CN101103985A - Folic acid dropping pill and its preparation method - Google Patents
Folic acid dropping pill and its preparation method Download PDFInfo
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Abstract
The invention relates to an oral folacin pill preparation which contains drug and expients; wherein the drug contains folacin and the excipient is one of or mixture of more than two (including two) of polyethyleneglycol, magnesium stearate, stearic acid, sodium stearate, poloxamer, polyoxyethylene dehydrous sorbitol fatty acid ester, polyoxyethylene (40) monostearate (S-40), sucrose fatty ester and glycerogelatin. The invention also relates to the preparation method of the folacin pill preparation and the purpose of the folacin pill preparation in preparation of drug for treating hyperhomocysteinemia. The folacin pill preparation provided in the invention, belonging to the pharmaceutical field has the advantages of full dissolution of the drug, quick effect and improvement of human bioavailability.
Description
Technical field
The present invention relates to a kind of oral folic acid dropping pill preparation.This dropping pill formulation is made up of medicine and adjuvant, medicine comprises folic acid, and adjuvant is one or more the mixture in Polyethylene Glycol, magnesium stearate, stearic acid, sodium stearate, poloxamer, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene (40) monostearate, sucrose fatty acid ester and the glycerin gelatine.The invention still further relates to the preparation method of this folic acid dropping pill preparation, and the purposes of this folic acid dropping pill preparation in the medicine of preparation treatment hyperhomocysteinemiainjury.The invention belongs to pharmaceutical field.
Background technology
Cardiovascular and cerebrovascular diseases such as atherosclerosis, coronary heart disease, apoplexy are except the hazard factor of past research, and Chinese scholars was discovered in the last few years, and hyperhomocysteinemiainjury is the new risk factor of cardiovascular and cerebrovascular disease.
Homocysteine (Hcy homosysteine) is a kind of essential amino acids of sulfur-bearing---methionine itself does not participate in proteinic synthetic at the intravital metabolite of people.The methionine molecule contains the S-methyl; After generating the S-ademetionine with adenosine triphosphate (ATP) effect, can pass through various transmethylations, the material that has important physiologically active for known about kind more than 50 in the body provides methyl.The S-ademetionine under the transmethylase effect with Methyl transporters to another material, generate the S-adenosyl homocysteine, the latter further sloughs adenosine, generates homocysteine.Homocysteine mainly carries out metabolism by two approach: the approach that methylates again and commentaries on classics sulfur approach.Approach again methylates: 50% homocysteine being arranged approximately under the effect of methionine synthase, is cofactor with the vitamin B12, is methyl donor with the N-5-methyl tetrahydrofolate, takes place to methylate again, and synthetic methionine is participated in the metabolism of body internal protein again.Methyl donor in this reaction (N-5-methyl tetrahydrofolate) is by N-5, and 10-Methylene tetrahydrofolate reductase (MTHFR, methylene tetrahydrofolate reductase) acts on N-5, and the 10-methylene tetrahydrofolate forms; And methionine synthetase reductase (MTRR, Methionine synthasereductase) is the cofactor of methionine synthase.In addition, about 50% homocysteine also can be by changeing the sulfur approach at cystathionine (CBS, under the catalysis of cystathionine β-synthase), be condensed into Guang sulfur enzyme with serine, the latter further generates cysteine and α-ketone butanoic acid, this process need pyridoxal 5-phosphate (active vitamin B6) is as cofactor [TIPS, 1990,11:411-416].
This shows that the metabolic process of homocysteine needs folic acid, vitamin B12 and B6 and participates in and could intactly carry out.In case this metabolic process generation obstacle just can cause too much homocysteine to pile up rising in blood, is called " hyperhomocysteinemiainjury " clinically.The homocysteine blood plasma level is too high, but vascular endothelial cell injury degeneration, promote thrombosis, and can strengthen low density lipoprotein, LDL just bad cholesterol atherosclerotic facilitation is increased the weight of lipid precipitation such as cholesterol and triglyceride, form atherosclerotic plaque, angiostenosis is followed the string, blood circulation slows down, as runs into hypertension, and the height direct stimulation just cordis and cerebral accident may take place.
The basis shows all that with clinical research homocysteine is an independently risk factor of cardiovascular and cerebrovascular disease in recent years.High tHCY mass formed by blood stasis can inspire all important cardiovascular and cerebrovascular diseases and take place, and comprises coronary heart disease, apoplexy, renal function injury, peripheral arterial disease etc. [angiocardiology progress, 2000,21:29].It is a wait indefinitely independent hazard factor [the The Homocysteine StudiesCollaboration.Homocysteine and risk of ischemic heart disease and stroke:a Metaanalysis.JAMA of cardiovascular and cerebrovascular disease and periphery obstructive angiopathy of myocardial infarction, cerebral infarction that Plasma Homocysteine raises, 2002,288:2015-2022; Kang SS, et al.Hyperhomocysteine mia as a riskfactor for occlusive vascular disease.AnnuRevNutr, 1992,12:279-298; Stampfer MJ, etal.A prospec tive study of plasma homocysteine and risk of myocardial infarction inUS physicians.JAMA, 1992,268:877-881].
The sickness rate of China's cardiovascular and cerebrovascular disease sharply increases, and the people of dyslipidemia is 1.6 hundred million, and the people Shang Wu diagnostic criteria accurately and the statistics of hyperhomocysteinemiainjury, but also high from Clinical Laboratory.The expert thinks that the task of top priority will be taked these effective measures of Supplement of folic acid of approval both at home and abroad.Folic acid participates in the metabolic process of homocysteine, and Supplement of folic acid can reduce methionine and produce less homocysteine in metabolic process, thus the protection tremulous pulse.American Studies confirms that if the folate content in the blood rises 2 times, then homocysteine can descend 7%.Folic acid participates in the metabolic process of homocysteine, make folic acid help the homocysteine essential methionine confession health utilization of synthesized human again, thereby also just reduced the concentration of the homocysteine in the blood plasma, and helped the treatment and the health care of cardiovascular and cerebrovascular disease.Vitamin B12 equally participates in the methionine metabolism with folic acid, can reduce the concentration of homocysteine in plasma, and therefore suggestion increases the food intake dose that is rich in B12.
Folic acid is as a kind of vitamin B group, the forties in 20th century of separated extraction and gaining the name from the leaf of spinach.Because the importance of folic acid in meals is familiar with gradually, particularly progressively go deep into the research of birth defect, cardiovascular and cerebrovascular disease and tumor, folic acid has become very important micronutrient.
The folic acid oral formulations of having developed has: tablet, oral cavity disintegration tablet, capsule, soft capsule etc., but because dosage form itself, they all exist following problem:
(1) disintegration rate is slow, and the effective ingredient rate of release is low;
(2) absorption difference, bioavailability is low, often influences the clinical efficacy of medicine;
(3) first pass effect problem: first pass effect (First-pass Effect) claim the first pass effect again, is meant oral drugs after gastrointestinal absorption, at first arrives liver through portal vein, enters the body circulation again.By metabolism, this phenomenon becomes first pass effect to some medicine by liver the time.Conventional oral formulations is easy to generate first pass effect owing to the reason major part of itself absorbs in gastrointestinal tract, its effective ingredient is reduced;
(4) child, old people, bed patient and dysphagia patients are taken inconvenience.
At the problem of above existence, we need a kind of efficient, quick-acting, bioavailability is high and the foliamin of taking convenience satisfies the needs of clinical practice.
Summary of the invention
The objective of the invention is to overcome above the deficiencies in the prior art, provide a kind of efficient, quick-acting, bioavailability is high and the foliamin of taking convenience.
The invention provides a kind of folic acid dropping pill preparation, it is made up of medicine and adjuvant, wherein medicine comprises folic acid, adjuvant is a water-soluble material, comprises in Polyethylene Glycol, magnesium stearate, stearic acid, sodium stearate, poloxamer, polyoxyethylene dehydration sorbic acid fatty acid ester, polyoxyethylene (40) monostearate (S-40), sucrose fatty acid ester and the glycerin gelatine one or more.
Medicine in the folic acid dropping pill preparation provided by the invention further comprises vitamin B12.
Folic acid in the folic acid dropping pill preparation provided by the invention can be the have similar bioactive chemical compound relevant with folic acid, as the active metabolite of formyl tetrahydrofolic acid, methyl tetrahydrofolate, methylene tetrahydrofolate, folate, folinate, folic acid or folate and metabolism and/or generate the material etc. of folic acid in vivo.
Vitamin B12 in the folic acid dropping pill preparation provided by the invention can be the have similar bioactive chemical compound relevant with vitamin B12, as the derivant of cobalamine, mecobalamin element, 5 '-deoxyadenosyl cobalamin, hydroxocobalamine and above-mentioned substance and metabolism and/or generate the material of this compounds in vivo.
Can further add correctives in the folic acid dropping pill preparation provided by the invention, comprise strawberry essence, Fructus Citri tangerinae essence, Herba Menthae essence, Fructus Citri Limoniae essence etc.
Folic acid dropping pill preparation of Chinese medicine provided by the invention is a folic acid, and adjuvant is a Polyethylene Glycol; The weight proportion of medicine and adjuvant is: folic acid 0.5%～20%, Polyethylene Glycol 80%～99.5%; The preferred weight proportioning is: folic acid 2%～8%, Polyethylene Glycol 92%～98%.
Folic acid dropping pill preparation of Chinese medicine provided by the invention is folic acid and vitamin B12, and adjuvant is a Polyethylene Glycol; The weight proportion of medicine and adjuvant is: folic acid 0.5%～20%, vitamin B12 0.3%～20%, Polyethylene Glycol 75%～98%; The preferred weight proportioning is: folic acid 2%～8%, vitamin B12 0.4%～15%, Polyethylene Glycol 80%～98%.
The adjuvant Polyethylene Glycol is Macrogol 4000, polyethylene glycol 6000 or its mixture in the folic acid dropping pill preparation provided by the invention, the mixture of preferred Macrogol 4000 and polyethylene glycol 6000, its weight proportion is: Macrogol 4000 10%～40%, polyethylene glycol 6000 90%～60%.
Another purpose of the present invention provides the preparation method of folic acid dropping pill, and step is as follows:
(1) with medicine and adjuvant mix homogeneously, fusion is stirred in heating, makes medicine dissolution complete;
(2) melting mixing liquid is moved into dropping-pill machine system;
(3) medicine liquid droplet cools off to liquid paraffin or dimethyl-silicon oil coolant, solidifies 30～40 minutes;
(4) remove coolant, select ball, promptly obtain folic acid dropping pill.
In the preparation method of folic acid dropping pill provided by the invention, melt temperature is 65～105 ℃ with dripping a system temperature, and a preferred melt temperature and a system temperature are 75～95 ℃, and optimum temperature is 85～90 ℃.
In the preparation method of folic acid dropping pill provided by the invention, dropping-pill machine head diameter is 1 millimeter～2 millimeters, and preferred water dropper diameter is 1 millimeter.
In the preparation method of folic acid dropping pill provided by the invention, preferred coolant is a liquid paraffin; Coolant temperature is preferably-10 ℃～5 ℃ for being lower than 10 ℃.
In the preparation method of folic acid dropping pill provided by the invention, the method for removing coolant normally blots with suction cloth.
Another object of the present invention provides the purposes of folic acid dropping pill preparation in the medicine of preparation treatment hyperhomocysteinemiainjury.
In the purposes of folic acid dropping pill preparation provided by the invention, described folic acid dropping pill preparation is made up of medicine and adjuvant, wherein medicine comprises folic acid, adjuvant is a water-soluble material, comprises in Polyethylene Glycol, magnesium stearate, stearic acid, sodium stearate, poloxamer, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene (40) monostearate (S-40), sucrose fatty acid ester and the glycerin gelatine one or more.
In the purposes of folic acid dropping pill preparation provided by the invention, described folic acid dropping pill preparation of Chinese medicine further comprises vitamin B12.
In the purposes of folic acid dropping pill preparation provided by the invention, described folic acid dropping pill preparation of Chinese medicine is a folic acid, and adjuvant is a Polyethylene Glycol; The weight proportion of medicine and adjuvant is: folic acid 0.5%～20%, Polyethylene Glycol 80%～99.5%; The preferred weight proportioning is: folic acid 2%～8%, Polyethylene Glycol 92%～98%.
In the purposes of folic acid dropping pill preparation provided by the invention, described folic acid dropping pill preparation of Chinese medicine is folic acid and vitamin B12, and adjuvant is a Polyethylene Glycol; The weight proportion of medicine and adjuvant is: folic acid 0.5%～20%, vitamin B12 0.3%～20%, Polyethylene Glycol 75%～98%; The preferred weight proportioning is: folic acid 2%～8%, vitamin B12 0.4%～15%, Polyethylene Glycol 80%～98%.
In the purposes of folic acid dropping pill preparation provided by the invention, the adjuvant Polyethylene Glycol is Macrogol 4000, polyethylene glycol 6000 or its mixture in the described folic acid dropping pill preparation, the mixture of preferred Macrogol 4000 and polyethylene glycol 6000, its weight proportion is: Macrogol 4000 10%～40%, polyethylene glycol 6000 90%～60%.
Folic acid dropping pill preparation provided by the invention is to utilize pharmaceutically acceptable auxiliaries such as Polyethylene Glycol and active constituents of medicine folic acid or folic acid and vitamin B12 fully to be mixed and made into solid dispersion, and medicine is dispersed in the adjuvant, and the total surface area of medicine is increased.And adjuvant is a hydrophilic, and medicine is had wetting action, can make medicine be separated into microgranular rapidly or is dissolved as liquidly, thereby makes the dissolving of medicine and absorb to accelerate, thereby improved bioavailability, has brought into play efficient, quick-acting effects.
Folic acid dropping pill preparation provided by the invention is by after solid drugs and adjuvant heating, being melt into liquid state, splashes in the not miscible condensing agent and makes, the stability of drug height, be difficult for oxidation, be not subject to the influence of crystal formation, thereby guaranteed drug quality, increase stability, helped improving curative effect.
Folic acid dropping pill preparation medicine content height provided by the invention, dose is little and convenient; Can sublingual administration, contact promptly with saliva and to dissolve rapidly, absorb by oral mucosa, directly enter blood circulation without gastrointestinal tract and liver, avoided the liver sausage first pass effect; The adding correctives more can improve the mouthfeel of buccal.
The advantage of folic acid dropping pill preparation provided by the invention is:
(1) the medicine stripping is fast, and release is quick, complete, and produce effects is fast;
(2) bioavailability height;
(3) can avoid first pass effect;
(4) stability and controllability are good, help improving curative effect;
(5) dose is little and convenient, is particularly suitable for child, old people, bed patient and dysphagia patients and takes;
(6) no dust takes place in preparation process, can not cause any pollution;
(7) safety is stronger, toxic and side effects is lower.
Description of drawings
Fig. 1 isThe dissolution curve ratio of folic acid dropping pill and folic acid ordinary tablet;
Fig. 2 isThe dissolution curve ratio of folic acid VB12 drop pill and folic acid VB12 ordinary tablet;
Fig. 3 isFolic acid blood drug level-time graph (n=6) behind oral folic acid dropping pill of domesticated dog and the folic acid ordinary tablet.
The specific embodiment
The present invention will be further described below in conjunction with the specific embodiment, is not limitation of the invention, all any this areas of carrying out according to content of the present invention be equal to replacement, all belong to protection scope of the present invention.
The consumption of the formulation preparation process of following pharmaceutical preparation embodiment and used material of preparation or the used material of preparation is not limited to character express; all preparation methoies that contains pharmaceutical preparation provided by the invention; all belong to protection scope of the present invention; but concrete experimental technique reference drug preparation quick-reference book is as " pharmaceutical necessities is used and preparation ", " pharmaceutics ", " Biopharmaceutics and Pharmacokinetics " etc.
Embodiment 1
Write out a prescription 1000
Folic acid 0.4g
Macrogol 4000 3g
Polyethylene glycol 6000 7.5g
Strawberry essence 0.1g
Preparation method:
Take by weighing folic acid, Polyethylene Glycol according to recipe quantity, mix homogeneously is heated to 85 ℃, stirs fusion, makes the folic acid dissolving fully; Add the strawberry essence correctives then, mixing.Keeping this temperature, melting mixing liquid is moved into the drop pill machine, is water dropper system of dripping under 85 ℃ of temperature of 1 millimeter with diameter; Medicine liquid droplet solidified 30～40 minutes to-10 ℃ liquid paraffin, filtered out drop pill, removed liquid paraffin, selected ball, made 1000 of drop pill.Every heavy 11mg of drop pill contains folic acid 0.4mg.
Write out a prescription 1000
Folic acid 0.8g
Macrogol 4000 6g
Polyethylene glycol 6000 15g
Fructus Citri tangerinae essence 0.1g
Preparation method:
Take by weighing folic acid, Polyethylene Glycol according to recipe quantity, mix homogeneously is heated to 85 ℃, stirs fusion, makes the folic acid dissolving fully; Add Fructus Citri tangerinae essence correctives then, mixing.Keeping this temperature, melting mixing liquid is moved into the drop pill machine, is water dropper system of dripping under 85 ℃ of temperature of 1 millimeter with diameter; Medicine liquid droplet solidified 30～40 minutes to-10 ℃ liquid paraffin, filtered out drop pill, removed liquid paraffin, selected ball, made 1000 of drop pill.Every heavy 21.9mg of drop pill contains folic acid 0.8mg.
Embodiment 3
Write out a prescription 1000
Folic acid 1.0g
Macrogol 4000 8g
Polyethylene glycol 6000 12g
Preparation method:
Take by weighing folic acid, Polyethylene Glycol according to recipe quantity, mix homogeneously is heated to 85 ℃, stirs fusion, makes the folic acid dissolving fully; Keeping this temperature, melting mixing liquid is moved into the drop pill machine, is water dropper system of dripping under 85 ℃ of temperature of 1 millimeter with diameter; Medicine liquid droplet solidified 30～40 minutes to-10 ℃ liquid paraffin, filtered out drop pill, removed liquid paraffin, selected ball, made 1000 of drop pill.Every heavy 21mg of drop pill contains folic acid 1.0mg.
Write out a prescription 1000
Folic acid 0.4g
Vitamin B12 0.05g
Macrogol 4000 3g
Polyethylene glycol 6000 7.5g
Strawberry essence 0.1g
Preparation method:
Take by weighing folic acid, vitamin B12, Polyethylene Glycol according to recipe quantity, mix homogeneously is heated to 85 ℃, stirs fusion, makes folic acid, vitamin B12 dissolving fully; Add the strawberry essence correctives then, mixing.Keeping this temperature, melting mixing liquid is moved into the drop pill machine, is water dropper system of dripping under 85 ℃ of temperature of 1 millimeter with diameter; Medicine liquid droplet solidified 30～40 minutes to-10 ℃ liquid paraffin, filtered out drop pill, removed liquid paraffin, selected ball, made 1000 of drop pill.Every heavy 11mg of drop pill contains folic acid 0.4mg, vitamin B12 0.05mg.
Embodiment 5
Write out a prescription 1000
Folic acid 0.4g
Vitamin B12 0.5g
Macrogol 4000 5g
Polyethylene glycol 6000 7.5g
Fructus Citri tangerinae essence 0.1g
Preparation method:
Take by weighing folic acid, vitamin B12, Polyethylene Glycol according to recipe quantity, mix homogeneously is heated to 85 ℃, stirs fusion, makes folic acid, vitamin B12 dissolving fully; Add Fructus Citri tangerinae essence correctives then, mixing.Keeping this temperature, melting mixing liquid is moved into the drop pill machine, is water dropper system of dripping under 85 ℃ of temperature of 1 millimeter with diameter; Medicine liquid droplet solidified 30～40 minutes to-10 ℃ liquid paraffin, filtered out drop pill, removed liquid paraffin, selected ball, made 1000 of drop pill.Every heavy 13.5mg of drop pill contains folic acid 0.4mg, vitamin B12 0.5mg.
Write out a prescription 1000
Folic acid 0.4g
Vitamin B12 2g
Macrogol 4000 4.6g
Polyethylene glycol 6000 8g
Preparation method:
Take by weighing folic acid, vitamin B12, Polyethylene Glycol according to recipe quantity, mix homogeneously is heated to 85 ℃, stirs fusion, makes folic acid, vitamin B12 dissolving fully; Keeping this temperature, melting mixing liquid is moved into the drop pill machine, is water dropper system of dripping under 85 ℃ of temperature of 1 millimeter with diameter; Medicine liquid droplet solidified 30～40 minutes to-10 ℃ liquid paraffin, filtered out drop pill, removed liquid paraffin, selected ball, made 1000 of drop pill.Every heavy 15mg of drop pill contains folic acid 0.4mg, vitamin B12 2mg.
Embodiment 7
Write out a prescription 1000
Folic acid 0.8g
Vitamin B12 2g
Macrogol 4000 6
Polyethylene glycol 6000 10
Preparation method:
Take by weighing folic acid, vitamin B12, Polyethylene Glycol according to recipe quantity, mix homogeneously is heated to 85 ℃, stirs fusion, makes folic acid, vitamin B12 dissolving fully; Keeping this temperature, melting mixing liquid is moved into the drop pill machine, is water dropper system of dripping under 85 ℃ of temperature of 1 millimeter with diameter; Medicine liquid droplet solidified 30～40 minutes to-10 ℃ liquid paraffin, filtered out drop pill, removed liquid paraffin, selected ball, made 1000 of drop pill.Every heavy 18.8mg of drop pill contains folic acid 0.8mg, vitamin B12 2mg.
Write out a prescription 1000
Folic acid 1.0g
Vitamin B12 2g
Macrogol 4000 8
Polyethylene glycol 6000 12
Preparation method:
Take by weighing folic acid, vitamin B12, Polyethylene Glycol according to recipe quantity, mix homogeneously is heated to 85 ℃, stirs fusion, makes folic acid, vitamin B12 dissolving fully; Keeping this temperature, melting mixing liquid is moved into the drop pill machine, is water dropper system of dripping under 85 ℃ of temperature of 1 millimeter with diameter; Medicine liquid droplet solidified 30～40 minutes to-10 ℃ liquid paraffin, filtered out drop pill, removed liquid paraffin, selected ball, made 1000 of drop pill.Every heavy 23mg of drop pill contains folic acid 1.0mg, vitamin B12 2mg.
Embodiment 9
Write out a prescription 1000
Folic acid 0.4g
Vitamin B12 2g
Polyethylene glycol 6000 10g
Sucrose fatty acid ester 2.6g
Preparation method:
Take by weighing folic acid, vitamin B12, polyethylene glycol 6000, sucrose fatty acid ester according to recipe quantity, mix homogeneously is heated to 85 ℃, stirs fusion, makes folic acid, vitamin B12 dissolving fully; Keeping this temperature, melting mixing liquid is moved into the drop pill machine, is water dropper system of dripping under 85 ℃ of temperature of 1 millimeter with diameter; Medicine liquid droplet solidified 30～40 minutes to-10 ℃ liquid paraffin, filtered out drop pill, removed liquid paraffin, selected ball, made 1000 of drop pill.Every heavy 15mg of drop pill contains folic acid 0.4mg, vitamin B12 2mg.
Write out a prescription 1000
Folic acid 0.4g
Vitamin B12 1g
Poloxamer 188 7g
S-40 4.6g
Preparation method:
Take by weighing folic acid, vitamin B12, poloxamer 188, S-40 according to recipe quantity, mix homogeneously is heated to 85 ℃, stirs fusion, makes folic acid, vitamin B12 dissolving fully; Keeping this temperature, melting mixing liquid is moved into the drop pill machine, is water dropper system of dripping under 85 ℃ of temperature of 1 millimeter with diameter; Medicine liquid droplet solidified 30～40 minutes to-10 ℃ liquid paraffin, filtered out drop pill, removed liquid paraffin, selected ball, made 1000 of drop pill.Every heavy 13mg of drop pill contains folic acid 0.4mg, vitamin B12 1mg.
Embodiment 11Folic acid dropping pill and folic acid VB12 drop pill dissolution are investigated
1. prepare folic acid ordinary tablet (1000)
Prescription
Folic acid 0.4g
Lactose 25g
CMS-Na 25g
Starch 45g
5%PVP K30 ethanol solution is an amount of
Magnesium stearate 0.5%
Preparation method:
(1) folic acid of getting recipe quantity is crossed behind 80 mesh sieves standby;
(2) other adjuvants are respectively 75 ℃ of dryings 2 hours;
(3) press behind the starch, lactose, CMS-Na mixing of recipe quantity again and crude drug equivalent incremental method mixing;
(4) the adding binding agent is an amount of, granulation, granulate, 40～45 ℃ of dryings;
(5) dried granule adds 0.5% magnesium stearate mixing, tabletting behind the assay.
2. prepare folic acid VB12 ordinary tablet (1000)
Prescription
Folic acid 0.4g
Vitamin B12 0.05g
Lactose 25g
CMS-Na 25g
Starch 45g
5%PVP K30 ethanol solution is an amount of
Magnesium stearate 0.5%
Preparation method:
(1) get the folic acid of recipe quantity and vitamin B12 cross 80 mesh sieves after mix homogeneously standby;
(2) other adjuvants are respectively 75 ℃ of dryings 2 hours;
(3) press behind the starch, lactose, CMS-Na mixing of recipe quantity again crude drug equivalent incremental method mixing with mix homogeneously;
(4) the adding binding agent is an amount of, granulation, granulate, 40～45 ℃ of dryings;
(5) dried granule adds 0.5% magnesium stearate mixing, tabletting behind the assay.
3. dissolution relatively
According to " the dissolution of the folic acid VB12 drop pill that folic acid dropping pill that Chinese Pharmacopoeia version appendix in 2000 XC dissolution method three therapeutic methods of traditional Chinese medicine mensuration embodiment 1 provides and embodiment 4 provide, and compare with the dissolution of self-control folic acid ordinary tablet and folic acid VB12 ordinary tablet, the results are shown in Table 1.Draw the stripping curve of folic acid dropping pill and folic acid VB12 drop pill, see Fig. 1 and Fig. 2.
Table 1 folic acid dropping pill preparation and conventional tablet dissolution are relatively
| Time (min) | 5 | 10 | 15 | 30 | 45 | 60 | |
| Dissolution (%) | Folic acid ordinary tablet embodiment 1 | 20.2 70.1 | 35.3 81.4 | 45.3 84.2 | 70.6 89.4 | 88.5 91.3 | 89.3 90.5 |
| Folic acid VB12 |
23.4 73.2 | 36.8 79.9 | 49.7 85.2 | 74.3 90.5 | 90.9 90.9 | 90.2 90.2 | |
By Fig. 1 and Fig. 2 as can be known, folic acid dropping pill provided by the invention and folic acid VB12 drop pill have significantly improved the dissolution rate of medicine, further illustrate feasibility of the present invention.
Embodiment 12Folic acid dropping pill preparation bioavailability and bioequivalence Journal of Sex Research
Experiment purpose: research folic acid dropping pill and folic acid ordinary tablet are in intravital pharmacokinetics of domesticated dog and relative bioavailability.
Method: 6 male dogs of health are divided into two groups at random, carry out the test of dual crossing own control.Adopt the drug level in the rp-hplc determination man dog plasma, calculate pharmacokinetic parameters with blood drug level-time data.
The result:
1. evaluation of bioequivalence
Folic acid dropping pill is pressed F=AUC with respect to the bioavailability of folic acid ordinary tablet
0 → t(T)/AUC
0 → t(R) * 100% be calculated as (122.5 ± 20.5) %.
2. pharmacokinetic parameters
The T of folic acid dropping pill and folic acid ordinary tablet
MaxBe respectively (1.25 ± 0.22) h and (2.50 ± 0.85) h; C
MaxBe respectively (1.37 ± 0.30) and (1.07 ± 0.17) μ gml
-1Illustrate that the folic acid dropping pill onset is fast than ordinary tablet, absorption rate is fast, and is more complete.
Conclusion: folic acid dropping pill is compared with the folic acid ordinary tablet, can significantly improve absorption rate, and Tmax obviously shortens, and bioavailability increases.
Claims (11)
1. folic acid dropping pill preparation, form by medicine and adjuvant, wherein medicine comprises folic acid, and adjuvant is selected from one or more the mixture in Polyethylene Glycol, magnesium stearate, stearic acid, sodium stearate, poloxamer, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene (40) monostearate, sucrose fatty acid ester and the glycerin gelatine.
2. the described folic acid dropping pill preparation of claim 1, it is characterized in that: described medicine is a folic acid, adjuvant is a Polyethylene Glycol; The weight proportion of medicine and adjuvant is: folic acid 0.5%～20%; Polyethylene Glycol 80%～99.5%.
3. the described folic acid dropping pill preparation of claim 2, it is characterized in that: the weight proportion of described medicine and adjuvant is: folic acid 2%～8%; Polyethylene Glycol 92%～98%.
4. the described folic acid dropping pill preparation of claim 1, it is characterized in that: described medicine further comprises vitamin B12.
5. the described folic acid dropping pill preparation of claim 4, it is characterized in that: described medicine is folic acid and vitamin B12, adjuvant is a Polyethylene Glycol; The weight proportion of medicine and adjuvant is: folic acid 0.5%～20%; Vitamin B12 0.3%～20%; Polyethylene Glycol 75%～98%.
6. the described folic acid dropping pill preparation of claim 5, it is characterized in that: the weight proportion of described medicine and adjuvant is: folic acid 2%～8%; Vitamin B12 0.4%～15%; Polyethylene Glycol 80%～98%.
7. each described folic acid dropping pill preparation of claim 1 to 6, it is characterized in that: described Polyethylene Glycol is the mixture of Macrogol 4000, polyethylene glycol 6000 or Macrogol 4000 and polyethylene glycol 6000;
8. the described folic acid dropping pill preparation of claim 7, it is characterized in that: described Polyethylene Glycol is the mixture of Macrogol 4000 and polyethylene glycol 6000, and its weight proportion is: Macrogol 4000 10%～40%, polyethylene glycol 6000 90%～60%.
9. the preparation method of each described folic acid dropping pill preparation of claim 1 to 8:
(1) with medicine and adjuvant mix homogeneously, fusion is stirred in heating, makes medicine dissolution complete, and melt temperature is 75～95 ℃;
(2) melting mixing liquid is moved into dropping-pill machine system, dripping the system temperature is 75～95 ℃, and dropping-pill machine head diameter is 1 millimeter～2 millimeters;
(3) medicine liquid droplet cools off to liquid paraffin or dimethyl-silicon oil coolant, and coolant temperature is for being lower than 10 ℃;
(4) remove coolant, select ball, promptly obtain folic acid dropping pill.
10. the preparation method of the described folic acid dropping pill preparation of claim 9 is characterized in that a melt temperature and a system temperature are 85～90 ℃; Dropping-pill machine head diameter is 1 millimeter; Coolant is a liquid paraffin, and coolant temperature is-10 ℃～5 ℃.
11. the purposes of any one described folic acid dropping pill preparation of claim 1 to 10 in the medicine of preparation treatment hyperhomocysteinemiainjury.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA2006100990261A CN101103985A (en) | 2006-07-14 | 2006-07-14 | Folic acid dropping pill and its preparation method |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN103145968A (en) * | 2012-11-23 | 2013-06-12 | 杭州师范大学 | Folate-conjugated polyethylene glycol monostearate, and preparation method and application thereof |
| CN105395554A (en) * | 2014-09-15 | 2016-03-16 | 北京斯利安药业有限公司 | Folic acid solid dispersion body and preparation method thereof |
| CN105496941A (en) * | 2014-09-26 | 2016-04-20 | 北京斯利安药业有限公司 | Folic acid solid preparation and preparation method thereof |
| WO2017182619A1 (en) * | 2016-04-22 | 2017-10-26 | Sven Reichwagen | Vitamin preparation |
| CN110151897A (en) * | 2018-01-10 | 2019-08-23 | 郑州轻工业学院 | A kind of chick-pea fatty acid dripping pill and preparation method thereof |
| CN113133976A (en) * | 2020-01-19 | 2021-07-20 | 成都百裕制药股份有限公司 | A dripping pill containing ginkgolide as effective component |
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2006
- 2006-07-14 CN CNA2006100990261A patent/CN101103985A/en active Pending
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN103145968A (en) * | 2012-11-23 | 2013-06-12 | 杭州师范大学 | Folate-conjugated polyethylene glycol monostearate, and preparation method and application thereof |
| CN103145968B (en) * | 2012-11-23 | 2015-01-14 | 杭州师范大学 | Folate-conjugated polyethylene glycol monostearate, and preparation method and application thereof |
| CN105395554A (en) * | 2014-09-15 | 2016-03-16 | 北京斯利安药业有限公司 | Folic acid solid dispersion body and preparation method thereof |
| CN105496941A (en) * | 2014-09-26 | 2016-04-20 | 北京斯利安药业有限公司 | Folic acid solid preparation and preparation method thereof |
| CN105496941B (en) * | 2014-09-26 | 2019-03-15 | 北京斯利安药业有限公司 | A kind of folic acid solid pharmaceutical preparation and preparation method thereof |
| WO2017182619A1 (en) * | 2016-04-22 | 2017-10-26 | Sven Reichwagen | Vitamin preparation |
| CN109195586A (en) * | 2016-04-22 | 2019-01-11 | 丹托尔生物科技股份有限公司 | Vitamin preparation |
| CN110151897A (en) * | 2018-01-10 | 2019-08-23 | 郑州轻工业学院 | A kind of chick-pea fatty acid dripping pill and preparation method thereof |
| CN113133976A (en) * | 2020-01-19 | 2021-07-20 | 成都百裕制药股份有限公司 | A dripping pill containing ginkgolide as effective component |
| CN113133976B (en) * | 2020-01-19 | 2022-03-04 | 成都百裕制药股份有限公司 | A dripping pill containing ginkgolide as effective component |
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