CN1249934A - 热稳定的抗酸消气混悬剂 - Google Patents
热稳定的抗酸消气混悬剂 Download PDFInfo
- Publication number
- CN1249934A CN1249934A CN99120707A CN99120707A CN1249934A CN 1249934 A CN1249934 A CN 1249934A CN 99120707 A CN99120707 A CN 99120707A CN 99120707 A CN99120707 A CN 99120707A CN 1249934 A CN1249934 A CN 1249934A
- Authority
- CN
- China
- Prior art keywords
- chemical compound
- cellulose
- preparation
- liquid antacid
- suspending agent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 230000001458 anti-acid effect Effects 0.000 title claims abstract description 44
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims abstract description 45
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims abstract description 43
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims abstract description 43
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims abstract description 41
- 238000002360 preparation method Methods 0.000 claims abstract description 40
- 229940069428 antacid Drugs 0.000 claims abstract description 33
- 239000003159 antacid agent Substances 0.000 claims abstract description 33
- 239000000375 suspending agent Substances 0.000 claims abstract description 26
- 239000007788 liquid Substances 0.000 claims abstract description 24
- 150000001875 compounds Chemical class 0.000 claims abstract description 19
- 239000002253 acid Substances 0.000 claims abstract description 12
- 229940071826 hydroxyethyl cellulose Drugs 0.000 claims description 40
- 238000009928 pasteurization Methods 0.000 claims description 20
- 238000001816 cooling Methods 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 8
- 229940122957 Histamine H2 receptor antagonist Drugs 0.000 claims description 6
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- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 6
- 239000003485 histamine H2 receptor antagonist Substances 0.000 claims description 6
- SEIGJEJVIMIXIU-UHFFFAOYSA-J aluminum;sodium;carbonate;dihydroxide Chemical compound [Na+].O[Al+]O.[O-]C([O-])=O SEIGJEJVIMIXIU-UHFFFAOYSA-J 0.000 claims description 5
- 239000007900 aqueous suspension Substances 0.000 claims description 4
- GXGAKHNRMVGRPK-UHFFFAOYSA-N dimagnesium;dioxido-bis[[oxido(oxo)silyl]oxy]silane Chemical compound [Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O GXGAKHNRMVGRPK-UHFFFAOYSA-N 0.000 claims description 4
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 claims description 4
- 229960001596 famotidine Drugs 0.000 claims description 4
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 4
- 239000001095 magnesium carbonate Substances 0.000 claims description 4
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 4
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims description 4
- 239000000347 magnesium hydroxide Substances 0.000 claims description 4
- 229910001862 magnesium hydroxide Inorganic materials 0.000 claims description 4
- 239000000391 magnesium silicate Substances 0.000 claims description 4
- 229940099273 magnesium trisilicate Drugs 0.000 claims description 4
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- 229960000620 ranitidine Drugs 0.000 claims description 4
- VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 claims description 4
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- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 claims description 3
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- SGXXNSQHWDMGGP-IZZDOVSWSA-N nizatidine Chemical compound [O-][N+](=O)\C=C(/NC)NCCSCC1=CSC(CN(C)C)=N1 SGXXNSQHWDMGGP-IZZDOVSWSA-N 0.000 claims description 2
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Abstract
本发明涉及一种热稳定性液体抗酸和/或消气制剂,它能够耐受60—100℃的巴氏消毒,该制剂在以羟乙基纤维素为悬浮剂的水性混悬剂中含有一种或多种酸中和化合物和/或消气化合物。
Description
本发明涉及液体抗酸组合物及其制备方法。更具体地说，本发明涉及热稳定的抗酸和消气液体制剂，其中包含能够在巴氏消毒时不胶凝、不与组合物中抗酸金属盐反应的悬浮剂。
抗胃酸药是中和或消除胃内容物中胃酸的药物。抗酸药被广泛用于治疗多种胃肠道疾病，例如消化道溃疡和胃炎。抗酸药还被用来缓解胃酸过多性消化不良、胃灼热、消化不良、胃酸过多、反流性食道炎等。临床应用抗酸药是因为它们能够中和胃酸，提高胃分泌物的pH。
目前使用的抗酸药是由多种无机盐制成的，例如碳酸钙、碳酸氢钠、镁盐和铝盐。氢氧化镁和氢氧化铝是镁盐和铝盐中最有效的，所以经常联合使用。此外，还使用氧化镁、碳酸镁、磷酸铝、水化铝酸镁、三硅酸镁和蔗糖硫酸铝。
消气制剂用作辅助性对症治疗肠胃胀气、功能性胃胀和术后气痛。临床应用二甲硅油之类消气药是因为它们的消泡特性。硅酮消泡剂在水性液体表面铺展，形成一层低表面张力的膜，由此造成泡沫的破裂。所以，能够缓解与产气有关的疼痛和不适症状。
已经有了混悬液和固体剂型的抗酸消气制剂。总的说来，混悬液比片剂或粉末好，因为前者溶解更快更充分，反应并中和胃酸和消气的能力更强。这类液体制剂的主要优点在于它们的起效速度。但是，液体制剂通常有一个难题，即对包装后成品的充分防腐处理和最终灭菌处理。这类产品的防腐处理十分重要，它们在被装入容器时应该尽可能不含微生物(即最终灭菌)。这样的灭菌可以是(i)包装时在产品中添加高氯酸钠或过氧化氢之类化学试剂(英国专利GB1275885)，或者(ii)热处理(巴氏消毒)液体抗酸药。
但是这些灭菌方法有某些缺点。方法(i)的缺点在于使得产品口味变差，而且要求产品在化学试剂变质-这与最初加入量有关-前装瓶。方法(ii)的主要问题是加热对制剂中成份的影响。一个特殊的问题是加热对用于维持抗酸药呈悬浮态的悬浮剂(胶质)的影响。该问题是：在巴氏消毒法使用的温度范围内，悬浮剂会发生热胶凝。目前，已经将可选的悬浮剂局限在不与金属离子反应的那些。在现有悬浮剂中，常规认为最合适的是羟丙基甲基纤维素(HPMC)，因为它具有与抗酸药(金属离子)的相容性，而且它可以经受60℃至70℃中等强度的巴氏消毒。
但是，上述温度范围内的巴氏消毒并不理想。另一个问题在于巴氏消毒单元因胶凝的HPMC而堵塞之前只可以通过有限量的产品。热胶凝是HPMC的一种已知现象(参见，A.Haque等，甲基纤维素的热胶凝，第二部：羟丙基的作用，Carbohydrate Polymers 22(1993)175-186)。所以，巴氏消毒过程中悬浮剂的热胶凝限制了生产能力，提高了制造成本。
所以，本发明的目的在于提供一种能够经60-100℃巴氏消毒而不胶凝、不与所含二价和/或三价抗酸金属盐反应的液体抗酸组合物。
本发明涉及能够耐受60-100℃巴氏消毒的热稳定性液体抗酸和/或消气制剂，其中以羟乙基纤维素作为悬浮剂的水性混悬液中含有一种或多种酸中和性和/或消气化合物。已经发现，用羟乙基纤维素(HEC)作为抗酸/消气混悬液的悬浮剂时，所得的产品具有以下特性：
(i)可方便地进行巴氏消毒而不必担心悬浮剂在巴氏消毒器中胶凝。这不同于使用HPMC或HPC等其它纤维素类胶质时的情形。
(ii)如果是含铝、钙或镁的抗酸组合物，HEC不会与溶液中微量的游离多价金属离子(例如A13+、Ca2+、或Mg2+阳离子)反应，这不同于使用其它黄原胶、角叉菜胶、聚羧乙烯、羧甲基纤维素钠、藻酸盐、刺槐豆胶之类悬浮剂时的情形。
(iii)瓜尔树胶、阿拉伯树胶、黄耆胶、刺槐豆胶之类的许多天然树胶本身具有很高的生物负荷(bioburden)，而HEC则没有。
在抗酸和/或消气混悬液(尤其是含有铝、镁或钙的那些)中使用HEC类作为悬浮剂的优点在于能够对产品通过巴氏消毒法进行最终灭菌。
具体地说，本发明涉及液体抗酸和/或消气制剂，其中包含有效量的一种或多种酸中和化合物和/或消气化合物、羟乙基纤维素(HEC)悬浮剂、还可选性地包含一种或多种药学上认可的添加剂。较好的是，该制剂含1.0mg-50mg/5ml HEC悬浮剂。
本发明中可用作活性酸中和化合物的抗酸化合物是常规用于液体抗酸组合物中的铝、镁和钙盐。总的说来，组合物含有约200mg-2000mg/5ml酸中和化合物。例如，可以将200-2000mg/5ml碳酸钙与碳酸镁、三硅酸镁、氢氧化铝和氢氧化镁或它们的混合物联用。制剂中抗酸剂的含量宜为组合物的5％-35％(w/v)。较好的是使用含约5％-15％(w/v)碳酸钙和约2％-8％(w/v)碳酸镁或三硅酸镁的混合物。也可以使用含量占约150-800mg/5ml的氢氧化铝凝胶。活性酸中和化合物一般以单独粉末的形式使用，微化粉末更好。
或者，除酸中和化合物外，组合物还可以含有二甲硅油之类消气化合物作为活性成份。所述的消气化合物是用于辅助对肠胃胀气、功能性胃胀和术后气痛的对症治疗的那些。对于自我给药的非处方制剂来说，二甲硅油之类消气化合物被用作抗肠胃胀气药来缓解包括上消化道胀、压、闷、堵等感觉在内与气体相关的症状。二甲硅油通常与诸如抗酸药、抗痉挛药或消化酶等胃肠道药物联用。二甲硅油应符合美国药典(USP XXII)中的有关定义，即一种充分甲基化的硅氧烷聚合物，所含的重复单元为(-(CH3)2SiO-)n，通过结构式为(-(CH3)3-SiO-)的三甲基硅烷氧基封端单元和二氧化硅稳定化。其它据有机聚硅氧烷消泡剂是本领域众所周知的，也可以在本发明中用作活性成份。这类有机聚硅氧烷消泡剂可参见美国专利5,458,886及其中的参考文献，本发明将其纳为参考。
固体口服剂型中二甲硅油或其它有机聚硅氧烷消泡剂的含量必须足以为正受多气或胃肠胀气及相关症状之苦的患者提供治疗有效剂量。对二甲硅油来说适宜的剂量范围是每剂量单位约20mg至125mg，一般不超过500mg/天。可以根据患者的年龄、体重以及症状严重性来改变剂量范围。
悬浮剂选择本领域公知的羟乙基纤维素(HEC)类聚合物。HEC是一种水溶性聚合物，由非离子性纤维素衍生得到，所以不会象其它阴离子纤维素醚聚合物那样受溶液中阳离子的作用。这一特性使得它适合与常用的二价和/或三价阳离子抗酸盐联用。HEC的生产是用氢氧化钠处理纤维素，并与环氧乙烷反应引入羟乙基，从而得到羟乙基醚。通过在特定条件下进行上述反应，可以控制羟基的取代程度。水溶性随取代程度的升高而升高。HEC的各种类型具有不同的粘度和溶解度，例如Hercules Incorporate，Wilmington DE的分公司Aqualon的NATROSOL，或Hoechst Celanese Corporation的TYLOSE。根据本发明，HEC在液体组合物中作为悬浮剂，在组合物中的含量为1mg/5ml至约100mg/5ml，或约0.02％(w/v)至约2％(w/v)。
液体抗酸混悬液还宜包含选自各种药学上认可的防腐剂的一种防腐组份。较好的是对羟基苯甲酸的烷基酯(例如，对羟基苯甲酸丁酯、对羟基苯甲酸甲酯和对羟基苯甲酸丙酯)，它们可以单独使用也可以联合使用。通常，对羟基苯甲酸酯的使用浓度约为0.02％(w/v)。其它防腐剂包括乙二胺四乙酸、对羟基苯甲酸丙酯、苯甲酸钠或山梨酸。
液体抗酸制剂中还宜含有组胺H2受体的拮抗剂或其它常用于胃肠治疗的活性药物。组胺H2受体拮抗剂被用来减少胃酸分泌，并对许多胃疾病具有疗效。将组胺H2受体拮抗剂与抗酸药一起给药是已知的，例如美国专利5,229,137和WO92/00102。任何已知的组胺H2受体拮抗剂均可使用，例如西米替丁、雷尼替丁、尼扎替丁和法莫替丁。典型制剂的每剂量单位(例如5ml)中将含有约100mg-400mg西米替丁，或约50mg-150雷尼替丁或10mg-40mg法莫替丁。通常，组胺H2受体拮抗剂以游离碱或以诸如雷尼替丁那样的盐酸盐等药学上认可的盐形式使用。制剂中还可以加入其它活性药物。例如，可以和其它胃肠药一起加入止痛药、止泻药或抗痉挛药，加入的剂量是治疗胃肠功能紊乱时的常规用量。
单位剂型的本发明组合物可以每天服用1至4次。剂量取决于所用的活性药物，所治疗的病症和患者的年龄及体重。一般剂量包括约5-30ml制剂，其中包含为达到要求的中和效果所选用的一定剂量的抗酸药。碳酸钙的合适剂量范围是200mg至2.0g。
本发明的液体组合物是水性混悬液，其中的活性成份与药学上认可的赋形剂混合在一起，这些赋形剂常见于口服水性混悬液中。所述的赋形剂可以是例如脱水山梨醇酯或卵磷脂等分散剂或润湿剂，表面改性剂，山梨醇溶液、乙醇或精炼植物油等水性或非水性媒质，或稀释剂。
组合物还可以含有香精、着色剂和/或甜味剂。合适的香精包括水果味、薄荷味、甘草味或泡泡糖味的。甜味剂可以是例如大用量甜味剂例如糖(例如蔗糖或果糖)或多元醇(例如麦芽醇、山梨醇)，和/或是增强甜味剂例如糖精、阿斯巴藤或acesulfame K。
此外，组合物可以含有甘油三乙酸酯之类三酯或二酯类缓冲剂，或酒石酸或柠檬酸之类其它缓冲剂和缓冲盐。
本发明的液体组合物可以根据制药业中公知的常规技术来制备。所以可以根据需要将抗酸药和悬浮剂与合适的赋形剂混合并分散在水性媒质中。
如前所述，本发明抗酸组合物中HEC悬浮剂的使用为需要使用悬浮剂来进行的液体抗酸组合物制造提供了显著的优点，因为可以用巴氏消毒来进行最终灭菌而不用担心悬浮剂在消毒器中胶凝。这与HPMC或HPC等其它纤维素类胶体的情形不同。这一点可以通过下文实施例1的结果得到验证，该实施例显示：包含HEC作为悬浮剂的本发明组合物在巴氏消毒过程中的流速高于包含HPMC作为悬浮剂的比较制剂。
为了进一步说明本发明及其优点，以下是具体实施例，必须理解的是，这些实施例只是用来说明本发明而不对本发明构成范围上的限定。
实施例1
比较HEC和HPMC的热稳定性
在Plant Scale APV换热器上进行循环实验。实验目的是比较用羟丙基甲基纤维素(HPMC)悬浮的抗酸制剂和用羟乙基纤维素(HEC)悬浮的相同制剂在换热器中的阻塞情况。
HPMC和HEC都是提高液体产品粘度的纤维素水凝胶。表I显示了该实验中使用的配方。必须指出的是，这些配方的RT粘度(Brookfield spindle #2 12速)都相等(225cp)。为了该实验而制备了两批各500加仑产品。经加工后均在1600psi均化，然后进行巴氏消毒。
表I原料 配方1(mg/5ml) 配方2(mg/5ml)山梨醇溶液 953 953纯水 3370.5 3381羟丙基甲基纤维素K4M* 28.028羟乙基纤维素TYLOSE 4000** 17.5微晶纤维素RC 581 13 10二甲硅油乳液(30％) 73.11 73.11氢氧化镁粉末 210.5 210.5氢氧化铝胶体(13％) 787.4 787.4对羟基苯甲酸丁酯 1 1对羟基苯甲酸丙酯 1.5 1.5薄荷油香精 0.233 0.233柠檬香精 18.1 18.1*Dow Chemical**Hoechst Celanese
表II显示与相当的目前所用的HPMC制剂相比，当本发明使用HEC时，换热器中的阻塞减少。产物循环5分钟，然后以约1.2gpm的速度人工脱水15分钟。然后，再循环5分钟，再脱水15分钟。如此重复进行210分钟。监测全过程中泵压的改变和泵％。压力和/或泵％的升高表示换热器被阻塞，最后可能需要提前关闭。表II显示了这些结果。结果显示，对于本发明的HEC制剂来说，上述参数没有明显改变，但是HPMC制剂却表现出泵压和泵％的明显升高。总之，以上结果表明，HEC制剂不会堵塞巴氏消毒器。
表II
配方1(HPMC)
| 加仑 | 泵压(psi) | 泵％ | GPM |
| 0 | 31 | 45 | 1.2 |
| 40 | 54 | 62 | 1.2 |
| 75 | 65 | 70 | 1.2 |
| 100 | 81 | 80 | 1.2 |
| 125 | 94 | 93 | 1.2 |
配方2(HEC)
| 加仑 | 泵压(psi) | 泵％ | GPM |
| 0 | 34 | 62 | 1.2 |
| 40 | 35 | 58 | 1.2 |
| 75 | 35 | 57 | 1.2 |
| 100 | 35 | 59 | 1.2 |
结论：在抗酸制剂中用HEC替换HPMC，产物产量明显提高，换热器未完全堵塞。
实施例2
含有氢氧化铝凝胶的制剂
mg/5mlAl(OH)3凝胶(13％Al2O3) 1538.5山梨醇(70％溶液) 1000.0羟乙基纤维素 15.0去离子水 3023.5香精 20.0对羟基苯甲酸丙酯NF 2.0对羟基苯甲酸丁酯NF 2.0
5591.0
将302.35g去离子水和200g 70％的山梨醇溶液加入一个配有IKA搅拌器的1.5升容器中。将搅拌器设定在高速，在上述水/山梨醇混合物中加入3g羟乙基纤维素。继续搅拌，直至羟乙基纤维素完全溶解。仍然在高速搅拌下，在容器中加入307.7g氢氧化铝胶体。胶体充分分散后，立即顺次加入以下成份：0.4g对羟基苯甲酸丁酯、0.4g对羟基苯甲酸丙酯、4.0g香精、最后加入302.35g去离子水。
然后将上述悬浮液混匀，并经巴氏消毒后装入塑料瓶中。
实施例3
含有CaCO3粉末和二甲硅油的制剂
mg/5ml
CaCO3粉末 1000.0
二甲硅油(30％乳液) 100.0
山梨醇(70％溶液) 1000.0
羟乙基纤维素 15.0
去离子水 3461.0
香精 20.0
对羟基苯甲酸丙酯NF 2.0
对羟基苯甲酸丁酯NF 2.0
5600.0
将500.0g去离子水和200g 70％的山梨醇溶液加入一个配有IKA搅拌器的1.5升容器中。将搅拌器设定在高速，加入CaCO3粉末。待CaCO3完全分散后，在混合物中加入3g羟乙基纤维素，继续搅拌至溶解。在高速搅拌下，在容器中加入20g二甲硅油乳液。待然二甲硅油乳液充分分散后，立即顺次加入以下成份：0.4g对羟基苯甲酸丁酯、0.4g对羟基苯甲酸丙酯、4.0g香精、最后加入192.2g去离子水。
然后将上述悬浮液混匀，并经巴氏消毒后装入塑料瓶中。
实施例4
含有碳酸二羟基铝钠(DASC)的制剂
mg/5ml
DASC 400.0
山梨醇(70％溶液) 1000.0
羟乙基纤维素 25.0
去离子水 3851.5
香精 22.0
糖精钠 1.5
5300.0
将385.15g去离子水和200g 70％的山梨醇溶液加入一个配有IKA搅拌器的1.5升容器中。将搅拌器设定在高速，在水/山梨醇混合物中加入羟乙基纤维素。然后继续搅拌，直至羟乙基纤维素完全溶解。在高速搅拌下，在容器中加入80.0gDASC。待DASC充分分散后，立即顺次加入以下成份：4.4g香精和0.3g糖精钠，最后加入385.15g去离子水。
然后将上述悬浮液混匀，并经巴氏消毒后装入塑料瓶中。
实施例5
含有二甲硅油的制剂
mg/0.6ml
二甲硅油(30％乳液) 140.48
微晶纤维素和CMC钠 0.60
麦芽醇 60.0
羟乙基纤维素 1.50
去离子水 418.54
柠檬酸 0.75
柠檬酸钠 0.30
苯甲酸钠 0.60
香精 1.20
色素 0.03
624.0
将792.0kg去离子水加入2000升罐中，加入1.136kg微晶纤维素，混合5分钟，然后加入2.839kg HEC，继续搅拌5分钟。按照以下顺序加入各成份：柠檬酸(1.42kg)；柠檬酸钠(0.568kg)；麦芽醇(113.6kg)和苯甲酸钠(1.136kg)。然后在充分搅拌的同时在容器中加入二甲硅油乳液(266kg)。待聚而甲硅氧烷乳液完全分散后，加入以下另外制备的混合物：分散在10kg去离子水中的57g色素和1.2kg香精。加完后继续搅拌30分钟。然后将混悬液混匀，经巴氏消毒后装入塑料瓶。
Claims (10)
1.一种热稳定的液体抗酸和/或消气制剂，它能够耐受60-100℃的巴氏消毒，该制剂在以羟乙基纤维素为悬浮剂的水性混悬剂中含有一种或多种酸中和化合物和/或消气化合物，还可以含有一种或多种其它药学上认可的添加剂。
2.根据权利要求1所述的液体抗酸制剂，它包含200mg-2000mg/5ml酸中和化合物和1mg-100mg/5ml羟乙基纤维素悬浮剂。
3.根据权利要求1所述的液体抗酸制剂，其中的酸中和化合物选自碳酸钙、碳酸二羟基铝钠、碳酸镁、三硅酸镁、氢氧化铝和氢氧化镁以及它们的化合物。
4.根据权利要求1所述的液体抗酸制剂，其中的酸中和化合物是碳酸钙。
5.根据权利要求1所述的液体抗酸制剂，其中的酸中和化合物是氢氧化铝凝胶。
6.根据权利要求1所述的液体抗酸制剂，它包含1-100mg/5ml羟乙基纤维素。
7.根据权利要求1所述的液体抗酸制剂，它还包含药学有效量的组胺H2受体拮抗剂。
8.根据权利要求11所述的液体抗酸制剂，其中的组胺H2受体拮抗剂选自西米替丁、雷尼替丁、尼扎替丁和法莫替丁。
9.根据权利要求12所述的的液体抗酸制剂，每5ml制剂包含5mg-40mg法莫替丁。
10.一种在对含有悬浮剂的液体抗酸和/或消气制剂用60-100℃的巴氏消毒最终灭菌的方法，包括使用羟乙基纤维素作为悬浮剂来提高流速。
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101797268A (zh) * | 2010-03-11 | 2010-08-11 | 重庆健能医药开发有限公司 | 一种稳定的复方二甲硅油铝碳酸镁混悬液 |
| CN104069126A (zh) * | 2014-07-02 | 2014-10-01 | 浙江康乐药业股份有限公司 | 一种治疗胃酸过多的药物及其制备方法 |
| CN109414406A (zh) * | 2017-04-13 | 2019-03-01 | 辽宁大熊制药有限公司 | 含有氢氧化铝和氢氧化镁的悬浮液及其制造方法 |
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| US20050163867A1 (en) * | 2004-01-23 | 2005-07-28 | James Schachtel | Composition and method of treating gastric ulcers in mammals |
| CA2987034C (en) | 2015-05-29 | 2023-03-07 | Johnson & Johnson Consumer Inc. | Use of an organic citrus extract with high antimicrobial capacity and xylitol as a preservative system in liquids, emulsions, suspensions, creams and antacids |
| CN107683145A (zh) * | 2015-05-29 | 2018-02-09 | 强生消费者公司 | 具有高抗微生物能力的有机柑橘类提取物作为液体、乳液、悬浮液、霜膏和抗酸剂中的防腐剂体系的用途 |
| CN112020350A (zh) | 2018-04-27 | 2020-12-01 | 强生消费者公司 | 液体口服药物剂型 |
| GR1009632B (el) * | 2018-07-09 | 2019-10-25 | Ιουλια Κλεωνος Τσετη | Διατροφικο συμπληρωμα για την απο του στοματος χορηγηση συνδυασμου λακτοφερινης, ξυλογλυκανης, προανθοκυανιδινων και σιμεθικονης, χρησιμων για την προληψη λοιμωξεων του γαστρεντερικου και ουροποιητικου συστηματος |
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| US3591680A (en) * | 1969-11-17 | 1971-07-06 | Smith Kline French Lab | Concentrated antacid compositions and method of producing antacid activity |
| JPS60161915A (ja) * | 1984-02-01 | 1985-08-23 | Sato Seiyaku Kk | 制酸剤含有内用液剤 |
| US4806354A (en) * | 1984-04-06 | 1989-02-21 | Green James P | Health food composition |
| US5112813A (en) * | 1986-03-07 | 1992-05-12 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Process for the preparation of a viscosity-stable antacid composition |
| JPH0692309B2 (ja) * | 1986-11-22 | 1994-11-16 | 富士化学工業株式会社 | 懸濁制酸剤 |
| US4949227A (en) * | 1989-10-31 | 1990-08-14 | General Electric Company | Upper and lower beam optical switch for line-of-light headlamps using opaque masks |
| US5455050A (en) * | 1993-11-12 | 1995-10-03 | Mcneil-Ppc, Inc. | Aqueous antacids with calcium carbonate and magnesium salt |
| GB9504599D0 (en) * | 1995-03-03 | 1995-04-26 | Reckitt & Colmann Prod Ltd | Improvements in or relating to organic compositions |
| US5674529A (en) * | 1995-06-06 | 1997-10-07 | Church & Dwight Co., Inc. | Alkalinizing potassium salt controlled release preparations |
| US5976578A (en) * | 1996-10-10 | 1999-11-02 | Mcneil-Ppc, Inc. | Liquid antacid compositions |
| US5874112A (en) * | 1997-03-31 | 1999-02-23 | Mcneil Ppc-Inc. | Translucent antacid suspension |
| US6110505A (en) * | 1997-04-01 | 2000-08-29 | Mcneil Ppc Inc. | Translucent antacid suspension containing co-dried dihydroxy aluminum sodium carbonate |
| US5914135A (en) * | 1997-04-16 | 1999-06-22 | Mcneil-Ppc, Inc. | Liquid antacid compositions |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101797268A (zh) * | 2010-03-11 | 2010-08-11 | 重庆健能医药开发有限公司 | 一种稳定的复方二甲硅油铝碳酸镁混悬液 |
| CN104069126A (zh) * | 2014-07-02 | 2014-10-01 | 浙江康乐药业股份有限公司 | 一种治疗胃酸过多的药物及其制备方法 |
| CN109414406A (zh) * | 2017-04-13 | 2019-03-01 | 辽宁大熊制药有限公司 | 含有氢氧化铝和氢氧化镁的悬浮液及其制造方法 |
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| HK1026636A1 (en) | 2000-12-22 |
| RU2223092C2 (ru) | 2004-02-10 |
| CN1158993C (zh) | 2004-07-28 |
| AR020489A1 (es) | 2002-05-15 |
| AU4759099A (en) | 2000-03-23 |
| CZ298028B6 (cs) | 2007-05-30 |
| HU9903201D0 (en) | 1999-11-29 |
| US20030215525A1 (en) | 2003-11-20 |
| JP2000136150A (ja) | 2000-05-16 |
| ZA996020B (en) | 2001-03-20 |
| EP0990438A1 (en) | 2000-04-05 |
| HUP9903201A2 (hu) | 2000-05-28 |
| HUP9903201A3 (en) | 2000-08-28 |
| NZ337864A (en) | 2000-06-23 |
| BR9904286A (pt) | 2000-09-26 |
| PL335516A1 (en) | 2000-03-27 |
| KR20000023335A (ko) | 2000-04-25 |
| CA2282893A1 (en) | 2000-03-21 |
| KR100726690B1 (ko) | 2007-06-12 |
| CZ333399A3 (cs) | 2000-04-12 |
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