CN105381159B - A compound aloe vera polysaccharide external gel for treating burns - Google Patents
A compound aloe vera polysaccharide external gel for treating burns Download PDFInfo
- Publication number
- CN105381159B CN105381159B CN201510739991.XA CN201510739991A CN105381159B CN 105381159 B CN105381159 B CN 105381159B CN 201510739991 A CN201510739991 A CN 201510739991A CN 105381159 B CN105381159 B CN 105381159B
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- CN
- China
- Prior art keywords
- parts
- polysaccharide
- aloe vera
- aloe
- barbadensis miller
- 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.)
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Links
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Classifications
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- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/886—Aloeaceae (Aloe family), e.g. aloe vera
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- A—HUMAN NECESSITIES
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- A61K9/0012—Galenical forms characterised by the site of application
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- A—HUMAN NECESSITIES
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
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Abstract
本发明公开了一种用于治疗烧伤的复方库拉索芦荟多糖外用凝胶,按重量份计由以下原料组分混合制成,1000重量份的原料组成为:主药20‑80份,基质3‑50份,保湿剂10‑90份,三乙醇胺1‑5份,磷酸盐缓冲液补足至1000份;所述主药为库拉索芦荟提取物,或库拉索芦荟库拉索芦荟提取物和纳米银粉、纳米锌粉中的一种或两种的组合。本发明具有绿色天然、安全无害、治疗烧伤效果显著、吸收较快、药效稳定持久、携带运输方便等优点,既提高了中药材资源的利用率,满足了医疗需要,又达到了扩大其临床应用的目的。The invention discloses a compound aloe vera polysaccharide external gel for treating burns, which is prepared by mixing the following raw material components in parts by weight. 3-50 parts, 10-90 parts of moisturizing agent, 1-5 parts of triethanolamine, and phosphate buffer to make up to 1,000 parts; the main drug is aloe vera extract, or aloe vera curacao extract One or a combination of nano-silver powder and nano-zinc powder. The invention has the advantages of green and natural, safe and harmless, obvious effect on treating burns, fast absorption, stable and lasting drug effect, convenient carrying and transportation, etc., which not only improves the utilization rate of Chinese medicinal material resources, satisfies the medical needs, but also achieves the expansion of its purpose of clinical application.
Description
技术领域technical field
本发明涉及一种医用凝胶,特别涉及一种用于治疗烧伤的复方库拉索芦荟多糖外用凝胶。The invention relates to a medical gel, in particular to a compound aloe vera polysaccharide external gel for treating burns.
背景技术Background technique
烧伤一般系指由于热力如沸液(水、油、汤)、炽热金属(液体或固体)、火焰、蒸汽和高温气体等所致的体表组织损害,主要是皮肤损害。严重者可伤及皮下组织、肌肉、骨骼、关节、神经、血管,甚至内脏。在烧伤治疗中,其创面处理是治疗烧伤的主要部分,局部抗菌用药是避免创面发生侵袭性感染的重要方法。该局部抗菌药物应有使用方便、抗菌谱广、副反应少以及难产生耐药性等特点。Burn generally refers to the damage to the body surface tissue, mainly skin damage, caused by heat such as boiling liquid (water, oil, soup), hot metal (liquid or solid), flame, steam and high temperature gas. In severe cases, subcutaneous tissue, muscles, bones, joints, nerves, blood vessels, and even internal organs can be injured. In the treatment of burns, the wound treatment is the main part of the treatment of burns, and local antibiotics are an important method to avoid invasive infection of the wounds. The topical antibacterial drug should have the characteristics of convenient use, broad antibacterial spectrum, few side effects, and difficulty in producing drug resistance.
当前治疗过程最为常用的药物就是西药,目前使用较多的是抗生素类药物。由于创面是导致侵袭性感染的入口,并且烧伤创面局部血管发生栓塞,全身抗生素用药很难到达局部。同时近年来抗生素的泛滥使用,使得烧烫伤感染的常见菌也不断发生改变,加之不同地域用药的不同,病原菌对药物的敏感程度也有不同,所以寻找开发新型、高效的烧伤药物是亟需解决的问题。The most commonly used drugs in the current treatment process are western medicines, and antibiotics are currently used more. Since the wound is the entry point for invasive infection and the local blood vessels of the burn wound are embolized, it is difficult for systemic antibiotics to reach the local area. At the same time, the widespread use of antibiotics in recent years has made the common bacteria of burns and scald infections continue to change. In addition to the differences in the use of drugs in different regions, the sensitivity of pathogenic bacteria to drugs is also different. Therefore, it is urgent to find and develop new and efficient burn drugs. question.
磺胺嘧啶银软膏是治疗烧伤创面的传统用药方式,具有抗菌及促进生长的作用。但磺胺嘧啶银会造成烧伤周围组织的小血管及早期毛细血管发生栓塞,在一定程度上加剧了创面的严重,而且对烧伤创面具有一定刺激性。Silver sulfadiazine ointment is a traditional medication for treating burn wounds, with antibacterial and growth-promoting effects. However, silver sulfadiazine can cause embolism of small blood vessels and early capillaries in the surrounding tissues of the burn, which aggravates the severity of the wound to a certain extent, and has certain irritation to the burn wound.
芦荟是百合科芦荟属多年生常绿多肉质草本植物,具有生命力强、药用价值高等特点,曾被冠以“万能良药”、“天然美容师”、“全能植物”等美称,是一种集医药、食用、美容和观赏于一体的重要经济植物。其性寒味苦,归肝、胃、大肠经,具有泻下通便,清肝泻火,杀虫疗疳的功效,用于热结便秘,惊痫,小儿疳积;外治癣疮等。芦荟以其独特的功效和广泛的用途逐渐受到全世界的关注。Aloe vera is a perennial evergreen and succulent herb of the Liliaceae family. It has the characteristics of strong vitality and high medicinal value. It is an important economic plant that integrates medicine, food, beauty and ornamental. It is cold in nature and bitter in taste. It belongs to the liver, stomach and large intestine meridians. It has the functions of laxative, clearing the liver and purging fire, and killing insects to treat chancre. . Aloe vera has gradually attracted worldwide attention for its unique efficacy and wide range of uses.
芦荟中的成分多达70多种,其中芦荟多糖是芦荟凝胶的主要生物活性组分。现代医药学研究显示,芦荟具有抗感染消炎、提高免疫力、抗肿瘤、抗胃溃疡、护肝、保护心肌缺血、降血脂血糖等多种功效。芦荟具有抑菌作用,薛春兰等对复方芦荟药膜抑菌效果的研究显示药膜对金黄色葡萄球菌、表皮葡萄球菌、大肠杆菌均有不同程度的抑菌效果,而对乙型溶血性链球菌、普通变形杆菌和铜绿假单胞抑菌效果不明显。There are more than 70 components in aloe vera, among which aloe vera polysaccharide is the main biologically active component of aloe vera gel. Modern medical research shows that aloe vera has anti-infection and anti-inflammatory, improving immunity, anti-tumor, anti-stomach ulcer, protecting liver, protecting myocardial ischemia, reducing blood lipid and blood sugar and other effects. Aloe vera has bacteriostatic effect. Xue Chunlan et al. have studied the bacteriostatic effect of compound aloe vera film. The bacteriostatic effect of cocci, Proteus vulgaris and Pseudomonas aeruginosa was not obvious.
凝胶剂指提取物与适宜基质制成具凝胶特性的半固体或稠厚液体制剂。按基质不同,凝胶剂可分为水性凝胶与油性凝胶。水性凝胶基质一般由水、甘油或丙二醇与纤维素衍生物、卡波姆和海藻酸盐、西黄蓍胶、明胶、淀粉等构成;油性凝胶基质由液状石蜡与聚氧乙烯或脂肪油与胶体硅或铝皂、锌皂构成。必要时可加入保湿剂、防腐剂、抗氧剂、透皮促进剂等附加剂。Gels refer to semi-solid or thick liquid preparations of extracts and suitable bases with gel properties. According to different substrates, gels can be divided into water-based gels and oil-based gels. The aqueous gel base is generally composed of water, glycerol or propylene glycol and cellulose derivatives, carbomer and alginate, tragacanth, gelatin, starch, etc.; the oily gel base is composed of liquid paraffin and polyoxyethylene or fatty oil It is composed of colloidal silicon or aluminum soap and zinc soap. Additives such as moisturizing agents, preservatives, antioxidants, and skin penetration enhancers may be added when necessary.
发明内容SUMMARY OF THE INVENTION
本发明的目的在于提供一种用于治疗烧伤的复方库拉索芦荟多糖外用凝胶,具有绿色天然、安全无害、治疗烧伤效果显著、吸收较快、药效稳定持久、携带运输方便等优点,既提高了中药材资源的利用率,满足了医疗需要,又达到了扩大其临床应用的目的。The object of the present invention is to provide a compound aloe vera polysaccharide external gel for treating burns, which has the advantages of being green and natural, safe and harmless, having remarkable effect on treating burns, fast absorption, stable and lasting drug effect, convenient carrying and transportation, etc. , which not only improves the utilization rate of Chinese herbal medicine resources, meets the medical needs, but also achieves the purpose of expanding its clinical application.
本发明解决其技术问题所采用的技术方案是:The technical scheme adopted by the present invention to solve its technical problems is:
一种用于治疗烧伤的复方库拉索芦荟多糖外用凝胶,按重量份计由以下原料组分混合制成,1000重量份的原料组成为:主药20-80份,基质3-50份,保湿剂10-90份,三乙醇胺1-5份,磷酸盐缓冲液补足至1000份;所述主药为库拉索芦荟提取物,或库拉索芦荟库拉索芦荟提取物和纳米银粉、纳米锌粉中的一种或两种的组合。A compound aloe vera polysaccharide external gel for treating burns is prepared by mixing the following raw material components in parts by weight, and 1000 parts by weight of the raw materials are composed of: 20-80 parts of main medicine and 3-50 parts of matrix , 10-90 parts of moisturizing agent, 1-5 parts of triethanolamine, phosphate buffer to make up to 1000 parts; the main medicine is aloe vera extract, or aloe vera curacao extract and nano silver powder , one or a combination of nano-zinc powder.
本发明的凝胶剂是一类具有半固体性质的大分子网络体系,它能够与作用部位较长时间的紧密粘附,有较好的生物相容性,且制备简单,易于操作。凝胶剂吸水溶胀后所形成的水化凝胶层对药物有一定的控释作用,使用凝胶剂治疗烧伤,可延长药物与皮肤的作用时间,并控制释药速率,从而减少给药次数,增加患者顺应性。所以,凝胶剂是非常适合烧伤创面的外用制剂。采用本发明的上述配方,治疗烧伤效果显著、吸收较快、药效稳定持久。纳米银粉能够抗菌,纳米锌粉能够促进伤口愈合。The gelling agent of the present invention is a macromolecular network system with semi-solid properties, which can closely adhere to the action site for a long time, has good biocompatibility, is simple in preparation and easy to operate. The hydrated gel layer formed after the gel absorbs water and swells has a certain controlled release effect on the drug. Using the gel to treat burns can prolong the action time of the drug and the skin, and control the release rate, thereby reducing the number of administrations. , increase patient compliance. Therefore, the gel is a very suitable external preparation for burn wounds. By adopting the above formula of the present invention, the treatment effect of burns is remarkable, the absorption is fast, and the drug effect is stable and lasting. Nano-silver powder is antibacterial, and nano-zinc powder can promote wound healing.
作为优选,所述基质选自卡波姆-940、卡波姆-934、卡波姆-980、羟丙基甲基纤维素-K4M、羟丙基甲基纤维素-K15M、羟丙基甲基纤维素-K100M、聚乙二醇-4000、羧甲基纤维素钠、甲基纤维素、西黄蓍胶、明胶、聚乙烯吡咯烷酮、聚卡波菲、海藻酸盐、聚丙烯酸钠、淀粉、壳聚糖中的一种或几种。Preferably, the matrix is selected from carbomer-940, carbomer-934, carbomer-980, hydroxypropyl methylcellulose-K4M, hydroxypropyl methylcellulose-K15M, hydroxypropyl methylcellulose Cellulose-K100M, polyethylene glycol-4000, sodium carboxymethyl cellulose, methyl cellulose, tragacanth, gelatin, polyvinylpyrrolidone, polycarbophil, alginate, sodium polyacrylate, starch , one or more of chitosan.
作为优选,按重量份计由以下原料组分混合制成,1000重量份的原料组成为:库拉索芦荟提取物20份,纳米银粉10份,纳米锌粉10份,卡波姆-980 5份,保湿剂50份,三乙醇胺2份,磷酸盐缓冲液补足至1000份。作为优选,所述库拉索芦荟提取物为库拉索芦荟多糖,或为库拉索芦荟多糖与库拉索芦荟醇提物按照20-30:1的重量比的混合物。Preferably, it is prepared by mixing the following raw material components in parts by weight, and 1000 parts by weight of raw materials are composed of: 20 parts of aloe vera extract, 10 parts of nano silver powder, 10 parts of nano zinc powder, 5 parts of carbomer-980 parts, 50 parts of humectant, 2 parts of triethanolamine, and phosphate buffer to make up to 1000 parts. Preferably, the Aloe vera extract is Aloe vera polysaccharide, or a mixture of Aloe vera polysaccharide and Aloe vera alcohol extract in a weight ratio of 20-30:1.
库拉索芦荟提取物为单一的库拉索芦荟多糖,对烧伤伤口的修复也有很好地效果。更优选的,是将库拉索芦荟多糖与库拉索芦荟醇提物按特定配比组合发挥功效,库拉索芦荟醇提物含有芦荟素、芦荟大黄素等成分,对烧伤伤口的修复有很好地效果,与库拉索芦荟多糖混合使用,协同发挥作用,效果明显优于单一的库拉索芦荟多糖。Aloe vera extract is a single polysaccharide of aloe vera, which also has a good effect on the repair of burn wounds. More preferably, Aloe vera polysaccharide and Aloe vera alcohol extract are combined in a specific proportion to exert their effects, and the alcohol extract of Aloe vera contains aloe vera, aloe-emodin and other components, which are effective in the repair of burn wounds. It has a very good effect. It is used in combination with Aloe vera polysaccharide, and it works synergistically, and the effect is obviously better than that of single Aloe vera polysaccharide.
作为优选,所述库拉索芦荟多糖的由以下方法制备而得:As preferably, the polysaccharide of Aloe vera is prepared by the following method:
(1)粗多糖提取:新鲜六年生库拉索芦荟,清洗、去刺,去离子水中浸泡以脱除表皮渗出的黄色汁液,去皮,刮取内层凝胶,称取凝胶1000g,榨汁得凝胶液,凝胶液离心,收集上清液,减压浓缩后,加入无水乙醇至乙醇终浓度为80%,4℃静置12h,收集沉淀,沉淀用无水乙醇洗涤,60℃真空干燥,粉碎后得粗多糖;(1) Crude polysaccharide extraction: fresh six-year-old Aloe vera, washed, de-thorn, soaked in deionized water to remove the yellow juice exuded from the epidermis, peeled, scraped the inner gel, weighed 1000g of the gel, Squeeze the juice to obtain a gel liquid, centrifuge the gel liquid, collect the supernatant, concentrate under reduced pressure, add absolute ethanol to a final ethanol concentration of 80%, stand at 4°C for 12 hours, collect the precipitate, and wash the precipitate with absolute ethanol, Vacuum drying at 60°C, and pulverizing to obtain crude polysaccharide;
(2)脱蛋白:将步骤(1)所得粗多糖加去离子水溶解得粗多糖提取液,粗多糖提取液与脱蛋白液按照1:0.2-0.3的体积比混匀,离心,收集上清液,重复上述操作3次,所得上清液真空减压浓缩除有机溶剂,冷冻干燥后得库拉索芦荟多糖粗粉;(2) Deproteinization: the crude polysaccharide obtained in step (1) is dissolved in deionized water to obtain a crude polysaccharide extract. The crude polysaccharide extract and the deproteinized solution are mixed in a volume ratio of 1:0.2-0.3, centrifuged, and the supernatant is collected. liquid, repeat the above-mentioned operation 3 times, the obtained supernatant is concentrated under reduced pressure to remove the organic solvent, and after freeze-drying, aloe vera polysaccharide coarse powder is obtained;
(3)超滤:库拉索芦荟多糖粗粉加去离子水溶解,离心,取上清液加去离子水稀释得浓度为0.5mg/mL的库拉索芦荟多糖溶液,库拉索芦荟多糖溶液用超滤膜截留,截留获得分子量大于10万的产物,真空干燥后得库拉索芦荟多糖。(3) Ultrafiltration: Aloe vera polysaccharide coarse powder is dissolved in deionized water, centrifuged, and the supernatant is diluted with deionized water to obtain a solution of aloe vera polysaccharide with a concentration of 0.5 mg/mL. The solution is intercepted by an ultrafiltration membrane, and a product with a molecular weight greater than 100,000 is obtained by intercepting, and the aloe vera polysaccharide is obtained after vacuum drying.
通过本发明的方法获得的库拉索芦荟多糖,尤其是选择分子量大于10万的产物,纯度高,治疗烧伤效果好。The aloe vera polysaccharide obtained by the method of the invention, especially the product with a molecular weight greater than 100,000, has high purity and good effect on treating burns.
作为优选,所述脱蛋白液为氯仿与正丁醇按照3:1的体积比混合而得。Preferably, the deproteinized solution is obtained by mixing chloroform and n-butanol in a volume ratio of 3:1.
作为优选,所述库拉索芦荟醇提物由以下方法制备而得:将库拉索芦荟冷冻干燥,然后在低温超微粉碎机中2-5℃下低温粉碎处理,得细度100-150目的芦荟低温粉,将芦荟低温粉与质量浓度95%的乙醇溶液按照1g:10-15ml的料液比混合均匀,超声功率为450-500w下超声提取30-50min,然后加热至50-60℃,提取1-2h,抽滤,在旋转蒸发仪上蒸发浓缩至黏稠状,冷冻干燥。通过本发明特定的提取方法获得的库拉索芦荟醇提物含有芦荟素、芦荟大黄素等成分,对烧伤伤口的修复有很好地效果。Preferably, the alcohol extract of Aloe vera is prepared by the following method: freeze-drying Aloe vera, and then pulverize it at a low temperature of 2-5°C in a low-temperature ultrafine pulverizer to obtain a fineness of 100-150 Objective Aloe vera low-temperature powder, aloe vera low-temperature powder and 95% mass concentration ethanol solution are mixed uniformly according to the material-liquid ratio of 1g: 10-15ml, ultrasonic extraction is performed under the ultrasonic power of 450-500w for 30-50min, and then heated to 50-60 ℃ , extracted for 1-2h, suction filtered, evaporated and concentrated to a viscous state on a rotary evaporator, and freeze-dried. The alcohol extract of Aloe vera obtained by the specific extraction method of the present invention contains aloe vera, aloe-emodin and other components, and has a good effect on the repair of burn wounds.
作为优选,所述保湿剂选自甘油、丙二醇、山梨醇、聚乙二醇中的一种或几种。Preferably, the moisturizing agent is selected from one or more of glycerin, propylene glycol, sorbitol and polyethylene glycol.
作为优选,所述磷酸盐缓冲液的pH为6.86。Preferably, the pH of the phosphate buffer is 6.86.
本发明的有益效果是:具有绿色天然、安全无害、治疗烧伤效果显著、吸收较快、药效稳定持久、携带运输方便等优点,既提高了中药材资源的利用率,满足了医疗需要,又达到了扩大其临床应用的目的,具有广阔的应用前景。The beneficial effects of the invention are as follows: it has the advantages of being green and natural, safe and harmless, obvious in treating burns, fast in absorption, stable and lasting in drug effect, convenient in carrying and transportation, etc., which not only improves the utilization rate of Chinese medicinal material resources, but also meets the medical needs. It has achieved the purpose of expanding its clinical application and has broad application prospects.
具体实施方式Detailed ways
下面通过具体实施例,对本发明的技术方案作进一步的具体说明。The technical solutions of the present invention will be further described in detail below through specific examples.
本发明中,若非特指,所采用的原料和设备等均可从市场购得或是本领域常用的。下述实施例中的方法,如无特别说明,均为本领域的常规方法。In the present invention, unless otherwise specified, the raw materials and equipment used can be purchased from the market or commonly used in the field. The methods in the following examples, unless otherwise specified, are conventional methods in the art.
本发明使用的磷酸盐缓冲液pH为6.86,参照中国药典(2010版)二部的方法配置。The pH of the phosphate buffer solution used in the present invention is 6.86, and is configured with reference to the method of Chinese Pharmacopoeia (2010 Edition) Part II.
实施例1:Example 1:
一种用于治疗烧伤的复方库拉索芦荟多糖外用凝胶,按重量份计由以下原料组分混合制成:库拉索芦荟多糖20份,羧甲基纤维素钠50份,甘油10份,三乙醇胺1份,磷酸盐缓冲液补足至1000份。A compound aloe vera polysaccharide external gel for treating burns is prepared by mixing the following raw material components in parts by weight: 20 parts of aloe vera polysaccharide, 50 parts of sodium carboxymethyl cellulose, and 10 parts of glycerin , 1 part of triethanolamine, and phosphate buffer to make up to 1000 parts.
实施例2:Example 2:
一种用于治疗烧伤的复方库拉索芦荟多糖外用凝胶,按重量份计由以下原料组分混合制成:库拉索芦荟多糖80份,卡波姆-940 5份,山梨醇、聚乙二醇90份,三乙醇胺5份,磷酸盐缓冲液补足至1000份。A compound aloe vera polysaccharide external gel for treating burns is prepared by mixing the following raw material components in parts by weight: 80 parts of aloe vera polysaccharide, 5 parts of carbomer-940, sorbitol, polysaccharide 90 parts of ethylene glycol, 5 parts of triethanolamine, and phosphate buffer to make up to 1000 parts.
实施例3:Example 3:
一种用于治疗烧伤的复方库拉索芦荟多糖外用凝胶,按重量份计由以下原料组分混合制成:库拉索芦荟多糖20份,纳米银粉(市售)10份,甲基纤维素20份,甘油20份,三乙醇胺2份,磷酸盐缓冲液补足至1000份。A compound aloe vera polysaccharide external gel for treating burns is prepared by mixing the following raw material components in parts by weight: 20 parts of aloe vera polysaccharide, 10 parts of nano silver powder (commercially available), methyl fiber 20 parts of vegetarian, 20 parts of glycerol, 2 parts of triethanolamine, and phosphate buffer to make up to 1000 parts.
实施例4:Example 4:
一种用于治疗烧伤的复方库拉索芦荟多糖外用凝胶,按重量份计由以下原料组分混合制成:库拉索芦荟提取物20份(库拉索芦荟多糖与库拉索芦荟醇提物按照20:1的重量比的混合物),纳米锌粉(市售)10份,羟丙基甲基纤维素-K4M 30份,甘油25份,三乙醇胺2份,磷酸盐缓冲液补足至1000份。A compound aloe vera polysaccharide external gel for treating burns is prepared by mixing the following raw material components in parts by weight: 20 parts of aloe vera extract (aloe vera polysaccharide and aloe vera alcohol) The mixture of extracts according to the weight ratio of 20:1), 10 parts of nano zinc powder (commercially available), 30 parts of hydroxypropyl methylcellulose-K4M, 25 parts of glycerol, 2 parts of triethanolamine, and phosphate buffer to make up to 1000 copies.
实施例5:Example 5:
一种用于治疗烧伤的复方库拉索芦荟多糖外用凝胶,按重量份计由以下原料组分混合制成:库拉索芦荟多糖20份,纳米银粉10份,纳米锌粉10份,卡波姆-980 5份,甘油50份,三乙醇胺2份,磷酸盐缓冲液补足至1000份。A compound aloe vera polysaccharide external gel for treating burns is prepared by mixing the following raw material components in parts by weight: 20 parts of aloe vera polysaccharide, 10 parts of nano silver powder, 10 parts of nano zinc powder, 5 parts of Bohm-980, 50 parts of glycerol, 2 parts of triethanolamine, and phosphate buffer to make up to 1000 parts.
实施例6:Example 6:
一种用于治疗烧伤的复方库拉索芦荟多糖外用凝胶,按重量份计由以下原料组分混合制成:库拉索芦荟提取物20份(库拉索芦荟多糖与库拉索芦荟醇提物按照25:1的重量比的混合物),纳米银粉10份,纳米锌粉10份,卡波姆-980 8份,甘油50份,三乙醇胺2份,磷酸盐缓冲液补足至1000份。A compound aloe vera polysaccharide external gel for treating burns is prepared by mixing the following raw material components in parts by weight: 20 parts of aloe vera extract (aloe vera polysaccharide and aloe vera alcohol) The extract is a mixture in a weight ratio of 25:1), 10 parts of nano silver powder, 10 parts of nano zinc powder, 8 parts of carbomer-980, 50 parts of glycerol, 2 parts of triethanolamine, and phosphate buffer to make up to 1000 parts.
实施例7:Example 7:
一种用于治疗烧伤的复方库拉索芦荟多糖外用凝胶,按重量份计由以下原料组分混合制成:库拉索芦荟提取物25份(库拉索芦荟多糖与库拉索芦荟醇提物按照30:1的重量比的混合物),纳米银粉7份,纳米锌粉8份,卡波姆-980 4份,甘油40份,三乙醇胺4份,磷酸盐缓冲液补足至1000份。A compound aloe vera polysaccharide external gel for treating burns is prepared by mixing the following raw material components in parts by weight: 25 parts of aloe vera extract (aloe vera polysaccharide and aloe vera alcohol) The extract is a mixture in a weight ratio of 30:1), 7 parts of nano silver powder, 8 parts of nano zinc powder, 4 parts of carbomer-980, 40 parts of glycerol, 4 parts of triethanolamine, and phosphate buffer to make up to 1000 parts.
本发明中库拉索芦荟多糖的由以下方法制备而得:Aloe vera polysaccharide in the present invention is prepared by the following method:
(1)粗多糖提取:新鲜六年生库拉索芦荟,清洗、去刺,去离子水中浸泡以脱除表皮渗出的黄色汁液,去皮,刮取内层凝胶,称取凝胶1000g,榨汁2min得凝胶液,凝胶液离心(8000r/min,15min),收集上清液,减压浓缩后(浓缩比为1:2),加入无水乙醇至乙醇终浓度为80%,4℃静置12h,收集沉淀,沉淀用无水乙醇洗涤,60℃真空干燥,粉碎后得粗多糖;(1) Crude polysaccharide extraction: fresh six-year-old Aloe vera, washed, de-thorn, soaked in deionized water to remove the yellow juice exuded from the epidermis, peeled, scraped the inner gel, weighed 1000g of the gel, Squeeze the juice for 2 min to obtain a gel liquid, centrifuge the gel liquid (8000 r/min, 15 min), collect the supernatant, concentrate under reduced pressure (the concentration ratio is 1:2), add absolute ethanol to the final concentration of 80% ethanol, Let stand at 4°C for 12h, collect the precipitate, wash the precipitate with absolute ethanol, vacuum dry at 60°C, and pulverize to obtain crude polysaccharide;
(2)脱蛋白:将步骤(1)所得粗多糖加去离子水溶解得粗多糖提取液(浓度1mg/mL),粗多糖提取液与脱蛋白液(氯仿与正丁醇按照3:1的体积比混合而得)按照1:0.2-0.3的体积比混匀,离心,收集上清液,重复上述操作3次,所得上清液真空减压浓缩除有机溶剂,冷冻干燥后得库拉索芦荟多糖粗粉;(2) Deproteinization: the crude polysaccharide obtained in step (1) is dissolved in deionized water to obtain a crude polysaccharide extract (concentration 1 mg/mL), the crude polysaccharide extract and the deproteinized solution (chloroform and n-butanol in a ratio of 3:1) Volume ratio mixing) according to the volume ratio of 1:0.2-0.3, mix well, centrifuge, collect the supernatant, repeat the above operation 3 times, the obtained supernatant is concentrated in vacuo to remove the organic solvent, freeze-drying to obtain Curacao Aloe vera polysaccharide meal;
(3)超滤:库拉索芦荟多糖粗粉加去离子水溶解,离心,取上清液加去离子水稀释得浓度为0.5mg/mL的库拉索芦荟多糖溶液,库拉索芦荟多糖溶液用超滤膜截留,截留获得分子量大于10万的产物,真空干燥后得库拉索芦荟多糖。(3) Ultrafiltration: Aloe vera polysaccharide coarse powder is dissolved in deionized water, centrifuged, and the supernatant is diluted with deionized water to obtain a solution of aloe vera polysaccharide with a concentration of 0.5 mg/mL. The solution is intercepted by an ultrafiltration membrane, and a product with a molecular weight greater than 100,000 is obtained by intercepting, and the aloe vera polysaccharide is obtained after vacuum drying.
本发明库拉索芦荟醇提物由以下方法制备而得:将库拉索芦荟冷冻干燥,然后在低温超微粉碎机中2-5℃下低温粉碎处理,得细度100-150目的芦荟低温粉,将芦荟低温粉与质量浓度95%的乙醇溶液按照1g:10-15ml的料液比混合均匀,超声功率为450-500w下超声提取30-50min,然后加热至50-60℃,提取1-2h,抽滤,在旋转蒸发仪上蒸发浓缩至黏稠状,冷冻干燥。制备方法以实施例5为例:The alcohol extract of Aloe vera of the present invention is prepared by the following method: freeze-drying Aloe vera, and then pulverize it at a low temperature of 2-5 DEG C in a low-temperature ultrafine pulverizer to obtain a low-temperature aloe vera with a fineness of 100-150 meshes. Powder, mix the aloe vera low-temperature powder and the ethanol solution with a mass concentration of 95% according to the material-liquid ratio of 1g: 10-15ml, and ultrasonically extract it for 30-50min under the ultrasonic power of 450-500w, then heat it to 50-60 ℃, extract 1 -2h, filtered with suction, evaporated and concentrated on a rotary evaporator to a viscous state, and freeze-dried. The preparation method takes Example 5 as an example:
先称取配方量的库拉索芦荟多糖,溶解于磷酸盐缓冲液中;First weigh the formula amount of Aloe vera polysaccharide and dissolve it in phosphate buffer;
称取配方量的基质,充分溶胀;Weigh the formula amount of matrix and fully swell;
称取配方方量的纳米银、纳米锌与甘油一起润研均匀;Weigh the amount of nano-silver, nano-zinc and glycerin in the formula and grind them evenly;
将上述三者混合,加磷酸盐缓冲液补足,在15-45℃下搅拌1.5-2.5h,最后加三乙醇胺调节pH至7.0左右。Mix the above three, add phosphate buffer to make up, stir at 15-45°C for 1.5-2.5h, and finally add triethanolamine to adjust the pH to about 7.0.
复方库拉索芦荟多糖凝胶的药效学研究Pharmacodynamic study of compound curacao polysaccharide gel
1.实验方法1. Experimental method
1.1大鼠二度烧伤模型的制备1.1 Preparation of rat second-degree burn model
以10%水合氯醛按0.3ml/100g体重对大鼠进行腹腔注射麻醉,于背部同一位置对大鼠进行脱毛处理,脱毛区域用生理盐水清洁。采用100℃沸水加棉纱垫(24层)法,造成大鼠背部皮肤烫伤模型,经病理切片证实为深Ⅱ度烧伤。本实验拟烫伤4cm×4cm体表面积。The rats were anesthetized by intraperitoneal injection with 10% chloral hydrate at 0.3ml/100g body weight, and the rats were depilated at the same position on the back, and the depilation area was cleaned with normal saline. Using 100 ℃ boiling water and cotton gauze pad (24 layers) method, a rat model of back skin scald was created, which was confirmed to be deep second-degree burns by pathological sections. This experiment intends to burn 4cm × 4cm body surface area.
1.2动物分组与处理1.2 Animal grouping and handling
80只SD雌性大鼠,购回后适应性喂养一周,称重后分组,分为空白对照组(n=10):正常饲养;模型对照组(n=10):造模成功后正常饲养;阳性对照组(n=10):造模成功后每日用磺胺嘧啶银乳膏外涂伤口区,给药剂量为1.0g/只/天(含Ag+10mg)。80 SD female rats were adaptively fed for one week after repurchase, grouped after weighing, and divided into blank control group (n=10): normal feeding; model control group (n=10): normal feeding after successful modeling; Positive control group (n=10): After successful modeling, silver sulfadiazine cream was applied to the wound area daily at a dose of 1.0 g/wound/day (containing Ag + 10 mg).
库拉索芦荟多糖凝胶剂组(n=10,库拉索芦荟多糖20份+卡波姆-9805份+甘油50份+三乙醇胺2份,磷酸盐缓冲液补足至1000份):造模成功后每日用多糖凝胶剂外涂伤口区,给药剂量为1.0g/只/天(含库拉索芦荟多糖20mg)。Aloe vera polysaccharide gel group (n=10, 20 parts of Aloe vera polysaccharide + 9805 parts of carbomer + 50 parts of glycerol + 2 parts of triethanolamine, phosphate buffer to make up to 1000 parts): modeling After success, the wound area was coated with polysaccharide gel every day at a dose of 1.0 g/wound/day (containing 20 mg of aloe vera polysaccharide).
锌银凝胶组(n=10,纳米银粉10份+纳米锌粉10份+卡波姆-9805份+甘油50份+三乙醇胺2份+磷酸盐缓冲液补足至1000份):造模成功后每日用锌银复方凝胶外涂伤口区,给药剂量为1.0g/只/天(含Ag、Zn各10mg)。Zinc-silver gel group (n=10, 10 parts of nano-silver powder + 10 parts of nano-zinc powder + 9805 parts of carbomer + 50 parts of glycerol + 2 parts of triethanolamine + phosphate buffer to make up to 1000 parts): successful modeling After that, the wound area was coated with zinc-silver compound gel every day at a dose of 1.0 g/wound/day (containing 10 mg of Ag and Zn each).
复方凝胶低剂量组(n=10):造模成功后每日用凝胶剂外涂伤口区,给药剂量为0.5g/只/天(含Ag、Zn各5mg,库拉索芦荟多糖10mg)。Compound gel low-dose group (n=10): After successful modeling, the gel was applied to the wound area every day at a dose of 0.5 g/wound/day (containing 5 mg of Ag and Zn, 5 mg of Aloe vera polysaccharide). 10 mg).
复方凝胶中剂量组(n=10):造模成功后每日用凝胶剂外涂伤口区,给药剂量为1.0g/只/天(含Ag、Zn各10mg,库拉索芦荟多糖20mg)。Compound gel medium-dose group (n=10): After successful modeling, the gel was applied to the wound area every day at a dose of 1.0 g/wound/day (containing 10 mg each of Ag and Zn, and Aloe vera polysaccharide). 20mg).
复方凝胶高剂量组(n=10):造模成功后每日用凝胶剂外涂伤口区,给药剂量为2.0g/只/天(含Ag、Zn各20mg,库拉索芦荟多糖40mg)。Compound gel high-dose group (n=10): After successful modeling, the gel was applied to the wound area every day at a dose of 2.0 g/wound/day (containing 20 mg of Ag, Zn, and Aloe vera polysaccharide). 40mg).
复方凝胶中剂量加醇提物组(n=10):造模成功后每日用凝胶剂外涂伤口区,给药剂量为1.0g/只/天(含Ag、Zn各10mg,库拉索芦荟多糖19.23mg+库拉索芦荟醇提物0.77mg)。Compound gel medium dose plus alcohol extract group (n=10): After successful modeling, the gel was applied to the wound area every day at a dose of 1.0 g/wound/day (containing 10 mg each of Ag and Zn, Aloe vera polysaccharide 19.23mg + Aloe vera alcohol extract 0.77mg).
共给药18d。A total of 18d was administered.
2、实验结果2. Experimental results
2.1药物对烧伤大鼠创面愈合的影响2.1 Effects of drugs on wound healing in burn rats
2.2大鼠创面上皮化率(epithelization rate,ER)2.2 Rat wound epithelization rate (ER)
烧伤后第1d,各组大鼠创面ER相近,第6d、12d、18d,各给药组大鼠ER明显高于模型组,具有统计学意义(P<0.05,n=10);库拉索芦荟多糖凝胶组、银锌凝胶组以及复方凝胶低剂量组大鼠ER均低于阳性对照组,具有统计学意义(P<0.05,n=10);复方凝胶中剂量组与复方凝胶高剂量组药物对大鼠ER的影响与阳性对照组基本相当;复方凝胶中剂量加醇提物组对大鼠ER的影响高于阳性对照组;复方凝胶低剂量组大鼠ER与库拉索芦荟多糖凝胶组几乎无差异;复方凝胶中剂量组、复方凝胶高剂量组、复方凝胶中剂量加醇提物组大鼠ER明显高于库拉索芦荟多糖凝胶组,具有统计学意义(P<0.05,n=10);复方凝胶低剂量组大鼠ER低于银锌凝胶组;复方凝胶中剂量组大鼠ER略高于银锌凝胶组;复方凝胶高剂量组大鼠ER明显高于银锌凝胶组,复方凝胶中剂量加醇提物组大鼠ER更高于银锌凝胶组,具有统计学意义(P<0.05,n=10)结果见表1。On the 1st day after burn, the wound ER of the rats in each group was similar, and on the 6th, 12th and 18th days, the ER of the rats in each administration group was significantly higher than that in the model group, with statistical significance (P<0.05, n=10); The ER of the aloe polysaccharide gel group, silver zinc gel group and compound gel low-dose group was lower than that of the positive control group, with statistical significance (P<0.05, n=10). The effect of drugs on the ER of the rats in the high-dose gel group was basically the same as that in the positive control group; the effect of the compound gel medium dose plus alcohol extract group on the ER of the rats was higher than that in the positive control group; the low-dose compound gel group had a higher effect on the ER of the rats There was almost no difference with the curacao aloe polysaccharide gel group; the ER of the rats in the compound gel medium dose group, the compound gel high dose group, and the compound gel medium dose plus alcohol extract group was significantly higher than that in curacao aloe polysaccharide gel. group, with statistical significance (P<0.05, n=10); the ER of the compound gel low-dose group was lower than that of the silver-zinc gel group; the ER of the compound gel medium-dose group was slightly higher than that of the silver-zinc gel group ; The ER of the rats in the high-dose compound gel group was significantly higher than that in the silver-zinc gel group, and the ER of the rats in the compound gel medium-dose plus alcohol extract group was higher than that in the silver-zinc gel group, with statistical significance (P<0.05, n=10) The results are shown in Table 1.
表1 复方库拉索芦荟多糖凝胶剂对大鼠ER的影响(n=10)Table 1 The effect of compound aloe vera polysaccharide gel on rat ER ( n=10)
注:*P<0.05,给药组与模型组比较,▲P<0.05,给药组与阳性对照组比较;△P<0.05,复方凝胶组与多糖凝胶组比较;●P<0.05,复方凝胶组与银锌凝胶组比较Note: *P<0.05, the comparison between the administration group and the model group, ▲P<0.05, the comparison between the administration group and the positive control group; △P<0.05, the comparison between the compound gel group and the polysaccharide gel group; ●P<0.05, Comparison between compound gel group and silver-zinc gel group
2.3大鼠创面组织中羟脯氨酸(hydroxyproline,Hyp)蛋白水平的检测2.3 Detection of hydroxyproline (Hyp) protein level in rat wound tissue
烧伤后从第6d至18d烧伤大鼠创面Hyp含量不断上升,各给药组Hyp含量明显高于模型组,具有统计学意义(P<0.05,n=10),结果提示药物能够提高大鼠烧伤创面的Hyp含量,促进皮肤增长愈合;第6d、12d,多糖组Hyp含量明显低于阳性对照组,具有统计学意义(P<0.05,n=10),第18d,明显高于阳性对照组,具有统计学意义(P<0.05,n=10);银锌凝胶组Hyp含量明显低于阳性对照组,具有统计学意义(P<0.01,n=10);复方凝胶低剂量组Hyp含量低于阳性对照组,具有统计学意义(P<0.01,n=10);复方凝胶中剂量组、复方凝胶高剂量组、复方凝胶中剂量加醇提物组在烧伤后18dHyp含量高于阳性对照组,具有统计学意义(P<0.01,n=10);实验结果提示,复方库拉索芦荟凝胶剂在烧伤治疗的后期能够有效地增加创面的Hyp含量,促进创面愈合。结果见表2。From the 6th day to the 18th day after the burn, the Hyp content in the wounds of the burned rats continued to increase, and the Hyp content in each administration group was significantly higher than that in the model group, with statistical significance (P<0.05, n=10). The Hyp content of the wound promotes skin growth and healing; on the 6th and 12th days, the Hyp content of the polysaccharide group was significantly lower than that of the positive control group, with statistical significance (P<0.05, n=10), and on the 18th day, it was significantly higher than that of the positive control group, There was statistical significance (P<0.05, n=10); the content of Hyp in the silver-zinc gel group was significantly lower than that in the positive control group (P<0.01, n=10); the content of Hyp in the low-dose compound gel group lower than that of the positive control group, with statistical significance (P<0.01, n=10); the content of Hyp in the middle-dose compound gel group, the compound gel high-dose group, and the compound gel medium-dose plus alcohol extract group increased at 18d after burn In the positive control group, it was statistically significant (P<0.01, n=10); the experimental results indicated that the compound aloe vera gel could effectively increase the Hyp content of the wound and promote wound healing in the later stage of burn treatment. The results are shown in Table 2.
表2 复方库拉索芦荟多糖凝胶剂对大鼠创面Hyp含量的影响(n=10)Table 2 The effect of compound curacao polysaccharide gel on the content of Hyp in rat wounds ( n=10)
注:☆P<0.05,☆☆P<0.01,模型组与空白组比较;*P<0.05,**P<0.01,给药组与模型组比较;▲P<0.05,▲▲P<0.01,给药组与阳性对照组比较;△P<0.05,△△P<0.01,复方凝胶组与多糖凝胶组比较;●P<0.05,●●P<0.01,复方凝胶组与银锌凝胶组比较Note: ☆P<0.05, ☆☆P<0.01, the model group was compared with the blank group; *P<0.05, **P<0.01, the treatment group was compared with the model group; ▲P<0.05, ▲▲P<0.01, Compared with the positive control group; △P<0.05, △△P<0.01, the compound gel group was compared with the polysaccharide gel group; ●P<0.05, ●●P<0.01, the compound gel group was compared with the silver zinc gel group Glue group comparison
2.4大鼠创面组织中表皮生长因子(epidermal growth factor,EGF)蛋白水平的检测2.4 Detection of epidermal growth factor (EGF) protein levels in rat wound tissue
烧伤后第6d至18d阳性对照组、复方凝胶高剂量组、复方凝胶中剂量加醇提物组大鼠创面EGF含量明显高于模型组,具有统计学意义(P<0.01,n=10),复方凝胶高剂量组与阳性对照组无显著性差异,复方凝胶中剂量加醇提物组与阳性对照组显有著性差异;结果提示高剂量的复方库拉索芦荟多糖凝胶剂与磺胺嘧啶银乳膏均能够快速、显著的提高创面EGF含量,二者治疗效果相当;中剂量的复方库拉索芦荟多糖加醇提物凝胶剂治疗效果优于磺胺嘧啶银乳膏;其余各给药组EGF含量均在18d时明显高于模型组,具有统计学意义(P<0.01,n=10);复方凝胶低剂量组、中剂量组对EGF含量的影响与多糖组、银锌组无显著差异,复方凝胶高剂量组EGF含量高于多糖凝胶组、银锌凝胶组,复方凝胶中剂量多糖加醇提物组EGF含量明显高于多糖凝胶组、银锌凝胶组。结果见表3。From the 6th day to the 18th day after burn, the content of EGF in the wound of the rats in the positive control group, the high-dose compound gel group, and the compound gel medium-dose plus alcohol extract group was significantly higher than that in the model group, with statistical significance (P<0.01, n=10). ), there was no significant difference between the compound gel high-dose group and the positive control group, and the compound gel medium-dose plus alcohol extract group was significantly different from the positive control group. Both with silver sulfadiazine cream can rapidly and significantly increase the EGF content of wounds, and the therapeutic effects of the two are equivalent; the therapeutic effect of compound aloe vera polysaccharide plus alcohol extract gel at a medium dose is better than that of silver sulfadiazine cream; other The EGF content of each administration group was significantly higher than that of the model group at 18 days, with statistical significance (P<0.01, n=10). There was no significant difference in the zinc group. The EGF content of the compound gel high-dose group was higher than that of the polysaccharide gel group and the silver-zinc gel group. Gel group. The results are shown in Table 3.
表3 复方库拉索芦荟多糖凝胶剂对大鼠创面EGF含量的影响(n=10)Table 3 Effects of compound curacao polysaccharide gel on EGF content in rat wounds ( n=10)
注:☆P<0.05,☆☆P<0.01,模型组与空白组比较;*P<0.05,**P<0.01,给药组与模型组比较;▲P<0.05,▲▲P<0.01,给药组与阳性对照组比较;△P<0.05,△△P<0.01,复方凝胶组与多糖凝胶组比较;●P<0.05,●●P<0.01,复方凝胶组与银锌凝胶组比较。Note: ☆P<0.05, ☆☆P<0.01, the model group was compared with the blank group; *P<0.05, **P<0.01, the treatment group was compared with the model group; ▲P<0.05, ▲▲P<0.01, Compared with the positive control group; △P<0.05, △△P<0.01, the compound gel group was compared with the polysaccharide gel group; ●P<0.05, ●●P<0.01, the compound gel group was compared with the silver zinc gel group Glue group comparison.
以上所述的实施例只是本发明的一种较佳的方案,并非对本发明作任何形式上的限制,在不超出权利要求所记载的技术方案的前提下还有其它的变体及改型。The above-mentioned embodiment is only a preferred solution of the present invention, and does not limit the present invention in any form, and there are other variations and modifications under the premise of not exceeding the technical solution recorded in the claims.
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