CN1089236C - Medicinal composition for preventing and curing hypokalemia. - Google Patents
Medicinal composition for preventing and curing hypokalemia. Download PDFInfo
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- CN1089236C CN1089236C CN99100214A CN99100214A CN1089236C CN 1089236 C CN1089236 C CN 1089236C CN 99100214 A CN99100214 A CN 99100214A CN 99100214 A CN99100214 A CN 99100214A CN 1089236 C CN1089236 C CN 1089236C
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- 208000019025 Hypokalemia Diseases 0.000 title claims abstract description 16
- 208000024896 potassium deficiency disease Diseases 0.000 title claims abstract description 13
- 239000000203 mixture Substances 0.000 title abstract description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000001508 potassium citrate Substances 0.000 claims abstract description 10
- 229960002635 potassium citrate Drugs 0.000 claims abstract description 10
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 claims abstract description 10
- 235000011082 potassium citrates Nutrition 0.000 claims abstract description 10
- 235000009508 confectionery Nutrition 0.000 claims abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 50
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 14
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 4
- 239000004375 Dextrin Substances 0.000 claims description 4
- 229920001353 Dextrin Polymers 0.000 claims description 4
- 229920002472 Starch Polymers 0.000 claims description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 4
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 4
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 4
- 229940109275 cyclamate Drugs 0.000 claims description 4
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 claims description 4
- 235000019425 dextrin Nutrition 0.000 claims description 4
- 239000008107 starch Substances 0.000 claims description 4
- 235000019698 starch Nutrition 0.000 claims description 4
- 108010011485 Aspartame Proteins 0.000 claims description 3
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 claims description 3
- 239000000605 aspartame Substances 0.000 claims description 3
- 235000010357 aspartame Nutrition 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
- 229960003438 aspartame Drugs 0.000 claims description 3
- 239000001856 Ethyl cellulose Substances 0.000 claims description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- KPQJOKRSYYJJEL-VLQRKCJKSA-K [Na+].[Na+].CC1(C)[C@H](CC[C@@]2(C)[C@H]1CC[C@]1(C)[C@@H]2C(=O)C=C2[C@@H]3C[C@](C)(CC[C@]3(C)CC[C@@]12C)C([O-])=O)O[C@H]1O[C@@H]([C@@H](O)[C@H](O)[C@H]1O[C@@H]1O[C@@H]([C@@H](O)[C@H](O)[C@H]1O)C([O-])=O)C([O-])=O Chemical compound [Na+].[Na+].CC1(C)[C@H](CC[C@@]2(C)[C@H]1CC[C@]1(C)[C@@H]2C(=O)C=C2[C@@H]3C[C@](C)(CC[C@]3(C)CC[C@@]12C)C([O-])=O)O[C@H]1O[C@@H]([C@@H](O)[C@H](O)[C@H]1O[C@@H]1O[C@@H]([C@@H](O)[C@H](O)[C@H]1O)C([O-])=O)C([O-])=O KPQJOKRSYYJJEL-VLQRKCJKSA-K 0.000 claims description 2
- 229920001249 ethyl cellulose Polymers 0.000 claims description 2
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 235000010981 methylcellulose Nutrition 0.000 claims description 2
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 2
- 239000000811 xylitol Substances 0.000 claims description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
- 235000010447 xylitol Nutrition 0.000 claims description 2
- 229960002675 xylitol Drugs 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 abstract description 30
- 229960003975 potassium Drugs 0.000 abstract description 16
- 239000011591 potassium Substances 0.000 abstract description 16
- 229910052700 potassium Inorganic materials 0.000 abstract description 16
- 238000002474 experimental method Methods 0.000 abstract description 15
- 239000000796 flavoring agent Substances 0.000 abstract description 7
- 235000019634 flavors Nutrition 0.000 abstract description 7
- 230000004936 stimulating effect Effects 0.000 abstract description 2
- 230000001502 supplementing effect Effects 0.000 abstract 2
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 238000009472 formulation Methods 0.000 abstract 1
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract 1
- 230000007721 medicinal effect Effects 0.000 abstract 1
- 230000002110 toxicologic effect Effects 0.000 abstract 1
- 231100000027 toxicology Toxicity 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 37
- 229940079593 drug Drugs 0.000 description 29
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical class [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 27
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 16
- 241000700159 Rattus Species 0.000 description 13
- 229960003883 furosemide Drugs 0.000 description 13
- 210000002966 serum Anatomy 0.000 description 12
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- 230000000694 effects Effects 0.000 description 9
- 241001465754 Metazoa Species 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000001103 potassium chloride Substances 0.000 description 6
- 235000011164 potassium chloride Nutrition 0.000 description 6
- 230000002159 abnormal effect Effects 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 208000007645 potassium deficiency Diseases 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 3
- 239000000470 constituent Substances 0.000 description 3
- 230000003203 everyday effect Effects 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000002483 medication Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 206010067484 Adverse reaction Diseases 0.000 description 2
- 206010053155 Epigastric discomfort Diseases 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 230000006838 adverse reaction Effects 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 239000013256 coordination polymer Substances 0.000 description 2
- 206010061428 decreased appetite Diseases 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 238000012449 Kunming mouse Methods 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000005374 Poisoning Diseases 0.000 description 1
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
- 208000001431 Psychomotor Agitation Diseases 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 235000019636 bitter flavor Nutrition 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- 150000001875 compounds Chemical group 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 229940083558 furosemide 20 mg Drugs 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000012155 injection solvent Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- SPRBJFWIUVWXBT-UHFFFAOYSA-K tripotassium 2-hydroxypropane-1,2,3-tricarboxylate 2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [K+].[K+].[K+].OC(=O)CC(O)(C(O)=O)CC(O)=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O SPRBJFWIUVWXBT-UHFFFAOYSA-K 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
- 210000004916 vomit Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The present invention relates to a medicinal composition for preventing and curing hypokalemia, which comprises 70 to 86.5 wt% of potassium citrate, 8 to 24.5 wt% of citric acid and 0.5 to 5 wt% of flavor correcting agent. The medicinal composition of the present invention is a granular formulation. Proved by a medicinal effect test and a toxicological test, the medicinal composition of the present invention has reliable potassium supplementing action; proved by a clinical experiment, the medicinal composition of the present invention has the advantages of cool and sweet flavor, daintiness, no salty or harsh flavor, no stimulating action on the gastrointestinal tract and good potassium supplementing effect.
Description
The present invention relates to a kind of pharmaceutical composition, particularly relate to a kind of pharmaceutical composition that contains the control hypokalemia of potassium citrate.
Potassium deficiency is clinical ubiquitous phenomenon, and potassium deficiency can lead to grave consequences.Correct the potassium deficiency phenomenon, except that active treatment causes the protopathy of potassium deficiency and recovers patient's the normal diet the additional potassium salt of normal need as early as possible.And the kalium replenishment mode is with oral the most convenient and safety.At present, clinical oral kalium replenishment medicine commonly used is potassium chloride class and organic acid potassium.Wherein, potassium chloride class kalium replenishment medicine not only has salty and bitter abnormal flavour sense, and the stimulating gastrointestinal road.And simple organic acid potassium kalium replenishment medicine stimulates corrosiveness though can improve to gastrointestinal, and mouthfeel is poor, and salty and bitter abnormal flavour is also arranged, and patient is difficult to accept.
The object of the present invention is to provide a kind of no salty and bitter flavor, fresh and sweet tasty and refreshing, do not stimulate and corrode gastrointestinal kalium replenishment pharmaceutical composition.
The invention provides a kind of pharmaceutical composition that contains the control hypokalemia of potassium citrate.In the prescription of said composition, effective ingredient and weight percentage ranges thereof are:
Potassium citrate 70-86.5%
Citric acid 8-24.5%
Correctives 0.5-5%;
Its preferred weight percent scope is:
Potassium citrate 72-81%
Citric acid 15.5-22%
Correctives 1.5-3.5%;
Its optimum weight percentage ratio is:
Potassium citrate 73%
Citric acid 17%
Correctives 2%
The correctives that the present invention uses is: steviosin, fragrant and sweet element, sucrose, disodium glycyrrhizinate, cyclamate, xylitol, aspartame etc.
Also contain excipient in the pharmaceutical composition of the present invention, the percentage ratio that excipient accounts for composition total weight is 5-21.5%, and preferred weight percent is 7-12%, and optimum weight percentage ratio is 8%.The excipient that the present invention uses can be: dextrin, starch, carboxymethyl cellulose, ethyl cellulose, microcrystalline Cellulose, methylcellulose etc.
The dosage form of pharmaceutical composition of the present invention is a granule.Prepare by following method: potassium citrate, citric acid, correctives and excipient are total to 1000g, take by weighing respectively in proportion, dry back mix homogeneously, pharmaceutical technology is made granule routinely.Be distributed into 500 bags, every bag of 2g.
Each component ratio sees the following form among the embodiment.
Each amounts of components
The effect experiment of pharmaceutical composition of the present invention
| Potassium citrate | Citric acid | Correctives | Excipient | |
| Embodiment 1 | 700g | 80g | The 5g steviosin | The 215g carboxymethyl cellulose |
| Embodiment 2 | 750g | 100g | The fragrant and sweet element of 50g | 100g starch |
| Embodiment 3 | 800g | 90g | The 10g cyclamate | 100g starch |
| Embodiment 4 | 850g | 115g | 5g sucrose | The 30g dextrin |
| Embodiment 5 | 700g | 80g | The 5g cyclamate | The 215g carboxymethyl cellulose |
| Embodiment 6 | 730g | 170g | The 20g aspartame | The 80g dextrin |
Experiment purpose: by observing the influence of the hypokalemia rat blood serum potassium concn that pharmaceutical composition of the present invention causes normal rat and furosemide, proved the kalium replenishment effect of pharmaceutical composition of the present invention, for the clinical research of pharmaceutical composition provides experimental basis
Tested medicine: the granule of making by embodiment 6 proportionings
Positive control medicine: clinical potassium chloride commonly used
Laboratory animal: the Wistar rat, body weight 200-300g, male and female half and half (are purchased the Experimental Animal Center in medicine institute of the Chinese Academy of Medical Sciences, the quality certification number: 9209R018).
Experimental technique and main experimental procedure:
1. pharmaceutical composition of the present invention is to the influence of normal rat blood serum potassium concn:
Get 50 of rats, be divided into 5 groups at random, every group of 10 rats, one group is the excipient matched group, one group is the potassium chloride matched group, in addition three groups of pharmaceutical composition groups of the present invention that are respectively variable concentrations.Behind the rat fasting 12h, press the ig method and use said medicine or normal saline 5ml/kg (consistent) with clinical plan route of administration, before the medication and after the medication 0.5,1,2,4,6h cuts the tail point respectively and gets blood 1-1.5ml, centrifugal 30min (3500r/min), get serum 0.3-0.5ml, measure serum potassium ion concentration with ion selective electrode method, the result represents with X ± SD, analyzes then.
2. the antagonism of the rat hypokalemia that pharmaceutical composition of the present invention causes furosemide:
Get 60 of rats, male and female half and half are divided into 6 groups at random, every group of 10 rats, and these 6 groups are respectively: (i) normal saline (ip)+excipient (ig) group; (ii) furosemide (ip) group+excipient (ig) is organized; (iii) furosemide (ip)+potassium chloride (ig) is organized; (iv, v, vi) furosemide (ip)+pharmaceutical composition of the present invention (low, in, high dose ig) group.Before the experiment, cut tail and get blood 1-1.5ml, measure the preceding serum potassium level of medication, then, ip furosemide 20mg/kg or normal saline, every day 2 times, totally 3 days, injection solvent was 2ml/kg, simultaneously ig potassium chloride 0.10g/kg or pharmaceutical composition of the present invention 0.07,0.14,0.28g/kg or excipient, every day 3 times, totally 3 days, the administration solvent was 5ml/kg, the 4th day, fasting 12h then cuts the tail point and gets blood 1-1.5ml, serum potassium level after the mensuration medication.The assay method of blood treatment mode, serum potassium and result treatment are with 1.
Experimental result
1. pharmaceutical composition of the present invention is to the influence of normal rat blood serum potassium concn
The variation (mmol/L) of the different time serum potassium concentration before and after the medication
Annotate:
*P＜0.05
*P＜0.01 (comparing) with vehicle group
| Group | Excipient | Potassium chloride (0.10g/kg) | Pharmaceutical composition of the present invention (0.07g/kg) | Pharmaceutical composition of the present invention (0.14g/kg) | Pharmaceutical composition of the present invention (0.28g/kg) | |
| Number of animals (only) | 10 | 8 | 8 | 10 | 9 | |
| Before the medication | 4.47±0.25 | 4.56±0.27 | 4.43±0.27 | 4.56±0.21 | 4.42±0.22 | |
| After the medication (h) | 0.5 | -0.02±0.29 | 0.24+0.53 | 0.59±0.41 ** | 0.38±0.25 ** | 0.57±0.26 ** |
| 1 | 0.07±0.24 | 0.64±0.47 * | 0.79±0.38 ** | 0.83±0.29 ** | 1.46±0.33 ** | |
| 2 | -0.09±0.31 | 1.01±0.41 ** | 0.96±0.39 ** | 1.14±0.31 ** | 2.17±0.22 ** | |
| 4 | 0.04±0.39 | 0.04+0.21 | 0.50±0.34 * | 0.35±0.33 | 0.79±0.35 ** | |
| 6 | -0.05±0.32 | -0.06±0.19 | 0.08±0.38 | -0.02±0.29 | 0.07±0.15 | |
2. pharmaceutical composition of the present invention sees the following form to the antagonism of the rat hypokalemia that furosemide causes:
Serum potassium concentration group number of animals serum potassium after the medication
Normal saline+excipient 10 4.59 ± 0.29 4.65 ± 0.22 furosemide+excipient 9 4.63 ± 0.33 2.51 ± 0.61 Δ Δ furosemide+sodium chloride (0.10g/kg), 10 4.47 ± 0.19 4.35+0.18 after the medication before (only) medication
*Furosemide+pharmaceutical composition of the present invention (0.07g/kg) 9 4.41+0.26 3.40 ± 0.14
*Furosemide+pharmaceutical composition of the present invention (0.14g/kg) 10 4.55 ± 0.29 4.28 ± 0.19
*Furosemide+pharmaceutical composition of the present invention (0.28g/kg) 10 4.50 ± 0.36 5.22 ± 0.19
*Annotate:
*P＜0.01 (comparing) with furosemide+vehicle group; Δ Δ p＜0.01 (comparing) with normal saline+vehicle group
Experiment conclusion
The influence of the hypokalemia rat blood serum potassium concn that normal rat and furosemide is caused by research pharmaceutical composition of the present invention, prove that pharmaceutical composition of the present invention has reliable kalium replenishment effect, can be used for the prevention and the treatment of potassium deficiency disease or hypokalemia.The toxicity test of pharmaceutical composition of the present invention
Experiment purpose: observe the toxicity of pharmaceutical composition of the present invention, for data for clinical drug use provides foundation.
Experiment material:
1. medicine: the granule of making by embodiment 6 proportionings
2. animal: Kunming mouse, body weight 20 ± 2g, male and female half and half are provided by Shandong Province's Experimental Animal Center.
Experimental technique and experimental result:
It is 21.5% solution that pharmaceutical composition of the present invention is made into concentration, and gastric infusion is pressed the administration of 0.8ml/20g body weight.
With 60 mice equilibriums at random be divided into 6 groups, 10 every group, by the body weight administration.About administration 6min, poisoning symptom appears in animal, and beginning is restlessness, occurs dyspnea then and death.Heavy dose of treated animal is all dead in 15min.All the other dead animals are dead in 3h, and surviving animals was observed 7 days, and viewing duration water, food are taken arbitrarily.The result shows, the LD of pharmaceutical composition of the present invention
50Be 4.32g/kg, its 95% credible 3.58-5.20g/kg that is limited to.The clinical experiment of pharmaceutical composition of the present invention
Experiment purpose: the kalium replenishment curative effect and the untoward reaction of checking pharmaceutical composition of the present invention.
Experimental technique and design
Indication: hypokalemia patient
Person's standard: age 18-65 year; Fasting blood potassium≤3.5mmol/L
Clinical verification design: collect patient's 200 examples, be divided into 2 groups at random, every group 100 example is respectively pharmaceutical composition group of the present invention and potassium chloride group, and two groups to be tried patient's age, sex, the preceding blood potassium of medication and other electrolyte level similar.The pharmaceutical composition of the present invention that uses wraps as 1.45g/, and is suitable with the 1g KCE content, and control drug is 10% Klorvess Liquid.Two groups of experimenters take respectively pharmaceutical composition 2 bags/time, and 10% Klorvess Liquid 20ml/ time, every day 3 times, totally 6 days.Before medication, medication the 4th day and experiment finish m seq venous blood samples on an empty stomach, measures relevant biochemical indicator.
The checking result:
Two groups of patients' physical data: pharmaceutical composition group 100 examples of the present invention, male 48 examples, women 52 examples, 52.0 ± 13.5 years old mean age; Potassium chloride group 100 examples, male 56 examples, women 44 examples, mean age 50.3+14.4 year, two groups of patient's each age group example number constituent ratios see the following form 1.Term harmonizations such as two groups of patient's sexes, age, there was no significant difference has comparability.
Table 1: two groups of patient's each age groups example pharmaceutical composition group of the present invention potassium chloride group in age several years (year) 53 53 61 61 liang of groups of the routine number constituent ratio of routine number constituent ratio (%) (%) 18-20 20 13 1335-, 27 27 26 2650-60 compare there was no significant difference.
Biochemical indicator sees the following form 2 before and after two groups of patient's medications.
6 days this group K of medication medication in 3 days before the medication of biochemical indicator (mean ± standard deviation) group observation index before and after the table 2 liang group patient medication
+(mmol/L) 3.10 ± 0.29 3.75 ± 0.48
* *4.16 ± 0.55
* *Send out and close Na
+(mmol/L) 136.0 ± 7.9 137.9 ± 6.2
* *138.6 ± 3.9
* *Bright thing Cl
-(mmol/L) 100.1 ± 9.7 101.3 ± 7.3
*103.2 ± 5.9
*Medicine group Mg
2+(mmol/L) 1.05 ± 0.20 1.14 ± 0.27
*1.15 ± 0.23
*Thing CO
2-CP (mmol/L) 24.2 ± 3.9 24.5 ± 4.0 23.9 ± 3.2
BUN(mmol/L) 6.0±4.9 6.2±4.7 6.1±4.3
Cr (mmol/L) 83.7 ± 37.6 77.3 ± 33.3 80.5 ± 37.9 chlorine K
+(mmol/L) 3.14+0.23 3.52 ± 0.31
* *3.95 ± 0.49
* *Change Na
+(mmol/L) 134.7 ± 5.8 135.4 ± 4.4
* *138.5 ± 4.4
* *Potassium Cl
-(mmol/L) 99.2 ± 8.5 100.9 ± 7.7
* *103.7 ± 6.2
* *Group Mg
2+Mmol/L) 1.09 ± 0.29 1.13 ± 0.26 114 ± 0.26 Δs
CO
2-CP(mmol/L) 24.4±3.5 24.3±3.3 24.0±3.4
BUN(mmol/L) 5.4±3.3 5.5±2.7 5.5±3.0
Cr (mmol/L) 76.2 ± 33.9 71.8 ± 31.1 76.2 ± 34.9
*P＜0.05
*P＜0.01
* *Compare before p＜0.001 Δ p=0.05 and the medication
Annotate: Mg
2+Pharmaceutical composition group n=35 of the present invention, potassium chloride group n=37; All the other indexs are respectively organized n=100
The preceding two groups of every blood biochemistry index of patient of medication do not have significant difference.Concentration of blood kalium was all than significantly raising Na in other index before the medication with after 6 days in 3 days for two groups of patient's medications
+, Cl
-With Mg
2+Rising is in various degree also arranged.
Two groups of patients' clinical efficacy sees the following form.
Two groups of patient's clinical efficacy group total inspection produce effects enabledisables
Example time example number percentage rate example number percentage rate example number percentage rate Ridit U
(%) (%) the present invention 100 3 days 42 42 28 28 30 30 2.893 of number (%)
*Medicine group 6 days 85 85 11 11 44 2.053
*100 3 days 24 24 27 27 49 49 potassium groups of compound group chlorination 6 days 68 68 25 25 77
*P＜0.05
*Compare with the potassium chloride group p＜0.01
Medication was compared two groups of patients' kalium replenishment curative effect with after 6 days in 3 days, and pharmaceutical composition group then of the present invention is better than the potassium chloride group.Untoward reaction after two groups of patient's medications sees the following form.
Two groups of adverse reactions of patients untoward reaction pharmaceutical composition group of the present invention potassium chloride groups
Person-time incidence rate (%) person-time incidence rate (%) abnormal flavour sense 33 29 29
*Feel sick 66 27 27
*Vomit 0044
*Inappetence 22 16 16
*Epigastric discomfort 77 31 31
*0011 diarrhoea of suffering from abdominal pain, the 1111 untoward reaction frequencies of occurrences (people) 15 15 54 54
*
*P＜0.05
*P＜0.0 1 a liang group is compared
After the medication, the abnormal flavour sense that the patient produced in the pharmaceutical composition group of the present invention, feel sick, vomiting, inappetence, epigastric discomfort and total untoward reaction frequency of occurrences all be starkly lower than the potassium chloride group, compare for two groups to have significant difference.Show that thus the digestive system untoward reaction that pharmaceutical composition group of the present invention occurs is starkly lower than 10% potassium chloride group.After the medication, two groups of patients' liver function, kidney merit and blood, urine, stool routine examination inspection there is no unusual or worsen.
Experiment conclusion
Pharmaceutical composition of the present invention has good kalium replenishment curative effect, compares with 10% Klorvess Liquid, and the former is better than the latter at the kalium replenishment effect, and adverse reaction rate is starkly lower than the latter, pharmaceutical composition clinical tolerance of the present invention is good, and the patient is easy to accept, and the kalium replenishment curative effect certainly.
Claims (6)
1, a kind of pharmaceutical composition of preventing and treating hypokalemia is characterized by and contains potassium citrate 70-86.5%, citric acid 8-24.7% and correctives 0.5-5% (percentage by weight).
2, the described pharmaceutical composition of claim 1, the percentage by weight that it is characterized by above-mentioned each component is: potassium citrate 72-81%, citric acid 15.5-22% and correctives 1.5-3.5%.
3, the described pharmaceutical composition of claim 2, the percentage by weight that it is characterized by above-mentioned each component is: potassium citrate 73%, citric acid 17% and correctives 2%.
4, the described pharmaceutical composition of claim 1 is characterized by and also contains the excipient that percentage by weight is 5-21.5%.
5, the described pharmaceutical composition of claim 1 is characterized by described correctives and is one or both and two or more combination in steviosin, fragrant and sweet element, disodium glycyrrhizinate, cyclamate, xylitol and the aspartame.
6, the described pharmaceutical composition of claim 4 is characterized by excipient and is: one or both in dextrin, starch, carboxymethyl cellulose, ethyl cellulose, microcrystalline Cellulose and the methylcellulose and two or more combination.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN99100214A CN1089236C (en) | 1998-05-26 | 1999-01-21 | Medicinal composition for preventing and curing hypokalemia. |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN98110245 | 1998-05-26 | ||
| CN98110245.X | 1998-05-26 | ||
| CN99100214A CN1089236C (en) | 1998-05-26 | 1999-01-21 | Medicinal composition for preventing and curing hypokalemia. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1236613A CN1236613A (en) | 1999-12-01 |
| CN1089236C true CN1089236C (en) | 2002-08-21 |
Family
ID=25744664
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN99100214A Expired - Lifetime CN1089236C (en) | 1998-05-26 | 1999-01-21 | Medicinal composition for preventing and curing hypokalemia. |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1089236C (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5432200A (en) * | 1988-01-05 | 1995-07-11 | Walsdorf; Neill B. | Method for increasing urinary excretion of electrolytes |
-
1999
- 1999-01-21 CN CN99100214A patent/CN1089236C/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5432200A (en) * | 1988-01-05 | 1995-07-11 | Walsdorf; Neill B. | Method for increasing urinary excretion of electrolytes |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1236613A (en) | 1999-12-01 |
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