CN104161746B - Sugarless type Lysinepuzinc particulate composition and preparation method - Google Patents
Sugarless type Lysinepuzinc particulate composition and preparation method Download PDFInfo
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- CN104161746B CN104161746B CN201410459627.3A CN201410459627A CN104161746B CN 104161746 B CN104161746 B CN 104161746B CN 201410459627 A CN201410459627 A CN 201410459627A CN 104161746 B CN104161746 B CN 104161746B
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- 229910052742 iron Inorganic materials 0.000 description 1
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- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
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- VIKNJXKGJWUCNN-XGXHKTLJSA-N norethisterone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 VIKNJXKGJWUCNN-XGXHKTLJSA-N 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
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- 230000000050 nutritive effect Effects 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
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- 229920003023 plastic Polymers 0.000 description 1
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- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
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- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
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- WGIWBXUNRXCYRA-UHFFFAOYSA-H trizinc;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound [Zn+2].[Zn+2].[Zn+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O WGIWBXUNRXCYRA-UHFFFAOYSA-H 0.000 description 1
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- 239000004246 zinc acetate Substances 0.000 description 1
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Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention relates to Sugarless type Lysinepuzinc particulate composition and preparation method.The invention belongs to pharmaceutical technology field, relate to a kind of supplementary lysine and the compositions of zinc particularly zinc gluconate, particularly relate to a kind of for supplementing lysine and the granule of zinc particularly zinc gluconate, more particularly to a kind of for supplementing lysine and the sugar-free granule of zinc particularly zinc gluconate.The invention still further relates to a kind of method preparing described compositions.The Lysinepuzinc granule that the present invention provides is minerals nonprescription drugs medicine.Growth retardation, malnutrition and the anorexia etc. caused for preventing and treating children's and teenager for want of lysine and zinc clinically.Lysine contained by Lysinepuzinc granule is one of necessary aminoacid maintaining human body nitrogen balance, has the effect promoting growth in humans；Zinc is the important composition composition of internal multiple enzyme, has enhancing development, improves the effect of the sense of taste.
Description
Technical field
The invention belongs to pharmaceutical technology field, relate to a kind of supplementary lysine and the compositions of zinc particularly zinc gluconate, particularly relate to one
Kind for supplementing lysine and the granule of zinc particularly zinc gluconate, it is used for supplementing lysine and zinc particularly more particularly to one
The sugar-free granule of zinc gluconate.The invention still further relates to a kind of method preparing described compositions.
Background technology
Lysine, also referred to as L-lysine hydrochloride, be a kind of essential amino acids.Lysine English name lysine, abridge Lys, aminoacid
One-letter abbreviations K, its chemical formula is H2NCH2CH2CH2CH2CH(NH2) COOH, molecular formula: C6H14N2O2, molecular weight 146.19,
CAS 56-87-1, chemical structural formula is:
The symptom lacking lysine includes fatigue, weak, feels sick, and vomiting is dizzy, does not has appetite, hypoevolutism, anemia etc..Can be
Lysine nutritional supplement is taked under medical professional's suggestion.The recommended intake of lysine every day is that child often weighs oneself 10 milligrams, adult
Every day is between 3000-9000 milligram.It is useful for having turned out it to some specified diseases.Effect of known lysine includes that treatment is simple
The herpes labialis that herpesvirus and herpes zoster cause.Take in lysine and can be greatly shortened the time of healing.Research is it has been shown that it has changes
Kind immune system, resists herpes simplex and effect of varicella zoster virus, and some researchs are it is also shown that effect of lysine is also possible that and prevents
Bone-loss (can cause osteoporosis), because it can help bodily tissue to absorb calcium.Skeleton vigor can be promoted in conjunction with other aminoacid,
And by increasing the pre-anti-osteoporosis of women collagen protein.Increase collagen protein and can promote that skeleton and connective tissue are more powerful and more pliable and tougher.
Research also shows, lysine is combined with some NSAID (non-steroidal anti-inflammatory drug), it is possible to successfully treatment is relevant to premenstrual syndrome and menarche
Migraine and abdominal colic.Although also needing to further study the answer obtained more precisely, but lysine improving the probability of these problems
Make research worker the most excited.
Lysine is a kind of aminoacid that human body needs, a kind of indispensable nutrient substance.It is known that protein is to constitute human body cell
Main Ingredients and Appearance, protein in food enters after human body through the first breaks down into amino acids of digestion, and then human body utilizes again these aminoacid to close again
The human body protein of Cheng Xin, if immune antibody, digestive enzyme, plasma protein, growth hormone etc. are all the human body proteins after synthesis.In synthesis
In the various aminoacid of protein, 1B is most important one, has lacked it, and other aminoacid is just restricted or is not used,
Scientist it be called human body the first essential amino acids.Scientist also finds, 1B is that the important substance controlling growth in humans presses down in long element
Important is also the most required composition, and nervus centralis and peripheral nervous system to people all play an important role.Human body can not self synthesis L-
Lysine, it is necessary to drawing lysine from food and be to aid in the key substance that other nutrient substance is fully absorbed by human body and utilizes, human body is only
Supplement enough 1Bs and could improve absorption and the utilization of food protein, reach balanced nutritious, enhancing development.Its effect has:
1. improve intelligence, promote growth, health invigorating；
2. appetite stimulator, improve malnutrition situation；
3. improve insomnia, improve memory；
4. help to produce antibody, hormone and enzyme, improve immunity, increase hematochrome；
5. helping the absorption of calcium, treatment prevents osteoporosis；
6. reduce the level of triglyceride in blood, the generation of prevention cardiovascular and cerebrovascular disease.
Lysine relevant modifications: methylating of its epsilon-amino is a kind of common post translational modification, forms monomethyl, dimethyl and trimethyl and relies
Propylhomoserin.Trimethyl lysine can occur in calmodulin, CaM.Modify it addition, lysine residue can also carry out acetylation and ubiquitination etc..Collagen
The oxylysine contained in albumen is through lysyl hydroxylase hydroxylating by lysine.In endoplasmic reticulum or Golgi body, oxylysine
The O-glycosylation of residue can be used to the secretion from cell of the labelling specific protein.
Lysine is nutrient substance necessary to human body, but health oneself can not produce it.It must be obtained by diet and nutritional supplement
?.As a kind of aminoacid, it is the requisite ingredient of protein.This nutrition serves for the suitable growth of health and development
Important function.It is the important component part that carnitine produces.Carnitine is responsible for some unsaturated fatty acids are converted into energy, additionally aids
Reduce cholesterol levels.
Lysine also has other effects in the body.It forms collagen protein together with other nutrition.Collagen protein at connective tissue, skeleton,
Muscle, tendon and articular cartilage play key player.Additionally, lysine also contributes to health absorbs calcium.
The situation lacking lysine in diet is relatively common.The people's incidence rate being a vegetarian under normal circumstances is higher, some athletes without
Suitable diet is taked also to there will be the problem that lysine lacks.Protein intake low (such as bean, Semen Pisi sativi, Radix Crotalariae szemoensis etc.) is likely to
Cause lysine intake low.
Suitably supplement lysine and can promote the growth promoter of child, lack for a long time lysine then can make child's growth retardation, react indifferent,
Pale complexion, xerosis cutis, of flaccid muscles, resistance reduction, serious also can affect intelligent development.
According to the dietary habit of Chinese residents, the food protein taken at ordinary times mostlys come from frumentum.But lysine contained in corn is relatively
Few, thus limit other several amino acid whose utilizations.Therefore, in the food (such as bread, rice, rice food) based on corn
It is properly added lysine, is just remarkably improved its nutritive value.
It should be noted that, owing to lysine is easily dissolved in water, therefore should avoid during processed food soaking for a long time.Additionally, lysine
Non-refractory, thus food to steam, to boil, stew preferably, and should avoid decocting, explode, quick-fried.
Generally speaking, the food being rich in protein all contains lysine, such as meat, fowl, egg, milk, fish, shrimp, shellfish, milk product and bean
Class, Semen Sesami Nigrum etc..It should be noted that cereals or Semen arachidis hypogaeae and do not contain the lysine ready-made, human body needs.
Zinc is present in numerous enzyme systems, such as carbonic anhydrase, respiratory enzyme, lactate dehydrogenase, superoxide dismutase, alkali phosphatase, DNA
In poly-with RNA in enzyme etc., required for nucleic acid, protein, the synthesis of carbohydrate and the utilization institute of vitamin A.It is raw that zinc has promotion
Long growth, improves the effect of the sense of taste.Occurring the sense of taste during zinc deficiency, olfactory sensation is poor, anorexia, and growth and intelligent development are less than normal.
1st generation inorganic zinc with zinc sulfate, zinc chloride, zinc nitrate etc. as main representative is the most original zinc supplement product, and zinc-iron alloy solution utilization rate is low (only
It is 7%)；They and internal gastric acid combine, and can produce zinc chloride, and zinc chloride is highly corrosive agents, and gastrointestinal tract is had stimulation, easily causes evil
The heart, vomiting etc.；Market is eliminated out in the representative of this generation zinc now the most substantially, rarely found, is used for surgical operation, to promote healing of wound
Close.The main representative of 2nd generation organic acid zinc has: zinc gluconate, zinc glycyrrhizate, zinc acetate, zinc citrate, amino-acid zinc, zinc lactate etc.,
They belong to weak acid and mild base salt together, and zinc-iron alloy solution utilization rate about 14% absorbance is much larger than inorganic zinc.
Zinc gluconate, its English name has Gluconic Acid Zinc, D-gluconic acid-zinc (2:1), zinc bis (2,3,4,5,6
Pentahydroxyhexanoate), zinc bis [(2R, 3S, 4R, 5R)-2,3,4,5,6-pentahydroxyhexanoate], also known as glucose monohydrate are sour
Zinc, its chemical formula: Zn (C6H11O7) 2, molecular weight 455.69, CAS accession number 4468-02-4, chemical structural formula:
Zinc gluconate belongs to conventional ancillary drug, for minerals nonprescription drugs medicine.Zinc gluconate is white crystals or particulate powder；
Soluble in water, insoluble in ethanol, chloroform ether.This product formulation requirements shading, airtight preservation.
Its common dosage forms has: Zinc Gluuconate Oral Solution, Zinc Gluconate Granules, mixture zinc gluconate, Zinc Gluconate Syrup, Fructus Vitis viniferae
Saccharic acid zinc chewable tablet etc..Except Zinc Gluuconate Oral Solution, Zinc Gluconate Granules, mixture zinc gluconate, Zinc Gluconate Syrup, Fructus Vitis viniferae
Outside saccharic acid zinc chewable tablet, the most also zinc gluconate of a kind, in capsule shape, claim zinc gluconate soft capsule.It is primarily directed to
Birth infant.
Mainly by intestinal absorption after zinc gluconate is oral, serum zinc concentration reached peak after 1 hour, within about 2 hours, began to decline.Can be extensively
It is distributed in liver, intestinal, spleen, pancreas, the heart, kidney, lung, muscle and central nervous system, in skeleton etc..Mainly drained by feces, pass through on a small quantity
Urine, milk is drained.
Zinc gluconate is zinc supplement, is mainly used in baby and old age, the growth retardation that gravid woman causes because of zinc deficiency, malnutrition,
Apositia, recurrent oral ulceration, the disease such as skin acne.
The preparation as active component with lysine and zinc gluconate has been had to use, such as Lysinepuzinc sheet, Lysinepuzinc granule etc..
Lysinepuzinc granule act as a kind of compound preparation, often comprises lysine 125 milligrams, and zinc gluconate 35 milligrams (is equivalent to zinc 5 milli
Gram).Lysinepuzinc granule is minerals nonprescription drugs medicine.It is used for clinically preventing and treating children's and teenager for want of lysine and zinc and causing
Growth retardation, malnutrition and anorexia etc..Lysine contained by Lysinepuzinc granule is the necessary aminoacid maintaining human body nitrogen balance
One of, there is the effect promoting growth in humans；Zinc is the important composition composition of internal multiple enzyme, has enhancing development, improves the sense of taste
Effect.
Standard No. is that the national drug standards of WS-10001-(HD-0387)-2002 disclose a kind of Lysinepuzinc granule, and its formula is: hydrochloric acid
Lysine: 125g, zinc gluconate: 35g, citric acid: 12.5g, sucrose: 4825g, coloring agent: appropriate, flavoring agent: appropriate, system
Become: 1000 bags.
Lysine hydrochloride prepared by known above-mentioned national standard prescription and the problem of Zinc Gluconate Granules at least five aspects.One is high
The sucrose of content makes lysine hydrochloride and Zinc Gluconate Granules be not suitable for diabetics；Also ND is allowed to take in unnecessary height
Energy；Its two, the ratio between supplementary material amount is excessive, easily cause wrap with bag between content uneven；Its three, the hardness of granule is the highest,
Easily pulverize in subpackage and transportation.Its four, mobility is bad, and content uniformity is big, and five, without essence in granule, mouthfeel is bad,
Child's patient compliance is poor.
This area still expects that the preparation having new supplementary lysine and zinc gluconate is particularly without the preparation of sucrose.
Summary of the invention
It is an object of the invention to provide a kind of there is excellent pharmaceutical properties comprise lysine hydrochloride and the sugar type granules system of zinc gluconate
Agent.It has been found, unexpectedly, the granule with feature of present invention presents the excellent pharmaceutical properties in terms of at least one.The present invention
Find based on this and be accomplished.
To this end, first aspect present invention provides a kind of compositions, it is Sugarless type Lysinepuzinc granule, and comprising: hydrochloric acid relies
Propylhomoserin, zinc gluconate, citric acid and mannitol.
The compositions of any embodiment according to a first aspect of the present invention, in terms of the lysine hydrochloride of every 125 weight portions, wherein zinc gluconate
Amount be 30～40 weight portions, such as 32～38 weight portions, such as 34～36 weight portions, such as 35 weight portions.
The compositions of any embodiment according to a first aspect of the present invention, in terms of the lysine hydrochloride of every 125 weight portions, the wherein amount of citric acid
It is 10～15 weight portions, such as 11～14 weight portions, such as 12～13 weight portions, such as 12.5 weight portions.
The compositions of any embodiment according to a first aspect of the present invention, in terms of the lysine hydrochloride of every 125 weight portions, the wherein amount of mannitol
It is 2000～3500 weight portions, such as 2500～3000 weight portions, such as 2600～2800 weight portions, such as 2650～2750 weight portions.
The compositions of any embodiment according to a first aspect of the present invention, the most also includes starch.
The compositions of any embodiment according to a first aspect of the present invention, in terms of the lysine hydrochloride of every 125 weight portions, wherein the amount of starch is
50～200 weight portions, such as 75～175 weight portions, such as 100～150 weight portions.
The compositions of any embodiment according to a first aspect of the present invention, it places 24 under conditions of temperature 25 ± 1 DEG C, relative humidity 75%
Hour, moisture absorption weightening finish percent is less than 10%, e.g., less than 5%, e.g., less than 4%, e.g., less than 3%.
The compositions of any embodiment according to a first aspect of the present invention, it is according to the double sieve of Chinese Pharmacopoeia two annex Ⅸ E the second methods of version in 2010
Point-score checks, it is impossible to is sieved by No. one and can pass through No. five summations sieved less than supplying the 15% of examination amount, such as less than supplying the 10% of examination amount.
The compositions of any embodiment according to a first aspect of the present invention, it is surveyed according to Chinese Pharmacopoeia two annex VIII L losss on drying of version in 2010
Method of determining measures, and is dried to constant weight at 105 DEG C, and less loss weight is less than 5%, e.g., less than 4%, e.g., less than 3%, e.g., less than 2%.
The compositions of any embodiment according to a first aspect of the present invention, wherein said starch is to add described compositions to the form of binding agent
In.
The compositions of any embodiment according to a first aspect of the present invention, wherein said starch is that the form of the binding agent pelletized in a wet process is added to
In described compositions.
The compositions of any embodiment according to a first aspect of the present invention, it is to prepare by the way of wet granulation.
The compositions of any embodiment according to a first aspect of the present invention, it is system by the way of carrying out wet granulation in fluid bed and being dried
For obtain.
The compositions of any embodiment according to a first aspect of the present invention, it is substantially prepared by a method comprising the following steps and obtains:
(1) make citric acid be dissolved in suitable quantity of water (amount of such as water is 70～120 times of citric acid weight, such as 80～110 times), then add successively
Enter zinc gluconate, lysine hydrochloride and make it dissolve, obtaining settled solution；
(2) again by appropriate amount of starch (such as accounting for the 40～60% of recipe quantity, such as account for the 50% of recipe quantity) the water furnishing pasty state of 2 times of weight,
Mixing homogeneously with step (1) gained solution, stirring is opened simultaneously and is heated to 60 DEG C～80 DEG C, obtains solution I, standby again；
(3) by the surplus starch water furnishing pasty state of 6～10 times of (such as 8 times) weight, stirring is opened simultaneously and is heated to 60 DEG C～80 DEG C,
Obtain solution II, standby；
(4) mannitol of recipe quantity is put in fluidised bed granulator, mix 5min, open and be heated to 60 DEG C～80 DEG C, spray into the molten I of liquid, connect
And spray into solution II；
(5) making material be dried 30～60min in fluid bed at a temperature of 60 DEG C～80 DEG C, the less loss weight measured to dry weightless mensuration is little
In 1.5%, discharging is standby；
(6) granulate: by pellet through sieves, collect the granule between 15-50 mesh, pack, to obtain final product.
It has been unexpectedly discovered that use the granule that inventive formulation and technique prepare, it has low hygroscopicity, particularly in temperature
Spending 25 ± 1 DEG C, place 24 hours under conditions of relative humidity 75%, moisture absorption weightening finish percent is typically smaller than 5%, than in not using this
The granule that bright method and/or technique prepare has the most excellent feature.Particularly, it has been unexpectedly discovered that work as and use starch slurry
The above results could be realized for binding agent and when using fluidized bed granulation technique.
Further, second aspect present invention provides the method for the compositions preparing Sugarless type Lysinepuzinc granule, and described compositions includes:
Lysine hydrochloride, zinc gluconate, citric acid and mannitol, the method is to carry out by the way of wet granulation.
The method of any embodiment according to a second aspect of the present invention, wherein said wet granulation is to carry out wet granulation in fluid bed and be dried
Method.
The method of any embodiment according to a second aspect of the present invention, in wherein said compositions in terms of the lysine hydrochloride of every 125 weight portions,
Wherein the amount of zinc gluconate is 30～40 weight portions, such as 32～38 weight portions, such as 34～36 weight portions, such as 35 weight portions.
The method of any embodiment according to a second aspect of the present invention, in wherein said compositions in terms of the lysine hydrochloride of every 125 weight portions,
Wherein the amount of citric acid is 10～15 weight portions, such as 11～14 weight portions, such as 12～13 weight portions, such as 12.5 weight portions.
The method of any embodiment according to a second aspect of the present invention, in wherein said compositions in terms of the lysine hydrochloride of every 125 weight portions,
Wherein the amount of mannitol is 2000～3500 weight portions, such as 2500～3000 weight portions, such as 2600～2800 weight portions, such as 2650～2750
Weight portion.
The method of any embodiment according to a second aspect of the present invention, also includes starch in wherein said compositions.
The method of any embodiment according to a second aspect of the present invention, in wherein said compositions in terms of the lysine hydrochloride of every 125 weight portions,
Wherein the amount of starch is 50～200 weight portions, such as 75～175 weight portions, such as 100～150 weight portions.
The method of any embodiment according to a second aspect of the present invention, wherein said starch is to add in described compositions with the form of binding agent
's.
The method of any embodiment according to a second aspect of the present invention, wherein said starch is that the form of the binding agent pelletized in a wet process adds institute to
State in compositions.
The method of any embodiment according to a second aspect of the present invention, it consists essentially of following steps:
(1) make citric acid be dissolved in suitable quantity of water (amount of such as water is 70～120 times of citric acid weight, such as 80～110 times), then add successively
Enter zinc gluconate, lysine hydrochloride and make it dissolve, obtaining settled solution；
(2) again by appropriate amount of starch (such as accounting for the 40～60% of recipe quantity, such as account for the 50% of recipe quantity) the water furnishing pasty state of 2 times of weight,
Mixing homogeneously with step (1) gained solution, stirring is opened simultaneously and is heated to 60 DEG C～80 DEG C, obtains solution I, standby again；
(3) by the surplus starch water furnishing pasty state of 6～10 times of (such as 8 times) weight, stirring is opened simultaneously and is heated to 60 DEG C～80 DEG C,
Obtain solution II, standby；
(4) mannitol of recipe quantity is put in fluidised bed granulator, mix 5min, open and be heated to 60 DEG C～80 DEG C, spray into the molten I of liquid, connect
And spray into solution II；
(5) making material be dried 30～60min in fluid bed at a temperature of 60 DEG C～80 DEG C, the less loss weight measured to dry weightless mensuration is little
In 1.5%, discharging is standby；
(6) granulate: by pellet through sieves, collect the granule between 15-50 mesh, pack, to obtain final product.
The method of any embodiment according to a second aspect of the present invention, wherein said compositions is in temperature 25 ± 1 DEG C, the condition of relative humidity 75%
Lower placement 24 hours, moisture absorption weightening finish percent is less than 10%, e.g., less than 5%, e.g., less than 4%, e.g., less than 3%.
The method of any embodiment according to a second aspect of the present invention, wherein said compositions is according to Chinese Pharmacopoeia two annex Ⅸ E of version in 2010
The double sieve method inspection of second method, it is impossible to sieved by No. one and No. five summations sieved can be passed through less than supplying the 15% of examination amount, such as less than supplying to try
The 10% of amount.
The method of any embodiment according to a second aspect of the present invention, wherein said compositions is according to Chinese Pharmacopoeia two annex VIII L of version in 2010
Dry weightless mensuration measures, and is dried to constant weight at 105 DEG C, and less loss weight is less than 5%, e.g., less than 4%, e.g., less than 3%, the least
In 2%.
Yet further, third aspect present invention provide lysine hydrochloride and zinc gluconate preparation for prevent and treat children's and teenager due to
Purposes in the compositions of the agent of low hygroscopicity of growth retardation that lysine and zinc deficiency cause, malnutrition, inappetence etc., Qi Zhongsuo
State as Sugarless type Lysinepuzinc granule, and said composition includes: lysine hydrochloride, zinc gluconate, citric acid and mannitol.
The purposes of any embodiment according to a third aspect of the present invention, in described compositions in terms of the lysine hydrochloride of every 125 weight portions, wherein
The amount of zinc gluconate is 30～40 weight portions, such as 32～38 weight portions, such as 34～36 weight portions, such as 35 weight portions.
The purposes of any embodiment according to a third aspect of the present invention, in described compositions in terms of the lysine hydrochloride of every 125 weight portions, wherein
The amount of citric acid is 10～15 weight portions, such as 11～14 weight portions, such as 12～13 weight portions, such as 12.5 weight portions.
The purposes of any embodiment according to a third aspect of the present invention, in described compositions in terms of the lysine hydrochloride of every 125 weight portions, wherein
The amount of mannitol is 2000～3500 weight portions, such as 2500～3000 weight portions, such as 2600～2800 weight portions, such as 2650～2750
Weight portion.
The purposes of any embodiment according to a third aspect of the present invention, the agent of low hygroscopicity of described compositions by compositions with binding agent
Form adds what starch realized.
The purposes of any embodiment according to a third aspect of the present invention, also includes starch in described compositions.
The purposes of any embodiment according to a third aspect of the present invention, in described compositions in terms of the lysine hydrochloride of every 125 weight portions, wherein
The amount of starch is 50～200 weight portions, such as 75～175 weight portions, such as 100～150 weight portions.
The purposes of any embodiment according to a third aspect of the present invention, starch described in described compositions be add to the form of binding agent described
In compositions.
The purposes of any embodiment according to a third aspect of the present invention, starch described in described compositions is the form of the binding agent pelletized in a wet process
Add in described compositions.
The purposes of any embodiment according to a third aspect of the present invention, the agent of low hygroscopicity of described compositions refers to, it is in temperature 25 ± 1 DEG C, relatively
Placing 24 hours under conditions of humidity 75%, moisture absorption weightening finish percent is less than 10%, e.g., less than 5%, e.g., less than 4%, e.g., less than
3%.
The purposes of any embodiment according to a third aspect of the present invention, described compositions is according to Chinese Pharmacopoeia two annex Ⅸ E second of version in 2010
The double sieve method inspection of method, it is impossible to sieved by No. one and No. five summations sieved can be passed through less than supplying the 15% of examination amount, such as less than supplying examination amount
10%.
The purposes of any embodiment according to a third aspect of the present invention, described compositions is dried according to Chinese Pharmacopoeia two annex VIII L of version in 2010
Weightless algoscopy measures, and is dried to constant weight at 105 DEG C, and less loss weight is less than 5%, e.g., less than 4%, e.g., less than 3%, e.g., less than
2%.
The purposes of any embodiment according to a third aspect of the present invention, the agent of low hygroscopicity of described compositions by compositions with binding agent
Form is added starch and realizes by the way of wet granulation (such as fluid bed wet granulation) prepares granule.
The purposes of any embodiment according to a third aspect of the present invention, described compositions is to prepare by the way of wet granulation.
The purposes of any embodiment according to a third aspect of the present invention, described compositions is by carrying out wet granulation and being dried in fluid bed
Mode prepares.
The purposes of any embodiment according to a third aspect of the present invention, described compositions is substantially prepared by a method comprising the following steps
Arrive:
(1) make citric acid be dissolved in suitable quantity of water (amount of such as water is 70～120 times of citric acid weight, such as 80～110 times), then add successively
Enter zinc gluconate, lysine hydrochloride and make it dissolve, obtaining settled solution；
(2) again by appropriate amount of starch (such as accounting for the 40～60% of recipe quantity, such as account for the 50% of recipe quantity) the water furnishing pasty state of 2 times of weight,
Mixing homogeneously with step (1) gained solution, stirring is opened simultaneously and is heated to 60 DEG C～80 DEG C, obtains solution I, standby again；
(3) by the surplus starch water furnishing pasty state of 6～10 times of (such as 8 times) weight, stirring is opened simultaneously and is heated to 60 DEG C～80 DEG C,
Obtain solution II, standby；
(4) mannitol of recipe quantity is put in fluidised bed granulator, mix 5min, open and be heated to 60 DEG C～80 DEG C, spray into the molten I of liquid, connect
And spray into solution II；
(5) making material be dried 30～60min in fluid bed at a temperature of 60 DEG C～80 DEG C, the less loss weight measured to dry weightless mensuration is little
In 1.5%, discharging is standby；
(6) granulate: by pellet through sieves, collect the granule between 15-50 mesh, pack, to obtain final product.
Yet further, fourth aspect present invention provides starch purposes in preparing agent of low hygroscopicity compositions.
The purposes of any embodiment according to a fourth aspect of the present invention, wherein said compositions is Sugarless type Lysinepuzinc granule, and this group
Compound includes: lysine hydrochloride, zinc gluconate, citric acid and mannitol, and the starch added with the form of binding agent.
The purposes of any embodiment according to a fourth aspect of the present invention, in described compositions in terms of the lysine hydrochloride of every 125 weight portions, wherein
The amount of zinc gluconate is 30～40 weight portions, such as 32～38 weight portions, such as 34～36 weight portions, such as 35 weight portions.
The purposes of any embodiment according to a fourth aspect of the present invention, in described compositions in terms of the lysine hydrochloride of every 125 weight portions, wherein
The amount of citric acid is 10～15 weight portions, such as 11～14 weight portions, such as 12～13 weight portions, such as 12.5 weight portions.
The purposes of any embodiment according to a fourth aspect of the present invention, in described compositions in terms of the lysine hydrochloride of every 125 weight portions, wherein
The amount of mannitol is 2000～3500 weight portions, such as 2500～3000 weight portions, such as 2600～2800 weight portions, such as 2650～2750
Weight portion.
The purposes of any embodiment according to a fourth aspect of the present invention, in described compositions in terms of the lysine hydrochloride of every 125 weight portions, wherein
The amount of starch is 50～200 weight portions, such as 75～175 weight portions, such as 100～150 weight portions.
The purposes of any embodiment according to a fourth aspect of the present invention, starch described in described compositions is the form of the binding agent pelletized in a wet process
Add in described compositions.
The purposes of any embodiment according to a fourth aspect of the present invention, the agent of low hygroscopicity of described compositions refers to, it is in temperature 25 ± 1 DEG C, relatively
Placing 24 hours under conditions of humidity 75%, moisture absorption weightening finish percent is less than 10%, e.g., less than 5%, e.g., less than 4%, e.g., less than
3%.
The purposes of any embodiment according to a fourth aspect of the present invention, described compositions is according to Chinese Pharmacopoeia two annex Ⅸ E second of version in 2010
The double sieve method inspection of method, it is impossible to sieved by No. one and No. five summations sieved can be passed through less than supplying the 15% of examination amount, such as less than supplying examination amount
10%.
The purposes of any embodiment according to a fourth aspect of the present invention, described compositions is dried according to Chinese Pharmacopoeia two annex VIII L of version in 2010
Weightless algoscopy measures, and is dried to constant weight at 105 DEG C, and less loss weight is less than 5%, e.g., less than 4%, e.g., less than 3%, e.g., less than
2%.
The purposes of any embodiment according to a fourth aspect of the present invention, the agent of low hygroscopicity of described compositions by compositions with binding agent
Form is added starch and realizes by the way of wet granulation (such as fluid bed wet granulation) prepares granule.
The purposes of any embodiment according to a fourth aspect of the present invention, described compositions is to prepare by the way of wet granulation.
The purposes of any embodiment according to a fourth aspect of the present invention, described compositions is by carrying out wet granulation and being dried in fluid bed
Mode prepares.
The purposes of any embodiment according to a fourth aspect of the present invention, described compositions is substantially prepared by a method comprising the following steps
Arrive:
(1) make citric acid be dissolved in suitable quantity of water (amount of such as water is 70～120 times of citric acid weight, such as 80～110 times), then add successively
Enter zinc gluconate, lysine hydrochloride and make it dissolve, obtaining settled solution；
(2) again by appropriate amount of starch (such as accounting for the 40～60% of recipe quantity, such as account for the 50% of recipe quantity) the water furnishing pasty state of 2 times of weight,
Mixing homogeneously with step (1) gained solution, stirring is opened simultaneously and is heated to 60 DEG C～80 DEG C, obtains solution I, standby again；
(3) by the surplus starch water furnishing pasty state of 6～10 times of (such as 8 times) weight, stirring is opened simultaneously and is heated to 60 DEG C～80 DEG C,
Obtain solution II, standby；
(4) mannitol of recipe quantity is put in fluidised bed granulator, mix 5min, open and be heated to 60 DEG C～80 DEG C, spray into the molten I of liquid, connect
And spray into solution II；
(5) making material be dried 30～60min in fluid bed at a temperature of 60 DEG C～80 DEG C, the less loss weight measured to dry weightless mensuration is little
In 1.5%, discharging is standby；
(6) granulate: by pellet through sieves, collect the granule between 15-50 mesh, pack, to obtain final product.
Arbitrary technical characteristic other any embodiment equally applicable that any embodiment of either side of the present invention or this either side is had
Or any embodiment of other either side, as long as they will not be conflicting, certainly at where applicable each other, if necessary can be to phase
Answer feature to make suitably to modify.It is further described with feature the most to various aspects of the present invention.
All documents recited in the present invention, their full content is incorporated herein by, and if implication expressed by these documents
Time inconsistent with the present invention, it is as the criterion with the statement of the present invention.Additionally, the various terms of present invention use and phrase have those skilled in the art
Known general sense, nonetheless, the present invention remains desirable at this, these terms and phrase are described in more detail and explained, mentions
Term and phrase, if any inconsistent with common art-recognized meanings, are as the criterion with the implication that the present invention is stated.
It is further described the most to various aspects of the present invention.
Existing many documents report Lysinepuzinc granule application achievements clinically.(Tan Changwei, Lysinepuzinc granule therapy is repeatedly for Tan Changwei
The clinical research of respiratory tract infection, contemporary Chinese doctor, 16 phases in 2008) have rated Lysinepuzinc granule therapy recurrent respiratory tract infection curative effect.
Method: select children with repeated respiratory tract infections 80 example, be randomly divided into treatment group 40 example, in addition to conventional anti-infection, symptomatic treatment, with relying ammonia
Portugal's zinc granule therapy recurrent respiratory tract infection；Matched group 40 example, only with conventional therapy.Clinical observation also follows up a case by regular visits to infant recurrent respiratory tract in the recent period
Number of times, serum levels of iron, zinc, the concentration of calcium and the situation of IgG, IgA, IgM infected.Result: nearly 1 year infant for the treatment of group is being exhaled repeatedly
Inhale the number of times infected in road to be significantly improved significantly lower than ferrum, zinc, IgG, IgA, IgM in matched group, and blood, exist through statistical test aobvious
Write sex differernce (P < 0.05).Conclusion: Lysinepuzinc granule therapy recurrent respiratory tract infection curative effect is obvious.
Liu wads a quilt with cotton, and (Liu wads a quilt with cotton clean etc. clean grade, and Lysinepuzinc auxiliary treatment occurs together the observation of curative effect of extrapulmonary lesion mycoplasma pneumonia in children, Hubei Institute For Nationalities
Journal (medicine), 04 phase in 2013) explore Lysinepuzinc auxiliary treatment and occur together the curative effect of extrapulmonary lesion mycoplasma pneumonia in children.Method:
The infant of the 76 concurrent extrapulmonary lesions of example mycoplasma pneumonia in children is randomly divided into conventional group and treatment group, and conventional group gives azithromycin treatment, treatment
Group is aided with Lysinepuzinc on the basis of conventional group, compares two groups of infant healing times, at the end of observation detects serum immune globulin.
Result: treatment group average cure time is significantly shorter than conventional group (P < 0.01).At the end for the treatment of, detection serum IgG compares two groups of differences has aobvious
Work property (P < 0.05).Conclusion: Lysinepuzinc auxiliary azithromycin treatment contributes to Shorten the Treatment Process, its mechanism may have with zinc preparation regulation immunity
Close.
Xu Naiwei (Xu Naiwei, the observation of Lysinepuzinc granule associating golden bifid preventing and treating infantile pneumonia Secondary cases diarrhoea, Chinese Medicine guide, 2013
12 phases of year) inquire into the clinical efficacy that Lysinepuzinc granule associating golden bifid preventing and treating infantile pneumonia Secondary cases is suffered from diarrhoea.Method: 328 example pneumonia are suffered from
Youngster, is randomly divided into treatment group 168 example and matched group 160 example, all uses the Primary Care that antibiotic and symptomatic treatment etc. are identical, and treatment group adds
Take Lysinepuzinc granule and golden bifid.Result: treatment group occurs that Secondary cases is suffered from diarrhoea 30 examples, sickness rate 17.8% continues former side after there is diarrhoea
Case is treated, total effective rate 96.7%, obvious effective rate 86.7%；Matched group occurs that Secondary cases is suffered from diarrhoea 75 examples, sickness rate 46.8%, after there is diarrhoea
Taking Lysinepuzinc granule and golden bifid treatment, total effective rate 92%, obvious effective rate 48%, treatment group sickness rate is significantly lower than matched group (P < 0.01),
Treatment curative effect is substantially better than matched group (P < 0.05).Conclusion: Lysinepuzinc granule and golden bifid preventing and treating infantile pneumonia Secondary cases diarrhoea clinical efficacy
Good, especially for being associated with the better of light moderate Anorexia Children, and without obvious adverse reaction.
Ma Haiyan (Ma Haiyan, the clinical observation on the therapeutic effect of Lysinepuzinc granule auxiliary treatment infantile rotavirus enteritis, the practical medicine of China, 2014
Year 07 phase) in its paper, observe the clinical efficacy of Lysinepuzinc granule therapy infantile rotavirus enteritis, provide reference for clinical position.
Method: select the court's in June, 2010～in May, 2013 to accept rotavirus enteritis 120 example for medical treatment, be randomly divided into matched group and observation group each 60
Example.Two groups of infants all give conventional Comprehensive Treatment, and observation group gives oral Lysinepuzinc on this basis, observes and compares two groups of curative effects.Knot
Really: compare with matched group, observation group's infant overall treatment effect is substantially better than matched group, and average antidiarrheal time, fever time, vomiting are alleviated
Time and hospital stays are significantly shorter than matched group, difference statistically significant (P < 0.05).Conclusion: use Lysinepuzinc granule auxiliary treatment baby
Child's rotavirus enteritis, can obtain satisfied therapeutic effect, clinic popularization and application.
Zhan Mingliang etc. (Zhan Mingliang etc., Lysinepuzinc granule therapy infantile rotavirus enteritis clinical observation, Chinese medicine engineering, 2012
12 phases) in its paper, inquired into the clinical efficacy of Lysinepuzinc granule therapy infantile rotavirus enteritis.Technique study object is in 2009
January in year accepts rotavirus enteritis patient 123 example for medical treatment in November, 2012, is randomly divided into treatment group (60 example) and matched group (63 example).Comparison
Group gives fluid infusion, maintains Water-Electrolyte acid-base balance, Xiyanping antiviral, and Kent order protection gastric mucosa, reasonable feeding (suspends breast milk, gives
Remove lactose formula milk)；Treatment group adds Lysinepuzinc granule (zinc element 20mg/d divides and takes for 2 times) treatment on the basis of matched group.Observe
The curative effect of two groups, i.e. feces character, number of times and recovery normal time.The cure rate of result treatment group is 93.3%, and the cure rate of matched group is
73.3%, both differences statistically significant (P < 0.01).After treatment, two groups of feces character and number of times are clearly better the most earlier above, but treatment group is more right
Become apparent from according to group effect, difference statistically significant (P < 0.01).Conclusion Lysinepuzinc granule can substantially shorten the course for the treatment of of diarrhoea, and raising is controlled
More rate, is to be worth one of Therapeutic Method of recommending in grass-roots unit.
Xie Peng (Xie Peng, Lysinepuzinc auxiliary treatment rotavirus enteritis observation of curative effect, Chinese medicine innovation, 34 phases in 2013) have studied often
On the basis of rule treatment rotavirus enteritis, oral Lysinepuzinc granule is to the curative effect of rotavirus enteritis and the shadow of Incidence of Diarrhea in 3 months
Ring.Method: the court 86 example children with rotavirus enteritis is divided into treatment group and each 43 examples of matched group, two groups of infants according to random digits table
All giving conventional therapy, treatment group adds on this basis treats with Lysinepuzinc, observes two groups of curative effects.Two groups of infants of Effect of follow-up visit by telephone 3 simultaneously
The situation that in month, diarrhoea occurs.Result: treatment group clinical cure rate is 93.0%, hence it is evident that higher than the 72.1% of matched group, comparing difference has system
Meaning (P < 0.05) learned by meter.The treatment group transference cure time is significantly faster than that matched group, hospital stays are considerably less than matched group, suffers from diarrhoea in 3 months again
The rate of sending out is significantly lower than matched group, comparing difference the most statistically significant (P < 0.05).Conclusion: Lysinepuzinc auxiliary treatment rotavirus enteritis can
Alleviating diarrhoea symptom, shortens the course of disease, and the generation again of effective pre-anti-diarrhea.
Zhong Lin (Zhong Lin, the effect analysis of Lysinepuzinc treatment infantile acute diarrhea, Contemporary Chinese medicine, 25 phases in 2013) visits in its paper
Beg for the effect of Lysinepuzinc treatment infantile acute diarrhea.Method: select in January, 2009～in December, 2012 to carry out the children's of the court's treatment suddenly
Property diarrhea patient 100 example, be randomly divided into experimental group (50 example) and matched group (50 example), experimental group row Supporting Therapy to the ill adds Lysinepuzinc treatment,
Matched group is given only Supporting Therapy to the ill, compares the curative effect of two groups.Result: experimental group effective percentage is higher than matched group, the hospital stays is significantly shorter than
Matched group, two groups of differences statistically significant (P < 0.05).Conclusion: Lysinepuzinc can significantly improve the therapeutic effect of infantile acute diarrhea, and
Safe and reliable.
Gou luxuriant (Gou is luxuriant, Lysinepuzinc granule therapy Acute Infantile Diarrhea curative effect and nursing observation, clinical medicine, 08 phase in 2013) discusses at it
Literary composition has been inquired into clinical efficacy and the nursing intervention of Lysinepuzinc granule auxiliary treatment Acute Infantile Diarrhea.Method: 186 example infant are anxious
Property Diarrhea be randomly divided into treatment group 95 example and matched group 91 example, two groups all give conventional therapy, and treatment group adds with Lysinepuzinc granule mouth
Clothes.Result: treatment group obvious effective rate is 73.7%, total effective rate is 93.7%；Matched group obvious effective rate is 60.4%, and total effective rate is 80.2%,
Two groups of comparing differences statistically significant (χ 2=7.49, P < 0.01).Conclusion: Acute Infantile Diarrhea adds with relying ammonia on the basis of conventional therapy
Portugal's zinc granule therapy and suitable nursing, can improve curative effect, shorten the course of disease.
Wang Meixiang (woman is healthy at home and abroad, 08 phase in 2011 for Wang Meixiang, the auxiliary treatment Acute Infantile Diarrhea clinical observation of Lysinepuzinc granule)
The clinical efficacy of Lysinepuzinc granule therapy Acute Infantile Diarrhea is observed in its paper.Method: 180 children with acute diarrhea are randomly divided into
Treatment group and each 90 examples of matched group, matched group is conventional therapy, and treatment group adds on basis of conventional therapy uses Lysinepuzinc granule, observes two groups
Curative effect.Result: treatment group higher than matched group, is all significantly shorter than matched group on total effective rate on effective time, healing time, and two groups are compared
Difference statistically significant (P < 0.05).Conclusion: evident in efficacy with Lysinepuzinc granule therapy Acute Infantile Diarrhea.
Present invention generally provides a kind of Lysinepuzinc granule with excellent pharmaceutical properties, it, can as minerals nonprescription drugs medicine
Growth retardation, malnutrition and the anorexia etc. caused for preventing and treating children's and teenager for want of lysine and zinc.
Detailed description of the invention
The present invention can be conducted further description by the following examples, but, the scope of the present invention is not limited to following embodiment.
One of skill in the art it is understood that on the premise of without departing substantially from the spirit and scope of the present invention, the present invention can be carried out various change and
Modify.The present invention to test used in material and test method carry out generality and/or concrete description.Although for realizing the present invention
Many materials and operational approach that purpose is used are to it is known in the art that still the present invention still describes in detail as far as possible at this.Following reality
Execute example further illustrate the present invention rather than limit the present invention.
Hereafter preparation process is for the purpose illustrated, and comparability based on each citing and make some specific description, those skilled in the art
Can therefrom summarize completely according to existing knowledge and obtain the method that the present invention prepares medicament.Prepare in various compositions, as the most additionally said below
Bright, total dosage of every batch is 5kg.But when listing formula and preparation process, illustrate with the composition of every bag of hydrochloric lysine 125mg and join
Side and preparation method.When subpackage, every bag of granule dosage is calculated as the amount subpackage of 125mg with lysine hydrochloride.Prepare in various compositions below,
If not otherwise indicated, the lysine of use is lysine hydrochloride.
A, the embodiment part of preparation compositions
Embodiment 1: prepare lysine Zinc Gluconate Granules agent compositions
Formula:
Preparation method:
(1) make citric acid be dissolved in suitable quantity of water 90 times of citric acid weight (amount of water be), sequentially add zinc gluconate, lysine hydrochloride
And make it dissolve, obtain settled solution；
(2) again by appropriate amount of starch (accounting for the 50% of recipe quantity) the water furnishing pasty state of 2 times of weight, then mix homogeneously with step (1) gained solution, stir
Mix to open simultaneously and be heated to 70 DEG C, obtain solution I, standby；
(3) by the surplus starch water furnishing pasty state of 8 times of weight, stirring is opened simultaneously and is heated to 70 DEG C, obtains solution II, standby；
(4) mannitol of recipe quantity is put in fluidised bed granulator, mix 5min, open and be heated to 70 DEG C, spray into the molten I of liquid, then spray into
Solution II；
(5) making material be dried 45min in fluid bed at a temperature of 70 DEG C, the less loss weight measured to dry weightless mensuration is less than 1.5%,
Discharging is standby；
(6) granulate: by pellet through sieves, collect the granule between 20-40 mesh, pack, to obtain final product.
Embodiment 2: prepare lysine Zinc Gluconate Granules agent compositions
Formula:
Preparation method:
(1) make citric acid be dissolved in suitable quantity of water 80 times of citric acid weight (amount of water be), sequentially add zinc gluconate, lysine hydrochloride
And make it dissolve, obtain settled solution；
(2) again by appropriate amount of starch (accounting for the 60% of recipe quantity) the water furnishing pasty state of 2 times of weight, then mix homogeneously with step (1) gained solution, stir
Mix to open simultaneously and be heated to 65 DEG C, obtain solution I, standby；
(3) by the surplus starch water furnishing pasty state of 6 times of weight, stirring is opened simultaneously and is heated to 75 DEG C, obtains solution II, standby；
(4) mannitol of recipe quantity is put in fluidised bed granulator, mix 5min, open and be heated to 65 DEG C, spray into the molten I of liquid, then spray into
Solution II；
(5) making material be dried 60min in fluid bed at a temperature of 60 DEG C, the less loss weight measured to dry weightless mensuration is less than 1.5%,
Discharging is standby；
(6) granulate: by pellet through sieves, collect the granule between 20-40 mesh, pack, to obtain final product.
Embodiment 3: prepare lysine Zinc Gluconate Granules agent compositions
Formula:
Preparation method:
(1) make citric acid be dissolved in suitable quantity of water 110 times of citric acid weight (amount of water be), sequentially add zinc gluconate, hydrochloric acid relies ammonia
Acid also makes it dissolve, and obtains settled solution；
(2) again by appropriate amount of starch (accounting for the 40% of recipe quantity) the water furnishing pasty state of 2 times of weight, then mix homogeneously with step (1) gained solution, stir
Mix to open simultaneously and be heated to 75 DEG C, obtain solution I, standby；
(3) by the surplus starch water furnishing pasty state of 10 times of weight, stirring is opened simultaneously and is heated to 75 DEG C, obtains solution II, standby；
(4) mannitol of recipe quantity is put in fluidised bed granulator, mix 5min, open and be heated to 75 DEG C, spray into the molten I of liquid, then spray into
Solution II；
(5) making material be dried 30min in fluid bed at a temperature of 80 DEG C, the less loss weight measured to dry weightless mensuration is less than 1.5%,
Discharging is standby；
(6) granulate: by pellet through sieves, collect the granule between 15-50 mesh, pack, to obtain final product.
Embodiment 4: prepare lysine Zinc Gluconate Granules agent compositions
Formula:
Preparation method:
(1) make citric acid be dissolved in suitable quantity of water 120 times of citric acid weight (amount of water be), sequentially add zinc gluconate, hydrochloric acid relies ammonia
Acid also makes it dissolve, and obtains settled solution；
(2) again by appropriate amount of starch (accounting for the 45% of recipe quantity) the water furnishing pasty state of 2 times of weight, then mix homogeneously with step (1) gained solution, stir
Mix to open simultaneously and be heated to 60 DEG C, obtain solution I, standby；
(3) by the surplus starch water furnishing pasty state of 9 times of weight, stirring is opened simultaneously and is heated to 80 DEG C, obtains solution II, standby；
(4) mannitol of recipe quantity is put in fluidised bed granulator, mix 5min, open and be heated to 60 DEG C, spray into the molten I of liquid, then spray into
Solution II；
(5) making material be dried 40min in fluid bed at a temperature of 75 DEG C, the less loss weight measured to dry weightless mensuration is less than 1.5%,
Discharging is standby；
(6) granulate: by pellet through sieves, collect the granule between 20-40 mesh, pack, to obtain final product.
Embodiment 5: prepare lysine Zinc Gluconate Granules agent compositions
Formula:
Preparation method:
(1) make citric acid be dissolved in suitable quantity of water 70 times of citric acid weight (amount of water be), sequentially add zinc gluconate, lysine hydrochloride
And make it dissolve, obtain settled solution；
(2) again by appropriate amount of starch (accounting for the 55% of recipe quantity) the water furnishing pasty state of 2 times of weight, then mix homogeneously with step (1) gained solution, stir
Mix to open simultaneously and be heated to 80 DEG C, obtain solution I, standby；
(3) by the surplus starch water furnishing pasty state of 7 times of weight, stirring is opened simultaneously and is heated to 60 DEG C, obtains solution II, standby；
(4) mannitol of recipe quantity is put in fluidised bed granulator, mix 5min, open and be heated to 80 DEG C, spray into the molten I of liquid, then spray into
Solution II；
(5) making material be dried 50min in fluid bed at a temperature of 65 DEG C, the less loss weight measured to dry weightless mensuration is less than 1.5%,
Discharging is standby；
(6) granulate: by pellet through sieves, collect the granule between 15-50 mesh, pack, to obtain final product.
Embodiment 6: prepare lysine Zinc Gluconate Granules agent compositions
Formula:
Preparation method:
(1) make citric acid be dissolved in suitable quantity of water 90 times of citric acid weight (amount of water be), sequentially add zinc gluconate, lysine hydrochloride
And make it dissolve, obtain settled solution；
(2) again by appropriate amount of starch (accounting for the 50% of recipe quantity) the water furnishing pasty state of 2 times of weight, then mix homogeneously with step (1) gained solution, stir
Mix to open simultaneously and be heated to 70 DEG C, obtain solution I, standby；
(3) by the surplus starch water furnishing pasty state of 8 times of weight, stirring is opened simultaneously and is heated to 70 DEG C, obtains solution II, standby；
(4) mannitol of recipe quantity is put in fluidised bed granulator, mix 5min, open and be heated to 70 DEG C, spray into the molten I of liquid, then spray into
Solution II；
(5) making material be dried 45min in fluid bed at a temperature of 70 DEG C, the less loss weight measured to dry weightless mensuration is less than 1.5%,
Discharging is standby；
(6) granulate: by pellet through sieves, collect the granule between 20-40 mesh, pack, to obtain final product.
Embodiment 7: prepare lysine Zinc Gluconate Granules agent compositions
Formula:
Preparation method:
(1) make citric acid be dissolved in suitable quantity of water 90 times of citric acid weight (amount of water be), sequentially add zinc gluconate, lysine hydrochloride
And make it dissolve, obtain settled solution；
(2) again by appropriate amount of starch (accounting for the 50% of recipe quantity) the water furnishing pasty state of 2 times of weight, then mix homogeneously with step (1) gained solution, stir
Mix to open simultaneously and be heated to 70 DEG C, obtain solution I, standby；
(3) by the surplus starch water furnishing pasty state of 8 times of weight, stirring is opened simultaneously and is heated to 70 DEG C, obtains solution II, standby；
(4) mannitol of recipe quantity is put in fluidised bed granulator, mix 5min, open and be heated to 70 DEG C, spray into the molten I of liquid, then spray into
Solution II；
(5) making material be dried 45min in fluid bed at a temperature of 70 DEG C, the less loss weight measured to dry weightless mensuration is less than 1.5%,
Discharging is standby；
(6) granulate: by pellet through sieves, collect the granule between 20-40 mesh, pack, to obtain final product.
Embodiment 8: prepare lysine Zinc Gluconate Granules agent compositions
Formula:
Preparation method:
(1) make citric acid be dissolved in suitable quantity of water 90 times of citric acid weight (amount of water be), sequentially add zinc gluconate, lysine hydrochloride
And make it dissolve, obtain settled solution；
(2) again by appropriate amount of starch (accounting for the 50% of recipe quantity) the water furnishing pasty state of 2 times of weight, then mix homogeneously with step (1) gained solution, stir
Mix to open simultaneously and be heated to 70 DEG C, obtain solution I, standby；
(3) by the surplus starch water furnishing pasty state of 8 times of weight, stirring is opened simultaneously and is heated to 70 DEG C, obtains solution II, standby；
(4) mannitol of recipe quantity is put in fluidised bed granulator, mix 5min, open and be heated to 70 DEG C, spray into the molten I of liquid, then spray into
Solution II；
(5) making material be dried 45min in fluid bed at a temperature of 70 DEG C, the less loss weight measured to dry weightless mensuration is less than 1.5%,
Discharging is standby；
(6) granulate: by pellet through sieves, collect the granule between 20-40 mesh, pack, to obtain final product.
Embodiment 9: prepare lysine Zinc Gluconate Granules agent compositions
Formula:
Preparation method:
(1) make citric acid be dissolved in suitable quantity of water 90 times of citric acid weight (amount of water be), sequentially add zinc gluconate, lysine hydrochloride
And make it dissolve, obtain settled solution；
(2) again by appropriate amount of starch (accounting for the 50% of recipe quantity) the water furnishing pasty state of 2 times of weight, then mix homogeneously with step (1) gained solution, stir
Mix to open simultaneously and be heated to 70 DEG C, obtain solution I, standby；
(3) by the surplus starch water furnishing pasty state of 8 times of weight, stirring is opened simultaneously and is heated to 70 DEG C, obtains solution II, standby；
(4) mannitol of recipe quantity is put in fluidised bed granulator, mix 5min, open and be heated to 70 DEG C, spray into the molten I of liquid, then spray into
Solution II；
(5) making material be dried 45min in fluid bed at a temperature of 70 DEG C, the less loss weight measured to dry weightless mensuration is less than 1.5%,
Discharging is standby；
(6) granulate: by pellet through sieves, collect the granule between 20-40 mesh, pack, to obtain final product.
9 samples of above example 1-9 gained can be designated as Ex1, Ex2 ..., Ex9 respectively.
Embodiment 11: prepare lysine Zinc Gluconate Granules agent compositions
In the present embodiment 11, respectively referring to formula and the preparation method of embodiment 1-9, different is only that starch therein is replaced with polyvidone
K30, obtains 9 samples, and they are designated as Ex111, Ex112 ..., Ex119 respectively.
Embodiment 12: prepare lysine Zinc Gluconate Granules agent compositions
In the present embodiment 12, respectively referring to formula and the preparation method of embodiment 1-9, different is only that starch therein is replaced with hydroxypropyl first
Base cellulose (on a kind of pharmaceutics conventional solid preparation binding agent), obtains 9 samples, they are designated as respectively Ex121, Ex122 ...,
Ex129。
Embodiment 13: prepare lysine Zinc Gluconate Granules agent compositions
In the present embodiment 13, respectively referring to formula and the preparation method of embodiment 1-9, different is only to be got rid of by starch therein, uses step
(1) gained settled solution is as solution I, and the solution II of step (3) is water, obtains 9 samples, they are designated as respectively Ex131, Ex132 ...,
Ex139。
Embodiment 14: prepare lysine Zinc Gluconate Granules agent compositions
In the present embodiment 14, respectively referring to formula and the preparation method of embodiment 1-9, different is only that mannitol therein is replaced with sucrose,
Obtain 9 samples, they are designated as respectively Ex141, Ex142 ..., Ex149.
Embodiment 15: prepare lysine Zinc Gluconate Granules agent compositions
In the present embodiment 15, respectively referring to formula and the preparation method of embodiment 1-9, different is only that mannitol therein is replaced with sorbitol,
Obtain 9 samples, they are designated as respectively Ex151, Ex152 ..., Ex159.
Embodiment 16: prepare lysine Zinc Gluconate Granules agent compositions
In the present embodiment 16, respectively referring to formula and the preparation method of embodiment 1-9, different is only that mannitol therein is replaced with lactose,
Obtain 9 samples, they are designated as respectively Ex161, Ex162 ..., Ex169.
Embodiment 17: prepare lysine Zinc Gluconate Granules agent compositions
In the present embodiment 17, respectively refer to the formula of embodiment 1-9, but preparation method change in the following manner into:
After all supplementary materials are pulverized respectively, cross 60 mesh sieves, join 18% starch fluid；The powder employing equivalent of solid is progressively increased after method mix homogeneously,
With starch fluid for binding agent soft material；16 mesh sieves are pelletized, and in 55-65 DEG C of oven drying, 16 mesh sieve granulate, obtain 9 samples, by them
It is designated as Ex171, Ex172 ..., Ex179 respectively.
Embodiment 18: prepare four kinds of lysine Zinc Gluconate Granules agent compositionss
Ex181: formula includes lysine hydrochloride 125 grams, zinc gluconate 35 grams, 791 grams of mannitol, steviosin 10 grams, citric acid
12.5 grams, 18% PVP K30 23.5 grams, Hami melon essence 5.0 grams；After all supplementary materials are pulverized respectively, cross 60 mesh sieves, join 18% and gather
Dimension ketone K30 aqueous solution；The powder employing equivalent of solid is progressively increased after method mix homogeneously, with PVP K30 aqueous solution for binding agent soft material；16
Mesh sieve is pelletized, and in 55-65 DEG C of oven drying, 16 mesh sieve granulate, is proportionally added into essence, mixing, seals subpackage, to obtain final product.
Ex182: formula includes lysine hydrochloride 130g, zinc gluconate 37g, mannitol 787.5g, Aspartane 5g, citric acid 10g,
PVP K30 20g, orange flavor 5g, after all supplementary materials are pulverized respectively, cross 65 mesh sieves, join 18% PVP K30 aqueous solution；Gu
The powder employing equivalent of body is progressively increased after method mix homogeneously, with PVP K30 aqueous solution for binding agent soft material；16 mesh sieves are pelletized, in 60 DEG C
Oven drying, 16 mesh sieve granulate, it is proportionally added into essence, mixing, seal subpackage, to obtain final product.
Ex183: formula includes lysine hydrochloride 100g, zinc gluconate 30g, lactose 788g, steviosin 12g, tartaric acid 50g, poly-dimension
Ketone K3015g, strawberry essence 10g, after all supplementary materials are pulverized respectively, cross 65 mesh sieves, join 18% PVP K30 aqueous solution；Solid
Powder employing equivalent is progressively increased after method mix homogeneously, with PVP K30 aqueous solution for binding agent soft material；16 mesh sieves are pelletized, in 60 DEG C of baking ovens
It is dried, 16 mesh sieve granulate, is proportionally added into essence, mixing, seal subpackage, to obtain final product.
Ex184: formula includes lysine hydrochloride 150g, zinc gluconate 40g, sorbitol 755g, sucralose 20g, fumaric acid 10g,
PVP K30 15g, cherry essence 8g, after all supplementary materials are pulverized respectively, cross 65 mesh sieves, join 18% PVP K30 aqueous solution；Gu
The powder employing equivalent of body is progressively increased after method mix homogeneously, with PVP K30 aqueous solution for binding agent soft material；16 mesh sieves are pelletized, in 60 DEG C
Oven drying, 16 mesh sieve granulate, it is proportionally added into essence, mixing, seal subpackage, to obtain final product.
Whole samples prepared by above example 1-9, embodiment 11-18, in final drying process, all make dry materials to being dried
The less loss weight that weightless algoscopy the measures degree less than 1.5%, and with aluminum-plastic composite membrane bag subpackage, every bag of content is calculated as with lysine hydrochloride
125mg.More such samples carry out investigation test hereafter.
Whole samples prepared by above example 1-9, according to the double sieve method inspection of Chinese Pharmacopoeia two annex Ⅸ E the second methods of version in 2010, no
Can be sieved by No. one and the summation of No. five sieves can be passed through all less than for the 7% of examination amount.Whole samples prepared by above example 1-9, in shining
State's pharmacopeia two annex VIII L dry weightless mensurations of version in 2010 measure, and are dried to constant weight at 105 DEG C, and less loss weight is respectively less than 1.5%,
With being on close level of technology controlling and process.
B, test example part
Test example 1: medicine hygroscopicity is investigated
By the whole samples prepared by above example 1-9, embodiment 11-18, cut a mouth to packaging bag, make they temperature 25 ± 1 DEG C,
Place 24 hours under conditions of relative humidity 75%, weigh the composition weight (W0) before this disposes and the composition weight (W1) herein postponed,
The weightening finish of the two difference moisture by being absorbed, is calculated as follows moisture absorption weightening finish percent (%):
Moisture absorption weightening finish percent (%)=[(W1-W0) ÷ W0] × 100%
Result: whole granule samples prepared by embodiment 11, embodiment 12,13 3 embodiments of embodiment, their moisture absorption weightening finish hundred
Mark is all in the range of 13～19%, and the moisture absorption weightening finish percent of such as Ex112 granule is 15.3%；Embodiment 14, embodiment 15, reality
Execute whole granule samples prepared by 16 3 embodiments of example, they moisture absorption weightening finish percent all in the range of 11～18%, such as Ex153
The moisture absorption weightening finish percent of granule is 13.6%；Whole granule samples prepared by embodiment 17,18 2 embodiments of embodiment, they
Moisture absorption weightening finish percent all in the range of 14～23%, the moisture absorption of such as Ex172 granule weightening finish percent is 18.2%；Embodiment 1 to
Whole granule samples prepared by 9 nine embodiments of embodiment, their moisture absorption weightening finish percent is respectively less than 3%, all 1.83～2.92% model
In enclosing, the moisture absorption weightening finish percent of such as Ex1 granule is 2.32%.Typically, as a kind of granule, under above-mentioned Disposal Conditions
Moisture absorption weightening finish percent be very gratifying less than 5%, and be commonly referred to be when this parameter is more than 5% particularly greater than 10% and be difficult to
Accept.
Test example 2: agent dissolving property is investigated
" A, the embodiment part of preparation compositions " preparation-obtained whole batch granules carry out melting investigation above.
Melting investigates method: the granule sample 10g taking batch to be measured puts in beaker, and add water 200ml, stirs 1 minute, observes granule
Dissolve situation.Typically, as the dosage form of granule, measuring and observe under the conditions of a little, result generally to meet claimed below: can
Molten granule should all dissolve or slight haze, but must not have foreign body.
Result shows, " A, the embodiment part of preparation compositions " preparation-obtained whole batch granules are carrying out melting investigation above
In test, all displays: soluble particles is all dissolved, and individual sample has slight haze, equal foreign or particulate matter.This result is also ability
The melting required standard to granule that territory is generally acknowledged；If there is having undissolved particulate matter or foreign body, then be commonly referred to be defective or
Person is difficult to accept.
Then the granule sample making these whole batches is put 42 DEG C in sealed states and is placed 5 months and (can be described as high temperature May in the present invention
Dispose), method of pressing again after 5 months tests the melting of each granule sample.Various granule samples postpone melting knot at high temperature May
Fruit is as follows: whole their meltings of granule sample prepared by embodiment 11, embodiment 12,13 3 embodiments of embodiment all show
Significantly undissolved particles thing；They dissolve of whole granule samples prepared by embodiment 14, embodiment 15,16 3 embodiments of embodiment
Property all shows obvious undissolved particles thing；They dissolve of whole granule samples prepared by embodiment 17,18 2 embodiments of embodiment
Property all shows obvious undissolved particles thing；Whole their meltings of granule sample prepared by 9 nine embodiments of embodiment 1 to embodiment
All show that granule all dissolves, have the slightest muddiness, and be showed no foreign body or undissolved particles thing.
Industrial applicability
The invention belongs to pharmaceutical technology field, relate to a kind of supplementary lysine and the compositions of zinc particularly zinc gluconate, particularly relate to one
Kind for supplementing lysine and the granule of zinc particularly zinc gluconate, it is used for supplementing lysine and zinc particularly more particularly to one
The sugar-free granule of zinc gluconate.The invention still further relates to a kind of method preparing described compositions.The Lysinepuzinc granule that the present invention provides
For minerals nonprescription drugs medicine.Clinically for prevent and treat children's and teenager for want of lysine and zinc and cause growth retardation,
Malnutrition and anorexia etc..Lysine contained by Lysinepuzinc granule is one of necessary aminoacid maintaining human body nitrogen balance, has promotion people
The effect of bulk-growth；Zinc is the important composition composition of internal multiple enzyme, has enhancing development, improves the effect of the sense of taste.
Claims (49)
1. a compositions, it is Sugarless type Lysinepuzinc granule, and comprising: lysine hydrochloride 125 weight portion, Fructus Vitis viniferae
Saccharic acid zinc 30 ~ 40 weight portion, citric acid 10 ~ 15 weight portion, mannitol 2000 ~ 3500 weight portion, starch 50 ~ 200 weight portion；
Said composition is prepared by a method comprising the following steps and obtains:
(1) make citric acid be dissolved in suitable quantity of water, sequentially add zinc gluconate, lysine hydrochloride and make it dissolve, obtaining
Settled solution；
(2) the water furnishing pasty state of 2 times of weight of 40 ~ 60% starch of recipe quantity will be accounted for again, then mix with step (1) gained solution
Uniformly, stirring is opened simultaneously and is heated to 60 DEG C～80 DEG C, obtains solution I, standby；
(3) by the surplus starch water furnishing pasty state of 6 ~ 10 times of weight, stirring is opened simultaneously and is heated to 60 DEG C～80 DEG C,
Solution II, standby；
(4) mannitol of recipe quantity is put in fluidised bed granulator, mix 5min, open and be heated to 60 DEG C～80 DEG C, spray into
Solution I, then sprays into solution II；
(5) material is made to be dried 30 ~ 60min in fluid bed at a temperature of 60 DEG C～80 DEG C, to dry weightless mensuration mensuration
Less loss weight is less than 1.5%, and discharging is standby；
(6) granulate: by pellet through sieves, collect the granule between 15-50 mesh, pack, to obtain final product.
Compositions the most according to claim 1, in terms of the lysine hydrochloride of every 125 weight portions, wherein the amount of zinc gluconate is
32 ~ 38 weight portions.
Compositions the most according to claim 1, in terms of the lysine hydrochloride of every 125 weight portions, wherein the amount of zinc gluconate is
34 ~ 36 weight portions.
Compositions the most according to claim 1, in terms of the lysine hydrochloride of every 125 weight portions, wherein the amount of zinc gluconate is
35 weight portions.
Compositions the most according to claim 1, in terms of the lysine hydrochloride of every 125 weight portions, wherein the amount of citric acid is 11 ~ 14
Weight portion.
Compositions the most according to claim 1, in terms of the lysine hydrochloride of every 125 weight portions, wherein the amount of citric acid is 12 ~ 13
Weight portion.
Compositions the most according to claim 1, in terms of the lysine hydrochloride of every 125 weight portions, wherein the amount of citric acid is 12.5
Weight portion.
Compositions the most according to claim 1, in terms of the lysine hydrochloride of every 125 weight portions, wherein the amount of mannitol be 2500 ~
3000 weight portions.
Compositions the most according to claim 1, in terms of the lysine hydrochloride of every 125 weight portions, wherein the amount of mannitol be 2600 ~
2800 weight portions.
Compositions the most according to claim 1, in terms of the lysine hydrochloride of every 125 weight portions, wherein the amount of mannitol is 2650
~ 2750 weight portions.
11. compositionss according to claim 1, in terms of the lysine hydrochloride of every 125 weight portions, wherein the amount of starch is 75 ~ 175
Weight portion.
12. compositionss according to claim 1, in terms of the lysine hydrochloride of every 125 weight portions, wherein the amount of starch be 100 ~
150 weight portions.
13. compositionss according to claim 1, it is placed 24 hours under conditions of 25 ± 1 ° of C of temperature, relative humidity 75%, inhales
Wet weightening finish percent is less than 10%.
14. compositionss according to claim 1, it is placed 24 hours under conditions of 25 ± 1 ° of C of temperature, relative humidity 75%, inhales
Wet weightening finish percent is less than 5%.
15. compositionss according to claim 1, it is placed 24 hours under conditions of 25 ± 1 ° of C of temperature, relative humidity 75%, inhales
Wet weightening finish percent is less than 4%.
16. compositionss according to claim 1, it is placed 24 hours under conditions of 25 ± 1 ° of C of temperature, relative humidity 75%, inhales
Wet weightening finish percent is less than 3%.
17. compositionss according to claim 1, it is according to the double sieve method inspection of Chinese Pharmacopoeia two annex Ⅸ E the second methods of version in 2010
Look into, it is impossible to be less than 15% for examination amount by a sieve and the summations that No. five sieves can be passed through.
18. compositionss according to claim 1, it is according to the double sieve method inspection of Chinese Pharmacopoeia two annex Ⅸ E the second methods of version in 2010
Look into, it is impossible to be less than 10% for examination amount by a sieve and the summations that No. five sieves can be passed through.
19. compositionss according to claim 1, it is surveyed according to Chinese Pharmacopoeia two annex VIII L dry weightless mensurations of version in 2010
Fixed, it is dried to constant weight at 105 DEG C, less loss weight is less than 5%.
20. compositionss according to claim 1, it is surveyed according to Chinese Pharmacopoeia two annex VIII L dry weightless mensurations of version in 2010
Fixed, it is dried to constant weight at 105 DEG C, less loss weight is less than 4%.
21. compositionss according to claim 1, it is surveyed according to Chinese Pharmacopoeia two annex VIII L dry weightless mensurations of version in 2010
Fixed, it is dried to constant weight at 105 DEG C, less loss weight is less than 3%.
22. compositionss according to claim 1, it is surveyed according to Chinese Pharmacopoeia two annex VIII L dry weightless mensurations of version in 2010
Fixed, it is dried to constant weight at 105 DEG C, less loss weight is less than 2%.
23. compositionss according to claim 1, wherein in step (1), make citric acid be dissolved in 70 ~ 120 times of citric acid weight
Water in.
24. compositionss according to claim 1, wherein in step (1), make citric acid be dissolved in 80 ~ 110 times of citric acid weight
Water in.
25. compositionss according to claim 1, wherein in step (2), by account for recipe quantity 50% the water of 2 times of weight of starch
Furnishing pasty state.
26. compositionss according to claim 1, wherein in step (3), by the surplus starch water furnishing pasty state of 8 times of weight.
The method of 27. compositionss preparing Sugarless type Lysinepuzinc granule, described compositions includes: lysine hydrochloride 125 weight
Amount part, zinc gluconate 30 ~ 40 weight portion, citric acid 10 ~ 15 weight portion, mannitol 2000 ~ 3500 weight portion, starch 50 ~ 200
Weight portion；The method is to carry out by the way of the wet granulation comprised the steps:
(1) make citric acid be dissolved in suitable quantity of water, sequentially add zinc gluconate, lysine hydrochloride and make it dissolve, obtaining
Settled solution；
(2) again by account for recipe quantity 40 ~ 60% the water furnishing pasty state of 2 times of weight of starch, then mix with step (1) gained solution
Closing uniformly, stirring is opened simultaneously and is heated to 60 DEG C～80 DEG C, obtains solution I, standby；
(3) by the surplus starch water furnishing pasty state of 6 ~ 10 times of weight, stirring is opened simultaneously and is heated to 60 DEG C～80 DEG C,
Solution II, standby；
(4) mannitol of recipe quantity is put in fluidised bed granulator, mix 5min, open and be heated to 60 DEG C～80 DEG C, spray into
Solution I, then sprays into solution II；
(5) material is made to be dried 30 ~ 60min in fluid bed at a temperature of 60 DEG C～80 DEG C, to dry weightless mensuration mensuration
Less loss weight is less than 1.5%, and discharging is standby；
(6) granulate: by pellet through sieves, collect the granule between 15-50 mesh, pack, to obtain final product.
28. methods according to claim 27, wherein in step (1), make citric acid be dissolved in 70 ~ 120 times of citric acid weight
Water in.
29. methods according to claim 27, wherein in step (1), make citric acid be dissolved in 80 ~ 110 times of citric acid weight
Water in.
30. methods according to claim 27, wherein in step (2), by account for recipe quantity 50% the water of 2 times of weight of starch
Furnishing pasty state.
31. methods according to claim 27, wherein in step (3), by the surplus starch water furnishing pasty state of 8 times of weight.
32. lysine hydrochlorides and zinc gluconate are used for preventing and treating children's and teenager in preparation and cause due to lysine and zinc deficiency
Growth retardation, malnutrition, inappetence etc. agent of low hygroscopicity compositions in purposes, wherein said compositions is
Sugarless type Lysinepuzinc granule, and said composition includes: lysine hydrochloride 125 weight portion, zinc gluconate 30 ~ 40 weight
Part, citric acid 10 ~ 15 weight portion, mannitol 2000 ~ 3500 weight portion, starch 50 ~ 200 weight portion；Said composition is by bag
The mode of the wet granulation including following steps prepares:
(1) make citric acid be dissolved in suitable quantity of water, sequentially add zinc gluconate, lysine hydrochloride and make it dissolve, obtaining
Settled solution；
(2) again by account for recipe quantity 40 ~ 60% the water furnishing pasty state of 2 times of weight of starch, then mix with step (1) gained solution
Closing uniformly, stirring is opened simultaneously and is heated to 60 DEG C～80 DEG C, obtains solution I, standby；
(3) by the surplus starch water furnishing pasty state of 6 ~ 10 times of weight, stirring is opened simultaneously and is heated to 60 DEG C～80 DEG C,
Solution II, standby；
(4) mannitol of recipe quantity is put in fluidised bed granulator, mix 5min, open and be heated to 60 DEG C～80 DEG C, spray into
Solution I, then sprays into solution II；
(5) material is made to be dried 30 ~ 60min in fluid bed at a temperature of 60 DEG C～80 DEG C, to dry weightless mensuration mensuration
Less loss weight is less than 1.5%, and discharging is standby；
(6) granulate: by pellet through sieves, collect the granule between 15-50 mesh, pack, to obtain final product.
33. according to the purposes of claim 32, wherein in step (1), makes citric acid be dissolved in 70 ~ 120 times of citric acid weight
Water in.
34. according to the purposes of claim 32, wherein in step (1), makes citric acid be dissolved in 80 ~ 110 times of citric acid weight
Water in.
35. according to the purposes of claim 32, wherein in step (2), by account for recipe quantity 50% the water of 2 times of weight of starch
Furnishing pasty state.
36. according to the purposes of claim 32, wherein in step (3), by the surplus starch water furnishing pasty state of 8 times of weight.
37. starch purposes in preparing agent of low hygroscopicity compositions；Described compositions is Sugarless type Lysinepuzinc granule, and
Said composition includes: lysine hydrochloride 125 weight portion, zinc gluconate 30 ~ 40 weight portion, citric acid 10 ~ 15 weight portion, manna
Alcohol 2000 ~ 3500 weight portion, starch 50 ~ 200 weight portion；
Described compositions is to prepare by the way of the wet granulation comprised the steps:
(1) make citric acid be dissolved in suitable quantity of water, sequentially add zinc gluconate, lysine hydrochloride and make it dissolve, obtaining
Settled solution；
(2) again by account for recipe quantity 40 ~ 60% the water furnishing pasty state of 2 times of weight of starch, then mix with step (1) gained solution
Closing uniformly, stirring is opened simultaneously and is heated to 60 DEG C～80 DEG C, obtains solution I, standby；
(3) by the surplus starch water furnishing pasty state of 6 ~ 10 times of weight, stirring is opened simultaneously and is heated to 60 DEG C～80 DEG C,
Solution II, standby；
(4) mannitol of recipe quantity is put in fluidised bed granulator, mix 5min, open and be heated to 60 DEG C～80 DEG C, spray into
Solution I, then sprays into solution II；
(5) material is made to be dried 30 ~ 60min in fluid bed at a temperature of 60 DEG C～80 DEG C, to dry weightless mensuration mensuration
Less loss weight is less than 1.5%, and discharging is standby；
(6) granulate: by pellet through sieves, collect the granule between 15-50 mesh, pack, to obtain final product.
38. according to the purposes of claim 37, wherein in step (1), makes citric acid be dissolved in 70 ~ 120 times of citric acid weight
Water in.
39. according to the purposes of claim 37, wherein in step (1), makes citric acid be dissolved in 80 ~ 110 times of citric acid weight
Water in.
40. according to the purposes of claim 37, wherein in step (2), by account for recipe quantity 50% the water of 2 times of weight of starch
Furnishing pasty state.
41. according to the purposes of claim 37, wherein in step (3), by the surplus starch water furnishing pasty state of 8 times of weight.
42. according to the purposes of claim 37, and the agent of low hygroscopicity of described compositions refers to, it is at temperature 25 ± 1 ° of C, relative humiditys
Placing 24 hours under conditions of 75%, moisture absorption weightening finish percent is less than 10%.
43. according to the purposes of claim 37, and the agent of low hygroscopicity of described compositions refers to, it is at temperature 25 ± 1 ° of C, relative humiditys
Placing 24 hours under conditions of 75%, moisture absorption weightening finish percent is less than 5%.
44. according to the purposes of claim 37, and the agent of low hygroscopicity of described compositions refers to, it is at temperature 25 ± 1 ° of C, relative humiditys
Placing 24 hours under conditions of 75%, moisture absorption weightening finish percent is less than 4%.
45. according to the purposes of claim 37, and the agent of low hygroscopicity of described compositions refers to, it is at temperature 25 ± 1 ° of C, relative humiditys
Placing 24 hours under conditions of 75%, moisture absorption weightening finish percent is less than 3%.
46. according to the purposes of claim 37, and described compositions is according to Chinese Pharmacopoeia two annex VIII L losss on drying of version in 2010
Algoscopy measures, and is dried to constant weight at 105 DEG C, and less loss weight is less than 5%.
47. according to the purposes of claim 37, and described compositions is according to Chinese Pharmacopoeia two annex VIII L losss on drying of version in 2010
Algoscopy measures, and is dried to constant weight at 105 DEG C, and less loss weight is less than 4%.
48. according to the purposes of claim 37, and described compositions is according to Chinese Pharmacopoeia two annex VIII L losss on drying of version in 2010
Algoscopy measures, and is dried to constant weight at 105 DEG C, and less loss weight is less than 3%.
49. according to the purposes of claim 37, and described compositions is according to Chinese Pharmacopoeia two annex VIII L losss on drying of version in 2010
Algoscopy measures, and is dried to constant weight at 105 DEG C, and less loss weight is less than 2%.
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| CN104857002B (en) * | 2015-05-05 | 2019-07-12 | 江西兼济堂农业开发有限公司 | The medical composition and its use of lysine vitamin comprising chiral photo-isomerisation compound |
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