CN102772427A - Compound polyethylene glycol electrolyte composition - Google Patents
Compound polyethylene glycol electrolyte composition Download PDFInfo
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- CN102772427A CN102772427A CN2012102957174A CN201210295717A CN102772427A CN 102772427 A CN102772427 A CN 102772427A CN 2012102957174 A CN2012102957174 A CN 2012102957174A CN 201210295717 A CN201210295717 A CN 201210295717A CN 102772427 A CN102772427 A CN 102772427A
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- polyethylene glycol
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- 239000000203 mixture Substances 0.000 title claims abstract description 197
- 229920001223 polyethylene glycol Polymers 0.000 title claims abstract description 180
- 239000002202 Polyethylene glycol Substances 0.000 title claims abstract description 172
- 239000003792 electrolyte Substances 0.000 title claims abstract description 25
- 150000001875 compounds Chemical class 0.000 title abstract description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 65
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims abstract description 64
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims abstract description 48
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims abstract description 36
- 239000001103 potassium chloride Substances 0.000 claims abstract description 32
- 235000011164 potassium chloride Nutrition 0.000 claims abstract description 32
- 239000011780 sodium chloride Substances 0.000 claims abstract description 31
- 235000017557 sodium bicarbonate Nutrition 0.000 claims abstract description 24
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims abstract description 24
- 238000000034 method Methods 0.000 claims description 61
- 239000000843 powder Substances 0.000 claims description 46
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 45
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 44
- 238000012360 testing method Methods 0.000 claims description 39
- 238000012937 correction Methods 0.000 claims description 38
- 239000000463 material Substances 0.000 claims description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 29
- 235000002639 sodium chloride Nutrition 0.000 claims description 24
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 22
- 238000004448 titration Methods 0.000 claims description 19
- 238000010298 pulverizing process Methods 0.000 claims description 16
- 230000008569 process Effects 0.000 claims description 13
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 claims description 12
- 238000012856 packing Methods 0.000 claims description 12
- KJFMBFZCATUALV-UHFFFAOYSA-N phenolphthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2C(=O)O1 KJFMBFZCATUALV-UHFFFAOYSA-N 0.000 claims description 12
- 238000001816 cooling Methods 0.000 claims description 11
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 claims description 10
- 239000011812 mixed powder Substances 0.000 claims description 10
- 229940093429 polyethylene glycol 6000 Drugs 0.000 claims description 10
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 9
- 238000002156 mixing Methods 0.000 claims description 8
- 238000003556 assay Methods 0.000 claims description 7
- 239000000796 flavoring agent Substances 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 6
- 238000009835 boiling Methods 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 235000013355 food flavoring agent Nutrition 0.000 claims description 4
- 239000008187 granular material Substances 0.000 claims description 4
- 108010011485 Aspartame Proteins 0.000 claims description 3
- 239000000605 aspartame Substances 0.000 claims description 3
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 3
- 235000010357 aspartame Nutrition 0.000 claims description 3
- 229960003438 aspartame Drugs 0.000 claims description 3
- 235000019634 flavors Nutrition 0.000 claims description 3
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 claims description 2
- 239000004376 Sucralose Substances 0.000 claims description 2
- 235000010358 acesulfame potassium Nutrition 0.000 claims description 2
- 229960004998 acesulfame potassium Drugs 0.000 claims description 2
- 239000000619 acesulfame-K Substances 0.000 claims description 2
- 239000003205 fragrance Substances 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- 235000019408 sucralose Nutrition 0.000 claims description 2
- 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 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 102
- 239000000243 solution Substances 0.000 description 69
- 230000000052 comparative effect Effects 0.000 description 39
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 27
- 239000002994 raw material Substances 0.000 description 26
- 238000002360 preparation method Methods 0.000 description 19
- 210000001072 colon Anatomy 0.000 description 14
- 230000008859 change Effects 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 206010010774 Constipation Diseases 0.000 description 10
- 239000000047 product Substances 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- 210000003608 fece Anatomy 0.000 description 7
- 241000792859 Enema Species 0.000 description 6
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 6
- 238000002835 absorbance Methods 0.000 description 6
- 239000007920 enema Substances 0.000 description 6
- 229940095399 enema Drugs 0.000 description 6
- 230000000968 intestinal effect Effects 0.000 description 6
- 239000005030 aluminium foil Substances 0.000 description 5
- 238000013459 approach Methods 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000004140 cleaning Methods 0.000 description 5
- 230000018044 dehydration Effects 0.000 description 5
- 238000006297 dehydration reaction Methods 0.000 description 5
- 239000012535 impurity Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- 206010056325 Faecaloma Diseases 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- AFGPCIMUGMJQPD-UHFFFAOYSA-L disodium;4,5-dihydroxynaphthalene-2,7-disulfonate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)C1=CC(O)=C2C(O)=CC(S([O-])(=O)=O)=CC2=C1 AFGPCIMUGMJQPD-UHFFFAOYSA-L 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 229940056944 golytely Drugs 0.000 description 4
- 229910017053 inorganic salt Inorganic materials 0.000 description 4
- 229920003023 plastic Polymers 0.000 description 4
- 239000004033 plastic Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000002746 orthostatic effect Effects 0.000 description 3
- 210000000664 rectum Anatomy 0.000 description 3
- 239000013558 reference substance Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 208000005392 Spasm Diseases 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000012490 blank solution Substances 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 230000000112 colonic effect Effects 0.000 description 2
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 206010016766 flatulence Diseases 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 2
- 229910001948 sodium oxide Inorganic materials 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000001117 sulphuric acid Substances 0.000 description 2
- 235000011149 sulphuric acid Nutrition 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- JECYNCQXXKQDJN-UHFFFAOYSA-N 2-(2-methylhexan-2-yloxymethyl)oxirane Chemical compound CCCCC(C)(C)OCC1CO1 JECYNCQXXKQDJN-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- FRPHFZCDPYBUAU-UHFFFAOYSA-N Bromocresolgreen Chemical compound CC1=C(Br)C(O)=C(Br)C=C1C1(C=2C(=C(Br)C(O)=C(Br)C=2)C)C2=CC=CC=C2S(=O)(=O)O1 FRPHFZCDPYBUAU-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- XTEGARKTQYYJKE-UHFFFAOYSA-M Chlorate Chemical class [O-]Cl(=O)=O XTEGARKTQYYJKE-UHFFFAOYSA-M 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 235000008708 Morus alba Nutrition 0.000 description 1
- 240000000249 Morus alba Species 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920002562 Polyethylene Glycol 3350 Polymers 0.000 description 1
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 1
- 206010067268 Post procedural infection Diseases 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000000799 cathartic agent Substances 0.000 description 1
- 238000002052 colonoscopy Methods 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000000498 cooling water Substances 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000016693 dipotassium tartrate Nutrition 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 210000004921 distal colon Anatomy 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
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- 238000001035 drying Methods 0.000 description 1
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- 239000000835 fiber Substances 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000008141 laxative Substances 0.000 description 1
- 230000002475 laxative effect Effects 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-O oxonium Chemical compound [OH3+] XLYOFNOQVPJJNP-UHFFFAOYSA-O 0.000 description 1
- 238000006068 polycondensation reaction Methods 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- -1 polyethylene Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- AVTYONGGKAJVTE-OLXYHTOASA-L potassium L-tartrate Chemical compound [K+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O AVTYONGGKAJVTE-OLXYHTOASA-L 0.000 description 1
- 230000001915 proofreading effect Effects 0.000 description 1
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Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a compound polyethylene glycol electrolyte composition, and in particular relates to a composition containing polyethylene glycol and electrolyte. The composition comprises the following components: polyethylene glycol, potassium chloride, sodium bicarbonate and anhydrous sodium sulfate. According to 6000 parts of polyethylene glycol, the composition comprises 118-178 parts of sodium chloride, 60-90 parts of potassium chloride, 137-205 parts of sodium bicarbonate and 461-692 parts of anhydrous sodium sulfate. The composition disclosed by the invention has good pharmaceutical properties.
Description
Technical field
The present invention relates to field of medicaments, relate to a kind of Polyethylene Glycol and electrolytical compositions and its method for preparing of comprising, particularly relate to a kind of polyethylene glycol electrolytes and loose and preparation method thereof.Said composition of the present invention can be used for treating constipation, feces infraction, faecal impaction, intestinal gas spasm, flatulence, also can be used for orthostatic lavage, colon cathartic or colon and cleans.
Background technology
Constipation is a kind of uncomfortable common situation that can cause usually.Feces is trapped in colon and/or rectum can cause uncomfortable and headache.Under extreme case, exist scybalum or argol piece can cause long constipation and dyschizia in the rectum.
People have developed the Therapeutic Method of a lot of constipation, comprise diet control (for example: increase fiber content and the not edible food that is considered to cause constipation in the food), cathartic and enema.Cathartic is the medicament that promotes and help relieving constipation.Infiltrative cathartic can make moisture be retained in colonic lumen, thereby offsets normal colon dehydration.Through suppressing the dehydration of colon, that infiltrative cathartic can produce is more soft, volume is bigger and the stream shape feces that is easier to discharge.
A lot of osmotic laxative treatments of using at present all comprise Polyethylene Glycol (PEG).Said composition can also comprise electrolyte.Movicol
be a on market Polyethylene Glycol and the electrolytical cathartic of comprising on sale.Movicol Britain and other countries can available from the Norgine company limited (Chaplin House, Widewater Place, Moorhall Road, Harefield, Middlesex UB96NS, UK).It takes on pouch and sells, and every bag contains the 13.8g powder.Every bag composition is formed as follows: Macrogol (Polyethylene Glycol) 3350:13.125g; Sodium chloride: 350.7mg; Sodium bicarbonate: 178.5mg; Potassium chloride: 46.6mg; And flavouring agent and sweeting agent (trace).This is little also to comprise instruction in packed, indicates that water with powder and 125mL is in harmonious proportion to take.
A lot of patients can feel that mouthfeel is bad and too salty when taking the cathartic of Powdered, graininess based on Polyethylene Glycol of Movicol or other, solution shape, suspension.These bad impressions can cause patient's resentment.
Before a lot of diagnosis and surgical operation, for example before colonoscopy, barium enema examination or colonic operation, all need carry out colon and clean.Colon cleans for the postoperative infection that prevents the low level intestinal also very effectively.The colon cleaning also is considered to colon and empties.
The method that a kind of colon cleans is an orthostatic lavage, promptly through drinking or pouring into a large amount of electrolyte by nasal feeding tube.This enema also is considered to intestinal or digestive tract cleanout fluid.Take in this solution and can cause bringing out property of body fluid diarrhoea, thereby reach the purpose of cleaning colon.The enema that great majority are commonly used all comprises Polyethylene Glycol.1980, Davis and his colleague reported a kind of progress of enema, as their said this enema be with the water of trace and electrolytical absorption or secretion link together (Davis GR.et al., Gastroenterology, 1980,78,991-995).This solution comprises sodium sulfate and Polyethylene Glycol.Of people such as Davis, this solution except comprise sodium sulfate (40.0mM, 5.68g/L) and Polyethylene Glycol (PEG4000 " carbowax "; 64g/L) in addition, also comprise sodium chloride (25mM, 1.463g/L), potassium chloride (10mM; 0.745g/L), sodium bicarbonate (20mM, 1.680g/L) and water.The taking dose of this solution is 4 liters, and very effective to cleaning gastrointestinal tract.A kind of related solution is become commercialized; Its trade name GoLYTELY
(Braintree Laboratories Inc; Braintree; Massachusetts, U.S.A.).
Commercial GoLYTELY
compositions of starting selling in August, 1996 is dry powdered; Comprise sodium sulfate (40.0mM; 5.685g/L), sodium chloride (25mM; 1.464g/L), potassium chloride (10mM; 0.743g/L), (20mM 1.685g/L) and PEG3350 Polyethylene Glycol (59g/L), and converts water to 4 liter with it to sodium bicarbonate.GoLYTELY
also sells with the form of aqueous solution.
With to take anti-constipation composition the same, the patient takes GoLYTELY
or other cleanout fluid based on PEG are felt the solution smell bad equally.These bad impressions can cause patient's resentment.
Faecal impaction or be called as feces and be detained and be meant that a large amount of feces are trapped in rectum or distal colon can not be unimpeded.The method that treatment feces is detained is roughly the same with the method for above-mentioned constipation of treatment and colon cleaning, but usually, dosage required under the situation of its dosage than the treatment constipation is bigger.
Therefore, the therapy of a kind of Movicol of use of recommendation is drunk in 6 hours as every day 8 pouch Movicol (every bag of amount that comprises composition as stated) being dissolved in 1 premium on currency, continues 3 days general at most.
The same as taking other cathartics with the bowel relieving compositions; A lot of patients are taking Movicol
or during with the treatment faecal impaction, can feel the solution smell bad based on the compositions of Polyethylene Glycol.These bad impressions can cause patient's resentment.It is thus clear that comprising Polyethylene Glycol and electrolytical compositions is that people expect very much in the improvement of mouthfeel.
In addition; Existing be used to treat that constipation, feces infraction, faecal impaction, intestinal gas spasm, flatulence, orthostatic lavage, colon cathartic or colon clean comprises Polyethylene Glycol and electrolytical compositions contains more Polyethylene Glycol usually, and the electrolyte ratio is considerably less comparatively speaking.For example the Polyethylene Glycol of 1 weight fraction is approximately the 0.05-0.5 weight portion corresponding to electrolytical total amount usually, particularly the 0.1-0.2 weight portion.In the case, need be to electrolytical amount special concern, for example in process of production, in the transporting procedures, in the disposal process, in the use, electrolytical variation is to need especially to pay close attention to for total formulation.
Summary of the invention
The objective of the invention is defective to above-mentioned one or more aspects; A kind of Polyethylene Glycol and electrolytical compositions of comprising is provided; Phase etc. its have following one or more advantages: have good mouthfeel, electrolyte has for example shelf stabilities of good pharmaceutical property in processes such as production, storing, disposal, use.The inventor finds that the compositions with prescription according to the invention has at least one above-mentioned advantage, has accomplished the present invention therefrom.
For this reason, first aspect present invention provides and has comprised Polyethylene Glycol and electrolytical compositions, comprises following component in the said composition: Polyethylene Glycol, sodium chloride, potassium chloride, sodium bicarbonate, anhydrous sodium sulfate.The present composition can be Powdered, graininess, by Powdered through add graininess that binding agent or wetting agent process, by forms such as bulk Powdered or that graininess is pressed into.
According to the compositions of first aspect present invention, in the Polyethylene Glycol of per 6000 weight portions, the amount of sodium chloride wherein is 118-178 part, preferred 133-163 part, for example about 148 parts.
According to the compositions of first aspect present invention, in the Polyethylene Glycol of per 6000 weight portions, the amount of potassium chloride wherein is 60-90 part, preferred 67-83 part, for example about 75 parts.
According to the compositions of first aspect present invention, in the Polyethylene Glycol of per 6000 weight portions, the amount of sodium bicarbonate wherein is 137-205 part, preferred 154-188 part, for example about 171 parts.
According to the compositions of first aspect present invention, in the Polyethylene Glycol of per 6000 weight portions, the amount of anhydrous sodium sulfate wherein is 461-692 part, preferred 520-635 part, for example about 577 parts.
According to the compositions of first aspect present invention, wherein comprise the component of following weight portion:
| Polyethylene Glycol | 6000 parts, |
| Sodium chloride | 118-178 part, |
| Potassium chloride | 60-90 part, |
| Sodium bicarbonate | 137-205 part, |
| Anhydrous sodium sulfate | 461-692 part. |
According to the compositions of first aspect present invention, wherein comprise the component of following weight portion:
| Polyethylene Glycol | 6000 parts, |
| Sodium chloride | 133-163 part, |
| Potassium chloride | 67-83 part, |
| Sodium bicarbonate | 154-188 part, |
| Anhydrous sodium sulfate | 520-635 part. |
According to the compositions of first aspect present invention, wherein comprise the component of following weight portion:
| Polyethylene Glycol | 6000 parts, |
| Sodium chloride | About 155 parts, |
| Potassium chloride | About 80 parts, |
| Sodium bicarbonate | About 165 parts, |
| Anhydrous sodium sulfate | About 570 parts. |
According to the compositions of first aspect present invention, wherein comprise the component of following weight portion:
| Polyethylene Glycol | 6000 parts, |
| Sodium chloride | About 148 parts, |
| Potassium chloride | About 75 parts, |
| Sodium bicarbonate | About 171 parts, |
| Anhydrous sodium sulfate | About 577 parts. |
According to the compositions of first aspect present invention, wherein comprise the component of following weight portion:
| Polyethylene Glycol | 6000 parts, |
| Sodium chloride | About 140 parts, |
| Potassium chloride | About 70 parts, |
| Sodium bicarbonate | About 175 parts, |
| Anhydrous sodium sulfate | About 585 parts. |
According to the compositions of first aspect present invention, wherein said Polyethylene Glycol has 2600 ~ 3400 mean molecule quantity (Mr).
According to the compositions of first aspect present invention, wherein said Polyethylene Glycol has 2600 ~ 3400 mean molecule quantity, and this mean molecule quantity is following mensuration:
The about 12.5g of taking polyethylene glycol test sample, the accurate title, decide, and puts in the withstand voltage conical flask of exsiccant 200ml tool plug, adds pyridine 25ml; Heating makes dissolving, puts coldly, and the accurate pyridine solution that adds phthalic anhydride (is got phthalic anhydride 14g, is dissolved among the anhydrous pyridine 100ml; Placement is spent the night, and is subsequent use) 25ml, shake up, put in 98 ± 2 ℃ of boiling water baths; Heated 30～60 minutes, and took out cooling, accurate sodium hydroxide volumetric solution (0.5mol/L) 50ml that adds; Pyridine solution (1 → 100) with phenolphthalein is an indicator, extremely shows red with sodium hydroxide volumetric solution (0.5mol/L) titration, and titrating result is proofreaied and correct with blank assay.Supply the product of examination amount (g) and 4000,, promptly get the mean molecule quantity of test sample divided by the volume (ml) of (in the titration process) hydrogen consuming sodium oxide volumetric solution (0.5mol/L).
According to the compositions of first aspect present invention, wherein said Polyethylene Glycol has 2600 ~ 3200 mean molecule quantity.
According to the compositions of first aspect present invention, it has 2600 ~ 3400 correction PEG molecular weight (cMr).
According to the compositions of first aspect present invention, it has 2600 ~ 3400 correction PEG molecular weight, and this correction PEG molecular weight is following mensuration:
Get the about 12.5g of present composition test sample (M, unit is gram), the accurate title, decide, and puts in the withstand voltage conical flask of exsiccant 200ml tool plug; Add pyridine 25ml, heating makes dissolving, puts coldly, and the accurate pyridine solution that adds phthalic anhydride (is got phthalic anhydride 14g; Be dissolved among the anhydrous pyridine 100ml, placement is spent the night, and is subsequent use) 25ml, shake up; Put in 98 ± 2 ℃ of boiling water baths, heated 30～60 minutes, take out cooling; Accurate sodium hydroxide volumetric solution (0.5mol/L) 50ml that adds be an indicator with the pyridine solution (1 → 100) of phenolphthalein, with sodium hydroxide volumetric solution (0.5mol/L) titration to apparent redness; Read the volume (V, unit are milliliter) of the sodium hydroxide volumetric solution that consumes in this titration process, and titrating result is proofreaied and correct with blank assay.Calculate the correction PEG molecular weight of present composition test sample with following formula (I):
Need to prove, owing to contain other material in the prescription of the present composition, the weight effect that these materials produce PEG; Therefore in following formula (I), f is the value of composition total weight divided by the weight gained of contained Polyethylene Glycol in the compositions, and in the present invention, f can be described as the weight effect factor or correction factor or weight correction factor.Because the weight effect of other material in the present composition, the effect positive divisor f of weight effect is between 1.129 ~ 1.194 on average, typically is f=1.162.For example, when f=1.162, can use the correction PEG molecular weight that calculates present composition test sample with following formula (II):
Above to the definition that f did in, " f is the value of composition total weight divided by the weight gained of contained Polyethylene Glycol in the compositions ", wherein " composition total weight remove " can obtain easily, promptly it can be to the acquisition of directly weighing of compositions finished product; And " weight of contained Polyethylene Glycol in the compositions " can obtain from two approach; A kind of approach is the PEG content that compositions indicates; Also have a kind of easy but accurately approach be can directly measure to obtain through certain method, for example measure the content that obtains PEG in the compositions through following HPLC method:
A: use high performance liquid chromatograph, chromatographic column is the hydroxyl post; Get sodium chloride 0.036g, potassium chloride 0.018g, sodium bicarbonate 0.04g, sodium sulfate 0.137g, add water to 100ml, as saline solution; Get the solution of above-mentioned saline solution 40ml thin up, as mobile phase to 1000ml; Use differential refraction detector; Detector temperature: 30 ℃.Number of theoretical plate should be not less than 2500, and separating degree should meet the requirements.
B: get composition sample an amount of (containing the about 60g of PEG), stable precision is put in the 1000ml measuring bottle, is dissolved in water, and is diluted to scale, shakes up, and the accurate 10ml that draws puts in the 500ml measuring bottle, adds water and is diluted to scale, shakes up, as need testing solution.Other gets the PEG reference substance, adds the used saline solution 20ml of preparation mobile phase, adds water and is made into the reference substance solution that concentration is 1.18mg/ml; Precision is measured reference substance solution and each 20 μ l injecting chromatograph of need testing solution, record chromatogram., promptly get with calculated by peak area by external standard method.
According to the compositions of first aspect present invention, it has 2600 ~ 3200 correction PEG molecular weight.
According to the compositions of first aspect present invention, its powder body more than 90% can pass through 24 eye mesh screens.In one embodiment, the powder body more than 95% of said composition can pass through 24 eye mesh screens.In one embodiment, the powder body more than 98% of said composition can pass through 24 eye mesh screens.
According to the compositions of first aspect present invention, its powder body more than 90% can pass through 50 eye mesh screens.In one embodiment, the powder body more than 95% of said composition can pass through 50 eye mesh screens.In one embodiment, the powder body more than 98% of said composition can pass through 50 eye mesh screens.
According to the compositions of first aspect present invention, its powder body more than 90% can pass through 65 eye mesh screens.In one embodiment, the powder body more than 95% of said composition can pass through 65 eye mesh screens.In one embodiment, the powder body more than 98% of said composition can pass through 65 eye mesh screens.
According to the compositions of first aspect present invention, its powder body more than 90% can pass through 80 eye mesh screens.In one embodiment, the powder body more than 95% of said composition can pass through 80 eye mesh screens.In one embodiment, the powder body more than 98% of said composition can pass through 80 eye mesh screens.
Compositions according to first aspect present invention; It is each material through pulverizing independently of one another or pulverize through two or more combinations arbitrarily, and cross the aperture less than 24 orders (preferably less than 50 orders, preferably less than 65 orders) sieve after; Through randomly mixing, obtain powdered composition.In one embodiment, said composition prepares through the said method of the arbitrary embodiment of second aspect.
According to the compositions of first aspect present invention, wherein can also comprise flavoring agent, for example the powdered flavor of various fragrance.
According to the compositions of first aspect present invention, wherein can also comprise sweeting agent, for example aspartame, sucralose, acesulfame potassium.
According to the compositions of first aspect present invention, it is pharmaceutical preparation.In one embodiment, it is medicine types such as powder, granule, tablet.
According to the compositions of first aspect present invention, wherein said Polyethylene Glycol has 45 ~ 65 hydroxyl value.
According to the compositions of first aspect present invention, wherein said Polyethylene Glycol has 45 ~ 65 hydroxyl value, and this hydroxyl value is that following method is measured: get m gram (about 10g) sample, stable precision places the dry conical flask that reflux condenser has been installed; Add the phthalic acid anhydride solution of 25.0ml, whirlpool makes dissolving, ebuillition of heated 60min under reflux condenser, cooling; Earlier wash condenser, add the phenolphthalein solution of 1.5ml again with 25ml pyridine and 25ml water, with the titration of 1M sodium hydroxide volumetric solution, until the faint pink of generation (volumetric solution volume v1, ml); With blank assay proofread and correct (volumetric solution volume v2, ml); Use the computes hydroxyl value:
Greater than 0.5% sample,, calculate hydroxyl value with dry product again for water content at 100-105 ℃ of dry 2h.
According to the compositions of first aspect present invention, wherein said Polyethylene Glycol has 45 ~ 60 hydroxyl value.
In addition; The inventor finds; Although add 10% ~ 15% the electrolyte except that Polyethylene Glycol of having an appointment in the present composition; Yet deduct these electrolytical qualitative factors, the weight effect factor promptly mentioned above or correction factor or weight correction factor f value, compositions of the present invention and its PEG raw material have suitable hydroxyl value.Be that the present composition can and be considered the f value with reference to the method for PEG raw material, can record the inherent specific hydroxyl value of said composition, can be described as the correction hydroxyl value of compositions in the present invention.In the present invention, hydroxyl value can be represented by english abbreviation HV, proofreaies and correct hydroxyl value and can represent with english abbreviation cHV.
According to the compositions of first aspect present invention, it has 45 ~ 65 correction hydroxyl value.
According to the compositions of first aspect present invention, it has 45 ~ 65 correction hydroxyl value, and this correction hydroxyl value is following mensuration: get m gram (about 12g) sample, stable precision places the dry conical flask that reflux condenser has been installed; Add the phthalic acid anhydride solution of 25.0ml, whirlpool makes dissolving, ebuillition of heated 60min under reflux condenser, cooling; Earlier wash condenser, add the phenolphthalein solution of 1.5ml again with 25ml pyridine and 25ml water, with the titration of 1M sodium hydroxide volumetric solution, until the faint pink of generation (volumetric solution volume v1, ml); With blank assay proofread and correct (volumetric solution volume v2, ml); Use computes to proofread and correct hydroxyl value:
be f such as according to the invention wherein.
Second aspect present invention provides the preparation first aspect present invention said method for compositions; It may further comprise the steps: make each material through pulverizing independently of one another or pulverizing through any two or more combinations; And cross the aperture less than 24 orders (preferably less than 50 orders; Preferably less than 65 orders) behind the sieve,, obtain powdered composition through randomly mixing.
Second aspect present invention also provides the preparation first aspect present invention said method for compositions, and it may further comprise the steps:
Make each material through pulverizing independently of one another or pulverizing through any two or more combinations;
Crossing the aperture through the material of pulverizing sieves less than 24 orders (preferably less than 50 orders, preferably less than 65 orders);
Randomly the material to each pulverizing mixes;
Mixing or unmixing each material are joined in the packing container independently or together, obtain powdered composition.
According to the method for second aspect present invention, it may further comprise the steps:
A) sodium chloride, potassium chloride, sodium bicarbonate, anhydrous sodium sulfate are pulverized independently of one another; Any two or more combinations in them are pulverized; Crossing the aperture independently of one another or in combination then sieves less than 24 orders (preferably less than 50 orders, preferably less than 65 orders);
B) Polyethylene Glycol is pulverized, crossed the aperture then and sieve less than 24 orders (preferably less than 50 orders, preferably less than 65 orders);
C) make the powder mixes of step a), obtain the electrolyte mixed-powder;
D) make the electrolyte mixed-powder of step c) and the Polyethylene Glycol powder mixes of step b), divide again to install in the packing container; Perhaps the Polyethylene Glycol powder of the electrolyte mixed-powder of step c) and step b) divides successively or simultaneously independently and installs in the packing container, obtains powdered composition.
According to the method for second aspect present invention, it may further comprise the steps:
A) making sodium chloride, potassium chloride, sodium bicarbonate, anhydrous sodium sulfate pulverize separately also cross the aperture sieves less than 24 orders (preferably less than 50 orders, preferably less than 65 orders);
B) Polyethylene Glycol is pulverized, crossed the aperture then and sieve less than 24 orders (preferably less than 50 orders, preferably less than 65 orders);
C) powder of step a) is mixed by the prescription proportioning, obtain the electrolyte mixed-powder;
D) make the electrolyte mixed-powder of step c) and the Polyethylene Glycol powder mixes of step b), divide again to install in the packing container, obtain powdered composition.
According to the method for second aspect present invention, it may further comprise the steps:
A) making sodium chloride, potassium chloride, sodium bicarbonate, anhydrous sodium sulfate pulverize separately also cross the aperture sieves less than 24 orders (preferably less than 50 orders, preferably less than 65 orders);
B) Polyethylene Glycol is pulverized, crossed the aperture then and sieve less than 24 orders (preferably less than 50 orders, preferably less than 65 orders);
C) powder of step a) is mixed by the prescription proportioning, obtain the electrolyte mixed-powder;
D) the Polyethylene Glycol powder of electrolyte mixed-powder and the step b) of step c) is divided independently successively or simultaneously and install in the packing container, obtain powdered composition.
Arbitrary technical characterictic that arbitrary embodiment had of the arbitrary aspect of the present invention or this arbitrary aspect is suitable for arbitrary embodiment of other arbitrary embodiment or other arbitrary aspect equally; As long as they can be not conflicting; Certainly at where applicable each other, necessary words can be done suitably to modify to individual features.Do further to describe with characteristics to various aspects of the present invention below.
All documents that the present invention quoted from, their full content is incorporated this paper by reference into, and if the expressed implication of these documents and the present invention when inconsistent, be as the criterion with statement of the present invention.In addition; Various terms and phrase that the present invention uses have the general sense of well known to a person skilled in the art; Nonetheless; The present invention still hopes at this more detailed explanation and explanation to be done in these terms and phrase, and term of mentioning and phrase are as the criterion with the implication that the present invention was explained if any inconsistent with known implication.
Further describe to various aspects of the present invention below.
In the present invention, as do not have other explanation, % is the percent of w/w.
In the present invention, expression screen cloth specification can be used order, is for example put down in writing in two notes on the use of version Chinese Pharmacopoeia in 2010, and for example 65 orders are corresponding to No. four sieves, and its sieve aperture internal diameter meansigma methods is 250 μ m ± 9.9 μ m.
In the present invention, in the every 100g powder of phrase " powder body more than 90% can pass through 65 eye mesh screens " expression, have the above powder of 90g can pass through 65 eye mesh screens, promptly the particle diameter of the powder more than the 90g is less than 250 μ m.
In the present invention; The term " nominal molecular weight " that is used to modify Polyethylene Glycol is meant the molecular weight of expression PEG molecular weight specification or model; Two the 1243rd page of kinds of recording " Macrogol 4000 " of Pharmacopoeia of People's Republic of China version in 2010 for example, wherein 4000 be Polyethylene Glycol " nominal molecular weight ".Need to prove that above-mentioned nominal molecular weight is different with the mean molecule quantity with the Polyethylene Glycol of the method for the invention practical measurement.
The Polyethylene Glycol that uses in the present invention has specific mean molecule quantity, for example has 2600 ~ 3400 mean molecule quantity, preferably has 2600 ~ 3200 mean molecule quantity.This mean molecule quantity can be to measure according to following method: the about 12.5g of taking polyethylene glycol test sample, and accurate the title, decide, and puts in the withstand voltage conical flask of exsiccant 200ml tool plug; Add pyridine 25ml, heating makes dissolving, puts cold; The pyridine solution of accurate adding phthalic anhydride (get phthalic anhydride 14g, be dissolved among the anhydrous pyridine 100ml, spend the night by placement; Subsequent use) 25ml, shake up, put in 98 ± 2 ℃ of boiling water baths; Heated 30～60 minutes, and took out cooling, accurate sodium hydroxide volumetric solution (0.5mol/L) 50ml that adds; Pyridine solution (1 → 100) with phenolphthalein is an indicator, extremely shows red with sodium hydroxide volumetric solution (0.5mol/L) titration, and titrating result is proofreaied and correct with blank assay.Supply the product of examination amount (g) and 4000,, promptly get the mean molecule quantity of test sample divided by the volume (ml) of (in the titration process) hydrogen consuming sodium oxide volumetric solution (0.5mol/L).
In the present composition, having most of material is Polyethylene Glycol (Polyethylene Glycol account for composition total weight 86%); And a little is weakly alkaline sodium bicarbonate titration measuring PEG molecular weight is not had influence (through calculating, the deviation that method is measured result's influence is less than 1%) basically.Therefore, the present composition is measured through titration method described herein, still can effectively characterize the wherein characteristic of PEG molecular weight.Because the weight effect of other material in the present composition, the effect positive divisor of weight effect is between 1.129 ~ 1.194 on average, typically is 1.162.Can be similar to the PEG molecular weight determination at the present composition, said composition has the typical PEG of a correction molecular weight after imitating positive divisor calculating, has defined " proofreading and correct the PEG molecular weight " of the present invention thus for this reason.
Thus, the present composition has specific correction PEG molecular weight, and particularly, the present composition has 2600 ~ 3400 correction PEG molecular weight, preferably has 2600 ~ 3400 correction PEG molecular weight.This correction PEG molecular weight can shine following method mensuration:
Get the about 12.5g of present composition test sample (M, unit is gram), the accurate title, decide, and puts in the withstand voltage conical flask of exsiccant 200ml tool plug; Add pyridine 25ml, heating makes dissolving, puts coldly, and the accurate pyridine solution that adds phthalic anhydride (is got phthalic anhydride 14g; Be dissolved among the anhydrous pyridine 100ml, placement is spent the night, and is subsequent use) 25ml, shake up; Put in 98 ± 2 ℃ of boiling water baths, heated 30～60 minutes, take out cooling; Accurate sodium hydroxide volumetric solution (0.5mol/L) 50ml that adds be an indicator with the pyridine solution (1 → 100) of phenolphthalein, with sodium hydroxide volumetric solution (0.5mol/L) titration to apparent redness; Read the volume (V, unit are milliliter) of the sodium hydroxide volumetric solution that consumes in this titration process, and titrating result is proofreaied and correct with blank assay.Correction PEG molecular weight with computes present composition test sample:
For example f is the value between 1.129 ~ 1.194, for example f=1.162.
In the present invention, used Polyethylene Glycol has used many decades at pharmaceutical industry, and extensive stock product and production technology are well known to those skilled in the art.The used Polyethylene Glycol of the present invention can be that commerce is buied, and can also synthesize according to those skilled in the art's existing knowledge, perhaps can synthesize with reference to prior art.For example, in the Polyethylene Glycol of the different size that each version Chinese Pharmacopoeia records, put down in writing its preparation method, for example through forming with oxirane and water polycondensation.Again for example; CN1890291A discloses preparation and has had the low formaldehyde content Polyethylene Glycol; Although only instantiation is provided in this patent documentation with preparation molecular weight about 200; Yet it will be apparent to those skilled in the art that the Polyethylene Glycol that can easily prepare desired molecular weight through the inventory that changes oxirane.Again for example, Zhao Zhexun (preparation of Polyethylene Glycol and application thereof, Tianjin Business College journal; 1993,13 (1): 18-21) a kind of method of synthesizing polyethylene glycol is disclosed, specific as follows: in the rustless steel autoclave; The solid base that adds ethylene glycol and pulverizing earlier, stirring and dissolving, heat temperature raising; Vacuum dehydration, water all takes off to the greatest extent in the time of 120 ℃, and time nitrogen makes up the number.After guaranteeing the interior no air of still, feed oxirane, be incubated 130 ~ 135 ℃, pressure 0.5 ~ 0.8MPa reacts.(synthetic different molecular weight polyethylene glycol has different proportional quantities) stops to feed (10 ~ 12 hours feeding time) when reaching proportional quantity Deng the amount of ethylene oxide that feeds, and the still internal pressure is landed automatically.Near normal pressure the time, be cooled to 100 ~ 110 ℃, add acetic acid under stirring and be neutralized to neutrality, discharging gets finished product.In addition; The Yu Jiankun of Liming chemical Inst of the Ministry of Chemical Industry (Luoyang) at its document (with the research of alkaline-earth metal catalyst synthesizing polyethylene glycol; Surfactant industry; 1994 the 4th phases, 38-42 page or leaf) a kind of synthetic method with PEG of Narrow Molecular Weight Distribution is disclosed in, specific as follows: as in the flask of 250ml, to add accurately 8 hydronium(ion) oxidation boron (Ba (OH) of metering
28H
2O) with in advance through double distilled diglycol, on the magnetic agitation heater in 90 ℃ oil bath evacuation dehydration 2 hours, weigh after the cooling, add the phosphoric acid (H of metering
3PO), vacuum dehydration is 1 hour again, till reaching theoretical water removal with the metering of decrement method.While hot the initiator that makes is added in the 3L control still, under stirring, be warming up to 100 ℃, fill nitrogen behind the evacuation; Repeatedly more than three times with air in the Ex-all still; Keep still internal pressure 0.25 ~ 0.5MPa, begin to drip the oxirane of handling through full gear (annotate: its consumption can suitably be adjusted according to the Polyethylene Glycol finished product molecular weight of desired design), in time remove the reaction liberated heat with recirculated cooling water; Control reaction temperature is no more than 120 ℃, adds up to the oxirane that measures.Be warming up to 130 ℃, reacted again 1 hour, cooling, evacuation, blowing.Aqueous sulfuric acid with 0.5% is neutralized to and is neutral, and heating and ageing are filtered, section, and packing promptly gets the Polyethylene Glycol finished product.In the specific embodiment of hereinafter of the present invention; As do not indicate in addition; Used Polyethylene Glycol is basically with reference to sword elder brother disclosed method and the suitable adjustment process parameter Polyethylene Glycol that obtains of oxirane ratio particularly; It has concrete indicated mean molecule quantity according to the present invention's titration measuring mentioned above, in preparing process, has also used for reference the content of formaldehyde in the method that CN1890291A the put down in writing reduction end-product.
In the present invention; Phrase " each material is through pulverize or pulverize through two or more combinations arbitrarily independently of one another; and cross the aperture less than 24 orders (preferably less than 50 orders; preferably less than 65 orders) sieve ", represent that various materials can pulverize separately individually, also can be wherein any two kinds perhaps more kinds of mixing pulverize; Or to sieve respectively behind the pulverize separately separately, also (mix ground) together behind the pulverize separately separately and sieve, any two kinds of perhaps more kinds of mixture that will pulverize again after pulverizing that mix that can also be wherein sieve.
In the present invention; Phrase " is crossed the aperture less than 24 orders (preferably less than 50 orders; preferably less than 65 orders) sieve ", and the expression corresponding powder can be the sieve (preferred powder body can through sieve aperture internal diameter less than 50 orders be internal diameter sieve less than 355 μ ms, preferred powder body can through sieve aperture internal diameter less than 65 orders be internal diameter sieve less than 250 μ ms) of internal diameter less than 850 μ m less than 24 orders through the sieve aperture internal diameter.
In addition; Those skilled in the art know that; Although the impurity in the raw material is to be controlled at low scope as far as possible, however the inventor find, in the used Polyethylene Glycol raw material of the present invention; When its aldehyde type impurities when for example content of formaldehyde is lower than 20ppm and particularly is lower than 15ppm, the present composition has beat all pharmaceutical property.Therefore, according to the compositions of first aspect present invention, the content of aldehyde type impurities is lower than 20ppm in the wherein said Polyethylene Glycol raw material, preferably is lower than 15ppm, preferably is lower than 10ppm.In one embodiment, described aldehyde type impurities is a formaldehyde.In one embodiment, said formaldehyde impurity is following mensuration: get PEG raw material test sample 1.00g, the accurate title, decide, and adds 0.6% sodium chromotropate solution 0.25ml; In frozen water, after the cooling, add 5.0ml sulphuric acid, shake up; Left standstill 15 minutes, and slowly quantitatively be transferred in the 25ml measuring bottle that fills 10ml water, put cold; Slowly add water to scale, shake up, as need testing solution; Other gets formaldehyde 0.860g, and accurate the title decides, and puts in the 100ml measuring bottle, and thin up is to scale; Precision is measured 1ml, adds water and quantitatively is diluted to 100ml, and precision is measured 1ml, from " adding 0.6% sodium chromotropate solution 0.25ml "; With the method operation,, be 30ppm as contrast solution; In addition, can suitably reduce the contrast solution of the formaldehyde amount of taking by weighing preparation 25ppm, 20ppm, 15ppm, 10ppm etc.; Get above-mentioned two kinds of solution,, measure absorbance, and use with the blank solution of method operation and proofread and correct in the 567nm wavelength according to ultraviolet visible spectrophotometry (two appendix IVA of Chinese Pharmacopoeia version in 2010); The need testing solution absorbance is lower than a certain concentration contrast solution, and promptly the formaldehyde amount is lower than the corresponding content of formaldehyde of this contrast solution in this test sample.When for example the test sample absorbance was lower than the contrast solution of preparing with 0.860g formaldehyde, content of formaldehyde in the test sample (FC) promptly was lower than 30ppm.
In addition; The inventor finds; Although add 10% ~ 15% the electrolyte except that Polyethylene Glycol of having an appointment in the present composition; Yet deduct these electrolytical qualitative factors, the weight effect factor promptly mentioned above or correction factor or weight correction factor f value, compositions of the present invention and its PEG raw material have suitable content of formaldehyde.Be that the present composition can and be considered the f value with reference to the method for PEG raw material, can record the inherent specific content of formaldehyde of said composition, can be described as the correction content of formaldehyde (cFC) of compositions in the present invention.In the present invention, content of formaldehyde can be represented by english abbreviation FC, proofreaies and correct content of formaldehyde and can represent with english abbreviation cFC.
According to the compositions of first aspect present invention, it has the correction content of formaldehyde that is lower than 20ppm, preferably has the correction content of formaldehyde that is lower than 15ppm, preferably has the correction content of formaldehyde that is lower than 10ppm.This correction content of formaldehyde is following mensuration:
Get that present composition test sample is an amount of (to be same as f * 1.00g) approximately, accurately to claim surely, add 0.6% sodium chromotropate solution 0.25ml; In frozen water, after the cooling, add 5.0ml sulphuric acid, shake up; Left standstill 15 minutes, and slowly quantitatively be transferred in the 25ml measuring bottle that fills 10ml water, put cold; Slowly add water to scale, shake up, as need testing solution; Other gets formaldehyde 0.860g, and accurate the title decides, and puts in the 100ml measuring bottle, and thin up is to scale; Precision is measured 1ml, adds water and quantitatively is diluted to 100ml, and precision is measured 1ml, from " adding 0.6% sodium chromotropate solution 0.25ml "; With the method operation,, be 30ppm as contrast solution; In addition, can suitably reduce the contrast solution of the formaldehyde amount of taking by weighing preparation 25ppm, 20ppm, 15ppm, 10ppm etc.; Get above-mentioned two kinds of solution,, measure absorbance, and use with the blank solution of method operation and proofread and correct in the 567nm wavelength according to ultraviolet visible spectrophotometry (two appendix IV of Chinese Pharmacopoeia version in 2010 A); The need testing solution absorbance is lower than a certain concentration contrast solution, and promptly the formaldehyde amount is lower than the corresponding content of formaldehyde of this contrast solution in this test sample.When for example the test sample absorbance was lower than the contrast solution of preparing with 0.860g formaldehyde, content of formaldehyde in the test sample (FC) promptly was lower than 30ppm.F such as according to the invention wherein.The inventor finds that other electrolytical existence in the compositions does not influence the mensuration of compositions content of formaldehyde.
In the present invention, the Polyethylene Glycol of use and sodium chloride, potassium chloride, sodium bicarbonate, anhydrous sodium sulfate and other optional material be powdered flavor, aspartame etc. for example, and they are food stage independently of one another; Preferably, they are pharmaceutical grade independently of one another.In addition, these materials can be homemade, also can buy from market, and the above-mentioned material with pharmaceutical grade that food reaches all can easily be buied from market.
Although the present invention is to provide a kind of pulverous compositions, it can be called powder in some embodiments.Yet preferably; Powdered composition of the present invention is wrapped with unit dosage form (for example 1,1/2,1/3,1/4 times of amount of each consumption) or is encapsulated in packing container; For example in the containers such as plastic bottle, vial, plastic bag, aluminium foil bag; Particularly preferably be wrapped or be encapsulated in the plastic bag, aluminium foil bag of types such as polyester, polyethylene, more particularly preferably be wrapped or be encapsulated in the aluminium foil bag.The compound membrane bag of being processed by composite that has at a distance from wet trapping of extensive stockization also is preferred.
In one embodiment of the invention; The polyethylene glycol electrolytes that provides loose to be by the method preparation of following steps: two kinds of chlorates, a kind of carbonate and a kind of sulfate and other the optional flavoring agent except that Polyethylene Glycol and/or sweeting agent mixing are obtained the inorganic salt raw material mixture, again with inorganic salt raw material mixture and Polyethylene Glycol PEG with two charging utensils respectively the charging branch install in the packaging bag.
The inventor finds that the compositions with special formulation of the present invention has like beat all effect of the present invention.
The specific embodiment
Further specify the present invention through concrete embodiment/experimental example below, still, be to be understood that into, these embodiment and experimental example are only used for the usefulness of explanation more in detail particularly, are used for limiting in any form the present invention and should not be construed as.
The present invention carries out generality and/or concrete description to the material and the test method that are used in the test.Though for realizing that employed many materials of the object of the invention and operational approach are well known in the art, the present invention still does to describe in detail as far as possible at this.It will be apparent to those skilled in the art that hereinafter, if do not specify that material therefor of the present invention and operational approach are well known in the art.
In the compositions that obtains below, can be with plastic bag or aluminium foil bag sealing, the amount of every bag of packing does not receive special restriction, can be the 20-200 gram in the PEG amount for example.As do not have other explanation, and the compositions that below obtains seals with aluminium foil bag, and the amount of every bag of packing can be 60.00 grams in the PEG amount.Among the embodiment, the mean molecule quantity that raw materials used Polyethylene Glycol indicated (Mr) obtains according to titration measuring mentioned above hereinafter.In the instance, prepared compositions has the correction PEG molecular weight (cMr) that is indicated through titration measuring mentioned above hereinafter.
Embodiment 1: prepare compositions of the present invention
Prescription (preparing) in every batch of total material 10kg:
| Polyethylene Glycol (Mr=3050, HV=55) | 6000 parts, |
| Sodium chloride | 155 parts, |
| Potassium chloride | 80 parts, |
| Sodium bicarbonate | 165 parts, |
| Anhydrous sodium sulfate | 570 parts, |
Method for making: 50 mesh sieves are pulverized and crossed to Polyethylene Glycol, and all the other each material pulverize separately are also crossed 65 mesh sieves, and 40-45 ℃ dry 2 hours down; With sodium chloride, potassium chloride, sodium bicarbonate, anhydrous sodium sulfate mix homogeneously, obtain electrolyte mixture; Again this electrolyte mixture and Polyethylene Glycol are gone up through equivalent incremental method mix homogeneously basically, obtained compositions of the present invention, encapsulation.
Embodiment 2: prepare compositions of the present invention
Prescription (preparing) in every batch of total material 10kg:
| Polyethylene Glycol (Mr=2800, HV=59) | 6000 parts, |
| Sodium chloride | 148 parts, |
| Potassium chloride | 75 parts, |
| Sodium bicarbonate | 171 parts, |
| Anhydrous sodium sulfate | 577 parts, |
Method for making: with embodiment 1.
Embodiment 3: prepare compositions of the present invention
Prescription (preparing) in every batch of total material 10kg:
| Polyethylene Glycol (Mr=3100, HV=53) | 6000 parts, |
| Sodium chloride | 140 parts, |
| Potassium chloride | 70 parts, |
| Sodium bicarbonate | 175 parts, |
| Anhydrous sodium sulfate | 585 parts, |
Method for making: will mix and obtain the inorganic salt raw material mixture through pulverizing and cross 80 purpose sodium chloride, potassium chloride, sodium bicarbonate, anhydrous sodium sulfate; Again with the inorganic salt raw material mixture with through pulverizing and cross 65 purpose Polyethylene Glycol PEG with the charging respectively of two feed hoppers; Be packaged in the packaging bag, promptly get.
Embodiment 4: prepare compositions of the present invention
Prescription (preparing) in every batch of total material 10kg:
| Polyethylene Glycol (Mr=2600, HV=65) | 6000 parts, |
| Sodium chloride | 118 parts, |
| Potassium chloride | 90 parts, |
| Sodium bicarbonate | 137 parts, |
| Anhydrous sodium sulfate | 692 parts, |
Method for making: with embodiment 1, the compositions that obtains is Powdered.This powdered composition can further be processed graininess, perhaps can be by Powdered through adding the graininess that binding agent or wetting agent are processed, and perhaps can be by forms such as bulk Powdered or that graininess is pressed into.
Embodiment 5: prepare compositions of the present invention
Prescription (preparing) in every batch of total material 10kg:
Method for making: with embodiment 1, obtain mixture of powders, it can be used for following test.In addition, this mixture of powders is granulated with 90% ethanol moistening, drying obtains can be described as the finished medicament of granule, and the particle of this granule more than 90% can pass through 24 mesh sieves.
Embodiment 6: prepare compositions of the present invention
Prescription (preparing) in every batch of total material 10kg:
Method for making: with embodiment 3.
Embodiment 7: prepare compositions of the present invention
Prescription (preparing) in every batch of total material 10kg:
| Polyethylene Glycol (Mr=2950, HV=54) | 6000 parts, |
| Sodium chloride | 133 parts, |
| Potassium chloride | 83 parts, |
| Sodium bicarbonate | 154 parts, |
| Anhydrous sodium sulfate | 635 parts, |
Method for making: with embodiment 1.
More than the compositions of each embodiment preparation, except as otherwise noted, they all are Powdered, the powder body of this powdered composition more than 98% can pass through 24 eye mesh screens, its powder body more than 95% can pass through 50 eye mesh screens.
Below each comparative example prepared and comprised Polyethylene Glycol and electrolytical compositions, said composition is Powdered thing, its powder body more than 95% can pass through 50 eye mesh screens:
Comparative example 1: except the Polyethylene Glycol Mr=3500 that uses in the prescription, outside the HV=42, other is with embodiment 2.
Comparative example 2: except the Polyethylene Glycol Mr=3850 that uses in the prescription, outside the HV=40, other is with embodiment 2.
Comparative example 3: except the Polyethylene Glycol Mr=4350 that uses in the prescription, outside the HV=35, other is with embodiment 2.
Comparative example 4: except the Polyethylene Glycol Mr=2400 that uses in the prescription, outside the HV=68, other is with embodiment 2.
Comparative example 5: except the Polyethylene Glycol Mr=2150 that uses in the prescription, outside the HV=71, other is with embodiment 2.
Comparative example 6: except the Polyethylene Glycol Mr=1850 that uses in the prescription, outside the HV=75, other is with embodiment 2.
Comparative example 7: except the Polyethylene Glycol Mr=3600 that uses in the prescription, outside the HV=41, other is with embodiment 6.
Comparative example 8: except the Polyethylene Glycol Mr=2150 that uses in the prescription, outside the HV=71, other is with embodiment 6.
Comparative example 9: except the Polyethylene Glycol Mr=3600 that uses in the prescription, outside the HV=41, other is with embodiment 7.
Comparative example 10: except the Polyethylene Glycol Mr=2150 that uses in the prescription, outside the HV=71, other is with embodiment 7.
Comparative example 11: except the Polyethylene Glycol Mr=3350 that uses in the prescription, outside the HV=50, other is with embodiment 2.
Test Example 1: the stability test of compositions
Each embodiment of preceding text and comparative example preparation, the compound membrane bag with gas and wet favorable sealing property packs respectively, and every packed amount is counted 60g with Polyethylene Glycol.Each sample is placed August in 42 ℃ calorstat, measure the bicarbonate radical percent change that each compositions is compared during with high-temperature treatment not behind high-temperature treatment, calculating formula is following:
The content assaying method of bicarbonate radical in compositions is following:
Get compositions test sample an amount of (comprising the about 60g of PEG), the accurate title, decide, and puts in the 1000ml measuring bottle, is dissolved in water, and is diluted to scale, shakes up, as need testing solution; Accurate to draw above-mentioned solution 100ml, put in the conical flask, methylate is red-and bromocresol green mixes 10 of indicator solutions; Is dark violet redness with hydrochloric acid volumetric solution (0.1mol/L) titration to solution by green transition; Boiled 2 minutes, and be cooled to room temperature, continue titration to solution and become mulberry by green.Every 1ml hydrochloric acid volumetric solution (0.1mol/L) is equivalent to the HCO of 6.102mg
3The percentage composition of bicarbonate radical in the calculation composition thus.
The result shows, places after 8 months for 42 ℃, and all between 97.5% ~ 101.7%, for example the bicarbonate radical percent change of embodiment 1,2,3 each compositions is respectively 99.6%, 98.2%, 99.3% to the bicarbonate radical percent change of each example composition; And the bicarbonate radical percent change of comparative example 1,2,3,7,9,11 compositionss is all between 88.6% ~ 94.8%, and for example the bicarbonate radical percent change of comparative example 1,2,3 each compositions is respectively 89.5%, 94.8%, 91.5%.The bicarbonate radical percent change of comparative example 4,5,6,8,10 compositionss is all between 96.6% ~ 99.8%.The inventor in other test, according to the method for embodiment 4 prepare compositions (Mr=2630 of synthetic PEG wherein, HV=72); Obtain comparative example 12 compositionss; (wherein the Mr=3380 of synthetic PEG HV=41), obtains comparative example 13 compositionss also to prepare compositions according to the method for embodiment 6.After 8 months, the bicarbonate radical percent change is respectively 92.6% and 93.9% to the same method of compositions of comparative example 12 and comparative example 13 42 ℃ of placements.
The PEG raw material that in above each embodiment and comparative example, uses, and by the compositions of its preparation, these PEG raw materials and compositions be through measuring, content of formaldehyde wherein all at 5ppm with below 10.0ppm.Through measuring; These samples 42 ℃ place 8 months after; Compare with sample without high-temperature treatment; The PEG molecular weight is constant basically or little reduction arranged, and PEG molecular weight percent change is in 98% ~ 101% scope (PEG molecular weight percent change is 42 ℃ and places 8 months sample molecular weight multiply by 100% gained divided by high-temperature process molecular weight analyte not value) all.In four other tests; Use prescription and the PEG performance identical with embodiment 2; The different PEG that is to use the different batches preparation; Content of formaldehyde wherein is 17.5ppm ~ 20ppm, 20ppm ~ 22.5ppm, 22.5ppm ~ 25ppm, 25ppm ~ 27.5ppm, obtains four and comprises PEG and electrolytical compositions; Unexpectedly find; Carry out 42 ℃ equally and place test in 8 months; The bicarbonate radical percent change of these four compositionss is between 84.8% ~ 90.3% (the bicarbonate radical percent change is 42 ℃ and places 8 months sample bicarbonate radical amounts multiply by 100% gained divided by high-temperature process sample bicarbonate radical amount not value) all; PEG molecular weight percent change particularly unexpectedly finds all in 83% ~ 89% scope, and more greatly then bicarbonate radical and the variation of PEG molecular weight be more greatly for content of formaldehyde.
Test Example 2: intestinal cleans clinical experimental study
The present invention uses the some compsns of preceding text preparation to carry out clinical trial.Every kind of reagent is arranged 20 ~ 24 adult male volunteers as a test group.Reagent: embodiment 1, embodiment 4 and embodiment 6 gained powder compositions; Comparative example 4, comparative example 5, comparative example 6, comparative example 8 and comparative example 10 gained powder compositions.Reagent compound method: get powder an amount of (PEG that wherein comprises is equivalent to 60g), be mixed with 1 liter solution with water dissolution.Usage and dosage: the about 2-4 liter of amount of being grown up 1 time, oral with per 1 hour about speed of 1 liter,, discharge liquor can finish administration when becoming transparency liquid; Total dosage can not be above 4 liters.A situation arises for the total effective rate of statistics different tests group and untoward reaction.The result shows: all between 95 ~ 100%, for example the total effective rate of embodiment 1 is 97.1% to the total effective rate of embodiment 1, embodiment 4,6 three test group of embodiment; The total effective rate 84.8% of comparative example 4, the total effective rate of comparative example 5, comparative example 8 and comparative example 10 is respectively 68.8%, 69.7% and 70.6%, and the total effective rate of comparative example 6 is 18.7%.Here, in the clinical trial that the polyethylene glycol electrolytes compositions of the PEG of the specific mean molecule quantity of the present invention preparation is carried out, it not only has good intestinal cleaning action, and does not demonstrate any side effect; Yet, show that unexpectedly the untoward reaction of 1-2 example vomiting all appears in each comparative example group, and 6 groups of untoward reaction that a routine creeping chill also occurs of comparative example.
Test Example 3: the physicochemical property of the test present composition
Use the mean molecule quantity algoscopy of Polyethylene Glycol mentioned above, and the correction PEG molecular weight determination method that is used for compositions, the mean molecule quantity of raw material PEG used in each embodiment or the comparative example and the correction PEG molecular weight of each compositions measured respectively.Use Polyethylene Glycol hydroxy value measuring method mentioned above, and the correction hydroxy value measuring method that is used for compositions, the hydroxyl value of raw material PEG used in each embodiment or the comparative example and the correction hydroxyl value of each compositions measured respectively.The result shows; Compositions for each embodiment and comparative example; It is proofreaied and correct the percent of PEG molecular weight for the mean molecule quantity of its raw material PEG and between 97 ~ 103%, (promptly proofreaies and correct the mean molecule quantity of PEG molecular weight divided by its raw material PEG, multiply by 100% again, the value of gained); For example the Mr of the raw material PEG of embodiment 1 is 3050, and the cMr of its compositions is 3070; The result also shows; Compositions for each embodiment and comparative example; It is proofreaied and correct the percent of hydroxyl value for its raw material PEG hydroxyl value and also between 97 ~ 103%, (promptly proofreaies and correct hydroxyl value divided by its raw material PEG hydroxyl value, multiply by 100% again, the value of gained); For example the hydroxyl value of the raw material PEG of embodiment 1 is 55, and the correction hydroxyl value of its compositions is 54.It is less to be illustrated in two kinds of molecular weight in preparation compositions front and back and hydroxyl value difference, promptly can reflect for example PEG kind of the used raw material type of preparation of compositions through the compositions as end product.In addition, use the content of formaldehyde algoscopy of Polyethylene Glycol mentioned above, and the correction content of formaldehyde algoscopy that is used for compositions, the content of formaldehyde of raw material PEG used in each embodiment or the comparative example and the correction content of formaldehyde of each compositions measured respectively.The result shows that for the compositions of each embodiment and comparative example, it proofreaies and correct the percent of content of formaldehyde for its raw material PEG content of formaldehyde between 98 ~ 103%.
Claims (10)
1. comprise Polyethylene Glycol and electrolytical compositions, comprise following component in the said composition: Polyethylene Glycol, sodium chloride, potassium chloride, sodium bicarbonate, anhydrous sodium sulfate.
2. according to the compositions of claim 1, in the Polyethylene Glycol of per 6000 weight portions, wherein:
The amount of sodium chloride is 118-178 part;
The amount of potassium chloride is 60-90 part;
The amount of sodium bicarbonate is 137-205 part; And/or
The amount of anhydrous sodium sulfate is 461-692 part.
3. according to each compositions of claim 1 to 2, wherein comprise the component of following weight portion:
Perhaps, the component that wherein comprises following weight portion:
Perhaps, the component that wherein comprises following weight portion:
Perhaps, the component that wherein comprises following weight portion:
Perhaps, the component that wherein comprises following weight portion:
4. according to each compositions of claim 1 to 3, wherein said Polyethylene Glycol has 2600 ~ 3400 mean molecule quantity.
5. according to each compositions of claim 1 to 4, it has 2600 ~ 3400 correction PEG molecular weight; Further, this correction PEG molecular weight is following mensuration:
Get the about 12.5g of compositions test sample (M, unit is gram), the accurate title, decide, and puts in the withstand voltage conical flask of exsiccant 200ml tool plug; Add pyridine 25ml, heating makes dissolving, puts coldly, and the accurate pyridine solution that adds phthalic anhydride (is got phthalic anhydride 14g; Be dissolved among the anhydrous pyridine 100ml, placement is spent the night, and is subsequent use) 25ml, shake up; Put in 98 ± 2 ℃ of boiling water baths, heated 30～60 minutes, take out cooling; Accurate sodium hydroxide volumetric solution (0.5mol/L) 50ml that adds be an indicator with the pyridine solution (1 → 100) of phenolphthalein, with sodium hydroxide volumetric solution (0.5mol/L) titration to apparent redness; Read the volume (V, unit are milliliter) of the sodium hydroxide volumetric solution that consumes in this titration process, and titrating result is proofreaied and correct with blank assay; Calculate the correction PEG molecular weight of present composition test sample with following formula (I):
In the formula (I), f is the value of composition total weight divided by the weight gained of contained Polyethylene Glycol in the compositions.
6. according to each compositions of claim 1 to 5, its:
Powder body more than 90% can pass through 24 eye mesh screens;
Powder body more than 90% can pass through 50 eye mesh screens;
Powder body more than 90% can pass through 65 eye mesh screens; And/or
Powder body more than 90% can pass through 80 eye mesh screens.
7. according to each compositions of claim 1 to 6, its:
Be each material through pulverizing independently of one another or pulverize through two or more combinations arbitrarily, and cross the aperture less than 24 mesh sieves after, through randomly mixing the powdered composition that obtains;
Can also comprise flavoring agent, for example the powdered flavor of various fragrance;
Can also comprise sweeting agent, for example aspartame, sucralose, acesulfame potassium.
8. according to each compositions of claim 1 to 7, it is pharmaceutical preparation; In one embodiment, it is medicine types such as powder, granule, tablet.
9. prepare each said method for compositions of claim 1 to 8; It may further comprise the steps: make each material through pulverizing independently of one another or pulverizing through any two or more combinations; And cross the aperture less than 24 mesh sieves after, through randomly mixing, obtain powdered composition.
10. prepare each said method for compositions of claim 1 to 8, it may further comprise the steps:
Each material is pulverized perhaps through is independently of one another pulverized through any two or more combinations,
Material through pulverizing is crossed the aperture less than 24 mesh sieves,
Randomly the material to each pulverizing mixes,
Mixing or unmixing each material are joined in the packing container independently or together, obtain powdered composition;
Perhaps, it may further comprise the steps:
A) sodium chloride, potassium chloride, sodium bicarbonate, anhydrous sodium sulfate are pulverized independently of one another, any two or more combinations in them are pulverized, cross the aperture less than 24 mesh sieves independently of one another or in combination then;
B) Polyethylene Glycol is pulverized, crossed the aperture then less than 24 mesh sieves;
C) make the powder mixes of step a), obtain the electrolyte mixed-powder;
D) make the electrolyte mixed-powder of step c) and the Polyethylene Glycol powder mixes of step b), divide again to install in the packing container; Perhaps the Polyethylene Glycol powder of the electrolyte mixed-powder of step c) and step b) divides successively or simultaneously independently and installs in the packing container, obtains powdered composition.
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| CN115040484A (en) * | 2022-05-20 | 2022-09-13 | 浙江和沐康医药科技有限公司 | Potassium chloride granules filled with powder directly and preparation method thereof |
| EP4009986A4 (en) * | 2019-08-07 | 2023-08-02 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | POLYETHYLENE GLYCOL POUCH FORMULATION |
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| EP4009986A4 (en) * | 2019-08-07 | 2023-08-02 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | POLYETHYLENE GLYCOL POUCH FORMULATION |
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| CN115040484A (en) * | 2022-05-20 | 2022-09-13 | 浙江和沐康医药科技有限公司 | Potassium chloride granules filled with powder directly and preparation method thereof |
| CN115040484B (en) * | 2022-05-20 | 2023-05-02 | 浙江和沐康医药科技有限公司 | Potassium chloride granules directly filled with powder and preparation method thereof |
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