WO2011000208A1 - Pharmaceutical composition containing dimethicone/ simethicone - Google Patents
Pharmaceutical composition containing dimethicone/ simethicone Download PDFInfo
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- WO2011000208A1 WO2011000208A1 PCT/CN2010/000857 CN2010000857W WO2011000208A1 WO 2011000208 A1 WO2011000208 A1 WO 2011000208A1 CN 2010000857 W CN2010000857 W CN 2010000857W WO 2011000208 A1 WO2011000208 A1 WO 2011000208A1
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- Prior art keywords
- dimethicone
- simethicone
- acetylcysteine
- pharmaceutical composition
- pharmaceutically acceptable
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
- A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
Definitions
- the present invention relates to the field of medical technology, and in particular to a pharmaceutical composition of acetylcysteine or a pharmaceutically acceptable salt thereof and dimethicone/silicone oil.
- Digestive endoscopy plays a very important role in the diagnosis of digestive tract diseases. It is popular among doctors because of its intuitiveness and simplicity, and is especially used in clinical diagnosis and treatment. However, due to the large amount of foam and mucus in the digestive tract, the visual field is unclear, the examination time is prolonged, the patient's pain is increased, and misdiagnosis and missed diagnosis are easily caused, which is not conducive to the early diagnosis of digestive tract diseases.
- Dimethicone (I) is the most commonly used medical defoamer in the clinic and is often used for preoperative defoaming in digestive endoscopy and treatment or abdominal imaging. Dimethicone is a dimethylsiloxane polymer which, due to its small surface tension, can change the surface tension of the bubble and cause it to rupture, thereby eliminating foaming. As early as the 1950s and 1960s, dimethicone was used as a defoaming agent in the medical field. Simethicone (II) is a composite of dimethicone and silica with the same or stronger defoaming ability as dimethicone. Dimethicone and simethicone are both pharmacological and physiologically inert substances, and their defoaming action is a physical process, and the substance itself does not involve chemical changes.
- the disulfide bond (-SS-) in the middle mucin polypeptide chain is broken, which reduces the viscosity of the mucus and liquefies it.
- Dysphagia, obstruction of the trachea, etc. can still be used for detoxification of acetaminophen poisoning.
- the object of the present invention is to provide a pharmaceutical composition containing dimethicone/silicone oil, which can eliminate the bubble in the digestive tract and remove the viscous liquid in the digestive tract; the pharmaceutical composition can be used As a preoperative adjuvant in digestive endoscopy and treatment or imaging.
- the present invention adopts the following technical solutions:
- a pharmaceutical composition containing dimethicone/silicone oil which is mainly prepared from the following raw materials by weight: acetylcysteine or a pharmaceutically acceptable salt thereof, 1 to 1000 parts, and dimethicone or simethicone 1 ⁇ 500 copies.
- dimethicone or simethicone Since dimethicone or simethicone has a strong defoaming effect, the effect of removing the mucus of the digestive tract is weak.
- the mucolytic effect of acetylcysteine can just make up for the weakening of dimethicone or simethicone in addition to mucus, and the pharmacological and physiological inertness of simethicone/simethicone makes it compatible with acetylcysteine. There are no incompatibility taboos. Therefore, the combination of simethicone or simethicone with acetylcysteine has a synergistic effect, without drug interactions, creating incompatibility. .
- acetylcysteine or a pharmaceutically acceptable salt thereof 50 to 500 parts, dimethicone or simethicone, 20 to 200 parts;
- acetylcysteine or a pharmaceutically acceptable salt thereof 80 to 200 parts, dimethicone or simethicone, 20 to 50 parts.
- the above composition is based on the weight of the proportion, in the case of a relatively constant ratio, according to the production regulations Description
- the amount of the pharmaceutical component of the present invention is obtained by extensive research by the inventors, and has good defoaming and slimming action in the above parts by weight.
- the pharmaceutically acceptable salt of acetylcysteine may be: an organic nitrogen salt, a hydrochloride salt, a sulfate salt, an acetate salt, a methanesulfonate. Acid salt, tartrate salt, maleate salt, fumarate salt, hydrobromide salt, aspartate salt.
- the dimethicone/silicone oil-containing pharmaceutical composition of the present invention may be added to one or more pharmaceutically acceptable carriers for oral administration.
- the dimethicone/silicone oil-containing pharmaceutical composition of the present invention can be prepared into an oral solid preparation such as granules, powders, dry suspensions and the like, or into an oral liquid preparation such as a suspension, an emulsion or the like.
- the dimethicone/silicone oil-containing pharmaceutical composition of the present invention can be produced by a conventional method in the prior art of pharmacy, and various pharmaceutically acceptable carriers can be added as needed.
- the carrier includes conventional fillers, binders, wetting agents, disintegrating agents, lubricating agents, suspending agents, emulsifiers, flavoring agents, preservatives, antioxidants and the like in the pharmaceutical field.
- the optional fillers are: starch, dextrin, sucrose, microcrystalline cellulose, mannitol, glucose, lactose, pregelatinized starch, etc.;
- binders are: sodium carboxymethylcellulose, povidone, hydroxypropylcellulose, starch syrup, etc.;
- Alternative disintegrators are: starch, crospovidone, croscarmellose sodium, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, and the like;
- Available lubricants are: magnesium stearate, talc, micronized silica gel, etc.;
- Alternative suspending or emulsifying agents are: tragacanth, acacia, xanthan gum, sodium alginate, sodium carboxymethylcellulose, hypromellose, ethylcellulose, hydroxyethylcellulose , Tween, Span, polyethylene glycol stearate, polyethylene glycol palmitate, glyceryl monostearate, etc.;
- the preservatives to be selected are: methylparaben or its sodium salt, ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate or its sodium salt, sorbic acid, benzyl alcohol, benzoic acid, glycerol, propylene glycol, etc.
- Optional antioxidants are: disodium edetate, sodium edetate, 2, 6-di Butyl p-cresol, butyl hydroxy anisole, etc.;
- the flavoring agent is selected from pharmaceutically useful sweeteners and aromatics, such as sodium saccharin, sucrose, aspartame, sucralose, stevioside, sorbitol, mannitol, various fruit flavors and the like.
- the present invention also provides the use of the above dimethicone/simethicone-containing pharmaceutical composition as an adjuvant for preoperative administration of digestive endoscopy and imaging or imaging. Since dimethicone or simethicone has a strong defoaming effect, the effect of removing the mucus of the digestive tract is weak, making it less effective when used alone in digestive endoscopy and treatment or imaging.
- the present invention is intended to be applied to digestive endoscopy and treatment or
- the foam in the digestive tract is eliminated, and the viscous liquid in the digestive tract can be removed, thereby improving the visibility of the examination, reducing misdiagnosis and missed diagnosis, and facilitating early diagnosis of digestive tract diseases.
- the pharmaceutical composition containing dimethicone/silicone oil of the present invention has the following advantages:
- a acetylcysteine or a pharmaceutically acceptable salt thereof and a dimethicone/simethicone are provided for the preparation of a medicament for defoaming and removing mucus before digestive endoscopy and imaging or imaging examination.
- the composition can be used for digestive endoscopy and treatment or imaging examination, which can effectively improve the visual field clarity of examination and treatment, and improve the diagnosis and treatment of digestive diseases, especially early lesions. Sex.
- composition of the present invention has the same composition as the blank control group and the dimethicone, simethicone or acetylcysteine group alone.
- the superior ability to defoam and remove mucus indicates that the composition is effective in defoaming and removing mucus, and the results are unexpected to those of ordinary skill in the art.
- the present invention prepares a composition of dimethicone or simethicone with acetylcysteine or a pharmaceutically acceptable salt thereof, which has an effective effect and provides a better choice for clinicians and patients. Even if the dimethicone or simethicone preparation and the acetylcysteine preparation are used in combination, the composition of the present invention makes it easier for the patient to take the medicine, and the trouble of taking the medicine for multiple times is omitted.
- a composition of simethicone or simethicone or acetylcysteine is referred to as an acesulfame oil composition.
- a composition of simethicone or simethicone or acetylcysteine is referred to as an acesulfame oil composition.
- the average defoaming capacity of the seven samples was 98%, 95%, 6%, 98%, 98%, 99%, 99%, respectively. It showed that the samples of the composition of the present invention had strong defoaming ability and the foam was almost complete. Elimination, equivalent to the defoaming ability of simethicone or simethicone alone, and the defoaming ability of acetylcysteine alone is weak. It also indicates that acetylcysteine in the composition does not affect the defoaming ability of simethicone or simethicone.
- Test item Dimethicone emulsion, trade name: ⁇ , produced by Japan Okubo Pharmaceutical Co., Ltd., Specification: 20mg/ml, Batch number: AXN2899; Simethicone emulsion, trade name: Bercy, Berlin Chemical Co., Germany Production, Specification: 40mg/ml, Batch No.: 74041; Suspension of acesulfame oil composition (self-made, see Method 3 for preparation).
- RESULTS The experimental animals were 4 male dogs of about 15 kg. There was no significant difference in body weight and health signs. The same food was fed two days before the test. After anesthesia with phenylcyclopiperidine hydrochloride, the lower esophagus is removed to the duodenum. Tighten the duodenum end of the stomach. Injected from the esophageal end: A.100tnl water; B. Dimethicone emulsion 10ml + water 100ml; C. Simethicone 5ml + water 100ml; D. Ethylene sulfonate composition suspension 4ml + water 100ml.
- the acetaminophen composition can significantly eliminate the mucus in the gastric cavity.
- the effect is significantly better than water and dimethicone or simethicone alone.
- Test sample Ethylene sulfonate composition emulsion (self-made, see Method 4 for preparation method).
- Test animals mice, 5 males and 5 males each, males weighing 24 to 26 g, females weighing 20 to 22 g.
- Route of administration Oral gavage.
- Suspension of acesulfame oil composition traits, sedimentation volume ratio, redispersibility, pH value, related substances, content, microbial limit
- Ethylene sulfonate composition emulsion traits, centrifugal stability Sex, pH, related substances, content, microbial limits.
- Acetyl silicone oil composition suspension accelerated stability test data
- acetyl means acetylcysteine
- silicone oil means dimethicone
- acetylcysteine and sucrose powder are passed through a 100 mesh sieve, and used;
- Dimethicone is mixed with silica, placed at 150 ° C for 3 hours, and then taken out after cooling;
- acetylcysteine is uniformly mixed with sucrose powder and starch, it is added to a mixture of dimethicone and silica, and mixed repeatedly to make a suitable soft material after using an appropriate amount of ethanol;
- Acetylcysteine, microcrystalline cellulose and xanthan gum are respectively passed through a 100 mesh sieve and used as spare; the purified water is boiled and deoxidized, and used as a reserve; sodium hydroxide is prepared into a sodium hydroxide solution having a concentration of 1 M, and is reserved. ;
- Acetylcysteine is uniformly mixed with microcrystalline cellulose and xanthan gum, added to mixture I, mixed repeatedly to make it uniform, and then slowly dispersed into glycerin and appropriate amount of purified water after stirring.
- Add solution I, solution II add purified water to nearly full amount, adjust the pH value to 6 ⁇ 7.5 with 1M sodium hydroxide solution, then make up to the whole amount with purified water, stir evenly and then pass through colloid mill to make the average particle size. After 50 ⁇ or less, after collecting the colloid mill effluent, mix again and evenly to obtain a semi-finished product;
- acetylcysteine is passed through a 100 mesh sieve, and is ready for use; the purified water is subjected to boiling deoxidation treatment and is reserved;
- Simethicone and Tween 80 and Span 80 are mixed, and then added with equal proportion of purified water, emulsified completely with a high shear dispersing emulsifier to obtain a milky white uniform colostrum, and slowly added to the solution in the colostrum with stirring.
- solution II, solution I and sorbic acid make up to the full amount with purified water, stir and mix evenly to obtain semi-finished products;
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Abstract
The present invention provides a pharmaceutical composition containing dimethicone/simethicone, mainly prepared from the following raw materials of portion by weight: acetylcysteine or pharmaceutically acceptable salts thereof 1-1000 portion and dimethicone or simethicone 1-500 portion. The composition can be prepared to form various kinds of pharmaceutically acceptable formulations. The composition can be used as an auxiliary medicine administrated before the gastrointestinal endoscopy and treatment or imaging examination. Compared with using acetylcysteine, dimethicone or simethicone alone at the same dosage, the composition of the present invention has stronger effects of defoaming and eliminating mucus.
Description
说 明 书 一种含二甲硅油 /西甲硅油的药物组合物 Description A pharmaceutical composition containing dimethicone / simethicone
本发明涉及医药技术领域，具体地涉及一种乙酰半胱氨酸或其药用盐和二甲 硅油 /西甲硅油的药物组合物。 The present invention relates to the field of medical technology, and in particular to a pharmaceutical composition of acetylcysteine or a pharmaceutically acceptable salt thereof and dimethicone/silicone oil.
背景技术 Background technique
消化内镜在诊断消化道疾病中具有非常重要的地位， 因其直观、 简单而受 到医生青睐， 在临床诊断和治疗中特别常用。 但由于消化道内存在大量泡沬和 黏液， 导致视野不清， 检査时间延长， 患者痛苦增加， 且容易造成误诊和漏诊， 更不利于消化道疾病的早期诊断发现。 Digestive endoscopy plays a very important role in the diagnosis of digestive tract diseases. It is popular among doctors because of its intuitiveness and simplicity, and is especially used in clinical diagnosis and treatment. However, due to the large amount of foam and mucus in the digestive tract, the visual field is unclear, the examination time is prolonged, the patient's pain is increased, and misdiagnosis and missed diagnosis are easily caused, which is not conducive to the early diagnosis of digestive tract diseases.
二甲硅油 （ I ) 为临床上最常用的医学消泡剂， 常用于消化内镜检査和治 疗或腹部影像学检査的术前消泡。 二甲硅油为二甲基硅氧烷聚合物， 由于其表 面张力小， 能改变气泡表面张力， 使其破裂， 从而消除泡沬。 早在二十世纪五、 六十年代， 二甲硅油就已作为消泡剂应用于医学领域。 西甲硅油 （II ) 为二甲 硅油与二氧化硅的复合物， 拥有与二甲硅油相同或更强的消泡能力。 二甲硅油 和西甲硅油均属于药理学和生理学惰性物质， 其消泡作用为物理过程， 物质本 身不涉及化学变化。 Dimethicone (I) is the most commonly used medical defoamer in the clinic and is often used for preoperative defoaming in digestive endoscopy and treatment or abdominal imaging. Dimethicone is a dimethylsiloxane polymer which, due to its small surface tension, can change the surface tension of the bubble and cause it to rupture, thereby eliminating foaming. As early as the 1950s and 1960s, dimethicone was used as a defoaming agent in the medical field. Simethicone (II) is a composite of dimethicone and silica with the same or stronger defoaming ability as dimethicone. Dimethicone and simethicone are both pharmacological and physiologically inert substances, and their defoaming action is a physical process, and the substance itself does not involve chemical changes.
HaC—HaC—
( I ) ( II ) ( I ) ( II )
乙酰半胱氨酸（ΙΠ)， 为 N-乙酰基 -L-半胱氨酸， 为粘液溶解剂， 具有较强的 粘痰溶解作用， 其分子中所含巯基 （-SH-) 能使粘液中黏蛋白多肽链中的二硫 键 （-S-S- ) 断裂， 降低粘液的粘滞性， 并使之液化。 目前临床上常用于大量粘 痰阻塞引起的呼吸困难， 如手术后的咯痰困难、 急生和慢性支气管炎、 支氨管 扩张、 肺结核、 肺炎、 肺气肿等引起的痰液粘稠、 咯痰困难、 痰阻气管等， 尚 可用于对乙酰氨基酚中毒的解毒。
Acetylcysteine (ΙΠ), which is N-acetyl-L-cysteine, is a mucolytic agent with strong viscous lysis, and its thiol group (-SH-) can make mucus The disulfide bond (-SS-) in the middle mucin polypeptide chain is broken, which reduces the viscosity of the mucus and liquefies it. At present, it is often used in clinical practice for dyspnea caused by a large number of phlegm obstruction, such as sputum difficulty after surgery, acute and chronic bronchitis, branch dilatation, tuberculosis, pneumonia, emphysema, etc. Dysphagia, obstruction of the trachea, etc., can still be used for detoxification of acetaminophen poisoning.
(III) (III)
发明内容 说 Summary of the invention
本发明的目的在于提供一种含二甲硅油 /西甲硅油的药物组合物， 该药物组 合物既能消除消化道内泡沬， 又能袪除消化书道内的黏性液体； 该药物组合物能 够用于在消化内镜检査与治疗或影像学检査中作为术前的辅助用药。 The object of the present invention is to provide a pharmaceutical composition containing dimethicone/silicone oil, which can eliminate the bubble in the digestive tract and remove the viscous liquid in the digestive tract; the pharmaceutical composition can be used As a preoperative adjuvant in digestive endoscopy and treatment or imaging.
为实现上述目的， 本发明采用如下技术方案： To achieve the above object, the present invention adopts the following technical solutions:
一种含二甲硅油 /西甲硅油的药物组合物，主要由下列重量份的原料药制成: 乙酰半胱氨酸或其药学上可接受的盐 1〜1000份和二甲硅油或西甲硅油 1〜500 份。 、 A pharmaceutical composition containing dimethicone/silicone oil, which is mainly prepared from the following raw materials by weight: acetylcysteine or a pharmaceutically acceptable salt thereof, 1 to 1000 parts, and dimethicone or simethicone 1 ~500 copies. ,
由于二甲硅油或西甲硅油消泡作用较强， 但袪除消化道黏液的作用较弱。 而乙酰半胱氨酸的黏液溶解作用， 正好可以弥补二甲硅油或西甲硅油袪除黏液 作用较弱的不足， 而且二甲硅油 /西甲硅油的药理学和生理学惰性使其与乙酰半 胱氨酸不存在配伍禁忌。 因此， 二甲硅油或西甲硅油与乙酰半胱氨酸组合应用 具有协同增效作用， 而不会发生药物相互作用， 产生配伍禁忌。 . Since dimethicone or simethicone has a strong defoaming effect, the effect of removing the mucus of the digestive tract is weak. The mucolytic effect of acetylcysteine can just make up for the weakening of dimethicone or simethicone in addition to mucus, and the pharmacological and physiological inertness of simethicone/simethicone makes it compatible with acetylcysteine. There are no incompatibility taboos. Therefore, the combination of simethicone or simethicone with acetylcysteine has a synergistic effect, without drug interactions, creating incompatibility. .
到目前为止， 未见有二甲硅油或西甲硅油与乙酰半胱氨酸或其药用盐的组 合物的研究和使用报道。 So far, no research and use reports have been made on the composition of simethicone or simethicone with acetylcysteine or a pharmaceutically acceptable salt thereof.
优选为： 乙酰半胱氨酸或其药学上接受的盐 50〜500份、 二甲硅油或西甲硅 油 20〜200份； Preferably, it is: acetylcysteine or a pharmaceutically acceptable salt thereof, 50 to 500 parts, dimethicone or simethicone, 20 to 200 parts;
进一步优选为： 乙酰半胱氨酸或其药学上接受的盐 80〜200份、 二甲硅油或 西甲硅油 20〜50份。 Further preferably, it is acetylcysteine or a pharmaceutically acceptable salt thereof, 80 to 200 parts, dimethicone or simethicone, 20 to 50 parts.
以上组成是按重量份作为配比的， 在比例相对不变的情况下可根据生产规
说 明 书 The above composition is based on the weight of the proportion, in the case of a relatively constant ratio, according to the production regulations Description
模调整用量。 Mode adjustment amount.
本发明药物组分的用量是经过发明人大量研究得出的， 在上述重量份范围 内都具有良好的消泡和袪除黏液作用。 The amount of the pharmaceutical component of the present invention is obtained by extensive research by the inventors, and has good defoaming and slimming action in the above parts by weight.
在本发明的含二甲硅油 /西甲硅油的药物组合物中， 所述乙酰半胱氨酸药学 上可接受的盐可以为： 有机氮盐、 盐酸盐、 硫酸盐、 醋酸盐、 甲磺酸盐、 酒石 酸盐、 马来酸盐、 富马酸盐、 氢溴酸盐、 门冬氨酸盐。 In the dimethicone/silicone oil-containing pharmaceutical composition of the present invention, the pharmaceutically acceptable salt of acetylcysteine may be: an organic nitrogen salt, a hydrochloride salt, a sulfate salt, an acetate salt, a methanesulfonate. Acid salt, tartrate salt, maleate salt, fumarate salt, hydrobromide salt, aspartate salt.
本发明的含二甲硅油 /西甲硅油的药物组合物可以添加一种或多种药学上可 接受的载体， 以口服给药的方式使用。 The dimethicone/silicone oil-containing pharmaceutical composition of the present invention may be added to one or more pharmaceutically acceptable carriers for oral administration.
本发明的含二甲硅油 /西甲硅油的药物组合物可将其制备成口服固体制剂， 如颗粒剂、 散剂、 干混悬剂等， 或制成口服液体制剂， 如混悬液、 乳剂等。 The dimethicone/silicone oil-containing pharmaceutical composition of the present invention can be prepared into an oral solid preparation such as granules, powders, dry suspensions and the like, or into an oral liquid preparation such as a suspension, an emulsion or the like.
本发明的含二甲硅油 /西甲硅油的药物组合物可采用现有制药领域中的常规 方法生产， 需要时可添加各种药学上可接受的载体。 The dimethicone/silicone oil-containing pharmaceutical composition of the present invention can be produced by a conventional method in the prior art of pharmacy, and various pharmaceutically acceptable carriers can be added as needed.
所述的载体包括药学领域常规的填充剂、 粘合剂、 湿润剂、 崩解剂、 润滑 剂、 助悬剂、 乳化剂、 矫味剂、 防腐剂、 抗氧剂等。 The carrier includes conventional fillers, binders, wetting agents, disintegrating agents, lubricating agents, suspending agents, emulsifiers, flavoring agents, preservatives, antioxidants and the like in the pharmaceutical field.
所述的可供选择的填充剂有： 淀粉、 糊精、 蔗糖、 微晶纤维素、 甘露醇、 葡萄糖、 乳糖、 预胶化淀粉等； The optional fillers are: starch, dextrin, sucrose, microcrystalline cellulose, mannitol, glucose, lactose, pregelatinized starch, etc.;
可供选择的粘合剂有： 羧甲基纤维素钠、 聚维酮、 羟丙基纤维素、 淀粉浆 等； ' Alternative binders are: sodium carboxymethylcellulose, povidone, hydroxypropylcellulose, starch syrup, etc.;
可供选择的崩解剂有： 淀粉、 交联聚维酮、 交联羧甲基纤维素钠、 羧甲基 淀粉钠、 低取代羟丙基纤维素等； Alternative disintegrators are: starch, crospovidone, croscarmellose sodium, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, and the like;
可供选择润滑剂有： 硬脂酸镁、 滑石粉、 微粉硅胶等； Available lubricants are: magnesium stearate, talc, micronized silica gel, etc.;
可供选择的助悬剂或乳化剂有： 西黄蓍胶、 阿拉伯胶、 黄原胶、 海藻酸钠、 羧甲基纤维素钠、 羟丙甲纤维素、 乙基纤维素、 羟乙基纤维素、 吐温类、 司盘 类、 聚乙二醇硬脂酸酯、 聚乙二醇棕榈酸酯、 单硬脂酸甘油酯等； Alternative suspending or emulsifying agents are: tragacanth, acacia, xanthan gum, sodium alginate, sodium carboxymethylcellulose, hypromellose, ethylcellulose, hydroxyethylcellulose , Tween, Span, polyethylene glycol stearate, polyethylene glycol palmitate, glyceryl monostearate, etc.;
可供选择的防腐剂有： 对羟基苯甲酸甲酯或其钠盐、 对羟基苯甲酸乙酯、 对羟基苯甲酸丙酯或其钠盐、 山梨酸、 苯甲醇、 苯甲酸、 甘油、 丙二醇等； 可选择的抗氧剂有： 乙二胺四乙酸二钠、 乙二胺四乙酸钙钠盐、 2， 6-二叔
丁基对甲酚、 丁基羟基茴香醚等； The preservatives to be selected are: methylparaben or its sodium salt, ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate or its sodium salt, sorbic acid, benzyl alcohol, benzoic acid, glycerol, propylene glycol, etc. Optional antioxidants are: disodium edetate, sodium edetate, 2, 6-di Butyl p-cresol, butyl hydroxy anisole, etc.;
矫味剂则选用药学上常用的甜味剂和芳香剂， 如糖精钠、 蔗糖、 阿司帕坦、 三氯蔗糖、 甜菊素、 山梨醇、 甘露醇、 各种果味香精等。 The flavoring agent is selected from pharmaceutically useful sweeteners and aromatics, such as sodium saccharin, sucrose, aspartame, sucralose, stevioside, sorbitol, mannitol, various fruit flavors and the like.
本发明还提供了上述含二甲硅油 /西甲硅油的药物组合物作为消化内镜检査 与治疗或影像学检査术前给予的辅助用药的用途。 由于二甲硅油或西甲硅油消 泡作用较强， 但袪除消化道黏液的作用较弱， 使得其在消化内镜检査与治疗或 影像学检査中单独应用时效果欠佳。 本发明旨在应用于消化内镜检查与治疔或 说 The present invention also provides the use of the above dimethicone/simethicone-containing pharmaceutical composition as an adjuvant for preoperative administration of digestive endoscopy and imaging or imaging. Since dimethicone or simethicone has a strong defoaming effect, the effect of removing the mucus of the digestive tract is weak, making it less effective when used alone in digestive endoscopy and treatment or imaging. The present invention is intended to be applied to digestive endoscopy and treatment or
影像学检查中消除消化道内泡沫的同时， 又能袪除消化道内的黏性液体， 从而 提高检査的可见度， 减少误诊和漏诊， 利于消化道疾病的早期诊断发现。 In the imaging examination, the foam in the digestive tract is eliminated, and the viscous liquid in the digestive tract can be removed, thereby improving the visibility of the examination, reducing misdiagnosis and missed diagnosis, and facilitating early diagnosis of digestive tract diseases.
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本发明含二甲硅油 /西甲硅油的药物组合物具有以下优点： The pharmaceutical composition containing dimethicone/silicone oil of the present invention has the following advantages:
( 1 )首次提供了一种乙酰半胱氨酸或其药用盐和二甲硅油 /西甲硅油配伍用 于制备消化内镜检査与治疗或影像学检査前消泡和袪除黏液的药物组合物和用 途， 该组合物应用后再进行消化内镜检査与治疗或影像学检査， 可有效提高检 査和治疗视野清晰度， 提高消化道疾病特别是早期病变的诊断和治疗的有效性。 (1) For the first time, a acetylcysteine or a pharmaceutically acceptable salt thereof and a dimethicone/simethicone are provided for the preparation of a medicament for defoaming and removing mucus before digestive endoscopy and imaging or imaging examination. Composition and use, the composition can be used for digestive endoscopy and treatment or imaging examination, which can effectively improve the visual field clarity of examination and treatment, and improve the diagnosis and treatment of digestive diseases, especially early lesions. Sex.
( 2 ) 首次对本明组合物的消泡及袪除黏液效果进行了体外研究， 发现与空 白对照组和单用二甲硅油、 西甲硅油或乙酰半胱氨酸组比较， 本发明组合物同 时具有较强的消泡和袪除黏液能力， 表明组合物在消泡和袪除黏液方面效果显 著， 其结果是本技术领域的普通技术人员所意想不到的。 (2) For the first time, the defoaming and exfoliation effects of the composition of the present invention were studied in vitro, and it was found that the composition of the present invention has the same composition as the blank control group and the dimethicone, simethicone or acetylcysteine group alone. The superior ability to defoam and remove mucus indicates that the composition is effective in defoaming and removing mucus, and the results are unexpected to those of ordinary skill in the art.
( 3 )本发明制备工艺简单， 药品质量均匀稳定， 能够保证临床用药的安全。 (3) The preparation process of the invention is simple, the quality of the medicine is uniform and stable, and the safety of the clinical medication can be ensured.
(4 )本发明将二甲硅油或西甲硅油与乙酰半胱氨酸或其药用盐制备成了组 合物， 其效果确切， 为临床医生和患者提供了较好的用药选择。 即使是分别将 二甲硅油或西甲硅油制剂和乙酰半胱氨酸制剂联合应用， 本发明组合物也使患 者服药更为简便， 省去了一次检查多次服药的麻烦。 (4) The present invention prepares a composition of dimethicone or simethicone with acetylcysteine or a pharmaceutically acceptable salt thereof, which has an effective effect and provides a better choice for clinicians and patients. Even if the dimethicone or simethicone preparation and the acetylcysteine preparation are used in combination, the composition of the present invention makes it easier for the patient to take the medicine, and the trouble of taking the medicine for multiple times is omitted.
以下通过实验例来进一步阐述本发明所述药物的有益效果。 下列实施例中： 二甲硅油或西甲硅油、 乙酰半胱氨酸的组合物简称乙氨硅油组合物。 The beneficial effects of the medicament of the present invention are further illustrated by experimental examples below. In the following examples: A composition of simethicone or simethicone or acetylcysteine is referred to as an acesulfame oil composition.
下列实施例中： 二甲硅油或西甲硅油、 乙酰半胱氨酸的组合物简称乙氨硅 油组合物。
说 明 书 In the following examples: A composition of simethicone or simethicone or acetylcysteine is referred to as an acesulfame oil composition. Instruction manual
实验例 1 Experimental example 1
乙氨硅油组合物药效研究——消泡能力测定试验 Study on the efficacy of ethoxylated silicone oil composition - defoaming capacity test
材料： 特里通 X- 100 (Triton X- 100)， SIGMA试剂； 二甲硅油乳剂， 商品名： 咖斯康， 日本橘生药品工业株式会社生产， 规格： 20mg/ml， 批号： AXN2899; 西甲硅油乳剂， 商品名： 柏西， 德国柏林化学股份公司生产， 规格： 40mg/ml, 批号： 74041； 乙酰半胱氨酸颗粒， 规格： O.lg/袋， 海南某制药公司生产； 乙氨 硅油组合物， 自制 （制备方法见实施例 1〜4)。 Material: Triton X-100, SIGMA reagent; Dimethicone emulsion, trade name: Gascon, produced by Nippon Orange Pharmaceutical Co., Ltd., Specification: 20mg/ml, Batch number: AXN2899; La Liga Silicone oil emulsion, trade name: Percy, produced by Berlin Chemical Co., Ltd., Specification: 40mg/ml, Batch number: 74041; Acetylcysteine granules, Specification: O.lg/bag, produced by a pharmaceutical company in Hainan; Ethylene sulfonate Composition, self-made (see Examples 1 to 4 for the preparation method).
方法： 取 1%特里通 X-100水溶液 100ml八份， 小心注入八个清洁的 250ml暈 筒中， 往量筒中分别加入二甲硅油乳剂 5ml、西甲硅油乳剂 2.5ml、 乙酰半胱氨酸 颗粒 1袋、 乙氨硅油组合物颗粒剂 1袋、 乙氨硅油组合物散剂 1/2袋、 乙氨硅油组 合物混悬剂 2ml、 乙氨硅油组合物乳剂 lml， 第八个量筒不加。 封住八个量筒端 口， 同时置于振荡筛强烈振摇 2分钟， 取出， 记录各量筒的泡沫高度。 以无样品 的第八个量筒的泡沫高度为 100%， 以各样品减少泡沫量百分比计算消泡能力。 重复三次， 取平均值。 Method: Take 100 parts of 100% of 1% Triton X-100 aqueous solution, carefully inject into eight clean 250ml halo tubes, add 5ml of dimethicone emulsion, 2.5ml of simethicone emulsion, and acetylcysteine particles1 to the measuring cylinder. Bag, acesulfame oil composition granules 1 bag, acetaminosilicon oil composition powder 1/2 bag, sulphate oil composition suspension 2ml, acetaminosilicon oil composition emulsion lml, the eighth cylinder is not added. The eight cylinder ends were sealed and shaken vigorously for 2 minutes on a vibrating screen. The foam height of each cylinder was recorded. The foam height of the eighth cylinder without the sample was 100%, and the defoaming ability was calculated by reducing the percentage of foam in each sample. Repeat three times and take the average.
结果： 七份样品的平均消泡能力分别为： 98%、 95%、 6%、 98%、 98%、 99%, 99%， 显示本发明组合物样品消泡能力均很强， 泡沫几乎完全消除， 与单 用二甲硅油或西甲硅油的消泡能力相当， 而单用乙酰半胱氨酸的消泡能力很弱。 同时也说明组合物中的乙酰半胱氨酸不会影响其中二甲硅油或西甲硅油的消泡 能力。 Results: The average defoaming capacity of the seven samples was 98%, 95%, 6%, 98%, 98%, 99%, 99%, respectively. It showed that the samples of the composition of the present invention had strong defoaming ability and the foam was almost complete. Elimination, equivalent to the defoaming ability of simethicone or simethicone alone, and the defoaming ability of acetylcysteine alone is weak. It also indicates that acetylcysteine in the composition does not affect the defoaming ability of simethicone or simethicone.
实验例 2 Experimental example 2
乙氨硅油组合物药效研究——袪除黏液能力测定试验 Study on the Efficacy of Ethylene Sulfate Oil Composition - Determination of Mucus Capability Test
供试品： 二甲硅油乳剂， 商品名： 咖斯康， 日本橘生药品工业株式会社生 产， 规格： 20mg/ml， 批号： AXN2899; 西甲硅油乳剂， 商品名： 柏西， 德国柏 林化学股份公司生产， 规格： 40mg/ml， 批号： 74041 ; 乙氨硅油组合物混悬剂 (自制， 制备方法见实施例 3)。 Test item: Dimethicone emulsion, trade name: 咖斯康, produced by Japan Okubo Pharmaceutical Co., Ltd., Specification: 20mg/ml, Batch number: AXN2899; Simethicone emulsion, trade name: Bercy, Berlin Chemical Co., Germany Production, Specification: 40mg/ml, Batch No.: 74041; Suspension of acesulfame oil composition (self-made, see Method 3 for preparation).
方法： 实验动物为约 15kg的雄性狗 4只， 体重及健康体征无明显差异， 试验 前两日喂食相同食物。 经盐酸苯环已哌啶麻醉后， 切除食道下端至十二指肠段，
将胃的十二指肠端扎紧。 自食道端分别注入： A.100tnl水; B.二甲硅油乳剂 10ml +水 100ml; C.西甲硅油 5ml+水 100ml; D. 乙氨硅油组合物混悬剂 4ml +水 100ml。 METHODS: The experimental animals were 4 male dogs of about 15 kg. There was no significant difference in body weight and health signs. The same food was fed two days before the test. After anesthesia with phenylcyclopiperidine hydrochloride, the lower esophagus is removed to the duodenum. Tighten the duodenum end of the stomach. Injected from the esophageal end: A.100tnl water; B. Dimethicone emulsion 10ml + water 100ml; C. Simethicone 5ml + water 100ml; D. Ethylene sulfonate composition suspension 4ml + water 100ml.
20分钟后， 自大侧弯切开， 采集胃体上部和幽门标本各一个， 并用伊文思兰着 色。 显微镜下观察标本中黏液附着情况。 After 20 minutes, the incision was made from the large side curve, and one of the upper part of the corpus and the pyloric specimen was collected and colored with Evansland. The adhesion of mucus in the specimen was observed under a microscope.
结果： A组仅用水冲洗胃内腔的胃体上部及幽门均附着大量黏液和气泡， 尤 其是幽门部位； B组和 C组采用二甲硅油或西甲硅油乳剂冲洗胃内腔后， 胃体上' 部及幽门气泡明显减少， 但仍附着部分黏液； 而采用乙氨硅油组合物混悬剂 4ml 说 RESULTS: In group A, only a large amount of mucus and air bubbles were attached to the upper part of the stomach and pylorus in the gastric cavity, especially the pyloric part. Group B and group C were treated with dimethicone or simethicone emulsion to wash the gastric cavity. 'The ventral and pyloric bubbles are significantly reduced, but some mucus is still attached; and the suspension of sulphate composition is 4ml.
+水 100ml冲洗胃内腔的 B组胃体上部及幽门仅附着少量黏液和气泡， 可清晰地 观察到胃小区和表面上皮细胞。 + Water 100ml Wash the stomach cavity. The upper part of the stomach and the pylorus of the group B only have a small amount of mucus and air bubbles attached, and the stomach cells and surface epithelial cells can be clearly observed.
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结论： 乙氨硅油组合物能明显消除胃腔体内的黏液。 其效果明显好于水和 单独使用二甲硅油或西甲硅油。 Conclusion: The acetaminophen composition can significantly eliminate the mucus in the gastric cavity. The effect is significantly better than water and dimethicone or simethicone alone.
实验例 3 Experimental example 3
乙氨硅油组合物乳剂急性毒性试验 Acute toxicity test of acesulfame oil composition emulsion
供试品： 乙氨硅油组合物乳剂 （自制， 制备方法见实施例 4)。 Test sample: Ethylene sulfonate composition emulsion (self-made, see Method 4 for preparation method).
受试动物： 小鼠， 每组雌雄各 5只， 雄性体重 24〜26g， 雌性体重 20〜22g。 给药途径： 经口灌胃。 Test animals: mice, 5 males and 5 males each, males weighing 24 to 26 g, females weighing 20 to 22 g. Route of administration: Oral gavage.
观察项目： 死亡数、 一般状态、 体重、 剖检， 计算半数致死量 LD5()。 Observation items: number of deaths, general status, weight, necropsy, and calculation of the median lethal dose LD 5() .
结果： 按照急性毒性试验要求进行预试， 确定每个剂量组给药剂量分别为- Results: Pre-test according to the requirements of the acute toxicity test, and the doses of each dose group were determined to be -
1.50ml/10g、 1.12ml/10g、 0.84ml/10g、 0.63ml/10g、 0.47ml/10g， 相邻两剂量比 值为 1 : 0.75 1.50ml/10g, 1.12ml/10g, 0.84ml/10g, 0.63ml/10g, 0.47ml/10g, the ratio of adjacent doses is 1: 0.75
计算公式： LD^Log—^Xm- i (∑P- 0.5) ]， 其中 Xm为最大剂量组对数值， i为
相邻两组间高低剂量比值的对数， ΣΡ为各组动物死亡率之和， 用小数表示。 计算结果： LD5。=0.8939ml/10g =89.39ml/kg。 Calculate the formula: LD^Log—^Xm- i (∑P- 0.5) ], where Xm is the logarithm of the maximum dose group, i is The logarithm of the high-low dose ratio between the two groups, ΣΡ is the sum of the mortality of each group, expressed as a decimal. Calculation result: LD 5 . = 0.8939 ml/10 g = 89.39 ml/kg.
试验结论： 本试验中乙氨硅油组合物乳剂 LD5Q为 89.39ml/kg， 相当于 50kg体 重人体推荐剂量的 1000倍左右。 表明本品毒性较低， 安全性高。 Test conclusion: In this test, the ED 5Q of the acesulfame oil composition emulsion is 89.39 ml/kg, which is equivalent to about 1000 times of the recommended dose of 50 kg body weight. This product indicates that the product is low in toxicity and high in safety.
实验例 4 Experimental example 4
乙氨硅油组合物加速稳定性试验结果 Acetyl silicone oil composition accelerated stability test results
考察样品： 乙氨硅油组合物混悬剂（见实施例 3 )、 乙氨硅油组合物乳剂（见 Samples for investigation: Suspension of acesulfame oil composition (see Example 3), emulsion of acesulfame oil composition (see
说 Say
实施例 4)。 Example 4).
考察条件： 温度 30±2°C、 相对湿度 65%±5%。 Conditions of investigation: Temperature 30 ± 2 ° C, relative humidity 65% ± 5%.
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考察时间： 0月、 1月、 2月、 3月、 6月。 Inspection time: 0 months, January, February, March, June.
考察指标： （1 ) 乙氨硅油组合物混悬剂： 性状、 沉降体积比、 再分散性、 pH值、 有关物质、 含量、 微生物限度； （2) 乙氨硅油组合物乳剂： 性状、 离心 稳定性、 pH值、 有关物质、 含量、 微生物限度。 Indicators for investigation: (1) Suspension of acesulfame oil composition: traits, sedimentation volume ratio, redispersibility, pH value, related substances, content, microbial limit; (2) Ethylene sulfonate composition emulsion: traits, centrifugal stability Sex, pH, related substances, content, microbial limits.
指标检测方法 （1 ) 乙氨硅油组合物混悬剂 Indicator test method (1) Ethylene sulfonate composition suspension
乙氨硅油组合物混悬剂加速稳定性试验数据 Acetyl silicone oil composition suspension accelerated stability test data
项目 0月 1月 2月 3月 6月 性状 乳白色均 乳白色均 乳白色均 乳白色均 乳白色均 匀混悬液 匀混悬液 匀混悬液 匀混悬液 匀混悬液 沉降体积比 1.00 0.99 0.99 0.98 0.98 再分散性 符合规定 符合规定 符合规定 符合规定 符合规定
pH值 6.6 6.6 6.5 6.5 6.6 有关物质 （％) 0.30 0.32 0.31 0.35 0.40 含 量 乙酰 101.4 101.3 100.9 100.9 100.2 (%) 硅油 99.8 99.8 99.7 99.7 99.7 微生物垠度 符合规定 符合规定 符合规定 符合规定 符合规定 含量测定中乙酰表示乙酰半胱氨酸， 硅油表示二甲硅油 Item: January, January, March, March, June, traits, milky white, milky white, milky white, white, milky white, uniform, white, uniform, suspension, homogenous suspension, uniform suspension, uniform suspension, uniform suspension, sedimentation volume ratio, 1.00 0.99 0.99 0.98 0.98 Dispersion meets the requirements and meets the requirements. pH 6.6 6.6 6.5 6.5 6.6 Related substances (%) 0.30 0.32 0.31 0.35 0.40 Content acetyl 101.4 101.3 100.9 100.9 100.2 (%) Silicone oil 99.8 99.8 99.7 99.7 99.7 Microbiological enthalpy meets the requirements Compliance with the regulations Compliance with the specified content Determination of acetyl Indicates acetylcysteine, silicone oil means dimethicone
(2) 乙氨硅油组合物乳剂 (2) Ethylene sulfonate composition emulsion
说 书 Book
乙氨硅油组合物乳剂加速稳定性试验数据 Ethylene sulfonate composition emulsion accelerated stability test data
含量测定中乙酰表示乙酰半胱氨酸， 硅油表示二甲硅油 In the content determination, acetyl means acetylcysteine, and silicone oil means dimethicone.
结果： 经加速 6个月试验考察， 与 0月数据比较， 乙氨硅油组合物混悬剂和 乙氨硅油组合物乳剂的各项考察指标均无明显变化， 表明本品混悬剂和乳剂组
合物基本稳定， 可预测有效期为 1.5〜2年。 RESULTS: After accelerated 6-month test, compared with the 0-month data, there was no significant change in the indicators of the suspension of the sulphite composition and the sulphate composition emulsion, indicating that the suspension and emulsion group of the product were compared. The composition is basically stable, and the predictable validity period is 1.5 to 2 years.
具体实施方式 下面结合具体实施方式对本实发明作进一步的说明， 但不应 将此理解为本发明上述主题的范围仅限于以下的实施例。 凡基于本发明上述内 容所实现的技术均属于本发明的范围。 以下实施例中各剂型的辅料可以用药学 上可接受的辅料替换， 或者减少、 增加。 BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be further described with reference to the specific embodiments, but it should be understood that the scope of the present invention is limited to the following embodiments. The techniques implemented based on the above-described contents of the present invention are all within the scope of the present invention. The excipients of the various dosage forms in the following examples may be replaced with pharmaceutically acceptable excipients, or reduced or increased.
实施例 1 Example 1
乙氨硅油组合物颗粒剂的制备 Preparation of acesulfame oil composition granules
说 Say
1、 处方: 1, prescription:
二甲硅油 100g Dimethicone 100g
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二氧化硅 5g Silica 5g
乙酰半胱氨酸 500g Acetylcysteine 500g
蔗糖粉 200g Sucrose powder 200g
乙醇 适量 Ethanol
共制成 1000袋 Made a total of 1000 bags
2、 具体步骤： 2. Specific steps:
( 1 ) 乙酰半胱氨酸与蔗糖粉分别过 100目筛， 备用； (1) acetylcysteine and sucrose powder are passed through a 100 mesh sieve, and used;
(2) 按处方量称取原辅料； (2) Weigh the raw materials according to the prescription amount;
( 3 ) 二甲硅油与二氧化硅混合后， 置 150°C放置 3小时， 冷却后取出； (3) Dimethicone is mixed with silica, placed at 150 ° C for 3 hours, and then taken out after cooling;
(4) 乙酰半胱氨酸与蔗糖粉、 淀粉混合均匀后， 加至二甲硅油与二氧化硅 的混合物中， 多次混合使其均勾， 用适量乙醇制成适宜软材后； (4) After acetylcysteine is uniformly mixed with sucrose powder and starch, it is added to a mixture of dimethicone and silica, and mixed repeatedly to make a suitable soft material after using an appropriate amount of ethanol;
( 5 ) 用 20目筛制备湿颗粒； (5) preparing a wet granule with a 20 mesh sieve;
(6) 湿颗粒于 60〜70°C条件下烘干； (6) The wet granules are dried at 60~70 °C;
( 7) 干颗粒 18目筛整粒； (7) dry granules 18 mesh sieve granules;
( 8) 用 10目筛和 80目筛进行筛分， 除去大颗粒及细粉后， 得半成品； (8) Screening with a 10-mesh sieve and an 80-mesh sieve to remove semi-finished products after removing large particles and fine powder;
(9) 半成品经检测外观及主药含量后， 灌装成袋， 得成品； (9) After the semi-finished product has been tested for appearance and main drug content, it is filled into bags to obtain finished products;
( 10 ) 成品检验合格后， 入库。
说 明 书 (10) After the finished product has passed the inspection, it will be put into storage. Instruction manual
3、 临床使用 3, clinical use
于消化内镜检查与治疗或影像学检查前 20分钟， 取乙氨硅油组合物颗粒 1 袋， 用大约 50毫升水溶解分散后口服， 20分钟后再作检査。 服药剂量可根据实 际效果酌情增减。 Twenty minutes before digestive endoscopy and treatment or imaging examination, take 1 bag of sulphate composition, dissolve it in about 50 ml of water, and take it orally. Check it after 20 minutes. The dosage can be increased or decreased as appropriate according to the actual effect.
实施例 2 Example 2
乙氨硅油组合物散剂的制备 Preparation of ethoxysilane oil composition powder
1、 处方： 1, prescription:
西甲硅油 50g Simethicone 50g
乙酰半胱氨酸 400g Acetylcysteine 400g
850g 850g
微粉硅胶 50g Micro-silica gel 50g
共制成 1000袋 Made a total of 1000 bags
2、 具体步骤： 2. Specific steps:
( 1 ) 乙酰半胱氨酸与葡萄糖分别过 100目筛， 备用； (1) acetylcysteine and glucose are passed through a 100 mesh sieve, respectively;
(2) 按处方量称取原辅料； (2) Weigh the raw materials according to the prescription amount;
(3 ) 用葡萄糖吸附西甲硅油， 充分混合使其均匀后， 再与乙酰半胱氨酸、 微粉硅胶混合均匀， 得半成品； (3) adsorbing simethicone with glucose, mixing well to make it uniform, and then mixing with acetylcysteine and microsilica gel to obtain semi-finished products;
(4) 半成品经检测外观及主药含量后， 灌装成袋， 得成品； (4) After the semi-finished product has been tested for appearance and main drug content, it is filled into bags to obtain finished products;
(5 ) 成品检验合格后， 入库。 (5) After the finished product has passed the inspection, it will be put into storage.
3、 临床使用 3, clinical use
于消化内镜检査与治疗或影像学检査前 20分钟， 取乙氨硅油组合物散剂 1 袋， 用大约 50毫升水溶解分散后口服， 20分钟后再作检査。 服药剂量可根据实 际效果酌情增减。 Twenty minutes before digestive endoscopy and treatment or imaging examination, take 1 bag of sulphuric acid oil composition, dissolve it in about 50 ml of water, and take it orally. Check it after 20 minutes. The dosage can be increased or decreased as appropriate according to the actual effect.
实施例 3 Example 3
乙氨硅油组合物混悬剂的制备 Preparation of suspension of acesulfame oil composition
1、 处方：
二甲硅油 50g 1, prescription: Dimethicone 50g
二氧化硅 2.5g Silica 2.5g
乙酰半胱氨酸 100g Acetylcysteine 100g
微晶纤维素 30g Microcrystalline cellulose 30g
黄原胶 5g Xanthan gum 5g
阿司帕坦 5g Aspartam 5g
对羟基苯甲酸乙酯 2g Ethyl p-hydroxybenzoate 2g
说 Say
乙二胺四乙酸二钠 ig Disodium edetate ig
乙醇 20g Ethanol 20g
书 Book
1M氢氧化钠溶液 适量 1M sodium hydroxide solution
纯化水 至 1000ml Purified water to 1000ml
2、 具体步骤: 2. Specific steps:
( 1 ) 乙酰半胱氨酸、 微晶纤维素、 黄原胶分别过 100目筛， 备用； 纯化水 经煮沸脱氧处理后， 备用； 氢氧化钠配制成浓度为 1M的氢氧化钠溶液， 备用； (1) Acetylcysteine, microcrystalline cellulose and xanthan gum are respectively passed through a 100 mesh sieve and used as spare; the purified water is boiled and deoxidized, and used as a reserve; sodium hydroxide is prepared into a sodium hydroxide solution having a concentration of 1 M, and is reserved. ;
(2) 按处方量称取原辅料； (2) Weigh the raw materials according to the prescription amount;
(3) 二甲硅油与二氧化硅混合后， 置 150°C放置 3小时， 冷却后取出， 得混 合物 I； 对羟基苯甲酸乙酯溶解于乙醇中， 得溶液 I， 备用； 乙二胺四乙酸二 钠和阿司帕坦用适量纯化水溶解完全， 得溶液 II， 备用； (3) Dimethicone is mixed with silica, placed at 150 ° C for 3 hours, and then taken out after cooling to obtain a mixture I; ethyl p-hydroxybenzoate is dissolved in ethanol to obtain a solution I, which is used; Disodium acetate and aspartame are dissolved completely with an appropriate amount of purified water to obtain solution II, which is ready for use;
(4) 乙酰半胱氨酸与微晶纤维素、 黄原胶混合均匀后， 加至混合物 I中， 多次混合使其均匀， 然后搅拌状态下缓慢分散到甘油和适量经处理后的纯化水 中， 加入溶液 I、 溶液 II， 加纯化水至近全量时， 用 1M氢氧化钠溶液调节 pH值 到 6〜7.5，再用纯化水定容至全量，搅拌均匀后过胶体磨，使其平均粒径为 50μπι 以下， 收集胶体磨流出液后， 再次混合均匀， 得半成品； (4) Acetylcysteine is uniformly mixed with microcrystalline cellulose and xanthan gum, added to mixture I, mixed repeatedly to make it uniform, and then slowly dispersed into glycerin and appropriate amount of purified water after stirring. Add solution I, solution II, add purified water to nearly full amount, adjust the pH value to 6~7.5 with 1M sodium hydroxide solution, then make up to the whole amount with purified water, stir evenly and then pass through colloid mill to make the average particle size. After 50μπι or less, after collecting the colloid mill effluent, mix again and evenly to obtain a semi-finished product;
(5) 半成品经检测外观及主药含量后， 灌装成 30ml/瓶， 得成品； (5) After the semi-finished product has been tested for appearance and main drug content, it is filled into 30ml/bottle to obtain the finished product;
(6) 成品检验合格后， 入库。 (6) After the finished product has passed the inspection, it will be put into storage.
3、 临床使用
说 明 书 3, clinical use Description
~~于消化内镜检査与治疗或影像学检查前 20分钟， 量取乙氨硅油组合物混悬 液 2〜4毫升， 加 100毫升水摇匀后口服， 20分钟后再作检査。 服药剂量可根据实 际效果酌情增减。 ~~ 20 minutes before digestive endoscopy and treatment or imaging examination, take 2 to 4 ml of the suspension of the sulphate composition, add 100 ml of water and shake well, then take it orally and check again after 20 minutes. The dosage can be increased or decreased as appropriate according to the actual effect.
实施例 4 Example 4
乙氨硅油组合物乳剂的制备 Preparation of ethoxysilicone oil composition emulsion
1、 处方： 1, prescription:
西甲硅油 20g Simethicone 20g
吐温 80 10g Tween 80 10g
司盘 80 10g Span 80 10g
乙酰半胱氨酸 80g Acetylcysteine 80g
羧甲基纤维素钠 6g Carboxymethylcellulose sodium 6 g
糖精钠 O.lg Saccharin sodium O.lg
山梨酸 lg Sorbic acid lg
2， 6-二叔丁基对甲酚 0.05g 2, 6-di-tert-butyl-p-cresol 0.05g
乙二胺四乙酸二钠 lg Disodium edetate lg
乙醇 10g Ethanol 10g
纯化水 至 1000ml Purified water to 1000ml
2、 具体步骤： 2. Specific steps:
( 1 ) 乙酰半胱氨酸过 100目筛， 备用； 纯化水经煮沸脱氧处理后， 备用； (1) acetylcysteine is passed through a 100 mesh sieve, and is ready for use; the purified water is subjected to boiling deoxidation treatment and is reserved;
( 2) 按处方量称取原辅料； (2) Weigh the raw materials according to the prescription amount;
( 3 ) 2， 6-二叔丁基对甲酚溶解于乙醇中， 得溶液 I , 备用； 乙二胺四乙酸 二钠、 乙酰半胱氨酸和糖精钠用适量纯化水溶解完全， 得溶液 II， 备用； 羧甲 基纤维素钠分散于适量纯化水中， 得均匀的分散溶液 III， 备用； (3) 2,6-di-tert-butyl-p-cresol is dissolved in ethanol to obtain solution I, which is ready for use; disodium edetate, acetylcysteine and sodium saccharin are dissolved in an appropriate amount of purified water to obtain a solution. II, spare; sodium carboxymethyl cellulose is dispersed in an appropriate amount of purified water to obtain a uniform dispersion solution III, ready for use;
( 4) 西甲硅油和吐温 80、 司盘 80混合， 再加入等比例纯化水后， 用高剪切 分散乳化机乳化完全， 得乳白色均匀的初乳， 搅拌下于初乳中缓慢加入溶液 III、 溶液 II、 溶液 I和山梨酸， 用纯化水定容至全量， 搅拌混合均匀， 得半成品；
说 明 书 (4) Simethicone and Tween 80 and Span 80 are mixed, and then added with equal proportion of purified water, emulsified completely with a high shear dispersing emulsifier to obtain a milky white uniform colostrum, and slowly added to the solution in the colostrum with stirring. , solution II, solution I and sorbic acid, make up to the full amount with purified water, stir and mix evenly to obtain semi-finished products; Instruction manual
(5)半成品经检测外观、 乳剂稳定性、 主药含量后， 灌装成 30ml/瓶， 得成 口 (5) After the semi-finished product is tested for appearance, emulsion stability, and main drug content, it is filled into 30ml/bottle.
BP ; BP ;
(6) 成 R np检验合格后， 入库。 (6) After passing the R n p test, it is put into storage.
3、 临床使用 3, clinical use
于消化内镜检査与治疗或影像学检查前 20分钟， 量取乙氨硅油组合物乳剂 4〜6毫升， 力 tU 00毫升水摇匀后口服， 20分钟后再作检査。 服药剂量可根据实际 效果酌情增减。
Twenty minutes before digestive endoscopy and treatment or imaging examination, take 4 to 6 ml of the acetaminophen composition emulsion, shake it vigorously with tU 00 ml of water, and then check it after 20 minutes. The dosage can be increased or decreased as appropriate according to the actual effect.
Claims
1、 一种含二甲硅油 /西甲硅油的药物组合物， 其特征在于主要由下列重量份 的原料药制成： 乙酰半胱氨酸或其药学上可接受的盐 1〜1000份和二甲硅油或 西甲硅油 1〜500份。 A pharmaceutical composition containing simethicone/simethicone, which is characterized in that it is mainly prepared from the following raw materials by weight: acetylcysteine or a pharmaceutically acceptable salt thereof, 1 to 1000 parts and dimethyl 1 to 500 parts of silicone oil or simethicone.
2、 如权利要求 1所述的含二甲硅油 /西甲硅油的药物组合物， 其特征在于： 所述的原料药的重量份数为： 乙酰半胱氨酸或其药学上可接受的盐 50〜500份 和二甲硅油或西甲硅油 20〜200份。 2. The dimethicone/silicone oil-containing pharmaceutical composition according to claim 1, wherein the weight of the drug substance is: acetylcysteine or a pharmaceutically acceptable salt thereof 50 ~500 parts and dimethicone or simethicone 20~200 parts.
3、 如权利要求 2所述的含二甲硅油 /西甲硅油的药物组合物， 其特征在于： 所述的原料药的重量份数为： 乙酰半胱氨酸或其药学上可接受的盐 80〜200份 和二甲硅油或西甲硅油 20〜50份。 3. The dimethicone/silicone oil-containing pharmaceutical composition according to claim 2, wherein the weight of the drug substance is: acetylcysteine or a pharmaceutically acceptable salt thereof. ~200 parts and dimethicone or simethicone 20~50 parts.
4、 如权利要求 1〜3任一权利要求所述的含二甲硅油 /西甲硅油的药物组合 物， 其特征在于： 所述的乙酰半胱氨酸药学上可接受的盐为： 有机氮盐、 盐酸 盐、 硫酸盐、 醋酸盐、 甲磺酸盐、 酒石酸盐、 马来酸盐、 富马酸盐、 氢溴酸盐、 门冬氨酸盐。 The dimethicone/silicone oil-containing pharmaceutical composition according to any one of claims 1 to 3, wherein the acetylcysteine pharmaceutically acceptable salt is: an organic nitrogen salt , hydrochloride, sulfate, acetate, methanesulfonate, tartrate, maleate, fumarate, hydrobromide, aspartate.
5、 如权利要求 1〜3任一权利要求所述的含二甲硅油 /西甲硅油的药物组合 物， 其特征在于： 所述的药物组合物与药学上可接受的辅料混合制成任何一种 临床上或药学上可接受的剂型。 The dimethicone/silicone oil-containing pharmaceutical composition according to any one of claims 1 to 3, wherein the pharmaceutical composition is mixed with a pharmaceutically acceptable adjuvant to prepare any one. A clinically or pharmaceutically acceptable dosage form.
6、 如权利要求 5所述的含二甲硅油 /西甲硅油的药物组合物， 其特征在于： 所述的临床上或药学上可接受的剂型为颗粒剂、 散剂、 混悬剂、 乳剂中的一种。 6. The dimethicone/silicone oil-containing pharmaceutical composition according to claim 5, wherein: the clinically or pharmaceutically acceptable dosage form is in the form of granules, powders, suspensions, emulsions. One.
7、 权利要求 1〜3任一权利要求所述的含二甲硅油 /西甲硅油的药物组合物 作为消化内镜检査与治疗或影像学检査术前辅助用药的用途。 7. A pharmaceutical composition comprising dimethicone/silicone oil according to any one of claims 1 to 3 for use as a pre-operative adjuvant for digestive endoscopy and treatment or imaging.
I斗
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| EP2845533A4 (en) * | 2012-04-25 | 2016-02-17 | Chongqing Skyforbio Co Ltd | Vision definition enhancement system and method for gastrointestinal endoscope diagnosis and treatment |
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| CN101596181A (en) * | 2009-07-03 | 2009-12-09 | 重庆健能医药开发有限公司 | A kind of pharmaceutical composition that contains dimeticone/simethicone |
| CN102048690A (en) * | 2011-01-14 | 2011-05-11 | 四川健能制药有限公司 | Dimeticone emulsion and preparation method thereof |
| CN103110961A (en) * | 2012-11-30 | 2013-05-22 | 江苏唯德康医疗科技有限公司 | Preparation method of high-definition endoscope mucus-removal defoaming composite preparation |
| CN107441508B (en) * | 2017-08-13 | 2020-11-20 | 重庆天如生物科技有限公司 | Simethicone composition |
| CN111991373B (en) * | 2020-09-21 | 2022-04-08 | 力品药业(厦门)股份有限公司 | Aripiprazole orally-dissolving film and preparation method thereof |
| CN112870382B (en) * | 2021-01-28 | 2023-05-26 | 复旦大学附属中山医院 | Combination of arabinose and silicone oil defoamer for intestinal tract preparation |
| CN114099434B (en) * | 2021-11-19 | 2022-12-16 | 海南鑫开源医药科技有限公司 | Preparation process of simethicone emulsion |
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| CN1450882A (en) * | 1999-11-04 | 2003-10-22 | 美国爱科赛尔制药有限公司 | Transdermal administration of huperzine |
| CN101596181A (en) * | 2009-07-03 | 2009-12-09 | 重庆健能医药开发有限公司 | A kind of pharmaceutical composition that contains dimeticone/simethicone |
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| CN1450882A (en) * | 1999-11-04 | 2003-10-22 | 美国爱科赛尔制药有限公司 | Transdermal administration of huperzine |
| CN101596181A (en) * | 2009-07-03 | 2009-12-09 | 重庆健能医药开发有限公司 | A kind of pharmaceutical composition that contains dimeticone/simethicone |
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| EP2845533A4 (en) * | 2012-04-25 | 2016-02-17 | Chongqing Skyforbio Co Ltd | Vision definition enhancement system and method for gastrointestinal endoscope diagnosis and treatment |
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