CN102824362B - Medicine composition of oral rehydration salt - Google Patents
Medicine composition of oral rehydration salt Download PDFInfo
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- CN102824362B CN102824362B CN201210348874.7A CN201210348874A CN102824362B CN 102824362 B CN102824362 B CN 102824362B CN 201210348874 A CN201210348874 A CN 201210348874A CN 102824362 B CN102824362 B CN 102824362B
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Abstract
The invention relates to a medicine composition of oral rehydration salt, which also can be called oral rehydration salt powder III in some embodiments. Specifically, the medicine composition of oral rehydration salt comprises potassium chloride, sodium chloride, sodium citrate and glucose. More specifically, the oral rehydration salt powder comprises 1 part of potassium chloride, 1.3-2.5 parts of sodium chloride, 1.5-2.5 parts of sodium citrate and 6-15 parts of glucose by weight. The oral rehydration salt powder provided by the invention has the characteristics that the preparation technology is simple, the process control is easy, the phenomena of crystallization and clustering are avoided in the preparation process, the product dissolution speed is high, and the like. The oral rehydration salt powder provided by the invention obviously overcomes some important technical problems often caused by the common powder, can provide an oral rehydration salt preparation with good pharmaceutical performance for clinical use, has significant innovation, and is certainly to bring tremendous social and economic benefits.
Description
Technical field
The invention belongs to medical technical field, relate to a kind of loose pharmaceutical composition of Powdered or granular oresol that is, also can be described as in some instances the loose III of oresol.In this medicine, comprise glucose and sodium chloride, potassium chloride, sodium citrate.
Background technology
Salt is one of indispensable composition in human life, according to A Palin (world-renowned former Soviet Union biochemist, 1894-1980) said in < < origin of life > >: " human mater is to all derivative evolution from sea water of all life; some life logs in, and some life is still stayed in sea water and lived.”
Originally the animal and plant of the mankind and all lands is all risen in ocean.Until today, nobody raises an objection to this theory.Sea is the mother of all life.In sea water, contain several mineral materials, the mineral that namely human body contains of the mineral in sea water.Potassium, sodium ions content in sea water are the highest, and potassium, sodium ion are also the two kinds of main cationes in our body.They preside over the inside and outside work of cell, the normal electrolyte balance of balance the body separately.If human body lacks these mineral, whole body will be greatly affected, and health will be impaired, and various abnormal body running situations can show in the mode of various diseases.Salinity is that human body is indispensable, if lacked salinity in human body, people will dizziness, malaise, anorexia, goes down for a long time and will cause numerous disease, and hair bleaches.
In hospital, we often can see patient infusion, and many is exactly sodium chloride normal saline (being that concentration is 0.9% saline solution).Blood in human body all contains Sal composition.Blood is comprised of erythrocyte and liquid blood plasma.Hemocyte has three kinds of erythrocyte, leukocyte and platelet, and wherein, erythrocyte accounts for the overwhelming majority.Cell membrane is exactly semipermeable membrane, and in normal situation, intracellular solution must maintain certain concentration with extracellular blood plasma liquid.People, when transfusion, enters the saline of blood plasma, and also must maintain certain concentration is 0.09%.If normal saline latting drown or misused distilled water, after transfusion, the concentration of blood plasma can be thinning so, like this, the moisture in blood plasma will permeate in the large hemocyte of concentration.Result just causes the expansion of hemocyte, even breaks, and haemolysis occurs.If saline overrich, so, the moisture in hemocyte, again can be to exosmosis.The mode that current people mend salt also rests on the traditional approach with medical form injecting normal saline at present, people is when supplementing salt, if not go to hospital, the more molten saline solution of staying at home exactly like this, cause like this mode of benefit salt very single, and bother very much.
The medicine of world health organisation recommendations treatment acute diarrhea dehydration is oresol, and these drug prescriptions form rationally, cheap and easy to get, convenience and high-efficiency, and the speed of its correct dehydration is better than intravenous drip.Be used for the treatment of the slight and moderate dehydration that infantile dyspepsia and rotavirus enteritis cause.Have been found that a kind of formula that effectively can be used for supplementing salt in body fluid, this formula comprises glucose, sodium chloride, potassium chloride and the sodium citrate as active component, and in this formula, can not add other material and directly be prepared into preparation, such as granule, powder etc.From pharmaceutical technology can handling, production cost, and the compliance of clinical practice says, for this formula, powder has many than the better advantage of granule.For example powder can be after pulverizing, mixing direct packaging in unit dose package medicated bag; And granule need to add aqueous binders granulation, dry after pulverizing, mixing, and then minute install in unit dose package medicated bag.For powder, the preparation technology of granule extends in the cycle greatly, and because needs have dry run, need to consume a large amount of energy.In addition, powder is because its granule is less than granule, dissolves sooner after being added to the water, and is therefore more conducive to clinical use.Yet in powder preparation process, and at finished product duration of storage, may run into variety of issue, such as occurring agglomerating, the phenomenons such as balling-up of uniting of caking in preparation process, can affect drugs packaging; In the dissolving that duration of storage caking is agglomerating may affect drug use time.
In addition, by traditional powder production method, mix, each composition of disposable pulverizing, full dose is mixed, or agglomerating, the phenomenons such as balling-up of uniting of more or less can luming in mixed process by general equivalent incremental method, the product obtaining should not disperse, and has affected mixing uniformity, also cannot carry out next step subpackage, it is qualified that the manufactured goods uniformity is difficult for.In addition, more than the granularity of the highest anhydrous glucose of our content is ground 80 orders, as 100 orders, 120 orders, after mixing homogeneously in every way with other compositions again, make finished product, when discovery is dissolved in water before finished product is used, there will be the agglomerating phenomenon of crystallization, the dissolving of product is slow, has a strong impact on use.
Therefore those skilled in the art need to have new method to overcome the problem existing in this powder process of preparation.
Summary of the invention
The inventor have been surprisingly found that, the powder that comprises glucose, sodium chloride, potassium chloride and sodium citrate as active component is accurately controlled at glucose granularity between 60～80 orders, and manufactured goods are very fast when dissolving.In addition, if the anhydrous glucose sugar of appropriate 60～80 object is first mixed with 0.5: 1～2.0: 1 part by weight with the potassium chloride of full dose, all the other composition additional mixing, finally both always mix together with the anhydrous glucose sugar of residue, in whole mixed process, there will not be agglomerating, the phenomenons such as balling-up of uniting of caking, make mixed process very by the way with quick.If substitute the potassium chloride in above method with other compositions, cannot realize its effect.Therefore the present invention is accomplished.
For this reason, first aspect present invention provides a kind of fine grained or pulverous compositions of being that can be referred to as powder, can also be called in the present invention oresol loose.Particularly, first aspect present invention provides a kind of oresol loose, wherein comprises potassium chloride, sodium chloride, sodium citrate and glucose.
Loose according to the oresol of first aspect present invention, wherein comprise:
The potassium chloride of 1 weight portion,
The sodium chloride of 1.3～2.5 weight portions,
The sodium citrate of 1.5～2.5 weight portions and
The glucose of 6～15 weight portions.
Loose according to the oresol of first aspect present invention, wherein comprise:
The potassium chloride of 1 weight portion,
The sodium chloride of 1.5～2.4 weight portions,
The sodium citrate of 1.6～2.2 weight portions and
The glucose of 7～14 weight portions.
Loose according to the oresol of first aspect present invention, wherein comprise:
The potassium chloride of 1 weight portion,
The sodium chloride of 1.56～1.91 weight portions,
The sodium citrate of 1.74～2.13 weight portions and
The glucose of 8～10 weight portions.
Loose according to the oresol of first aspect present invention, wherein comprise:
The potassium chloride of 1 weight portion,
The sodium chloride of 1.65～1.82 weight portions,
The sodium citrate of 1.84～2.03 weight portions and
The glucose of 8.55～9.45 weight portions.
Loose according to the oresol of first aspect present invention, wherein comprise:
The potassium chloride of 1 weight portion,
The sodium chloride of approximately 1.73 weight portions,
The sodium citrate of approximately 1.93 weight portions and
The glucose of approximately 9 weight portions.
Loose according to the oresol of first aspect present invention, wherein comprise:
The potassium chloride of 1 weight portion,
The sodium chloride of 2.1～2.57 weight portions,
The sodium citrate of 1.74～2.13 weight portions and
The glucose of 12～14.67 weight portions.
Loose according to the oresol of first aspect present invention, wherein comprise:
The potassium chloride of 1 weight portion,
The sodium chloride of 2.22～2.45 weight portions,
The sodium citrate of 1.84～2.03 weight portions and
The glucose of 12.67～14 weight portions.
Loose according to the oresol of first aspect present invention, wherein comprise:
The potassium chloride of approximately 1 weight portion,
The sodium chloride of approximately 2.33 weight portions,
The sodium citrate of approximately 1.93 weight portions and
The glucose of approximately 13.3 weight portions.
Loose according to the oresol of first aspect present invention, wherein said sodium citrate is anhydrous citric acid sodium or its hydrate.In one embodiment, described sodium citrate is the dihydrate of sodium citrate.
Loose according to the oresol of first aspect present invention, wherein said glucose is anhydrous glucose or its hydrate.In one embodiment, described glucose is anhydrous glucose.
Loose according to the oresol of first aspect present invention, wherein more than 70% glucose particle footpath is between 60 order～80 orders.In the present invention, if not otherwise indicated, % refers to percetage by weight.
Loose according to the oresol of first aspect present invention, wherein more than 80% glucose particle footpath is between 60 order～80 orders.
Loose according to the oresol of first aspect present invention, wherein more than 90% glucose particle footpath is between 60 order～80 orders.
Loose according to the oresol of first aspect present invention, wherein more than 80% potassium chloride, sodium chloride and/or sodium citrate particle footpath are between 65 order～120 orders.
Loose according to the oresol of first aspect present invention, wherein more than 80% potassium chloride, sodium chloride and/or sodium citrate particle footpath are between 80 order～120 orders.
Loose according to the oresol of first aspect present invention, wherein more than 80% potassium chloride, sodium chloride and/or sodium citrate particle footpath are between 80 order～100 orders.
Loose according to the oresol of first aspect present invention, its granularity is: more than 65% particle footpath is between 50 order～80 orders.
Loose according to the oresol of first aspect present invention, its granularity is: more than 70% particle footpath is between 50 order～80 orders.
Loose according to the oresol of first aspect present invention, its granularity is: more than 75% particle footpath is between 50 order～80 orders.
Loose according to the oresol of first aspect present invention, it is that the method for shining following steps prepares:
(1) glucose is pulverized;
(2) potassium chloride, sodium chloride, sodium citrate are pulverized respectively;
(3) get the potassium chloride powder of the recipe quantity that step (2) obtains, pulverize with appropriate step (1) the glucose powder obtaining and mix;
(4) get sodium chloride and two kinds of powder mix homogeneously of sodium citrate of the recipe quantity that step (2) obtains;
(5) step (1) the gained glucose powder three of step (3) gained mixture, step (4) gained mixture and residue recipe quantity is mixed together evenly, obtains final mixture, packing, obtains.
In above-mentioned oresol is loose, in its preparation process, step (1) be glucose powder is broken into more than 70% (for example, more than 80%, for example, more than 90%) glucose particle footpath between 60 order～80 orders.
In above-mentioned oresol is loose, in its preparation process, step (2) is that potassium chloride, sodium chloride, sodium citrate are for example ground into respectively to more than 80% particle footpath, for example, at (more than 80% particle footpath is between 80 order～120 orders, and more than 80% particle footpath is between 80 order～100 orders) between 65 order～120 orders.
In above-mentioned oresol is loose, in its preparation process, step (3) is to get the potassium chloride powder of the recipe quantity that step (2) obtains, and (is that glucose is 0.5～2.0 with the weight ratio of potassium chloride: step 1) (1) is pulverized the glucose powder obtaining and mixed with 0.5～2.0 times of weight.
Loose according to the oresol of first aspect present invention, it is that the method for shining following steps prepares:
(1) the glucose particle footpath that glucose powder is broken into more than 70% (for example, more than 80%, for example, more than 90%) is between 60 order～80 orders;
(2) for example potassium chloride, sodium chloride, sodium citrate are ground into respectively to more than 80% particle footpath, for example, at (more than 80% particle footpath is between 80 order～120 orders, and more than 80% particle footpath is between 80 order～100 orders) between 65 order～120 orders;
(3) getting the potassium chloride powder of the recipe quantity that step (2) obtains, (is that glucose is 0.5～2.0 with the weight ratio of potassium chloride: step 1) (1) is pulverized the glucose powder obtaining and mixed with 0.5～2.0 times of weight;
(4) get sodium chloride and two kinds of powder mix homogeneously of sodium citrate of the recipe quantity that step (2) obtains;
(5) step (1) the gained glucose powder three of step (3) gained mixture, step (4) gained mixture and residue recipe quantity is mixed together evenly, obtains final mixture, packing, obtains.
In above-mentioned oresol is loose, in its preparation process, while mixing in step (4), do not add glucose and potassium chloride.
Loose according to the oresol of first aspect present invention, it is 3-50 gram through being distributed into every bag or weight per package, for example be distributed into the amount of every bag of about 5.125g or its 2 times, 2.5 times, 3 times, 4 times, 5 times, or be distributed into the amount of every bag of about 5.58g or its 2 times, 2.5 times, 3 times, 4 times, 5 times.
Second aspect present invention provides the method for preparing oresol loose (for example described in the arbitrary embodiment of first aspect present invention, oresol is loose), this oresol Bales Off chloride containing potassium, sodium chloride, sodium citrate and glucose, the method comprises the following steps:
(1) glucose is pulverized;
(2) potassium chloride, sodium chloride, sodium citrate are pulverized respectively;
(3) get the potassium chloride powder of the recipe quantity that step (2) obtains, pulverize with appropriate step (1) the glucose powder obtaining and mix;
(4) get sodium chloride and two kinds of powder mix homogeneously of sodium citrate of the recipe quantity that step (2) obtains;
(5) step (1) the gained glucose powder three of step (3) gained mixture, step (4) gained mixture and residue recipe quantity is mixed together evenly, obtains final mixture, packing, obtains.
According to the method for second aspect present invention, wherein step (1) be glucose powder is broken into more than 70% (for example, more than 80%, for example, more than 90%) glucose particle footpath between 60 order～80 orders.
According to the method for second aspect present invention, wherein step (2) is that potassium chloride, sodium chloride, sodium citrate are for example ground into respectively to more than 80% particle footpath, for example, at (more than 80% particle footpath is between 80 order～120 orders, and more than 80% particle footpath is between 80 order～100 orders) between 65 order～120 orders.
According to the method for second aspect present invention, wherein step (3) is to get the potassium chloride powder of the recipe quantity that step (2) obtains, and (is that glucose is 0.5～2.0 with the weight ratio of potassium chloride: step 1) (1) is pulverized the glucose powder obtaining and mixed with 0.5～2.0 times of weight.
According to the method for second aspect present invention, the method comprises the following steps:
(1) the glucose particle footpath that glucose powder is broken into more than 70% (for example, more than 80%, for example, more than 90%) is between 60 order～80 orders;
(2) for example potassium chloride, sodium chloride, sodium citrate are ground into respectively to more than 80% particle footpath, for example, at (more than 80% particle footpath is between 80 order～120 orders, and more than 80% particle footpath is between 80 order～100 orders) between 65 order～120 orders;
(3) getting the potassium chloride powder of the recipe quantity that step (2) obtains, (is that glucose is 0.5～2.0 with the weight ratio of potassium chloride: step 1) (1) is pulverized the glucose powder obtaining and mixed with 0.5～2.0 times of weight;
(4) get sodium chloride and two kinds of powder mix homogeneously of sodium citrate of the recipe quantity that step (2) obtains;
(5) step (1) the gained glucose powder three of step (3) gained mixture, step (4) gained mixture and residue recipe quantity is mixed together evenly, obtains final mixture, packing, obtains.
According to the method for second aspect present invention, while wherein mixing in step (4), do not add glucose and potassium chloride.
According to the method for second aspect present invention, wherein said powder is 3-50 gram through being distributed into every bag or weight per package, for example be distributed into the amount of every bag of about 5.125g or its 2 times, 2.5 times, 3 times, 4 times, 5 times, or be distributed into the amount of every bag of about 5.58g or its 2 times, 2.5 times, 3 times, 4 times, 5 times.
According to the method for second aspect present invention, wherein said oresol Bales Off contains:
The potassium chloride of 1 weight portion,
The sodium chloride of 1.3～2.5 weight portions,
The sodium citrate of 1.5～2.5 weight portions and
The glucose of 6～15 weight portions.
According to the method for second aspect present invention, wherein said oresol Bales Off contains:
The potassium chloride of 1 weight portion,
The sodium chloride of 1.5～2.4 weight portions,
The sodium citrate of 1.6～2.2 weight portions and
The glucose of 7～14 weight portions.
According to the method for second aspect present invention, wherein said oresol Bales Off contains:
The potassium chloride of 1 weight portion,
The sodium chloride of 1.56～1.91 weight portions,
The sodium citrate of 1.74～2.13 weight portions and
The glucose of 8～10 weight portions.
According to the method for second aspect present invention, wherein said oresol Bales Off contains:
The potassium chloride of 1 weight portion,
The sodium chloride of 1.65～1.82 weight portions,
The sodium citrate of 1.84～2.03 weight portions and
The glucose of 8.55～9.45 weight portions.
According to the method for second aspect present invention, wherein said oresol Bales Off contains:
The potassium chloride of 1 weight portion,
The sodium chloride of approximately 1.73 weight portions,
The sodium citrate of approximately 1.93 weight portions and
The glucose of approximately 9 weight portions.
According to the method for second aspect present invention, wherein said oresol Bales Off contains:
The potassium chloride of 1 weight portion,
The sodium chloride of 2.1～2.57 weight portions,
The sodium citrate of 1.74～2.13 weight portions and
The glucose of 12～14.67 weight portions.
According to the method for second aspect present invention, wherein said oresol Bales Off contains:
The potassium chloride of 1 weight portion,
The sodium chloride of 2.22～2.45 weight portions,
The sodium citrate of 1.84～2.03 weight portions and
The glucose of 12.67～14 weight portions.
According to the method for second aspect present invention, wherein said oresol Bales Off contains:
The potassium chloride of approximately 1 weight portion,
The sodium chloride of approximately 2.33 weight portions,
The sodium citrate of approximately 1.93 weight portions and
The glucose of approximately 13.3 weight portions.
According to the method for second aspect present invention, wherein said sodium citrate is anhydrous citric acid sodium or its hydrate.In one embodiment, described sodium citrate is the dihydrate of sodium citrate.
According to the method for second aspect present invention, wherein said glucose is anhydrous glucose or its hydrate.In one embodiment, described glucose is anhydrous glucose.
According to the method for second aspect present invention, the glucose particle footpath during wherein said oresol is loose more than 70% is between 60 order～80 orders.In the present invention, if not otherwise indicated, % refers to percetage by weight.
According to the method for second aspect present invention, the glucose particle footpath during wherein said oresol is loose more than 80% is between 60 order～80 orders.
According to the method for second aspect present invention, the glucose particle footpath during wherein said oresol is loose more than 90% is between 60 order～80 orders.
According to the method for second aspect present invention, potassium chloride, sodium chloride and/or sodium citrate particle footpath during wherein said oresol is loose more than 80% are between 65 order～120 orders.
According to the method for second aspect present invention, potassium chloride, sodium chloride and/or sodium citrate particle footpath during wherein said oresol is loose more than 80% are between 80 order～120 orders.
According to the method for second aspect present invention, potassium chloride, sodium chloride and/or sodium citrate particle footpath during wherein said oresol is loose more than 80% are between 80 order～100 orders.
According to the method for second aspect present invention, the granularity that wherein said oresol is loose is: more than 65% particle footpath is between 50 order～80 orders.
According to the method for second aspect present invention, the granularity that wherein said oresol is loose is: more than 70% particle footpath is between 50 order～80 orders.
According to the method for second aspect present invention, the granularity that wherein said oresol is loose is: more than 75% particle footpath is between 50 order～80 orders.
Loose according to the oresol of first aspect present invention or prepared by second aspect method oresol is loose, in its formula, except potassium chloride, sodium chloride, sodium citrate and four kinds of materials of glucose, does not substantially add in addition other material.Yet those skilled in the art understand, in the present composition, also can add appropriate non-active ingredient, for example can add a small amount of correctives, for example add a little saccharin sodium to improve mouthfeel, or for example add a little coloring agent and using as distinguishing packing dosage use, these a little additive can not produce harmful effect to the object of the invention.
Below the present invention is further illustrated.
Present invention relates in general to a kind of oresol obtaining by special process loose, this oresol Bales Off is containing the preparation method of the oresol of anhydrous glucose, potassium chloride, by controlling the order that mixes of the granularity of anhydrous glucose and anhydrous glucose and other composition, make whole preparation process there will not be agglomerating phenomenon, mix homogeneously and finished product dissolve rapidly.First the present invention controls anhydrous glucose granularity between 60～80 orders, then the anhydrous glucose sugar of part is mixed with 0.5: 1～2.0: 1 part by weight with the potassium chloride of full dose, and all the other composition additional mixing, finally both always mix together with the anhydrous glucose sugar of residue.
In the present invention, term " weight portion " represents the amount that can calculate with any unit of weight or mass unit, and this amount can be integer number, can also be smallest number.For example, in an example of the present composition, for example, in a formula, described every 1 " weight portion " can represent about 0.375g.Thus, in the formula of an example, the present composition comprises about 0.375g potassium chloride, about 0.65g sodium chloride, 0.725g sodium citrate and 3.375g glucose.
In an example of the present invention, described sodium citrate is the dihydrate of sodium citrate, i.e. compound shown in following formula:
In an example of the present invention, described glucose is anhydrous glucose, i.e. compound shown in following formula:
In the present invention, phrase " more than 65% particle footpath is between 50 order～80 orders " is the physical size of pulverous compositions powder body for characterizing the present invention, its implication is, in the present composition, have the above particle of 65% (w/w), these particles can be sieved but can not be sieved by 80 object medicines by 50 object medicines.The phrase of other similar statement also has similar meaning.The phrase " more than 65% particle footpath is between 50 order～80 orders " that one of ordinary skill in the art will readily recognize that the physical size of above-mentioned characterize combinations powder body at least by the following method A is measured and is obtained:
Method A: method is according to two (Chinese Pharmacopoeia Commission's volumes of Pharmacopoeia of People's Republic of China of version in 2010, Chinese Medicine science and technology publishing house publishes, ISBN 978-7-5067-4438-6, in the present invention can be referred to as two of version Chinese Pharmacopoeias in 2012) the second method (sieve method) in appendix IX E " granularity and particle size distribution method ", with " two sieve method " in " rider point-score ", carry out; Upper strata Yao Shai Wei50Mu， lower floor medicine sieve is 80 orders; Get and be trapped in two granule/powder between medicine sieve, weighed weight, calculates its proportion (%).
If this measurement result more than 65%, meets the regulation of phrase " more than 65% particle footpath is between 50 order～80 orders ".In addition, if measurement result is 75%, represent said composition have 75% particle can be by 50 mesh sieves but can not pass through 80 mesh sieves.
It should be noted that, the method of sign or mensuration present composition granule/powder physical size has many, for example, in two appendix IX E of Pharmacopoeia of People's Republic of China " granularity and particle size distribution method " of version in 2010, also described some other assay method.In the context of the invention, if not explanation in addition, the method that characterizes or measure present composition granule/powder physical size is used said method A to carry out.
Need to be by various crushing materials to the particle size of stipulating while in the present invention, preparing the present composition.With regard to realizing the object of the invention, method and the device therefor pulverized are not particularly limited, for example can use stirring-type comminuting method (for example shear agitation), can also use polishing (such as ball-milling method) etc., as long as monitor the grain size characteristic of the present composition in crushing process.
In the present invention, " order " that represent particle size or medicine sieve specification has the implication of well known to a person skilled in the art, especially, for the present invention, it has two notes on the use of Pharmacopoeia of People's Republic of China " metering " lower the 28 article of (9) money of version in 2010 about the implication of this pharmacopeia institute medication sieve.
The specific embodiment
The present invention is described in further detail by the following examples, but the present invention should not be limited to these embodiment.In embodiment, while forming with " weight portion " statement formula, all the amount with preparation total amount 5kg compositions feeds intake below.Below in embodiment, while mentioning glucose, if not otherwise indicated, use be anhydrous glucose.Below in embodiment, while mentioning sodium citrate, if not otherwise indicated, use be sodium citrate dihydrate.Below in embodiment, the compositions of preparation can pack in paper aluminum composite membrane bag, every bag can be about 3g～30g, the amount of every bag of about 5.125g or its 2 times, 2.5 times, 3 times, 4 times, 5 times for example, or the amount of every bag of about 5.58g or its 2 times, 2.5 times, 3 times, 4 times, 5 times for example, if not otherwise indicated, every bag dispensed loading amount is 5.125g.
embodiment 1
prescription:the glucose of the sodium citrate of the sodium chloride of the potassium chloride of 375 weight portions, 650 weight portions, 725 weight portions and 3375 weight portions.The compositions obtaining can be designated as R1, and below the gained present composition can similarly represent.
preparation method:
(1) glucose powder is broken into more than 80% glucose particle footpath between 60 order～80 orders;
(2) potassium chloride, sodium chloride, sodium citrate are ground into respectively to more than 80% particle footpath between 80 order～120 orders;
(3) get the potassium chloride powder of the recipe quantity that step (2) obtains, pulverize with the step (1) of 1.5 times of weight the glucose powder obtaining and mix, mixability reaches the requirement of [the outward appearance uniformity] inspection technique regulation under two appendix powder items of version Chinese Pharmacopoeia in 2012;
(4) get sodium chloride and two kinds of powder mix homogeneously of sodium citrate of the recipe quantity that step (2) obtains, mixability reaches the requirement of [the outward appearance uniformity] inspection technique regulation under two appendix powder items of version Chinese Pharmacopoeia in 2012;
(5) step (1) the gained glucose powder three of step (3) gained mixture, step (4) gained mixture and residue recipe quantity is mixed together evenly, obtains final mixture, packing, obtains
The process control of step (5) mixability:
(a) in the process that three kinds of materials are mixed, according to [the outward appearance uniformity] inspection technique under two appendix powder items of version Chinese Pharmacopoeia in 2012, check and requirement up to specification, to guarantee potassium chloride, sodium chloride and the uniformity of sodium citrate three in material;
(b) think by rule of thumb after abundant mixing, guarantee the relative standard deviation (RSD of sodium citrate content and potassium content, (it is preferred that RSD is less than 5% %) to be less than 5%, when RSD is greater than 7.5%, people can produce doubt to drug quality, and when RSD is greater than 10%, this medicine can not be accepted by those skilled in the art substantially).Relative standard deviation test/computational methods are: get at random 20 parts of samples, test the content of sodium citrate in each part of sample, with sodium citrate shared percent in compositions, represent sodium citrate content, then calculate meansigma methods and the standard deviation of sodium citrate content, and calculate the relative standard deviation (RSD, %) of sodium citrate content in 20 samples of each batch sample; Similar test calculate the relative standard deviation (RSD, %) of potassium content in 20 samples of each batch sample in addition.Wherein:
The content assaying method of sodium citrate is: get the about 2.1g of compositions, and accurately weighed, put in 100ml measuring bottle, add glacial acetic acid 80ml, jolting, is heated to 50 ℃, let cool, add glacial acetic acid and be diluted to scale, shake up, standing, precision measures supernatant 20ml, add 1 of crystal violet indicator solution, with perchloric acid titration liquid (0.1mol/L), be titrated to solution aobvious blue, and titration results is proofreaied and correct with blank assay.Every 1ml perchloric acid titration liquid (0.1mol/L) is equivalent to the C of 9.803mg
6h
5na
3o
72H
2o.
The content assaying method of potassium is: the 105 ℃ of potassium chloride that are dried to constant weight of learning from else's experience, and accurately weighed, be dissolved in water and quantitatively dilute the solution of making chloride containing potassium 50 μ g in every 1ml, shake up, in contrast product solution.Get the about 2.7g of compositions, accurately weighed, put in 100ml measuring bottle, be dissolved in water and be diluted to scale, shake up, obtain solution (1); Precision measures solution (1) 2ml, puts in 100ml measuring bottle, is diluted with water to scale, shakes up, and obtains solution (2); Precision measures solution (2) 5ml, puts in 100ml measuring bottle, adds 2% strontium chloride solution 3.0ml, is diluted with water to scale, shakes up, as need testing solution.Precision measures reference substance solution 3ml, 4ml, 5ml, puts respectively in 100ml measuring bottle, respectively adds 2% strontium chloride solution 3.0ml, is diluted with water to scale, shakes up.By above-mentioned each solution and need testing solution, according to atomic absorption spectrophotometry (two appendix IV D first methods of Chinese Pharmacopoeia version in 2010), at the wavelength place of 767nm, measure, calculate, obtain.
Preparation process and product evaluation:
(i) agglomeration: each blend step does not have agglomerate to occur;
(ii) incorporation time: step (5) is mixed required time 0.8h;
(iii) dissolution time: dissolution time 110s.
Dissolution time assay method: get testing sample 1 bag, impouring is equipped with in the beaker of 100ml distilled water, and beaker capacity is 500ml, diameter 9.2cm; To in water during impouring sample, impouring as soon as possible, and at the bottom of being evenly distributed on beaker as far as possible; In whole process, beaker is standing, does not stir; Calculating is from impouring sample to the consoluet time, and each sample repeats 5 times, get average as the dissolution time of this sample (second, s).
Above compositions R1 is prepared into powder, it is a kind of hypotonic oresol, in the present invention and those skilled in the art can be described as " oresol fall apart III " or similar title, can be packaged into specification is 5.125g, this be a kind of be not containing the formula of adjuvant, be the low sodium of selecting World Health Organization (WHO) and international United Nations Children's Fund to recommend, the new formula of low sugar, write out a prescription as follows
embodiment 2
prescription:the glucose of the sodium citrate of the sodium chloride of the potassium chloride of 1 weight portion, 2.33 weight portions, 1.93 weight portions and 13.3 weight portions.The present composition obtaining can be designated as R2.
preparation method:method with reference to embodiment 1 is carried out, result:
(i) agglomeration: each blend step does not have agglomerate to occur;
(ii) incorporation time: step (5) is mixed required time 0.7h;
(iii) dissolution time: dissolution time 85s.
embodiment 3
prescription:the glucose of the sodium citrate of the sodium chloride of the potassium chloride of 1 weight portion, 2.4 weight portions, 1.6 weight portions and 14 weight portions.
preparation method:method with reference to embodiment 1 is carried out, result:
(i) agglomeration: each blend step does not have agglomerate to occur;
(ii) incorporation time: step (5) is mixed required time 0.9h;
(iii) dissolution time: dissolution time 90s.
embodiment 4
prescription:the glucose of the sodium citrate of the sodium chloride of the potassium chloride of 1 weight portion, 1.5 weight portions, 2.2 weight portions and 7 weight portions.
preparation method:method with reference to embodiment 1 is carried out, result:
(i) agglomeration: each blend step does not have agglomerate to occur;
(ii) incorporation time: step (5) is mixed required time 1.1h;
(iii) dissolution time: dissolution time 105s.
embodiment 5
prescription:the glucose of the sodium citrate of the sodium chloride of the potassium chloride of 1 weight portion, 1.65 weight portions, 2.03 weight portions and 8.55 weight portions.
preparation method:method with reference to embodiment 1 is carried out, result:
(i) agglomeration: each blend step does not have agglomerate to occur;
(ii) incorporation time: step (5) is mixed required time 0.6h;
(iii) dissolution time: dissolution time 140s.
embodiment 6
prescription:the glucose of the sodium citrate of the sodium chloride of the potassium chloride of 1 weight portion, 1.82 weight portions, 1.84 weight portions and 9.45 weight portions.
preparation method:method with reference to embodiment 1 is carried out, result:
(i) agglomeration: each blend step does not have agglomerate to occur;
(ii) incorporation time: step (5) is mixed required time 0.9h;
(iii) dissolution time: dissolution time 125s.
embodiment 7
prescription:the glucose of the sodium citrate of the sodium chloride of the potassium chloride of 1 weight portion, 2.45 weight portions, 1.84 weight portions and 14 weight portions.
preparation method:method with reference to embodiment 1 is carried out, result:
(i) agglomeration: each blend step does not have agglomerate to occur;
(ii) incorporation time: step (5) is mixed required time 0.9h;
(iii) dissolution time: dissolution time 105s.
embodiment 8
prescription:the glucose of the sodium citrate of the sodium chloride of the potassium chloride of 1 weight portion, 2.22 weight portions, 2.03 weight portions and 12.67 weight portions; The saccharin sodium that adds in addition total weight of material 0.01%, for improving mouthfeel.
preparation method:method with reference to embodiment 1 is carried out, result:
(i) agglomeration: each blend step does not have agglomerate to occur;
(ii) incorporation time: step (5) is mixed required time 1.0h;
(iii) dissolution time: dissolution time 95s.
embodiment 9
Write out a prescription identical with embodiment 1, in step (3), being designed to respectively glucose is 0.2,0.4,0.5,1,2,2.5,3,3.5,4,5,7,9 than the ratio R of potassium chloride amount (being that glucose amount is potassium chloride amount multiple), prepares the compositions that a plurality of different process processes obtain.Result shows, R be 0.2 or 0.4 o'clock or R be more than or equal at 4 o'clock, reach enough mixabilities, step (5) is mixed required time all over 3.2 hours, between 3.2h to 7.9 hour, for example the incorporation time of R=0.4 is 3.6h, and the incorporation time of R=5 is 6.2h.And R is in 0.5 to 2 scope, mix required time all lower than 1.5 hours.And R is greater than in whole samples of 2 hours, dissolve all over 4 minutes, in the scope of 4.2～7.5 minutes.For example, during R=2.5, incorporation time 2.3 hours, dissolution time 4.2 minutes, for example, during R=4, incorporation time 4.5 hours, dissolution time 5.6 minutes.And find, only having R is 0.5～2 sample, and step (5) is mixed required time short (in 1.5 hours) and dissolution time short (in 2.5 minutes).
Find in addition, in the longer compositions of these incorporation times, for example, in R=0.2,0.4,2.5,3,3.5,4,5,7, each compositions preparation process of 9, all occurred that the agglomerate differing in size in various degree occurs, this may be the reason that causes incorporation time to extend.But all there is not clustering phenomena in each compositions preparation process of R=0.5～2.
embodiment 10
In some tests, write out a prescription identical with embodiment 1, in step (3), make full dose sodium chloride mix (and potassium chloride mixes with sodium citrate in step (4)) with glucose, and being designed to respectively glucose is 0.5,1,2 than the ratio R of sodium chloride amount, prepare the compositions that a plurality of different process processes obtain.Result shows, three compositionss that different R values obtain, incorporation time all between 2.1～3.7 hours, dissolution time all between 3～5min, for example, between the compositions incorporation time 2.1 hours of R=1, dissolution time 4.5min.
In other tests, write out a prescription identical with embodiment 1, in step (3), make full dose sodium citrate mix (and potassium chloride mixes with sodium chloride in step (4)) with glucose, and being designed to respectively glucose is 0.5,1,2 than the ratio R of sodium citrate amount, prepare the compositions that a plurality of different process processes obtain.Result shows, three compositionss that different R values obtain, incorporation time all between 1.9～3.5 hours, dissolution time all between 2.5～5min, for example, between the compositions incorporation time 2.4 hours of R=1, dissolution time 2.5min.
In other tests, write out a prescription identical with embodiment 1, in step (3), be about to whole materials and be mixed together, between result incorporation time 6.2 hours, dissolution time 4.5min, and in mixed process, have agglomerate appearance.
In other tests, write out a prescription identical with embodiment 1, in step (3), soon potassium chloride, sodium chloride, sodium citrate three are mixed together, then this mixture is mixed with glucose, between the 4.6 hours time that result is mixed with glucose, dissolution time 4.2min, and in mixed process, have agglomerate to occur.
In above embodiment 1-10, the compositions of preparation is that the granularity that oresol of the present invention is loose is: more than 70% particle footpath is between 50 order～80 orders.
embodiment 11
The inventor attempts to increase the granularity of glucose and investigates.Formula and method according to embodiment 1, but in step (1), make more than 80% glucose particle footpath be controlled between 50 order～60 orders, result, in the mixed process of step (5), reach satisfactory mixability, and incorporation time is more than 7.5 hours.
In addition, the granularity that the inventor attempts to reduce glucose is investigated.Formula and method according to embodiment 1, but in step (1), make more than 80% glucose particle footpath be controlled between 80 order～120 orders, result is in the mixed process of step (5), reach satisfactory mixability, incorporation time is more than 6.5 hours, and often occur agglomerate, dissolution time is also more than 3min.
In addition, the impact of the granularity that inventor has also investigated potassium chloride, sodium chloride, sodium citrate three kinds of materials on technique, result shows, different grain size is little on dissolution time impact, but influential to incorporation time, particularly, when more than 80% potassium chloride, sodium chloride and sodium citrate particle footpath are between 80 order～120 orders, incorporation time is relatively short for other particle size range of three kinds of materials.
Claims (12)
1. an oresol is loose, wherein comprises: the glucose of the sodium chloride of the potassium chloride of 1 weight portion, 1.3～2.5 weight portions, the sodium citrate of 1.5～2.5 weight portions and 6～15 weight portions;
Wherein more than 80% glucose particle footpath is between 60 order～80 orders, and more than 80% potassium chloride, sodium chloride and sodium citrate particle footpath are between 80 order～120 orders;
This oresol is loose is that the method for shining following steps prepares:
(1) glucose powder is broken into more than 80% glucose particle footpath between 60 order～80 orders;
(2) potassium chloride, sodium chloride, sodium citrate are ground into respectively to more than 80% particle footpath between 80 order～120 orders;
(3) get the potassium chloride powder of the recipe quantity that step (2) obtains, pulverize with the step (1) of 0.5～2.0 times of weight the glucose powder obtaining and mix;
(4) get sodium chloride and two kinds of powder mix homogeneously of sodium citrate of the recipe quantity that step (2) obtains;
(5) step (1) the gained glucose powder three of step (3) gained mixture, step (4) gained mixture and residue recipe quantity is mixed together evenly, obtains final mixture, packing, obtains,
Wherein, described sodium citrate is sodium citrate dihydrate, and described glucose is anhydrous glucose.
2. loose according to the oresol of claim 1, wherein comprise: the glucose of the sodium chloride of the potassium chloride of 1 weight portion, 1.5～2.4 weight portions, the sodium citrate of 1.6～2.2 weight portions and 7～14 weight portions.
3. loose according to the oresol of claim 1, wherein comprise: the glucose of the sodium chloride of the potassium chloride of 1 weight portion, 1.56～1.91 weight portions, the sodium citrate of 1.74～2.13 weight portions and 8～10 weight portions.
4. loose according to the oresol of claim 1, wherein comprise: the glucose of the sodium chloride of the potassium chloride of 1 weight portion, 1.65～1.82 weight portions, the sodium citrate of 1.84～2.03 weight portions and 8.55～9.45 weight portions.
5. loose according to the oresol of claim 1, wherein comprise: the glucose of the sodium chloride of the potassium chloride of 1 weight portion, 1.73 weight portions, the sodium citrate of 1.93 weight portions and 9 weight portions.
6. loose according to the oresol of claim 1, wherein comprise: the glucose of the sodium chloride of the potassium chloride of 1 weight portion, 2.22～2.45 weight portions, the sodium citrate of 1.84～2.03 weight portions and 12.67～14 weight portions.
7. loose according to the oresol of claim 1, wherein comprise: the glucose of the sodium chloride of the potassium chloride of 1 weight portion, 2.33 weight portions, the sodium citrate of 1.93 weight portions and 13.3 weight portions.
8. loose according to the oresol of claim 1, wherein more than 70% particle footpath is between 50 order～80 orders.
9. loose according to the oresol of claim 1 to 8 any one, it is 3-50 gram through being distributed into every bag or weight per package.
10. loose according to the oresol of claim 1 to 8 any one, it is through being distributed into the amount of every bag of 5.125g or its 2 times, 2.5 times, 3 times, 4 times, 5 times.
11. is loose according to the oresol of claim 1 to 8 any one, and it is through being distributed into the amount of every bag of 5.58g or its 2 times, 2.5 times, 3 times, 4 times, 5 times.
The loose method of oresol of 12. preparation claim 1 to 11 any one, the method comprises the following steps:
(1) glucose powder is broken into more than 80% glucose particle footpath between 60 order～80 orders;
(2) potassium chloride, sodium chloride, sodium citrate are ground into respectively to more than 80% particle footpath between 80 order～120 orders;
(3) get the potassium chloride powder of the recipe quantity that step (2) obtains, pulverize with the step (1) of 0.5～2.0 times of weight the glucose powder obtaining and mix;
(4) get sodium chloride and two kinds of powder mix homogeneously of sodium citrate of the recipe quantity that step (2) obtains;
(5) step (1) the gained glucose powder three of step (3) gained mixture, step (4) gained mixture and residue recipe quantity is mixed together evenly, obtains final mixture, packing, obtains.
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| CN104027351A (en) * | 2013-03-05 | 2014-09-10 | 肖云彩 | Oral composition of supplement |
| CN103380900A (en) * | 2013-06-19 | 2013-11-06 | 安徽恒星制药有限公司 | Preparation method for novel corrective flavor type oral rehydration salt powders and novel corrective flavor type oral rehydration salt powders |
| CN103479664B (en) * | 2013-09-24 | 2015-01-07 | 辽宁亿灵科创生物医药科技有限公司 | Liquid oral rehydration salt |
| CN103610692B (en) * | 2013-12-05 | 2015-11-18 | 厦门恩成制药有限公司 | A kind of preparation method of low-permeability oral rehydration salt |
| CN104258370A (en) * | 2014-10-14 | 2015-01-07 | 北京国仁堂医药科技发展有限公司 | Drug composition of oral rehydration salt and preparation method of drug composition |
| EA033940B1 (en) * | 2014-11-19 | 2019-12-11 | Калмарна Лимитед | Oral rehydration solution and method for preparation thereof |
| CN104857019B (en) * | 2015-06-23 | 2018-01-12 | 安徽恒星制药有限公司 | A kind of new oral fluid infusion salt and its production and use |
| CN107296198A (en) * | 2017-07-19 | 2017-10-27 | 东莞市山河电脑科技有限公司 | A kind of electuary or beverage of microelement-supplementing and energy |
| CN108272084A (en) * | 2018-01-11 | 2018-07-13 | 中国人民解放军第二军医大学 | It is a kind of prevent thermoplegia composition and its application |
| CN110693933A (en) * | 2019-10-08 | 2020-01-17 | 安徽九华华源药业有限公司 | Stable oral rehydration salt powder (III) and preparation method thereof |
| CN116870026A (en) * | 2023-09-07 | 2023-10-13 | 中国人民解放军总医院第四医学中心 | Oral rehydration salt pharmaceutical composition and preparation method thereof |
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