Two-component packaging response type chlorine dioxide tablet and preparation method thereof
Technical field
The invention belongs to the disinfection by chlorine dioxide technical field, be specifically related to a kind of binary reaction type solid preparation of chlorine dioxide that is formed by combining alkali metal such as sodium chlorite or alkaline earth metal chlorite, solid acid and other promoter.The invention still further relates to the preparation method of this solid pharmaceutical preparation.
Background technology
Chlorine dioxide is as a kind of water-soluble strong oxidizer; Has sterilizing ability efficient, wide spectrum; And can the oxidation Decomposition bacterium, amino acid and other reducing substanceses in microorganism such as virus and the protein, can also react with organic matter and multiple inorganic ions; And, be product with respect to other chlorine, can not produce organohalogen compounds such as aberration inducing, carcinogenesis, mutagenic chloroform during chlorine dioxide antiseptic, the effect of kill virus, bacterium, deodorizing, bleaching etc. is Cl
22.5 times, The World Health Organization (WHO) classifies its safety as the A1 level.Based on the oxidation and the sterilization idiocratic of chlorine dioxide, it also can be used as the bleaching agent of industries such as paper pulp, weaving; The disinfection sanitizer of food and drink, health, epidemic prevention etc.; The air purification agent of living room, toilet, automobile etc.; The algicide of Treatment of Industrial Water, drinking water treatment and Treatment of Sludge and water treatment agent.
But in actual use, because gas chlorine dioxide character is unstable, is difficult to process Compressed Gas, and has blast characteristics, inconvenience is transported and is stored, and the liquid chlorine dioxide is volatile again, is difficult for concentrating, so has limited the use of chlorine dioxide.And the stable ClO 2 solution moisture is big, and chlorine dioxide active ingredient is low, need add acidic activator during use and could use; Simultaneously, activator species is different, and usage amount is different, causes the difference of activation effect, and sterilization effect is caused negative effect in various degree.Moreover though there is chlorine dioxide generator on the market, the generator cost is high, be inappropriate for small sized applications such as civilian, and Operation and Maintenance needs the professional.It is thus clear that, no matter be gas chlorine dioxide or stable ClO 2 solution, all bring many inconvenience in transportation, storage with in using.In order to overcome this limitation, the product of chlorine dioxide solid form arises at the historic moment.
Solid preparation of chlorine dioxide is meant under certain operation condition can discharge ClO
2The solid, shaped goods of gas, these products can be the solid, shaped of colloid, lotion, Powdered, tablet, agglomerate and other different shapes.The type preparation generally is to be that primary dose, organic solid acid or mineral acid material etc. are that the primary raw material of acidulant is prepared from chlorite or stable ClO 2 solution.With respect to other forms of chlorine dioxide, solid chlorine dioxide is simple to operate except having, ClO
2Outside content height, stable in properties, transportation and the advantage such as easy to use, also have some specific functions sometimes, for example slow-release function etc.
Different by preparation method and principle and preparation function, solid preparation of chlorine dioxide generally can be divided into three types of absorbent-type, response type and spacetabs types.
1, absorbent-type solid chlorine dioxide.
The preparation of absorbent-type solid chlorine dioxide is simple, is the ClO that at first produces higher degree generally speaking
2Gas absorbs chlorine dioxide with the aqueous solution that contains stabilizing agent then, obtains stable ClO
2Solution, last, utilize some these solution of solid absorbent absorption.
When the preparation of absorbent-type solid chlorine dioxide; Adsorbent as the solid chlorine dioxide carrier should have bigger adsorption capacity, bigger specific surface and bigger particle diameter, and the pH value of adsorbent preferably is controlled between the 8.5-9.0; Solution premature decomposition to avoid adsorbing discharges chlorine dioxide.Absorption carrier can be divided into two big types, and one type is inorganic adsorbent, can adopt porous materials such as silica gel, calcium silicates, diatomite, talcum powder, molecular sieve and active carbon.Another kind of is organic adsorbent, like high-hydroscopicity polyacrylic acid resin, agar, superpower polymeric adsorbent, carboxymethyl cellulose etc.
In the process of preparation the type solid pharmaceutical preparation; Need the highly purified chlorine dioxide of prepared beforehand; Because the high concentration of gas chlorine dioxide and the strong oxidizing property of chlorine dioxide, etching apparatus is higher to equipment requirements easily; In case and leaking appears in equipment in suitability for industrialized production, with the serious threat workers'health.When preparation absorbent-type chlorine dioxide preparation, need to consider to select suitable adsorbing medium and stabilizing agent, reach requirement to guarantee the solid pharmaceutical preparation that makes.
This formulation also need add activator in use and discharge to impel chlorine dioxide.This just requires on the packing of product, to adopt binary or polynary packing, during use use is mixed in the water-soluble respectively back of two kinds of components, and once Kaifeng; Need once use up; Otherwise be prone to lose efficacy, cause the significant wastage of product, increase the working concentration and the disinfection cost of product.In addition, the activator that adds during use is excessive, can cause that pH value of solution is too small, causes secondary pollution.
The adsorbent that said preparation adopts particularly organic adsorbent has bigger adsorption capacity, meets water and is prone to expand.So require the type preparation preserve, should strict control its environment, particularly ambient humidity in the accumulating, lost efficacy in case product is met water (or big steam) in placement.
2, response type solid chlorine dioxide.
The response type solid chlorine dioxide is that different solid reaction raw materials is mixed according to a certain percentage, makes it directly to take place chemical reaction slowly, in the long time, discharges chlorine dioxide.Add the water of certain multiple when this series products uses or place the bigger environment of relative moisture can accomplish chemistry or priming reaction at short notice product, discharge the active ingredient chlorine dioxide.As add stabilizing agent in the preparation, add and then can be mixed with stability chlorine dioxide behind the water and use.
In the preparation of response type solid pharmaceutical preparation, the chloride that the someone proposes in the raw material thing, to add alkali metal or alkaline earth metal utilizes its water absorbing properties to reach dry purpose as passivator.This passivation means cause product unstable because the passivator water imbibition is strong, and the holding time is short, particularly one open bag inefficacy soon.
Adopt embedding method that the raw material thing is coated and can obtain effect preferably, but actual production with use in should be specifically noted that character and the embedding of covering after to the factors such as influence of environment.In some technology, need at first carry out the preparation of clad material, more obtained material is coated on the sodium chlorite surface, not only complex process, and equipment drops into high.And, influence the solvability and the solute effect of final products owing to the covering poorly water-soluble that uses.Also can cause solid insoluble ratio rising in the product on the other hand, the covering of dissolving also can cause the pollution of water quality.
3, slow-release solid chlorine dioxide.
The slow released ClO 2 solid pharmaceutical preparation is meant and can slowly discharges ClO
2The solid pharmaceutical preparation of gas, its rate of release wants much little than adsorptivity and response type solid pharmaceutical preparation, and said preparation generally is divided into gel-type and powder-type.Say absorbent-type and response type ClO on the stricti jurise
2The solid pharmaceutical preparation product all has slow release ClO
2The function of gas.
Spacetabs type ClO
2Solid pharmaceutical preparation (adsorptivity) is to utilize the absorption property of solid absorbent, with stable ClO
2Solution absorbs is mixed with solid acidifier again, makes it reaction, discharges ClO slowly, constantly
2Gas is used for sterilizing, air cleaning, deodorizing and fresh-keeping etc.Solid acidifier can be a solid peracid, or adsorbs a kind of generation H
+Acid or a kind of ackd salt, comprise citric acid, ferric trichloride, aluminum sulfate, tartaric acid etc.In the preparation use,, can control ClO in several ways in order to reach certain application target
2The burst size of gas is for example controlled the addition of solid acid or the intensity of acid etc.
Spacetabs type ClO
2Solid pharmaceutical preparation (reactivity) is with solid NaClO
2Or other primary dose put together with solid acidifier, adds other assistant agent, makes it to slow down ClO
2Rate of release, reach the purpose of slow release.This series products can be processed paste, gel, powdery, is positioned over suitable place, has sterilizing, air cleaning, deodorizing and function such as fresh-keeping equally.
Spacetabs type ClO
2Solid pharmaceutical preparation has certain application value, and the space disinfectant that in real life, can be used as living room, automobile, toilet and other occasions uses, and has bigger development space.But in practical application, should be specifically noted that how to control the gas chlorine dioxide concentration that said preparation discharges, to guarantee within effective threshold value.
Having investigated on the domestic market after the production method of solid preparation of chlorine dioxide, discover that in the solid pharmaceutical preparation of several types, it is simple relatively that the response type solid preparation of chlorine dioxide has production technology, operation is prone to the advantage of row.Yet still there are some shortcomings in the type preparation of selling on the market, and, stability low such as conversion ratio is difficult to guarantee etc.
Summary of the invention
The objective of the invention is to address the above problem, provide that a kind of operation is simple, good stability, high, the simple relatively two-component packaging response type chlorine dioxide tablet of production technology of conversion ratio, and method of making preparation.
Two-component packaging response type chlorine dioxide tablet of the present invention comprises the tablet A and the tablet B of independent packaging, wherein:
The usage amount of the various raw materials of said tablet A is respectively: primary dose of 55~65wt%, lytic agent 8~12wt%, foaming agent 8~11wt%, binding agent 8~11wt%, forming agent 8~11wt%, releasing agent 0.01~0.5wt%.Wherein, said primary dose is one or more mixture in alkali metal or the alkaline earth metal chlorite; Said lytic agent is a solid acid, is one or more the mixture in sulfamic acid, citric acid, oxalic acid, tartaric acid, the niter cake; Said foaming agent is one or both the mixture in sodium bicarbonate or the sodium carbonate; Said binding agent is one or both the mixture in beta-schardinger dextrin-, the polyvinylpyrrolidone; Said releasing agent is one or both the mixture in dolomol, the talcum powder; Said forming agent is one or both the mixture in polyethylene glycol, the polyvinylpyrrolidone;
The usage amount of the various raw materials of said tablet B is respectively: acidulant 35~50wt%, catalyzer 20~30wt%, foaming agent 3~8wt%, binding agent 10~15wt%, forming agent 10~15wt%, releasing agent 0.05~0.2wt%.Wherein, said acidulant is a solid acid, is one or more the mixture in sulfamic acid, citric acid, oxalic acid, tartaric acid, the niter cake; Said catalyzer is one or more the mixture in alkali metal bromide, alkali metal or the alkaline earth metal persulfate; Said foaming agent is one or both the mixture in sodium bicarbonate or the sodium carbonate; Said binding agent is one or both the mixture in beta-schardinger dextrin-, the polyvinylpyrrolidone; Said releasing agent is one or both the mixture in dolomol, the talcum powder; Said forming agent is one or both the mixture in polyethylene glycol, the polyvinylpyrrolidone.
Among the present invention, said tablet A and tablet B all use enough seed coating medicines to carry out dressing, and described seed coating medicine is one or both the mixture in polyethylene glycol, the polyvinylpyrrolidone.
The preparation method of two-component packaging response type chlorine dioxide tablet of the present invention may further comprise the steps.
1) each raw material is ground the back and cross 100~120 mesh sieves, the raw material of granularity in the middle of leaving and taking is in 40~120 ℃ of oven dry down.
2) take by weighing primary dose of 55~65wt%, lytic agent 8~12wt%, foaming agent 8~11wt%, binding agent 8~11wt%, forming agent 8~11wt%, releasing agent 0.01~0.5wt% respectively, after mixing, be pressed into binary reaction type titanium dioxide chlorine tablets A.
3) take by weighing acidulant 35~50wt%, catalyzer 20~30wt%, foaming agent 3~8wt%, binding agent 10~15wt%, forming agent 10~15wt%, releasing agent 0.05~0. 2wt% respectively, after mixing, be pressed into binary reaction type titanium dioxide chlorine tablets B.
4) use dissolve with ethanol solution to be mixed with the coating solution of concentration as 6wt% seed coating medicine, dressing, drying obtain monobasic packing response type chlorine dioxide tablet A and tablet B respectively to above-mentioned binary reaction type titanium dioxide chlorine tablets A and B.
5) use the medical polyvinyl film that two-component packaging response type chlorine dioxide tablet A and tablet B are carried out mmic package respectively.
The representative formula of two-component packaging response type chlorine dioxide tablet of the present invention is following.
Tablet A: primary dose of 55~65wt%, lytic agent 9~11wt%, foaming agent 8~10wt%, binding agent 8~10wt%, forming agent 8~10wt%, releasing agent 0.1~0.2wt%.
Tablet B: acidulant 40%~45wt%, catalyzer 23%~27wt%, foaming agent 4~7wt%, binding agent 11~13wt%, forming agent 11~13wt%, releasing agent 0.07~0.15wt%.
Further; Among the two-component packaging response type chlorine dioxide tablet A of the present invention, said primary dose of preferred sodium chlorite, said lytic agent optimization citric acid; The preferred sodium carbonate of said foaming agent; The preferred beta-schardinger dextrin-of said binding agent, the preferred polyethylene glycol of said forming agent (molecular weight 6000), the preferred dolomol of said releasing agent.Among the tablet B; The mixture of preferred sulfamic acid of said acidulant and niter cake mass ratio 1:2; The preferred sodium bromide of said catalyzer, the preferred sodium bicarbonate of said foaming agent, the preferred beta-schardinger dextrin-of said binding agent; The preferred polyethylene glycol of said forming agent (molecular weight 6000), the preferred dolomol of said releasing agent.
The preparation method of the preferred two-component packaging response type of the present invention chlorine dioxide tablet may further comprise the steps.
1) 100~120 mesh sieves are crossed in each raw material grinding back, the raw material of granularity in the middle of leaving and taking is dried 2h down respectively at 40~120 ℃.
2) take by weighing sodium chlorite 55~65wt% respectively, citric acid 9~11wt%, sodium carbonate 8~10wt%; Beta-schardinger dextrin-8~10wt%, polyethylene glycol (molecular weight 6000) 8~10wt%, dolomol 0.1~0.2wt%; After mixing, be pressed into binary reaction type titanium dioxide chlorine tablets A.
3) take by weighing sulfamic acid+niter cake (mass ratio 1:2) 40%~45wt% respectively; Sodium bromide 23%~27wt%, sodium bicarbonate 4~7wt%, beta-schardinger dextrin-11~13wt%; Polyethylene glycol (molecular weight 6000) 11~13wt%; Dolomol 0.07~0.15wt% after mixing, is pressed into binary reaction type titanium dioxide chlorine tablets B.
4) adopting concentration is the dissolve with ethanol solution polyethylene glycol of 75wt%; Being mixed with concentration is the polyethylene glycol coating solution of 6wt%; Use coating pan to 2), 3) the binary reaction type titanium dioxide chlorine tablets A and the B that make carry out dressing respectively, drying obtains two-component packaging response type chlorine dioxide tablet A and tablet B.
5) use the medical polyvinyl film that two-component packaging response type chlorine dioxide tablet A and tablet B are carried out mmic package respectively.
The present invention is primary dose with alkali metal or alkaline earth metal chlorite; Add materials such as acidulant, promoter; Make binary reaction type titanium dioxide chlorine tablets through adding binding agent, lubricant and blowing agent, adopt packaging technique to carry out obtaining product of the present invention behind the dressing then.Products obtained therefrom of the present invention is a binary reaction type chlorine dioxide tablet; This product in use; Only need difference, the tablet A and the tablet B of different amounts joined in the gasifying agent in proportion, under the effect of gasifying agent according to use occasion; Highly purified gas chlorine dioxide be can produce, sterilization, the sterilization of space environment are used for.
With respect to existing solid preparation of chlorine dioxide, tablet of the present invention has the following advantages: (1) primary dose of sodium chlorite conversion ratio reaches more than 97%, and the availability of acidulant is greater than more than 80%, and feed stock conversion is high.(2) the gas purity of chlorine dioxide that is produced is high, has reached more than 95%, and the content of chlorine is lower than 4%, has really realized the preparation of high-pure gas chlorine dioxide.Improved the safety that the gas chlorine dioxide uses.(3) two kinds of times that tablet reacts, the used time of complete reaction was less than 30min less than 5min.(4) adopt A, B tablet separating type, be convenient to storage, the transportation of tablet more, guaranteed the safety of medicament to greatest extent.(5) adopt polyvinyl chloride film that product is packed, thereby guaranteed the term of validity of product further.(6) experiment confirm, the effective storage life of A of the present invention, B tablet product is more than 1 year.
Product of the present invention is convenient to preserve, not volatile, product stability is high.During use, according to the content of the difference of use occasion and chlorine dioxide with tablet dissolved in water, behind reaction 15~30min, can play desirable disinfection effect.
Embodiment
Embodiment 1
1) 100~120 mesh sieves are crossed in each raw material grinding back, the raw material of granularity in the middle of leaving and taking is dried 2h down respectively at 40~120 ℃;
2) take by weighing sodium chlorite 6Kg respectively, citric acid 1Kg, sodium carbonate 1Kg, beta-schardinger dextrin-1Kg, polyethylene glycol (molecular weight 6000) 0.8Kg, dolomol 0.02Kg after mixing, is pressed into binary reaction type titanium dioxide chlorine tablets A;
3) take by weighing sulfamic acid+niter cake (mass ratio 1:2) 4.3Kg respectively, sodium bromide 2.5Kg, sodium bicarbonate 0.6Kg, beta-schardinger dextrin-1.2Kg, polyethylene glycol (molecular weight 6000) 1.2Kg, dolomol 0.01Kg is pressed into binary reaction type titanium dioxide chlorine tablets B;
4) employing concentration is 75% dissolve with ethanol solution polyethylene glycol; The concentration that is mixed with enough volumes is 6% polyethylene glycol coating solution; Use coating pan to 2), 3) the binary reaction type titanium dioxide chlorine tablets A and the B that make carry out dressing respectively, drying obtains two-component packaging response type chlorine dioxide tablet A and tablet B;
5) use the medical polyvinyl film that two-component packaging response type chlorine dioxide tablet A and tablet B are carried out mmic package respectively.
Embodiment 2
1) take by weighing sodium chlorite 5.5Kg respectively, citric acid 1.1Kg, sodium carbonate 1Kg, beta-schardinger dextrin-1Kg, polyethylene glycol (molecular weight 6000) 1Kg, dolomol 0.02Kg after mixing, is pressed into binary reaction type titanium dioxide chlorine tablets A;
2) take by weighing sulfamic acid+niter cake (mass ratio 1:2) 4Kg respectively, sodium bromide 2.7Kg, sodium bicarbonate 0.7Kg, beta-schardinger dextrin-1.3Kg, polyethylene glycol (molecular weight 6000) 1.2Kg, dolomol 0.01Kg is pressed into binary reaction type titanium dioxide chlorine tablets B;
3) other preparation process is with embodiment 1.
Embodiment 3
1) take by weighing sodium chlorite 6.5Kg respectively, citric acid 0.9Kg, sodium carbonate 0.8Kg, beta-schardinger dextrin-0.8Kg, polyethylene glycol (molecular weight 6000) 0.8Kg, dolomol 0.02Kg after mixing, is pressed into binary reaction type titanium dioxide chlorine tablets A;
2) take by weighing sulfamic acid+niter cake (mass ratio 1:2) 4.3Kg, sodium bromide 2.4Kg, sodium bicarbonate 0.6Kg respectively; Beta-schardinger dextrin-1.3Kg; Polyethylene glycol (molecular weight 6000) 1.2Kg, dolomol 0.01Kg is pressed into binary reaction type titanium dioxide chlorine tablets B;
3) other preparation process is with embodiment 1.
Embodiment 4
1) take by weighing sodium chlorite 6Kg respectively, oxalic acid 1.2Kg, sodium bicarbonate 0.8Kg, polyvinylpyrrolidone 1Kg, polyethylene glycol (molecular weight 6000) 0.8Kg, dolomol 0.02Kg after mixing, is pressed into binary reaction type titanium dioxide chlorine tablets A;
2) take by weighing sulfamic acid+citric acid (mass ratio 1:2) 4Kg respectively, sodium bromide 2.5Kg, sodium bicarbonate 0.7Kg, beta-schardinger dextrin-1.3Kg, polyethylene glycol (molecular weight 6000) 1.3Kg, dolomol 0.01Kg is pressed into binary reaction type titanium dioxide chlorine tablets B;
3) other preparation process is with embodiment 1.
Embodiment 5
1) takes by weighing sodium chlorite 6.5Kg respectively, oxalic acid+citric acid (1:1) 1Kg, sodium carbonate 0.9Kg; Polyvinylpyrrolidone 0.8Kg, polyethylene glycol (molecular weight 6000) 0.7Kg, dolomol 0.02Kg; After mixing, be pressed into binary reaction type titanium dioxide chlorine tablets A;
2) take by weighing sulfamic acid+niter cake (mass ratio 1:2) 4.5Kg respectively, sodium bromide 2.2Kg, sodium bicarbonate 0.7Kg, beta-schardinger dextrin-1.3Kg, polyvinylpyrrolidone 1.2Kg, dolomol 0.01Kg is pressed into binary reaction type titanium dioxide chlorine tablets B;
3) other preparation process is with embodiment 1.