技术领域technical field
本发明属于医药领域中的麻醉药物，具体涉及一种小儿麻醉术前镇静的隐形鼻贴制剂及其制备方法。The invention belongs to anesthetics in the field of medicine, and in particular relates to an invisible nasal patch preparation for preoperative sedation of children under anesthesia and a preparation method thereof.
背景技术Background technique
目前国际上小儿麻醉诱导的主流方法使气体麻醉的吸入诱导，在吸入诱导无法实施的时候，患儿必须口服或肌注一些麻醉药才能入手术室进行常规麻醉诱导，而国内相对落后，主要的小儿麻醉诱导的方案是肌注或者静脉注射镇静药物，针刺会对清醒的小儿造成心理伤害，增加术后各种并发症的发生率，国内外口服的小儿麻醉诱导剂型主要有各类型糖浆混合镇静药的制剂，其给药方式是通过口服固体或液体镇静药配以一定量的水后达到镇静的目的，服药对部分小儿接受度较差，麻醉诱导前饮水，可能增加返流误吸的风险。盐酸右美托咪定是一有效的、高选择性的α2受体激动剂，具有镇静、镇痛、抗焦虑、阻滞交感神经、节俭阿片类药物等作用，提供了独特的镇静类型即“保留意识的镇静”，患者似乎处于睡眠状态，但是容易被唤醒，能与检查者交流合作。At present, the mainstream method of anesthesia induction for children in the world is inhalation induction of gas anesthesia. When inhalation induction cannot be implemented, children must take orally or intramuscularly inject some anesthetics before entering the operating room for routine anesthesia induction. The scheme of pediatric anesthesia induction is intramuscular injection or intravenous injection of sedative drugs. Acupuncture will cause psychological harm to awake children and increase the incidence of various postoperative complications. The oral anesthesia induction dosage forms for children at home and abroad mainly include various types of syrup mixture The preparation of sedative drugs is administered by oral solid or liquid sedative drugs mixed with a certain amount of water to achieve the purpose of sedation. Taking the drug is not acceptable to some children. Drinking water before induction of anesthesia may increase the risk of reflux and aspiration. risk. Dexmedetomidine hydrochloride is an effective, highly selectiveα2 receptor agonist, which has the effects of sedation, analgesia, anxiolysis, sympathetic nerve block, and thrift opioids. It provides a unique type of sedation that is In "sedation with preserved consciousness," the patient appears to be asleep, but is easily aroused and able to communicate and cooperate with the examiner.
基础药理及临床研究表明盐酸右美托咪定鼻腔粘膜吸收生物利用度高，起效快，作用时间相对较短，短期镇静是安全的。此外，它几乎不引起呼吸抑制，还能预防术后恶心呕吐及寒战。迎香穴位皮肤渗透贴敷药物，避免了鼻粘膜喷药的不适及不良反应，又具有穴位刺激疏通经络和药物的双重作用。它是以中医经络学说为理论基础，属于传统中医外治方法的一种重要技术，是祖国医学宝库的一个重要组成部分。内治之理即外置治理，内治之药即是外治之药。穴位贴敷药物不经胃肠给药，无损伤脾胃之弊，通过对局部穴位的刺激作用，经过皮肤透入和经络传导等起作用，且无创伤无痛苦，对惧针者，或不肯服药之人，尤为适宜。Basic pharmacology and clinical studies have shown that dexmedetomidine hydrochloride has high bioavailability of nasal mucosa absorption, rapid onset of action, relatively short duration of action, and short-term sedation is safe. In addition, it causes little respiratory depression and prevents postoperative nausea, vomiting and chills. Yingxiang acupoint skin penetration and application of medicines avoids the discomfort and adverse reactions of nasal mucous membrane spraying, and also has the dual functions of stimulating acupoints to dredge meridians and medicines. It is based on the meridian theory of traditional Chinese medicine, an important technique of traditional Chinese medicine external treatment, and an important part of the motherland's medical treasure house. The principle of internal treatment is external treatment, and the medicine of internal treatment is the medicine of external treatment. Acupoint sticking drugs are not administered through the stomach and intestines, and have no disadvantages of damaging the spleen and stomach. They stimulate local acupoints, penetrate through the skin and conduct through the meridians, and are non-invasive and painless. It is especially suitable for people who take medicine.
发明内容Contents of the invention
本发明所要解决的技术问题在于针对上述技术的不足，提供一种新型的小儿术前镇静的鼻贴剂型。该鼻贴，选用高分子生物材料为载体，具有药效稳定，结构小巧隐形，使用方便舒适，可在穴位靶向给药，药效显著，起效迅速等优点。The technical problem to be solved by the present invention is to provide a new type of nasal patch formulation for children's preoperative sedation in view of the deficiencies of the above technologies. The nasal patch uses high molecular biomaterials as the carrier, and has the advantages of stable drug effect, small and invisible structure, convenient and comfortable use, targeted drug delivery at acupoints, significant drug effect, and rapid onset of effect.
本发明的具体技术方案如下：Concrete technical scheme of the present invention is as follows:
一种小儿麻醉术前镇静的隐形鼻贴,包括透明背贴和贴合于透明背贴上的含有药物成分的弹性生物胶体。An invisible nasal strip for sedation before anesthesia for children, comprising a transparent back patch and an elastic biological colloid containing medicinal ingredients attached to the transparent back patch.
作为优选项：所述透明背贴为生物纤维索膜；所述弹性生物胶体由生物骨架材料与药物β-环糊精包合物制成。As a preferred item: the transparent back sticker is a biological fiber cable film; the elastic biological colloid is made of a bio-skeleton material and a drug β-cyclodextrin inclusion compound.
作为优选项：所述生物骨架材料由基质材料、黏合剂和保湿剂构成；所述基质材料、黏合剂和保湿剂按质量份数比为1：1：1。As a preferred item: the bio-skeleton material is composed of a matrix material, a binder and a moisturizing agent; the ratio of the matrix material, the binder and the moisturizing agent is 1:1:1 in parts by mass.
作为优选项：所述基质材料为明胶和中粘度聚乙烯醇两种的混合物；黏合剂为透明质酸；保湿剂为丙三醇。As a preferred item: the matrix material is a mixture of gelatin and medium-viscosity polyvinyl alcohol; the binder is hyaluronic acid; the moisturizing agent is glycerol.
作为优选项：所述药物β-环糊精包合物由药用量的盐酸右美托咪定与精油的混合物通过β-环糊精包合技术制成，所述精油和盐酸右美托咪定混合物的体积与药物β-环糊精的质量比为体积/质量=1：4。As a preference: the drug β-cyclodextrin inclusion complex is made from a mixture of a medicinal amount of dexmedetomidine hydrochloride and essential oil through β-cyclodextrin inclusion technology, and the essential oil and dexmedetomidine hydrochloride The volume ratio of the mididine mixture to the drug β-cyclodextrin is volume/mass=1:4.
作为优选项：所述精油为茉莉精油或玫瑰精油或辛夷精油或薰衣草精油。As a preferred item: the essential oil is jasmine essential oil or rose essential oil or magnolia essential oil or lavender essential oil.
本发明还提供一种制备上述的小儿麻醉术前镇静的隐形鼻贴的方法,步骤如下：The present invention also provides a method for preparing the above-mentioned invisible nasal strip for preoperative sedation of children under anesthesia, the steps are as follows:
（1）药物β-环糊精包合物的制备：采用饱和水溶液法或超声法将β-环糊精溶于蒸馏水制成饱和溶液，加入精油和盐酸右美托咪定组合物，制成药物β-环糊精包合物；(1) Preparation of drug β-cyclodextrin inclusion compound: using saturated aqueous solution method or ultrasonic method to dissolve β-cyclodextrin in distilled water to make a saturated solution, add essential oil and dexmedetomidine hydrochloride composition to prepare Drug β-cyclodextrin inclusion complex;
（2）弹性生物胶体的制备：将制备生物骨架材料的基质材料完全溶于水，在温度50-60℃条件下加入黏合剂，保湿剂及药物β-环糊精包合物，搅拌均匀制成弹性生物胶体；(2) Preparation of elastic biocolloid: the matrix material for preparation of bioskeleton material is completely dissolved in water, and the binder, humectant and drug β-cyclodextrin inclusion compound are added at a temperature of 50-60°C, and the mixture is stirred evenly to prepare into elastic biocolloids;
（3）将弹性生物胶体倒入涂膜机压入塑封模板，制成目标产品，然后与背贴材料贴合在一起，即得。(3) Pour the elastic biological colloid into the film coating machine and press it into the plastic sealing template to make the target product, and then stick it together with the back sticker material to get the product.
作为优选项：所述步骤（1）过程为：采用超声法，称取β-环糊精，溶于45℃蒸馏水中配制β-环糊精饱和溶液，向β-环糊精饱和溶液中加入精油和右美托咪定的组合物，混匀，45℃恒温超声处理30min后置冰箱中冷藏24h，取出抽滤，弃去滤液，收集产物，用少许无水乙醇洗涤产物3次后真空干燥24h，即得β-环糊精包合物。As a preference item: the process of the step (1) is: use ultrasonic method to weigh β-cyclodextrin, dissolve it in 45°C distilled water to prepare a saturated solution of β-cyclodextrin, add to the saturated solution of β-cyclodextrin The composition of essential oil and dexmedetomidine, mix well, 45 ℃ constant temperature ultrasonic treatment for 30 minutes, put it in the refrigerator for 24 hours, take it out and filter it with suction, discard the filtrate, collect the product, wash the product with a little absolute ethanol 3 times, and then dry it in vacuum After 24 hours, the inclusion compound of β-cyclodextrin was obtained.
作为优选项：所述步骤（2）过程中基质材料为明胶和聚乙烯醇的混合物时，基质材料处理方法：将明胶与聚乙烯醇分别在水中浸泡4-8小时，在水浴70℃条件下搅拌聚乙烯醇溶液，待完全溶解时缓缓加入明胶溶液，搅拌溶解完全，即得。As a preference: when the matrix material is a mixture of gelatin and polyvinyl alcohol in the process of step (2), the treatment method of the matrix material is to soak the gelatin and polyvinyl alcohol in water for 4-8 hours respectively, in a water bath at 70°C Stir the polyvinyl alcohol solution, and when it is completely dissolved, slowly add the gelatin solution, stir to dissolve completely, and the product is obtained.
与现有技术相比，本发明具有以下有益效果：Compared with the prior art, the present invention has the following beneficial effects:
1、本发明以中医学理论为依据，鼻贴药物含特殊配伍的天然植物精油，精油具有超强的渗透能力，可迅速进入皮下；并且其香味易于被小儿接受，诱导方便易行，父母满意度好；茉莉精油被称为“精油之王”，有缓解神经过敏、促进放松和停止紧张的功效；玫瑰精油被誉为“液体黄金”，可减缓疲劳、镇静安神和舒缓压力的功效；辛夷精油有调节心侓，缓和呼吸急促等症状，且可以镇定及松弛神经，减轻紧张和焦虑的情绪；薰衣草精油被誉为精油之萃，有舒缓减压，放松心情，治疗失眠的功效；右美托咪定具有独特的“保留意识的镇静”作用，使患者处于可唤醒的睡眠状态，且不影响呼吸；1. The present invention is based on the theory of traditional Chinese medicine. The nasal paste medicine contains natural plant essential oils with special compatibility. The essential oils have super penetrating ability and can quickly enter the subcutaneous area; and its fragrance is easy to be accepted by children, and the induction is convenient and easy. Parents are satisfied Jasmine essential oil is known as the "king of essential oils", which has the effect of relieving nervousness, promoting relaxation and stopping tension; rose essential oil is known as "liquid gold", which can relieve fatigue, calm the nerves and relieve stress; magnolia Essential oils can regulate heart disease, alleviate shortness of breath and other symptoms, and can calm and relax nerves, relieve tension and anxiety; lavender essential oil is known as the essence of essential oils, and it has the effect of relieving stress, relaxing the mood, and treating insomnia; Tomidine has a unique "consciousness-preserving sedation" effect, which puts the patient in a wakeable sleep state without affecting breathing;
2、本发明通过β-环糊精包合技术和生物骨架材料结合，制成直径5-10mm的贴合穴位的特殊结构，使其在迎香穴释放，透皮吸收，不仅可起到按摩，扩张鼻腔的作用，而且无创伤无痛苦，对惧针及不肯服药的患儿，尤为适宜；2. The present invention combines β-cyclodextrin inclusion technology with bio-skeleton materials to make a special structure with a diameter of 5-10mm that fits the acupoints, so that it can be released at the Yingxiang acupoint and absorbed through the skin, which can not only massage , the effect of dilating the nasal cavity, and without trauma and pain, it is especially suitable for children who are afraid of needles and who refuse to take medicine;
3、本发明通过隐形材料的使用和特殊的成型工艺，结构微小，材料色彩与皮肤一致，起到隐形的效果，由于贴剂体积较小，对于听话合作的大龄患儿还可以直接贴到鼻腔内部，使用方便舒适且起效更快；3. Through the use of invisible materials and a special molding process, the present invention has a small structure, and the color of the material is consistent with the skin, which has an invisible effect. Due to the small size of the patch, it can also be directly attached to the nasal cavity for older children who are obedient and cooperative. Internal, convenient and comfortable to use and faster onset;
4、本发明的小儿麻醉术前镇静鼻贴，可防止口服固体药剂所带来的误吸至气管造成窒息；4. The preoperative sedative nasal patch for children under anesthesia can prevent suffocation caused by oral inhalation of solid medicaments into the trachea;
5、本发明的小儿麻醉术前镇静鼻贴不需要特殊的环境和设备，患儿无液体摄入，胃内容物返流误吸概率小。5. The pre-anesthesia sedative nasal patch for children of the present invention does not require a special environment and equipment, and the child has no liquid intake, and the probability of gastric content reflux and aspiration is small.
且本发明通过特殊安全性试验证明，本发明的鼻贴对皮肤无刺激不过敏，药效稳定。And the present invention proves through the special safety test that the nasal paste of the present invention has no irritation and no allergy to the skin, and the drug effect is stable.
附图说明Description of drawings
图1为本发明鼻贴贴于迎香穴的结构示意图；Fig. 1 is the structural representation of sticking nasal paste of the present invention on Yingxiang point;
图2为本发明鼻贴贴于鼻腔的结构示意图；Fig. 2 is a structural representation of the nasal patch of the present invention attached to the nasal cavity;
其中：透明背贴1，弹性生物胶体2。Among them: transparent back sticker 1, elastic biological colloid 2.
具体实施方式detailed description
下面结合实施例和附图对本发明做进一步说明。The present invention will be further described below in conjunction with the embodiments and accompanying drawings.
实施例1：Example 1:
（1） 采用超声法，称取β-环糊精约4g，溶于蒸馏水（45℃）配制饱和溶液。加入茉莉精油和右美托咪定的组合物1ml混匀，45℃恒温超声处理30min，置冰箱中冷藏24h，取出抽滤，用少许无水乙醇洗涤3次。将粉末置真空干燥器中干燥24h，即得β-环糊精包合物；(1) Using ultrasonic method, weigh about 4g of β-cyclodextrin and dissolve it in distilled water (45°C) to prepare a saturated solution. Add 1ml of the composition of jasmine essential oil and dexmedetomidine, mix well, ultrasonically treat at a constant temperature of 45°C for 30min, put it in the refrigerator for 24h, take it out for suction filtration, and wash with a little absolute ethanol for 3 times. Dry the powder in a vacuum dryer for 24 hours to obtain the inclusion compound of β-cyclodextrin;
（2）取明胶5g加入溶解量的水浸泡4-8小时，聚乙烯醇5g加入溶解量的水浸泡4-8小时，在水浴70℃条件下搅拌聚乙烯醇溶液，待完全溶解时缓缓加入明胶溶液，搅拌溶解完全后将温度降到50℃，加入透明质酸10g，丙三醇10g，β-环糊精包合物5g，搅拌均匀后倒入涂膜机压入塑封模板，包装成品。(2) Take 5g of gelatin and add dissolved amount of water to soak for 4-8 hours, add 5g of polyvinyl alcohol and add dissolved amount of water to soak for 4-8 hours, stir the polyvinyl alcohol solution in a water bath at 70°C, and slowly dissolve it when it is completely dissolved Add gelatin solution, stir to dissolve completely, lower the temperature to 50°C, add 10g of hyaluronic acid, 10g of glycerol, and 5g of β-cyclodextrin inclusion compound, stir well, pour into a film coating machine, press into a plastic sealing template, and pack finished product.
（3）模具制成直径2-5mm的契合迎香穴位形状的小半圆球形或半椭圆形，背贴材料透明的生物纤维索膜，直径5-10mm或5×20mm长条状，涂以亲水性粘性涂层，色彩与皮肤一致，起到隐形的效果，将制成的胶体平面黏贴于背贴中央。(3) The mold is made into a small semi-spherical or semi-elliptical shape with a diameter of 2-5mm that fits the shape of Yingxiang acupoints, and the back is pasted with a transparent bio-fiber cable membrane, with a diameter of 5-10mm or 5×20mm long strips, coated with pro- Water-based viscous coating, the color is consistent with the skin, and has an invisible effect. Paste the finished colloid plane on the center of the back sticker.
实施例2：Example 2:
（1）采用超声法，称取β-环糊精约4g，溶于蒸馏水（45℃）配制饱和溶液。加入玫瑰精油和右美托咪定的组合物1ml混匀，45℃恒温超声处理30min，置冰箱中冷藏24h，取出抽滤，用少许无水乙醇洗涤3次。将粉末置真空干燥器中干燥24h，即得β-环糊精包合物。(1) Using ultrasonic method, weigh about 4g of β-cyclodextrin and dissolve it in distilled water (45°C) to prepare a saturated solution. Add 1ml of the composition of rose essential oil and dexmedetomidine, mix well, ultrasonically treat at a constant temperature of 45°C for 30min, store in the refrigerator for 24h, take it out for suction filtration, and wash 3 times with a little absolute ethanol. Dry the powder in a vacuum dryer for 24 hours to obtain the β-cyclodextrin inclusion compound.
（2）取明胶5g加入溶解量的水浸泡4-8小时，聚乙烯醇5g加入溶解量的水浸泡4-8小时，在水浴70℃条件下搅拌聚乙烯醇溶液，待完全溶解时缓缓加入明胶溶液，搅拌溶解完全后将温度降到50℃，加入透明质酸10g，丙三醇10g，β-环糊精包合物5g，搅拌均匀后倒入涂膜机压入塑封模板，包装成品。(2) Take 5g of gelatin and add dissolved amount of water to soak for 4-8 hours, add 5g of polyvinyl alcohol and add dissolved amount of water to soak for 4-8 hours, stir the polyvinyl alcohol solution in a water bath at 70°C, and slowly dissolve it when it is completely dissolved Add gelatin solution, stir to dissolve completely, lower the temperature to 50°C, add 10g of hyaluronic acid, 10g of glycerol, and 5g of β-cyclodextrin inclusion compound, stir well, pour into a film coating machine, press into a plastic sealing template, and pack finished product.
（3）模具制成直径2-5mm的契合迎香穴位形状的小半圆球形或半椭圆形，背贴材料透明的生物纤维索膜，直径5-10mm或5×20mm长条状，涂以亲水性粘性涂层，色彩与皮肤一致，起到隐形的效果，将制成的胶体平面黏贴于背贴中央。(3) The mold is made into a small semi-spherical or semi-elliptical shape with a diameter of 2-5mm that fits the shape of Yingxiang acupoints, and the back is pasted with a transparent bio-fiber cable membrane, with a diameter of 5-10mm or 5×20mm long strips, coated with pro- Water-based viscous coating, the color is consistent with the skin, and has an invisible effect. Paste the finished colloid plane on the center of the back sticker.
实施例3：Example 3:
（1）采用超声法，称取β-环糊精约4g，溶于蒸馏水（45℃）配制饱和溶液。加入辛夷精油和右美托咪定的组合物1ml混匀，45℃恒温超声处理30min，置冰箱中冷藏24h，取出抽滤，用少许无水乙醇洗涤3次。将粉末置真空干燥器中干燥24h，即得β-环糊精包合物。(1) Using ultrasonic method, weigh about 4g of β-cyclodextrin and dissolve it in distilled water (45°C) to prepare a saturated solution. Add magnolia essential oil and 1ml of the composition of dexmedetomidine, mix well, ultrasonically treat at a constant temperature of 45°C for 30min, put it in the refrigerator for 24h, take it out for suction filtration, and wash with a little absolute ethanol for 3 times. Dry the powder in a vacuum dryer for 24 hours to obtain the β-cyclodextrin inclusion compound.
（2）取明胶5g加入溶解量的水浸泡4-8小时，聚乙烯醇5g加入溶解量的水浸泡4-8小时，在水浴70℃条件下搅拌聚乙烯醇溶液，待完全溶解时缓缓加入明胶溶液，搅拌溶解完全后将温度降到50℃，加入透明质酸10g，丙三醇10g，β-环糊精包合物5g，搅拌均匀后倒入涂膜机压入塑封模板，包装成品。(2) Take 5g of gelatin and add dissolved amount of water to soak for 4-8 hours, add 5g of polyvinyl alcohol and add dissolved amount of water to soak for 4-8 hours, stir the polyvinyl alcohol solution in a water bath at 70°C, and slowly dissolve it when it is completely dissolved Add gelatin solution, stir to dissolve completely, lower the temperature to 50°C, add 10g of hyaluronic acid, 10g of glycerol, and 5g of β-cyclodextrin inclusion compound, stir well, pour into a film coating machine, press into a plastic sealing template, and pack finished product.
（3）模具制成直径2-5mm的契合迎香穴位形状的小半圆球形或半椭圆形，背贴材料透明的生物纤维索膜，直径5-10mm或5×20mm长条状，涂以亲水性粘性涂层，色彩与皮肤一致，起到隐形的效果，将制成的胶体平面黏贴于背贴中央。(3) The mold is made into a small semi-spherical or semi-elliptical shape with a diameter of 2-5mm that fits the shape of Yingxiang acupoints, and the back is pasted with a transparent bio-fiber cable membrane, with a diameter of 5-10mm or 5×20mm long strips, coated with pro- Water-based viscous coating, the color is consistent with the skin, and has an invisible effect. Paste the finished colloid plane on the center of the back sticker.
实施例4：Example 4:
（1）采用超声法，称取β-环糊精约4g，溶于蒸馏水（45℃）配制饱和溶液。加入薰衣草精油和右美托咪定的组合物1ml混匀，45℃恒温超声处理30min，置冰箱中冷藏24h，取出抽滤，用少许无水乙醇洗涤3次。将粉末置真空干燥器中干燥24h，即得β-环糊精包合物。(1) Using ultrasonic method, weigh about 4g of β-cyclodextrin and dissolve it in distilled water (45°C) to prepare a saturated solution. Add 1ml of the composition of lavender essential oil and dexmedetomidine, mix well, ultrasonically treat at a constant temperature of 45°C for 30min, put it in the refrigerator for 24h, take it out for suction filtration, and wash with a little absolute ethanol for 3 times. Dry the powder in a vacuum dryer for 24 hours to obtain the β-cyclodextrin inclusion compound.
（2）取明胶5g加入溶解量的水浸泡4-8小时，聚乙烯醇5g加入溶解量的水浸泡4-8小时，在水浴70℃条件下搅拌聚乙烯醇溶液，待完全溶解时缓缓加入明胶溶液，搅拌溶解完全后将温度降到50℃，加入透明质酸10g，丙三醇10g，β-环糊精包合物5g，搅拌均匀后倒入涂膜机压入塑封模板，包装成品。(2) Take 5g of gelatin and add dissolved amount of water to soak for 4-8 hours, add 5g of polyvinyl alcohol and add dissolved amount of water to soak for 4-8 hours, stir the polyvinyl alcohol solution in a water bath at 70°C, and slowly dissolve it when it is completely dissolved Add gelatin solution, stir to dissolve completely, lower the temperature to 50°C, add 10g of hyaluronic acid, 10g of glycerol, and 5g of β-cyclodextrin inclusion compound, stir well, pour into a film coating machine, press into a plastic sealing template, and pack finished product.
（3）模具制成直径2-5mm的契合迎香穴位形状的小半圆球形或半椭圆形，背贴材料透明的生物纤维索膜，直径5-10mm或5×20mm长条状，涂以亲水性粘性涂层，色彩与皮肤一致，起到隐形的效果，将制成的胶体平面黏贴于背贴中央。(3) The mold is made into a small semi-spherical or semi-elliptical shape with a diameter of 2-5mm that fits the shape of Yingxiang acupoints, and the back is pasted with a transparent bio-fiber cable membrane, with a diameter of 5-10mm or 5×20mm long strips, coated with pro- Water-based viscous coating, the color is consistent with the skin, and has an invisible effect. Paste the finished colloid plane on the center of the back sticker.
实施例4：Example 4:
（4）采用超声法，称取β-环糊精约4g，溶于蒸馏水（45℃）配制饱和溶液。加入薰衣草精油和右美托咪定的组合物1ml混匀，45℃恒温超声处理30min，置冰箱中冷藏24h，取出抽滤，用少许无水乙醇洗涤3次。将粉末置真空干燥器中干燥24h，即得β-环糊精包合物。(4) Using ultrasonic method, weigh about 4 g of β-cyclodextrin and dissolve it in distilled water (45°C) to prepare a saturated solution. Add 1ml of the composition of lavender essential oil and dexmedetomidine, mix well, ultrasonically treat at a constant temperature of 45°C for 30min, put it in the refrigerator for 24h, take it out for suction filtration, and wash with a little absolute ethanol for 3 times. Dry the powder in a vacuum dryer for 24 hours to obtain the β-cyclodextrin inclusion compound.
（5）取明胶5g加入溶解量的水浸泡4-8小时，聚乙烯醇5g加入溶解量的水浸泡4-8小时，在水浴70℃条件下搅拌聚乙烯醇溶液，待完全溶解时缓缓加入明胶溶液，搅拌溶解完全后将温度降到50℃，加入透明质酸10g，丙三醇10g，β-环糊精包合物5g，搅拌均匀后倒入涂膜机压入塑封模板，包装成品。(5) Take 5g of gelatin and add dissolved amount of water to soak for 4-8 hours, add 5g of polyvinyl alcohol and add dissolved amount of water to soak for 4-8 hours, stir the polyvinyl alcohol solution in a water bath at 70°C, and slowly dissolve it when it is completely dissolved Add gelatin solution, stir to dissolve completely, lower the temperature to 50°C, add 10g of hyaluronic acid, 10g of glycerol, and 5g of β-cyclodextrin inclusion compound, stir well, pour into a film coating machine, press into a plastic sealing template, and pack finished product.
模具制成直径2-5mm的契合迎香穴位形状的小半圆球形或半椭圆形，背贴材料透明的生物纤维索膜，直径5-10mm或5×20mm长条状，涂以亲水性粘性涂层，色彩与皮肤一致，起到隐形的效果，将制成的胶体平面黏贴于背贴中央。The mold is made into a small semi-spherical or semi-elliptical shape with a diameter of 2-5mm that fits the shape of Yingxiang acupoint, and the back is pasted with a transparent biological fiber cable film, with a diameter of 5-10mm or a strip of 5×20mm, coated with hydrophilic adhesive Coating, the color is consistent with the skin, has an invisible effect, and the colloid plane is pasted in the center of the back sticker.
局部刺激性和过敏性评价：Evaluation of local irritation and allergy:
1、参照《中药、天然药物刺激性和溶血性研究技术指导原则》2005.3，皮肤刺激性试验，结果表明：本鼻贴对白兔的完整皮肤和破损皮肤均不产生刺激性，提示鼻贴外用不产生刺激性反应。1. Referring to the "Technical Guidelines for Irritation and Hemolytic Research of Traditional Chinese Medicine and Natural Medicines" 2005.3, skin irritation test, the results showed that the nasal paste did not cause irritation to the intact skin and damaged skin of white rabbits, suggesting that the nasal paste is not irritating for external use. Produce an irritating reaction.
2、参照《中药、天然药物免疫毒性（过敏性、光过敏反应）研究的技术指导原则》2005.3，主动皮肤过敏试验，结果表明：本鼻贴对豚鼠皮肤不产生过敏性，提示鼻贴外用不产生过敏反应。2. Referring to "Technical Guiding Principles for the Study of Immunotoxicity (Allergies, Photosensitivity) of Traditional Chinese Medicines and Natural Medicines" 2005.3, the active skin allergy test showed that the nasal patch does not produce allergies to the skin of guinea pigs, suggesting that the nasal patch is not suitable for external use. Allergic reaction.
本实施例制备的小儿麻醉术前镇静鼻贴制剂分为以下等级：The preoperative sedative nasal patch preparation for children with anesthesia prepared in this embodiment is divided into the following grades:
无药剂型：适用于医生或者父母贴敷，用以引导小儿贴敷；Non-pharmaceutical form: suitable for doctors or parents to apply to guide children to apply;
5μg(每支剂型中右美托咪定的含量)：适用于体重小于等于5kg的小儿；5μg (the content of dexmedetomidine in each dosage form): suitable for children weighing less than or equal to 5kg;
10μg(每支剂型中右美托咪定的含量)：适用于体重大于5kg小于等于10kg的小儿；10μg (the content of dexmedetomidine in each dosage form): suitable for children weighing more than 5kg and less than or equal to 10kg;
15μg(每支剂型中右美托咪定的含量)：适用于体重大于10kg小于等于15kg的小儿；15μg (the content of dexmedetomidine in each dosage form): suitable for children weighing more than 10kg and less than or equal to 15kg;
20μg(每支剂型中右美托咪定的含量)：适用于体重大于15kg小于等于20kg的小儿；20μg (the content of dexmedetomidine in each dosage form): suitable for children weighing more than 15kg and less than or equal to 20kg;
30μg(每支剂型中右美托咪定的含量)：适用于体重大于20kg的小儿。30μg (the content of dexmedetomidine in each dosage form): suitable for children weighing more than 20kg.
本发明的小儿麻醉术前镇静鼻贴的使用方法如下：The usage method of the preoperative sedative nasal patch for children with anesthesia of the present invention is as follows:
该鼻贴可由小儿父母于手术术前1h贴于小儿迎香穴或鼻腔内，术前半小时进入手术等待区，并哄其入睡，一般一支药剂约45-60分钟起效，入睡后将患儿平放于手术推车上，而后由麻醉医生平车推入（或抱入）手术内，在手术床上应用七氟醚等吸入气体常规诱导至一定麻醉深度后，行动静脉穿刺术和后续麻醉。The nasal patch can be pasted on the child's Yingxiang acupoint or in the nasal cavity by the parents of the child 1 hour before the operation, enter the waiting area for the operation half an hour before the operation, and coax the child to fall asleep. Generally, one medicine will take effect in about 45-60 minutes, and the patient will be relieved after falling asleep. The infant is placed flat on the surgical trolley, and then pushed (or held) into the operation by the anesthesiologist on the flat trolley. After routine induction to a certain depth of anesthesia with sevoflurane and other inhaled gases on the operating bed, venipuncture and subsequent anesthesia are carried out. .
本发明制备的盐酸右美托咪定鼻贴制剂，对于准备行手术的患儿，通过将鼻贴制剂贴于迎香穴或鼻腔形式使鼻贴制剂中所含的镇静药物盐酸右美托咪定经鼻粘膜迅速吸收，达到麻醉前镇静的目的且不影响呼吸，避免了肌注或静脉注射针刺给小儿带来的不良心理作用。The dexmedetomidine hydrochloride nasal patch preparation prepared by the present invention, for children who are going to undergo surgery, can make the sedative drug dexmedetomidine hydrochloride contained in the nasal patch preparation The drug is quickly absorbed through the nasal mucosa, achieving the purpose of sedation before anesthesia without affecting breathing, and avoiding the adverse psychological effects on children caused by intramuscular injection or intravenous injection of acupuncture.
应当理解的是，本说明书未详细阐述的部分均属于现有技术。It should be understood that the parts not described in detail in this specification belong to the prior art.
应当理解的是，上述针对较佳实施例的描述较为详细，并不能因此而认为是对本发明专利保护范围的限制，本领域的普通技术人员在本发明的启示下，在不脱离 本发明权利要求所保护的范围情况下，还可以做出替换或变形，均落入本发明的保护范围之内，本发明的请求保护范围应以所附权利要求为准。It should be understood that the above-mentioned descriptions for the preferred embodiments are relatively detailed, and should not therefore be considered as limiting the scope of the patent protection of the present invention. Within the scope of protection, replacements or modifications can also be made, all of which fall within the protection scope of the present invention, and the scope of protection of the present invention should be based on the appended claims.
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611119213.1ACN106727443A (en) | 2016-12-08 | 2016-12-08 | Preoperative calm stealthy nose paste preparation of a kind of pediatric anesthesia and preparation method thereof |
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611119213.1ACN106727443A (en) | 2016-12-08 | 2016-12-08 | Preoperative calm stealthy nose paste preparation of a kind of pediatric anesthesia and preparation method thereof |
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| CN106727443Atrue CN106727443A (en) | 2017-05-31 |
| Application Number | Title | Priority Date | Filing Date |
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| CN201611119213.1AWithdrawnCN106727443A (en) | 2016-12-08 | 2016-12-08 | Preoperative calm stealthy nose paste preparation of a kind of pediatric anesthesia and preparation method thereof |
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| CN110893186A (en)* | 2018-09-12 | 2020-03-20 | 宜昌人福药业有限责任公司 | Pharmaceutical composition and preparation method and application thereof |
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