CN109288859A - A kind of haemodialysis solid pharmaceutical preparation and preparation method thereof - Google Patents

A kind of haemodialysis solid pharmaceutical preparation and preparation method thereof Download PDF

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Publication number
CN109288859A
CN109288859A CN201811367193.9A CN201811367193A CN109288859A CN 109288859 A CN109288859 A CN 109288859A CN 201811367193 A CN201811367193 A CN 201811367193A CN 109288859 A CN109288859 A CN 109288859A
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chloride
preparation
solid pharmaceutical
haemodialysis
sodium
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孟宪伯
周森林
佟凯
佟博弘
朱广渊
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Qinhuangdao Maisong Medical Equipment Co Ltd
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Qinhuangdao Maisong Medical Equipment Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock

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  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Inorganic Chemistry (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

The present invention provides a kind of haemodialysis solid pharmaceutical preparations, it is made of sodium chloride, potassium chloride, calcium chloride, magnesium chloride and pH adjusting agent, wherein, the solid pharmaceutical preparation is granule, and potassium chloride, calcium chloride, magnesium chloride and pH adjusting agent are adhered to the surface of the sodium chloride jointly.The present invention also provides the preparation methods of the haemodialysis solid pharmaceutical preparation.The ingredients such as potassium chloride, calcium chloride are adhered to sodium chloride surface and form solid particle preparation by solid pharmaceutical preparation provided by the invention, the uniformity may be up to 99% or more, effectively reduce the fine powder ratio in formulation products, the storage time of product is obviously prolonged, compared with similar product in the market, quality and performance are greatly improved；For preparation method of the invention without using complicated production equipment, simple process, mild condition, preparation cost is not high, can be suitable for mass production.

Description

A kind of haemodialysis solid pharmaceutical preparation and preparation method thereof
Technical field
The present invention relates to medical material or formulation arts, and in particular to a kind of haemodialysis solid pharmaceutical preparation and its preparation side Method.
Background technique
Haemodialysis removes harmful substance and excess moisture in blood using disperse, ultrafiltration and convective principles, is most often One of renal replacement therapies method is primarily adapted for use in end-stage renal disease, acute kidney injury, medicine or poisonous substance and is poisoned, is tight Heavy water, electrolyte and disturbance of acid-base balance etc..
Haemodialysis preparation can be divided into acid concentrate (A concentrate) and bicarbonate concentrate (B concentrate).Its In, A concentrate is the acidic mixture containing salt, and when use is configured to dialyse by designated ratio water for dialysis and B concentrate Liquid is treated for clinical dialysis.
A concentrate is usually to be made of sodium chloride, potassium chloride, calcium chloride, magnesium chloride and pH adjusting agent.Currently on the market Product after each group lease making batch weighing, will usually be placed in two dimension or three-dimensional mixing arrangement and mix, and according to doses In (1 person-portion or more person-portions) packing to plastics package.Since the ratio of each component differs greatly, (wherein, weight sodium chloride accounts for about A The 90% of concentrate), grain diameter and bulk density also have larger difference, cause product mix efficiency and mixture homogeneity lower (uniformity only can control 95% or so).In addition, the calcium chloride, magnesium chloride in A concentrate are the compound containing the crystallization water, It easily absorbs the hydrone in air under conventional humid control working condition and deliquesces, increased after material moisture absorption by The probability of pollution and the uncertainty of content, after being dispensed into plastics package, storage a period of time will go out the material after moisture absorption Now different degrees of hardened, agglomeration etc. had both been unfavorable for technique realization, and had also been unfavorable for clinical application.Due to grain graininess in product Abnormal distribution dispersion, and containing a large amount of superfine powder (100 mesh particle accountings of the granularity less than 0.15mm are up to 10%), cause It is also easy to produce a large amount of dust when preparation is put into dissolver, increases pollution risk.
Moreover, because being formed, the raw material sources of A concentrate, batch are different, or by personnel in production process, equipment It influences, wherein may include the pollutant components such as cilium, block, particulate matter, bacterium, aforementioned hybrid technique can not be effective Remove pollutant component, can only rely on material quality situation or technology controlling and process, the A concentrate of thus obtained dry powder often with There is higher level of pollution, easily causes dialysis patient infection, fever, haemolysis, dialysis pipeline blockage etc. bad anti-after dissolving use Should and complication, be highly detrimental to clinical application.
Summary of the invention
To overcome, the uniformity is low, fine powder content is high, product is easy existing for existing haemodialysis solid pharmaceutical preparation (A concentrate) Hardened or agglomeration, pollutant component contain a series of defects such as more, improve the quality of formulation products, an object of the present invention is A kind of haemodialysis solid pharmaceutical preparation is provided.
It is a further object of the present invention to provide the preparation methods of the haemodialysis solid pharmaceutical preparation.
Haemodialysis solid pharmaceutical preparation provided by the invention is by sodium chloride, potassium chloride, calcium chloride, magnesium chloride and pH adjusting agent Composition, wherein the solid pharmaceutical preparation is granule, and the potassium chloride, calcium chloride, magnesium chloride and pH adjusting agent are adhered to institute jointly State the surface of sodium chloride.
In haemodialysis solid pharmaceutical preparation provided by the invention, the sodium chloride, potassium chloride, calcium chloride, magnesium chloride, pH tune The dosage for saving agent can be the amount ranges of existing haemodialysis preparation.Further, the sodium chloride, potassium chloride, chlorination Calcium, magnesium chloride, pH adjusting agent weight ratio can be 100 ﹕, 1~4 ﹕, 2~5 ﹕, 1~3 ﹕ 1~10.Preferably, the sodium chloride, chlorine Change potassium, calcium chloride, magnesium chloride, pH adjusting agent weight ratio can be 100 ﹕, 2~3 ﹕, 3~4 ﹕, 1.5~2.5 ﹕ 3~6.
In haemodialysis solid pharmaceutical preparation provided by the invention, haemodialysis formulation art institute is can be selected in the pH adjusting agent There is the pH adjusting agent of frequent species, including common solid acid, liquid acids or their salt, specific example includes but is not limited to Citric acid, sodium citrate, L MALIC ACID, L MALIC ACID sodium, D-malic acid, D-malic acid sodium, DL-malic acid, DL-malic acid Sodium, sodium diacetate, lactic acid, sodium lactate etc..In haemodialysis solid pharmaceutical preparation of the invention, it is preferable to use solid peracid or its Salt more preferably uses citric acid as pH adjusting agent.
In haemodialysis solid pharmaceutical preparation provided by the invention, fine powder accounting of the granularity less than 0.15mm is 3% or less；Into One step, fine powder accounting is 2% or less.
In haemodialysis solid pharmaceutical preparation provided by the invention, after the solid pharmaceutical preparation is configured to blood dialysis solution, The uniformity is 99% or more.
In haemodialysis solid pharmaceutical preparation provided by the invention, after the solid pharmaceutical preparation is configured to blood dialysis solution, The particle of partial size >=10 μm may be controlled to 5 every milliliter hereinafter, the particle of partial size >=25 μm may be controlled to 0.5 every milliliter Hereinafter, bacterial endotoxin may be controlled to every milliliter of 0.25EU or less.Further, that the solid pharmaceutical preparation is configured to blood is saturating After analysing liquid, the particle of partial size >=10 μm may be controlled to 4 every milliliter hereinafter, the particle of partial size >=25 μm may be controlled to often Milliliter 0.3 is hereinafter, bacterial endotoxin may be controlled to every milliliter of 0.22EU or less.
The preparation method of haemodialysis solid pharmaceutical preparation provided by the invention the following steps are included:
S1: potassium chloride, calcium chloride, magnesium chloride and pH adjusting agent are dissolved to form solution with water；
S2: the step S1 solution formed is sprayed onto sodium chloride surface and carries out wet granulation；And
S3: by particle drying made from step S2 up to the haemodialysis solid pharmaceutical preparation.
In preparation method provided by the invention, the step S1 further include: the solution of formation, which is passed sequentially through aperture, is The two-stage filter that 0.45~1 μm of first level filtering device and aperture are 0.1~0.22 μm.
Present inventor have discovered that pollutant component common in A concentrate is mostly from the electrolyte components for dissolution, especially The materials such as calcium chloride, magnesium chloride, preparation method of the invention dissolves these components to form solution after, can respectively to pollution at Divide and be filtered removal, thus can further promote the quality and safety of formulation products.Moreover, subsequent granulation, back tender Skill will not introduce new pollutant component.
Wherein, first level filtering device can retain fiber of corresponding size, cilium, solid particulate matter etc., so as to reduce meat The level of pollution of the visible cilium of eye, block and particulate matter.First level filtering device can be a filter, filter material material Polypropylene (PP), polyether sulfone (PES) etc. may be selected in matter, and aperture may be selected 0.45 μm, 0.65 μm, 1 μm etc..Wherein, filter material is preferred Polypropylene material, aperture are preferably 0.45 μm.
Two-stage filter is used for aseptic filtration, active microorganism and metabolite can be retained, so as to reduce bacterium Contaminated with endotoxins is horizontal.Two-stage filter can be a sterilizing filter, and polyether sulfone (PES), hydrophilic may be selected in filter material material Polytetrafluoroethylene (PTFE) (PTFE) etc., aperture may be selected 0.1 μm, 0.22 μm etc..Wherein, filter material is preferred hydrophilic polytetrafluoroethylmicroporous (PTFE) Material, aperture are preferably 0.22 μm.
In preparation method provided by the invention, the weight ratio of the dosage of the water in the step S1 and the sodium chloride can be with For 9~14 ﹕ 100, the dosage of the water in step S1 and the sprinkling pelleting of subsequent technique are closely related, moreover, the dosage of water also shadow Manufacturing cost, energy consumption size are rung, the water consumption that the present invention selects can reduce water while guaranteeing sprinkling pelleting quality and technique Dosage, with reduce cost, reduce energy consumption.Further, the dosage of water and weight sodium chloride ratio can be 9.5~11 ﹕ 100.
In preparation method provided by the invention, the spray pressure of solution can be 0.03~0.2MPa in the step S2, When spray pressure is too small, Granulation time extends, and gained particle is cut repeatedly, easily causes the increase of fine powder content, so as to cause Fine powder content is excessively high in final products, and when spray pressure is excessive, the electrolyte ingredient of dissolution cannot connect with whole sodium chloride Touching, sodium chloride granulation is insufficient, and the ingredient uniformity of dissolution is easily caused to decline.Further, the spray pressure of solution can be 0.05~0.1MPa.
In preparation method provided by the invention, pelletized in the step S2 using wet granulator, the wet process system The stirring blade revolving speed of grain machine can be 80~250rpm, when stirring blade revolving speed is too small, sodium chloride can not be made sufficiently to roll, solution In electrolyte ingredient cannot be with sodium chloride uniformly, fully contact, under the uniformity for easily causing the electrolyte ingredient in solution Drop, and when stirring blade revolving speed is excessive, material heating is too fast, excessively high, and the electrolyte ingredient of dissolution is easily done during spray It is dry, lead to not pelletize.Further, the stirring blade revolving speed of the wet granulator can be 100~200rpm.
In preparation method provided by the invention, the cutter revolving speed of the wet granulator can be 800~2000rpm, When cutting speed is too small, sodium chloride is easily united blocking, influences to pelletize, and when cutting speed is excessive, gained particle is cut repeatedly, Fine powder content is easily caused to rise.Further, the cutter revolving speed of wet granulator can be 1000~1500rpm.
In preparation method provided by the invention, time for pelletizing in the step S2 can be 15~40min, granulation when Between, the easily performances such as the uniformity, fine powder content of influence products obtained therefrom associated with spray above-mentioned, granulating process, moreover, too long Granulation time also will cause the rising of manufacturing cost.Further, the time of granulation can be 20~30min.
In preparation method provided by the invention, in the step S3, to dry particle inlet air temperature can for 50~ 100 DEG C, when inlet air temperature is too low, particle drying is insufficient, and particle water content is big, easily unites blocking, influences the uniformity, and enters the wind When the temperature is excessively high, magnesium chloride, calcium chloride, which easily decompose, becomes non-active ingredients, influences the quality of the pharmaceutical preparations and safety in utilization.Further Ground, inlet air temperature can be 75~90 DEG C.
The ingredients such as potassium chloride, calcium chloride are adhered to by haemodialysis provided by the invention with solid pharmaceutical preparation and preparation method thereof The most sodium chloride surface of accounting weight forms solid particle preparation, has the advantage that
(1) present invention, which sufficiently dissolves the ingredients such as potassium chloride, calcium chloride, magnesium chloride, forms solution, and each component may make to fill Divide ground mutually dispersion, and pass through on spray adhesion to sodium chloride particle, so as to keep final formulation products acquisition higher Evenness, up to 99% or more.
(2) present invention can be such that the fine particles such as calcium chloride, magnesium chloride mutually bond, and effectively reduce gained formulation products In fine powder proportion, can be reduced to 3% hereinafter, thus substantially reduced dust pollution situation when using.
(3) present invention will be pelletized, be dried etc. after the dissolution of deliquescent component process, so as to avoid because of solid State absorb moisture and caused by content inaccuracy problem, meanwhile, product start it is hardened, agglomeration storage time prolonged from 4 months It has grown to 9 months, compared with similar product in the market, quality and performance are greatly improved.
(4) preparation method of the invention can during the preparation process purify raw material, to effectively prevent making Bring pollutes when in use for agent, it is seen that the ingredients such as solid pollutant, insoluble granule, bacterium can significantly be gone It removes, the quality of the pharmaceutical preparations is excellent and stablizes.
(5) preparation method of the invention is without using complicated production equipment, simple process, mild condition, preparation cost It is not high, it can be suitable for mass production.
Specific embodiment
Below by embodiment, the present invention is described in detail, so that the features and advantages of the present invention become apparent from.But it answers This points out that for embodiment for understanding design of the invention, the scope of the present invention is not limited only to reality listed herein Apply example.
Experimental method used in following embodiments is conventional method unless otherwise specified.Institute in following embodiments Material, reagent etc., are commercially available unless otherwise specified.
Sodium chloride as used in the following examples, potassium chloride, calcium chloride, magnesium chloride, citric acid molecular formula be respectively NaCl、KCl、CaCl2·2H2O、MgCl2·6H2O、C6H8O7·H2O.Sodium chloride, potassium chloride, calcium chloride and citric acid therein Meet " the Chinese people are total to republic's pharmacopeia " quality requirement, magnesium chloride meets the regulation of WS-10001- (HD-0476) -2002.Under It states process water used in embodiment and meets Pharmacopoeia of the People's Republic of China purified water and " haemodialysis water " (YY0572) quality requirement of water for dialysis.Production environment locating for the preparation process of following embodiments should meet " aseptic medical Utensil production management specification " (YY 0033-2000) 100,000 grades of toilet's (area) air purity requirements.
Embodiment 1
300kg sodium chloride is added in high efficiency wet granulator, the process water of 28.5kg is added in dissolving tank, Then 7.43kg potassium chloride, 10.99kg calcium chloride, 5.07kg magnesium chloride and 11.1kg citric acid are added sequentially to dissolving tank In, addition while, is stirred, and after material is completely dissolved, the solution that dissolution is obtained passes through the spray of efficient granulator spray head Onto sodium chloride particle, start the agitating paddle and cutter of efficient granulator when spray simultaneously, the spray pressure of spray head is 0.05MPa, the revolving speed of stirring blade are 100rpm, and the revolving speed of cutter is 1000rpm, continuous granulation 30 minutes.After the completion of granulation Gained particle is transferred to vibration fluid bed dryer to be dried, inlet air temperature when dry is 75 DEG C, sufficiently after drying i.e. Obtain A concentrate.
Embodiment 2
300kg sodium chloride is added in high efficiency wet granulator, the process water of 33kg is added in dissolving tank, so 7.43kg potassium chloride, 10.99kg calcium chloride, 5.07kg magnesium chloride and 11.1kg citric acid are added sequentially to dissolving tank afterwards In, addition while, is stirred, and after material is completely dissolved, the solution that dissolution is obtained passes through the spray of efficient granulator spray head Onto sodium chloride particle, start the agitating paddle and cutter of efficient granulator when spray simultaneously, the spray pressure of spray head is 0.1MPa, the revolving speed of stirring blade are 200rpm, and the revolving speed of cutter is 1500rpm, continuous granulation 20 minutes.It will after the completion of granulation Gained particle is transferred to vibration fluid bed dryer and is dried, and inlet air temperature when dry is 90 DEG C, sufficiently up to A after drying Concentrate.
Embodiment 3
After potassium chloride, calcium chloride, magnesium chloride and citric acid are added to dissolving tank dissolution, resulting solution is successively led to 0.45 μm and 0.22 μm of filter are crossed, is then sprayed on sodium chloride particle by efficient granulator spray head, other same embodiments 1。
Embodiment 4
After potassium chloride, calcium chloride, magnesium chloride and citric acid are added to dissolving tank dissolution, resulting solution is successively led to 0.45 μm and 0.22 μm of filter are crossed, is then sprayed on sodium chloride particle by efficient granulator spray head, other same embodiments 2。
Comparative example 1
By 300kg sodium chloride, 7.43kg potassium chloride, 10.99kg calcium chloride, 5.07kg magnesium chloride and 11.1kg citric acid It being added sequentially in three-dimensional mixer, starts mixing machine, electric machine frequency is 25Hz (mixing drum revolving speed 7rpm), it mixes 25 minutes, Obtain A concentrate.
Comparative example 2
By 300kg sodium chloride, 7.43kg potassium chloride, 10.99kg calcium chloride, 5.07kg magnesium chloride and 11.1kg citric acid It being added sequentially in three-dimensional mixer, starts mixing machine, electric machine frequency is 30Hz (mixing drum revolving speed 8rpm), it mixes 20 minutes, Obtain A concentrate.
Test case 1
Embodiment 1-2 and comparative example 1-2 are subjected to uniformity test and long range production character observation respectively, as a result such as table Shown in 1-3.
The test comparison result of table 1 embodiment 1 and 1 product of comparative example
By 1 result of table can be seen that 1 product of embodiment in low-level sampling amount the uniformity 99% or more, And with the increase of sampling amount, significant change and variation also do not occur for uniformity.1 product of comparative example is in identical sampling level When, the uniformity is far below embodiment product, and not up to qualified horizontal.The 1 product uniformity of embodiment is higher than comparative example, and It is more stable on different sampling levels, it was demonstrated that the uniformity of 1 product of embodiment is more excellent.Use 1 product configuration dialyzate of embodiment When, can according to actual use situation prepare any specification (1 person-portion or more person-portions), also can while using while prepare.In addition, embodiment The fine powder content of 1 product is more considerably lower than comparative example.
The test comparison result of table 2 embodiment 2 and 2 product of comparative example
By 2 result of table can be seen that 2 product of embodiment in low-level sampling amount the uniformity 99% or more, And with the increase of sampling amount, significant change and variation also do not occur for uniformity.2 product of comparative example is in identical sampling level When, the uniformity is far below embodiment product, and not up to qualified horizontal.The 2 product uniformity of embodiment is higher than comparative example, and It is more stable on different sampling levels, it was demonstrated that the uniformity of 2 product of embodiment is more excellent.Use 2 product configuration dialyzate of embodiment When, can according to actual use situation prepare any specification (1 person-portion or more person-portions), also can while using while prepare.In addition, embodiment The fine powder content of 2 products is more considerably lower than comparative example.
The long-term observation comparing result of 3 embodiment of table and comparative example product
It is stored 8 months under defined condition of storage by the product that 3 result of table can be seen that embodiment 1,2 and remains to protect Loose condition (of surface) is held, and is had preferable mobility；Comparative example 1,2 product of comparative example just occurred hardened, agglomeration at 4th month now As, and with the extension of time, it is hardened, agglomeration gradually increases, agglomerate is gradually increased, until at 9th month, whole bag production board Knot.Due to product is hardened, agglomeration after, product dissolution time extend or cannot sufficiently dissolve, be unfavorable for clinical use, therefore explanation The product of embodiment is substantially better than the product of comparative example.
Test case 2
Embodiment 3,4 and character after the product dissolution of Comparative Examples 1 and 2 are observed, and measures bacteria endotoxin content, as a result such as Shown in table 4,5.
The test comparison result of table 4 embodiment 3 and 1 product of comparative example
It can be seen that 3 product of embodiment under different sampling levels by 4 result of table, do not find macroscopic Cilium and block, and there is no rising appreciably for particulate matter and bacterial endotoxin, wherein >=10 μm of particles Average For 3.6/ml, >=25 μm of particles Average is 0.2/ml, and bacterial endotoxin average value is 0.216EU/ml.Comparative example 1 Product is under different sampling levels, and macroscopic cilium and block increase obviously, and particulate matter >=10 μm is micro- Grain content is 5 times or more of 3 product of embodiment, and >=25 μm of fraction of particle is 10 times or more of 3 product of embodiment.Embodiment 3 Product is substantially better than the product of comparative example 1.
The test comparison result of table 5 embodiment 4 and 2 product of comparative example
It can be seen that 4 product of embodiment under different sampling levels by 5 result of table, do not find macroscopic Cilium and block, and there is no rising appreciably for particulate matter and bacterial endotoxin, wherein >=10 μm of particles Average For 3.1/ml, >=25 μm of particles Average is 0.2/ml, and bacterial endotoxin average value is 0.205EU/ml.Comparative example 2 Product is under different sampling levels, and macroscopic cilium and block increase obviously, and particulate matter >=10 μm is micro- Grain content is 6 times or more of 4 product of embodiment, and >=25 μm of fraction of particle is 10 times or more of 4 product of embodiment.Embodiment 4 Product is substantially better than the product of comparative example 2.
Unless limited otherwise, term used herein is the normally understood meaning of those skilled in the art.
Embodiment described in the invention is merely for exemplary purpose, the protection scope being not intended to limit the invention, Those skilled in the art can be made within the scope of the invention various other replacements, changes and improvements, thus, the present invention is not limited to Above embodiment, and be only defined by the claims.

Claims (10)

1. a kind of haemodialysis solid pharmaceutical preparation, is made of sodium chloride, potassium chloride, calcium chloride, magnesium chloride and pH adjusting agent, special Sign is that the solid pharmaceutical preparation is granule, and the potassium chloride, calcium chloride, magnesium chloride and pH adjusting agent are adhered to described jointly The surface of sodium chloride.
2. haemodialysis solid pharmaceutical preparation according to claim 1, which is characterized in that the sodium chloride, potassium chloride, chlorination Calcium, magnesium chloride, pH adjusting agent weight ratio be 100 ﹕, 1~4 ﹕, 2~5 ﹕, 1~3 ﹕ 1~10.
3. haemodialysis solid pharmaceutical preparation according to claim 1 or 2, which is characterized in that the pH adjusting agent be selected from One of lower substance is a variety of: citric acid, sodium citrate, L MALIC ACID, L MALIC ACID sodium, D-malic acid, D-malic acid sodium, DL-malic acid, DL-sodium malate, sodium diacetate, lactic acid and sodium lactate.
4. haemodialysis solid pharmaceutical preparation according to claim 1-3, which is characterized in that the solid pharmaceutical preparation is matched It is made after blood dialysis solution, the particle of partial size >=10 μm is 5 every milliliter hereinafter, the particle of partial size >=25 μm is every milliliter 0.5 hereinafter, bacterial endotoxin is every milliliter of 0.25EU or less.
5. the preparation method of the described in any item haemodialysis solid pharmaceutical preparations of claim 1-4, which is characterized in that including following Step:
S1: potassium chloride, calcium chloride, magnesium chloride and pH adjusting agent are dissolved to form solution with water；
S2: the step S1 solution formed is sprayed onto sodium chloride surface and carries out wet granulation；And
S3: by particle drying made from step S2 up to the haemodialysis solid pharmaceutical preparation.
6. preparation method according to claim 5, which is characterized in that the step S1 further include: by the solution of formation according to The two-stage filter that the secondary first level filtering device and aperture for being 0.45~1 μm by aperture is 0.1~0.22 μm.
7. preparation method according to claim 5 or 6, which is characterized in that the dosage of the water in the step S1 with it is described The weight ratio of sodium chloride is 9~14 ﹕ 100.
8. preparation method according to claim 5 or 6, which is characterized in that the spray pressure of solution is in the step S2 0.03~0.2MPa.
9. preparation method according to claim 5 or 6, which is characterized in that in the step S2 using wet granulator into Row granulation, the stirring blade revolving speed of the wet granulator are 80~250rpm, and the cutter revolving speed of the wet granulator is 800 ~2000rpm.
10. preparation method according to claim 5 or 6, which is characterized in that in the step S3, the dry particle Inlet air temperature is 50~100 DEG C.
CN201811367193.9A 2018-11-16 2018-11-16 A kind of haemodialysis solid pharmaceutical preparation and preparation method thereof Pending CN109288859A (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0399918B1 (en) * 1989-05-26 1995-10-11 Terumo Kabushiki Kaisha Preparation for blood dialysis and method for production thereof
CN1448145A (en) * 2003-04-30 2003-10-15 广州康盛生物科技有限公司 Bicarbonate dry powder composition for hemodialysis
CN1917888A (en) * 2004-02-09 2007-02-21 尼普洛株式会社 Solid formulation for dialysis and process for producing the same
CN1938058A (en) * 2004-03-30 2007-03-28 尼普洛株式会社 Solid pharmaceutical preparation for dialysis

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0399918B1 (en) * 1989-05-26 1995-10-11 Terumo Kabushiki Kaisha Preparation for blood dialysis and method for production thereof
CN1448145A (en) * 2003-04-30 2003-10-15 广州康盛生物科技有限公司 Bicarbonate dry powder composition for hemodialysis
CN1917888A (en) * 2004-02-09 2007-02-21 尼普洛株式会社 Solid formulation for dialysis and process for producing the same
CN1938058A (en) * 2004-03-30 2007-03-28 尼普洛株式会社 Solid pharmaceutical preparation for dialysis

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