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CN105749250A - Application of antibacterial peptides of wood frogs to preparing medicines for treating onychomycosis - Google Patents

Application of antibacterial peptides of wood frogs to preparing medicines for treating onychomycosis Download PDF

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CN105749250A
CN105749250A CN201610143384.1A CN201610143384A CN105749250A CN 105749250 A CN105749250 A CN 105749250A CN 201610143384 A CN201610143384 A CN 201610143384A CN 105749250 A CN105749250 A CN 105749250A
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rana
onychomycosis
antimicrobial peptide
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preparation
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滕乐生
王迪
谢晶
孟庆繁
逯家辉
王贞佐
滕利荣
程瑛琨
刘艳
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Jilin University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56Materials from animals other than mammals
    • A61K35/65Amphibians, e.g. toads, frogs, salamanders or newts

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Abstract

本发明公开了林蛙抗菌肽的一种新用途,具体为所述林蛙抗菌肽在治疗灰指甲的药物制备中的用途。其使用方法简单,有效率及治愈率高,且适用于不同的年龄段,无副作用,复发率低。The invention discloses a new application of the Rana antibacterial peptide, specifically the application of the Rana antibacterial peptide in the preparation of medicine for treating onychomycosis. The use method is simple, the effective rate and the cure rate are high, and it is suitable for different age groups, has no side effect, and has a low recurrence rate.

Description

林蛙抗菌肽在治疗灰指甲的药物制备中的用途Application of Rana antibacterial peptide in the preparation of medicine for treating onychomycosis

技术领域technical field

本发明涉及林蛙抗菌肽的一种新的医药用途,尤其涉及其在治疗灰指甲的药物制备中的用途。The invention relates to a new medical application of the Rana antibacterial peptide, in particular to its application in the preparation of medicine for treating onychomycosis.

背景技术Background technique

甲癣,俗称“灰指甲”,是指皮癣菌侵犯甲板或甲下所引起的疾病。甲癣常由红色毛癣菌、须癣毛癣菌、絮状表皮癣菌等各种真菌引起。少数由其他丝状真菌、酵母样菌及酵母菌引起,偶尔也可由孢子菌、镰刀菌及土色曲霉等引起,大多见于营养不良的甲。Onychomycosis, commonly known as "onychomycosis", refers to a disease caused by dermatophytes invading the nail plate or under the nail. Onychomycosis is often caused by various fungi such as Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton flocculum. A few are caused by other filamentous fungi, yeast-like bacteria and saccharomyces, and occasionally it can also be caused by sporozoites, Fusarium and Aspergillus terrescens, etc., mostly seen in malnourished nails.

甲癣为皮肤癣菌病中最顽固难治的一种。可口服、外用药物,或手术拔甲。手指甲和脚趾甲的生长速度不同,完全替换一个新的指甲,手指甲需要100天,而脚趾甲大约要300天,所以治疗灰指甲必须要有耐心。目前常用的治疗手段有:Onychomycosis is the most stubborn and intractable type of dermatophytosis. It can be taken orally, externally, or surgically. The growth rate of fingernails and toenails is different. It takes 100 days to completely replace a new nail, while it takes about 300 days for toenails, so you must be patient in the treatment of onychomycosis. Currently commonly used treatments include:

(1)手术拔甲(1) Surgical nail removal

适于单发的指甲,局麻下,将患甲拔除。这种方法创面大,出血,易引起感染。手术后一般会感觉较疼痛,容易重新感染复发,临床现已较少使用。心脏病、高血压、糖尿病等患者,不宜手术治疗。It is suitable for single nail, under local anesthesia, remove the affected nail. This method has a large wound, bleeding, and easy to cause infection. After the operation, you will generally feel more pain, and it is easy to re-infect and relapse, so it is rarely used in clinical practice. Patients with heart disease, high blood pressure, and diabetes are not suitable for surgical treatment.

(2)内服药物(2) Oral medicine

适于多个指(趾)甲。如每日口服特比萘芬片250mg,连服6~12周;伊曲康唑400mg/天,连服7天、休息21天为一疗程,持续3~6个疗程;每周1~2次服氟康唑150mg,连续4月以上。可治愈80%以上的甲癣及甲真菌病。但因为这类药必须达到真菌所寄生的甲板处才能发挥抗菌作用,用药量大,用药时间长,应定期监测药物不良反应。Suitable for multiple nails. For example, take 250 mg terbinafine tablets orally daily for 6 to 12 weeks; itraconazole 400 mg/day, take 7 days and rest for 21 days as a course of treatment for 3 to 6 courses; 1 to 2 weeks a week Take fluconazole 150mg every time for more than 4 months. More than 80% of onychomycosis and onychomycosis can be cured. However, because this type of drug must reach the deck where the fungus is parasitic, it can exert its antibacterial effect, the dosage is large, and the medication time is long, so the adverse drug reactions should be monitored regularly.

(3)外用疗法(3) External therapy

根据药剂不同,主要局部涂药和封包削治等方法:According to different medicaments, the main methods are topical application and packet cutting:

(1)使用指甲锉(非专业人士切忌用刀片,以免出血感染其他疾病)将不规则坏甲磨薄,磨甲周期为2天一次为佳;(1) Use a nail file (non-professionals should not use blades to avoid bleeding and infection of other diseases) to thin irregular nails, and the nail grinding cycle is preferably once every 2 days;

(2)30%冰醋酸外涂或10%冰醋酸泡病甲,每日1次,持续3~6个月以上。涂药前若先将病甲削薄,疗效更佳。涂甲之前注意用温和药膏保护甲周的皮肤;(2) Topically apply 30% glacial acetic acid or 10% glacial acetic acid to soak the diseased nails once a day for more than 3 to 6 months. If the sick nail is thinned before applying the medicine, the curative effect will be better. Pay attention to protect the skin around the nail with mild ointment before applying the nail;

(3)选用特比萘芬酊、阿莫罗芬甲搽剂、环吡酮胺酮甲涂剂等抗真菌外用药局部涂抹。(3) Use terbinafine tincture, amorolfine A liniment, ciclopirox ketone A varnish and other antifungal topical drugs for topical application.

可见,目前的治疗方法多存在用药时间长、治疗方法复杂、药效不稳定、复发率高、易感染、毒副作用等缺点。It can be seen that the current treatment methods mostly have disadvantages such as long medication time, complicated treatment methods, unstable drug efficacy, high recurrence rate, susceptibility to infection, and toxic and side effects.

发明内容Contents of the invention

为了解决现有技术中存在的上述问题,本发明在这一领域进行了大量的实验,研究发现林蛙抗菌肽可以用于制备治疗灰指甲的药物。In order to solve the above-mentioned problems in the prior art, the present invention has carried out a large number of experiments in this field, and found that the Rana antibacterial peptide can be used to prepare a drug for treating onychomycosis.

抗菌肽(Antimicrobialpeptides,AMPs)是生物体内部防御系统的一个重要组成部分。抗菌肽具有抗革兰氏阳性菌、革兰氏阴性菌、真菌、包被病毒、原生生物和耐药菌的能力,目前被应用于食品保鲜盒医药领域。Antimicrobial peptides (AMPs) are an important part of the internal defense system of organisms. Antimicrobial peptides have the ability to resist Gram-positive bacteria, Gram-negative bacteria, fungi, coated viruses, protozoa and drug-resistant bacteria, and are currently used in the field of food preservation boxes and medicine.

林蛙作为两栖类生物,其栖息地环境使得其皮肤具有功能复杂的活性物质,在公开号为CN1216768A的中国专利申请中,公开了林蛙抗菌肽的制备方法。Rana is an amphibian, and its habitat environment makes its skin have active substances with complex functions. In the Chinese patent application with publication number CN1216768A, a method for preparing Rana antimicrobial peptides is disclosed.

本发明在其制备林蛙抗菌肽的基础上,发现了林蛙抗菌肽的新用途,即将其用于制备治疗灰指甲的药物。On the basis of preparing the Rana antibacterial peptide, the present invention discovers a new application of the Rana antibacterial peptide, that is, it is used to prepare medicine for treating onychomycosis.

本发明所述林蛙抗菌肽可以由购买或制备途径得到。所述制备方法包括但不限于浸提法、超声波提取法、微波提取法等。任意方法得到的林蛙抗菌肽均可以用于制备治疗灰指甲的药物。The Rana antimicrobial peptide of the present invention can be obtained by purchase or preparation. The preparation method includes but not limited to extraction method, ultrasonic extraction method, microwave extraction method and the like. The Rana antimicrobial peptide obtained by any method can be used to prepare medicine for treating onychomycosis.

林蛙抗菌肽的具体制备方法比如:公开号为CN101456910A的中国专利申请中,公开了一种浸提法制备林蛙抗菌肽的方法;公开号为CN103073628A的中国专利申请中,公开了一种超声波提取法制备林蛙抗菌肽的方法;公开号为CN1216768A的中国专利申请中,公开了一种浸提法制备林蛙抗菌肽的方法。The specific preparation method of the Rana antimicrobial peptide is such as: in the Chinese patent application with the publication number CN101456910A, a method for preparing the Rana antimicrobial peptide by leaching method is disclosed; in the Chinese patent application with the publication number CN103073628A, an ultrasonic A method for preparing Rana antimicrobial peptides by extraction method; in the Chinese patent application with publication number CN1216768A, a method for preparing Rana antimicrobial peptides by leaching method is disclosed.

所述制备治疗灰指甲的药物可以为多种剂型,所述剂型包括但不限于林蛙抗菌肽凝胶剂、林蛙抗菌肽喷雾剂、林蛙抗菌肽消毒制剂、林蛙抗菌肽软膏剂、林蛙抗菌肽洗剂等。The medicine for preparing and treating onychomycosis can be in various dosage forms, and the dosage forms include but are not limited to Rana antimicrobial peptide gel, Rana antimicrobial peptide spray, Rana antimicrobial peptide disinfection preparation, Rana antimicrobial peptide ointment, Rana antibacterial peptide lotion, etc.

公告号为CN1583165A的授权专利中公开了一种林蛙抗菌肽凝胶剂及其制备方法。The authorized patent whose notification number is CN1583165A discloses a Rana antimicrobial peptide gel and a preparation method thereof.

公开号为CN1583166A的中国专利申请中公开了一种林蛙抗菌肽喷雾剂及其制备方法。The Chinese patent application whose publication number is CN1583166A discloses a Rana antimicrobial peptide spray and a preparation method thereof.

公开号为CN101491245A的中国专利申请中公开了一种含林蛙抗菌肽消毒制剂及其制备方法。A Chinese patent application with publication number CN101491245A discloses a disinfectant preparation containing Rana antibacterial peptide and a preparation method thereof.

公开号为CN101496773A的中国授权专利中公开了一种林蛙抗菌肽洗剂及其制备方法。The Chinese authorized patent with the publication number CN101496773A discloses a Rana antibacterial peptide lotion and a preparation method thereof.

公开号为CN104173382A的中国专利申请中公开了一种林蛙提取混合液软膏剂及其制备方法。The Chinese patent application with the publication number CN104173382A discloses a wood frog extract mixed liquid ointment and a preparation method thereof.

本发明发现,含有林蛙抗菌肽的任意剂型均可以用于治疗灰指甲。使用林蛙抗菌肽制成的制剂治疗灰指甲,使用方法简单,有效率及治愈率高,适用人群广,无副作用,复发率低。The present invention finds that any dosage form containing the Rana antibacterial peptide can be used for treating onychomycosis. Onychomycosis is treated with the preparation made of Rana antimicrobial peptide, the method of use is simple, the effective rate and cure rate are high, the applicable population is wide, there is no side effect, and the recurrence rate is low.

具体实施方式detailed description

下面结合实施例对本发明作进一步描述。The present invention will be further described below in conjunction with embodiment.

实施例1Example 1

按照公告号为CN1583165A专利中的实施例1所述方法制备林蛙抗菌肽凝胶剂,对其进行药效学研究。According to the method described in Example 1 in the CN1583165A patent, the Rana antimicrobial peptide gel was prepared, and its pharmacodynamics was studied.

本发明对200例患者进行临床观察治疗,其中男性118例,女性82例,年龄为21至70岁,均为灰指甲。The present invention carries out clinical observation and treatment to 200 patients, including 118 males and 82 females aged 21 to 70 years old, all of whom are onychomycosis.

(1)治疗方法:(1) Treatment method:

外用,每日将所述的林蛙抗菌肽凝胶剂涂抹患处4次,涂抹时要均匀覆盖患处,每个患处每次用量约为1-2ml,连续涂抹60天。For external use, apply the Rana antimicrobial peptide gel to the affected area 4 times a day, cover the affected area evenly, and use about 1-2ml each time for each affected area, and apply it continuously for 60 days.

(2)疗效评定标准:(2) Evaluation criteria for curative effect:

治愈:甲板变色、凹陷或翘起、粗糙不平等临床症状体征消失,功能活动恢复正常。Cure: Discoloration, sunken or warped deck, rough and uneven clinical symptoms and signs disappear, and functional activities return to normal.

有效:临床症状明显好转或基本消失。Effective: the clinical symptoms were significantly improved or basically disappeared.

无效:临床症状体征无改善。Ineffective: no improvement in clinical symptoms and signs.

(3)治疗效果:(3) Treatment effect:

临床治愈168例,占84%;有效34例,占17%;无效0例;总有效率100%。168 cases were clinically cured, accounting for 84%; 34 cases were effective, accounting for 17%; 0 cases were ineffective; the total effective rate was 100%.

停药30天后未发现复发。No recurrence was found 30 days after drug withdrawal.

实施例2Example 2

按照公开号为CN1583166A的专利申请中的实施例1所述方法制备林蛙抗菌肽喷雾剂,对其进行药效学研究。According to the method described in Example 1 of the patent application whose publication number is CN1583166A, the Rana antimicrobial peptide spray was prepared, and its pharmacodynamic study was carried out.

本发明对100例患者进行临床观察治疗,其中男性63例,女性37例,年龄为21至70岁,均为灰指甲。The present invention carries out clinical observation and treatment to 100 patients, including 63 males and 37 females, aged from 21 to 70 years old, all of whom are onychomycosis.

(1)治疗方法:(1) Treatment method:

外用,每日将所述的林蛙抗菌肽喷雾剂喷洒患处4次,喷洒时要均匀覆盖患处,每个患处每次用量约为1-2ml,连续使用60天。For external use, the Rana antimicrobial peptide spray is sprayed on the affected part 4 times every day, and the affected part will be evenly covered when spraying. Each dosage of each affected part is about 1-2ml, and it is used continuously for 60 days.

(2)疗效评定标准:(2) Evaluation criteria for curative effect:

治愈:甲板变色、凹陷或翘起、粗糙不平等临床症状体征消失,功能活动恢复正常。Cure: Discoloration, sunken or warped deck, rough and uneven clinical symptoms and signs disappear, and functional activities return to normal.

有效:临床症状明显好转或基本消失。Effective: the clinical symptoms were significantly improved or basically disappeared.

无效:临床症状体征无改善。Ineffective: no improvement in clinical symptoms and signs.

(3)治疗效果:(3) Treatment effect:

临床治愈79例,占79%;有效21例,占21%;无效0例;总有效率100%。79 cases were clinically cured, accounting for 79%; 21 cases were effective, accounting for 21%; 0 cases were ineffective; the total effective rate was 100%.

停药30天后未发现复发。No recurrence was found 30 days after drug withdrawal.

实施例3Example 3

按照公告号为CN101491245A专利中的实施例1所述方法制备含有林蛙抗菌肽消毒制剂,对其进行药效学研究。According to the method described in Example 1 in the CN101491245A patent, a disinfection preparation containing Rana antimicrobial peptide was prepared, and its pharmacodynamics was studied.

本发明对70例患者进行临床观察治疗,其中男性39例,女性31例,年龄为25至60岁,均为灰指甲。The present invention carries out clinical observation and treatment to 70 patients, including 39 males and 31 females, aged 25 to 60, all of whom are onychomycosis.

(1)治疗方法:(1) Treatment method:

外用,每日将患处浸泡在所述的林蛙抗菌肽消毒制剂中4次,每次浸泡5分钟,连续使用60天。For external use, the affected part is soaked in the described Rana antibacterial peptide disinfection preparation 4 times every day, soaked for 5 minutes each time, and used continuously for 60 days.

(2)疗效评定标准:(2) Evaluation criteria for curative effect:

治愈:甲板变色、凹陷或翘起、粗糙不平等临床症状体征消失,功能活动恢复正常。Cure: Discoloration, sunken or warped deck, rough and uneven clinical symptoms and signs disappear, and functional activities return to normal.

有效:临床症状明显好转或基本消失。Effective: the clinical symptoms were significantly improved or basically disappeared.

无效:临床症状体征无改善。Ineffective: no improvement in clinical symptoms and signs.

(3)治疗效果:(3) Treatment effect:

临床治愈61例,占87%;有效9例,占13%;无效0例;总有效率100%。61 cases were clinically cured, accounting for 87%; 9 cases were effective, accounting for 13%; 0 cases were ineffective; the total effective rate was 100%.

停药30天后未发现复发。No recurrence was found 30 days after drug withdrawal.

实施例4Example 4

按照公告号为CN101496773A专利中的实施例1所述方法制备林蛙抗菌肽洗剂,对其进行药效学研究。According to the method described in Example 1 in the CN101496773A patent, the Rana antibacterial peptide lotion was prepared, and its pharmacodynamics was studied.

本发明对70例患者进行临床观察治疗,其中男性32例,女性38例,年龄为25至55岁,均为灰指甲。The present invention carries out clinical observation and treatment to 70 patients, wherein 32 cases are males, 38 cases are females, aged 25 to 55 years old, all of them are onychomycosis.

(1)治疗方法:(1) Treatment method:

外用,每日将患处浸泡在所述的林蛙抗菌肽洗剂中4次,每次浸泡5分钟,连续使用60天。For external use, the affected part is soaked in the Rana antimicrobial peptide lotion 4 times every day, soaked for 5 minutes each time, and used continuously for 60 days.

(2)疗效评定标准:(2) Evaluation criteria for curative effect:

治愈:甲板变色、凹陷或翘起、粗糙不平等临床症状体征消失,功能活动恢复正常。Cure: Discoloration, sunken or warped deck, rough and uneven clinical symptoms and signs disappear, and functional activities return to normal.

有效:临床症状明显好转或基本消失。Effective: the clinical symptoms were significantly improved or basically disappeared.

无效:临床症状体征无改善。Ineffective: no improvement in clinical symptoms and signs.

(3)治疗效果:(3) Treatment effect:

临床治愈59例,占84%;有效11例,占16%;无效0例;总有效率100%。59 cases were clinically cured, accounting for 84%; 11 cases were effective, accounting for 16%; 0 cases were ineffective; the total effective rate was 100%.

停药30天后未发现复发。No recurrence was found 30 days after drug withdrawal.

实施例5Example 5

按照公告号为CN104173382A专利申请中的实施例二所述方法制备林蛙抗菌肽软膏剂,对其进行药效学研究。According to the method described in Example 2 of the CN104173382A patent application, the Rana antimicrobial peptide ointment was prepared, and its pharmacodynamics was studied.

本发明对64例患者进行临床观察治疗,其中男性35例,女性29例,年龄为25至70岁,均为灰指甲。The present invention carries out clinical observation and treatment to 64 patients, wherein 35 cases are males, 29 cases are females, aged 25 to 70 years old, all of them are onychomycosis.

(1)治疗方法:(1) Treatment method:

外用,每日将所述的林蛙抗菌肽软膏剂涂抹患处4次,涂抹时要均匀覆盖患处,每个患处每次用量约为1-2ml,连续使用60天。For external use, apply the Rana antibacterial peptide ointment to the affected part 4 times every day, and cover the affected part evenly when smearing. The dosage of each affected part is about 1-2ml, and it is used continuously for 60 days.

(2)疗效评定标准:(2) Evaluation criteria for curative effect:

治愈:甲板变色、凹陷或翘起、粗糙不平等临床症状体征消失,功能活动恢复正常。Cure: Discoloration, sunken or warped deck, rough and uneven clinical symptoms and signs disappear, and functional activities return to normal.

有效:临床症状明显好转或基本消失。Effective: the clinical symptoms were significantly improved or basically disappeared.

无效:临床症状体征无改善。Ineffective: no improvement in clinical symptoms and signs.

(3)治疗效果:(3) Treatment effect:

临床治愈55例,占86%;有效9例,占14%;无效0例;总有效率100%。55 cases were clinically cured, accounting for 86%; 9 cases were effective, accounting for 14%; 0 cases were ineffective; the total effective rate was 100%.

停药30天后未发现复发。No recurrence was found 30 days after drug withdrawal.

Claims (2)

1.林蛙抗菌肽在治疗灰指甲的药物制备中的用途。1. The use of Rana antibacterial peptide in the preparation of medicine for the treatment of onychomycosis. 2.根据权利要求1所述的用途,其特征在于:所述治疗灰指甲的药物为林蛙抗菌肽凝胶剂、林蛙抗菌肽喷雾剂、林蛙抗菌肽消毒制剂、林蛙抗菌肽软膏剂或林蛙抗菌肽洗剂。2. purposes according to claim 1, it is characterized in that: the medicine of described treatment onychomycosis is Rana antimicrobial peptide gel, Rana antimicrobial peptide spray, Rana antimicrobial peptide disinfection preparation, Rana antimicrobial peptide ointment agent or Rana antimicrobial peptide lotion.
CN201610143384.1A 2016-03-14 2016-03-14 Application of antibacterial peptides of wood frogs to preparing medicines for treating onychomycosis Pending CN105749250A (en)

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Citations (4)

* Cited by examiner, † Cited by third party
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CN101208355A (en) * 2005-06-28 2008-06-25 Ai2有限公司 Treatment of fungal and/or protist infections
WO2009059379A1 (en) * 2007-11-07 2009-05-14 Dynamic Microbials Limited Antimicrobial compositions, formulations and uses thereof
CN101491245A (en) * 2009-02-25 2009-07-29 吉林大学 Disinfection preparation containing forest frog antibacterial peptide and preparation method and use thereof
CN101496773A (en) * 2009-02-25 2009-08-05 吉林大学 Antimicrobial lotion containing wood frog antimicrobial peptide and preparation method thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101208355A (en) * 2005-06-28 2008-06-25 Ai2有限公司 Treatment of fungal and/or protist infections
WO2009059379A1 (en) * 2007-11-07 2009-05-14 Dynamic Microbials Limited Antimicrobial compositions, formulations and uses thereof
CN101491245A (en) * 2009-02-25 2009-07-29 吉林大学 Disinfection preparation containing forest frog antibacterial peptide and preparation method and use thereof
CN101496773A (en) * 2009-02-25 2009-08-05 吉林大学 Antimicrobial lotion containing wood frog antimicrobial peptide and preparation method thereof

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Title
田晓乐 等: "林蛙抗菌肽凝胶剂的制备及抑菌试验", 《吉林大学学报》 *

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Application publication date: 20160713