: 200g, cane sugar powder: 100g, lactose: 400g, sodium carboxymethylstarch: 100g, 6% hydroxypropyl methylcellulose RT5 ethanol liquid: an amount of, Pulvis Talci: 10.0g, magnesium stearate: 5.0g; Gross weight 1420g; Make 10000.Coating fluid prescription: hypromellose 60RT5 100g, pectin green lake: 6g, titanium dioxide: 20g, glycerol: 20g, ethanol (95%): 300, water adds to 1000g.
Embodiment 4:(tablet) plain sheet: folic acid: 10g, vitamin B
6: 1000.0g, vitamin B
12: 10g, microcrystalline Cellulose: 400g, starch: 200g, cane sugar powder: 100g, lactose: 400g, sodium carboxymethylstarch: 100g, 6% hydroxypropyl methylcellulose RT5 ethanol liquid: an amount of, Pulvis Talci: 10.0g, magnesium stearate: 5.0g; Gross weight 1270g; Make 10000.Coating fluid prescription: hypromellose 60RT5 100g, pectin green lake: 6g, titanium dioxide: 20g, glycerol: 20g, ethanol (95%): 300, water adds to 1000g.
Embodiment 5:(tablet) plain sheet: folic acid: 5.0g, vitamin B
6: 70.0g, vitamin B
12: 0.5g, microcrystalline Cellulose: 400g, starch: 200g, Icing Sugar: 100g, lactose: 400g, sodium carboxymethylstarch: 100g, 6% hydroxypropyl methylcellulose RT5 ethanol liquid: an amount of, Pulvis Talci: 10.0g, magnesium stearate: 5.0g; Gross weight 1270g; Make 10000.Coating fluid prescription: hypromellose 60RT5 100g, pectin green lake: 6g, titanium dioxide: 20g, glycerol: 20g, ethanol (95%): 300, water adds to 1000g.Above raw material is crossed 100 mesh sieves respectively, take by weighing according to the prescription precision then, adopt the equivalent incremental method to mix, twice mixing of each mistake 100 mesh sieves made soft material in right amount with 6% hydroxypropyl methylcellulose 60RT5 ethanol liquid, crossing 20 mesh sieves granulates, in 50 ℃ of oven dry 4 hours, add 1.0g Pulvis Talci and 0.56g magnesium stearate behind the granulate, fully behind the mixing, with spill punch die tabletting, average sheet heavily is that 125～230mg does not wait.The slice, thin piece of making according to above method for making is carried out the dissolution test result is: folic acid is leachable more than 95% in the time of 20 minutes; Vitamin B
6Leachable more than 80%; Vitamin B
12Leachable more than 90%; Remove vitamin B in the time of 40 minutes
6Still have 10% not outside the stripping, all 100% strippings of all the other two kinds of vitamin.
Embodiment 6:(injection) folic acid: 20mg, vitamin B
6100mg, vitamin B
12: 20mg, water adds to 1000ml.Add dilute hydrochloric acid and make PH4～8 in right amount, make 1ml, or 2ml, or single agent of 5ml.
Embodiment 7:(granule) granules of main drug:
Folic acid: 2g,
Vitamin B
6: 20g,
Vitamin B
12: 0.1g, kaolin: 30g, dextrin: 30g, stearic acid: 15g.Add suitable sweeting agent.Above supplementary material sieves, mixing, and after sieve, mixing again; With making granule after the suitable syrup moistening, in 40 ℃ of dryings, again with the zein coating.The zein coating method: get zein 25～50g, add 95% ethanol 1000ml, slight fever makes its dissolving in water-bath, leaves standstill a few hours, gets supernatant, spray coating, and every 100g granule spray 8～10ml sprays 5～10 times altogether.Excipient granule:
Icing Sugar: 200g, carboxymethyl cellulose: 10g.Above raw material is sieved, and mixing is made granule with syrup equally, drying; Measure usefulness on demand.Get the compound mormula folic acid granule that different granules of main drug and excipient granule can be made into different content.
Embodiment 8:(capsule) folic acid: 2g, vitamin B
6: 25g, vitamin B
12: 0.02g, take by weighing above raw material according to the side, mixing is crossed 60 mesh sieves and is added an amount of adhesive mixed pelletization, and it is encapsulated or directly encapsulated with former powder to be converted into recipe quantity.
Claims (7)
- What 1, be used to prevent and treat hyperhomocysteinemiainjury and relevant disease thereof contains folic acid, vitamin B 6, vitamin B 12Compound preparation; Its unit prescription is:Folic acid: 0.1～5mg;Vitamin B 6: 1～20mg;Vitamin B 12: 0.01～2mg.
- 2, according to claim 1 be used to prevent and treat hyperhomocysteinemiainjury and relevant disease thereof contain folic acid, vitamin B 6, vitamin B 12Compound preparation, wherein: folic acid: 0.2～1mg.
- 3, according to claim 1 be used to prevent and treat hyperhomocysteinemiainjury and relevant disease thereof contain folic acid, vitamin B 6, vitamin B 12Compound preparation, wherein: vitamin B 6: 5～10mg.
- 4, according to claim 1 be used to prevent and treat hyperhomocysteinemiainjury and relevant disease thereof contain folic acid, vitamin B 6, vitamin B 12Compound preparation, wherein: vitamin B 12: 0.01～1mg.
- 5, according to claim 1, or 2, or 3, or 4 described be used to prevent and treat hyperhomocysteinemiainjury and relevant disease thereof contain folic acid, vitamin B 6, vitamin B 12Compound preparation, add suitable adjuvant, make tablet.
- 6, according to claim 1, or 2, or 3, or 4 described be used to prevent and treat hyperhomocysteinemiainjury and relevant disease thereof contain folic acid, vitamin B 6, vitamin B 12Compound preparation, add suitable adjuvant, make injection.
- 7, according to claim 1, or 2, or 3, or 4 described be used to prevent and treat hyperhomocysteinemiainjury and relevant disease thereof contain folic acid, vitamin B 6, vitamin B 12Compound preparation, add suitable adjuvant, make capsule.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 01115679 CN1383829A (en) | 2001-05-08 | 2001-05-08 | Compound folic acid prepn for preventing and treating homocysteinemia and relevant diseases |
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|---|---|---|---|
| CN 01115679 CN1383829A (en) | 2001-05-08 | 2001-05-08 | Compound folic acid prepn for preventing and treating homocysteinemia and relevant diseases |
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| WO2009046632A1 (en) * | 2007-09-28 | 2009-04-16 | Beijing Huaanfo Biomedical Research Center, Inc | Pharmaceutical composition containing angiotensin ii receptor blocker and b family vitamins and use thereof |
| CN101897706A (en) * | 2009-05-27 | 2010-12-01 | 北京奥萨医药研究中心有限公司 | Composition containing folic acid and B vitamins and applications thereof |
| CN101406478B (en) * | 2007-10-10 | 2012-01-18 | 北京华安佛医药研究中心有限公司 | Pharmaceutical composition for reducing homosysteine |
| CN103070831A (en) * | 2013-02-02 | 2013-05-01 | 常州市新鸿医药化工技术有限公司 | Method for preparing 10-90% folic acid granules |
| CN102099044B (en) * | 2008-05-16 | 2014-06-11 | 益生菌股份公司 | Use of probiotic bacteria for the treatment of hyperhomocysteinaemia |
| CN107772458A (en) * | 2017-09-29 | 2018-03-09 | 赤峰赛佰诺制药有限公司 | A kind of formula powder for hyperhomocysteinemiainjury and preparation method thereof |
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2001
- 2001-05-08 CN CN 01115679 patent/CN1383829A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009046632A1 (en) * | 2007-09-28 | 2009-04-16 | Beijing Huaanfo Biomedical Research Center, Inc | Pharmaceutical composition containing angiotensin ii receptor blocker and b family vitamins and use thereof |
| CN101406478B (en) * | 2007-10-10 | 2012-01-18 | 北京华安佛医药研究中心有限公司 | Pharmaceutical composition for reducing homosysteine |
| CN102099044B (en) * | 2008-05-16 | 2014-06-11 | 益生菌股份公司 | Use of probiotic bacteria for the treatment of hyperhomocysteinaemia |
| CN101897706A (en) * | 2009-05-27 | 2010-12-01 | 北京奥萨医药研究中心有限公司 | Composition containing folic acid and B vitamins and applications thereof |
| CN103070831A (en) * | 2013-02-02 | 2013-05-01 | 常州市新鸿医药化工技术有限公司 | Method for preparing 10-90% folic acid granules |
| CN107772458A (en) * | 2017-09-29 | 2018-03-09 | 赤峰赛佰诺制药有限公司 | A kind of formula powder for hyperhomocysteinemiainjury and preparation method thereof |
| CN113230273A (en) * | 2021-05-11 | 2021-08-10 | 北京里肯营养科学研究有限公司 | Compound preparation containing choline, B vitamins, folic acid and zinc for preventing and treating hyperhomocysteinemia |
| CN113974125A (en) * | 2021-10-26 | 2022-01-28 | 姚关兵 | Edible salt composition for hyperhomocysteinemia and edible method |
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