公开(公告)号：WO2014126681A1

公开(公告)日：2014-08-21

申请号：PCT/US2014/012378

申请日：2014-01-21

Applicant: HELIX BIOMEDIX INC.

Inventor： ZHANG, Lijuan ,  CARMICHAEL, Robin

IPC: A61K38/16 ,  C07K14/435

CPC classification number: A61K38/1767 ,  A61K8/64 ,  A61K38/00 ,  A61K2800/74 ,  A61Q19/00 ,  A61Q19/08 ,  C07K5/1013 ,  C07K5/1021 ,  C07K7/06 ,  C07K14/43563 ,  C12Q1/6876 ,  G01N33/5014 ,  G01N33/5044

Abstract: Peptides having four to six amino acid residues are disclosed that possess biological activity. These peptides constitute short fragments of the peptide HB-107 (MPKEKVFLKIEKMGRNIRN), which itself is a fragment of the antimicrobial protein cecropin B, and exhibit cell stimulatory and migratory properties. The inventive peptides comprise four to six contiguous amino acid residues located between position 11 and 16 of HB107 (MPKEKVFLKIEKMGRNIRN), namely EKMGRN. The disclosed peptides comprise a useful agent for the medical treatment of injury to the skin, such as from diabetic ulcers. The peptides also are effective in preventing and reversing skin surface damage resulting from various environmental insults. Importantly, the therapeutic effects of the peptides manifest at concentrations equal to or greater than those of peptide HB-107, and thus represent a less expensive, more versatile means for developing effective therapies. Methods for the production and use of these peptides are also disclosed.

Abstract translation: 披露具有4-6个氨基酸残基的肽具有生物活性。 这些肽构成肽HB-107（MPKEKVFLKIEKMGRNIRN）的短片段，其本身是抗微生物蛋白质天蚕素B的片段，并且具有细胞刺激和迁移性质。 本发明的肽包含位于HB107（MPKEKVFLKIEKMGRNIRN）的位置11和16之间的四至六个连续的氨基酸残基，即EKMGRN。 所公开的肽包括用于治疗皮肤损伤的有用试剂，例如来自糖尿病性溃疡。 这些肽也有效地预防和逆转由各种环境污染引起的皮肤表面损伤。 重要的是，肽的治疗效果以等于或大于肽HB-107的浓度表现，因此代表开发有效疗法的较便宜，更通用的手段。 还公开了生产和使用这些肽的方法。

公开(公告)号：WO2012003176A1

公开(公告)日：2012-01-05

申请号：PCT/US2011/042123

申请日：2011-06-28

Applicant: FALLA, Timothy, J. ,  ZHANG, Lijuan ,  HELIX BIOMEDIX, INC.

Inventor： FALLA, Timothy, J. ,  ZHANG, Lijuan

IPC: A61K31/20 ,  A61K8/44

CPC classification number: A61K31/198 ,  A61K8/42 ,  A61K8/44 ,  A61K31/20 ,  A61K45/06 ,  A61Q19/06 ,  C07C237/12

Abstract: The invention relates to small molecules having biological and therapeutic activity. Particularly, the invention relates to small molecules having lipolytic and anti-adipogenic activity. Two examples of such molecules are 4-methyl-2-(octanoylamino) pentanoic acid and N-isopentyloctanamide. The invention further relates to methods of preventing or treating skin conditions such as cellulite using small molecules having lipolytic and anti-adipogenic activity.

Abstract translation: 本发明涉及具有生物和治疗活性的小分子。 特别地，本发明涉及具有脂肪分解和抗脂肪生成活性的小分子。 这些分子的两个实例是4-甲基-2-（辛酰氨基）戊酸和N-异戊基辛酰胺。 本发明还涉及使用具有脂肪分解和抗脂肪生成活性的小分子预防或治疗皮肤病症如脂肪团的方法。

公开(公告)号：WO2018085565A2

公开(公告)日：2018-05-11

申请号：PCT/US2017/059756

申请日：2017-11-02

Applicant: HELIX BIOMEDIX, INC.

Inventor： ZHANG, Lijuan ,  CARMICHAEL, Robin

IPC: A61K47/69 ,  A61K38/16

Abstract: Advanced glycation end products (AGEs) represent a non-enzymatic post-translational protein modification. AGEs are very stable and the accumulation over time can be used as markers of carbonyl stress which are responsible for the malfunction of bioactive macromolecules in the body. Disclosed herein are a series of short peptides for blocking activity of advanced glycation end products (AGEs), the peptide being derived from a V-region of an sRAGE protein, wherein the V-region is given by SEQ ID NO:61. These peptides effectively inhibit the progress of a Maillard reaction, blocking the AGEs and inhibiting dicarbonyl induced cell apoptosis and death. The peptides can be used as, for example, an anti-glycation agent, a skin anti-aging agent, or an anti-diabetic complication agent.

Abstract translation: 晚期糖基化终产物（AGEs）代表非酶促翻译后蛋白质修饰。 AGEs非常稳定，随着时间的推移累积可以用作羰基应激的标记，这是造成体内生物活性大分子故障的原因。 本文公开了用于阻断晚期糖基化终产物（AGE）活性的一系列短肽，所述肽源自sRAGE蛋白的V区，其中V区由SEQ ID NO：61给出。 这些肽有效抑制美拉德反应的进展，阻断AGEs并抑制二羰基诱导的细胞凋亡和死亡。 这些肽可以用作例如抗糖化剂，皮肤抗衰老剂或抗糖尿病并发症剂。

公开(公告)号：WO2008085494A1

公开(公告)日：2008-07-17

申请号：PCT/US2007/026368

申请日：2007-12-27

Applicant: HELIX BIOMEDIX INC. ,  HARRIS, Scott, M. ,  ZHANG, Lijuan ,  FALLA, Timothy, J.

Inventor： HARRIS, Scott, M. ,  ZHANG, Lijuan ,  FALLA, Timothy, J.

IPC: C07K14/435 ,  A61K38/00

CPC classification number: C07K14/43563 ,  A61K38/00 ,  C07K5/1024 ,  C07K7/08

Abstract: Peptides having four to fourteen residues are disclosed that possess biological activity. These peptides constitute short fragments of the peptide HB-107 (SEQ ID NO:1), which itself is a fragment of the antimicrobial protein cecropin B, and exhibit cell stimulatory, migratory and anti-inflammatory properties. As keratinocytes are especially sensitive to these effects, the disclosed peptides comprise a useful agent for the medical treatment of injury to the skin, such as from diabetic ulcers. The peptides also are effective in preventing and reversing skin surface damage resulting from various environmental insults. Importantly, the therapeutic effects of the peptides manifest at concentrations equal to or greater than those of peptide HB-107, and thus represent a less expensive, more versatile means for developing effective therapies. Methods for the production and use of these peptides are also disclosed.

Abstract translation: 披露具有四至十四个残基的肽具有生物活性。 这些肽构成肽HB-107（SEQ ID NO：1）的短片段，其本身是抗微生物蛋白质天蚕素B的片段，并且具有细胞刺激性，迁移性和抗炎性质。 由于角质形成细胞对这些作用特别敏感，所公开的肽包括用于治疗皮肤损伤（例如糖尿病性溃疡）的有用试剂。 这些肽也有效地预防和逆转由各种环境污染引起的皮肤表面损伤。 重要的是，肽的治疗效果以等于或大于肽HB-107的浓度表现，因此代表开发有效疗法的较便宜，更通用的手段。 还公开了生产和使用这些肽的方法。

公开(公告)号：WO2019108484A3

公开(公告)日：2019-06-06

申请号：PCT/US2018/062477

申请日：2018-11-26

Applicant: HELIX BIOMEDIX, INC.

Inventor： ZHANG, Lijuan ,  CARMICHAEL, Robin

IPC: A61K38/00 ,  A61K45/06 ,  A61Q19/00

Abstract: Disclosed herein is a composition including a peptide consisting of the sequence of SEQ ID NO: 1 for increasing the production of melanin. The present disclosure provides methods and formulations for the treatment of pigmentation disorders or conditions. In some embodiments, provided herein are compositions and methods for sunless tanning. In other embodiments, the present disclosure is directed to such compositions that are formulated for use as pharmaceuticals and cosmetic products, and to medical devices comprising the disclosed compositions.

公开(公告)号：WO2019108484A2

公开(公告)日：2019-06-06

申请号：PCT/US2018/062477

申请日：2018-11-26

Applicant: HELIX BIOMEDIX, INC.

Inventor： ZHANG, Lijuan ,  CARMICHAEL, Robin

IPC: A61K38/08

Abstract: Disclosed herein is a composition including a peptide consisting of the sequence of SEQ ID NO: 1 for increasing the production of melanin. The present disclosure provides methods and formulations for the treatment of pigmentation disorders or conditions. In some embodiments, provided herein are compositions and methods for sunless tanning. In other embodiments, the present disclosure is directed to such compositions that are formulated for use as pharmaceuticals and cosmetic products, and to medical devices comprising the disclosed compositions.

公开(公告)号：WO2014200651A1

公开(公告)日：2014-12-18

申请号：PCT/US2014/037978

申请日：2014-05-14

Applicant: HELIX BIOMEDIX INC.

Inventor： ZHANG, Lijuan ,  CARMICHAEL, Robin

IPC: A61K38/07 ,  C07K14/52

CPC classification number: A61K38/07 ,  A61K8/64 ,  A61K38/00 ,  A61K2800/74 ,  A61Q7/02 ,  A61Q19/02 ,  A61Q19/08 ,  C07K14/521

Abstract: Tetrapeptides consisting of (I or V)-X1-K-X2, where X1 can be selected from E, Q or K, and X2 can be selected from M, F, I, W, or V, exhibit diverse bioactivities. They are multi-functional effector molecules to stimulate keratinocytes migration; neutralize the proinflammatory effect of bacterial cell wall components such as lipoteichoic acids of the Gram-positive S. aureus; and induce angiogenesis in cultured human umbilical vein endothelial cells. The downregulation of pro-inflammatory condition was also demonstrated using SOR-300-FT psoriasis skin model for representative peptide. The bioactivity was also supported by gene profiling study upon treatment of normal skin tissues using EPIDERM TM skin substitutes. The inventive peptides with diverse bioactivities are useful for treating various skin conditions including, but not limited to, acute or chronic wounds, striae distensae, aging skin, hair control, inflammatory skins such as psoriasis, atopic dermatitis and rosacea and for unwanted hair removal or for conditions such as removal of skin tags.

Abstract translation: 由（I或V）-X1-K-X2组成的四肽，其中X1可以选自E，Q或K，X2可以选自M，F，I，W或V，表现出不同的生物活性。 它们是多功能效应分子刺激角质细胞迁移; 中和细菌细胞壁组分如革兰氏阳性金黄色葡萄球菌的脂磷壁酸的促炎作用; 并在培养的人脐静脉内皮细胞中诱导血管生成。 使用代表性肽的SOR-300-FT牛皮癣皮肤模型也证实了促炎症状的下调。 使用EPIDERMTM皮肤替代品治疗正常皮肤组织时，生物活性也得到基因谱学研究的支持。 具有不同生物活性的本发明的肽可用于治疗各种皮肤病症，包括但不限于急性或慢性伤口，纹状裂纹，老化皮肤，毛发控制，炎性皮肤如牛皮癣，特应性皮炎和酒渣鼻，以及不需要的毛发去除 用于除去皮肤标签等条件。

公开(公告)号：WO2013142088A1

公开(公告)日：2013-09-26

申请号：PCT/US2013/029696

申请日：2013-03-07

Applicant: HELIX BIOMEDIX INC

Inventor： ZHANG, Lijuan ,  CARMICHAEL, Robin

IPC: A61K47/48 ,  C07K5/09 ,  A61K38/34

CPC classification number: C07K5/06086 ,  A61K38/05 ,  A61K38/06 ,  A61K38/34 ,  A61K47/542 ,  C07K5/0815 ,  Y02A50/473

Abstract: Disclosed are peptides having biological and therapeutic activity. Particularly disclosed are lipidated di- or tri- peptides analogs of KPV or KdPT that exhibit antimicrobial activity. In particular, the peptides of this invention provide enhanced anti-microbial activity over the base tri -peptides, lysine -proline- valine and lysine-d-proline-tyrosine. The disclosed peptides have the general formula of C12-18 lipid— KXZ-NH 2 i wherein K is lysine; X is proline, d-proline, histidine or arginine; Z is optional and if present Z is valine, threonine, alanine or leucine; and the terminal COOH is NH 2 amidated. The C12-18 lipid is preferably the lipid moiety of lauric acid (C12), myristic acid (C14), pentadecanoic acid (C15), palmitic acid (C16), or stearic acid (C18). The invention is further related to methods of using of these peptides to treat various insults, inflammations or bacterial infections affecting the skin and other related mucosal body surfaces such as the oral cavity.

Abstract translation: 公开了具有生物和治疗活性的肽。 特别公开了表现出抗微生物活性的KPV或KdPT的脂化二或三肽类似物。 特别地，本发明的肽相对于碱基三肽，赖氨酸 - 脯氨酸 - 缬氨酸和赖氨酸-d-脯氨酸 - 酪氨酸提供增强的抗微生物活性。 所公开的肽具有通式C12-18脂质KXZ-NH2i，其中K是赖氨酸; X是脯氨酸，脯氨酸，组氨酸或精氨酸; Z是任选的，如果存在Z是缬氨酸，苏氨酸，丙氨酸或亮氨酸; 并且末端COOH是NH 2酰胺化的。 C12-18脂质优选为月桂酸（C12），肉豆蔻酸（C14），十五烷酸（C15），棕榈酸（C16）或硬脂酸（C18）的脂质部分。 本发明还涉及使用这些肽来治疗影响皮肤和其它相关粘膜体表如口腔的各种侮辱，炎症或细菌感染的方法。

公开(公告)号：WO2018085565A3

公开(公告)日：2018-05-11

申请号：PCT/US2017/059756

申请日：2017-11-02

Applicant: HELIX BIOMEDIX, INC.

Inventor： ZHANG, Lijuan ,  CARMICHAEL, Robin

IPC: A61K38/00 ,  A61K38/04 ,  A61K38/06

Abstract: Advanced glycation end products (AGEs) represent a non-enzymatic post-translational protein modification. AGEs are very stable and the accumulation over time can be used as markers of carbonyl stress which are responsible for the malfunction of bioactive macromolecules in the body. Disclosed herein are a series of short peptides for blocking activity of advanced glycation end products (AGEs), the peptide being derived from a V-region of an sRAGE protein, wherein the V-region is given by SEQ ID NO:61. These peptides effectively inhibit the progress of a Maillard reaction, blocking the AGEs and inhibiting dicarbonyl induced cell apoptosis and death. The peptides can be used as, for example, an anti-glycation agent, a skin anti-aging agent, or an anti-diabetic complication agent.

公开(公告)号：WO2009058244A1

公开(公告)日：2009-05-07

申请号：PCT/US2008/012191

申请日：2008-10-28

Applicant: HELIX BIOMEDIX INC. ,  ZHANG, Lijuan ,  HARRIS, Scott, M. ,  FALLA, Timothy, J.

Inventor： ZHANG, Lijuan ,  HARRIS, Scott, M. ,  FALLA, Timothy, J.

IPC: C07K5/10

CPC classification number: C07K5/1024 ,  A61K8/64 ,  A61K38/00 ,  A61K2800/782 ,  A61Q19/08

Abstract: The disclosed invention provides tetrapeptides with the amino acid sequence proline- glutamine-glutamate-X (P-Q-E-X), where X can be either lysine (K) or isoleucine (I). These tetrapeptides inhibit ultraviolet light (UV)-induced expression of the pro-inflammatory cytokine interleukin-6 (IL-6) by skin epithelial cells and fibroblasts. Furthermore, the tetrapeptides repress the upregulation of matrix metalloproteinase-1 (MMP-1) by skin fibroblasts induced by either direct exposure to UV rays or treatment with media conditioned by UV-treated keratinocytes. The small size and bio-activity of the tetrapeptides render them suitable for use in therapies directed to inflammatory skin disorders and as active ingredients in skin care products.

Abstract translation: 所公开的发明提供四肽与氨基酸序列脯氨酸 - 谷氨酰胺 - 谷氨酸酯-X（P-Q-E-X），其中X可以是赖氨酸（K）或异亮氨酸（I）。 这些四肽通过皮肤上皮细胞和成纤维细胞抑制紫外线（UV）诱导的促炎细胞因子白细胞介素-6（IL-6）的表达。 此外，四肽通过直接暴露于紫外线诱导的皮肤成纤维细胞抑制基质金属蛋白酶-1（MMP-1）的上调或通过经紫外线处理的角质形成细胞调节的培养基来治疗。 四肽的小尺寸和生物活性使其适合用于治疗炎症性皮肤病症和作为皮肤护理产品中的活性成分。