WO2017080048A1 - 一种用于浅度烧伤的喷膜剂及其制备方法 - Google Patents

一种用于浅度烧伤的喷膜剂及其制备方法 Download PDF

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WO2017080048A1
WO2017080048A1 PCT/CN2015/098898 CN2015098898W WO2017080048A1 WO 2017080048 A1 WO2017080048 A1 WO 2017080048A1 CN 2015098898 W CN2015098898 W CN 2015098898W WO 2017080048 A1 WO2017080048 A1 WO 2017080048A1
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extract
film
comfrey
white peony
water
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French (fr)
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谭惠娟
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谭惠娟
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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
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • 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
    • A61K31/13—Amines
    • A61K31/14—Quaternary ammonium compounds, e.g. edrophonium, choline
    • 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
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • 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
    • A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
    • 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
    • A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
    • A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
    • 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
    • A61K31/74—Synthetic polymeric materials
    • A61K31/785—Polymers containing nitrogen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/75—Rutaceae (Rue family)
    • A61K36/756—Phellodendron, e.g. corktree
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/18—Growth factors; Growth regulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Definitions

  • the invention relates to the field of medicine, in particular to a spray coating agent.
  • Burns are a common type of injury that usually occurs in everyday life and can also occur in accidents, experiments, and wars. Burns generally refer to heat, including tissue damage caused by hydrothermal fluids, vapors, hot gases, flames, hot metal liquids or solids, mainly refers to the skin and / or mucous membranes, and severe cases can also damage subcutaneous or / and submucosal tissue. Such as muscles, bones, joints and even internal organs. For the severity of burns, the three-degree four-point method is currently used to judge:
  • I degree (erythema): only damage the superficial layer of the epidermis - the stratum corneum, the transparent layer, the granular layer or the wounded spine layer, but the layer is alive. Local redness, slight swelling, burning pain, no blistering. Healed in 3-5 days, removes fines and leaves no scars.
  • the reticular layer of the dermis is partially affected, and the hair follicles and sweat glands in the deep dermis are still active. It usually takes 3 to 4 weeks to heal and has scars after healing.
  • Mild burns generally refer to burns that the wound healed by itself within 21 days after injury, including grade I burns and shallow second degree and some shallow deep second degree burns.
  • the present invention provides a spray coating agent for shallow burns and a preparation method thereof.
  • the spray agent for shallow burn of the present invention is composed of the following components by weight: 0.1 to 5% of silver sulfadiazine, 0.1 to 3% of antibacterial agent, 0.01 to 0.1% of epidermal growth factor, and 0.05 to 1 of local anesthetic agent. %, borneol 0.1 to 1%, comfrey extract 0.5 to 5%, white peony extract 1 to 8%, Phellodendron extract 1 to 8%, Polygonum cuspidatum extract 2 to 10%, film forming agent 0.1 to 5%, glycerin 1 to 10%, water balance.
  • silver sulfadiazine 2% antibacterial agent 1%
  • epidermal growth factor 0.05% epidermal growth factor 0.05%
  • local anesthetic 0.3% local anesthetic 0.3%
  • borneol 0.5% comfrey extract 2%
  • white peony extract 4 % white peony extract 4 %
  • Phellodendron extract 4% Polygonum cuspidatum extract 6%
  • film former 1% glycerin 6%
  • the film former is carboxymethyl chitosan having a degree of deacetylation of greater than 85%.
  • the antibacterial agent is selected from any one of chlorhexidine acetate, chlorhexidine gluconate, benzalkonium bromide, and polyhexamethylene fluorene. Among them, chlorhexidine gluconate is preferred.
  • the local anesthetic is selected from one of procaine, lidocaine or tetracaine.
  • the preparation method of the spray agent for shallow burn of the present invention comprises the following steps:
  • the preparation method of the comfrey extract, the white peony extract, the cork extract and the Polygonum cuspidatum extract is: after washing and pulverizing the comfrey, the white peony, the yellow cypress and the knotweed, respectively, according to 1 g of comfrey, white peony, cork or The ratio of Polygonum cuspidatum to 5g of water was boiled to extract 2/3 volume of water, and the residue was filtered off. The resulting solution was the extract of comfrey, white peony, cork and Polygonum cuspidatum.
  • Carboxymethyl chitosan has good water solubility and can inhibit the growth and reproduction of some fungi, bacteria, and viruses. It also has the effect of promoting blood coagulation and can be used as a hemostatic agent. It can also be used as a wound filler material, which has the functions of sterilization, promoting wound healing, absorbing wound exudate, and not easily dehydrating and contracting.
  • Lithosperm (Latin name: Arnebiae radix), cold and bitter, into the heart envelope, liver. It has the effects of clearing heat and cooling blood, promoting blood circulation and detoxification, and removing rash and eliminating spots. For blood heat poisoning, rash purple, measles impervious, sores, eczema and water fire burns. On the surface of modern pharmacology research, comfrey has an inhibitory effect on viruses and bacteria in vitro, and can accelerate epithelial growth and treat burns. Local application can promote wound healing.
  • White pheasant (Latin name: Angelicae dahuricae radix): Weixin, warm, lung, spleen, stomach. It has the effect of dissolving cold, phlegm and pain, clearing the nose, dampness and stagnation, reducing swelling and pus, and relieving itch.
  • white peony is the main medicine of Yangming, so it can cure blood diseases and fetal diseases, and relieves pain and relieves pain.
  • Cork (Latin name: Phellodendri chinensis cortex): bitter, cold, kidney, bladder. It has the effects of clearing heat and dampness, purging fire and steaming, detoxifying and treating sore.
  • Polygonum cuspidatum (Latin name: Polygoni cuspidate rhizome et radix): slightly bitter taste, slightly cold, return to the liver, gallbladder, lung. For damp heat jaundice, turbid, under the belt, rheumatism and pain, swollen sores, water and fire burns, amenorrhea, symptoms, assault, lungs Hot cough.
  • the spray film for shallow burn of the invention can quickly form a protective film on the surface of the burn; can quickly relieve pain; the chitosan itself has antibacterial activity, the composite silver sulfadiazine and the cationic surfactant make the present
  • the invention has strong sterilization and disinfection effect on wounds; supplemented by traditional Chinese medicines such as comfrey, white peony, cork and Polygonum cuspidatum which have therapeutic effects on burns; epidermal growth factor can make burns recover faster.
  • the spray film of the present invention is convenient to use and is suitable for shallow burns.
  • the preparation method of the spray agent for shallow burn of the present invention comprises the following steps:
  • Test samples Samples and commercial products obtained in Examples 1 to 5 of the present invention (now Fusheng)
  • Test method Five subjects participated in a double-blind experiment, and three kinds of sprays were sprayed on the skin, and fluidity, dryness, and film formation were used as indicators for evaluating the film formation effect.
  • the liquidity scoring criteria are: 1 point - very easy to lose, 2 points - easier to flow, 3 points - rarely flow; dryness scoring criteria are: 1 is divided into drying time > 6min, 2 minutes drying time is 3-6min 3 is divided into drying time ⁇ 3min; filming property scoring standard is: 1 point - no obvious film, 2 points - can form incomplete film, 3 points - can form an obvious intact film. Accumulate all scores and calculate the total score for all subjects. The higher the score, the better the film formation. The results are shown in Table 2:
  • Test sample Samples and commercial products (SD-Ag) prepared in Examples 1 to 5 of the present invention
  • Test method 70 rats, half male and half female, 6-8 weeks old, were randomly divided into 7 groups, 10 in each group. It was divided into the groups of Examples 1 to 5, the commercial product group, and the control group. Intraperitoneal injection of 10% chloral hydrate (0.7ml), use electric push to shave the hair about 3cm ⁇ 3cm in the back, spray 75% ethanol, mark 3cm ⁇ 2cm area with a marker, use the ophthalmology scissors to remove the back hair. The wound area was recorded after drying for 1 h. The corresponding experimental samples were given to each group. The drug solution was sprayed from the distance of 5-10 cm (pressed twice), the thickness of SD-Ag applied was 0.2 mm, and the drug was administered three times a day.
  • # is the ratio of the control group, p ⁇ 0.05; * is p ⁇ 0.05 compared with the commercial group.
  • # is the ratio of the control group, p ⁇ 0.05; * is p ⁇ 0.05 compared with the commercial group.
  • Examples 1 to 5 and SD-Ag of the present invention were determined in accordance with GB 15979-2002 "Sanitary Standard for Sanitary Hygiene Products", Appendix C.
  • Test bacteria bacteria: Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 25922);
  • Yeast Candida albicans (ATCC 10231).
  • Preparation of bacterial solution Take fresh culture of slanted surface of nutrient agar medium of strains 3 to 14 for 18 to 24 hours, wash the lawn with 5 ml of 0.03 mol/L phosphate buffer (hereinafter referred to as PBS), and suspend the bacteria evenly.
  • PBS 0.03 mol/L phosphate buffer
  • test cultivar 24h slant culture was washed with PBS to prepare a bacterial suspension.
  • the required concentration was: 100 ⁇ l was dropped on the control swatch, and the number of bacteria recovered was 1 ⁇ 10 4 to 9 ⁇ 10 4 cfu/tablet.
  • test piece 2.0 cm ⁇ 3.0 cm
  • control piece Four pieces of the test piece (2.0 cm ⁇ 3.0 cm) and the control piece were taken, and divided into four groups and placed in four sterilized dishes.
  • the control sample is of the same size as the sample, but is of the same size but does not contain an antibacterial material and is sterilized.
  • Analgesic test example (mouse hot plate method)
  • the experiment used healthy Kunming mice, female, weighing 20-23g. They were randomly divided into control group, futalin cream group and example group. Each mouse was tested for pain threshold (55 ⁇ 0.5 ° C constant temperature water bath) before the experiment, and animals with pain threshold less than 5 seconds and greater than 30 seconds were excluded.
  • the sample prepared in Example 3 was applied, and the Futalin cream group was applied with a fustatin cream, and the control group was not applied with a drug. After applying the dose to the two posterior toes for 0.5 hours according to the dose in Table 5, the foot drug was washed away with alcohol.
  • mice After the alcohol was volatilized, the mice were placed on a 55 ⁇ 0.5°C constant temperature water bath aluminum plate, covered with a glass cover, and the time after the mice were put into the mice and the mice began to add their own hind paws was compared as a pain threshold after administration.
  • the difference in pain threshold before and after the drug was statistically processed and listed in Table 6:
  • # is compared with the control group, p ⁇ 0.05; * is p ⁇ 0.05 compared with the futalin cream group.
  • Burns 54 cases of face and neck, 91 cases of upper limbs, 41 cases of lower limbs and 10 cases of trunk. Burn depth: shallow II degree, burn area less than 10%, no other comorbid diseases. They were randomly divided into the control group (100 cases) and the control group (96 cases). The age, sex, burn site, depth, area, and health status of the two groups were all P>0.05, which was comparable.
  • Example group The spray film prepared in Example 3 of the present invention was used, and the control group used silver sulfadiazine cream (SD-Ag).
  • Evaluation method observe and record the wound condition and ask the patient's feeling every day. 1 Record the pain of the two groups of wounds (no irritation, mild irritation, pain, but can endure, severe pain can not bear a total of 4) and the disappearance of secretions. 2 cure rate: the wound disappeared after the second degree of injury (complete epithelialization) for the cure. The average healing time of the two groups (including those infected with infection) was recorded. 3 observe the systemic and local irritation symptoms, allergic reactions and other adverse reactions after administration.

Abstract

一种用于浅度烧伤的喷膜剂及其制备方法，该喷膜剂由以下重量百分比的组分组成：磺胺嘧啶银0.1-5%、抗菌剂0.1-3%、表皮生长因子0.01-0.1%、局麻剂0.05-1%、冰片0.1-1%、紫草提取液0.5-5%、白芷提取液1-8%、黄柏提取液1-8%、虎杖提取液2-10%、成膜剂0.1-5%、甘油1-10%、水余量。制备该喷膜剂方法包括先将局麻剂、冰片和表皮生长因子溶解于甘油的水溶液中，再将磺胺嘧啶银、抗菌剂和成膜剂溶解于少量水中，最后再与紫草提取液、白芷提取液、黄柏提取液、虎杖提取液和余量水混合均匀即得。

Description

一种用于浅度烧伤的喷膜剂及其制备方法 技术领域
本发明涉及医药学领域，特别涉及一种喷膜剂。
背景技术
烧伤是一种比较常见的伤害，通常发生于日常生活中，也可发生于意外事故、实验及战争中。烧伤一般指热力，包括热液、蒸气、高温气体、火焰、炽热金属液体或固体等所引起的组织损害，主要指皮肤和/或黏膜，严重者也可伤及皮下或/和黏膜下组织，如肌肉、骨、关节甚至内脏。对烧伤的严重程度，目前多采用三度四分法进行判断：
Ⅰ度(红斑性)：仅伤及表皮浅层――角质层、透明层、颗粒层或伤及棘状层，但发生层健在。局部发红，微肿、灼痛、无水疱。3－5天内痊愈、脱细屑、不留瘢痕。
Ⅱ度(水泡性)：分为浅Ⅱ度烧伤和深Ⅱ度烧伤。浅Ⅱ度烧伤：有较大水泡，水肿伴剧痛，皮肤感觉过敏。浅Ⅱ度烧伤虽然伤及大部分皮肤基底层，但未伤及真皮层的乳头结构。正是由于浅Ⅱ度烧伤还存在部分健康的基底层，而基底层又是皮肤干细胞最密集的部位，所以皮肤浅Ⅱ度烧伤后基底层的固有干细胞可以不断分裂、增殖。最终会完成损伤皮肤的再生修复，实现无瘢痕愈合，一般需1～2周。深Ⅱ度烧伤除表皮、全部真皮乳头层烧毁外，真皮网状层部分受累，位于真皮深层的毛囊及汗腺尚有活力。一般需3～4周痊愈，愈合后有瘢痕。
Ⅲ度(焦痂性)：皮肤苍白或焦黄炭化，干燥，皮革状，皮肤感觉迟钝，疼痛不明显。创面愈合较慢，多数需植皮，愈合后留有瘢痕或/和畸形。
浅度烧伤一般指创面在伤后21天内自行愈合的烧伤，包括Ⅰ度烧伤和浅Ⅱ度和部分较浅的深Ⅱ度烧伤。
烧伤往往会带来比较剧烈的痛苦体验，特别是面部的烧伤会给患者带来沉重的心理负担。因此提供一种能够减轻患者身体痛苦并有益于康复的烧伤药品有着十分现实的意义。
发明内容
针对上述技术问题，本发明提供一种用于浅度烧伤的喷膜剂及其制备方法。本发明的用于浅度烧伤的喷膜剂由以下重量百分比的组分组成：磺胺嘧啶银0.1～5％、抗菌剂0.1～3％、表皮生长因子0.01～0.1％、局麻剂0.05～1％、冰片0.1～1％、紫草提取液0.5～5％、白芷提取液1～8％、黄柏提取液1～8％、虎杖提取液2～10％、成膜剂0.1～5％，甘油1～10％、水余量。
进一步地，由以下重量百分比的组分组成：磺胺嘧啶银0.5～3％、抗菌剂0.5～2％、表皮生长因子0.03～0.08％、局麻剂0.1～0.5％、冰片0.3～0.8％、紫草提取液3～5％、白芷提取液3～5％、黄柏提取液3～5％、虎杖提取液4～8％、成膜剂0.5～3％，甘油2～8％、水余量。
具体地，由以下重量百分比的组分组成：磺胺嘧啶银2％、抗菌剂1％、表皮生长因子0.05％、局麻剂0.3％、冰片0.5％、紫草提取液2％、白芷提取液4％、黄柏提取液4％、虎杖提取液6％、成膜剂1％，甘油6％、水余量。
具体地，所述成膜剂为脱乙酰度大于85％的羧甲基壳聚糖。
具体地，所述抗菌剂选自醋酸氯己定、葡萄糖酸氯己定、苯扎溴铵、聚六亚甲基胍中的任意一种。其中优选为葡萄糖酸氯己定。
具体地，所述局麻剂选自普鲁卡因、利多卡因或丁卡因中的一种。
本发明的用于浅度烧伤的喷膜剂的制备方法包括以下步骤：
(1).按配方量，将甘油和同体积的水混合后，将局麻剂、冰片和表皮生长因子溶解于其中；
(2).按配方量，将磺胺嘧啶银、抗菌剂和成膜剂溶解于少量水中；
(3).将步骤(1)和(2)所制得的溶液混合后加入紫草提取液、白芷提取液、黄柏提取液、虎杖提取液和余量水，混合均匀即得。
具体地，所述紫草提取液、白芷提取液、黄柏提取液和虎杖提取液的制备方法为：将紫草、白芷、黄柏和虎杖分别洗净粉碎后，按1g紫草、白芷、黄柏或虎杖加5g水的比例，分别将紫草、白芷、黄柏和虎杖煮沸至蒸发掉2/3体积的水，滤去残渣，所得溶液即为紫草、白芷、黄柏和虎杖提取液。
羧甲基壳聚糖具有较好的水溶性，能抑制一些真菌、细菌、和病毒的生长繁殖。也具有促进血液凝固的作用，可用作止血剂。它还可用于伤口填料物质，具有灭菌、促进伤口愈合、吸收伤口渗出物、不易脱水收缩等作用。
紫草(拉丁名：Arnebiae radix)，性寒味苦，入心包络、肝经。具有清热凉血、活血解毒、透疹消斑之功效。用于血热毒盛、斑疹紫黑、麻疹不透、疮疡、湿疹和水火烧伤。现代药理学研究表面，紫草体外对病毒和细菌有抑制作用，并能加速上皮生长以及治疗烧伤，局部应用可促进创伤愈合。
白芷(拉丁名：Angelicae dahuricae radix)：味辛，性温，归肺，脾，胃经。具有解表散寒，祛风止痛，通鼻窍，燥湿止带，消肿排脓，祛风止痒之功效。《本草纲目》中记载：白芷为阳明主药，故又能治血病、胎病，而排脓生肌止痛。
黄柏(拉丁名：Phellodendri chinensis cortex)：味苦，性寒，归肾、膀胱经。具有有清热燥湿，泻火除蒸，解毒疗疮之功效。
虎杖(拉丁名：Polygoni cuspidate rhizome et radix)：味微苦，性微寒，归肝、胆、肺经。用于湿热黄疸，淋浊，带下，风湿痹痛，痈肿疮毒，水火烫伤，经闭，症瘕，趺打损伤，肺 热咳嗽。
本发明的用于浅度烧伤的喷膜剂喷在烧伤处表面可迅速形成一层保护膜；能够快速止痛；壳聚糖本身就有着抗菌活性，复合磺胺嘧啶银和阳离子表面活性剂，使得本发明对伤口具有很强的杀菌消毒作用；辅之以紫草、白芷、黄柏和虎杖等对烧伤有治疗效果的中药；表皮生长因子可以使烧伤处更快的恢复。相比较传统的软膏剂，本发明的喷膜剂使用方便，适用于浅度烧伤。
为了更好地理解和实施，下面详细说明本发明。
具体实施方式
制备实施例
本发明的用于浅度烧伤的喷膜剂的制备方法包括以下步骤：
(1).将紫草、白芷、黄柏和虎杖分别洗净粉碎后，按1g紫草、白芷、黄柏或虎杖加5g水的比例，分别将紫草、白芷、黄柏和虎杖煮沸至蒸发掉2/3体积的水，滤去残渣，所得溶液即为紫草、白芷、黄柏和虎杖提取液。
(2).按表1配方量，将甘油和同体积的水混合后，将局麻剂、冰片和表皮生长因子溶解于其中；
(3).按表1配方量，将磺胺嘧啶银、抗菌剂和成膜剂溶解于少量水中；
(4).将步骤(2)和(3)所制得的溶液混合后加入步骤(1)制得的紫草提取液、白芷提取液、黄柏提取液、虎杖提取液和余量水，混合均匀即得。
<表1各组分配方量，以重量百分比计(％)>
Figure PCTCN2015098898-appb-000001
Figure PCTCN2015098898-appb-000002
成膜效果实施例
试验样品：本发明实施例1～5所制得样品及市售品(今福生)
试验方法：5名受试者参与双盲实验，将三种喷剂喷于皮肤上，以流动性、干燥性、成膜性为:成膜效果的评价指标。其中流动性评分标准为：1分-非常容易流失、2分-较容易流动、3分-很少流动；干燥性评分标准为：1分为干燥时间>6min、2分干燥时间为3-6min、3分为干燥时间<3min；成膜性评分标准为：1分-感觉不到明显膜、2分-能形成不完整的膜、3分-能形成明显完整的膜。累加所有分数，并计算出所有受试者的总分，分值越高则表示成膜效果越好。结果见表2：
<表2>
Figure PCTCN2015098898-appb-000003
由成膜效果评分结果可以看出，双盲实验中本发明实施例1～5的样品的成模性好、流动性小，其成膜效果优于市售品。
促进伤口愈合试验实施例
试验样品：本发明实施例1～5所制得样品及市售品(SD-Ag)
试验方法：70只大鼠，雌雄各半，6-8周龄，随机分成7组，每组10只。分为实施例1～5组、市售品组和对照组。腹腔注10％水合氯醛0.7ml，使用电推剃去背部约3cm×3cm大小的毛发，喷洒75％乙醇消毒后用记号笔标记3cm×2cm的区域，用眼科剪剪去背部去毛皮肤，干燥1h后记录伤口面积，各组分别给予相应实验样品，药液从距离5-10cm处喷涂(按压两次)，SD-Ag的涂敷厚度为0.2mm，每日3次给药；对照组不给药。每天观察大鼠创伤部位的伤口情况，并在术后3、5、10、15、20天动态观察大鼠创面愈合情况，测量创面面积并计 算愈合率，愈合率＝(原创面面积-现创面面积)/原创面面积，一般认为创伤伤口表面干燥不流脓，血痂自然脱落，伤口呈粉嫩正常皮肤状视为愈合。结果见表3和表4：
<表3平均创伤面积(mm2)>
Figure PCTCN2015098898-appb-000004
#为与对照组比，p＜0.05；*为与市售品组相比，p＜0.05。
<表4平均愈合率(％)>
Figure PCTCN2015098898-appb-000005
#为与对照组比，p＜0.05；*为与市售品组相比，p＜0.05。
杀菌试验实施例
根据GB 15979-2002《一次性使用卫生用品卫生标准》附录C测定本发明实施例1～5和SD-Ag的抗菌效果。
试验菌：细菌：金黄色葡萄球菌(ATCC 6538)，大肠杆菌(ATCC 25922)；
酵母菌：白色念珠菌(ATCC 10231)。
菌液制备:取菌株第3～14代的营养琼脂培养基斜面新鲜培养物18～24h，用5ml 0.03mol/L磷酸盐缓冲液(以下简称PBS)洗下菌苔，使菌悬浮均匀后用上述PBS稀释至所需浓度。
操作步骤：
将试验菌24h斜面培养物用PBS洗下，制成菌悬液，要求的浓度为：用100μl滴于对照样片上，回收菌数为1×104～9×104cfu/片。
取被试样片(2.0cm×3.0cm)和对照样片各4片，分成4组置于4个灭菌平皿内。所述对照样片与试样同质材料，同等大小，但不含抗菌材料，且经灭菌处理。
取上述菌悬液.分别在每个被试样片和对照样片上滴加100μl，均匀涂布，开始计时，作用2min，用无菌镊分别将样片投人含5m1，相应中和剂的试管内，充分混匀，作适当稀释，然后取其中2-3个稀释度，分别吸取0.5ml，置于两个平皿，用凉至40-45'℃的营养琼脂培养基(细菌)或沙氏琼脂培养基(酵母菌)15m1作倾注，转动平皿，使其充分均匀，琼脂凝固后翻转平板，35℃士2℃培养48h(细菌)或72h(酵母菌)，作活菌菌落计数。试验重复3次，按下式计算杀菌率：X＝(A-B)/A×100％
式中：X---杀菌率，％；
A---对照样品平均菌落数；
B---被试样品平均菌落数。
评价标准：杀菌率≥90％，产品有杀菌作用。结果如表5：
<表5杀菌率，作用浓度为1:1>
Figure PCTCN2015098898-appb-000006
*为与SD-Ag相比，p＜0.05。
镇痛试验实施例(小鼠热板法)
实验选用健康昆明小鼠，雌性，体重20-23g。随机分为对照组、扶他林乳膏组和实施例组。各小鼠实验前均先测痛阈(55±0.5℃的恒温水浴槽)，剔除痛阈小于5秒和大于30秒的动物。实施例组涂抹实施例3所制得的样品，扶他林乳膏组涂抹扶他林乳膏，对照组不涂抹药物。按表5中剂量于两后足趾处涂药0.5小时后，用酒精洗去足部药物。待酒精挥发以后，将小鼠置55±0.5℃恒温水浴槽铝板上，盖以玻璃罩，记录投入小鼠后至小鼠开始添自己后足的时间，作为给药后痛阈比较各组给药前后痛阈的差异，结果经统计学处理后列于表6：
<表6.本发明的用于浅度烧伤的喷膜剂对小鼠热板法的镇痛作用(X±SD)>
Figure PCTCN2015098898-appb-000007
#为与对照组比，p＜0.05；*为与扶他林乳膏组相比，p＜0.05。
临床试验实施例
于2014年1～9月治疗的烧伤患者196例，男112例、女84例，年龄3岁至65岁，烧伤部位：面颈部54例，上肢91例，下肢41例，躯干10例。烧伤深度：浅Ⅱ度，烧伤面积小于10％，无其他并存疾病。随机分为实施例组(100例)和对照组(96例)，两组患者年龄，性别，烧伤部位、深度、面积，健康状况比较，均P>0.05，具有可比性。
使用药物：实施例组使用本发明实施例3制备的喷膜剂，对照组使用磺胺嘧啶银乳膏剂(SD-Ag)。
使用方法：两组创面均用0.05％氯己定液清创，去除水泡及已经分离的表皮，实施例组将实施例3的喷膜剂喷于创面上，待结干痂后逐渐停药，保持创面清洁干燥。对照组局部涂SD-Ag，一次性涂药护痂，局部出现分泌物及时清除后再涂药，两组均行暴露疗法。
评价方法：每天观察并记录创面情况及询问患者感受。①记录两组创面疼痛(分无刺激痛、轻微刺激痛、疼痛明显，但能忍受、剧痛难忍耐共4级)和分泌物消失的时间。②治愈率：浅Ⅱ度伤后创面消失(完全上皮化)为治愈。记录两组平均治愈时间(含感染治愈者)。③观察用药后全身及局部刺激症状，过敏反应及其他不良反应。
统计学方法：计量资料用t检验，计数资料用χ2检验。
结果如下：①两组疼痛和分泌物消失情况比较，结果见表2；②两组治愈率和治愈时间比较，结果见表7和表8。
<表7两组疼痛和分泌物消失时间>
Figure PCTCN2015098898-appb-000008
*表示与对照组相比，p<0.05
<表8两组治愈率和治愈时间比较>
Figure PCTCN2015098898-appb-000009
*表示与对照组相比，p<0.05
实施例组仅由1例发生了创面感染，发生率为1％，对照组有5例发生创面感染，发生率为5.2％，两组均未发现不良反应和过敏情况。
本发明并不局限于上述实施方式，如果对本发明的各种改动或变形不脱离本发明的精神 和范围，倘若这些改动和变形属于本发明的权利要求和等同技术范围之内，则本发明也意图包含这些改动和变形。

Claims (9)

  1. 一种用于浅度烧伤的喷膜剂，其特征在于由以下重量百分比的组分组成：磺胺嘧啶银0.1～5％、抗菌剂0.1～3％、表皮生长因子0.01～0.1％、局麻剂0.05～1％、冰片0.1～1％、紫草提取液0.5～5％、白芷提取液1～8％、黄柏提取液1～8％、虎杖提取液2～10％、成膜剂0.1～5％，甘油1～10％、水余量。
  2. 根据权利要求1所述的用于浅度烧伤的喷膜剂，其特征在于由以下重量百分比的组分组成：磺胺嘧啶银0.5～3％、抗菌剂0.5～2％、表皮生长因子0.03～0.08％、局麻剂0.1～0.5％、冰片0.3～0.8％、紫草提取液3～5％、白芷提取液3～5％、黄柏提取液3～5％、虎杖提取液4～8％、成膜剂0.5～3％，甘油2～8％、水余量。
  3. 根据权利要求2所述的用于浅度烧伤的喷膜剂，其特征在于由以下重量百分比的组分组成：磺胺嘧啶银2％、抗菌剂1％、表皮生长因子0.05％、局麻剂0.3％、冰片0.5％、紫草提取液2％、白芷提取液4％、黄柏提取液4％、虎杖提取液6％、成膜剂1％，甘油6％、水余量。
  4. 根据权利要求1～3任意一项所述的用于浅度烧伤的喷膜剂，其特征在于：所述成膜剂为脱乙酰度大于85％的羧甲基壳聚糖。
  5. 根据权利要求1～3任意一项所述的用于浅度烧伤的喷膜剂，其特征在于：所述抗菌剂选自醋酸氯己定、葡萄糖酸氯己定、苯扎溴铵、聚六亚甲基胍中的任意一种。
  6. 根据权利要求5所述的用于浅度烧伤的喷膜剂，其特征在于：所述抗菌剂为葡萄糖酸氯己定。
  7. 根据权利要求1～3任意一项所述的用于浅度烧伤的喷膜剂，其特征在于：所述局麻剂选自普鲁卡因、利多卡因或丁卡因中的一种。
  8. 一种制备权利要求1～3任意一项所述的用于浅度烧伤的喷膜剂的方法，其特征在于包括以下步骤：
    (1).按配方量，将甘油和同体积的水混合后，将局麻剂、冰片和表皮生长因子溶解于其中；
    (2).按配方量，将磺胺嘧啶银、抗菌剂和成膜剂溶解于少量水中；
    (3).将步骤(1)和(2)所制得的溶液混合后加入紫草提取液、白芷提取液、黄柏提取液、虎杖提取液和余量水，混合均匀即得。
  9. 根据权利要求8所述的用于浅度烧伤的喷膜剂的制备方法，其特征在于：所述紫草提取液、白芷提取液、黄柏提取液和虎杖提取液的制备方法为：将紫草、白芷、黄柏和虎杖分别洗净粉碎后，按1g紫草、白芷、黄柏或虎杖加5g水的比例，分别将紫草、白芷、黄柏和虎 杖煮沸至蒸发掉2/3体积的水，滤去残渣，所得溶液即为紫草、白芷、黄柏和虎杖提取液。
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